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 microfabrication 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 microfabrication 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.