Thefeasibilityoflaser-based,detectionofcarbon-14atAcceleratorMassSpectrometer(AMS)sensitivities hasbeendemonstrated,buttheseinstrumentsrequirelargesamplessizesandlackcompatibilitywithsystems common to biological labs?such as liquid chromatography-mass spectrometry (LC-MS). With their ability to quickly detect and quantify ever smaller amounts of material, LC-MS systems are valued for their capacity to isolateindividualbiomolecules.Asaresult,LC-MScouplingisnowstipulatedforthesuccessandadoption of new biological instrumentation. Consequently, we propose to develop a laser-based, carbon-14 spectrometer forbiologyusingsaturated-absorptioncavityring-downspectroscopy(SCARS).Thisinstrumentwillhavesimilar sensitivitytoAMS(~10-1514C/Climit-of-detection),theabilitytohandlenanogramtomicrogramsizedsamples, and the capability to measure analytes separated by LC systems. This level of carbon-14 sensitivity and the techniques it affords are currently restricted to room-sized AMS instruments that cost millions of dollars and require several dedicated Ph.D. level scientists for operation. The SCAR instrument would be much smaller (table-topsized),cheaper,andeasiertooperate.Theaccessibilitycoupledwiththeextremesensitivityofthis technologywillenablehigh-throughput,small-sample-sizeexperimentsandbringcarbon-14measurementsinto the modern biological laboratory. This instrument will enhance LC/MS systems?providing a means to quantitatively analyze complex biochemical systems in any research lab. This will have an impact on biology frombasicscienceexperimentstomoreappliedhumansubjectstudiesindrugdevelopment.
Usingtheradioisotopecarbon-14tolabelorganicmoleculesinbiologicalsystemsallowsscientiststotracesmall doses of nutrients, toxins, and therapeutics in humans and animals, but detecting these small carbon-14 quantities for these experiments has traditionally required complex, expensive, room-sized instruments. If funded,thisprojectwilldevelopatable-topsizedinstrumentthatwouldmakethesetechniquesavailabletoany biomedical lab in the world, and the instrument could be coupled to modern analytical tools such as liquid chromatography and mass spectrometry. This will enable new regimes of experimentation;? offering a more precisetoolfortrackingtargetspeciesthroughcomplexbiochemicalsystems,allowingforbetteranimalstudies, andprovidingapathtotransitionfromcostlyandoftenunrepresentativeanimalmodelstophase-0micro-dosing humantrialsforthedevelopmentofnewpharmaceuticals.
