Abstract
Microliter-scale separation processes are important for biomedical research and point-of-care diagnostics with small-volume clinical samples. Analytical assays such as mass spectrometry and field effect sensing necessitate sample desalting, but too low a salt concentration can disrupt protein structures and biomolecular interactions. In this work, we investigated whether salt extraction from a protein solution can be controlled by dynamic dialysis parameters. A microfluidic counter-flow dialyzer with a 5 kDa molecular weight cut-off cellulose membrane was fabricated by laser cutting and operated with a wide range of feed and dialysis flow rates. It was found that with the appropriate flow conditions, most notably the feed flow rate, retentate salt concentrations from 0.1 to 99% of the input NaCl concentration can be achieved. The experimental data were in good agreement with a theoretical diffusion-based mass transfer model. The salt dialysis performance was similar in the presence of 50 mg/mL albumin, approximating blood plasma protein content, and did not deteriorate with overnight continuous dialysis, indicating minimal membrane fouling. The dialyzer construction method is compatible with all planar membranes, enabling implementation of tuneable dynamic dialysis for a wide range of on-line microfluidic biomolecular separations.
Highlights
Membrane-facilitated molecular separations play a key role in many large-scale industrial processes, ranging from seawater desalination to fruit juice clarification, and in milliliter-scale sample processing in biomedical research laboratories
Buffer exchange, mass transport over the membrane is driven by pressure-induced flux; while mass transport in a dialysis process is primarily determined by concentration gradients over the membrane (Saxena et al 2009)
Cross sections of regenerated cellulose UF membranes were visualized with electron microscopy, revealing the typical ultrastructure of membranes synthesized by phase inversion (Cuperus and Smolders 1991)
Summary
Membrane-facilitated molecular separations play a key role in many large-scale industrial processes, ranging from seawater desalination to fruit juice clarification, and in milliliter-scale sample processing in biomedical research laboratories (van Reis and Zydney 2007; Saxena et al 2009; Kazemi et al 2016). Cross-flow, implying that the dialysate stream is perpendicular to the sample stream (e.g., crossing a bundle of hollow fiber membranes), had an intermediate performance (Yeh and Hsu 1999). It was demonstrated experimentally, for a flow cell with a planar microporous cellulose ester membrane, that countercurrent operation results in more efficient dialysis than cocurrent flow (Yeh and Chang 2005). To establish to which extent the separation performance can be modulated by the hydrodynamic conditions, we quantified salt transfer over a regenerated cellulose membrane in a lasermachined microfluidic counter-flow dialyzer for a wide range of feed and dialysate flow rates. Flow-controlled microfluidic diffusion dialysis, enables applications such as tuneable desalting of biomolecular samples, where a physiological salt concentration interferes with analytical assays but too low a salt concentration induces protein denaturation or modifies biomolecular interactions (Xu et al 1998; Zhou and Pang 2018)
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