Point‐of‐care (PoC) and organ‐on‐chip (OoC) devices represent promising microfluidic applications for in vitro analysis and miniaturized analytical studies, reducing the need for traditional animal‐based tests for drug discovery and toxicity studies. Using thermoplastics in microfluidic device manufacturing provides interesting functionalities for expansion of these devices into market. However, market growth requires manufacturing large quantities for low cost, which can be achieved using injection molding techniques. This work involves the design of a microfluidic device with different aspect ratio channels to compare injection molding (IM) and injection‐compression molding (ICM) processes, as well as the design and manufacturing of a metallic insert containing machined inverted microstructures. Injected parts are validated visually, dimensionally, and functionally. The differences between both techniques and two grades of cyclic olefin copolymer materials are analyzed to evaluate microfluidic device mass production feasibility concluding that although the machining process for inverted high aspect ratio microstructures is not mature yet, both IM and ICM processes allow the mass manufacturing of microfluidic devices in thermoplastic. Parts processed by ICM show better replicability of microfluidic structures and less internal stresses generate during the injection process than IM parts, highlighting the potential of this process to achieve thermoplastic microfluidic devices to market.

Organ-on-chip (OoC) technology is one of the most promising in vitro tools to replace the traditional animal experiment-based paradigms of risk assessment. However, the use of OoC in drug discovery and toxicity studies remain still limited by the low capacity for high-throughput production and the incompatibility with standard laboratory equipment. Moreover, polydimethylsiloxanes, the material of choice for OoC, has several drawbacks, particularly the high absorption of drugs and chemicals. In this work, we report the development of a microfluidic device, using a process adapted for mass production, to culture liver cell line in dynamic conditions. The device, made of cyclic olefin copolymers, was manufactured by injection moulding and integrates Luer lock connectors compatible with standard medical and laboratory instruments. Then, the COC device was used for culturing HepG2/C3a cells. The functionality and behaviour of cultures were assessed by albumin secretion, cell proliferation, viability and actin cytoskeleton development. The cells in COC device proliferated well and remained functional for 9 days of culture. Furthermore, HepG2/C3a cells in the COC biochips showed similar behaviour to cells in PDMS biochips. The present study provides a proof-of-concept for the use of COC biochip in liver cells culture and illustrate their potential to develop OoC.

Precision micromilling is currently widely used for the fabrication of injection mold inserts for the mass production of microfluidic devices. However, for complex devices with micrometer-scale and high density of structures, micromilling results in high production times and costs for production runs of hundreds or thousands of units. Femtosecond laser (fs-laser) technology has emerged as a promising solution for high-precision micromachining. This study analyzes the potential of fs-laser micromachining for the fabrication of injection mold inserts for the large-scale production of thermoplastic microfluidic devices. For the evaluation of technology, a reference design was defined. The parameters of the fs-laser process were optimized to achieve high resolution of the structures and optimal surface quality, aiming to minimize production times and costs while ensuring the quality of the final part. The microstructures were replicated in two different grades of COC (Cyclic Olefin Copolymer) by injection molding. The dimensional tolerance of the structures and the surface finish achieved both in the insert and the polymer parts were characterized by scanning electron microscopy (SEM) and confocal microscopy. The surface quality of the final parts and its suitability for microfluidic fabrication were also assessed performing chemical bonding tests. The fs-laser machining process has shown great potential for the mass production of microfluidic devices. The developed process has enabled for a reduction of up to 90% in the fabrication times of the insert compared to micromilling. The parts exhibited very smooth surfaces, with roughness values (Sa) of 64.6 nm for the metallic insert and 71.8 nm and 72.9 nm for the COC E-140 and 8007S-04 replicas, respectively. The dimensional tolerance and the surface quality need to be improved to be competitive with the finishes achieved with precision micromilling. Nonetheless, there is still room for improvement considering the significant reduction in the production times through new laser processing strategies.

Luer slip is one of the gold standards for chip-to-world interface in microfluidics. They have outstanding mechanical and operational robustness in a broad range of applications using water and solvent-based liquids. Still, their main drawbacks are related to their size: they have relatively large dead volumes and require a significant footprint to assure a leak-free performance. Such aspects make their integration in systems with high microchannel density challenging. To date, there has been no geometrical optimization of the Luer slips to provide a solution to the mentioned drawbacks. This work aims to provide the rules toward downscaling the Luer slips. To this effect, seven variations of the Luer slip male connectors and five variations of Luer slip female connectors have been designed and manufactured focusing on the reduction of the size of connectors and minimization of the dead volumes. In all cases, female connectors have been developed to pair with the corresponding male connector. Characterization has been performed with a tailor-made test bench in which the closure force between male and female connectors has been varied between 7.9 and 55 N. For each applied closure force, the test bench allows liquid pressures to be tested between 0.5 and 2.0 bar. Finally, the analysis of a useful life determines the number of cycles that the connectors can withstand before leakage.