Home / Application-based use cases / Blood-brain barrier on a chip
blood-brain barrier (BBB) model on a PDMS microfluidic chip- Elveflow

Gut on a chip

Use case

Intestinal cell coculture under flow to replicate gut physiology
Talk to an expert

Gut-on-a-chip

Complete microfluidic setup included for quick and easy assembly.

Dynamic culture conditions

Precisely controlled shear stress under laminar flow, ensuring efficient medium distribution.

Advanced in vitro / ex vivo

Optimized incubation parameters closely mimic physiological conditions for more accurate results.

Microfluidic Blood-brain BARRIER-ON-A-CHIP overview

The Blood-Brain Barrier (BBB) is a selective barrier that shields the brain and Central Nervous System (CNS), maintaining a stable environment. It comprises endothelial cells, pericytes, glial cells, and the extracellular matrix, ensuring integrity. Dysfunction in the BBB, linked to diseases like Alzheimer’s and Parkinson’s, allows harmful substances into the CNS. Advanced BBB models now enable better study of these diseases by developing targeted therapies, and identifying potential neurotoxic xenobiotics, representing a significant step forward in neuroscience and pharmacology (1,2).

Traditional methods for studying the blood-brain barrier (BBB), like transwell assays, and animal models, face limitations like oversimplification, poor physiological relevance, and cross–species differences.
Microfluidic BBB models (μBBB) address these issues by mimicking in vivo BBB functions with engineered systems. These models allow precise control of the environment, support cell co-culture, apply shear stress, and replicate human brain conditions. μBBB devices enable high-resolution imaging, intracellular monitoring, and extracellular response analysis, making them ideal for CNS disease research, therapeutic screening, and neurotoxicity testing. They offer great potential for advancing BBB studies (2).

An ideal in vitro blood-brain barrier (BBB) model should replicate the key characteristics of the in vivo BBB, including:

  • A 3D vessel-like structure of endothelial cells (ECs);
  • Cell-cell interactions;
  • Shear stress on ECs induced by fluid flow; 
  • A thin porous basal membrane (BM) 

One of the most challenging aspects of mimicking the BBB in vitro is accurately replicating the native BM, which plays a critical role in processes such as cell differentiation, homeostasis, tissue maintenance, and structural support. Ideally, an artificial BM should be fabricated from biocompatible materials and have a thickness of approximately 100 nm.

Microfluidic device design 

Sandwich design 

This μBBB design features an upper and lower polydimethylsiloxane (PDMS) channel separated by a porous membrane. Polycarbonate membranes with pore diameters ranging from 0.2 to 3 μm are typically used, resembling the transwell system. Endothelial cells are generally seeded in the upper channel, while pericytes, astrocytes, or other brain cells are cultured in the lower channel.

Alternative transparent membranes, such as polytetrafluoroethylene, enable high-resolution imaging and real-time biomolecule transport and cell growth monitoring. Additionally, reversing the cell seeding configuration, and culturing endothelial cells (ECs) in a 3D vessel-like structure in the lower channel while seeding pericytes and astrocytes in the upper channel, enhances the observation of cell-cell interactions.

Sandwich design
Illustration of a sandwich design BBB on a chip. (A) Exploded view of the chip, comprising top and bottom sections, each containing eight channels, separated by a porous PDMS membrane. (B) Schematic representation of the two-layer device design, featuring two identical PDMS parts, one inverted and bonded to the other. (C) Demonstration of generating eight distinct conditions within the two-layer devices (2).
Parallel design-bbb
Schematic illustration and images of BBB on a chip. A. Schematic illustration showing the tissue compartment in the center of the device surrounded by two independent vascular channels with flow access openings. B. Schematic illustration of cell culture in the design. C. The device is assembled on a microscope glass slide with plastic tubes (dark blue) allowing access to individual vascular channels and the tissue compartment.(3)
Parallel design
Two horizontally aligned channels are separated by a PDMS microchannel array, replacing traditional polycarbonate membranes with a PDMS-based micropillar ‘membrane’ (3-μm gaps). This design enables co-culture with astrocytes or brain tumor cells and simplifies assembly by removing the need for extra chemical modifications. The planar layout improves cell interactions and imaging.

The device features a central tissue compartment flanked by two vascular channels with flow access, assembled on a microscope slide with plastic tubes for channel access.
3D tubular structure design
Photolithography typically produces PDMS-based μBBB models with rectangular microchannels, but this can cause uneven flow and shear stress, impacting endothelial cell behavior. To address this, some μBBB systems use cylindrical microchannels for uniform shear stress. For example, 3D collagen-based microvascular tubes (75–150 μm) are created with microneedles, allowing precise diameter adjustment through fluid flow rates, and are integrated into μBBB devices.
Illustration of a brain microvasculature system
Illustration of a brain microvasculature system. (4)

Blood-brain barrier integrated on a chip Experimental setup

schémas set up BBB

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

Benefits of Elveflow EQUIPMENT for the experiment 

  • OB1 Pressure controller : 
    • Precise Fluid Flow Control: The OB1 utilizes piezoelectric regulators, offering rapid and stable pressure adjustments. This precision ensures that the microfluidic environment closely mimics physiological conditions, which is essential for accurately replicating the BBB’s dynamic nature.
    • Dynamic Perfusion Capabilities: In BBB on-a-chip setups, maintaining appropriate shear stress is crucial for endothelial cell function. The OB1 allows for controlled fluid flow, enabling dynamic perfusion that simulates in vivo blood flow conditions, thereby enhancing the physiological relevance of the model.
  • MUX Distribution : 
    • Automated Sequential Injection: The valve allows for the programmed delivery of various reagents, drugs, or media into the BBB chip. This automation is crucial for conducting dynamic perfusion experiments that closely mimic in vivo conditions, enhancing the physiological relevance of the model.
  • MUX Recirculation : 
    • Simulating Physiological Flow Conditions: The MUX Recirculation allows for precise, programmable recirculation of fluids, which is critical for replicating the shear stress and fluid dynamics experienced by endothelial cells in the BBB.
    • Controlled recirculation ensures realistic blood flow patterns, essential for maintaining endothelial cell morphology and function.
    • Drug Testing and Toxicity Screening : Introduction of drugs or nanoparticles in a controlled manner and recirculate them to study their interaction with the BBB over time.
    • Dynamic Co-Culture Systems: It ensures continuous perfusion, which is critical for cell viability and the maintenance of tight junctions.
    • Reduced Contamination Risk: Closed-loop recirculation minimizes the risk of contamination, a common challenge in open perfusion systems.

Neurological diseases Modeling

  • Brain Tumor 

Blood–brain barrier (BBB) models are employed to investigate how vascular glioma-initiating cells; key players in brain tumor invasion-interact within their environment. Moreover, using in vitro BBB systems enables a clearer understanding of the mechanisms behind brain tumor metastasis. By integrating patient-derived glioblastoma spheroids into microfluidic systems, these models provide a highly efficient platform for screening drugs with strong tumor-killing capacity.

  • Neurological Disorder Disease

The inflammatory response in neural disease lesions results from the aggregation and migration of immune cells, including neutrophils, glial cells, and astrocytes. In models of neurological disorders, such as Alzheimer’s disease, neuroinflammation is driven by the activation of microglia and astrocytes. Activated immune cells release inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1. During this response, cytokines and immune cells contribute to the disruption of the blood-brain barrier (BBB), often causing blood to infiltrate the brain and leading to irreversible brain tissue damage.

  • Neurobiology Research 

Controlling the microenvironment around neuronal cells, including cell–cell and cell–extracellular matrix (ECM) interactions within microfluidic platforms, enables the creation of an in vivo-like niche for neural stem cells to differentiate into components of the nervous system.

By integrating microfluidic technology with neurobiology, several technical challenges in the field can be addressed, such as culturing central nervous system (CNS) neurons, isolating axons, patterning cultured neurons, directing neurite outgrowth to model axonal injury, and studying processes like local protein synthesis in axons, axonal regeneration, and axonal transport.

In vitro drug development 

BBB-on-chip systems provide advanced platforms for assessing drug permeability across the blood-brain barrier under dynamic and physiologically relevant conditions, addressing limitations of traditional in vitro models. They enable the evaluation of drug-loaded nanoparticles, including receptor-mediated transcytosis and nanocarrier optimization for CNS-targeted delivery. By replicating the cellular complexity of the BBB, these models facilitate testing neuroprotective agents and antibodies under disease-specific conditions. Integrated sensors offer insights into drug toxicity, neuronal activity, and synaptic behavior. Using patient-derived cells, they support personalized drug screening and disease-specific studies (5).

Brain-Axis on chip 

Multi-organ chips provide an advanced platform to study interactions between the brain and other organs in the context of diseases and drug development. They enable the investigation of complex conditions such as brain metastasis of lung cancer, where dynamic processes can be replicated and studied in detail.  These chips also help unravel the communication pathways in the microbiota-gut-brain axis, shedding light on how gut health impacts neurological diseases. By simulating interconnected organ systems, such as the liver-brain axis in hepatic encephalopathy or immune modulation via the brain-spleen axis, multi-organ chips offer an integrated approach to understanding systemic diseases. Their ability to mimic dynamic physiological environments facilitates groundbreaking research in inter-organ communication and therapeutic development​. 
References

  1. X. Chen ; C. Liu ; L. Muok ; C. Zeng and Y. Li, Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases, Cells, 2021

  2. M. Zakharova ;  M. A. Palma do Carmo ; M. W. van der Helm ;  H. Le-The ;  M. N. S. de Graaf ; V. Orlova ; A. van den Berg ; A. D. van der Meer ; K. Broersen  and  L. I. Segerink, Multiplexed blood–brain barrier organ-on-chip, Lab on a Chip, 2020.

  3. S. P. Deosarkar ; B. Prabhakarpandian ; B. Wang ; J. B. Sheffield ; B. Krynska and M. F. Kiani, A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip, PlosOne, 2015

  4. J.A. Kim ; H.N. Kim ; S-K. Im ; S. Chung ; J.Y. Kang and N.Choi, Collagen-based brain microvasculature model in vitro using three-dimensional printed template, Biomicrofluidics, 2015

  5. X. Wang ; Y. Hou ; X. Ai ; J. Sun ; B. Xu ; X. Meng ; Y. Zhang and S. Zhang, Potential applications of microfluidics based blood brain barrier (BBB)-on-chips for in vitro drug development, Biomedicine & Pharmacotherapy, 2020

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

Features & Benefits

Need help or advice?

Contact us for expert help in microfluidics!

Contact us
Contact
How can we help you?
Quoteor technical request Job application Job
application Collaboration or partnerships Collaborations
or partnerships Customer support Customer
support Others questions Other

    Get a quote




    We will answer within 24 hours

    By filling in your info you accept that we use your data.

    Contacting for
    a job application?     We are happy that you are interested in Elveflow. You can apply to our open jobs or send us your open application on WelcomeToTheJungle. Over here!

      Collaborations




      We will answer within 24 hours

      By filling in your info you accept that we use your data.

        Need customer support?







        I hereby agree that Elveflow uses my personal data

        We will answer within 24 hours

          How can we help you?




          We will answer within 24 hours

          By filling in your info you accept that we use your data.