What is multi-electrode array electrophysiology?
Multi-electrode array electrophysiology employs arrays of microscopic electrodes distributed over a small surface area at the bottom of a multi-well plate or a single well (chip) to investigate electrochemical changes in cells or neural networks. Electroactive cells, including neurons or cardiomyocytes, can be cultured over the electrodes, forming cohesive networks over time. The functional behavior of the network can be captured to identify changes in electrical activity, either spontaneous or induced (via electrical or pharmacological stimulation).
MEA electrophysiology is highly versatile and can be used for the real-time measurement of excitable cell activity across the drug development pipeline to:
- Assess pharmacological manipulation for drug or phenotypic screening
- Investigate multiple parameters of neuronal activity in wild-type and neurological disease cell models
- Investigate drug effects on cardiomyocyte function
- Determine potential for cardiotoxicity, as part of CiPA initiatives
- Screen compounds for seizure liability
How does a multi-electrode array work?
Tissues or cells cultured over a microelectrode array generate an extracellular field potential (voltage changes) that is subsequently recorded. If the tissues or cells lack spontaneous activity, electrical or pharmacological stimulation can be applied to induce voltage changes against which drug-induced changes can be measured. These changes are then processed into a single neuronal structure (waveform), decoding neural connectivity and firing frequency. For MEA using primary or iPSC-derived cells, our scientists utilize the Maestro Pro™ MEA assay system from Axion BioSystems.
Data processing and analysis are initially conducted using the software from instrument manufacturers and in-house developed scripts. In collaboration with Genedata, we have customized their Screener® automated assay analysis platform, resulting in a highly efficient analysis workflow that unlocks the vast potential of MEA data. It employs a non-biased principal component analysis (PCA) to identify metrics that are biologically relevant to each individual experiment.
MEA Electrophysiology in Drug Discovery
Multi-electrode array electrophysiology is a highly versatile technology that has applications in the drug discovery process, including screening of lead candidates, in vitro efficacy studies, disease model phenotyping, and exploratory toxicology, across different CNS diseases and multiple therapeutic modalities.
See how MEA electrophysiology can be used with primary cells and human iPSC-derived cells across different stages of drug discovery in our on-demand webinar.
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In vitro screening for anti-seizure activity
MEA electrophysiology can be used to determine anti-seizure activity of novel compounds being developed to treat epilepsy. Seizure-like activity is induced with compounds such as picrotoxin or 4-AP in a co-culture of iPSC-derived glutamatergic and GABAergic neurons and measured by MEA. The data below shows Raster plots generated by MEA of neuronal activity in this neuron co-culture. The effect of a positive control (cenobamate, a common anti-seizure medication) and test compound (Cmpd01) on induced seizure activity, measured by the inter-burst interval coefficient of variance (IBI CoV).
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Phenotypic profiling of ultra rare disease patient neurons
Ultra-rare diseases present a unique challenge for drug discovery due to the lack of preclinical models to determine therapeutic efficacy. Using patient-derived cells and physiological readouts can develop a phenotypic profile of disease against which novel therapies can be tested. In a recent N=1, Dup15q syndrome drug discovery project, our scientists used MEA to identify seizure-like activity in patient-derived glutamatergic and GABAergic neuron co-culture, compared to CRISPR-edited ‘corrected’ cells. Candidate therapeutic anti-sense oligonucleotides (ASOs) could then be screened for their potential to reverse this disease phenotype.
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Cardiotoxicity assessment in iPSC-derived cardiomyocytes
When used with human iPSC-derived cardiomyocytes, MEA can be used to investigate drug effects on cardiac function as part of a preliminary cardiotoxicity screen. Readouts of cardiomyocyte function that correlate to QT interval (field potential duration; FPD) and arrhythmia (local action potential duration) can be measured, with novel compounds compared to compounds known to affect cardiomyocyte function such as Quinidine (NaV1.5 channel blocker) and Verapamil (calcium channel blocker). The data below shows that Quinidine increases FPD and action potential duration (A and C), and Verapamil decreases beat period, FPD, and action potential duration (B and D).
Benefits of the Multi-Electrode Array
High-Throughput
Assays run in 48-well MEA plates
Versatile
Applications across lead optimization, phenotyping and toxicology
Multiplexing
Multiple readouts from the same experiment
Customizable
Readouts customized to your questions
Frequently Asked Questions (FAQs) About Multi-Electrode Array Electrophysiology
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What is the future of MEA in drug discovery?
Current advancements in drug discovery include the development and use of advanced in vitro models such as spheroids and organoids. The use of MEA in these types of models, particularly multi-cell brain organoids, would generate efficacy data in a model that is more physiologically relevant than single-cell culture.
However, there are technical challenges to be overcome as the structure of the commercially available multi-electrode arrays means that they cannot penetrate an organoid structure to detect and measure neuronal activity beyond the outer edge. Innovations are ongoing in this area, and our scientists are at the forefront of testing and applying these innovations in drug discovery.
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What is the difference between multi-electrode arrays and patch clamp electrophysiology?
MEA records the field potential electrical activity from the extracellular space of a population of neurons. Patch clamp electrophysiology records the action potential electrical activity from the intracellular space of a single neuron.