SphereChip attaches spheroids and organoids to planar multielectrode arrays with microfluidics

Human cardiac and neuronal stem cell-derived spheroids and organoids are emerging models for drug discovery and drug safety studies. Their electrical properties are frequently investigated by means of multielectrode arrays (MEAs). However, it is difficult to establish adequate electrode contacts between planar MEAs and these round, 3D cell models. Contractions of cardiac 3D models and movement artefacts during the application of test solutions can also disrupt the recordings. As a solution, we present a microfluidics device (hereinafter referred to as SphereChip) that enables quick and stable attachment of free-floating spherical cell models such as cardiospheres, cardioids and neurospheres to conventional planar MEAs. The device reduces motion artifacts and enables complete solution exchange. It was successfully used with two different MEA designs for field potential measurements and simultaneous imaging using fluorescent probes on small cardio- and neurospheres (diameter 300 to 500 μm) and larger cardioids (800 to 900 μm). We observed concentration-dependent prolongation of action and field potentials of cardiospheres by the potassium channel (Kv1.11) inhibitors E4031 and dofetilide. In neurospheres, application of a potassium channel (Kv7.2/7.3) activator ML213 reduced spiking and bursting. We present these results as proof of concept for the microfluidics device as a means to enable organ-on-a-chip studies combining field potential measurements with simultaneous imaging on spherical cell models using planar MEAs. The method is applicable to different MEA formats and holds promise as a workable platform for drug testing and toxicity studies.