SBIR-STTR Award

This Small Business Innovation Research (SBIR) Phase I project is the development of a lung tissue model based on a new cell culturing platform utilizing nanoparticle-based reagents and magnetic fields to levitate tissue samples and allow three-dimensional (3D) growth. This method naturally grows tissue at the air-liquid interface and is well suited for co-culturing, which are crucial for an accurate in vitro lung model. The application and market for this product will be drug discovery and toxicity screening. In the early stages of drug development, candidate compounds are screened for efficacy and toxicity in in vitro model systems. Currently, these tests are performed in high-throughput assays using two-dimensional (2D) tissue, but 2D culturing alters cellular responses and often leads to misleading results. Subsequent tests in animal models are costly, ethically contentious, and sometimes inaccurate since model organisms may not faithfully reproduce human responses.The broader impact of this proposal follows from the potential to use the tissue model for improved in vitro efficacy and toxicity assays to reduce the cost of drug development. The reduction of animal testing is also an important goal for ethical reasons. In addition, a lung tissue model that recapitulates natural tissue properties and responses can also find application in toxicity screening of environmental, cosmetic, and industrial factors. The current worldwide expenditure for animal toxicity testing is over $10 billion/yr, and replacement in vitro methods are already over $200 million/yr and growing rapidly. An improved lung model will have significant impact in these areas.

This Small Business Innovation Research (SBIR) Phase II project will use in vitro three-dimensional (3D) cell culturing enabled by the magnetic levitation method (MLM) as an improved tool for toxicity testing. This work will probe the effects of common agents on the lung, liver and kidney, three organs that play a central role in drug metabolism and are predisposed to toxic injury. 2D cell culture, commonly utilized for testing the cytotoxic effects of drugs, displays limited accuracy in predicting toxicity in vivo due to fundamental differences in the cellular microenvironment. While better representations of the 3D architecture of in vivo tissue are provided by animal models, they fail to accurately reflect whether or not drugs will cause cellular damage in humans as a result of biological differences between species. Our preliminary data shows that magnetic levitation maintains cells in culture in an arrangement that allows the cells to develop and communicate in a manner that is much closer to the in vivo environment than other in vitro systems.The broader impacts of this research are to improve assessment of drug toxicity and chemical hazards, reduce the use of animals, and advance the fields of in vitro toxicology testing and drug discovery. Commercial potential includes expansion of the device into high-throughput screening, generation of a prototype of a gas delivery system with capabilities to perform live cell microscopy, and development of a label-free viability assay for drug discovery and toxicity testing.