Ion Liquid Chromatography System On-a-Chip with Beads-Packed Parylene Column (2004)

ION LIQUID CHROMATOGRAPHY ON-A-CHIP WITH BEADS-PACKED PARYLENE COLUMN Qing He, 1 Changlin Pang, 1 Yu-Chong Tai, and 2 Terry D. Lee Caltech Micromachining Lab, California Institute of Technology, CA, USA Beckman Research Institute, City-of-Hope, CA, USA ABSTRACT single chip. The two main reasons are the lacks of: (1) a process to integrate various components for an LC system; (2) high-pressure compatibility of the microfluidic devices needed for running HPLC. This work deals with both problems. In terms of introduction and retaining LC stationary phase materials into the column, several approaches have been proposed, including open-tubular [2], coating micromachined posts arrays [3], coating microchannel with nanoparticles [4], monolith [5], packing [6], and packing without frit [7]. In this work, packing with conventional beads is chosen because of the following advantages. First, without introducing new surface chemistry, the extensively established separation knowledge can be utilized. Secondly, extreme flexibility is there to perform different types of liquid chromatography and/or to optimize particular separations, by choosing bead type, size, pore size, porosity, and functional group. Thirdly, packed column can achieve reproducible column performance, which is usually a problem in other methods. A parylene-MEMS ion-exchange Liquid Chromatography (LC) chip is presented here. The chip is integrated with microfluidic I/O ports, a separation column, frits/filters, and a conductivity detector. The column is packed with conventional LC stationary phase support materials, i.e. micro-beads with surface functional groups. To withstand high pressure normally encountered in High Performance Liquid Chromatography (HPLC), a self-aligned, channel- anchoring technique is developed to increase the pressure rating of the Parylene microfluidic devices from 30 to at least 800psi. On-chip injection, separation and detection of anions in water, with ~25ppm concentration, have been successfully demonstrated. To our knowledge, this is the first demonstration of microbeads-packed column ion liquid chromatography (LC) on a chip. 1. INTRODUCTION High Performance Liquid Chromatography (HPLC) is one of the most popular, powerful, and versatile separation techniques for chemical analysis. Although LC column is normally made of capillary tubes due to fluidics limitations, the miniaturization of the column can actually improve separation performance. As shown in Fig. 1 [1] where same separation chemistry applies, separated peak width is independent of column ID, while peak heights are larger for smaller columns and/or smaller beads. In short, further down-sizing could be favorable in liquid chromatography. 2. DESIGN AND FABRICATION The LC-on-a-chip device is made using parylene MEMS technology. The chip has four access ports, as shown in Fig. 2. LC mobile phase flows from port #1 to #2. Nanolitre volume sample injection is achieved with a cross channel injection method [8] from #3 to #4. Beads are packed externally into the on-chip column from port #1. Filters (channel with a height smaller than the bead size) trap beads in the main channel and prevent beads from entering the side injection channels. The bead-packed column inlet is near the sample output port #4, which is the injected sample plug front. The column outlet is at the filter/sensor edge (Fig. 2(b)). This integrated design minimizes dead volume, thus minimizing extra-column peak broadening. Off-chip pumps and valves are used in testing. A conductivity sensor is used as the detector for ion sensing. Interdigital electrodes are patterned in the detector cell to monitor liquid conductivity. The conductivity of the mobile phase solution provides a baseline signal. When separated ion plugs pass by the detector, changes of solution conductivity are detected. Chromatogram is then obtained by recording conductivity of the solution flowing in the detection cell over time. To increase sensitivity, electrode width and spacing should be small, and the total electrode area should be maximized. However, the electrode design should be compromised in considerations of minimizing peak broadening and multiple-peak detection. Injection Column Peak in Eluate Figure 1. Separated peak shapes obtained with different column and bead size. Compared to electrophoresis, however, little has been published about the integration of HPLC system onto a