Thermoplastic Elastomer Microfluidic Devices for Biology and Chemistry

Since its emergence, microfluidics has proven to be a powerful tool in chemistry and the life sciences. Microfluidic devices, consisting of networks of micron-scale flow channels, leverage high surface-area-to-volume ratios and precision fluid control to provide advantages over conventional methods in chemistry and biology. In chemistry, reactions with greater speed, selectivity, and safety can be achieved thanks to fast mixing and efficient heat transfer. In biology, greater control over mechanical and biochemical microenvironments allow cell culture studies with greater relevance to living organisms.

The progression of microfluidics over the past three decades, however, has not lived up to the high expectations that were held at its beginnings. While numerous factors can be identified as bottlenecks in the continued development of microfluidics, one critical element is the need for new microfluidic materials. Microfluidic devices, or “chips,” can be fabricated from a variety of different materials, such as silicon, glass, and polymers, with each one possessing its intrinsic advantages and drawbacks, as discussed in Chapter 1. A material must possess suitable material properties for the microfluidic application at hand, but one must also evaluate its fabrication and cost as factors key to its accessibility and transferability across manufacturing scales. The most common microfluidic material, an elastomer called polydimethylsiloxane (PDMS), possesses numerous drawbacks in its material properties that make it unideal for many biology applications and unusable for many chemistry applications. Moreover, the techniques used for its fabrication are low-throughput, limiting the possibility of large-scale implementation (i.e., a transfer from academic research to industry). A group of materials called soft thermoplastic elastomers (sTPE) have been recently developed for microfluidics, with preliminary reports in literature demonstrating their favorable material properties and transferable fabrication methodologies. This PhD, conducted between academia and industry, focuses on two distinct sTPE materials, Flexdym™ and Fluoroflex, and their use for cell culture and flow chemistry applications, respectively. It aims to evaluate the properties of these novel sTPE materials and capitalize on them by providing sTPE device demonstrations that give scope for broader and more widespread microfluidic applications in these fields.

Chapter 2 describes the development of a composite microfluidic platform for membrane-based cell culture, consisting of two micropatterned Flexdym™ layers separated by a commercially available porous polycarbonate membrane. Membrane-based cell culture can be used to simulate tissue-tissue interface, valuable for drug development and disease modeling, and provides the basis for cutting-edge organ-on-chip technology. The thermoplastic platform leverages the rapid hot embossing and self-sealing property of Flexdym™, as well as the simplicity of the off-the-shelf polycarbonate membrane, to improve upon the fabrication time and complexity of similar microfluidic geometries made in PDMS. The pressure capacity of the bond formed between Flexdym™ and polycarbonate was characterized and found to be sufficient for cell culture applications (> 500 mbar). To validate the device’s utility for membrane-based cell culture, cell culture trials were performed, showing cell adhesion and proliferation inside the device.

Chapter 3 reports the extensive material characterization of Fluoroflex and the development of a modular microfluidic platform using the material. Fluoroflex was found to exhibit good chemical resistance in comparison to PDMS and other polymers, allowing its use with common organic solvents, such as toluene, dichloromethane, and hexane. Key optical, mechanical, and surface properties of Fluoroflex were also characterized, and showed the material’s appropriateness for use as a microfluidic device. A 30 s hot embossing protocol was developed, allowing for the rapid micropatterning of Fluoroflex. Like Flexdym™, Fluoroflex possesses an intrinsic adhesive property, allowing spontaneous bonding with itself to occur after the formation of conformal contact. This self-sealing was evaluated through burst testing and found to withstand a pressure of 1.4 bar after only five minutes of conformal contact between two Fluoroflex surfaces. This fast, reversible bonding was used to create a modular microfluidic platform, with which microfluidic droplet generation (water in toluene) of variable size was demonstrated.

Chapter 4 expands on the microfluidic applications of Fluoroflex by presenting the preliminary work toward a microfluidic packed bed photoreactor consisting of a Fluoroflex microchannel and PDMS microbeads. PDMS microbeads were synthesized and subsequently injected into a Fluoroflex microchannel and trapped by a micropillar array. An on-chip functionalization protocol was used to create an aminosilane surface layer on the microbeads, to which fluorescein was then coupled. Separately, a derivative of perixanthenoxanthene (PXX), a photoactive molecule, was coupled to PDMS microbeads (off-chip) in a similar manner, and subsequently shown to retain its photocatalytic properties through a debromination reaction. These results provide a proof-of-concept and clear next steps toward the implementation of microbead-supported heterogeneous photocatalysis in a Fluoroflex device.

Finally, Chapter 5 consists of a market evaluation of flow chemistry microreactors, aimed at providing industrial context to the Fluoroflex characterization and microfluidic development work. A competitive landscape analysis summarizes commercially available microreactors. Interviews of flow chemistry researchers were conducted to understand the needs of microreactor end-users and any technological difficulties they face. Lastly, a market size assessment is conducted, in which publication metrics are used to estimate the size, value, and growth trends of the flow chemistry research market for a Fluoroflex microreactor offering.