How does organ-on-chip work?

In biomedical research, organ-on-chip technology is changing the way we study human physiology and diseases. This blog will provide a detailed overview of how organ-on-chip systems work. The article is based on the DynamicOrgan System, a dynamic, mebrane based organ-on-chip technology, which is commonly used for establishing organ models. If you would like to learn which other types of organ-on-chip technologies exist take a look here.

What we will be talking about:

1. In short – what is organ-on-chip technology?

2. The heart of the system – the biochip

3. The workflow

Step 1: Preparation of the biochip

Step 2: Cultivation of cells and tissues

Step 3: Addition of microbes or immune components

Step 4: The perfusion set-up

Step 5: Treatment of the organ model

In short – what is organ-on-chip technology?

Organ-on-chip (OoC) technology consists of small, advanced cell culture systems designed to mimic human organ functions accurately. By utilizing microfluidic systems, these biochips recreate physiological conditions, allowing real-time observation of interactions between human tissues and body fluids. This innovative approach bridges the gap between traditional 2D cell cultures and complex animal experiments, significantly reducing animal testing while offering more relevant in vitro models for drug development, toxicity testing, and disease modeling.

If you’re interested in learning more about organ-on-chip (OoC) technology, check out this article from our OoC basics series.

The heart of the system – the biochip

Organ-on-chip models join the essential cellular components of an organ with the biomechanical forces of the human body by combining tissue culture with microfluidics.

Cells that make up the organ tissue in an OoC model are cultured on our biochip within parallel or connected compartments. Typically, they contain one upper and one lower channel (such as our BC002) divided by a porous membrane. The different channels allow to cultivate organ-specific tissue compartments such as an endothelial and epithelial layer. The porous membrane that separates these layers allows for small molecules to pass through, supporting proper nutrition, cell-cell communication and physiological responses. Furthermore, coating of the membrane with an extracellular matrix aids cellular attachment.

During culture, biochips are connected to peristaltic or syringe pumps allowing for fluid flow. This perfusion simulates biomechanical forces from the human body such as blood flow in a vasculature, peristalsis in the gut or breathing of the lung. This feature in turn not only allows for a more physiological growth of the tissues than in 2D cultures but also allows for immune invasion and vascular drug application.

Key features of the D42 biochip include:

• • Dimensions: microscopic slide format
  • Material: medical grade, biocompatible plastics with low drug adsorption
  • Membrane: available in various pore sizes
  • Compatibility: tubing connects to biochip via standard luer ports, ports and cavities arranged in microtiter plate positions
  • Optics: clear top and bottom bonding foils enable brightfield and fluorescence microscopy (glass bottoms also available)
  • Assay compatible: supernatant sampling and high tissue recovery
  • Quality: manufacturing under ISO 9001:2015 standard

The workflow

The following chapter provides an introduction into the steps conducted in the lab to set up an organ model with the DynamicOrgan System. Explaining steps such as biochip sterilization, cell seeding and perfusion set up.

Step 1: Preparation of the biochip

The first step is rather short and prepares the biochip for coating and cell seeding. The biochip is sterilized with 70% ethanol, rinsed thoroughly with ultrapure water and then stored under sterile conditions until use.

Step 2: Cultivation of cells and tissues

Before seeding the first cells onto the biochip, the biochip is coated with a cell-specific coating solution to enhance adhesion. Next cells can be seeded into the biochip, at a density optimal for the specific cell type. Depending on where the cell layer should be placed, cells are either seeded in the top or bottom channel of the biochip. Once cells are properly adhered further cell types can be seeded in the opposing channel. In between regular medium exchanges are required to maintain cell viability. Once the cell layers have reached confluency the biochip set-up can be changed from static to perfused.

Step 3: Addition of microbes or immune components

Once the desired cell or tissue layers have been established further components can be added to the model. This might include components of the immune systems such as macrophages or dendritic cells or microbes such as bacteria or fungi.

Step 4: The perfusion set-up

Perfusion mimics blood flow, providing continuous nutrient supply and waste removal. The DynamicOrgan® System uses the Harvard Peristaltic Pump P-70, ensuring precise flow control. This dynamic environment promotes tissue maturation and long-term viability.

At first, the peristaltic pump is installed inside the incubator (pump head only). Next, the tubing and reservoirs are being connected to the biochip. Inside the incubator the tubing can now be connected to the peristaltic pump and flow is adjusted according to the experimental needs.

If you’d like to see how to assemble the system exactly and take a closer look at steps like biochip sterilisation, cell seeding, and perfusion, watch this video presented by our scientist Anne.

Step 5: Treatment of the organ model

Especially during the preclinical drug development phase, toxicity testing and determination of optimal dosage formulation of novel compounds requires human relevant systems. The treatment of cells in a biochip set-up can be carried out via vascular perfusion which conveniently mimics intravenous treatment in vitro. The application is carried out by adding the active ingredient to the medium and filling it into the reservoir of the biochip.

Conclusion

In conclusion, organ-on-chip technology represents a significant advancement in biomedical research, offering a more accurate and dynamic model of human organ functions. By integrating microfluidic systems with cultured cells, these biochips provide a versatile platform for studying physiological processes, drug responses, and disease modeling. The DynamicOrgan® System exemplifies the potential of this technology, enhancing our understanding of complex biological interactions while reducing the reliance on traditional animal testing. As research progresses, organ-on-chip systems will undoubtedly play a crucial role in the future of personalized medicine and drug development.

For more information, contact Dynamic42 GmbH at info@dynamic42.com or visit dynamic42.com.

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