Device and Method for Direct Measurement of Isotopes of Expired Gases: Application in Research of Metabolism and Metabolic Disorders, and in Medical Screening and Diagnostics

The technology offered for licensing and for further development concerns a novel device for intervallic collection of expired gas from subjects and subsequent measurement of the isotopic content of such expired gases. The device is specifically designed for medical research and clinical applications, and in particular in the area of metabolic disorders. The device may facilitate the development and testing of new therapies for such disorders and may be used for medical screening and diagnostics of metabolic diseases. The unique design of the device includes a constant volume respiratory chamber equipped with a series of valves and stopcocks to allow precise and repetitive removal of expired gases, and addition of air or other gas to maintain the chamber at a constant volume. Also included is a vacuum tube adapter linked to a port on a three-way stopcock to allow facile transfer of the chamber gases to vacuum tubes for subsequent chemical analyses. The device also includes gas sensors operably linked to detectors and inserted to the chamber through airtight ports; this allows the operator to independently and directly measure the carbon dioxide production rate and oxygen consumption of the test subject while the expired gases are removed for study.

The experimental subject (e.g. mammal) is first contacted with a substrate (e.g. amino acid, fatty acid, organic acid) containing an isotope (e.g. ¹³C) and placed in the chamber. The unique design allows easy gas removal and addition while maintaining a constant chamber volume. Precisely measured air samples are collected from the chamber by the syringe and subsequently transferred to a self-sealing vacuum tube which is then removed for analysis. Subsequent sampling is accomplished in the exact same manner, after an equivalent volume of ambient air, or other gas such as pure oxygen, is reinjected in the chamber to maintain pressure and volume. Air samples from the chamber are collected periodically and the content of the isotope (¹³C) accumulated in the chamber gas due to metabolism and the formation of ¹³CO₂ is measured (e.g. via Isotope Ratio Mass Spectroscopy (IRMS)) from the collected samples. The rate of the metabolite's development (i.e. ¹³CO₂) can thus be determined and can thus provide information on the metabolic status of the subject, such as the rate and extent of oxidation of the administered isotope. Furthermore, results of such analysis can provide fundamental information on the ability of the subject to metabolize a compound, quantitate the effectiveness of an experimental therapy (i.e. enzyme replacement, gene therapy, hormone administration, etc.) and thus facilitate progress in the development of interventional therapies.