MaxWell Biosystems’
High-Density
Microelectrode Array Technology

Why microelectrode arrays?

Also known as multi-electrode arrays

Neurons communicate with each other by generating action potentials, brief electrical impulses that travel across the nervous system and throughout the body. Understanding the nature of these electrical signals through electrophysiology is key to unraveling brain function, studying disease conditions, and accelerating the development of life-changing treatments.

Patch clamp is a gold-standard electrophysiological technique commonly performed in-vitro. By guiding a glass micropipette to form a tight seal with a neuron, patch clamp provides detailed electrical measurements directly from inside the cell (intracellular). While powerful and can be done label-free, it is limited to one cell at a time. In contrast, optical methods such as calcium or voltage imaging with fluorescent indicators capture activity from many neurons simultaneously, but only offer an indirect view of the underlying electrical events.

Microelectrode arrays (MEAs) or multi-electrode arrays combine the strengths of both approaches. They enable non-invasive, label-free recording of neuronal activity. This approach captures rich extracellular data from many neurons at once, delivering direct, high-throughput functional insights from every sample.

Evolution of MEA technology:
MaxWell Biosystems’ innovation story

The growing demand to understand neuronal functional activity at scale has driven continuous innovation in MEA technology. A widely cited review by Obien et al. (2015) provides a comprehensive overview of MEA technologies and applications. When selecting an MEA for a given application and biological sample, four important factors must be considered: Sensing Area, Electrode Density, Noise Performance, and Channel Number.

Sensing area

Electrode density

Noise performance

MaxWell Biosystems' HD-MEAs: powered by switch-matrix technology

Sensing area

The Sensing Area defines the physical region where electrodes capture electrical signals. Traditional MEAs typically have a limited sensing area, often restricting access to the full sample. On the other hand, Complementary Metal Oxide Semiconductor (CMOS)-based MEAs feature a much larger sensing area densely packed with electrodes. This enables functional characterization of many more cells simultaneously, unlocking deeper insights into network activity and spatial dynamics. MaxWell Biosystems has defined a sensing area of 2 × 4 mm², providing ample coverage for different types of biological samples while maintaining high spatial resolution and electrode density.

Electrode density

Unlike traditional MEAs, which feature relatively large electrodes spaced far apart, CMOS-based MEAs use thousands of smaller electrodes packed closely together. This dense configuration has made CMOS MEA synonymous with High-Density MEAs (HD-MEAs), significantly increasing spatial resolution and data richness.

Traditional MEAs often detect only a small subset of the neuronal population, providing an averaged view of electrical activity across multiple cells. In contrast, CMOS HD-MEAs, particularly MaxWell Biosystems HD-MEAs, capture electrical signals with unprecedented precision.

Each well contains 26,400 electrodes at a density of 3,265 electrodes per square millimeter, with an electrode pitch of just 17.5 micrometers (electrode center-to-center distance). This ensures that every plated cell is recorded by at least one optimally positioned electrode. Beyond capturing population-wide network activity, MaxWell Biosystems HD-MEAs resolve the activity of individual cells at single-cell and even subcellular resolution. This enables advanced analyses such as tracking of axonal activity propagation and novel readouts such as axonal branch length and conduction velocity, revealing new dimensions of neuronal function.

Noise performance

With the unparalleled Electrode Density and large Sensing Area, MaxWell Biosystems HD-MEAs clearly stand apart from traditional MEAs. Beyond these advantages, the most critical differentiator between MaxWell Biosystems HD-MEAs and other CMOS HD-MEAs is Noise Performance.

To achieve high electrode density, CMOS MEAs must reduce amplifier size. This design constraint often leads to an increase in noise levels, especially in systems that use Active Pixel Sensory (APS) technology. In APS-based designs, the amplifier sits directly beneath each electrode, limiting the space available for optimized amplifier circuitry. As a result, these APS HD-MEAs typically exhibit higher noise and, thus, lower signal-to-noise ratio, which in turn hampers the ability to reliably detect action potentials, leading to missed signals and reduced data quality.

MaxWell Biosystems overcomes this challenge by employing Switch-Matrix (SM) technology (Frey et al., 2010). In this architecture, the electrodes and amplifiers are physically separated, enabling a more powerful amplifier design that minimizes noise. This leads to a significantly improved signal-to-noise ratio and ensures even the smallest neuronal signals can be captured with confidence. With the SM approach, the amplifiers are placed outside the electrode array, allowing for a more compact electrode design and higher electrode density across the array. This design makes it possible to include far more electrodes than available readout channels, enabling high-resolution recordings while maintaining system flexibility and efficiency.

In addition, this physical separation between electrodes and amplification circuitry has another key advantage: reduced artifacts due to light changes. By physically restricting visible light stimulation to the electrode area while avoiding the nearby amplifier circuits, light artifacts can be minimized (Fiscella et al., 2012). This feature is especially valuable for applications involving optical stimulation, such as retina research and optogenetics in systems neuroscience.

MaxWell Biosystems' HD-MEAs: powered by switch-matrix technology

The Switch-Matrix (SM) approach intelligently routes any selected set of electrodes to readout circuits via programmable switches. This enables flexible electrode selection tailored to each sample, enhances signal acquisition at regions of interest, and supports scalable, high-content experimental designs.

In MaxWell Biosystems HD-MEAs (MxW HD-MEAs), any of the 26,400 electrodes can be routed to up to 1,020 readout channels. This flexibility ensures optimal electrode placement to capture neuronal activity where it is most relevant. It also unlocks advanced functional readouts, such as detailed mapping of axonal branches and precise measurement of conduction velocities based on signal propagation.

Up to 32 stimulation buffers on each MxW HD-MEA can be flexibly assigned to any of the 26,400 electrodes, enabling spatially precise electrical stimulation, even at subcellular resolution, while simultaneously recording activity from both nearby and distant neurons. This unmatched flexibility in selecting electrodes for recording and stimulation, combined with exceptional spatiotemporal resolution and electrode coverage, positions MxW HD-MEAs as a transformative platform for neurocomputing. Moreover, the ability to program MaxWell Biosystems’ HD-MEA through a powerful Application Programming Interface (API) empowers users to develop custom systems with the HD-MEA at the core. This level of control and integration supports the creation of next-generation, brain-inspired technologies and advances the pursuit of a true Brain Processing Unit.

At the core of this capability is MaxWell Biosystems’ Switch-Matrix (SM) technology, a Swiss-engineered architecture that dynamically routes signals across thousands of electrodes. This design achieves an optimal balance of pixel area, power efficiency, and low noise, enabling ultra-high electrode density without compromising signal fidelity.

High electrode density ensures single-cell resolution, allowing researchers to precisely capture the most relevant signals at the finest scale. Low noise levels unlock the detection of even the smallest action potentials, which is essential for extracting deep insights and reaching confident conclusions.

For teams in the pharmaceutical and biotechnology sectors, MaxWell Biosystems HD-MEAs empower you to focus on what matters: identifying the most promising signals, capturing a large representative part of the network reducing variability and eliminating noise, driving faster and more confident decision-making in drug discovery and safety testing. For academic researchers, the system offers unprecedented access to the true dynamics of your samples and modulate neuronal activity by stimulation, allowing you to adapt in real time and make new discoveries by uncovering signals that were previously out of reach.

Every cell has a story to tell. With MaxWell Biosystems’ unique HD-MEA, you are empowered to listen to those stories, transforming complex neuronal signals into actionable results, driven by precision and reliability of Swiss innovation.

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