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Rapid, On-Site SARS-CoV‑2 Variant Detection and Differentiation Using GLAD-Pristine Silver Nanorod Arrays and Machine
Sneha Senapati1, Arvind Kaushik2, Rajan1
1School of Interdisciplinary Research (SIRe), IIT Delhi, New Delhi 110016, India.
ACS Omega
|October 13, 2025
Summary
This study developed a machine learning (ML)-based surface-enhanced Raman scattering (SERS) method to detect and differentiate SARS-CoV-2 variants and subvariants in clinical samples. The integrated approach achieved high accuracy, aiding in pandemic management.
Area of Science:
- Nanotechnology and Spectroscopy
- Biomedical Engineering
- Infectious Disease Diagnostics
Background:
- The emergence of SARS-CoV-2 variants necessitates advanced diagnostic tools for effective pandemic control.
- Current diagnostic methods may struggle with precise differentiation of closely related viral strains.
- Surface-enhanced Raman scattering (SERS) offers high sensitivity for molecular detection.
Purpose of the Study:
- To develop and validate a machine learning (ML)-integrated SERS methodology for accurate detection and differentiation of SARS-CoV-2 variants and subvariants.
- To assess the performance of Support Vector Machine (SVM) and Bidirectional Long Short-Term Memory (BiLSTM) models in classifying viral strains using SERS data.
- To establish a sensitive and specific platform for on-site COVID-19 variant identification.
Main Methods:
- Fabrication of silver nanorod substrates using glancing angle deposition for SERS analysis.
- Detection and differentiation of SARS-CoV-2 wildtype, kappa, delta, omicron variants, and omicron subvariants (BA.1, BA.2, BA.5, XBB).
- Application of SVM and BiLSTM machine learning models to SERS spectral data from 122 clinical nasopharyngeal swab samples.
Main Results:
- The SERS platform demonstrated a detection limit of approximately 100 pfu/mL for SARS-CoV-2 variants.
- The SVM classifier achieved 88.79% accuracy for variant classification and 95.83% for omicron subvariant classification on the validation set.
- The BiLSTM model achieved 85.98% accuracy for variant classification on the validation set, with both models showing promising results on blind test sets.
Conclusions:
- The integrated ML-SERS approach provides a sensitive and specific method for differentiating SARS-CoV-2 variants and subvariants in clinical samples.
- This methodology holds potential for on-site disease prediction and enhanced pandemic management strategies.
- Further validation and optimization could lead to widespread clinical application for rapid variant identification.

