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Micromachines
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Lab-on-a-Chip Systems for Toxicology
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Lab-on-a-Chip Systems for Toxicology

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

Deadline for manuscript submissions: closed (1 March 2020) | Viewed by 29444

Special Issue Editors

Prof. Dr. Donald Wlodkowic

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Guest Editor
School of Science, RMIT University, Bundoora West Campus, PO Box 71, Bundoora, VIC 3083, Australia
Interests: chemobehavioral phenomics; neuropharmacology; neurotoxicology; ecotoxicology; programmed cell death; lab-on-a-chip
Special Issues, Collections and Topics in MDPI journals
Dr. Olivia Campana

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Guest Editor
Dpt. Physical Chemistry, University of Cadiz , Andalusian Center for Marine Science and Technology, CACYTMAR , Campus Universitario Puerto Real, 11510 Puerto Real, Spain
Interests: ecotoxicology; environmental risk assessment; sediment quality guidelines; aquatic contamination

Special Issue Information

Dear Colleagues,

Miniaturized perfusion-based systems, commonly known as Lab-on-a-Chip technologies, are experiencing explosive growth worldwide with a substantial promise of a direct impact on biosciences. They represent a unique approach that enables specific biological questions to be addressed with technological advances that provide fundamentally new capabilities in the spatio-temporal analysis of molecules, cells, and small metazoan model organisms. The development of innovative microperfusion technologies can bring substantial benefits for a number of research areas in a broadly understood field of toxicology.

This Special Issue will showcase recent developments of chip-based technologies for toxicology. Our aim is to outline a very broad scope of applications that include but are not limited to drug discovery, predictive toxicology, experimental biology, and ecotoxicology/environmental risk assessment. We are interested in contributions covering both molecular and cell-based assays, organs-on-a-chip as well as applications of chip-based systems for biotests utilizing small model organisms. We invite both full research papers and short technical communications, as well as review articles and perspectives.

Prof. Donald Wlodkowic
Dr. Olivia Campana
Guest Editors

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

  • Toxicology
  • Ecotoxicology
  • Experimental biology
  • Lab-on-a-chip
  • Microperfusuon
  • Bioassay

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Published Papers (4 papers)

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Research

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10 pages, 4545 KiB  
Article
Micropillar/Microwell Chip Assessment for Detoxification of Bisphenol A with Korean Pear (Pyrus pyrifolia)
by Dong Woo Lee, Moo-Yeal Lee, Sukkil Koh and Mihi Yang
Micromachines 2020, 11(10), 922; https://doi.org/10.3390/mi11100922 - 3 Oct 2020
Cited by 7 | Viewed by 3963
Abstract
A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In [...] Read more.
A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear (Pyrus pyrifolia) extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC50 values. The IC50 value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (Ps < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Systems for Toxicology)
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Review

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28 pages, 2304 KiB  
Review
Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
by Giuseppe Caruso, Nicolò Musso, Margherita Grasso, Angelita Costantino, Giuseppe Lazzarino, Fabio Tascedda, Massimo Gulisano, Susan M. Lunte and Filippo Caraci
Micromachines 2020, 11(6), 593; https://doi.org/10.3390/mi11060593 - 15 Jun 2020
Cited by 33 | Viewed by 6288
Abstract
The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are [...] Read more.
The last decades of biological, toxicological, and pharmacological research have deeply changed the way researchers select the most appropriate ‘pre-clinical model’. The absence of relevant animal models for many human diseases, as well as the inaccurate prognosis coming from ‘conventional’ pre-clinical models, are among the major reasons of the failures observed in clinical trials. This evidence has pushed several research groups to move more often from a classic cellular or animal modeling approach to an alternative and broader vision that includes the involvement of microfluidic-based technologies. The use of microfluidic devices offers several benefits including fast analysis times, high sensitivity and reproducibility, the ability to quantitate multiple chemical species, and the simulation of cellular response mimicking the closest human in vivo milieu. Therefore, they represent a useful way to study drug–organ interactions and related safety and toxicity, and to model organ development and various pathologies ‘in a dish’. The present review will address the applicability of microfluidic-based technologies in different systems (2D and 3D). We will focus our attention on applications of microchip electrophoresis (ME) to biological and toxicological studies as well as in drug discovery and development processes. These include high-throughput single-cell gene expression profiling, simultaneous determination of antioxidants and reactive oxygen and nitrogen species, DNA analysis, and sensitive determination of neurotransmitters in biological fluids. We will discuss new data obtained by ME coupled to laser-induced fluorescence (ME-LIF) and electrochemical detection (ME-EC) regarding the production and degradation of nitric oxide, a fundamental signaling molecule regulating virtually every critical cellular function. Finally, the integration of microfluidics with recent innovative technologies—such as organoids, organ-on-chip, and 3D printing—for the design of new in vitro experimental devices will be presented with a specific attention to drug development applications. This ‘composite’ review highlights the potential impact of 2D and 3D microfluidic systems as a fast, inexpensive, and highly sensitive tool for high-throughput drug screening and preclinical toxicological studies. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Systems for Toxicology)
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22 pages, 1873 KiB  
Review
The Influence of Chronic Liver Diseases on Hepatic Vasculature: A Liver-on-a-chip Review
by Alican Özkan, Danielle Stolley, Erik N. K. Cressman, Matthew McMillin, Sharon DeMorrow, Thomas E. Yankeelov and Marissa Nichole Rylander
Micromachines 2020, 11(5), 487; https://doi.org/10.3390/mi11050487 - 9 May 2020
Cited by 20 | Viewed by 7634
Abstract
In chronic liver diseases and hepatocellular carcinoma, the cells and extracellular matrix of the liver undergo significant alteration in response to chronic injury. Recent literature has highlighted the critical, but less studied, role of the liver vasculature in the progression of chronic liver [...] Read more.
In chronic liver diseases and hepatocellular carcinoma, the cells and extracellular matrix of the liver undergo significant alteration in response to chronic injury. Recent literature has highlighted the critical, but less studied, role of the liver vasculature in the progression of chronic liver diseases. Recent advancements in liver-on-a-chip systems has allowed in depth investigation of the role that the hepatic vasculature plays both in response to, and progression of, chronic liver disease. In this review, we first introduce the structure, gradients, mechanical properties, and cellular composition of the liver and describe how these factors influence the vasculature. We summarize state-of-the-art vascularized liver-on-a-chip platforms for investigating biological models of chronic liver disease and their influence on the liver sinusoidal endothelial cells of the hepatic vasculature. We conclude with a discussion of how future developments in the field may affect the study of chronic liver diseases, and drug development and testing. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Systems for Toxicology)
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24 pages, 8564 KiB  
Review
Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review
by Ye Cong, Xiahe Han, Youping Wang, Zongzheng Chen, Yao Lu, Tingjiao Liu, Zhengzhi Wu, Yu Jin, Yong Luo and Xiuli Zhang
Micromachines 2020, 11(4), 381; https://doi.org/10.3390/mi11040381 - 3 Apr 2020
Cited by 89 | Viewed by 10782
Abstract
Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation [...] Read more.
Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Systems for Toxicology)
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