3D Micro-instrumentation for Organoid Intelligence (OI)

C. Acha, D. George, K. Murugesan, A. Pantula, D-M Alam El Din, D. Patel, L. Smirnova, D. Gracias
Johns Hopkins Univerisity,
United States

Keywords: Organoid Intelligence


Brain organoids are three-dimensional aggregates of self-organized stem cells that partially recreate the structure and function of the human cortex and potentially having the capability of advancing the field of neuroscience. Conventional models such as planar mammalian cell culture and animal studies have become limited in their offerings a neuronal activity, while clinical trials remain invasive and ethically challenging. Recently, the concept of “Organoid Intelligence” or OI was described to enable biological computing using stem cell derived organoids[1]. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells offer great potential in understanding organogenesis. 2D, flexible MEAs showcase promising potentials for in-vivo biological tissue, however, mapping the three-dimensional shape of a human brain or brain organoid for lab scale still proved challenging. For OI, new kinds of 3D MEAs have emerged to match the novel architecture of brain organoids[2]. Inspired by MEA caps, we’ve developed and previously reported a self-folding polymer leaflet that is capable of conducting electrophysiology studies on brain organoid from 400-600 μm in size.2 Here, we summarize prior results and describe new developments in the use of 3D MEA and related shells. Our lab demonstrates the potential of 3D shell MEAs’ ability for high signal-to-noise ratio in 3D spatiotemporal recordings. We successfully stimulated and recorded brain organoid for electrophysiology; envisioning brain organoid biocomputing systems to allow for faster decision-making, continuous learning during tasks, and greater energy and data efficiency. References: 1. L. Smirnova, B. S. Caffo, D.H. Gracias, Q. Huang, I. E. Morales Pantoja, B. Tang, D.J. Zack, C.A.Berlinicke, J. Lomax Boyd, T.D. Harris, E.C. Johnson, B.J. Kagan, J. Kahn, A.R. Muotri, B.L. Paulhamus, J.C. Schwamborn, J. Plotkin, A.S. Szalay, J.T. Vogelstein, P. F. Worley, T. Hartung, Organoid Intelligence (OI): The new frontier in biocomputing and intelligence-in-a-dish, Frontiers in Science, 1:1017235 (2023). 2. Q. Huang, B. Tang, J. C. Romero, Y. Yang, S. K. Elsayed, G. Pahapale, T.-J. Lee, I. E. Morales Pantoja, F. Han, C. Berlinicke, T. Xiang, M. Sollazo, T. Hartung, Z. Qin, B. Caffo, L. Smirnova, D.H. Gracias, Shell microelectrode arrays (MEAs) for brain organoids, Science Advances 8, eabq5031(2022).