Causes and Solutions for Air Bubbles in Microfluidic Systems

Formation of gas bubbles in microfluidic systems can sometimes be desirable. For example, they enhance mass and heat transfer inside the system. However, they usually create complications, such as clogging of microchannels, and they have a very destructive effect on long term cell culture experiments. Undesirable gas bubbles always occur in microfluidic systems, especially when gas permeable materials, such as polydimethylsiloxane (PDMS), are used, because they increase the chance of bubble formation. What complicates the problem is that these bubbles are very difficult to remove.

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Air bubbles can form in microfluidic channels as a result of one or more of the following reasons:

  • Temperature variations: If the liquid in the channel contains dissolved gas, it will be emitted as a result of changing the temperature during experiments.
  • Channel filling: Bubbles can be introduced during the process of filling the channel with liquid.
  • Faulty connections: Bubbles can also be introduced as a result of inappropriate configuration of any of the system components and accessories, such as syringe pump systems, valves, and connectors
  • Inappropriate system design: Channel design plays an important role in maximizing or minimizing the air bubble formation.
  • Leaks: If present, leaks are a principle cause for bubble formation in the system.
  • Replacing liquids: Bubbles can form during the process of replacing the liquid in the channels with another.

How to remove bubbles from microfluidic systems?

To prevent or at least minimize the air bubble formation in the microchannels, the design, installation, and configuration of the system components should be correctly conducted as follows:

  • Design optimization: Geometries that increase the possibility of generating bubbles, such as sharp angles and corners should be avoided as much as possible in the design of microfluidic devices.
  • Correct installation and configuration: All system components should be correctly installed, such as a properly loaded syringe, so that no air is allowed into the system.
  • Using closed system: The microfluidic pump system should remain completely closed during the liquid replacement in the microchannels, e.g. by using injection valves.
  • Checking fitting and connection: All fittings should be checked for leaks before the beginning of the experiment.
    In addition, bubble trapping and removal devices should be installed to remove any bubble that may form in the system:
  • Bubble traps: Bubble traps prevent bubbles from traveling across the microfluidic systems. They can be an integrated (online) or a stand-alone component of the microfluidic system. Stand- alone microfluidic bubble traps are the common type, because there are still some difficulties in fabricating microfluidic chips with integrated traps.
  • Bubble removal: Bubbles can be removed after trapping through gas/liquid separation using membranes.

References:

  1. 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, Biomed. Microdevices. 14 (2012) 419–426. doi:10.1007/s10544-011-9618-3.
  2. J. Xu, R. Vaillant, D. Attinger, Use of a porous membrane for gas bubble removal in microfluidic channels: Physical mechanisms and design criteria, Microfluid. Nanofluidics. 9 (2010) 765–772. doi:10.1007/s10404-010-0592-5.
  3. K. ZióÅ‚kowska, I. Hofman, A. Dybko, Z. Brzózka, Integrated Passive Bubble Trap for Long-Term Cell Culture Microfluidic Systems, Rsc.Org. (2012) 938–940. http://www.rsc.org/images/loc/2012/pdf/T.1.27.pdf.

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