Microfluidic device development strategies and flow control methods in the analog and digital regimes

Microfluidics is the field of study involving the manipulation of fluid in devices with micron scale length dimensions and, typically, nano- to picoliter fluid volumes. Miniaturization gives rise to specific advantages in the field of chemistry and chemical analysis including reduced reagent consumption, automation, integration, improved throughput, and increased sensitivity. Microfluidic devices are typically designed to achieve a specific task, with the development and validation of new devices representing a significant investment of time, cost, and labor. For this reason, the development of new microfluidic devices remains largely the domain of academic and basic science research labs, despite the benefits that these technologies could provide in a wide range of commercial and deployable applications. New microfluidic technologies are typically developed via an iterative cycle of device design, fabrication, and experimental validation which may be repeated dozens of times before a device is produced that achieves the desired performance. This dissertation describes new tools and methods that can significantly reduce the time, cost, and labor invested in the development of microfluidic devices.;Fabrication of glass microfluidic devices represents a large portion of the labor and cost involved in the development of new devices. Additionally, traditional fabrication methods involve the use of reagents that pose a serious personal and environmental hazard. A method for rapid fabrication of glass microfluidics by direct laser ablation is described in Chapter 2. This method reduces the cost and time invested in device fabrication. The resulting devices are not identical to counterparts fabricated by traditional methods, bearing different topologies. While electrophoretic performance in laser ablated devices was reduced compared to conventionally fabricated devices, this rapid fabrication protocol is a viable option to accelerate device development in applications that are not limited by electrophoretic performance.;The development of new microfluidic devices can be accelerated when new device geometries are evaluated by computer simulation rather than experimentally. The simulation-aided development of a microfluidic fraction collection device is described in Chapter 3. Computer simulations of electroosmotic flow were achieved by finite element analysis of coupled partial differential equations describing electric field, laminar flow, and transport of dilute species in models representing various device geometries. An optimized device geometry was identified by a multivariate statistical method, and only the optimized device geometry was fabricated. Fluid flow in the fabricated device agreed well with simulations, and the device successfully performed electrophoretic separations followed by continuous flow isolation of separated fractions.;A new technology in microfluidics, Digital microfluidics (DMF), allows for some analyses to be performed on devices of standardized geometry, thereby eliminating the need for the device development cycle. The versatility of DMF analyses is, therefore, governed largely by the detection strategies that can be employed. Chapter 4 describes the development of a system to achieve online coupling of DMF devices to electrospray ionization mass spectrometry (ESI-MS). This system operates on the Venturi effect, and addresses two primary challenges: 1) the induction of flow in droplets that are unconfined by fluidic channels and at ambient pressure, and 2) the integration of AC voltage (DMF) with high DC voltage (ESI-MS) in a single integrated system. A multivariate approach is used to characterize and optimize the operating parameters of the DMF-ESI-MS system, and semi-quantitative analysis of DMF droplet contents is demonstrated. Future development of this system is described in Chapter 5.