Speaker
Description
HYCON: A Hydrogel-based Conformable Electrode Array for Noninvasive Electrophysiological Recording of Brain Organoids
Introduction:
Brain organoids have become an essential tool for modeling human brain development, neurological disorders, and therapeutic interventions. However, designing reliable interfaces for these 3D, delicate structures remains a key challenge. Current electrophysiological approaches either rely on penetrating mesh electrodes that grow into the organoid over time1, or on predefined 3D structures such as basket-shaped micro electrode arrays (MEAs)2 or kirigami-inspired MEAs3 that constrain organoid morphology and eventually penetrate the organoids. While effective in some contexts, these strategies have major limitations: poor adaptability to organoid-to-organoid variability; risk of mechanical stress, and; complex fabrication or integration steps.2
Methods:
To address these limitations, we developed the HYCON array (Hydrogel-based Conformable Electrode Array), a mechanically adaptive platform that allows for conformal contact of electrodes with brain organoids without the need for invasive penetration or rigid 3D structures. The HYCON array consists of a soft, stretchable MEA fabricated using PEDOT-PSS on a styrene-butadiene-styrene (SBS) substrate, which is freely layered on top of a biocompatible hydrogel. The hydrogel with a tunable stiffness of 0.5–2 kPa, acts as a compliant support layer underneath the MEA. A similarly soft hydrogel pocket holds the organoid in place atop the HYCON array. This geometry enables passive conformation of the electrode layer around the curved organoid surface, accommodating organoid shape variation and minimizing compression of the organoid.
Results:
Mechanical characterization of the HYCON array demonstrated that the soft hydrogel layer deforms under mild mechanical loading to conform the PEDOT-based MEA around the organoid without requiring predefined mechanical shaping. Unlike basket-type or rigid supports, the HYCON array adapts to different organoid geometries. The stack is fully flat when fabricated, which simplifies the fabrication process and makes it easier to integrate with standard recording hardware. The conformable interface remains stable even after an organoid has been repositioned on top of it multiple times.
Discussion:
The HYCON array is the first fabricated in-vitro neural interface of its kind, as it relies on hydrogel compliance and passive deformation of the electrodes, rather than predefined or invasive structures, to enable contact with organoids. This design provides mechanical support and matches organoid curvature without risking damage or requiring fixed organoid dimensions. This approach is particularly advantageous for dynamic or large-scale organoid experiments, where shape variability is high and minimal perturbation is critical.
References:
1. Li, T. L., Liu, Y., Forro, C., Yang, X., Beker, L., Bao, Z., Cui, B. & Pașca, S. P. Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids. Biomaterials 290, 121825 (2022).
2. Lee, J. & Liu, J. Flexible and stretchable bioelectronics for organoids. Med-X 3, (2025).
3. Yang, X., Forró, C., Li, T. L., Miura, Y., Zaluska, T. J., Tsai, C. T., Kanton, S., McQueen, J. P., Chen, X., Mollo, V., Santoro, F., Pașca, S. P. & Cui, B. Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids. Nat. Biotechnol. 42, 1836–1843 (2024).
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