To date, molecule sensors not only have a profound impact on various areas in clinical diagnostics, but also find applications in medicine, pharma, food and process control, environmental monitoring, defense and security. However, a low-cost and scalable manufacturing capability for ultra-sensitive and selective electronic molecule sensors has yet to be achieved. This Engineering Research Initiation (ERI) project will develop a novel and broadly applicable platform for detecting molecules at the single molecule scale in real-time, using nanoparticle organized single-molecule sensors patterned on a highly scalable sensor array chip. The manufacturing method is highly reproducible, scalable and of extremely low cost, due to its inherent “bottom-up” manufacturing strategy. Such electronic molecule sensor arrays are both practically manufacturable in the near term, and have a durable long-term scaling roadmap, thus providing an ideal way to bring the power of advanced manufacturing to the broad area of molecule sensing. The outcome of this project will greatly impact a variety of fields with beneficial economic and workforce implications, transition fundamental scientific discoveries into useful technologies that benefit society, promote scientific progress, increase national prosperity, and maintain US leadership in advanced manufacturing. In addition, this project will establish a program of integrated research and education, promoting education and interdisciplinary approaches in the areas of science, technology, engineering, and mathematics.<br/><br/>The goal of this project is to develop a novel, robust and scalable manufacturing process for ultra-sensitive and selective electronic molecule sensor arrays to enable real time and label-free detection of targe molecule in an all-electronic format compatible with field deployment on integrated circuit chips by leveraging recent advances in singe-molecule charge transport and colloidal cracking. This project offers solutions to two key challenges in the field. The first is creating electronic molecule sensors capable of switching ON (i.e., from insulating to conductive state) in response to target molecule binding at single molecule scale that can be seamlessly integrated on chips. The second is scalable and low-cost manufacturing method at device scale for electrode pattern with extremely small gap between electrodes so that it can yield effective sensing current, and therefore, ultra-high sensitivity. Moreover, this project advances knowledge of charge transport in molecule sensor over three distinct length scales: single molecule, single nanoparticle, and assembled molecule-nanoparticle network. This work has potentially transformative impact in realizing a long-term endeavor towards advanced manufacturing - integrating single molecules into electronic chips for molecule sensor manufacturing to achieve the ultimate miniaturization of molecular electronics.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.