Point-of-Care

CASE STUDY:

SELF-SUSTAINING
PRESSURE DRIVEN FLOWIN MICROFLUIDICS

Point-of-CarePoint-of-Care

Case Study:

SELF-SUSTAINING
PRESSURE DRIVEN FLOWIN MICROFLUIDICS

Focus topics of this case study:

Contamination-free

Accurate dosing even at very low
flowrates

Miniature in size, cost, power
consumption

Stand-alone/No air pressure line
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Introduction
Microfluidics - the fine art of creation and manipulation of small portions of fluids, often
realized by flow within small, sub-millimeter-scale channels - is coming. What started off
in academia and university labs has now fully arrived in industrial labs and commercial
applications. Yet, commercial use of microfluidics is evolving every day and there is anever-increasing number of interesting use cases ahead of us. The interest in microfluidics
is tremendous – for several reasons. A high precision flow control is facilitated by thesmall dimensions. Further, due to the low volumes involved, microfluidics operates withminimal resources such as space, reagents, and energy, which makes it highly attractive
for portable applications. Based on these advantageous properties, the implementation ofmicrofluidics in commercially available devices for analysis and diagnostics is highlyrelevant to the life science industry. Many life science applications today already benefit
from microfluidics – yet, in order to fully benefit from this advancement with automatedand highly functional devices and equipment, suitable concepts and components areneeded. It is these concepts and components that stand in the spotlight of this case study.

The concept of pressure driven flow in
microfluidics
Microfluidic dosing is one of these use cases ahead, leading to a lot of novel applications
and innovation. Currently, it is widely observed in the modern lab and can, in general, berealized by different approaches to drive a flow. One of them is pressure driven flow,which offers a number of specific advantages, e.g. pulsation-free operation and costeffectiveness. Another advantage particularly useful for contamination-free dosing is thatneither a pressure source nor flow control elements have to come into direct contact withsample fluids, which makes pressure-driven flow a perfect technology for operating
disposable fluidic chips and cartridges intended for one-time use.

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These advantages specific to pressure driven flow are combined with the generaladvantages of microfluidics, such as a minimum use of sample fluids and reagents.
Building on these advantages, microfluidic dosing turns out to be a perfect match to therising number of point-of-care (PoC) applications, especially related to testing anddiagnostics. However, until today, the field of microfluidics is one of largely passive
structures and is therefore fighting with a low level of dosing precision, as active fluid
control encounters various challenges in mobile use:
1.
2.
3.
4.

How to create a mobile pressure source?
How to enable contamination-free fluid handling in a compact system?
Are active components energy-efficient enough to be operated by batteries?
Can an active fluid control system be small and thus portable enough to be used at thePoC?

More generally speaking, the question is: Can the advantages of microfluidics beleveraged in an active and automated system that can be operated outside of wellequipped labs, directly at the PoC?

Yes it can!
In a first step, it is important to create a clear picture of the overall functionality of thedosing system. Once this is reached, the implementation in a miniaturized format needs
to be addressed. The main requirements are:
1. The system should have active fluid control capabilities allowing a certain degree ofautomation to reduce potential errors originating from manual use;
2. The system is intended for use at the Point-of-Care. Therefore it should be a dosing
system that is characterized by small dimensions, weight and low energyconsumption;
3. The system should consist of two separate parts, one that performs the analysis in
direct contact with sample liquids and will therefore be contaminated, but that can bedisposed economically after usage. The second part is reusable and contains theactive components allowing for active and automated fluid control;
4. Dosing should be relatively precise with 5-10% tolerance, which is difficult to achieveby passive components creating pressure and flow.
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Point-of-CareA very good fit for these requirements during the ideation and feasibility stage of thedevelopment is the principle of pressure driven flow. In a pressure driven flow system, apressure source is linked to a fixed volume containing the fluid to be dosed. As thepressure source increases the pressure in this fixed volume the fluid will be displaced
through an outlet channel. By controlling the pressure precisely, dosing of the fluid can becontrolled in a very stable manner. As a consequence, the basic principle of pressure
driven flow builds on a controllable pressure source and a fixed volume to be filled with adosing fluid. The advantage of pressure driven flow becomes clear very quickly. As soon as
the pressure is controlled precisely and electronically, the dosing itself can be automatedwith a high degree of precision. In addition, the control unit (which is the pressure source)
is not in contact with the fluid to be displaced. Therefore, this part will be surely
contamination-free, whereas the fixed volume containing the fluid and the outlet
channels need to be exchanged for each individual experiment or analysis.

Implementing pressure driven flow in an
active microfluidic system
In general, the pressure source used is compressed air which is easily available in onpremises systems or centralized labs. Yet, in order to create a mobile system, the pressuresource and its control need to become mobile. In order to realize this, the necessarycomponents need to be small, lightweight and ideally highly energy-efficient. As aconsequence, we sourced several micro components to realize the overall system,
containing§ 1 piezoelectric micropump to provide sufficient pressure (Bartels Mikrotechnik, model:
mp6 micropump)§ 1 pressure sensor providing a control parameter for closed-loop control of the pump
(Honeywell, ABP series)§ 1 fixed volume (glass cartridge)§ 1 active microvalve to offset pressure in the cartridge and atmospheric pressure inorder to reduce dosing volume/ speed (memetis, custom valve based on model:
bistable valve BV1101)-4-

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The glass cartridge containing the liquid sample is equipped with a special cap having two
openings: the first one ends in the cap above the liquid level (later to be connected to thepump and valves); the second opening ends in a tube at the bottom of the cartridge. Assoon as a positive pressure is applied to the first opening in this setup, liquid will bepressed into the tube and leave the cartridge through the second opening in a continuous,pulsation-free stream. The cartridge and its cap are the only components that come into
direct contact with sample liquid, so that this part of the system can be designed as adisposable, if necessary.
In the next step, a fluidic connection between the sample container (glass cartridge) andthe active components (pump and valves) needs to be established. For this purpose, afluidic manifold is designed and fabricated by 3D-printing from a biocompatible resin. The
pump will act as a pressure source to displace sample liquid from the cartridge, whereas
two valves will be used to quickly turn on and off the overpressure applied to thecartridge. The connector manifold is designed with a T-shaped channel, one branch being
connected to the outlet of the piezo pump in series to a microvalve, the second branchconnected to a second microvalve with its outlet open to the ambient, and the third
branch connected to the cap of the sample cartridge by a tube. This design can be easily
extended to operate multiple cartridges using the same pump, by just adding additional
valves and pressure output lines. The operation principle is schematically shown in Fig. 1.

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Point-of-CareFig. 1: Operation Principle

With this setup, several requirements defined appear to be sufficiently addressed. Yet, it
is important to characterize the system’s performance, in particular in terms of dosing
accuracy. Thus, a high-resolution flow sensor (Sensirion, SLF3x series) is connected to theoutlet tube of the sample cartridge and a pressure sensor (Honeywell, ABP series) iscoupled to the tube between fluid control manifold and sample cartridge cap, using anadditional T-junction.

Discussion of self-sustaining pressure
driven flow system
In order to evaluate the developed self-sustaining pressure driven flow system, therequirements defined above will serve as a guideline.
One key objective defined is to create a system that is composed of active components,
thereby allowing for automated operation. The selected fluid control components allclassify as active components, whereby a Bartels Mikrotechnik mp6 micropump provides
the necessary pressure and memetis microvalves allow for quick start and stop ofpumping.
A second key objective is to create a dosing system that is characterized by smalldimensions, weight and low energy consumption. In order to achieve a system fulfillingthese requirements, the individual components need to stand out in terms of low weight,
size and energy consumption. This holds true for all components used within thepresented system. Bartels Mikrotechnik mp6 micropump demonstrates a very low energy-6-

Point-of-Careconsumption of 150 mW, with high performance in a small package (size: 30 x 15 x 3,8mm³; weight: 2 g).
The bistable microvalves of memetis only require 75mJ per switching. With less than 2gram and an overall size of a sugar cube, this valve is highly portable. All of thecomponents chosen can be operated by a battery. Therefore, the system’s fit to PoCrequirements has successfully been demonstrated.
Third, the system should consist of a disposable part and a reusable unit, thereby allowing
contamination free operation. This is achieved by connecting the pump-valve-system tothe air inlet of the (cheap and potentially disposable) glass cartridge, so that it never getsin touch with the fluid to be dosed.
Lastly, the most crucial requirement remains to be demonstrated: dosing accuracy with 515% tolerance. Based on the setup from Fig. 1 three cases have been investigated:
1. Achieving a defined flow rate by pumping air inside the cartridge utilizing a closedloop principle between liquid flow sensor and micropump
2. Comparing the changing behavior between flow rates actively forced by active valvesand passively without the use of a valve
3. Dosing stop behavior with and without active valves

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Time [s]Flowrate [ul/min]

Flowrate [ul/min]

Flowrate [ul/min]

Pressure [mbar]

Pressure [mbar]

Pressure [mbar]

Fig. 2: PID regulated dosing with micropump and liquid flow sensor-7-300Pressure [mbar]

Flow Rate [µl/min]

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According to the first investigation target, Fig. 2 shows the dosing performance of thepressure driven flow system consisting of the micropump and a liquid flow sensor
measuring the flow that is dosed out of the cartridge. The flow sensor gives back afeedback to a microcontroller that is able to adjust the parameters of the pump driveraligning the correct performance and generating a very accurate flow rate. So even if thepump does not directly transport the medium that is measured by the liquid flow sensor,
it is possible to realize a functioning alignment for the regulation. It is obvious that themeasured pressure follows the defined liquid flow rate. This result supports the fact that apressure regulated system will also be adequate for realizing an indirect dosing system
which allows the user to minimize the contaminated components to a minimum.
Next, one needs to consider the question how shifting between flow rates of the pump oreven stopping the pump, will influence the dosing process. Fig. 3 and Fig. 4 show thebehavior of switching between flow rates of the pump and “waiting” until the system
passively and actively (utilizing active valves) reduces the pressure value that fits to thedesired flow rate of the overall system. From Fig. 3 it is obvious that changing the flowrate from 5 ml/min down to 3 ml/min roughly takes 50 s which is too much for many
applications. Fig. 4 shows a reasonable solution to that problem. Using active valves, thelower flow rate can be adjusted with a much faster response time. In this case the system
is able to switch between 5 ml/min and 4 ml/min within 1 s. In addition, using active
valves to control a change in pressure, a high precision dosing within the set tolerance
range of 5-10% can be achieved.

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Fig. 3: Flow Rate shift - passively-8-300

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Flow Rate [µl/min]

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Fig. 4: Flow Rate shift - actively with active valves

This observation becomes even clearer when investigating the stopping behavior. Fig. 5and Fig. 6 give an impression on how much time it takes to end the dosing process.

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Fig. 5: Stop dosing process - passively

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Fig. 6: Stop dosing process - actively

The combination of a micropump as a pressure source and active valves for pressure
control appears best suited to address the key objective 4, as it enables precise dosing
also in case of a variation in dosing volume.

Conclusion
Using lightweight piezo pumps and shape-memory-driven valves, a self-sustaining pressure
driven flow system was built that has the potential to bring microfluidics into mobile
applications directly at the point-of-care. The system was carefully designed in a way thatomits any contact between sample fluid and the active component, hence it is perfectly
suited for operating disposable sample cartridges, e.g. for medical quick tests, food orenvironmental analyses. Due to their low power consumption, pump and valves can beconveniently powered by battery. The whole microfluidic system can be smaller than acigarette box and does not produce any disturbing noise nor does it dissipate considerable
waste heat. Using a miniaturized pressure driven flow system as presented above, all theadvantages of disposable microfluidic cartridges can be combined with an increased levelof automatization and intelligence – at a competitive price, since the active fluid control
part of the system is reusable.
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Components and systems used
mp6 micropumpby Bartels Mikrotechnik
The available, industrialized and commercialized
example is the mp6 micropump by Bartels
Mikrotechnik GmbH. This micro pump is apositive displacement membrane pump utilizing
piezo buzzers. The alternating displacement of
the piezo actuators lead to the following typical
fluidic values of the pump:§§Liquid flow range (water) = 5 - 8000 µl/minand pressure < 600 mbar
Gas flow range < 25 ml/min and pressure <150 mbar

BV 1101 bistable valve
by memetis
The innovative shape memory actuator
technology developed by memetis GmbH not
only ensures increased miniaturization of fluidic
components and systems but also allows forsilent switching, very low power consumption
and highly flexible customization. The bistable
valve “BV1101” is characterized by high lifetime,a broad range of wetted material options andvery low energy consumption enabling battery
operation.
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Acknowledgement

Our Partner, memetis from Karlsruhe, Germany, was instrumental in defining ourresearch path, whereby we were able to develop a great solution for contamination
free dosing by pressure driven flow. For that, we are extremely grateful, and we arelooking forward to our close collaboration. In case you are interested in the abovedescribed microfluidic components or if you are interested in getting in touch witheither one of us, memetis or Bartels Mikrotechnik, please feel free to contact us. You
can find the contact details below. Also, check out the memetis website to learn more
about their whole portfolio: https://www.memetis.com/en/
Contact memetis:
memetis GmbH
Gablonzer Straße 27
76185 Karlsruhe Germany

Follow memetis:
www.memetis.com
info@memetis.com
Tel: +49-721-47000-240

Bartels Mikrotechnik is a globally active manufacturer and development service
provider in the field of microfluidics. In the microEngineering division, the company
supports industrial customers in the modification, adaptation and new development ofhigh-performance and market-oriented product solutions through the innovative meansof microsystems technology. The second division, microComponents, produces anddistributes microfluidic products and systems, especially for miniaturized and portableapplications. Our key products are micropumps that convey smallest quantities of gases
or liquids and are used in a variety of ways in biotechnology, pharmaceuticals, medicaltechnology and numerous other applications.
Bartels Mikrotechnik with passion for microfluidics!
Contact us:
Bartels Mikrotechnik GmbH
Konrad-Adenauer-Allee 1144263 Dortmund Germany

Follow Bartels:www.bartels-mikrotechnik.de
info@bartels-mikrotechnik.de
Tel: +49-231-47730-500- 12 -