Title: Impedance-Based Affinity Micro and Nanosensors for Continuous Glucose Monitoring
Description: Diabetes mellitus is a metabolic disease with abnormally high concentration of glucose in blood in patients. Continuous glucose monitoring, which involves measuring glucose concentration in the patient throughout the day and night, can significantly reduce the risk of diabetes-related complications. Commercially available CGM sensors are not yet suited for long-term applications due to reliability and accuracy issues associated with the irreversible, consumptive nature of the underlying electrochemical reactions. Affinity sensing methods, which are based on reversible affinity binding between glucose and a recognition molecule, hold the potential to address these challenges in CGM applications. These methods do not involve the consumption of glucose and can offer improved stability and accuracy for CGM. When combined with impedance-based transduction methods, affinity sensors can also offer a high level of miniaturization, allow low-cost instrumentation, and are amenable to physical and functional integration.

The affinity sensors investigated in this thesis include hydrogel-based affinity microsensors and graphene-based affinity nanosensors. We first present a dielectric affinity microsensor that consists of a pair of coplanar electrodes functionalized in situ with a glucose-responsive hydrogel for dielectrically based affinity measurement of glucose in subcutaneous tissue. We present a study of the effects of the choice of hydrogel compositional parameters on the characteristics of the hydrogel-based microsensor, allowing the identification of the optimal hydrogel composition for the microsensor to sensitively and rapidly respond to changes in glucose concentration. A differential design is then demonstrated, both in vitro and in vivo, to effectively minimize the influence of fluctuations in the environmental conditions, thereby allowing the hydrogel-based microsensor to function appropriately as a subcutaneously implanted device. In addition, we present a preliminary study on affinity nanosensors for non-invasive monitoring of glucose concentrations in physiological media such as tears.

The affinity nanosensor is based on a chemically modified graphene field-effect transistor for the electrical measurement of glucose concentrations. The study explores the sensing mechanism of the nanosensors and demonstrates a device with high sensitivity and low limit of detection, which satisfies the requirement for monitoring glucose concentrations in tears. Experimental results demonstrate that these affinity micros and nanosensors are capable of measuring glucose concentrations with a suitable sensitivity and dynamic range for the intended physiological media, with potential applications to minimally invasive or non-invasive continuous glucose monitoring in diabetes care.