A Viscosity-Dependent Affinity Sensor for Continous Monitoring of Glucose in Biological Fluids

For fifty years, tremendous efforts have been directed towards the development of glucose sensors for tight glycemic control of diabetic patients. Today, millions of diabetics test their blood glucose level daily, making glucose the most commonly tested analyte. Recently, subcutaneous implantable needle-type sensors became commercially available for continuous glucose monitoring. However, these devices require frequent calibrations and are lacking accuracy and reliability. They are based on electrochemical detection, which is strongly affected by the biological environment in which the sensor is placed. In addition, an accurate and reliable continuous glucose sensor would also be of great interest for tight glycemic control in intensive care units of hospitals. However, despite the many impressive breakthroughs, the development of clinically accurate continuous glucose sensors remains a challenge. In this context, alternative approaches to overcome the limitation of electrochemical methods have been actively investigated. Among these, affinity sensing should offer several intrinsic advantages for in vivo monitoring. In this thesis, we investigate a novel viscosity-dependent affinity sensor for continuous monitoring of glucose in biological fluids such as blood and plasma. The sensing principle relies upon the viscosity variation of a sensitive fluid with glucose concentration. The sensitive fluid is based on the competitive binding of glucose and dextran with a glucosespecific binding protein, Concanavalin A. Basically, the sensor is filled with the sensitive fluid, and includes both an actuating and a sensing piezoelectric diaphragm as well as a flow-resistive microchannel. In addition, a nanoporous alumina membrane completely retains the sensitive fluid within the sensor whilst allowing glucose permeation through the membrane. The sensor was extensively tested in isotonic saline solution for physiological blood glucose concentrations between 2 and 20 mM, demonstrating