Protein Separation and Hemocompatibility of Nitride Membranes in Microfluidic Filtration Systems

Abstract

Improving the health outcomes for end-stage renal Disease (ESRD) patients on hemodialysis (HD) requires new technologies for wearable HD such as a highly efficient membrane that can achieve standard toxic clearance rates in small device footprints. Our group has developed nanoporous silicon nitride (NPN) membranes which are 100 to 1000 times thinner than conventional membranes and are orders-ofmagnitude more efficient for dialysis. Counter flow dialysis separation experiments were performed to measure urea clearance while microdialysis experiments were performed in a stirred beaker to measure the separation of cytochrome-c and albumin. Hemodialysis experiments testing for platelet activation as well as protein adhesion were performed. Devices for the counter flow experiments were constructed with polydimethylsiloxane (PDMS) and a NPN membrane chip. The counter flow devices reduced the urea by as much as 20%. The microdialysis experiments showed a diffusion of ~ 60% for the cytochrome-c while clearing ~ 20% of the Albumin. Initial hemocompatibility studies show that the NPN membrane surface is less prone to both protein adhesion and platelet activation when compared to positive control (glass).

Figure 1

A. Membrane Fabrication. Thick NPN-O process starts with 75 nm thick silicon Nitride layer below nanoporous pnc-Si mask. Oxidation step thickens and strengthens mask allowing for long DRIE etch though 75 nm silicon Nitride Channels etched in Si substrate forming membrane regions. B: Nanoporous silicon nitride filter chip. Active membrane are (center of chip) is 1 mm × 3 mm) C. Sieving curves for the various membranes comparing membrane thickness and old non-Oxide process. D. Chip shown in fluidic device, upper channel (filled with red fluid) passes into trench in membrane surface. Lower channel (outboard ports) passes along the flat bottom of the chip.

Figure 2

Upper Callout: 3D fluid velocity in COMSOL. Cente: 3D Fluid volume model, Analyte flows through upper channel in the chip and Dialysate flows across flat side of chip in lower flow channel. Lower Callout: Urea Concentration shown in central portion of device, Urea at 100% concentration enters in upper right channel, exits at 80% on left.

Figure 3

A: Single Pass Small-molecule clearance in a counter-flow system at 4 hours and 6 hours B: Microdialysis separation of BSA and Cytochrome-C C: Comparison of Albumin adsorption on Glass, and NPN D: Platelet Activation on Glass and NPN