National Resource for Biomedical Accelerator Mass Spectrometry

National Resource for Biomedical Accelerator Mass Spectrometry

Research Emphasis

The National Resource for Biomedical Accelerator Mass Spectrometry was established to make accelerator mass spectrometry (AMS) available to biomedical investigators who have a need for accurately measuring very low levels of carbon-14 in their research. The resource has three major functions: to develop and refine methods and instrumentation for the use of AMS in biomedical research; to provide biological researchers with access to AMS through either collaborative or service arrangements; and to demonstrate new applications for AMS and provide outreach activities for educating researchers and students on the use of biological AMS.

Current Research

Building on the initial development of sample preparation methodology, the current focus of the resource is on expanding capabilities by developing methods to: 1) study biochemical pathways and cellular processes at the level of the single cell; 2) quantify endogenous processes in higher organisms; and 3) develop a routine sample preparation methodology for tritium AMS.

To these ends, collaborative studies have been established to: 1) quantify metabolites in single yeast cells; 2) quantitative biomarkers of DNA and protein oxidation; and 3) facilitate the measurement of tritium or dual-isotope labeled biological samples through sample-spectrometer interface development.

The ongoing effort continues the investigation of methods to study protein biochemistry and cell biology and develop isotope derivatization approaches. The resource aims to analyze ¹⁴C and/or ³H in tissues, macromolecules, and metabolite extracts. Applications under investigation include studies to determine the effects of toxicants in humans; to identify protein targets for drugs, nutrients, and toxicants; and to determine the pharmacokinetics of micronutrients.

Resource Capabilities

Methods

Lawrence Livermore National Laboratory is a national laboratory organized to facilitate multidisciplinary sharing of facilities. The AMS resource supports biomedical laboratories and a wide range of equipment for the characterization and analysis of biological samples. It supports sample preparation laboratories for the conversion of biological samples containing ¹⁴C and ³H to forms capable of being analyzed efficiently by AMS.

Instruments

A 1-MV spectrometer dedicated to biochemical quantitation forms the core instrumentation, with access to a 10-MV spectrometer possible on a time-available basis. The spectrometers consist of a cesium sputter source, a low-energy injection beam line, a high-energy mass spectrometer, and an ionization detector for energy measurements. Approximately 100 samples containing 1 attomole to 1 picomole of ¹⁴C are measured per 8 hours on either spectrometer.

Special Features

The resource's Web site provides background information on AMS and instructions for gaining access. A listing of the publications resulting from the resource and its collaborators is included on the Web site, illustrating the contribution of AMS to a broad range of research. The resource is available to consult with investigators on the feasibility of using AMS in specific research projects and proposals and to provide guidance on experimental design, sample preparation, and data interpretation.

Publications

1. Tompkins, E. M., Farmer, P. B., Lamb, J. H., Jukes, R., Dingle, K., Ubick, E., Turteltaub, K.W., et al., A novel ¹⁴C-postlabeling assay using accelerator mass spectrometry for the detection of O(6)-methyldeoxy-guanosine adducts. Rapid Communications in Mass Spectrometry 20:883–891, 2006.

2. Spalding, K. L., Bhardwaj, R. D., Buchholz, B. A., Druid, H., and Frisen, J., Retrospective birth dating of cells in humans. Cell 122:133–143, 2005.

3. Brown, K., Dingley, K. H., and Turteltaub, K.W., Accelerator mass spectrometry for biomedical research. In: AL Burlingame, Ed. Methods in Enzymology 402:423–443, 2005 (Review).

4. Lin, Y., Ducker, S. R., Follett, J. R., et al., Quantitation of in vivo folate metabolism. American Journal of Clinical Nutrition 80:680–691, 2004.