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Device and Method for Direct Measurement of Isotopes of Expired Gases: Application in Research of Metabolism and Metabolic Disor

Posted Jul 04 2012 8:00pm

Description of Invention:
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.

Applications:
  • Research in the area of metabolic disorders
  • Development of therapies (including enzyme replacement and gene therapy) for metabolic disorders
  • Potential applications in screening and diagnostics of metabolic disorders
  • Assessment of non-invasive breath tests to study metabolism


Advantages:
  • The device of this invention is uniquely designed for precise periodic collection of expired gas samples from a test subject and their transfer for analytical processing while the carbon dioxide production rate and oxygen consumption rate are independently and simultaneously measured.
  • The unique configuration of the device and the manner in which the valves and stopcocks are attached to the main chamber facilitates the performance of repetitive measurements in a seamless, precise and reliable fashion.
  • The technique and device uses stable isotopes, so treated animals can be returned to the cage after study with no concerns of radioactive contamination. This also allows animals that are difficult and expensive to create, such as genetically engineered rodents, to be repeatedly studied, pre- and post-intervention(s) and with various compounds at different times.
  • The device can be readily fabricated in a relatively inexpensive manner and operated with simple instructions.


Development Status:
Prototype

Inventors:
Charles P Venditti (NHGRI)
Randy J Chandler (NHGRI)


Patent Status:
HHS, Reference No. E-099-2009/0
US, Application No. 12/418,795 filed 06 Apr 2009


Relevant Publication:
  1. Venditti CP, Manoli E, Chandler RJ. A Method To Determine The In Vivo Oxidative Capacity For 13C Isotopomers In Mice : Use To Study Intermediary Metabolism And To Monitor Transgene Activity. Presented at the American Society of Gene Therapy 12th Annual Meeting, May 2009.
  2. Chandler RJ, Venditti CP. [ PMID 19861951 ]


Collaborative Research Opportunity:
The Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology or related laboratory interests. Please contact Claire T. Driscoll at cdriscol@mail.nih.gov for more information.


For Licensing Information Please Contact:
Michael Shmilovich Esq.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: shmilovm@mail.nih.gov
Phone: 301-435-5019
Fax: 301-402-0220


Ref No: 2046

Updated: 07/2012

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