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Related Experiment Video

Updated: Jul 13, 2025

Microfabricated Platforms for Mechanically Dynamic Cell Culture
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Controlling bead and cell mobility in a recirculating hanging-drop network.

Nassim Rousset1, Martina de Geus1, Vittoria Chimisso2

  • 1Bio Engineering Laboratory, Department of Biosystems Science and Engineering, ETH Zürich, Basel, CH, Switzerland. nassim.rousset@bsse.ethz.ch.

Lab on a Chip
|October 19, 2023
PubMed
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Researchers optimized a hanging drop system to control cell flow in microfluidic devices. They found that drop height precisely dictates whether cells flow or stagnate, enabling controlled cell residence times for body-on-a-chip applications.

Area of Science:

  • Biotechnology
  • Microfluidics
  • Cell Biology

Background:

  • Integrating flowing cells into microphysiological systems is vital for body-on-a-chip applications.
  • Controlling cell recirculation in microfluidic devices presents significant challenges due to boundary conditions and laminar flow.
  • Open microfluidic devices, like hanging drop networks (HDNs), offer potential for tunable cell flow dynamics.

Purpose of the Study:

  • To optimize a hanging-drop-integrated pneumatic-pump system for closed-loop recirculation of particles (beads or cells).
  • To investigate and overcome particle stagnation observed at the air-liquid interface (ALI) in HDNs.
  • To establish precise control over cell flow and stagnation for advanced body-on-a-chip models.

Main Methods:

  • Development and optimization of a hanging-drop-integrated pneumatic-pump system.

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  • Characterization of the air-liquid interface using transmission electron microscopy and dynamic light scattering.
  • Finite element method simulations to analyze particle forces and optimize HDN design parameters (drop aperture, drop height).

    • Main Results:

    • Particle stagnation at the ALI was identified as a pseudo-no-slip boundary condition caused by medium component aggregation.
    • A phase diagram was generated, delineating conditions for particle flow versus stagnation based on HDN design and operation.
    • Experimental validation confirmed that drop height controls particle behavior: >300 μm causes stagnation, <300 μm allows flow.

    Conclusions:

    • The study successfully optimized HDNs for controlled particle recirculation, overcoming ALI-induced stagnation.
    • Precise control of cell flow and stagnation is achievable by actuating hanging drop height.
    • This technology provides a foundation for controlling single-cell residence times around 3D organ models in microphysiological systems.