Scientists from IIT Madras and Massachusetts Institute of Technology (MIT) have grown small amounts of self-organizing brain tissue, called organoids, in a tiny low-cost 3D-printed system that allows continuous observation during growth and development.?
Their seminal work aimed at improving brain research is published in peer-reviewed scientific journal Biomicrofluidics.
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Currently, real-time observation of growing organoids is done by using commercial culture dishes, which are costly and only compatible with specific microscopes. And because the dishes are sealed shut to avoid contamination from microorganisms in the air, adding nutrients like amino acids, vitamins, salts and glucose is impossible. As a result, the cells usually die within a few days.
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Recent advances have used a novel technique called microfluidics, where a nutrient medium is delivered via small tubes that are connected to a tiny platform or chip. However these devices, too, are expensive and quite difficult to manufacture. Not to forget their opaque design that doesn¡¯t allow scientists to observe what is happening inside.
Ikram Khan at IIT Madras and his colleagues at MIT looked to address that problem. They used 3D printing to create a reusable and easily adjustable platform that costs only about $5 per unit to fabricate--cheaper than a KFC bucket.
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The device, referred to as a ¡°microfluidic bioreactor¡±, includes imaging wells for the growth of brain organoids and is filled with nutrient-rich fluid that is pumped in and out automatically, mimicking the fluids in the human brain.
The new, simpler device 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. And before the living cells are placed in the wells, the printed chip is sterilized by exposing it to UV light.
The researchers used human brain-differentiated stem cells to test their system and examined the brain tissue develop for a full week with a microscope. During that time, they found that the small bit of brain tissue developed a cavity or ventricle surrounded by a self-organizing structure that resembles a developing neocortex.
And while some cells in the organoid died during this one-week period, its percentage was smaller in the 3D-printed device than in regular culture conditions.
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¡°One advantage offered by our microfluidic device is that it allows constant perfusion of the culture chamber, which more closely mimics a physiological tissue perfusion than conventional culture, and thus reduces cell death at the organoid core,¡± lead author Khan said.