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Trends in Analytical Chemistry, Vol. 44, 2013 In the news

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Imaging shows insulin-producing cells in diabetes

Figure 1. Near-infrared optical projec-tion tomography (NIR-OPT) enables thevisualization of several cell types in largepreparations. The image of a pancreasfrom a mouse with Type-1 diabetesshows the insulin-producing islets of Lan-gerhans in blue, blood vessels in red, andinfiltrating autoimmune cells that breakdown the insulin-producing cells ingreen.

An imaging method for studyinginsulin-producing cells in diabetesfeatures in a biomedical videojournal [1].

Researchers at Umea Universityin Sweden, who developed thetechniques, recently received agrant of SEK 4.3m (US$0.7m) fromthe European Union to link togetherresearch teams in Europe in thefield of diabetes imaging.

Professor Ulf Ahlgren and hisassociates at the Umea Center forMolecular Medicine (UCMM) elabo-rated the technology for biomedicalimaging with optical projection to-mography (OPT). Initially, themethod could be used on relativelysmall preparations only, but fiveyears ago the scientists at Umeawere able to adapt the technologyto study whole organs including thepancreas from adult mice.

The present findings describefurther development of the OPTtechnology by going from ordinaryvisible light to the near-infrared(NIR) spectrum. NIR light haslonger wavelengths that can moreeasily penetrate tissue, so the ima-ging platform enables studies ofconsiderably larger samples thanpreviously possible, including therat pancreas, which is importantbecause rats as laboratory animalsare thought to be physiologicallymore similar to humans.

NIR light also makes it possible tostudy more, different cell types inone organ preparation. In the videoarticle, the scientists show the pos-sibility of simultaneously trackingthe insulin-producing islets of Lan-gerhans, the autoimmune infiltrat-ing cells and the distribution of

0165-9936/$ - see front matter doi:10.1016/j.trac.2013

blood vessels in a model system forType-1 diabetes (Fig. 1).

Internationally, huge resourcesare being committed to the devel-opment of non-invasive imagingmethods for study of the number ofinsulin cells remaining in patientsdeveloping diabetes. However, amajor problem is to find suitablecontrast agents that specificallybind to the insulin-producing cellsof the pancreas to allow imaging. Inthis context, NIR-OPT technologycan play an important role, as itenables the evaluation of new con-trast agents. It may also be used as

.01.003

a tool to calibrate the non-invasiveread out (e.g., by magnetic re-sonance imaging).

The study is presented in theJournal of Visualized Experiments, thefirst scientific journal to offer thevideo format for publication in thelife sciences. Visualization in videopresentations clearly facilitates theunderstanding and the descriptionof complex experimental technolo-gies. It can help address two majorchallenges facing bioscience re-search:

• the low transparency and poorreproducibility of biologicalexperiments; and,

• the large amounts of time andwork needed to learn newexperimental technologies.

Contact:Professor Ulf AhlgrenUmea Center for MolecularMedicineUmea University, SwedenTel.: +46 (0)90-785 44 34E-mail: [email protected]

Reference[1] A.U. Eriksson, et al., J. Vis. Exp. 71

(2013) e50238 (DOI: 10.3791/50238).

Multi-photon micro-scopy maps lipids

A non-invasive method can observein situ how assemblies of lipids areoriented in biological tissues [1].

Developed by physicists from theCNRS Laboratory for Optics andBiosciences (LOB), France, it doesnot require any labeling or

iii

http://dx.doi.org/10.1016/j.trac.2013.01.003

In the news Trends in Analytical Chemistry, Vol. 44, 2013

TrAC’s Top 10 cited articlespublished since 2008*

1. Ambient desorption ionization

mass spectrometry

by A. Venter, M. Nefliu and R. Graham

Cooks

Trends Anal. Chem. 27 (2008) 284.

2. Aptamer-based biosensors

by S. Song, L. Wang, J. Li, C. Fan and J.

Zhao


3. Green Analytical Chemistry

by S. Armenta, S. Garrigues and M. de la

Guardia


4. Liquid-phase microextraction

by A, Sarafraz-Yazdi and A. Amiri


5. Biomolecule-nanoparticle hybrids

for electrochemical biosensors

by S. Guo and S. Dong


6. Carbon nanostructures as sorbent

materials in analytical processes

by M. Valcarcel, M. Cardenas, B.M.

Simonet, Y. Moliner-Martı and R. Luce-

na


7. Functionalized carbon nanotubes

and nanofibers for biosensing ap-

plications

by J. Wang and Y. Lin


8. Fate and toxicity of emerging

pollutants, their metabolites and

transformation products in the

aquatic environment

by M.I. Farre, S. Perez, L. Kantiani and

D. Barcelo


9. Quantitative metabolomics using

NMR

preparation. It should enable thedetection and the characterizationof certain pathologies associatedwith molecular disorders in the skinor in the nervous tissue.

Multi-lamellar assemblies of li-pids (fats) play a key role in certainphysiological functions, not justwithin the skin (which serves as aprotective barrier againstexternal aggressions) but also in theway neurons function. The dis-organization of these assemblies isoften linked to serious pathologies.

The techniques normally used todetermine the arrangement of mo-lecules (e.g., X-ray scattering ornuclear magnetic resonance) areunsuitable for studying intact bio-logical tissues with good cellularresolution. Also, they often requirelabeling and/or significant samplepreparation.

First developed in the 1990s,multi-photon microscopy (MPM)allows intact biological tissue to beobserved in three dimensions withsub-cellular resolution at depthsexceeding several hundred lm. TheLOB researchers identified a newindicator, known as P-THG (polar-ized third-harmonic generation),which is sensitive to molecular or-der in multi-layer lipid assemblies.Thanks to this source of opticalcontrast, it is now possible to mapthe general orientation and degree

Figure 2. Polarized third-harmonic generation (Porientation in an amalgamation of multi-lamellarobtained without labeling, shows that the molecterfaces (ª Ecole Polytechnique, CNRS, INSERM

iv http://www.elsevier.com/locate/trac

of alignment of lipid assemblies inthree dimensions and also to ob-serve their possible disorganization.This novel MPM technique providesa non-invasive tool for probingmolecular alignment in situ in bio-logical media.

This approach enables scientiststo map, with unparalleled sensitiv-ity and contrast, the organization oflipids in human-skin biopsies with-out prior preparation or labeling(Fig. 2). This work lays the foun-dations for future developments inMPM as a method for measuringmolecular order in intact biologicalmedia and opens the way to po-tential novel applications for de-tecting and studying the earlystages of pathologies linked to mo-lecular disorders.

Contact:Emmanuel BeaurepaireLaboratory for Optics and Bios-ciencesEcole Polytechnique, CNRSPalaiseau, FranceTel.: +33 (0)1 69 33 50 211E-mail: [email protected]

Reference[1] M. Zimmerley, P. Mahou, D. Debarre,

M.-C. Schanne-Klein, E. Beaurepaire,

Phys. Rev. X 3 (2013) 011002.

-THG) microscopy mapping of molecularlipid vesicles. This virtual optical section,

ules are oriented perpendicularly at the in-/American Physical Society).

by D.S. Wishart


10. Bioactive paper provides a low-

cost platform for diagnostics

by R. Pelton


*Extracted from SciVerse Scopus, 21

January 2013

How gold binds tosurfaces

The strong binding of gold on elec-tronically-modified calcium oxidecan now be understood in detail [1].

In a computational study, re-searchers Karoliina Honkala andcolleagues at the University ofJyvaskyla Nanoscience Center,


Finland, showed how redoxchemistry entirely determines theadsorption strength of gold on themodified oxide where one metalatom is replaced with molybdenum(Fig. 3).

The research team applied theso-called Born-Haber cycle to ana-lyze how different terms contributeto adsorption energy. The calcula-tions were done at supercomputersby employing quantum mechanicalsimulation methods.

In the oxide lattice, themolybdenum atom donates twoelectrons into the oxide. When agold atom adsorbs on the oxidesurface, a redox reaction takes place.In this process, a third electrontransferred by the dopant is gainedby gold, and energy is released. Byvarying the dopant among severaltransition-metal atoms, the re-searchers found that the amount ofenergy released linearly correlatedwith the ability of the dopant to give

Figure 3. Visualization of the atomic structurecharge (-I) gold atom is adsorbed on molybdenudopant has an oxidation state of +III. The adsorpand Coulombic contributions. Gold – yellow; moxygen – red.

an electron. The trend can be used toestimate how much a guest atomstabilizes gold adsorption withoutcalculating the adsorption energy.

The research results areimportant for understandingcatalyst-support interactions. Theresults fully support the experi-mental observation where goldnanoparticles have been seen toform flat structures over modifiedcalcium-oxide surfaces. A Born-Haber cycle similar to that appliedin this study can also be employedto analyze oxide-catalyzed chemi-cal reactions that follow the redoxmechanism.

Catalysts are commonly used byindustry (e.g., in the production offuels, plastics, fertilizers and othersimilar products). Metal-oxide sur-faces are widely used as supportmaterials for metal-catalyst parti-cles. The binding properties andthe shape of metal nanoparticlessensitively depend on the interac-

of the studied system where a negatively-m-doped calcium oxide. The molybdenumtion energy comprises ionocovalent, redoxolybdenum – green; calcium – blue; and,

tion between the support and thecatalyst. By tuning this interac-tion, it is possible to affect thenumber and the properties of cat-alytically-active sites, or even cre-ate new sites. One way to modifythe interaction is to dope the oxidewith guest metal atoms that candonate extra electrons into a ma-terial.

Contact:Karoliina HonkalaNanoscience Center, Department ofChemistryUniversity of Jyvaskyla, FinlandTel.: +358 40 805 3686E-mail: [email protected]

Reference[1] J. Andersen, J. Nevalaita, K. Honkala,

H. Hakkinen, Angew. Chem., Int. Ed.

Engl. (2012) (DOI: 10.1002/anie.

201208443).

Blood test targets foodallergies

Rapid diagnosis of food allergiesusing blood samples is the aim ofresearchers at the Institute of Ma-terials Science of the University ofValencia, Spain, in consortium withEuropean companies and institu-tions.

They are developing a systembased on photonic biosensorsin a project funded by the EuropeanUnion (EU). They aim to make alow-cost instrument that in 15 minwith a single drop of blood willperform effective allergy tests forhundreds of foods simultaneouslyand without risk to patients.

‘‘Currently, the most commonallergy tests are expensive tests andespecially traumatic for children, aswell as posing a risk of adverse re-actions,’’ said POSITIVE project co-ordinator Daniel Hill. ‘‘Beyond theproject, the idea is to be able to puta food allergy diagnostic instrumentthat is fast, effective and safe in the

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surgery of every pediatrician, sothat they can test during the firstfew years of life.’’

POSITIVE is a multidisciplinaryproject focused on the developmentof a system of biosensors for therecognition of biomolecules symp-tomatic of allergic reactions to foodfrom patients.

The system was due to be fin-ished by last month (February) andinclude certain elements (e.g., afluidically-compatible porous mem-brane with biosensor functions, thefirst polymeric material developedespecially for microfluidic devices, amodule for filtering blood improveson previous systems, a more stablemeasuring instrument, and a dis-posable cartridge for the detectionof biomolecules responsible for al-lergic reactions.

The instrument is due to be readyto begin clinical trials with patientsfrom June, and testing will takeplace at the Medical UniversityHospital, Berlin, Germany.

‘‘According to our calculations,from the bioassays using non-hu-man molecule samples, the finalprototype will be able to detect up to10 different food-allergy measure-ments,’’ said Hill. ‘‘The objective,once the project has ended, is tobuild a commercial instrumentcapable of detecting all food aller-gies at the same time, quickly,safely and at a very low cost.’’

Contact:Daniel HillUniversity of Valencia, SpainE-mail: [email protected]

Luminescent bacteriapinpoint pollutants

Natural sensory systems, such asbacteria engineered to detect pollu-tion and placed in a self-containedportable box, could be the most ef-fective way to track pollutants, ac-cording to the team involved in theBIOMONAR project, funded by theEuropean Union (EU).

vi http://www.elsevier.com/locate/trac

The project team relied on bac-teria coupled to a molecular re-porter system that is easily visible.As a result, bacteria light upthrough bioluminescence once thetarget chemicals are sensed.

‘‘Much of what we do is design-ing and testing genetic circuits,small pieces of DNA which containthe necessary information for thecell to produce the reporter signal inresponse to the environmental tar-get compound,’’ Professor Jan vander Meer, project microbiologist atthe University of Lausanne, Swit-zerland, told youris.com.

He has developed a biosensor todetect arsenic as a contaminant indrinking water by genetically en-gineering Escherichia coli bacteria.

This approach has limitations.Biosensors developed by the BIO-MONAR project scientists do not re-veal what is in the water; just that itis toxic to the bacteria. However, themethod compares favorably withchemical-pollution sensors.

There are further challenges thatmust be overcome before suchbacterial alarms are widely de-ployed.

‘‘You can use genetically modifiedmicroorganisms for your own use inthe laboratory and in some cases in aclosed and defined area, but not in theenvironment,’’ said Gerald Thouand,a scientist at the University of Nantes,France, not connected to the BIOMO-NAR project. He is working on bac-terial sensors for detecting heavymetal pollutants at wastewatertreatment plants.

Releasing live species into theenvironment is very different from acontainment process in a labora-tory, according to Professor BrianWynne, Lancaster University, UK.

‘‘I think people will rightly askquestions about whether we cantrust the containment process,’’ hetold youris.com.

However, he noted that micro-organisms may well prove easier tocontain than genetically-modifiedcrop plants.

The next big problem that scien-tists must address, according toThouand, is mixed pollutants.

‘‘A pollutant can be more toxicor less toxic when in contact withother chemicals,’’ he said. ‘‘For theenvironment, we need to addressthis problem in the decades to comeand only live cells will answer theproblem.’’

Contact:Professor Jan van der MeerUniversity of LausanneSwitzerlandTel.: +41 21-692 56 30E-mail: [email protected]

DNA chip diagnosesADHD

A DNA chip could improve not onlythe diagnosis of Attention DeficitHyperactivity Disorder (ADHD), themost common childhood neu-ropsychiatric disorder, but also thetherapeutics for it, according toAlaitz Molano in her PhD thesis inPharmacology from the UPV/EHU-University of the Basque Country,Spain [1].

The prevalence of ADHD is 8–12% among the infant-adolescentpopulation worldwide, of whomhalf continue with the symptomsinto adult life. Children with ADHDhave difficulty paying attention, donot complete the tasks they havebeen assigned and are frequentlydistracted. They may also displayimpulsive behavior and excessive,inappropriate activity in the contextthey find themselves in, and ex-perience great difficulty restrainingtheir impulses.

‘‘All these symptoms seriouslyaffect the social, academic andworking life of the individuals, andimpact greatly upon their familiesand milieu close to them,’’ saidMolano.

In her PhD thesis, she set out todevelop and clinically to validate agenotyping tool that could help to

Figure 4. Alaitz Molano: ‘‘On the basisof genetics, the children that belong toone sub-type or another are different. ’’


confirm the diagnosis, to predicthow it will evolve, and to select themost suitable pharmacologicaltreatment in each case.

Molano studied how geneticpolymorphisms (that is, variationsin the DNA sequence betweendifferent individuals) are associatedwith ADHD.

‘‘We looked for all the associa-tions that had been describedpreviously in the literature world-wide, and did a clinical study to seewhether these polymorphisms alsooccurred in the Spanish population(because) genetic associations varya lot between some populations andothers.’’

Molano analyzed about 400 sal-iva samples of patients with ADHDand a further 400 samples fromhealthy controls without a historyof psychiatric diseases. The use ofover 250 polymorphisms led to thediscovery of 32 polymorphisms as-sociated with not only the diagnosisof ADHD but also the evolution ofthe disorder, the ADHD sub-type,the severity of symptoms and thepresence of comorbidities.

On the basis of these results, Mo-lano is proposing a DNA chip withthese 32 polymorphisms, whichcould be updated with new poly-morphisms, as a tool for not onlydiagnosing but also calculating ge-netic susceptibility to different vari-ables (e.g., responding well to drugs,and normalization of symptoms).

The study also confirmed theexistence of the 3 ADHD sub-types:lack of attention, hyperactivity, anda combination.

‘‘It can be seen that, on the basisof genetics, the children that belongto one sub-type or another aredifferent,’’ said Molano (Fig. 4).

However, no direct associationwas found between the polymorph-isms analyzed and the response topharmacological treatment (ato-moxetine and methylphenidate) –possibly a data-collection issue.Molano will pursue her researchalong this line.

‘‘We want to concentrate on thedrug-response aspect, obtain more,better characterized samples, andmonitor the variables in takingdrugs very closely, whether theywere actually being taken or not,and so on,’’ she said.

Reference[1] A. Molano, Development of a genotyping

system to be applied in Attention Deficit

Hyperactivity Disorder and its pharma-

cogenetics (Desarrollo de un sistema de

genotipado para la aplicacion en el

‘trastorno por deficit de atencion con

hiperactividad’ y su farmacogenetica),

PhD Thesis, University of the Basque

Country, Spain, 2012.

Fluorescence findshidden cells

Funding to improve leukemiatreatment will investigate howcancer cells hide to avoid che-motherapy drugs using high-pow-ered microscopes in the Facility forImaging by Light Microscopy(FILM), Imperial College London,UK, to observe cancer cells usingfluorescent light.

Scientists hope to improve leu-kemia treatment by investigatinghow cancer cells use ‘‘hidingplaces’’ in the body to avoidchemotherapy drugs.

Each year 300 British childrenare diagnosed with acute lympho-blastic leukemia, a cancer of theblood (Fig. 5). Most respond well tocurrent therapies, but the diseasereturns in a quarter of patients. Thelong-term outlook for adults ismuch worse, with initial treatmentsbeing effective in fewer than half ofall patients.

Now, the researchers are begin-ning a three-year project to explorehow some cancer cells evade treat-ment, thanks to funding fromblood-cancer charity Leukaemia &Lymphoma Research.

‘‘We believe that some evasivecancer cells hide in protective

compartments inside the bodywhile patients receive treatment,’’said lead researcher, Cristina LoCelso, Lecturer in Immunology inthe Department of Life Sciences. ‘‘Ifwe understand where the cancercells hide, we will be able to developbetter ways to treat patients byeliminating all cancer cells andavoiding disease relapse.’’

Blood cells are produced in thebone marrow, where they grow andtake on a variety of forms withincompartments called niches insidebones. Lo Celso’s team believe that,in the bones of leukemia patients,some of these compartments havebeen ‘‘hijacked’’ by leukemia cells,and serve as effective hiding placesduring treatment.

‘‘Once we can see how this hap-pens, drugs can be developed thattarget the hiding places. This willhave a dramatic impact on the de-sign of new drugs for blood cancerslike acute lymphoblastic leukemia,’’she said.

Lo Celso and colleague EdwinHawkins will use their technique totrack the movement of the evasiveleukemia cells in laboratory miceand hope to learn where these cellsgo during cancer treatment.

‘‘Leukaemia occurs when themachinery that controls how bloodcells grow and die breaks down,’’said Professor Chris Bunce, Re-

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Figure 5. Acute lymphoblastic leukemia, microscope slide.


search Director at Leukaemia &Lymphoma Research. ‘‘We nowknow that both normal blood cellsand leukemia cells are produced bya small number of stem cells thatlive inside compartments in ourbone marrow. Understanding howthese leukemia cells hide frompowerful anti-cancer drugs is vitalto creating treatments for patientsthat will work faster and preventthe disease from returning.’’

Contact:Professor Tony MageeFacility for Imaging by Light Mi-croscopy (FILM)Imperial College London, UKTel.: +44 (0)20 7594 3135E-mail: [email protected]

Chemical imaging isfocus at Pittcon 2013

‘‘Chemical Imaging Spectroscopy’’is the topic of the 2013 James L.Waters Annual Symposium on 18March at Pittcon 2013, being heldat the Pennsylvania ConventionCenter, Philadelphia, PA, USA, 17–21 March.

It will focus on the commerciali-zation of chemical imaging, whichhas enabled advancements in thefields of pharmaceutical analysis,polymer characterization and iden-

viii http://www.elsevier.com/locate/trac

tification of defects in semi-conductor materials. It continues tobe a key tool in these and in manyother medical and homeland-se-curity applications.

The speakers chosen for thesymposium are pioneers in this fieldand are well qualified to discuss thedevelopment of chemical imagingand its commercialization. The ses-sion will also focus on the currentstate of the technique and what thefuture holds for chemical imaging.Speakers include:

• E. Neil Lewis, ChemicalImaging: Those Are Pretty Pic-tures but Who Gives a Darn!

• Patrick J. Treado, Birth toYoung Adulthood of MolecularChemical Image

• Richard Crocombe, TheDevelopment of InfraredSpectroscopic Imaging andFocal-plane Array Detectors:Are FPAs Enabling Technol-ogy, Achilles’ Heel, or Both?

• Joachin Koenen, ConfocalRaman Microscopy: From Sin-gle Spectra Acquisition toRoutine 3D Raman Imaging

Contact:Website: www.pittcon.org

Food Labs Conference co-locatesPittcon and Innovative PublishingCompany, publisher of Food Safety

Tech, an eJournal and producer ofFood Labs Conference, have formed astrategic partnership that includesthe co-location of Food Labs Con-ference in conjunction with Pittcon2013.

The agreement provides that theregistration fee to attend the two-day Food Lab Conference, 19 and 20March, will also include unlimitedweek-long admission to the Pittcon2013 exposition floor and technicalprogram.

The Food Labs Conference will takea more holistic approach to bestpractices in managing food testingand analyses needs as opposed tofocusing on only one discipline(e.g., microbiology or chemistry).An advisory committee comprisingindustry, academia, technologysuppliers and consultants is devel-oping the conference curriculum.Food Labs Conference attendees willbe able to take away practical,hands-on information that will helpthem to improve laboratory pro-ductivity and efficiency.

‘‘The food industry is one ofPittcon’s top industries for growth,’’according to Ron Bargiel, Presidentof Pittcon Conference & Expo 2013.‘‘We are excited about this newlyformed partnership with Food SafetyTech and look forward to workingjointly to increase Pittcon’s pre-sence in the food industry.’’

‘‘Co-locating with Pittcon makesperfect sense for everyone,’’ saidRick Biros, President of InnovativePublishing and Publisher of FoodSafety Tech. ‘‘This partnershipmakes it possible for food-industrylab managers to benefit sig-nificantly from the first Food LabsConference focused on their needsalong with having access to thou-sands of laboratory-technologysuppliers at Pittcon 2013 – all underone roof.’’

Contact:Website: www.FoodLabsConference.com

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