Advancing Design and Fabrication of Microfluidic Devices for Biomedical Applications
Date
2024-03-12
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Doctoral
Abstract
Applications of engineering methods to biology have grown with a desire to build devices for integrating various tests on cells, called Lab-On-a-Chip (LOC), and for mimicking biological systems, called Organ-On-a-Chip (OOC). Such devices have “small” channels (around micrometer to nanometer) and manipulate “small” amounts of fluids to flow (typically micro-litre, nano-litre up to milli litre) and therefore are called microfluidic devices. While LOC is useful for diseases diagnosis, OOC goes much beyond, not only for the improved capability of diseases diagnosis but also for drug development at cellular levels, as well as research into more understanding of cellular behaviours, by providing a biomimetic environment for cells, including the facility of stressing cells. There is no doubt that the OOC technology is a disruptive one to biology and medicine. Due to the need of high compatibility (chemical, physical and biological) with LOC and OOC, polymer materials are usually employed. This thesis aims to advance the technology of design and fabrication of (polymeric based) microfluidic devices of both LOC and OOC for biomedical and healthcare applications. This thesis conducted four specific studies.
The first study aims to advance our understanding of the additive manufacturing (AM) technology with the material of polydimethylsiloxane (PDMS). This is achieved by categorizing and classifying all AM processes in literature. As a result, AM processing of PDMS is divided into two categories, namely (1) direct approach and (2) indirect approach. The literature in both categories was critically reviewed, leading to the identification of five knowledge gaps. The study also presented the author’s preliminary experiment on the indirect approach, printed mold approach in this case. Specifically, the experiment leads to the finding of the optimal post heat treatment of the mold for PDMS casting for the material of Full cure835 Vero white plus, namely (1) the heat treatment of the mold at 65° C for a time duration of 4 h and overnight cooling, followed by (2) oxygen plasma treatment at 50 watts, 45 millitorrs of O2, for a time duration of 30 s and (3) silanization of mold for a time duration of 1 h, and (4) casting of the PDMS and curing it under room temperature for curing at 24 °C) for a time duration of 24 h.
The second study concerns bonding of two polydimethylsiloxane (PDMS) parts, an important step to construct PDMS microfluidic devices. Two main requirements on the bonding are such that (1) the bonding strength is as high as possible, and (2) the alignment of two parts is as accurate as possible. The study developed a simple yet effective bonding process for PDMS-to-PDMS using isopropyl alcohol (IPA). Specifically, the process aligns two PDMS parts and adheres them with IPA prior to the plasma treatment and subsequent post treatment of the assembly, followed by natural curing of the assembly. The result with this process significantly improves bonding strength from 1.9 MPa (the best bonding strength reported in literature) to 3.060 MPa. The mechanism behind this improved performance with the proposed process is also proposed in this study. The study can conclude that the proposed bonding process is very promising in the bonding of two PDMS parts with high strength as well as the potentially improved accuracy in alignment of two PDMS parts.
The third study concerns the development of a biocompatible OOC, which is capable of (1) programmable stretching of cells in the X, Y, Z directions (3D stretching in short), (2) generation of static, cyclic, and randomized stretching forces to cells, (3) nutrients transfer, and (4) wastes discharge. Design as well as fabrication of such an OOC made from PDMS is a challenge. In this study, the OOC was designed to have three layered modules (top, middle, bottom) with each having a chamber. The middle module and the bottom module are separated by a porous membrane, so the chamber of the middle module is on the top side of the membrane, and the chamber of the bottom module is on the bottom side of the membrane. The middle module, porous membrane, and bottom modules are bonded together. Cells are anchored upon the top side of the porous membrane, and they reside in the middle chamber, while the nutrients and wastes are inside the bottom chamber. Four ports (two along the X direction, the other two along the Y direction) surround the middle chamber and bottom chamber, respectively, and these ports are filled with the air. By regulating the air pressures inside these ports, the side walls of the chambers deform in the X and Y directions, so does the porous membrane, thereby resulting in the stretching of cells in the X and Y directions. The top module is responsible for the stretching of cells in the Z direction by regulating the air inside its chamber to deform its bottom part, thereby generating the pressure on cells along the Z direction. All these modules were made from PDMS, and they were fabricated using the printed mold approach. In this study, the preliminary experiment was performed on (1) the deformations in the X, Y, and Z directions, (2) the programmability of these deformations, and (3) characteristics of the deformations (static, cycle, randomized). By preliminary it was meant that the quantitative measurement and assessment of the deformation response of the device were not attempted. The result of the experiment showed that the foregoing requirements were satisfied with however one problem, that is, the bonding of the porous membrane with the middle module as well as bottom module is weak in terms of fatigue strength. The study can conclude that (1) the developed OOC has a potential to meet the requirements and (2) the problem of weak bonding needs to be addressed and a potential solution may be to use a stronger bonding process or to change the design of the interface structure between the porous membrane and the middle or bottom module.
The fourth study concerns the so-called sliding microfluidic device. The main challenge with such a device was in the interface of two components which can perform a relative sliding motion. This challenge was addressed by a new design concept called a “step” structure. This structure also eliminates the need for putting “chemical lubricant” on the interface to prevent leakage, which was used extensively in literature. Another challenge was the difficulty to fabricate a high aspect ratio step structure by using the traditional lithography approach. The study found that the AM technology can overcome this difficulty. The developed devices was tested for sorting poly(vinyl alcohol) (PVA) particles, which were regarded a good substitute of real cells in literature. The study can conclude that (1) the design concept of the step structure is valid, and (2) the sorting accuracy (85%) can be achieved, which was excellent at that time.
Overall, besides the specific conclusions drawn in each of the four specific studies, this thesis has the following general conclusions: First, the current AM technology can build PDMS microfluidic devices to meet the requirements of OOC. Second, there is room to further improve the functionality of the PDMS microfluidic device by improving the fabrication technology, including the AM and the development of new materials that possess the merits of PDMS but with improved manufacturability by AM.
Description
Keywords
Additive manufacturing, Microfluidics, Cell sorting, Cell stretching, Lab-on-a-Chip, Organ-on-a-Chip, MEMS, PDMS
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Mechanical Engineering
Program
Mechanical Engineering