Skip to main content
SpringerLink
Log in

Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review

  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

We have developed a range of disposable and colorless tear glucose sensing contact lenses, using off-the-shelf lenses embedded with new water soluble, highly fluorescent and glucose sensitive boronic acid containing fluorophores. The new lenses are readily able to track tear glucose levels and therefore blood glucose levels, which are ideally suited for potential use by diabetics. The fluorescence responses from the lenses can be monitored using simple excitation and emission detection devices. The novelty of our approach is two fold. Firstly, the notion of sensing extremely low glucose concentrations in tears, which track blood levels, by our contact lens approach, and secondly, the unique compatibility of our new glucose signaling probes with the internal mildly acidic contact lens environment. The new lenses are therefore ideal for the non-invasive and continuous monitoring of tear glucose, with about 15-min response time, and a measured shelf life in excess of 3 months. In this review article, we show that fluorescence based signaling using plastic disposable lenses, which have already been industrially optimized with regard to vision correction and oxygen/analyte permeability etc, may a notable alternative to invasive and random finger pricking, the most widely used glucose monitoring technology by diabetics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Leonid Poretsky (Ed.) (2002). Principles of Diabetes Mellitus, Kluwer Academic/Plenum, Norwell, MA.

    Google Scholar 

  2. V. C. Medvei (1993). In The History of Clinical Endocrinology: A Comprehensive Account of Endocrinology from Earliest Times to Present Day, Parthenon, New York.

    Google Scholar 

  3. M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, and P. L. Robinson (1992). Non-invasive glucose monitoring in diabetic patients: A preliminary evaluation. Clin. Chem. 38, 1618–1622.

    Google Scholar 

  4. H. M. Heise, R. Marbach, T. H. Koschinsky, and F. A. Gries (1994). Non-invasive blood glucose sensors based on near-infrared spectroscopy. Ann. Occup. Hyg. 18, 439–447.

    Google Scholar 

  5. W. F. March, B. Rabinovitch, R. Adams, J. R. Wise, and M. Melton (1982). Ocular Glucose sensor. Trans. Am. Soc. Artif. Intern. Organs 28, 232–235.

    Google Scholar 

  6. B. Rabinovitch, W. F. March, and R. L. Adams (1982).Non-invasive glucose monitoring of the aqueous humor of the eye, Part 1: Measurement of very small optical rotations.Diabetes Care 5,254–258.

    Google Scholar 

  7. G. M. Schier, R. G. Moses, I. E. T. Gan, and S. C. Blair (1988). An evaluation and comparison of reflolux Iiand Glucometer II, two new portable reflectance meters for capillary blood glucose determination. Diabetes Res. Clin. Pract. 4, 177–181.

    Google Scholar 

  8. W. Clarke, D. J. Becker, D. Cox, J. V. Santiago, N. H. White, J. Betschart, K. Eckenrode, L. A. Levandoski, E. A. Prusinki, L. M. Simineiro, A. L. Snyder, A. M. Tideman, and T. Yaegar (1988). Evaluation of a new system for self blood glucose monitoring. Diabetes Res. Clin. Pract. 4, 209–214.

    Google Scholar 

  9. W. Trettnak and O. S. Wolfbeis (1989). Fully reversible fiberoptic glucose biosensor based on the intrinsic fluorescence of glucose-oxidase. Anal. Chim. Acta 221, 195–203.

    Google Scholar 

  10. D. Meadows and J. S. Schultz (1988). Fiber optic biosensor based on fluorescence energy transfer. Talanta 35, 145–150.

    Article  Google Scholar 

  11. L. Tolosa, H. Malak, G. Rao, and J. R. Lakowicz (1997). Optical assay for glucose based on the luminescence decay time of the long wavelength dye Cy5. Sens. Actuators B 45, 93–99.

    Google Scholar 

  12. L. Tolosa, I. Gryczynski, L. R. Eichorn, J. D. Dattelbaum, F. N. Castellano, G. Rao, and J. R. Lakowicz (1999). Glucose sensors for low cost lifetime-based sensing using a genetically engineered protein. Anal. Biochem. 267, 114–120.

    PubMed  Google Scholar 

  13. S. D'Auria, N. Dicesare, Z. Gryczynski, I. Gryczynski, M. Rossi, and J. R. Lakowicz (2000). A thermophilic apoglucose dehydrogenase as a nonconsuming glucose sensor. Biochem. Biophys. Res. Commun. 274, 727–731.

    Google Scholar 

  14. R. Badugu, J. R. Lakowicz, and C. D. Geddes (2004). The noninvasive continuous monitoring of physiological glucose using a novel monosaccharide-sensing contact lens. Anal. Chem. 76, 610–618.

    Google Scholar 

  15. 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, 371–374.

    Google Scholar 

  16. C. D. Geddes, R. Badugu, and J. R. Lakowicz (2004). Contactlenses may provide window to blood glucose. Biophotoincs int. February(2), 50–53.

  17. R. Badugu, J. R. Lakowicz, and C. D. Geddes (2004). Ophthalmic glucose sensing: A novel monosaccharide sensing disposable and colorless contact lens. The Analyst 129, 516–521.

    Google Scholar 

  18. J. M. Sugihara and C. M. Bowman (1958). Cyclic benzeneboronate esters.J. Am. Chem. Soc. 80(10), 2443–2446.

    Google Scholar 

  19. J. P. Lorand and J. O. Edwards (1959). Polyol complexes and structure of the benzeneboronate ion. J. Org. Chem. 24(6), 769–774.

    Google Scholar 

  20. G. Springsteen and B. Wang (2002). A detailed examination of boronic acid-diol complexation. Tetrahedron 58(26), 5291–5300.

    Google Scholar 

  21. T. D. James, K. R. A. S. Sandanayake, and S. Shinkai (1995). Chiral discrimination of monosaccharides using a fluorescent molecular sensor. Nature 374, 345.

    Google Scholar 

  22. J. C. Norrild and H. Eggert (1995). Evidence for monodentate and bidentate boronate complexes of glucose in the furanose form-Application of (1)J(C-C)-coupling-constants as a structural probe. J. Am. Chem. Soc. 117(5), 1479–1484.

    Google Scholar 

  23. H. Eggert, J. Frederiksen, C. Morin, and J. C. Norrild (1999).A new glucose-selective fluorescent bisboronic acid. First report of strong alpha-furanose complexation in aqueous solution at physiological pH.J. Org. Chem. 64(11),3846–3852.

    Article  Google Scholar 

  24. W. Yang, H. He, and D. G. Drueckhammer (2001). Computerguided design in molecular recognition: Design and synthesis of a glucopyranose receptor. Angew. Chem. Int. Ed. 40(9), 1714–1718.

    Article  Google Scholar 

  25. W.Wang, S. Gao, and B.Wang (1999). Building fluorescent sensors by template polymerization: The preparation of a fluorescent sensor for D-fructose. Org. Lett., 1(8), 1209–1212.

    Google Scholar 

  26. S. Gao, W.Wang, and B.Wang (2001). Building fluorescent sensors for carbohydrates using template-directed polymerizations. Bioorg. Chem. 29, 308–320.

    Google Scholar 

  27. J. J. Lavigne and E. V. Anslyn (1999). Teaching old indicators new tricks: A colorimetric chemosensing ensemble for tartrate/malate in beverages. Angew. Chem. Int. Ed. 38(24), 3666–3669.

    Google Scholar 

  28. J. Yoon and A. W. Czarnik (1992). Fluorescent chemosensors of carbohydrates. A means of chemically communicating the binding of polyols in water based on chelation-enhanced quenching. J. Am. Chem. Soc. 114, 5874–5875.

    Google Scholar 

  29. B. D. Smith, S. J. Gardiner, T. A. Munro, M. F. Paugam, and J. A. Riggs (1998). Facilitated transport of carbohydrates, catecholamines, and amino acids through liquid and plasticized organic membranes. J. Incl. Phenom. Mol. Recogn. Chem. 32, 121–131.

    Google Scholar 

  30. S. Soundararajan, M. Badawi, C. M. Kohlrust, and J. H. Hagerman (1989). Boronic acids for affinity-chromatography-spectral methods for determinations of ionization and diol-binding constants. Anal. Biochem. 178, 125–134.

    PubMed  Google Scholar 

  31. T. D. James, K. R. A. S., and S. Shinkai (1994). A glucose-selective molecular fluorescence sensor. Angew, Chem. Int. Ed. 33(21), 2207–2209.

    Google Scholar 

  32. T. D. James, K. R. A. S. Sandanayake, R. Iguchi, and S. Shinkai (1995). Novel saccharide-photoinduced electron-transfer sensors based on the interaction of boronic acid and amine. J. Am. Chem. Soc. 117(35), 8982–8987.

    Google Scholar 

  33. N. Dicesare and J. R. Lakowicz (2001). Evaluation of two synthetic glucose probes for fluorescence-lifetime based sensing. Anal. Biochem. 294, 154–160.

    Google Scholar 

  34. N. Dicesare and J. R. Lakowicz (2001). Wavelength-ratiometric probes for saccharides based on donor-acceptor diphenylpolyenes. J. Photochem. Photobiol. A: Chem. 143, 39–47.

    Article  Google Scholar 

  35. N. Dicesare and J. R. Lakowicz (2001). New color chemosensors for monosaccharides based on Azo dyes. Org. Lett. 3(24), 3891–3893.

    Article  PubMed  Google Scholar 

  36. N. Dicesare and J. R. Lakowicz (2002). Chalcone-analogue fluorescent probes for saccharides signaling using the boronic acid group. Tet. Lett. 43, 2615–2618.

    Article  Google Scholar 

  37. . V.V. Karnati, X. Gao, S. Gao, W.Yang, W. Ni, S. Sankar, and B.Wang (2002). A glucose-selective fluorescence sensor based on boronic acid-diol recognition. Bioorg. Med. Chem. Lett. 12, 3373–3377.

    Article  Google Scholar 

  38. N. Dicesare and J. R. Lakowicz (2002). Charge transfer fluorescent probes using boronic acids for monosaccharide signaling. J. Biomed. Opt. 7(4), 538–545.

    Article  Google Scholar 

  39. R. Badugu, J. R. Lakowicz, and C. D. Geddes (manuscript submitted for publication). Fluorescence sensors for monosaccharides based on the 6-methylquinolinium nucleus and boronic acid moiety: Application to ophthalmic diagnostics. Talanta.

  40. R. Badugu, J. R. Lakowicz, and C. D. Geddes (manuscript submitted for publication). Boronic acid fluorescent sensors for monosaccharide signaling based on the 6-methoxyquinolinium heterocyclic nucleus: Progress towards noninvasive and continuous glucose monitoring. Bioorg. Med. Chem.

  41. J. R. Lakowicz (1997). Principles of Fluorescence Spectroscopy 2nd ed., Kluwer/Academic Plenum, New York.

    Google Scholar 

  42. N. J. Turro, B. H. Baretz, and P. I. Kuo (1984). Photoluminescence probes for the investigation of interactions between sodium dodecylsulfate and water-soluble polymers. Macromolecules 17(7), 1321–1324.

    Google Scholar 

  43. K. Kalyanasundaram and J. K. Thomas (1977). Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems.J. Am. Chem. Soc. 99(7), 2039–2044.

    Google Scholar 

  44. N. Dicesare and J. R. Lakowicz (2001). Spectral properties of fluorophores combining the boronic acid group with electron donor or withdrawing groups. Implication in the development of fluorescence probes for saccharides. J. Phys. Chem. A 105(28), 6834–6840.

    Article  Google Scholar 

  45. C. D. Geddes (2001). Optical halide sensing using fluorescence quenching: Theory, simulations and applications-A review. Meas. Sci. Tech. 12(9), R53.

    Article  Google Scholar 

  46. O. S. Wolfbeis and E. Urbano (1982). J. Heterocyclic Chem. 19, 841–843.

    Google Scholar 

  47. C. D. Geddes, K. Apperson, J. Karolin, and D. J. S. Birch (2001). Chloride sensitive probes for biological applications. Dyes Pigments 48, 227–231.

    Article  Google Scholar 

  48. M. A. Fox and M. Chanon (Eds.) (1998). Photoinduced Electron Transfer Parts A-D, Elsevier, New York.

    Google Scholar 

  49. G. J. Kavarnos (1993). Fundamentals of Photoinduced Electron Transfer VCH, New York.

    Google Scholar 

  50. N. J. Van Haeringen (1981). Climical biochemistry in tears. SurveyOphthalmol. 26(2), 84–96

    Article  Google Scholar 

  51. N. Chandrasekharan and L. Kelly (2004). in C. D. Geddes and J. R. Lakowicz (Eds.), Reviews in Fluorescence 2003, Kluwer Academic/Plenum, New York.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Center for Fluorescence Spectroscopy, Medical Biotechnology Center, University of Maryland School of Medicine, Baltimore, Maryland

    Ramachandram Badugu, Joseph R. Lakowicz & Chris D. Geddes

Authors
  1. Ramachandram Badugu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph R. Lakowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chris D. Geddes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph R. Lakowicz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Badugu, R., Lakowicz, J.R. & Geddes, C.D. Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review. Journal of Fluorescence 14, 617–633 (2004). https://doi.org/10.1023/B:JOFL.0000039349.89929.da

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:JOFL.0000039349.89929.da

Search

Navigation