Microfluidic low-flow liquid flow meter : a review
Liquid flow meters are compulsory elements of microfluidic systems requiring a control of the sample volume dispensed and/or, obviously, the sample flow rate (e.g. to avoid cellular stress).
Many liquid flow meters have been developed for large scale industries like food & beverage, pharmaceuticals or oil & gas companies, but microfluidics require rather high-accuracy low-flow liquid flow meters for the microliters and nanoliters per minutes range.
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This review will focus on low-liquid flow meters that thus can be easily used for all microfluidic applications. Since microfluidics are quite recent, we will see that many flow-sensing technologies are not yet well adapted.
Many sensor technologies can be used. The main ones are presented here, with their respective advantages and drawbacks discussed. For most researchers it remains crucial to carefully choose flow sensors, since when using a high-precision microfluidic flow controller it remains the most limiting element of the setup .
These technologies are listed here by their physical domains.
Thermal low-flow liquid flow meters
There are 3 main categories of thermal low-flow liquid flow meters:
Calorimetric low-flow liquid flow meter
A calorimetric thermal low-flow liquid flow meter measures the asymmetry of a temperature profile modulated by the fluid flow by using 2 different heat sensors surrounding a central heating element.
These types of sensors are the ones used for the Elveflow microfluidic liquid flow meter because they are highly sensitive and then can measure ultra low flow rates (e.g. nl/min).
Because of the symetric position of the sensors, flow with both directions also can be easily quantified.
Hot wire low-flow liquid flow meters
Those thermal low-flow liquid flow meters measure the effect of the flowing fluid on a resistive element which it is used also as the heat sensor. The sensors work in 2 modes:
- they measure the resistance modification with a constant heating power to then determine the corresponding cooling flow value.
- they measure the increase of heating power to maintain a constant heater temperature. This mode involves a feedback loop and is thus more complicated to implement but yields a better resolution and frequency response .
Since these hot-wire low-flow liquid flow meters require a unique heating and sensing element, they are easier to conceive than other thermal low-flow liquid flow meters.
Nevertheless, they require a preliminary characterization to correlate the fluid flow with the resistance/power measurements and also materials with both a high resistivity for a good heat sensitivity (thus a good flow rate sensitivity) and a good temperature coefficient of resistivity which correlates the resistance with the flow rate .
Time-of-flight low-flow liquid flow meters
These thermal low-flow liquid flow meters measure the transit time of a heat pulse over a known distance. For that, one heater is placed upstream and one sensor downstream.
The heater must be thus thermally isolated from the sensor.
Compared to the other types of thermal liquid flow meters, thermal time-of-flight liquid flow meters are much less developed. This may be due to the fact that at low-flow rates, thermal diffusion can mask more easily the sensor signals .
Unlike hot-wire and calorimetric low-flow liquid flow meters, the asymmetry of this type of thermal sensors complicates its use for liquid flowing in both directions.
From Kuo et al. Micromachines 2012 .
In general for all these thermal technologies, thermal low-flow liquid flow meters present the advantages to have a great sensitivity, especially for low flow rates used in microfluidics (e.g. 70 nl/min), and a large measurement range.
Nevertheless, thermal low-flow liquid flow meters are non-linear over their temperature range (i.e. sensitivity non constant) and therefore require some correction process. Thermal sensors are also highly sensitive to the presence of dust and thus require a thorough cleaning process after each use [4,5]. Finally, since these technologies rely on the sample thermal properties, different calibrations are required for samples with different thermal properties.
Mechanical low-flow liquid flow meters
Differential pressure low-flow liquid flow meters
These low-flow liquid flow meters are based on Bernoulli’s laws from fluid mechanics stating that flow velocity variations are correlated with pressure drops.
Thus, by adding restrictions within the fluid channel, the increased velocity along the restriction induces a pressure drop measured with connected pressure sensors and then correlated with flow velocity and consequently flow rate.
In general, differential pressure low-flow liquid flow meters have two main advantages: their conception and fabrication are relatively easy, they are power efficient.
Nevertheless, the main issue for high-performance differential pressure low-flow liquid flow meters is to increase the detection sensitivity so that the interference due to the sensor on the flow is reduced (e.g. increased fluidic resistance) while a high level of measurement accuracy is maintained . Indeed, this fluidic resistance increase can particularly be a problem for microfluidic applications already presenting a high fluidic resistance, even more at a low flow range (e.g. tens of nl/min).
Positive displacement meter low-flow liquid flow meters
This type of low-flow liquid flow meter implies that the sample flow displaces mechanically components with known volumes. By recording the amount of displaced elements, one can then determine the flow volume.
The sensitivity of this type of sensor at low flow rate is so limited by the components dimensions and mechanical sensitivity. This type of system is thus rather useful for large fluidic systems than for microfluidics due to their incapacity to quantify low flow rates (minimum range ∼ 20ml/min). The interaction of the measurement unit with samples may be also problematic for assays with sensitive sample.
Nevertheless, this detection method is very accurate.
Coriolis low-flow liquid flow meters
The Coriolis flow sensors are actually Coriolis mass flow sensors. They are resonators of one or several tubes oscillating thanks to an external exciter (e.g. an electrode).
The sample flowing within these tubes modify their mass and thus make them twist in the perpendicular direction, modification detected by an external sensing system (e.g. optics).
This movement is correlated to the mass flowing within the tubes and thus the flow rate.
As for positive displacement flow sensors, Coriolis flow sensors are rather used for large volume applications due to the weak Coriolis forces . Minimum ranges for microfluidic applications can reach ∼ 2 µl/min (∼ 28 times higher than with thermal low-flow sensors).
From Haneveld et al., IEEE MEMS 2008 .
Nowadays, MEMS technology is used to develop integrated Coriolis flow sensor for low flow rate ranges used for example in microfluidic applications [7,8] but industrial systems for these applications are still lacking. To cover en even broader flow rate range, integrated thermal and Coriolis can be combined .
Another problem of Coriolis flow sensors is the dependence of flow density to determine flow rate which requires thus a temperature compensation .
Cantilever low-flow liquid flow meters
Cantilever low-flow liquid flow meters are cantilever microstructures placed perpendicularly within the fluid flow thus measuring the flow rate by the cantilever deflection or inflection. To quantify this displacement, piezoelectric microresistors placed on the cantilever structure is the sensing technology most often used but optical detection can also be employed.
Interestingly, academic devices show a potential very high sensitivity thanks to miniaturization technologies (e.g. 1 nl/min ).
On the other hand, like with sensitive thermal low-flow liquid flow meters, dust and other residues may disturb the sensor functioning. In addition, the direct contact of the sensor with potential sensitive species within the sample flow is even more invasive than thermal flow sensors.
From Wang et al., Symposium on Design, Test, Integration and Packaging of MEMS/MOEMS 2008 .
Cantilever low-flow liquid flow meters may also be expensive to manufacture due to their complex fabrication process which can explain why, like integrated Coriolis low-flow liquid flow meters, industrial cantilever flow sensors for microfluidics are still currently lacking and devices rather remain academic prototypes.
Vortex low-flow liquid flow meters
Vortex flow sensors use a bluff body through a sample flow. This obstacle create vortexes right behind it and alternatively from each of its sides.
The frequency of these alternating vortexes is correlated to the flow velocity and measured thanks to a mechanical piezoelectric sensor or an ultrasonic beam placed in the vortexes path.
For low flow rate ranges, vortexes may be too weak to be detected. In this case, a channel restriction may be needed to increase flow section and thus velocity. Like with differential pressure low-flow liquid flow meters, this kind of set-up can be so complicated for versatile applications of vortex flow sensors and notably microfluidics using already narrow channels. Vortex flow sensors are rather adapted to the industrial handling of very large volume since its minimal flow rate range remains around several liters per minutes.
In general for all these technologies, mechanical low-flow liquid flow meters present the advantage to be well adapted to large volume analysis but, on the other hand, are not yet applicable for microfluidics and its much lower flow-rates under the µL/min range, even if development in this field is on-going.
Acoustic-Ultrasonic low-flow liquid flow meters
Acoustic flow sensors are actually ultrasonic flow sensors. The main ultrasonic technology for flow sensing uses the fact that ultrasonic signals propagate faster in the flow direction than in its opposite direction. These sensors are often called time-of-flight ultrasonic flow sensors or transit-times ultrasonic flow sensors.
For this purpose, ultrasonic transducers are placed so that ultrasonic pulses will be propagated in the flow direction and in its opposite way. Therefore, the ultrasonic pulses propagated in the flow direction accelerate while the ones propagated in the opposite direction are slowed down. The differential transit times of these ultrasonic signals are thus proportional to the fluid velocity.
Note that the acoustic transducers can be placed so the acoustic waves can be either directly propagated between them or either reflected in the fluid channel.
One main advantage of acoustic flow sensor is that they can be used by avoiding any contact with samples and thus yields a totally non-invasive measurement method like with clamp-on sensors for example. They also can be used for very large flow volume (e.g. 4m diameter tube).
Nevertheless, ultrasonic transit-time flow sensors are very sensitive to perturbations like air bubbles or particles in high concentration which can attenuate acoustic signals. Flows must also be laminar to avoid any acoustic dispersion.
For fluid with particles, ultrasonic Doppler flow sensor can rather be used. Like their name implies, they apply the Doppler effect, i.e. the frequency shift between the transmitted and the reflected acoustic signals from the moving particles within the fluid. So, importantly, the particles within these fluids need to be reflective.
We see here a major problem of acoustic low-flow liquid flow meters: their versatility for the diverse microfluidic applications and samples.
For lab-on-chip and integration purpose, surface acoustic wave (SAW) flow sensors are also currently developed .
Optical low-flow liquid flow meters
Optical Doppler low-flow liquid flow meters
Basically, this technique relays on the same Doppler effect than the ultrasonic Doppler flow sensors but with the detection of laser beams frequency shift. As ultrasonic flow sensors, they can be totally non invasive since they can be placed out of the sample flow.
The much shorter optical wavelengths enable to analyze low flow rates undetectable with ultrasonic sensors.
Nevertheless, this technique is limited by high background noise and low signals due to multiple scattering.
Particle Image Velocimetry
Particle injected in the sample can be used to measure its velocity and other useful properties.
For this purpose, glass or plastic micrometric beads with a refractive index different than the medium one are used with high-speed camera and adapted laser.
Since this technique requires complex setup and is obviously invasive, it is more used in research and education. It also can be implemented for microfluidic assays though .
Electro-Magnetic low-flow liquid flow meters
Electro-magnetic flow sensors use field coils to generate a constant magnetic field across sample way. Sensing electrodes are placed perpendicularly to this field coils.
Magnetic field applies force to charged particles carried in the sample flow and so negatively and positively charged particles are separated and thus create a voltage detected by the electrodes. This voltage is proportional to the flow velocity.
Electro-magnetic flow sensors can be very precise (0,2% ) due to the electronic-magnetic detection technology but it requires to use conductive samples and to carefully isolate the sample channel with the measuring electrodes.
From efunda website .
It is important to carefully choose flow sensors since using a high precision microfluidic flow controller remains the most limiting element of the setup. Currently, thermal low-flow liquid flow meters remains the most relevant sensing technique for microfluidics due to their accuracy and large flow rate range, covering especially the low flow rates used in microfluidics.
Optical low flow liquid sensors still have some practical issues.
Besides, mechanical and acoustic low flow liquid sensors present some great potentialities. Indeed, other techniques based on MEMS and micro technologies like notably Coriolis, cantilever and SAW flow sensors are currently developed and could later represent interesting alternatives with better sensitivities and ranges.
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For more tutorial about microfluidics, please visit our other tutorials here: «Microfluidics tutorials». The photos in this article come from the Elveflow® data bank, Wikipedia or elsewhere if precised. Article written by Timothée Houssin.
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