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A Non-Aggregative, Thermally Stable Glucose Sensor for Continuous Glucose Monitoring
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Diabetes mellitus is a disease that affects the regulation of a person’s blood glucose levels. Fully implantable continuous glucose monitoring (CGM) has the potential to improve diabetes management by improving patient compliance and more importantly, providing patients with a more detailed trend of their glucose level on a daily basis. One such approach in the development of a CGM device is the use of the lectin Concanavalin A (ConA) in a competitive glucose binding assay. The current set back to these ConA based assay has to do with its stability, and sensitivity. Furthermore, current CGM devices face longevity issues due to the nature of the implant and attack from the immune system. Therefore, the overall goal of the project is to develop a fully implantable, minimally invasive CGM device that would overcome issues pertaining to longevity, stability and sensitivity. Towards this goal, the current work aimed to first develop a non-aggregative thermally stable glucose sensing assay. First, ConA’s thermal stability at body temperature (37°C) was evaluated and based on the resulting instability, ConA was modified with poly (ethylene glycol) chains to improve its thermal stability at 37°C. Results showed that the presence of these PEG chains improved ConA’s thermal stability without significantly hindering its ability to bind to a competing ligand and sense changes in glucose concentrations within the physiologically relevant range. Next, this worked characterized the sensitivity and FRET efficiency of the newly modified ConA based assay, paired with the recently introduced monovalent competing ligand, mannotetraose. These characteristics was compared to current traditional ConA/dextran based glucose sensing assay. It was determined that across the desired glucose concentration range of 0 to 600 mg/dL, the new PEGylated ConA/mannotetraose based assay had improved sensitivity and FRET efficiency when compared to a PEGylated ConA/dextran based assay. Finally, this work aimed to encapsulate the modified assay within the proposed biocompatible membrane, PNIPAAm, and evaluate its ability to sense changes in external glucose concentration. To accomplish this, different encapsulation techniques such as calcium carbonate microspheres, alginate microspheres and layer by layer (LbL) deposition on PNIPAAm copolymer AMPS (AMPS-PNIPAAm) hydrogels were investigated to achieve minimal leaching without significantly impacting the glucose sensing of the assay within a hollow rod shaped membrane. The work also investigated the modification of the assay to increase the size of the smaller assay component as an alternative means to try and retain the assay within the biocompatible membrane. The deposition of LbL on the inner wall of the AMPS-PNIPAAm rods proved to be more efficient with an approximate 50% change in FRET signal for changes in glucose concentration ranging from 0 to 600 mg/dL and a mean absolute relative difference (MARD) of ~10%.
continuous glucose monitoring
competitive binding assay
Locke, Andrea Kristine (2016). A Non-Aggregative, Thermally Stable Glucose Sensor for Continuous Glucose Monitoring. Doctoral dissertation, Texas A & M University. Available electronically from