scholarly journals Microfluidic organ-on-chip technology for blood-brain barrier research

2016 ◽  
Vol 4 (1) ◽  
pp. e1142493 ◽  
Author(s):  
Marinke W van der Helm ◽  
Andries D van der Meer ◽  
Jan C T Eijkel ◽  
Albert van den Berg ◽  
Loes I Segerink
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Chip Technology ◽  
On Chip

scholarly journals Multiplexed blood–brain barrier organ-on-chip

Lab on a Chip ◽  
2020 ◽  
Vol 20 (17) ◽  
pp. 3132-3143 ◽  
Author(s):  
M. Zakharova ◽  
M. A. Palma do Carmo ◽  
M. W. van der Helm ◽  
H. Le-The ◽  
M. N. S. de Graaf ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Visual Inspection ◽  
Brain Barrier ◽  
Pdms Membrane ◽  
Blood Brain ◽  
On Chip

The developed multiplexed chip contains 8 channels that can be accessed individually or simultaneously with increased throughput. The visual inspection of cells in the device was improved with our fabricated 2 μm-thick porous PDMS membrane.

EXTH-17. A FOCUSED ULTRASOUND BLOOD BRAIN BARRIER DISRUPTION MODEL TO TEST THE INFLUENCE OF TIGHT JUNCTION GENES TO TREAT BRAIN TUMORS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi167-vi167
Author(s):  
Jayashree Iyer ◽  
Adam Akkad ◽  
Nanyun Tang ◽  
Michael Berens ◽  
Frederic Zenhausern ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Cell Junctions ◽  
Brain Barrier ◽  
Western Blots ◽  
Protective Function ◽  
Blood Brain ◽  
On Chip

Abstract Treating primary or metastatic tumors in the brain (glioblastomas, melanoma, lung cancer, breast cancer) proves challenging by virtue of the protective function of the blood brain barrier (BBB). The tight junction proteins (TJPs) binding the specialized endothelial cells of the BBB largely contribute to the limited permeability of cancer-therapeutic drugs. In both preclinical and clinical models, low intensity focused ultrasound (LIFU) coupled with microbubbles has been proven to safely and transiently open the BBB. Despite this method being established, potential genetic influences on the durability and vulnerability of tight junctions to LIFU have not been elucidated, nor have the determinants of tight junction repair post LIFU been thoroughly investigated. We report the development of an ultrasound transparent organ-on-chip model populated by iPSC-derived endothelial cells (iPSC-EC) co-cultured with astrocytes. We aim to probe the contributions of various tight junction genes to barrier integrity along with the subsequent protein topology involved in reassembly post ultrasound. Thus, this model serves to determine parameters for ultrasound disruption for precision opening of the BBB. The BBB-On-Chip was successfully fabricated and assembled with an optimized technique that has an 80% yield of leak-free devices, with stable cavitation post nanobubble injection. Furthermore, Western blots show expression of claudin-5, a key TJP, in our iPSC-ECs. We have also demonstrated by confocal microscopy that another component of the TJP complex, ZO-1, can be visualized at iPSC-derived cell junctions. Further benchmarking of device-ultrasound interactions, successful iPSC differentiation, tight junction formation, and fabrication of nanobubbles and their assistance in ultrasound BBB disruption will be presented. Efforts are underway to characterize the contributions of tight junction genes and their variations to the integrity and disruption of the BBB.

BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

2012 ◽  
Vol 15 (1) ◽  
pp. 145-150 ◽  
Author(s):  
L. M. Griep ◽  
F. Wolbers ◽  
B. de Wagenaar ◽  
P. M. ter Braak ◽  
B. B. Weksler ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Function ◽  
Brain Barrier ◽  
Microfluidic Platform ◽  
Blood Brain ◽  
On Chip

scholarly journals Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Jacquelyn A. Brown ◽  
Simona G. Codreanu ◽  
Mingjian Shi ◽  
Stacy D. Sherrod ◽  
Dmitry A. Markov ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Neurovascular Unit ◽  
Brain Barrier ◽  
Blood Brain ◽  
On Chip

scholarly journals Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier

2016 ◽  
Vol 110 (2) ◽  
pp. 503-513 ◽  
Author(s):  
Mohammad Bonakdar ◽  
Elisa M. Wasson ◽  
Yong W. Lee ◽  
Rafael V. Davalos
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Endothelial Cells ◽  
Blood Brain ◽  
On Chip

scholarly journals Continuous monitoring reveals protective effects of N-acetylcysteine amide on an isogenic microphysiological model of the neurovascular unit

2021 ◽  
Author(s):  
Isabelle Matthiesen ◽  
Dimitrios Voulgaris ◽  
Polyxeni Nikolakopoulou ◽  
Thomas E Winkler ◽  
Anna Herland
Keyword(s):  
Blood Brain Barrier ◽  
Nitrosative Stress ◽  
Neurovascular Unit ◽  
Induced Pluripotent Stem Cell ◽  
Brain Barrier ◽  
Protective Effects ◽  
Drug Induced ◽  
Blood Brain ◽  
On Chip

Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. We report the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2-minute temporal resolution. We showcase its capabilities in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol-ene epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell-substrate endothelial resistance monitoring allows us to capture formation and breakdown of our blood-brain barrier model, consisting of co-cultured hiPSC-derived endothelial-like and astrocyte-like cells. We observe clear cellular disruption when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and report on the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide. Using metabolomic network analysis, we further find drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like ours opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.

scholarly journals A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1474
Author(s):  
Behnam Noorani ◽  
Aditya Bhalerao ◽  
Snehal Raut ◽  
Ehsan Nozohouri ◽  
Ulrich Bickel ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Time Course ◽  
Induced Pluripotent Stem Cell ◽  
Brain Barrier ◽  
Blood Brain ◽  
Chip Technology ◽  
Blood Brain Barrier Model ◽  
Induced Pluripotent ◽  
Permeability Studies

Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [13C12] sucrose and [13C6] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model.

Sign in / Sign up

Export Citation Format

Share Document