Using 3D-Printed Bioreactor Scientists Grew Tiny Brains

Scientists from MIT and the Indian Institute of Technology Madras have grown small amounts of self-organizing brain tissue, known as organoids

A 3D-printed microfluidic bioreactor for organ-on-chip cell culture. Credit: Ikram Khan

Small device includes wells to grow, develop and study small pieces of tissue in real time.

MIT scientists and the Madras Indian Technology Institute have cultivated small quantities of self-organizing brain tissue called organoids in a minute 3D system which allows observation during growth and development. The work will be reported by AIP Publishing in Biomicrofluidics.

Current technology to monitor growing organoids in real time involves the use of commercial cultivated food with many wells placed under a microscope in a glass-bottomed plate. The plate is costly and only microscopically compatible. They do not allow a nutrient medium to flow or replenish the tissue.

Recent advances have used a technique known as microfluidism, by which small tubes connected to a small platform or chip provide a nutrient medium. However, these microfluidic devices are costly and difficult to manufacture.

The present advance uses 3D printing to develop a platform that can be re-used and easily adjusted and costs about $5. The design comprises imaging wells that support tissue growth for the growing organoids and microfluidic channels.

For the 3D-printed device, a biocompatible resin type was used in dental operations. The printed chip was cured by exposure to UV light before living cells were placed in the wells. Sterilization was done. The nutrient medium and drugs for use in the study have been added by the small port inlet after sealing the top of the wells with a glass slide.

“Our design costs are significantly lower than traditional petri dish- or spin-bioreactor-based organoid culture products,” said author Ikram Khan. “In addition, the chip can be washed with distilled water, dried, and autoclaved and is, therefore, reusable.”

The researchers tested their apparatus with human cells organoids. They monitored the growth of brain organoids with a microscope and were able to monitor their development and growth successfully for 7 days. A cavity and a ventricle surrounded by a self organisation, similar to a developing Neocortex, developed a small piece of brain tissue.

In the 3D printed device, the number of cells that died during this period of a week was less than in regular conditions of culture in the core of the organoid. The researchers believe that the small growing brain is protected by the cell design.

Khan said, “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.”

The researchers hope to increase their device’s capacity by increasing the number of available water supplies. Additional improvements will make it possible to integrate additional instruments into the design.

Reference: “A low-cost 3D printed microfluidic bioreactor and imaging chamber for live-organoid imaging” by Ikram Khan, Anil Prabhakar, Chloe Delepine, Hayley Tsang, Vincent Pham and Mriganka Sur, 6 April 2021, Biomicrofluidics.
DOI: 10.1063/5.0041027

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