Comparison of SERS pH probe responses after microencapsulation within hydrogel matrices

Significance: Personalized medicine requires the tracking of an individual’s metabolite levels over time to detect anomalies and evaluate the body’s response to medications. Implanted sensors offer effective means to continuously monitor specific metabolite levels, provided they are accurate, stable over long time periods, and do no harm. Aim: Four types of hydrogel embedded with pH-sensitive sensors were evaluated for their accuracy, sensitivity, reversibility, longevity, dynamic response, and consistency in static versus dynamic conditions and long-term storage. Approach: Raman spectroscopy was first used to calibrate the intensity of pH-sensitive peaks of the Raman-active hydrogel sensors in a static pH environment. The dynamic response was then assessed for hydrogels exposed to changing pH conditions within a flow cell. Finally, the static pH response after 5 months of storage was determined. Results: All four types of hydrogels allowed the surface-enhanced Raman spectroscopy (SERS) sensors to respond to the pH level of the local environment without introducing interfering signals, resulting in consistent calibration curves. When the pH level changed, the probes in the gels were slow to reach steady-state, requiring several hours, and response times were found to vary among hydrogels. Only one type, poly(2-hydroxyethyl methacrylate) (pHEMA), lasted five months without significant degradation of dynamic range. Conclusions: While all hydrogels appear to be viable candidates as biocompatible hosts for the SERS sensing chemistry, pHEMA was found to be most functionally stable over the long interval tested. Poly(ethylene glycol) hydrogels exhibit the most rapid response to changing pH. Since these two gel types are covalently cross-linked and do not generally degrade, they both offer advantages over sodium alginate for use as implants.