3D cell cultures, such as cell spheroids and organoids, offer a much better representation of the physiological conditions observed in vivo compared with 2D cell cultures. For this reason, such 3D cell aggregates have become very popular as an experimental platform in the fields of tissue engineering and regenerative medicine. Spheroids are commonly assembled in microplates treated for low cell adhesion; however, they usually show high size variability and involve a lengthy and costly process. This study proposes an alternative for spheroid assembly that relies on a microfluidic device equipped with a pinched flow geometry. This notion considers previous results that indicate that such an approach is well-suited for handling microparticles’ assembly very precisely. We hypothesize that through this approach it is possible to reduce costs and facilitate the controlled assembly of spheroids in shorter times compared with conventional approaches. To study the formation of spheroids with the proposed device, a laminar two-phase, level set simulation was implemented in COMSOL Multiphysics. Cells were initially trapped in a set of droplets that were suspended in a paramagnetic medium, and then they were allowed to interact with each other. Droplets are trapped in the chambers of the device by employing a Pinched Flow approach, which relies on different geometries to identify possible optimization routes. After capturing the droplets, a magnetic field generated by two permanent magnets, positioned perpendicular to the chambers and parallel to each other, brings the paramagnetic medium to the edges of the spheroid, and by Newtown's third law, guides cells to aggregate in the center to form the spheroids. The simulation results showed that the proposed microfluidic device is able to generate spheroids faster than the conventional microplate assembly method. This relevant result is attributed to the joint action of the geometries and the application of a magnetic field. We are currently validating experimentally the device with very encouraging results. Future work will be dedicated to optimizing the device performance even further by the input of experimental parameters into the models.

Design, simulation, and testing of a low-cost microfluidic device based on a pinched flow geometry to produce highly-uniform spheroids for applications in 3D bioprinting

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ACS Fall 2022

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