A Scalable, Rapidly Reconfigurable Microfluidic Platform Enables Dynamic Flow Conditions ‘On-Chip’

Microfluidic devices, or “organ-chips”, are an emergent technology that bridges the gap between in-vitro and in-vivo models. With growing pressure from the EPA and other government agencies to reduce or eliminate the use of animals in research, microfluidics offer a robust alternative. However, the most common production method (soft lithography) is expensive and requires specialized equipment, preventing widespread use and adoption of this technology. With recent advances in three-dimensional (3D) printing technology, the chip fabrication process may be simplified considerably without sacrificing the micron-scale resolution required to simulate physiological environments in-vitro.<br/><br/>In this work, a scalable and rapidly reconfigurable chip platform is realized by interfacing our previously validated laser-cut and assembly-based method with 3D printing technology [1]. Laser-cut poly (methyl methacrylate) (PMMA) sheets are used to build the culture and flow compartments of the chip, and stereolithography (SLA) 3D printed resin “tops” provide the described functionality. The chip is built layer-by-layer with 1.6 mm PMMA sheets and a 4.8 mm resin upper layer. Each layer has uniform rectangular dimensions of 22 mm by 40 mm. 50 μm double-sided adhesive tape is sandwiched between each PMMA sheet to bond the lower layers together. Magnets compress a 0.4 mm thick fluoroelastomer rubber gasket at the resin-PMMA interface, forming a reversible seal for removal and re-use of chip tops. Leak tests conducted using water and a 1 mL syringe show complete sealing at pressures well above standard operating conditions.<br/><br/>The chip top features 3 mm by 10 mm dovetail style joints that interlock, like puzzle pieces, with up to four independent 3D printed “chip connectors”. Joints between tops and connectors fit together with a simple ‘push-to-fit’ action, enabling rapid setup and reconfiguration of scalable chip arrays. Internal microchannels pass through the center plane of both the top and connector, allowing fluid flow from one chip to another via in/outlets at each of the joint faces. Fluoroelastomer O-rings embedded in the face of each top-connector joint reversibly seal, preventing leakage. Fluid flow within, and across, chips is directed using 3D printed hand-operated valves. The integrated valves enable flow path customization by simply redirecting or blocking off flow at set points on the chip top or connector. With all individual components prepared, an array of chips may be assembled, or rearranged from a previous configuration, in minutes. Overall, we propose a microfluidic platform that is scalable, modular, and enables dynamic control of microfluidic flow conditions on-chip without the need to adjust offline components such as syringe pumps or reservoirs. Ongoing work is focused on leveraging the current platform to include integrated characterization on-chip towards spatiotemporal data collection. Interfacing SLA 3D printing with established chip fabrication methods opens opportunities for full customization of in-vitro models to recapitulate physiologically relevant conditions on-chip.<br/><br/>[1] S. Hosic <i>et al.</i>, ACS Biomater. Sci. Eng. <b>7</b>, 2949-2963 (2021)