Plasmonic Electronic Raman Scattering as Internal Standard for Spatial and Temporal Calibration in Quantitative Surface-Enhanced Raman Spectroscopy

Abstract

Ultrasensitive surface-enhanced Raman spectroscopy (SERS) still faces difficulties in quantitative analysis because of its susceptibility to local optical field variations at plasmonic hotspots in metallo-dielectric nanostructures. Current SERS calibration approaches using Raman tags have inherent limitations due to spatial occupation competition with analyte molecules, spectral interference with analyte Raman peaks, and photodegradation. Herein, we report that plasmon-enhanced electronic Raman scattering (ERS) signals from metal can serve as an internal standard for spatial and temporal calibration of molecular Raman scattering (MRS) signals from analyte molecules at the same hotspots, enabling rigorous quantitative SERS analysis. We observe a linear dependence between ERS and MRS signal intensities upon spatial and temporal variations of excitation optical fields, manifesting the |E|4 enhancements for both ERS and MRS processes at the same hotspots in agreement with our theoretical prediction. Furthermore, we find that the ERS calibration’s performance limit can result from orientation variations of analyte molecules at hotspots.

Towards practical and sustainable SERS: a review of recent developments in the construction of multifunctional enhancing substrates

“…Another worth-noting strategy that has recently been proposed for calibrating SERS signals is the use of the plasmon-enhanced electronic Raman scattering signals from the enhancing metal as the internal standard which has been successfully utilized to improve SERS analysis performed in living biological systems. 214,215 In summary, utilizing the SERS/Raman signals of intrinsically present reference materials as an internal standard is a convenient approach to construct calibration-enhancement-in-one SERS substrates. Moreover, the approach does not rely on surface modifications of the enhancing materials which leaves the enhancing substrate accessible for analyte molecules.…”

Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis

“…10B). 132 ERS-calibrated Raman signals were verified and found to be insensitive to variations of local field intensities from different hot spots by spatial correlation. 2D mapping of surface-immobilized test molecules showed significant improvement of the SERS quantitative analysis by removing the effects of local field variations among hot spots.…”

“…Reproduced with permission. 132 Copyright 2020, American Chemical Society. (C) Top view of an SEM image showing the highly malignant breast cancer cells cultured on the specially designed nanolaminated SERS substrates, along with bright-field and 2D Raman mapping images of the same living cells.…”

“…(B) Illustration of plasmonic enhancement of ERS and MRS signals at hot spots along with representative 2D Raman images for I MRS before and after ERS spatial and temporal calibration. Reproduced with permission 132. Copyright 2020, American Chemical Society.…”

Microporous Multiresonant Plasmonic Meshes by Hierarchical Micro–Nanoimprinting for Bio‐Interfaced SERS Imaging and Nonlinear Nano‐Optics

“…We calibrated SERS signal intensities with the electronic Raman scattering (ERS) internal standard for Raman peaks across different measurements. [ 41 ] Briefly, the control SERS spectrum measured from LB broth exhibits major bands at 732 and 1002 cm –1 that reflect constituent purines (adenine) and proteins (phenylalanine). For P. syringae colonies after seeding at t = 0 h, the measured SERS spectrum shows reduced peak intensities at 732 and 1001 cm –1 related to LB broth components and a new lipid peak at 1444 cm –1 , possibly originating from the lipid outer membrane of the cells, [ 42 ] manifesting an intimate interface of SERS hotspots with P. syringae cells to probe membrane components but with reduced access to LB broth components.…”