Automated Recirculation Perfusion System

Easy Recirculation

Continuous, unidirectional flow over samples

Automatic Recirculation

No need to switch between reservoirs

Incubator-independent

The cell culture pump replaces the need for a CO2 incubator

Fail-safe mechanism

No more losing your experiment due to clogging

Automated recirculation perfusion system

Our automated recirculation perfusion system is designed to maintain a stable and controlled environment for long-term cell culture. The continuous recirculation allows for real-time monitoring and provides more accurate data on the experimental conditions. Moreover, the recirculation perfusion system reduces the needed reagents compared to single-pass systems, giving you even more control over your experiments.

Moreover, it ensures continuous nutrient supply at constant O2 and CO2 levels without the need for a CO2 incubator. This precision also provides a more physiologically relevant cell microenvironment by sustaining a continuous unidirectional flow through a microfluidic chip laden with cells.

From reservoir 1 to reservoir 2:

Unidirectional flow recirculation-setup check valves, level sensors and cell culture pump

From reservoir 2 to reservoir 1:

Unidirectional flow recirculation-setup 2 check valves, level sensors and cell culture pump

Automated recirculation perfusion system applications

The automated recirculation perfusion system setup includes:

cell culture pump perfusion system

Cell Culture Pump with Gas Control

Keep the pH and oxygen of your media constant outside the incubator

✓ Gas control for incubator-free setup

✓ Stable long-tem flow

✓ Versatile

Cell culture pump

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Level Sensors for Microfluidics

Fail-safe instrument for automated recirculation experiments

✓ Easy recirculation

✓ Fail-safe mechanism

✓ Up to 3-week long experiments

✓ Plug-and-play

Level sensors

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Check Valve System Pack for Recirculation

Flow control for long-term unidirectional microfluidic experiments

✓ Up to 3 weeks long term perfusion

✓ Setup compatible with incubation

✓ Passive valves, no backflow

✓ Easily stackable for parallelization

Check valves (recirculation bridge)

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Microfluidic Flow Rate Sensor

Low flow rate microfluidic flow sensor with automatic clogging detection

✓ Low flow rates

✓ Detect clogging inside the sensor

✓ No drift

Microfluidic flow sensor (eg. Galileo)

Several Schott bottles

Tubings and fittings

Microfluidic chip

User guide

Software (Galileo user interface)

And many more! 

The automated recirculation perfusion system setup includes:

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Stem Cell Culture

Automated and fail-safe long-term microfluidic cell culture system. 

✓ Highly controlled microenvironment

✓ Fail-safe mechanism

✓ Automated sequences

Stem Cell Culture

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Microfluidic Spheroid Cell Culture

Plug-and-play instrument pack for automated scaffold-free 3d cell culture technique.

✓ Multiple Parallel culture of Spheroids

✓ Automated Spheroid Perfusion

✓ More Physiologically Relevant Model

Microfluidic Spheroid Cell Culture

Blood-brain barrier on a chip mouse cappillaries

Blood-brain Barrier on Chip

Plug-and-play instrument pack for long term BBB on a chip study

✓ Relevant microenvironment

✓ Automatized organ-on-chip perfusion

✓ Plug-and-play microfluidic platform

Blood-brain Barrier on Chip

neuron culture bioreactor

Sheer Stress

Cell culture system for shear-sensitive cell lines

✓ Safe Neuron Culture Under Flow

✓ Highly Controlled Microenvironment

✓ Up to 3-week Long Cell Cultures

Sheer Stress

And many more! 

Have a look at this review comparing this unidirectional automated recirculation system to unidirectional recirculation with a peristaltic pump.

Check this review comparing different bidirectional and unidirectional recirculation systems.

Automated recirculation perfusion system

With microfluidics it is possible to flow medium continuously over cells in culture. A microfluidic recirculation perfusion system involves fluid’s continuous and controlled circulation through microchannels.

Recirculation perfusion systems

Most recirculation perfusion systems rely on the initial fluid volume and desired flow rates to estimate the time it takes for one reservoir to flow most of its volume through the sample before switching to the other reservoir.

However, these systems don’t detect changes and thus continue functioning as programmed. If one of the reservoirs empties before expected due to biofouling or clogging, air enters the system, damaging the cells and ruining the experiment.

In addition, a recirculation perfusion system requires the medium to be supplied with CO2 inside the chip. This can be done using a gas-permeable material, a CO2-independent medium for short periods (about 2 hours), or a CO2 incubator.

One pack for an automated recirculation perfusion system

We have combined the cell culture pump, check valves, and level sensors in one pack for automated recirculation perfusion.

cell culture pump perfusion system

The cell culture pump can be used in the setup as a pressure controller that consumes less gas than other pressure-driven controllers. Pressuring the media reservoir with the correct gas mix prevents the gas in the media from diffusing into the atmospheric air. 

 

The constant media flow ensures that the correct composition always reaches the cells, even if the rest of the system is not gas-tight. 

The cell culture pump allows recirculation outside of a CO2 incubator. In this case, an additional stage-top incubator might be used to keep the temperature stable for long periods of time, allowing for high-quality live cell imaging experiments.

The check valve recirculation bridge keeps the flow unidirectional inside the connected microfluidic chip via four passive check valves that are adjusted to quickly and efficiently transfer fluid between reservoirs.

 

In the figure below, the small red arrows indicate the direction of flow inside each check valve. Corner number 1 marks the common exit from the bridge.

Unidirectional flow direction through check valves
The small red arrows indicate the direction of flow inside each check valve. The common exit from the bridge is marked by corner number 1.
Bridgeassembly-part1
Bridge assembly

Check this application note for more information on how to assemble the recirculation bridge and set up your experiment.

level sensors perfusion system

The level sensors automate the perfusion system based on the media volume level inside reservoirs, ensuring continuous perfusion. In addition, the level sensors introduce a fail-safe mechanism that considers the ever-evolving nature of a perfusion system, such as fouling the tubing with dead cell debris, leakage due to clogging, and other blockage-related issues, such as air entry. 

 

For example, in case of leakage due to extensive clogging, the level sensors will stop the flow, preventing air from being pushed into the system and preserving the sample.

A highly-performant flow sensor for clogging detection

Our engineers have developed a new highly-performant flow sensor, Galileo. This sensor offers <5% flow rate accuracy for sensing ranges from 0.5 to 10,000 µL/min. 

 

Galileo allows for bi-directional flow rate measurement and automatic detection of internal clogging, which will be shown on the small screen of the flow sensor. In case of cross-contaminations or clogging, it’s possible to replace the cartridge for an entirely new flow path. The Galileo flow sensor is a key component that ensures the system’s accuracy and reliability.

Galileo-software
Bridge assembly part 3
Connecting the flow sensor to the Bridge

Check the whole video here.

Level sensor technical specifications

The following table summarizes the main specifications of the level sensors:

Components Specifications
Dimensions (mm) Sensing area: 2 x 1 cm
Material Plastic
Reservoir compatibility 100 mL Schott bottle
Control Cell culture pump

Cell culture pump technical specifications

The cell culture pump can come with 1 to 4 channels. Each channel connects to a flow sensor with a feedback loop between pressure and flow rate. Each channel has the following specifications (tested with a set pressure value of 2 bar):

Characteristics Specifications
Accuracy -27.75 mbar
Air consumption 0.24 L/min
Response time 140 ms
Settling time 2750 ms
Overshoot 0.12 mbar

Customize your pack

Our instruments can benefit from your feedback, so you can take advantage of the extra flexibility to adapt them according to your specific needs. Our microfluidic specialists will advise you on the best instruments and accessories based on your needs and will accompany you during the setup of the recirculation perfusion system.

All the instruments are controlled by the same software, allowing workflow automation and easy integration in your program with free available libraries.

Frequently asked questions

Is the recirculation perfusion system compatible with reservoirs other than bottles?

The current version is compatible with 100 mL bottles, but other options, such as for well-plates, are being developed. Don’t hesitate to contact us if you need a different reservoir type.

To guarantee the sterility of the used gases, we advise adding a small disposable filter at the gas inlet of the reservoir.

The cell culture pump can be connected to any microfluidic chip using the correct connectors.

The cell culture pump is intended to replace the need for a CO2 incubator.

The system works well with the range of 0-5ml/min.

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Funding and Support

The LIFESAVER project, funded by the European Union’s H2020-LC-GD-2020-3, grant agreement No. 101036702 (LIFESAVER), helped develop the level sensors. 
The Tumor-LN-oC project, funded by the European Union’s H2020-NMBP-TR-IND-2020 grant agreement No. 953234 (Tumor-LN-oC), helped develop the cell culture pump.
The ALTERNATIVE project, funded by the European Union’s H2020-LC-GD-2020-3 grant agreement No. 101037090, helped develop the check valve system.
The Galileo project, funded by the European Union’s Horizon research and innovation program under HORIZON-EIC-2022-TRANSITION-01 grant agreement No. 101113098 (GALILEO), helped develop the Galileo flow sensor. 

Products & Associated Accessories

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