Design and fabrication of microfluidic integrated circuits using normally-closed elastomeric valves

Microfluidics and other fluid-handling technologies are valuable tools both for biochemical assays and for patterning biomolecules and cells to better mimic in vivo microenvironments. However, many of these techniques are not widely used because they require the experimenter to perform many tasks that often are not in a familiar platform. Currently most microfluidic devices capable of performing fluid switching operations require external control systems that are expensive and cumbersome. This dissertation has two parts: the first will present networks of normally-closed elastomeric valves as a novel control system for performing automated switching operations in microfluidic devices. Since all functionality can be embedded into the architecture of the device, the user is only required to plug in a fluid flow source to operate the device. Fundamental fluidic operations such as cascading and oscillatory fluid switching are demonstrated as a proof-of-principle for achieving dynamic functionality. In addition, scalable fabrication techniques of essential components for these control systems will be described. The scalable integration of many components is the first hurdle for practical fabrication of more complex devices that use this embedded control system. The second part of the dissertation describes methods developed for patterning cells and biomolecules at the micro-scale. Within a microfluidic device, patterning is typically achieved using laminar flow of two or more streams to spatially position cells/biomolecules. Although this technique is straightforward, there are many practical issues involved in the control of the laminar streams, hindering many users from taking advantage of these technologies. Described is the use of embedded porous filters to help control laminar flows in a microfluidic device. Also described is the utility of aqueous two-phase systems (ATPS) to pattern both biomolecules and cells in a conventional Petri dish platform. This new technology enables contact-free printing on delicate substrates such as cells and hydrogels. Such fluid handling technologies will be a stepping-stone for the development of user-friendly devices and methods that can be utilized by nonspecialized users outside the field.