# Design, Implementation, and Advances in Indirect SERS Sensors for Biomedical and Human-Health-Related Analyte Detection

## TL;DR

This review explains how SERS nanotags are designed and used to detect health-related molecules with high sensitivity and specificity, offering insights into their structure, function, and future applications.

## Contribution

The paper provides a comprehensive overview of indirect SERS nanotag design and applications, emphasizing recent trends and integration into diagnostic systems.

## Key findings

- SERS nanotags enhance Raman signals for ultrasensitive detection of health-related analytes.
- Recent advances in AI and machine learning are accelerating the design and optimization of SERS nanotags.
- SERS nanotags are being integrated into point-of-care diagnostic formats like lateral flow assays and microfluidic devices.

## Abstract

What are the main findings?
This review provides an overview of SERS nanotags, explaining their structural design, functional components, and underlying mechanisms for Raman signal enhancement.This work summarizes the applications of SERS nanotags for the detection and diagnosis of human-health-related analyte detection, highlighting recent trends in assay design and application.

This review provides an overview of SERS nanotags, explaining their structural design, functional components, and underlying mechanisms for Raman signal enhancement.

This work summarizes the applications of SERS nanotags for the detection and diagnosis of human-health-related analyte detection, highlighting recent trends in assay design and application.

What are the implications of the main findings?
By unifying the fundamental principles and current biosensing applications of SERS nanotags, this review serves as a broad overview for researchers seeking to design, apply, or further develop SERS-based nanosensors.The insights presented help identify key contributors, emerging trends, and future directions in SERS nanotag research, promoting collaboration and accelerating translation of these technologies into clinical and real-world use.

By unifying the fundamental principles and current biosensing applications of SERS nanotags, this review serves as a broad overview for researchers seeking to design, apply, or further develop SERS-based nanosensors.

The insights presented help identify key contributors, emerging trends, and future directions in SERS nanotag research, promoting collaboration and accelerating translation of these technologies into clinical and real-world use.

Novel, accurate molecular diagnostics are driving new advances across medicine, public health, and environmental monitoring. Surface-enhanced Raman spectroscopy (SERS) nanotags are powerful platforms for ultrasensitive, multiplexed, and quantitative detection of molecular targets. This review focuses on indirect sensing strategies, where SERS nanotags act as signal transducers, resulting in enhanced and unique Raman spectra upon binding of target analytes (high specificity) and allowing for ultralow limits of detection. These indirect SERS sensors typically consist of a plasmonic core, a Raman reporter molecule, and a ligand that targets the analyte of interest. Each of these components contributes to the sensitivity, stability, and selectivity of the system. Rational design of SERS nanotags requires balancing enhancement efficiency with reproducibility, biocompatibility, and assay integration. The choice of reporter molecules, for instance, governs spectral uniqueness and enables multiplexed detection of multiple analytes within a single sample. Recent advances in artificial intelligence and machine learning are accelerating nanotag development by enabling predictive control over nanostructure geometry, composition, and optical response. SERS nanotags are increasingly being integrated into diagnostic formats, such as lateral flow assays and microfluidic devices, offering both qualitative and quantitative analysis at the point of care. This review provides an overview of key design principles, common strategies for nanostructure functionalization and stabilization, and emerging biosensing applications, serving as a practical guide for researchers seeking to design and implement SERS nanotags.