(a) Schematic of the pumpless four-organ microfluidic system, showing the acrylic housing holding PDMS gaskets that define the microfluidic pathway and the organ compartments along the path: representative images of hepatocytes on coverslip (i), cardiomyocytes on cantilever chip (CL) (ii) and patterned on customized MEA (cMEA) chips (iii), skeletal muscle myotubes on CL chips (iv), and motoneurons patterned on cMEA chips (v) show each cell type in a different location in the system. Representative functional readouts of the coculture are shown for the different compartments: the supernatant is used to quantify hepatic function (i); the contractile machinery of cardiomyocytes and myotubes is challenged on the CL chips using a laser-deflection based apparatus that records CL movement and a wave amplitude (ii and iv); the electrical signal of cardiomyocytes and motoneurons is recorded from the cMEAs connected to an amplifier via a printed circuit board and an elastomeric connector, translating current changes detected on the electrodes into field potential waveforms (iii and v). Adapted from Ref. [176] with permission from Advanced Functional Materials. (b) Schematic of the modular perfusion-driven three-organ-on-a-chip microfluidic system (i): individual microfluidic microreactor units house each organoid or tissue model and are connected via a central fluid routing breadboard. Quantitative analysis of cardiac beating rates (ii) following incorporation of liver organoids show an altered response of the cardiac organoids to both 0.1 μM propranolol and 0.5 μM epinephrine. The assessment of the interplay between the two drugs (iii) shows that BPM (Beats per Minute) values increase from baseline with epinephrine 0.5 μM and increases from epinephrine are blocked by 0.1 μM propranolol in the cardiac organoid-only system. When liver organoids are present and permitted to metabolically inactivate 0.1 μM propranolol, 0.1 μM epinephrine induces an increased BPM value. If 2D-cultured hepatocytes are substituted for the liver organoids, this effect is not observed. Statistical significance: * p < 0.05. Adapted from Ref. [178] with permission from Springer Nature.