Raman Imaging of Silicon Structures - Advanstar Communications

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Raman Imaging of Silicon Structures

Quality Agreements for Contract Drug Manufacturing

Diagnosing Cancer with Raman Spectroscopy

September 2013 Volume 28 Number 9 wwwspectroscopyonlinecom

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Tom Ehardt Executive Vice-President Chief Administrative Officer amp Chief Financial Officer

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Francis Heid Vice-President Media Operations

Michael Bernstein Vice-President Legal

J Vaughn Vice-President Electronic Information Technology

wwwspec t roscopyonl ine com6 Spectroscopy 28(9) September 2013

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CONTENTS

Spectroscopy (ISSN 0887-6703 [print] ISSN 1939-1900 [digital]) is published monthly by Advanstar Communications Inc 131 West First Street Duluth MN 55802-2065 Spectroscopy is distributed free of charge to users and specifiers of spectroscopic equip-ment in the United States Spectroscopy is available on a paid subscription basis to nonqualified readers at the rate of US and pos-sessions 1 year (12 issues) $7495 2 years (24 issues) $13450 CanadaMexico 1 year $95 2 years $150 International 1 year (12 issues) $140 2 years (24 issues) $250 Periodicals postage paid at Duluth MN 55806 and at additional mailing of fices POSTMASTER Send address changes to Spectroscopy PO Box 6196 Duluth MN 55806-6196 PUBLICATIONS MAIL AGREEMENT NO 40612608 Return Undeliverable Canadian Addresses to IMEX Global Solutions P O Box 25542 London ON N6C 6B2 CANADA Canadian GST number R-124213133RT001 Printed in the USA

September 2013 Volume 28 Number 9

v 28 n 9s 2013

COLUMNS

Molecular Spectroscopy Workbench 12Raman Imaging of Silicon StructuresWhat exactly is a ldquoRaman imagerdquo and how is it rendered The authors explain those points and demonstrate the use of Raman imaging for the characterization of thin-film and ion-implanted silicon structures High spectral resolution makes it possible to resolve or contrast the substrate silicon and polysilicon film in Raman images and thus aids in the chemical or physical differentiation of spectrally similar materials

David Tuschel

Mass Spectrometry Forum 22Eponymous Mass Spectrometry The Brubaker Prefilter and Kendrick MassAn important method of recognition in the scientific community is to use an individualrsquos name in a description of the contribution known as an eponymous tribute Mass spectrometry showcases a number of inventions named after the inventor Here we explain two the Brubaker prefilter and Kendrick mass

Kenneth L Busch

Focus on Quality 28Why Do We Need Quality AgreementsIn pharmaceutical contract manufacturing the work of analytical scientists is covered by a quality agreement which is prepared by personnel in the quality control or quality assurance department and focuses on the laboratory analyses provided But what exactly are quality agreements why do we need them who should be involved in writing them and what should they contain Here we answer those questions

RD McDowall

PEER-REVIEWED ARTICLE

The Use of Raman Spectroscopy in Cancer Diagnostics 36Raman spectroscopy and surface-enhanced Raman spectroscopy (SERS) are proving to be valuable tools in biomedical research and clinical diagnostics This review looks at two examples the use of traditional Raman spectroscopy for the assessment of breast cancer and the use of SERS for the screening of pancreatic cancer biomarkers

Robert Thomas Katherine Bakeev Michael Claybourn and Robert Chimenti

Cover image courtesy ofDavid Tuschel

ON THE WEBFACSS-SCIX PODCAST SERIES

Combining Spectroscopic and Chromatographic Techniques

An interview with Charles Wilkins the winner of the 2013 ACS Division of Analytical Chemistry Award in Chemical Instrumentation which will be presented this fall at SciX

spectroscopyonlinecompodcasts

WEB SEMINARS

How to Avoid Bad Data When Analyzing Routine QAQC Industrial Samples Using ICP-OES and ICP-MS

James Hannan and Julian WillsThermo Fisher Scientific

USP lt232gt and lt233gt Practical Considerations for Compliance with the New Requirements on Elemental Impurities

Tim Cuff and Kevin Kingston PerkinElmerNathan Saetveit Elemental Scientific

spectroscopyonlinecomwebseminars

Like Spectroscopy on Facebook wwwfacebookcomSpectroscopyMagazine

Follow Spectroscopy on TwitterhttpstwittercomspectroscopyMag

Join the Spectroscopy Group on LinkedInhttplinkdinSpecGroup

DEPARTMENTS News Spectrum 11Fran Adar Joins Spectroscopyrsquos Editorial Advisory BoardRigaku and Emerald Bio Create Strategic Alliance

Products amp Resources 44

Calendar 48

Ad Index 50

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10 Spectroscopy 28(9) September 2013

Editorial Advisory Board

wwwspec troscopyonl ine com

Fran Adar Horiba Jobin Yvon

Ramon M Barnes University of Massachusetts

Matthieu Baudelet University of Central Florida

Paul N Bourassa Blue Moon Inc

Michael S Bradley Thermo Fisher Scientific

Deborah Bradshaw Consultant

Kenneth L Busch Wyvern Associates

Ashok L Cholli Polnox Corporation

David M Coleman Wayne State University

David Lankin University of Illinois at Chicago College of Pharmacy

Barbara S Larsen DuPont Central Research and Development

Ian R Lewis Kaiser Optical Systems

Rachael R Ogorzalek Loo University of California Los Angeles David Geffen School of Medicine

Howard Mark Mark Electronics

RD McDowall McDowall Consulting

Gary McGeorge Bristol-Myers Squibb

Linda Baine McGown Rensselaer Polytechnic Institute

Robert G Messerschmidt Rare Light Inc

Francis M Mirabella Jr Mirabella Practical Consulting Solutions Inc

John Monti Montgomery College

Michael L Myrick University of South Carolina

John W Olesik The Ohio State University

Jim Rydzak GlaxoSmithKline

Jerome Workman Jr Unity Scientific

Contributing Editors


David W Ball Cleveland State University



Volker Thomsen Consultant


Spectroscopy rsquos Editorial Advisory Board is a group of distinguished individuals assembled to help the publication fulfill its editorial mission to promote the effec-tive use of spectroscopic technology as a practical research and measurement tool With recognized expertise in a wide range of technique and application areas board members perform a range of functions such as reviewing manuscripts suggesting authors and topics for coverage and providing the editor with general direction and feedback We are indebted to these scientists for their contributions to the publica-tion and to the spectroscopy community as a whole

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wwwspec t roscopyonl ine com September 2013 Spectroscopy 28(9) 11

News SpectrumNews Spectrum

Figure caption Figure caption Figure caption

Fran Adar Joins Spectroscopyrsquos Editorial Advisory Board

Spectroscopy is pleased to announce the addition of Fran Adar to its editorial advisory board Adar was a post-doctoral Fellow and Assistant Professor at the Johnson Foundation Department of Biophysics University of Pennsylvania (Philadelphia Pennsylvania) from 1972 to 1978 She has been a Raman applications scientist manager and principal scientist at Jobin YvonHoriba Scientific (Edison New Jersey) since 1978 Drawing on her background in education and experience in physics and biophysics Adar has developed applications for the Raman microscope These application areas include semiconductors ceramics containment identification polymer morphology catalysts metal oxides and pharmaceuticals Adar has received awards from the local Microbeam Society (Irene Dion Payne) the Federation of Analytical Chemistry and Spectroscopy Societies (Charles Mann Award) the Coblentz Society (William-Wright Award) and has delivered an address at the prestigious Waters Symposium at the Pittsburgh Conference on the history of the development of Raman instrumentation In 2012 Adar was

invited to be a fellow of the Society for Applied Spectroscopy (Frederick Maryland) She continues to work with new and experienced Raman users developing applications and pushing instrumentation developments to accommodate new applications enabled by evolving techniques Adar has been writing the ldquoMolecular Spectroscopy Workbenchrdquo column for Spectroscopy since 2007 She now coauthors that column with her colleague David Tuschel

Rigaku and Emerald Bio Create Strategic AllianceRigaku (The Woodlands Texas) has acquired the crystallization reagent and consumables business including crystallization screening kits from Emerald Bio (Bainbridge Island Washington) The companies have agreed to work together to develop new products and solutions for the field of protein science ldquoThe addition of these consumables and screening kits is another step in creating a single contact point for our instrumentation customers improving the efficiency of their workflowrdquo said Catherine Klein president of Rigaku Americas Corporationrsquos Life Sciences Division ldquoFurther having Emerald Bio as a development partner and customer will help ensure that we are at the forefront of new product needs in protein sciencerdquo ldquoHaving Rigaku the world leading protein crystallography instrumentation company as a development partner is ideal for Emeraldrdquo said Johan Pontin CEO of Emerald Bio ◾

Raman spectroscopy has developed into a key analytical

tool for the pharmaceutical industry Both portable

and benchtop Raman systems are now widely used for

applications in the pharmaceutical industry Despite a

challenging economy demand

from the pharmaceutical

industry is holding its own and

should return to typical growth

rates by next year

Within the pharmaceutical

industry one of the biggest

applications now is the

identification of incoming raw

materials and finished product

inspection for which there are

numerous new portable and

handheld models available for on-dock or production

area analysis The other major application is the

analysis of polymorphs and salt forms in both quality

control (QC) and product development variations of

which can lead to dramatically different performance of

a pharmaceutical product

Worldwide demand for laboratory and portable

Raman spectroscopy instrumentation from the

pharmaceutical industry was about $36 million in

2012 Global economic conditions and major cuts in

government spending will clearly

make 2013 a challenging year

for the overall Raman market

However the numerous new

product introductions and market

entrants over the last two years

will help keep demand from

the pharmaceutical industry in

positive territory in 2013 if only

slightly until much stronger

growth returns most likely

in 2014

The foregoing data were extracted from SDirsquos market

analysis and perspectives report titled The Global Assessment Report 12th Edition The Laboratory Life Science and Analytical Instrument Industry October 2012 For more information visit

wwwstrategic-directionscom

Market Profile Raman Spectroscopy in the Pharmaceutical Industry

Fran Adar

Thermo Scientific - 24

Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32

Laboratory and portable Raman mdash pharmaceutical vendor share 2012

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Raman spectroscopy has developed into a key analytical tool for the pharmaceutical industry Both portable and benchtop Raman systems are now widely used for applications in the pharmaceutical industry Despite a challenging economy demand from the pharmaceutical industry is holding its own and should return to typical growth rates by next year Within the pharmaceutical industry one of the biggest applications now is the identification of incoming raw materials and finished product inspection for which there are numerous new portable and handheld models available for on-dock or production area analysis The other major application is the analysis of polymorphs and salt forms in both quality control (QC) and product development variations of which can lead to dramatically different performance of a pharmaceutical product

Worldwide demand for laboratory and portable Raman spectroscopy instrumentation from the pharmaceutical industry was about $36 million in 2012 Global economic conditions and major cuts in

government spending will clearly make 2013 a challenging year for the overall Raman market However the numerous new product introductions and market entrants over the last two years will help keep demand from the pharmaceutical industry in positive territory in 2013 if only slightly until much stronger growth returns most likely

in 2014 The foregoing data were extracted from SDirsquos market analysis and perspectives report titled The Global Assessment Report 12th Edition The Laboratory Life Science and Analytical Instrument Industry October 2012 For more information visit wwwstrategic-directionscom


Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel

Here we examine what is commonly called a Raman image and discuss how it is rendered We consider a Raman image to be a rendering as a result of processing and interpreting the origi-nal hyperspectral data set Building on the hyperspectral data rendering we demonstrate the use of Raman imaging for the characterization of thin-film and ion-implanted silicon (Si) struc-tures A Raman image does not self-reveal solid-state structural effects and requires either the informed selection and assignation of the as-acquired hyperspectral data set by the spectrosco-pist or the use of statistical software applications High spectral resolution allows us to clearly resolve the substrate Si Raman scattering from that of the polysilicon film Consequently high spectral resolution allows us to strongly resolve (structurally not spatially) or contrast the sub-strate Si and polysilicon film in Raman images that is the spectral resolution contributes to the chemical or physical differentiation of spectrally similar materials in thin-film structures


Molecular Spectroscopy Workbench

The primary goals of this column installment are to first examine in more detail what is commonly called a ldquoRaman imagerdquo and to discuss how it is ldquorenderedrdquo

and second to demonstrate the use of Raman imaging for the characterization of thin-film and ion-implanted silicon (Si) structures The Raman images of Si and their render-ing from the hyperspectral data sets presented here should encourage the reader to think more broadly of Raman imag-ing applications of semiconductors in electronic and other devices such as microelectromechanical systems (MEMS) Raman imaging is particularly useful for revealing the spa-tial heterogeneity of solid-state structures in semiconductor devices Here test structures consisting of substrate silicon silicon dioxide polycrystalline silicon and ion-implanted silicon are analyzed by Raman imaging to characterize the solid-state structure of the materials

Before we begin our discussion on Raman imaging of silicon structures we need to carefully consider and under-stand what actually constitutes a ldquoRaman imagerdquo Consider the black and white photograph perhaps the most basic type

of image with which we are familiar One can think of it as a three-coordinate system with two spatial coordinates and one brightness (independent of wavelength) coordinate Progressing to a color photograph we now have a four-co-ordinate system by adding a chromaticity coordinate to the original three of a black and white image That chromaticity coordinate in the color photograph is the key to thinking about hyperspectral imaging in general and Raman imag-ing in particular Whether color discrimination is due to the cone cells in our eyes the wavelength sensitive dyes in color photographic film or the color filters fabricated onto charge-coupled device (CCD) sensors a wavelength selec-tion is imposed on the image That color discrimination may not faithfully render a color image that corresponds to the true color of the object for example people who are color blind may not see the true colors of an object In our daily lives it is the combination of shape (two spatial coordinates) brightness (intensity coordinate) and color (chromaticity coordinate) that we interpret in the images we see to draw meaning and respond to the objects from which

copy20

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012

Perk

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0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

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they originate In that sense image interpretation comes naturally to us and we begin to do it from a very early age without giving it much analytical thought

When applying these same basic imaging principles of the four-coordinate system to hyperspectral imaging the interpretation of the spectral (chromaticity) and intensity (brightness) coordinates are no longer ldquonaturalrdquo and require mathematical thinking for proper interpretation This mathematical thinking by the spectroscopist comes in the form of direct selection of spectral band posi-tion width shape and resolution from closely spaced bands The intensity coordinate is most often interpreted as the value at one particular peak or wavelength relative to that of another However even the simple application of an intensity coordinate requires the removal of background light unrelated to the spectroscopic phenomenon of interest Furthermore there are band-fitting operations and width and shape measurements that can be made and plotted against the two spatial coor-dinates to render an image One can also apply any number of statistical and chemometric tools found in most scientific software Therefore whether

the spectroscopist is directly engaged in the selection of spectral features and processing of the hyperspectral data set or simply uses statistical software operations the spectral image is still the rendered product from a group of mathematical functions operating on the data

Now letrsquos apply these hyperspectral imaging considerations to Raman imaging We are all too familiar with the fluorescent background that often accompanies Raman scattering In some instances the spectroscopist will digitally subtract the fluorescent background before rendering a spec-trum that consists almost exclusively of Raman data By analogy we might expect the same practice to hold if we wish to call an image a ldquoRaman imagerdquo rather than a ldquospectral imagerdquo (one that includes data from all light from the object) For example if the signal strength in a hyperspectral image de-tected at a particular Raman shift con-sists of 90 fluorescence and only 10 Raman scattering it would not be cor-rect to call that a Raman image How-ever if the fluorescent background and any contribution from a light source other than Raman scattering is first re-moved then we have a Raman image Having done that we are not neces-

sarily finished rendering our Raman image If we wish to spatially assign chemical identity or another physical characteristic to the image the data must be interpreted either through a spectroscopistrsquos understanding of chemistry and physics or through the statistical treatment of the data The spectral image data as acquired are not self-selecting or -interpreting It is only after applying the spectroscopistrsquos judgment or statistical tools that one renders a color coded Raman image of compound A compound B and so on

I hope that you can see (pun in-tended) that Raman imaging is not an entirely simple matter or as intuitive as photography Rather it requires careful attention to the mathematical opera-tion on the data and interpretation of the results A Raman image is rendered as a result of processing and interpret-ing the original hyperspectral data set The proper interpretation of the data to render a Raman image requires an un-derstanding or at least some knowledge of the processes by which the image was generated

Imaging Strain and Microcrystallinity in PolysiliconThe development of Raman spec-troscopy for the characterization of semiconductors began in earnest in the mid-1970s and micro-Raman methods for spatially resolved semi-conductor analysis were being used in the early 1980s An account of the work in those early years can be found in the excellent book by Perkowitz (1) Perhaps even more surprising to young readers is the fact that one can find the words ldquoRaman imagerdquo in ei-ther the title or text of some of those 1980s publications (2ndash4) Much of that early work involved the development of micro-Raman spectroscopy for the characterization of polycrystalline sili-con (5ndash8) also known as polysilicon which is still used extensively in fab-ricated electronic devices Theoretical and experimental work was directed toward an understanding of how strain microcrystallinity and crystal lattice defects or disorder can all affect the Raman band shape position and scattering strength of single and poly-

Polysilicon A

Polysilicon B

Figure 1 Raman hyperspectral data set from a polysilicon test structure with white reflected light image in lower right corner The Raman image (lower left) corresponds to the color-coded bracketed regions in the spectral traces The single spectrum (upper right) corresponds to the crosshairs in the Raman and white reflected light images

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Perk

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A

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adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

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crystalline silicon (9ndash11) The presence of nanocrystalline Si in polysilicon was confirmed through the combination of transmission electron microscopy and Raman spectroscopy and the effects of extremely small Si grain dimensions on the Raman spectra were attributed to phonon confinement (12ndash15) As the crystalline grain size becomes smaller comparable to the wavelength of the incident laser light or less the Raman band broadens and shifts rela-tive to that obtained from a crystalline domain significantly larger than the excitation wavelength This has been explained in part by phonon confine-ment in which the location of the pho-non becomes more certain as the grain size becomes smaller and therefore the energy of the phonon measured must become less certain consistent with the Heisenberg uncertainty principle Now with all that as historical background letrsquos take a fresh look at the Raman im-aging of Si structures with work done and Raman images rendered in the first months of 2013

A collection of data from a polysili-con test structure is shown in Figure 1 A reflected white light image of the structure appears in the lower right-hand corner and a Raman image corre-sponding to the central structure in the reflected light image appears to its left The plot on the upper left consists of all of the Raman spectra acquired over the image area and the upper right-hand plot is of the single spectrum associ-ated with the cursor location in the Raman and reflected light images The Raman data were acquired using 532-nm excitation and a 100times Olympus objective and by moving the stage in 200-nm increments over an approxi-mate area of 25 μm times 25 μm Now we make our first selection and operation on the hyperspectral data set In this particular case the Raman image is rendered through a color-coded plot of Raman signal strength over the corre-sponding color-bracketed Raman shift positions in the two upper traces

Letrsquos discuss the reasoning behind our choice of the brackets and how they relate to differences in the solid-state structure of Si If we were to have a merely elemental compositional

Ion-implanted Si

Figure 3 Raman hyperspectral data set from an ion-implanted polysilicon test structure with white reflected light image in the lower right corner The Raman image (lower left) corresponds to the color-coded bracketed regions in the spectral traces The single spectrum (upper right) corresponds to the lower left-hand corner of the Raman image The ion-implanted Si yields only a weak Raman spectrum that resembles amorphous silicon thereby appearing black in the Raman image To get a better perspective on the importance of Raman imaging registration with the corresponding white light image see the YouTube video called ldquoRaman Image Registrationrdquo (wwwyoutubecomwatchv=rhHCOz-YEtcampfeature=youtube)

X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10

Figure 2 The Raman image from Figure 1 Red corresponds to single crystal silicon green is the strained and microcrystalline polysilicon and blue is the nanocrystalline silicon Polysilicon B (in the center) was deposited on the wider underlying polysilicon A


image of this particular structure we would expect it to be entirely uniform without spatial variation because Si would appear in every pixel of the image However if we distinguish the different solid-state structures of the Si by identifying pristine Si with the Brillouin zone center Raman band of 5207 cm-1 isolated in red brackets microcrystalline and strained Si in green brackets and a distribution of nanocrystallinity and strain in the blue brackets we can render the Raman image in the lower left-hand corner To some degree strain microcrystal-linity and nanocrystallinity are com-mingled in the polysilicon regions of our images however we can make a crude distinction by attributing the blue regions as primarily a result of the nanocrystalline grain size

Now letrsquos take a close look at what our rendering reveals in our Raman image expanded for more detailed ex-amination in Figure 2 The red regions consist of either substrate Si or grown single-crystal Si with different oxide thicknesses The spatial variation of the single-crystal Raman signal strengths corresponds precisely with the physical optical effects of the oxide thicknesses and even small contaminants or de-fects seen in the reflected light image Furthermore because of the thinness of the polysilicon A alone one can see through the green polysilicon A com-ponent to the underlying red substrate Si particularly on the left and right of the upper and lower portions of Figure 2 The spatial variation of the micro-crystalline or strained Si green com-ponent signal strength corresponds to both the central strip consisting of polysilicon B deposited on polysilicon A and the granular variation of poly-silicon A seen in the reflected light im-ages Note that the polysilicon A bright green speckles in the Raman image correspond precisely to black speckles in the reflected light image Careful examination of the central strip reveals these same speckles in the polysilicon A blurred somewhat by the polysilicon B deposited on top of it

Next letrsquos turn our attention to the blue nanocrystalline portion of the image The formation of nano-

crystalline Si occurs almost exclu-sively in polysilicon A and only on top of the central single-crystal Si structure and not the substrate Si Note that the nanocrystallinity oc-curs primarily along the edge of the polysilicon A but disappears as the polysilicon A continues along the Si substrate Also we see that some of the polysilicon A speckles appear blue thereby revealing nanocrystal-linity over the central structure but not over the Si substrate

In summary the intensity varia-tions of the single-crystal Si comport with the physical optical effects of varying oxide film thickness and sur-face contaminants Also this Raman image reveals the spatially varying nanocrystallinity microcrystallin-ity and strain in polysilicon We can infer that these structural differences occur either as a result of processing conditions or from interactions with the adjacent or underlying materials in which the polysilicon is in contact

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This exercise clearly demonstrates that a Raman image does not self-reveal solid-state structural effects without the informed selection and assignation of the as acquired hyperspectral data set

Imaging Crystal Lattice Damage Induced by Ion ImplantationNext we examine the Raman imaging of that portion of our polysilicon test structure in which single-crystal silicon and polysilicon portions have been subjected to high energy ion implantation for the placement of dopants in the cir-cuitry The entire hyperspectral data set of one such region is shown in Figure 3 Again we have a structure consisting of Si substrate isolated single-crystal Si polysilicon A and B silicon oxides and a region implanted at high energy with As+ The Raman spectra were acquired over an area of approximately 30 μm times 30 μm using a 100times Olympus objective with 532-nm excitation and moving the electroni-cally controlled stage in 200-nm increments

High energy ion implants disrupt the crystal lattice to varying degrees depending on the atomic mass dose and kinetic energy of the implanted ions In this case the heavy arsenic ions have completely damaged the crystal lattice The long-range translational symmetry of the Si has been disrupted such that the Raman scat-tering from the ion-implanted Si arises from phonons throughout the Brillouin zone and not just the Brillouin

zone center as in crystals Consequently ion-implanted Si yields only a weak Raman spectrum that resembles amorphous silicon (16ndash20) For this reason the implant appears dark in the Raman image Note that ion implan-tation affects the reflectance of the Si and that is why the implanted regions appear lighter than the adjacent unimplanted Si in the white reflected light image There-fore we have a good way of confirming the accuracy of our Raman image rendering by its registration with the white reflected light image To get a better perspective on the importance of Raman imaging registration with the corresponding white light image see the YouTube video called ldquoRaman Image Registrationrdquo (wwwyoutubecomwatchv=rhHCOz-YEtcampfeature=youtube)

Letrsquos more carefully examine the expanded Raman image of the implanted structure shown in Figure 4 The substrate and isolated single-crystal Si can be seen in the lower half of the image and can also be seen underneath the polysilicon structures in the upper half The spatial variations of the red intensities correspond well to the edges and contaminants or defects in the white reflected light image The ion-implanted region contrasts strongly with single-crystal Si and polysilicon because of the weakness of the Raman signal from implanted amor-phized Si in all three of the bracketed spectral regions Single-crystal Si and the lower edge of polysilicon A have both been implanted and the Raman image reveals the damage to the crystal lattice of both forms of Si Also note the sharpness of the Raman image and its registra-tion with the reflected light image which reveal the effi-cacy of Raman imaging as a means for ion implant place-ment and registration To get a better perspective on how ion implantation affects the Raman image and to view individual spectra in the implant region see the YouTube video called ldquoRaman Imaging of Implanted Si and Poly-siliconrdquo (httpwwwyoutubecomwatchv=Cf41DKhPzCsampfeature=youtube)

The polysilicon portions of the structure reveal the bright speckles from the polysilicon A that directly cor-respond to each of the black speckles in the white light reflected image In contrast to the Si structures shown in Figures 1 and 2 the processes or adjacent materials have not induced the same degree of nanocrystallinity in this location of polysilicon A Here again we have a structure with both forms of polysilicon and isolated Si but the edges induced only a small amount of nanocrystallinity as revealed by the light blue streak along the polysilicon edge Also we are again able to ldquoseerdquo through the polysili-con to the Si substrate or isolated single-crystal Si Note that the low energy limit of the red bracket begins at 520 cm-1 and so the red region does reasonably differentiate substrate and isolated single-crystal Si from polysilicon The Raman images in the next section allow us more in-sight into this effect

Imaging and the Importance of Spectral ResolutionNow we address the importance of spectral resolution for

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the generation of Raman images of thin-film structures in general and diffusely reflecting Si-based elec-tronic devices in particular Figure 5 shows the hyperspectral data set the white reflected light image and the approximately 14 μm times 22 μm Raman image from that portion of the test structure that consists only of polysilicon A and B on substrate Si The L-shaped region of the im-ages consists of (from bottom to top) substrate Si polysilicon A and poly-silicon B Note that the Raman bands of the different forms of Si in the hyperspectral data set (upper left) are better resolved than those in Figures 1ndash4 This is entirely because of dif-ferences in the solid-state structure of the polysilicon because the same spectrometer grating (1800 grmm) and microscope objective were used for all data acquisition reported here Raman spectra consisting wholly of broad low energy bands peaking be-tween 490 and 510 cm-1 clearly reveal the presence of nanocrystallinity in the polysilicon

Letrsquos more carefully examine the material contrast in the expanded Raman image of the polysilicon structure shown in Figure 6 As we saw in the previous Raman images polysilicon A shows a far greater propensity for forming nanocrystal-line Si at the edges and distributed in some of the speckle Polysilicon B also shows some nanocrystallinity at the edges however it is to a far lesser degree than in polysilicon A The increased thickness of polysilicon B on top of A accounts for the bright green signal in the L-shaped region and the very dim red contribution from the underlying Si substrate In that region with only one layer of polysilicon A covering the substrate Si the underlying red single-crystal Si signal emerges strongly through that of the green polysilicon A The high spectral resolution allows us to clearly resolve the single-crystal Si Raman bands in the red bracket from those of the polysilicon in the green bracket Consequently in this particular structure of only polysili-con on Si substrate the high spec-

tral resolution allows us to strongly resolve (structurally not spatially) or contrast the substrate Si and poly-

silicon in Raman images that is the spectral resolution contributes to the chemical or physical differentiation

Polysilicon B

Polysilicon A

Figure 5 Raman hyperspectral data set from a polysilicon test structure with white reflected light image in lower right corner The Raman image (lower left) corresponds to the color-coded bracketed regions in the spectral traces The single spectrum (upper right) corresponds to the upper right-hand corner of the Raman image

X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si

Figure 4 The Raman image from Figure 3 Red corresponds to single-crystal silicon green corresponds to strained and microcrystalline polysilicon and blue corresponds to nanocrystalline silicon The ion-implanted Si yields only a weak Raman spectrum that resembles amorphous silicon thereby appearing black in the Raman image To get a better perspective on how ion implantation affects the Raman image and to view individual spectra in the implant region see the YouTube video called ldquoRaman Imaging of Implanted Si and Polysiliconrdquo (wwwyoutubecomwatchv=Cf41DKhPzCsampfeature=youtube)


of spectrally similar materials in thin-film structures

Excitation wavelength also plays an important role in depth profil-ing semiconductor structures (19) An excitation wavelength shorter than 532 nm would have a shallower depth of penetration in Si (21) and so we might expect the Raman images generated using different excitation wavelengths to look different At some shorter excitation wavelength depending on the thickness of the polysilicon one would no longer be able to detect the underlying Si substrate or single-crystal Si because of the shallow depth of penetration Wersquoll have to save Raman image depth profiling by excitation wave-length selection for another install-ment of ldquoMolecular Spectroscopy Workbenchrdquo

ConclusionsWe have examined in more detail what is commonly called a Raman image and discussed how it is ren-dered We claim that a Raman image is rendered as a result of process-ing and interpreting the original hyperspectral data set The proper interpretation of the data to render

a Raman image requires an under-standing or at least some knowledge of the processes by which the image was generated Building on the hy-perspectral data rendering we dem-onstrate the use of Raman imaging for the characterization of thin-film and ion-implanted silicon structures We show that a Raman image does not self-reveal solid-state structural effects but requires either the in-formed selection and assignation of the as acquired hyperspectral data set by the spectroscopist or the use of statistical software applications High spectral resolution allows us to clearly resolve the substrate Si Raman scattering from the polysilicon film Consequently high spectral resolu-tion allows us to strongly resolve (structurally not spatially) or con-trast the substrate Si and polysilicon film in Raman images that is the spectral resolution contributes to the chemical or physical differentiation of spectrally similar materials in thin-film structures

References (1) S Perkowitz Optical Characteriza-

tion of Semiconductors Infrared Raman and Photoluminescence

6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6

Figure 6 The Raman image from Figure 5 Red corresponds to substrate silicon green corresponds to strained and microcrystalline polysilicon and blue corresponds to nanocrystalline silicon

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Spectroscopy (Academic Press London UK 1993) Chap 6

(2) K Mizoguchi Y Yamauchi H Harima S Nakashima T Ipposhi and Y InoueJ Appl Phys 78 3357ndash3361 (1995)

(3) S Nakashima K Mizoguchi Y Inoue M Miyauchi A Mitsuishi T Nishimura and Y Akasaka Jpn J Appl Phys 25 L222ndashL224 (1986)

(4) K Kitahara A Moritani A Hara and M Okabe Jpn J Appl Phys 38 L1312ndashL1314 (1999)

(5) Y Inoue S Nakashima A Mitsuishi T Nishimura and Y Akasaka Jpn J Appl Phys 25 798ndash801 (1986)

(6) DR Tallant TJ Headley JW Meder-nach and F Geyling Mat Res Soc Symp Proc 324 255ndash260 (1994)

(7) DV Murphy and SRJ Brueck Mat Res Soc Symp Proc 17 81ndash94 (1983)

(8) G Harbeke L Krausbauer EF Steig-meier AE Widmer HF Kappert and G Neugebauer Appl Phys Lett 42 249ndash251 (1983)

(9) G-X Cheng H Xia K-J Chen W Zhang and X-K Zhang Phys Stat Sol (a) 118 K51ndashK54 (1990)

(10) N Ohtani and K Kawamura Solid State Commun 75 711ndash715 (1990)

(11) H Richter ZP Wang and L Ley Solid State Commun 39 625ndash629 (1981)

(12) Z Iqbal and S Veprek SPIE Proc794 179ndash182 (1987)

(13) VA Volodin MD Efremov and VA Gritsenko Solid State Phenom57ndash58 501ndash506 (1997)

(14) Y He C Yin G Cheng L Wang X Liu and GY Hu J Appl Phys 75 797ndash803 (1994)

(15) H Xia YL He LC Wang W Zhang XN Liu XK Zhang D Feng and HE Jackson J Appl Phys 78 6705ndash6708 (1995)

(16) R Tripathi S Kar and HD Bist J Raman Spec 24 641ndash644 (1993)

(17) D Kirillov RA Powell and DT Hodul J Appl Phys 58 2174ndash2179 (1985)

(18) DD Tuschel JP Lavine and JB Rus-sell Mat Res Soc Symp Proc 406549ndash554 (1996)

(19) DD Tuschel and JP Lavine Mat Res Soc Symp Proc 438 143ndash148 (1997)

(20) JP Lavine and DD Tuschel Mat Res Soc Symp Proc 588 149ndash154 (2000)

(21) Raman and Luminescence Spectroscopy of Microelectronics Catalogue of Optical and Physical Parameters ldquoNostradamusrdquo Project SMT4-CT-95-2024(European Commission Science Research and Development Luxembourg 1998) p 20

David Tuschel is a Raman applications man-ager at Horiba Scientific in Edison New Jersey where he works with Fran Adar David is sharing authorship of this column

with Fran He can be reached atdavidtuschelhoribacom

For more information on this topic please visit our homepage at wwwspectroscopyonlinecom

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Mass Spectrometry Forum

Kenneth L Busch

The time is ripe for further recognition of the breadth of analytical mass spectrometry Other than awards prizes and fellowships an alternative method of recognition in the community is to use an individualrsquos name in a description of the contribution mdash an eponymous tribute Eponymous terms enter into the literature independently of prize or award and are often linked to a singular specific and timely achievement Here we highlight the Brubaker prefilter and Kendrick mass

Eponymous Mass Spectrometry The Brubaker Prefilter and Kendrick Mass

The 2013 annual meeting of the American Society for Mass Spectrometry (ASMS) concluded a few months ago The continued growth of that conference and the

breadth of research and application in mass spectrometry (MS) evident there and described in other professional re-search conferences reflects the vitality of modern MS That growth seems to continue with few limits The growth is cata-lyzed by a need for analysis in new application venues at bet-ter sensitivities but growth is also supported by innovation in instrumentation and information processing The 2013 ASMS conference celebrated 100 years of MS and Michael Gross gave a presentation ldquoThe First Fifty Years of MS Build-ing a Foundationrdquo It is still an unattainable ideal to reliably forecast the future simply by examining the past and truly significant advances often seem to appear from nowhere As is true in most scientific research MS develops predomi-nantly through incremental improvements We can generally predict such improvements More singular revolutionary ad-vances still recognized over the perspective of years should be recognized through research awards such as the Nobel Prize A third type of advancement lies between the two and is neither simply iterative (which belongs to everyone in a sense) or transformative (which is recognized by a singular prize such as the Nobel) These important achievements are recognized within the community by awards of professional

organizations but also through high citation in the literature of specific publications as well as the eponymous citation Eponymous citations interestingly enough sometimes do not include a traditional citation and reference to a publication Often the use of a name stands alone For example in recent columns in this series we have described the use of Girardrsquos reagents in derivatization Penning ionization and the Fara-day cup detector Current scientific publications that use that method or those devices may not cite all the way back to the original publication and may not include any citation at all Using the name alone seems to suffice

In some fields of science such as organism biology the naming rights for a newly discovered organism go to its discoverer and the scientistrsquos name can be part of the term eventually approved by scientific nomenclators In astronomy naming rights for celestial bodies may also link to the first discoverer or organizations may provide recognition of past achievements through the use of names Features on the Moon and Mars for example reflect significant past scientific achievements The instruments still roving Mars are provid-ing a large number of ldquonaming opportunitiesrdquo some of which seem to be tongue-in-cheek In chemistry organic chemists who develop a certain reaction often see their names associ-ated with that reaction (1ndash3) Ion fragmentation reactions in MS can follow this tradition the McLafferty rearrangement

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is a significant eponymous example In instrumentation and engineering devices and mechanical inventions are also often named after their inventors (4) Sometimes even when the inventor shuns publicity (5) the device is so perfect for its application that it remains in use for decades Thus users en-counter the Brannock device without ever knowing the name perhaps but the cognoscenti are familiar with its history

Mass spectrometers are complex instruments encompass-ing technologies from vacuum science ion optics materials science electronics information and computer science and more Instrumental MS showcases a number of inventions named after the inventor We describe some here in this column These represent eponymous terms that are like the Brannock device so widely used or are such an integral part

of the science that they are referred to by name without cita-tion or explanation Table I includes a few eponymous terms that should be familiar to mass spectrometrists In some cases as for the several eponymous terms containing the name of AOC Nier the pioneering contributions have been described in honorific publications (6) The list in Table I is not comprehensive and does not include underlying epony-mous terms in basic science such as Taylor cone Fourier transform Coulombrsquos law Franck-Condon transitions or the like Some eponymous terms are in limited use or they may appear in the literature only a few times these occurrences are both hard to discover and difficult to document From the perspective of 50 or 100 years in laying the foundation for MS there may be a few things that we have always known that we did not actually know until somebody pointed it out The goal in this column is not to revisit some obscure contri-bution but rather to provide an appreciation of contributions that support modern MS

Brubaker PrefilterThe basic concept of the quadrupole mass filter and the quad-rupole ion trap was first disclosed in 1953 it was 36 years later that the contribution was recognized by the award of the 1989 Nobel Prize in Physics Contrast that period of 36 years with the shortened period of only a few years between the awarding of the Nobel prize and discovery of deuterium and the neutron as was described in a recent ldquoMass Spectrometry Forumrdquo column in July 2013 By 1989 successful quadrupole-based commercial instrumentation had been on the market for almost 20 years The rapid rise of gas chromatography coupled with mass spectrometry (GCndashMS) and later liquid chromatography with mass spectrometry (LCndashMS) can be linked directly to quadrupole devices Quadrupole mass filters and quadrupole ion traps represented a fundamental change mdash they were smaller cheaper and their performance measures dovetailed with the needs of the hyphenated cou-pling

The Nobel prize recognized the transformative accom-plishment (7) Continuous design innovations over many years created a more capable and reliable instrument and these are described in an overview by March (8) selected from among the many that are available In concordance with the theme of personal developments in the advancement of mass spectrometry Staffordrsquos retrospective (9) discusses the development of the ion trap at one commercial vendor

Letrsquos consider the four-rod classical quadrupole mass filter A key concept of this mass analyzer is its operation through application of radio frequency (rf) and direct current (DC) voltages to create ldquoregionsrdquo of ion stability and instability within its structure The term region applies to the physical volume subject to the electronic fields and gradients each physical volume in the device is a certain distance from each of the four rods that make up the quadrupole mass filter and a certain distance from either the source or the detector end and the electric fields can be controlled In simple terms ions that pass through the filter from the source to the detector remain within stable regions Those ions that enter regions of

Figure 1 A figure from Brubakerrsquos original patent showing three of the four rods in the prefilter The ions move along the z direction from lower left to upper right and into the main structure of the quadrupole mass filter

Table I A sampling of other eponymous terms in mass spectrometry

Types of traps Kingdon trap Paul trap Penning trap

Sector geometries

Dempster Mauttach-Herzog Nier-Johnson Nier-Roberts Bainbridge-Jordan Hinterberger-Konig Takeshita Matsuda

Other mass analyzers

Wien filter

SourcesNier electron ionization source Knudsen source

Devices

Faraday cup Mamyrin reflector Daly detector Langmuir-Taylor detector Bradbury-Nielsen filter Wiley-McLaren focusing Ryhage jet separator Llewellyn-Littlejohn membrane separa-tor Turner-Kruger entrance lens

ProcessesPenning ionization McLafferty rear-rangement Stevensonrsquos rule

Data and unitsVan Krevelen diagram Dalton Thomson Kendrick


instability do not they are ejected from the filter entirely or collide with the rods themselves The quadrupole rods may be manufactured with different dimensions and the rods may be of vari-ous lengths The applied fields vary in frequency and amplitude Each of these factors influences the performance metrics in predictable ways Given an entering ion with known kinetic energy and a defined known trajectory the performance of the quadrupole mass filter is predictable

However ions (plural) are an unruly lot It is not one ion that needs to pass through the quadrupole but hundreds of thousands of ions created in an ion source with its own physical design and operational characteristics There-fore the population of ions exiting the source and entering the mass analyzer has a spread of ion kinetic energies and a range of ion trajectories as well as a diversity of ion masses and charge states The stable ions may represent just a small fraction of that overall popula-tion which would limit the transmis-sion of the filter and result in decreased sensitivity for the analysis As in other mass analyzers used in mass spectrom-etry we might use lenses slits or other sectors (such as an electric sector in a double focusing geometry instrument) to tailor the kinetic energies and trajec-tories and pass a larger fraction of the ion population into the mass analyzer

Or in quadrupoles we might use a

Brubaker prefilter (sometimes called a Brubaker lens) situated in front of the mass-analyzing quadrupole Wilson M Brubaker was granted patent 3129327 (and later a related patent 3371204) for this device the first patent was filed in December 1961 and granted in April 1964 (see Figure 1 for the first page of this granted patent) Brubaker worked for Consolidated Electrodynamics Corporation in Pasadena California in the early 1960s He was active in fundamental studies of the motions of ions in strong electric fields and in the development of small quadrupoles used to study the composition of the Earthrsquos upper atmosphere He also worked for

Analog Technology Corporation and was the chief scientist for earth sciences at Teledyne Corporation It was at this last position that Brubaker developed a miniature mass spectrometer (based on a quadrupole) for breath analysis for astronauts which garnered a newspaper story on October 31 1969 Brubakerrsquos photograph that accompanied the arti-cle shows him posing with the sampling port of the mass spectrometer and the photo is now available on eBay

A Brubaker prefilter (10) (Figure 2) consists of a set of four short cylindri-cal electrodes (sometimes called stub-bies) mounted colinearly and in front of the main quadrupole electrodes

Ion trajectories

Prefilter Quadrupole

Figure 2 A simplified schematic (looking along the y-axis) of a Brubaker prefilter and the main quadrupole structure

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Without the prefilter ions from the source may not enter the quadrupole because of fringing fields at the front end which are created by the exposed ends of the rods themselves Transmis-sion decreases because of this front-end loss The Brubaker prefilter is driven with the same AC voltage (that is the radio frequency voltage) applied to the main rods and acts to guide ions in to the main quadrupole It is an ldquorf-onlyrdquo quadrupole that was later used in triple-quadrupole MS-MS instruments The dynamics of these devices have been widely studied (1112) and they serve several functions in the triple quad-rupole instrument depending on the pressure within the device With the use of a Brubaker prefilter in a single-quad-rupole instrument the transmission of ions is greatly increased although the increase is known to be mass-depen-dent These devices are almost univer-sally designed into quadrupoles It is interesting that Brubakerrsquos invention of the prefilter was a consequence of his need to maintain ion transmission in very small quadrupoles such as what might be carried aboard the probes into the upper atmosphere or in spacecrafts Transmission losses because of fringing fields are especially severe in these small devices Nowadays quadrupole mass filters can be microfabricated with the prefilter and filter assembly only 32

cm in length Wright and colleagues describe the incorporation of the Bru-baker prefilter in miniature quadrupole mass filters (13)

Kendrick MassAs Table I shows devices used in MS are often linked to the names of their inventors or designers Modern MS is not only about the instrumentation but also about the immense amounts of data generated by those instruments From the first compilations of mass spectra in a three-ring binder from the American Petroleum Institute to the Eight Peak Index of Mass Spectral data (designed for searching of the most intense peaks in the mass spectrum) to larger modern databases scientists have worried how to archive present and search mass spectral data Mass spectral data are always at least two-dimensional (2D) (the mz of an ion and its abun-dance) Time (as in information re-corded with elution time in GCndashMS or LCndashMS) adds another dimension Both higher resolution data and MS-MS data add dimensionality A recent ldquoMass Spectrometry Forumrdquo column (14) discussed the data management issue in MS Large data sets can be mined for both their explicit first-order content and other meaningful secondary mea-sures can sometimes be extracted In-sightful means of data presentation help

tame the data glut For example time-resolved ion intensity plots for multiple-reaction-monitoring data highlight the underlying pattern Three-dimensional (3D) color-coded plots for MS-MS data provide a portrait of mixture complex-ity and reactivity Statistical evaluation of large amounts of data or processing and display of data by computer aid in presentation and interpretation Often-times these methods rely on the same fundamental perspectives in presenting data

What if one changed the perspective More than that how about changing a really basic approach In a previous installment of this column (15) we discussed the standard definition of the kilogram and the standard definition of the dalton The consensus standards provide an underlying uniformity for our data and our discussions With data processing we can now easily shift standards and alter perspective But 50 years ago consider the value of such a new perspective (16)

The problems of computing storing and retrieving precise masses of the many combinations of elements likely to occur in the mass spectra of organic compounds are considerable They can be significantly reduced by the adoption of a mass scale in which the mass of the CH2 radical is taken as 140000 mass units The advantage of this scale is that ions differing by one or more CH2 groups have the same mass defect The precise masses of a series of alkyl naphthalene parent peaks for example are 1279195 14191 95 15591 95 etc Because of the identical mass defects the similar origin of these peaks is recognizable without reference to tables of masses

That quote is from the abstract of a 1963 article (16) by Edward Kendrick from the Analytical Research Division of Esso Research and Engineering Kendrick confronted the reality that high resolution data (then measured at a resolving power of 5000) could be obtained for ions up to mz 600 and concluded that ldquoover one and a half mil-lion entries would be required to cover the ions up to mass 600 A mass scale with C12 = 1400000 enables the same data mdash [that is] up to mass 600 mdash to be expressed in less than 100000 entries This reduction is a consequence of the same defectrsquos being repeated at intervals

Ken

dri

ck m

ass

defe

ct

Kendrick mass

Figure 3 A Kendrick mass analysis plot with Kendrick mass defect on the y-axis and Kendrick mass on the x-axis Successive dots on an x-axis line represent ions observed (or not observed a binary observation) from related compounds separated by a methylene unit (see red bar) Figure adapted from reference 22


of 14 mass units mdash [that is] one (CH2) grouprdquo It is not difficult to understand that a scientist at Esso would deal with a great many compounds that could dif-fer by an integral number of methylene units (CH2) Given this challenge the proposed approach and a shift in per-spective was extraordinarily insightful The eponymous term is the Kendrick mass scale and the difference between the standard mass scale and that pro-posed is called the Kendrick mass defect A mass unit called the kendrick (Ke) has also been used

The original publication by Kend-rick (16) provides the rationale for this change in perspective and contains multiple tables used to illustrate its use-fulness A short summary is provided here In the Kendrick perspective the mass of the methylene (CH2) unit is set at exactly 14 Da The International Union of Pure and Applied Chemistry (IUPAC) mass in daltons can be con-verted to the mass on the Kendrick scale by division by 10011178 The basis in the methylene unit can also be shifted to other functional groups creating a mass scale linked to that group The Kendrick mass defect is the difference between the nominal Kendrick mass and the exact Kendrick mass in parallel to the IUPAC definitions The value of this shift in perspective advocated by Kendrick is illustrated in the process called a Kendrick mass analysis In this analysis the Kendrick mass defect is plotted against the nominal Kendrick mass for ions in the mass spectrum (Figure 3) Successive members of a ho-mologous series (differing in the num-ber of methylene units) are represented by dots (representing ions observed in the mass spectrum) on the horizontal axis After the composition of one ion is established the composition of other ions can be established via the position on the plot The Van Krevelen diagram described in 1950 also adopted a per-spective-shifting approach but focused on other functional groups (17)

Kendrick was confronting a daunt-ing world of MS data recorded at a resolving power of 5000 We have advanced to the routine measurement of petroleomics data at 10ndash15times that resolving power (18) and extending

to 10times higher mass but the need for a meaningful display of the data persists The Kendrick mass defect is just one of several ldquomass defectsrdquo that can inform our interpretation of mass spectrometric data (19) Increasingly the methods of informatics give us new tools to approach the mass spec-trometric data The use of Kendrick mass data and Van Krevelen diagrams have been discussed within the larger context of high-precision frequency measurements recorded by many instrumental platforms and the use of those data to discern complex mo-lecular structures (2021)

ConclusionsWe use eponymous terms in mass spectrometry because they efficiently convey information as well as crystal-lize and honor the achievements of an individual Table I presents only a few such eponymous terms many more may be in limited and specialized use Whether they enter a more general use ultimately depends on the consensus of the community which develops over years Discovering the background of eponymous terms used in mass spec-trometry provides a useful perspective of the development of the field

References (1) httpwwworganic-chemistryorg

namedreactions (2) httpwwwmonomerchemcom

display4html (3) httpwwwchemoxacukvrchem-

istrynor (4) httpenwikipediaorgwikiList_of_

inventions_named_after_people (5) CF Brannock as described in the

New York Times of June 9 2013 See httpwwwbrannockcomcgi-binstartcgibrannockhistoryhtml

(6) J De Laeter and M D Kurz J Mass Spectrom 41 847ndash854 (2006)

(7) W Paul and H Steinwedel Zeitschrift fuumlr Naturforschung 8A 448ndash450 (1953)

(8) RE March J Mass Spectrom 32 351ndash369 (1997)

(9) G Stafford Jr J Amer Soc Mass Spectrom 13 589ndash596 (2002)

(10) WM Brubaker Adv Mass Spectrom 4 293ndash299 (1968)

(11) W Arnold J Vac Sci Technol 7191ndash194 (1970)

(12) PE Miller and MB Denton Int J Mass Spectrom Ion Proc 72 223ndash238 (1986)

(13) S Wright S OrsquoPrey RRA Syms G Hong and AS Holmes J Microme-chanical Syst 19 325ndash337 (2010)

(14) KL Busch Spectroscopy 27(1) 14ndash19 (2012)


(16) E Kendrick Anal Chem 35 2146ndash2154 (1963)

(17) DW Van Krevelen Fuel 29 269ndash284 (1950)

(18) CA Hughey CL Hendrickson RP Rodgers AG Marshall and K Qian Anal Chem 73 4676ndash4681 (2001)

(19) L Sleno J Mass Spectrom 47 226ndash236 (2012)

(20) N Hertkorn C Ruecker M Meringer R Gugisch M Frommberger EM Perdue M Witt and P Schmitt-Koplin Anal Bioanal Chem 389 1311ndash1327 (2007)

(21) T Grinhut D Lansky A Gaspar M Hertkorn P Schmitt-Kopplin Y Hadar and Y Chen Rapid Comm Mass Spectrom 24 2831ndash2837 (2010)

(22) httpsenwikipediaorgwikiKend-rick_mass

Kenneth L Buschdoesnrsquot have anything in mass spectrometry named after him or any pictures for sale on eBay As a consolation prize he does have beer a theme

park and gardens and a company that markets vacuum equipment all of which carry the name ldquoBuschrdquo None of these have any connection to the author but the ldquoBuschrdquo neon sign purchased at the brewery gift shop sometimes provides a new perspective This column is the sole responsibility of the author who can be reached at wyvernassocyahoocom



Focus on Quality

RD McDowall

What are quality agreements why do we need them who should be involved with writing them and what should they contain

Why Do We Need Quality Agreements

In May the Food and Drug Administration (FDA) pub-lished new draft guidance for industry entitled ldquoCon-tract Manufacturing Arrangements for Drugs Quality

Agreementsrdquo (1) I just love the way the title rolls off the tongue donrsquot you You may wonder what this has to do with spectroscopy or indeed an analytical laboratory which is a fair question The answer comes on page one of the document where it defines the term ldquomanufacturingrdquo to include processing packing holding labeling testing and operations of the ldquoQuality Unitrdquo Ah has the light bulb been turned on yet Testing and operations of the quality unit mdash could these terms mean that a laboratory is in-volved Yes indeed

Paddling across to the other side of the Atlantic Ocean the European Union (EU) issued a new version of Chapter 7 of the good manufacturing practices (GMP) regulations that became effective on January 31 2013 (2) The docu-ment was updated because of the need for revised guidance on the outsourcing of GMP regulated activities in light of the International Conference on Harmonization (ICH) Q10 on pharmaceutical quality systems (3) The chapter title has been changed from ldquoContract Manufacture and Analysisrdquo to ldquoOutsourced Activitiesrdquo to give a wider scope to the regulation especially given the globalization of the pharmaceutical industry these days You may also remem-ber from an earlier ldquoFocus on Qualityrdquo column (4) dealing with EU GMP Annex 11 on computerized systems (5) that agreements were needed with suppliers consultants and contractors for services These agreements needed the scope of the service to be clearly stated and that the re-sponsibilities of all parties be defined At the end of clause 31 it was also stated that IT departments are analogous (5) mdash oh dear

Also ICH Q7 which is the application of GMP to active pharmaceutical ingredients (APIs) has section 16 entitled ldquoContract Manufacturing (Including Laboratories)rdquo This document was issued as ldquoGuidance for Industryrdquo by the FDA (6) and is Part 2 of EU GMP (7) Section 16 states that ldquoThere should be a written and approved contract or formal agreement between a company and its contractors that defines in detail the GMP responsibilities includ-ing the quality measures of each partyrdquo As noted in the title of the chapter the scope includes any contract labo-ratories which means that there needs to be a contract or formal agreement for services performed for the API manufacturer or any third-party laboratory performing analyses on their behalf

Therefore what we discuss in this gripping installment of ldquoFocus on Qualityrdquo is quality agreements why they are important for laboratories and what they should contain for contract analysis The principles covered here should also be applicable to laboratories accredited to Interna-tional Organization for Standardization (ISO) 17025 and also to third-party providers of services to regulated and quality laboratories

What Are Quality AgreementsAccording to the FDA a quality agreement is a compre-hensive written agreement that defines and establishes the obligations and responsibilities of the quality units of each of the parties involved in the contract manufacturing of drugs subject to GMP (1) The FDA makes the point that a quality agreement is not a business agreement covering the commercial terms and conditions of a contract but is prepared by quality personnel and focuses only on the quality of the laboratory service being provided


Note that a quality agreement does not absolve the contractor (typically a pharmaceutical company) from the responsibility and accountability of the work carried out A contract labo-ratory should be viewed as an exten-sion of the companyrsquos own facilities

Why Do We Need Quality AgreementsPut at its simplest the purpose of a quality agreement is to manage the expectations of the two parties in-volved from the perspective of the quality of the work and the compli-ance with applicable regulations Under the FDA there is no explicit regulation in 21 CFR 211 (8) but it is a regulatory expectation as discussed in the guidance (1)

In contrast in Europe the require-ment is not guidance but the law that defines what parties have to do when outsourcing activities as (2)

Any activity covered by the GMP Guide that is outsourced should be appropri-ately defined agreed and controlled in order to avoid misunderstandings which could result in a product or op-eration of unsatisfactory quality There must be a written Contract between the Contract Giver and the Contract Acceptor which clearly establishes the duties of each party The Quality Man-agement System of the Contract Giver must clearly state the way that the Qualified Person certifying each batch of product for release exercises his full responsibility

Who Is Involved in a Quality Agreement (Part I)Typically there will just be two parties to a quality agreement these are defined as the contract giver (that is the pharmaceutical company or sponsor) and the con-tract acceptor (contract laboratory) according to EU GMP (2) Alter-natively the FDA refers to ldquoThe Ownerrdquo and the ldquoContracted Facil-ityrdquo (1) Regardless of the names used there are typically two parties involved in making a quality agree-ment unless of course you happen to be the Marx Brothers (the party of the first part the party of the second part the party of the 10th part and so forth) (9)

If the contact acceptor is going to subcontract part of their work to a third party then this must be in-cluded in the agreement mdash with the option of veto by the sponsor and the right of audit by the owner or the contracted facility

Figure 1 shows condensed re-quirements of EU GMP Chapter 7 regarding the contract giver or owner and the contract acceptor or contracted facility to carry out the work Responsibilities of the owner

are outlined on the left-hand side of the figure and those of the contracted facility are outlined on the right-hand side of the diagram The content of the contract or quality agreement is presented in the lower portion of the figure These points will be discussed as we go through the remainder of this column

What Should a Quality Agreement ContainAccording to the FDA (1) a quality

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agreement has the following sections as a minimumtPurpose or scopetTerms (including effective date and

termination clause)tResponsibilities including commu-

nication mechanisms and contactstChange control and revisions tDispute resolutiontGlossary

Although quality agreements can cover the whole range of pharmaceu-tical development and manufactur-ing for the purposes of this column we will focus on the laboratory In this discussion the term laboratory will apply to a laboratory undertaking regulated analysis either during the research and development (RampD) or manufacturing phases of a drug prod-uctrsquos life including instances where the whole manufacturing and testing is outsourced to a contract manu-facturing organization (CMO) the whole analysis is outsourced to a con-tract research organization (CRO) or testing laboratory or just specialized assays are outsourced by a company In fact there are specific laboratory requirements that are discussed in the FDA guidance (1)

Scope

The scope of a quality agreement can cover one or more of the following compliance activities

tQualification calibration and maintenance of analytical instru-ments It may be a requirement of the agreement that only specified instruments are to be used for the ownerrsquos analysistValidation of laboratory computer-

ized systems tValidation or verification of analyti-

cal procedures under actual con-ditions of use This will probably involve technology transfer so the agreement will need to specify how this will be handledtSpecifications to be used to pass or

fail individual test resultstSupply handling storage prepara-

tion and use of reference standards For generic drugs a United States Pharmacopeia (USP) or European Pharmacopoeia (EP) reference stan-dard may be used but for some eth-ical or RampD compounds the owner may supply reference substances for use by a contract laboratorytHandling storage preparation and

use of chemicals reagents and solu-tionstReceipt analysis and reporting of

samples These samples can be raw materials in-process samples fin-ished goods stability samples and so ontCollection and management of

laboratory records (for example complete data) including electronic

records (10) resulting from all of the above activitiestDeviation management (for exam-

ple out-of-specification investiga-tions) and corrective and preventa-tive action plans (CAPA)tChange control specifying what

can be changed by the laboratory and what changes need prior ap-proval by the owner All activities under the scope of the

quality agreement must be conducted to the applicable GMP regulations

More Detail on Sections in a Quality Agreement Now I want to go into more detail about some selected sections of a quality agreement I would like to emphasize that this is my selection and for a full picture readers should refer to the source guidance (1) or regulation (2)

Procedures and Specifications

In the majority of instances the owner or contract giver will supply their own analytical procedures and speci-fications for the contract laboratory to use These will be specified in the quality agreement Part of the qual-ity agreement should also define who has the responsibility for updating any documents If the owner updates any document within the scope of the agreement then they have a duty

+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp

Figure 1 Summary of EU GMP Chapter 7 requirements for outsourced activities


to pass on the latest version and even offer training to the contract facil-ity To ensure consistency the owner could require the contract laboratory to follow the ownerrsquos procedure for out-of-specification results

Responsibilities

The responsibilities of the two groups signing the agreement will depend on the amount of work devolved to the contract laboratory and the degree of autonomy that will be allowed For example if a laboratory is used for carrying out one or two specialized tests rather than complete release testing then the majority of the work will remain with the ownerrsquos qual-ity unit The latter will handle the release process and the majority of work In contrast when the whole package of work is devolved to a CMO then the responsibilities will be greatly enlarged for the contract laboratory and communication of re-sults especially exceptions will be of greater importance

In any case the communication process between the laboratory and the owner needs to be defined for routine escalation and emergency cases How should the communica-tion be achieved The choices could be phone fax scanned documents e-mail on-line access to laboratory sys-tems or all of the above However it is no good having the communication processes defined as they will be op-erated by people therefore analysts quality assurance (QA) staff and their deputies involved on both sides have to be nominated and understand their roles and responsibilities

Communication also needs to define what happens in case of dis-putes that can be raised from either party The agreement should docu-ment the mechanism for resolving disputes and in the last resort which countryrsquos legal system will be the beneficiary of the financial lar-gesse of both organizations as they fight it out in the courts Unsurpris-ingly Irsquom in the camp with the great

spectroscopist ldquoDick the Butcherrdquo who said ldquoThe first thing we do letrsquos kill all the lawyersrdquo (11)

Records of Complete Data

Just in case you missed it above the contract laboratory must generate complete data as required by GMP for all work it undertakes This will include both paper and electronic records that I discussed in an earlier ldquoFocus on Qualityrdquo column (10) The FDA guidance makes it clear that the quality agreement must document how the requirement for ldquoimmediate retrievalrdquo will be met by either the owner or the contract laboratory (1) Both types of records must be pro-tected and managed over the record retention period

Change Control

The agreement needs to specify which controlled and documented changes can be made by the contract labora-tories with only the notification to the owner and those that need to be

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discussed reviewed and approved by the owner before they can be implemented Of course some changes espe-cially to validated methods or computerized systems may require some or complete revalidation to occur which in turn will create documentation of the activities

Glossary

To reduce the possibility of any misunderstanding a glos-sary that defines key words and abbreviations is an essen-tial component of a quality agreement

FDA Focus on Contract Laboratories In the quality agreement guidance (1) the FDA makes the point that contract laboratories are subject to GMP regulations and discusses two specific scenarios These are presented in overview here please see the guidance for the full discussion

Scenario 1

Responsibility for Data Integrity

in Laboratory Records and Test Results

Here the owner needs to audit the contract laboratory on a regular basis to assure themselves that the work carried out on their behalf is accurate complete data are gener-ated and that the integrity of the records is maintained over the record retention period This helps ensure that there will be no nasty surprises for the owner when the FDA drops in for a cozy fireside chat

Scenario 2

Responsibilities for Method

Validation Under Actual Conditions of Use

Here a contract laboratory produces results that are often out of specification (OOS) and has inadequate laboratory investigations The root cause of the problem is that the method has not been validated under actual conditions of use as required by 21 CFR 194(a)(2) The suitability of all testing methods used shall be verified under actual condi-tions of use (8)

Trust But Verify The Role of AuditingAs that great analytical chemist Ronald Reagan said ldquotrust but verifyrdquo (this is the English translation of a Rus-sian proverb) Auditing is used before a quality agreement and confirms that the laboratory can undertake the work with a suitable quality system Afterwards when the anal-ysis is on-going auditing confirms that the work is being carried out to the required standards Both the FDA and the EU require the owner or contract giver to audit facili-ties they entrust work to

There are three types of audit that can be usedtInitial audit This audit assesses the contract laboratoryrsquos

facilities quality management system analytical instru-mentation and systems staff organization and train-ing records and record keeping procedures The main purpose of this audit is to determine if the laboratory is a suitable facility to work with The placing of work

-

- -

- -

-

- - -

-

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with a laboratory may be dependent on the resolution of any major or critical findings found during this audit Alternatively the owner may decide to walk away and find a different laboratory that is better suited or more compliant tRoutine audits Dependent on the criticality of the

work placed with a contract laboratory the owner may want to carry out routine audits on a regular basis which may vary from annually to every 2ndash3 years In essence the aim of this audit is to confirm that the laboratoryrsquos quality management system operates as documented and that the analytical work carried out on behalf of the owner has been to the standards in the quality agreement including the required records of complete data tFor cause audits There may be problems arising that re-

quire an audit for a specific reason such as the failure of a number of batches or problems with a specific analysis or even suspected falsificationAudits are a key mechanism to provide the confidence

that the contact laboratory is performing to the require-ments of the quality agreement or contract If noncompli-ances are found they can be resolved before any regula-tory inspection

Who Is Involved in a Quality Agreement (Part II)There will be a number of people within the quality func-tion of both organizations involved in the negotiation and operation of a quality agreement Typically some of the roles involved could betQuality assurance coordinatortHead of laboratory from the sponsor and the corre-

sponding individual in the contract laboratorytSenior scientists for each analytical technique from each

laboratorytAnalytical scientiststAuditor from the sponsor company for routine assess-

ment of the contract laboratoryOne of the ways that each role is carried out is to define

them in the agreement which can be wordy An alterna-tive is to use a RACI (pronounced ldquoracyrdquo) matrix which stands for responsible accountable consulted and in-formed This approach defines the activities involved in the agreement and for each role assigns the appropriate activity For example the release of the batch would be the responsibility of the sponsorrsquos quality unit in the United States or the qualified person in Europe tResponsible This is the person who performs a task

Responsibilities can be shared between two or more in-dividuals tAccountable This is the single person or role that is ac-

countable for the work Note that although responsibili-ties can be shared there is only one person accountable for a task equally so it is possible that the same individ-ual could be both responsible and accountable for a task tConsulted These are the people asked for advice before

or during a task

-

- -

- -

-

- - -

-

The PIKE MIRacleTM is a universal sampling

accessory for analysis of solids liquids pastes

gels and intractable materials It is a single

reflection ATR with highest IR throughput

making it ideal for sample identification and

QAQC applications Advanced options include

three reflection ATR crystal plates to optimize

for lower concentration components Easily

change crystal plates to analyze a broad

spectrum of sample types

PIKE MIRacle

FTIR sampling made easier

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TM


tInformed These are the people who are informed after the task is com-pleted A simple RACI matrix for the trans-

fer of an analytical procedure between laboratories is shown in Table I The table is constructed with the tasks involved in the activity down the left hand column and the individuals in-volved from the two organizations in the remaining five columns The RACI responsibilities are shared among the various people involved

Further Information on Quality AgreementsFor those that are interested in gain-ing further information about quality agreements there are a number of resources availabletThe Active Pharmaceutical Ingre-

dients Committee (APIC) offers some useful documents such as ldquoQuality Agreement Guideline and Templatesrdquo (12) and ldquoGuide-line for Qualification and Man-agement of Contract Quality Con-

trol Laboratoriesrdquo (13) available at wwwapicorg The scope of the latter document covers the identi-fication of potential laboratories risk assessment quality assess-ment and on-going contract labo-ratory management (monitoring and evaluation) Finally there is an auditing guidance available for download (14)tThe Bulk Pharmaceutical Task

Force (BPTF) also has a quality agreement template (15) available for download from their web site

SummaryThe FDA acknowledges in the con-clusions to the draft guidance (1) that written quality agreements are not explicitly required under GMP regulations However this does not relieve either party of their respon-sibilities under GMP but a quality agreement can help both parties in the overall process of contract analy-sis mdash defining establishing and documenting the roles and responsi-

Table I An example of a RACI (responsible accountable consulted and informed) matrix for method transfer

Organization Owner Contract Facility

Role QA Lab Head Scientist Scientist Lab Head

Write method

transfer protocol A R C C C

Prepare samples I R I I

Receive samples I I R I

Analyze samples I R R I

Report and collate results I R R I

Write method transfer

report R A R C C

GLASS EXPANSIONQuality By Design

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bilities of all parties involved in the process In contrast under EU GMP quality agreements are a legal and regulatory requirement

References (1) FDA ldquoContract Manufacturing Ar-

rangements for Drugs Quality Agree-mentsrdquo draft guidance for industry May 2013

(2) European Union Good Manufactur-ing Practices (EU GMP) Outsourced Activities Chapter 7 effective January 31 2013

(3) International Conference on Harmo-nization ICH Q10 Pharmaceutical Quality Systems step 4 (ICH Geneva Switzerland 1997)

(4) RD McDowall Spectroscopy 26(4) 24ndash33 (2011)

(5) European Commission Health and Consumers Directorate-General EudraLex The Rules Governing Medicinal Products in the European Union Volume 4 Good Manufactur-ing Practice Medicinal Products for Human and Veterinary Use Annex 11 Computerised Systems (Brussels Belgium 2010)

(6) FDA ldquoGMP for Active Pharmaceutical Ingredientsrdquo guidance for industry Federal Register (2001)

(7) European Union Good Manufactur-ing Practices (EU GMP) Part II - Basic Requirements for Active Substances used as Starting Materials effective July 31 2010

(8) 21 CFR 211 ldquoCurrent Good Manufac-turing Practice for Finished Pharma-ceutical Productsrdquo (2009)

(9) Marx Brothers ldquoA Night At The Operardquo MGM Films (1935)


(11) W Shakespeare Henry V1 Part II Act IV Scene 2 Line 77

(12) ldquoQuality Agreement Guideline and Templatesrdquo Version 01 Active Phar-maceutical Ingredients Committee December 2009 httpapicceficorgpublicationspublicationshtml

(13) ldquoGuideline for Qualification and Man-agement of Contract Quality Control Laboratoriesrdquo Active Pharmaceuti-cal Ingredients Committee January 2012 httpapicceficorgpublica-tionspublicationshtml

(14) Audit Programme (plus procedures and guides) Active Pharmaceutical Ingredients Committee July 2012 httpapicceficorgpublicationspublicationshtml

(15) Quality Agreement Template Bulk Pharmaceutical Task Force 2010 httpwwwsocmacomAssociationManagementsubSec=9amparticleID=2889

RD McDowall is the principal of McDowall Consulting and the director of RD McDowall Limited and the editor of the ldquoQuestions of Qualityrdquo

column for LCGC Europe Spectroscopyrsquos sister magazine Direct correspondence to spectroscopyeditadvanstarcom

For more information on this topic please visit our homepage at wwwspectroscopyonlinecommcdowall

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In recent years Raman spectroscopy has gained widespread acceptance in applications that span from the rapid identifi-cation of unknown components to detailed characterization

of materials and biological samples The techniquersquos breadth of application is too wide to reference here but examples in-clude quality control (QC) testing and verification of high pu-rity chemicals and raw materials in the pharmaceuticals and food industries (1ndash3) investigation of counterfeit drugs (4) classification of polymers and plastics (5) characterization of tumors and the detection of molecular biomarkers in disease diagnostics (6ndash8) and theranostics (9)

One of the most exciting application areas is in the bio-medical sciences The major reason behind this surge of interest is that Raman spectroscopy is an ideal technique for molecular fingerprinting and is sensitive to the chemical changes associated with disease Furthermore components in the tissue matrix principally those associated with water and bodily f luids give a weak Raman response thereby improving sensitivity for those changes associated with a diseased state (10) The growing body of knowledge in our understanding of the science of disease diagnostics and im-provements in the technology has led to the development of fit-for-purpose Raman systems designed for use in surgical theaters and doctorsrsquo surgeries without the need for sending samples to the pathology laboratory (8)

Surface-enhanced Raman spectroscopy (SERS) is a more sensitive version of Raman spectroscopy relying

on the principle that Raman scattering is enhanced by several orders of magnitude when the sample is deposited onto a roughened metallic surface The benefit of SERS for these types of applications is that it provides well-defined distinct spectral information enabling characterization of various states of a disease to be detected at much lower levels Some of the many applications of Raman and SERS for biomedical monitoring include tExamination of biopsy samplestIn vitro diagnosticstCytology investigations at the cellular leveltBioassay measurements tHistopathology using microscopytDirect investigation of cancerous tissuestSurgical targets and treatment monitoring tDeep tissue studiestDrug efficacy studies

The basics of Raman spectroscopy are well covered elsewhere in the literature (11) However before we pres-ent some typical examples of both Raman and SERS ap-plications in the field of cancer diagnostics letrsquos take a closer look at the fundamental principles and advantages of SERS

Principles of Surface-Enhanced Raman SpectroscopyThe principles of SERS are based on amplifying the Raman scattering using metal surfaces (usually Ag Au or


Both Raman spectroscopy and surface enhanced Raman spectroscopy (SERS) are proving to be invaluable tools in the field of biomedical research and clinical diagnostics The robust compact fit-for-purpose Raman spectrometer designs are appropriate for use in surgical pro-cedures to help surgeons assess tumors and allow rapid decisions to be made Raman systems are also being developed for molecular diagnostic testing to detect and measure human cancer biomarkers Based on the SERS technique this approach potentially could change the way bio-assays are performed to improve both the sensitivity and reliability of testing The two applica-tions highlighted in this review together with other examples of the use of Raman spectrom-etry in biomedical research areas such as the identification of bacterial infections are clearly going to make the technique an important part of the medical toolbox as we continually strive to improve diagnostic techniques and bring a better health care system to patients

The Use of Raman Spectroscopy in Cancer Diagnostics

September 2013 Spectroscopy 28(9) 37wwwspec t roscopyonl ine com

Cu) which have a nanoscale rough-ness with features of dimensions 20ndash300 nm The observed enhancement of up to 107-fold can be attributed to both chemical and electromagnetic effects The chemical component is based on the formation of a charge-transfer state between the meta l and the adsorbed scattering compo-nent in the sample and contributes about three orders of magnitude to the overal l enhancement The re-mainder of the signal improvement is generated by an electromagnetic ef fect from the collective osci l la-tion of excited electrons that results when a metal is irradiated with light This process known as the surface plasmon resonance (SPR) effect has a wavelength dependence related to the roughness and atomic structure of the metallic surfaces and the size and shape of the nanoparticles For a more detailed discussion of SERS and its applications see reference 12

Detect ion by SERS has severa l benefits Firstly f luorescence is in-herently quenched for an adsorbate analyte on a SERS surface resulting in f luorescence-free SERS spectra This is primarily because the Raman signal is enhanced by the metal sur-face and the f luorescence signal is not As a result the relative intensity of the f luorescence is significantly lower than the Raman signal and in many occasions is not observable Secondly signal averaging can be extended to increase sensitivity and lower detection levels Finally SERS spectral bands are very sharp and well-defined which improves data quality interpretability and masking by interferents Recent work using silver nanoparticles as the enhancing substrate has shown that SERS can be applied to single-molecule detection rivaling the performance of f luores-cence measurements (13)

Although SERS has many advan-tages it also has several disadvantages that are worth noting The first is that unlike traditional Raman spectros-copy SERS requires sample prepara-tion The ability to measure samples in vivo without the need for sample pre-treatment is one of the major advan-

tages of traditional Raman spectros-copy For that reason it is important to understand the signal enhance-ment benefits of SERS compared to the ease of sampling of traditional Raman spectroscopy when deciding which technique to use (14) Second high performance SERS substrates are difficult to manufacture and as a result there is typically a high de-gree of spatial nonuniformity with re-spect to the signal intensity (15) For example the SERS substrates used in

the research being carried out by the University of Utah (described later in this article) tend to have much higher concentrations of analyte on the edges of the sampling area than in the cen-ter Lastly it is important to note that when the sample is deposited onto the surface the molecular structure (the nature of the analyte) can be altered slightly resulting in differences be-tween traditional Raman spectra and SERS spectra (16) However it should be emphasized that there have been

1395 QE10x better dark

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()15 μm pixel)+

+30 mm wide array)

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Key Applications

$

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-$)

)

)


improvements in the quality of sub-strates being manufactured today and new materials such as Klarite (Ren-ishaw Diagnostics) are showing a great deal of promise in terms of consistency and performance (17)

Raman Spectroscopy Applied to Biomedical StudiesThere are several important functional groups related to biomedical testing that have characteristic Raman fre-quencies Tissue samples include com-

ponents such as lipids fatty acids and protein all of which have vibrations in the Raman spectrum The most signifi-cant spectral regions includetX-H bonds (for example C-H

stretches) 4000ndash2500 cm-1 region tMultiple bonds (such as NequivC)

2500ndash2000 cm-1 regiontDouble bonds (for example C=C

N=C) 2000ndash1500 cm-1 region tComplex patterns (such as C-O

C-N and bands in the fingerprint region) 1500ndash600 cm-1 regionThe identification and measurement

of Raman scattering in these spectral regions can be applied to the following biomedical applicationstMeasurement of biological macro-

molecules such as nucleic acids pro-teins lipids and fatstInvestigation of blood disorders

such as anemia leukemia and thal-assemias (inherited blood disorder)tDetection and diagnosis of various

cancers including brain breast pan-creatic cervical and colon tAssaying of biomarkers in studying

human diseasestUnderstanding cell growth in bac-

teria phytoplankton viruses and other microorganismstAnalysis of abnormalities in tis-

sue samples such as brain arteries breast bone cervix embryo media esophagus gastrointestinal tract and the prostate glandSome typical examples of Raman spec-

tra of biological molecules are shown in Figure 1 Figure 2 gives a summary of some common biochemical functional groups with their molecular vibrational modes and frequency ranges which are observed in compounds such as proteins carbohydrates fats lipids and amino acids (681018ndash20) Identification of these func-tional groups can be used as a qualitative or quantitative assessment of a change or anomaly in a sample under investigation

Letrsquos take a look at two examples of the use of both conventional Raman spectroscopy and SERS specifically for cancer diagnostic purposes The first example uses traditional Raman spectroscopy for the assessment of breast cancer and the second example takes a look at SERS for the screening of pancreatic cancer biomarkers

Frequency range (cm-1)

4000 3000 2000 1500 1000 500

Vibrational

modeAssignment Mainly observed in

O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch

C-O stretchP-O stretch

C-C or C-O C-Oor PO2 C-N O-

P-O

C=C C=N C-H inring structure

C-C ringbreathing O-P-O

PO4

-3 sym

StretchC-C

Skeletalbackbonephosphate

Proline valine proteinconformation glycogen

hydroxapatite

Ether PO2

- sym Carbohydrates phospholipidsnucleic acids

Lipids nucleic acids proteinscarbohydrates

C-C twist C-Cstretch C-S

stretch

Phenylalanine tyrosine cysteine

Proline tryptophan tyrosinehydroxyproline DNA

Symmetric ringbreathing mode

Phenylalanine

Nucleotides

CO3

-2 HydroxyapatiteCarbonate

C-H rocking LipidsAliphatic-CH2

PO4

-3 HydroxyapatitePhosphate

S-S Stretch Cysteine proteinsDisulfide bridges

Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins

Lipids adenine cytosine collagen

Amino acids lipids

Proteins

Lipids nucleic acids

Figure 2 Some common functional groups with their molecular vibrational modes and frequency ranges observed in various biochemical compounds Adapted from reference 18

12000

Cholesterol

Triolene

Actin

DNACollagen 1Oleic acid

Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)

Figure 1 Raman spectra of various biological compounds Adapted from reference 21


Detection and Diagnosis of Breast Cancer The surgical management of breast cancer for some patients involves two or more operations before a sur-geon can be assured of removing all cancerous tissue The first operation removes the visible breast cancer and samples the lymph nodes for signs of the disease spreading Intraoperative methods for testing the health of the lymph nodes involve classical tissue mapping techniques such as touch imprint cytology and histopatholog-ical frozen section microscopy The problem with both of these methods is that they have poor sensitivity and require an experienced pathologist to interpret the data and relay the ldquobe-nignrdquo or ldquomalignantrdquo diagnostic re-port to the surgeon For that reason these intraoperative methods have not been widely adopted by the medi-cal community and as a result most procedures still require samples to be sent to a laboratory for further test-ing If tests confirm that the cancer

has spread then the patient must un-dergo an additional surgery to remove all the nodes in the affected area

A preferable approach would be for an intraoperative assessment which would allow for the immediate excision

Figure 3 Raman spectral peaks of lymph nodes of benign breast tissue (blue) together with a malignant breast tumor (red) Adapted from reference 21

007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)

copy2013 Newport Corporation

4 Up to 01 nm resolution4 4001 signal-to-noise ratio4 UV to NIR useable spectral range4 Intuitive spectroscopic application software

When a 2-D array bench top spectrometer is over budget and a mini-spectrometer just doesnrsquot meet the requirements ndash consider the new LineSpec Spectrometer from Oriel This user-configurable linear CCD array system with 18 m tunable spectrograph offers superior resolution and great flexibility Gratings and slits are interchangeable and the input can be configured for free space or fiber optic delivery

Learn more about Orielrsquos new LineSpec Spectrometer today pleasecall 800-714-5393 or visit wwwnewportcomLineSpec-8

Orielreg LineSpectrade SpectrometersWhen a Mini-spectrometer Just Wonrsquot Do


of all of the axillary lymph nodes if re-quired Studies by researchers at Cran-field University and Gloucestershire Royal Hospital in the United Kingdom have shown that Raman spectroscopy can detect differences in tissue compo-sition particularly a wide range of can-cer pathologies (22) This group used a portable Raman spectrometer with a 785-nm excitation laser wavelength and a fiber-optic probe (MiniRam BampW Tek) and principal component analysis

(PCA) along with linear discriminant analysis (LDA) data processing to evalu-ate the Raman spectra of lymph nodes They confirmed that the technique can match the sensitivities and specificities of histopathological techniques that are currently being used

The initial work in this study in-volved taking Raman spectra of the same samples that were being evaluated by the traditional intraoperative tech-niques The study which assessed 38 (25

negative and 13 positive) axillary lymph nodes from 20 patients undergoing sur-gery for newly diagnosed breast cancer compared the results with a standard histopathological assessment of each node The results showed a specificity of 100 and sensitivity of 92 when differentiating between normal and metastatic nodes These results are an improvement on alternative intraopera-tive approaches and reduce the likeli-hood of false positive or false negative assessment (20) Typical Raman spectra of lymph nodes from benign breast tis-sue and malignant tumors are shown in Figure 3 It can be seen that while there are very subtle differences between the two spectra the data classes can be discriminated using multivariate clas-sification tools such as PCA-LDA and support vector machine (SVM) classi-fication applied over the 800ndash1800 cm-1

spectral range By using such super-vised classification tools Raman spec-troscopy is sensitive enough to pick up the differences in the chemistry of the diseased state compared to that of the healthy tissue For example in Figure 3 subtle differences in the fatty acid peaks at 1300 and 1435 cm-1 and of collagen peaks at 1070 cm-1 are highlighted from the loadings plots from PCA analysis of the data (19)

More work is currently being done to support these findings at the University of Exeter and other research facilities If confirmed the next stage is to introduce the probe-based Raman spectrometer into an operating theater where it can be used to assess the node as soon as it is removed from the patient

Additionally many other groups are working on different approaches to cancer screening using Raman spec-troscopy Recent studies at the Massa-chusetts Institute of Technology (MIT) have shown that this technique has the potential to be built in to a biopsy nee-dle allowing doctors to instantaneously identify malignant or benign growths before an operation (23) Recent studies have indicated that the efficacy of these techniques can be enhanced by includ-ing a wider spectral region beyond 1800 cm-1 in the model to increase specific-ity (24) Finally for the characteriza-tion of highly f luorescent biological

Figure 5 Sandwich immunoassay and readout process Adapted from reference 30

Step 3 Sandwich immunoassay

Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass

Figure 4 Preparation of labels and capture substrate Adapted from reference 30

Step 1 Preparation of Entrinsic Raman Labels (ERLs)

Step 2 Preparation of Capture Substrate

Dithiobis (succinimidyl nitrobenzoate) Dithiobis (succinimidyl propionate)

= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O


tissues such as liver and kidney sam-ples researchers have shown evidence to suggest that shifting the excitation laser wavelength to 1064 nm provides a cleaner Raman response with reduced fluorescence compared to excitation at 785 nm (25) Dispersive Raman technol-ogy at 1064 nm is relatively new and is slowly gaining traction Most biological tissues produce fluorescence to a greater or lesser extent so reducing this effect will improve the Raman signal and po-tentially improve the analysis and the quality or accuracy of the diagnostic outcome

SERS Immunoassay for Pancreatic Cancer Biomarker ScreeningPancreatic adenocarcinoma is the fourth most common cause of cancer deaths in the United States with a 5 year survival rate of ~6 and an average sur-vival rate of lt6 months The reason for this high ranking is that the disease can only be detected and diagnosed by con-ventional radiological and histopatho-logical detection methods when it has progressed to an advanced stage After it has been diagnosed resection (partial removal) of the pancreas is the normal treatment (26)

There are potentially more than 150 biomarkers found in serum for the de-tection of pancreatic and other cancers One of the most prevalent is carbohy-drate antigen 19-9 (CA 19-9) a mucin type glycoprotein sialosyl Lewis antigen (SLA) which shows elevated levels in ~75 of patients with pancreatic ad-enocarcinoma (27) The most common diagnostic test for these biomolecular compounds is enzyme-linked immuno-sorbent assay (ELISA) which is a well-established bioassay that uses a solid-phase enzyme immunoassay to detect the presence of an antigen in serum samples It works by attaching the sam-ple antigen to the surface of the sorbent Then a specific monoclonal antibody which is linked to the enzyme is applied over the surface so it can bind to the an-tigen In the final step a substance con-taining the enzymersquos substrate is added which generates a reaction to produce a color change in the substrate (28) Even though this technique is widely used for bioassays it does have some limi-

tations with regard to the detection of cancer biomarkers For example early stage markers are present at levels well below current detection capabilities In addition 100ndash200 μL of sample is typi-cally required to achieve a low enough limit of detection Moreover CA 19-9 is unlikely to be detected in patients with tumors smaller than 2 cm It is further complicated by the fact that an estimated 15 of the population can-not even synthesize CA 19-9 The limi-tations in the ELISA approach (29) have

led to the investigation of alternative methods including an immunoassay based on SERS This offers the exciting possibility of an alternative faster way of detecting many different biomarkers in the same assay

A portable Raman spectrometer (MiniRam BampW Tek) was used in a recent study at the University of Utahrsquos Nano Institute to detect and quantify the CA 19-9 antigen in human serum samples (30) It showed the advantages of generating a SERS-derived signal

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from a Raman reporter molecule at-tached to the biomolecule marker analyte using gold nanoparticles This process is carried out using an ana-lyte sandwich immunoassay in which monoclonal antibodies are covalently bound to a solid gold substrate to spe-cifically capture the antigen from the sample The captured antigen is in turn bound to the corresponding detec-tion antibody This complex is joined together with gold nanoparticles that are labeled with different reporter mol-ecules which serve as extrinsic Raman labels (ERLs) for each type of antibody The presence of specific antigens is con-firmed by detecting and measuring the characteristic SERS spectrum of the re-porter molecule Letrsquos take a closer look at how this works in practice for these biomarkers and how the sample is pre-pared and read-out in particular

The first step is the preparation of the ERLs This is done by coating a 60-nm gold nanoparticle with the Raman re-porter molecule which in this case is 55ʹ-dithiobis(succinimidyl-2- nitro-benzoate (DSNB) This complex is then coated with a target or tracer antibody using N-hydroxysuccinimide (NHS) coupling chemistry The DSNB serves two purposes The nitrobenzoate group is the reporter molecule and the NHS group enables the protein to be coupled to the nanoparticle surface

The second step is to prepare the substrate for capture This is done by resistively evaporating solid gold under vacuum using thin film deposition on a glass microscope slide and then growing a monolayer of dithiobis(succinimidyl propionate) (DSP) on the surface of the slide to link the capture antibody to the gold surface Next the appropriate anti-body is attached to the substrate based on the biomarker of interest

The third step is to make the immu-noassay sandwich This step involves incubating the slide with serum con-taining the CA 19-9 or MMP-7 anti-gens which are then captured by sur-face-bound monoclonal antibodies and labeled with the ERLs

The fourth and final step is to read out the Raman signal of the functional group of interest using a spot size of ~85 μm with a laser excitation wavelength

of 785 nm In the study the symmetric nitro stretch band of the DNSB molecule at 1336 cm-1 was used for quantitation by measuring the peak height to construct a calibration curve for various concentra-tions of the antigens spiked into serum Real-world serum samples are then quantified using this calibration curve

The four steps of this procedure are shown in Figures 4 and 5 which show the preparation of the ERLs and capture substrate together with the sandwich immunoassay and readout process Using the nitro stretch band at 1336 cm-1 the SERS techniquersquos detection capability for the CA 19-9 antigen was approximately 30ndash35 ngmL which was similar to that of the ELISA method Preliminary results on real-world human serum samples have shown that both techniques are gen-erating very similar quantitative data which is extremely encouraging if SERS is going to be used for the diagnostic testing of pancreatic and other types of cancers in a clinical testing environ-ment However the investigation is still ongoing particularly in looking for ways to lower the level of detection in human serum samples Some of the pro-cedures being investigated to optimize assay conditions include faster incuba-tion times different buffers and the use of surfactants and blocking agents Additionally the bioassays in this study were initially carried out using an array format on a microscope slide but have now been adapted to a standard 96-well plate format used for traditional clini-cal testing bioassays By adopting these method enhancements there is strong evidence that the SERS results could po-tentially be far superior and more cost effective than the ELISA method

ConclusionBoth Raman spectroscopy and SERS are proving to be invaluable tools in the field of biomedical research and clini-cal diagnostics The robust compact fit-for-purpose Raman spectrometer designs are appropriate for use in sur-gical procedures to help surgeons as-sess tumors and allow rapid decisions to be made Raman systems are also being developed for molecular diag-nostic testing to detect and measure

human cancer biomarkers Based on the SERS technique this could po-tentially change the way bioassays are performed to improve both the sensi-tivity and reliability of testing The two applications highlighted in this review together with other examples of the use of Raman spectrometry in biomedical research areas such as the identifica-tion of bacterial infections are clearly going to make the technique an impor-tant part of the medical toolbox as we continually strive to improve diagnos-tic techniques and bring a better health care system to patients

References (1) E Lozano Diaz and RJ Thomas Pharma-

ceutical Manufacturing (January 2013)

httpwwwpharmamanufacturingcom

articles2013006htmlpage=1

(2) B Diehl CS Chen B Grout J Hernandez S

OrsquoNeill C McSweeney JM Alvarado and M

Smith Eur Pharm Rev Non-destructive Ma-

terials Identification Supplement 17(5) 3ndash8

(2012)

(3) D Yang and RJ Thomas Am Pharm

Rev (December 2012) ht tpwww

americanpharmaceuticalreviewcom

Featured-Articles126738-The-Benefits-

of-a-High-Performance-Handheld-Raman-

Spectrometer-for-the-Rapid-Identification-

of-Pharmaceutical-Raw-Materials

(4) M Ribick and G Dobler Eur Pharm Rev Non-

destructive Materials Identification Supple-

ment 17(5) 11ndash15 (2012)

(5) Vibrational Spectroscopy of Polymers Prin-

ciples and Practice NJ Everall J Chalmers

and PR Griffiths Eds (John Wiley and Sons

Chichester United Kingdom 2007)

(6) MB Fenn P Xanthopoulos G Pyrgiotakis

SR Grobmyer PM Pardalos and LL Hench

Advances in Optical Technologies Article ID

213783 Volume 2011

(7) N Jing RJ Lipert GB Dawson and MD Por-

ter Anal Chem 71(21) 4903ndash4908 (1999)

(8) Q Tu and C Chang Nanomedicine 8 545ndash

558 (2012)

(9) AA Bhirde G Liu A Jin R Iglesias-Barto-

lome AA Sousa RD Leapman J Silvio

Gutkind S Lee and X Chen Theranostics 1

310ndash321 (2011)

(10) L-P Choo-Smith HGM Edwards HP Endtz

JM Kros F Heule H Barr JS Robinson Jr

HA Bruining and GJ Puppels Biopolymers

67(1) 1ndash9 (2002)

(11) Handbook of Raman Spectroscopy IR Lewis


and HGM Edwards Eds (Marcel Dekker

New York 2001)

(12) G McNay D Eustace WE Smith K Faulds

and D Graham Appl Spectrosc 65(8) 825ndash

837 (2011)

(13) K Kneipp and H Kneipp Appl Spectrosc 60

322a (2006)

(14) R Lewandowska Raman Technology for To-

dayrsquos Spectroscopists supplement to Spec-

troscopy 28(6s) 32ndash42 (2013)

(15) EC Le Ru and PG Etchegoin Principles of

Surface-Enhanced Raman Spectroscopy and

Related Plasmonic Effects (Elsevier BV Am-

sterdam The Netherlands 2009)

(16) Surface-Enhanced Raman Scattering ndash Phys-

ics and Applications 103 K Kneipp M Mos-

kovits and H Kneipp Eds (Springer Berlin

Heidelberg 2006)

(17) S Botti S Almaviva L Cantarini A Palucci A

Puiu and A Rufoloni J Raman Spectrosc 44

463ndash468 (2013)

(18) S-Y Lin M-J Li and W-T Cheng Spectroscopy

21(1) 1ndash30 (2007)

(19) J Horsnell P Stonelake J Christie-Brown G

Shetty J Hutchings C Kendalla and N Stone

Analyst 135 3042ndash3047 (2010)

(20) C Kallaway LM Almond H Barr J Wood J

Hutchings C Kendall and N Stone Photo-

diagn Photodyn Ther (2013) httpdxdoi

org101016jpdpdt201301008

(21) JD Horsnell unpublished data (2010)

(22) JD Horsnell JA Smith M Sattlecker A

Sammon J Christie-Brown C Kendalland

N Stone The Surgeon 10(3) 123ndash127 (2011)

(23) A Saha I Barman NC Dingari LH Galindo

A Sattar W Liu D Plecha N Klein R Rao

RR Dasari and M Fitzmaurice Anal Chem

84(15) 6715ndash6722 (2012)

(24) S Duraipandian W Zheng J Ng JJ Low A

Ilancheran and Z Huang SPIE Proceedings

Vol 8572 Advanced Biomedical and Clinical

Diagnostic Systems March 2013

(25) CA Lieber H Wu and W Yang SPIE Proceed-

ings Vol 8572 Advanced Biomedical and

Clinical Diagnostic Systems March 2013

(26) ldquoCancer Facts and Figures 2013rdquo Atlanta

American Cancer Society 2013

(27) KS Goonetilleke and AK Siriwardena Jour-

nal of Cancer Surgery 33 266ndash270 (2007)

(28) Principles of ELISA The ELISA Encyclopedia

httpwwwelisa-antibodycomELISA-Intro-

duction

(29) JH Granger MC Granger MA Firpo SJ

Mulvihill and MD Porter The Analyst 138(2)

410ndash416 (2013)

(30) ldquoApplications of Raman Spectroscopy in

Biomedical Diagnosticsrdquo M Kayat and JH

Granger Spectroscopy on-line webinar

httpbwtekcomwebinarapplications-of-

raman-spectroscopy-in-biomedical-diagnos-

tics-spectroscopy

Dr Katherine Bakeev is the director of analytical services and sup-port at BampW Tek in Newark DelawareMichael Claybourn is a consul-tant with Biophotonics in Medicine in Chartres FranceRobert Chimenti is the market-ing manager at BampW Tek and an adjunct

professor in the department of physics and astronomy at Rowan University in Glassboro New JerseyRobert Thomas is the principal consultant at Scientific Solutions Inc in Gaithersburg Maryland Direct correspon-dence to katherinebbwtekcom ◾


High-performing and

user-friendly The BampW

Tek Raman line-up is on

your side The first amp only

name in mobile molecular

spectroscopy


wwwbwtekcom

Designed for your most challenging biological samples

Do MoreWITH 1064

1-855-BW-RAMAN


PRODUCTS amp RESOURCEShead_productstext_products text_products text_products text_products text_products text_products text_products company

name address website

head_productstext_products text_products text_products text_products text_products text_products text_products company






head_productstext_products text_products text_products text_products text_products text_products text_products company name

address website


address website


address website


address website

PRODUCTS amp RESOURCESInternal standard kitGlass Expansionrsquos modular Trident in-line reagent kit has a mixing tee that is designed to provide efficient mixing with minimal washout time According to the company all capillary tubing and con-nectors are included along with a sipper probe for the reagent being added Glass Expansion Inc Pocasset MA wwwgeicpcom

Digital pulse processorThe MXDPP-50 digital pulse processor from Moxtek is designed for use in analytical X-ray and gamma-ray instru-ments According to the com-pany the instrument digitizes detector output signals achieving high throughput and pile-up rejection Moxtek

Orem UTwwwmoxtekcom

FT-IR and NIR detector optionsPerkinElmerrsquos extended detector options for the com-panyrsquos Spotlight 400 FT-IR NIR imaging systems are designed to support sensitive high-performance NIR imag-ing for food feeds and longer wavelength MIR FT-IR imaging for inorganics polymer and semiconductor applications The companyrsquos Spectrum Touch Devel-oper software module reportedly enables the creation of IR work-flows for QA and QC routine analytical laboratory and field measure-ment PerkinElmer Waltham MA wwwperkinelmercom

Portable Raman analyzer software enhancementsRigaku Ramanrsquos software enhancements for its Xan-tus-2 portable analyzer are designed for enhanced com-pliance with 21 CFR Part II guidelines According to the company the software includes a redesigned account manage-ment user interface for stronger instrument security and data protectionRigaku Raman Technologies Tucson AZwwwrigakucom

X-ray fluorescence analyzerThe MESA 50 X-ray fluores-cence analyzer from Horiba Scientific is designed for businesses needing to screen samples containing hazardous elements such as lead cad-mium chromium mercury bromide for RoHS chlorine for halogen-free As and Sb applications According to the company the analyzer includes three analysis diameters suitable for samples such as thin cables electronic parts and bulk samplesHoriba Scientific Edison NJ wwwhoribacom

High-throughput spectrometersVentana high-throughput spec-trometers from Ocean Optics are designed for Raman and low-light applications Accord-ing to the company the spec-trometers combine an optical bench configuration with high collection efficiency and a vol-ume phase holographic grating with high diffraction efficiency Preconfigured spectrometers for both 532- and 785-nm excitation wavelength Raman and visible to near-IR fluorescence applications reportedly are available Ocean

Optics Dunedin FL wwwoceanopticscomproductsventanaasp

Sealed sample chamberA sealed sample chamber for the MIR-acle single-reflection ATR accessory from PIKE Technologies is designed with a high-pressure clamp with a chamber that attaches to diamond ZnSe or Ge crystal plates which reportedly enables the assembly to be moved from the spectrometer to a protective environment for sample loading and handling According to the company typical applications include studies of toxic or chemically aggres-sive solids and powders PIKE Technologies Madison WI wwwpiketechcom

UVndashvis spectrophotometersShimadzursquos compact UVndashvis spectrophotometers are designed to reduce stray light According to the company the instruments are suitable for both routine analysis and demanding research applica-tions The UV-2600 spectro-photometer reportedly has a measurement wavelength range that extends to 1400 nm using the ISR-2600Plus two-detector integrating sphere The UV-2700 spectrophotometer reportedly achieves stray light of 000005 T at 220 nm Shimadzu Scientific Instruments Columbia MD wwwssishimadzucom


Handheld NIR spectrometerThe handheld microPHAZIR AG analyzer from Thermo Scientific is designed to allow manufacturers to perform on-site NIR analysis to test ingredients and finished feeds to optimize nutrient formulations reduce manufacturing costs and improve consistency According to the company results can be directly exported into spreadsheets labora-tory information management sys-tems or feed control systemsThermo Fisher Scientific San Jose CA wwwthermoscientificcomfeed

Triple-quadrupole ICP-MS systemThe model 8800 ICP-QQQ triple-quadrupole ICP-MS sys-tem from Agilent Technologies is designed to provide supe-rior performance sensitivity and flexibility compared with single-quadrupole ICP-MS sys-tems According to the com-pany the systemrsquos ORS3 col-lisionndashreaction cell provides precise control of reaction processes for MS-MS operation The system is intended for use in semiconductor manufacturing advanced materials analysis clinical and life-science research and other applications in which interferences can hamper measurements with single-quadrupole ICP-MSAgilent Technologies Santa Clara CA wwwagilentcom

Raman coupler systemThe RayShield coupler from WITec is available for the companyrsquos alpha300 and alpha500 micro-scope series According to the company the device allows the acquisition of Raman spectra at wavenumbers down to below 10 rel cm-1 The coupler reportedly is available for a variety of laser wave-lengths from 488 to 785 nmWITec

Ulm Germany wwwwitecde

Portable Raman systemThe i-Raman EX 1064-nm por-table Raman spectrometer from BampW Tek is designed as an exten-sion of the companyrsquos i-Raman portable spectrometer According to the company the system is equipped with a high-sensitivity inGaAs array detector with deep TE cooling and a high dynamic rangeBampW Tek

Newark DEwwwbwtekcomproductsi-raman-ex

Michael W Allen

PhD

Director Marketing amp

Product Development Ocean Optics

Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics

WHAT ARE YOU MISSING NEW TECHNIQUES IN RAMAN SPECTROSCOPYRegister Free at wwwspectroscopyonlinecomraman

LIVE WEBCAST Thursday

September 26 2013

at 100pm EDT

For questions contact Kristen Farrell at

kfarrelladvanstarcom

Event OverviewRecent advances in Raman sampling and data analysis make compound identification easier and more reliable From analyzing incoming raw materials to identifying explosives learn how new sampling methods can dramatically improve the accuracy of your results

Key Learning Objectives

Understand the value of average power sampling for delicate samples

See application examples of sampling improvements

Hear how more reliable sampling improves library matching and can help improve your companyrsquos bottom line

Who Should Attend

Anyone interested in how sampling affects Raman microscopy

Quality Control specialists who are looking for more reliable library matching

Users of handheld Raman instruments unhappy with their current results

PRESENTERS MODERATOR

Laura Bush

Editorial Director Spectroscopy

Presented by

Sponsored by











address website


address website


address website


address website

Raman analyzersThe ProRaman-L series Raman spectrometers from Enwave Optronics are designed to provide mea-surement capability down to low parts-per-million levels According to the company the instruments are suitable for process analytical method developments and other measurements requiring high sensitivity and high speed analysis Enwave Optronics Inc

Irvine CA wwwenwaveoptcom

Application note for diesel analysis An application note from Applied Rigaku Technologies describes the measurement of sulfur in ultralow-sulfur die-sel using the companyrsquos NEX QC+ high-resolution benchtop EDXRF analyzer The analysis reportedly complies with stan-dard test method ISO 13032 Applied Rigaku

Technologies

Austin TX wwwrigakuedxrfcomedxrfapp-noteshtmlid=1272_AppNote

Microwave sample preparation systemThe Titan MPS microwave sample preparation system from PerkinElmer is designed to monitor and control diges-tions with contact-free and connection-free sensing via direct pressure control and direct temperature control monitoring systems According to the company the system is available in 8- and 16-vessel configurationsPerkinElmer

Waltham MAwwwperkinelmercomtitanmps

Surface plasmon resonance imaging systemHoriba Scientificrsquos OpenPlex surface plasmon resonance imaging system is designed for real-time analysis of label-free molecular interactions in a multi-plex format According to the company the system allows measurements of up to hundreds of interactions in a single experiment and can give qualitative and quantitative information of the interac-tions including concentration affinity and association and dissociation rates Molecular interactions involving pro-teins DNA polymers and nanoparticles reportedly can be character-ized and quantified Horiba Scientific Edison NJ wwwhoribacom

Laboratory-based LIBS analyzersChemScan laboratory-based analyzers from TSI are designed to use laser-induced breakdown spectros-copy to provide identification of materials and chemical composition of solids According to the company the analyzers are equipped with the companyrsquos ChemLyt-ics softwareTSI Incorporated

St Paul MN wwwtsicomChemScan

MALDI TOF-TOF mass spectrometerThe MALDI-7090 MALDI TOF-TOF mass spectrometer from Shimadzu is designed for proteomics and tissue imaging research According to the company the system features a solid-state laser 2-kHz acquisition speed in both MS and MS-MS modes an integrated 10-plate loader and the companyrsquos MALDI Solutions software Shimadzu Scientific Instruments

Columbia MD wwwssishimadzucom

Cryogenic grinding millRetschrsquos CryoMill cryogenic grinding mill is designed for size reduction of sample materials that cannot be processed at room temperature According to the company an integrated cooling system ensures that the millrsquos grinding jar is con-tinually cooled with liquid nitrogen before and during the grinding processRetsch

Newtown PAwwwretschcomcryomill

DetectorAndorrsquos iDus LDC-DD 416 plat-form is designed to provide a combination of low dark noise and high QE According to the company the detector is suit-able for NIR Raman and pho-toluminescence and can reduce acquisition times removing the need for liquid nitrogen cooling Andor Technology

South Windsor CT wwwandorcom


Benchtop spectrometersBaySpecrsquos SuperGamut bench-top spectrometers incorpo-rate multiple spectrographs and detectors optional light sources and sampling optics According to the company customers can choose wave-length ranges from 190 to 2500 nm combining one two or three multiple spectral engines depending on wavelength range and resolution requirementsBaySpec Inc San Jose CAwwwbayspeccom

Photovoltaic measurement systemNewport Corporationrsquos Oriel IQE-200 photovoltaic cell measurement system is designed for simultaneous measure-ment of the external and internal quan-tum efficiency of solar cells detectors and other photon-to-charge converting devices The system reportedly splits the beam to allow for concurrent mea-surements The system includes a light source a monochromator and related electronics and software According to the company the system can be used for the measurement of silicon-based cells amorphous and monopoly crystalline thin-film cells copper indium gallium diselenide and cadmium telluride Newport Corporation Irvine CA wwwnewportcom

Raman microscopeRenishawrsquos inVia Raman micro-scope is designed with a 3D imaging capability that allows users to collect and display Raman data from within trans-parent materials According to the company the instrumentrsquos StreamLineHR feature collects data from a series of planes within materials processes it and displays it as 3D volume images representing quantities such as band intensity Renishaw

Hoffman Estates ILwwwrenishawcomraman

Data reviewing and sharing iPad appThe Thermo Scientific Nano-Drop user application for iPad is designed to enable users of the companyrsquos NanoDrop instruments to take sample data on the go According to the company the app allows users to import and view data and compare concentration purity and spectral informationThermo Fisher Scientific San Jose CAwwwthermoscientificcomnanodropapp

Register Free at httpwwwspectroscopyonlinecomImpurities

EVENT OVERVIEW

You most likely already know the basics of USP lt232gt and lt233gt the new chapters on

elemental impurities mdash limits and procedures This new webcast will focus on the practical

considerations of using the full suite of trace metal analytical tools to comply with the new

requirements in a GMP environment You will learn about the tools available to rapidly get

your operation compliant mdash how to choose the right technique how to use the PerkinElmer

ldquoJrdquo value calculator the critical role of 21 CFR Part 11 compliance software and how you can

simplify the setup calibration and maintenance of your system And even though these new

chapters have been deferred your lab will

need to be ready in the future to meet these

challenging new guideline

Who Should Attend

Pharmaceutical (APIrsquos etc) and

Pharmaceutical analytical and QC managers

Pharmaceutical chemists and method

development teams

Analytical chemists in nutraceutical and

dietary supplement operations


How to calculate the J value to

set up your analysis

How using a method SOP

template can give you a great

head start How maintenance

and stability affect throughput

and quality in your lab

21 CFR Part 11 compliance

plays a critical rolemdasha closer

look

Understanding the role of an

intelligent auto-dilution system

in making your job easier and

provide higher-quality results


Tim CuffICP-MS Business Development Manager North AmericaPerkinElmer Inc

Nathan SaetveitScientist Elemental Scientific

Kevin KingstonSenior Training Specialist PerkinElmer Inc

Moderator

Laura BushEditorial DirectorSpectroscopy

Sponsored by

Presented by

For questions contact Kristen Farrell at kfarrelladvanstarcom

PRESENTERS

LIVE WEBCAST Thursday September 19 2013 at 100 pm EDT


Calendar of EventsSeptember 201324ndash26 Analitica Latin AmericaSao Paulo Brazil wwwanaliticanetcombrenindexphppgID=home

29 Septemberndash4 October SciX2013 ndash The Great SCIentific eXchange Milwaukee WI wwwscixconferenceorgeventscon-ference-registrationentryadd

30 Septemberndash2 October 10th Confocal Raman Imaging Symposium Ulm Germany wwwwitecdeevents10th-raman-symposium

October 201318ndash19 Annual Meeting of the Four Corners Section of the American Physical SocietyDenver CO wwwaps4cs2013info

18ndash22 ASMS Asilomar Conference on Mass Spectrometry in Environmental Chemistry Toxicology and HealthPacific Grove CA wwwasmsorgconferencesasilomar-conference

27ndash31 5th Asia-Pacific NMR Symposium (APNMR5) and 9th Australian amp New Zealand Society for Magnetic Resonance (ANZMAG) MeetingBrisbane Australia apnmr2013org

27 Octoberndash1 November AVS 60th International Symposium amp Exhibition (AVS-60)Long Beach CA www2avsorgsymposiumAVS60pagesgreetingshtml

November 20134ndash5 Eighth International MicroRNAs Europe 2013 Symposium on MicroRNAs Biology to Development and Disease Cambridge UK wwwexpressgenescommicrornai2013mainhtml

18ndash20 EAS Eastern Analytical Symposium amp Exhibition Somerset NJ easorg

Register Free at wwwspectroscopyonlinecomavoid

EVENT OVERVIEW

Ensure you achieve the highest quality data from your routine QAQC industrial

sample analysis using ICP-OES and ICP-MS

Join this educational webinar and discover

how to avoid the common errors that

result in bad data and learn how to achieve

ldquoright first timerdquo data We have considered

feedback from a cross-section of industrial

ICP-MS and ICP-OES users in routine QA

QC environments and have identified the

root causes and best practices for success

In this web seminar we will discuss choices

in sample preparation techniques and

introduction systems corrections to inter-

ference verifications to data quality and

best practices for data reporting


1 How to select the correct sample

preparation techniques amp intro-

duction systems for your application

2 Achieve successful interference

corrections to mitigate false positives

3 How to verify your data quality

4 Best practices for data reporting

Who Should Attend

Trace elemental QAQC Managers

QAQC Lab Instrument operators

PRESENTERS

Julian WillsApplications SpecialistThermo Fisher Scientific Bremen

James Hannan ICP Applications Chemist Thermo Fisher Scientific

MODERATOR

Steve BrownTechnical EditorSpectroscopy

Sponsored by

Presented by


How to Avoid Bad Data When Analyzing Routine QAQCIndustrial Samples Using ICP-OES and ICP-MS

LIVE WEBCAST Tuesday September 10 2013 800 am PDT 1100 am EDT 1600 BST 1700 CEDT

Meeting Chairs

Jose A Garrido Technische Universitaumlt Muumlnchen

Sergei V Kalinin Oak Ridge National Laboratory

Edson R Leite Federal University of Sao Carlos

David Parrillo The Dow Chemical Company

Molly Stevens Imperial College London

Donrsquot Miss These Future MRS Meetings

2014 MRS Fall Meeting amp Exhibit

November 30-December 5 2014

Hynes Convention Center amp Sheraton Boston Hotel Boston Massachusetts

2015 MRS Spring Meeting amp Exhibit

April 6-10 2015

Moscone West amp San Francisco Marriott Marquis San Francisco California

FZTUPOFSJWFt8BSSFOEBMF131

5FMtBY

JOGPNSTPSHtXXXNSTPSH

ENERGY

A Film-Silicon Science and Technology

B Organic and Inorganic Materials for Dye-Sensitized Solar Cells

$ 4ZOUIFTJTBOE1SPDFTTJOHPG0SHBOJDBOE1PMZNFSJDBUFSJBMT for Semiconductor Applications

BUFSJBMTGPS1IPUPFMFDUSPDIFNJDBMBOE1IPUPDBUBMZUJD4PMBSampOFSHZ Harvesting and Storage

amp ampBSUICVOEBOUOPSHBOJD4PMBSampOFSHZ$POWFSTJPO

F Controlling the Interaction between Light and Semiconductor BOPTUSVDUVSFTGPSampOFSHZQQMJDBUJPOT

( 1IPUPBDUJWBUFE$IFNJDBMBOEJPDIFNJDBM1SPDFTTFT on Semiconductor Surfaces

) FGFDUampOHJOFFSJOHJO5IJOJMN1IPUPWPMUBJDBUFSJBMT

I Materials for Carbon Capture

+ 1IZTJDTPG0YJEF5IJOJMNTBOE)FUFSPTUSVDUVSFT

BOPTUSVDUVSFT135IJOJMNTBOEVML0YJEFT Synthesis Characterization and Applications

- BUFSJBMTBOEOUFSGBDFTJO4PMJE0YJEFVFM$FMMT

VFM$FMMT13ampMFDUSPMZ[FSTBOE0UIFSampMFDUSPDIFNJDBMampOFSHZ4ZTUFNT

3FTFBSDISPOUJFSTPOampMFDUSPDIFNJDBMampOFSHZ4UPSBHFBUFSJBMT Design Synthesis Characterization and Modeling

0 PWFMampOFSHZ4UPSBHF5FDIOPMPHJFTCFZPOE-JJPOBUUFSJFT From Materials Design to System Integration

1 FDIBOJDTPGampOFSHZ4UPSBHFBOE$POWFSTJPO Batteries Thermoelectrics and Fuel Cells

Q Materials Technologies and Sensor Concepts for Advanced Battery Management Systems

3 BUFSJBMT$IBMMFOHFTBOEOUFHSBUJPO4USBUFHJFTGPSMFYJCMFampOFSHZ Devices and Systems

4 DUJOJEFTBTJD4DJFODF13QQMJDBUJPOTBOE5FDIOPMPHZ

5 4VQFSDPOEVDUPSBUFSJBMT From Basic Science to Novel Technology

SOFT AND BIOMATERIALS

U Soft Nanomaterials

V Micro- and Nanofluidic Systems for Materials Synthesis Device Assembly and Bioanalysis

8 VODUJPOBMJPNBUFSJBMTGPS3FHFOFSBUJWFampOHJOFFSJOH

Y Biomaterials for Biomolecule Delivery and Understanding Cell-Niche Interactions

JPFMFDUSPOJDTBUFSJBMT131SPDFTTFTBOEQQMJDBUJPOT

AA Advanced Multifunctional Biomaterials for Neuroprosthetic Interfaces

ELECTRONICS AND PHOTONICS

BUFSJBMTGPSampOEPG3PBENBQFWJDFTJO-PHJD131PXFSBOEFNPSZ

$$ FXBUFSJBMTBOE1SPDFTTFTGPSOUFSDPOOFDUT13PWFMFNPSZ and Advanced Display Technologies

4JMJDPO$BSCJEFBUFSJBMT131SPDFTTJOHBOEFWJDFT

ampamp EWBODFTJOOPSHBOJD4FNJDPOEVDUPSBOPQBSUJDMFT and Their Applications

5IF(SBOE$IBMMFOHFTJO0SHBOJDampMFDUSPOJDT

GG Few-Dopant Semiconductor Optoelectronics

)) 1IBTF$IBOHFBUFSJBMTGPSFNPSZ133FDPOmHVSBCMFampMFDUSPOJDT and Cognitive Applications

ampNFSHJOHBOPQIPUPOJDBUFSJBMTBOEFWJDFT

++ BUFSJBMTBOE1SPDFTTFTGPSPOMJOFBS0QUJDT

3FTPOBOU0QUJDTVOEBNFOUBMTBOEQQMJDBUJPOT

-- 5SBOTQBSFOUampMFDUSPEFT

NANOMATERIALS

MM Nanotubes and Related Nanostructures

NN 2D Materials and Devices beyond Graphene

OO De Novo Graphene

11 BOPEJBNPOETVOEBNFOUBMTBOEQQMJDBUJPOT

22 $PNQVUBUJPOBMMZampOBCMFEJTDPWFSJFTJO4ZOUIFTJT134USVDUVSF BOE1SPQFSUJFTPGBOPTDBMFBUFSJBMT

RR Solution Synthesis of Inorganic Functional Materials

SS Nanocrystal Growth via Oriented Attachment and Mesocrystal Formation

55 FTPTDBMF4FMGTTFNCMZPGBOPQBSUJDMFT Manufacturing Functionalization Assembly and Integration

66 4FNJDPOEVDUPSBOPXJSFT4ZOUIFTJT131SPQFSUJFTBOEQQMJDBUJPOT

VV Magnetic Nanomaterials and Nanostructures

GENERALmdashTHEORY AND CHARACTERIZATION

88 BUFSJBMTCZFTJHOFSHJOHEWBODFEIn-situ Characterization XJUI1SFEJDUJWF4JNVMBUJPO

99 4IBQF1SPHSBNNBCMFBUFSJBMT

YY Meeting the Challenges of Understanding and Visualizing FTPTDBMF1IFOPNFOB

ZZ Advanced Characterization Techniques for Ion-Beam-Induced ampGGFDUTJOBUFSJBMT

AAA Applications of In-situ Synchrotron Radiation Techniques in Nanomaterials Research

EWBODFTJO4DBOOJOH1SPCFJDSPTDPQZGPSBUFSJBM1SPQFSUJFT

CCC In-situ $IBSBDUFSJ[BUJPOPGBUFSJBM4ZOUIFTJTBOE1SPQFSUJFT BUUIFBOPTDBMFXJUI5amp

UPNJD3FTPMVUJPOOBMZUJDBMampMFDUSPOJDSPTDPQZPGJTSVQUJWF BOEampOFSHZ3FMBUFEBUFSJBMT

ampampamp BUFSJBMTFIBWJPSVOEFSampYUSFNFSSBEJBUJPO134USFTTPS5FNQFSBUVSF

SPECIAL SYMPOSIUM

ampEVDBUJOHBOEFOUPSJOHPVOHBUFSJBMT4DJFOUJTUT for Career Development

wwwmrsorgspring2014

April 21-25 San Francisco CA

CTUSBDUFBEMJOFtPWFNCFS13

CTUSBDU4VCNJTTJPO4JUF0QFOTt0DUPCFS13

2014

SPRING MEETING amp EXHIBIT

S

50 Spectroscopy 28(9) September 2013 wwwspec t roscopyonl ine comreg

Agilent Technologies 3

Amptek 10

Andor Technology Ltd 37

Applied Rigaku Technologies 31

Avantes BV 50

BampW Tek Inc BRC 29 43

BaySpec Inc 21

Cobolt AB 20

Eastern Analytical Symposium 18

EMCO High Voltage Corp 4

Enwave Optronics Inc 17

Glass Expansion 34

Hellma Cells Inc 25

Horiba Scientific CV4

Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49

New Era Enterprises Inc 50

Newport Corporation 39

Nippon Instruments North America 50

Ocean Optics Inc 23 45

PerkinElmer Corp 13 15 47

PIKE Technologies 32 33 50

Renishaw Inc 6

Retsch Inc INSERT

Rigaku Raman Technologies 5

Shimadzu Scientific Instruments WALLCHART 9

Thermo Fisher Scientific CV2 48

TSI Incorporated 35

WITEC GmbH 41

Ad IndexADVERTISER PG ADVERTISER PG ADVERTISER PG

398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404

398435forallforall398435 398435existamp398404

398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components

Supplier Hitting the Mark

Innovative Solutions

1 Customer Satisfaction

Quality Products

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wwwpiketechcom

New Accessory Catalog

IS YOUR

MEETING YOUR EXPECTATIONS

MA-3000

Direct Mercury Analysis

MERCURYANALYZER

hg-nicusNippon Instruments North America

18772477241

Call for Application Notes

Spectroscopy is planning to publish the next edition of The Application Notebook in

December 2013 As always the publication will include paid position vendor applica-

tion notes that describe techniques and applications of all forms of spectroscopy that are of immediate interest to users in industry academia and government If

your company is interested in participating in this special supplement contact

Michael J Tessalone (SPVQ1VCMJTIFSt

Edward Fantuzzi 1VCMJTIFSt

orStephanie Shaffer East Coast Sales BOBHFSt

Introducing the

SPECTROSCOPY APP for your iPhone or iPad

Designed for both the iPhone and iPad Spectroscopyrsquos new

app may be found on iTunes under the Business category

and downloaded for free Exploring the latest news and

trends for spectroscopists has never been easier

Download it for free today at

httpwwwspectroscopyonlinecomSpectroscopyApp

The Art of RAMAN

wwwhoribacomramanemail adsci-spectyhoribacom

+25$6FLHQWLiquestF offers a complete spectrum of Raman solutions that transforms Raman from complicated science to an easy art form

From our new XploRA ONE Confocal One-Shot Microscope to RXUDE5$0+5(YROXWLRQRXZLOOiquestQGDQHDVWRXVH5DPDQ LQVWUXPHQWGHVLJQHGWRiquestWRXUUHTXLUHPHQWVDQGRXUEXGJHW without needing to compromise

And our instruments are backed by unsurpassed application and customer support all from

+25$6FLHQWLiquestFWKH leader in Raman spectroscopy

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DownsampleGrayImages true GrayImageDownsampleType Bicubic GrayImageResolution 150 GrayImageDepth -1 GrayImageMinDownsampleDepth 2 GrayImageDownsampleThreshold 150000 EncodeGrayImages true GrayImageFilter DCTEncode AutoFilterGrayImages true GrayImageAutoFilterStrategy JPEG GrayACSImageDict ltlt QFactor 130 HSamples [2 1 1 2] VSamples [2 1 1 2] gtgt GrayImageDict ltlt QFactor 015 HSamples [1 1 1 1] VSamples [1 1 1 1] gtgt JPEG2000GrayACSImageDict ltlt TileWidth 256 TileHeight 256 Quality 30 gtgt JPEG2000GrayImageDict ltlt TileWidth 256 TileHeight 256 Quality 30 gtgt AntiAliasMonoImages false CropMonoImages false MonoImageMinResolution 300 MonoImageMinResolutionPolicy OK DownsampleMonoImages true MonoImageDownsampleType Bicubic MonoImageResolution 150 MonoImageDepth -1 MonoImageDownsampleThreshold 150000 EncodeMonoImages true MonoImageFilter CCITTFaxEncode MonoImageDict ltlt K -1 gtgt AllowPSXObjects true CheckCompliance [ None ] PDFX1aCheck false PDFX3Check false PDFXCompliantPDFOnly false PDFXNoTrimBoxError true PDFXTrimBoxToMediaBoxOffset [ 000000 000000 000000 000000 ] PDFXSetBleedBoxToMediaBox true PDFXBleedBoxToTrimBoxOffset [ 000000 000000 000000 000000 ] PDFXOutputIntentProfile () PDFXOutputConditionIdentifier () PDFXOutputCondition () PDFXRegistryName () PDFXTrapped False CreateJDFFile false Description ltlt ARA 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 BGR ltFEFF04180437043f043e043b043704320430043904420435002004420435043704380020043d0430044104420440043e0439043a0438002c00200437043000200434043000200441044a0437043404300432043004420435002000410064006f00620065002000500044004600200434043e043a0443043c0435043d04420438002c0020043c0430043a04410438043c0430043b043d043e0020043f044004380433043e04340435043d04380020043704300020043f043e043a0430043704320430043d04350020043d043000200435043a04400430043d0430002c00200435043b0435043a04420440043e043d043d04300020043f043e044904300020043800200418043d044204350440043d04350442002e002000200421044a04370434043004340435043d043804420435002000500044004600200434043e043a0443043c0435043d044204380020043c043e0433043004420020043404300020044104350020043e0442043204300440044f0442002004410020004100630072006f00620061007400200438002000410064006f00620065002000520065006100640065007200200036002e00300020043800200441043b0435043404320430044904380020043204350440044104380438002egt CHS ltFEFF4f7f75288fd94e9b8bbe5b9a521b5efa7684002000410064006f006200650020005000440046002065876863900275284e8e5c4f5e55663e793a3001901a8fc775355b5090ae4ef653d190014ee553ca901a8fc756e072797f5153d15e03300260a853ef4ee54f7f75280020004100630072006f0062006100740020548c002000410064006f00620065002000520065006100640065007200200036002e003000204ee553ca66f49ad87248672c676562535f00521b5efa768400200050004400460020658768633002gt CHT ltFEFF4f7f752890194e9b8a2d7f6e5efa7acb7684002000410064006f006200650020005000440046002065874ef69069752865bc87a25e55986f793a3001901a904e96fb5b5090f54ef650b390014ee553ca57287db2969b7db28def4e0a767c5e03300260a853ef4ee54f7f75280020004100630072006f0062006100740020548c002000410064006f00620065002000520065006100640065007200200036002e003000204ee553ca66f49ad87248672c4f86958b555f5df25efa7acb76840020005000440046002065874ef63002gt CZE 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 DAN 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 DEU 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 ENU (Use these settings to create Adobe PDF documents best suited for on-screen display e-mail and the Internet Created PDF documents can be opened with Acrobat and Adobe Reader 60 and later) ESP 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 ETI 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 FRA 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 GRE ltFEFF03a703c103b703c303b903bc03bf03c003bf03b903ae03c303c403b5002003b103c503c403ad03c2002003c403b903c2002003c103c503b803bc03af03c303b503b903c2002003b303b903b1002003bd03b1002003b403b703bc03b903bf03c503c103b303ae03c303b503c403b5002003ad03b303b303c103b103c603b1002000410064006f006200650020005000440046002003c003bf03c5002003b503af03bd03b103b9002003ba03b103c42019002003b503be03bf03c703ae03bd002003ba03b103c403ac03bb03bb03b703bb03b1002003b303b903b1002003c003b103c103bf03c503c303af03b103c303b7002003c303c403b703bd002003bf03b803cc03bd03b7002c002003b303b903b100200065002d006d00610069006c002c002003ba03b103b9002003b303b903b1002003c403bf0020039403b903b1002d03b403af03ba03c403c503bf002e0020002003a403b10020005000440046002003ad03b303b303c103b103c603b1002003c003bf03c5002003ad03c703b503c403b5002003b403b703bc03b903bf03c503c103b303ae03c303b503b9002003bc03c003bf03c103bf03cd03bd002003bd03b1002003b103bd03bf03b903c703c403bf03cd03bd002003bc03b5002003c403bf0020004100630072006f006200610074002c002003c403bf002000410064006f00620065002000520065006100640065007200200036002e0030002003ba03b103b9002003bc03b503c403b103b303b503bd03ad03c303c403b503c103b503c2002003b503ba03b403cc03c303b503b903c2002egt HEB 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 HRV ltFEFF005a00610020007300740076006100720061006e006a0065002000500044004600200064006f006b0075006d0065006e0061007400610020006e0061006a0070006f0067006f0064006e0069006a006900680020007a00610020007000720069006b0061007a0020006e00610020007a00610073006c006f006e0075002c00200065002d0070006f0161007400690020006900200049006e007400650072006e0065007400750020006b006f00720069007300740069007400650020006f0076006500200070006f0073007400610076006b0065002e00200020005300740076006f00720065006e0069002000500044004600200064006f006b0075006d0065006e007400690020006d006f006700750020007300650020006f00740076006f00720069007400690020004100630072006f00620061007400200069002000410064006f00620065002000520065006100640065007200200036002e0030002000690020006b00610073006e0069006a0069006d0020007600650072007a0069006a0061006d0061002egt HUN 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 ITA 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 JPN ltFEFF753b97624e0a3067306e8868793a3001307e305f306f96fb5b5030e130fc30eb308430a430f330bf30fc30cd30c330c87d4c7531306790014fe13059308b305f3081306e002000410064006f0062006500200050004400460020658766f8306e4f5c6210306b9069305730663044307e305930023053306e8a2d5b9a30674f5c62103055308c305f0020005000440046002030d530a130a430eb306f3001004100630072006f0062006100740020304a30883073002000410064006f00620065002000520065006100640065007200200036002e003000204ee5964d3067958b304f30533068304c3067304d307e305930023053306e8a2d5b9a3067306f30d530a930f330c8306e57cb30818fbc307f3092884c306a308f305a300130d530a130a430eb30b530a430ba306f67005c0f9650306b306a308a307e30593002gt KOR ltFEFFc7740020c124c815c7440020c0acc6a9d558c5ec0020d654ba740020d45cc2dc002c0020c804c7900020ba54c77c002c0020c778d130b137c5d00020ac00c7a50020c801d569d55c002000410064006f0062006500200050004400460020bb38c11cb97c0020c791c131d569b2c8b2e4002e0020c774b807ac8c0020c791c131b41c00200050004400460020bb38c11cb2940020004100630072006f0062006100740020bc0f002000410064006f00620065002000520065006100640065007200200036002e00300020c774c0c1c5d0c11c0020c5f40020c2180020c788c2b5b2c8b2e4002egt LTH 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 LVI 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 NLD (Gebruik deze instellingen om Adobe PDF-documenten te maken die zijn geoptimaliseerd voor weergave op een beeldscherm e-mail en internet De gemaakte PDF-documenten kunnen worden geopend met Acrobat en Adobe Reader 60 en hoger) NOR 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 POL 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 PTB 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 RUM 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 RUS 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 SKY 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 SLV 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 SUO 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 SVE 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 TUR ltFEFF0045006b00720061006e002000fc0073007400fc0020006700f6007200fc006e00fc006d00fc002c00200065002d0070006f00730074006100200076006500200069006e007400650072006e006500740020006900e70069006e00200065006e00200075007900670075006e002000410064006f006200650020005000440046002000620065006c00670065006c0065007200690020006f006c0075015f007400750072006d0061006b0020006900e70069006e00200062007500200061007900610072006c0061007201310020006b0075006c006c0061006e0131006e002e00200020004f006c0075015f0074007500720075006c0061006e0020005000440046002000620065006c00670065006c0065007200690020004100630072006f0062006100740020007600650020004100630072006f006200610074002000520065006100640065007200200036002e003000200076006500200073006f006e0072006100730131006e00640061006b00690020007300fc007200fc006d006c00650072006c00650020006100e70131006c006100620069006c00690072002egt UKR ltFEFF04120438043a043e0440043804410442043e043204430439044204350020044604560020043f043004400430043c043504420440043800200434043b044f0020044104420432043e04400435043d043d044f00200434043e043a0443043c0435043d044204560432002000410064006f006200650020005000440046002c0020044f043a0456043d04300439043a04400430044904350020043f045604340445043e0434044f0442044c00200434043b044f0020043f0435044004350433043b044f043404430020043700200435043a04400430043d044300200442043000200406043d044204350440043d043504420443002e00200020042104420432043e04400435043d045600200434043e043a0443043c0435043d0442043800200050004400460020043c043e0436043d04300020043204560434043a0440043804420438002004430020004100630072006f006200610074002004420430002000410064006f00620065002000520065006100640065007200200036002e0030002004300431043e0020043f04560437043d04560448043e04570020043204350440044104560457002egt gtgt ExportLayers ExportVisibleLayers Namespace [ (Adobe) (Common) (10) ] OtherNamespaces [ ltlt AsReaderSpreads false CropImagesToFrames true ErrorControl WarnAndContinue FlattenerIgnoreSpreadOverrides false IncludeGuidesGrids false IncludeNonPrinting false IncludeSlug false Namespace [ (Adobe) (InDesign) (40) ] OmitPlacedBitmaps false OmitPlacedEPS false OmitPlacedPDF false SimulateOverprint Legacy gtgt ltlt AddBleedMarks false AddColorBars false AddCropMarks false AddPageInfo false AddRegMarks false BleedOffset [ 9 9 9 9 ] ConvertColors ConvertToRGB DestinationProfileName (sRGB IEC61966-21) DestinationProfileSelector UseName Downsample16BitImages true FlattenerPreset ltlt PresetSelector MediumResolution gtgt FormElements false GenerateStructure false IncludeBookmarks false IncludeHyperlinks true IncludeInteractive false IncludeLayers false IncludeProfiles true MarksOffset 6 MarksWeight 0250000 MultimediaHandling UseObjectSettings Namespace [ (Adobe) (CreativeSuite) (20) ] PDFXOutputIntentProfileSelector NA PageMarksFile RomanDefault PreserveEditing false UntaggedCMYKHandling UseDocumentProfile UntaggedRGBHandling UseDocumentProfile UseDocumentBleed true gtgt ltlt AllowImageBreaks true AllowTableBreaks true ExpandPage false HonorBaseURL true HonorRolloverEffect false IgnoreHTMLPageBreaks false IncludeHeaderFooter false MarginOffset [ 0 0 0 0 ] MetadataAuthor () MetadataKeywords () MetadataSubject () MetadataTitle () MetricPageSize [ 0 0 ] MetricUnit inch MobileCompatible 0 Namespace [ (Adobe) (GoLive) (80) ] OpenZoomToHTMLFontSize false PageOrientation Portrait RemoveBackground false ShrinkContent true TreatColorsAs MainMonitorColors UseEmbeddedProfiles false UseHTMLTitleAsMetadata true gtgt ]gtgt setdistillerparamsltlt HWResolution [600 600] PageSize [612000 792000]gtgt setpagedevice

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reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













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55Fe

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ITS EVERYTHING

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Ion-implanted Si


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Sector geometries



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Responsibilities







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Key Applications

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4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

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in

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Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

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(cts

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= Antigen

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O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN
















revolution


ATOMICSPECTROSCOPY

onAIRRU

NS


reg

50


aste











($2200 total)











advanstarcom






























Tel (USA) +1-925-218-1885

(Canada) +1-416-840-4991






High stability

















ownership












reg


(732) 596-0276 Fax (732) 647-1235




(508) 481-5885

EDITORIALLaura Bush



































Apply innovation

Improve your images


wwwrenishawcomraman


Raman images

now in

high def


reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN








reg

50


aste











($2200 total)











advanstarcom






























Tel (USA) +1-925-218-1885

(Canada) +1-416-840-4991






High stability

















ownership












reg


(732) 596-0276 Fax (732) 647-1235




(508) 481-5885

EDITORIALLaura Bush



































Apply innovation

Improve your images


wwwrenishawcomraman


Raman images

now in

high def


reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN















ownership












reg


(732) 596-0276 Fax (732) 647-1235




(508) 481-5885

EDITORIALLaura Bush



































Apply innovation

Improve your images


wwwrenishawcomraman


Raman images

now in

high def


reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN







reg


(732) 596-0276 Fax (732) 647-1235




(508) 481-5885

EDITORIALLaura Bush



































Apply innovation

Improve your images


wwwrenishawcomraman


Raman images

now in

high def


reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN








reg

CONTENTS



v 28 n 9s 2013

COLUMNS


David Tuschel


Kenneth L Busch


RD McDowall









WEB SEMINARS











Calendar 48

Ad Index 50








FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN














FTIR analysis













High

-Sen

sitiv

ity







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN












































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D
















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


alpha300 SR


alpha500 AR


alpha300 R


PIONEERS

WITec Headquarters




















(2012)










ment 17(5) 11ndash15 (2012)








213783 Volume 2011




558 (2012)




310ndash321 (2011)




67(1) 1ndash9 (2002)




New York 2001)



837 (2011)


322a (2006)











Heidelberg 2006)



463ndash468 (2013)


21(1) 1ndash30 (2007)



Analyst 135 3042ndash3047 (2010)




org101016jpdpdt201301008








84(15) 6715ndash6722 (2012)














duction



410ndash416 (2013)






tics-spectroscopy




High-performing and





spectroscopy


wwwbwtekcom


Do MoreWITH 1064

1-855-BW-RAMAN











address website


address website


address website


address website



Orem UTwwwmoxtekcom















Michael W Allen

PhD



Yvette Mattley PhD

Senior Applications

Scientist

Ocean Optics



September 26 2013

at 100pm EDT








Who Should Attend





Laura Bush


Presented by

Sponsored by











address website


address website


address website


address website




Technologies




















EVENT OVERVIEW











Who Should Attend




development teams













look









Moderator


Sponsored by

Presented by


PRESENTERS













EVENT OVERVIEW
























Who Should Attend



PRESENTERS



MODERATOR


Sponsored by

Presented by




Meeting Chairs











April 6-10 2015



5FMtBY


ENERGY








































NANOMATERIALS



OO De Novo Graphene


















SPECIAL SYMPOSIUM


wwwmrsorgspring2014




2014


S



Amptek 10



Avantes BV 50


BaySpec Inc 21

Cobolt AB 20




Glass Expansion 34

Hellma Cells Inc 25


Mightex Systems 4

Moxtek Inc 7 50

MRS Fall 2013 49







Renishaw Inc 6

Retsch Inc INSERT




TSI Incorporated 35

WITEC GmbH 41


398401398401398401398401398401398401398402398403398404398405398404398406398407398403398404

398408398409398404398405398404398409398416398417398404398405398404398418398419398401

398404398404398404398416398403398404398405398404398418398420398416398403398404

398404398404398404398421398421398404398405398404398416398422398407398404

398401398401398402398403398404398405398406398407398408398409398401398402398416398405398405398406398407398417398418398401398419398401398420398421398421398417398418398418398422398423398407398417398418398401

398404398424398416398406398406398401398425398403398432398403398406398422398409398418398401398433398407398432398434398401398435398423398407398421398407398408398409398404398404398423398423398423398424398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

398401398432398423398404398406398433398434398404398406398425398439398432398433398437398433398448398436398432398436398449398404398416398425398438398424398404


398404398404398438398436ni398425398432398423398432398433398434398435398436398437398432398438398439398433398440398424398438398440398441398404

MOXTEKreg

Is your

X-RAY Components




Quality Products

wwwmoxtekcom

452 W 1260 N

Orem UT 84057

18007583110


wwwpiketechcom


IS YOUR


MA-3000


MERCURYANALYZER


18772477241









Introducing the








The Art of RAMAN






















rates by next year





























in 2014





Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

986

32



BampW TEK IS GIVING

YOU THE CHANCE TO



wwwPortableRamancom

WINA NEW iPAD

1-855-BW-RAMAN







































Complete XRF System

OEM Components

wwwamptekcom

64

keV

125 eV FWHM

Energy (keV)

Co

un

ts

59

keV

25 mm2 x 500 μm


PB Ratio 200001

55Fe

reg


S D D









from anywhere














Fran Adar


Horiba - 21

Renishaw - 9

Bruker - 8

JASCO - 6

Other - 32

$36M

24

21

98

6

32



David Tuschel








copy20

11-2

012

Perk

inEl

mer

Inc

40

0261

_01

All

righ

ts r

eser

ved

Per

kinE

lmer

reg is

a r

egis

tere

d tr

adem

ark

of P

erki

nElm

er I

nc A

ll ot

her

trad

emar

ks a

re t

he p

rope

rty

of t

heir

resp

ecti

ve o

wne

rs

















Polysilicon A

Polysilicon B









copy 2

013

Perk

inEl

mer

In

c 4

0027

8_02

A

ll tr

adem

arks

or

regi

ster

ed t

rade

mar

ks a

re t

he p

rope

rty

of P

erki

nElm

er

Inc

and

or

its s

ubsi

diar

ies


ITS EVERYTHING

BEHIND IT





Ion-implanted Si


X (μm)

Y (

μm

)

-10 -5 0 5 1510

14

10

6

2

-2

-6

-10













LABORATORY RAMAN

131313

131313

FIELD PORTABLE

+131

13-1313

HANDHELD RAMAN

amp13131313

+13

(1313-1313131131313131313

PROCESS RAMAN

13013131313

+131313)1313


























is your only choice


Jaw CrusherBB 300



Pellet PressPP 40



JAW CRUSHERS



lt05 mm)





materials







available

wwwretschcombb300







wwwretschcom




Jaw Crusher

BB 300

Jaw Crusher

BB 50

Jaw Crusher

BB 100

Jaw Crusher

BB 200







Pellet Press PP 40



high throughput

operation Pressure

up to 40 tons

wwwretschcompp


abrasive substances

VIBRATORY DISC MILL







sample materials


with graphics

display

n Sealed noise-

insulated grinding

chamber

n Robust and safe

wwwretschcomrs200



SAMPLE DIVIDER




sub-samples

wwwretschcompt100









run unsupervised



chamber allows wet

grinding with

solvents



grinding of up to


wwwretschcompm400

Planetary Ball Mill

PM 400

Product videos at

wwwretschcomvideos

Sample Divider

PT 100

Vibratory Disc Mill

RS 200

Pellet Press

PP 25

Pellet Press

PP 40


74 Walker Lane

Newtown PA 18940

Toll free (866) 473-8724

Phone (267) 757-0351

Fax (267) 757-0358



Subje

ct

to t

echnic

al m

odific

ations a

nd e

rrors

middot

991001071U

S-0

7-2

012



MILLIN

GS

IEV

IN

GA

SS

IS

TIN

G






Disc MillDM 200






Cyclone MillTWISTER








Rapid DryerTG 200










Polysilicon B

Polysilicon A


X (μm)

Y (

μm

)

-10 -5 0 5 15 10

10

6

2

-6

-10

-14

-18

-15

-2

Ion-implanted Si









6

4

2

-2

-4

-6

0

X (μm)

Y (

μm

)

-8 -6 0 2 8 10-4-10 -2 4 6


wwwcoboltse











warranty





























NomadicTM












Kenneth L Busch




















Sector geometries



Wien filter


Devices











Ion trajectories



Cells




Micro Flow Channels









Look how easy it is












Ken

dri

ck m

ass

defe

ct

Kendrick mass



































Focus on Quality

RD McDowall



















Innovative






OUFHSBUJPO5JNF















Scope

















+ $$(

+ $$($(

+ amp$

$($

$(

+ $(

$$$

+ 13amp$

$(

amp$

+ $(

+ $$$

$ amp(

$

+ $$$$

amp$ amp

+ $)

$

+ $$$$amp$

$$$( $

+ $

$

+ T$($$ $(

$$

+

$ $

+ $$$

amp$$ (

$$($amp$$

$

+ $$$$$

$amp$$$(

$$

$(

t

$$

$

$$

$(

$$amp




Responsibilities







Change Control






Glossary



Scenario 1




Scenario 2







-

- -

- -

-

- - -

-




Add options as your




Analyze Everything

with PIKE MIRacleTM


wwwpiketechcom

tel 608-274-2721













or during a task

-

- -

- -

-

- - -

-











PIKE MIRacle


PIKE Technologies

wwwpiketechcom

tel 608-274-2721

TM












Write method







report R A R C C




l

l

l

l


Request our catalog
























chemical analysis












OF SOLID MATERIALS




















()15 μm pixel)+

+30 mm wide array)

)())

$(-95ordmCamp

)Ultravac trade))))

)))))

Key Applications

$

)ampamp)

-$)

)

)



















4000 3000 2000 1500 1000 500

Vibrational


O-H stretch

N-H stretch

=C-H stretch

ndashC-H stretch

C=H stretch

C=O stretch

C=O stretch

C-O stretch

C=C stretch

C=C stretch

C=C stretch

N-H bend

C-H bend

C-O stretch

N-H bend

P-O stretch



P-O



PO4

-3 sym

StretchC-C



hydroxapatite

Ether PO2




stretch




Phenylalanine

Nucleotides

CO3



PO4



Hydroxyl

Amide I

Unsaturated

Saturated

C=H stretch

Ester

Carboxylic acid

Amide I

Nonconjugated

Trans

Cis

Amide II

Aliphatic-CH2

Carboxylates

Amide III

PO2

- sym

H2O

Fingerprint Region

Proteins

Lipids

Lipids

Lipids fatty acids

Lipids amino acids

Lipids amino acids

Proteins

Lipids

Lipids

Lipids

Proteins


Amino acids lipids

Proteins



12000

Cholesterol

Triolene

Actin


Glycogen

Lycopene

10000

8000

6000

4000

2000

600 800 1000 1200 1400 1600 18000

Wavenumber (cm-1)







007

Peak 1

Peak 2

Peak 3

Peak 4

Peak 5

Peak 6

Peak 7

Peak 8

Peak 9

Peak 10

Negative nodes

374

1087

1153

1270

1530

1680

1751

1305 1457

1444

Positive nodes

006

005

004

003

002

001

0800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800

No

rmalized

Ram

an

in

ten

sity

Raman shift (cm-1)
















Step 4 Readout

Symmetric

nitro

stretch

1336 cm-1

Wavenumber (cm-1)

Peak h

eig

ht

(cts

s)

= Antigen

O2 N

O

OO

OOO

OO O O O O

OO

30000

20000

10000

0500 700 900 1100 1300 1500 1700

S

S SS S

SSS

SS S S

N NN

N

NN

N

N NN

N N

ERL

Gold film on glass





= DSNB = Antibody

60 mm

Gold colloid

Gold film on glass

O2 N NO2

O

O

O

O

O

O O

O

O

O O

O

OOOO

SS S

S

N

NN

N

S SS S

SS

N

N N NN

N

DSP

DSNB DSNB

=Antibody

O

OO

OO

OO

OO O

OO

OO

O
















5 μm

alpha300 AR+


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Introducing the








The Art of RAMAN







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Raman Imaging of Silicon Structures - Advanstar Communications

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