A novel device has been developed that features four adaptable petals with platinum electrodes. When exposed to the liquid that maintains the cell structure, these petals curl around a spheroid. This curling action is made possible by the expansion of a soft hydrogel, which ensures the device is gentle on tissue and user-friendly. The e-Flower has been created to work seamlessly with current electrophysiological systems, providing a plug-and-play solution for researchers. This innovation eliminates the need for complicated external actuators or harmful solvents. By utilizing this technology on organoids, researchers will be able to record electrical activity from every angle, leading to a deeper understanding of brain functions. There is hope that this will unveil new findings related to neurodevelopment, recovery from brain injuries, and neurological disorders.
Neural spheroids, or clusters of brain cells in three dimensions, are proving to be vital for examining neural networks and investigating neurological diseases in laboratory settings. The e-Flower from EPFL, shaped like a flower and acting as a 3D microelectrode array (MEA), enables researchers to observe the electrical activities of these spheroids in a previously unachievable manner. This significant advancement, documented in Science Advances, paves the way for more advanced studies on brain organoids, which are intricate, miniature representations of brain tissue.
“With the e-Flower, we can record neural activities from a larger part of the neural spheroids in real-time, an ability that earlier tools lacked. Our flexible technology allows us to obtain precise recordings without harming the delicate 3D neural structures, enhancing our understanding of their complex circuitry,” explains Stéphanie Lacour, the paper’s lead author and head of the Laboratory for Soft Bioelectronic Interfaces (LSBI) at the Neuro X Institute.
Why focus on neural spheroids?
“We chose to study neural spheroids because they offer a simple and approachable model,” says Eleonora Martinelli, a leading researcher on the project.
Neural spheroids consist of three-dimensional clusters of neurons that imitate some essential functions of actual brain tissue. They are less complex than organoids, which incorporate various cell types and more accurately reflect brain structure. The LSBI team at Campus Biotech collaborated with Luc Stoppini and Adrien Roux from the Tissue Engineering Laboratory (HEPIA-HESGE), who have extensive experience with neural spheroids and their electrophysiology.
“Spheroids are fairly easy to create and manage in a lab setting, making them perfect for initial testing phases,” Martinelli adds. “However, our aim is to eventually adapt the e-Flower for use with brain organoids, which more closely resemble brain development and disorders.”
“Organoids present an exciting opportunity for both neuroscience research and advanced neurotechnology,” remarks Stéphanie Lacour. “They connect simplified in vitro models with the complexities found in human brains. Our work with the e-Flower is a vital advance towards exploring these 3D models.”
The fortunate coincidence behind the device
Interestingly, the e-Flower emerged from a surprising twist of fate. Outman Akouissi, a collaborator, faced an issue while creating soft implants for peripheral nerves: the hydrogels he was using caused unexpected curling of his devices upon contact with water. What began as a setback transformed into a significant breakthrough when Akouissi and Martinelli recognized they could use this curling motion for a different purpose—encasing neural spheroids.
“This illustrates how chance can spark innovation,” states Martinelli. “An obstacle in one project turned into the answer for another.”
A fresh perspective on neural electrophysiology
The device contains four flexible petals fitted with platinum electrodes that curl around the spheroid upon exposure to the supportive liquid. This movement is facilitated by the swelling of a soft hydrogel, which ensures the device is gentle on tissues while remaining user-friendly.
The e-Flower was designed to integrate easily with existing electrophysiological systems, providing researchers with a plug-and-play solution and bypassing the need for intricate external actuators or toxic solvents.
By applying this technology to organoids, researchers can record electrical activity from all directions, offering a more complete understanding of brain functions. It is anticipated that this will lead to fresh insights in neurodevelopment, recovery from brain injuries, and neurological diseases.
