| Microfluidic devices have a unique capability for manipulating small fluid volumes in micro-scale environments. As a result, they are becoming increasingly important tools for a wide range of biological applications, such as DNA sequencing, polymerase chain reaction (PCR), enzymatic assays, diagnostics, electrophoresis, cell culture, and cell-based sensors, to name a few. Since silicon- or glass-based microfluidic devices are expensive to fabricate, inexpensive replica-molded microfluidic devices made of poly(dimethylsiloxane) (PDMS) have attracted widespread attention for biological applications. Despite the advantages of fast prototyping and low cost, existing PDMS devices are essentially static and two-dimensional (e.g. the channels contain single-height features that have fixed cross-section geometry). Thus, their functionality is limited to being a simple conduit for the fluids. This thesis presents a set of techniques to address the above limitations including a fabrication method for making open-architecture and three-dimensional PDMS devices, a micro-molding technique for making PDMS devices with complex features, and a tunable microfluidic technique that adds functional elements to microchannels in PDMS devices. Several devices are presented in this thesis, including a three-dimensional PDMS microfluidic chip with open architectures that was demonstrate with micropipette manipulation of single cells within the chip; a open-architecture microfluidic device that can generate concentration gradients of biological factors to study cell migrations, micro-tunable molds that can be used to fabricate complex PDMS devices, and tunable microfluidic devices for mixing and trapping fluids. In sum, we have developed a new generation of microfluidic devices that, by virtue of their 3D architecture, have tunable functionalities and flexible applicability to biology. |
