Potential and Challenges for Mid-Infrared Sensors in Breath Diagnostics

Abstract

Exhaled breath contains more than 1000 constituents at trace level concentrations, with a wide variety of these compounds potentially serving as biomarkers for specific diseases, physiologic status, or therapeutic progress. Some of the compounds in exhaled breath (EB) are well studied, and their relationship with disease pathologies is well established. However, molecularly specific analysis of such biomarkers in EB at clinically relevant levels remains an analytical and practical challenge due to the low levels of such biomarkers frequently below the ppb (v/v) range in EB. In this contribution, mid-infrared (MIR) spectroscopic sensing techniques are reviewed for potential application in breath diagnostics. While the spectral regime from 3-20 m has already been utilized for fundamental studies on breath analysis, significant further improvements are in demand for substantiating MIR spectroscopy and sensing techniques as a suitable candidate for clinically deployable breath analyzers. Several advantageous features including inherent molecular selectivity, real-time monitoring capability, comparable ease of operation, potentially low costs, and a compact device footprint promise reliable optical diagnostics in the MIR. Hence, while the application of MIR spectroscopy and sensing systems to breath analysis yet appear in their infancy, recent progress on advanced MIR light sources, waveguides, and device concepts forecasts next-generation optical sensing platforms suitable for addressing the challenges of in situ breath diagnostics.

Recent Advances in 3.5 μm Erbium-Doped Mid-Infrared Fiber Lasers

“…Significant attention has been given to sources such as optical parametric oscillators (OPOs) and amplifiers (OPAs), quantum cascade lasers (QC) and fiber lasers. The improvement in these sources have opened up many new possible applications in defense [1], environmental monitoring [2] and medicine [3]. Despite the advances, midinfrared sources operating in the 3-4 µm band have lagged behind in terms of output power, portability, efficiency and beam quality.…”

Numerical Modeling of <inline-formula> <tex-math notation="LaTeX">$3.5~ {\mu }\text{m}$ </tex-math> </inline-formula> Dual-Wavelength Pumped Erbium-Doped Mid-Infrared Fiber Lasers

“…N EW mid-infrared laser sources will enable significant advances in a wide range of applications including spectroscopy [1], remote sensing [2], non-invasive medical diagnosis [3], and defense countermeasure [4]. The midinfrared spectral range is of particular interest in molecular spectroscopy [5], since strong absorption features of many molecules (including hydrocarbons) are found there.…”

Miniaturized Optical Sensors for Medical Diagnostics

“…MIR absorption spectroscopy appears to be an ideal complementary platform for the detection of biomarkers in medical diagnostics, with the analysis of EB and exhaled breath condensate (EBC) among the most promising clinical fields of application [22]. EB is known to contain more than 1 000 different volatile organic compounds (VOCs) [23][24][25][26][27][28][29].…”