The formation of gas bubbles in microfluidic systems can sometimes be desirable (e.g., enhancing mass and heat transfer). However, bubbles more often create complications such as clogging microchannels and disrupting long-term cell culture experiments. Undesirable bubbles are common—especially when gas-permeable materials like polydimethylsiloxane (PDMS) are used—and are often difficult to remove.
Causes of Air Bubble Formation
Air bubbles can form in microfluidic channels for one or more of the following reasons:
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Temperature variations: Dissolved gases in the liquid can come out of solution when temperature changes during experiments.
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Channel filling: Bubbles can be introduced during the process of filling the channel with liquid.
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Faulty connections: Inappropriate configuration or poorly seated components (syringes, valves, connectors, etc.) can introduce air.
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Inappropriate system design: Channel geometry influences bubble formation; features such as sharp angles and corners increase bubble likelihood.
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Leaks: Any leaks provide a pathway for air to enter the system.
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Replacing liquids: Exchanging one fluid for another can create bubbles.
How to Prevent and Remove Bubbles
To prevent or minimize bubble formation, pay attention to design, installation, and system configuration:
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Design optimization: Avoid geometries that favor bubble generation, e.g., sharp corners and acute angles.
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Correct installation and configuration: Ensure all components are correctly installed (for example, properly loaded syringes) so no air is introduced.
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Use a closed system: Keep the microfluidic pump system closed during liquid replacement (for example, using injection valves) to prevent air ingress.
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Check fittings and connections: Verify all fittings and connections for leaks before beginning experiments.
In addition, install bubble-trapping and removal devices to handle any bubbles that form:
Bubble traps
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Bubble traps prevent bubbles from traveling across microfluidic systems.
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They can be integrated (on-chip/online) or stand-alone components.
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Stand-alone bubble traps are commonly used because integrating traps into microfluidic chips can be challenging.
Bubble removal
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After trapping, bubbles can be removed by gas/liquid separation using membranes (porous or hydrophobic membranes that allow gas to pass but retain liquid).
References
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Y. Wang, D. Lee, L. Zhang, H. Jeon, J. E. Mendoza-Elias, T. A. Harvat, S. Z. Hassan, A. Zhou, D. T. Eddington, J. Oberholzer, Systematic prevention of bubble formation and accumulation for long-term culture of pancreatic islet cells in microfluidic device, Biomedical Microdevices, 14 (2012) 419–426. https://doi.org/10.1007/s10544-011-9618-3
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J. Xu, R. Vaillant, D. Attinger, Use of a porous membrane for gas bubble removal in microfluidic channels: Physical mechanisms and design criteria, Microfluidics and Nanofluidics, 9 (2010) 765–772. https://doi.org/10.1007/s10404-010-0592-5
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K. Ziółkowska, I. Hofman, A. Dybko, Z. Brzózka, Integrated Passive Bubble Trap for Long-Term Cell Culture Microfluidic Systems, LOC 2012, 938–940. http://www.rsc.org/images/loc/2012/pdf/T.1.27.pdf