Ultrasensitive, real-time analysis of biomarkers in breath using tunable external cavity laser and off-axis cavity-enhanced absorption spectroscopy

Abstract

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.

Applications of external cavity diode laser-based technique to noninvasive clinical diagnosis using expired breath ammonia analysis: chronic kidney disease, epilepsy

“…To determine the line strength S, the integrated CEAS signal is plotted as a function of the pressure in our previous work. 19 The slope of the linear fit through the data points gives a value for S of 2.5 × 10 −21 cm −1 ∕molecule cm −2 , which is in agreement with the result reported by Webber et al 21 In our earlier work, the integrated absorption ½ðI 0 ∕IÞ − 1∕d is also plotted as function of the NH 3 concentration, on the basis of Eq. (1).…”

“…1). 19,20 Briefly, a broadly coarse wavelength tuning range of 170 nm (720 cm −1 ) for the spectral range between 1451 and 1621 nm is achieved by rotating the diffraction grating forming ECL configuration in single-mode operation. A mode-hop-free tuning range of 1.85 cm −1 is obtained.…”

Investigation of acetone, butanol and carbon dioxide as new breath biomarkers for convenient and noninvasive diagnosis of obstructive sleep apnea syndrome

“…To analyze the levels of carbon dioxide, we used our home‐made ECL‐based OA‐CEAS setup (Bayrakli and Akman, ; Bayrakli, ). In our recently published work (Bayrakli and Akman, ) it was shown that our CEAS system is able to detect any molecules in breath at concentrations to the ppbv range that have suitable absorption lines in the spectral range between 1450 and 1620 nm.…”

“…To analyze the levels of carbon dioxide, we used our home‐made ECL‐based OA‐CEAS setup (Bayrakli and Akman, ; Bayrakli, ). In our recently published work (Bayrakli and Akman, ) it was shown that our CEAS system is able to detect any molecules in breath at concentrations to the ppbv range that have suitable absorption lines in the spectral range between 1450 and 1620 nm. This setup is based on a wide wavelength‐tunable (170 nm, 720 cm −1 ), narrow‐linewidth (<140 kHz), single‐mode ECL operated at around 1550 nm in Littrow configuration and a high‐finesse CEAS cell formed by two highly reflective mirrors positioned 50 cm apart with a reflectivity of >99.96% over a spectral range of 700–1650 nm with a 2.54 cm diameter and a radius of curvature of 1 m (LayerTec GmbH; Figure ).…”

Breath analysis using external cavity diode lasers: a review

“…They found that the linewidths are little affected by the presence of an AR coating on the diode facet and that the grating resolution has a larger effect on the linewidth than the grating reflectivity. 38 The laser linewidth can be determined using several methods, such as optical cavity measurements, 29 heterodyne measurements, 37 homodyne/heterodyne interferometry using a long interferometer delay, 39 measurements from the frequency noise power spectral density, 40 measurements from root-meansquare frequency deviation, 41 and saturation spectroscopy. 42 Tkach and Chraplyvy 43 reported that there are five distinct regimes of feedback effects, with well-defined transitions between them as a function of feedback power ratio.…”