Abstract

Integration of Cells with Silicon Devices for the Development of Functional Organ-on-a-Chip Systems for Preclinical Drug Discovery and Toxicology

James Hickman, Professor, University of Central Florida

One of the primary limitations in drug discovery and toxicology research is the lack of good model systems between the single cell level and animal or human systems. In addition, with the banning of animals for toxicology testing in the EU, the development of body-on-a-chip systems to replace animals with human mimics is essential for product development and safety testing. Our research focus is on the establishment of functional in vitro systems to address this deficit where we seek to create organ mimics and their subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac conduction and force generation. The idea is to integrate microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems in a circulating serum-free medium. Our philosophy is to start with 2D systems and only add complexity as needed to address biological questions to keep cost of the system at a minimum. We are using this ability to manipulate biological systems and integrate them with silicon-based systems to create body-on-a-chip systems for high content drug discovery. Examples will be given of some of the more advanced body-on-a-chip systems including a recent 4-organ system, neuromuscular junction system, and integrated cancer subsystems that are being developed as well as the results of five workshops held at NIH to explore what is needed for validation and qualification of these platforms.