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HOW TO SELECT THE RIGHT MICROFLUIDIC PUMP?

Introduction

next generation core V2

Controlling flow rate is critical for most microfluidic applications. Downscaling macro experiments to micrometer scales increases their sensitivity and resolution but also makes them more susceptable to external factors. Flow rate is one of the key parameters to control as a pipetting error can create sufficient hydrostatic pressure to induce uncontrollable flow rates inside chips. To circumvent this issue, external flow controllers are connected to the chip. Syringe pumps, peristaltic pumps or our pressure driven pump are the most commonly used systems to deliver flow and provide the best control of the fluids at the microfluidic scale.

The goal of this article is to compare the pros and cons of these 3 types of devices, in order to help you to choose the best solution for your microfluidic application. To do this, a short description of each instrument and their main advantages and drawbacks will be presented.

In order to thouroughly compare their performance, in-house tests were performed under similar experimental conditions to evaluate the stability and response time of each  pump presented. The experiments were performed with distilled water using a 254µm ID tubing (510µm and 640µm ID with perstaltic pump).

Finally, the main features and comparisons between instruments are summarized.

Overview of microfluidic pumps

Peristaltic pumps:

Peristaltic pumps deliver a pulsatile flow. The fluidic tubing used is flexible and coiled around the pump rotor. The rollers on the pump rotor move the fluid by periodically compressing the tubes. The users sets a flow rate or rpm which corresponds to the mean value of the pulsatile flow delivered by the instrument. The amplitude and frequency of the pulsations depend on the internal diameter of the fluidic tubing, the number of rollers and their rotation speed. The flow rate of such instruments ranges from 2µL/min to more than 10L/min.

Peristaltic pumps are broadly used to to recirculate as well as to dispense large volumes.

volumetric control peristaltic pump

Figure 1: Peristaltic pump

Advantages:

Price: This method of fluid delivery is relatively inexpensive.

Easy to use: Peristaltic pumps are easy to use and to connect.

High flow rate range: This is a good option for large volumes and high flow rates as well as for fluid recirculation.

Reversible: It can work in both rotation directions. This advantage allows for recircualtion of a fluid, wich can be useful for some biological applications.

Throughput: Depending in the rotor design, up to 24 samples can be perfused in parallel.  

Sealing: The rotational effect of the rollers on the rotor causes the displacement of the sealing pressure all along the tube, minimizing any leakage or backflow.

Drawbacks:

Pulsatile flow: The flow delivered by peristaltic pumps is pulsatile due to the compression of the tubing, (as shown on the graph below). This is not suitable for most microfluidic applications where the flow rate has to be constant. As an example, some cells may be highly sensitive to shear stress, this acute pulsation can activate an inflammatory reponse. [1]

No complex flow profiles available: Since the flow is pulatile complex flow patterns such as ramps, pulses or sine waves cannot be achieved.

No pressure control:  The only parameter that is accessible and can be set on a peristaltic pump is the mean flow rate delivered by the instrument.  There is no control on the pressure applied to the fluid, which may be an issue for microbiology studies where pressure control on the cells is needed.

Response time: Because of the pulsatile flow, it is difficult to determine the response time of this device.

Experimental results:

A 25µL/min flow rate was set on a peristaltic pump and the flow rate was measured with the flow-unit.

Peristaltic flow rate graph                 
             Figure 2: Graph of the flow rate delivered by a peristaltic pump over time depending on the internal diameter of the tubing

 

Using the tubing’s internal diameter of 0.64 mm, the flow varied between 0-35µL/min over a period of 270 seconds. Although the average flow rate was around the set value (25µL/min) it sometimes reached negative values. Nevertheless, the periodicity and the pattern of the oscillation are reproducible over time.

Using a tubing with an internal diameter of 0.51 mm, a decrease of both the amplitude and the period was observed.  This experiment shows that decreasing the internal diameter of tubing induces more oscillations, but also reduces flow variations.

In conclusion, the influence of the internal diameter of the tubing on the flow rate pattern is important and should be carrefully selected depending on the application.

Syringe pumps:

Syringe Pumps are widely used in millifluidic (biomedical field) and in microfluidic applications. Once a syringe is filled with the liquid of interest, it is placed on the syringe pump, based on a moving piston which is pushed (or pulled) by a motor Figure 3.  The force applied on the syringe piston by the motor’s rotation of a screw corresponds to the flow rate. A large range of quality and price exist in the market, delivering flow rates ranging from 0.012 nL/min to 300 mL/min.

Syringe Pump

Figure 3: Syringe Pump

Advantages:

Stability: Syringe pumps are designed to deliver stable, constant flow rate. Depending on the quality of the syringe pump, the oscillation induced by the rotation of the motor and screw drive can be reduced.

Easy to use: Intuitive user interfaces make them very easy to use.

Accuracy: Working with the right syringe volume (2mL) and type (glass) and with a quality syringe pump enables one to deliver volumes down to the nanoliter scale.

Throughput: For some models, up to 10 samples can be perfused in parallel, with one single pusher.

Drawbacks:

Volume limitations: Syringe pumps are limited by the syringe volume.

No pressure control: As for perstaltic pumps, there is no control on pressure applied on the fluid, which can create issues for biological applications. High pressure can induce mechanical stress on cells.

Solution homogeneity:  Syringe pumps are not the best instruments to mix cells in solution. As the syringes do not move, cells in suspension can sediment.

Experimental results:

Commands of 5 µL/min, and then 25 µL/min flow rates were sent to the syringe pump and the flow rate was measured with the Fluigent’s Flow-Unit.

 

Syringe Pump Flow rate Graph

Figure 4: Graph of the response time of a syringe pump

 

The flow rate set on the syringe pump is represented in orange and the flow-rate effectively delivered by the syringe pump and measured by the flow meter is represented in blue. After the command to switch from 5 µL/min to 25 µL/min flow rate was sent, the flow delivered by the syringe pump increased slowly to reach the set value.

The response time was estimated to be 1: 43min; which can be too long for many applications. For instance, stop flow lithography needs sharpe stop-flow transitions in order to generate reproducible hydrogel particles.

Stability and Accuracy Flo rate Syringe Pump

Figure 5: Graph of the stability of the flow rate delivered by a syringe pump

 

To assess the stability of syringe pumps, the flow rate was recorded once the pump was stabilized at 25µL/min. The variation obtained was about 0.4% of the desired value. This high stability demonstrates the precision of  syringe pumps.

Pressure driven pumps (pressure controllers):

Pressure controllers control the flow rate by applying a pressure to a sealed reservoir. The pressure applied by the air above the liquid surface pushes the liquid out of the reservoir through the microfluidic tubing. Either pressure or flow rate can be controlled with this device. The flow rate can be recorded by adding a flowmeter in the fluidic line. The flow rate can be set by the flowmeter through a feedback loop that regulates the pressure.

Advantages:

Reactivity: Pressure controllers have a very fast response time (see figure 7).

Pressure control: Pressure controllers are the only device available to measure and control  the pressure applied to a system. This is more consistent with physiological conditions  i.e blood pressure, ocular pressure, etc.. In addition, working with a pressure controller and a flowmeter is the only combination that gives access to the resistance of the microfluidic circuit. In the microfluidic circuit, flow rate and pressure drop are related as follows: (?P=Q*R) controlling the pressure and recording the flowrate enables to measure the resistance of the system.

Flow profile range: Thanks to the high response time of pressure based flow controllers, complex flow patterns can be generated. This can be useful to reproduce complex flow patterns such as aortic pressure.

Stability: Due to the excellent regulation of the gas pressure controllers, one may achieve flow rates with high stability from nanoliter/min to milliliter/min. For example,  laminar flow  in  blood capillaries can be faithfully reproduced. Stable flow is essential to maintain the physiological phenotype of  endothelial cells that are highly responsive  to shear stress.

Versatile system: Coupling the pressure controller with  flow rate sensors enables one to monitor flow rate and pressure during the course of an experiment. Either the flow rate or the pressure can be set and the resultin in terms of the respective pressure or flow rate variations can recorded. This can be particularly useful to evaluate changes in resistance of a fluidic system during the experiment. Pressure and flow rate are related following the linear equation: P= Q x R (P: pressure, Q flow rate, R resistance of the system). Pressure adjustments required to maintain  constant flow rate directly correlate with a change in resistance.

Gas composition: Pressure controllers can be interfaced with any compressed air source. Therefore, the user can select the composition of the gas that pressurizes the liquid. This is particularly useful for cell biologists that usually buffer cell culture media with 5% CO2.

Resevoirs:  Pressure controllers are compatible with a range of reservoirs from mL to liter sizeThis is a major advantage compared to syringe pumps.

Combination of fluidic functions: Pressure controllers can be easily interfaced with switching valves to combine fluidic functions (injection, sampling, recirculation) and fully automate protocols.

Microfluidic Setup Pressure Controller

Figure 6: Scheme of a microfluidic set up controlled with a pressure controller

Drawbacks:

Nano-volume injection: Due to the measurement errors of the flow sensors, this technology is not the most effective to inject volumes smaller than 1µL.

Flow sensor: To control or monitor flow rates, flow sensors should be added in the microfuidic circuit. Additional connections are  needed which increase the total internal volume of the flow path.

Pressure source: A compressed air source is needed to use pressure controllers.

Experimental results:

Commands of 5 µL/min, and then 25 µL/min flow rate waere sent to the 1 Bar LineUP™ Flow-EZ™ .The flow rate was measured with the Fluigent’s Flow-Unit.

LineUP™ Flow-EZ™ Pressure controller Flow rate Graph

Figure 7: Graph of the response time of a LineUP™ Flow-EZ™

 

The  pressure  instantaneously switches from 5 µL/min to the 25 µL/min flow rate. The response time obtained was about 5 seconds, which is significantly faster than other devices (for instance, it’s 1280% faster than for syringe pumps).

Stability LineUP™ Flow-EZ™ Pressure Controller

Figure 8: Graph of the stability of the flow rate delivered by a LineUP™ Flow-EZ™

 

As for syringe pumps, the flow stability was assessed at 25 µL/min. The variation was approx. 0.3%. which demonstrates the stability of the LineUP™ Flow-EZ™.

Advantages/disadvantages of each type of microfluidics pumps

Peristaltic pump Syringe pump Pressure driven pump
 Flow stability Low High Excellent
    Response time High Low Excellent
Precision Bad Medium Excellent
Volume limitation (for the liquid to be injected) None Yes (depends on the syringe volume) None
 Fluid recirculation Possible Not possible Possible (with an additional switch)
Injection of small volume sample Bad Good (use very small volume syringe) Medium (Difficult for less than 1µL)
 Gas injection No No Yes
 Sample agitation Possible (as the sample is in separated reservoir) Not possible Possible (as the sample is in separated reservoir)
 Sample T°C control Possible (you can put the reservoir in thermal bath) Not possible Possible (you can put the reservoir in thermal bath)
Possibility to create (program) complex flow profile No Yes Yes (LineUp series)
Pressure control No No Yes
Flow rate control Yes (but need calibration) Yes Yes (if a flow sensor is added)
High flow rates Yes Not suitable as it is difficult to refill the syringe Yes

REFERENCES

  • [1] High pulsatility flow induces acute endothelial inflammation through overpolarising cells to activate NF-kB, Min Li et al, Cardiovasc Eng Technol, 2013;4(1):26-38.
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