Functional measurements of modular neural network by NTT: 3D electrode array used as basic technology for brain-mimicking cultured models

On May 24, NTT announced that it has developed a new method for successful long-term measurement of neural activity from a neural network consisting of cell clusters formed by aggregation of cells. In this, graphene—a two-dimensional material consisting of a single layer of carbon atoms that is highly conductive, transparent, and biocompatible—is applied to a polymer thin film to induce spontaneous bending of the film to form a three-dimensional (3D) roll.

The technology is expected to be used as a basic technology for brain-on-a-chip (brain-mimicking culture model), which will accelerate embryology and drug discovery research. Details regarding this achievement were published in the American scientific journal Advanced Functional Materials on May 1.

NTT successfully measured the activity of 3D cell clusters grown inside graphene by using 3D graphene as a measuring electrode. Because the 3D cell clusters are formed inside the cylindrical 3D electrode, this technology can easily form a pair of 3D cell clusters and electrodes and maintain stable contact between them.

In this study, it was demonstrated that the measured neural activity was three times of that measured when 3D cell clusters were cultured on flat electrodes; the measurement was stable over a period of 70 days. Specifically, an electrode array was fabricated by arranging stereotactic electrodes at multiple points (8 × 8 points), and measurement from multiple 3D cell clusters was realized. Independent signal measurement from the 3D cell cluster corresponding to each electrode rendered it possible to measure the activity of neural networks connected to individual 3D cell clusters.

In conventional two-dimensional electrodes, cultured cells form a planar and uniform network and synchronized activity between cells is dominant. In contrast, the present 3D cell-cluster network generated diverse spatiotemporal patterns of neuronal activity with a mixture of synchronous and asynchronous activities, and these patterns changed as the days passed in culture. In the real brain, the structure of cell clusters as individual modules is known to generate diverse patterns.

By combining the formation of 3D cell clusters and signal measurement techniques, it was shown that cultured nerves with characteristic structures (3D and modular structures) found in the brain have patterns of neural activity similar to those in the brain, with a mixture of synchronous and asynchronous activities. In addition, the growth phase was also monitored.

The brain is an organ that functions as a network of neuronal elements; yet, many aspects of these elements, such as their assembly, function, and growth, are still not understood. Due to this, for investigating the mechanism from the level of neurons as elements to the brain as an aggregate in an integrated manner, brain-on-a-chip has gained attention in recent years. In this, cultured brain-like tissues are formed by stacking cells and biological information is collected on a device chip. However, although device technologies have been developed to measure neural activity from 3D cell clusters, it has been difficult to place and measure from electrodes on each of the multiple 3D cell clusters.

NTT's technology used in this research has realized measurement from multiple 3D cell clusters by reproducing part of a brain-like neural network formation on a chip and is expected to be useful for research on brain functions.

Journal Information
Publication: Advanced Functional Materials
Title: Self-Folding Graphene-Based Interface for Brain-Like Modular 3D Tissue
DOI: 10.1002/adfm.202301836