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Metal test of Expired Breath

#3287


Metal-Test of Expired Breath – New Way to Noninvasive Diagnostic

Tech Area / Field

  • CHE-ANL/Analytical Chemistry/Chemistry
  • MED-DID/Diagnostics & Devices/Medicine
  • BIO-OTH/Other/Biotechnology
  • MED-OTH/Other/Medicine

Status
3 Approved without Funding

Registration date
26.05.2005

Leading Institute
Research Institute of Technology, Russia, Leningrad reg., Sosnovy Bor

Supporting institutes

  • North-West Scientific Center for Hygiene and Public Health, Russia, St Petersburg

Collaborators

  • National Research Council Canada / Institute for National Measurement Standards, Canada, ON, Ottawa\nMenssana Research, Inc., USA, NJ, Fort Lee\nTexas Technical University / Department of Chemistry and Biochemistry, USA, TX, Lubbock\nUniversiteit Antwerpen, Belgium, Antwerpen\nMedical University of Innsbruck, Austria, Innsbruck

Project summary

The project’s goal is to develop an instrument for separation of volatile metal traces from exhaled human breath for the medical diagnosis of acute and chronic poisoning and, as a perspective, other somatic diseases.

A rapid diagnosis is crucial for effective treatment of patients infected with toxic agents, especially, with low doses of heavy metals such as lead, mercury, and cadmium.

The today’s most widely used methods for identifying toxicants in the human body involve taking assay samples of blood, hair, nails, etc. Simple organic and certain inorganic gaseous substances can be determined from metabolism products in expired air, using sensitive chromatographic and mass-spectrometric methods. Trace elements (heavy metals) are determined in blood samples by spectral methods. Bleeding for analysis (blood assay is the method most frequently used for trace element identification) is a hazard as far as hepatitis and AIDS are concerned. The mentioned methods involve sample preparation steps. As to the final spectrum analysis, e.g. by atomic absorption spectrometry (AAS), it generates high noise and non-selective absorption, adding difficulty to the analysis and data interpretation procedures.

One way to solve the problem of monitoring and analyzing trace elements present in the human body is to change from invasive to non-invasive methods such as analyses of expired air. Blood and breath have equilibrium concentrations of a number of dissolved gases. There exist instruments for direct identification of CO and NO in expired air for medical diagnosis purposes.

M. Philips has presented outlook for methods of identifying organic (non-metal) volatiles (OV) in expired air as markers of non-infectious respiratory and system diseases. Mobile devices for separation, collection, and mass-spectrometric analysis of OV are being developed. OV markers in expired air are used to recognize lung and breast cancers. Identification and measurement of metal volatiles is little used for medical diagnosis because of technical problems such as shortage of collection devices (incomplete inverse desorption) and difficulties in interfacing such devices and highly sensitive metal analyzers by atomic absorption, atomic emission, etc. Only few studies on this topic are reported in the literature and the research direction is not sufficiently advanced.

The main idea of the project is to change from checking of blood or other samples for HM to separation of metal volatiles from expired air, their collection in graphite tube under corona discharge, and analysis by atom absorption with non-flame atomization. The problem of heavy metal back desorption from the collector is overcome in the proposed method by using special technical solutions. Volatile concentrations can be invasively measured at different times so that their dependence on patient condition is determined.

The project authors have the appropriate technology and managerial base and all necessary permits for carrying out the project activities. NITI scientists have developed a methodology for identification of metal traces in air and water, using preliminary sample accumulation in graphite tube. This method allows the concentration detection limits to be reduced by nearly 3 orders of magnitude as compared to the existing methods. NITI researchers have performed preliminary experiments with deposition and accumulation in graphite tube of chemical analogues of exhaled metal volatiles: volatile β-diketonates of beryllium, copper, and lead. Results of the experiments are encouraging for the proposed project. They are published and presented at international conferences.

As to basic research, the use of EA-AAS suggests a new direction in air monitoring applications. High efficiency of metal deposition (near 100%) makes it possible to cut a sample volume to 50 l with LOD at the level of pg*l-1.

As to applied research, the authors plan to develop a portable accumulation device and determine the best conditions for effective separation of airborne particles from atmospheric and expired air. Concentrations of metal volatiles in expired breath will be measured for patients with different amounts of inhaled metals and metal markers of heavy metal poisoning will be suggested. The proposed device in combination with other diagnosis methods can be used in clinical routine for metal poisoning diagnosis and preventive examinations.

Relations between metal concentrations in breath and blood will be derived and used to optimize the diagnosis of acute and chronic poisoning and, probably, other somatic diseases. Clearly, an investigation of chemical volatiles, advances in analysis methods, and better understanding of relations between the chemical concentrations in expired air and the clinical status will help in both diagnosis practice and basic research.

The project will provide Russian weapons scientists and engineers opportunities to participate in fundamental and applied research and technology development for peaceful purposes, notably in the public health field. During the project, they will hold scientific contacts with foreign collaborators and discuss with them the project work plans and results, and attend international scientific meetings and conferences where the results will be presented and discussed. Information exchange will promote integration of Russian scientists into the international scientific community. Researchers from NITI and NWSC for Hygiene and Public Health will be given financial support to continue their work in Russia.

The project authors from NITI plan to design a model prototype of portable collector, devises and methodology for deposition metal volatiles from air. The project authors from the NWSC for Hygiene and Public Health have an appropriate technical and legal base for carrying out biological examinations of patients who inhale airborne metals at their work places, there plan to make blood and breath condensates analysis for HM.

The estimated project duration is three years.

The total estimated project cost is 250,000 USD.

During the first year, NITI team will design and manufacture prototype models of the collector-analyzer components to the graphite cell, and study the operating parameters to arrive at optimal performance of the method. Results of this work will be used in the next step activities, specifically, for carrying out a series of investigations and analyses of atmospheric air and finding practical ways to combine the atomic absorption spectrometry technique with varied corona discharge regimes, different cell designs, and analysis conditions. The model prototype of the device will be tried out in NWSC for Hygiene and Public Health.

For the second year, the authors plan to continue activities for optimization of NITI-developed methodology and apparatus and to test same at NWSC for Hygiene and Public Health. Based on clinical trial data, diagnostic problems which could be resolved with the help of the proposed apparatus will be defined.

For the third year, it is scheduled to manufacture a prototype of the developed collector-analyzer, develop and test procedures for collecting specific compounds using the proposed deposition device, and carry out laboratory and clinical trials at NWSC for Hygiene and Public Health. Finally, a joint report on the analysis results will be prepared.

Concerted action of scientists from NITI and NWSC for Hygiene and Public Health is good reason to believe that an analysis of exhaled breath will greatly help in understanding human metabolism and its influence on human health problems.


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