Breath Ammonia Measurement Based On Photoacoustic Spectroscopy For Medical Application

Exhaled breath contains more than3000constituents at trace level concentrations, with a wide variety of these compounds potentially serving as biomarkers for specific diseases, physiologic status, or therapeutic progress. Breath ammonia in vivo comes from the nitrogenous metabolism, which has a good linear relationship with the blood urea nitrogen(BUN). The correlation between breath ammonia and BUN suggests that breath ammonia analysis have the potential to be an effective surrogate for BUN for monitoring haemodialysis(HD) efficacy. Photoacoustic spectroscopy can be used as a technique to measure real-time levels of ammonia in exhaled breath for its advantages such as high sensitivity, simultaneous and continuous measurement of multiple gases and so on. The paper is aimed at the theoretical and clinical experimental studies of breath ammonia monitoring based on photoacoustic trace gas detection technique, the main contents are as follows:This thesis reviews the development history and technique of exhaled gas analysis, and introduces current status of breath ammonia detection study. On the base of gas absorption spectrum theory, the elementary principles of photoacoustic spectroscopy are discussed in detail, which includes the generation of photoacoustic signal and the technologies of wavelength modulation and harmonic detection. The mechanism and pathology of exhaled ammonia are discussed, which provide the theoretical basis for breath ammonia detection in the application of monitoring haemodialysis efficacy.The photoacoustic spectrometer based on tunable erbium doped fiber laser(TEDFL)and erbium doped fiber amplifier(EDFA) was optimized to meet the requirement of breath gas detection, a photoacoustic cell with PTFE materials was designed, the temperature control system as well as a respiratory gas acquisition device was increased, a high performance breath ammonia analyzer based on photoacoustic trace gas detection technique was developed. Based on the algorithm of multi-gas measurement, the breath ammonia analyzer can detect breath ammonia with high sensitivity under the conditions of high concentrations of CO2and H2O. And then the simulated exhaled gas experiment was carried out in order to establish calibration models.Based on the theory and experimental analysis of breath ammonia monitor, a clinical trial on the breath ammonia levels of several healthy volunteers and patients with end-stage renal disease(ESRD) in the hemodialysis process was carried out. The experiment of exhaled ammonia concentration in healthy volunteers yields an average level of breath ammonia of300ppb, ranging from200ppb to500ppb. And the breath ammonia levels in eight patients with ESRD while they were undergoing hemodialysis decline similar to the index trend in the dialysis process. The initial levels of breath ammonia at the beginning of dialysis are between1800ppb and2200ppb.These levels drop very sharply in the first30min intervals during the dialysis, the reduction in breath ammonia concentration is relatively slow from this point on to the end of dialysis treatment, at which point the levels taper off at200to600ppb, which close to the levels of healthy subjects. The decline rate of exhaled ammonia is more than65%, which is in agreement with the BUN test used in clinical dialysis. These preliminary data indicate that the breath ammonia analyzer has the clinical application value of the real-time monitoring of dialysis efficacy of ESRD patients and determining the endpoint of hemodialysis.