Neuroscience Research & CNS Drug Development
Study the human neurovascular unit with greater physiological relevance
Developing effective therapies for the central nervous system requires understanding not only neurons, but also the blood-brain barrier (BBB), glial cells, vascular cells, and the interactions between them.
Emulate Organ-on-a-Chip technology enables researchers to study these components together in a dynamic, human-relevant microenvironment. With the Brain-Chip R1, researchers can model key features of the human neurovascular unit (NVU) to investigate BBB transport, neuroinflammatory mechanisms, and the effects of therapeutic candidates.
THE CHALLENGE
Better human models are needed for CNS drug development
The human brain and blood-brain barrier present distinct challenges for drug discovery and development. The BBB tightly regulates the movement of molecules between the circulatory system and the brain, while interactions among endothelial cells, neurons, astrocytes, microglia, and pericytes influence both normal neurovascular function and responses to disease or injury.
Traditional animal models can provide important biological insights, but species differences in BBB transporters, receptors, and inflammatory responses can limit translation to humans. Conventional in vitro models often simplify this biology further, lacking the multicellular complexity, vascular flow, and tissue-tissue interactions of the human neurovascular unit.
Human-relevant in vitro models that recreate more of this biology can help researchers investigate CNS drug transport and neuroinflammatory mechanisms earlier in development.
A Human-Relevant Model of the Neurovascular Unit
Five iPSC-derived cell types in one isogenic Organ-Chip model
The Emulate Brain-Chip R1 is a perfused, isogenic Organ-Chip model designed to recapitulate key cellular and functional features of the human neurovascular unit.
The model integrates five human iPSC-derived cell types from a single donor line: GABAergic neurons, astrocytes, microglia, pericytes, and Emulate’s proprietary brain microvascular endothelial cells (BMECs).
These cells are co-cultured within the two-channel Chip-R1 Rigid Chip. Neurons, astrocytes, microglia, and pericytes populate the brain channel, while BMECs form the vascular channel. Proprietary media support the model’s stable resting state, BBB tightness, and transporter expression, while continuous flow creates a dynamic microenvironment that supports barrier function, cell-cell communication, and neuroinflammatory responses.
Because all five cell types originate from a common iPSC donor line, Brain-Chip R1 reduces donor-to-donor variability between cell populations and provides a consistent genetic background for studying neurovascular interactions.
Neuroscience Applications
Blood-Brain Barrier Transport and Permeability
Quantitatively evaluate how therapeutic candidates interact with the human BBB
Reaching the brain is a fundamental challenge in CNS drug development. The blood-brain barrier restricts the passage of many molecules while using specialized transport mechanisms to regulate movement between the circulatory system and brain.
Brain-Chip R1 forms a tight, stable BBB-like barrier and expresses key blood-brain barrier transporters, including P-glycoprotein (P-gp), GLUT1, and transferrin receptor 1 (TfR1).
By combining human brain microvascular endothelial cells with other components of the neurovascular unit under flow, Brain-Chip R1 enables BBB transport studies in a multicellular human environment rather than an endothelial monoculture alone.
NEUROINFLAMMATION
Investigate inflammatory responses across the neurovascular unit
Neuroinflammation involves coordinated interactions among microglia, astrocytes, neurons, vascular cells, and inflammatory signaling pathways. Models that begin in an activated state or exclude key cell populations can make these mechanisms difficult to resolve.
Brain-Chip R1 maintains microglia and astrocytes in a resting state under baseline culture conditions while preserving their ability to respond to inflammatory stimulation.
This resting-but-responsive phenotype provides a defined baseline from which researchers can investigate the initiation, progression, and modulation of neuroinflammatory pathways.
Neurovascular Unit Biology
Study interactions between neural, glial, perivascular, and endothelial cells
The neurovascular unit regulates communication between the brain and circulation through coordinated interactions among neurons, astrocytes, microglia, pericytes, and brain microvascular endothelial cells.
Brain-Chip R1 brings these five cell types together within a single perfused model, providing access to both neural and vascular compartments.
Independent access to the brain and vascular channels also enables researchers to introduce compounds through different routes and collect compartment-specific samples throughout an experiment.
CNS Drug Discovery and Development
Generate human-relevant mechanistic data earlier in development
Brain-Chip R1 can be incorporated into CNS drug discovery workflows to investigate questions that are difficult to address using traditional static culture alone.
Multiple assay modalities can be combined within the same experiment, including microscopy, effluent analysis, permeability measurements, cytokine profiling, and endpoint molecular analysis.
Researchers can use Emulate’s Organ-Chip consumables to develop custom models tailored to specific scientific questions. In peer-reviewed studies, independent research teams have created human Organ-Chip models to investigate neurodegenerative disease, neuroinflammation, and blood-brain barrier function.
Brain-Chip R1 Characterization
Characterized for Human Neurovascular Research
Barrier function
Brain microvascular endothelial cells form a stable barrier with well-defined tight junctions.
BBB phenotype
BMECs express endothelial and BBB-associated markers and transporters, including ZO-1, GLUT1, P-gp, and TfR1.
Resting glial state
Microglia and astrocytes maintain resting-state characteristics under baseline culture conditions.
Inflammatory response
Following IL-1β stimulation, the model generates a coordinated inflammatory response, demonstrating that its glial populations remain capable of responding to perturbation.
Compartment-Specific Sampling
Independent access to the brain and vascular channels enables researchers to collect effluent from each compartment over time, supporting longitudinal measurement of cytokines, biomarkers, permeability, and other secreted factors without disrupting the model.
Multimodal analysis
Researchers can combine imaging, effluent sampling, permeability measurements, cytokine profiling, and endpoint molecular analyses to investigate neurovascular responses from multiple perspectives in a single experiment .
FAQ
What is the Brain-Chip R1?
Brain-Chip R1 is an isogenic, human iPSC-derived Organ-Chip model of the neurovascular unit. It incorporates neurons, astrocytes, microglia, pericytes, and brain microvascular endothelial cells in a perfused two-channel microfluidic device.
What can Brain-Chip R1 be used to study?
Brain-Chip R1 is designed for studies of blood-brain barrier transport and permeability, neuroinflammatory mechanisms, neurovascular unit biology, and CNS drug development.
Which cell types are included in Brain-Chip R1?
The model contains five iPSC-derived human cell types: GABAergic neurons, astrocytes, microglia, pericytes, and Emulate’s proprietary brain microvascular endothelial cells.
Why is Brain-Chip R1 isogenic?
All five cell populations originate from the same iPSC donor line. This provides a shared genetic background across the model and reduces variability that can arise when neurovascular cell populations come from different donors.
Can Brain-Chip R1 model neuroinflammation?
Yes. Brain-Chip R1 maintains resting glial populations at baseline that respond to inflammatory stimulation. Researchers can measure outcomes including cytokine secretion, cellular morphology, barrier integrity, and gene expression to investigate neuroinflammatory mechanisms.
Can Brain-Chip R1 be used for blood-brain barrier permeability studies?
Yes. Brain-Chip R1 forms a stable BBB-like barrier and expresses key BBB-associated transporters. The model is built on the minimally drug-absorbing Chip-R1 Rigid Chip to support compound recovery and quantitative permeability measurements.
Is Brain-Chip R1 an animal replacement?
Brain-Chip R1 is a human in vitro research model designed to recreate selected features of the neurovascular unit. Whether it can replace a particular animal study depends on the scientific question, experimental context, and applicable regulatory requirements.
Can Brain-Chip R1 be used to model diseases?
Brain-Chip R1 was designed to be a healthy model of the human neurovascular unit that can respond to inflammatory stimuli. For disease modeling beyond neuroinflammation, we recommend using one of our Basic Research Kits and patient-derived iPSCs to model your disease of interest.
Supported Models
Brain-Chip R1
Study human physiology, disease, and drug effect in a comprehensive model of the neurovascular unit. The Brain-Chip R1 BioKit includes Chip-R1 consumables, Brain-Chip media, and pre-qualified cells.
Basic Research Kits
Users can create their own Organ-Chip models of the central nervous system using their own cell sources and blank Organ-Chip consumables through one of our Basic Research Kits.
