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Blood-brain Barrier-ON-A chip

Use Case

Easy-to-use instrument package for extended BBB on a chip research.

Required microenvironment

Simulate in vivo environments using applied shear stress and dynamic culture

Automated organ-on-chip perfusion

With microfluidic valves, achieve simple unidirectional recirculation flow

Plug-and-play microfluidic setup

Microfluidic instrument kit for beginners with comprehensive user manuals

Highlights

Enhance your analysis of blood-brain extracellular fluid interactions with microfluidics. This advanced, user-friendly, and customizable blood-brain barrier on-a-chip system enables dynamic perfusion experiments that closely mimic in vivo conditions, delivering physiologically accurate results. Seamlessly integrate microscopy with this setup for real-time data acquisition.

Advantages of Microfluidics-Based Blood-Brain Barrier Models:
Table 1, adapted from Chin et al. [1], highlights the benefits and limitations of in vivo models compared to various in vitro techniques. Key advantages of microfluidics include lower costs, enhanced physiological accuracy due to shear stress, and controlled environments.

The microfluidic blood-brain barrier on-a-chip model stands out as a promising approach for drug screening, blood-brain barrier analysis, and personalized medicine applications. The ability to synchronize imaging systems with the model for real-time culture monitoring is a critical feature of this platform [2].

bbb-on-chip advantages table

Table 1. Comparison of the different models used in BBB research.

Blood-brain barrier on-a-chip model using microfluidics is the most promising strategy for BBB analysis, drug screening and breakthrough personalized medicine applications. Another critical feature compatible with using a microfluidic platform is to couple and synchronize imaging systems with the model to perform real-time monitoring of the cultures [2].

 

Blood-brain barrier instrument setup integrated on a chip

The accurate OB1 flow controller (Elveflow) and, if required, a microfluidic membrane chip made up of two channels—one for the blood and the other for the brain—separated by a membrane are both included in the setup.

Long-term dynamic cocultures of endothelial cells and neural cells (neurons, astrocytes, and pericytes) enable you to investigate the activities of the blood-brain barrier (BBB) and carry out drug screening in order to create novel treatments. We offer comprehensive and ongoing customer support to assist you in selecting the right instruments and achieving your experimental objectives.

It is challenging to create a static monolayer culture blood-brain barrier model that replicates in vivo behavior due to the inadequate microenvironment recapitulation. For dynamic culture, the blood-brain barrier on-a-chip microfluidic setup provides improved microenvironment replication and shear stress management.

A number of essential features are included in this user-friendly blood-brain barrier on-a-chip setup, such as software for flexible sequence scheduling and automatization, recirculation of various solutions, and an exact and flawlessly controlled flow rate. These features increase repeatability and precision while lowering costs.

On-chip, the perfused medium unidirectionally recirculates through the blood-brain barrier through a number of valves that are controlled by programmable sequential automation.

The blood-brain barrier model resides within a microfluidic chip that may have been created with various layouts in mind. Usually, this chip has two channels—one for the nervous system and one for the blood vessels—separated by a porous membrane.

To suit particular requirements, chips with varying shapes can be handcrafted from PDMS. As an alternative, commercial membrane chips like the fluidic 480, which is compatible with cell culture and optically clear, can be obtained from microfluidic ChipShop. This pack of chips can have particular channel dimensions—height, width, length, and material—included in it.

The greatest approach to incorporate microfluidics into your experiment for the first time is with application-focused instruments. They are easy to assemble, controlled by a single piece of software, and thoughtfully built to prevent incompatibilities between microfluidic parts.

schémas set up BBB

 

Blood-Brain Barrier on-a-chip setup contains:

  • OB1 MK4 flow controller
  • Manifold
  • MUX recirculation
  • MUX distribution
  • MUX wire
  • 3/2 valves
  • Microfluidic flow sensor
  • Fittings, tubings & luers
  • Reservoirs
  • Microfluidic chip for blood-brain barrier on a chip model
  • Microfluidic software
 

chen 2021 bbb-on-chip schematics

Schematic Overview: An example blood-brain barrier model schematic illustrates the major components, cell types, and their spatial arrangement: endothelial cells lining the vascular chamber, astrocytes and pericytes on the opposite side of the filter membrane, and neurons within the brain’s extracellular matrix (ECM). Figure adapted from [4].

By integrating microfluidics into your blood-brain barrier research, you can achieve more accurate, efficient, and scalable results, making it an ideal choice for cutting-edge biomedical research and applications.

  1. Chin E, Goh E. Blood-brain barrier on a chip. Methods Cell Biol. 2018; 146:159-182.
  2. Bhatia, S., Ingber, D. Microfluidic organs-on-chips. Nat Biotechnol 32, 760–772 (2014).
  3. Brown, Jacquelyn A., et al. “Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor.” Biomicrofluidics 9.5 (2015).
  4. Chen, X.; Liu, C.; Muok, L.; Zeng, C.; Li, Y. Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases. Cells 202110, 3183.

principleS of blood-brain barrier on-a-chip

 

The blood-brain barrier, or BBB, is a diffusion barrier that keeps the majority of chemicals in the blood out of the brain and is essential for maintaining brain homeostasis. It is created by endothelial cells, astrocytes, and pericytes [1, 2].

It is challenging to do research on the BBB, because studies based on animal models or cell culture cannot be accurately replicated. But since the BBB is linked to several illnesses, such as epilepsy and Alzheimer’s disease, which pose significant health and financial costs globally, improving the model is crucial [3, 4].

Endothelial cells require a different setting than static cell culture because they must undergo shear stress from blood circulation in order to more closely replicate the blood-brain barrier [5]. The only technology that can accurately replicate the BBB’s multicellular, intricate structure under dynamic settings in vitro is microfluidics.

Although entire cell complexity is incorporated into the usage of in vivo animal models, there are significant disadvantages including physiological differences with humans, costs, and ethical issues. Eighty percent of medications that passed animal testing but failed human clinical trials [6].

As a result, several microfluidic chip layouts with or without a membrane have been used to create microfluidic model techniques that imitate the BBB on-a-chip [7–10].

  1. Praveen Ballabh; Alex Braun; Maiken Nedergaard (2004). The blood–brain barrier: an overview: Structure, regulation, and clinical implications., 16(1), 0–13.
  2. Chin E, Goh E. Blood-brain barrier on a chip. Methods Cell Biol. 2018;146:159-182. doi: 10.1016/bs.mcb.2018.06.003. Epub 2018 Jul 13. PMID: 30037460.
  3. Xiuli, G., Meiyu, G. & Guanhua, D. Glucose Transporter 1, Distribution in the Brain and in Neural Disorders: Its Relationship With Transport of Neuroactive Drugs Through the Blood-Brain Barrier. Biochem Genet 43, 175–187 (2005).
  4. Hsu D, Marshall GA. Primary and Secondary Prevention Trials in Alzheimer Disease: Looking Back, Moving Forward. Curr Alzheimer Res. 2017;14(4):426-440. doi:10.2174/1567205013666160930112125
  5. Cucullo, L., Hossain, M., Puvenna, V. et al. The role of shear stress in Blood-Brain Barrier endothelial physiology. BMC Neurosci 12, 40 (2011). https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-12-40
  6. Perrin, S. Preclinical research: Make mouse studies work. Nature 507, 423–425 (2014).
  7. Deosarkar, Sudhir P., et al. “A novel dynamic neonatal blood-brain barrier on a chip.” PloS one 10.11 (2015): e0142725.
  8. Prabhakarpandian, Balabhaskar, et al. “SyM-BBB: a microfluidic blood brain barrier model.” Lab on a Chip 13.6 (2013): 1093-1101.
  9. Achyuta, Anil Kumar H., et al. “A modular approach to create a neurovascular unit-on-a-chip.” Lab on a Chip 13.4 (2013): 542-553.
  10. Griep, L.M., Wolbers, F., de Wagenaar, B. et al. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed Microdevices 15, 145–150 (2013).

Personalize your instrument setup for the microfluidic BBB

Two in- and output ports above and below the membrane enable molecular transfer in the fluidic 480 cross-flow membrane chip from microfluidic ChipShop. There are other options for pore sizes, materials, and chip geometries with more inlets.

Fluidic-480-for-BBB-on-a-chip-Elveflow

You can completely customize our setup to make it exactly what you need. We have experts and specialists in microfluidics who can assist you in selecting the appropriate tools and accessories. They will help you set up the microfluidic platform and stay with you until you get the first results of your experiments.

We also put together an endothelial cell culture setup and a gut-on-a-chip setup for organ-on-chips.

If you have any questions regarding this BBB on a chip setup or how it may be customized to your requirements, get in touch with our specialists!

Examine our other use cases for a range of applications.

Blood-brain Barrier-ON-A chip

Use Case

Easy-to-use instrument package for extended BBB on a chip research.

Talk to an expert

Required microenvironment

Simulate in vivo environments using applied shear stress and dynamic culture

Automated Perfusion for Organ-on-a-Chip Systems

With microfluidic valves, achieve simple unidirectional recirculation flow

Complete microfluidic setup

Every microfluidic instrument you need to achieve your experiment.

Talk to an expert
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