Critical flux behavior of ultrathin membranes in protein-rich solutions

Abstract

Critical flux defines the ideal operating conditions in tangential flow filtration (TFF). Below this value a TFF process can, in principle, proceed indefinitely without membrane fouling. The critical flux behavior of ultrathin membranes, which are particularly valuable for small volume processing, has not yet been explored. Here we investigate the critical flux behavior of ultrathin nanoporous silicon nitride (NPN) membranes in concentrated protein solutions using a microfluidic TFF device. We find that NPN (~19% porosity; 60 nm average pore size; 100 nm thick) has the ability to process bovine serum albumin (BSA) solutions as concentrated as 10 mg/mL at 30 μL/min without exceeding a critical flux threshold. At 30 mg/mL and 60 mg/mL, NPN enables 40% and 20% of the supply to be filtered without fouling. In these experiments, NPN membranes achieve critical flux values as high as ~1200 LMH, which is 5x larger than 0.2 μm polyethersulfone (PES) membranes processing 5 mg/mL BSA and an order of magnitude higher than track-etch polymeric membranes (10 μm thick; 80 nm pores) in direct comparisons. The effects of nanoparticle capture on critical flux are also studied here, simulating the capture of small extracellular vesicles (sEVs) in forthcoming diagnostic applications. Our work not only demonstrates the utility of ultrathin membranes for processing concentrated protein solutions, it illustrates the value of applying membrane science principles developed for macroscale systems (e.g. critical flux, TFF) to the micro/nano scale.