The classic means of determining stable isotope composition of the organic elements C, H, N, O, and S at high precision is by specialized gas isotope ratio mass spectrometers (IRMS) optimized for the task. The instruments differ from conventional mass spectrometers in that they accept only CO2, H2, N2, or SO3/SF6, ionize these gases in highly sensitive electron impact sources, and continuously monitor the relevant ion beams with multiple dedicated detectors.
The commercial introduction of the continuous flow technique in the 1990s brought a revolution in instrumentation that had gone unchanged for decades. Minimum sample size has been reduced by three orders of magnitude, high precision isotope ratios are now routinely determined for individual compounds in complex mixtures, realms of applications appear yearly.
Our research focuses on the development of instrumentation for high-precision IRMS and its application to biomedical and biological problems. In 1992, we introduced the first interface from a liquid source to IRMS and showed its applicability to several classes of molecules; the first continuous reduction system for rapid analysis of water; the first system for high precision determination of D/H ratios in organic compounds; and most recently the first system capable of high-precision intramolecular determination of C-isotope ratios.
Figure one shows the compound-specific D/H instrument. A gas chromatograph (GC) separates a complex mixture into components, which are combusted and reduced continuously in microreactors. The resulting H2/HD gas in He carrier passes through a heated Pd foil, which directs all other gases to waste. This system rapidly produces isotope ratios with precisions of four significant figures, a rate of accuracy nearly that of more cumbersome and time-consuming methods.
Our biomedical work has focused on the application of a stable isotope tracer approach we introduced in 1992, based on highly enriched tracer molecules and high precision IRMS.
Premature birth is an increasingly important health issue, particularly with respect to development of the retina and brain and their function in later life. Nutritional requirements of premature infants are ill-defined. In collaboration with colleagues in the New York State College of Veterinary Medicine, we administer tracer doses of essential fatty acids to pregnant primates and analyze fetal tissues to determine levels of accumulation and metabolism. This work has shown that essential fatty acids are metabolized in large amounts in pathways other than those required for essential components of neural tissue, indicating that the role of these fatty acids is more complex and probably even more critical than previously supposed.
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