Microfluidic SERS devices: brightening the future of bioanalysis

Abstract

A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described.

The Emerging Role of Raman Spectroscopy as an Omics Approach for Metabolic Profiling and Biomarker Detection toward Precision Medicine

“…268 In addition to sandwich immunoassays discussed above, SERS-based POC diagnostics have also advanced real-time detection of multiple proteins with the utility of lateral flow assays, paper-based swabs, and microfluidic devices that include both traditional and pump-free paper microfluidics. 269 In POC devices, spatial and barcode-based multiplexing have enabled rapid, low-cost, and highly sensitive detection. Spatial multiplexing is created with spatially separated zones where multiple molecular targets are assayed on the same platform but physically separated.…”

“…(e) In vivo tumor targeting and spectral detection of cRGDfk-Raman beads with high signal in tumors. Adapted with permission from ref . Copyright 2019 American Chemical Society.…”

Microfluidics for Profiling miRNA Biomarker Panels in AI-Assisted Cancer Diagnosis and Prognosis

“…SERS achieves enhancement of the regular Raman spectroscopy signal of analytes (including single-molecule miRNAs) by a factor of ∼ 10 10 -10 11 , either directly via adsorption onto metal nanostructured surfaces or indirectly via a reporter mechanism, and with a spectral profile tailored for multiplexing and stable quantitative readouts. 114 SPR refers to the collective coherent oscillations of excited delocalized electrons on a thin metal surface due to light incident at a particular angle to the surface. The specific angle of incidence is a function of the characteristic target such as miRNAs, leading to differential detectable signals.…”

Advancing Breath‐Based Diagnostics: 3D Mesh SERS Sensor Via Dielectrophoretic Alignment of Solution‐Processed Au Nanoparticle‐Decorated TiO2 Nanowires

“…[17] Nevertheless, significant challenges keep the commercial development of SERS-based detection methods. [18,19] To date, the majority of reported SERS substrates are based on the bottom-up assembly approach, as it offers a simple, fast, and cost-effective solution for SERS substrate preparation. [20] This approach can be further categorized into colloidal and non-colloidal substrates.…”

“…In both categories, the controllable aggregation of NPs is important for the formation of hot-spots and the production of an effective SERS sensor. [18,25] An effective alternative for controlling the state of aggregation of plasmonic NPs is by binding them onto nanowires (NWs). Assembly of NPs on NWs has attracted interest for SERS diagnostic applications, due to the high enhancement factors and low detection limits reported, yielding various types of NPdecorated NWs.…”