Aptamer-based Bioelectronic Sensors for Modular and Miniaturizable Molecular Monitoring

Life-saving medical advancements are guided by the ability to measure and understand molecular signals throughout the body. Thus, the tools we have to measure these signals are fundamental to our ability to treat and heal patients. There are a variety of laboratory and point-of-care devices that have made significant contributions to modern medical diagnostics, but each technique has major drawbacks. Except for glucose, there are few sensors on the market for continuous and point-of-care molecular monitoring. One challenge in achieving this technology is the ability to selectively and reversibly detect the analyte of interest. A second challenge is the ability to readout a signal from binding with sufficient sensitivity and limit of detection. This thesis presents a platform to meet both challenges, developed in three stages. First, steps for achieving stable organic electrochemical transistors (OECTs) are outlined as groundwork for an amplifying platform to address the signal readout challenge. Second, electrochemically modified, structure-switching aptamers are incorporated onto the OECTs, enabled by a novel transistor operation method for kinetics-sensitive measurement. Finally, considerations for translation to point-of-care, blood-based applications are characterized. Through this development, I show the aptamer-based OECT (AB-OECT) platform substantially amplifies aptamer signals, providing two orders of magnitude improvement in sensitivity. The amplification also enables miniaturization. I show the previous benefits of aptamer-based sensors are maintained, including reversibility and operation in whole blood. The presented platform technology aims to fill the point-of-care chemical sensing gap to empower physicians and patients with real-time, quantitative healthcare monitoring. The AB-OECT platform represents development in both the aptamer and in the bioelectronics fields. This expands prospects for molecular tracking in vivo, instant blood-based analysis, and continuous monitoring systems.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Bidinger, Sophia

Advisor dc:contributor.advisor

• Hasan, Tawfique

• aptamer
• biosensor
• organic electrochemical transistor

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/96724b0b-dd10-4e71-a953-7237f1136d87/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.101937

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/358128