Quantification of Microscale Mixing Time with Microfluidic Mixer System

By AZoNano.com Staff Writers

Topics Covered

Experimental Setup
Experimental Results
About Dolomite Microfluidics


The commercialization of microreactor technologies and their adoption across many different industries has given rise to a need for accurate, dependable blending systems for small volumes of liquids. Miniaturizing mixers leads to more efficient and more complete mixing, as well as providing many other benefits.

However, the very small dimensions involved in micromixers mean that the liquids will be in laminar flow. This produces diffusion-dominated mixing, which may produce relatively long mixing times in channels under 100um in diameter.

The presence of macromolecules can also affect diffusion due to their large size, potentially lowering diffusion coefficients by one or two orders of magnitude. In scenarios like these, augmented mixing techniques can be considered to maintain the benefits of miniaturization.

No additional energy input is required in passive mixing, which promotes homogenous mixing through a split-and-recombine approach. Ramping up flow rates is another ability of passive mixing that contributes the advantages of chaotic advection to improve mixing. Dolomite has incorporated these key features in the design of its micromixer microfluidic devices, thereby facilitating rapid mixing.

A typical micromixer system consists of the microfluidic device, fluidic elements, precision pumping and relevant software. The dispense volume or flow rate can be varied over time to control the addition of liquid reagent automatically. Advanced flow rate profiles can also be generated.

This article describes a mixing process involving a rapid chemical reaction that causes a color change as the indication of mixing. Color or intensity changes of a dye or pH indictor are observed and quantified on the microscale during its mixing with a strong alkali. Reaction times under various conditions are parametrically analyzed.

Experimental Setup

The micromixer system is fitted with a syringe pump, but other options such as the Mitos P Pump can be used. The Micromixer Chip is a lamination-based compact glass microfluidic device, which facilitates swift mixing of two or three fluid streams in each of the two independent mixing geometries.

The Micromixer Chip is equipped with an H Interface and a Linear Connector 4-way to provide fluidic connection between the chip and the tubing. Schematic showing the test system setup is depicted in Figure 1.

Figure 1. Schematic showing test system setup.

The two fluids are delivered at volumetric flow rates to the chip using the Mitos Duo XS Pump. FEP tubing is employed to transfer the fluids throughout the system. The single FEP tube is split into two separate FEP tubes leading to the Linear Connector 4-way by a T-Connector ETFE with sodium hydroxide.

The reaction products leave the chip through the same edge as the input. A high speed camera and microscope system is used to visualize the Micromixer Chip.

The chip interface is mounted over a Hotplate Adaptor as depicted in Figure 2. The temperature is set to 25°C to hinder transient effects in the mixing due to changes in ambient temperature.

The hotplate is digitally controlled with an external thermocouple located in the hotplate adaptor for better control over reaction temperature. A maximum temperature setting ascertains safe interference-free operation.

The temperature range is between room temperature and +300°C. The two fluidic components to be mixed are phenolphthalein (organic) and sodium hydroxide (aqueous) solution.

Figure 2. Hotplate Adaptor – Chip Holder H with Chip Interface H and 2 Linear Connector 4-way

Figure 3 illustrates the geometry of the microfluidic device (chip) in detail. The large channel is etched onto the lower piece of the glass (125µm deep, 350µm wide), whereas the smaller ‘herring bone’ channels are etched onto the upper piece (50µm deep, 125µm wide).

The low dead volume of this micromixer chip ensures optimum fluid recovery and facilitates accurate data.

Figure 3. Chip geometry showing connections for using 1 mixing path.

In addition, this micromixer chip enables great access for optical inspection systems by delivering high degree of visibility. With a broad temperature and pressure range as well as outstanding chemical compatibility, this microfluidic micromixer chip is suitable for a myriad of microfluidic applications.

Experimental Results

The validation of the Mitos Micromixer Chip involves mixing of phenolphthalein with sodium hydroxide. The solution color changes to bright pink following the reaction between the fluids. The uniformity in color of the solution is an indicator of the degree of mixing.

A high concentration of sodium hydroxide is used to achieve color change to a great extent in the phenolphthalein. Despite the high pH value, there were no reactions between the substrate and the sodium hydroxide stream. Figure 4 shows a simplified schematic of the fluid flow path in the micromixer stage.

Figure 4. A simplified schematic of the fluid flow path in the micromixer stage

The mixing ability of the Mitos Micromixer Chip is measured by optically determining the extent of color change in the phenolphthalein during the mixing process. More mixing stages are needed at low flow rates due to domination of the diffusional mixing. This leads to an increase in the viscosity.

The number of stages needed for perfect mixing is determined at different viscosities and flow rates. Based on this information, the mixing time is estimated.

Figure 5 is the high magnification image at the junction and in the mixing stages of the Micromixer Chip, showing the gradual color change of the different flows that enter as clear fluids into dark pink. This color change is an indication of mixing.

Figure 5. High magnification image at the junction and in the mixing stages of the Micromixer Chip

It is also possible to evaluate mixing by taking into account the homogeneity of the intensity in the imaged fluid volume. The homogeneity can be measured by estimating the deviation of the pixel intensity values Di in a specific image from the optimum intensity value. The value of Di is zero for a fully mixed channel. Images captured during the data collection process enable analysis of the mixing.

Graphs where 12 or more stages are needed for thorough mixing reveal the lack of complete mixing in the output from the 12 stage mixing chip. Options are to employ a second mixer chip in-line, or return the output as input into the on the same chip (Figure 6). The number of stages needed is determined by extrapolating the image processing data acquired from stage #12.

Figure 6. Flowpath schematic for double mixing option – extending the mixing stages from 12 to 24.

Mixing takes place through the cumulative action of mass diffusion and advection (Figure 7). Mass diffusion means mixing on molecular level and advection means generation of heterogeneous mixture.

The width of the pink streak that shows the reaction rapidly increases due to mass diffusion. Furthermore, the width of the pink streaks lowers with higher flow rates caused by suppressed lateral diffusion.

Figure 7. Left: Low magnification view of the junction. Right: Magnified view of the region marked in the left image.

The compact mixing chip provides an effective combination of diffusive and advective mixing through splitting, stretching, and recombining flow (Figure 8). Most microfluidic chips are dominated by laminar flow as they have low flow rate.

Conversely, the Micromixer Chip is designed to suppress the laminarity of the flow, allowing chaotic advection to dominate. This leads to significant reduction in the mixing length, which decreases continuously with increasing flow rates.

This is the point of transition and provides the basis for decreasing the count of mixing stages needed at higher flow rates.

Figure 8. Top: Laminar flow and diffusive mixing. Bottom: Chaotic flow and advective mixing

Figure 9 shows the plotting of the mixing length as a function of the total flow rate of the fluids in the mixer chip. The minimum length to complete diffusion of a simple microfluidic reactor that assumes laminar flow is inversely proportional to the diffusivity, and directly proportional to the flow rate. The red line represents the mixing strategy applied.

Figure 9. Transition from laminar mixing to chaotic mixing causes a reduction in the mixing length, which is seen in the lower number of mixing stages required for complete mixing.


The results clearly show the efficiency of the Mitos Micromixer chip to mix fluids at different flow rates and at viscosities. The system was shown to be user friendly, with each part easily accessible for inspection.

Moreover, the easy accessibility facilitates process integration as well as integration of more diagnostic components across the system.

The Mitos Micromixer chip is suitable for applications, including nanoparticle synthesis, rapid crystallization, improved reaction selectivity, sample dilution and reaction kinetics. It is also useful in biological procedures, including protein folding, DNA hybridization, immunoassays, enzyme reactions, and cell activation.

About Dolomite Microfluidics

Dolomite is a world leader in Productizing Science™ and an innovator in creating microfluidic devices and solutions. We sell the coolest microfluidic products around the world, often working with partner companies to extend the range of technology available to our customers. Productizing Science™ means creating marketable and commercially successful products from scientific discovery, and Dolomite excels in commercialising microfluidic products which exceed expectations.

We offer modular, standard microfluidic systems benefiting a wide range of applications, always adhering to the principles of having multiple functionalities, scalability, user-friendly design and a cost-effective, flexible solution for our customers.

Moreover, we offer Productizing Science™ as a service, which is a product development & manufacturing partnership creating microfluidic solutions for problems which span an extremely wide range of applications. Customers come to Dolomite with their technical challenges, and Dolomite helps solve these problems using its extensive background technology.

Dolomite also designs & manufactures a wide range of world leading standard components such as OEM products, microfluidic connectors & interfaces, chips, pumps, valves, detectors, sensors & accessories. Finally, we offer design consultancy to create customized chips or connectors and/or a prototyping service for the supply of glass, metal or polymer devices, and custom microfluidic connectors.

This information has been sourced, reviewed and adapted from materials provided by Dolomite Microfluidics.

For more information on this source, please visit Dolomite Microfluidics.

Date Added: May 21, 2014 | Updated: May 21, 2014
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