Self-Referenced Surface-Enhanced Raman Scattering Nanosubstrate for the Quantitative Detection of Neurotransmitters

Quantitative, label-free detection of neurotransmitters is of vital importance to the diagnosis and treatment of neurologic diseases. The surface-enhanced Raman scattering (SERS) effect has great application prospects in the field of biosensing and bioimaging because of its unique nondestructive testing and its capability of being used in molecular fingerprint identification. However, the quantitative SERS analysis of neurotransmitters is still a great challenge because of the poor reproducibility of the SERS-active sites, as well as the small Raman cross-section and low physiological concentration of neurotransmitter molecules. Here, we report the development of a stellate gold nanostructure with a 1 nm interior gap for the quantitative detection of neurotransmitters. The internal reference embedded into the hollow gap of the stellate gold nanoparticle allows the calibration of the signal of analytes absorbed on the surface, which improves the R-squared value of the linear fitting curve from 0.56 to 0.97 for quantitative dopamine detection. Our developed self-referenced SERS substrate holds great potential for label-free, quantitative SERS-based biosensing.