The team has developed a new method for ultrasensitive radiocarbon detection. The laser-based technology allows the measurement of trace amounts, on the order of one part per one trillion, of radioactive label in organic compounds. The proposed analyzer has the potential to change the way the pharmaceutical industry conducts metabolic and toxicity studies with radio-labeled carbon for its drug discovery and development programs long before human clinical trials. A commercialized version of this analyzer technology would enable scientists to conduct ultrasensitive measurements more quickly on-site and with small samples and thus less radioactivity.
Existing Accelerator Mass Spectrometer technology effectively counts atoms as they are accelerated across a large equipment platform that takes up a large room and is expensive to maintain. It is complex and expensive; only a few such systems exist for the purposes of Biological Radiocarbon studies, and samples must be outsourced to such facilities with long turnaround times. Existing Liquid Scintillation Counter (LSC) technology must use samples 3-4 orders of magnitude larger with much higher radiation because the beta-decay counting technique lacks the sensitivity for many metabolic and toxicity studies. The proposed laser based technology effectively tickles the CO2 molecules with a laser millions of times per second in an electrical discharge and obtains an electronic response (known as the Optogalvanic Effect). The proposed technology has the potential to reduce the costs associated with new drug development by enabling pharmacokinetic studies to be initiated in humans sooner than currently possible and will thus accelerate the time to approval and market.
In 2008 we reported[1] a sensitive laser-based analytical technique that could meet the unmet need for radiocarbon quantitation at extremely low levels in a laboratory-based instrument. The basic laser technology upon which the technique is based was first demonstrated for stable carbon isotope analysis of 13C in 1994[2] and used for G-I disease breath testing[3]. Now with the National Science Foundation Innovation Corps (I-Corps) support we are working to bring the radiocarbon technology to the marketplace. We have conducted scores of interviews with potential users in the drug development and environmental monitoring communities to determine their needs and desired instrument specifications. Manufacturing and distribution channels have also been explored. The best value proposition is a device that is similar in concept to a high performance scintillation counter (LSC) system where the laser is analogous to the scintillation detector and a gas discharge tube is analogous to the scintillation cocktail. Sensitivity however will be hundreds of times greater than that of an LSC. Samples will be introduced as carbon dioxide from oxidation of biological samples or extraction from environmental samples such as air, water or soil gas. A consensus of potential customers indicated that the system should include an interface for various forms of sample introduction including multi-well plates for pipetted liquids and collected chromatography column fractions. The instrument layout anticipates ancillary sample handling options including continuous flow from oxidation of gas or liquid chromatography column fractions, simple operation and a versatile digital interface. Performance metrics are motivated by the large amount of work performed in the past decade using accelerator mass spectrometry (AMS), the only competing method available for direct radiocarbon counting. Work is in progress to build prototype instruments for testing and evaluation by early adaptors. [1] Daniel Murnick, Ozgur Dogru and Erhan Ilkmen, 14C Analysis via Intracavity Optogalvanic Spectroscopy, Analytical Chemistry 80, 4820–4824 (2008) [2] Murnick, D.E. and Peer, B. J., Laser-based analysis of Carbon Isotope Ratios, Science, 263, 945-94 (1994) [3] Van Der Hulst RW. Lamouliatte H. Megraud F. Pounder RE. Stolte M. Vaira D. Williams M. Tytgat GN, Laser assisted ratio analyzer 13C-urea breath testing, for the detection of H. pylori: A prospective diagnostic European multicentre study, Alimentary Pharmacology & Therapeutics. 13(9):1171-7, (1999)
