UC Santa Barbara

This thesis focuses on the design, fabrication, and characterization of gold microelectrode array (MEA) devices for applications in electrochemical aptamer-based (EAB) sensing. EAB sensors leverage target-induced conformational changes in surface-bound aptamers to transduce molecular recognition phenomena into measurable electrochemical signals, enabling real-time, reversible, and reagentless detection of target molecules in complex biological environment. Such sensors are highly necessary for pharmacokinetic measurements, where continuous monitoring of target concentrations is required.Motivated by the need to extend EAB sensing beyond single-point measurements toward spatially resolved target monitoring, this work develops planar, multi-site gold microelectrode arrays fabricated using standard microfabrication techniques. The MEAs were designed to support dense packing of sensing sites while maintaining well-defined electrode geometry and compatibility with aptamer functionalization. A custom PCB interface was developed to enable reliable electrical connections to external instrumentation.Electrochemical characterization of the fabricated devices was performed using cyclic voltammetry and square-wave voltammetry to assess electrode quality, surface area, and stability before and after aptamer immobilization. Sensor performance was evaluated using kinetic differential measurements (KDM) to enhance signal robustness and suppress common-mode drift. The effects of electrode geometry, square wave frequency, and biological media on signal stability were analysed.This thesis demonstrates that MEA based EAB sensors exhibit comparable electrochemical behavior and sensing performance to conventional gold wire electrode, while additionally enabling multi-site, spatially resolved measurements.Importantly, this work also shows that planar gold microelectrode arrays can be functionalized with aptamers without electrochemical surface roughening while still achieving kinetic differential measurement (KDM) responses comparable to electrochemically roughened gold wire control electrodes. This simplifies sensor fabrication while preserving robust EAB signaling, supporting the use of planar, microfabricated platforms for scalable EAB sensor implementations. Overall, this thesis lays the foundation for reproducible and scalable MEA-based platform for EAB sensing and for the future implementation of densely packed, minimally invasive sensor arrays capable of spatially resolved pharmacokinetic measurements real-time continuous in vivo monitoring.