A small accelerator mass spectrometer with a gas chromatographic inlet/interface.

NSI/MITNewton Scientific, Inc./Massachusetts Institute of Technology

A small accelerator mass spectrometerwith a gas chromatographic inlet/interface.

Paul Skipper, John Mehl, Pete Wishnok, Steve TannenbaumMIT Division of Bioengineering and Environmental Health

Barbara Hughey, Bob Klinkowstein, Ruth SheferNewton Scientific, Inc.


Comparing AMS to scintillation counting

10 μg carbon

6 X 105 atoms 14C

ß-

AMS scintillation counter

1 attomole 14C

1000 countsin

2 minutes

1000 countsin

14 years

(t = 5730 years)

AMS counts the numberof atoms in tbe sample, while scintillationcounters measure theinfrequent radioactivedecay events in the sample.


Applications of accelerator mass spectrometry

Drug developmentToxicology (low-level, I.e., ambient dose-response)

Human metabolism and distributionTrace analysis by post-labeling

Geochemistry - radiocarbon dating

AMS can be used for any experiment that is currently done by scintillation counting, but is faster and requires much less radioactivity.

• Experiments can be done on humans• Minimum precautions needed during synthesis of reagents• No regulations involved in disposal


Why is accelerator mass spectrometry not widely used?

1. Current instruments are generally large and expensive, and often require dedicated facilites and an operational staff.

2. Sample preparation is time-consuming and skill-intensive.


Schematic of a GC-AMS system

gas-fedion-sourceoxidizergas

chromatograph

AMSaccelerator system

withlow- and high-

energy analyzers

detector

14C2+C-

and other negative ions

CO2

complexorganic

molecules

sample separation and injection interface AMS accelerator and detection system

• GC:• Oxidizer:

• AMS system:

sends pure compounds into the oxidizing interface.converts these compounds into a chemical form amenable to gas-fed ion-source.measures the amount of carbon-14 in the sample.


Q. Why can such low levels of 14C be quantitated?

A. Because the natural abundance is also low.

With a low backround, anything much above background can be measured; there is very little interference. This is especially useful in experiments with samples that have been enriched with carbon-14 since very little enrichment is needed in order to have detectable signal.


Q. But why does it take a complex, expensive system toquantitate the 14C?

A. Because - even though there is very little 14C relative to 12C, there is a very high abundance of other substances with very similar atomic or molecular weights:

12CH2 13CH N

A combination of negative-ion formation followed by high-energy collisions with gas or thin foils eliminates interference from these substances.


Schematic of the NSI/MIT GC-AMS

Cesium SputterNegative Ion Source

Low EnergyAnalyzing Magnet

Low Energy Accelerating TubeCarbon Stripping Foil Carousel

High Energy Accelerating Tube

High EnergyAnalyzing Magnet

Detector

Electrostatic analyzer

OxidizerGC

People standing around


Oxidation and ionization

sample CO2

16O-

oxidizerCs sputter

source 12C-

13C-

14C- 13CH- 12CH2- N-

CuO750oC

As each compound elutes from the GC,it’s converted to CO2 by an on-line oxidizer.

The CO2 (and ambient nitrogen)is converted to negative ions by bombardment with high-energy Cs ions.

N- is unstable, and decomposes.


Oxidation and ionization

sample CO2

16O-

oxidizerCs sputter

source 12C-

13C-

14C- 13CH- 12CH2-

CuO750oC

As each compound elutes from the GC,it’s converted to CO2 by an on-line oxidizer.

The CO2 (and ambient nitrogen)is converted to negative ions by bombardment with high-energy Cs ions.

N- is unstable, and decomposes.


Isolation of the 14 Da isobars

16O-

12C-

13C-

14C- 13CH- 12CH2-

magnet 114C- 13CH- 12CH2

-

16O-

12C-

13C-

The negative ions of higher and lower weight are easilyremoved with a low-energy magnetic sector, sending onlythe 14-dalton substances into the accelerator.


Conversion to atomic ions

accelerator/stripper14C- 13CH- 12CH2

- 14Cn+ 13Cn+ 12 Cn+

The isobars are then accelerated to(a maximum of) 1 MEV and collidedwith a thin foil.

• Polyatomic structures are destroyed.• Some electrons are stripped, leaving positive ions.


Detection of 14C

electrostatic sector14Cn+ 13Cn+ 12 Cn+

These ions - now with different m/z values - are brought down to ground potential and sent through an electrostatic analyzer and a high-energy magnetic sector to send (finally) only carbon-14 into the detector.

magnetic sector14Cn+


Our original test mixture.

OCO

C

CO

OOC2H5

OC2H5

SCH3 O ClNHCOCH3

1methyl phenyl sulfide

C7H8S

2acetanilide

C8H9NO

7phenanthrene

C14H10

44-chlorodiphenyl ether

C12H9ClO

69-fluorenone

C13H8O

5benzophenone

C13H10O

3diethylphthalate

C12H14O4

These were chosen because they were handy, because they were aromatic and thus potentially difficult to oxidize, and because they contained a variety of heteroatoms.


Online oxidation of organics to CO2

Retention time4.00 5.00 6.00 7.00 8.00

12

34

5 67

m/z = 44

In this experiment, the previous mixture was separated by capillary GC and then sent through the CuO oxidizer into a small mass spectrometer that was set todetect only m/z 44. The number of carbons in the mixture was the same for eachcomponent. The oxidizer cleanly and efficiently converted each component to CO2.


Conversion of CO2 to C-

Time (min)0 1 2 3 4 5 6

200

250

300

350

CH4CO2 CO2 CO2 CO2 CO2CH4 CH4 CH4

CH4

12C

- cur

rent

(μA

)

each injection = 100 pmoles

In this experiment, alternate injections of CO2 and methane were flow-injectedthrough the oxidizer and into the Cs sputter ion source. The methane wasquantitatively converted into CO2, giving essentially identical C- signals for each substance.


New test mixture, old GC column.

Retention time

3.00 4.00 5.00 6.00

2

3 4

5 67

m/z = 44

A new version of the test mixture was prepared without methylphenyl sulfide.(It decomposed, and it smelled bad.) This experiment is identical with the earlier oneusing the small mass spectrometer as a CO2 detector. The oxidizer is working well, but the chromatography has deteriorated - peaks 3 and 4 are no longer resolved.


Online conversion of CO2 from organic molecules into C-

Time (min)5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0

70

75

80

85

90

95

100

105

110

2

3+4

56

7

12C- current (nA)

The previous test mixture was separated by capillary GC, sent through the CuOoxidizer and through the Cs sputter ion-source. The negative ion current fromcarbon-12 was detected by a Faraday cup after the low-energy magnet. The chromatographic peak shapes are acceptable.


Detection of a 14CO2 pulse.

Cou

nts

in 14

C w

indo

w

Time (sec)0 10 20 30 40 50

0

200

400

600

800

1000

1200

1400

0.2

0.3

0.4

0.5

0.6

Carbon-14 windowMass-13 Faraday cup

Mas

s-13

neg

ativ

e io

n cu

rren

t (μA

)

Enriched CO2 was flow injected into the Cs sputter ion source, carbon-13 was detectedby a Faraday cup after the low-energy magnet and carbon-14 was detected as positiveions at the end of the entire AMS system with essentially no memory effect.


Summary

We’ve shown so far that:

• The oxidizing interface works;• The chromagraphy is pretty good;• The ion-source works;• The accelerator/stripper works;• The device transmits 14C.

I.e., that all the parts are in place.

What we’ll do next:

• Optimize 14C ion transmission;• Characterize the complete GC-AMS system;• Finish development of LC-AMS interface;• Run some real samples.


Thanks

Tom Doucette, Dennis Clarke, and Andrew Dart are NSI engineers who’vehelped with design and construction.

Naomi Fried and Kaisheng Jiao were postdoctoral fellows who helped with the earlyexploratory experiments.

Financial support has been primarily through small business grants from The National Institutes of Health and the National Science Foundation



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A small accelerator mass spectrometer with a gas chromatographic inlet/interface.

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