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Fluid mixing at microscale

What is fluid mixing?

mixing plug and play microfluidic setup

Fluid mixing represents a unit operation in industrial process engineering that involves the handling of a heterogeneous physical (gas or liquid) system to make it more homogeneous. Fluid mixing is for instance, employed to enhance  heat and/or mass transfer between various components of a single system.

Fluid mixing can be described as the incorporation of one immiscible liquid into another immiscible liquid. For instance while making emulsions (water in oil or oil in water).

Fluid mixing can also imply the incorporation of gas into a liquid phase. For example, when a foam is being generated by injecting gas at high-shear rate into a solution containing soap.

What drives fluid mixing at microscale?

Fluid mixing at micro-scale behaves very differently than at macro-scale. Indeed, at this scale, diffusion is dominant and normal advection does not occur unless it is forced by a hydraulic pressure gradient.

Diffusion is a slow mechanism. Therefore, many researchers looked for ways to enhance fluid mixing, and created microfluidic micromixers. 

To evaluate the mixing efficiency, and the dominant mechanisms at stake during the mixing process, an adimensional number named the Peclet number (Pe) is commonly employed – It describes the ratio of advection to diffusion. For Pe > 1:  advection dominates & For Pe < 1, diffusion dominates.

Pe = (flow velocity × mixing path) / diffusion coefficient

Active development and improvement of microfluidic devices have led to make tremendous progress in various engineering fields of application from biomedical diagnostics studies, development of miniaturized microfluidic and nanofluidic biosensors, in DNA analysis, chemical synthesis to genomics studies.

Indeed, the channel dimensions in microfluidic systems are measured in micrometers. This allows the operator to decrease drastically sample/reagent consumption which is an important advantage for many fields of application.

How to implement fluid mixing at microscale?

Sample flow at microscale is laminar which corresponds to a small Reynolds number. Thus, in such a laminar flow, traditional turbulent mixing between two liquids cannot occur. Nevertheless, controllable and fast mixing is critical for many field of application which led to many subsequent practical development of microfluidic and lab-on-chip devices often used for assays involving many reagents and samples.

Numerous microfluidic techniques were found by researchers to enhance mixing from the use of Y junction and T junction devices, three-way intersections and designs where the interfacial area between the two fluids is enhanced to twisting channels (multilayered, looped, wavy) to force two fluids to mix.

Serpentine micromixer pilot pack montage

Example of microfluidic serpentine mixer in a microfluidic setup

Various microfluidic fluid mixers were developed over the past two decades. Two categories of microfluidic fluid mixers: passive and active fluid mixers.

Microfluidic passive mixers with elongated channels allow to enforce diffusion mixing with for instance so-called “herringbone” mixing structure.

Microfluidic active mixers with integrated stir bars enable to generate mixtures with a wider range of mixing ratios (up to 1:10 mixing ratio) such as serpentine mixers.

What are the differences between passive vs active fluid mixers?

Passive microfluidic fluid mixers

Passive microfluidic mixing implies that no active elements are involved in the mixing process. In this case, channels geometry is designed to increase the contact area or/and the contact time between the fluids involved in the mixing process.

The first passive method to increase mixing between liquids involves enhancing diffusive effects between samples. To do so, samples can be flowed through various holes incorporated in a microfluidic chip, or samples can be split between multiple smaller channels.

The second passive approach is to increase the contact area and the duration of contact between the two fluids to be mixed.

Depending on the type of passive micromixer, mixing time can vary from tens to hundreds of milliseconds (see Table I).

Table I: Comparative table of performances for different passive micromixers (2).

Comparison of different passive micro mixers

Microfluidic passive micromixers also comprise of the following:

  • T and Y Shaped microfluidic mixers
  • Microfluidic mixing using lamination
  • Hydrodynamic flow-focusing microfluidic mixer

Please refer to “Microfluidic mixers – a short review” for more insights.

Active microfluidic fluid mixers

In an active approach, mixing efficiency is increased by external forces applied to the samples.

To perform active microfluidic mixing, specific mechanical transducers should be incorporated into the microfluidic chip.

To implement “active” fluid mixing, various techniques can be used from acoustic waves, pressure perturbations, magnetic field, and thermal methods. For example, generation of acoustic waves in the mixing area will increase interfusion between samples. However the involved external forces could influence the studied samples. Another drawback for active approach can be found for ultrasonic waves: they can provoke non negligible sample heating that can cause undesirable reactions between the samples specifically for biological application where samples are very sensitive to external perturbations and temperature variations. Mixing time and effectiveness depend also on the type of active mixer (see Table II).

Table II: Comparative table of performances of different active micromixers (2).

Comparison of different active micro mixers

However, mixing efficiency can be increased by the combination of active and passive methods resulting in  more complex channel geometries. Microfluidic active micromixers also comprise the following:

  • Mixing using pressure field disturbance
  • Electrokinetic active micro-mixer
  • Ultrasound microfluidic mixing

Please refer to “Microfluidic mixers – a short review” for more insights

  1. Soo Kyung Kwona,Songzi Koua, Ha Na Kima, Xiaoqiang Chena et al, Tetrahedron Letters, V. 49, Issue 26, pp 4102–4105 (2008).
  2. Chian-Yen Lee, Chin-Lung Chang et al, Int. J. Mol. Sci. V. 12, pp. 3263-3287 (2011).
  3. L. Capretto, W. Cheng, M. Hill, and X. Zhang, Top Curr Chem V. 304, pp. 27–68 (2011).
  4. Nguyen N-T, Wu Z. Micromixers—a review. J Micromechanics Microengineering. 2005;15(2):R1.
  5. Junghun Cha, Jinseok et al, J. Micromech. Microeng. V. 16, pp. 1778–1782 (2006).
  6. J. Knight, A. Vishwanath, J. Brody and R. Austin, Phys Rev Lett V 80, pp. 3863–3866 (1998).
  7. Yiou Wang, Prashanta Dutta, Benjamin T. Chung and Jiang Zhe, J. Fluids Eng. V. 129, pp. 395-403 (2006).
  8. Daniel Ahmed, Xiaole Mao, Bala Krishna Juluri and Tony Jun Huang, Microfluid Nanofluid V. 7, pp. 727–731 (2009).
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