WASHINGTON, June 10, 2025 – Human development is a beautiful, complex process. Beginning from just two germ cells, the cells divide and double until an entire organism is developed in just under a year.
While studying embryos in vitro can have many ethical and technical complications, there is a model that serves as an excellent substitute. Named after the early-development stage of gastrulation, two-dimensional "gastruloids" are made from colonies of human pluripotent stem cells that can replicate the third week of gestation in which the three germ layers of the body are established.
In APL Bioengineering, by AIP Publishing, researchers from the University of Washington and the Brotman Baty Institute for Precision Medicine in Seattle developed a way to sort these gastruloids quickly and automatically.
"Researchers can grow arrays of hundreds of consistently sized gastruloids at a time within a few days, thus gastruloids are straightforward to manipulate and track for a variety of experiments," said author Ian Jan. "However, the lack of an automated sorting platform to isolate individual gastruloids hinders studies of the differences between each gastruloid."
Studying how these cells develop can give researchers insight into how genetic diseases are passed on. For instance, gastruloid models showed that Huntington's disease can be detected within the first two weeks of embryo development.
"Another example is using gastruloids to model the presence of abnormal numbers of chromosomes, known as aneuploidy. Notably, gastruloids with varying proportions of aneuploid cells revealed a self-correction mechanism that sheds light on the robust nature of embryonic development," Jan said.
To create gastruloids, scientists confine human pluripotent stem cells into circular colonies on glass slides or plastic dishes. Introducing a small molecule to the colonies encourages the cell signaling that trigger in the gastruloids the types of development found in embryos.
Once all the gastruloids are developed, counting, sorting, and identifying them by hand takes time. This is where Jan's system comes in.
The sorting system is comprised of a microscope, a camera, a sorting stage, and devices for collecting and releasing the microrafts that the gastruloids are grown on. It's controlled by custom software that automates the sorting process.
The researchers can then scan the images for abnormalities and isolate the unique gastruloids for further research.
"The analogy that I frequently use is, imagine a claw machine, but instead of stuffed animals, you have microrafts with cells," Jan said.
The sorting system is ready for large-scale screening of gastruloids, so next, the team is working on incorporating neural networks into the image analysis pipeline.
"The lack of an automated sorting platform to isolate individual gastruloids hinders studies of the heterogeneity between each gastruloid, which is composed of multiple cells all undergoing dramatic changes," said Jan. "Probing single gastruloids can reveal intrinsic variation that could reflect the diversity of how human embryos develop."
