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Compact mid-infrared fiber probe for in vivo multi-compound monitoring demonstrated using ex vivo human skin
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  • Published: 09 March 2026

Compact mid-infrared fiber probe for in vivo multi-compound monitoring demonstrated using ex vivo human skin

  • Tse-Ang Lee1 &
  • Tanya Hutter  ORCID: orcid.org/0000-0001-8106-18301,2 

Nature Communications , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Characterization and analytical techniques
  • Diagnostic markers
  • Infrared spectroscopy
  • Sensors and probes

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 availability

Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon request.

References

  1. Clish, C. B. Metabolomics: an emerging but powerful tool for precision medicine. Cold Spring Harb. Mol. Case Stud. 1, a000588 (2015).

    Google Scholar 

  2. Gowda, G. N. et al. Metabolomics-based methods for early disease diagnostics. Expert Rev. Mol. Diagn. 8, 617–633 (2008).

    Google Scholar 

  3. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Tamborlane, W. V. et al. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N. Engl. J. Med. 359, 1464–1476 (2008).

    Google Scholar 

  4. Deulkar, P., Singam, A., Mudiganti, V. N. K. S. & Jain, A. Lactate monitoring in intensive care: a comprehensive review of its utility and interpretation. Cureus 16, e66356 (2024).

    Google Scholar 

  5. Lozano, A. et al. Glucose and lactate concentrations in cerebrospinal fluid after traumatic brain injury. J. Neurosurg. Anesthesiol. 32, 162 (2020).

    Google Scholar 

  6. Cappon, G., Vettoretti, M., Sparacino, G. & Facchinetti, A. Continuous glucose monitoring sensors for diabetes management: a review of technologies and applications. Diab. Metab. J. 43, 383–397 (2019).

    Google Scholar 

  7. Chertoff, J., Chisum, M., Garcia, B. & Lascano, J. Lactate kinetics in sepsis and septic shock: a review of the literature and rationale for further research. J. Intensive Care 3, 39 (2015).

    Google Scholar 

  8. Paprocki, S., Qassem, M. & Kyriacou, P. A. Review of ethanol intoxication sensing technologies and techniques. Sensors 22, 6819 (2022).

    Google Scholar 

  9. Kreisberg, R. A., Siegal, A. M. & Owen, W. C. Glucose-lactate interrelationships: effect of ethanol. J. Clin. Invest. 50, 175–185 (1971).

    Google Scholar 

  10. Krebs, H. A., Freedland, R. A., Hems, R. & Stubbs, M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem. J. 112, 117–124 (1969).

    Google Scholar 

  11. Polson, J. & Lee, W. M. American Association for the Study of Liver Disease, AASLD position paper: the management of acute liver failure. Hepatol. Baltim. Md 41, 1179–1197 (2005).

    Google Scholar 

  12. Bjorkli, C. et al. In vivo microdialysis in mice captures changes in alzheimer’s disease cerebrospinal fluid biomarkers consistent with developing pathology. J. Alzheimer’s. Dis. 84, 1781–1794 (2021).

    Google Scholar 

  13. Le Prieult, F., Barini, E., Laplanche, L., Schlegel, K. & Mezler, M. Collecting antibodies and large molecule biomarkers in mouse interstitial brain fluid: a comparison of microdialysis and cerebral open flow microperfusion. mAbs 13, 1918819 (2021).

    Google Scholar 

  14. Moon, B.-U., de Vries, M. G., Cordeiro, C. A., Westerink, B. H. C. & Verpoorte, E. Microdialysis-coupled enzymatic microreactor for in vivo glucose monitoring in rats. Anal. Chem. 85, 10949–10955 (2013).

    Google Scholar 

  15. Kim, S. et al. Brain microdialysis coupled to LC-MS/MS revealed that CVT-10216, a selective inhibitor of aldehyde dehydrogenase 2, alters the neurochemical and behavioral effects of methamphetamine. ACS Chem. Neurosci. 12, 1552–1562 (2021).

    Google Scholar 

  16. Saputra, H. A. & Karim, M. M. Enzymatic and enzyme-free electrochemical lactate sensors: a review of the recent developments. Electrochem. Sci. Adv. 5, e202400021 (2025).

    Google Scholar 

  17. Hassan, M. H., Vyas, C., Grieve, B. & Bartolo, P. Recent advances in enzymatic and non-enzymatic electrochemical glucose sensing. Sensors 21, 4672 (2021).

    Google Scholar 

  18. Poletti, F. et al. Continuous capillary-flow sensing of glucose and lactate in sweat with an electrochemical sensor based on functionalized graphene oxide. Sens. Actuators B Chem. 344, 130253 (2021).

    Google Scholar 

  19. Fande, S., Sriram, D. & Goel, S. Real-time multiplex electrochemical biosensor for simultaneous quantification of glucose and lactate in cell and bodily fluids. Electrochim. Acta 531, 146421 (2025).

    Google Scholar 

  20. Yamazaki, T. et al. Smart integrated sensor for multiple detections of glucose and L-lactate using on-chip electrochemical system. J. Sens. 2011, 190284 (2011).

    Google Scholar 

  21. Zhu, B., Li, X., Zhou, L. & Su, B. An overview of wearable and implantable electrochemical glucose sensors. Electroanalysis 34, 237–245 (2022).

    Google Scholar 

  22. E. Demir, K. K. Kırboga, M. Işık, Chapter 8 - An overview of stability and lifetime of electrochemical biosensors, in: J. G. Manjunatha (Ed.), Nov. Nanostructured Mater. Electrochem. Bio-Sens. Appl. 129–158 (Elsevier, 2024).

  23. Golcuk, K. et al. Is photobleaching necessary for Raman imaging of bone tissue using a green laser. Biochim. Biophys. Acta BBA - Biomembr. 1758, 868–873 (2006).

    Google Scholar 

  24. De Ridder, F. et al. Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol. PLoS ONE 19, e0301041 (2024).

    Google Scholar 

  25. Li, Z. et al. Reagent-free simultaneous determination of glucose and cholesterol in whole blood by FTIR-ATR. Spectrochim. Acta A. Mol. Biomol. Spectrosc. 178, 192–197 (2017).

    Google Scholar 

  26. Koyama, T. et al. A compact mid-infrared spectroscopy system for healthcare applications based on a wavelength-swept, pulsed quantum cascade laser. Sensors 20, 3438 (2020).

    Google Scholar 

  27. Christie, L., Rutherford, S., Palmer, D. S., Baker, M. J. & Butler, H. J. Bioprocess monitoring applications of an innovative ATR-FTIR spectroscopy platform. Front. Bioeng. Biotechnol. 12, 1349473 (2024).

    Google Scholar 

  28. Yu, S. et al. In vitro glucose measurement using tunable mid-infrared laser spectroscopy combined with fiber-optic sensor. Biomed. Opt. Express 5, 275–286 (2014).

    Google Scholar 

  29. Lu, R. et al. High-sensitivity infrared attenuated total reflectance sensors for in situ multicomponent detection of volatile organic compounds in water. Nat. Protoc. 11, 377–386 (2016).

    Google Scholar 

  30. Heise, H. M., Küpper, L. & Butvina, L. N. Mid-infrared attenuated total reflection spectroscopy of human stratum corneum using a silver halide fiber probe of square cross-section and adhesive tape stripping. J. Mol. Struct. 661, 381–389 (2003).

    Google Scholar 

  31. Basov, S., Dankner, Y., Weinstein, M., Katzir, A. & Platkov, M. Technical Note: noninvasive mid-IR fiber-optic evanescent wave spectroscopy (FEWS) for early detection of skin cancers. Med. Phys. 47, 5523–5530 (2020).

    Google Scholar 

  32. I. L. Jernelv, K. Strøm, D. R. Hjelme, A. Aksnes, Mid-infrared spectroscopy with a fiber-coupled tuneable quantum cascade laser for glucose sensing, in: Opt. Fibers Sens. Med. Diagn. Treat. Appl. XX, 105–113 (SPIE, 2020).

  33. Lee, T.-A., Xiao, Z., Burghoff, D. P. & Hutter, T. Mid-infrared spectroscopy on a fiber tip for molecular monitoring. Opt. Eng. 64, 076102 (2025).

    Google Scholar 

  34. Plyler, E. K. Infrared spectra of methanol, ethanol, and n-propanol. J. Res. Natl. Bur. Stand. 48, 281 (1952).

    Google Scholar 

  35. Max, J.-J.,Chapados, C. Glucose and fructose hydrates in aqueous solution by IR spectroscopy. J. Phys. Chem. A 111, 2679–2689 (2007).

  36. Goulden, J. D. S. Infra-red spectra of lactates in aqueous solution. Spectrochim. Acta 16, 715–720 (1960).

    Google Scholar 

  37. S. Delbeck, L. K. Iv, S. Delbeck, H. M. Heise, Applications of tapered flat silver halide fiber elements for infrared biospectroscopy with aspects of optical stability and biocompatibility, in: Opt. Fibers Sens. Med. Diagn. Treat. Appl. XVIII, 84–96 (SPIE, 2018).

  38. Holford, N. H. G. Clinical Pharmacokinetics of Ethanol. Clin. Pharmacokinet. 13, 273–292 (1987).

    Google Scholar 

  39. Franckson, J. R. M. et al. Glucose kinetics in human obesity. Diabetologia 2, 96–103 (1966).

    Google Scholar 

  40. Vincent, J.-L., Quintairos e Silva, A., Couto, L. & Taccone, F. S. The value of blood lactate kinetics in critically ill patients: a systematic review. Crit. Care 20, 257 (2016).

    Google Scholar 

  41. Kvitek, L. et al. Antibacterial activity and toxicity of silver – nanosilver versus ionic silver. J. Phys. Conf. Ser. 304, 012029 (2011).

    Google Scholar 

  42. Olszowy, H. A., Rossiter, J., Hegarty, J. & Geoghegan, P. Background levels of bromide in human blood. J. Anal. Toxicol. 22, 225–230 (1998).

    Google Scholar 

  43. Raut, S. K. et al. Chloride ions in health and disease. Biosci. Rep. 44, BSR20240029 (2024).

    Google Scholar 

  44. Lee, T.-A., Gonzales, R. & Hutter, T. Parametric study of a microdialysis probe and study of depletion effect using ethanol as a test analyte. Biochem. Biophys. Res. Commun. 637, 136–143 (2022).

    Google Scholar 

  45. Ren, J., Li, Z. & Wong, F.-S. A new method for the prediction of pore size distribution and MWCO of ultrafiltration membranes. J. Membr. Sci. 279, 558–569 (2006).

    Google Scholar 

  46. Abrahao, K. P., Salinas, A. G. & Lovinger, D. M. Alcohol and the brain: neuronal molecular targets, synapses, and circuits. Neuron 96, 1223–1238 (2017).

    Google Scholar 

  47. Weil, Z. M., Corrigan, J. D. & Karelina, K. Alcohol use disorder and traumatic brain injury. Alcohol Res. Curr. Rev. 39, 171–180 (2018).

    Google Scholar 

  48. Freund, G. Chronic central nervous system toxicity of alcohol. Annu. Rev. Pharmacol. Toxicol. 13, 217–227 (1973).

    Google Scholar 

  49. Zierler, K. Whole body glucose metabolism. Am. J. Physiol. Endocrinol. Metab. 276, E409–E426 (1999).

    Google Scholar 

  50. Tirone, T. A. & Brunicardi, F. C. Overview of glucose regulation. World J. Surg. 25, 461–467 (2001).

    Google Scholar 

  51. Jalloh, I. et al. Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings. Metab. Brain Dis. 30, 615–632 (2015).

    Google Scholar 

  52. Chandel, N. S. Glycolysis. Cold Spring Harb. Perspect. Biol. 13, a040535 (2021).

    Google Scholar 

  53. Phypers, B. & Pierce, J. T. Lactate physiology in health and disease. Contin. Educ. Anaesth. Crit. Care Pain. 6, 128–132 (2006).

    Google Scholar 

  54. de, R. S. et al. Intracellular shuttle: the lactate aerobic metabolism. Sci. World J. 2012, 420984 (2012).

    Google Scholar 

  55. Gattinoni, L. et al. Understanding lactatemia in human sepsis. potential impact for early management. Am. J. Respir. Crit. Care Med. 200, 582–589 (2019).

    Google Scholar 

  56. Masyuk, M. et al. Prognostic relevance of serum lactate kinetics in critically ill patients. Intensive Care Med. 45, 55–61 (2019).

    Google Scholar 

  57. Veech, R. L., Guynn, R. & Veloso, D. The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. Biochem. J. 127, 387–397 (1972).

    Google Scholar 

  58. Broskey, N. T., Zou, K., Dohm, G. L. & Houmard, J. A. Plasma lactate as a marker for metabolic health. Exerc. Sport Sci. Rev. 48, 119–124 (2020).

    Google Scholar 

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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.

Author information

Authors and Affiliations

  1. Walker Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX, USA

    Tse-Ang Lee & Tanya Hutter

  2. Materials Science and Engineering Program and Texas Materials Institute, The University of Texas at Austin, Austin, TX, USA

    Tanya Hutter

Authors
  1. Tse-Ang Lee
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  2. Tanya Hutter
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Contributions

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.

Corresponding author

Correspondence to Tanya Hutter.

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Competing interests

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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  • Received: 10 October 2025

  • Accepted: 23 February 2026

  • Published: 09 March 2026

  • DOI: https://doi.org/10.1038/s41467-026-70300-x

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