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Microfluidic Tools for High-Throughput Screening

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Analytical Chemistry".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 38503

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Special Issue Editor

Prof. Dr. R. Michael van Dam

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Guest Editor

1. Crump Institute of Molecular Imaging, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA
2. Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
Interests: microfluidics; radiochemical synthesis; radiochemical analysis; automation; molecular imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There has been tremendous progress over the last several years in the development and commercialization of microfluidic technologies for high-throughput screening (HTS) and library generation. Across a wide range of applications, microfluidic HTS has numerous advantages over conventional tools, including reduced sample and reagent volumes, improved measurement sensitivity, higher density of assays and reagent/sample storage, and implementation of multi-step assays in simple multifunctional microfluidic devices.

HTS has been implemented in diverse types of microfluidic devices including (1) analogs of microplates in which assays are performed in an array of tiny wells or chambers, (2) array-based systems in which samples/reagents are flowed over an array of immobilized or trapped reagents/samples to perform assays, or (3) droplet-in-oil based systems in which assays are performed in a series of isolated droplets separated by an oil stream. Depending on the assay, the devices may manipulate single cells, 2D or 3D cell cultures, tissues, spheroids, small organisms, or biomolecules (e.g., proteins, nucleic acids, peptides), etc. In order to identify “hits”, readout may rely on fluorescence, luminescence, nanoparticle binding, electrical impedance, radioactivity, microscopy (e.g., cell morphology, crystal formation), size, PCR amplification and a multitude of other outputs.

For this Special Issue, we invite original research or review papers that focus on the many current and emerging microfluidic platforms for high-throughput screening, as well as their diverse applications.

Prof. R. Michael van Dam
Guest Editor

Manuscript Submission Information

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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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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
micro total analysis systems
lab on a chip
combinatorial synthesis
high-throughput screening
parallelism

Published Papers (7 papers)

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Research

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13 pages, 5567 KiB

Open AccessArticle

Systematic Investigation of Insulin Fibrillation on a Chip

by Hoon Suk Rho, Henk-Willem Veltkamp, Alexander Thomas Hanke, Marcel Ottens, Christian Breukers, Pamela Habibović and Han Gardeniers

Molecules 2020, 25(6), 1380; https://doi.org/10.3390/molecules25061380 - 18 Mar 2020

Cited by 5 | Viewed by 2875

Abstract

A microfluidic protein aggregation device (microPAD) that allows the user to perform a series of protein incubations with various concentrations of two reagents is demonstrated. The microfluidic device consists of 64 incubation chambers to perform individual incubations of the protein at 64 specific conditions. Parallel processes of metering reagents, stepwise concentration gradient generation, and mixing are achieved simultaneously by pneumatic valves. Fibrillation of bovine insulin was selected to test the device. The effect of insulin and sodium chloride (NaCl) concentration on the formation of fibrillar structures was studied by observing the growth rate of partially folded protein, using the fluorescent marker Thioflavin-T. Moreover, dual gradients of different NaCl and hydrochloric acid (HCl) concentrations were formed, to investigate their interactive roles in the formation of insulin fibrils and spherulites. The chip-system provides a bird’s eye view on protein aggregation, including an overview of the factors that affect the process and their interactions. This microfluidic platform is potentially useful for rapid analysis of the fibrillation of proteins associated with many misfolding-based diseases, such as quantitative and qualitative studies on amyloid growth. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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12 pages, 2615 KiB

Open AccessArticle

Development of a Microfluidic Array to Study Drug Response in Breast Cancer

by María Virumbrales-Muñoz, Megan K. Livingston, Mehtab Farooqui, Melissa C. Skala, David J. Beebe and Jose M. Ayuso

Molecules 2019, 24(23), 4385; https://doi.org/10.3390/molecules24234385 - 30 Nov 2019

Cited by 9 | Viewed by 3297

Abstract

Luminal geometries are common structures in biology, which are challenging to mimic using conventional in vitro techniques based on the use of Petri dishes. In this context, microfluidic systems can mimic the lumen geometry, enabling a large variety of studies. However, most microfluidic models still rely on polydimethylsiloxane (PDMS), a material that is not amenable for high-throughput fabrication and presents some limitations compared with other materials such as polystyrene. Thus, we have developed a microfluidic device array to generate multiple bio-relevant luminal structures utilizing polystyrene and micro-milling. This platform offers a scalable alternative to conventional microfluidic devices designed in PDMS. Additionally, the use of polystyrene has well described advantages, such as lower permeability to hydrophobic molecules compared with PDMS, while maintaining excellent viability and optical properties. Breast cancer cells cultured in the devices exhibited high cell viability similar to PDMS-based microdevices. Further, co-culture experiments with different breast cell types showed the potential of the model to study breast cancer invasion. Finally, we demonstrated the potential of the microfluidic array for drug screening, testing chemotherapy drugs and photodynamic therapy agents for breast cancer. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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10 pages, 2360 KiB

Open AccessArticle

A Microfluidic Spheroid Culture Device with a Concentration Gradient Generator for High-Throughput Screening of Drug Efficacy

by Wanyoung Lim and Sungsu Park

Molecules 2018, 23(12), 3355; https://doi.org/10.3390/molecules23123355 - 18 Dec 2018

Cited by 67 | Viewed by 8719

Abstract

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for three days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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Review

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21 pages, 4371 KiB

Open AccessReview

The Microfluidic Toolbox for Analyzing Exosome Biomarkers of Aging

by Jonalyn DeCastro, Joshua Littig, Peichi Peggy Chou, Jada Mack-Onyeike, Amrita Srinivasan, Michael J. Conboy, Irina M. Conboy and Kiana Aran

Molecules 2021, 26(3), 535; https://doi.org/10.3390/molecules26030535 - 20 Jan 2021

Cited by 11 | Viewed by 4278

Abstract

As the fields of aging and neurological disease expand to liquid biopsies, there is a need to identify informative biomarkers for the diagnosis of neurodegeneration and other age-related disorders such as cancers. A means of high-throughput screening of biomolecules relevant to aging can facilitate this discovery in complex biofluids, such as blood. Exosomes, the smallest of extracellular vesicles, are found in many biofluids and, in recent years, have been found to be excellent candidates as liquid biopsy biomarkers due to their participation in intercellular communication and various pathologies such as cancer metastasis. Recently, exosomes have emerged as novel biomarkers for age-related diseases. Hence, the study of exosomes, their protein and genetic cargo can serve as early biomarkers for age-associated pathologies, especially neurodegenerative diseases. However, a disadvantage of exosome studies includes a lack in standardization of isolating, detecting, and profiling exosomes for downstream analysis. In this review, we will address current techniques for high-throughput isolation and detection of exosomes through various microfluidic and biosensing strategies and how they may be adapted for the detection of biomarkers of age-associated disorders. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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36 pages, 6698 KiB

Open AccessReview

Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening

by Siraprapa Boobphahom, Mai Nguyet Ly, Veasna Soum, Nayoon Pyun, Oh-Sun Kwon, Nadnudda Rodthongkum and Kwanwoo Shin

Molecules 2020, 25(13), 2970; https://doi.org/10.3390/molecules25132970 - 28 Jun 2020

Cited by 38 | Viewed by 7134

Abstract

Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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31 pages, 5340 KiB

Open AccessReview

Microfluidics in Haemostasis: A Review

by Heta Jigar Panchal, Nigel J Kent, Andrew J S Knox and Leanne F Harris

Molecules 2020, 25(4), 833; https://doi.org/10.3390/molecules25040833 - 14 Feb 2020

Cited by 18 | Viewed by 6255

Abstract

Haemostatic disorders are both complex and costly in relation to both their treatment and subsequent management. As leading causes of mortality worldwide, there is an ever-increasing drive to improve the diagnosis and prevention of haemostatic disorders. The field of microfluidic and Lab on a Chip (LOC) technologies is rapidly advancing and the important role of miniaturised diagnostics is becoming more evident in the healthcare system, with particular importance in near patient testing (NPT) and point of care (POC) settings. Microfluidic technologies present innovative solutions to diagnostic and clinical challenges which have the knock-on effect of improving health care and quality of life. In this review, both advanced microfluidic devices (R&D) and commercially available devices for the diagnosis and monitoring of haemostasis-related disorders and antithrombotic therapies, respectively, are discussed. Innovative design specifications, fabrication techniques, and modes of detection in addition to the materials used in developing micro-channels are reviewed in the context of application to the field of haemostasis. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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31 pages, 3267 KiB

Open AccessReview

Microfluidic Technologies for High Throughput Screening Through Sorting and On-Chip Culture of C. elegans

by Daniel Midkiff and Adriana San-Miguel

Molecules 2019, 24(23), 4292; https://doi.org/10.3390/molecules24234292 - 25 Nov 2019

Cited by 22 | Viewed by 5186

Abstract

The nematode Caenorhabditis elegans is a powerful model organism that has been widely used to study molecular biology, cell development, neurobiology, and aging. Despite their use for the past several decades, the conventional techniques for growth, imaging, and behavioral analysis of C. elegans can be cumbersome, and acquiring large data sets in a high-throughput manner can be challenging. Developments in microfluidic “lab-on-a-chip” technologies have improved studies of C. elegans by increasing experimental control and throughput. Microfluidic features such as on-chip control layers, immobilization channels, and chamber arrays have been incorporated to develop increasingly complex platforms that make experimental techniques more powerful. Genetic and chemical screens are performed on C. elegans to determine gene function and phenotypic outcomes of perturbations, to test the effect that chemicals have on health and behavior, and to find drug candidates. In this review, we will discuss microfluidic technologies that have been used to increase the throughput of genetic and chemical screens in C. elegans. We will discuss screens for neurobiology, aging, development, behavior, and many other biological processes. We will also discuss robotic technologies that assist in microfluidic screens, as well as alternate platforms that perform functions similar to microfluidics. Full article

(This article belongs to the Special Issue Microfluidic Tools for High-Throughput Screening)

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