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Brain Organoid on a Chip: Next-level Brain Modeling
Brain organoids and microfluidic chips become groundbreaking tools for in vitro studies of the complexity of the human brain. These miniature three-dimensional models provide extraordinary insights into brain development, disease mechanisms, and potential therapeutic interventions. However, despite their power, traditional organoids remain limited in their scalability, reproducibility, and ability to mimic the complex physiology of the human brain. To address these challenges, scientists are turning to innovative approaches, such as brain organoids on a chip, which promise to take brain modeling to the next level.
Creative Biolabs explores advances in brain organoid technology and the potential of brain organoids on a chip to revolutionize neuroscience research. We also provide services related to brain organoid construction.
| Services | What We Do | Advantages |
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| Custom Brain Organoid Services | Based on our advanced platforms, Creative Biolabs now provides custom brain organoid services, including forebrain organoid, cerebellar organoid, whole-brain organoid, as well as retinal organoid. |
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| Whole-brain Organoid | Brain organoids can be widely used to reveal pathogenic cellular mechanisms in neurodevelopmental diseases. With a solid foundation and an excellent team of experts, we have developed a comprehensive customized brain organoid platform. |
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| Forebrain Organoid | Creative Biolabs offers a simple and standardized forebrain organoid culture system. The most important feature and advantage of this system is the high efficiency and reproducibility of PSC-derived organoids. As a stable and reliable cell-based modeling system, disease models can be generated in vitro. |
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| Cerebellar Organoid | Creative Biolabs develops a dynamic 3D culture system for the production of iPSC-based cerebellar organoids. It is a disposable vertical wheel bioreactor equipped with a large vertical impeller to provide optimal culture conditions. Different types of cerebellar neurons can be observed during the maturation process. |
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Introductions to Brain Organoids on a Chip
Brain organoids are three-dimensional cellular models of miniature self-organizing structures derived from pluripotent stem cells, such as embryonic stem cells or iPSCs. These cells are capable of differentiating into the various cell types found in the brain, including neurons, astrocytes, and oligodendrocytes, thereby recreating key aspects of brain development in a petri dish. The process of generating brain organoids involves culturing stem cells in a specialized environment that mimics the conditions required for brain development, including the presence of specific growth factors and signaling molecules.
Fig. 1 Approaches for making brain organoids.1
While traditional organoids of the brain contain an array of neurons and helper cells similar to the diversity found within the human brain, they are not without limitations. A major challenge is the lack of scalability and reproducibility. Another limitation is their simplified microenvironment. In addition, conventional brain organoids lack the ability to mimic dynamic processes such as blood brain barrier function, immune cell infiltration, and neuronal circuit activity. These limitations hamper their utility in the study of certain neurological disorders and limit their potential for drug screening and development.
To overcome the limitations of traditional brain organoids, researchers are turning to microfluidics to create brain organoids on a chip. These microengineering platforms provide precise control over the cellular microenvironment, allowing researchers to reconstruct key features of the brain in a more controlled and reproducible manner.
By incorporating brain organoid tissues into microengineered environments often referred to as "organs-on-a-chip" or "microphysiological systems," researchers can more accurately reproduce the cellular and mechanical aspects of the human brain.
- At the heart of the brain organoids on a chip is a microfluidic device, which consists of a network of microchannels and microcompartments designed to mimic the structure and function of the brain. Stem cells are implanted into the device and differentiate and self-organize into brain organoids under carefully controlled conditions.
- The microfluidic system provides continuous perfusion of nutrients and oxygen to ensure organoid viability and growth, while removing waste products and maintaining a stable microenvironment.
- By standardizing microfluidic device design and culture protocols, researchers can generate large numbers of uniform organoids with consistent properties, facilitating high-throughput experiments and enabling more robust statistical analysis.
Progress in Brain Organoid on a Chip Technology
While the concept of brain-on-a-chip organoids is relatively new, the progress made is truly remarkable. Some of the research advances further enhance the functionality of brain-on-chip organoids and expand their potential applications in neuroscience research.
| Technological Advances | Descriptions | Applications |
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| Techniques for integrating vascularization into brain organoid on a chip | By integrating endothelial cells and perfusable microvessels into microfluidic devices, researchers can create vascularized brain organoids that more closely resemble the in vivo brain environment. These vascularized organoids exhibit improved neuronal maturation, enhanced synaptic activity, and increased resistance to oxidative stress. |
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| Technology to continuously supply nutrients and oxygen to organ tissues | Researchers at the Massachusetts Institute of Technology (MIT) have developed a technique for culturing brain organ tissue on a microfluidic chip. This chip continuously supplies nutrients and oxygen to the organ tissues, thus creating a dynamic in vitro environment that better reproduces in vivo conditions. |
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| Technology for integrating immune cells into brain organoids on a chip | By co-culturing brain organoids with immune cells such as microglia and peripheral monocytes, researchers can study the complex interactions between neurons and the immune system in a controlled environment. |
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| Electrophysiological recording technology with brain-on-a-chip organoid integration | Microelectrode arrays (MEA) and membrane clamp electrodes can be integrated into microfluidic devices to monitor the electrical activity of neurons in real time. |
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Additionally, advances in imaging and analysis techniques have also facilitated the function of brain organoids on a chip. High-resolution imaging modalities, such as confocal microscopy and two-photon microscopy, enable researchers to observe neuronal morphology, synaptic connections, and calcium influx in real time. Computational tools for image analysis and data processing allow quantitative assessment of neuronal activity, network connectivity and drug response, providing valuable insights into brain function and dysfunction.
Applications of Brain Organoids on a Chip
The development of the brain organoid on a chip opens up exciting possibilities for neuroscience research and biomedical applications.
Fig. 2 Human brain organoid-on-chips as physiologically relevant and reproducible models for the study of brain biological organization.2
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Custom CNS disease modeling
By using patient-derived iPSC, researchers can generate personalized brain organoids that encapsulate the genetic and phenotypic characteristics. These disease models can be used to study disease progression, identify biomarkers and screen for potential treatments in patient-specific conditions. -
Drug screening and development
The ability to generate large numbers of homogeneous organoids with reproducible properties enables high-throughput screening of drug candidates for efficacy and safety. In addition, brain organoids on a chip can be used to study the blood-brain barrier permeability of drug molecules and assess their potential for CNS penetration, providing valuable information for drug delivery optimization. -
Neurotoxicity testing and environmental exposure
By exposing brain organoids to a variety of toxins and contaminants in controlled environments, researchers can assess their effects on neuronal viability, synaptic function, and neurodevelopmental processes. This information can inform regulators and policy makers about the potential risks of chemical exposure and guide the development of safer, more environmentally friendly products. -
Neuroprostheses and brain-computer interfaces
By connecting brain organoids to external electronic devices, researchers can establish bi-directional communication between neural networks and external systems, enabling applications such as neural control of prosthetics, brain-computer interfaces for communication and control, and closed-loop neurostimulation therapies for neurological disorders.
By combining the strengths of stem cell technology, microfluidic engineering and advanced analytical techniques, researchers are creating complex models that faithfully encapsulate key aspects of brain development, function and dysfunction. These miniature brain models offer unprecedented opportunities to improve our understanding of neurological disorders, discover new therapeutic strategies and develop innovative neurotechnologies.
Despite the impressive achievements of brain-on-a-chip organoid modeling technology, challenges still need to be addressed. For example, current brain organoids lack certain cell types and structures, such as microglia and myelinated axons, which are critical for brain function. In addition, organoid generation protocols need to be standardized to ensure reproducibility across laboratories.
References
- Qian, Xuyu, et al. "Brain organoids: advances, applications and challenges." Development 146.8 (2019): dev166074.
- Castiglione, Héloïse, et al. "Human Brain Organoids-on-Chip: Advances, Challenges, and Perspectives for Preclinical Applications." Pharmaceutics 14.11 (2022): 2301.
For Research Use Only. Not For Clinical Use.