Laser spectroscopy for breath analysis: towards clinical implementation

Abstract

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.

Fig. 1

a Schematic drawing of a typical mid-infrared TDLAS setup employing an ICL, a circular, low-volume MPC, and WMS (with permission from [39]). LDC: laser diode controller, LiA: lock-in amplifier, FGen: function generator, PT: pressure transducer, PD: photodetector. b Real-time, exhalation profiles (breath cycles) of CO and CO₂ measured with an EC-QCL, and a CO₂ profile recorded with NDIR spectroscopy (capnography) (with permission from [36]). The three exhalation phases (dead space/airways, transition region, and alveolar region) are indicated

Fig. 2

a Schematic of the multichannel absorption spectrometer and pneumotachograph within the MFS measurement head. The bi-directional gas path (blue) is shown along with the two mesh screens (gray), across which pressure drop is measured. Radiation used for probing O₂ is injected into an optical cavity constructed from a pair of highly reflective mirrors (red) and collected by a photodiode (PD 1) positioned along the optical axis (green). Radiation probing CO₂ and H₂O vapor is launched into the v-path (yellow), reflected by a concave mirror, and collected by the photodiode (PD 2). The physical length of the optical cavity is commensurate with the diameter of a standard medical ventilation tube. b, c Dry gas fractions of N₂ (purple), O₂ (green), and CO₂ (red) measured in real time (every 10 ms) as a participant breathes through the measurement head. The dry fraction of N₂ is determined by the subtracting the dry fractions of O₂ and CO₂ from unity. b Data from an air breathing phase. c Data from the early stage of a nitrogen washout procedure

Fig. 3

Contour plots for the bivariate log normal distributions for (standardized) compliance and conductance for three participant groups: young, old, and COPD. Contour intervals are values for the probability density function. The increased lung inhomogeneity for COPD cohort is readily apparent from the widths of the distribution. Further details can be found in Mountain et al. [44]

Fig. 4

a CO measurements performed by OF-CEAS on an ex vivo pig lung during slow warming after cold ischemia. The response time allows to monitor both inspiration and expiration phases imposed by the ventilator (respiratory rate is 12 per min). The baseline corresponds to CO concentration in the medical gas supply. b Lungs were progressively ventilated and rewarmed by a perfusion solution

Fig. 5

Laser-based photoacoustic detector (ETD-300, Sensor Sense) in the cardiothoracic surgery department at Harefield hospital, UK (photo by S. Cristescu)

Fig. 6

Intraoperative real-time monitoring of ethylene measured by LPAS in patients undergoing off-pump coronary artery bypass surgery. a Example of continuous monitoring during of the entire operation. At t = 0 h the patient was connected to the sampling line; DT = diathermy electrocautery with high-frequency electric currents (adapted from [67]). b An example of a grafting procedure. The high-resolution peaks are associated with ethylene induced by lipid peroxidation during the reperfusion events

Fig. 7

A scheme of the fiber-coupled off-beam QEPAS sensor for CO₂ isotopic ratio determination [73]. L1, AR-coated aspheric lens; L2, optical focuser; QTF, quartz tuning fork; mR, micro-resonator; DAQ, data acquisition system