[Paper Review] Quartz-enhanced photoacoustic spectroscopy as a platform for non-invasive trace gas analyser targeting breath analysis

Jan C. Petersen, Laurent Lamard+4 more|arXiv (Cornell University)|Apr 24, 2017

Spectroscopy and Laser Applications17 references3 citations

TL;DR

This paper presents a novel quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor with acoustically coupled micro-resonators and a 20 kHz quartz tuning fork (QTF) for non-invasive breath gas analysis. It achieves a detection limit of 32 ppbv@190s for methane using a nanosecond pulsed mid-infrared OPO, demonstrating sub-ppb sensitivity with background noise limited only by QTF thermal noise, enabling high-precision, low-cost, and portable medical diagnostics via breath biomarker detection.

ABSTRACT

An innovative and novel quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor for highly sensitive and selective breath gas analysis is introduced. The QEPAS sensor consists of two acoustically coupled micro-resonators (mR) with an off-axis 20 kHz quartz tuning fork (QTF). The complete acoustically coupled mR system is optimized based on finite element simulations and experimentally verified. Due to the very low fabrication costs the QEPAS sensor presents a clear breakthrough in the field of photoacoustic spectroscopy by introducing novel disposable gas chambers in order to avoid cleaning after each test. The QEPAS sensor is pumped resonantly by a nanosecond pulsed single-mode mid-infrared optical parametric oscillator (MIR OPO). Spectroscopic measurements of methane and methanol in the 3.1 $μ$m to 3.7 $μ$m wavelength region is conducted. Demonstrating a resolution bandwidth of 1 cm$^{-1}$. An Allan deviation analysis shows that the detection limit at optimum integration time for the QEPAS sensor is 32 ppbv@190s for methane and that the background noise is solely due to the thermal noise of the QTF. Spectra of both individual molecules as well as mixtures of molecules were measured and analyzed. The molecules are representative of exhaled breath gasses that are bio-markers for medical diagnostics.

Motivation & Objective

• To develop a low-cost, portable, and highly sensitive non-invasive trace gas analyser for medical diagnostics using breath analysis.
• To overcome limitations of conventional gas chromatography and mass spectrometry by enabling real-time, in-situ screening with high sensitivity and selectivity.
• To introduce disposable gas chambers to eliminate post-test cleaning and reduce contamination risks.
• To achieve sub-ppb detection limits for biomarkers like methane and methanol in exhaled breath using a compact, robust QEPAS platform.
• To demonstrate the feasibility of QEPAS with a high-power, widely tunable nanosecond pulsed mid-infrared OPO for clinical applications.

Proposed method

• The QEPAS sensor uses two acoustically coupled micro-resonators (mR) with an off-axis 20 kHz quartz tuning fork (QTF) to enhance photoacoustic signal detection.
• The system is pumped resonantly by a nanosecond pulsed single-mode mid-infrared optical parametric oscillator (MIR OPO) tuned to 3.314 µm for methane detection.
• Finite element simulations were used to optimize the mR geometry, and experimental validation confirmed the design's performance.
• The QTF's high Q-factor (up to 100,000 in vacuum) enables detection of weak photoacoustic signals in small gas volumes.
• Signal processing uses a lock-in amplifier with a 300 ms time constant, and Allan deviation analysis determines optimal integration time.
• Spectra are acquired by scanning the OPO wavelength in 0.5 nm steps, with calibration against known methane concentrations for quantitative detection of mixtures like methanol.

Experimental results

Research questions

• RQ1 Can a QEPAS sensor with off-axis acoustically coupled micro-resonators achieve sub-ppb detection limits for trace gases in breath?
• RQ2 Is the background noise in the system dominated by thermal noise of the QTF, indicating minimal interference from stray light or cell absorption?
• RQ3 What is the optimal integration time for maximizing sensitivity in a QEPAS system using a nanosecond pulsed MIR OPO?
• RQ4 Can the QEPAS platform resolve and quantify multiple biomarkers like methane and methanol in a single breath sample?
• RQ5 Can the sensor achieve sufficient sensitivity and selectivity for clinical breath analysis while maintaining low fabrication cost and disposability?

Key findings

• The QEPAS sensor achieved a detection limit of 32 ppbv@190s for methane, with white noise as the dominant noise source at this integration time.
• Background noise was found to be solely due to QTF thermal noise, with no significant contribution from stray light or cell absorption.
• The resolution bandwidth of the instrument was measured to be approximately 1 cm⁻¹, enabling clear resolution of Q-, R-, and P-branches in methane spectra.
• Spectra of both individual gases and mixtures (methane and methanol) were successfully measured and differentiated, with methanol concentrations estimated at 35±5 ppm and 15±5 ppm in two test cases.
• The system demonstrated high sensitivity and selectivity using a nanosecond pulsed MIR OPO, which is a novel combination in QEPAS for trace gas sensing.
• The use of disposable gas chambers enables contamination-free, rapid, and low-cost operation, enhancing practicality for clinical deployment.