Utilizing 3D Chip Models to Revolutionize our Understanding of the Brain

The brain is one of the most convoluted structures to ever exist—a fascinating enigma. Researchers at the Georgia Institute of Technology were one step closer to understanding the complex structure of the brain. YongTae Kim and Allan I. Levey MacDonald were able to engineer a model of the Blood Brain Barrier (BBB) utilizing computer chips.

 What is the Blood Brain Barrier? According to the researchers mentioned above, it is a “highly functionalized vascular border of the central nervous system (CNS) that regulates the transport of substances between the blood and brain” (Anh). In other words, it is a barrier consisting of blood vessels that act as a membrane, filtering what chemicals and messages can enter the brain and what cannot. The researchers were able to successfully build a model out of computer chips and mimic the functions of the blood brain barrier, including gene expression, nanoparticle distribution, and chemical uptake. By using brain implants, or more specifically, “Brain-on-chips,” that are used specifically to imitate parts of the brain through it’s program, they were able to create a model which performs higher brain functions (such as filtration, uptake, metabolism etc.) that closely mimic the brain electrical signals and tasks. Ultimately, the goal  of the model is to develop an in-vitro model that has the potential to cure brain-related diseases such as Parkinsons and Alzhiemers. 

The modeling process was rigorous. The first step was to make a design and rough layout of the model, making the dimensions 400 µm, 300 µm, and 200 µm and the height of all channels is 100 µm, the most reliable metric to imitate the brain cells while also getting maximum function. To further develop the model, they utilized computational fluid dynamics and cultured cells, or the “on-chips”. They further developed the nano-particle structure by creating the Blood Brain Barrier chip system that was placed in an incubator to develop a working model. To determine the viability of the model, the researchers developed several tests. To measure cell gene expression, they utilized a PCR (Polymerase Chain Reaction) test, where they used fluorescent markers to demonstrate how well the chips functioned (the more fluorescent light, the more genes were expressed). To visualize which specific cells marked each gene expression, they performed immunocytochemistry, a laboratory technique used to locate specific cells. This way, the researchers were able to test the effectiveness of the model through measuring what genes were being expressed, how expressive they were and comparing it to how it mirrored the real Blood Brain Barrier. Further tests were also performed, such as permeability measurement tests to see what chemicals the chip allowed to pass, as well as concentration gradient measurements to see the nanoparticle distribution. As a result, the model was successful and was able to mirror the Blood Brain Barrier in various aspects.

This model is revolutionary and helps scientists get a better understanding of how the brain functions and be manipulated to cure diseases. With this new found method of mimicking brain chemical permeability, researchers can potentially find ways to suppress or allow certain chemicals that lead to balance brain endorphins to prevent certain mental disorders. The researchers’ next step is to share their model to other labs and institutions so that the model can be adopted as a useful tool in more research.


References

  1. Ahn, Song Ih, et al. “Microengineered Human Blood–Brain Barrier Platform for Understanding Nanoparticle Transport Mechanisms.” Nature Communications, vol. 11, no. 1, 2020, doi:10.1038/s41467-019-13896-7.

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