Perfusion Systems

Selection Guide & Review

Perfusion system for cell culture is a device with the passage of fluid through the circulatory system or lymphatic system to a bioreactor for cell culture. There are different types of cell perfusion systems, including microfluidic perfusion systems, gravity or pressure-driven perfusion systems, bioreactor perfusion systems, and small-mammal organ perfusion systems.
These perfusion systems are convenient tools for a variety of applications, such as multi-reagent delivery, culturing cells at microscales, etc.

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  • Drug screening

  • Toxicity tests

  • Calcium imaging

  • Bioreactor research

Applications:

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  • Droplets cell culture on the chip

  • Cell response to medium change

  • Live cell imaging

  • 3D cell culture

  • Stem cells assays

Key Factors for Perfusion System Selection

Media Recirculating or Non-recirculating System
It depends on the whether the cell to cell chemical interaction is essential or not in your experiment.
 
Recirculation perfusion system uses a given volume of culture medium and recirculates the medium throughout the perfusion flow. By using the same culture medium, the molecules secreted by the cells are kept in the same culture flow.
 
Non-recirculating perfusion system can be used for experiments where cell-cell chemical communication is not important or these chemical cues should be ruled out. This perfusion system allows to remove secreted factors, waste products and thus wash cells through the media flow. 
Shear Stress
In perfusion cell culture, hydrodynamic shear stress can be a limiting factor.
 
Lower shear stress is desired in order to eliminate its effects by different approaches. One way is to lower the perfusion flow rate. Another way to reduce shear stress is to use microfluidic chips with dedicated geometries. For example, microfluidic chips with a porous membrane can be used as a barrier for the medium flow to minimize the shear stress.
 
On the other hand, some experiments use high level of shear stress to investigate endothelial cell function with different shear stress conditions in in-vivo conditions. 
Bubble Issue
Air bubbles have a significant detrimental effect on cell culture. First, the liquid flow can obstructed seriously by bubbles trapped inside tubing or microfluidic channels. Second, cells can be killed at their gas-liquid interface of the bubbles in the culture flow.
 
One way to eliminate bubbles is to flush the system by applying a high flow rate before the cells are seeded. Adding proper soft surfactant (i.e. SDS) is very effective way to release air bubble from perfusion chamber. Another way is to add an inline bubble trap in the perfusion flow to remove the bubble generated during the cell culture.
Temperature control
For long-term live cells studies, temperature is a critical parameter of the cell environment.
Keeping the cells at a proper temperature with temperature control system is required for the perfusion experiment. PreciGenome also offers temperature control solutions. 
 

Perfusion Chambers

Perfusions chambers are a critical aspect of cell perfusion, especially for live-cell imaging. They have to meet two important requirements: maintain cells in a healthy state and allow the living cells to be observed with the highest possible resolution. 
 
A wide range of commercial perfusion and imaging chambers are now available. It includes conventional perfusion chambers, i.e. glass bottom Petri dishes, multi-well chambers mounted on microscope slides, heating stages with a variety of interchangeable perfusion adapters, or microfluidic chips. Depending on your experiment, some chambers will be more suited to your needs.
 
PreciGenome offers a variety of microfluidic chips in different materials to meet most of our customers' application requirements.  Three types of materials, including polymers, glass and silicon, are commonly used to fabricate microfluidic chips. Material of the chip is selected depending on the application requirements, including chip design, types of solvent or reagent used for experiment, needs of the application, budget, and fabrication time,etc. 

Perfusion Systems 

The choice of a perfusion system depends on the type of experiment. For simple live cell imaging experiments, pressure-driven flow controller, syringe or peristaltic pumps can be used. For experiments requiring more control over cells environment, injection at precise low flow rates or switch between different media, pressure-driven are preferred to use for the applications.
PreciGenome offers a variety of perfusion systems to select for different requirements of your applications. Our system offers pulse-free flow perfusion with our microfluidic and pressure-driven technology.   
 
It allows control over microenvironmental cues, such as cell-cell and cell-matrix interactions; the potential to scale experiments; the use of small culture volumes; and the ability to integrate with microsystem technologies for on-chip experimentation. It also allows precise and on-demand delivery and removal of biochemical reagent in the extracellular microenvironment, and controlled application of mechanical forces exerted via fluid flow.
Touchscreen version 
Perfusion controller
Light version 
Multi-reagents selection flow unit
Flow unit with 1.5ml, 15ml, 50ml or 100ml reservoir kit options
Recirculating flow unit
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UI Software and API library for complex process control and real-time data monitoring
 

Option 1: 

Duplex Perfusion System 

Type A

System Content:​

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  • PG-MFC-LT-2CH controller, 1 pc

  • Reservoir kit, 2 sets

  • Tubing and fittings, 1 set

  • 3-way valve, 1 pc 

  • Liquid flow sensor (optional)

  • Stop valve, 1 pc (optional)

  • Bubble trap, 1 pc (optional)

 

Part #: PG-PF-LT2-A

System diagram of duplex perfusion system (Type A). The system is able to perfusion 2 reagents with up to 2 independent experiments simultaneously. 
System diagram of duplex perfusion system (Type B). The system is able to perfusion 2 reagents with up to 2 independent experiments simultaneously. 

Type B

System Content:​

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  • PG-MFC-LT-2CH controller, 1 pc

  • Reservoir kits, 2 sets

  • Tubing and fittings, 1 set

  • Liquid flow sensor (optional)

  • Stop valve, 2 pc (optional)

  • Bubble trap, 2 pc (optional)

 

Part #: PG-PF-LT2-B

Setup example of Duplex Perfusion System
 

Option 2: 

Multi-Reagent Perfusion System

Many perfusion applications, such as organ-on-a-chip and cell culture, require switching between multiple reagents.  Combining PG-MFC pressure controller with a rotary valve, our system enables users to do multiple reagent switching. Our careful selected rotary valve has small internal channels (low dead volume) and an accurate positioning system which makes it ideal for precise liquid handling. Our system achieves fast switching without pushing a large amount of reagent to clean up the previous reagent during switching. Connected with a flow sensor, the system is capable of maintaining a constant flow rate through the feedback loop during the course of their experiments.
Setup example of multi-reagent perfusion system with up to 5 reagents selection. 

 System Benefits:​

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  • Automation

  • Fast switching time

  • Minimal cross-contamination between reagents

  • Pressure and flow-rate control

  • Easy setup and optimization

  • Low cost

  • OEM and custom design available

  • Temperature control module is also available to integrate into the system

The video demonstrates multi-reagent switching with different colors using our system. The switching is fast and minimum cross-contamination.
System diagram of multi-reagent perfusion system with up to 10 reagents selection. The system is able to run 2 independent experiments simultaneously. 

 System Specs:​

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  • 2 Independent pressure channels

  • Max 2 sets of perfusion units running simultaneously

  • Reservoir volume: 15mL/50ml/1.5ml, larger volume options also available

  • Manifold: 10 to 1 Liquid flow rate: from 10nL/min to 5 ml/min

  • Dead volume: 4.5uL excluding the outlet tubing volume

 System Content:​

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  • PG-MFC-LT-2CH controller, 1 pc (PG-MFC with touch screen is available to upgrade)

  • Rotary valve, 1to10 ports, 1 pc

  • Reservoir kits (15mL, 50ml or 1.5ml reservoir volume), 5Sets

  • Liquid flow sensor (optional)

  • Tubings and Fittings

 

Part #: PG-PF-8-MRD  (Touch screen controller)

            PG-PF-LT2-MRD (Light version controller)

 

Option 3: 

Recirculation Perfusion System 

Combining our PG-MF controller with a 3-way/2-position rotary valve, PreciGenome provides a perfusion system dedicated to cell culture in perfusion chambers with controlled shear force. This fully integrated solution includes all the necessary elements (hardware and software) to create a continuous and recirculated (unidirectional or bidirectional) flow and controlled flow rate (shear force) applied onto cells.

PG-MFC controller is used to provide pressure to pump reagent from reservoir 1 through perfusion chamber to reservoir 2 through the valve. Combining PG-MFC pressure controller with the rotary valve ( extra two 3-way valves required for light version controller), the system allows flowing buffers in two separate reservoirs back and forth, but still keeps the flow in the microfluidic chip uni-directional.

System Benefits:​

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  • Controlled shear stress

  • Long duration experiments

  • Automation

  • Controllable flow rates

  • Ready to connect with the incubator

  • Temperature control module is also available to integrate into the system

  • OEM and custom design available

Work Modes:​

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  • Unidirectional flow control

  • Bidirectional flow control

  • Pulse flow control

3.1 Recirculation Perfusion System with PG-MFC Controller 

As showing in the schematics below, in position 1, reagent flows out from reservoir 1, through the 3-way/2-position rotary valve, enters the microfluidic chip from its left side, and flows into reservoir 2. In this position, the 3-way valve on the left side connects pressure source to reservoir 1 and the other 3-way valve connects to the atmosphere.

 

In position 2, reagent flows out from reservoir 2, enters the microfluidic chip from its left side, and flows into reservoir 1. In this position, the 3-way valve on the right side connects pressure source to reservoir 2 and the other 3-way valve connects to the atmosphere. In this application, only a single pressure source is needed.

 System Content:​

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  • PG-MFC controller, 1 pc (4Channel , 8Channel or custom version available)

  • Bidirectional 3-way/2-position rotary valve, 1 pc

  • Reservoir kits (options: 15ml, 50ml or 100ml),  2 sets

  • Liquid flow sensor (optional)

  • Tubings and fittings, 1set

Part #:  PG-PF-4-REC (PG-MFC-4CH, Touchscreen version)

            PG-PF-8-REC (PG-MFC-8CH, Touchscreen version)

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