Design and fabrication of novel microfluidic systems for microsphere generation

In this thesis, a study of the rational design and fabrication of microfluidic systems for microsphere generation is presented. The required function of microfluidic systems is to produce microspheres with the following attributes: (i) the microsphere size being around one micron or less, (ii) the size uniformity (in particular coefficient of variation (CV)) being less than 5%, and (iii) the size range being adjustable as widely as possible. Micro-electro-mechanical system (MEMS) technology, largely referring to various micro-fabrication techniques in the context of this thesis, has been applied for decades to develop microfluidic systems that can fulfill the foregoing required function of microsphere generation; however, this goal has yet to be achieved. To change this situation was a motivation of the study presented in this thesis. The philosophy behind this study stands on combining an effective design theory and methodology called Axiomatic Design Theory (ADT) with advanced micro-fabrication techniques for the microfluidic systems development. Both theoretical developments and experimental validations were carried out in this study. Consequently, the study has led to the following conclusions: (i) Existing micro-fluidic systems are coupled designs according to ADT, which is responsible for a limited achievement of the required function; (ii) Existing micro-fabrication techniques, especially for pattern transfer, have difficulty in producing a typical feature of micro-fluidic systems - that is, a large overall size (~ mm) of the device but a small channel size (~nm); and (iii) Contemporary micro-fabrication techniques to the silicon-based microfluidic system may have reached a size limit for microspheres, i.e., ~1 micron. Through this study, the following contributions to the field of the microfluidic system technology have been made: (i) Producing three rational designs of microfluidic systems, device 1 (perforated silicon membrane), device 2 (integration of hydrodynamic flow focusing and crossflow principles), and device 3 (liquid chopper using a piezoelectric actuator), with each having a distinct advantage over the others and together having achieved the requirements, size uniformity (CV ≤ 5%) and size controllability (1-186 µm); (ii) Proposing a new pattern transfer technique which combines a photolithography process with a direct writing lithography process (e.g., focused ion beam process); (iii) Proposing a decoupled design principle for micro-fluidic systems, which is effective in improving microfluidic systems for microsphere generation and is likely applicable to microfluidic systems for other applications; and (iv) Developing the mathematical models for the foregoing three devices, which can be used to further optimize the design and the microsphere generation process