Organ-on-a-chip: recent breakthroughs and future prospects

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Abstract

The organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

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Microfluidics: Fluid physics at the nanoliter scale

Todd Squires, Stephen Quake (2005)

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Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Skarphedinn Halldorsson, Edinson Lucumi, Rafael Gómez-Sjöberg … (2015)

Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture.

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Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB).

Ross H Booth, Hanseup Kim (2012)

The blood-brain barrier (BBB), a unique selective barrier for the central nervous system (CNS), hinders the passage of most compounds to the CNS, complicating drug development. Innovative in vitro models of the BBB can provide useful insights into its role in CNS disease progression and drug delivery. Static transwell models lack fluidic shear stress, while the conventional dynamic in vitro BBB lacks a thin dual cell layer interface. To address both limitations, we developed a microfluidic blood-brain barrier (μBBB) which closely mimics the in vivo BBB with a dynamic environment and a comparatively thin culture membrane (10 μm). To test validity of the fabricated BBB model, μBBBs were cultured with b.End3 endothelial cells, both with and without co-cultured C8-D1A astrocytes, and their key properties were tested with optical imaging, trans-endothelial electrical resistance (TEER), and permeability assays. The resultant imaging of ZO-1 revealed clearly expressed tight junctions in b.End3 cells, Live/Dead assays indicated high cell viability, and astrocytic morphology of C8-D1A cells were confirmed by ESEM and GFAP immunostains. By day 3 of endothelial culture, TEER levels typically exceeded 250 Ω cm(2) in μBBB co-cultures, and 25 Ω cm(2) for transwell co-cultures. Instantaneous transient drop in TEER in response to histamine exposure was observed in real-time, followed by recovery, implying stability of the fabricated μBBB model. Resultant permeability coefficients were comparable to previous BBB models, and were significantly increased at higher pH (>10). These results demonstrate that the developed μBBB system is a valid model for some studies of BBB function and drug delivery.

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Author and article information

Contributors

Qirui Wu: wuqirui@shu.edu.cn

Jinfeng Liu: Perpethere@shu.edu.cn

Xiaohong Wang: wxh0201@t.shu.edu.cn

Lingyan Feng: lingyanfeng@t.shu.edu.cn

Jinbo Wu: jinbowu@t.shu.edu.cn

Xiaoli Zhu: xiaolizhu@shu.edu.cn

Weijia Wen: phwen@ust.hk

Xiuqing Gong:

ORCID: http://orcid.org/0000-0001-8519-1317

gongxiuqing@shu.edu.cn

Journal

Journal ID (nlm-ta): Biomed Eng Online

Journal ID (iso-abbrev): Biomed Eng Online

Title: BioMedical Engineering OnLine

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-925X

Publication date (Electronic): 12 February 2020

Publication date PMC-release: 12 February 2020

Publication date Collection: 2020

Volume: 19

Electronic Location Identifier: 9

Affiliations

[1 ]ISNI 0000 0001 2323 5732, GRID grid.39436.3b, Materials Genome Institute, , Shanghai University, ; Shanghai, 200444 China

[2 ]ISNI 0000 0001 2323 5732, GRID grid.39436.3b, School of Life Sciences, , Shanghai University, ; Shanghai, 200444 China

Author information

Xiuqing Gong http://orcid.org/0000-0001-8519-1317

Article

Publisher ID: 752

DOI: 10.1186/s12938-020-0752-0

PMC ID: 7017614

PubMed ID: 32050989

SO-VID: ce9685b6-7d02-4ab5-96f3-537aef8dc2fe

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 11 November 2019

Date accepted : 5 February 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 21775101

Award Recipient : Xiuqing Gong

Funded by: Shanghai Pujiang Program

Award ID: 17PJ1402800

Award Recipient : Xiuqing Gong

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ScienceOpen disciplines: Biomedical engineering

Keywords: organ-on-a-chip,microfluidic chip,physiological model,human organs,stem cell

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ScienceOpen disciplines: Biomedical engineering

Keywords: organ-on-a-chip, microfluidic chip, physiological model, human organs, stem cell

Organ-on-a-chip: recent breakthroughs and future prospects

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Most cited references 103

Microfluidics: Fluid physics at the nanoliter scale

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB).

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