Toward rapid infectious disease diagnosis with advances in surface-enhanced Raman spectroscopy

In a pandemic era, rapid infectious disease diagnosis is essential. Surface-enhanced Raman spectroscopy (SERS) promises sensitive and specific diagnosis including rapid point-of-care detection and drug susceptibility testing. SERS utilizes inelastic light scattering arising from the interaction of incident photons with molecular vibrations, enhanced by orders of magnitude with resonant metallic or dielectric nanostructures. While SERS provides a spectral fingerprint of the sample, clinical translation is lagged due to challenges in consistency of spectral enhancement, complexity in spectral interpretation, insufficient specificity and sensitivity, and inefficient workflow from patient sample collection to spectral acquisition. Here, we highlight the recent, complementary advances that address these shortcomings, including (1) design of label-free SERS substrates and data processing algorithms that improve spectral signal and interpretability, essential for broad pathogen screening assays; (2) development of new capture and affinity agents, such as aptamers and polymers, critical for determining the presence or absence of particular pathogens; and (3) microfluidic and bioprinting platforms for efficient clinical sample processing. We also describe the development of low-cost, point-of-care, optical SERS hardware. Our paper focuses on SERS for viral and bacterial detection, in hopes of accelerating infectious disease diagnosis, monitoring, and vaccine development. With advances in SERS substrates, machine learning, and microfluidics and bioprinting, the specificity, sensitivity, and speed of SERS can be readily translated from laboratory bench to patient bedside, accelerating point-of-care diagnosis, personalized medicine, and precision health.