Multi-Electrode Array (MEA)
In addition to classical electrophysiological methodology, Creative Bioarray offers ex vivo test systems based on Microelectrode Array (MEA) recordings in order to analyze complex drug effects on ion channel interactions and cell signaling in cellular networks including stem-cell derived approaches, tissue slices and isolated organs.
A Multi-Electrode Array is an array made of microscopic metal electrodes (10-30 μm of diameter) distributed on a small surface area (~0.8-6 mm²). They are either regularly distributed or can be arranged to match closely the spatial organization of the tissue investigated. In neuroscience research, these small electrodes (coated with an inert and biocompatible metal) are used for recording electrical signals related to neuronal activities within the slice. MEA recordings allow mid-throughput testing capabilities for compound screening and profiling. The MEA technology enables parallel and multi-site extra-cellular recordings within a single brain slice and provides an exceptional macroscopic view of neuronal networks.
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Fig.1 High resolution phase contrast photomicrograph of DRG tissue seeded on a microelectrode array after a 2-day culture.
Microelectrode array (MEA) is one of the most sophisticated and efficacious technologies for measuring changes in spontaneously-active cells, such as cardiomyocytes and neurons. With our decades expertise in the production of MEA test, we are experts in the development and application of MEA-based drug screening approaches.
In cardiac safety analysis, our MEA tests can be applied for human-induced pluripotent stem cell-derived ventricular cardiomyocytes functional detection. The iPSC-derived cardiomyocytes are suitable for electrophysiology-based microelectrode array (MEA) assays that are relevant for predictive preclinical safety pharmacology, toxicology and efficacy testing. The combination of iPSC-derived Cardiomyocytes and our MEA system enables detailed electrophysiological detection of potential cardiotoxic/pro-arrhythmic effects of compounds (e.g. ion-channel blockers) in a non-invasive, label-free throughput up to 96 wells. MEA, as a high-throughput functional platform, can be applied to the detection of prolongation, alterations in beat rate, proarrhythmic events, and dysregulation of conduction by measuring the extracellular voltage of beating cardiomyocyte cultures.
Advantages
Your compounds can be evaluated in vitro under most physiologically relevant conditions. All receptors, channels, enzymes, are the native ones with all signaling and regulating pathways being functional.
In cardiac safety analysis
High quality results
Detect proarrhythmia signals as well as early after-depolarizations, tachycardia & bradycardia
Perform beat to beat variability analysis
Classify cells as atrial or ventricular phenotypes
Test cardiomyocytes against longer drug exposures without deteriorating
In neuroscience research: slices can be prepared from many different brain regions with all neurons and glial cells in place and connected to each other, as they are in vivo.
Increases the robustness of the data: record multiple evoked-responses in parallel at different electrodes within a single slice and within the same region of interest increases the reliability of the data and their subsequent statistical processing.
Provides an exceptional macroscopic view of neuronal networks: region-specific effects can be readily observed over the MEA electrode surface area. As an example, layer-specific activities can be resolved into stratified structures such as hippocampus or cortex slices.
Facilitates the screening of a series of compounds in parallel, with a remarkably quick turnaround (mid-throughput screening).
Constitutes a well-suited technique for functional series of compound testing as they are much faster than classical glass electrode recordings and as they can be standardized.
Creative Bioarray provides central phenotypic assay platforms including manual patch-clamp and multi-electrode array (MEA) techniques to establish compound target validation, target engagement and species selectivity. Alternatively, these methods can be used to electro-physiologically characterize cells with different etiology. Physiological activity is monitored from native tissue such as rodent cortical neurons or other cell types such as those derived from stem cells.
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Fig.2 Long super-burst activity in hippocampal cultures recorded by the microelectrode array at DIV35.
Readouts from MEA-based electrophysiology
Basal synaptic transmission
Ortho- and antidromically evoked field potentials
Input-output relationships
Short-term plasticity
Paired-pulse facilitation
Paired-pulse depression
Post-tetanic potentiation
Long-term plasticity
High-frequency long-term potentiation
Theta-burst long-term potentiation
EPSP-spike (E-S) potentiation
Chemical long-term potentiation
Low-frequency long-term depression
Chemical long-term depression
Spontaneous activity
Action potential discharges by single neurons in slices (e.g., Purkinje cells, neocortical neurons, dorsal raphe neurons, etc.)
Network oscillations (hippocampal CA3 area, medial prefrontal cortex, etc.）
References
Renna JM, et al. Dorsal root ganglia neurite outgrowth measured as a function of changes in microelectrode array resistance. PLoS One. 2017; 12: 1–9.
Gladkov A, et al. Theta rhythm-like bidirectional cycling dynamics of living neuronal networks in vitro. PLoS One. 2018; 13: 1–22.
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