Studies On Microfluidic High Throughput Sample Introduction Systems

The objective of microfluidic analysis is to integrate all of the function units performed in a lab, including sample introduction, pretreatment, reaction, separation and detection, on a microchip to achieve the miniaturization, automatization and integration of whole analytical systems. One of the major bottle-neck in the development of microfluidic chips lies in world-to-chip interface, which has significant influence on the development and application of microfluidic chips. The topic of this dissertation is focused on the development of microfluidic high-throughput sample introduction techniques and their applications in flow injection analysis (FIA), sequential injection analysis (SIA) and multiphase droplet generation and manipulation.In Chapter 1, the development of high throughput sample introduction techniques based on reservoir array, flow-through interface and sampling probe was reviewed. The recent progress in microfluidic flow-injection, sequential injection and multiphase droplet analysis systems was also introduced.In Chapter 2, a novel sample introduction approach using a capillary sampling probe and an array of horizontally positioned micro-sample vials with a slot fabricated on the bottom of each vial was developed. High throughput sample introduction was achieved by linear moving of the slotted-vial array, allowing the probe inlet to sequentially enter the solutions filled in the vials through the slots. Based on this technique, a robust and automated microfluidic chip-based FIA system with gravity driven flows was developed. Sample loading and injection were performed by alternate introduction of samples and carrier, without resorting to valves and pumps. A 20-mm long Teflon AF 2400 capillary was connected to the chip to achieve liquid-core waveguide (LCW) absorbance detection. The system provides highest sampling throughput of 1000 per hour, lowest sample consumption of only 0.6 nL, and good reproducibility of 0.6% RSD (n = 18), which were lower than those in the previously reported chip-based FIA systems.In Chapter 3, an automated microfluidic sequential injection analysis system (μSIA) based on a short fused-silica capillary is described. The system was built without need of complicated microfabrication techniques. Sample and reagents zones were sequentially introduced via gravity driven flow by scanning the capillary tip through the vial slots, and rapidly mixed by diffusion and convection within the carrier flow, demonstrating a behavior that conformed well to the Taylor Dispersion Phenomenon. Potentials for using the system in high throughput screening were demonstrated by the enzyme inhibition assay ofβ-galactosidase. A low sample/reagent comsuption of 4.2 nL was achieved with a high throughput of 300 assays per hour. In order to further enhance the versatility, chemiluninesence and LCW absorbance detection systems were developed to couple with theμSIA system.In Chapter 4, a novel approach for flexible and precise generation of droplets in the picoliter to nanoliter range was developed. The system comprised a capillary with a tapered tip, a syringe pump and a slotted-vial array sampling system. High speed generation of droplets with diffenent size and composition was achieved for the first time, which is quite important for the application of microfluidic droplet system in high throughput screening and drug discovery. Potential application of the system in screening of protein crystallization conditions was preliminarily demonstrated.