SERS-Active Smart Hydrogels With Modular Microdomains: From pH to Glucose Sensing

A sensing hydrogel was demonstrated using pH-sensitive surface-enhanced Raman scattering (SERS) reporters embedded in modular microdomains. The gold nanoparticle-based pH probes capped with 4-mercaptobenzonic acid (MBA-AuNPs) were encapsulated within polyelectrolyte multilayer microcapsules within a surrounding hydrogel matrix. The materials were fully characterized for pH sensitivity and reproducibility of Raman scattering, which revealed low background (hydrogel) signals and a sigmoidal response curve for ratiometric intensity changes at 1430 and 1078 cm
^-1
, respectively. The analytical range was pH 4.43-8.07 (pKa~5.80) with an average sensitivity of 0.07 pH
^-1
. To assess the potential for sensing enzymatic substrates, hydrogels were prepared with the MBA-AuNPs co-encapsulated with glucose oxidase. Raman spectra recorded from hydrogels exposed to physiological glucose levels (0-400 mg/dL) exhibited apparent trends of decreasing pH from pH ~6.50 to pH ~4.50 due to glucose oxidization within the microdomains. The glucose diffusion into the capsules was controlled by crosslinking the polyelectrolyte multilayers with glutaraldehyde, showing an approach to adjust the balance of oxygen and glucose flux into the microcavities, yielding a tunable sensitivity of the glucose-proportional change at steady-state pH. These findings illustrate the potential of hydrogel hosts for a flexible approach to pseudo-solid-state SERS sensing devices for multiple small molecule targets.