Surface-Enhanced\nRaman Scattering Nanoendoscope for\nQuantification of a Protein Released under Physiological Stimulation\nin Brain Tissue

A surface-enhanced\nRaman scattering (SERS) biosensor with minimal\ninvasiveness and high spatial resolution has been developed as a nanoendoscope\nto detect changes in protein concentrations at specific sites in biological\ntissues. While generally applicable to various tissues or proteins,\nthe SERS nanoendoscope is demonstrated for the quantitative detection\nof S100β, an astrocytic protein whose plasmatic levels are known\nto vary in several neuropathologies such as Alzheimer’s disease,\nschizophrenia, Down syndrome, Parkinson’s disease and epilepsy,\nbut for which intratissular levels have not been locally monitored,\ndemonstrating key attributes of the SERS nanoendoscope. The SERS nanoendoscope\nis fabricated with densely and well-dispersed deposited gold nanoparticles\nmodified with anti-S100β primary antibody on pulled optical\nfibers with a tip diameter of 700 nm, conducive to noninvasive and\nregiospecific detection of the S100β protein in different regions\nof mouse brain slices under different physiological stimuli with micrometer\nresolution. Quantification was performed ex vivo using SERS-active\nnanotags with secondary antibodies with detection limits of 5 and\n7 nM in phosphate-buffered saline solution and mouse brain slice,\nrespectively. Various physiological stimuli were then applied ex vivo\nto wild-type and S100β-knockout mouse brain slices to demonstrate\nthe SERS nanoendoscope under physiological conditions. The average\nconcentration of S100β was increased to 27, 45, and 48 nM upon <i>N</i>-methyl-d-aspartate, electrical, and optogenetic\nstimulation, respectively, statistically higher than all controls,\ndemonstrating the ability of the SERS nanoendoscope to quantify protein\nrelease in biological tissues.