Novel Sheet-Membrane Dialyzer for Wearable Hemodialysis

用于可穿戴血液透析的新型片膜透析器

基本信息

批准号：
10092447
负责人：
Dean G Johnson
金额：
$ 31.27万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
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/10092447
关键词：
Address Adoption Albumins American Animal Model Animals Area Arteries Artificial Kidney Binding Proteins Biological Assay Blood Blood Platelets Blood Pressure Blood Vessels Blood flow Cardiovascular system Cell Adhesion Cells Clinical Coagulation Process Complement Activation Cresol Detection 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 experimental study flexibility hemocompatibility improved instrument male nanomembrane novel operation portability pressure prevent programs silicon nitride treatment duration wearable sensor technology

项目摘要

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.

抽象的 2017 年，美国有超过 520,000 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，这导致了中心仪器的主导地位。基于透析的 HD 输送空间可用于改善临床结果。通过连续透析，可提高终末期肾病 (ESRD) 患者的生活质量。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，但这是不可避免的。其代价是增加生活方式的负担、访问故障的风险以及间歇性的医疗费用。治疗没有足够的时间来去除大毒素（小扩散系数）和蛋白质结合毒素。障碍在于当前薄膜的尺寸，体积庞大且不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。重大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。我们的团队开发了多种超薄（< 100 nm）纳米多孔硅基膜，并具有确立了其在提高分子分离效率和精度方面的价值。纳米膜比传统血液透析膜薄 100 至 1000 倍，我们勇敢地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提升技术。生产与支撑体分离的纳米多孔氮化物（NPN）膜材料片的技术我们建议使用 COMSOL Multiphysics 建模开发两级血液透析器。将两个 NPN 膜片串联起来，第一个 NPN 膜片（100 nm 孔径）将被滤除。细胞材料产生血浆，然后由第二层膜（20 nm 至 30 nm）透析双过滤系统将在台式上测试其从整体中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）。测试他们承受体外血流施加的压力的能力的长凳，并设计两级血液透析器将在小动物模型（雄性和雌性斯普拉格）中进行测试。 Dawley 大鼠），根据之前基于芯片的 NPN 膜的清除研究，我们预计 NPN 片状膜可用于构建机械可靠的血液透析装置，从而实现通过连续操作实现毒素的稳态水平，通过小形式实现有效的血液透析，我们的膜技术不仅将加速可穿戴高清疗法的采用，而且还将加速便携式和高清疗法的采用植入式 HD 疗法支持最近创建的“促进美国肾脏健康倡议”。改变 ESRD 治疗的实施方式。