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Micromachines
Special Issues
Microfluidic for High-Throughput Screening
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Microfluidic for High-Throughput Screening

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "C：Chemistry".

Deadline for manuscript submissions: closed (25 February 2020) | Viewed by 23759

Special Issue Editor

Dr. Michele Zagnoni

E-Mail Website
Guest Editor
Centre for Microsystems and Photonics, EEE Department, University of Strathclyde, Glasgow G1 1XW, UK
Interests: microfludics; organ-on-a-chip; in vitro models; drug screening
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microfluidics and lab-on-a-chip technologies have increasingly been used in the past two decades for miniaturizing biochemical analysis and cell-based screening assays. Following the rapid development of a variety of single-phase and multi-phase microfluidic techniques, scalable and complex architectures have been proposed for both single-cell analysis and in vitro models of disease. Therefore, by combining the miniaturization benefits of microfluidics with advances in microfabrication techniques, these systems provide an excellent platform for high-throughput screening applications, offering cost-saving opportunities compared to a standard well-plate based system. Such features offer unique capabilities for screening limited samples of human tissue, ultra-low sample volumes, stem cell research, and for innovating drug discovery, all of which can impact biological investigation, clinical practice, and industrial procedures. In particular, the integration of physiologically relevant in vitro models of disease has great potential to reduce animal-based research and aid precision medicine.

Accordingly, this Special Issue seeks to showcase research papers, short communications, and review articles that focus on novel microfluidic systems and novel methodological application of microfluidic techniques for high-throughput and high content screening, high-throughput experimentation, automation, and large-scale identification/manipulation of biological tissue.

Dr. Michele Zagnoni
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Microfluidics
  • High-throughput screening
  • Large-scale experimentation
  • High content screens
  • Miniaturized drug discovery

Published Papers (6 papers)

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Research

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19 pages, 6235 KiB  
Article
Droplet-Based Screening for the Investigation of Microbial Nonlinear Dose–Response Characteristics System, Background and Examples
by Jialan Cao, Felix Richter, Michael Kastl, Jonny Erdmann, Christian Burgold, David Dittrich, Steffen Schneider, J. Michael Köhler and G. Alexander Groß
Micromachines 2020, 11(6), 577; https://doi.org/10.3390/mi11060577 - 08 Jun 2020
Cited by 8 | Viewed by 2970
Abstract
Droplet-based microfluidics is a versatile tool to reveal the dose–response relationship of different effectors on the microbial proliferation. Traditional readout parameter is the temporal development of the cell density for different effector concentrations. To determine nonlinear or unconventional dose–response relationships, data with high [...] Read more.
Droplet-based microfluidics is a versatile tool to reveal the dose–response relationship of different effectors on the microbial proliferation. Traditional readout parameter is the temporal development of the cell density for different effector concentrations. To determine nonlinear or unconventional dose–response relationships, data with high temporal resolution and dense concentration graduation are essential. If microorganisms with slow microbial growth kinetics are investigated, a sterile and evaporation-free long-term incubation technique is required. Here, we present a modular droplet-based screening system which was developed to solve these issues. Beside relevant technical aspects of the developed modules, the procedural workflow, and exemplary dose–response data for 1D and 2D dose–response screenings are presented. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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12 pages, 2358 KiB  
Article
Improving Single-Cell Encapsulation Efficiency and Reliability through Neutral Buoyancy of Suspension
by Hangrui Liu, Ming Li, Yan Wang, Jim Piper and Lianmei Jiang
Micromachines 2020, 11(1), 94; https://doi.org/10.3390/mi11010094 - 15 Jan 2020
Cited by 26 | Viewed by 5553
Abstract
Single-cell analysis is of critical importance in revealing cell-to-cell heterogeneity by characterizing individual cells and identifying minority sub-populations of interest. Droplet-based microfluidics has been widely used in the past decade to achieve high-throughput single-cell analysis. However, to maximize the proportion of single-cell emulsification [...] Read more.
Single-cell analysis is of critical importance in revealing cell-to-cell heterogeneity by characterizing individual cells and identifying minority sub-populations of interest. Droplet-based microfluidics has been widely used in the past decade to achieve high-throughput single-cell analysis. However, to maximize the proportion of single-cell emulsification is challenging due to cell sedimentation and aggregation. The purpose of this study was to investigate the influence of single-cell encapsulation and incubation through the use of neutral buoyancy. As a proof of concept, OptiPrep™ was used to create neutrally buoyant cell suspensions of THP-1, a human monocytic leukemia cell line, for single-cell encapsulation and incubation. We found that using a neutrally buoyant suspension greatly increased the efficiency of single-cell encapsulation in microdroplets and eliminated unnecessary cell loss. Moreover, the presence of OptiPrep™ was shown to not affect cellular viability. This method significantly improved the effectiveness of single-cell study in a non-toxic environment and is expected to broadly facilitate single-cell analysis. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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15 pages, 4295 KiB  
Article
A Potential Application of Triangular Microwells to Entrap Single Cancer Cells: A Canine Cutaneous Mast Cell Tumor Model
by Dettachai Ketpun, Alongkorn Pimpin, Tewan Tongmanee, Sudchaya Bhanpattanakul, Prapruddee Piyaviriyakul, Weerayut Srituravanich, Witsaroot Sripumkhai, Wutthinan Jeamsaksiri and Achariya Sailasuta
Micromachines 2019, 10(12), 841; https://doi.org/10.3390/mi10120841 - 01 Dec 2019
Cited by 5 | Viewed by 2743
Abstract
Cellular heterogeneity is a major hindrance, leading to the misunderstanding of dynamic cell biology. However, single cell analysis (SCA) has been used as a practical means to overcome this drawback. Many contemporary methodologies are available for single cell analysis; among these, microfluidics is [...] Read more.
Cellular heterogeneity is a major hindrance, leading to the misunderstanding of dynamic cell biology. However, single cell analysis (SCA) has been used as a practical means to overcome this drawback. Many contemporary methodologies are available for single cell analysis; among these, microfluidics is the most attractive and effective technology, due to its advantages of low-volume specimen consumption, label-free evaluation, and real-time monitoring, among others. In this paper, a conceptual application for microfluidic single cell analysis for veterinary research is presented. A microfluidic device is fabricated with an elastomer substrate, polydimethylsiloxane (PDMS), under standard soft lithography. The performance of the microdevice is high-throughput, sensitive, and user-friendly. A total of 53.1% of the triangular microwells were able to trap single canine cutaneous mast cell tumor (MCT) cells. Of these, 38.82% were single cell entrapments, while 14.34% were multiple cell entrapments. The ratio of single-to-multiple cell trapping was high, at 2.7:1. In addition, 80.5% of the trapped cells were viable, indicating that the system was non-lethal. OCT4A-immunofluorescence combined with the proposed system can assess OCT4A expression in trapped single cells more precisely than OCT4A-immunohistochemistry. Therefore, the results suggest that microfluidic single cell analysis could potentially reduce the impact of cellular heterogeneity. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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12 pages, 3753 KiB  
Article
A New Self-Activated Micropumping Mechanism Capable of Continuous-Flow and Real-Time PCR Amplification Inside 3D Spiral Microreactor
by Kangning Wang, Di Wu and Wenming Wu
Micromachines 2019, 10(10), 685; https://doi.org/10.3390/mi10100685 - 11 Oct 2019
Cited by 4 | Viewed by 2975
Abstract
A self-activated micropump which is capable of stable velocity transport for a liquid to flow a given distance inside a 3D microchannel has been a dream of microfluidic scientists for a long time. A new self-activated pumping mechanism has been proposed in this [...] Read more.
A self-activated micropump which is capable of stable velocity transport for a liquid to flow a given distance inside a 3D microchannel has been a dream of microfluidic scientists for a long time. A new self-activated pumping mechanism has been proposed in this paper. It is different from the authors’ previous research which relied on the fluid resistance of a quartz capillary tube or end-blocked gas-permeable silicone or a polydimethylsiloxane (PDMS) wall to automate the flow. In this research, an end-open stretched Teflon tube was utilized for passive transport for the first time. A new fluid transmission mode was adopted with the assistance of a cheaper easily accessible oil mixture to achieve stable continuous flow. Finally, this novel micropump has been applied to real-time continuous-flow polymerase chain reactions (PCRs), with an amplification efficiency similar to that of a commercial PCR cycler instrument. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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Review

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19 pages, 1415 KiB  
Review
The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review
by Kena Song, Guoqiang Li, Xiangyang Zu, Zhe Du, Liyu Liu and Zhigang Hu
Micromachines 2020, 11(3), 297; https://doi.org/10.3390/mi11030297 - 11 Mar 2020
Cited by 22 | Viewed by 5185
Abstract
Microfluidic systems have been widely explored based on microfluidic technology, and it has been widely used for biomedical screening. The key parts are the fabrication of the base scaffold, the construction of the matrix environment in the 3D system, and the application mechanism. [...] Read more.
Microfluidic systems have been widely explored based on microfluidic technology, and it has been widely used for biomedical screening. The key parts are the fabrication of the base scaffold, the construction of the matrix environment in the 3D system, and the application mechanism. In recent years, a variety of new materials have emerged, meanwhile, some new technologies have been developed. In this review, we highlight the properties of high throughput and the biomedical application of the microfluidic chip and focus on the recent progress of the fabrication and application mechanism. The emergence of various biocompatible materials has provided more available raw materials for microfluidic chips. The material is not confined to polydimethylsiloxane (PDMS) and the extracellular microenvironment is not limited by a natural matrix. The mechanism is also developed in diverse ways, including its special physical structure and external field effects, such as dielectrophoresis, magnetophoresis, and acoustophoresis. Furthermore, the cell/organ-based microfluidic system provides a new platform for drug screening due to imitating the anatomic and physiologic properties in vivo. Although microfluidic technology is currently mostly in the laboratory stage, it has great potential for commercial applications in the future. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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19 pages, 2635 KiB  
Review
Microfluidic Technologies for cfDNA Isolation and Analysis
by Zheyun Xu, Yi Qiao and Jing Tu
Micromachines 2019, 10(10), 672; https://doi.org/10.3390/mi10100672 - 03 Oct 2019
Cited by 15 | Viewed by 3724
Abstract
Cell-free DNA (cfDNA), which promotes precision oncology, has received extensive concern because of its abilities to inform genomic mutations, tumor burden and drug resistance. The absolute quantification of cfDNA concentration has been proved as an independent prognostic biomarker of overall survival. However, the [...] Read more.
Cell-free DNA (cfDNA), which promotes precision oncology, has received extensive concern because of its abilities to inform genomic mutations, tumor burden and drug resistance. The absolute quantification of cfDNA concentration has been proved as an independent prognostic biomarker of overall survival. However, the properties of low abundance and high fragmentation hinder the isolation and further analysis of cfDNA. Microfluidic technologies and lab-on-a-chip (LOC) devices provide an opportunity to deal with cfDNA sample at a micrometer scale, which reduces required sample volume and makes rapid isolation possible. Microfluidic platform also allow for high degree of automation and high-throughput screening without liquid transfer, where rapid and precise examination and quantification could be performed at the same time. Microfluidic technologies applied in cfDNA isolation and analysis are limited and remains to be further explored. This paper reviewed the existing and potential applications of microfluidic technologies in collection and enrichment of cfDNA, quantification, mutation detection and sequencing library construction, followed by discussion of future perspectives. Full article
(This article belongs to the Special Issue Microfluidic for High-Throughput Screening)
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