Abstract: We propose to assemble nanowire devices with optoelectronic and electrical functionalities to probe intra- and inter-cellular dynamics with unprecedented spatial and temporal resolution. Arrays of electrically pumped nanowire waveguides, lasers, light emitting diodes, and photodetectors combined along with their ability to function as nanoelectrodes will be utilized to probe organelles and other subcellular targets with nanoscale resolution and measure in real-time chemical reaction kinetics, signal propagation, and reactions due to a locally delivered drug, amongst other complex phenomena occurring over any relevant length scales. The arrays of nanowire probes will be functionalized with fluorophores, quantum dots, plasmonic nanocrystals, either at their tips or on their surfaces to enable almost any type of biological imaging technique. Using a general nanowire probe platform will lead to the development of a very broad set of tools with novel functionalities, to enable imaging and electrical probing with label-free techniques with the unique capability of probing any desired spatial domain within living cells. These nanowire-probe substrates can be easily integrated with AFM cantilevers or the tips of conventional fibers, which can then be combined with standard 3-D nanopositioning systems, external electrical circuitry, and optical microscopes to probe specific domains of intracellular organelles/components. As an example, these nanowire devices will be used to create novel nanoscale interfaces with neurons and neuronal networks in the hippocampus to study neuronal signal integration and network functioning and then utilized to investigate the pathophysiology of diseases such as epilepsy. The integration of optoelectronic and electrical functionalities of nanowires on a common platform would lead to a new generation of nanosystems with unprecedented sensitivity and selectivity in probing subcompartments of living cells at the molecular level, which could revolutionize our knowledge of these biological systems and tremendously aid in future drug discoveries. Public Health Relevance: The ability to visualize in vitro intra- and inter- cellular processes in real time with multiplexed and nanoscale resolution detection with the proposed combined optoelectronic and electrical nanowire probes will elucidate new chemical and electrochemical processes and signaling pathways. Detailed knowledge of suband inter- cellular processes using nanowire probes will lead to a much better understanding of overall cellular processes and will aid the design of new drugs for a large number of diseases thereby impacting public health.