Practical workflows for microfluidic device design and fabrication for molecular diagnostics

Abstract

Rapid design and fabrication of microfluidic devices is essential for accelerating the development of molecular diagnostic tools. However, there is a gap between academic prototyping and the refined fabrication methods needed for scalable, industrial production. This thesis addresses that challenge by evaluating and refining two rapid prototyping workflows for creating microfluidic devices: digital light processing (DLP) 3D printing and micromilling in cyclic-olefin copolymer. Then, future work is proposed for scaling manufacturing by hot embossing COC. First, DLP 3D printing was performed with a commercially available printer (MiiCraft 50) and resin (CADworks3D clear microfluidic resin V0.7a) to produce curved microchannels less than 100 microns in width. A comprehensive workflow is presented for accessible fabrication and device integration, including design strategies, bonding methods, thermal stability evaluation, and development of a prototype chip-to-world interface. Postprocessing treatments were also investigated to determine whether toxic inhibitory chemicals could be leached from the resin, with the goal of improving compatibility with sensitive biochemical assays. Second, a low-cost workflow for micromilling COC devices was developed using a desktop CNC mill (Nomad 3, Carbide 3D). By prototyping directly in an industry standard material, this approach facilitates smoother scaling to commercial manufacturing. A method was established for fabricating machinable COC plaques and critical milling parameters were evaluated to enable reproducible fabrication of complex microchannels as small as 200 microns. Then, a refined chip-to-world interface was designed and used to perform proof-of-concept recombinase polymerase amplification (RPA) within the micromilled chips. Third, hot embossing was evaluated as scalable manufacturing technique suitable for resource limited academic settings. Initial tests using PDMS molds were limited by mold deformation under heat and pressure, motivating future work a rigid epoxy mold to improve resolution and reliability. In conclusion, this thesis presents accessible, reproducible methods for fabricating microfluidic devices tailored for diagnostic applications. Ultimately, these workflows aim to lower technical barriers and accelerate the path from research innovation to practical impact.