RUI: Chronometric Biosensors

Early detection and frequent monitoring of infectious disease and chemical threat agents are critical to safeguarding national health and security. Rapid point-of-care (POC) biosensors play a critical role in allowing widespread testing at home and in the field, but current devices are limited in their applications because they are qualitative, not sensitive enough to detect very low concentrations of the analytes of interest, or too expensive to be deployed widely.

This project aims to develop a new class of quantitative POC biosensor that uses time as the signal for the assay and has the sensitivity of more sophisticated laboratory-based tests. Time is an ideal signal for a POC biosensor because it can be measured accurately with a simple watch, which will reduce the cost and footprint of the device, and time is not subjective the way color changes can be.

The proposed work could lead to a new class of low-cost POC biosensors capable of addressing the urgent need for point-of-care detection of disease markers, environmental contaminants, and security threats. The project will also provide an extraordinary opportunity for undergraduate students at Cal Poly to engage in basic science and engineering research with real-world applications and will encourage this next generation of scientists to pursue careers in STEM fields.

The objective of this project is to develop a new class of paper-based chronometric biosensors that will enable quantitative detection of analytes with the simplicity and low cost of lateral-flow immunoassays (LFAs) and the limits of detection of enzyme-linked immunosorbent assays (ELISAs). Most biosensors rely on optical or electrochemical signals, which require sophisticated instrumentation to be measured accurately.

The proposed biosensors will use time as the signal for the assay, which can be measured accurately with a simple watch, and could be applied broadly for the quantitative detection of biological analytes in the field. The proposed biosensors will consist of a paper-based channel, a barrier made from a biodegradable polymer that will slow or stop capillary wicking in the channel, and a simple timer for measuring the amount of time it takes for a liquid sample to wick across the polymer barrier.

By harnessing the catalytic activity of polymer degrading enzymes (PDEs), the biosensors will be able to achieve the low limits of detection that are characteristic of other enzymatic signal amplification techniques. The project will optimize different polymer-PDE pairs to enable biosensors that are compatible with a wide variety of samples with minimal interferences.

By coupling the sensor with a selection step to specifically identify biomarkers of interest, point-of-care diagnostic tests for a wide variety of analytes can be developed. Model analytes for the project will include protein, nucleic acid, and small molecule targets. The technology will help address the urgent and unmet need for quantitative and rapid point-of-care diagnostics that can be adapted rapidly to address emerging threats such as novel infectious agents.

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.