Opportunities for high-pressure microfluidics in biomedical applications

Pressure lies at the basis of operation of most microfluidic systems, and is a determinant factor in the extent of miniaturization and in limiting the throughput and time constant of the microfluidic assays. Despite the apparent importance given to fluidic and reagent exchange control in the reported biomedical assays in microfluidic systems, high-pressure enabled systems are not studied in depth until now. Therefore, this thesis deals with realization of high-pressure microfluidics, microfabrication methods that are at the basis of high pressure-resistant devices, and their potential to address and solve biologically and clinically relevant questions. We first develop a microfabrication technology that helps realization of high pressure-resistant microfluidic devices for diverse applications. This requires a bonding technology that can be performed using multiple bonding interfaces and at low temperature to enable integration with other technologies required for realizing a complete diagnostic assay. In a first study, we introduce a new low temperature (280°C) parylene-C wafer bonding technique, where parylene-C deposited on a Pyrex wafer bonds directly to a silicon wafer with either a Si, SiO2 or Si3N4 surface, with a bonding strength up to 23 MPa, and this by using a single layer of parylene-C. Moreover, the process is compatible for bonding any type of wafer with small-sized micropatterned features, or containing microfluidic channels and electrodes. This technique presents an alternative for conventional bonding methods like anodic bonding in applications requiring a low temperature and diverse bonding interfaces. This is an important point when integrating high-pressure microfluidic devices with additional electrical and biological functionalities. Following this, we use the bonding technique to fabricate standard packaged microfluidic devices and also develop a high-pressure microfluidic and electrical integration technology, eliminating special fluidic interconnections and wire-bonding steps. Finally, we introduce an easy, low-cost and efficient method for realizing high-pressure microfluidics-to-CMOS integrated devices. Exploiting parylene-C-to-SiN bonding technology, we demonstrate a microfluidic chip burst pressure as high as 16 MPa, while metalelectrodestructures on the CMOS wafer remain functional after bonding. Using the developed technologies, we immediately show that such integration can be key to realize CMOS-integrated flow focusing devices for monolithic cytometer applications, since such integration is appealing only if such down-scaling does not compromise the fluidic throughput. By assuming throughput-per-footprint (TPFP) as the main parameter determining the performance and unit assay cost for this kind of applications, we explore the scaling limits of TPFP in inertial focusing, by studying the interplay between theory, the effect of channel Reynolds numbers up to 1500 on focusing, the entry length for the laminar flow to d