Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2

Area of Science:

• Nanotechnology and Spectroscopy
• Biomedical Sensing
• Infectious Disease Diagnostics

Background:

• Accurate and early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for preventing its spread.
• Existing methods often lack the required sensitivity, speed, or reliability for real-time infectious disease monitoring.
• Development of advanced nanoprobes and digital analysis is needed for ultrasensitive pathogen detection.

Purpose of the Study:

• To develop a novel sensing platform for the ultrasensitive and quantitative detection of SARS-CoV-2.
• To utilize a bumpy core-shell surface-enhanced Raman spectroscopy (SERS) nanoprobe with single-nanoparticle (SNP) digital analysis.
• To assess the platform's capability in detecting viral variants and its potential for broader infectious disease applications.

Main Methods:

• Synthesis of tailorable bumpy core-shell SERS nanoprobes incorporating 4-nitrobenzenethiol Raman reporters.
• Implementation of single-nanoparticle (SNP)-based digital SERS analysis for direct visualization and quantification.
• Testing the platform's detection limit, dynamic range, and specificity against SARS-CoV-2 spike proteins and variants.

Main Results:

• The nanoprobe generated strong, uniform, and reproducible SERS signals with an enhancement factor of 2.1 × 10^8 to 2.2 × 10^9.
• The platform achieved ultrasensitive detection of SARS-CoV-2 spike protein with a limit of detection of 7.1 × 10^-16 M.
• The system successfully detected mutated spike proteins from Alpha, Beta, Gamma, Delta, and Omicron variants, outperforming ELISA.

Conclusions:

• The bumpy core-shell SERS nanoprobe combined with SNP digital analysis provides a highly sensitive and reliable sensing platform.
• This technology enables accurate and early detection of SARS-CoV-2 and its variants.
• The adaptable platform holds promise for the ultrasensitive detection of other highly infectious diseases.