Recent advances in the design of SERS substrates and sensing systems for (bio)sensing applications: Systems from single cell to single molecule detection [version 1; peer review: awaiting peer review]

The Raman effect originates from spontaneous inelastic scattering of photons by matter. These photons provide a characteristic fingerprint of this matter, and are extensively utilized for chemical and biological sensing. The probability of generation, and hence the detection of these Raman scattered photons, is very low; hence, it is difficult to use this directly for sensing in complex matrices. To amplify this signal, surface-enhanced Raman spectroscopy (SERS) has been extensively investigated and has emerged as a powerful analytical tool for sensing diverse analytes, including ions, small molecules, inorganics, organics, radionucleotides, and cells. Plasmonic nanoparticles, called hotspots, exhibit localized surface plasmon resonance (LSPR). This amplifies the Raman signal and may offer up to a 10 10-fold SERS signal enhancement. The development of SERS active substrates requires further consideration and optimization of several critical features such as surface periodicity, hotspot density, mitigation of sample or surface autofluorescence, tuning of surface hydrophilicities, use of specific (bio) recognition elements with suitable linkers and bioconjugation chemistries, and use of appropriate optics to obtain relevant sensing outcomes in terms of sensitivity, cross-sensitivity, limit of detection, signal-to-noise ratio (SNR), stability, shelf-life, and disposability. This article details the optimization of the aforementioned considerations in the use of disposable materials such as commercial grades of paper, textiles, glasses, polymers, and some specific substrates such as blue-ray digital versatile discs (DVDs) for use as SERS-active substrates for point-of-use (POU) sensing applications. The advancements in these technologies have been reviewed and critiqued for analyte detection in resource-limited settings, highlighting the prospects of applications ranging from single-molecule to single-cell detection.