Development of glucose and pH sensitive hydrogels for microfabricated biomedical sensor arrays

This dissertation is concerned with the development of glucose-sensitive hydrogels and pH-sensitive hydrogels for biomedical sensor applications. The research is motivated by the limitations of current glucose sensors and an urgent societal need, which has not yet been met, for a continuous glucose monitoring sensor suitable for implantation and long-term use in diabetic patients. The sensing approach is the confinement of thin smart hydrogels between the diaphragm of a piezoresistive pressure sensor and a rigid porous membrane through which analyte diffusion occurs. Such a sensor is termed a "chemomechanical sensor." First, a macrosize chemomechanical sensor is used to screen various totally synthetic phenylboronic acid (PBA) containing glucose-sensitive hydrogels (GSHs) on the basis of (1) magnitude of osmotic swelling pressure response to glucose concentration change, (2) selectivity for glucose relative to fructose, and (3) response kinetics. All testing was performed in vitro, and a polyampholytic GSH is found to be the best choice. Next, polyampholytic GSHs are synthesized without use of potentially toxic acrylamide monomer and tested in the macrosize glucose sensor. Finally a UV-curing process is developed for in-situ synthesis of GSHs on integrated sensing chips containing custom-designed piezoresistive pressure sensors. Preliminary in vitro results for a microchip glucose sensor with pressure transducer diaphragms measuring 1 mm by 1 mm are presented. The results of this thesis will aid the long-term development of a smart hydrogels based sensor array suitable for subcutaneous implantation that is able to simultaneously measure glucose and pH values in real-time on a long-term basis for diabetic patients.