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Microfluidics application note

Microfluidic valve switching: How to control the flow while changing flow line with a Mux Distributor ?

Maintain a controlled flow rate?

This application note aims to help you maintain a controlled flow rate during microfluidic valve switching thanks to the Mux Distributor. This valve allows to switch between up to 10 lines to inject several fluids sequentially in your system. It has many applications such as sequential sample injection for biochemistry and flow chemistry, or medium switch for cell biology on chip.

Because the flow switch introduces temporary flow rate diminution, it is important to tune the parameters of the PID flow rate control to have the optimal performances for your set-up. The following sections will walk you through the steps to easily perform this optimal regulation.

microfluidic valve switching: Mux Distributor working principle

The Mux Distributor is a 10 to 1 valve that can be used in both directions: to distribute your liquid sample in different lines or to inject in your setup different liquids samples. This allows you to perform microfluidic valve switching. Thanks to the Elveflow® Smart Software, you will be able to command the Mux Distributor and even to choose how much time you want each connection to be on. Another advantage of the Mux Distributor, is the guarantee of no back flow and thus no contamination between samples.

We will here focus on how to regulate the flow after a sample switch. Indeed, although the switch occurs in a few hundred of ms, it induces a flow rate fall during microfluidic valve switching.

One can use any method to generate the flow. In order to get to a quick and precise flow control we will use the OB1® pressure controller. One advantage of using this instrument is the integrated flow control system provided in the software.

In this set-up, the flow settled by an OB1 is measured thanks to a microfluidic flow sensor. A PID algorithm determines the OB1 pressure output value according to the flow measurement. This algorithm has two parameters – the gain parameter and the integration time parameter – that can be tuned by the user (the D parameter is preset). According to your setup behavior, you may change these parameters to find the best combination to have both a good response time and stability.

If you want to go further in the understanding of this algorithm, check out our dedicated tutorial: how to choose flow regulation parameters.

  • Cell culture on chip
  • Live cell imaging
  • Cell response to medium change
  • Biosensor calibration
  • Biochemical sensor calibration
  • Electrochemical sensor calibration
  • Drug screening
  • Toxicity tests
  • Stem cells assays
  • Sensor test rig
  • Seq-Fish

This section explains how to inject sequentially several fluids at a controlled flow rate in the device of your choice (microfluidic device, perfusion chamber etc…)

Components list

For this setup, the following Elveflow® devices are needed:

  • Elveflow® pressure & flow control instrument (OB1)
  • Microfluidic Tubing for the fluidic connection of the setup elements
  • Microfluidic Fittings & Connectors
  • Bronkhorst flow sensor

We here use the Flow Sensor with the OB1 MK3 in pressure control mode and a MUX Distributor.

Schema_Rheodyne_valve_bidirectional_10way_injection

Tips : For a faster switch, place your microfluidic chips as close as possible to the Mux Distributor. It also allows a more accurate volume control with less liquid in the tubing.

Once the circuit is mounted, the next step is to optimize flow regulation. The algorithm can be tuned in accordance to your needs in order to find the right balance between responsiveness and accuracy.

In order to find the best relation between both flow regulation parameters (gain and integration time), you can use the “auto-tune” functionality”. If it is not enough, go to this tutorial which explains exactly how to choose flow regulation parameters.

The optimal parameters can be different from one line to another (depending of the properties of your fluids). The Elveflow® software allows you to save different configurations and to load them easily : you can create configurations for all your lines, the algorithm parameters will also be saved.

Tips : To minimize the perturbations caused by the mechanical switch, plug your samples as far as possible in neighbor lines of the Mux distributor. It will reduce the switch time.

Make sure that all the cables and tubing are well connected to your Elveflow® instruments (USB cable, 24V DC, Flow sensor data cable, etc). Perform leakage tests and remove any air bubbles before starting your experiment.

The flow sensor is very sensitive to vibrations and movement perturbations so it is recommended to tighten it to a stable surface as often as possible.

rheodyne-microfluidic-valve-bidirectional

1) Launch Elvefow® smart interface and
add the OB1® pressure controller and
the Mux Distributor.

rheodyne-microfluidic-valve-bidirectional1

2) Connect the flow sensor on the used
pressure channel of your OB1®.

rheodyne-microfluidic-valve-bidirectional2

3) Launch the OB1® and the Mux distributor. To switch manually which line is connected to the output, simply click on the line you want to select.

It is also possible to rename the lines like in this screenshot.

rheodyne-microfluidic-valve-bidirectional3

4) Go to the sensor controlled mode and set the parameters as explained in the previous section.

You may have to do several tests to find the best parameters. The optimal parameters can be different from one line to another.

rheodyne-microfluidic-valve-bidirectional5

5)  Launch the regulation. You can follow the flow rate evolution on a graph.

In this example at time t=27s, a line switch was performed.

When switching the flow rate first decreases when the flow is blocked. To compensate this stop, the pressure increases and makes the flow rate overshoot the set value before going back to this value in less than 1s.

This example shows how to switch between samples when a specific volume of liquid is reached. It is not the most precise way to control experiment because even if the computer gives the volume of liquid, the switch has to be done manually.

However, it can be very useful if you want to use the Mux Distributor to perform injections in your microfluidic device and this process is particularly easy to follow.

rheodyne-microfluidic-valve-bidirectional6

1) Launch the flow regulation with the OB1® pressure controller and open the Mux Distributor control panel.

You may change the name of the Mux Distributor lines.

rheodyne-microfluidic-valve-bidirectional7

2) Connect the flow sensor to the Mux Distributor using the panel on the right of the screen.

You will now see, for each line, the volume of liquid which went through
the line. If you don’t need too much precision, you can switch manually between the lines when the volume of a sample reached the one you wanted to inject.

Connect the flow sensor with the Mux Distributor using the panel on the right of the screen.

You will now see for each line, the volume of liquid which went through the line.

If you don’t need too much precision, you can switch manually between the lines when the volume of a sample reached the one you wanted to inject.

rheodyne-microfluidic-valve-bidirectional8

1) First, for each line create a configuration with the adapted flow rate and flow control parameters. Save these configurations.

Tips : You can also create a “finish” configuration to stop the flow rate at the end of the experiment.

rheodyne-microfluidic-valve-bidirectional9

2) Go back to the main panel and launch the sequence planner.

rheodyne-microfluidic-valve-bidirectional10

3) Add to the sequence planner the event corresponding to the line switches and the load of the different configurations in the OB1 ®.

Then set the time you want to stay in each configuration using the “wait” command.

rheodyne-microfluidic-valve-bidirectional11

4) You can now play the sequence ! If the response of one of the channel does not correspond to your need, go back to the configuration and adapt the flow controls parameters.

Do not forget that, even if you can’t avoid a little bit of disturbance during a line switch because of the flow rate brief stop, you can minimize it with microfluidic valve switching between neighboring lines.

Congratulations, you can now run your experiment and control up to 10 lines with a low switch time and an accurate flow regulation!

Stop by the Bronkhorst® flow sensor product webpage.

FLOW REGULATION

Mux Distributor basics, a simple tutorial if you want to perform a switch with no flow control constraint:

Microfluidic-Valve-Rheodyne

A complete tutorial on the PID control in a more general case:

Microfluidic-flow-control-Full-Setup-image

Mux Distributor product page where you can find the datasheet and all the technical specifications:

microfluidics-flow-switch-matrix-valvess

Explore other ways to perform switches with all the Elveflow® Mux range, and find the solution that best fits for your set-up! Mux Wire for fast microfluidic valve switching with multiple inputs :

Microfluidic-Valves-Controler

A comparison between multiples ways to perform switches :

Microfluidic-fast-medium-switch2

Want to run a similar experiment? Feel free to contact us at: contact@elveflow.com
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