scholarly journals Organ-on-chip applications in drug discovery: an end user perspective

Author(s):  
Naomi Clapp ◽  
Augustin Amour ◽  
Wendy C. Rowan ◽  
Pelin L. Candarlioglu

Organ-on-chip (OoC) systems are in vitro microfluidic models that mimic the microstructures, functions and physiochemical environments of whole living organs more accurately than two-dimensional models. While still in their infancy, OoCs are expected to bring ground-breaking benefits to a myriad of applications, enabling more human-relevant candidate drug efficacy and toxicity studies, and providing greater insights into mechanisms of human disease. Here, we explore a selection of applications of OoC systems. The future directions and scope of implementing OoCs across the drug discovery process are also discussed.

2020 ◽  
Vol 2020 ◽  
pp. 1-41
Author(s):  
Aida Rodriguez-Garcia ◽  
Jacqueline Oliva-Ramirez ◽  
Claudia Bautista-Flores ◽  
Samira Hosseini

The past few decades have shown significant advancement as complex in vitro humanized systems have substituted animal trials and 2D in vitro studies. 3D humanized platforms mimic the organs of interest with their stimulations (physical, electrical, chemical, and mechanical). Organ-on-chip devices, including in vitro modelling of 3D organoids, 3D microfabrication, and 3D bioprinted platforms, play an essential role in drug discovery, testing, and assessment. In this article, a thorough review is provided of the latest advancements in the area of organ-on-chip devices targeting liver, kidney, lung, gut, heart, skin, and brain mimicry devices for drug discovery, development, and/or assessment. The current strategies, fabrication methods, and the specific application of each device, as well as the advantages and disadvantages, are presented for each reported platform. This comprehensive review also provides some insights on the challenges and future perspectives for the further advancement of each organ-on-chip device.


2020 ◽  
Vol 16 (1) ◽  
pp. 13-23
Author(s):  
Nazmina Vhora ◽  
Ujjal Naskar ◽  
Aishwarya Hiray ◽  
Abhijeet S. Kate ◽  
Alok Jain

BACKGROUND: A higher rate of attenuation of molecules in drug discovery has enabled pharmaceutical companies to enhance the efficiency of their hit identification and lead optimization. Selection and development of appropriate in-vitro and in-vivo strategies may improve this process as primary and secondary screening utilize both strategies. In-vivo approaches are too relentless and expensive for assessing hits. Therefore, it has become indispensable to develop and implement suitable in-vitro screening methods to execute the required activities and meet the respective targets. However, the selection of an appropriate in-vitro assay for specific evaluation of cellular activity is no trivial task. It requires thorough investigation of the various parameters involved. AIM: In this review, we aim to discuss in-vitro assays for type 2 diabetes (T2D), which have been utilized extensively by researchers over the last five years, including target-based, non-target based, low-throughput, and high-throughput screening assays. METHODS: The literature search was conducted using databases including Scifinder, PubMed, ScienceDirect, and Google Scholar to find the significant published articles. DISCUSSION and CONCLUSION: The accuracy and relevance of in-vitro assays have a significant impact on the drug discovery process for T2D, especially in assessing the antidiabetic activity of compounds and identifying the site of effect in high-throughput screening. The report reviews the advantages, limitations, quality parameters, and applications of the probed invitro assays, and compares them with one another to enable the selection of the optimal method for any purpose. The information on these assays will accelerate numerous procedures in the drug development process with consistent quality and accuracy.


2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Luis E Contreras-Llano ◽  
Cheemeng Tan

Abstract The incorporation of cell-free transcription and translation systems into high-throughput screening applications enables the in situ and on-demand expression of peptides and proteins. Coupled with modern microfluidic technology, the cell-free methods allow the screening, directed evolution and selection of desired biomolecules in minimal volumes within a short timescale. Cell-free high-throughput screening applications are classified broadly into in vitro display and on-chip technologies. In this review, we outline the development of cell-free high-throughput screening methods. We further discuss operating principles and representative applications of each screening method. The cell-free high-throughput screening methods may be advanced by the future development of new cell-free systems, miniaturization approaches, and automation technologies.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Maximilian Benz ◽  
Arndt Asperger ◽  
Meike Hamester ◽  
Alexander Welle ◽  
Stefan Heissler ◽  
...  

Abstract Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the whole drug discovery process lengthy and expensive. Here, we demonstrate a chemBIOS platform combining on-chip chemical synthesis, characterization and biological screening. We developed a dendrimer-based surface patterning that enables the generation of high-density nanodroplet arrays for both organic and aqueous liquids. Each droplet (among > 50,000 droplets per plate) functions as an individual, spatially separated nanovessel, that can be used for solution-based synthesis or analytical assays. An additional indium-tin oxide coating enables ultra-fast on-chip detection down to the attomole per droplet by matrix-assisted laser desorption/ionization mass spectrometry. The excellent optical properties of the chemBIOS platform allow for on-chip characterization and in-situ reaction monitoring in the ultraviolet, visible (on-chip UV-Vis spectroscopy and optical microscopy) and infrared (on-chip IR spectroscopy) regions. The platform is compatible with various cell-biological screenings, which opens new avenues in the fields of high-throughput synthesis and drug discovery.


2020 ◽  
Vol 48 (10) ◽  
pp. 849-860
Author(s):  
Kenichi Umehara ◽  
Carina Cantrill ◽  
Matthias Beat Wittwer ◽  
Elisa Di Lenarda ◽  
Florian Klammers ◽  
...  

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