Document Type



Doctor of Philosophy (PhD)



First Advisor's Name

Yi Xiao

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Bruce McCord

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Wenzhi Li

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Xiaotang Wang

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Yuk-Ching Tse-Dinh

Fifth Advisor's Committee Title

Committee member


Electrochemical aptamer-based sensor, small molecules, sensing, multianalyte detection

Date of Defense



Electrochemical aptamer-based (E-AB) sensors have been applied for diverse applications such as forensic science, pharmaceutical diagnostics, food safety, environmental monitoring, and personal medical care due to their rapid, accurate, and specific detection of analytes in complex samples. However, limited sensitivity and a lack of portable devices for point-of-care applications have greatly hindered the maturation of E-AB sensors from proof-of-concept designs to commercial systems. This dissertation describes several novel strategies to improve the sensitivities of E-AB sensors and fabricate portable paper-based devices to remedy these problems. We first detail the development of a novel approach to utilize a defined mixture of two bioreceptors that exhibit different binding profiles to tune the sensitivity and extend the dynamic range of E-AB sensors for the detection and analysis of drug families. We successfully measure 12 synthetic cathinones, a family of dangerous illicit designer drugs, with high cross-reactivity while minimizing the influence of 17 interferents. We then further enhance the sensitivity of E-AB sensors from the microscale level by developing a generalizable target-assisted immobilization strategy to control the spatial morphology of aptamers modified onto the electrode surface and thereby achieve maximum signal output. We immobilize the aptamers in a bound and folded state to ensure that the modified aptamers have sufficient space for efficient target-induced folding and signal transduction. This approach greatly improves E-AB sensor sensitivity and signal-to-noise ratio (SNR) compared to sensors fabricated by conventional methods. Finally, building on the optimal E-AB sensor design developed in my first two projects, we focus on developing portable paper-based electrochemical devices to convert these E-AB sensors from benchtop-based platforms to on-site applications. Specifically, we utilize filter paper to fabricate multiplexed aptamer-modified paper electrochemical devices (mPEDs) via ambient vacuum filtration. The fabrication process is simple, low-cost, and environmentally friendly. Moreover, the resulting postage stamp-sized paper-based devices are portable, enabling accurate and specific multianalyte detection in a microliter of a single biological sample within seconds. We believe our paper-based devices have the potential to enable sensitive and precise on-site detection for multiple analytes.



Previously Published In

Anal. Chem. 2020, 92, 7, 5041–5047, citation: 14.

ACS Appl. Mater. Interfaces 2021, 13, 8, 9491–9499, citation: 16.

ACS Appl. Mater. Interfaces 2021, 13, 15, 17330–17339,citation: 1.

Available for download on Friday, June 14, 2024



Rights Statement

Rights Statement

In Copyright. URI:
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).