Linear SPAD array for protein sequencing through surface-enhanced Raman spectroscopy

Abstract

Surface-Enhanced Raman Spectroscopy (SERS) is a robust technique for molecular analysis, using metallic nanostructures to intensify Raman signal. In this work, we propose a 128 × 1 SPAD camera to perform protein sequencing through SERS, employing plasmonic nanopores to achieve amplification of the Raman signal. We quantitatively discuss the enhancement of the camera Photon Detection Efficiency with the use of a custom microlens array and assess the spectral resolution of the system. We demonstrate how the presented setup can already be used to optically detect single molecule translocation through the nanopore at 10 μs time resolution, and how a robust Raman fingerprint of the translocating molecule can be obtained. We also propose an innovative strategy to improve signal intensity based on real-time translocation detection and suggest the use of the camera gating capability for fluorescence reduction. Our future work will include the validation of these solutions to enable progress toward single-molecule sequencing.