Applied Physics B Lasers and Optics Spectroscopic detection of biological NO with a quantum cascade laser

Two configurations of a continuous wave quantum cascade distributed feedback laser-based gas sensor for the detection of NO at a parts per billion (ppb) concentration level, typical of biomedical applications, have been investigated. The laser was operated at liquid nitrogen temperature near λ = 5.2 μm. In the first configuration, a 100 m optical path length multi-pass cell was employed to enhance the NO absorption. In the second configuration, a technique based on cavity-enhanced spectroscopy (CES) was utilized, with an effective path length of 670 m. Both sensors enabled simultaneous analysis of NO and CO2 concentrations in exhaled air. The minimum detectable NO concentration was found to be 3 ppb with a multi-pass cell and 16 ppb when using CES. The two techniques are compared, and potential future developments are discussed. PACS: 42.62. Be; 82.80. Ch; 87.64. Je Sensitive, selective and on-line laser-based trace gas detection can be an effective tool in various aspects of noninvasive medical diagnostics. The detection and quantification of a number of gases such as NO, CO, CO2 and NH3 play an important role in monitoring biomedical functions [1–4]. In recent years, the detection of CO2 in human breath has become a diagnostic technique (for example, for the detection of helicobacter pylori, which causes ventricular ulcers [5]). Detection of biomedically-produced NO and its chemical products is also important because of their critical role in human physiology. Nitric oxide (NO) is produced in the human body and controls different physiological (and pathophysiological) processes, such as the diameter of blood vessels and immune reactions, and it is present in neuronal tissue [6]. NO can be detected in exhaled human breath and is a marker for diseases like asthma or inflammatory processes [7, 8]. NO levels in breath range from several parts per billion by volume (ppb) ∗Corresponding author. (Fax: +49-228/733-474, E-mail: menzel@iap.uni-bonn.de) ∗∗Present address: Institut für Angewandte Physik, Universität Bonn, Wegeler Str. 8, Germany to several hundred ppb. To date, most medical laboratories rely on chemiluminescence-based devices such as the Sievers NOATM 280, which can measure NO concentration in air down to 1 ppb level with a time resolution of 0.2 s. However, the chemiluminescence approach suffers from several intrinsic limitations. The presence of other species in the gas sample can influence the results. For example, ammonia also produces a chemiluminescence signal [9], and water leads to quenching of the chemiluminescent reaction. Furthermore, the chemiluminescence technique is not isotopic selective. An alternative approach to quantification of ultra-low concentrations of NO is the use of high-resolution infrared absorption spectroscopy (IAS). IAS has been demonstrated to be a sensitive and selective tool for the detection of different trace gas components in ambient air (see for example [10, 11]). NO has a strong fundamental absorption band near λ = 5.2 μm, which can be used for monitoring purposes [12, 13]. Specific absorption lines can be selected to avoid interference from other species such as CO2 and H2O absorbing in this spectral region. IAS is also intrinsically isotopically selective. Further sensitivity enhancement can be obtained with laser magnetic resonance spectroscopy (LMRS), which exploits the property of NO to rotate light polarization in a magnetic field [14, 15]. However, LMRS adds complexity, which may not be justified for medical instrumentation. IAS requires a single-frequency light source with sufficient power. Recently developed cw and pulsed distributed feedback quantum cascade lasers (QC-DFB) can be utilized as a convenient spectroscopic mid-IR source [16] for implementation into IR absorption-based biomedical gas sensors. Presently, cw operation of QC-DFB lasers requires cryogenic cooling, which adds inevitable bulkiness to an optical cryostat. However, it is generally believed that nearroom temperature cw QC-DFB lasers will be available in the future [17]. In this paper, we describe and compare two QC-DFB IAS-based approaches to detection of NO at ppb concentration levels that are typical for biological applications. In both cases, the same cw single-frequency QC-DFB laser, operating near λ = 5.2 μm, was used as a tunable midIR source.