High-resolution chiral separation using microfluidics-based membrane chromatography.

ABSTRACT

A plastic microfluidic system, containing porous poly(vinylidene fluoride) (PVDF) membranes adsorbed with bovine serum albumin (BSA), is demonstrated for high resolution chiral separation of racemic tryptophan and thiopental mixtures. Microfluidic networks on poly(dimethylsiloxane) (PDMS) substrates are fabricated by capillary molding technique. This miniaturized chiral separation system consists of two layers of PVDF membranes which are sandwiched between two PDMS slabs containing microchannels facing the membranes. On-line adsorption of BSA onto the membranes is employed for the preparation of chiral stationary phase and the evaluation of solution conditions in an effort to achieve maximum protein adsorption. Variations in the mobile phase conditions, including solution pH and ammonium sulfate concentration, are studied for their effects on chiral separation. Based on the large surface area to volume ratio of porous membrane media, adsorbed BSA onto the PVDF membranes enables high resolution separation of racemic mixtures with sample consumption of sub-nanogram or less in the integrated microfluidic networks. In addition, the membrane pore diameter in the submicron range eliminates the constraints of diffusional mass-transfer resistance during protein adsorption and chiral chromatographic processes.