Development and Validation of a Compliant Reversible Actuator and Detector Leveraging Electrophysiology for Organoids (Organoid-CRADLE)

PROJECT SUMMARY This proposal will develop a multi-functional interface to measure and modulate the activity of neural organoid cultures. The first generation of this Compliant Reversible Actuator and Detector Leveraging Electrophysiology (Organoid-CRADLE) will include a multi-electrode array (MEA) and light-emitting diodes (LEDs) for optogenetic experiments. The LEDs will interface with NeuroLux’s existing suite of hardware and software for optogenetic experiments, while the MEA will interface with hardware from other established vendors. The Organoid-CRADLE will have several transformational advantages over status quo technologies. The Organoid-CRADLE will use a revolutionary soft robotic structure to grip non-adherent organoid cultures and position electrodes and µLEDs on the organoid surface. Conventional MEAs are flat, making them incompatible with the curved shape of an organoid. Even next-generation 3D MEAs that are curved for compatibility with organoids currently have a static shape. Therefore, it is difficult to design them to perform well with multiple organoids because organoids vary significantly in size and shape, even within a single batch. Our device solves this problem because it has soft arms that gradually curl up from a flat position when pressurized. Instead of being designed to match the shape of a target organoid, the device is designed to conform to the size and shape of whatever organoid it encounters, making it much more versatile than other state-of-the-art devices. Another problem with competing devices is that the contact is not reversible. The Organoid-CRADLE can disengage from the organoid at any time without damaging the device or injuring the organoid. As a result, a single device can record from several different organoids in rotation. Also, an organoid that is used for recording can be released unharmed for use in other procedures. Neither of these approaches is possible with competing devices and both will be highly valued by our target customers. We will prepare this revolutionary product for market by focusing on its geometry, MEA functionality, and optical stimulation functionality. We will optimize the geometry to maximize contact area without inducing injury. We will demonstrate that an array of electrodes can be embedded in the device and validate their ability to record the activity of the organoid. Finally, we will demonstrate that tiny µLEDs can be attached to the device and used to induce activity in appropriately-prepared, light sensitive organoids. The capacity to capture an organoid without injuring it and then release it is useful independent of the other functionality of the device. Similarly, MEA and optical stimulation functionality are also independently valuable. In combination, these features will move organoid electrophysiology from being a challenging assay available only to large, well- resourced labs to being a routine assay available to startups and small academic labs across the world. Therefore, we anticipate that this product will not only quickly dominate the market for organoid electrophysiology but also ultimately expand it by making it more accessible.