This PFI: AIR Technology Translation project focuses on translating research activities in high flow rate microfluidics and bioactive surface coatings to fill the need for improved technologies for therapeutic removal of blood constituents, with an emphasis on the treatment of sepsis (blood infection). The project will result in a proof of concept of the proposed microfluidic adsorption technology for safe and efficient removal of bacterial endotoxin from blood. This technology has the following unique features: microscale architecture designed to enhance adsorption at the device surface and a biocompatible surface coating with strong binding affinity for bacterial pathogens in the presence of blood. These features will enable greatly improved adsorption efficiency, as well as improved safety and reduced damage to blood cells when compared to existing technologies for adsorption-based removal of blood constituents. The microfluidic adsorption technology is important because it will enable improved treatment of a variety of medical conditions that are mediated by the blood, including sepsis, as well as autoimmune diseases such as lupus. In particular, sepsis affects 750,000 people per year in the US and accounts for nearly $17 billion in treatment costs. There is no cure for sepsis; approximately 1 in 3 people who develop sepsis will die. Thus, clinical translation of the proposed technology will have important ramifications for both patient health and treatment costs. The potential economic impact is a platform technology for safe and efficient removal of blood constituents, with a product targeting removal of endotoxin anticipated in the next 5 years. This will contribute to the U.S. competitiveness in medical devices for blood processing. Because numerous medical conditions are mediated by the blood, extracorporeal devices for targeted removal of specific blood constituents offer enormous therapeutic potential. However, a common challenge faced by such an approach is the efficient removal of target entities without damaging blood cells. To overcome this challenge we plan to develop highly parallelized microfluidic devices that are capable of operating at clinically relevant flow rates, with a microscale geometry that is optimized for harnessing red blood cell migration to enhance adsorption at the device surface. To ensure biocompatibility and selective adsorption, the internal surface of the device will be coated with a nonfouling polyethylene oxide (PEO) brush layer, and a bioactive agent with high binding affinity for bacterial pathogens will be immobilized to the PEO chain ends.
