Advances in Glucose Sensing Techniques: Novel Non-Invasive and Continuous Electrochemical Glucose Monitoring Systems

Abstract

Diabetes mellitus (or diabetes) is a chronic, lifelong condition that affects the body's ability to utilize the stored chemical potential energy found in our food. Frequent measurement and tight control of blood glucose is essential to avoiding life-threatening hyper- and hypoglycemic events and associated serious, long-term complications. In this dissertation, a novel non-invasive tear glucose measurement approach and various continuous electrochemical glucose sensor-based monitoring devices with nitric oxide (NO) release are examined and evaluated for their potential application for diabetes management. Tear glucose measurements have been previously suggested as a potential alternative to blood glucose monitoring for diabetic patients, although this approach has not been thoroughly established. In Chapter 2, the first use of commercial blood glucose test strips to measure glucose in tears is examined. Roche AccuChek test strips are shown to exhibit the low detection limit required for quantitating glucose concentration in tears. Measurements of glucose in tears from nine normal (nondiabetic) fasting human subjects using strips yielded glucose values within the range of 5–148 μM, similar to glucose measurements for human tears reported by others via LC-MS methods. Chapter 3 evaluates the origin of the high sensitivity and selectivity of the Roche test strips and demonstrates that the use of pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (GDH) in combination with a nitrosoaniline derivative as an electron transfer mediator provides the low limits of quantitation (ca. 9 µM) and enhanced selectivity achieved with these strips. In Chapter 4, the test strips are used to measure glucose levels in tear fluids from human subjects with type 2 diabetes after fasting and then for 90 min after ingesting sugar while concurrently measuring the blood glucose values. A moderate correlation between tear and blood glucose levels is demonstrated. Tight glycemic control helps reduce life-threatening hyper- and hypoglycemic events that can cause serious long-term complications for hospitalized critically ill patients. Therefore, the development of continuous glucose monitoring systems to quantitate blood glucose levels intravascularly (IV) could improve patient outcomes. In Chapter 5, the compatibility of nitric oxide (NO) release coatings with implantable enzymatic glucose sensors based on osmium (III/II) mediated electrochemical detection is examined for the first time. Nitric oxide (NO) is a potent inhibitor of platelet activation and adhesion. NO-releasing osmium-mediated glucose sensors are prepared using a S-nitrosothiol impregnated outer tubing and are tested in vitro in both phosphate buffer (pH 7.4) and heparinized whole porcine blood. After 3 days of continuous NO release at or above physiological levels, no negative effects on the osmium mediated electrochemical currents are observed. These results suggest that improved performance of both intravascular and, potentially, subcutaneous Os(III/II) mediated glucose sensors may be realized by incorporating NO’s well-known anticlotting, anti-inflammatory, and antimicrobial properties.