Diffusive Silicon Nanopore Membranes for Hemodialysis Applications

Abstract

Hemodialysis using hollow-fiber membranes provides life-sustaining treatment for nearly 2 million patients worldwide with end stage renal disease (ESRD). However, patients on hemodialysis have worse long-term outcomes compared to kidney transplant or other chronic illnesses. Additionally, the underlying membrane technology of polymer hollow-fiber membranes has not fundamentally changed in over four decades. Therefore, we have proposed a fundamentally different approach using microelectromechanical systems (MEMS) fabrication techniques to create thin-flat sheets of silicon-based membranes for implantable or portable hemodialysis applications. The silicon nanopore membranes (SNM) have biomimetic slit-pore geometry and uniform pores size distribution that allow for exceptional permeability and selectivity. A quantitative diffusion model identified structural limits to diffusive solute transport and motivated a new microfabrication technique to create SNM with enhanced diffusive transport. We performed in vitro testing and extracorporeal testing in pigs on prototype membranes with an effective surface area of 2.52 cm2 and 2.02 cm2, respectively. The diffusive clearance was a two-fold improvement in with the new microfabrication technique and was consistent with our mathematical model. These results establish the feasibility of using SNM for hemodialysis applications with additional scale-up.

Silicon nanoporous membranes as a rigorous platform for validation of biomolecular transport models

“…The reduced pore size necessarily results in a decrease in the membrane surface porosity. For pore sizes in this range, there is complete rejection of albumin as confirmed by previous studies [23][24][8]. This method assumes that the PEG chains grafted on the membrane pore surface form a uniform, dense structure and the large majority of the fluid flows in the open pore region.…”

Second Generation Nanoporous Silicon Nitride Membranes for High Toxin Clearance and Small Format Hemodialysis

“…Measuring clearance as a function of flow rate, we found that the area normalized urea clearance reached a maximum of ≈45 000 mL min −1 m −2 in the presence of 100% serum, and ≈60 000 mL min −1 m −2 in the absence of serum ( Figure a). These values are orders of magnitude greater than the mass transfer coefficient, K o , of conventional hemodialysis membranes (<1000 mL min −1 m −2 theoretical) and the values reported for silicon slit‐pore membranes (≈150 mL min −1 m −2 ) …”

“…In an effort to improve both health outcomes and quality of life for those on HD, research groups, including ours, are working on technologies for portable, wearable, or implantable HD . Such devices would not only provide lifestyle benefits in the form of mobility and convenience, they could also improve treatment outcomes by enabling more frequent or continuous dialysis (keeping uremic toxin levels steady with consistent water‐, electrolyte‐, and acid/base‐balance) that more closely replicates a functioning kidney.…”

Protein Separation and Hemocompatibility of Nitride Membranes in Microfluidic Filtration Systems

“…Additionally, the membrane pore sizes can be tuned to match specific molecular separation goals [13] and the silicon platform allows for scalable manufacturing and straightforward integration with fluidics. Other groups are also working on silicon-based filter membranes [14] but have not achieved the thinness of our nanoporous nitride membranes and therefore cannot achieve the clearance rates with the same surface area.…”