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

Abstract

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.

multiSero: open multiplex-ELISA platform for analyzing antibody responses to SARS-CoV-2 infection

“…The printing technology is the most expensive aspect of the pipeline, and access to the antigen array printer is a limiting factor in wide-spread deployment of multiplexed ELISA to resource-poor regions. Advances in bioprinting technology enable the possibility of an open arrayer (39). Partnerships with non-governmental organizations and multi-or bi-lateral agencies with global health missions can provide support for hardware or cold chain storage of surface-printed arrays.…”

Multi-excitation Raman Spectroscopy Complements Whole Genome Sequencing for Rapid Detection of Bacterial Infection and Resistance in WHO Priority Pathogens

“…SERS has been used to distinguish isolates of E. coli based on their sensitivity to carbapenem antibiotics 11 , and to identify pathogens common in Cystic Fibrosis sufferers in pellets with silver nanoparticles 12 . SERS has also been used to map colonies of Pseudomonas aeruginosa via laser scanning and tracking of a P. aeruginosa biomarker [13][14][15][16][17] Despite being sensitive and fast, SERS has several drawbacks. Most importantly it requires the introduction of exogenous nanomaterials for signal enhancement.…”

Challenges of SERS technology as a non-nucleic acid or -antigen detection method for SARS-CoV-2 virus and its variants

“…As there is a slow decline in the amount of live virus after symptoms appear, and an increase in the amount of dead virus increases due to seroconversion, during the later stages of infection, both live and dead viruses could be detected through SERS at the same time. With a highly sensitive and selective SERS diagnosis, this could be a powerful tool in quantitative studies investigating the dynamics of live and dead viruses in a host over the course of an infection ( Khan and Rehman, 2020 ; Tadesse et al, 2020 ).…”