Development of a commercial Automated Laser Gas Interface (ALGI) for AMS

Daniel, R.E.; Mores, M.; Kitchen, R.L.; Sundquist, M. L.; Hauser, T.; Stodola, Mark; Tannenbaum, Steven R.; Skipper, Paul L.; Liberman, Rosa G.; Young, Graeme; Corless, Steven; Tucker, Mark

doi:10.1016/j.nimb.2012.02.019

Nuclear Instruments and Methods in Physics Research Section B:

2013

DOI: 10.1016/j.nimb.2012.02.019

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Development of a commercial Automated Laser Gas Interface (ALGI) for AMS

R.E. Daniel¹,

M. Mores²,

R.L. Kitchen³

et al.

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Cited by 2 publications

(3 citation statements)

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“…Consequently, sample extraction is a prerequisite, there is a limited choice in eluents compatible with the AMS, and when a total count analysis is required, LC separation becomes superfluous. Another possibility to increase sample throughput is by using an automated laser gas interface . Samples are loaded into a 96-well plate (stainless steel wells), which contains copper oxide.…”

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confidence: 99%

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Automated Combustion Accelerator Mass Spectrometry for the Analysis of Biomedical Samples in the Low Attomole Range

Duijn¹,

Sandman²,

Grossouw³

et al. 2014

Anal. Chem.

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The increasing role of accelerator mass spectrometry (AMS) in biomedical research necessitates modernization of the traditional sample handling process. AMS was originally developed and used for carbon dating, therefore focusing on a very high precision but with a comparably low sample throughput. Here, we describe the combination of automated sample combustion with an elemental analyzer (EA) online coupled to an AMS via a dedicated interface. This setup allows direct radiocarbon measurements for over 70 samples daily by AMS. No sample processing is required apart from the pipetting of the sample into a tin foil cup, which is placed in the carousel of the EA. In our system, up to 200 AMS analyses are performed automatically without the need for manual interventions. We present results on the direct total (14)C count measurements in <2 μL human plasma samples. The method shows linearity over a range of 0.65-821 mBq/mL, with a lower limit of quantification of 0.65 mBq/mL (corresponding to 0.67 amol for acetaminophen). At these extremely low levels of activity, it becomes important to quantify plasma specific carbon percentages. This carbon percentage is automatically generated upon combustion of a sample on the EA. Apparent advantages of the present approach include complete omission of sample preparation (reduced hands-on time) and fully automated sample analysis. These improvements clearly stimulate the standard incorporation of microtracer research in the drug development process. In combination with the particularly low sample volumes required and extreme sensitivity, AMS strongly improves its position as a bioanalysis method.

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confidence: 99%

“…Another possibility to increase sample throughput is by using an automated laser gas interface. 25 Samples are loaded into a 96-well plate (stainless steel wells), which contains copper oxide. After the liquid samples are dried, CO 2 is released after laser ablation.…”

mentioning

confidence: 99%

Automated Combustion Accelerator Mass Spectrometry for the Analysis of Biomedical Samples in the Low Attomole Range

Duijn¹,

Sandman²,

Grossouw³

et al. 2014

Anal. Chem.

View full text Add to dashboard Cite

show abstract

“…LS-AMS is also capable of accepting a continuous flow of fluid directly from an HPLC instrument, which can lead to increased sensitivity, better temporal peak resolution, and substantial reduction of AMS instrument time. Other approaches to couple biochemical separation instrumentation for the analysis of nonvolatile compounds to AMS have been developed, including systems that use a chemical agent or a laser , to oxidize the sample. However, these systems are either more restrictive or not compatible with direct coupling of HPLC to AMS, either due to mobile phase limitations or an off-line solvent removal step.…”

mentioning

confidence: 99%

Directly Coupled High-Performance Liquid Chromatography–Accelerator Mass Spectrometry Measurement of Chemically Modified Protein and Peptides

et al. 2013

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Quantitation of low-abundance protein modifications involves significant analytical challenges, especially in biologically important applications, such as studying the role of post-translational modifications in biology and measurement of the effects of reactive drug metabolites. 14C labeling combined with accelerator mass spectrometry (AMS) provides exquisite sensitivity for such experiments. Here, we demonstrate real-time 14C quantitation of high-performance liquid chromatography (HPLC) separations by liquid sample accelerator mass spectrometry (LS-AMS). By enabling direct HPLC-AMS coupling, LS-AMS overcomes several major limitations of conventional HPLC-AMS, where individual HPLC fractions must be collected and converted to graphite before measurement. To demonstrate LS-AMS and compare the new technology to traditional solid sample AMS (SS-AMS), reduced and native bovine serum albumin (BSA) was modified by 14C-iodoacetamide, with and without glutathione present, producing adducts on the order of 1 modification in every 106 to 108 proteins. 14C incorporated into modified BSA was measured by solid carbon AMS and LS-AMS. BSA peptides were generated by tryptic digestion. Analysis of HPLC-separated peptides was performed in parallel by LS-AMS, fraction collection combined with SS-AMS, and (for peptide identification) electrospray ionization and tandem mass spectrometry (ESI-MS/MS). LS-AMS enabled 14C quantitation from ng sample sizes and was 100 times more sensitive to 14C incorporated in HPLC-separated peptides than SS-AMS, resulting in a lower limit of quantitation of 50 zmol 14C/peak. Additionally, LS-AMS turnaround times were minutes instead of days, and HPLC trace analyses required 1/ 6th the AMS instrument time required for analysis of graphite fractions by SS-AMS.

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Development of a commercial Automated Laser Gas Interface (ALGI) for AMS

Cited by 2 publications

References 8 publications

Automated Combustion Accelerator Mass Spectrometry for the Analysis of Biomedical Samples in the Low Attomole Range

Automated Combustion Accelerator Mass Spectrometry for the Analysis of Biomedical Samples in the Low Attomole Range

Directly Coupled High-Performance Liquid Chromatography–Accelerator Mass Spectrometry Measurement of Chemically Modified Protein and Peptides

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