Approximately 20 million Americans and ten times that many persons worldwide have diabetes mellitus.This disease is a chronic disorder that requires careful regulation of glucose levels within tight limits in order toprevent severe secondary complications involving the patient's eyes, kidneys, nerves, and blood vessels.Recent research from our group has demonstrated that surface-enhanced Raman spectroscopy (SERS) is anew approach to this important public health problem that offers significant promise as a means to measurereal-time, in vivo glucose levels. Many of the potential problems envisioned at the outset of this project suchas: (1) glucose had never been measured by SERS; (2) temporal stability; (3) reversibility; (4) real-timeresponse; (5) resistance to protein interference; and (6) complications from interfering small molecule analyteshave been demonstrated to be non-existent or have been overcome.The research proposed herein is focused on the remaining fundamental scientific and technical challengesassociated with developing in vivo SERS as robust, portable biosensor platform for glucose in biological fluids.Four specific aims to designed to achieve this goal are: (1) synthesize and optimize new partition layers thatreduce spectral overlap with target analytes, increase sensitivity, and increase in vivo operating lifetime; (2)improve the chemometric data analysis and calibration methods used to extract the glucose level from the rawsignal ; (3) develop both fiber optic and free-space excitation/collection approaches to transdermal SERS; and(4) use a rat model to quantify glucose levels in unrestrained, unanaesthetized animals for periods up to 5days. New partition layers will be created through synthetic chemistry to minimize spectral overlap. Theoperating lifetime of the partition layer will be dramatically increased using a novel approach based on atomiclayer deposition to eliminate the weak Ag-S or Au-S bond. Calibration will be improved by measuring theglucose partition coefficient using liquid chromatography and by using a robust internal Raman standard(diamond). Transdermal SERS studies will be carried out to demonstrate the viability of free-space laserexcitation and collection. Preliminary results are presented indicating that this is possible. In vivo SERS will becross-validated using an implanted electrochemical sensor (MiniMed) and ex vivo monitoring of glucose byliquid chromatography/mass spectrometry.
|Effective start/end date||9/15/08 → 7/31/11|
- National Institute of Diabetes and Digestive and Kidney Diseases (1 R56 DK078691-01A2)