Cells from living animals are very small, and yet measuring them and manipulating them are critical for producing new medical therapies. There are encouraging new methods to understand and control cells one at a time, but there really isn't now the technology to measure and control individually the thousands or millions of cells needed for a therapy. New approaches to individually measure and control cells using multiple nanoscopic devices are sorely needed. This award will study a method to control and measure many cells simultaneously. The base technology is a high-density platform of nanoscopic wires that interact with the cells in a culture system. The scalable nanomanufacturing of nanowire devices will make it possible to build "nanolab-on-a-chip" machines. Such tiny "laboratories", combined with a patient's own growing cells could create low-cost, predictive drug-screening platforms to accelerate drug discovery and personalized treatments. The project provides training opportunities for undergraduate, high school, and under-represented minority students in interdisciplinary research in materials science, engineering, and medicine. It augments and improves the course curriculum, and fosters a robust translational exchange with industry partners.
The project aims to overcome the barriers in developing a nanowire array-based system that enables multi-use, non-destructive, high-sensitivity measurements in 3D networks that are not possible with patch-clamp, automated patch, or microelectrode array techniques. Human-derived neurons and cardiomyocytes, which are highly relevant human models for drug screening, are studied. The project explores nanoimprint lithography as a scalable nanomanufacturing method to develop a wafer-scale nanowire neurophysiology platform scalable to 8000 simultaneous data points for 250 wells with 32 nanowire electrodes each. This scalable fabrication method enables the integration of nanowires in high densities and large numbers in integrated systems that comprise on-chip acquisition and digitization electronics and microfluidic drug intervention channels and wells. Furthermore, new architectures of multiple height nanowires are devised for screening the effects of drugs from 3D neuronal and cardiomyocyte networks and fully integrate readout electronics with the nanowire sensors. Finally, all components on a single, low cost platform scalable to 1820 wells and 115,840 simultaneous measurement points are monolithically integrated and the platform validated with a panel of drugs at the Sanford Burnham Prebys Medical Discovery Institute and UC San Diego. These technical innovations should enable non-destructive intracellular potential measurements across the depth of a tissue.
