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

Abstract

Conventional hemodialysis (HD) uses floor‐standing instruments and bulky dialysis cartridges containing ≈2 m2 of 10 micrometer thick, tortuous‐path membranes. Portable and wearable HD systems can improve outcomes for patients with end‐stage renal disease by facilitating more frequent, longer dialysis at home, providing more physiological toxin clearance. Developing devices with these benefits requires highly efficient membranes to clear clinically relevant toxins in small formats. Here, the ability of ultrathin (<100 nm) silicon‐nitride‐based membranes to reduce the membrane area required to clear toxins by orders of magnitude is shown. Advanced fabrication methods are introduced that produce nanoporous silicon nitride membranes (NPN‐O) that are two times stronger than the original nanoporous nitride materials (NPN) and feature pore sizes appropriate for middle‐weight serum toxin removal. Single‐pass benchtop studies with NPN‐O (1.4 mm2) demonstrate the extraordinary clearance potential of these membranes (105 mL min−1 m−2), and their intrinsic hemocompatibility. Results of benchtop studies with nanomembranes, and 4 h dialysis of uremic rats, indicate that NPN‐O can reduce the membrane area required for hemodialysis by two orders of magnitude, suggesting the performance and robustness needed to enable small‐format hemodialysis, a milestone in the development of small‐format hemodialysis systems.

Macrophage Membrane‐Coated, Nanostructured Adsorbent Surfaces in a Microfluidic Device for Extracorporeal Blood Cleansing in Bacterially Induced Sepsis

“…[22] Perfusion rates in our microfluidic devices were adjusted to 1 mL min −1 , as shown by others not to affect systolic blood pressure or heartbeat rate in rats. [19,23] Results with murine blood indicated that E. coli-activated macrophage membrane-coated SiNW adsorbent surfaces are more effective for extracorporeal cleansing of blood in a microfluidic device than commercially available hemofiltration membranes. Importantly, cleansing of blood from healthy human donors using macrophage membrane-coated adsorbent surfaces does not affect healthy cytokine levels.…”

Nanoelectrochemistry at liquid/liquid interfaces for analytical, biological, and material applications

“…The ultrathin nanoporous membranes can be molecularly thin (B10 nm in thickness) and, subsequently, much more permeable than traditional nanoporous membranes but still robust enough to be self-standing in the solution. 71 The ultrathin nanoporous membranes can be considered as superior alternatives for hemodialysis 72 and cell co-culture 73 and also as enabling nanomaterials for wearable artificial kidney 74 and tissue-on-chips. 75 The dimensions of ultrathin solid-state nanopore membranes can be similar to those of the nuclear envelope perforated by nuclear pore complexes with a pore length of 35 nm and a pore radius of 24 nm.…”

The Dual Roles of Protein-Bound Solutes as Toxins and Signaling Molecules in Uremia

“…Moreover, membranes should be ultrathin to guarantee a large surface area in a small device and should have sufficient strength and appropriate pore sizes to allow middle molecular weight molecules' removal. This might be offered by nanoporous siliconnitride-based membranes, with a diameter of pores typically 100 nanometers or smaller [9]. Novel membranes that contain mesoporous carbons, i.e., nanoporous material containing pores with diameters between 2 and 50 nm, as sorbents with dual-porosity (micro/meso) or sorbent particles for selective and efficient removal of protein-bound uremic toxins as well as cytokines from human plasma, may provide promising alternatives [10][11][12].…”