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Thinking outside the box to Fabricate Customized 3D Neural Chips
<(From Left) Professor Yoonkey Nam, Dr. Dongjo Yoon from the Department of Bio and Brain Engineering>
Cultured neural tissues have been widely used as a simplified experimental model for brain research. However, existing devices for growing and recording neural tissues, which are manufactured using semiconductor processes, have limitations in terms of shape modification and the implementation of three-dimensional (3D) structures.
By "thinking outside the box," a KAIST research team has successfully created a customized 3D neural chip. They first used a 3D printer to fabricate a hollow channel structure, then used capillary action to automatically fill the channels with conductive ink, creating the electrodes and wiring. This achievement is expected to significantly increase the design freedom and versatility of brain science and brain engineering research platforms.
On the 25th, KAIST announced that a research team led by Professor Yoonkey Nam from the Department of Bio and Brain Engineering has successfully developed a platform technology that overcomes the limitations of traditional semiconductor-based manufacturing. This technology allows for the precise fabrication of "3D microelectrode array" (neural interfaces with multiple microelectrodes arranged in a 3D space to measure and stimulate the electrophysiological signal of neurons) in various customized forms for in vitro culture chips.
Existing 3D microelectrode array fabrication, based on semiconductor processes, has limited 3D design freedom and is expensive. While 3D printing-based fabrication techniques have recently been proposed to overcome these issues, they still have limitations in terms of 3D design freedom for various in vitro neural network structures because they follow the traditional sequence of "conductive material patterning → insulator coating → electrode opening."
The KAIST research team leveraged the excellent 3D design freedom provided by 3D printing technology and its ability to use printed materials as insulators. By reversing the traditional process, they established an innovative method that allows for more flexible design and functional measurement of 3D neuronal network models for in vitro culture.
<Schematic Diagram of an Integrated Cell Culture Substrate-Microelectrode Array Platform for In Vitro Cultured 3D Neural Network Models>
First, they used a 3D printer to print a hollow 3D insulator with micro-tunnels. This structure was designed to serve as a stable scaffold for conductive materials in 3D space while also supporting the creation of various 3D neuronal networks. They then demonstrated that by using capillary action to fill these internal micro-tunnels with conductive ink, they could create a 3D scaffold-microelectrode array with more freely arranged microelectrodes within a complex 3D culture support structure.
The new platform can be used to create various chip shapes, such as probe-type, cube-type, and modular-type, and supports the fabrication of electrodes using different materials like graphite, conductive polymers, and silver nanoparticles. This allows for the simultaneous measurement of multichannel neural signals from both inside and outside the 3D neuronal network, enabling precise analysis of the dynamic interactions and connectivity between neurons.
Professor Nam stated, "This research, which combines 3D printing and capillary action, is an achievement that significantly expands the freedom of neural chip fabrication." He added that it will contribute to the advancement of fundamental brain science research using neural tissue, as well as applied fields like cell-based biosensors and biocomputing.
Dr. Dongjo Yoon from KAIST's Department of Bio and Brain Engineering participated as the first author of the study. The research findings were published online in the international academic journal Advanced Functional Materials (June 25th issue).
※Paper Title: Highly Customizable Scaffold-Type 3D Microelectrode Array Platform for Design and Analysis of the 3D Neuronal Network In Vitro
This research was supported by the Consolidator Grants Program and the Global Basic Research Laboratory Program of the National Research Foundation of Korea.
2025.09.26 View 1887 -
KAIST Successfully Implements 3D Brain-Mimicking Platform with 6x Higher Precision
<(From left) Dr. Dongjo Yoon, Professor Je-Kyun Park from the Department of Bio and Brain Engineering, (upper right) Professor Yoonkey Nam, Dr. Soo Jee Kim>
Existing three-dimensional (3D) neuronal culture technology has limitations in brain research due to the difficulty of precisely replicating the brain's complex multilayered structure and the lack of a platform that can simultaneously analyze both structure and function. A KAIST research team has successfully developed an integrated platform that can implement brain-like layered neuronal structures using 3D printing technology and precisely measure neuronal activity within them.
KAIST (President Kwang Hyung Lee) announced on the 16th of July that a joint research team led by Professors Je-Kyun Park and Yoonkey Nam from the Department of Bio and Brain Engineering has developed an integrated platform capable of fabricating high-resolution 3D multilayer neuronal networks using low-viscosity natural hydrogels with mechanical properties similar to brain tissue, and simultaneously analyzing their structural and functional connectivity.
Conventional bioprinting technology uses high-viscosity bioinks for structural stability, but this limits neuronal proliferation and neurite growth. Conversely, neural cell-friendly low-viscosity hydrogels are difficult to precisely pattern, leading to a fundamental trade-off between structural stability and biological function. The research team completed a sophisticated and stable brain-mimicking platform by combining three key technologies that enable the precise creation of brain structure with dilute gels, accurate alignment between layers, and simultaneous observation of neuronal activity.
The three core technologies are: ▲ 'Capillary Pinning Effect' technology, which enables the dilute gel (hydrogel) to adhere firmly to a stainless steel mesh (micromesh) to prevent it from flowing, thereby reproducing brain structures with six times greater precision (resolution of 500 μm or less) than conventional methods; ▲ the '3D Printing Aligner,' a cylindrical design that ensures the printed layers are precisely stacked without misalignment, guaranteeing the accurate assembly of multilayer structures and stable integration with microelectrode chips; and ▲ 'Dual-mode Analysis System' technology, which simultaneously measures electrical signals from below and observes cell activity with light (calcium imaging) from above, allowing for the simultaneous verification of the functional operation of interlayer connections through multiple methods.
< Figure 1. Platform integrating brain-structure-mimicking neural network model construction and functional measurement technology>
The research team successfully implemented a three-layered mini-brain structure using 3D printing with a fibrin hydrogel, which has elastic properties similar to those of the brain, and experimentally verified the process of actual neural cells transmitting and receiving signals within it.
Cortical neurons were placed in the upper and lower layers, while the middle layer was left empty but designed to allow neurons to penetrate and connect through it. Electrical signals were measured from the lower layer using a microsensor (electrode chip), and cell activity was observed from the upper layer using light (calcium imaging). The results showed that when electrical stimulation was applied, neural cells in both upper and lower layers responded simultaneously. When a synapse-blocking agent (synaptic blocker) was introduced, the response decreased, proving that the neural cells were genuinely connected and transmitting signals.
Professor Je-Kyun Park of KAIST explained, "This research is a joint development achievement of an integrated platform that can simultaneously reproduce the complex multilayered structure and function of brain tissue. Compared to existing technologies where signal measurement was impossible for more than 14 days, this platform maintains a stable microelectrode chip interface for over 27 days, allowing the real-time analysis of structure-function relationships. It can be utilized in various brain research fields such as neurological disease modeling, brain function research, neurotoxicity assessment, and neuroprotective drug screening in the future."
The research, in which Dr. Soo Jee Kim and Dr. Dongjo Yoon from KAIST's Department of Bio and Brain Engineering participated as co-first authors, was published online in the international journal 'Biosensors and Bioelectronics' on June 11, 2025.
※Paper: Hybrid biofabrication of multilayered 3D neuronal networks with structural and functional interlayer connectivity
※DOI: https://doi.org/10.1016/j.bios.2025.117688
2025.07.16 View 3559