brain organoids

An organoid grown in a microfluidic bioreactor

MIT and IIT Madras

It is now possible to grow and culture human brain tissue in a device that costs little more than a cup of coffee. With a $5 washable and reusable microchip, scientists can watch self-organising brain samples, known as brain organoids, growing in real time under a microscope.

The device, dubbed a “microfluidic bioreactor”, is a 4-by-6-centimetre chip that includes small wells in which the brain organoids grow. Each is filled with nutrient-rich fluid that is pumped in and out automatically, like the fluids that flush through the human brain.

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Using this system, Ikram Khan at the Indian Institute of Technology Madras in Chennai and his colleagues at the Massachusetts Institute of Technology (MIT) have now reported the growth of a brain organoid over seven days. This demonstrates that the brain cells can thrive inside the chip, says Khan.

Culturing brain tissue in a laboratory would theoretically let scientists test how individual patients’ brains might react to different kinds of medications.

Devices for growing brain organoids already exist, but because the dishes are sealed shut to avoid contamination from microorganisms in the air, it is impossible to add nutrients like amino acids, vitamins, salts and glucose or to remove the waste produced by the cells. As a consequence, the cells usually die within a few days.

To combat that problem, researchers have previously added tiny tubes to deliver nutrients to the brain tissue. But the opaque design of these devices makes it impossible to watch what is happening inside the dish – a significant problem, especially if scientists want to know how the tissue reacts to drugs.

So Khan and his colleagues engineered a new, simpler device that combines a growing platform, tiny tubes, drug-injection channels and even a fluid-warming compartment all onto a single chip, which can be 3D-printed using the same kind of biocompatible resin used in dental surgery. The bioreactors control the flow of replenishing fluid and waste extraction through tubes in an enclosed incubator while providing full visibility.

To test their system, the researchers placed human brain-differentiated stem cells in the wells and programmed fluid flow through the chip. Using a microscope above the platform, they could watch the brain tissue develop for a full week – essentially until the organoids ran out of space in their tiny wells.

During that time, they saw that the cells multiplied and formed a ventricle-like structure, similar to the cavities seen in real brains, says Chloé Delépine at MIT. The ventricle was surrounded by tissue that appeared similar to that of the neocortex, a brain layer responsible for higher-order functions like thinking, reasoning and language comprehension.

Human brain organoids have reached such a level of development in a laboratory before, but this marks the first time it has happened in a device that allows such good visibility of the tissue, and so inexpensively, says Delépine.

“My goal is to see this technology reach people throughout the world who need access to it for their healthcare needs,” says Khan, who has since created a start-up company in India to realise this objective.

Journal reference: Biomicrofluidics, DOI: 10.1063/5.0041027

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