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UBC Theses and Dissertations

Microfluidic technologies for the integration of liquid chromatography Huft, Jens


The microfabrication technique of Multilayer Soft Lithography (MSL) has emerged as the dominant platform for the development of microfluidic devices in biomedical research. However, Multilayer Soft Lithography, as originally developed, has technological limitations that restrict its effectiveness and versatility in implementing laboratory operations on chip. This thesis solves two of these limitations, namely that channel routing is restricted to planar geometries and that no established methods exist for creating solid-phase columns needed to perform on-chip analytical and preparative separations. The first technological advancement is the development of a new fabrication method using laser ablation that enables the automated fabrication of interlayer connections in MSL-based microfluidic devices. Real-time image recognition and computer control allow for robust wafer-scale registration of laser ablation features with moulded channel structures. This new functionality removes the constraint that all connected device features lie in a single plane, significantly enhancing achievable feature density and fluid handling complexity. To further extend the range of accessible bioanalytical applications using MSL-based devices, this thesis also presents the development of a novel microfluidic column geometry that allows rapid packing of multiple microcolumns in parallel with near-perfect yield. These microcolumns are shown to be of high quality, with plate heights comparable to conventional high-performance capillary columns and superior to what has previously been reported for packed microfluidic columns. Finally, this thesis shows how these new capabilities allow for the implementation of the first fully integrated microfluidic liquid chromatography system that exploits advantages of automation, small sample volume and parallel processing. All elements required for automated sample loading, programmable gradient generation, separation, fluorescent detection, and sample recovery are integrated on a single device. The ability to reliably fabricate three-dimensional microfluidic devices and to integrate highly optimized solid-phase columns will open many new opportunities for on-chip integration, bringing the ultimate goal of complete lab-on-a-chip integration closer to reality.

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Attribution-NonCommercial-NoDerivatives 4.0 International