[Application and prospect of microfluidic chip in central nervous system diseases].

In recent years, many human central nervous systems (CNS) of microfluidic platforms and related disease models in vitro have been built with the continuous development of the microfluidic technology and biological microelectronics mechanical systems technology. Microplatforms have emerged to provide a better approximation of the in vivo scenario with better control of the structure, microenvironment and stimuli. This review summarized the basic technology of microfluidic chips in CNS and the application in CNS diseases. In addition, the research of microfluidic chip in CNS diseases has been also prospected. We also highlight challenges that can be addressed with interdisciplinary efforts to achieve more biomimicry.

[1]  Jung Keun Hyun,et al.  Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease. , 2015, Lab on a chip.

[2]  J. Winderickx,et al.  Digital ELISA for the quantification of attomolar concentrations of Alzheimer's disease biomarker protein Tau in biological samples. , 2018, Analytica chimica acta.

[3]  Virginia Chu,et al.  A Novel Microfluidic Cell Co-culture Platform for the Study of the Molecular Mechanisms of Parkinson's Disease and Other Synucleinopathies , 2016, Front. Neurosci..

[4]  Jianrong Li,et al.  Multi-compartment neuron-glia co-culture platform for localized CNS axon-glia interaction study. , 2012, Lab on a chip.

[5]  R. Kodzius,et al.  Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips , 2017, Genes.

[6]  M. Yarmush,et al.  An organotypic uniaxial strain model using microfluidics. , 2013, Lab on a chip.

[7]  Roger D. Kamm,et al.  Modeling the Blood-Brain Barrier in a 3D triple co-culture microfluidic system , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[8]  Roger D. Kamm,et al.  A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. , 2017, Lab on a chip.

[9]  Bryson M. Brewer,et al.  Glia co-culture with neurons in microfluidic platforms promotes the formation and stabilization of synaptic contacts. , 2013, Lab on a chip.

[10]  Sang-Hoon Lee,et al.  Size-controllable networked neurospheres as a 3D neuronal tissue model for Alzheimer's disease studies. , 2013, Biomaterials.

[11]  Rosanne M. Guijt,et al.  Mild and repetitive very mild axonal stretch injury triggers cystoskeletal mislocalization and growth cone collapse , 2017, PloS one.

[12]  Ali Khademhosseini,et al.  Gradient static-strain stimulation in a microfluidic chip for 3D cellular alignment. , 2014, Lab on a chip.

[13]  Bo Liu,et al.  The Role of Microfluidics for Organ on Chip Simulations , 2017, Bioengineering.

[14]  Nathalie Y. R. Agar,et al.  Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents , 2017, Nature Communications.

[15]  Julio Saez-Rodriguez,et al.  A microfluidics platform for combinatorial drug screening on cancer biopsies , 2018, Nature Communications.

[16]  Hyun Soo Kim,et al.  A Microchip for High-Throughput Axon Growth Drug Screening , 2016, Micromachines.

[17]  Nitish Thakor,et al.  A two-compartment organotypic model of mammalian peripheral nerve repair , 2014, Journal of Neuroscience Methods.

[18]  T. Gillis,et al.  Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. , 2012, Cell stem cell.

[19]  Xiaoming Chen,et al.  Droplet Microfluidic System with On-Demand Trapping and Releasing of Droplet for Drug Screening Applications. , 2017, Analytical chemistry.

[20]  B. Hyman,et al.  Microfluidic Chemotaxis Platform for Differentiating the Roles of Soluble and Bound Amyloid-β on Microglial Accumulation , 2013, Scientific Reports.

[21]  Sang-Hoon Lee,et al.  Central Nervous System and its Disease Models on a Chip. , 2015, Trends in biotechnology.

[22]  Justin C. Williams,et al.  Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment. , 2007, Lab on a chip.

[23]  Bruce C Wheeler,et al.  Designing Neural Networks in Culture: Experiments are described for controlled growth, of nerve cells taken from rats, in predesigned geometrical patterns on laboratory culture dishes. , 2010, Proceedings of the IEEE. Institute of Electrical and Electronics Engineers.

[24]  Shelly E. Sakiyama-Elbert,et al.  A microdevice platform for visualizing mitochondrial transport in aligned dopaminergic axons , 2012, Journal of Neuroscience Methods.

[25]  M. Sastre,et al.  Modulation of inflammation in transgenic models of Alzheimer’s disease , 2014, Journal of Neuroinflammation.

[26]  Labchan Rajbhandari,et al.  Toll/Interleukin-1 Receptor Domain-Containing Adapter Inducing Interferon-β Mediates Microglial Phagocytosis of Degenerating Axons , 2012, The Journal of Neuroscience.

[27]  Qing Yang,et al.  Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor. , 2015, Biomicrofluidics.

[28]  Nitish Thakor,et al.  Investigation of nerve injury through microfluidic devices , 2014, Journal of The Royal Society Interface.

[29]  Anja Kunze,et al.  Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies. , 2011, Biotechnology and bioengineering.

[30]  F. Gomez,et al.  Application of a computational neural network to optimize the fluorescence signal from a receptor–ligand interaction on a microfluidic chip , 2015, Electrophoresis.

[31]  Qin Tu,et al.  Dynamic trapping and high-throughput patterning of cells using pneumatic microstructures in an integrated microfluidic device. , 2012, Lab on a chip.

[32]  Mathias J. Aebersold,et al.  Simple and Inexpensive Paper-Based Astrocyte Co-culture to Improve Survival of Low-Density Neuronal Networks , 2018, Front. Neurosci..

[33]  Wenming Liu,et al.  Investigation of hypoxia-induced myocardial injury dynamics in a tissue interface mimicking microfluidic device. , 2013, Analytical chemistry.

[34]  Jichul Kim,et al.  Development and characterization of a microfluidic chamber incorporating fluid ports with active suction for localized chemical stimulation of brain slices. , 2011, Lab on a chip.

[35]  Xuehong Zhang,et al.  A microfluidics-based mobility shift assay to identify new inhibitors of β-secretase for Alzheimer’s disease , 2017, Analytical and Bioanalytical Chemistry.

[36]  Yoonsuck Choe,et al.  A microchip for quantitative analysis of CNS axon growth under localized biomolecular treatments , 2014, Journal of Neuroscience Methods.

[37]  M. Zagnoni,et al.  A Microfluidic Platform for the Characterisation of CNS Active Compounds , 2017, Scientific Reports.

[38]  C. Moussa,et al.  Tau deletion impairs intracellular β-amyloid-42 clearance and leads to more extracellular plaque deposition in gene transfer models , 2014, Molecular Neurodegeneration.

[39]  K. C. Brennan,et al.  Minimum conditions for the induction of cortical spreading depression in brain slices. , 2014, Journal of neurophysiology.

[40]  David T. Eddington,et al.  Precise Spatial and Temporal Control of Oxygen within In Vitro Brain Slices via Microfluidic Gas Channels , 2012, PloS one.

[41]  Yoonkey Nam,et al.  Agarose microwell based neuronal micro-circuit arrays on microelectrode arrays for high throughput drug testing. , 2009, Lab on a chip.

[42]  Jean-Louis Viovy,et al.  Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers. , 2011, Lab on a chip.

[43]  Yana Pigareva,et al.  Design of Cultured Neuron Networks in vitro with Predefined Connectivity Using Asymmetric Microfluidic Channels , 2017, Scientific Reports.

[44]  A. Lees The Parkinson chimera , 2009, Neurology.

[45]  M. Radisic,et al.  Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies. , 2018, Advanced healthcare materials.

[46]  H. R. Lu,et al.  Do in vitro assays in rat primary neurons predict drug‐induced seizure liability in humans? , 2018, Toxicology and applied pharmacology.

[47]  Jing Liu,et al.  Perfused drop microfluidic device for brain slice culture-based drug discovery , 2016, Biomedical microdevices.

[48]  Yoonkey Nam,et al.  Development of astroglial cells in patterned neuronal cultures , 2007, Journal of biomaterials science. Polymer edition.

[49]  B. Vogt,et al.  Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic‐anterior cingulate slice , 2011, Epilepsia.

[50]  A. A. Castrejón-Pita,et al.  Microfluidic chambers using fluid walls for cell biology , 2018, Proceedings of the National Academy of Sciences.

[51]  Daniel Irimia,et al.  Differential effect of three‐repeat and four‐repeat tau on mitochondrial axonal transport , 2009, Journal of neurochemistry.

[52]  Andre Levchenko,et al.  Brain-on-a-chip model enables analysis of human neuronal differentiation and chemotaxis. , 2016, Lab on a chip.

[53]  Harald Sontheimer,et al.  Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine , 2017, Stem Cell Reviews and Reports.