SERS-based microdevices for use as in vitro diagnostic biosensors.

Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional in vitro diagnostic methods, such as fluorescence and chemiluminescence, owing to its high sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.

A strategy to enhance SERS detection sensitivity through the use of SiO2 beads in a 1536-well plate.

The development of rapid and accurate assays is crucial to prevent the rapid spread of highly contagious respiratory infections such as coronavirus (COVID-19). Here, we developed a surface-enhanced Raman scattering (SERS)-enzyme-linked immunosorbent assay (ELISA) method that allows for the screening of multiple patient samples with high sensitivity on a 1536-well plate. As the well number on the ELISA well plate increases from 96 to 1536, the throughput of the assay increases but the sensitivity decreases due to the low number of biomarkers and the increase in non-specific binding species. To address this problem, silica (SiO2) beads were used to increase the surface-to-volume ratio and the loading density of biomarkers, thereby enhancing sensitivity. Using a three-dimensional gold nanoparticle (AuNP)@SiO2 SERS assay platform on a 1536-well plate, an immunoassay for the nucleocapsid protein biomarker of SARS-CoV-2 was performed and the limit of detection (LoD) decreased from 273 to 7.83 PFU/mL compared to using a two-dimensional assay platform with AuNPs. The proposed AuNPs@SiO2 SERS immunoassay (SERS-IA) platform is expected to dramatically decrease the false-negative diagnostic rate of the currently used lateral flow assay (LFA) or ELISA by enabling the positive diagnosis of patients with low virus concentrations.

Dual-mode SERS-based lateral flow assay strips for simultaneous diagnosis of SARS-CoV-2 and influenza a virus.

Since COVID-19 and flu have similar symptoms, they are difficult to distinguish without an accurate diagnosis. Therefore, it is critical to quickly and accurately determine which virus was infected and take appropriate treatments when a person has an infection. This study developed a dual-mode surface-enhanced Raman scattering (SERS)-based LFA strip that can diagnose SARS-CoV-2 and influenza A virus with high accuracy to reduce the false-negative problem of the commercial colorimetric LFA strip. Furthermore, using a single strip, it is feasible to detect SARS-CoV-2 and influenza A virus simultaneously. A clinical test was performed on 39 patient samples (28 SARS-CoV-2 positives, 6 influenza A virus positives, and 5 negatives), evaluating the clinical efficacy of the proposed dual-mode SERS-LFA strip. Our assay results for clinical samples show that the dual-mode LFA strip significantly reduced the false-negative rate for both SARS-CoV-2 and influenza A virus.