Fabrication, integration and simulation: a complete design cycle of polystyrene microfluidic systems using LCD 3D printing and injection moulding

Carvalhal Calhau de Menezes, Pedro Duarte (2025) Fabrication, integration and simulation: a complete design cycle of polystyrene microfluidic systems using LCD 3D printing and injection moulding. PhD thesis, University of Glasgow.

Abstract

Microfluidics is a rapidly evolving field of science with high potential and growing applications across life science research and industry. By controlling fluidics at the microscale, it achieves faster reaction times, lower sample volumes, and greater analytical power to that of classical techniques. For the past two decades, microfluidic research has relied upon, and thrived with, polydimethylsiloxane (PDMS) as the standard material for device fabrication. However, despite its many advantages, replica moulding techniques using PDMS are limited in throughput and automation, which currently encourages the field to transition to more scalable materials, such as thermoplastics. This thesis sets out to develop a novel design cycle for polystyrene-based microfluidic devices, encompassing scalable fabrication, integration and simulation.

A new fabrication protocol was established, using liquid crystals display (LCD)three-dimensional (3D) printing and injection moulding as the two overarching technologies in the development of rapid tooling for polystyrene (PS) microfluidic devices. The dominant process parameters impacting the compatibility, quality, and scalability of the respective procedure were identified and optimized. This way, a protocol was defined, capable of delivering sub 50 µm feature resolution, high optical transparency, and scalable production (≈ 500 parts) of microfluidic devices. Importantly, it also provided a turnaround time from computer-aided design (CAD) to a fully functional device of only ≈ 2 h 30 min, and from CAD to 500 replicas of ≈ 8 h, this way providing unique potential to rapid prototyping and scalable manufacturing.

The functionalization of the respective devices began by exploring different bonding strategies. Thermal fusion was seen as the most promising technique, providing reliable, high-quality seals, for channels and polystyrene membranes, with little to no deformation. Ultrasonic welding was instead seen as extremely efficient in bonding and stretching polyester membranes. Fluidic interfacing was then explored, from which the integration of an injection moulded well plate layer established a standardized interface for both pressure- and gravity-driven fluidics. A protocol for the development of elastic membranes for plug-and-play microvalving was also established by exploring elastomer prepolymer resins using single-layer masked exposure with ultra-violet (UV) light and spin coating. Not only were the physical and mechanical properties of membranes characterized, but also their performance for fluidic switching and dynamic control over concentration gradient generation.

To enhance microfluidic design, in particular with porous membranes, a finite element method (FEM) model was established to study the kinetics of flow and transport as a function of membrane, channel geometry, fluidic and diffusion parameters. By doing so, a comprehensive study was conducted, discretizing the influence of each individual parameter and hierarchizing their impact on fluid flow, shear stress, transient transport and molecular concentration. Based on the provided guidelines, the dominant influence of flow over permeability properties in determining porous transport was found to be especially critical for microfluidic and organ-on-chip (OOC) applications. On chip experiments were performed to validate the respective numerical data by studying the transport of fluorescein and evaluating the effect of Cytochalasin D on cultured cells, as a function of flow and permeability. By doing so, the experimental relevance of the provided numerical data was demonstrated. This was further reiterated by extending the model to investigate the unique kinetics of transport in convection-driven devices with recirculating flow.

Ultimately, this thesis provides a framework for the scalable production of microfluidic and OOC devices, with compatible solutions for microfluidic integration and extensive characterization of microenvironments with porous barriers, in regard to fluid dynamics and transport kinetics.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Research Council of Norway 262613.
• Subjects: T Technology > T Technology (General)
• Colleges/Schools: College of Science and Engineering > School of Engineering
• Funder's Name: Research Council of Norway
• Supervisor's Name: Gadegaard, Professor Nikolaj
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85313
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 07 Aug 2025 09:57
• Last Modified: 07 Aug 2025 10:01
• Thesis DOI: 10.5525/gla.thesis.85313
• URI: https://theses.gla.ac.uk/id/eprint/85313