T.-A. Lee, T. Hutter
The University of Texas at Austin,
United States
Keywords: optical fiber probe, mid-infrared, real-time sensing, microdialysis, ethanol
Summary:
Alcohol use disorder (AUD) is a major public health problem, with negative impacts on individuals, their families, and society as a whole, including extensive medical issues and economic burdens. Currently, only three pharmacotherapies are approved for AUD treatment in the United States. However, their efficacy is modest, and they are not suitable for everyone, highlighting the urgent need for new treatment options. Advancing therapeutics for AUD relies on continued exploration of the neuropharmacological mechanisms underlying brain changes caused by ethanol consumption. A major limitation in this field is the lack of tools to monitor ethanol levels in tissues, including the brain, in real-time. Such tools would enable researchers to design more effective experiments and better interpret neurophysiological and neurochemical changes induced by ethanol. In this study, ethanol was first measured using a widely adopted in vivo sampling technique—microdialysis—and its limitations were investigated. The lab-fabricated microdialysis probe consisted of fused silica tubing (inlet and outlet) housed within a regenerated cellulose membrane with a molecular weight cut-off of 13 kDa. The probe's working distance, defined by the length difference between the two silica tubing segments within the membrane, was set to 3 mm by applying epoxy to seal unused portions of the membrane. Experimental setup and the parameters used were included in the supporting information. The samples were analyzed using gas chromatography with flame ionization detection (GC-FID). With the conjunction of a GC-FID, this method enabled a low detection limit for ethanol measurement, which is less than 1 mM. However, the measurement is offline and has poor temporal resolution. Additionally, the diffusion-based technique may cause local analyte depletion in the tissue, potentially leading to misinterpretation of results. To address these limitations, we developed a novel optical fiber probe sensor. The sensor features a controlled optical pathlength of 56 µm and was fabricated using silver halide polycrystalline fiber paired with a gold-coated fiber that serves as a mirror. A custom-designed connector was used to align these components, ensuring an accurate optical pathlength in the sensing region. The probe has an overall outer diameter of approximately 850 µm. The sensor was Integrated with a quantum cascade laser, allowing for sensitive detection of chemical substances at low concentrations. The measuring time for each sample is 68 seconds. The sensor operates by directing light through the fiber and enabling interaction with analytes within the optical pathlength in the sensing area. The reflected signal is then directed to the detector. Ethanol solutions at physiological concentration levels were measured using the C–O stretch absorption band at 1046 cm⁻¹ for quantification, achieving a limit of detection of approximately 23.62 µM, determined as three times the blank sample's signal (water). The measuring time can be further reduced to under one minute. To further enhance the sensor’s performance, future work will focus on minimizing back reflections at the fiber-air interface by polishing the fiber at an angle. These findings demonstrate the optical fiber sensor's performance and its potential for in vivo molecular monitoring applications.