Advanced Science (Mar 2024)

Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons

  • Xiaotian Zhang,
  • Zhi Dou,
  • Seung Hyun Kim,
  • Gaurav Upadhyay,
  • Daniel Havert,
  • Sehong Kang,
  • Kimia Kazemi,
  • Kai‐Yu Huang,
  • Onur Aydin,
  • Raymond Huang,
  • Saeedur Rahman,
  • Austin Ellis‐Mohr,
  • Hayden A. Noblet,
  • Ki H. Lim,
  • Hee Jung Chung,
  • Howard J. Gritton,
  • M. Taher A. Saif,
  • Hyun Joon Kong,
  • John M. Beggs,
  • Mattia Gazzola

DOI
https://doi.org/10.1002/advs.202306826
Journal volume & issue
Vol. 11, no. 11
pp. n/a – n/a

Abstract

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Abstract Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

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