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Microfluidic devices possess many advantages over conventional hardware, including the ability to precisely manipulate small volumes and the integration of multiple functional elements onto a single platform. These characteristics make microfluidic devices ideal for performing multi-dimensional separations. Recently, we have developed a hybrid multi-dimensional separations platform coupling capillary liquid chromatography (LC) with microchip capillary electrophoresis-electrospray ionization (CE-ESI). By coupling microfluidic CE-ESI with commercial LC, our multi-dimensional design offers high separation power, sensitivity, and speed while minimally increasing experimental complexity. The speed and simplicity of this method are similar to conventional LC-MS analyses, and most current LC-MS methods can be converted to LC-CE-MS using this design. This method is capable of performing rapid and powerful separations, achieving a peak capacity of 1400 in 50 minutes for a complex peptide mixture. This method can impact a wide range of applications where sample complexity requires high separation power, such as proteomics, metabolomics, biomarker discovery, and therapeutic treatment monitoring. Current research efforts are focusing on improving the sample transfer between LC and CE dimensions and developing microfluidic circuitry to optimize the separations.

The figure on the left shows the 2D experimental set-up using a commercial HPLC system connected to our CE-ESI microchip. By controlling the voltages at the channels on the microchip, discrete injections into the serpentine separation channel can be made. The figure on the right shows a 2D image plot with the capillary run time on the y-axis and CE migration time on the x-axis.