人体呼出氨气的光声光谱检测技术研究
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摘要
呼出气检测是一种重要的无损诊断技术。由于人呼出气中NH3的含量与BUN存在良好的线性关系,因此通过检测呼出气中的NH3可以实现对肾衰竭患者血液透析效果的间接评价,进而得以对血液透析过程进行实时监测。光声光谱技术凭借其检测灵敏度高且可以实现多组分气体同时检测的优势,在人类健康医学诊断领域的微量气体检测中得到了广泛的应用。
本论文首先介绍了各种呼出气检测技术及特点,指出光声光谱检测技术的优点；详细的分析了光声光谱技术的理论,描述了光声信号的产生以及光声信号的检测,并指出使用波长调制与二次谐波探测技术能够提高系统信噪比；然后分析呼出气体与疾病的关系,着重分析了氨气可作为肾衰竭患者透析程度监测手段的原因和呼出气中氨气检测的特点,为在实验中使用光声光谱技术进行呼出氨气检测提供了理论支持。
在实验优化基于TEDFL和EDFA的光声光谱系统的基础上,利用LabVIEW程序编写了整个系统控制与数据处理程序,完成了波长标定,实现了测量结果实时分析；之后分析呼出气的成分以及可能会对氨气测量产生影响的优势气体,主要分析了氨气和水、二氧化碳在近红外1.5μm带的吸收线,通过谱线选择确定对1522.44nm处呼出氨气进行检测,排除高浓度水和二氧化碳的干扰；最后在氨气的检测极限灵敏度为8ppb的情况下,实现了常温常压下对模拟呼出气中微量氨气的检测,并完成了模拟呼出氨气标定模型的建立,并在标定模型的基础上,完成对3名健康志愿者呼出气中氨气含量的实际检测,结果分别为313ppb、208ppb、559ppb,与其他学者的测量结果对比,证明系统基本符合临床肾透析患者透析水平实时监测的需求。
本论文的意义在于：1)利用光声光谱技术实现了人体呼出氨气的实时监测,解决了高效的HD治疗效果检验方法这一难题；2)进一步实现了光声光谱技术用于呼出气检测的实际应用,加快了呼出气检测的临床医学应用推广的步伐。
Measurement of breath ammonia is an important non-invasive diagnostic technique for end-stage renal disease (ESRD). According to a good linear relationship between NH3 in exhaled breath and blood urea nitrogen (BUN), this technique not only can realize real-time monitoring for hemodialysis (HD), but also can give an estimated effect of HD on renal failure patients. Photoacoustic spectroscopy is widely applied in trace gas detection of medical diagnosis area for its advantages such as high sensitivity and multi component in vivo detection.
In this paper, many kinds of methods, used to measure the breath ammonia in vivo, are reviewed. The advantages of the photoacoustic spectroscopy are introduced. The theory of photoacoustic spectroscopy including the generation and detection of photoacoutic signal is discussed in detail. And also, technologies of wavelength modulation and harmonic detection are introduced to improve the signal to noise ratio. The relationship between the breath ammonia and renal failure patients is discussed, and this forms the theoretical basis on photoacoustic spectroscopy used for breath ammonia detection in vivo.
Photoacoustic spectrometer based on tunable erbium doped fiber laser (TEDFL) and erbium doped fiber amplifier (EDFA) is optimized, including realizing real-time wavelength demodulation and completing system control through programming by LabVIEW. Considering that high concentration of H2O and CO2 in exhaled breath may cause interferences to the measurement of ammonia. The absorption line at 1522.44nm for NH3 is chosen as a feature line, based on the spectrum analysis of NH3、H2O and CO2, specific at 1.5μm. And then stimulated breath ammonia is detected. The experimental results demonstrated that at room temperature and atmospheric pressure, the detection limit of ammonia reaches 8ppb and the interferences of H2O and CO2 is successfully eliminated. Based on the stimulated breath ammonia measurement, the system is applied to measure real breath ammonia of three healthy volunteers. And the concentrations of the ammonia are 313ppb、208ppb and 559ppb respectively. These preliminary results demonstrate that the photoacoustic spectrometer can roughly meet the requirement of clinical monitoring for kidney dialysis.
In conclusion, the photoacoustic spectrometer in this dissertation realized real-time monitoring for breath ammonia in vivo. It can give an estimated effect of HD by non-invasive diagnostic technique. This work would be helpful for pushing the wide application of photoacoustic spectroscopy in exhaled breath diagnosis.
本论文首先介绍了各种呼出气检测技术及特点,指出光声光谱检测技术的优点；详细的分析了光声光谱技术的理论,描述了光声信号的产生以及光声信号的检测,并指出使用波长调制与二次谐波探测技术能够提高系统信噪比；然后分析呼出气体与疾病的关系,着重分析了氨气可作为肾衰竭患者透析程度监测手段的原因和呼出气中氨气检测的特点,为在实验中使用光声光谱技术进行呼出氨气检测提供了理论支持。
在实验优化基于TEDFL和EDFA的光声光谱系统的基础上,利用LabVIEW程序编写了整个系统控制与数据处理程序,完成了波长标定,实现了测量结果实时分析；之后分析呼出气的成分以及可能会对氨气测量产生影响的优势气体,主要分析了氨气和水、二氧化碳在近红外1.5μm带的吸收线,通过谱线选择确定对1522.44nm处呼出氨气进行检测,排除高浓度水和二氧化碳的干扰；最后在氨气的检测极限灵敏度为8ppb的情况下,实现了常温常压下对模拟呼出气中微量氨气的检测,并完成了模拟呼出氨气标定模型的建立,并在标定模型的基础上,完成对3名健康志愿者呼出气中氨气含量的实际检测,结果分别为313ppb、208ppb、559ppb,与其他学者的测量结果对比,证明系统基本符合临床肾透析患者透析水平实时监测的需求。
本论文的意义在于：1)利用光声光谱技术实现了人体呼出氨气的实时监测,解决了高效的HD治疗效果检验方法这一难题；2)进一步实现了光声光谱技术用于呼出气检测的实际应用,加快了呼出气检测的临床医学应用推广的步伐。
Measurement of breath ammonia is an important non-invasive diagnostic technique for end-stage renal disease (ESRD). According to a good linear relationship between NH3 in exhaled breath and blood urea nitrogen (BUN), this technique not only can realize real-time monitoring for hemodialysis (HD), but also can give an estimated effect of HD on renal failure patients. Photoacoustic spectroscopy is widely applied in trace gas detection of medical diagnosis area for its advantages such as high sensitivity and multi component in vivo detection.
In this paper, many kinds of methods, used to measure the breath ammonia in vivo, are reviewed. The advantages of the photoacoustic spectroscopy are introduced. The theory of photoacoustic spectroscopy including the generation and detection of photoacoutic signal is discussed in detail. And also, technologies of wavelength modulation and harmonic detection are introduced to improve the signal to noise ratio. The relationship between the breath ammonia and renal failure patients is discussed, and this forms the theoretical basis on photoacoustic spectroscopy used for breath ammonia detection in vivo.
Photoacoustic spectrometer based on tunable erbium doped fiber laser (TEDFL) and erbium doped fiber amplifier (EDFA) is optimized, including realizing real-time wavelength demodulation and completing system control through programming by LabVIEW. Considering that high concentration of H2O and CO2 in exhaled breath may cause interferences to the measurement of ammonia. The absorption line at 1522.44nm for NH3 is chosen as a feature line, based on the spectrum analysis of NH3、H2O and CO2, specific at 1.5μm. And then stimulated breath ammonia is detected. The experimental results demonstrated that at room temperature and atmospheric pressure, the detection limit of ammonia reaches 8ppb and the interferences of H2O and CO2 is successfully eliminated. Based on the stimulated breath ammonia measurement, the system is applied to measure real breath ammonia of three healthy volunteers. And the concentrations of the ammonia are 313ppb、208ppb and 559ppb respectively. These preliminary results demonstrate that the photoacoustic spectrometer can roughly meet the requirement of clinical monitoring for kidney dialysis.
In conclusion, the photoacoustic spectrometer in this dissertation realized real-time monitoring for breath ammonia in vivo. It can give an estimated effect of HD by non-invasive diagnostic technique. This work would be helpful for pushing the wide application of photoacoustic spectroscopy in exhaled breath diagnosis.
引文
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