Abstract
Surface-enhanced Raman spectroscopy (SERS) is a sensitive, chemically specific, and short-time response probing method with significant potential in biomedical sensing. This paper reports the integration of SERS with microneedle arrays as a minimally invasive platform for chemical sensing, with a particular view toward sensing in interstitial fluid (ISF). Microneedle arrays were fabricated from a commercial polymeric adhesive and coated with plasmonically active gold nanorods that were functionalized with the pH-sensitive molecule 4-mercaptobenzoic acid. This sensor can quantitate pH over a range of 5 to 9 and can detect pH levels in an agar gel skin phantom and in human skin in situ. The sensor array is stable and mechanically robust in that it exhibits no loss in SERS activity after multiple punches through an agar gel skin phantom and human skin or after a month-long incubation in phosphate-buffered saline. This work is the first to integrate SERS-active nanoparticles with polymeric microneedle arrays and to demonstrate in situ sensing with this platform.