Low-Cost 3D-Printed Microfluidic Bioreactor Proves Its Worth for Growing Tiny "Brains"

A team of scientists from MIT and the Indian Institute of Technology Madras have published a paper detailing the growth of tiny brains in a custom 3D-printed bioreactor.

"Organoids are biological systems grown in vitro and are observed to self-organize into 3D cellular tissues of specific organs," the team writes in the paper's abstract. "Brain organoids have emerged as valuable models for the study of human brain development in health and disease. Researchers are now in need of improved culturing and imaging tools to capture the in vitro dynamics of development processes in the brain."

"Here, we describe the design of a microfluidic chip and bioreactor, to enable in situ tracking and imaging of brain organoids on-chip. The low-cost 3D printed microfluidic bioreactor supports organoid growth and provides an optimal imaging chamber for live-organoid imaging, with drug delivery support. This fully isolated design of a live-cell imaging and culturing platform enables long-term live-imaging of the intact live brain organoids as it grows. We can thus analyze their self-organization in a controlled environment with high temporal and spatial resolution."

Using an off-the-shelf Formlabs Form 2 3D printer, a surgical-grade resin designed for dental work, and the popular SolidWorks modeling software, the team was able to design a microfluidic chip with four culture and imaging wells — plus a non-printed glass window for observation.

Each chip connects to an incubator with culture media, constantly-refreshed nutrition from which was fed to the organoids using a peristaltic pump from Adafruit drive by the pulse-width modulated (PWM) output of a Microchip ATmega328P microcontroller — with a second being used to control the temperature of the oven portion of the complete bioreactor.

"Our design costs are significantly lower than traditional Petri dish or spin-bioreactor based organoid culture products that can cost tens of dollars," the researchers write. "For 3D printing, approximately 15ml resin was used including the resin used for the scaffold, at a cost of only around $5 per chip. We also note that the culture medium used is just around 764μl per refill."

"We demonstrated the use of this bioreactor for imaging of a brain organoid expansion and cell morphology tracking for up to 7 days. Our 3D printed microfluidic bioreactor for the culture and live imaging of 3D biological tissues can find its applications in many research or industrial laboratories where organoids can be modeled to study development, diseases, or interactions between human host organoids and pathogens like coronavirus SARS-COV2."

The team's work has been published under open-access terms in the journal AIP Biomicrofluidics.