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Advanced Photonics Laboratory

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> Multiwell array surface-enhanced Raman spectroscopy (SERS), which integrates multiwell substrates into a standardized plate format, has emerged as a promising high-throughput screening platform for the analysis of complex biochemical fluids. However, its widespread adoption has been hindered by the lack of suitable high-speed Raman probing systems, significantly limiting practical screening throughput. To address this challenge, we recently developed a novel array-scan confocal Raman spectromicroscope, termed optical-switch Raman spectroscopy (OSRS) (Lee et al. in BioChip J 17:318–328, 2023), which shown the possibility of a highly sensitive and rapid analysis of multiwell arrays. In this work, we demonstrate high-throughput screening of multiwell array SERS using the advanced OSRS system that employs a miniaturized optical-switch Raman probe array optimized for standard two-dimensional well plates and is fully automated for Raman signal acquisition and detection. Remarkably, it achieves a measurement time of 316 s for a 96-well plate, with a detection sensitivity between 10–4 and 10–9 M, corresponding to a throughput exceeding 26,000 wells per day. This exceptional performance was validated using novel plasmonic well plates designed for liquid-phase Raman-active samples. The proposed assay represents a significant advancement in high-throughput SERS-based screening, offering transformative potential for rapid, on-site diagnostics of human biofluids in healthcare facilities.
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