Droplet Microfluidics: Fundamentals and Its Advanced Applications

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B:Biology and Biomedicine".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 12512

Special Issue Editor

Department of Biosciences, Rice University, George R. Brown Hall W200I, Houston, TX, USA
Interests: microfluidics; antibiotic resistance; drug discovery; fluorescence-activated droplet sorting; fluorescence imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Droplet-based microfluidics has been utilized in many innovative approaches in the biology, biomedical, and microbiology research fields due to its unique advantages over the decades. This system possesses excellent biocompatibility with encapsulated cells in microdroplets and many biological reagents. One application is that millions of functional screenings of individual cells in a spatially segregated microenvironment are assayed with one mL of emulsion by being used with fluorescent protein expression. The isolation of specific target cells among the population can be achieved by utilizing high-throughput fluorescent active droplets sorting or standard fluorescence-activated cell sorters. Accordingly, this Special Issue seeks to showcase research papers and review articles that focus on the fundamentals of microdroplet formation as well as novel microdroplets applications. 

We look forward to receiving your submissions.

Dr. Seokju Seo
Guest Editor

Manuscript Submission Information

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Keywords

  • droplet
  • emulsion
  • microfluidics
  • microdroplets
  • microchannel

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Published Papers (9 papers)

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Research

14 pages, 27135 KiB  
Article
A Simple Non-Embedded Single Capillary Device for On-Demand Complex Emulsion Formation
by Mohammad Mahdi Karim Khani, Mehrnaz Oveysi, Vahid Bazargan and Marco Marengo
Micromachines 2024, 15(2), 239; https://doi.org/10.3390/mi15020239 - 4 Feb 2024
Viewed by 755
Abstract
This study includes an examination of the design, fabrication, and experimentation of a rudimentary droplet generator. The device has potential applications in on-demand double and higher-order emulsions as well as tailored emulsions with numerous cores. The phenomenon of a pendant double droplet creation [...] Read more.
This study includes an examination of the design, fabrication, and experimentation of a rudimentary droplet generator. The device has potential applications in on-demand double and higher-order emulsions as well as tailored emulsions with numerous cores. The phenomenon of a pendant double droplet creation is observed when an inner phase is transported through a capillary, while a middle phase envelops the external surface of the capillary. This leads to the occurrence of a pinching-off process at the tip of the pulled capillary. Following this, the double droplet is introduced into a container that is filled with the outer phase. The present study examines the force equilibrium throughout the droplet break-up process and aims to forecast the final morphology of the droplets within the container by considering the impact of interfacial tension ratios. The shell thickness in a core–shell formation can be calculated based on the inner and middle phase flow rates as well as the middle droplet formation period. The present platform, which enables the simple production of double and higher emulsions, exhibits promising prospects for the controlled manufacturing of complex emulsions. This technology holds potential for various applications, including the experimental exploration of collision behavior or electro-hydrodynamics in emulsions as well as millimeter-size engineered microparticle fabrication. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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11 pages, 3263 KiB  
Article
Image-Based Feedback of Multi-Component Microdroplets for Ultra-Monodispersed Library Preparation
by Christy Cantwell, John S. McGrath, Clive A. Smith and Graeme Whyte
Micromachines 2024, 15(1), 27; https://doi.org/10.3390/mi15010027 - 22 Dec 2023
Viewed by 923
Abstract
Using devices with microfluidic channels can allow for precise control over liquids flowing through them. Merging flows of immiscible liquids can create emulsions with highly monodispersed microdroplets within a carrier liquid, which are ideal for miniaturised reaction vessels which can be generated with [...] Read more.
Using devices with microfluidic channels can allow for precise control over liquids flowing through them. Merging flows of immiscible liquids can create emulsions with highly monodispersed microdroplets within a carrier liquid, which are ideal for miniaturised reaction vessels which can be generated with a high throughput of tens of thousands of droplets per second. Control of the size and composition of these droplets is generally performed by controlling the pumping system pushing the liquids into the device; however, this is an indirect manipulation and inadequate if absolute precision is required in the size or composition of the droplets. In this work, we extend the previous development of image-based closed-loop feedback control over microdroplet generation to allow for the control of not only the size of droplets but also the composition by merging two aqueous flows. The feedback allows direct control over the desired parameters of volume and ratio of the two components over a wide range of ratios and outperforms current techniques in terms of monodispersity in volume and composition. This technique is ideal for situations where precise control over droplets is critical, or where a library of droplets of different concentrations but the same volume is required. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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16 pages, 4539 KiB  
Article
Microfluidically Assisted Synthesis of Calcium Carbonate Submicron Particles with Improved Loading Properties
by Alexey V. Ermakov, Sergei V. Chapek, Ekaterina V. Lengert, Petr V. Konarev, Vladimir V. Volkov, Vladimir V. Artemov, Mikhail A. Soldatov and Daria B. Trushina
Micromachines 2024, 15(1), 16; https://doi.org/10.3390/mi15010016 - 21 Dec 2023
Cited by 2 | Viewed by 1126
Abstract
The development of advanced methods for the synthesis of nano- and microparticles in the field of biomedicine is of high interest due to a range of reasons. The current synthesis methods may have limitations in terms of efficiency, scalability, and uniformity of the [...] Read more.
The development of advanced methods for the synthesis of nano- and microparticles in the field of biomedicine is of high interest due to a range of reasons. The current synthesis methods may have limitations in terms of efficiency, scalability, and uniformity of the particles. Here, we investigate the synthesis of submicron calcium carbonate using a microfluidic chip with a T-shaped oil supply for droplet-based synthesis to facilitate control over the formation of submicron calcium carbonate particles. The design of the chip allowed for the precise manipulation of reaction parameters, resulting in improved porosity while maintaining an efficient synthesis rate. The pore size distribution within calcium carbonate particles was estimated via small-angle X-ray scattering. This study showed that the high porosity and reduced size of the particles facilitated the higher loading of a model peptide: 16 vs. 9 mass.% for the particles synthesized in a microfluidic device and in bulk, correspondingly. The biosafety of the developed particles in the concentration range of 0.08–0.8 mg per plate was established by the results of the cytotoxicity study using mouse fibroblasts. This innovative approach of microfluidically assisted synthesis provides a promising avenue for future research in the field of particle synthesis and drug delivery systems. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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13 pages, 6828 KiB  
Article
Particle Separation in a Microchannel with a T-Shaped Cross-Section Using Co-Flow of Newtonian and Viscoelastic Fluids
by Jinhyeuk Song, Jaekyeong Jang, Taehoon Kim and Younghak Cho
Micromachines 2023, 14(10), 1863; https://doi.org/10.3390/mi14101863 - 28 Sep 2023
Viewed by 881
Abstract
In this study, we investigated the particle separation phenomenon in a microchannel with a T-shaped cross-section, a unique design detailed in our previous study. Utilizing a co-flow system within this T-shaped microchannel, we examined two types of flow configuration: one where a Newtonian [...] Read more.
In this study, we investigated the particle separation phenomenon in a microchannel with a T-shaped cross-section, a unique design detailed in our previous study. Utilizing a co-flow system within this T-shaped microchannel, we examined two types of flow configuration: one where a Newtonian fluid served as the inner fluid and a viscoelastic fluid as the outer fluid (Newtonian/viscoelastic), and another where both the inner and outer fluids were Newtonian fluids (Newtonian/Newtonian). We introduced a mixture of three differently sized particles into the microchannel through the outer fluid and observed that the co-flow of Newtonian/viscoelastic fluids effectively separated particles based on their size compared with Newtonian/Newtonian fluids. In this context, we evaluated and compared the particle separation efficiency, recovery rate, and enrichment factor across both co-flow configurations. The Newtonian/viscoelastic co-flow system demonstrated a superior efficiency and recovery ratio when compared with the Newtonian/Newtonian system. Additionally, we assessed the influence of the flow rate ratio between the inner and outer fluids on particle separation within each co-flow system. Our results indicated that increasing the flow rate ratio enhanced the separation efficiency, particularly in the Newtonian/viscoelastic co-flow configuration. Consequently, this study substantiates the potential of utilizing a Newtonian/viscoelastic co-flow system in a T-shaped straight microchannel for the simultaneous separation of three differently sized particles. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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9 pages, 2627 KiB  
Article
All-Optical Rapid Formation, Transport, and Sustenance of a Sessile Droplet in a Two-Dimensional Slit with Few-Micrometer Separation
by Yuka Takamatsu, Chizuru Yamato, Masashi Kuwahara, Yuta Saito and Toshiharu Saiki
Micromachines 2023, 14(7), 1460; https://doi.org/10.3390/mi14071460 - 21 Jul 2023
Viewed by 808
Abstract
We present a sessile droplet manipulation platform that enables the formation and transport of a droplet on a light-absorbing surface via local laser-beam irradiation. The mechanism relies on solutocapillary Marangoni flow arising from a concentration gradient in a binary mixture liquid. Because the [...] Read more.
We present a sessile droplet manipulation platform that enables the formation and transport of a droplet on a light-absorbing surface via local laser-beam irradiation. The mechanism relies on solutocapillary Marangoni flow arising from a concentration gradient in a binary mixture liquid. Because the mixture is strongly confined in a two-dimensional slit with a spacing of a few micrometers, the wetting film is stably sustained, enabling the rapid formation, deformation, and transport of a sessile droplet. In addition, to sustain the droplet in the absence of laser irradiation, we developed a method to bridge the droplet between the top and bottom walls of the slit. The bridge is stably sustained because of the hydrophilicity of the slit wall. Splitting and merging of the droplet bridges are also demonstrated. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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16 pages, 9615 KiB  
Article
Silicon-Based 3D Microfluidics for Parallelization of Droplet Generation
by Diego Monserrat Lopez, Philipp Rottmann, Martin Fussenegger and Emanuel Lörtscher
Micromachines 2023, 14(7), 1289; https://doi.org/10.3390/mi14071289 - 23 Jun 2023
Cited by 1 | Viewed by 1679
Abstract
Both the diversity and complexity of microfluidic systems have experienced a tremendous progress over the last decades, enabled by new materials, novel device concepts and innovative fabrication routes. In particular the subfield of high-throughput screening, used for biochemical, genetic and pharmacological samples, has [...] Read more.
Both the diversity and complexity of microfluidic systems have experienced a tremendous progress over the last decades, enabled by new materials, novel device concepts and innovative fabrication routes. In particular the subfield of high-throughput screening, used for biochemical, genetic and pharmacological samples, has extensively emerged from developments in droplet microfluidics. More recently, new 3D device architectures enabled either by stacking layers of PDMS or by direct 3D-printing have gained enormous attention for applications in chemical synthesis or biomedical assays. While the first microfluidic devices were based on silicon and glass structures, those materials have not yet been significantly expanded towards 3D despite their high chemical compatibility, mechanical strength or mass-production potential. In our work, we present a generic fabrication route based on the implementation of vertical vias and a redistribution layer to create glass–silicon–glass 3D microfluidic structures. It is used to build different droplet-generating devices with several flow-focusing junctions in parallel, all fed from a single source. We study the effect of having several of these junctions in parallel by varying the flow conditions of both the continuous and the dispersed phases. We demonstrate that the generic concept enables an upscaling in the production rate by increasing the number of droplet generators per device without sacrificing the monodispersity of the droplets. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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11 pages, 4373 KiB  
Article
Monodisperse Micro-Droplet Generation in Microfluidic Channel with Asymmetric Cross-Sectional Shape
by Youngseo Cho, Jungwoo Kim, Jaewon Park, Hyun Soo Kim and Younghak Cho
Micromachines 2023, 14(1), 223; https://doi.org/10.3390/mi14010223 - 15 Jan 2023
Cited by 1 | Viewed by 2130
Abstract
Micro-droplets are widely used in the fields of chemical and biological research, such as drug delivery, material synthesis, point-of-care diagnostics, and digital PCR. Droplet-based microfluidics has many advantages, such as small reagent consumption, fast reaction time, and independent control of each droplet. Therefore, [...] Read more.
Micro-droplets are widely used in the fields of chemical and biological research, such as drug delivery, material synthesis, point-of-care diagnostics, and digital PCR. Droplet-based microfluidics has many advantages, such as small reagent consumption, fast reaction time, and independent control of each droplet. Therefore, various micro-droplet generation methods have been proposed, including T-junction breakup, capillary flow-focusing, planar flow-focusing, step emulsification, and high aspect (height-to-width) ratio confinement. In this study, we propose a microfluidic device for generating monodisperse micro-droplets, the microfluidic channel of which has an asymmetric cross-sectional shape and high hypotenuse-to-width ratio (HTWR). It was fabricated using basic MEMS processes, such as photolithography, anisotropic wet etching of Si, and polydimethylsiloxane (PDMS) molding. Due to the geometric similarity of a Si channel and a PDMS mold, both of which were created through the anisotropic etching process of a single crystal Si, the microfluidic channel with the asymmetric cross-sectional shape and high HTWR was easily realized. The effects of HTWR of channels on the size and uniformity of generated micro-droplets were investigated. The monodisperse micro-droplets were generated as the HTWR of the asymmetric channel was over 3.5. In addition, it was found that the flow direction of the oil solution (continuous phase) affected the size of micro-droplets due to the asymmetric channel structures. Two kinds of monodisperse droplets with different sizes were successfully generated for a wider range of flow rates using the asymmetric channel structure in the developed microfluidic device. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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16 pages, 4540 KiB  
Article
Hydrodynamics of Droplet Sorting in Asymmetric Acute Junctions
by He Yang and Tuomas P. J. Knowles
Micromachines 2022, 13(10), 1640; https://doi.org/10.3390/mi13101640 - 29 Sep 2022
Viewed by 1164
Abstract
Droplet sorting is one of the fundamental manipulations of droplet-based microfluidics. Although many sorting methods have already been proposed, there is still a demand to develop new sorting methods for various applications of droplet-based microfluidics. This work presents numerical investigations on droplet sorting [...] Read more.
Droplet sorting is one of the fundamental manipulations of droplet-based microfluidics. Although many sorting methods have already been proposed, there is still a demand to develop new sorting methods for various applications of droplet-based microfluidics. This work presents numerical investigations on droplet sorting with asymmetric acute junctions. It is found that the asymmetric acute junctions could achieve volume-based sorting and velocity-based sorting. The pressure distributions in the asymmetric junctions are discussed to reveal the physical mechanism behind the droplet sorting. The dependence of the droplet sorting on the droplet volume, velocity, and junction angle is explored. The possibility of the employment of the proposed sorting method in most real experiments is also discussed. This work provides a new, simple, and cost-effective passive strategy to separate droplets in microfluidic channels. Moreover, the proposed acute junctions could be used in combination with other sorting methods, which may boost more opportunities to sort droplets. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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9 pages, 2027 KiB  
Communication
Optimization of Electrode Patterns for an ITO-Based Digital Microfluidic through the Finite Element Simulation
by Ze-Rui Song, Jin Zeng, Jia-Le Zhou, Bing-Yong Yan, Zhen Gu and Hui-Feng Wang
Micromachines 2022, 13(10), 1563; https://doi.org/10.3390/mi13101563 - 21 Sep 2022
Cited by 2 | Viewed by 1498
Abstract
Indium tin oxide (ITO)-based digital microfluidics (DMF) with unique optical and electrical properties are promising in the development of integrated, automatic and portable analytical systems. The fabrication technique using laser direct etching (LDE) on ITO glass has the advantages of being rapid, low [...] Read more.
Indium tin oxide (ITO)-based digital microfluidics (DMF) with unique optical and electrical properties are promising in the development of integrated, automatic and portable analytical systems. The fabrication technique using laser direct etching (LDE) on ITO glass has the advantages of being rapid, low cost and convenient. However, the fabrication resolution of LDE limits the minimum line width for patterns on ITO glasses, leading to a related wider lead wire for the actuating electrodes of DMF compared with photolithography. Therefore, the lead wire of electrodes could affect the droplet motion on the digital microfluidic chip due to the increased contact line with the droplet. Herein, we developed a finite element model of a DMF with improved efficiency to investigate the effect of the lead wire. An optimized electrode pattern was then designed based on a theoretical analysis and validated by a simulation, which significantly decreased the deformation of the droplets down to 0.012 mm. The performance of the optimized electrode was also verified in an experiment. The proposed simulation method could be further extended to other DMF systems or applications to provide an efficient approach for the design and optimization of DMF chips. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Fundamentals and Its Advanced Applications)
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