Design of a microfluidic device for comprehensive spatial two-dimensional liquid chromatography

This study discusses the design aspects for the construction of a microfluidic device for comprehensive spatial two-dimensional liquid chromatography. In spatial two-dimensional liquid chromatography each peak is characterized by its coordinates in the plane. After completing the first-dimension separation all fractions are analyzed in parallel second-dimension separations. Hence, spatial two-dimensional liquid chromatography potentially provides much higher peak-production rates than a coupled column multi-dimensional liquid chromatography approach in which the second-dimension analyses are performed sequentially. A chip for spatial two-dimensional liquid chromatography has been manufactured from cyclic olefin copolymer and features a first-dimension separation channel and 21 parallel second-dimension separation channels oriented perpendicularly to the former. Compartmentalization of first- and second-dimension developments by physical barriers allowed for a preferential flow path with a minimal dispersion into the second-dimension separation channels. To generate a homogenous flow across all the parallel second-dimension channels, a radially interconnected flow distributor containing two zones of diamond-shaped pillars was integrated on-chip. A methacrylate ester based monolithic stationary phase with optimized macroporous structure was created in situ in the confines of the microfluidic chip. In addition, the use of a photomask was explored to localize monolith formation in the parallel second-dimension channels. Finally, to connect the spatial chip to the liquid chromatography instrument, connector ports were integrated allowing the use of Viper fittings. As an alternative, a chip holder with adjustable clasp locks was designed that allows the clamping force to be adjusted.