In contrast to conventional surface-enhanced Raman scattering (SERS) platforms implemented on non-biological substrates, silk fibroin has the unique advantages of long-term biosafety and controllable biodegradability for in vitro and in vivo biomedical applications, as well as flexibility and process-compatibility. In this study, a silk fibroin film was developed to fabricate a flexible SERS sensor template with nanogap-rich gold nanoislands. The proposed biological SERS platform presents fairly good enhancements in detection performance such as detection limit, sensitivity, and signal-to-noise ratio. In particular, the sensitivity improvement was by more than 10 times compared to that of the counterpart sample, and an excellent spatial reproducibility of 2.8% was achieved. In addition, the near-field calculation results were consistent with the experimental results, and the effect of surface roughness of the silk substrate was investigated in a quantitative way. It is believed that biological SERS-active sensors could provide the potential for highly sensitive, cost-effective, and easily customizable nanophotonic platforms that include new capabilities for future healthcare devices.
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