The Aptamer BioResistor: A Broadly Applicable Protein Biosensor with Dip-and-Read Simplicity for Point-of-Care Diagnostics

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The urine test administered by an individual’s physician is not designed for the detection of any diseases. The goal of this project is to develop a simple, single-use, disposable sensor that can be dipped into a urine sample for the purpose of detecting a variety of diseases, including urinary tract infections, kidney disease, and cancers. These sensors must be inexpensive, reliable, and fast enough to test urine in a few minutes in a doctor’s office. Sensors capable of such performance are not yet available, but in previous research, a new sensor design was developed that could meet these requirements. It’s called the Impedance Transduced BioResistor or ITBR. The ITBR uses virus particles as “receptors” to do sensing. But virus particles capable of detecting disease, as required for the ITBR, are difficult to produce. The goal of this project is to adapt the ITBR so that a more common and more versatile receptor called an aptamer can be used in place of virus particles. Aptamers for some diseases are already commercially available. For other diseases, the investigators will prepare the aptamers. Aptamers are much smaller than viruses so the design of the ITBR will need to be appropriately modified. The Broader Impacts of this project include the inclusion of high school students into a summer research program in which they will learn how to make ITBRs containing aptamers.The goal of this project is to develop an Aptamer BioResistor (AptBR), in which aptamers are substituted as receptors for M13 virus particles in the Impedance-Transduced BioResistor (ITBR) developed in previous research. The Intellectual Merit of this project is in the development and characterization of an ultra thin (~100 nm) aptamer-presenting a bioaffinity layer that is compliant with the BioResistor architecture. The AptBR requires a process for the rapid and highly reproducible deposition of aptamer-conductive polymer composite films that: (1). present aptamers to a contacting solution, (2) facilitate permeation of the bioaffinity layer by target protein, and (3) electrically transduce the binding of a target protein, using the unique mechanism that operates in the ITBR. With clear design rules for the AptBR bioaffinity layer and for a new biosensor employing it, the AptBR will emerge from this project. The project has four Broader Impacts: First, the AptBR will increase the number of disease markers that can be measured using the BioResistor architecture. Second, the AptBR will be able to operate at the point-of-care to detect these diseases in animals and humans. Third, the proposal supports NEXTech 202X, an outreach program for high school students, providing hands-on laboratory science and classroom training that is keyed to the biosensor development theme of the project. Fourth, this grant will support graduate training emphasizing versatility and problem solving. These graduate students will become experienced with a broad range of tools including electron microscopy, XPS, AFM, and many others, as well as electrochemistry and microfabrication methods.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.