Novel Sheet-Membrane Dialyzer for Wearable Hemodialysis

用于可穿戴血液透析的新型片膜透析器

• 批准号: 10450175
• 负责人: Dean G Johnson
• 金额: $ 30.5万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10450175
• 关键词: Address; Adoption; Albumins; American; Animal Model; Animals; Area; Arteries; Artificial Kidney; Binding Proteins; Blood; Blood Platelets; Blood Pressure; Blood Vessels; Blood flow; Cardiovascular system; Cell Adhesion; Cells; Clinical; Coagulation Process; Complement Activation; Cresol; Devices; Dialysis procedure; Diffusion; End stage renal failure; Excision; Female; Filtration; Floor; Generations; Health; Health Care Costs; Heart Rate; Hemodialysis; Hemolysis; Homeostasis; Hour; Human; Infusion procedures; Injections; Kidney; Life Style; Lifting; Measures; Mechanics; Membrane; Metabolic; Metabolic Clearance Rate; Modeling; Molecular; Nanoporous; Outcome; Patients; Plasma; Preparation; Proteins; Public Health; Quality of life; Rattus; Research; Risk; Route; Sampling; Series; Silicon; Sprague-Dawley Rats; System; Techniques; Technology; Testing; Time; Toxin; Treatment Protocols; Ultrafiltration; Urea; Water; Weight; Whole Blood; base; beta-2 Microglobulin; cost; design; detection assay; detection limit; experimental study; flexibility; hemocompatibility; improved; instrument; male; nanomembrane; novel; operation; portability; pressure; prevent; programs; silicon nitride; treatment duration; wearable sensor technology

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.

摘要 2017年，美国有超过52万名终末期肾病（ESRD）患者接受了常规透析。 传统的血液透析（HD）使用落地式仪器，这有助于中心- 基于透析的HD输送空间。可穿戴HD系统可用于改善临床结果 和生活质量为终末期肾病患者通过启用连续透析。可穿戴高清还可以实现频繁的 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， 其代价是增加了生活方式的负担、接入故障的风险和卫生保健费用。此外，Episodic 处理提供的时间不足以去除大毒素（小扩散系数）和蛋白质结合的毒素。 屏障是当前膜的大小，其体积庞大并且不容易集成到可穿戴系统中 并且需要大量的体外血流来实现适当的毒素清除。实现 显著的改进将需要高效的膜，其能够在小的环境中去除规定的毒素。 设备格式。 我们的小组已经开发了各种纳米多孔（< 100 nm）硅基膜，并已 确立了它们在提高分子分离效率和精度方面的价值。因为 纳米膜比传统的血液透析膜薄100到1000倍，我们假设 他们能够将血液透析的形式减少几个数量级。我们最近开发了一种升空 一种生产与载体分离的纳米多孔氮化物（NPN）膜材料片的技术 硅晶片我们建议使用COMSOL Multiphysics建模开发一种两级血液透析器 包括两个串联的NPN膜片。第一个NPN片膜（100纳米孔）将过滤出 产生血浆的细胞材料然后被第二膜（20-nm至30-nm）透析 孔）。双过滤器系统将在实验台上测试其分离尿毒症毒素的能力， 血液并测量血液相容性（溶血、补体激活等）。这些设备还将 实验室测试其承受体外血流施加的压力的能力， 超滤将在小动物模型（雄性和雌性Sprague- 道利大鼠）。根据先前对芯片型NPN膜的清除研究，我们预计， 片状膜可用于构造机械可靠的血液透析装置 通过持续的运作来维持体内毒素水平。通过使有效的血液透析成为小格式， 我们的膜技术不仅将加速可穿戴HD疗法的采用， 植入式HD治疗。这项努力支持最近创建的“推进美国肾脏健康倡议” 来改变ESRD治疗的方式。