Med-X | Flexible and stretchable bioelectronics for organoids

Organoids have gained significant interest due to their ability to recapitulate the structural, molecular, and functional complexity of corresponding organs. While methods have been developed to characterize and benchmark organoid structural and molecular properties, capturing the functional development and maturation of organoids remains challenging.

To address this, the development of multifunctional bioelectronics for interfacing with organoids has been actively pursued. However, conventional electronics face limitations in achieving multifunctional recording and control across the entire three-dimensional (3D) volume of organoids in a long-term stable manner due to the large morphological and cellular composition changes during development.

The team led by Jaeyong Lee and Jia Liu from Harvard University first discusses the application of conventional electronics for organoid interfacing. They then focus on the development of flexible and stretchable electronics designed to create organoid/electronics hybrids for chronically stable interfaces. The researchers also review recent advancements in flexible multifunctional electronics for charting multimodal cell activities throughout development. Furthermore, they explore the integration of flexible bioelectronics with other characterization modalities for comprehensive multimodal charting of cells within 3D tissues. Finally, the authors discuss the potential of integrating artificial intelligence into the organoid system through embedded electronics, harnessing organoid intelligence for biosymbiotic computational systems. These advancements could provide valuable tools for characterizing organoid functional development and maturation, establishing patient-specific models, developing therapeutic opportunities, and exploring novel computational strategies.

Conclusion

Long-term electrophysiological recording of organoids offers promising models for studying development, disease, and drug discovery. Flexible electronics have revolutionized this field by enabling electrophysiological recordings from 3D organoids. The development of organoid/electronics hybrids, or cyborg organoids, has enabled long-term, stable electrophysiological recording at the single-cell level across 3D tissues throughout development. When combined with in situ sequencing, organoid/electronics hybrids have provided novel opportunities for multimodal profiling of single cells throughout 3D organoids, potentially uncovering the molecular basis of functionally specific types of cells. Flexible electronics interfacing with brain organoid can further advance organoid intelligence by enabling cognitive function training through stimulation and recording of biological neural networks. Additionally, the development of flexible, multifunctional electronics for precise cell stimulation with light or chemicals will enhance the characterization and study of organoid models.

Highlights

• Comprehensive review of bioelectronics for 3D interfacing with organoids.

• Recent advancements in flexible multifunctional electronics for multimodal charting organoid functional properties.

• Discussion of emerging fields; multimodal profiling of single cells in organoids and organoid intelligence.