CZ Biohub’s game-changing microscope seeks to inspire an international community of builders

When Chan Zuckerberg Biohub scientists published a paper earlier this year on a new light-sheet microscope they had built – a tool called DaXi, which can capture a space about 18 times larger than existing single-objective light-sheet microscopes – their hope was that scientists around the world would build their own versions of DaXi (pronounced “dah-shee”). 

They made the design details freely available and put out the call. “The goal is to nucleate an international community of builders of DaXi microscopes,” says Loic Royer, a Biohub group leader and lead developer of DaXi. “LEGO and IKEA have shown that ordinary people can build complex systems when provided clear instructions. Can we do the same with state-of-the-art microscopes?”

Several groups took on the challenge. One, the Synthetic Physiology Lab of Francesco Pasqualini at Pavia University in Italy, decided to send a researcher to San Francisco for the summer to learn how to build a DaXi scope while also creating documentation for others to follow. (When completed the documentation will be available at Github.)

DaXi is ideal for the field of developmental biology, which is concerned with studying how embryos develop. “Our group in Italy is interested in cardiac disease, and one of the models for studying it is ‘cardioids,’ which are organoids that mimic cardiac tissue,” says Melissa Pezzotti, a PhD student in Pasqualini’s group who came to the Biohub to build a DaXi device from scratch. “We need an optical system to track development of these organoids, and DaXi is the perfect solution for us.”

Pezzotti is working with Xiyu Yi, an optical scientist who joined Royer’s lab earlier this year to further develop DaXi. “DaXi can work on large samples at high temporal and spatial resolution with a large field of view,” she says. “So it really covers an important niche for biological research that requires large samples, such as a whole embryo. And, speaking as a microscopist, this microscope is just so cool!”

The cost of the parts is around $250,000, about half the price of similar commercially available microscopes, says Royer. “Our group looked at commercial systems, and we found that DaXi gives us better performance and a custom system at a lower cost,” Pezzotti says. 

Royer summarizes his philosophy on technology development: “It is not enough to build great tools for our own purposes and show that we can push one or another technological limit – we also have to make efforts to put our tools in as many scientists’ hands as possible.”