Project Summary Key questions of the 21st century in medicinal and biochemical areas are focused on the intimate operation and functionality of biomolecule at the molecular level. By understanding the physical properties of biomolecules at the nanoscale we can envision how to control them and use them for various applications. The proposal below is aimed to promote these key questions via the use of nanoscale electrochemistry. I am very excited to share with you some of our preliminary results and future vision dealing with both the applied and fundamental sides of Bioelectrochemistry. The first part of the proposal is focused on merges the lab expertise in nanoelectrochemistry and charge transport phenomena and focuses on an innovative method to measure the electronic response of individual enzymes during catalysis. By that, we hope to unravel by electronic means the way that enzymes operate and fluctuate with respect to their catalytic activity at the molecular level. Gained information can guide us towards the control and design of enzymes both from fundamental aspects and industrial applications. The second part of the research program offers a template for a paradigm shift in the way we think about electrochemical biosensors. We propose to construct a chemically amplified electrochemical system that enables the detection and analytical sizing of insulating materials, one at a time. We plan to use this experimental approach for designing a sensor for rapid pathogen detection. The main goal here is to innovate a sensor that can be used in a personalized fashion, without the need of complex device operation. Realization of such sensor can potentially mitigate the number of unnecessary antibiotics given at the point of care.