Things you should know when integrating fluidics into your system

 

Scientific progress and workflow automation have driven the transition from manual processing to automated solutions in laboratories. Automation is  essential for in vitro diagnostics (IVD), molecular analysis, flow cytometry, next-generation sequencing (NGS) or cell biology systems. The choice of the right method of fluid management can often determine the success of a project, as well as the overall time and cost of manufacturing. Here is what you need to consider and be aware of when integrating fluidic control into your system.

Fluid considerations

How will pulsatile flow affect system performance?

flow pulsations

Droplet-based applications: droplet digital PCR or cell encapsulation for single-cell analysis usually make use of droplets generated by the microfluidic technology. These applications require liquid handling systems with  flow with very low to no pulsation to obtain homogeneous droplets, which is vital for the success of these applications.

Flow cytometry and surface plasmon resonance (SPR) are based on real-time analytical measurements of samples passing by a detection area. They require a fluid handling delivery system with a stable flow rate to deliver fluids through the fluidic channels.

Live cell imaging: In live-cell imaging applications with fluid perfusion,  pulsatile flow leads to variable shear stress imposed on cells and may impact cell viability. Liquid flow should be stable and controlled.

In some applications, a steady flow rate is a prerequisite for reliable operation:

Flow rate

For these applications, pressure-based fluid delivery can deliver flow rates at the microliter-per-minute or nanoliter-per-minute range with a stable flow rate (high precision and accuracy) and no pulsation.

Do you require fast settling times?

Some applications require to alternate between several flow rates in a short period of time. This is common for flow cytometry, cell sorting, or fluorescent activated cell sorting (FACS). In the latter, 3 flow rate modes are usually available: slow, medium, and fast, and one can switch from one to another.

For such applications, consider using a fluid delivery system that allows for rapid response time (a few seconds).

Flow rate

Is sterility a need?

Many biological applications such as cell culture under perfusion, immunostaining, organoid culture, organ on a chip, drug discovery, single-cell analysis, and cell cytometry amongst others require a sterile environment. When using fluids such as culture media, PBS, buffers, blood, or plasma, every component in the fluidic path should be disposable, or able to be sterilized.

For these applications pressure-based liquid delivery systems that do not contact fluids or have components that can be sterilized are ideal.

Do you need to handle multiple fluid streams?

This is of benefit for operations that perform several tests simultaneously, such as for drug screening where different drug candidates are tested, for instance for personalized medicine applications that make use of tumor biopsy studies. It is also sometimes convenient and cost-effective, to separate a fluid originating from one liquid delivery system into two distinct paths.

It is important to choose the right liquid delivery system that allows for multiplexing. Depending on your choice, increased number of systems can be highly expensive and integration will be cumbersome. Using fluidic valves or quake valves can also be an interesting alternative as they allow fluid management with a reduced amount of fluid delivery systems.

What are the volumes to be dispensed?

Volumes to be injected highly depend on your application. For instance, in cell biology applications such as cellular imaging, or dynamic cell culture, fluids can be injected for several days. Consequently, high reservoir volumes (up to 1 L) are required. Conversely, drug screening applications can make use of expensive liquids, and very small amount of fluids should be used (< 100 µL).

Depending on the liquid delivery system used, reservoir size can affect the precision and accuracy. For example, using syringe pumps, smaller syringes maximize accuracy for small volumes but require frequent refilling for larger volumes. Larger syringes will increase capacity but will lose accuracy and become pulsatile at lower flow rates.

Do you need to control or measure flow rate?

Although liquid delivery is performed by setting the flow rate in many fluid delivery systems, the actual flow rate value is not controlled. To overcome this issue, one can add flow rate sensors into a system. There are several flow sensing technologies based on different physical properties. The best one for a particular application will depend on the required flow response time, sterility requirements, and other parameters.

Integration considerations

Time to market?

To accelerate development, consider pre-built components or solutions. It can be for instance liquid handling elements that can quickly be integrated into your system or prototype. Fluigent’s standard and customizable liquid handling OEM components offer flexibility and are easy to integrate into your device. Using a readymade solution will avoid dealing with multiple fluid handling issues and provide more time to focus on your core expertise and application.

Do you have all the resources for in-house development?

Integrating fluidic parts into a system is an option when developing an automated liquid handling system. The concept, design, and development of the system will require engineering expertise in the mechanical, electrical, software, and manufacturing areas.

When developing a system internally, you need to make sure you have the experience and engineering knowledge to translate your proof-of-concept device into a reliable and efficient automated system. The whole product development is at risk if you are missing some of the listed resources.

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