Multi-Sensor Origami Platform: A Customizable System for Obtaining Spatiotemporally Precise Functional Readouts in 3D Models.

Bioprinting technology offers unprecedented opportunities to construct in vitro tissue models that recapitulate the 3D morphology and functionality of native tissue. Yet, it remains difficult to obtain adequate functional readouts from such models. In particular, it is challenging to position sensors in desired locations within pre-fabricated 3D bioprinted structures. At the same time, bioprinting tissue directly onto a sensing device is not feasible due to interference with the printer head. As such, a multi-sensing platform inspired by origami that overcomes these challenges by "folding" around a separately fabricated 3D tissue structure is proposed, allowing for the insertion of electrodes into precise locations, which are custom-defined using computer-aided-design software. The multi-sensing origami platform (MSOP) can be connected to a commercial multi-electrode array (MEA) system for data-acquisition and processing. To demonstrate the platform, how integrated 3D MEA electrodes can record neuronal electrical activity in a 3D model of a neurovascular unit is shown. The MSOP also enables a microvascular endothelial network to be cultured separately and integrated with the 3D tissue structure. Accordingly, how impedance-based sensors in the platform can measure endothelial barrier function is shown. It is further demonstrated the device's versatility by using it to measure neuronal activity in brain organoids.