A Novel Thioredoxin Mimetic Prodrug for Prevention of Bronchopulmonary Dysplasia

DESCRIPTION (provided by applicant): The merging of cell culture and microfluidic technology has resulted in improved in vitro models for toxicity studies, drug development, and biomedical research. The reason for which microfluidic approaches provide a more accurate in vitro model of in vivo effects is because devices can be designed with unique properties to closely mimic the in vivo environment. Specifically the micrometer dimensions in the devices allow for a high surface area to volume ratio, leading to more effective nutrient transfer, and allowing a more in vivo-like cellular environment in terms of cell secretion and signaling. Furthermore there is no turbulence in the microchannels as fluid flow is laminar, allowing the only means of mass transportto be through diffusion, similar to a cell's natural environment. Consequently microfluidic approaches allow for biomolecular gradients to be imitated, and additionally microfluidic devices allow for 3D cell culture. Although much research has been performed in this exciting, emerging area, it nearly exclusively has focused on the microfluidic devices themselves, leaving the means of interfacing the technology with the macro-world largely ignored. As conventional, macro detectors and fluid pumps are proven, established technology, it is desirable for microfluidic approaches to employ these industry standards. And although many acknowledge that development of micro-to-macro interface technology is vital to the future of the field as well as to the commercialsuccess of the technology, alarming little progress has been made. To date the rudimentary technique of gluing tubing to microchips for use in large, cumbersome incubators is the norm. Therefore CorSolutions proposes to develop and evaluate a universal platform, the CorCardio, to interface a wide variety of microfluidic devices to the macro-world. The platform will incorporate technology previously developed at CorSolutions including non-permanent, compression, fluidic interconnects and accurate, pulse-free fluid delivery pumps, with a heated insert design that will offer a simple alternative to an incubator. The proposed platform will be reliable, compatible with all substrate materials, easy to use with little training, flexible for use with chips having varied architectures, chemically compatible, allow for maximum field of view for optical assessment, leak-free over a wide-range of flow rates and backpressures, low cost, and have potential for automation. Thus the user-friendly platform will offer an interconnect solution with the potential of becoming the standard for cells-on-a-chip applications. This platform will allow for cells-on-a- chip applications to become pervasive in toxicology studies, lowering the high attrition rate of drugs in clinical trial while also limiting the number of animals needed for biomedical research. Furthermore the platform will allow for point-of-care applications, where patient-derived cells will permit individualized drug testing, improving therapeutic outcomes. Insummary, the interconnect platform will assist in the commercialization of cells-on-a- chip applications, enabling scientifc breakthroughs and greater understanding of complex biological systems. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Culturing cells in microfluidic devices has led to development of improved in vitro models that are able to more closely mimic in vivo environments than classic cell culture, offering more accurate correlation with in vivo results for toxicology, drug development and biomedical research. However in this emerging area, the focus has been placed on microfabrication of the devices themselves and in contrast, little attention has been placed on the essential need to interface these devices with the established, proven technologies of the macro-world. To meet this need, CorSolutions proposes to develop a flexible, universal platform, capable of interfacing a wide variety of devices with the macro-world, in a user-friendly, robust and reliable manner.