SERS-based Virus Detection and Study of Viral Evolution
Emerging viral pathogens such as SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, can transmit undetected from person to person often without apparent symptoms. This feature largely facilitates its rapid spread and underscores the importance of the development and deployment of infectious disease surveillance systems at the early stages to test, isolate, and trace the viral spread in efforts to contain an outbreak and mitigate damage. Rapid evolution in RNA viruses gives the ability to some viruses to jump from species to species, leading to spillover events. This genetic drift is also responsible for the low effectiveness or the lack of vaccines for certain RNA pathogens. The impact on the healthcare systems worldwide and the repercussions on patients are substantial, as we are witnessing. Understanding viral mutations holds significant importance because of its wide impact on new vaccine design, drug resistance management, and prediction of new pathogenesis. Furthermore, approaches that are designed to study viral evolution can be adapted to implement effective diagnostic platforms.
In our research, we focus on the implementation of SERS probes for the identification and quantification of viral RNA in intact individual cells, leveraging an ON-OFF SERS signal switching that is triggered by the conformational changes in the sequence-specific oligonucleotides bound to the gold nanostar-based probes. In our work we have demonstrated that individual nanostars can provide measurable signal, and that their response is only partially affected by the formation of protein corona in media, cell lysate, or intact cells. Furthermore, these probes are sensitive to base mutations within the target RNA, and are selective toward their intended target, even within individual cells. In order to expand our technology to the clinic, we complement the SERS-based method with a nanoparticle design that enables fluorescence transduction on the same nanostars and on nanoflare systems designed for similar targets. These unique probes are promising because they are uniquely suited to provide response on population outliers that could be indicative of a superspreader behavior, and because they can be easily adapted to target any viral RNA, individually and in multiplex, to enable the implementation of effective diagnostic platforms with high sensitivity and throughput. Therefore, one of our interests is also the implementation of cutting-edge diagnostic devices that break away from PCR amplification and could be integrated with low cost, portable Raman spectrometers for an effective integration in the clinic.