Integration of nanoporous membranes for sample filtration/preconcentration in microchip electrophoresis

Microfluidic devices integrating membrane-based sample preparation with electrophoretic separation are demonstrated. These multilayer devices consist of 10 nm pore diameter membranes sandwiched between two layers of PDMS substrates with embedded microchannels. Because of the membrane isolation, material exchange between two fluidic layers can be precisely controlled by applied voltages. More importantly, since only small molecules can pass through the nanopores, the integrated membrane can serve as a filter or a concentrator prior to microchip electrophoresis under different design and operation modes. As a filter, they can be used for separation and selective injection of small analytes from sample matrix. This has been effectively applied in rapid determination of reduced glutathione in human plasma and red blood cells without any off-chip deproteinization procedure. Alternatively, in the concentrator mode, they can be used for online purification and preconcentration of macromolecules, which was illustrated by removing primers and preconcentrating the product DNA from a PCR product mixture.