Leveraging Soft Microelectrode Arrays for Brain Organoid Electrophysiology

Traditional two-dimensional microelectrode arrays (MEAs) fall short in capturing the complexity of three-dimensional brain organoids. This study introduces two innovative MEA designs to address this limitation, enhancing the study of brain organoid electrophysiology.<br/>The first design features a stretchable MEA tailored to monitor the electrophysiological activity of brain spheroids under varying mechanical loads. These MEAs are fabricated using thin-film technology, comprising a platinum layer sandwiched between polyimide films. Stretchability is achieved through a Kirigami-based patterning technique, incorporating Y-shaped motifs that facilitate out-of-plane deflections. The soft MEAs can sustain strains up to 10% without a notable increase in electrode impedance. Additionally, PEDOT coating on the electrodes enhanced both their electrical and mechanical performance, making them ideal for prolonged neural activity recording from brain spheroids.<br/>Another compliant MEA design integrates soft actuation with flexible MEAs. We developed the e-Flower, a flower-shaped MEA that can envelop sub-millimeter brain spheroids. Inspired by soft micro-grippers, the e-Flower uses the swelling properties of a polyacrylic acid hydrogel grafted onto a polyimide substrate hosting electrical interconnects. Upon the addition of cell culture medium, the e-Flower actuates to envelop the spheroid, achieving a tunable curvature for comprehensive neural signal recording across the spheroid surface. This actuation mechanism requires no additional equipment or solvents and is compatible with standard electrophysiology recording systems.<br/>The e-Flower demonstrated the ability to detect spontaneous neural activity across the entire surface of brain spheroids, highlighting its potential for detailed electrophysiological studies. Meanwhile, the stretchable MEA’s capacity to record neural activity under mechanical strain opens new avenues for studying the effects of mechanical loading on neural tissues, mimicking conditions such as traumatic brain injury.