Non-technical Abstract Conventional diagnostic tests for viral infections focus on the biochemical properties of pathogens; they require costly reagents and multiple processing steps by highly trained personnel. This RAPID program instead uses fast and inexpensive optical techniques to detect the physical properties of viral pathogens. The breakthrough that enables this new approach to medical diagnostics is a technique called holographic particle characterization (HPC). HPC creates laser holograms of specially prepared test beads and uses those holograms to monitor small changes in the beads’ properties that occur when molecules or virus particles bind to their surfaces. Originally developed for fundamental research in soft condensed matter physics, HPC already has been demonstrated to provide fast and sensitive immunoassays in model systems. These measurements are fast, inexpensive and can be performed automatically with minimal human intervention. The next step is to create libraries of test beads for different target diseases and to demonstrate that HPC can diagnose those diseases - first in the research laboratory, and then in a clinical setting. The anticipated product of this work is a new platform for diagnosing viral infections that can meet the need for fast, accurate and cost-effective testing under the strains imposed by public health crises.
There is an urgent need for new technologies to detect viral pathogens. Holographic binding assays can detect the presence of virus particles and antibodies in fluid media through their influence on the optical properties of functionalized probe beads. The micrometer-scale beads that will be developed for this program will incorporate chemical groups on their surfaces to selectively bind specific targets, such as the SARS-CoV-2 virus responsible for COVID-19 or the antibodies that are produced in response to infection. Bound targets increase the apparent size of a bead and alter its light-scattering properties. Both of these effects can be resolved directly by holographic particle characterization, a comparatively new platform technology that has the demonstrated ability to measure the diameter and refractive index of micrometer-scale colloidal spheres with part-per-thousand precision. A statistical sample consisting of thousands of single-bead measurements can be completed in a matter of minutes using commercial instrumentation for holographic particle characterization. Specialized reagents are not required. Multiplexed assays for multiple targets can be performed with libraries of functionalized beads that are distinguished by their base diameters and refractive indexes. Each such assay can therefore simultaneously diagnose a viral infection both by the presence of virions, and also by the presence of antibodies. This RAPID program will deliver scalable syntheses of probe beads for diagnosing viral infection and automated protocols for performing holographic binding assays, enabling high-throughput medical diagnostics.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
