Active fluidic chip produced using 3D-printing for combinatorial therapeutic screening on liver tumor spheroid.

Known for their capabilities in automated fluid manipulation, microfluidic devices integrated with pneumatic valves are broadly used for researches in life science and clinical practice. The application is, however, hindered by the high cost and overly complex fabrication procedure. Here, we present an approach for fabricating molds of active fluidic devices using a benchtop 3D printer and a simple 2-step protocol (i.e. 3D printing and polishing). The entire workflow can be completed within 6 h, costing less than US$ 5 to produce all necessary templates for PDMS replica molding, which have smooth surface and round-shaped pneumatic valve structures. Moreover, 3D printing can create unique bespoke on-off objects of a wide range of dimensions. The millimeter- and centimeter-sized features allow examination of large-scale biological samples. Our results demonstrate that the 3D-printed active fluidic device has valve control capacities on par with those made by photolithography. Controlled nutrients and ligands delivery by on-off active valves allows generation of dynamic signals mimicking the ever-changing environmental stimuli, and combinatorial/sequential drug inputs for therapeutic screening on liver tumor spheroid. We believe that the proposed methodology can pave the way for integration of active fluidic systems in research labs, clinical settings and even household appliances for a broad range of application.