Tuning of salt separation efficiency by flow rate control in microfluidic dynamic dialysis

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.