UC Santa Barbara

The ability to track the concentrations of specific molecules in the body in real time would vastly improve our ability to diagnose, understand, and treat disease. Most real-time molecular sensing technologies, however, rely on the adsorption of target to a receptor-modified surface. Because of this, they fail when challenged directly in complex biological media, such as whole blood. In such media, proteins, cells, and other interferents bind to the sensing interface, which leads to false positives or poor quantification. Electrochemical aptamer-based (EAB) sensors, in contrast, report on the concentration of their target via a binding-induced change in electron transfer from a redox reporter attached to a target-recognizing aptamer. They thus enable real-time molecular sensing directly in undiluted blood and even in situ in the living body. And because aptamers can be artificially selected for many target species, EAB sensors are a platform technology generalizable to a range of small molecules, metabolites, and proteins. Consistent with this, to date, EAB sensors have enabled real-time, in vivo measurements of numerous pharmaceuticals, drugs of abuse, and metabolites.

In this thesis, I described my work focused on the improvement of EAB sensor time resolution, spatial resolution, and accuracy. Specifically, I first detailed the application of the phase component of electrochemical impedance spectroscopy to push EAB time resolution to sub-second measurements. Then, with the aim of rendering them less invasive and improving their spatial resolution, I miniaturized the sensors by six-fold using nanoporous gold substrates. Finally, I improved the calibration used for in vivo quantification by examining how media selection, temperature, and age impact the accuracy of EAB sensor measurements.