By coupling the specific and selective binding of biomolecules with conformation-linked signaling and electrochemical outputs, electrochemical aptamer-based sensors (E-AB sensors) provide a unique ability to measure molecules in real-time directly in complex media. Because E-AB sensors do not require washing steps or reagent additions, they open the door for measurements directly where they are needed – in complex sample streams such as foodstuffs, clinical samples, and even directly within the living body. To further advance this promising technology, my work has addressed both improvements in the physical sensor and improvements in how we use the electron transfer kinetics underlying the signaling in these sensors to circumvent the drift associated with performing measurements directly in complex media. That is, using new electrode formats and new analytical signal-processing techniques, my thesis work created fully realized devices capable of measuring specific molecular targets in real time in relevant, highly complex sample streams. As examples, in my thesis I describe sensors supporting the measurement of a mycotoxin directly within the flowing sample stream of a foodstuff affected by that mycotoxin, the measurement of a malaria diagnostic protein in clinically-relevant ranges directly in a fingerprick-sized sample of human serum, a new technique to measure a protein of interest directly in unprocessed whole blood – without pre-calibration, and new deployments of thin, surgically-implanted wire electrodes with sensors that measure, for the first time, in vivo blood concentrations in real time of a variety of small-molecule drugs as well as an arbitrary circulating protein of interest
