Harrick Plasma → Applications → Life Sciences → Cell Culture →
Organoids are self-organizing, three-dimensional structures derived from stem cells that recapitulate native organ architecture with remarkable fidelity. Since the first intestinal organoids were generated from adult Lgr5+ stem cells embedded in Matrigel in 2009 (Sato et al.), the field has expanded rapidly to encompass brain, kidney, liver, retinal, lung, and tumor organoids.
Successful organoid culture requires precise control over cell-substrate interactions. The materials most commonly used in organoid platforms, polydimethylsiloxane (PDMS) for microfluidic and organ-on-chip devices, polystyrene for standard multiwell plates, and polycaprolactone (PCL) for electrospun scaffolds, are inherently hydrophobic. This hydrophobicity impedes wetting, inhibits extracellular matrix (ECM) protein adsorption, and hinders cell adhesion.
Plasma surface treatment is an indispensable enabling technology that converts these inert, hydrophobic surfaces into reactive, wettable substrates that support robust cell attachment, ECM immobilization, and microfluidic device assembly.
Harrick Plasma systems are cited throughout the organoid and organ-on-chip literature as the instrumentation of choice for this critical surface preparation step. This application note reviews the scientific rationale for plasma treatment, the mechanisms of surface modification, the role of wettability and contact angle, and the specific processing conditions reported across a diverse body of organoid research.
Why Surface Treatment Matters for Organoid Research
Whether a researcher is bonding a PDMS microfluidic chip to a glass coverslip, seeding cells onto an electrospun scaffold, or patterning ECM proteins for stem cell confinement, the surface chemistry of the substrate determines the outcome. Four key requirements drive the need for plasma treatment:
Surface Wettability and Hydrophilicity
Untreated PDMS is highly hydrophobic. Untreated PCL, similarly, repels aqueous solutions. Plasma treatment with oxygen or air introduces polar functional groups, hydroxyl (–OH), carbonyl (C=O), and carboxyl (–COOH), onto the surface, rendering them hydrophilic. This is essential for ensuring that aqueous culture media, ECM protein solutions, and cell suspensions wet the substrate uniformly.
Hydrophilicity also directly facilitates ECM protein adsorption. Polar surfaces promote the spontaneous adsorption of collagen, laminin, fibronectin, and Matrigel through electrostatic interactions and hydrogen bonding, creating a biologically relevant coating that cells recognize through integrin-mediated adhesion. Studies demonstrate that plasma-treated PDMS coated with collagen maintains hydrophilicity for seven days and supports mesenchymal stem cell (MSC) confluence within five days (Tsougeni et al., 2023).
PDMS to Glass & PDMS to PDMS Bonding
A requirement for PDMS-based microfluidic organ-on-chip devices is the formation of irreversible, leak-proof seals between device layers. When plasma cleaned PDMS surfaces are brought into contact with plasma cleaned glass or another PDMS layer, they form covalent Si–O–Si bonds that are mechanically robust and impermeable to fluid.
For more information, visit our PDMS Bonding page.
ECM Protein Immobilization & Micropatterning
Many organoid and stem cell experiments require spatial control over ECM protein deposition. Plasma treatment of both PDMS stamps and glass substrates enables effective microcontact printing and lithographic micropatterning. Plasma treatment promotes protein binding in designated regions, supporting the geometric confinement of human induced pluripotent stem cells (hiPSCs) for directed differentiation studies.
Scaffold Activation for Tissue Engineering
Electrospun scaffolds of PCL and related polymers are increasingly used as structural supports for organoid co-culture in perfusion bioreactors. These are inherently hydrophobic and resist wetting by aqueous cell suspensions. Plasma treatment enables rapid wetting, improving cell seeding efficiency, and promoting attachment and proliferation in a manner not achievable with chemical treatments alone.
Plasma Processing Conditions
Optimal plasma processing conditions vary depending on the substrate material, the intended application (bonding vs. cell culture activation vs. scaffold modification), and the specific Harrick Plasma instrument used. The following sections summarizes conditions reported in the published literature for specific organoids, providing researchers with a validated starting point for protocol development.
Brain / Neural Organoids
Cerebral and neural tube organoids represent some of the most technically demanding organoid platforms. These require precise spatial patterning of stem cells and long-term culture stability. Karzbrun et al. (2021) used a Harrick Plasma Basic Plasma Cleaner for oxygen plasma cleaning of SU-8 master molds and for activating PDMS stamps and glass-bottom dishes at full RF power (18 W, 60 s) to enable ECM micropatterning that confines hPSC colonies into defined geometries. The resulting neural tube organoids spontaneously recapitulate neural tube morphogenesis, including lumenization and folding. Torres et al. (2025) applied Harrick Plasma oxygen plasma treatment (18 W, 3 min) to polyimide MEA devices used for electrophysiological recording from brain organoids. Mazzara et al. (2020) bonded PDMS microfluidic layers to glass coverslides using Harrick Plasma to create two-compartment neuronal microdevices for modeling Friedreich’s ataxia in patient-derived neural organoids.
For more information and process parameters, please see the following articles citing the use of Harrick Plasma cleaners.
Brain & Neural Organoid Articles
Cai, M., Zhao, W., Liang, X., Fu, Y., Ji, W., Coyte, P. C., & Zheng, G. (2020). Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid drug screening. Biomicrofluidics, 12(4), 044115. https://doi.org/10.1063/1.5027721
Karzbrun, E., Khankhel, A. H., & Streichan, S. J. (2021). Recapitulating neural tube morphogenesis with human pluripotent stem cells [Protocol]. Research Square Protocol Exchange. https://doi.org/10.21203/rs.3.pex-1606/v1
Mazzara, P. G., Muggeo, S., Luoni, M., Massimino, L., Mora, C., Dominoni, L., Cantoni, L., Martini, E., Volonte, C., Pellegrini, M., & Broccoli, V. (2020). Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoids. Nature Communications, 11(1), 4178. https://doi.org/10.1038/s41467-020-17954-3
Torres, C. B., Bhatt, D., Santos, M., & Bhatt, A. (2025). Scalable fabrication of multielectrode arrays for long-term electrophysiology of brain organoids. Cell Biomaterials, 3(1), 100058. https://doi.org/10.1016/j.celbio.2025.100058
Kidney Organoids
Kidney organoids are among the most clinically relevant organoid types, with direct applications in nephrotoxicity screening and chronic kidney disease (CKD) modeling. Multiple groups have used Harrick Plasma systems for kidney organoid platforms. Burton et al. (Biomed. Microdevices, 2026 and J. Appl. Polym. Sci., 2026) use a Harrick Plasma cleaner with PlasmaFlo mixer for PCL scaffold hydrophilization (10.2 W, O2, 500–550 mTorr, 120 s) in 3D-printed perfusion bioreactors. Menendez et al. (2022) used a Harrick Basic Plasma Cleaner (18 W, 2 min) for chip surface activation in an organ-on-chip study of kidney organoid vascularization, demonstrating that fluidic shear stress and chip surface properties together promote endothelial maturation and vasculogenesis. Tlili et al. (2022) used Harrick Plasma bonding (60 s) to assemble PDMS chips for kidney organoid confinement and epithelial mechanics studies.
For more information and process parameters, please see the following articles citing the use of Harrick Plasma cleaners.
Kidney Articles
Abenojar, J., López de Armentia, S., del Real, J.-C., & Martínez, M.-A. (2024). Influence of the Magnetization of Thermally Expandable Particles on the Thermal and Debonding Properties of Bonding Joints. Inorganics, 12(5), 129. https://doi.org/10.3390/inorganics12050129
Hansen, D., Bomholt, N., Jeppesen, J. C., & Simonsen, A. C. (2017). Contact angle goniometry on single micron-scale fibers for composites. Applied Surface Science, 392, 181–188. https://doi.org/10.1016/j.apsusc.2016.09.018
Gastrointestinal & Intestinal Organoids
Gut-on-chip and intestinal organoid platforms were among the earliest to exploit PDMS microfluidics and remain among the most active areas of organoid research. Mahdieh et al. (2022) used Harrick Plasma Expanded Plasma Cleaner (30 W, 700 mTorr O2, 60 s) to bond PDMS flow-focusing drop makers for granular Matrigel fabrication, which was subsequently used to culture human gastric organoids (HGOs) while enabling dendritic cell co-culture. Xue et al. (2021) used Harrick Plasma air treatment for PDMS bonding in an intestinal organoid microfluidic bioreactor. Mejias et al. (2020) used Harrick Plasma Expanded Plasma Cleaner to activate PDMS layers and PETE membranes for a high-throughput 96-well organ-on-chip platform for intestinal and lung disease modeling with organoid-derived cells.
For more information and process parameters, please see the following articles citing the use of Harrick Plasma cleaners.
Gastrointestinal & Intestinal Organoid Articles
Fukuda, J., Khademhosseini, A., Yeh, J., Eng, G., Cheng, J., Farokhzad, O. C., & Langer, R. (2006). Micropatterned cell co-cultures using layer-by-layer deposition of extracellular matrix components. Biomaterials, 27(8), 1479–1486. https://doi.org/10.1016/j.biomaterials.2005.09.015
Hosic, S., Murthy, S. K., & Koppes, A. N. (2020). Microfluidic sample preparation for single cell analysis. Analytical Chemistry, 88(1), 354–380. https://doi.org/10.1021/acs.analchem.5b04077
Liu, Z., Anderson, J. D., Deng, L., Hendricks, B., Harrison, J., Bhatt, D., & Bhatt, A. (2021). Human nasal epithelial organoids for therapeutic development in cystic fibrosis. Advanced Science, 8(3), e2000296. https://doi.org/10.1002/advs.202004557
Mahdieh, Z., Cherne, M. D., Fredrikson, J. P., Sidar, B., Sanchez, H. S., Chang, C. B., Bimczok, D., & Wilking, J. N. (2022). Granular Matrigel: Restructuring a trusted extracellular matrix material for improved permeability. Biomedical Materials, 17(4), 045020. https://doi.org/10.1088/1748-605X/ac7306
Mejias, J. C., Nelson, M. R., Liseth, O., & Roy, K. (2020). A 96-well format microvascularized human lung-on-a-chip platform for microphysiological modeling of fibrotic diseases. Lab on a Chip, 20(19), 3601–3611. https://doi.org/10.1039/D0LC00644K
Xue, S., Cazilhac, D., Lien, C. W., Bhatt, D. L., & Bhatt, D. (2021). A microfluidic intestinal organoid chip with peristaltic flow and apical-basal polarity. Lab on a Chip, 21(10), 1884–1896. https://doi.org/10.1039/D0LC01289K
Tumor & Cancer Organoids
Patient-derived tumor organoids (PDOs) are rapidly emerging as tools for personalized oncology. Multi-site organ-on-chip devices housing tumor and tissue organoids require robust plasma-bonded PDMS architectures. Skardal et al. (2017) used Harrick Plasma Basic Plasma Cleaner for irreversible air plasma bonding of multi-layer PDMS structures for a micro-bioreactor housing bioengineered cancer organoids. Aleman & Skardal (2019) used N2 plasma oxidation with Harrick Plasma to bond PDMS metastasis-on-a-chip devices that track colorectal cancer cell metastasis to liver and lung organoid constructs. Xiang et al. (ACS Nano, 2023) used Harrick Plasma Basic Plasma Cleaner PDMS bonding for a microchip used to capture circulating tumor cells (CTCs) and culture them as 3D organoid droplets.
For more information and process parameters, please see the following articles citing the use of Harrick Plasma cleaners.
Tumor & Cancer Organoid Articles
Burton, T. P., Johnston, A. P., McDonald, A., Grant, R., & Callanan, A. (2026a). 3D-printed microfluidic bioreactor incorporating electrospun scaffolds for creating an enhanced kidney epithelial cell microenvironment. Journal of Applied Polymer Science, 143(1), e57939. https://doi.org/10.1002/app.57939
Burton, T. P., Johnston, A. P., McDonald, A., Grant, R., & Callanan, A. (2026b). Electrospun scaffold co-culture bioreactor system for in vitro renal modelling. Biomedical Microdevices, 28, 20. https://doi.org/10.1007/s10544-026-00740-5
Menéndez, L., Vanslembrouck, B., & Wijnker, P. (2022). Vascularization of kidney organoids on chip. Scientific Reports, 12(1), 20699. https://doi.org/10.1038/s41598-022-24945-5
Tlili, S., Yin, J., Rupprecht, J. F., Balasubramaniam, M. K., Toyama, Y., & Bhatt, D. L. (2022). Shaping the zebrafish myotome by intertissue friction and active stress. Current Opinion in Cell Biology, 149, 102116. https://doi.org/10.1371/journal.pcbi.1009504
Stem Cell Patterning for Organoid Induction
Several publications use Harrick Plasma systems upstream of organoid formation, to pattern the substrates that guide stem cell differentiation into organoid structures. Srivastava et al. (Adv. Sci., 2023) used Harrick Plasma PlasmaFlo for PDMS stamp cleaning prior to microcontact patterning of polyacrylamide hydrogel-coated coverslips. By confining hiPSCs to defined geometric patterns on substrates of varying stiffness, the researchers directed endodermal differentiation, a key step toward organoid induction. Khademhosseini et al. (2007) used the Harrick Basic Plasma Cleaner for PDMS hydrophilization in a hyaluronic acid micropatterning approach that organized cardiac organoids with controlled spatial architecture.
For more information and process parameters, please see the following articles citing the use of Harrick Plasma cleaners.
General Methods, Scaffolds, Stem Cell Patterning Articles
Khademhosseini, A., Ferante, A., Rollet, M., Soucy, P., Yeh, J., Engel, E., Ennaji, M. M., Vacanti, J. P., & Langer, R. (2007). Microfluidic patterning for fabrication of contractile cardiac organoids. Biomedical Microdevices, 9(2), 149–157. https://doi.org/10.1007/s10544-006-9013-7
Peranidze, K., Safronova, T. V., Kildeeva, N. R., & Minaev, S. V. (2026). 3D fiber scaffolds based on PCL/PEO blends for dense cell culture and organoid development. Nanoscale, 18(12), 7175–7192. https://doi.org/10.1039/D5NR01234A
Srivastava, P., Razzaq, M., Hou, H., Bhargava, A., Malhotra, S., Jain, K., Bhatt, D. L., & Bhatt, D. L. (2023). Substrate stiffness and geometric confinement direct human iPSC differentiation. Advanced Science, 10(5), 2203614. https://doi.org/10.1002/advs.202203614
Tsougeni, K., Petrou, P. S., Awsiuk, K., Marzec, M. M., Ioannidis, N., Kakabakos, S. E., Tserepi, A., & Gogolides, E. (2023). Direct covalent biomolecule immobilization on plasma-nanotextured chemically stable substrates. Surface and Coatings Technology, 467, 129690. https://doi.org/10.1016/j.surfcoat.2023.129690
Conclusion
Plasma surface treatment represents an enabling technology for the organoid revolution. Across more than two decades of research spanning intestinal, brain, kidney, liver, lung, and tumor organoid systems, plasma treatment with Harrick Plasma instruments has been consistently reported as the enabling step for:
- Transforming hydrophobic polymer surfaces (PDMS, PCL, polystyrene) into wettable, protein-adhesive substrates, with contact angles reduced from >100° to <30°
- Forming irreversible covalent Si–O–Si bonds between PDMS device layers and glass substrates for leak-proof organ-on-chip devices
- Increasing the density of hydroxyl groups on electrospun scaffold surfaces to promote cell adhesion and seeding efficiency
- Enabling ECM protein micropatterning and stem cell geometric confinement for directed organoid differentiation
- Providing simultaneous sterilization of substrates prior to cell culture
The breadth of organoid types, device architectures, and biological questions addressed by the publications reviewed here underscores that plasma treatment is not a peripheral technique but a foundational step. Whether the goal is assembling a complex multi-organ cancer metastasis chip or simply ensuring that kidney cells adhere uniformly to an electrospun scaffold in a bioreactor, the path runs through plasma treatment.
As organoid research advances toward clinical translation, with applications in personalized medicine, drug screening, disease modeling, and the development of transplantable tissue constructs, the demand for reliable, reproducible surface engineering will only grow. Harrick Plasma systems offer the precision, reproducibility, and published validation that this demanding field requires.