The evaluation of electrically-active cells has historically been tedious, requiring months of training to painstakingly study single cells in low throughputs. By culturing a network of cells over the high electrode count arrays available in each well of our MEA plates, Axion BioSystems’ MEA systems capture activity across an entire population of cells—with far greater data points per well—detecting activity patterns that would otherwise elude traditional assays.
Axion’s contribution to establishing microelectrode array (MEA) technology as an accessible, versatile research tool cannot be defined by a single advantage. It’s the cumulative effect of our commitment to growing our MEA platform to include instruments, accessories and software working in unison.
Our microelectrode array (MEA) is a grid of tightly spaced electrodes in a planar array at the bottom of a cell culture plate. Electrically active cells, such as neurons or cardiomyocytes, can be cultured over the electrodes. Over time, as the cultures become established, they form cohesive networks and present an electrophysiological profile. The resulting electrical activity—spontaneous or induced firing of neurons, or the uniform beat of cardiomyocytes—is captured from each electrode on a microsecond timescale providing both temporally and spatially precise data.
In contrast to traditional electrophysiology approaches such as patch clamp, the electrical activity measured on each MEA electrode is the total extracellular change in ions, reported as changes in voltage. “Extracellular field potential” provides access to electrophysiological data without disrupting the cellular membrane (non-invasive) or requiring dyes (label-free). Thus MEA recordings can be taken over time on the same culture (hours-long continual data collection or repeated reads of the same plate over days, hours, or months), an advantage traditional techniques cannot provide.
Additionally, each electrode on the microelectrode array is capable of recording or stimulating the overlying cell culture allowing you to monitor and control cellular network behavior in each well. With these capabilities you can fully explore complex biological networks, learning how a cell’s circuitry functions together further advancing applications such as disease modeling, stem cell development, drug discovery and safety/toxicity testing.
- Functionality – Neurons within the population produce spontaneous action potentials. The mean firing rate (MFR) counts action potentials over time to quantify functionality.
- Excitability – Neurons may fire multiple action potentials within a short time period, called a burst. Established algorithms detect and quantify burst behavior.
- Connectivity – Synaptic connections between neurons in a population may lead to coincident action potentials. Network burst and synchrony measurements quantify connectivity.
Neural action potentials are detected as changes in voltage above a user-defined threshold. A simple view of this activity is a raster plot where each detected action potential is represented by a “tick” mark to denote the spike time.
The timing of the spikes contains all of the information required to calculate measures like mean firing rate (activity over time) or bursting (clusters of action potential activity).
When analyzing cellular networks, mixed cell populations or variable activity may make complete characterization of the population difficult. Electrical stimulation using electrodes in the MEA well is one possible way to control cellular and network behavior. However, electrical stimulation is not targeted to specific cell types and can produce data artifacts.
Optogenetic stimulation is a light-based technique providing artifact-free, selective control over cultured cell networks. A simple viral transduction process introduces light-sensitive, membrane ion channels called opsins into specific cell types through genetic targeting. The opsin family contains a diverse group of ion channels that allow passage of charged ions through the membrane when stimulated at specific wavelengths. For example, Channelrhodopsin-2 (ChR2) is a non-specific cation channel that depolarizes electrically active cells causing action potentials to fire when irradiated with blue light. Other opsins, such as archaerhodopsin (Arch) or halorhodopsin (NpHR) are anion channels that respond to green or orange light, respectively, with membrane hyperpolarization, suppressing cell activity.
When used in conjunction with an MEA assay, opsins can be easily introduced into cultured cells on the MEA plate. A viral vector, prepackaged to contain the desired opsin (e.g. ChR2), the desired promoter (which targets the opsin to a selected cell type, e.g. a universal CAG promoter), and a fluorescent tag (to later visualize which cells are expressing the opsins, e.g. GFP) is added to cells in culture. Within a few days, cells express the opsin and are ready for experimentation. The MEA plate is placed in the Maestro where it records cellular activity from the bottom of the plate, while Lumos provides simultaneous optical stimulation and advanced cellular control from the top.
Axion BioSystems has revolutionized in vitro optogenetics with Lumos by providing optical stimulation with the highest commercially available throughput and flexibility. The 48-well format, together with four individually-controlled LEDs spanning the spectrum of the most commonly used opsins, provides complete assay customization. Each of the 192 LEDs have been tuned for optimal power providing a range of intensity for full illumination and activation per well. Complete integration into AxIS provides a user-friendly interface to generate flexible stimulation profiles.
Take control of specific neurons in a mixed population or unify beat rate of cardiomyocytes across the plate for accurate and predictive cardiac safety assays. Axion innovation makes it all possible with a single integrated platform.
Until Axion BioSystems created the first multi-well platform, adoption of MEA technology was limited by single-well MEA analysis. Because of the biological variability in independent cell cultures, many single well plates were required to fully examine a single cell type or test a drug’s therapeutic potential. So, adoption of MEA technology on any large-scale was not feasible. To overcome this obstacle, Axion BioSystems introduced the Maestro multi-well MEA system to enable more practical MEA experimentation, fully realizing the potential of MEA technology. By giving you the ability to choose from 12, 48 or 96 well plates, each containing the industry’s largest number of electrodes, you can perform detailed cellular analysis at the throughput you need, when you need it, generating a flexible, reliable assay format.
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