Surface Enhanced Raman Spectroscopy Based Biosensor with a Microneedle Array for Minimally Invasive In Vivo Glucose Measurements

To monitor blood glucose levels reliably, diabetic patients usually have to undergo frequent fingerstick tests to draw out fresh blood, which is painful and inconvenient with the potential risk of cross contamination especially when the lancet is reused or not properly sterilized. This work reports a novel surface-enhanced Raman spectroscopy (SERS) sensor for the in situ intradermal detection of glucose based on a low-cost poly(methyl methacrylate) microneedle (PMMA MN) array. After incorporating 1-decanethiol (1-DT) onto the silver-coated array surface, the sensor was calibrated in the range of 0-20 mM in skin phantoms then tested for the in vivo quantification of glucose in a mouse model of streptozocin (STZ)-induced type I diabetes. The results showed that the functional poly(methyl methacrylate) microneedle (F-PMMA MN) array was able to directly measure glucose in the interstitial fluid (ISF) in a few minutes and retain its structural integrity without swelling. The Clarke error grid analysis of measured data indicated that 93% of the data points lie in zones A and B. Moreover, the MN array exhibited minimal invasiveness to the skin as the skin recovered well without any noticeable adverse reaction in 10 min after measurements. With further improvement and proper validation, this polymeric MN array-based SERS biosensor has the potential to be used in painless glucose monitoring of diabetic patients in the future.