Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved ...

SERS-Activated Platforms for Immunoassay: Probes, Encoding Methods, and Applications

The SERS effect was initially discovered in the 1970s. Early research focused on understanding the phenomenon and increasing enhancement to achieve single molecule detection. From the mid-1980s to early 1990s, research started to move away from obtaining a fundamental understanding of the phenomenon to the exploration of analytical applications. At the same time, significant developments occurred in the field of photonics that led to the advent of inexpensive, robust, compact, field-deployable Raman systems. The 1990s also saw rapid development in nanoscience. This convergence of technologies (photonics and nanoscience) has led to accelerated development of SERS substrates to detect a wide range of chemical and biological analytes. It would be a monumental task to discuss all the different kinds of SERS substrates that have been explored. Likewise, it would be impossible to discuss the use of SERS for both chemical and biological detection. Instead, a review of the most common metallic (Ag, Cu, and Au) SERS substrates for chemical detection only is discussed, as well as SERS substrates that are commercially available. Other issues with SERS for chemical detection have been selectivity, reversibility, and reusability of the substrates. How these issues have been addressed is also discussed in this review.

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Review of SERS Substrates for Chemical Sensing.

Modern Raman Spectroscopy: A Practical Approach

Label and label-free based surface-enhanced Raman scattering for pathogen bacteria detection: A review.

Noble metals-TiO2 nanocomposites: From fundamental mechanisms to photocatalysis, surface enhanced Raman scattering and antibacterial applications

Raman spectroscopy has enabled researchers to map the specific chemical makeup of surfaces, solutions, and even cells. However, the inherent insensitivity of the technique makes it difficult to use and statistically complicated. When Raman active molecules are near gold or silver nanoparticles, the Raman intensity is significantly amplified. This phenomenon is referred to as surface-enhanced Raman spectroscopy (SERS). The extent of SERS enhancement is due to a variety of factors such as nanoparticle size, shape, material, and configuration. The choice of Raman reporters and protective coatings will also influence SERS enhancement. This review provides an introduction to how these factors influence signal enhancement and how to optimize them during synthesis of SERS nanoparticles.

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Nanoparticle Properties and Synthesis Effects on Surface-Enhanced Raman Scattering Enhancement Factor: An Introduction

Background
Surface-enhanced Raman scattering (SERS) is a powerful light scattering technique that can be used for sensitive immunoassay development and cell labeling. A major obstacle to using SERS is the complexity of fabricating SERS probes since they require nanoscale characterization and optical uniformity. The light scattering response of SERS probes may also be modulated by the substrate used for SERS analysis. A typical SERS substrate such as quartz can be expensive. Polystyrene is a cheaper substrate option but can decrease the SERS response due to interfering Raman emission peaks and high background fluorescence. The goal of this research is to develop an optimized process for fabricating Raman-labeled nanoparticles for a SERS-based immunoassay on a polystyrene substrate.

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Rational design of Raman-labeled nanoparticles for a dual-modality, light scattering immunoassay on a polystyrene substrate.

Immunoassays are used to detect proteins based on the presence of associated antibodies. Because of their extensive use in research and clinical settings, a large infrastructure of immunoassay instruments and materials can be found. For example, 96- and 384-well polystyrene plates are available commercially and have a standard design to accommodate ultraviolet-visible (UV-Vis) spectroscopy machines from various manufacturers. In addition, a wide variety of immunoglobulins, detection tags, and blocking agents for customized immunoassay designs such as enzyme-linked immunosorbent assays (ELISA) are available.
Despite the existing infrastructure, standard ELISA kits do not meet all research needs, requiring individualized immunoassay development, which can be expensive and time-consuming. For example, ELISA kits have low multiplexing (detection of more than one analyte at a time) capabilities as they usually depend on fluorescence or colorimetric methods for detection. Colorimetric and fluorescent-based analyses have limited multiplexing capabilities due to broad spectral peaks. In contrast, Raman spectroscopy-based methods have a much greater capability for multiplexing due to narrow emission peaks. Another advantage of Raman spectroscopy is that Raman reporters experience significantly less photobleaching than fluorescent tags1. Despite the advantages that Raman reporters have over fluorescent and colorimetric tags, protocols to fabricate Raman-based immunoassays are limited. The purpose of this paper is to provide a protocol to prepare functionalized probes to use in conjunction with polystyrene plates for direct detection of analytes by UV-Vis analysis and Raman spectroscopy. This protocol will allow researchers to take a do-it-yourself approach for future multi-analyte detection while capitalizing on pre-established infrastructure.

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Fabricating a UV-Vis and Raman Spectroscopy Immunoassay Platform.

https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=5640&context=etd

Nathan D. Israelsen

Papers

Nanoparticle Properties and Synthesis Effects on Surface-Enhanced Raman Scattering Enhancement Factor: An Introduction

Rational design of Raman-labeled nanoparticles for a dual-modality, light scattering immunoassay on a polystyrene substrate.

Fabricating a UV-Vis and Raman Spectroscopy Immunoassay Platform.

Surface-enhanced Raman spectroscopy-based biomarker detection for B-cell malignancies