Lab-on-fiber SERS optrodes for biomedical applications

Surface-enhanced Raman scattering (SERS) has established itself as powerful tool for molecular sensing in biology and medicine. The integration of SERS systems with optical fiber is a challenging but potentially very rewarding endeavour. However, efforts to transfer the technology from the laboratory to the clinic have been frustrated by the lack of robust stable and sensitive substrates on the fiber tip, as well as the complexity of interfacing between sample and the substrate itself. Here, we propose the Lab-on-Fiber SERS optrodes, realized on the optical fiber tip by nanosphere lithography. Three types of highly ordered and reproducible SERS-active substrates have been realized: close-packed array (CPA); CPA after sphere removal (SR) and sparse array (SA) of polystyrene nanospheres, covered by a gold thin layer. To optimize the SERS probes, we compared the SERS performances in terms of Enhancement Factor (EF) and reproducibility pertaining to different patterns with different nanosphere diameters and gold thicknesses using the biphenyl-4-thiol (BPT), as target molecule. Moreover, we analysed and compared the SERS spectra of two representative biological probes, bovine serum albumin (BSA, medium molecule) and red blood cells (RBCs), in order to correlate the SERS response to the morphology and hysteric hindrance of the biological target. The SERS analysis indicated that the CPA substrate amplifies the BPT Raman intensity twice as well as the SR and SA substrates, while BSA and RBCs, with the CPA substrate, provide signals comparable to those of SR and SA substrates. Finally, we have optimized a Raman system for SERS optrode operation with efficient lighting and collection via optical fiber.