Brain-On-A-Chip Model Development Service

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The blood-brain barrier (BBB) is an important physical and chemical barrier to maintain the homeostasis of the brain. Here at Creative Biolabs, our R&D team actively develops experimental models that can accurately simulate and reproduce the physiological characteristics and functions of the BBB, and manipulate fluids at the micron scale to create ideal BBB research tools.

Microenvironment and Key Features of BBB

The BBB is an important structure to maintain the homeostasis of the central nervous system. It keeps potentially dangerous substances and pathogens away from the CNS but also limits the brain absorption of most neurotherapeutic drugs. The BBB is primarily composed of brain microvascular endothelial cells (BMECs) supported by a discontinuous layer of various cellular components, including pericytes, microglia, astrocytes, and various types of macrophages. The function of the BBB is closely dependent on the interaction between BMECs. Endothelial cells form a tight junction cell monolayer through a variety of intercellular adhesion proteins. The BBB realizes the selective transport of various substances and molecules through this cell layer.

Cellular components and microenvironment of the BBB Fig 1. Cellular components and microenvironment of the BBB. (Augustine, 2021)

Standard BBB Chip

An ideal model should maintain the same BBB-associated cell types and their spatial distribution, as well as resemble the in vivo structure as much as possible. Our transwell chamber is the main tool for BBB in vitro research and the most widely used cell model in vitro. Although the transwell model does not reflect all key features of the BBB, it is cost-effective and allows the control of experimental conditions. We also provide multi-layer chips that use porous membranes for channel separation. Based on the perfusion medium, the physical and chemical microenvironment around the cells can be precisely controlled. You may seed endothelial cells on one side of the membrane to form the luminal layer, and astrocytes and/or pericytes to form the extraluminal layer on the other side. This design allows non-invasive estimation of barrier permeability using transendothelial electrical resistance (TEER) measurements, more efficient drug permeability screening, reduced experimental animal numbers, and reagent consumption.

Contact and non-contact BBB cell co-culture on chip. Fig 2. Contact and non-contact BBB cell co-culture on chip. (Noorani, 2021)

Advanced BBB Chip

With the advancement of micro-processing technology, more complex and advanced BBB chips have also been developed. Our advanced BBB chip uses a micro-gap or micro-pillar array structure to separate epithelial cells from other cells. After cell seeding, it forms a tightly connected cell layer, with good expression of receptors and transporters, and then simulates the material transport process and pathway, showing high selective permeability to different substances. The transparent material ensures direct visualization at the cellular level and real-time monitoring of cell morphology, and additionally allows measurement of protein localization information and precise interactions of particles of interest with the BBB.

BBB chip ensures direct visualization of co-culture cells. Fig 3. BBB chip ensures direct visualization of co-culture cells. (Brown, 2018)

Our Services

The diversity of 3D cell culture models may impact the ability to more accurately estimate drug transport in healthy and diseased systems, so it is not practical to use the same BBB chip design for all studies. With our biological knowledge and advanced microfabrication technology platform, Creative Biolabs provides classic transwell chips, basement membrane chips and more advanced BBB in vitro models for customers all over the world. In addition, we are also able to design and characterize new chip structures and physical microenvironments according to the specific needs of our clients, so as to realize the development of 3D brain-like structure chips that are more realistic or have more research significance. We believe that the microfluidic BBB chip will play an important role in the field of neuroscience and drug research, and we will be the best partner to provide you with BBB in vitro models or develop new structures, so don’t hesitate to contact us for more information.

References

  1. Augustine, R.; et al. Bioengineered microfluidic blood-brain barrier models in oncology research. Translational Oncology. 2021, 14: 101087.
  2. Noorani, B.; et al. A Quasi-physiological microfluidic blood-brain barrier model for brain permeability studies. Pharmaceutics. 2021, 13: 1474.
  3. Brown, T.D.; et al. A microfluidic model of human brain (μHuB) for assessment of blood brain barrier. Bioengineering & Translational Medicine. 2018, 4: 10126.

For Research Use Only. Not For Clinical Use.

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