Novel Sheet-Membrane Dialyzer for Wearable Hemodialysis

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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.