Toward Plasmonic Neural Probes: SERS Detection of Neurotransmitters through Gold-Nanoislands-Decorated Tapered Optical Fibers with Sub-10 nm Gaps

Integration of plasmonic nanostructures with fiber-optics-based neural probes enables label-free detection of molecular fingerprints via surface-enhanced Raman spectroscopy (SERS), and it represents a fascinating technological horizon to investigate brain function. However, developing neuroplasmonic probes that can interface with deep brain regions with minimal invasiveness while providing the sensitivity to detect biomolecular signatures in a physiological environment is challenging, in particular because the same waveguide must be employed for both delivering excitation light and collecting the resulting scattered photons. Here, a SERS-active neural probe based on a tapered optical fiber (TF) decorated with gold nanoislands (NIs) that can detect neurotransmitters down to the micromolar range is presented. To do this, a novel, nonplanar repeated dewetting technique to fabricate gold NIs with sub-10 nm gaps, uniformly distributed on the wide (square millimeter scale in surface area), highly curved surface of TF is developed. It is experimentally and numerically shown that the amplified broadband near-field enhancement of the high-density NIs layer allows for achieving a limit of detection in aqueous solution of 10−7 m for rhodamine 6G and 10−5 m for serotonin and dopamine through SERS at near-infrared wavelengths. The NIs-TF technology is envisioned as a first step toward the unexplored frontier of in vivo label-free plasmonic neural interfaces.
M.D.V. and Fe.P. contributed equally to this work and are co-last-authors. D.Z., Li.C., R.M.-B., A.B., C.C., F.T., F.D.A., L.M.P., M.V., M.D.V., and Fe.P. acknowledge funding from the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No. 828972. Fi.P., A.B., B.S., and Fe.P. acknowledge funding from the European Research Council under the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No. 677683. Lu.C. acknowledges financial support by the Italian Ministry of Economic Development through the Project "GENESI"-Development of innovative radiopharmaceuticals and biomarkers for the diagnosis of tumors of the male and female reproductive apparatus (cod. F/180003/01-03/X43, Call MISE "Intelligent Factory, Agri food and Life Sciences"). Fi.P., M.D.V., and Fe.P. acknowledge that this project has received funding from the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No. 101016787. M.P., Fe.P., and M.D.V. were funded by the U.S. National Institutes of Health (Grant No. 1UF1NS108177-01).