Microfluidics for Organ-on-chip Cell culture

The science of flow control for organ-on-a-chip cell culture & its applications

Organ-on-a-chip (OOAC) is the concept of mimicking the organ-level function of human physiology or disease using cells inside a microfluidic chip. Microfluidics enables one the unique ability to control the cellular microenvironment with high spatiotemporal precision and to present cells with mechanical and biochemical signals in a more physiologically relevant context. The manipulation of the micro-liter volumes of liquids has made these models a platform where scaling, and dynamic crosstalk between cells can be achieved. Microfluidic chips can now use geometries and structures to permit the use of physiological length scales, concentration gradients, and the mechanical forces generated by fluid flow to mimic the in vivo microenvironment experienced by cells. These biomimetic platforms overcome many drawbacks encountered with conventional tissue culture models.
Main benefits
  • In-vitro model
  • Better mimicked and controlled microenvrionment
  • Cost-effective
  • Scaling possible

Main Applications of Organ-on-chip Cell Culture

Therapy development

Organ-on-a-chip cell culture platforms have proven potential in providing tremendous flexibility and robustness in drug screening and development by employing engineering techniques and materials. More importantly, there is a clear upward trend in studies that utilize human-induced pluripotent stem cells (hiPSC) to develop personalized tissue or organ models. For this purpose, the use of cell culture chips allows users to study complex culture configurations by joining a culture well with a microfluidic channel via a porous membrane. This is the optimal device for Air Liquid Interface (ALI) culture, endothelium/epithelium barrier and crosstalk studies.

organ-on-chip cell culture drug discovery

Drug discovery

The development of emerging in-vitro tissue culture platforms can be useful for predicting the human response to new compounds.Recently, several in-vitro tissue-like microsystems, also known as ‘organ-on-a-chip studies’, have emerged to provide new tools for better evaluating the effects of various chemicals on human tissue.

Organ-on-a-chip cell culture models can therefore be used for accurate prediction and mechanistic investigation of dose-limiting human toxicities of prospective drugs, as well as for the exploration of new therapeutic approaches to mitigate the observed toxic effects. In the drug discovery pipeline, predictions made by these models could inform and facilitate early efforts to identify, modify and optimize lead compounds, thus developing safer drugs with an increased likelihood of success in clinical trials.

organ-on-chip cell culture regenerative medicine

Regenerative medicine

Organoid technology and organ-on-a-chip engineering have emerged as two distinct approaches for stem cell-derived 3D tissue preparation. Their strategic integration can address each approach’s limitations and provide a path toward a superior, synergistic strategy of constructing tissues that will truly deliver on the promise of regenerative and precision medicine.


Importance of fluid handling for organ on chip cell culture

In many labs, considerable effort is put into choosing the right chip design, but the impact of flow control is still undetermined. It is our intent to create awareness of the importance of flow and its effects on one’s studies.

Fluigent, in partnership with Beonchip, offers a wide range of cell culture chips according to the field of application: to study cell culture under flow, to explore the crosstalk between different 2D and 3D cultures in  biomimetic environments, to apply electrochemical gradients to 3D cell cultures, and to study complex culture configurations by joining a culture within a microfluidic channel via a porous membrane.

Optimized cell culture activity: Constant perfusion enables the continuous renewal of nutrients and oxygen to promote cell growth and maintain optimal activity during long-term cell cultures.

Biomechanics: Organ on chip cell culture technology has paved the way for investigating the impact of mechanical strains in cell biology research by reproducing key aspects of an in-vivo cellular microenvironment. Combining microfluidics and microfabrication enables one to reproduce mechanical forces experienced by living tissues at the cell scale.

Passive stimulation induced by shear flow: Liquid flow usually induces shear stress on cells or tissues cultured on the device. This is called shear flow, and the effect is substantial on cell growth, phenotype, and genetic expression.

Active mechanical stimulations originate from the function of the organ. Organs like lungs, muscles and intestines are in active motion. Cells in those organs are mainly subjected to compression and stretching. Organ-on-a-chip cell culture can simulate these environments, allowing for more realistic and detailed results to be obtained. 

Biochemical studies: Cells are constantly exposed to biochemical stimulation from the early embryonic stage to adult life. The spatiotemporal regulation of these signals is essential as it determines cell fate, phenotype, metabolic activity as well as pathological behaviors. The fast response and high stability of Fluigent instruments make them the best solution available on the market to reproduce these complex variations in-vitro. 

Read our expertise page to know more about the benefits of flow control in cell culture, learn more about our products and those of our partners (Beonchip), and reach out to our team of experts to find a solution that best meets your needs.

Flow control systems and Fluigent’s added value

Implementing perfusion and automated fluid delivery in organ on chip cell culture protocols offers major advantages. Compared to manual pipetting, Automation increases reproducibility, saves time, and improves the level of control in the experiment as all the parameters are tightly regulated (time of delivery, volume, and speed of injection).
Multiple flow control technologies are available for sub-millimeter range fluid management. As demand for microfluidic pumps with higher flow stability, fast response time, versatility, and automation capabilities have increased, pressure controllers have become the device of choice.

organ-on-chip cell culture flow control
responsiveness organ-on-chip cell culture

Response time and stability

The working principle of such pumps is to pressurize the sample reservoirs to control the pressure drop between the inlet and the outlet of the microfluidic system. The responsiveness of the generated flow rate depends on the responsiveness of the pressure pump.

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