•  
  •  
 

Bulletin of Chinese Academy of Sciences (Chinese Version)

Keywords

organs-on-a-chip; microfluidic; biosensing and devices; disease model; drug evaluation

Document Type

Article

Abstract

Human organs-on-a-chip is a newly emerging and frontier technology involving with different disciplines in recent years. It refers to a biomimetic microphysiological system created on a bioengineered microfluidic device, representing the organ-level functional units. It can recapitulate the physiologically relevant structures and functions of the organs, as well as the interaction between multiple organs as in vivo, thereby offering alternative models for predicting human responses to various drugs and environmental stimulus. Organs-on-a-chip technology has wide application potentials in many fields such as life science, drug discovery, personalized medicine, food/environment monitoring and biological defense et al. The emergence of this technology has attracted much attention from the government, scientific community and industry due to its unique features and promising applications. It has been selected as the "Top Ten Emerging Technologies" by the World Economic Forum in 2016. Considering the huge market in industrialization, several companies have started to get involved in this area and the pace of industrialization has been accelerated rapidly. Human organs-on-a-chip scan not only reproduce the physiopathology of human organ, but it can also enable researchers to witness and study various biological behaviors of the organism in an unprecedented way. It could be used to analyze the occurrence and development of the complicated human diseases in a new perspective, and is expected to bring about a revolution in the traditional fields including biomedical research, drug testing, personalized medicine, toxicity prediction, biodefensive fields. Here, we summarize the origins, development, and application fields of human organson-a-chip technology. We also discuss the existing challenges and give perspectives for the development of this technology in future.

First page

1281

Last Page

1289

Language

Chinese

Publisher

Bulletin of Chinese Academy of Sciences

References

Reardon S. 'Organs-on-chips' go mainstream. Nature, 2015, 523(7560):266-266.

Sin A, Chin K C, Jamil M F, et al. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors. Biotechnology Progress, 2004, 20(1):338-345.

Huh D, Matthews B D, Mammoto A, et al. Reconstituting organlevel lung functions on a chip. Science, 2010, 328(5986):1662-1668.

Huh D, Fujioka H, Tung Y C, et al. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. PNAS, 2007, 104(48):18886-18891.

Huh D, Leslie D C, Matthews B, et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Science Translational Medicine, 2012, 4(159):147-159.

Ma H P, Zhang M, Qin J H, et al. Probing the role of mesenchymal stem cells in salivary gland cancer on biomimetic microdevices. Integrative Biology, 2012, 4(5):522-530.

Liu T J, Lin B C, Qin J H. Carcinoma-associated fibroblasts promoted tumor spheroid invasion on a microfluidic 3D co-culture device. Lab on a Chip, 2010, 10(13):1671-1677.

Zhang Q, Liu T J, Qin J H. A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime. Lab on a Chip, 2012, 12(16):2837-2842.

Xu H, Shervin R, Cody L N, et al. Activation of hypoxia signaling induces phenotypic transformation of glioma cells:implications for bevacizumab antiangiogenic therapy. Oncotarget, 2015, 6(14):11882-11893.

Douville N J, Zamankhan P, Tung Y C, et al. Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model. Lab on a Chip, 2011, 11(4):609-619.

Benam K H, Villenave R, Lucchesi C, et al. Small airway-ona-chip enables analysis of human lung inflammation and drug responses in vitro. Nature Methods, 2016, 13(2):151-157.

McCuskey R S. The hepatic microvascular system in health and its response to toxicants. Anatomical Record, 2008, 291(6):661-671.

Cho C H, Park J, Tilles A W, et al. Layered patterning of hepatocytes in co-culture systems using microfabricated stencils. Biotechniques, 2010, 48(1):47-52.

Bartholomew J K, Michael J Z, Martin L Y, et al. Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes. Analytical Chemistry, 2006, 78(13):4291-4298.

Khetani S R, Bhatia S N. Microscale culture of human liver cells for drug development. Nature Biotechnology, 2008, 26(1):120-126.

Lee P J, Hung P J, Lee L P. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnology and Bioengineering, 2007, 97(5):1340-1346.

Lee S A, No D Y, Kang E, et al. Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects. Lab on a Chip, 2013, 13(18):3529-3537.

Du C, Narayanan K, Leong M F, et al. Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering. Biomaterials, 2014, 35(23):6006-6014.

Weinberg E, Kaazempur M M, Borenstein J. Concept and computational design for a bioartificial nephron-on-a-chip. The International Journal of Artificial Organs, 2008, 31(6):508-514.

Jang K J, Mehr A P, Hamilton G, et al. A Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integrative Biology, 2013, 5(9):1119-1129.

Duan Y, Gotoh N, Yan Q, et al. Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes. PNAS, 2008, 105(32):11418-11423.

Zhou M Y, Ma H P, Lin H L, et al. Induction of epithelial-tomesenchymal transition in proximal tubular epithelial cells on microfluidic devices. Biomaterials, 2014, 35(5):1390-1401.

Shao X J, Gao D, Chen Y L, et al. Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening. Analytica Chimica Acta, 2016, 934:186-193.

Wang J D, Khafagy E S, Khanafer K, et al. Organization of endothelial cells, pericytes, and astrocytes into a 3D microfluidic in vitro model of the blood-brain barrier. Molecular Pharmaceutics, 2016, 13(3):895-906.

Xu H, Li Z Y, Yu Y, et al. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumor. Scientific Reports, 2016, 6:36670.

Oleaga C, Bernabini C, Smith A S, et al. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Scientific Reports, 2016, 6:20030.

Zhang W J, Zhang Y S, Bakht S M, et al. Elastomeric free-form blood vessels for interconnecting organs on chip systems. Lab on a Chip, 2016, 16(9):1579-1586.

Esch M B, Smith A S, Prot J M, et al. How multi-organ microdevices can help foster drug development. Advanced Drug Delivery Reviews, 2014, 69:158-169.

Maschmeyer I, Lorenz A K, Schimek K, et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab on a Chip, 2015, 15(12):2688-2699.

Zhang Y S, Aleman J, Shin S R, et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. PNAS, 2017, 114(12):e2293-2302.

Esch M B, Mahler G J, Stokor T, et al. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab on a Chip, 2014, 14(16):3081-3092.

Sung J H, Kam C, Shuler M L. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab on a Chip, 2010, 10(4):446-455.

Sung J H, Dhiman A, Shuler M L. A Combined pharmacokineticpharmacodynamic (PK-PD) model for tumor growth in the rat with UFT administration. Journal of Pharmaceutical Sciences, 2009, 98(5):1885-1904.

Li Z Y, Guo Y Q, Yu Y, et al. Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip. Integrative Biology, 2016, 8(10):1022-1029.

Li Z Y, Jiang L, Zhu Y J, et al. Assessment of hepatic metabolismdependent nephrotoxicity on an organs-on-a-chip microdevice. Toxicology in Vitro, 2018, 46:1-8.

Li Z Y, Su W T, Zhu Y J, et al. Drug absorption related nephrotoxicity assessment on an intestine-kidney chip. Biomicrofluidics, 2017, 11(3):034114.

Kim H J, Li H, Collins J J, et al. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. PNAS, 2016, 113 (1):7-15.

Wang L, Tao T T, Su W T, et al. A disease model of diabetic nephropathy in aglomerulus-on-a-chip microdevice. Lab on a Chip, 2017, 17:1749-1760.

Wang G, McCain M L, Yang L, et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nature Medicine, 2014, 20(6):616-623.

Zhu Y J, Wang L, Yin F C, et al. Hollow fiber system for simple generation of human brain organoids. Integrative Biology, 2017, 9:774-781.

Zhu Y J, Wang L, Yu H, et al. In situ generation of human brain organoids on a micropillar array. Lab on a Chip, 2017, 17:2941-2950.

Rebelo S A, Dehne E M, Brito C, et al. Validation of bioreactor and human-on-a-chip devices for chemical safety assessment. Validation of Alternative Methods for Toxicity Testing, 2016, 856:299-316.

Alberti M, Dancik Y, Sriram G, et al. Multi-chamber microfluidic platform for high-precision skin permeation testing. Lab on a Chip, 2017, 17(9):1625-1634.

Share

COinS