Title Page

ABSTRACT

Contents

Nomenclature 19

Chapter 1. Introduction 21

1.1. Introduction to microfluidics 21

1.2. Design and manufacture of three-dimensional microfluidic platforms 24

1.3. Recent applications of 3D microfluidic platforms 30

1.4. Overview of the dissertation 35

Chapter 2. Fabrication of 3D Microfluidic Devices Based on Through-Hole Interlayer Films (TIFs) 39

2.1. Introduction 39

2.2. Materials and methods 40

2.3. Results and discussion 42

Chapter 3. Controlled Evaporative Liquid Foaming Enabled by Micro-Textured TIFs for its application to Liquid-Mediated Material Patterning 44

3.1. Introduction 44

3.2. Materials and methods 45

3.3. Results and discussion 46

3.4. Conclusion 64

Chapter 4. Microchannel-Engraved TIFs for Pixelated and Programmable Generation of Concentration Fields 66

4.1. Introduction 66

4.2. Materials and methods 67

4.3. Results and discussion 69

4.4. Conclusion 79

Chapter 5. Mixed-Scale Channel-Engraved TIFs for Generation of Full-Combinational Multi-Chemical Concentration Gradients 81

5.1. Introduction 81

5.2. Materials and methods 82

5.3. Results and discussion 83

5.4. Conclusion 87

Chapter 6. Conclusion and Future Perspective 88

References 90

Curriculum Vitae 99

Many studies have shown that a fluid is essential for processing samples in biomedical, material, and chemical analyses to understand the mechanisms of natural phenomena such as physiological functions, chemical reactions, and mass transport. For this reason, microfluidics has received considerable attention because micro/nanoscale fluidic systems have sophisticated properties that can be used to control and investigate physical quantities of fluids with reduced inertial effects. Moreover, the practical advantages and simplicities derived from miniaturization have facilitated the utilization of microfluidics ranging from laboratory to industry. However, further advances in the development of more complex and higher dimensioned miniaturized fluidic systems and their further applications have been impeded by the lack of a standardized scheme for fabricating microfluidic platforms. To date, two-dimensional (2D) microfluidic channel networks have served as the frameworks for routing microchannel networks and the integration of many microfluidic components on a chip, which originates from the popularization of photolithography and soft lithography, allowing facile prototyping at the research level. These 2D platforms have geometrical constraints not only in the integration of functional microfluidic components but also when mimicking the natural fluidic systems that exist in the three-dimensional (3D) world.

In this context, 3D microfluidics to extend 2D microfluidics to 3D microfluidic channel routing have emerged in recent years with the commercialization of additive manufacturing. The improved degrees of freedom provided by this extension have shown three main unique advantages involving massive parallelization for high-throughput operations, the realization and investigation of physiochemically new physical boundary conditions, and multiplexed spatiotemporal controllability. Considering these advantages, optical scanning systems for curing resin are becoming mainstream in 3D microfluidics, because they have higher resolution than other 3D manufacturing methods. This method has become a powerful tool for prototyping simplified microfluidic components at a level that can be used for a proof-of-concept demonstration. However, the method is not suitable for fabricating single-use chips and has practical and technological issues such as difficulties in the post-functionalization of printed channels, waste of uncured parts of an object, trade-off between the resolution and printing time or area, and reduction of the actual resolution depending on the printed microchannel networks. Therefore, in parallel with additive manufacturing specialized for simple prototyping, there is a continuous need for complementary fabrication approaches that can better satisfy more diverse technological requests and industrial standards.

This dissertation focuses on principles of fabricating and utilizing various types of through-hole interlayer films (TIFs) for the film-by-film construction of novel 3D microfluidic platforms with potential applications in biological, material, and chemical processing. In manufacturing, a two-step material curing system and soft-lithography approach are employed to print and stack films with in-plane microfluidic channel networks and out-of-plane interconnecting channels. Based on the key fabrication and design techniques, various types of TIFs, including standard TIFs, microtextured TIFs, microchannel-engraved TIFs, stepped TIFs, and mixed-sale channel-engraved TIFs have been developed to increase the structural complexity. Different types of TIFs have been used to construct a new class of 3D microfluidic platforms with functions and performances that could not be realized by 2D platforms.

First, standard TIFs and microtextured TIFs were utilized to develop a 3D platform to control liquid-mediated material formation. This novel method for manipulating the complex and uncontrollable physical characteristics of a liquid foam revealed the physical mechanism of 2D-liquid-foam generation in the absence of Ostwald ripening, thereby enabling the micro-/nanopatterning of various liquid-mediated materials in a low-cost, simple, fast, scalable, and precisely controllable manner. Based on template-guided forming, transparent heaters on objects with non-zero Gaussian curvature surfaces could be fabricated in a single-step and strain-free manner at a sub-micron resolution within several minutes with minimum loss of noble metals. The foaming method potentially opens new ways for developing all-liquid-processed functional 3D optoelectronics and wearable electronics.

Second, microchannel-engraved TIFs were utilized to develop a 3D platform for the active and stable control of concentration fields on a chip in an unprecedented, programmable, and pixelated manner. The proposed dimensional extension of microfluidic channel networks innovated conventional concentration gradient generators by significantly enhancing the flexibility to configure and control their chemical sources/sinks. The 3D platform for pixelated concentration fields provides promising avenues for developing future technological and scientific studies in which the mechanisms are related to the chemical concentrations.

Third, mixed-scale channel-engraved TIFs were utilized to develop a 3D platform capable of generating a full combination of multiple chemical species at various concentrations. The gradient generation of two different chemicals was achieved by the strategic routing of microfluidic networks, which allowed the orthogonal integration of conventional concentration gradient generators. The generated gradients could be introduced into the microreactor array to form combinational chemical environments without the need for complex, expensive, or cumbersome microscale liquid manipulators. The demonstration implied the high potential of 3D designs in the field of in vitro cell-based multi-drug combinational drug screening.