A bill for thousands

A lab-on-a-chip can test thousands of stem cells simultaneously

Lina Medvedeva, XX2 century

Researchers from the Institute of Molecular Engineering at the University of Chicago (Institute for Molecular Engineering at the University of Chicago) have developed a "laboratory-on-a-chip" that allows thousands of individual cells to be examined within a week. With its help, you can conduct experiments that require more than a million steps in a conventional laboratory.

Article by Zhang et al. Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation published in the journal Science Advances.

The credit card-sized device not only saves time and money, but also allows you to take a fresh look at the reaction of individual stem cells to various molecules and the environment.

When scientists examined neural stem cells on this device and analyzed the data, they discovered several new patterns that determine the timing and sequence of the signals needed for cell differentiation or renewal. This result may have implications for understanding brain development and for immunotherapy.

"We wanted to develop a micro–jet device for automatic sorting, visualization and cultivation of individual cells, which has a high throughput," says Professor Savas Tay, lead author of the study. – We have achieved this, now we have an understanding of how stem cells make decisions. It's amazing."

Cells in our body constantly respond to various signals and changes in the environment. For example, signals in stem cells received at different points in time determine the choice of how the cell will develop. One signal can lead to transformation into a new cell, the other to the preservation of the form.

Now researchers do not have the opportunity to study the signals of molecules on individual cells inside the body. Such an analysis will require a laboratory with expensive long-term experiments, and in the end it will be impossible to verify all possible results.

A micro-jet device with small compartments, tunnels and valves allowed researchers to speed up and automate the process of studying reactions in cells. But these devices had a limited number of compartments, which meant that researchers could only test a certain number of conditions for each cell, and could not keep the cells alive long enough to be able to comprehensively study them.

Tai and his colleagues solved these problems. They have developed a micro-jet device with 1500 automatic compartments, which is much higher than the earlier ones (less than 100 compartments) similar devices. The device can perform several tasks: cell stimulation, cultivation, image creation and sorting. Previously, they were performed by separate devices. It can grow cells in different modes, so it is possible to study different types of cells at the same time.

Also, the device can support the life of cells for a much longer time thanks to the new technology of spreading the medium in the grown cells. Usually, in order to keep the cells alive, researchers had to change the environment in which they are kept every few hours. Such replacements are always stressful for the cell, and after several stresses, the cells die. The new technique spreads the medium into the inner space of the electrolyzer, this is a softer process, without abrupt changes, without stress for the cells.

In the first experiment with the device, the researchers studied how different signals of molecules affect the result of the work of mouse neural stem cells. Such experiments generate huge amounts of data; in order to find patterns in them, Tai, in collaboration with Andrey Rzhetsky, professor of medicine and genetics at the University of Chicago (UChicago), passed them through a neural network.

They found that some combinations of signals add up and cause cells to differentiate, while other molecules stop this process. The timing of the signals is also of great importance. If the molecule is delivered at the right time, it can affect the type of stem cell change, stimulating, for example, self-renewal instead of differentiation.

"There are some sequences of highly optimal signals, and their location in time matters," says Tai. "Previously, there was no way to observe them dynamically, and it was impossible to understand the principles of their reaction."

In the future, the researchers hope to use the device to study organoids, growing tissues from stem cells organized into small organs.

As a result, such a device can be used for immunotherapy, when the patient's immune system is stimulated to help him fight the disease. The patient's stem cells can be taken from him, placed in a device – and so the correct combination of molecules is revealed, the cells are developed into a certain line and subsequently placed back into the body.

"We want to learn how to use this device to solve a variety of problems in cell biology," concluded Tai.

Portal "Eternal youth" http://vechnayamolodost.ru