Mixing Within Droplets: Solving Dispersion Issues with Microfluidics


Droplet-based microfluidics offers a straightforward solution for mixing reagents and controlling reactions on a chip. Droplet generation at micro scales has numerous applications in Life Sciences research and the pharmaceutical industry, especially in drug screening.

But before you start working with this technique, your lab should meet a few basic requirements. This article will discuss droplet microfluidics for sample and reagent mixing. We´ll also show you the materials needed to start your experiments right away.


Dispersion and mixing challenges and droplet microfluidics

Working with microscales brings several benefits like low sample and reagent consumption, minimal human intervention, decreased error chances, and high sensitivity. But some sample or reagent dispersion and mixing problems may arise, [1].

Because of that, researchers developed microfluidic devices to improve mixing, and control dispersion. One way of achieving that is by isolating the aqueous phase in an immiscible carrier fluid, [1]. But researchers discovered that the mixing process was still slow in continuous microfluidics due to the predominant laminar flow, and there was a considerable contamination risk, [2].

Droplet-based microfluidics solves this issue as molecules are encapsulated into separate droplets along the microchannel, [2]. These droplets of uniform size can easily move through the microfluidic channel while the solute concentration remains unchanged, [1]. The cross-contamination risk is significantly smaller since the analytes of interest are isolated inside the droplets, [2].

However, many applications require a complete mixing of multiple reagents. In this case, it may be necessary to create droplets containing multiple reagents or merge droplets containing reactants. So, although the dispersion problem is solved, we still have some mixing issues, [1].


How to control reactions on a chip?

Once you generate these merged droplets, you may control the rate at which their components mix. Some components require a quicker mixing than others. Also, you may need to mix all of these components faster than diffusion allows thoroughly, [1].

Without any mixing strategy, the components will mix within the droplet by diffusion. In the presence of immiscible reactants, the products remain in the interface for some time affecting the flow, [1].

Factors affecting the mixing rate

The mixing rate within the moving droplet depends on several factors such as:

  • Reagents position

  • Capillary size

  • Droplet/capillary ratio

  • Flow rate

One of the most effective strategies for rapid mixing is controlling the droplet size in relation to the capillary size. The optimal droplet size is about 1-2 times the channel height, [1].

In droplet microfluidics, the circular flow produced by shear for the droplets touching the solid channel walls enhances mixing.

Additionally, flowing the droplets through microchannels containing bends and turns creates a chaotic advection phenomenon. This geometry manipulation stretches and folds the fluid halves inside the droplets, improving mixing further, [2]. Incorporating an alternative path direction such as a bend or serpentine pattern may also help.


How viscosity affects mixing?

Microfluidic solutions are often concentrated and contain additives like polyethylene glycol, which increases their viscosity in relation to water or dilute buffers. This is the case of enzymes used in drug screening, [1].

Surprisingly, viscosity differences don´t seem to affect mixing. In many conditions, the mixing speed is actually faster than for reagents with similar viscosities. Additionally, putting the higher viscosity material to the front or back of a droplet may also decrease mixing time, [1].


What do you need to get started?

Running reactions in droplets offers many advantages such as robust mixing, fast mass and heat transfer, lower reagent use, and lower exposure to hazardous material. The technique is versatile and allows various applications, including gene expression analysis to drug discovery and screening, [2].

If you're interested in taking this technique into your lab, you're going to need some basic materials.


  • 2 x Microfluidic pumps (or 2x channels on one pump) – to control the flow of the continuous (oil) phase and dispersed (water) phase. Depending on the application, we recommend the 4U pressure pump or 2x ExiGo microfluidic syringe pumps. 4U pressure pump has a stable and accurate flow rate and enables independent control of 4 different channels, controlling both pressure and flow. You can program your flow profile and efficiently manage all the pump features using your smartphone.

  • 2 x Flow sensors to provide feedback of the flow control of both oil and water phases.

  • Microfluidic Chip with appropriate geometry creates droplets to ensure droplet size is optimal.

  • Stable Channel Surface Chemistry to ensure droplet stability.

  • Surfactant stabilizes the interface between the oil and water phase, giving stability to the droplets.

  • Oil for continuous phase to improve droplet stability. Tubing to connect from your pumps to the microfluidic chip.

Cellix can supply the complete kit or just the components you wish. To learn more about our products, contact Cellix or simply request a quote now.


References

  1. Esposito, E. Droplet Microfluidics: Mixing within Droplets. Available: https://openwetware.org/wiki/Droplet_Microfluidics:_Mixing_within_Droplets_-_Edward_Esposito. Access: 02/09/2022.

  2. Hassan, Sammer-ul, Xunli Zhang, and Xize Niu. "Droplet-based microfluidics: formation, detection, and analytical characterization." Research & Development in Material Science 11.5 (2019): 1227-1233.






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