# Multiplexed Detection of Cancer Biomarker Using a Dual-Mode Colorimetric-SERS Lateral Flow Immunoassay Based on Elongated Rod Ag Nanoshell (ERNS) SERS Tags

## TL;DR

This paper introduces a new dual-mode immunoassay that can detect multiple cancer biomarkers in blood with high sensitivity and visual readout, suitable for point-of-care testing.

## Contribution

A novel ERNS-based SERS nanotag design enables multiplexed, sensitive, and visual detection of cancer biomarkers in a single lateral flow strip.

## Key findings

- The ERNS nanotags allow for both colorimetric and SERS-based detection of PSA and CA19-9.
- The assay achieved detection limits 500-fold and 685-fold lower than clinical thresholds for PSA and CA19-9, respectively.
- The platform supports rapid screening and quantitative analysis on a single strip.

## Abstract

Early detection of cancer biomarkers in blood is critical for improving patient outcomes; however, conventional immunoassays often rely on complex instrumentation and are not well suited for point-of-care testing or multiplexed analysis. Herein, we present a dual-mode colorimetric–surface-enhanced Raman scattering (SERS) lateral flow immunoassay (LFIA) platform for multiplexed detection of cancer biomarkers, employing elongated rod-shaped silver nanoshells (ERNSs) as SERS nanotags. The ERNS features a rough Ag shell with internally incorporated Raman labeling compounds (RLCs), enabling plasmonic extinction for visual readout and strong SERS signals for quantitative analysis while preserving the external metal surfaces for efficient antibody conjugation. Leveraging these advantages, a multiplex LFIA capable of simultaneously detecting prostate-specific antigen (PSA) and carbohydrate antigen 19-9 (CA19-9) on a single strip was successfully demonstrated. Visual inspection enabled rapid discrimination of samples at or near clinically relevant cut-off levels, while Raman analysis achieved limits of detection of 8.0 × 10−3 ng/mL for PSA and 5.4 × 10−2 U/mL for CA19-9, corresponding to approximately 500-fold and 685-fold lower concentrations than their respective clinical thresholds. This ERNS-based colorimetric–SERS LFIA integrates rapid screening and highly sensitive quantification within a single platform and offers a versatile nanoprobe design strategy for multiplex biomarker detection and liquid biopsy-based diagnostic applications, with potential relevance to point-of-care settings.