CASE
STUDY

Passive, semi-activeand active fluid mixing
in microfluidics forbioprocesses in lifesciences

December 2022
Author:Florian Siemenroth

Case study: Passive, semi-active and active fluid mixing
December 2022

Microfluidic fluid mixing

Diagnostics, biosensing,
DNA analysis & sequencing

Fluid mixing is the principle of merging two immiscible fluids to a homogenous ratio. As microfluidics
is an enabling technology for bioprocesses in life sciences, mixing plays a very big role in applications
such as biotechnological diagnostics, biosensing, DNA analysis and sequencing, but also in flow
chemistry and micro reaction applications.
In microfluidics, turbulent flow leads to cross-flows which fasten mixing. Adding active mixing
principles like agitation completes the efficient mixing processes. In microfluidics laminar flowcommonly is the governing flow type. The lack of cross-flows leads to the fact diffusion is the governing
mixing principle. Diffusion is a very slow process and this would need very long flow channels which
would lead the characteristics of microfluidics ad absurdum. So, scientists have developed many
principles for introducing cross-flows artificially. Even active mixing is possible at microfluidic footprint.
The objective of this case study is to give a quick overview of the general mixing behavior in
microfluidics and to demonstrate three different mixing principles.

What is microfluidics?

Microfluidics is the fine art of creation and manipulation of small portions of fluids, often realized byflow within small, sub-millimeter-scale channels. These small dimensions allow the fluid flow to becontrolled with exquisite precision (Seifert, Thiele; 2020).

About the mp6 micropump

The available, industrialized and commercialized example is the mp6 micropump by Bartels
Mikrotechnik GmbH. This micro pump is a positive displacement membrane pump utilizing piezo
buzzers. The alternating displacement of the piezo acutators lead to the following typical fluidic valuesof the pump:
▪
#"
#"
▪

Liquids (eta = 1 mPas): q = 5 - 8000 µl/min in free flow and p > 600 mbar
Gas: q > 25 ml/min in free flow and p > 150 mbar

All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Passive, semi-active and active fluid mixing
December 2022

Flow Types
There exist two different flow types in fluid dynamics: Laminar flow and turbulent flow.

Figure 1 Laminar flow (top), Turbulent flow (bottom), Source: https://www.gunt.de/de/produkte/rohrreibung-bei-laminarerturbulenter-stroemung/070.15001/hm150-01/glct-1:pa-119:pr-548

These flow types are described by the nondimensional Reynolds number:𝜌𝑣𝑑𝜂
Whereas ρ is the density, v the flow speed, d a characteristic dimension (commonly diameter) and ηthe viscosity. For Re > 2300 there is turbulent flow, for Re < 2300 there is laminar flow. It is objectivethat variables v and d are governing if one compares micro- and macrofluidics. In microfluidics there
are only very small dimensions and very slow speeds. So laminar flow is usually the governing flow
type.
𝑅𝑒 =Diffusion
Diffusion is the principle of two regimes distributing heterogeneously. It is defined by Fick’s law:
𝜕𝑛𝐽 = −𝐷𝜕𝑥Whereas J is the particle current density, D is the diffusion coefficient, n is the concentration and x isthe path. Diffusion is dependent on temperature and a very slow process. Whether a regime isgoverned by diffusion or advection can be estimated utilizing the Peclet number:
𝐿∗𝑣
𝑃𝑒 =𝑎
Whereas L is the path, v is the flow speed and a the thermal conductivity. For Pe > 1 there is advection
and for Pe < 1 there is diffusion.
In microfluidics there is mainly diffusion. Mixing at high ratios would need very long channels which
would not make sense from the microfluidic perspective. Therefore, cross-flows for advection need tobe introduced. Scientists have researched and developed microfluidic structures that evoke thenecessary advections.

Passive Micro Mixers
Many passive micro mixers have been developed. In this case study, we point out three different types.
The meander and pearl-chain mixer have an increased flow path which leads to an increased diffusion
driven mixture since the contact time is increased. Plus, the pearl-chains evoke cross-flows, soadvection takes place also. In the figure below one can see an example of a pearl-chain mixer byAll values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Passive, semi-active and active fluid mixing
December 2022
microfluidic ChipShop. Two differently colored water samples are induced by two micropumps. The
setup has got a very small, well-plate format. One can see that at the beginning there is only diffusion,
so nearly no mixing process as the colored water samples are separated from each other. As soon asthe two regimes reach the meander, pear-chain structure a more efficient mixture process starts.

Figure 2 Pearl-Chain mixer setup driven by micropumps on a well-plate format

Another option of mixing in microfluidics is the herringbone mixer. It evokes an asymmetric flow
behavior and therefore cross-flows for advection. The speed of the mixing process is increased.

Figure 3 Example of a Herringbone mixer by microfluidic ChipShop
Source: https://www.asicon-tokyo.com/pdf/CS_Catalogue.pdf

A third alternative for mixing is a 3D structured microfluidic chip, the 3D serpentine chip. It forces theflow into different directions. Again, cross-flows for advection is increased and the efficiency of mixing
is boosted.

Figure 4 3D Serpentine mixer by microfludic ChipShop
Source: https://www.asicon-tokyo.com/pdf/CS_Catalogue.pdf
All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Passive, semi-active and active fluid mixing
December 2022
The benefit of these passive processes is- mixing within an in-line flow is possible and- one does not need an active unit which saves space, costs and power.
On the other hand, the mixture results can be poorer than the results from the active mixing processes.

Semi-active mixing
The semi-active principle is an extension of the passive mixing principle. It is based on passive
structures, but it also utilizes active microfluidic units moving a mixture back and forth. That leads toa high contact time within in the mixing region and evokes more advection and a higher mixing ratio
compared to the passive mixing principles. Here, an example is displayed in which one-directional
micropumps have been combined with a logic arrangement of valves realizing a bi-direction flow forpumping liquid column within the pearl-chain mixer realizing a much higher mixture ratio.

Figure 5 Semi-Active Fluid mixing utilizing unidirectional micropumps and logic valve arrangements

Two concepts for semi-active fluid mixing are possible. On the one hand, utilizing two 2/2- way valves
and two micropumps for a separately controllable back and forth way (below on the left). On the otherhand, there is the option of utilizing four 2/2-way valves or two 2/3-way valves and one micropump
decreasing the amount of micropump parameters (below on the right).

Figure 6 Two valve concepts for bi-directional flow utilizing one-directional micropumps

The advantage is that one is able to achieve high mixing ratios, but the issue is that these processes
are appropriate for in-line processes as it always has a percentage of an iterative process.

All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Passive, semi-active and active fluid mixing
December 2022

Active Mixing
A third option of mixing is the full active mixing principles known from macrofluidics, i.e. stirring forinstance. There are industrialized microfluidic structures or chips that offer the possibility of stir bar
activated mixing processes that evoke advection offering an intense ration of mixtures.

Figure 7 Stir bar activated chip by microfluidic ChipShop
Source: https://www.asicon-tokyo.com/pdf/CS_Catalogue.pdf

In these cases, it is hardly possible to realize a dynamic in-line mixing procedure and it has the needof a complex equipment of the microfluidic structures such as adding stir bars. But of course, as
stated before, the mixing result is highly heterogeneous.

Conclusion
As one can see microfluidics is not as trivial as macrofluidics at certain points. Due to its fluid dynamic
characteristics, mixing in microfluidics bares some issues that are uncommon in macrofluidics. Only
relying on diffusion would require very long channels and therefore it would not fit to the idea ofmicrofluidics. Scientists and engineers have developed a bunch of reasonable passive and active
mixing principles that go with many different applications.

Components used••••

mp-Multiboard2 incl. mp6 micropump drivers and valve drivers by Bartels Mikrotechnik
mp6 micropumps by Bartels Mikrotechnik
microfluidic mixer chips by microfluidic Chipshop: Fluidic 286, Fluidic 1079, Fluidic 658 &Fluidic 187
NC-valve series09 by memetis

Acknowledgement:
Our partners microfluidic ChipShop from Jena and memetis from Karlsruhe were instrumental in
defining our research path, whereby we were able to develop great solutions for fluid mixing. For that,
we are extremely grateful and we are looking forward to our close collaboration. In case you areinterested in the above-described microfluidic components or if you are interested in getting in touchwith either one of us, microfluidic ChipShop, Memetis or Bartels Mikrotechnik, please feel free tocontact us. You can find the contact details below.

All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

Case study: Passive, semi-active and active fluid mixing
December 2022

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 of highperformance and market-oriented product solutions through the innovative means ofmicrosystems 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 orliquids 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

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

All values are approximate and no guarantee of specific technical properties.
Changes in the course of technical progress are possible without notice.

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