Magnetic Nanoparticle-based Cytokine Filtering During Cardiopulmonary Bypass



 DESCRIPTION: Cardiopulmonary bypass, a procedure that re-routes the blood from the heart for extracorporeal processing during open-heart surgery, is performed some 350,000 times per year in the US. While often a life-saving procedure, it is also associated with relatively high rats of post-surgical complications. This is primarily due to the activation of inflammatory processes associated with the extracorporeal processing of the blood during surgery. These complications can be serious and may include peripheral edema, thrombosis, fever, systemic inflammation, kidney failure, lung failure, and transplant rejection. Theses complications also add significantly to the cost of post-operative care and can increase these costs by as much as 240%. Clearly, there is a significant need for technologies that have the potential to reduce this inflammatory response and the side-effects and complications associated with it. Here we propose to develop a novel magnetic nanoparticle-based filtration system that can be incorporated into existing extracorporeal blood processing devices during cardiopulmonary bypass surgery. The system proposed here is based on bio-functionalization of nano-scale iron oxide particles with molecules that target pro-inflammatory cytokines secreted during extracorporeal blood processing. The novelty of this technology is two-fold. It lies first in the design and synthesis o antibody fragments and nucleic acid aptamers, which will be attached to the particles. These antibody fragments and aptamers will target and rapidly bind pro-inflammatory molecules released during the cardiopulmonary bypass procedure with ultra-high specificity. The second novel concept is the design of the filtration/magnetic capture system. This system will incorporate a sheet flow geometry with the blood flowing over arrays of rare earth magnets designed to produce exceptionally high magnetic field gradients and, hence, strong capturing forces on the particle/inflammatory molecule complex. The target for this prototype system is to capture 90% of two important pro-inflammatory molecules, interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-a), that will be introduced into pig blood as a demonstration of the technology. Successful demonstration of magnetic capture of these pro-inflammatory molecules will be followed by development of a clinical system that will be the focus of the next application