Magnetic Nanoparticle-based Cytokine Filtering During Cardiopulmonary Bypass

 描述：体外循环是一种在心内直视手术期间将血液从心脏重新路由到体外处理的程序，在美国每年大约进行350,000次。虽然通常是挽救生命的手术，但它也与手术后并发症的相对较高的大鼠有关。这主要是由于手术过程中与血液体外处理相关的炎症过程的激活。这些并发症可能很严重，可能包括外周水肿、血栓形成、发热、全身炎症、肾功能衰竭、肺功能衰竭和移植排斥反应。这些并发症还显著增加了 增加了术后护理费用，可能会使这些费用增加高达240%。显然，非常需要有可能减少这种炎症反应以及与之相关的副作用和并发症的技术。在这里，我们建议开发一种新的基于磁性纳米颗粒的过滤系统，该系统可以在体外循环手术期间整合到现有的体外血液处理设备中。这里提出的系统是基于纳米级氧化铁颗粒与分子的生物功能化，这些分子针对体外血液处理过程中分泌的促炎细胞因子。这项技术的新颖性是双重的。它首先在于抗体片段和核酸适配子的设计和合成，这些片段和核酸适配子将附着在颗粒上。这些抗体片段和适配子将靶向并快速结合体外循环过程中释放的促炎分子，具有超高的特异性。第二个新颖的概念是过滤/磁捕获系统的设计。该系统将结合薄层流动几何结构，使血液流经稀土磁体阵列，以产生极高的磁场梯度，从而对颗粒/炎症分子复合体产生强大的捕获力。这个原型系统的目标是捕获两种重要的促炎分子--白介素6(IL6)和肿瘤坏死因子-α(TNF-α)--的90%，这两种分子将被引入猪血中，作为该技术的演示。在成功展示这些促炎分子的磁性捕获之后，将开发一种临床系统，这将是下一步应用的重点

 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