Magnetic Nanoparticle-based Cytokine Filtering During Cardiopulmonary Bypass

 产品说明：心脏搭桥术是一种在心脏直视手术期间将血液从心脏重新输送到体外处理的手术，在美国每年进行约350，000次。虽然这通常是一种挽救生命的手术，但它也与术后并发症相对较高的大鼠相关。这主要是由于手术期间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、发烧、全身炎症、肾衰竭、肺衰竭和移植排斥反应。这些并发症也大大增加了 手术后护理的成本，并可能增加这些成本高达240%。显然，有一个显着的技术，有可能减少这种炎症反应和与之相关的副作用和并发症的需求。在这里，我们建议开发一种新的磁性纳米粒子为基础的过滤系统，可以纳入现有的体外循环血液处理设备在心肺转流手术。本文提出的系统是基于纳米级氧化铁颗粒的生物功能化，其分子靶向体外血液处理过程中分泌的促炎细胞因子。这项技术的新奇是双重的。它首先在于抗体片段和核酸适体的设计和合成，它们将附着在颗粒上。这些抗体片段和适体将以超高特异性靶向并快速结合心肺转流手术期间释放的促炎分子。第二个新概念是过滤/磁性捕获系统的设计。该系统将结合薄片流几何形状，其中血液流过稀土磁体阵列，该稀土磁体阵列被设计成产生异常高的磁场梯度，并因此产生对颗粒/炎性分子复合物的强捕获力。该原型系统的目标是捕获90%的两种重要的促炎分子，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），这两种分子将被引入猪血中作为该技术的演示。磁捕获这些促炎分子的成功演示将随后开发临床系统，这将是下一个应用的重点

 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