Phase-changing sacrificial materials for interfacing microfluidics with ion-permeable membranes to create on-chip...

We have developed a novel approach for interfacing ionically conductive membranes with microfluidic systems using phase-changing sacrificial layers. Imprinted microchannels in a polymer substrate are filled with a heated liquid that solidifies at room temperature, a monomer solution is placed over the protected channels and polymerized to form a rigid semipermeable copolymer, and then the protective layer is melted and removed, leaving an open microchannel interfaced with a polymer membrane. We have applied this method in miniaturizing electric field gradient focusing (EFGF) and carrying out on-chip protein preconcentration. A semipermeable copolymer in the EFGF microchips fills a region of changing cross-sectional area, which allows a gradient in electric field to be established when an electrical potential is applied. Our technique provides microchip EFGF devices that offer 3-fold improved resolution in protein focusing compared with capillary-based systems. In addition, these EFGF microchips can separate peptide samples with resolution similar to what is obtained in capillary electrophoresis microdevices, and the micro-EFGF systems enrich analytes by a factor of >150. Finally, we have fabricated membrane-integrated microfluidic devices that can concentrate protein samples (R-phycoerythrin) over 10 000-fold to facilitate microchip capillary electrophoresis. Interfacing microchannels with ion-permeable membranes has great potential to enhance microchip analysis of biomolecules.