Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis

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-clin...

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Main Authors: Giuseppe Caruso, Nicolò Musso, Margherita Grasso, Angelita Costantino, Giuseppe Lazzarino, Fabio Tascedda, Massimo Gulisano, Susan M. Lunte, Filippo Caraci
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Micromachines
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Online Access:https://www.mdpi.com/2072-666X/11/6/593
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author Giuseppe Caruso
Nicolò Musso
Margherita Grasso
Angelita Costantino
Giuseppe Lazzarino
Fabio Tascedda
Massimo Gulisano
Susan M. Lunte
Filippo Caraci
author_facet Giuseppe Caruso
Nicolò Musso
Margherita Grasso
Angelita Costantino
Giuseppe Lazzarino
Fabio Tascedda
Massimo Gulisano
Susan M. Lunte
Filippo Caraci
author_sort Giuseppe Caruso
collection DOAJ
description 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.
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spelling doaj.art-50c614a277164049a89e3edb7162dd062023-11-20T03:52:32ZengMDPI AGMicromachines2072-666X2020-06-0111659310.3390/mi11060593Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip ElectrophoresisGiuseppe Caruso0Nicolò Musso1Margherita Grasso2Angelita Costantino3Giuseppe Lazzarino4Fabio Tascedda5Massimo Gulisano6Susan M. Lunte7Filippo Caraci8Oasi Research Institute—IRCCS, 94018 Troina (EN), ItalyDepartment of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95125 Catania, ItalyOasi Research Institute—IRCCS, 94018 Troina (EN), ItalyDepartment of Drug Sciences, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95125 Catania, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Drug Sciences, University of Catania, 95125 Catania, ItalyRalph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USAOasi Research Institute—IRCCS, 94018 Troina (EN), ItalyThe 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.https://www.mdpi.com/2072-666X/11/6/593toxicologydrug screeningmicrochip electrophoresiscarnosineorgans-on-a-chiporganoids
spellingShingle Giuseppe Caruso
Nicolò Musso
Margherita Grasso
Angelita Costantino
Giuseppe Lazzarino
Fabio Tascedda
Massimo Gulisano
Susan M. Lunte
Filippo Caraci
Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
Micromachines
toxicology
drug screening
microchip electrophoresis
carnosine
organs-on-a-chip
organoids
title Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
title_full Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
title_fullStr Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
title_full_unstemmed Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
title_short Microfluidics as a Novel Tool for Biological and Toxicological Assays in Drug Discovery Processes: Focus on Microchip Electrophoresis
title_sort microfluidics as a novel tool for biological and toxicological assays in drug discovery processes focus on microchip electrophoresis
topic toxicology
drug screening
microchip electrophoresis
carnosine
organs-on-a-chip
organoids
url https://www.mdpi.com/2072-666X/11/6/593
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