Digital Microfluidics for Liquid Handling and Biochemical Analysis

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "E:Engineering and Technology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 15198

Special Issue Editors

Center for Microflows and Nanoflows, School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China
Interests: droplet microfluidics; soft matter; lab-on-a-chip; miniaturized reactors/sensors
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Guest Editor
Queensland Micro- and Nanotechnology Centre, Griffith University, West Creek Road, Nathan, QLD 4111, Australia
Interests: microfluidics; nanofluidics; micro/nanomachining technologies; micro/nanoscale science; instrumentation for biomedical applications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Digital microfluidics (DMF) is an emerging technology for the transportation of liquids at a small scale, especially discrete droplets, in a controllable manner. Compared to the closed channels of conventional microfluidics, DMF devices enable the precise manipulation of droplets containing target samples on a two-dimensional planar chip or even in a three-dimensional open environment. Due to its unique features, DMF presents a great potential for implementing droplet manipulation tasks with a higher efficiency and automation. The handling tasks include but not limited to dispersing, trapping, moving, mixing, and reacting, with all these tasks able to be completed through well-established controlling techniques such as electrowetting on dielectric (EWOD) and dielectrophoresis (DEP). Thus, DMF coupled with suitable analytical methods has versatile applications in chemical and biomedical fields and, as such, this Special Issue seeks to showcase research papers and review articles focusing on novel methodological developments and promising biochemical applications in droplet-based digital microfluidics.

We look forward to receiving your submissions.

Dr. Jing Jin
Prof. Dr. Nam-Trung Nguyen
Guest Editors

Manuscript Submission Information

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Keywords

  • droplet microfluidics
  • open microfluidics
  • manipulation
  • electrowetting on dielectric
  • dielectrophoresis
  • biosensors
  • microreactors
  • liquid marbles
  • lab-on-a-chip

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Published Papers (7 papers)

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Research

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13 pages, 6676 KiB  
Article
Three-Dimensional Printing Enabled Droplet Microfluidic Device for Real-Time Monitoring of Single-Cell Viability and Blebbing Activity
by Meiai Lin, Ting Liu, Yeqian Liu, Zequan Lin, Jiale Chen, Jing Song, Yiya Qiu and Benqing Zhou
Micromachines 2023, 14(8), 1521; https://doi.org/10.3390/mi14081521 - 28 Jul 2023
Cited by 1 | Viewed by 1294
Abstract
Droplet-based microfluidics with the characteristics of high throughput, low sample consumption, increasing reaction speed, and homogeneous volume control have been demonstrated as a useful platform for biomedical research and applications. The traditional fabrication methods of droplet microfluidics largely rely on expensive instruments, sophisticated [...] Read more.
Droplet-based microfluidics with the characteristics of high throughput, low sample consumption, increasing reaction speed, and homogeneous volume control have been demonstrated as a useful platform for biomedical research and applications. The traditional fabrication methods of droplet microfluidics largely rely on expensive instruments, sophisticated operations, and even the requirement of an ultraclean room. In this manuscript, we present a 3D printing-based droplet microfluidic system with a specifically designed microstructure for droplet generation aimed at developing a more accessible and cost-effective method. The performance of droplet generation and the encapsulation capacity of the setup were examined. The device was further applied to measure the variation in cell viability over time and monitor the cell’s blebbing activity to investigate its potential ability and feasibility for single-cell analysis. The result demonstrated that the produced droplets remained stable enough to enable the long-time detection of cell viability. Additionally, cell membrane protrusions featuring the life cycle of bleb initiation, expansion, and retraction can be well-observed. Three-dimensional printing-based droplet microfluidics benefit from the ease of manufacture, which is expected to simplify the fabrication of microfluidics and expand the application of the droplet approach in biomedical fields. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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13 pages, 13201 KiB  
Article
The Recognition Algorithm of Two-Phase Flow Patterns Based on GoogLeNet+5 Coord Attention
by Jinsong Zhang, Xinpeng Wei and Zhiliang Wang
Micromachines 2023, 14(2), 462; https://doi.org/10.3390/mi14020462 - 16 Feb 2023
Viewed by 1241
Abstract
The two-phase flow in a microchannel consists of liquid–liquid and gas–liquid material components. The automatic recognition of flow patterns using deep learning approaches has been emerging. This study aimed to improve the recognition accuracy of flow patterns in the two-phase flow images. The [...] Read more.
The two-phase flow in a microchannel consists of liquid–liquid and gas–liquid material components. The automatic recognition of flow patterns using deep learning approaches has been emerging. This study aimed to improve the recognition accuracy of flow patterns in the two-phase flow images. The different convolutional kernels in the GoogLeNet algorithm extracted the image features with different scales. In order to strengthen the important channel and spatial features, this paper proposes the combined five-layer Coord attention and GoogLeNet algorithm to enhance the accuracy of the new algorithm. The optimized algorithm model was derived from image datasets with different liquid–liquid two-phase flows (NaAlg–Oil, GaInSn–Water), and its accuracy was 95.09% in training and 98.12% in testing. This new model was also applied to predict the flow patterns, with a recognition accuracy of more than 97% in both the liquid–liquid and gas–liquid two-phase flows (water–soybean oil, water–lubricating oil, and argon–water). Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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14 pages, 2409 KiB  
Article
The Effect of Non-Uniform Magnetic Field on the Efficiency of Mixing in Droplet-Based Microfluidics: A Numerical Investigation
by Masoud Rezaeian, Moein Nouri, Mojtaba Hassani-Gangaraj, Amir Shamloo and Rohollah Nasiri
Micromachines 2022, 13(10), 1661; https://doi.org/10.3390/mi13101661 - 02 Oct 2022
Cited by 7 | Viewed by 1852
Abstract
Achieving high efficiency and throughput in droplet-based mixing over a small characteristic length, such as microfluidic channels, is one of the crucial parameters in Lab-on-a-Chip (LOC) applications. One solution to achieve efficient mixing is to use active mixers in which an external power [...] Read more.
Achieving high efficiency and throughput in droplet-based mixing over a small characteristic length, such as microfluidic channels, is one of the crucial parameters in Lab-on-a-Chip (LOC) applications. One solution to achieve efficient mixing is to use active mixers in which an external power source is utilized to mix two fluids. One of these active methods is magnetic micromixers using ferrofluid. In this technique, magnetic nanoparticles are used to make one phase responsive to magnetic force, and then by applying a magnetic field, two fluid phases, one of which is magneto-responsive, will sufficiently mix. In this study, we investigated the effect of the magnetic field’s characteristics on the efficiency of the mixing process inside droplets. When different concentrations of ferrofluids are affected by a constant magnetic field, there is no significant change in mixing efficiency. As the magnetic field intensifies, the magnetic force makes the circulation flow inside the droplet asymmetric, leading to chaotic advection, which creates a flow that increases the mixing efficiency. The results show that the use of magnetic fields is an effective method to enhance the mixing efficiency within droplets, and the efficiency of mixing increases from 65.4 to 86.1% by increasing the magnetic field intensity from 0 to 90 mT. Besides that, the effect of ferrofluid’s concentration on the mixing efficiency is studied. It is shown that when the concentration of the ferrofluid changes from 0 to 0.6 mol/m3, the mixing efficiency increases considerably. It is also shown that by changing the intensity of the magnetic field, the mixing efficiency increases by about 11%. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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14 pages, 6020 KiB  
Article
Droplet Microfluidic Device for Chemoenzymatic Sensing
by Anton S. Yakimov, Ivan A. Denisov, Anton S. Bukatin, Kirill A. Lukyanenko, Kirill I. Belousov, Igor V. Kukhtevich, Elena N. Esimbekova, Anatoly A. Evstrapov and Peter I. Belobrov
Micromachines 2022, 13(7), 1146; https://doi.org/10.3390/mi13071146 - 20 Jul 2022
Cited by 4 | Viewed by 2351
Abstract
The rapid detection of pollutants in water can be performed with enzymatic probes, the catalytic light-emitting activity of which decreases in the presence of many types of pollutants. Herein, we present a microfluidic system for continuous chemoenzymatic biosensing that generates emulsion droplets containing [...] Read more.
The rapid detection of pollutants in water can be performed with enzymatic probes, the catalytic light-emitting activity of which decreases in the presence of many types of pollutants. Herein, we present a microfluidic system for continuous chemoenzymatic biosensing that generates emulsion droplets containing two enzymes of the bacterial bioluminescent system (luciferase and NAD(P)H:FMN–oxidoreductase) with substrates required for the reaction. The developed chip generates “water-in-oil” emulsion droplets with a volume of 0.1 μL and a frequency of up to 12 drops per minute as well as provides the efficient mixing of reagents in droplets and their distancing. The bioluminescent signal from each individual droplet was measured by a photomultiplier tube with a signal-to-noise ratio of up to 3000/1. The intensity of the luminescence depended on the concentration of the copper sulfate with the limit of its detection of 5 μM. It was shown that bioluminescent enzymatic reactions could be carried out in droplet reactors in dispersed streams. The parameters and limitations required for the bioluminescent reaction to proceed were also studied. Hereby, chemoenzymatic sensing capabilities powered by a droplet microfluidics manipulation technique may serve as the basis for early-warning online water pollution systems. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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13 pages, 4547 KiB  
Article
Digital Microfluidic Mixing via Reciprocating Motions of Droplets Driven by Contact Charge Electrophoresis
by Jaewook Kim, Taeyung Kim, Inseo Ji and Jiwoo Hong
Micromachines 2022, 13(4), 593; https://doi.org/10.3390/mi13040593 - 10 Apr 2022
Cited by 4 | Viewed by 2209
Abstract
Contact charge electrophoresis (CCEP) is an electrically controllable manipulation technique of conductive droplets and particles by charging and discharging when in contact with the electrode. Given its straightforward operation mechanism, low cost, and ease of system construction, it has gained traction as a [...] Read more.
Contact charge electrophoresis (CCEP) is an electrically controllable manipulation technique of conductive droplets and particles by charging and discharging when in contact with the electrode. Given its straightforward operation mechanism, low cost, and ease of system construction, it has gained traction as a versatile and potential strategy for the realistic establishment of lab-on-a-chip (LOC) in various engineering applications. We present a CCEP-based digital microfluidics (DMF) platform with two parallel electrode modules comprising assembled conventional pin header sockets, allowing for efficient mixing through horizontal and vertical shaking via droplet reciprocating motions. The temporal chromic change caused by the chemical reaction between the pH indicator and base solutions within the shaking droplets is quantitatively analyzed under various CCEP actuation conditions to evaluate the mixing performance in shaking droplets by vertical and horizontal reciprocating motions on the DMF platform. Furthermore, mixing flow patterns within shaking droplets are successfully visualized by a high-speed camera system. The suggested techniques can mix samples and reagents rapidly and efficiently in droplet-based microreactors for DMF applications, such as biochemical analysis and medical diagnostics. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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8 pages, 2191 KiB  
Article
Precise Droplet Dispensing in Digital Microfluidics with Dumbbell-Shaped Electrodes
by Wei Wang
Micromachines 2022, 13(3), 484; https://doi.org/10.3390/mi13030484 - 20 Mar 2022
Cited by 2 | Viewed by 2141
Abstract
Electro-wetting-on-dielectric (EWOD) enables the manipulation of droplets on a two-dimensional surface, which provides a versatile technique for digital microfluidics at a micro- or nano-scale. However, the deficiency of the dispensing precision has long limited its applications in micro total analysis systems (μ-TAS) where [...] Read more.
Electro-wetting-on-dielectric (EWOD) enables the manipulation of droplets on a two-dimensional surface, which provides a versatile technique for digital microfluidics at a micro- or nano-scale. However, the deficiency of the dispensing precision has long limited its applications in micro total analysis systems (μ-TAS) where the accuracy of assays is largely determined by the volume control of the reagent dosing. This paper proposes optimum electrode designs and carries out characterization experiments to demonstrate the reproducibility of on-chip droplet generation with no extra external apparatus. The coefficient variation of the volumes of consecutively dispensed droplets from a non-refilling reservoir can be limited to below 0.3%, indicating the validity of the new electrode structure in practical applications. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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Review

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28 pages, 3745 KiB  
Review
Core–Shell Particles: From Fabrication Methods to Diverse Manipulation Techniques
by Ajeet Singh Yadav, Du Tuan Tran, Adrian J. T. Teo, Yuchen Dai, Fariba Malekpour Galogahi, Chin Hong Ooi and Nam-Trung Nguyen
Micromachines 2023, 14(3), 497; https://doi.org/10.3390/mi14030497 - 21 Feb 2023
Cited by 2 | Viewed by 2892
Abstract
Core–shell particles are micro- or nanoparticles with solid, liquid, or gas cores encapsulated by protective solid shells. The unique composition of core and shell materials imparts smart properties on the particles. Core–shell particles are gaining increasing attention as tuneable and versatile carriers for [...] Read more.
Core–shell particles are micro- or nanoparticles with solid, liquid, or gas cores encapsulated by protective solid shells. The unique composition of core and shell materials imparts smart properties on the particles. Core–shell particles are gaining increasing attention as tuneable and versatile carriers for pharmaceutical and biomedical applications including targeted drug delivery, controlled drug release, and biosensing. This review provides an overview of fabrication methods for core–shell particles followed by a brief discussion of their application and a detailed analysis of their manipulation including assembly, sorting, and triggered release. We compile current methodologies employed for manipulation of core–shell particles and demonstrate how existing methods of assembly and sorting micro/nanospheres can be adopted or modified for core–shell particles. Various triggered release approaches for diagnostics and drug delivery are also discussed in detail. Full article
(This article belongs to the Special Issue Digital Microfluidics for Liquid Handling and Biochemical Analysis)
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