On January 14th, the KAIST research team led by Professor Hyunjoo J. Lee from the School of Electrical Engineering in collaboration with Dr. Mi-Young Son and Dr. Mi-Ok Lee at Korea Research Institute of Bioscience and Biotechnology (KRIBB) announced the development of a highly stretchable microelectrode array (sMEA) designed for non-invasive electrophysiological signal measurement of organoids.

Organoids* are highly promising models for human biology and are expected to replace many animal experiments. Their potential applications include disease modeling, drug screening, and personalized medicine as they closely mimic the structure and function of humans.

*Organoids: three-dimensional in vitro tissue models derived from human stem cells

Despite these advantages, existing organoid research has primarily focused on genetic analysis, with limited studies on organoid functionality. For effective drug evaluation and precise biological research, technology that preserves the three-dimensional structure of organoids while enabling real-time monitoring of their functions is needed. However, it’s challenging to provide non-invasive ways to evaluate the functionalities without incurring damage to the tissues. This challenge is particularly significant for electrophysiological signal measurement in cardiac and brain organoids since the sensor needs to be in direct contact with organoids of varying size and irregular shape. Achieving tight contact between electrodes and the external surface of the organoids without damaging the organoids has been a persistent challenge.

< Figure 1. Schematic image of highly stretchable MEA (sMEA) with protruding microelectrodes. >

The KAIST research team developed a highly stretchable microelectrode array with a unique serpentine structure that contacts the surface of organoids in a highly conformal fashion. They successfully demonstrated real-time measurement and analysis of electrophysiological signals from two types of electrogenic organoids (heart and brain). By employing a micro-electromechanical system (MEMS)-based process, the team fabricated the serpentine-structured microelectrode array and used an electrochemical deposition process to develop PEDOT:PSS-based protruding microelectrodes. These innovations demonstrated exceptional stretchability and close surface adherence to various organoid sizes. The protruding microelectrodes improved contact between organoids and the electrodes, ensuring stable and reliable electrophysiological signal measurements with high signal-to-noise ratios (SNR).

< Figure 2. Conceptual illustration, optical image, and fluorescence images of an organoid captured by the sMEA with protruding microelectrodes.>

Using this technology, the team successfully monitored and analyzed electrophysiological signals from cardiac spheroids of various sizes, revealing three-dimensional signal propagation patterns and identifying changes in signal characteristics according to size. They also measured electrophysiological signals in midbrain organoids, demonstrating the versatility of the technology. Additionally, they monitored signal modulations induced by various drugs, showcasing the potential of this technology for drug screening applications.

< Figure 3. SNR improvement effect by protruding PEDOT:PSS microelectrodes>

Prof. Hyunjoo Jenny Lee stated, “By integrating MEMS technology and electrochemical deposition techniques, we successfully developed a stretchable microelectrode array adaptable to organoids of diverse sizes and shapes. The high practicality is a major advantage of this system since the fabrication is based on semiconductor fabrication with high volume production, reliability, and accuracy. This technology that enables in situ, real-time analysis of states and functionalities of organoids will be a game changer in high-through drug screening.”

This study led by Ph.D. candidate Kiup Kim from KAIST and Ph.D. candidate Youngsun Lee from KRIBB, with significant contributions from Dr. Kwang Bo Jung, was published online on December 15 in ‘Advanced Materials’ (IF: 27.4).

< Figure 4. Drug screening using cardiac spheroids and midbrain organoids.>

This research was supported by a grant from 3D-TissueChip Based Drug Discovery Platform Technology Development Program (No. 20009209) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea), by the Commercialization Promotion Agency for R&D Outcomes (COMPA) funded by the Ministry of Science and ICT (MSIT) (RS-2024-00415902), by the K-Brain Project of the National Research Foundation (NRF) funded by the Korean government (MSIT) (RS-2023-00262568), by BK21 FOUR (Connected AI Education & Research Program for Industry and Society Innovation, KAIST EE, No. 4120200113769), and by Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM4722432).