Molecular Neurobiology

, Volume 56, Issue 12, pp 8489–8512 | Cite as

Microfluidic Brain-on-a-Chip: Perspectives for Mimicking Neural System Disorders

  • Mirza Ali Mofazzal Jahromi
  • Amir Abdoli
  • Mohammad Rahmanian
  • Hassan Bardania
  • Mehrdad Bayandori
  • Seyed Masoud Moosavi Basri
  • Alireza Kalbasi
  • Amir Reza Aref
  • Mahdi KarimiEmail author
  • Michael R HamblinEmail author


Neurodegenerative diseases (NDDs) include more than 600 types of nervous system disorders in humans that impact tens of millions of people worldwide. Estimates by the World Health Organization (WHO) suggest NDDs will increase by nearly 50% by 2030. Hence, development of advanced models for research on NDDs is needed to explore new therapeutic strategies and explore the pathogenesis of these disorders. Different approaches have been deployed in order to investigate nervous system disorders, including two-and three-dimensional (2D and 3D) cell cultures and animal models. However, these models have limitations, such as lacking cellular tension, fluid shear stress, and compression analysis; thus, studying the biochemical effects of therapeutic molecules on the biophysiological interactions of cells, tissues, and organs is problematic. The microfluidic “organ-on-a-chip” is an inexpensive and rapid analytical technology to create an effective tool for manipulation, monitoring, and assessment of cells, and investigating drug discovery, which enables the culture of various cells in a small amount of fluid (10−9 to 10−18 L). Thus, these chips have the ability to overcome the mentioned restrictions of 2D and 3D cell cultures, as well as animal models. Stem cells (SCs), particularly neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) have the capability to give rise to various neural system cells. Hence, microfluidic organ-on-a-chip and SCs can be used as potential research tools to study the treatment of central nervous system (CNS) and peripheral nervous system (PNS) disorders. Accordingly, in the present review, we discuss the latest progress in microfluidic brain-on-a-chip as a powerful and advanced technology that can be used in basic studies to investigate normal and abnormal functions of the nervous system.


Nervous system Brain Neurodegenerative diseases Microfluidic brain-on-a-chip Stem cells 







Alzheimer’s disease


adsorption, distribution, metabolism, excretion


amyotrophic lateral sclerosis




blood–brain barrier


brain endothelial cells


basic fibroblast growth factor


brain microvascular endothelial cells


Brain Research through Advancing Innovative Neurotechnologies


cluster of differentiation


central nervous system


chicken ovalbumin upstream promoter transcription factor-interacting protein 2


Defense Advanced Research Projects Agency






extracellular matrix


endothelial cells


embryonic germ cells


epidermal growth factor receptor


epidermal growth factor


embryonic stem cells


Food and Drug Administration


fluorescein isothiocyanate


forkhead box protein G1


glioblastoma multiforme


granulocyte colony-stimulating factor


glial fibrillary acidic protein


human brain microvascular endothelial cells


Human Brain Project


Huntington’s disease


human-induced pluripotent stem cells


human umbilical vein endothelial cells


insulin gene enhancer protein 1


insulin-transferrin–sodium selenite supplement




early growth response 2 (egr2)






multiple sclerosis


National Center for Advancing Translational Sciences


neurodegenerative diseases


National Institutes of Health


neural progenitor cells


neural stem cells


National Science Foundation


neuron glial antigen 2


neural stem/progenitor cells


neurovascular chip


Parkinson’s disease


paired box gene 2/6




poly(ethylene) glycol diacrylate




peripheral nervous system




phosphatase and tensin homolog


real-time polymerase chain reaction


stem cells




scanning electron microscopy


sex determining region Y-box 2


stage-specific embryonic antigen


traumatic brain injury


T-box brain 1


trans-endothelial electrical resistance


tumor necrosis factor-alpha


neuron-specific class III beta-tubulin


terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling


zonula occludens-1; GFP, green fluorescent protein; human cerebral microvascular endothelial cell, hCMEC/D3; human umbilical veinendothelial cell, HUVEC.



M.R.H. was supported by US NIH Grants R01AI050875 and R21AI121700.

Compliance with Ethical Standards

Competing Interests

M.R.H. is on the following Scientific Advisory Boards:

Transdermal Cap Inc., Cleveland, OH.

BeWell Global Inc., Wan Chai, Hong Kong.

Hologenix Inc., Santa Monica, CA.

LumiThera Inc., Poulsbo, WA.

Vielight, Toronto, Canada.

Bright Photomedicine, Sao Paulo, Brazil.

Quantum Dynamics LLC, Cambridge, MA.

Global Photon Inc., Bee Cave, TX.

Medical Coherence, Boston MA.

NeuroThera, Newark DE.

JOOVV Inc., Minneapolis–St. Paul, MN.

AIRx Medical, Pleasanton, CA.

FIR Industries, Inc. Ramsey, NJ.

UVLRx Therapeutics, Oldsmar, FL.

Ultralux UV Inc., Lansing MI.

Illumiheal & Petthera, Shoreline, WA.

MB Lasertherapy, Houston, TX.

ARRC LED, San Clemente, CA.

Varuna Biomedical Corp., Incline Village, NV.

Niraxx Light Therapeutics, Inc., Boston, MA.

M.R.H. has been a consultant for:

Lexington Int, Boca Raton, FL.

USHIO Corp, Japan.

Merck KGaA, Darmstadt, Germany.

Philips Electronics Nederland B.V.

Johnson & Johnson Inc., Philadelphia, PA.

Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.

M.R.H. is a stockholder in:

Global Photon Inc., Bee Cave, TX.

Mitonix, Newark, DE.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mirza Ali Mofazzal Jahromi
    • 1
    • 2
  • Amir Abdoli
    • 2
    • 3
    • 4
  • Mohammad Rahmanian
    • 2
    • 5
  • Hassan Bardania
    • 6
  • Mehrdad Bayandori
    • 7
    • 8
  • Seyed Masoud Moosavi Basri
    • 9
  • Alireza Kalbasi
    • 10
  • Amir Reza Aref
    • 11
  • Mahdi Karimi
    • 7
    • 8
    • 12
    • 13
    • 14
    Email author
  • Michael R Hamblin
    • 14
    • 15
    • 16
    Email author
  1. 1.Department of Advanced Medical Sciences & Technologies, School of MedicineJahrom University of Medical SciencesJahromIran
  2. 2.Research Center for Noncommunicable Diseases, School of MedicineJahrom University of Medical SciencesJahromIran
  3. 3.Department of Parasitology and Mycology, School of MedicineJahrom University of Medical SciencesJahromIran
  4. 4.Zoonoses Research CenterJahrom University of Medical SciencesJahromIran
  5. 5.Department of Anesthesiology, Critical Care, and Pain MedicineJahrom University of Medical SciencesJahromIran
  6. 6.Cellular and Molecular Research CenterYasuj University of Medical SciencesYasujIran
  7. 7.Oncopathology Research CenterIran University of Medical SciencesTehranIran
  8. 8.Department of Medical Nanotechnology, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran
  9. 9.Civil & Environmental Engineering DepartmentShahid Beheshti UniversityTehranIran
  10. 10.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  11. 11.Department of Cancer Biology, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Department of GeneticsHarvard Medical SchoolBostonUSA
  12. 12.Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
  13. 13.Research Center for Science and Technology in MedicineTehran University of Medical SciencesTehranIran
  14. 14.Wellman Center for Photomedicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  15. 15.Department of DermatologyHarvard Medical SchoolBostonUSA
  16. 16.Harvard-MIT Division of Health Sciences and TechnologyCambridgeUSA

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