Graduate Defense: Timothy Hachigian

Dissertation Information

Title: A DNA Aptamer Transducer Designed Toward Rapid Biosensor Development: A Novel Approach to Modular Biosensing Platforms

Program: Doctor of Philosophy in Materials Science and Engineering

Advisor: Dr. Jeunghoon Lee, Chemistry and Biochemistry

Committee Members: Dr. Elton Graugnard, Materials Science and Engineering; Dr. Lisa Warner, Chemistry and Biochemistry; and Dr. Eric Hayden, Biological Sciences

Abstract

Aptamer-based biosensors have garnered significant interest due to their versatility in detecting a wide range of analytes across various applications. In this work, a customizable Aptamer Transducer (AT) was introduced as a non-enzymatic and modular duplexed aptamer biosensing platform. The design modularity was accomplished by separating the aptamer input domain from the output domain. The AT was demonstrated to be capable of fully transducing an adenosine signal into arbitrary DNA outputs using a structure-switching aptamer design. The AT design utilized strand displacement reactions via toehold mediated strand displacement with fluorescence based reporting for signal detection. Furthermore, the AT was incorporated with two catalytic amplification networks to further demonstrate its customizability. In a subsequent study, the kinetic behavior and performance of modified ATs were investigated, and a high-throughput approach was developed for modifying ATs toward improving sensitivity based on an aptamer complimentary element selection method. Modular biosensing platforms based on duplexed aptamers are advantageous for rapid development of low-cost tests since sensing and output domains can be easily customized, and studies that aim to develop such platforms are beneficial for the future development of selective and sensitive assays.