Breath Analysis Using Photoionization Mass Spectrometry

REMPI (Resonantly Enhanced Multi Photon Ionization) is an ultra-sensitive analytical technique based on the unique combination of laser spectroscopy and mass spectrometry that can rapidly identify and quantify vapor-phase constituents present at part per trillion levels. We have used this method to examine human breath samples for biomarkers of infection. Based on the observed results, we estimate our limit of detection for the photoionization system is a factor of 40-100 times lower than we can achieve using the newest GC/MS instrument. Of more importance perhaps, compounds such as benzene, toluene or even dichlorobenzene can readily be detected using this method. INTRODUCTION The threat posed by the use of biological weapons against military or civilian targets and their potential for mass destruction form a major national concern. Developing an appropriate response involves first detecting the use of a chemical or biological warfare (CW/BW) agent. This can be accomplished either by direct detection of the agent or by diagnosing the health of the affected persons. We have been investigating the latter approach through the use of volatile biomarkers in exhaled breath. These compounds can be produced by the infectious biological agent or through the host response. From the small amount of previous work in this general area, we anticipate that different suites of such compounds will be associated with specific diseases. One of the chief technical challenges to the use of breath analysis as a health diagnostic in general, and a monitor for BW exposure in particular, is a rapid, sensitive, and chemically selective detector. Given the nature of most BW-induced diseases, it is crucial to detect them very early in the infection stage. When typical symptoms become apparent, it is often too late to apply traditional countermeasures, i.e., the administration of antibiotics and antidotes. However, when countermeasures are applied early, they can be quite successful. Thus, we have focused on the detection and identification of biological activity indicating exposure and the early onset of disease. We describe here the use of SRI’s ultratrace detection system, already developed and tested for other applications. This system consists of a tunable, narrow-band, laser and a time-of-flight mass spectrometer to rapidly and selectively measure compounds in the breath with very high sensitivity. Specific compounds found in exhaled breath are known to be associated with specific diseases and can, in principle, be used as a noninvasive medical diagnostic. Little progress has been made in this field, and conclusions have been hampered by ambiguous results, perhaps due to the lack of sensitivity of the conventional analytical methods used in these studies. Our ultratrace method can already rapidly detect Report Documentation Page Form Approved OMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number.