We propose to develop a table-top sized spectroscopic method to quantify 14C in milligram sized biological samples at levels down to the natural isotopic abundance, using a technique called Cavity Ring Down Spectroscopy. This system will be much cheaper to acquire and to operate, and could eventually replace the current state of the art technology -- accelerator mass spectrometry. This approach will lead to a new paradigm for 14C analysis in allowing studies to be carried out on the metabolism, disposition, fate and mass balance of 14C-labeled therapeutic entities for drug development, potential toxicants for risk assessment, and analysis of biomarkers for personalized medicine. Given the expected cost and simplicity of operation, this new technique will enable much greater access to high sensitivity 14C analysis than now currently available as any biomedical or biochemistry laboratory could afford to operate such an instrument.

Public Health Relevance

The development of a highly sensitive, table-top sized spectroscopic instrument to quantify 14C in biological samples will lead to a new paradigm in research to understanding, detecting, treating and preventing a wide range of diseases related to human health. Specifically, this technology would enable studies to be carried out on the metabolism, disposition, fate and mass balance of 14C-labeled therapeutic entities for drug development and on potential toxicants for risk assessment directly in humans at much lower cost than now possible. It would allow lower cost analysis of biomarkers for personalized medicine with assays requiring 14C and would allow the routine use of levels of 14C in humans that are significantly lower and safer than now common.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21GM111242-01
Application #
8743804
Study Section
Special Emphasis Panel (ZGM1-BBCB-A (ID))
Program Officer
Friedman, Fred K
Project Start
2014-09-22
Project End
2017-06-30
Budget Start
2014-09-22
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$234,368
Indirect Cost
$109,368
Name
Lawrence Livermore National Laboratory
Department
Type
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
McCartt, A Daniel; Ognibene, Ted J; Bench, Graham et al. (2016) Quantifying Carbon-14 for Biology Using Cavity Ring-Down Spectroscopy. Anal Chem 88:8714-9
McCartt, A D; Ognibene, T; Bench, G et al. (2015) Measurements of Carbon-14 With Cavity Ring-Down Spectroscopy. Nucl Instrum Methods Phys Res B 361:277-280
McCartt, A D; Ognibene, T J; Bench, G et al. (2014) Model-Based, Closed-Loop Control of PZT Creep for Cavity Ring-Down Spectroscopy. Meas Sci Technol 25: