Electrochemical Glucometers

Diabetes Diabetes affects 17 million Americans and 171 million people worldwide. Two Major Types Type I: Pancreas produces very little or no insulin; affects younger patients Type II: Pancreas does not produce enough insulin or does not use produced insulin effectively (insulin resistant); affect middle-aged to older patients Other Types: Gestational Diabetes during pregnancy 1. http://www.who.int/diabetes/facts/world_figures/en/index3.html Heller, A. and B. Feldman. Chemical Reviews. (2008)108: 2482-2505 Electrochemical Glucose Sensors and Their Applications in Diabetes Management

Blood Glucose Insulin hormone that circulates in the blood helps body use and store glucose Low levels of insulin: body cannot store glucose After eating, blood glucose rises as food is broken down High blood glucose levels damage the eyes, kidneys, nerves, and heart over time Normal glucose levels: 82 to 110 mg/dL 1. http://www.diabetes.org/diabetes-basics/type-2/facts-about-type-2.html

Management of Diabetes Diet Exercise Oral Medication Insulin Therapy: injection of exogenous insulin analogs when blood glucose levels are high http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/ Image: public domain

Electrochemical Glucometers Measure glucose in blood At home testing requires minimal amounts of blood Utilizes disposable electrochemical cell electrical current is created from the oxidation of glucose 1. http://electrochem.cwru.edu/encycl/art-g01-glucose.htm Type I check 4 times/day Type II check 2 times/day

Traditional Electrochemistry Components Working electrode: Silver electrode Where reaction of interest takes place Reference electrode: Standard hydrogen electrode Measure current flowing between electrodes H2 gas Cl- Leary and Skoog. Principles of Instrumental Analysis. Orlando: Sauders College Publishing (1992). Ag+

Chemical Reactions Oxidation of Glucose by Enzyme glucose + GOD(ox)  gluconolactone + GOD(red) glucose  gluconolactone + 2e- 2e- + GOD(ox)  GOD(red) D-glucose Glucose Oxidase (GOD) is an enzyme directly oxides Glucose Cass, Anthony E. G. Analytical Chemistry. (1984)56:667-671 Ferrocene-mediated enzyme electrode for amperometric determination of glucose Reduction of Enzyme by Mediator GOD(red) + 2Fecp2R+  GOD(ox) + 2Fecp2R + 2H+ 2Fecp2R 2Fecp2R + 2e- Ferrocene monocarboxylic acid (Fecp2R) Mediator transports electrons to working electrode

Test Strips When blood added, glucose is oxidized by enzyme coated on working electrode Voltage applied between working and reference electrode Measure current between working and reference electrode 1. http://electrochem.cwru.edu/encycl/art-g01-glucose.htm

Amperometric Analysis Current measured 5-15 seconds after blood is drawn Current levels directly proportional to glucose levels 1. http://electrochem.cwru.edu/encycl/art-g01-glucose.htm Cass, Anthony E. G. Analytical Chemistry. (1984)56:667-671 Ferrocene-mediated enzyme electrode for amperometric determination of glucose Calibration curve for glucose enzyme electrode in (*) argon, (0) air, and (+) oxygen-saturated buffer. Steady-state current was measured at 160 mV vs. SCE, pH 7.0, and 25 OC.

Advantages Disadvantages Fast Disposable Strip No Instrument Contamination Disadvantages 1. Newman, Jeffery D. And Anthony P.F. Turner. Biosensors and Bioelectronics. (2005)20:2435-2453. Home blood glucose biosensors: a commercial perspective Discomfort of pricking finger Non-continuous measurement

Implantable Glucose Sensor Advantage: continuous glucose monitoring Could be coupled with continuous subcutaneous insulin infusions Problems: Sensor stability Calibration Biocompatibility 1. Newman, Jeffery D. And Anthony P.F. Turner. Biosensors and Bioelectronics. (2005)20:2435-2453. Home blood glucose biosensors: a commercial perspective

Recent Study 1. Gilligan, Barbara J. et. Al. Diabete Technology & Therapeutics. (2004)6:378-388. Feasibility of Continuous Long-Term Glucose Monitoring from a Subcutaneous Glucose Sensor in Human Designed Implantable sensor recorded glucose values every 128 s Longest sensor (of 5 subjects) lasted 103 days in vivo!