Label-free functional characterization of human brain organoids at single-cell resolution
Poster #220 @ ISSCR 2021
Three dimensional organ-like cell aggregates (organoids) that originate from human induced pluripotent stem cells (h-iPS Cs) are emerging as promising tools for investigating development and disease progression, as well as for drug discovery. Organoids from h-iPSC-derived neurons recapitulate the architectures and characteristic functions of different brain areas that can be used to model human disease in-vitro. In order to adopt brain organoids for rapid and cost-effective drug screenings, it is necessary to assess their cell type composition, gene expression patterns and physiological function.
The electrical activity of brain, retina or muscle organoids can now be easily captured, label free, at single-cell resolution by using high-density microelectrode array (HD-MEA) technology. The HD-MEA’s large sensor array, featuring 26,400 electrodes at high-resolution enables recording of neuronal activity across different scales, from the network level, single-cell level, down to the sub-cellular level.
Three different neuronal assays have been implemented and used to evaluate the spontaneous a ctivity of brain organoids. (A) The ActivityScan Assay allows detection and identification of all active areas in the organoid. Firing rate and amplitude of the action potentials can be extracted. (B) The Network Assay enables the analysis of network bursts and synchronicity, indicating formation of connectivity between neurons. (C) The AxonTracking assay identifies single neurons and provides metrics such as axonal conduction velocity.
In this work, we present results from organoids modeling different brain compartments and will demonstrate the potential of HD-MEA technology for characterizing the physiological function of human brain organoids and for testing compounds.
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|Dr. Szilárd Sajgó|
R&D Scientist, MaxWell Biosystems
Szilárd obtained his PhD in Biology from National Institutes of Health, National Eye Institute, Retinal Circuit and Genetics Unit, U.S.A., a graduate partnership program with Babeș-Bolyai University in Romania. After attaining Postdoctoral positions at the NIH, National Eye Institute, Retinal Circuit and Genetics Unit in U.S.A. and Aarhus University, Danish Research Institute of Transnational Neuroscience (DANDRITE), in Denmark, Szilárd Sajgó is, since 2019, a R&D Scientist at MaxWell Biosystems. With 10 years research experience in the field of ophthalmology, covering multiple aspects of retina analysis from developmental RNA-sequencing to behavior, physiology and human disease modelling, Szilárd is a highly collaborative, self-motivated, analytical, published scientist adept to independently manage projects and communicate scientific progress with accurate scientific reasoning.
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High-content, label-free functional imaging of human iPSC-derived neuronal cell lines by means of high-density microelectrode arrays
Poster #421 @ ISSCR 2021
Recent advances in the field of cellular reprogramming have opened a route to studying the fu ndamental mechanisms underlying common neurological disorders. High‐density microelectrode‐arrays (HD‐MEAs) provide unprecedented means for high-content electrical imaging of neurons at different scales, ranging from network through single‐neuron to subcellular features. In this work, HD‐MEAs are used in vitro to characterize and compare human induced‐pluripotent‐stem‐cell‐derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson’s disease and amyotrophic lateral sclerosis. Reproducible electrophysiological network, single‐cell and subcellular metrics are used for phenotype characterization and drug testing. Metrics, such as burst shape and axonal velocity, enable the distinction of healthy and diseased neurons. The HD‐MEA metrics can also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, it is shown that the ability to detect drug effects and the observed culture‐to‐culture varia bility critically depend on the number of available recording electrodes.
|Dr. Michele Fiscella|
VP Scientific Affairs, MaxWell Biosystems
Michele Fiscella is the Vice President, Scientific Affairs at MaxWell Biosystems and a member of the founding team. Michele is an expert in retina physiology, neuroscience and biotechnology with strong skills in electrophysiology techniques and statistics applied to biological data and analysis/modeling of neural signals. He discovered the physiological role of a gene involved in a human disease of vision, by MEA technology.
Michele obtained his Master in Molecular and Industrial Biotechnology from University of Bologna and his PhD degree from ETH Zurich.
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