Development of a mid-infrared transflection probe and in-vitro feasibility for ethanol monitoring

Real-time in vivo ethanol monitoring is important for understanding its physiological mechanisms and developing treatments for alcohol-related disorders. Mid-infrared (mid-IR) fiber sensors enable highly specific and sensitive detection of chemical species due to unique molecular vibrational absorption bands. This study presents the first mid-IR transflection optical fiber probe that is small enough to be suitable for in vivo monitoring. Ethanol quantification using mid-IR spectroscopy was demonstrated in synthetic solutions and in a biofluid, rat brain dialysate, spiked with ethanol at physiological concentrations using standard Fourier-transform infrared spectrometer (FTIR). The results showed a linear relationship between absorbance and concentration, with a limit of detection (LoD) of ∼4 mmol/L in each fluid. The optical probe was fabricated using a 500 μm silver halide polycrystalline fiber aligned with a gold-coated short fiber, acting as a mirror, in a connector to maintain a predetermined distance between two fibers. The sample cavity was formed between the optical fiber and the gold-coated fiber. For performance optimization, optical back reflections were analyzed experimentally and numerically in fibers with end-face surfaces polished at varying angular deviations from the fiber axis. Experimental data were used to estimate and subtract back reflections from the detected signals to improve the signal-to-noise ratio (SNR) resulting in an LoD of 4 mmol/L for ethanol in synthetic solutions. The effects of optical pathlength and fiber end-face angle on probe's performance were investigated, showing that a fiber with an end-face whose surface normal deviated by 10° from the fiber axis (averaged optical pathlength of 68 μm) achieved a 32.7 % higher SNR compared to fiber with a surface normal aligned with the fiber axis (optical pathlength of 64 μm). This study is important for optimizing the sensor design, paving the way for advanced biomedical applications such as monitoring alcohol levels in tissues or detecting ethanol in various clinical scenarios.