Rapid Diagnostics for Infectious Diseases Using Gold Nanoparticles

Abstract: The global COVID-19 pandemic has underscored the need for innovations in disease diagnostics.  Paper immunoassays, such as lateral flow assays, have been a critical tool for infectious diseases. These assays are low-cost, can be used in rugged environments, and possess sample-to-answer times of minutes, so they are attractive for widespread deployment for disease surveillance, quarantining, and treatment.  Biological fluids such as blood or saliva is added to the paper strip, which wicks through. Readout by eye is made possible by the gold nanoparticles, which have a strong absorption due to their nanoparticle surface plasmon resonance. Traditionally, paper immunoassays have been used only in a binary manner, providing solely yes/no information. We are interested in novel ways to develop and also use these immunoassays beyond conventional use cases. We have found that we can extend their capabilities by using them as selective sensors as opposed to specific ones, and also by exploiting the unique size and material dependent properties of the nanoparticles in the assay. By doing so, we can repurpose antibodies raised for one target (dengue and zika viruses) to construct an assay for another (yellow fever virus) by using gold nanoparticles of different colors and machine learning of the test lines colors. In addition, we can hack existing diagnostics to detect other targets of interest.  We are creating adaptive SARS-CoV-2 assays that can detect and distinguish emerging variants without the need for raising new antibodies for every variant. In addition, we discuss routes to increase the sensitivity of paper-based immunoassays via surface enhanced Raman spectroscopy (SERS). We also discuss challenges associated with the biotic-abiotic interface in paper based immunoassays, which result in undesirable side effects such as non-specific adsorption and false positives.