Brain-On-A-Chip Model Development Service

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Overview of BBB Standard BBB Chip Advanced BBB Chip Services Features Q&As Resources

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.

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.

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.

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.

Features and Benefits

Mimics Complex Brain Physiology

The Brain-On-A-Chip model closely replicates the complex physiology of the human brain, including neural networks and cellular interactions, providing a more accurate platform for studying brain functions and diseases compared to traditional cell cultures and animal models.

Replicates Blood-Brain Barrier

The model includes a functional blood-brain barrier, allowing for the study of its integrity and interactions with drugs or pathogens. This feature is crucial for understanding neurodegenerative diseases and developing treatments that can cross the barrier.

Dynamic Microenvironment

The Brain-On-A-Chip provides a dynamic microenvironment with fluid flow, enhancing cell viability and functionality. This results in more physiologically relevant cell behavior and gene expression profiles, closely mimicking in vivo conditions.

Advanced Disease Modeling

This model enables the detailed study of neurological diseases, such as Parkinson’s and Alzheimer’s, by replicating disease-specific conditions. Researchers can investigate disease mechanisms and test therapeutic interventions in a controlled, reproducible setting.

Customizable and Flexible

The Brain-On-A-Chip can be customized to model specific brain regions or diseases, allowing researchers to tailor the system to their unique experimental needs. This flexibility makes it a versatile tool for various neurological studies.

References

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

Q&As

Q: How does the Brain-On-A-Chip model replicate the human brain environment?

A: The Brain-On-A-Chip model uses a combination of human-derived cells and advanced microfluidic technology to create a dynamic and interactive environment. This setup mimics the 3D architecture, cellular interactions, and physiological conditions of the human brain.

Q: What types of cells are included in the Brain-On-A-Chip model?

A: The model includes a variety of human brain cells, such as neurons, astrocytes, microglia, pericytes, and endothelial cells. This diversity allows for a comprehensive simulation of the neurovascular unit and enhances the physiological relevance of the model.

Q: What makes the Brain-On-A-Chip model superior to traditional cell cultures?

A: The Brain-On-A-Chip model offers a 3D environment and dynamic conditions that are not possible in traditional 2D cell cultures. It provides better cell viability, interaction, and functionality, closely mimicking in vivo conditions and leading to more reliable experimental results.

Q: How does the Brain-On-A-Chip model facilitate real-time monitoring of brain activities?

A: The Brain-On-A-Chip model incorporates advanced microfluidic systems that allow for real-time monitoring of cellular activities, such as electrophysiological responses and neurotransmitter release. This capability enables researchers to observe dynamic processes and interactions within the brain model, providing deeper insights into neural mechanisms.

Q: Can the Brain-On-A-Chip model be customized for specific research needs?

A: Yes, the Brain-On-A-Chip model can be customized to replicate specific brain regions or disease conditions. This flexibility allows researchers to tailor the system to their unique experimental requirements, making it a versatile tool for various neurological studies.