SERS Nanosensors for in vivo Glucose Sensing

The goal of this program is to develop small and sensitive nanosensors for the continuous glucose monitoring in living tissue without the need for drawing blood. A major advantage of the transdermal sensors we are developing is to directly detect glucose itself not the byproducts of its transformation. The technique we use surface-enhanced Raman spectroscopy SERS is based on light and informs on the presence of glucose on or near metallic nanosensors. In Year 1, we have worked on the development of i sensitive nanosensors, ii selective capture layers that can be immobilized onto metal surfaces, and iii the integration of both. We have successfully developed a novel SERS nanoplatform that integrates gold nanorods with biocompatible hydrogels of variable stiffness. The fabrication of SERS-active microneedle patches has been successfully initiated and demonstrated over the first 12 months of the program using stiff hydrogels. Several approaches have been taken and validated against SERS activity. We have shown that water-soluble molecules can diffuse through the hydrogel pores and be detected in the mM range, where glucose is physiologically relevant. In Year 2, we have implemented the glucose-capture ligand on the gold nanorod surface that are already integrated with the microneedle patches. The stability of the nanorods in buffer conditions as well as organic solvents was evaluated. Additionally, SERS activity and device performance were investigated on a skin phantom. The plasmonic patch fabrication protocols were modified in such a way that the SERS activity can be selectively localized at the microneedles tip. Extended studies on sensing measurement sand theoretical calculations were done on evaluating boronic acid derivatives for glucose recognition. Finally, the plasmonic microneedle patches were validated as a SERS-based biosensing device by measuring reversible pH change from solution.