A Novel Approach
Neurons communicate within a network via action potentials (APs) propagating along axons. The capability to access axonal physiology is crucial for studying information processing among neurons in healthy and diseased states. However, axonal signals are difficult to measure at a large-scale. Therefore, the combination of reliability, ease of use, throughput, long-term and non-invasive measurement are necessary to monitor and understand neuronal function at a scale that was previously not possible.
High-density microelectrode array (HD-MEA) measurements at unprecedented resolution and high signal quality, using MaxOne and MaxTwo systems, allow to detect the AP propagation from the initiation site down to distal axonal branches. With the AxonTracking Assay, the identification of the axonal paths is fully automated at the micrometer scale. This live-cell recording and analysis provides novel functional and structural readouts applicable for phenotypic characterization, disease modeling, and drug screening studies.
|The fully automated platform is easy to use and
allows for simultaneous recordings of multiple
neurons and axonal branches in multiple wells.
|Characterize neuronal maturation, development
or treatment effects by recording from your
culture over multiple days and weeks.
|The electrical recordings are noninvasive and
label-free, which avoids introducing side effects
from dyes etc.
HD-MEA Technology for Recording Axonal Signals
Powered by MaxOne and MaxTwo
|High Spatio-Temporal Resolution
Reconstruct axonal paths by tracking Action Potential propagation at
thousands of sites, thanks to the densely packed microelectrode array.
|Large Sensor Area
Detect long axonal branches of multiple neurons at the same time with
a large sensor area, applicable for 2D and 3D samples.
|High Signal Quality
Catch the smallest signals propagating along axons, down to single
micro-volts-range, with low-noise recording channels
Record the active neurons
identified with the ActivityScan
Reveal the axonal morphologies
through a series of processing steps:
◉ Spike sorting
◉ Spike-triggered averaging
◉ Footprint extraction
Identify individual axonal branches
and reconstruct the morphology of the
neurite outgrowth using an unsuper- vised object-tracking algorithm.
1 – Neuron Conduction Velocity
2 – Total Detected Axon Length
3 – Longest Branch Length
4 – Longest Latency
5 – Longest Distance from Initiation Site
6 – Amplitude at Initiation Site
AxonTracking Assay in Human Neurons
Propagating APs along axonal processes recorded from different human induced pluripotent stem cells-derived (iPSC-derived) neuronal cell lines.
1 – Human Glutamatergic Neurons
2 – Human Dopaminergic Neurons
3 – Human Motor Neurons
AxonTracking Assay in Long-Term Neuronal Cultures
Neurons and propagating APs can be resolved even in cultures with long and dense axonal processes (iPSC derived glutamatergic neurons, DIV 63)
1 – Activity map
2 – AxonTracking Assay
3 – Propagating AP of individual neurons resolved
AP Propagation Along Axons
Propagating APs along the axonal processes of a rat primary cortical neuron shown in a time-series:
Bakkum, D. J., Frey, U., Radivojevic, M., Russell, T. L., Müller, J., Fiscella, M., Takahashi, H., & Hierlemann, A. “Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites.” Nat Commun. 4, 2181 (2013).
Bullmann, T., Radivojevic, M., Huber, S. T., Deligkaris, K., Hierlemann, A., & Frey, U. “Large Scale Mapping of Axonal Arbors Using High-Density Microelectrode Arrays.” Front. Cellular Neurosci. 13, 404 (2019).
AxonTracking Assay Brochure
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