Microfluidic mixers : a short review

Why do we need mixing in Microfluidics ?

microfluidic micro mixerActive development and improvement of microfluidic devices have allowed to make significant progress in biomedical diagnostics study, development of miniaturized microfluidic and nanofluidic biosensors, in DNA analysis, chemical synthesis and genomics study, etc. The channel dimensions in microfluidic systems are measured in micrometers and in nanofluidics they go down to nanometers. This allowed to noticeably reduce surface to volume ratios and thus, to decrease samples/reagents consumption and obtain compact devices.

 

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However, sample flows in such miniaturized channels are extremely laminar and not turbulent, which corresponds to small Reynolds number values. Consequently, in such laminar flows, traditional turbulent mixing between two liquids cannot occur. However, controllable and fast mixing is critical for subsequent practical development of microfluidic and lab-on-chip devices often used for assays involving many reagents and samples. That’s why different mixing techniques were developed and studied by various research groups.

Passive micro-mixers in microfluidic devices

In laminar flows,  mixing only occurs through molecular diffusion. Naturally, one method to increase mixing between liquids is to enhance diffusive effects between samples. For that, samples may be flowed through various holes incorporated in the microfluidic chip or sample may be separated between multitudes of smaller channels.

Another approach is to increase the contact area between mixing reagents, as well as the contact time. Both of these concepts belong to the so-called “passive” microfluidic mixing because no active elements are involved in the mixing process. In this case, channels geometry is designed in a way that enables to increase the contact area or/and the contact time between reagents involved in the mixing process. Depending on the type of passive micro mixer, 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

T and Y Shaped micro-mixers

One of the easiest methods of passive mixing is realized with the use of T or Y shaped micro-channels. They consist of two inlets and one outlet. In the case of T shaped micromixers, two inlets microchannels with two mixing samples are flowed perpendicularly to each other (Figure 2.a) and in the case of T shaped micromixers, they are placed at a certain angle. Classically, mixing appears in the contact surface between two fluids and strongly depends on the diffusion process which occurs at the interface. That is why for this type of mixer, mixing time is quite long. However, it can be controlled by varying fluids’ flow rates values (slowing down the flow decreases mixing speed and, in contrast, at high flow rates, mixing time would be reduced). Mixing efficiency can be increased by adding some barriers and obstacles in mixing channels, which creates additional perturbations (Figure 2.b).

(a)Microfluidic T junction 

(b)Microfluidic chaotic mixer with grooves

Figure 2: (a) Example of T shaped microfluidic passive mixer. Fluid 1 and Fluid 2 enters from two separate inlets. Mixing occurs while flowing in the common channel (3). (b) Introduction of grooves in the mixing channel increases mixing efficiency and reduces mixing time (4).

Microfluidic mixing using lamination

Microfluidics Laminar mixers

Figure 3: Schematic representation of the chessboard micromixer: two flows (blue and red) are divided into smaller flows and then divided again into even thinner flows. Diffusion occurs through multiple vials between microchannels. (3, 5)

Another method of passive mixing is the lamination method. It requires the creation of a multitude of thin parallel channels within microfluidic chips. Two (or more) fluids flows are split and then gathered again as a multitude of small streams (Figure 3). This enables to increase contact area between flows. The more channels are involved, the faster the mixing is. For each supplemental n splitting capillary, the mixing speed is faster by a factor of n^2.

Microfluidic mixing using flow focusing

One of the important parameters for mixing efficiency is the mixing path. The shorter it is, the more compact the mixer is. Consequently, it will be easier to integrate in the general scheme of a microfluidic chip. One of the methods enabling the reduction of the mixing pass is mixing through flow focusing. The basic scheme of flow focusing microfluidic mixer consists of three inlets micro-channels and one central outlet channel (Figure 4a). Samples from three inlets flow in parallel in a central channel. Consequently, fluid from middle inlet (focused stream) is enveloped by fluids from side channels (sheath flows). Then, the central stream width is controlled by adjusting the flow rates of sheath flows. Hence, the central stream parameters depend on the flow rate ratio between internal and external flows (Figure 4b). The more significant the flow rate difference is, the thinner is the focused stream, and the shorter the mixing time is. To control such a system, independent control of each flow is required. For that, flow controlling systems with multiple pressure outlets could be used.

hydrodynamic focusing micro mixer

Figure 4: (a) Schematic diagram of hydrodynamic focusing mixer. (b) Examples a-b show influence of the side streams flow rates on the width of the central stream (3, 6).

Active microfluidic micro-mixers

Another important mixing class is called the “active” mixing. In this case, mixing efficiency is increased by external forces applied to the samples. To obtain an active mixing scheme, some specific mechanical transducer should be incorporated into the microfluidic chip. To implement “active” fluid mixing and influence mixing process, different physical phenomenon can be involved: acoustic waves, pressure perturbations, magnetic field, thermal methods. For example, generation of acoustic waves in the mixing zone increases interfusion between samples. However the involved external forces could influence the studied samples. For example, the use of ultrasonic waves could provoke non negligible sample heating which could then cause undesirable or precipitated reactions between mixed samples. Spatially, it is necessecary  to be very accurate with the use of biological samples that are sensitive to external perturbations and temperature variations. As for “passive” mixing, mixing time and efficient mixing zone length varies depending on the type of active micro mixer (see Table II). However, mixing efficiency can be increased by the combination of active methods with passive ones creating complex channels geometry.

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

Comparison of different active micro mixers

Mixing using pressure field disturbance

One method to create local irregularities in laminar flows is to manipulate the pressure field profile inside the channel. For example, it can be done by the integration of micro pumps inside the microchip which would alternatively push and stop the flow. As well, the abrupt change of mixing fluids flows rates can be used for an efficient mixing. The important point noticed by a group in Glasgow is that the mixing efficiency is increased if both flow rates are varied with a 180° phase shift and are perpendicular to each other (2,3).

Electrokinetic active micro-mixer

In case of the electrokinetic active mixing, fluids mixing is activated by the fluctuation of electric field. Electrokinetic instabilities induced by the fluctuation of electric field values induce local squeezing and stretch of the mixing samples at their interfaces. Nevertheless, this method requires fluids with different electric conductivities.

electrokinetic active micro mixer

Figure 5: Schematic model of the electrokinetic active micro-mixers (7).

Ultrasound active microfluidic mixing

acoustic microfluidic micro mixer

Figure 6: Schematic diagram of the microfluidic mixer based on acoustically driven sidewall-trapped microbubbles (8).

Propagation of ultrasonic waves provokes a stirring of the sample fluids. For that, piezoelectric ceramic transducers were integrated into the microfluidic chip. The acoustic waves generated cause fluid mixing in the direction perpendicular to the direction of the flow. To enhance mixing efficiency, the surface exposed to the acoustic waves can be increased, for example by introducing small air bubbles in the mixing zone (3).

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For more tutorials 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 specified. Article written by Guilhem Velvé Casquillas and Timothée Houssin and revised by Lauren Durieux.

References

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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)