This Feature describes the different particle manipulation techniques available in the droplet microfluidics toolbox to handle particles encapsulated inside droplets and to manipulate whole droplets. We address the advantages and disadvantages of the different techniques to guide new users.
In this paper, we utilise bulk acoustic waves to control the position of microparticles inside droplets in two-phase microfluidic systems and demonstrate a method to enrich the microparticles. In droplet microfluidics different unit operations are combined and integrated on-chip to miniaturise complex biochemical assays. We present a droplet unit operation capable of controlling the position of microparticles during a trident shaped droplet split. An acoustic standing wave field is generated in the microchannel, and the acoustic forces direct the encapsulated microparticles to the centre of the droplets. The method is generic and requires no labelling of the microparticles, and is operated in a non-contact fashion. It was possible to achieve 2+fold enrichment of polystyrene beads (5 µm in diameter) in the centre daughter droplet with an average recovery of 89% of the beads. Red blood cells were also successfully manipulated inside droplets. These results show the possibility to use acoustophoresis in two-phase systems to enrich microparticles, and opens up for new dropletbased assays that are not possible to perform today.
We show a method for separation of two particle species with different acoustic contrasts originally encapsulated in the same droplet in a continuous two-phase system. This was realized by using bulk acoustic standing waves in a 380 lm wide silicon-glass microfluidic channel. Polystyrene particles (positive acoustic contrast particles) and in-house synthesized polydimethylsiloxane (PDMS) particles (negative acoustic contrast particles) were encapsulated inside water-in-oil droplets either individually or in a mixture. At acoustic actuation of the system at the fundamental resonance frequency, the polystyrene particles were moved to the center of the droplet (pressure node), while the PDMS particles were moved to the sides of the droplet (pressure anti-nodes). The acoustic particle manipulation step was combined in series with a trifurcation droplet splitter, and as the original droplet passed through the splitter and was divided into three daughter droplets, the polystyrene particles were directed into the center daughter droplet, while the PDMS particles were directed into the two side daughter droplets. The presented method expands the droplet microfluidics toolbox and offers new possibilities to perform binary particle separation in droplet microfluidic systems.
To transfer cell- and bead-assays into droplet-based platforms typically requires the use of complex microfluidic circuits, which calls for methods to switch the direction of the encapsulated particles. We present a microfluidic chip where the combination of acoustic manipulation at two different harmonics and a trident-shaped droplet-splitter enables direction-switching of microbeads and yeast cells in droplet microfluidic circuits. At the first harmonic, the encapsulated particles exit the splitter in the center daughter droplets, while at the second harmonic, the particles exit in the side daughter droplets. This method holds promises for droplet-based assays where particle-positioning needs to be selectively controlled.
The aim of this paper is to study resonance conditions for acoustic particle focusing inside droplets in two-phase microfluidic systems. A bulk acoustic wave microfluidic chip was designed and fabricated for focusing microparticles inside aqueous droplets (plugs) surrounded by a continuous oil phase in a 380-μm-wide channel. The quality of the acoustic particle focusing was investigated by considering the influence of the acoustic properties of the continuous phase in relation to the dispersed phase. To simulate the system and study the acoustic radiation force on the particles inside droplets, a simplified 3D model was used. The resonance conditions and focusing quality were studied for two different cases: (1) the dispersed and continuous phases were acoustically mismatched (water droplets in fluorinated oil) and (2) the dispersed and continuous phases were acoustically matched (water droplets in olive oil). Experimentally, we observed poor acoustic particle focusing inside droplets surrounded by fluorinated oil while good focusing was observed in droplets surrounded by olive oil. The experimental results are supported qualitatively by our simulations. These show that the acoustic properties (density and compressibility) of the dispersed and continuous phases must be matched to generate a strong and homogeneous acoustic field inside the droplet that is suitable for high-quality intra-droplet acoustic particle focusing.
The generation of hydrogel droplets using droplet microfluidics has emerged as a powerful tool with many applications in biology and medicine. Here, a microfluidic system to control the position of particles (beads or astrocyte cells) in hydrogel droplets using bulk acoustic standing waves is presented. The chip consisted of a droplet generator and a 380 µm wide acoustic focusing channel. Droplets comprising hydrogel precursor solution (polyethylene glycol tetraacrylate or a combination of polyethylene glycol tetraacrylate and gelatine methacrylate), photoinitiator and particles were generated. The droplets passed along the acoustic focusing channel where a half wavelength acoustic standing wave field was generated, and the particles were focused to the centre line of the droplets (i.e. the pressure nodal line) by the acoustic force. The droplets were cross-linked by exposure to UV-light, freezing the particles in their positions. With the acoustics applied, 89 ± 19% of the particles (polystyrene beads, 10 µm diameter) were positioned in an area ± 10% from the centre line. As proof-of-principle for biological particles, astrocytes were focused in hydrogel droplets using the same principle. The viability of the astrocytes after 7 days in culture was 72 ± 22% when exposed to the acoustic focusing compared with 70 ± 19% for samples not exposed to the acoustic focusing. This technology provides a platform to control the spatial position of bioparticles in hydrogel droplets, and opens up for the generation of more complex biological hydrogel structures.
Production of cell-laden hydrogel droplets as miniaturized niches for 3D cell culture provides a new route for cell-based assays. Such production can be enabled by droplet microfluidics and here we present a droplet trapping system based on bulk acoustic waves for handling hydrogel droplets in a continuous flow format. The droplet trapping system consists of a glass capillary equipped with a small piezoelectric transducer. By applying ultrasound (4 MHz), a localized acoustic standing wave field is generated in the capillary, trapping the droplets in a well-defined cluster above the transducer area. The results show that the droplet cluster can be retained at flow rates of up to 76 μl/min, corresponding to an average flow speed of 3.2 mm/s. The system allows for important operations such as continuous perfusion and/or addition of chemical reagents to the encapsulated cells with in situ optical access. This feature is demonstrated by performing on-chip staining of the cell nuclei. The key advantages of this trapping method are that it is label-free and gentle and thus well-suited for biological applications. Moreover, the droplets can easily be released on-demand, which facilitates downstream analysis. It is envisioned that the presented droplet trapping system will be a valuable tool for a wide range of multistep assays as well as long-term monitoring of cells encapsulated in gel-based droplets.
We have fabricated a silicon-glass two-phase droplet microfluidic system capable of generating sub 100 µm-sized, ⌀ = (74 ± 2) µm, spherical droplets at rates of up to hundreds of hertz. By implementing a two-dimensional (2D) acoustophoresis particle-positioning method, we show a fourfold improvement in both vertical and lateral particle positioning inside the droplets compared to unactuated operation. The efficiency of the system has been optimized by incorporating aluminum matching layers in the transducer design permitting biocompatible operational temperatures (<37 °C). Furthermore, by using acoustic actuation, (99.8 ± 0.4)% of all encapsulated microparticles can be detected compared to only (79.0 ± 5.1)% for unactuated operation. In our experiments we observed a strong ordering of the microparticles in distinct patterns within the droplet when using 2D acoustophoresis; to explain the origin of these patterns we simulated numerically the fluid flow inside the droplets and compared with the experimental findings.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.