Liquid marbles: a cost-effective platform to generate cardiospheres from co-cultured cardiomyocytes and cardiac fibroblast for disease modelling

Scope of the method

The Method relates to
  • Human health
The Method is situated in
  • Basic Research
Type of method
  • In vitro - Ex vivo
This method makes use of
  • Human derived cells / tissues / organs
Specify the type of cells/tissues/organs
Human pluripotent stem cell derived cardiomyocytes and human pluripotent stem cell derived cardiac fibroblast


Method keywords
  • Liquid marble
  • Cardiomyocyte
  • cardiac fibroblast
  • 3D cardiospheres
  • induced pluripotent stem cells
  • cardio
Scientific area keywords
  • cardiac disease modelling
  • cardiovascular disorders
  • in vitro 3D modelling
  • Coculture model
Method description

Advances in three-dimensional (3D) culture techniques have shown several advantages over 2D cultures, especially by more accurately mimicking the in vivo environment. This has led to improved reproducibility and reliability of experimental results, which are important criteria in disease modelling and toxicity testing. Induced pluripotent stem cells (iPSC) provide an unlimited source for the derivation of all cell types of the adult body, including cardiomyocytes. To improve the current culture methods for multicellular cardiac spheroids, such as the hanging drop method, we explored the use of hydrophobic powders. Fumed silica nanoparticles can be used to encapsulate liquid drops, which could serve as a microenvironment for cell cultures. This microbioreactor stimulates cell coalescence and 3D aggregation while providing optimal gas exchange between the interior and the surrounding environment. Moreover, the properties of liquid marble microbioreactors render them ideal for co-culture experiments. This liquid marble technique has been previously explored and optimized for other cell types. Here we describe a protocol that allows for the derivation of functional cardiac mini organoids, consisting of co-cultured cardiomyocytes and cardiac fibroblasts. These cardiospheres can be valuable for modelling cardiac diseases in vitro and assessing cell interactions to decipher disease mechanisms.

Lab equipment
  • - Biosafety cabinet;
  • - Incubator.
Method status
  • Still in development
  • Published in peer reviewed journal

Pros, cons & Future potential

  • - Inexpensive;
  • - Easy to learn;
  • - No specialized equipment required;
  • - Versatile applications;
  • - Formation of 3D structures in relatively short time (24h);
  • - Small volumes and cell numbers required.

Susceptible to environment changes such as temperature and humidity.

Future & Other applications

Liquid marble technology in principle can be applied with other cell types to generate 3D structures.

References, associated documents and other information


J. Aalders, L. Léger, T. Tuerlings, S. Ledda, and J. van Hengel, “Liquid marble technology to create cost-effective 3D cardiospheres as a platform for in vitro drug testing and disease modelling,” METHODSX, vol. 7, 2020. doi:10.1016/j.mex.2020.101065

J. Aalders, L. Léger, D. Piras, J. van Hengel, and S. Ledda, “Use of transparent liquid marble : microbioreactor to culture cardiospheres,” in Next generation culture platforms for reliable in vitro models, vol. 2273, T. Brevini, A. Fazeli, and K. Turksen, Eds. Humana, 2021, pp. 85–102. doi:10.1007/978-1-0716-1246-0_5

Liquid marbles for disease modelling (poster presentation)

Contact person

Jolanda van Hengel


Ghent University (UGent)
Faculty of Medicine and Health Sciences
Flemish Region