# Plasmon-enhanced Stimulated Raman Scattering Microscopy with Single-molecule Detection Sensitivity

## TL;DR

This paper introduces plasmon-enhanced stimulated Raman scattering (PESRS) microscopy, achieving single-molecule detection sensitivity for label-free chemical imaging, enabling ultrasensitive analysis of molecular events in biomedical systems.

## Contribution

The study demonstrates a novel PESRS microscopy technique that combines pico-Joule laser excitation, background subtraction, and denoising to detect single molecules without labels.

## Key findings

- Achieved robust single-molecule SRS spectra.
- Verified detection using isotopologues of adenine.
- Applied PESRS to map adenine release from bacteria.

## Abstract

Stimulated Raman scattering (SRS) microscopy allows for high-speed label-free chemical imaging of biomedical systems. The imaging sensitivity of SRS microscopy is limited to ~10 mM for endogenous biomolecules. Electronic pre-resonant SRS allows detection of sub-micromolar chromophores. However, label-free SRS detection of single biomolecules having extremely small Raman cross-sections (~10-30 cm2 sr-1) remains unreachable. Here, we demonstrate plasmon-enhanced stimulated Raman scattering (PESRS) microscopy with single-molecule detection sensitivity. Incorporating pico-Joule laser excitation, background subtraction, and a denoising algorithm, we obtained robust single-pixel SRS spectra exhibiting the statistics of single-molecule events. Single-molecule detection was verified by using two isotopologues of adenine. We further demonstrated the capability of applying PESRS for biological applications and utilized PESRS to map adenine released from bacteria due to starvation stress. PESRS microscopy holds the promise for ultrasensitive detection of molecular events in chemical and biomedical systems.

---
Source: https://tomesphere.com/paper/1903.05167