Modeling the microscopic electrical properties of thrombin binding aptamer (TBA) for label-free biosensors

TL;DR

This paper develops a microscopic impedance network model of the thrombin-binding aptamer (TBA) and its complex, validated with experimental data, proposing resistance measurements as a new method for testing aptamer-target affinity in biosensors.

Contribution

It introduces a novel impedance network model for TBA and its complex, advancing proteotronics and biosensor design by linking structure, function, and electrical properties.

Findings

Model accurately reproduces experimental impedance data

Proposes resistance as a new affinity testing tool

Enhances understanding of aptamer-electrode interactions

Abstract

Aptamers are chemically produced oligonucleotides, able to bind a variety of targets such as drugs, proteins and pathogens with high sensitivity and selectivity. Therefore, aptamers are largely employed for producing label-free biosensors, with significant applications in diagnostics and drug delivery. In particular, the anti-thrombin aptamers are biomolecules of high interest for clinical use, because of their ability to recognize and bind the thrombin enzyme. Among them, the DNA 15-mer thrombin-binding aptamer (TBA), has been widely explored concerning both its structure, which was resolved with different techniques, and its function, especially about the possibility of using it as the active part of biosensors. This paper proposes a microscopic model of the electrical properties of TBA and the aptamer-thrombin complex, combining information from both structure and function. The novelty consists in describing both the aptamer alone and the complex as an impedance network, thus going deeper inside the issues addressed in an emerging electronics branch known as proteotronics. The theoretical results are compared and validated with Electrochemical Impedance Spectroscopy measurements reported in the literature. Finally, the model suggests resistance measurements as a novel tool for testing aptamer-target affinity.