Most techniques that are used for diagnosis and therapy of diseases are invasive. Reliable noninvasive methods are always needed for the comfort of patients. Owing to its noninvasiveness, ease of use, and easy repeatability, exhaled breath analysis is a very good candidate for this purpose. Breath analysis can be performed using different techniques, such as gas chromatography mass spectrometry (MS), proton transfer reaction-MS, and selected ion flow tube-MS. However, these devices are bulky and require complicated procedures for sample collection and preconcentration. Therefore, these are not practical for routine applications in hospitals. Laser-based techniques with small size, robustness, low cost, low response time, accuracy, precision, high sensitivity, selectivity, low detection limit, real-time, and point-of-care detection have a great potential for routine use in hospitals. In this review paper, the recent advances in the fields of external cavity lasers and breath analysis for detection of diseases are presented.
An external cavity laser (ECL)-based off-axis cavity-enhanced absorption spectroscopy was applied to noninvasive clinical diagnosis using expired breath ammonia analysis: (1) the correlation between breath ammonia levels and blood parameters related to chronic kidney disease (CKD) was investigated and (2) the relationship between breath ammonia levels and blood concentrations of valproic acid (VAP) was studied. The concentrations of breath ammonia in 15 healthy volunteers, 10 epilepsy patients (before and after taking VAP), and 27 patients with different stages of CKD were examined. The range of breath ammonia levels was 120 to 530 ppb for healthy subjects and 710 to 10,400 ppb for patients with CKD. There was a statistically significant positive correlation between breath ammonia concentrations and urea, blood urea nitrogen, creatinine, or estimated glomerular filtration rate in 27 patients. It was demonstrated that taking VAP gave rise to increasing breath ammonia levels. A statistically significant difference was found between the levels of exhaled ammonia (NH3) in healthy subjects and in patients with epilepsy before and after taking VAP. The results suggest that our breath ammonia measurement system has great potential as an easy, noninvasive, real-time, and continuous monitor of the clinical parameters related to epilepsy and CKD.
A robust biomedical sensor for ultrasensitive detection of biomarkers in breath based on a tunable external cavity laser (ECL) and an off-axis cavity-enhanced absorption spectroscopy (OA-CEAS) using an amplitude stabilizer is developed. A single-mode, narrow-linewidth, tunable ECL is demonstrated. A broadly coarse wavelength tuning range of 720 cm−1 for the spectral range between 6890 and 6170 cm−1 is achieved by rotating the diffraction grating forming a Littrow-type external-cavity configuration. A mode-hop-free tuning range of 1.85 cm−1 is obtained. The linewidths below 140 kHz are recorded. The ECL is combined with an OA-CEAS to perform laser chemical sensing. Our system is able to detect any molecule in breath at concentrations to the ppbv range that have absorption lines in the spectral range between 1450 and 1620 nm. Ammonia is selected as target molecule to evaluate the performance of the sensor. Using the absorption line of ammonia at 6528.76 cm−1, a minimum detectable absorption coefficient of approximately 1×10−8 cm−1 is demonstrated for 256 averages. This is achieved for a 1.4-km absorption path length and a 2-s data-acquisition time. These results yield a detection sensitivity of approximately 8.6×10−10 cm−1 Hz−1/2. Ammonia in exhaled breath is analyzed and found in a concentration of 870 ppb for our example.
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