MEA

# MEA assay techniques based on extensive experience

Since first reporting MEA measurements of human iPSC-derived neurons in 2014, we have conducted MEA measurements on over 100 types of iPSC-derived neurons (both central and peripheral neurons), and have developed optimized culturing and data analysis techniques. We have extensive experience in safety evaluations and pharmacological efficacy testing of compounds using healthy or disease iPSC-derived neurons. We perform toxicity predictions and mechanism of action (MoA) predictions with extrapolations to in vivo. Additionally, we possess techniques for acute brain slice MEA testing (including LTP tests) and MEA testing of human iPSC-derived cardiomyocytes.

Reference papers (excerpts)
Central Nervus System(CNS)

Y. Ishibashi, N Nagafuku, S Kimura, X Han, I Suzuki*,  Development of an evaluation method for addictive compounds based on electrical activity of human iPS cell-derived dopaminergic neurons using microelectrode array, Addiction Biology. 29:e13443, 2024 DOI

Y. Ishibashi, N Nagafuku, K Kinoshita, A Okamura, T shirakawa, I Suzuki*,  Verification in seizure liability of compounds based on comparison between in vitro functional activity in cultured neurons and in vivo cerebrospinal fluid concentration for approaching in vitro to in vivo extrapolation, Toxicology and Applied pharmacology. 476;116675, 2023 DOI

Y. Ishibashi, N. Nagafuku, Y. Kanda, I. Suzuki*, Evaluation of neurotoxicity for pesticide-related compounds in human iPS cell-derived neurons using microelectrode array. Toxicology in vitro. 93;105668, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

X Han, N Matsuda, Y Ishibashi, A Odawara; S Takahashi; N Tooi, K Kinoshita, I Suzuki*, “A functional neuron maturation device provides convenient application on microelectrode array for neural network measurement” Biomaterials Research, 26, 84, 1-17,2022 DOI

N Matsuda, A Odawara, Y Ishibashi, K Kinoshita, A Okamura, T Shirakawa, I Suzuki*. Raster plots machine learning to predict the seizure liability of drugs and to identify drugs. Sci Rep. 2022 12(1):2281. DOI

Y. Ishibashi, S. Kimura, I Suzuki*,  Responses to antibiotics in human iPSC-derived neurons based on the clinical antibiotic associated encephalopathy classification, 2022, 47(10), p429-437. The Journal of Toxicological Sciences. DOI

R Yokoi, T Kuroda, N Matsuda, A Odawara, I Suzuki*. Electrophysiological responses to seizurogenic compounds dependent on E/I balance in human iPSC-derived cortical neuronal networks. Journal of Pharmacological Sciences. 2022 148(2):267-278. DOI

Shirakawa T, Suzuki I*. “Approach to Neurotoxicity using Human iPSC Neurons: Consortium for Safety Assessment using Human iPS Cells”. Current Pharmaceutical Biotechnology. 2019 21(9):780-786, DOI

Yokoi R, Okabe N, Matsuda N, Odawara A, Karashima A, Suzuki I*. “Impact of sleep-wake-associated neuromodulators and repetitive low-frequency stimulation on human iPSC-derived neurons.” Frontiers in Neuroscience. 2019 May, 13:554,1-15, DOI

Odawara, A., Matsuda N., Ishibashi Y., Yokoi R., and Suzuki, I.* “Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system” Scientific Reports, 8(1), 10416(2018)DOI

Matsuda N, Odawara A, Katoh H, Okuyama N, Yokoi R, Suzuki, I.* Detection of synchronized burst firing in cultured human induced pluripotent stem cell-derived neurons using a 4-step method. Biochem Biophys Res Commun. 2018, 497, 612-618.DOI

Odawara, A., Katoh, H., Matsuda N., and Suzuki, I.* “Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture” Scientific Reports, 6, 26181(2016)DOI

Odawara, A., Katoh, H., Matsuda N., and Suzuki, I.* “Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons.” Biochem Biophys Res Commun. (2016)469(4):856-62. DOI

Odawara, A., Gotoh, M., and Suzuki, I.* “Long-term electrophysiological activity and pharmacological response in human induced pluripotent stem cell derived neuron and astrocyte co-culture” Biochem Biophys Res Commun. (2014)443(4):1176-81.DOI

Sensory neurons

X. Han, N. Matsuda, M. Yamanaka, I Suzuki*, Development of a Novel Microphysiological System for Peripheral Neurotoxicity Prediction Using Human iPSC-Derived Neurons with Morphological Deep Learning, Toxics, 12(11), 809, 2024 DOI

X. Han, N. Matsuda, Y. Ishibashi, M. Shibata, I Suzuki*, An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity, Pharmaceutics, 15(12), 2788, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

A Odawara, M Shibata, Y Ishibashi, N Nagafukum N matsuda, I Suzuki* In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array. Toxicological Sciences. 2022 188(1):131-141. DOI

We possess analytical techniques for low-frequency components in MEA measurements of astrocytes and brain organoids.

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Reference paper
Astrocyte

T. Kuroda, N. Matsuda, Y. Ishibashi, I Suzuki*,  Assessment of astrocytic electrophysiological responses to seizurogenic compounds using planner microelectrode array, Frontiers in Neuroscience. 16:1050150, 2022, DOI

Brain Organoids

R. Yokoi, N Nagafuku, Y. Ishibashi, N. Matsuda, I Suzuki*,  Contraindicated Drug Responses in Dravet Syndrome Brain Organoids Utilizing Micro Electrode Array Assessment Methods, Organoids 2(4) 177-191, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

Yokoi R, Shibata M, Odawara A, Ishibashi Y, Nagafuku N, Matsuda N, Suzuki I*. Analysis of signal components < 500 Hz in brain organoids coupled to microelectrode arrays: a reliable test- bed for preclinical seizure liability assessment of drugs and screening of antiepileptic drugs. Biochem and Biophys Res. 2021 28:101148. DOI

 

Multiple assays of impedance, extracellular potential, and cell morphology in the same sample are performed to analyze compound response from multiple aspects.

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Reference paper
Impedance

X. Han, N. Matsuda, Y. Ishibashi, M. Shibata, I Suzuki*, An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity, Pharmaceutics, 15(12), 2788, 2023 DOI