Harrick Plasma → Applications → Life Sciences → Cell Culture →
Microelectrode arrays (MEAs) are widely used for extracellular recording of neural activity, requiring consistent and uniform cell adhesion across the electrode surface. However, MEA substrates such as glass and silicon are inherently hydrophobic, which limits cell attachment, spreading, and long-term culture stability.
Plasma cleaning is a key surface preparation step that addresses this limitation. Exposure to a low-pressure gas plasma oxidizes the MEA surface, introducing polar functional groups that increase surface energy and render the substrate hydrophilic. This process produces a clean surface that is immediately suitable for coating with extracellular matrix (ECM) proteins or adhesion molecules.
Importantly, the hydrophilic effect of plasma treatment is transient and typically diminishes within a few days. As a result, plasma cleaning should be performed shortly before cell seeding to ensure optimal surface conditions.
Role of Plasma Cleaning in MEA Preparation Workflows
A complete MEA preparation workflow typically includes detergent cleaning, rinsing, sterilization, and surface activation. Plasma cleaning serves as the final activation step prior to biological use.
A commonly used workflow includes:
- Detergent cleaning: Soaking MEAs in a 1% enzymatic detergent solution (e.g., Terg-A-Zyme) followed by thorough rinsing with distilled water
- Drying and sterilization: Air drying and, where appropriate, autoclaving (121 °C, 30 minutes)
- Contact cleaning: Wiping contact pads and amplifier pins with ethanol or isopropanol to reduce electrical noise
- Plasma activation: Treating the MEA surface immediately prior to coating or cell seeding
Plasma cleaning complements these steps by removing residual organic contaminants and ensuring a uniformly hydrophilic surface, which is critical for reproducible biological outcomes.
Plasma Cleaning Process and Parameters
Typical operating parameters for MEAs include:
- Pressure: 200-800mTorr
- Power: 30W
- Treatment time: 1–2 minutes
- Process Gas: Ambient air or Oxygen
These conditions reliably produce a clean, residue-free, and wettable surface. Because plasma treatment is a dry process, it leaves no chemical residues that could interfere with downstream electrophysiological recordings.
Applications in Neural Culture Models
Plasma activation has been validated across a wide range of MEA-based neural culture systems:
- iPSC-Derived Neural Networks: Engineered human neuron circuits on multi-channel MEAs are often plasma-cleaned prior to polylysine coating. Similar approaches are used in 3D “brain-on-chip” platforms, where devices are plasma-treated before seeding neurons and astrocytes.
- Retinothalamic Co-cultures: Glass MEAs are commonly cleaned with detergents and alcohol, dried, and then plasma-treated (~2 minutes at moderate power) to ensure uniform coating with adhesion molecules such as poly-D-lysine and laminin.
- Hippocampal Organotypic Cultures: For long-term slice cultures, brief plasma treatment is used prior to coating, creating a hydrophilic substrate that supports stable tissue attachment.
- 3D and Brain-on-Chip Systems: Platforms integrating hydrogels and microfluidics frequently use plasma pretreatment to enable PDMS bonding and uniform cell seeding.
These examples demonstrate that plasma cleaning is broadly compatible with MEA workflows across a wide range of neural culture models.
Microelectrode Array Articles
Amos, G., Ihle, S. J., Clément, B. F., Duru, J., Girardin, S., Maurer, B., Delipinar, T., Vörös, J., & Ruff, T. (2024). Engineering an in vitro retinothalamic nerve model. Frontiers in Neuroscience, 18. https://doi.org/10.3389/fnins.2024.1396966
Baltz, T., & Voigt, T. (2015). Interaction of electrically evoked activity with intrinsic dynamics of cultured cortical networks. Frontiers in Cellular Neuroscience, 9. https://doi.org/10.3389/fncel.2015.00272
Bogguri, C., George, V. K., Amiri, B., Ladd, A., Hum, N. R., Sebastian, A., Enright, H. A., Valdez, C. A., Mundhenk, T. N., Cadena, J., & Lam, D. (2024). Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent. Frontiers in Cellular Neuroscience, 18. https://doi.org/10.3389/fncel.2024.1378579
Corna, A., Ramesh, P., Jetter, F., Lee, M., Macke, J. H., & Zeck, G. (2021). Discrimination of simple objects decoded from retinal ganglion cells upon sinusoidal electrical stimulation. Journal of Neural Engineering, 18(4), 046086. https://doi.org/10.1088/1741-2552/ac0679
Dollt, M., Reh, M., Metzger, M., Heusel, G., Kriebel, M., Bucher, V., & Zeck, G. (2020). Low-Temperature atomic layer deposited oxide on titanium nitride electrodes enables culture and physiological recording of electrogenic cells. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.552876
Jones, P. D., Molina-Martínez, B., Niedworok, A., & Cesare, P. (2024). A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture. Lab on a Chip, 24(6), 1750–1761. https://doi.org/10.1039/d3lc00963g
Girardin, S., Clément, B., Ihle, S. J., Weaver, S., Petr, J. B., Mateus, J. C., Duru, J., Krubner, M., Forró, C., Ruff, T., Fruh, I., Müller, M., & Vörös, J. (2022). Topologically controlled circuits of human iPSC-derived neurons for electrophysiology recordings. Lab on a Chip, 22(7), 1386–1403. https://doi.org/10.1039/d1lc01110c
Girardin, S., Ihle, S. J., Menghini, A., Krubner, M., Tognola, L., Duru, J., Fruh, I., Müller, M., Ruff, T., & Vörös, J. (2023). Engineering circuits of human iPSC-derived neurons and rat primary glia. Frontiers in Neuroscience, 17. https://doi.org/10.3389/fnins.2023.1103437
Lam, D., Enright, H. A., Cadena, J., George, V. K., Soscia, D. A., Tooker, M., Peters, S. K. G., Karande, P., Ladd, A., Bogguri, C., Wheeler, E. K., & Fischer, N. O. (2023). Spatiotemporal analysis of 3D human iPSC-derived neural networks using a 3D multi-electrode array. Frontiers in Cellular Neuroscience, 17. https://doi.org/10.3389/fncel.2023.1287089