Development of Next Generation Plasmonic Nanosensors for Ultrasensitive, High-Throughput Nucleic Acid and Protein Assays

Indiana University, Bloomington IN

Investigators

Abstract

As evidenced in the SARS-CoV-2 pandemic, there is an ever-increasing need for highly accurate and specific biosensors to diagnose, monitor, and manage illnesses. Existing technologies generally operate with a focus on a single disease biomarker and are unable to perform ultrasensitive assays for multiple biomarkers simultaneously, leading ultimately to false test results, specifically at the disease onset. The goal of this project is to address this limitation by constructing ultrasensitive optical-based biosensors, termed plasmonic nanosensors, that can detect marker nucleic acids and proteins by analyzing blood and urine samples. The sensors developed have the potential to substantially improve the clinical diagnostic approach for early-stage detection of various diseases such as COVID-19 and cancer. The potential applications for plasmonic nanostructures span chemical- and biochemical-sciences, clinical science, and bioengineering, as well as nanotechnology in general. The project is expected to affect efforts to provide multifaceted research and educational approaches to prepare the next generation of entrepreneurial science, technology, engineering, and mathematics (STEM) innovators through mentored-research and the integration of data and concepts into both college coursework and existing community outreach efforts. The goal of this project is to use localized surface plasmon resonance (LSPR)-active metal nanostructures to design and construct optical-based biosensors that can assay different classes of disease biomarkers, such as nucleic acids and proteins, utilizing simple UV-vis absorption spectrophotometer by measuring the LSPR peak shift before and after analyte attachment to biosensors. The LSPR-active metal nanostructures are functionalized with photoswitchable molecules (PSMs) that act as receptor binding motifs allowing the biosensor to be reversible and regenerative, thus reusable, upon repeated exposure to ultraviolet and visible light. A combined experimental and theoretical calculation approach enables selection of the most suitable chemical structure of the PSM and organic ligands connecting it to the nanostructures to enhance the biosensing sensitivity. The integration of this biosensing approach into a multi-well plate format allows construction of a high-throughput assay analyzing a few tens of patient samples with standardization in a single instrument run using a plate reader in the absorption mode. This leads to shorter assay time, with the potential to improve clinical disease diagnosis. 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.