OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 4 — Apr. 1, 2012
  • pp: 667–680

Glucose sensing in human epidermis using mid-infrared photoacoustic detection

Jonas Kottmann, Julien M. Rey, Joachim Luginbühl, Ernst Reichmann, and Markus W. Sigrist  »View Author Affiliations

Biomedical Optics Express, Vol. 3, Issue 4, pp. 667-680 (2012)

View Full Text Article

Enhanced HTML    Acrobat PDF (1884 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



No reliable non-invasive glucose monitoring devices are currently available. We implemented a mid-infrared (MIR) photoacoustic (PA) setup to track glucose in vitro in deep epidermal layers, which represents a significant step towards non-invasive in vivo glucose measurements using MIR light. An external-cavity quantum-cascade laser (1010–1095 cm−1) and a PA cell of only 78 mm3 volume were employed to monitor glucose in epidermal skin. Skin samples are characterized by a high water content. Such samples investigated with an open-ended PA cell lead to varying conditions in the PA chamber (i.e., change of light absorption or relative humidity) and cause unstable signals. To circumvent variations in relative humidity and possible water condensation, the PA chamber was constantly ventilated by a 10 sccm N2 flow. By bringing the epidermal skin samples in contact with aqueous glucose solutions with different concentrations (i.e., 0.1–10 g/dl), the glucose concentration in the skin sample was varied through passive diffusion. The achieved detection limit for glucose in epidermal skin is 100 mg/dl (SNR=1). Although this lies within the human physiological range (30–500 mg/dl) further improvements are necessary to non-invasively monitor glucose levels of diabetes patients. Furthermore spectra of epidermal tissue with and without glucose content have been recorded with the tunable quantum-cascade laser, indicating that epidermal constituents do not impair glucose detection.

© 2012 OSA

OCIS Codes
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.6510) Medical optics and biotechnology : Spectroscopy, tissue diagnostics
(110.5125) Imaging systems : Photoacoustics
(140.5965) Lasers and laser optics : Semiconductor lasers, quantum cascade

ToC Category:
Noninvasive Optical Diagnostics

Original Manuscript: January 11, 2012
Revised Manuscript: February 16, 2012
Manuscript Accepted: February 17, 2012
Published: March 1, 2012

Jonas Kottmann, Julien M. Rey, Joachim Luginbühl, Ernst Reichmann, and Markus W. Sigrist, "Glucose sensing in human epidermis using mid-infrared photoacoustic detection," Biomed. Opt. Express 3, 667-680 (2012)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. WHO, “Diabetes,” http://www.who.int/mediacentre/factsheets/fs312/en/ .
  2. E. Renard, “Monitoring glycemic control: the importance of self-monitoring of blood glucose,” Am. J. Med.118, 12S–19S (2005). [CrossRef]
  3. C. E. F. do Amaral and B. Wolf, “Current development in non-invasive glucose monitoring,” Med. Eng. Phys.30, 541–549 (2008). [CrossRef]
  4. O. S. Khalil, “Spectroscopic and clinical aspects of noninvasive glucose measurements,” Clin. Chem.45, 165–177 (1999). [PubMed]
  5. O. S. Khalil, “Non-invasive glucose measurement technologies: An update from 1999 to the dawn of the millennium,” Diabetes Technol. Ther.6, 660–697 (2004). [CrossRef]
  6. R. J. McNichols and G. L. Coté, “Optical glucose sensing in biological fluids: an overview,” J. Biomed. Opt.5, 5–16 (2000). [CrossRef] [PubMed]
  7. C. Chou, C. Han, W. Kuo, Y. Huang, C. Feng, and J. Shyu, “Noninvasive glucose monitoring in vivo with an optical heterodyne polarimeter,” Appl. Opt.37, 3553–3557 (1998). [CrossRef]
  8. B. H. Malik, “Real-time, closed-loop dual-wavelength optical polarimetry for glucose monitoring,” J. Biomed. Opt.15, 017002 (2010). [CrossRef] [PubMed]
  9. A. M. K. Enejder, T. G. Scecina, J. Oh, M. Hunter, W. Shih, S. Sasic, G. L. Horowitz, and M. S. Feld, “Raman spectroscopy for noninvasive glucose measurements,” J. Biomed. Opt.10, 031114 (2005). [CrossRef] [PubMed]
  10. J. L. Lambert, C. C. Pelletier, and M. Borchert, “Glucose determination in human aqueous humor with Raman spectroscopy,” J. Biomed. Opt.10, 031110 (2005). [CrossRef] [PubMed]
  11. R. Marbach, T. Koschinsky, F. A. Gries, and H. M. Heise, “Noninvasive blood glucose assay by near-infrared diffuse reflectance spectroscopy of the human inner lip,” Appl. Spectrosc.47, 875–881 (1993). [CrossRef]
  12. K. Maruo, M. Tsurugi, M. Tamura, and Y. Ozaki, “In vivo noninvasive measurement of blood glucose by near-infrared diffuse-reflectance spectroscopy,” Appl. Spectrosc.57, 1236–1244 (2003). [CrossRef] [PubMed]
  13. C. Vrancic, A. Fomichova, N. Gretz, C. Herrmann, S. Neudecker, A. Pucci, and W. Petrich, “Continuous glucose monitoring by means of mid-infrared transmission laser spectroscopy in vitro,” Analyst136, 1192–1198 (2011). [CrossRef] [PubMed]
  14. I. Gabriely, R. Wozniak, M. Mevorach, J. Kaplan, Y. Aharon, and H. Shamoon, “Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia,” Diabetes Care22, 2026–2032 (1999). [CrossRef] [PubMed]
  15. G. Spanner and R. Niessner, “New concept for the non-invasive determination of physiological glucose concentrations using modulated laser diodes.” Fresenius J. Anal. Chem.355, 327–328 (1996).
  16. C. D. Malchoff, K. Shoukri, J. I. Landau, and J. M. Buchert, “A novel noninvasive blood glucose monitor,” Diabetes Care25, 2268–2275 (2002). [CrossRef] [PubMed]
  17. X. Guo, A. Mandelis, A. Matvienko, K. Sivagurunathan, and B. Zinman, “Wavelength-modulated differential laser photothermal radiometry for blood glucose measurements,” J. Phys. Conf. Ser.214, 012025 (2010). [CrossRef]
  18. R. Ballerstadt, C. Evans, A. Gowda, and R. McNichols, “In vivo performance evaluation of a transdermal near-infrared fluorescence resonance energy transfer affinity sensor for continuous glucose monitoring,” Diabetes Technol. Ther.8, 296–311 (2006). [CrossRef] [PubMed]
  19. W. March, D. Lazzaro, and S. Rastogi, “Fluorescent measurement in the non-invasice contact lens glucose sensor,” Diabetes Technol. Ther.8, 312–317 (2006). [CrossRef] [PubMed]
  20. J. Kottmann, J. M. Rey, and M. W. Sigrist, “New photoacoustic cell design for studying aqueous solutions and gels,” Rev. Sci. Instrum.82, 084903 (2011). [CrossRef] [PubMed]
  21. G. Spanner and R. Niessner, “Noninvasive determination of blood constituents using an array of modulated laser diodes and a photoacoustic sensor head.” Fresenius J. Anal. Chem.354, 306–310 (1996).
  22. Z. Zhao, “Pulsed photoacoustic techniques and glucose determination in human blood and tissue,” Ph.D. thesis (University of Oulu, 2002).
  23. K. H. Hazen, M. A. Arnold, and G. W. Small, “Measurement of glucose in water first-overtone near-infrared spectra,” Appl. Spectrosc.52, 1597–1605 (1998). [CrossRef]
  24. J. T. Olesberg, M. A. Arnold, C. Mermelstein, and J. Schmitz, “Tunable laser diode system for noninvasive blood glucose measutements.” Appl. Spectrosc.59, 1480–1484 (2005). [CrossRef]
  25. J. J. Burmeister and M. A. Arnold, “Evaluation of measurement sites for noninvasive blood glucose sensing with near-infrared transmission spectroscopy,” Clin. Chem.45, 1621–1627 (1999). [PubMed]
  26. A. Duncan, J. Hannigan, S. S. Freeborn, and H. A. MacKenzie, “A portable non-invasive blood glucose monitor,” in The 8th International Conference on Solid-State Sensors and Actuators, 1995 and Eurosensors IX. Transducers ’95 (1995), pp. 455–458. [CrossRef]
  27. H. Ashton, H. A. MacKenzie, P. Rae, Y. C. Shen, S. Spiers, and J. Lindberg, “Blood glucose measurements by photoacoustics,” in Proceedings of the 10th International Conference on Photoacoustic and Photothermal Phenomena, Vol. 463 of AIP Conference Proceedings (AIP, 1999), pp. 570–572. [PubMed]
  28. H. A. MacKenzie, H. Ashton, S. Spiers, and Y. Shen, “Advances in photoacoustic noninvasive glucose testing,” Clin. Chem.45, 1587–1595 (1999). [PubMed]
  29. K. M. Quan, G. B. Christison, H. A. MacKenzie, and P. Hodgson, “Glucose determinaton by a pulsed photoa-coustic techinque: an experimental study using a gelatin-based tissue phantom.” Phys. Med. Biol.38, 1911–1922 (1993). [CrossRef] [PubMed]
  30. H. D. Downing and D. Williams, “Optical constants of water in the infrared,” J. Geophys. Res.80, 1656–1661 (1975). [CrossRef]
  31. F. A. DuckPhysical Properties of Tissue (Academic, London, 1990).
  32. S. Gebhart, M. Faupel, R. Fowler, C. Kapsner, D. Lincoln, V. McGee, J. Pasqua, L. Steed, M. Wangsness, F. Xu, and M. Vanstory, “Glucose sensing in transdermal body fluid collected under continuous vacuum pressure via micropores in the stratum corneum,” Diabetes Technol. Ther.5, 159–166 (2003). [CrossRef] [PubMed]
  33. M. Venugopal, K. E. Feuvrel, D. Mongin, and , “Clinical evaluation of a novel interstitial fluid sensor system for remote continuous alcohol monitoring.” IEEE Sensors J.8, 71–80 (2008). [CrossRef]
  34. Y. Huang, J. Fang, P. Wu, T. Chen, M. Tsai, and Y. Tsai, “Noninvasive glucose monitoring by back diffusion via skin: chemical and physical enhancements,” Biol. Pharm. Bull.26, 983–987 (2003). [CrossRef] [PubMed]
  35. W. Groenendaal, K. A. Schmidt, G. von Basum, N. A. W. van Riel, and P. A. J. Hilbers, “Modeling glucose and water dynamics in human skin,” Diabetes Technol. Ther.10, 283–293 (2008). [CrossRef] [PubMed]
  36. P. Garidel, “Mid-FTIR-microspectroscopy of stratum corneum single cells and stratum corneum tissue,” Phys. Chem. Chem. Phys.4, 5671–5677 (2002). [CrossRef]
  37. K. C. Madison, “Barrier function of the skin: ”La raison d’être” of the epidermis,” J. Invest. Dermatol.121, 231–241 (2003). [CrossRef] [PubMed]
  38. R. Vonach, “Application of mid-infrared transmission spectrometry to the direct determination of glucose in whole blood,” Appl. Spectrosc.52, 820–822 (1998). [CrossRef]
  39. M. Brandstetter, A. Genner, K. Anic, and B. Lendl, “Tunable external cavity quantum cascade laser for simultaneous determination of glucose and lactate in aqueous phase,” Analyst135, 3260–3265 (2010). [CrossRef] [PubMed]
  40. G. B. Christison and H. A. MacKenzie, “Laser photoacoustic determination of physiological glucose concentrations in human whole blood,” Med. Biol. Eng. Comput.31, 284–290 (1993). [CrossRef] [PubMed]
  41. H. von Lilienfeld-Toal, M. Weidenmüller, A. Xhelaj, and W. Mäntele, “A novel approch to non-invasive glucose measurement by mid-infrared spectroscopy: The combination of quantum cascade lasers (QCL) and photoacoustic detection,” Vib. Spectrosc.38, 209–215 (2005). [CrossRef]
  42. M. Pleitez, H. von Lilienfeld-Toal, and W. Mäntele, “Infrared spectroscopic analysis of human interstitial fluid in vitro and in vivo using FT-IR spectroscopy and pulsed quantum cascade lasers (QCL): Establishing a new approach to non invasive glucose measurement,” Spectrochim. Acta A85, 61–65 (2012). [CrossRef]
  43. A. Rosencwaig and A. Gersho, “Theory of photoacoustic effect with solids,” J. Appl. Phys.47, 64–69 (1976). [CrossRef]
  44. A. C. Tam, “Applications of photoacoustic sensing techniques,” Rev. Mod. Phys.58, 381–431 (1986). [CrossRef]
  45. J. Kottmann, J. M. Rey, and M. W. Sigrist, “New photoacoustic cell with diamond window for mid-infrared investigations on biological samples,” Proc. SPIE8223, 8223–44 (2012).
  46. H. Günzler and H. U. Gremlich, IR-Spektroskopie (Wiley-VCH, 2003).
  47. R. W. Barry, H. G. M. Edwards, and A. C. Williams, “Fourier transform Raman and infrared vibrational study of human skin: Assignment of spectral bands,” J. Raman Spectrosc.23, 641–645 (1992). [CrossRef]
  48. G. W. Lucassen, G. N. A. van Veen, and J. A. J. Jansen, “Band analysis of hydrated human skin stratum corneum attenuated total reflectance fourier transform infrared spectra in vivo,” J. Biomed. Opt.3, 267–280 (1998). [CrossRef]
  49. R. O. Potts, B. G. Guzek, R. R. Harris, and J. E. McKie, “A noninvasive, in vivo technique to quantitatively measure water concentration of the stratum corneum using attenuated total-reflectance Infrared spectroscopy,” Arch. Dermatol. Res.277, 489–495 (1985). [CrossRef] [PubMed]
  50. M. Gloor, G. Hirsch, and U. Willebrand, “On the use of infrared spectroscopy for the in vivo measurement of the water content of the horny layer after application of dermatologic Ointments,” Arch. Dermatol. Res.271, 305–313 (1981). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited