Abstract
Simultaneous monitoring of multiple biomarkers in tissues is critical for biomedical applications. However, few existing platforms enable concurrent in vivo detection. This study presents a compact mid-infrared transflection optical fiber probe for label-free, simultaneous monitoring of three physiologically relevant biomarkers – ethanol, glucose, and lactate. The probe comprises two silver halide fibers - one with an angled tip and one gold-coated as mirror - housed in polyetheretherketone tubing and surrounded by a semi-permeable membrane. With an outer diameter of only 1.1 mm, this is the smallest mid-infrared transflection probe reported to date. Coupled with a quantum cascade laser, the probe achieves ~1 mM detection limits for the three compounds. Peak deconvolution was deployed to resolve overlapping spectral features, enabling quantification of individual compounds in mixtures. Validation was performed in ex vivo human skin against microdialysis. Additionally, monitoring of the concentration changes for all three compounds in the skin was demonstrated.
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Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon request.
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Acknowledgements
Research reported in this publication was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) under Award Number R21AA029770 (T.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. T.-A.L. would like to acknowledge the financial support provided by the Fred Murphy Jones and Homer Lindsey Bruce Endowed Fellowship from the Waggoner Center for Alcohol and Addiction Research at The University of Texas at Austin.
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T.-A.L: Conceptualization, data curation, formal analysis, investigation, methodology, visualization, writing – original draft; T.H.: conceptualization, funding acquisition, project administration, resources, supervision, writing – review and editing.
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The authors declare that Tanya Hutter and Tse-Ang Lee are inventors on a pending and unpublished U.S. provisional patent application (No. 63/749,262) related to the work described in the manuscript, and it is owned by The University of Texas at Austin.
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Lee, TA., Hutter, T. Compact mid-infrared fiber probe for in vivo multi-compound monitoring demonstrated using ex vivo human skin. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70300-x
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DOI: https://doi.org/10.1038/s41467-026-70300-x


