A Zebrafish Egg Sorting Machine

Credit: Ecole Polytechnique Federale de Lausanne

Zebrafish eggs are among the most widely used model organisms in genetic, developmental and toxicological research. A device developed by EPFL spin-off Bionomous reduces the time it takes to sort these embryos from a few hours to just a few minutes.

Zebrafish are only four or five inches long and bear little resemblance to humans. So it may come as a surprise to learn that they share 70% of their genes with us. This biological characteristic, coupled with the fact that their eggs are abundant and transparent, makes these tiny freshwater minnows particularly valuable to science. In fact, the past two decades have seen a boom in zebrafish-based research in everything from myopathy and other genetic disorders to cancer, Alzheimer’s disease, drug discovery and toxicology screening.

But there is a fundamental stumbling block with this new model organism: the painstaking work of examining the eggs under a microscope to identify healthy specimens that can be used in research. EPFL spin-off Bionomous has combined micro-engineering and artificial intelligence to develop a machine that reduces this sorting exercise from a few hours to just minutes. After completing an initial fundraising round earlier this year, the company is gearing up to launch its machine in the fall. It is also working on a larger-capacity version of the device, which could speed up the sorting process for other types of eggs and seeds.

Analyzing Fluorescent Fish

The benefits of using zebrafish in research were first revealed about 20 years ago. Since then, many research institutions, including EPFL, have opened dedicated breeding facilities. “A key benefit of zebrafish is that they develop outside the mother’s body at a very early stage,” said Frank Bonnet, the CEO and co-founder of Bionomous. “This makes them a more ethical choice than other models such as mice, and supports a wide range of research into fish and, by extension, vertebrates development.”

For his dissertation, Bonnet worked on developing a robotic fish capable of infiltrating schools of flesh-and-blood zebrafish. He came up with the idea for his device after seeing other researchers peering over a microscope for hours to select viable eggs.

With his Ph.D. under his belt, Bonnet began designing a machine that could process an entire test tube — containing thousands of eggs — in one go. It uses a microfluidic system to capture individual specimens and eject them one at a time onto a notched wheel. As the wheel spins, the eggs go under a camera. The images are then processed by an artificial intelligence system: healthy specimens are pipetted onto a sieve plate or into a petri dish, while rejected samples are sent to a separate container. The machine also supports fluorescent imaging in genetically modified specimens, allowing scientists to observe features such as blood vessels and neurons in real time. The deep learning algorithms can be adapted to researchers’ requirements, classifying eggs by fertilization status, developmental stage, morphological features or specific biomarkers.

A new version in preparation for sorting other small entities

Since filing a patent application in 2017, the company has secured seed funding from a variety of sources and tested their technology in a range of labs, including Sweden’s Karolinksa Institute, one of Europe’s largest animal research facilities. “One of our machines is a fixture at Oregon State University, which has also placed an order for several next-generation devices,” says Bonnet.

In 2021, the spin-off raised 1.3 million Swiss francs in a first fundraising round. It used the capital injection to finalize the machine, which it will launch this fall. Now the company is working on a new version to support research into other small biological entities.

“In industries like agriculture and fish farming, researchers still spend countless hours sorting massive amounts of eggs and seeds,” said COO and co-founder Ana Hernando. As a member of the Venture Leaders Biotech cohort, Bonnet will travel to the United States in mid-September to meet international investors and leading players in this niche market.

Machine learning algorithm automatically sorts zebrafish eggs

Provided by Ecole Polytechnique Federale de Lausanne

Quote: A Zebrafish Egg Sorting Machine (2022, Aug. 19) retrieved Aug. 19, 2022 from https://phys.org/news/2022-08-machine-zebrafish-eggs.html

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