In this report the group combined the spatiotemporal resolution of microelectrodes and the chemical specificity of folding aptamer-based recognition to create sensors with improved sensitivities over macroscale sensors. Specifically, they reported for the first time the use of 25-μm-diameter gold electrodes as a platform for the fabrication of reproducible E-AB sensors for two representative targets – adenosine triphosphate (ATP) and the aminoglycoside antibiotic tobramycin. In order to circumvent small sensor currents and large background currents, they electro-deposited dendritic gold nanostructures to increase electrode surface area while maintaining the microelectrode geometric footprint. They found that the use of a nanostructured surface improved sensor performance in terms of signal-to-noise and stability. Furthermore, they observed that employing the microsensors in 100% undiluted fetal bovine serum decreased background currents from the reduction of dissolved oxygen thus allowing for improved sensor performance and demonstrated that the nonspecific adsorption on serum proteins act to further passivate the electrode surface area. As this is a work in progress, they highlight the challenges and prospects of electrochemical, aptamer-based sensors built on small-scale electrodes. The protocols presented represent general guidelines for the development of electrochemical sensors with unprecedented spatiotemporal resolution and chemical specificity.