Novel Sheet-Membrane Dialyzer for Wearable Hemodialysis

摘要 2017年，美国有超过52万名终末期肾病患者接受了常规透析。 传统的血液透析(HD)使用落地式仪器，这导致了中心- 高清分娩空间的基础透析。可穿戴HD系统可用于改善临床结果 通过实现持续透析，提高终末期肾病患者的生活质量。可穿戴式高清还支持频繁 根据灵活的治疗计划进行透析。虽然更频繁的透析有潜在的好处，但这是 代价是增加了生活方式的负担、接入故障的风险和医疗保健成本。还有，插曲 治疗没有足够的时间来清除大毒素(扩散系数小)和结合蛋白质的毒素。 障碍是当前膜的大小，这些膜很笨重，不容易集成到可穿戴系统中 并需要大量的体外血流来实现适当的毒素清除。实现 重大的改进将需要高效的膜，能够在小范围内去除规定的毒素 设备格式。 我们团队已经开发了各种超薄(100 Nm)纳米多孔硅基薄膜，并 确定了它们在提高分子分离的效率和精度方面的价值。因为 我们推测，纳米膜比传统的血液透析膜薄100到1000倍 他们能够将血液透析的形式减少几个数量级。我们最近研制出了一种升空装置 从支撑体分离的纳米多孔氮化物(NPN)膜材料片材的制备技术 硅片。我们建议使用COMSOL多物理模型开发一种两级血液透析器 将两片NPN膜串联在一起。第一层NPN薄膜(100 nm孔)将被过滤掉 产生血浆的细胞材料，然后通过第二层膜(20 nm到30 nm)进行透析 毛孔)。双过滤系统将在桌面上测试其将尿毒症毒素与整体分离的能力 并测量血液相容性(溶血、补体激活等)。这些设备还将被 试验台测试他们承受体外血流所施加的压力的能力，并设计 超滤。两级血液透析器将在小动物模型上进行测试(雄性和雌性Sprague. 道利大鼠)。我们预计，基于先前对基于芯片的NPN膜的清除研究，NPN 片状薄膜可以用来构造机械上可靠的血液透析装置，从而实现 通过连续操作实现毒素的动态平衡水平。通过实现有效的血液透析是小形式的， 我们的膜技术不仅将加速采用可穿戴式高清疗法，而且还将加速采用便携式和 植入式HD疗法。这一努力支持最近创建的“推进美国肾脏健康倡议” 以改变ESRD治疗的提供方式。

Abstract More than 520,000 patients with End Stage Renal Disease (ESRD) underwent routine dialysis in the US in 2017. Conventional hemodialysis (HD) uses floor-standing instruments, which contributes to the dominance of center- based dialysis for the HD delivery space. Wearable HD systems could be employed to improve clinical outcomes and quality of life for patients with ESRD by enabling continuous dialysis. Wearable HD also enables frequent dialysis on a flexible treatment schedule. While there are potential benefits of more frequent dialysis, this comes at a cost of increased burden on lifestyle, risks of access malfunction, and health care costs. Also, episodic treatments provide insufficient time to remove large toxins (small diffusion coefficients) and protein-bound toxins. The barrier is the size of the current membranes which are bulky and not easily integrated into a wearable system and require large amounts of extracorporeal blood flow to achieve appropriate toxin clearances. Achieving significant improvements will require highly efficient membranes that enable prescribed toxin removal in small device formats. Our group has developed a variety of ultrathin (< 100 nm) nanoporous, silicon-based membranes and have established their value in improving the efficiency and precision of molecular separations. Because nanomembranes are 100 to1000 times thinner than conventional hemodialysis membranes, we hypothesize their ability to reduce the format for hemodialysis by orders of magnitude. We have recently developed a lift-off technique to produce sheets of nanoporous nitride (NPN) membrane material separated from the supporting silicon wafer. We propose to develop, using COMSOL Multiphysics modeling, a two-stage hemodialyzer incorporating two NPN membrane sheets in series. The fist NPN sheet membrane (100-nm pores) will filter out the cellular material generating plasma that will then be dialyzed by the second membrane (20-nm to 30-nm pores). The two-filter system will be tested on the benchtop for its ability to separate uremic toxins from whole blood and measured for hemocompatibility (hemolysis, complement activation etc.). The devices will also be bench tested for their ability to withstand the pressures exerted by the extracorporeal blood flow and designed ultrafiltration. The two-stage hemodialyzers will be tested in a small-animal model (male and female Sprague- Dawley rats). We expect, based on previous clearance studies with chip-based NPN membranes, that NPN sheet membranes can be used to construct a mechanically reliable hemodialysis device that achieves homeostatic levels of toxins through continuous operation. By enabling effective hemodialysis is small formats, our membrane technology will hasten the adoption of not only wearable HD therapies, but of portable and implantable HD therapies. This effort supports the recently created “Advancing American Kidney Health initiative” to transform how ESRD therapy is delivered.