Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration.

An amperometric needle-type electrochemical glucose sensor intended for tear glucose measurements is described and employed in conjunction with a 0.84 mm i.d. capillary tube to collect microliter volumes of tear fluid. The sensor is based on immobilizing glucose oxidase on a 0.25 mm o.d. platinum/iridium (Pt/Ir) wire and anodically detecting the liberated hydrogen peroxide from the enzymatic reaction. Inner layers of Nafion and an electropolymerized film of 1,3-diaminobenzene/resorcinol greatly enhance the selectivity for glucose over potential interferences in tear fluid, including ascorbic acid and uric acid. Further, the new sensor is optimized to achieve very low detection limits of 1.5 ± 0.4 μM of glucose (S/N = 3) that is required to monitor glucose levels in tear fluid with a glucose sensitivity of 0.032 ± 0.02 nA/μM (n = 6). Only 4-5 μL of tear fluid in the capillary tube is required when the needle sensor is inserted into the capillary. The glucose sensor was employed to measure tear glucose levels in anesthetized rabbits over an 8 h period while also measuring the blood glucose values. A strong correlation between tear and blood glucose levels was found, suggesting that measurement of tear glucose is a potential noninvasive substitute for blood glucose measurements, and the new sensor configuration could aid in conducting further research in this direction.

[1]  Hiroyuki Kudo,et al.  A soft and flexible biosensor using a phospholipid polymer for continuous glucose monitoring , 2009, Biomedical microdevices.

[2]  Alexander M. Yacynych,et al.  Electropolymerized films to prevent interferences and electrode fouling in biosensors , 1991 .

[3]  J. Jakubowski,et al.  Acute Hyperglycemia Induced by Ketamine/Xylazine Anesthesia in Rats: Mechanisms and Implications for Preclinical Models , 2005, Experimental biology and medicine.

[4]  C. D. Geddes,et al.  Fluorescence sensors for monosaccharides based on the 6-methylquinolinium nucleus and boronic acid moiety: potential application to ophthalmic diagnostics. , 2005, Talanta.

[5]  D K Sen,et al.  Tear glucose levels in normal people and in diabetic patients. , 1980, The British journal of ophthalmology.

[6]  Justin T. Baca,et al.  Mass spectral determination of fasting tear glucose concentrations in nondiabetic volunteers. , 2007, Clinical chemistry.

[7]  Yukio Yamada,et al.  Noninvasive Near-Infrared Blood Glucose Monitoring Using a Calibration Model Built by a Numerical Simulation Method: Trial Application to Patients in an Intensive Care Unit , 2006, Applied spectroscopy.

[8]  L. Colón,et al.  Evaluation of lacrimal fluid as an alternative for monitoring glucose in critically ill patients , 2005, Intensive Care Medicine.

[9]  Robin Felder,et al.  Flexible Rolled Thick‐Film Miniaturized Flow‐Cell for Minimally Invasive Amperometric Sensing , 2008 .

[10]  P. Cho,et al.  Reflex Tear Ascorbate in Hong Kong Chinese Subjects: Method Comparison and Biological Variation , 2003, Optometry and vision science : official publication of the American Academy of Optometry.

[11]  L A Colón,et al.  Determination of Glucose in Submicroliter Samples by CE-LIF Using Precolumn or On-Column Enzymatic Reactions. , 1997, Analytical chemistry.

[12]  G. S. Wilson,et al.  Design and in vitro studies of a needle-type glucose sensor for subcutaneous monitoring. , 1991, Analytical chemistry.

[13]  Carlos Eduardo Ferrante do Amaral,et al.  Current development in non-invasive glucose monitoring. , 2008, Medical engineering & physics.

[14]  J. G. Lewis.  Tear-test for Glucose , 1957 .

[15]  Katsuhiko Kuwa,et al.  Noninvasive measurement of glucose by metabolic heat conformation method. , 2004, Clinical chemistry.

[16]  Joseph R Lakowicz,et al.  A glucose-sensing contact lens: from bench top to patient. , 2005, Current opinion in biotechnology.

[17]  R. Potts,et al.  Glucose monitoring by reverse iontophoresis , 2002, Diabetes/metabolism research and reviews.

[18]  Jeff Blyth,et al.  Towards the real-time monitoring of glucose in tear fluid: holographic glucose sensors with reduced interference from lactate and pH. , 2008, Biosensors & bioelectronics.

[19]  R. Bartlett,et al.  The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer. , 2010, Biomaterials.

[20]  Giridharan Gokulrangan,et al.  Mediation of in vivo glucose sensor inflammatory response via nitric oxide release. , 2005, Journal of biomedical materials research. Part A.

[21]  Joseph R. Lakowicz,et al.  Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review , 2004, Journal of Fluorescence.

[22]  T. Mattila,et al.  Influence of Intensive versus Conventional Glucose Control on Microvascular and Macrovascular Complications in Type 1 and 2 Diabetes Mellitus , 2010, Drugs.

[23]  Edward H. Leiter,et al.  Non-invasive glucose measurements in mice using mid-infrared emission spectroscopy , 2009 .

[24]  Justin T. Baca,et al.  Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. , 2007, The ocular surface.

[25]  P Cho,et al.  Ascorbic acid concentration and total antioxidant activity of human tear fluid measured using the FRASC assay. , 2000, Investigative ophthalmology & visual science.