One-Step Drug Screening System Utilizing Electrophysiological Activity in Multiple Brain Organoids

Abstract

Human-induced pluripotent stem cell (iPSC)-derived brain organoids have attracted significant attention as promising models for drug screening owing to their remarkable resemblance to the human brain. The advent of disease model organoids, derived from patient's cells, has further elevated expectations for drug screening and personalized medicine. Nevertheless, the absence of a comprehensive platform for administering drugs and assessing their efficacy based on functional changes in brain organoids has remained a challenge. In this study, we introduce a one-step drug screening system designed designed to investigate functional changes induced by diverse drug doses in multiple brain organoids, utilizing electrophysiological signal measurements. Our system comprises a specialized culture chamber with a microfluidic chip capable of accommodating 10 organoids and delivering varying doses of two drugs to each organoid. Additionally, we integrate a three dimentional microelectrode array (3D MEA) with ten shanks, enabling functional assessment of 10 brain organoids. This approach facilitates dose-dependent drug screening across multiple organoids. We demonstrate the effectiveness of our system through real-time analysis of neural activity changes triggered by different doses of pottassium chloride (KCl). Furthermore, sodium channel protein type 2 subunit alpha (SCN2A)-epileptic organoids to demonstrate utility in disease-model-based drug screening. Our platform enables functional screening and personalized medicine using brain organoids.