Electrochemistry serves as a sensitive and rapid signal transduction platform for sensing applications. In contrast to commonly used diagnostic platforms which rely on polymerase-chain reaction for target amplification or immunological recognition, electrochemical-based systems are generalizable to many targets at various length-scales. At the ensemble scale, electrochemical aptamer-based (EAB) sensors convert target-recognition into an electrochemical signal via the binding-induced change in electron transfer from a redox reporter. Because aptamers are artificially selected for the detection of a wide range of small molecule, metabolite, and protein targets, EAB sensors are not restricted to chemically specific ligand-binding events and represent a generalizable platform technology that enable real-time, in vivo measurements. On a single particle scale, single-entity electrochemistry (SEE) offers unparalleled insights into the fundamental electron-transfer events that enable life. With this technique, we can parse individual differences, typically masked by some average thermodynamic response, by studying biological molecules one at a time. Doing so, we can size molecules, determine individual catalytic activity, and more broadly, characterize heterogeneous behaviors.

In this dissertation, I describe my work focused on utilizing electrochemistry to poke, prod, and improve bioanalytical sensing systems. I first address the practical needs of transitioning EAB sensors from the laboratory to the clinic; namely, I use electrochemistry to characterize disinfected or stored EAB sensors to ensure optimal device performance. Second, I tackle a longstanding issue within the electrochemistry literature that has resulted in imprecise SEE measurements. I discovered that by introducing a homogeneous chemical reaction in solution, I was able to shift the rate limiting step in current generation at an electrode from mass transport of a redox mediator to its local regeneration by a substrate. Doing so, I can achieve a ten-fold gain in measurement precision when sizing insulating particles using nanoimpact electrochemistry. Finally, with the imprecision associated with SEE greatly reduced, I lay out a foundation to explore biological interactions at a nano-scale electrode. In closing, I hope this work adds to the current body of literature establishing electrochemistry as a powerful tool for nanoscale bioanalytical systems.