Micro- to Nanoscale Neurochemical Sensors Abstract Current methods to measure neurochemicals in the extracellular space are limited by poor chemical, spatial, and temporal resolution. Researchers are therefore unable to investigate brain chemistries dynamically, particularly at the level of neural circuits and across broad arrays of signaling molecules. To understand cell signaling at the time scales pertinent to intrinsically encoded information, truly transformative sensors are needed that will provide highly multiplexed readouts of changes in extracellular neurochemical concentrations with sub-second response times. The objective of this proposal is to design, develop, test, and optimize neurochemical sensors that approach these critical attributes. Molecular recognition will occur via DNA sequences (aptamers) linked to field-effect transistor (FET) sensor arrays for electronic transduction of reversible binding events via conductance changes. Microscale FETs will be employed initially, followed by the development and implementation of multiplexed nanowire FETs. Lithographically fabricated FETs on silicon microprobes, and the aptamers they are functionalized with will be validated in vitro, ex vivo, and implanted for performance evaluation in vivo. By carrying out the proposed research, we will integrate and extend the unique and diverse capabilities of the members of our team to make critical advances in neurochemical sensing technologies that will enable unprecedented insight into how information is coded in cell signaling. The impact will be towards understanding the function of the healthy brain in relation to complex behaviors, and corresponding dysfunction in psychiatric and neurodegenerative disorders to ultimately identify new therapeutic targets for these diseases.