Microbubbles formation using the RayDrop

Introduction

The microfluidic community is becoming more interested in microbubble formation due to its potential in a variety of applications (industry, life science, medicine, material sciences, etc.) (1).

Controlled generation of microbubbles in microfluidic devices generates great interest in medicine due to the ability to non-invasively image molecular events with targeted microbubbles. In the future, imaging methods will be increasingly commonly used to define pathophysiology as well as to create and test new therapeutic approaches for the treatment of conditions including inflammatory disorders, cancer, and cardiovascular disease (2).

Fundamental medical applications of micron-size bubbles range from ultrasound contrast agents to thrombus destruction, targeted drug delivery, tumor destruction, and even as a flotation column. In addition, intravenous injection of a stabilized solution of sufficiently small bubbles might be used in acute lung dysfunction (4). Microbubble formation can also be used for the study of gas-liquid physical processes such as the dissolution of CO₂ in solvents, CO₂ reaction and sequestration. Closely related to gas bubbles are foams, which are formed by trapping pockets of gas in a liquid or solid (5).

The formation of air bubbles in a liquid appears very similar to the formation of liquid or oil droplets. It begins with an elongation of the flowing material (oil, water or air), and eventually a thinning and pinch-off of the “neck” connecting the droplet or bubble to the flowing material. That pinch-off then allows the droplet or bubble to collapse into a spherical shape.

In microbubble formation, the control of its size and distribution is critical in all the applications mentioned above. Monodisperse microbubbles are more useful for fundamental studies because the interpretation of experimental results is much simpler than that of polydispersed microbubbles. They can also serve as useful systems for measuring important properties of microbubbles (3, 4).

The best production mode to obtain stable and monodispersed droplets and/or microbubbles follows the dripping regime, with the droplet/bubble detaching from the jet at the junction between the two immiscible phases. 

Therefore, in this application note, we demonstrate that a stable and continuous microbubble formation can be achieved using both RayDrop Single Emulsion and RayDrop Double Emulsion technologies. 

In addition, we also studied in depth the parameters that affect microbubble production, such as nozzle geometry and continuous phase flow rate. 

We found that, when using RayDrop Single Emulsion, the low-viscosity continuous phase has little impact on microbubble size formation. Consequently, in this case, the microbubble size is a function of capillary size. Therefore, the nozzle geometry only influences the microbubble size when decoupled from the continuous phase flow.

On the other hand, we found that, using RayDrop Double Emulsion technology, the production of microbubbles with tunable size and a polydispersity index value of less than 1% is possible.

We conclude, therefore, that the process of microbubble formation using the double emulsion RayDrop technique seems to be more suitable for controlling the size and monodispersity of microbubbles.

Experimental procedure

The double emulsion Raydrop (Secoya Technologies) was used to produce microbubbles through the injection of air (core phase) into an aqueous shell phase, further engulfed by the continuous phase (Figure 1). Both the shell and continuous phases are liquid phases made of 1% polyvinyl alcohol solution. Bubbles were formed by pumping the three components with a pressure controller (Flow EZ, Fluigent). Flow rates were controlled using flowmeters (Flow Unit, Fluigent).

Three different geometries were used in this note (Figure 2) to assess the advantages of using double emulsion for accurate bubble size control.

Geometry 1: 

• a = 30 µm
• b = 70 µm
• c = 150 µm

Geometry 2:

• a = 90 µm
• b = 160 µm
• c = 450 µm

Geometry 3:

• a = 90 µm
• c = 450 µm

Figure 2: The three geometries used in the study

Results

Geometry 3 and Geometry 2 were chosen to compare the simple emulsion nozzle with the double emulsion nozzle to produce bubbles and results are presented in Figure 3. This clearly shows the influence of the shell stream on the size of the bubbles.

b) Images from human skin (five cycles, 15 of 19 parameters shown). Scale bars: 200 µm (left), 25 µm (insets). Keratin 10 (K10), Keratin 14 (K14).

Using single emulsion nozzle (Geometry 3) and a low viscosity liquid, the size of the bubbles is almost totally constrained by the geometrical parameters the lowest size will be limited by the diameter of the extraction capillary (Figure 4).

With the double emulsion nozzle (Geometry 1 and 2), the lowest size achievable is determined by both the geometrical parameters and the stream of the shell phase (Figure 5). The presence of the shell phase stream shifts the achievable size range towards lower values.

With constant shell and core flowrates, the increase of the continuous phase has no effect on the bubbles size (see Figure 6).

The geometry of the nozzle-capillary system is the most influential factor on bubble size. To optimize the system one should make the inside diameter of the capillary equivalent to the targeted bubble size. Local restriction can be obtained by using a second nozzle attached on the entry of the extraction capillary (Figure 9). With this specific geometry, air bubbles of 30 µm diameter were generated in water at hundreds kHz.

Download the application note for more results.

References

1. Lindner, Jonathan R. Innovation: Microbubbles in medical imaging: current applications and future directions (2004).  3(6), 527–533. doi:10.1038/nrd1417
2. J. I. Park, A. Saffari, S. Kumar, A. G ̈unther, E. Kumacheva, Microfluidic synthesis of polymer and inorganic particulate materials. Annu. Rev. Mater Res. 40, 415–443 (2010)
3. E. Amstad et al., Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator. Science 349, 956–960 (2015)
4. Mikaela D, Haut B, Scheid B. Bubbly flow and gas-liquid mass transfer in square and circular microchannels for stress-free and rigid interfaces: dissolution model. Microfluid Nanofluid (2015) DOI 10.1007/s10404-015-1619-8
5. Dewandre, A., Rivero Rodriguez, J., Vitry, Y., Sobac, B., & Scheid, B. (2020). Microfluidic droplet generation based on non-embedded co-flow-focusing using 3D printed nozzle. Scientific reports, 10(1), 21616. doi:10.1038/s41598-020-77836-y