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. 2021 Jun:74:105556.
doi: 10.1016/j.ultsonch.2021.105556. Epub 2021 Apr 15.

Ultrasound-assisted production and optimization of mini-emulsions in a microfluidic chip in continuous-flow

Erick Nieves  1 , Giselle Vite  2 , Anna Kozina  2 , Luis F Olguin  3
Affiliations

Ultrasound-assisted production and optimization of mini-emulsions in a microfluidic chip in continuous-flow

Erick Nieves et al. Ultrason Sonochem. 2021 Jun.

Abstract

The use of ultrasound to generate mini-emulsions (50 nm to 1 μm in diameter) and nanoemulsions (mean droplet diameter < 200 nm) is of great relevance in drug delivery, particle synthesis and cosmetic and food industries. Therefore, it is desirable to develop new strategies to obtain new formulations faster and with less reagent consumption. Here, we present a polydimethylsiloxane (PDMS)-based microfluidic device that generates oil-in-water or water-in-oil mini-emulsions in continuous flow employing ultrasound as the driving force. A Langevin piezoelectric attached to the same glass slide as the microdevice provides enough power to create mini-emulsions in a single cycle and without reagents pre-homogenization. By introducing independently four different fluids into the microfluidic platform, it is possible to gradually modify the composition of oil, water and two different surfactants, to determine the most favorable formulation for minimizing droplet diameter and polydispersity, employing less than 500 µL of reagents. It was found that cavitation bubbles are the most important mechanism underlying emulsions formation in the microchannels and that degassing of the aqueous phase before its introduction to the device can be an important factor for reduction of droplet polydispersity. This idea is demonstrated by synthetizing solid polymeric particles with a narrow size distribution starting from a mini-emulsion produced by the device.

Keywords: High-power ultrasound; In-line emulsification; Microfluidics; Polymeric particles synthesis; Ultrasonic emulsification; W/o and o/w emulsions.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Example of the flow rates employed to prepare the W:O = 9:1 mini-emulsions set with different mixtures of Span 80 and Tween 80 solutions to obtain distinct HLB values at fixed W:O ratios. The total flow was always 1 mL/h. Seven different HLB values for this set of mini-emulsions are indicated with vertical dotted red lines. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2
Fig. 2
a) PDMS microfluidic device for mini-emulsions generation. Four inlet channels labeled i1 to i4 help to introduce water and oil phases with or without surfactants and merge the liquids into a single serpentine channel. The microchip is bound to a glass slide together with a Langevin piezoelectric transducer. Introducing the liquids in continuous flow and energizing the piezoelectric produces mini-emulsions. b) Finite element method (FEM) simulation of the vibration displacements in the Z-axis of the microfluidic slide at the piezoelectric resonant frequency of 61 kHz.
Fig. 3
Fig. 3
Effect of the electrical power on the mini-emulsification process and on the mean droplet diameter. (a) Within the range of 0–0.9 W, stable micron-size droplet formation is observed. (b) In the range of 0.9 – 1.9 W, some droplet coalescence is observed. (c) At 2.0 W the cavitation threshold is reached and emulsification starts to occur, but several zones showed poor emulsification. This behavior is observed up to 4.8 W. (d) Above 4.8 and up to 25 W (maximum power tested), a homogeneous mini-emulsion was produced in all the microchannels. (e) The average droplet diameters of ten different experiments in the 4.8–25 W range are plotted in the graph (red dots). The mean of all data (280 nm) is shown with a green line and the standard deviation is represented with a shaded green area (±30 nm). Total flow = 1000 μL/h; water:hexadecane ratio is 9:1 with 2% w/w of Tween 80. Scale bar = 300 µm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
Ultrasound effect on deionized water or hexadecane inside the microchannels. a) Bubbles attached to the glass surface are observed when water without degasification treatment is flown through the microdevice and the piezoelectric turned on. Scale bar = 70 µm. b) A section of the serpentine microchannel with flowing water and the piezoelectric turned off. The PDMS structures were shaded for clarity of the picture. Scale bar = 300 µm. c) The same section of the microchannel as in b) but with the piezoelectric turned on. Many cavitation bubbles are observed mainly along the PDMS walls. Scale bar = 300 µm. d-f) A cavitation bubble on top of a PDMS wall oscillates and fragments into secondary bubbles that move in opposite directions. Scale bar = 10 µm. g-j) A cavitation bubble moves along a PDMS walls in counterflow. Scale bar = 10 µm. k) Microphotograph of a channel section filled with pure water degassed for 30 min before its injection into the microchip. Only a few bubbles are observed when the piezoelectric is turned on. Scale bar = 70 μm. l) Microchannel section filled with pure hexadecane without degasification and the piezoelectric turned on. Only a few bubbles are observed (enclosed by the red circles). Scale bar = 70 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5
Fig. 5
a) Microvortex generated by a cavitation bubble as an emulsifying element captured by a fast camera at 20,000 fps (Video 2). W:O ratio 2:1 with 2% w/w of Tween 80. Total flow rate is 300 µL/h. Scale bar = 10 µm. b–e) Microphotographs of a large water droplet disrupted by a trapped air bubble (red arrow) presenting microstreaming captured at 60 fps (Video 3). O = hexadecane with 2% w/w of Span 80; W = water; E = emulsion. W:O ratio 1:1. Total flow rate 400 µL/h. The time interval between each microphotograph is 79 ms. Scale bar = 300 µm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 6
Fig. 6
(a-c) Color microphotographs of a micrometer-size droplet of water with fluorescein sodium salt in a continuous medium of hexadecane with Nile red. a) Bright field. b) Fluorescent image acquired with filters for fluorescein in water. c) Fluorescent image acquired with filters for Nile red in hexadecane. d–f) Color microphotographs of a W/O mini-emulsion stained with fluorescein and Nile red in bright field and the same filter sets mentioned above. g–i) Color microphotographs of an air bubble surrounded with the mini-emulsion stained with fluorescein and Nile red. The air bubble does not fluoresce with any filter set. W:O ratio is 1:9 and 2% w/w of Span 80. Scale bar = 300 μm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 7
Fig. 7
Droplet diameter and PDI of emulsions prepared in the ultrasound-assisted microfluidic device at seven different HLB values over the accessible range using Span 80 and Tween 80 (4.3 to 15). Three different water:hexadecane ratios were prepared: Left: water:hexadecane 9:1; Middle: water:hexadecane 1:1 and right: water:hexadecane 1:9. Colors represent different types of emulsions. Blue: O/W; yellow: W/O; white: bicontinuous and green: instable (immediate phase separation). Each point represents the average of three independent experiments and the error bars are the standard deviation. All the formulations contained 2% w/w of surfactants. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 8
Fig. 8
SEM micrographs of polymeric particles for different degasification times of the aqueous phase (a) 0 min, b) 5 min and c) 30 min) and volume weighted particle size distribution for the same polymeric particles (d) 0 min, e) 5 min and f) 30 min).
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