Journal of Fluorescence

, Volume 14, Issue 5, pp 513–520 | Cite as

Current Problems and Potential Techniques in In Vivo Glucose Monitoring



Accurate in vivo monitoring of glucose concentration would be a valuable asset, particularly for management of diabetes and preterm infants during critical care. In vivo glucose monitoring devices can be divided into two categories: implanted and non-invasive. Extensive research into in vivo glucose monitoring over recent decades has not resulted in the widespread use of clinically reliable monitoring systems. For implanted devices, poor biocompatibility of the materials used for fabrication remains a major challenge, whilst progress in the commercial development of non-invasive devices is hampered by the problem of multiple interference between the detected signals and the biological components. In this review, the methods available for in in-vivo glucose monitoring are described and the associated problems are discussed.

Glucose sensor in vivo monitoring non-invasive implantable transducers biocompatibility 


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  1. 1.
    The Diabetes Control and Complications Trial Research Group (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. N. Eng. J. Med. 329(14), 977–986.Google Scholar
  2. 2.
    J. Mastrototaro (1999). The MiniMed Continuous Glucose Monitoring System (CGMS). J. Pediatr. Endocrinol. Metab. 12(Suppl. 3), 751–758.Google Scholar
  3. 3.
    C. Kapitza, V. Logwig, K. Obermaier, K. J. Wienjes, K. Hoogenberg, and L. Heinemann (2003). Continuous glucose monitoring: Reliable measurements for up to 4 days with the SCGM1 system. Diabetes Technol. Ther. 5(4), 609–614.Google Scholar
  4. 4.
    C. Morgan, S. J. Newell, D. A. Ducker, J. Hodgkinson, D. K. White, C. J. Morley, and J. M. Church (1999). Continuous neonatal blood gas monitoring using a multiparameter intra-arterial sensor. Arch.Dis. Child. 80(2), F93–F98.Google Scholar
  5. 5.
    M. E. Collison and M. E. Meyerhoff (1990). Chemical sensors for bedside monitoring of critically ill patients. Anal. Chem. 62(7), 425A–437A.Google Scholar
  6. 6.
    M. E. Meyerhoff (1990). New in vitro analytical approaches for clinical chemistry measurements in critical care. Clin. Chem. 36(2), 1567–1572.Google Scholar
  7. 7.
    L. C. Clark and C. Lyons (1962). Electrode systems for continuous monitoring in cardiovascular system. Ann. N.Y. Acad. Sci. 102, 29–45.Google Scholar
  8. 8.
    S. J. Updike, M. C. Shults, R. K. Rhodes, B. J. Gilligan, J. O. Luebow, and D. von Heimburg (1994). Enzymatic glucose sensors. Improved long-term performance in vitro and in vivo. TIASAIO J. 40(2), 157–163.Google Scholar
  9. 9.
    M. E. Meyerhoff (1993). In vivo blood gas and electrolyte sensors: Progress and challenges. Trac-Trend. Anal. Chem. 12(2), 257–266.Google Scholar
  10. 10.
    D. S. Bindra, Y. Zhang, G. S. D. Wilson, R. Sternberg, D. R. Thevenot, D. Moatti, and G. Reach (1991).Design and in vitro studies of a needle-type glucose sensor for subscutaneous monitoring.Anal. Chem.63(17),1692–1696.Google Scholar
  11. 11.
    Q. Yang, P. Atanasov, and E. Wilkins (1997). A needle-type sensor for monitoring glucose in whole blood. Biomed. Instrum. Technol. 31(1), 54–62.Google Scholar
  12. 12.
    C. Meyerhoff, F. Bischof, F. Sternberg, H. Zier, and E. F. Pfeiffer (1992). On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis. Diabetologia 35(11), 1087–1092.Google Scholar
  13. 13.
    A. Maran, C. Crepaldi, A. Tiengo, G. Grassi, E. Vitali, G. Pagano, S. Bistoni, G. Calabrese, F. Santeusanio, F. Leonetti, M. Ribaudo, U. Di Mario, G. Annuzzi, S. Genovese, G. Riccardi, M. Previti, D. Cucinotta, F. Giorgino, A. Bellomo, R. Giorgino, A. Poscia, and M. Varalli (2002). Continuous subcutaneous glucose monitoring in diabetic patients: A multicenter analysis. Diabetes Care. 25(2), 347–352.Google Scholar
  14. 14.
    L. Heinemann (2003). Continuous glucose monitoring by means of the microdialysis technique: Underlying fundamental aspects. Diabetes Technol. Ther. 5(4), 545–561.Google Scholar
  15. 15.
    J. Pickup (2000). Sensitive glucose sensing in diabetes. Lancet 355(9202), 426–427.Google Scholar
  16. 16.
    M. S. Boyne, D. M. Silver, J. Kaplan, and C. D. Saudek (2003). Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor. Diabetes 52(11), 2790–2794.Google Scholar
  17. 17.
    M. A. Arnold (1996). Non-invasive glucose monitoring. Curr. Opin. Biotech. 7(1), 46–49.PubMedGoogle Scholar
  18. 18.
    S. Nicklin, I. A. A. Hassan, Y. Wickramasinghe, and S. A. Spencer (2003). The light still shines, but not that brightly? The current status of perinatal near infrared spectroscopy. Arch. Dis. Child. 88(4), F263–F268.Google Scholar
  19. 19.
    J. Pickup, L. McCartney, O. Rolinski, and D. Birch (1999). In vivo glucose sensing for diabetes management: Progress towards noninvasive monitoring. TIBMJ 319(7220), 1289–1300.Google Scholar
  20. 20.
    J. S. Schultz, S. Mansouri, and I. J. Goldstein (1982). Affinity sensor: A new technique for developing implantable sensors for glucose and other metabolites. Diabetes Care 5(3), 245–253.Google Scholar
  21. 21.
    R. Ballerstadt and J. S. Schultz (2002). Affinity sensor: A new technique for developing implantable sensors for glucose and other metabolites. Anal. Chem. 72(12), 4185–4192.CrossRefGoogle Scholar
  22. 22.
    R. Ballerstadt, A. Polak, A. Beuhler, and J. Frye (2004). In vitro long-term performance study of a near-infrared fluorescence affinity sensor for glucose monitoring. Biosens. Bioelectron. 19(8), 905–914.CrossRefPubMedGoogle Scholar
  23. 23.
    D. Meadows and J. S. Schultz (1988). Fibre-optic biosensors based on fluorescence energy transfer. Talanta 35(2), 145–150.CrossRefGoogle Scholar
  24. 24.
    O. J. Rolinski, D. J. S. Birch, L. J. McCartney, and J. C. Pickup (2000). A time-resolved near-infrared fluorescence assay for glucose: Opportunities for trans-dermal sensing. J. Photochem. Photobiol. B: Biol. 54(1), 26–34.Google Scholar
  25. 25.
    K. Ye and J. S. Schultz (2003). Genetic engineering of an allosterically based glucose indicator protein for continuous glucose monitoring by fluorescence resonance energy transfer. Anal. Chem. 75(14), 3119–3127.Google Scholar
  26. 26.
    J. R. Lakowicz and H. Szmacinski (1993). Fluorescence lifetimebased sensing of pH, Ca2+, K+ and glucose. Sens. Actuators B 11(1-3), 133–143.CrossRefGoogle Scholar
  27. 27.
    M. E. Lippitsch, S. Draxler, and D. Kieslinger (1997). Luminescence lifetime-based sensing: New materials, new devices. Sens. Actuators B 38/39(1-3), 96–102.CrossRefGoogle Scholar
  28. 28.
    A. Caduff, E. Hirt, Y. Feldman, Z. Ali, and L. Heinemann (2003). First human experiments with a novel non-invasive, non-optical continuous glucose monitoring system. Biosens. Bioelectron. 19(3), 209–217.CrossRefPubMedGoogle Scholar
  29. 29.
    M. Scheffler, E. Hirt, and A. Caduff (2003). Wrist-wearable medical devices: Technologies and applications. Med. Device Technol. 14(7),26–30.Google Scholar
  30. 30.
    H.-I. Seo, C.-S. Kim, T. Yeow, M.-T. Son, and M. Hasard (1997). ISFET glucose sensor based on a newprinciple using the electrolysis of hydrogen peroxide. Sens. Actuators B 40(1), 1–5.CrossRefGoogle Scholar
  31. 31.
    K.-Y. Park, S.-B. Choi, M. Lee, B.-K. Sohn, and S.-Y. Choi (2002).ISFET glucose sensor system with fast recovery characteristics by employing electrolysis.Sens. Actuators B 83(1-3),90–97.Google Scholar
  32. 32.
    N. Sekkat, A. Naik, Y. N. Kalia, P. Glikfeld, and R. H. Guy (2002). Reverse iontophoretic monitoring in premature neonates: Feasibility and potential. J. Control Release 81(1/2), 83–89.CrossRefPubMedGoogle Scholar
  33. 33.
    J. A. Tamada, N. J. V. Bohannon, and R. O. Potts (1995). Measurement of glucose in diabetic subjects using nonivasive transdermal extraction. Nat. Med. 1(11), 1198–1201.Google Scholar
  34. 34.
    R. O. Potts, J. A. Tamada, and M. J. Tierney (2002). Glucose monitoring by reverse iontophoresis. Diabetes Metab. Res. Rev. 18(Suppl. 1), S49–S53.CrossRefPubMedGoogle Scholar
  35. 35.
    K. M. Quan, G. B. Christison, H. A. MacKenzie, and P. Hodgson (1993). Glucose determination by a pulsed photoacoustic technique: An experimental study using a gelatine-based tissue phantom. Phys. Med. Biol. 38(12), 1911–1922.PubMedGoogle Scholar
  36. 36.
    H. A. MacKenzie, H. S. Ashton, S. Spiers, Y. Shen, S. S. Freeborn, J. Hannigan, J. Lindberg, and P. Rae (1999). Advances in photoacoustic noninvasive glucose testing. Clin. Chem. 45(9), 1587–1595.PubMedGoogle Scholar
  37. 37.
    A. Kadish (1964). Automation control of blood glucose: A servo mechanism for glucose monitoring and control. Am. J. Med. Electron. 3, 82–86.Google Scholar
  38. 38.
    S. J. Updike and G. P. Hicks (1967). The enzyme electrode. Nature 214, 986–988.Google Scholar
  39. 39.
    T. Yao and K. Takashima (1998). Amperometric biosensor with a composite membrane of sol-gel derived enzyme film and electrochemically generated poly(1,2-diaminobenzene) film. Biosens. Bioelectron. 13(1), 67–73.CrossRefPubMedGoogle Scholar
  40. 40.
    J.Wu, J. Suls, and W. Sansen (1999). Ameperometric glucose sensor with enzyme covalently immobilized by sol-gel technology. Anal. Sci. 15(10), 1029–1032.Google Scholar
  41. 41.
    A. Kros, M. Gerritsen, V. S. J. Sprakel, N. A. J. M. Sommerdijk, J. A. Jansen, and J. M. Nolte (2001). Silica-based hybrid materials as biocompatible coatings for glucose sensors. Sens. Actuators B 81(1), 68–75.CrossRefGoogle Scholar
  42. 42.
    X. H. Chen, N. Matasumoto, Y. B. Hu, and G. S. Wilson (2002). Electrochemically mediated electrodeposition/electropolymerization to yield a glucose microbiosensor with improved characteristics. Anal. Chem. 74(2), 368–372.CrossRefPubMedGoogle Scholar
  43. 43.
    M. Jablecki and D. A. Gough (2002). Simulations of the frequency response of implantable glucose sensors. Anal. Chem. 72(8), 1853–1859.CrossRefGoogle Scholar
  44. 44.
    D. Chapman (1993). Biocompatible surfaces based upon the phospholipids asymmetry of biomembranes. Biochem. Soc. Trans. 21(2), 258–262.PubMedGoogle Scholar
  45. 45.
    N. Nakabayashi and D. F. Williams (2003). Preparation of nonthrombogenic materials using 2-methacryloyloxyethyl phosphorylcholine. Biomaterials 24(13), 2431–2435.PubMedGoogle Scholar
  46. 46.
    K. Ishihara, T. Ueda, and N. Nakabayashi (1990). Preparation of phospholipid polymers and their properties as polymer hydrogel membranes. Polymer J. 22(5), 355–360Google Scholar
  47. 47.
    Y. Yang, S. F. Zhang, M. K. Kingston, G. Jones, G. Wright, and S. A. Spencer (2002).Glucose sensor with improved haemocompatibilty.Biosens. Bioelectron. 15(5/6),221–227CrossRefGoogle Scholar
  48. 48.
    C. Y. Chen, Y. C. Su, K. Ishihara, N. Nakabayashi, E. Tamiya, and I. Karibe (1993). Biocompatible needle-type glucose sensor with potential for use in vivo. Electroanalysis 5(4), 269–276.Google Scholar
  49. 49.
    S. F. Zhang, Y. A. B. D. Wickramasinghe, and P. Rolfe (1996). Investigation of an optical fibre pH sensor with the membrane based on phospholipid copolymer. Biosens. Bioelectron. 11(1/2), 11–16.CrossRefGoogle Scholar
  50. 50.
    S. Zhang, G. Wright, M. A. Kingston, and P. Rolf (1996). Improved performance of intravascular pO(2) sensor incorporating poly(MPCco-BMA) membrane. Med. Biol. Eng. Comput. 34(4), 313–315.PubMedGoogle Scholar
  51. 51.
    W. Sharp, D. Gardner, and G. Anderson (1966). A Bioelectric polyurethane elastomer for intravascular replacement. Trans. Am. Soc. Artif. Intern. Organs. 12, 179–183.Google Scholar
  52. 52.
    M. C. Frost, M. M. Batchelor, Y. Lee, H. Zhang, Y. Kang, Oh B, G. S. Wilson, R. Gifford, S. M. Rudich, and M. E. Meyerhoff (2003). Preparation and characterization of implantable sensors with nitric oxide release coating. Microchem. J. 74(3), 277–288.Google Scholar
  53. 53.
    J.W. Moses, M. B. Leon, J. J. Popma, P. J. Fitzgerald, D. R. Holmes, C. O'Shaughnessy, R. P. Caputo, D. J. Kereiakes, D. O. Williams, P. S. Teirstein, J. L. Jaeger, and R. E. Kuntz (2003). Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med. 349(14), 1315–1323.CrossRefPubMedGoogle Scholar
  54. 54.
    M. Degertekin, E. Regar, K. Tanabe, P. Lemos, C. H. Lee, P. Smits, P. de Feyter, N. Bruining, E. Sousa, A. Abizaid, J. Ligthart, and P.W. Serruys (2003). Evaluation of coronary remodeling after sirolimuseluting stent implantation by serial three-dimensional intravascular ultrasound. Am. J. Cardiol. 91(9), 1046–1050.CrossRefPubMedGoogle Scholar
  55. 55.
    V. Lodwig and L. Heinemann (2003). Continuous glucose monitoring with glucose sensors: Calibration and assessment criteria. Diabetes Technol. Ther. 5, 527–586.CrossRefGoogle Scholar
  56. 56.
    L. Heinemann and R. G. Schmelzeise (1998). Non-invasive continuous glucose monitoring in type I diabetic patients with optical glucose sensors. Diabetologia 41(7), 848–854.CrossRefPubMedGoogle Scholar
  57. 57.
    R. Badugu, J. R. Lakowicz, and C. D. Geddes (2003). A glucose sensing contact lens: A non-invasive technique for continuous physiological glucose monitoring. J. Fluorescence 13(5), 371–374.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  1. 1.Centre for Science and Technology in Medicine, School of MedicineKeele University/University Hospital of North StaffordshireStoke-on-TrentUnited Kingdom
  2. 2.University Hospital of North StaffordshireStoke-on-TrentUnited Kingdom

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