24 February 2022

Everything is ready to move in

When will an organism-on-a-chip appear in Russia

Alexey Ognev, RIA Novosti

An organism-on-a—chip is one of the most advanced concepts in biotechnology, which in the future allows us to move to personalized medicine. Research in this area is actively conducted in Russia. A RIA Novosti correspondent spoke with engineers from Bauman Moscow State Technical University working on the creation of a brain-on-a-chip.


Anatomical theater of the XXI century

Drug testing is a complex and expensive process. For example, in 2019, US pharmaceutical companies spent more than $ 83 billion on this. Moreover, according to statistics, only 14 percent of the tested drugs receive approval from the American Food and Drug Administration (FDA).

Promising drugs are tested first on cell cultures, then on animals. According to some estimates, almost 200 million of them are required for this purpose per year. Then there are several stages of clinical trials. And anyway, this or that medicine may not be suitable for a particular patient.

Everything is going to personalized medicine. Scientists suggest testing drugs on models of the human body. They take the patient's cells, create a prototype of his brain, heart, liver in miniature and check whether the medicine is suitable for him. It sounds fantastic, but this technology already exists. This is called "organ-on-a-chip" or "organism-on-a-chip".

Living cells are placed in cells on a chip the size of a smartphone. Microchannels allow you to simulate blood flow or the exchange of tissue fluids — for example, lymph. All this is placed in a special chamber in which a certain temperature and gas composition are maintained, nutrient solutions are pumped through the chip, and metabolic products are removed from the cells.

The idea belongs to Donald Ingber, founder and director of the Wiss Institute for Biological Engineering at Harvard University. In 2010, he and his colleagues created the first device of this kind — light-on-a-chip. It was pierced by two-level channels separated by a porous membrane. One section contained a layer of lung cells and was filled with air, the other — a layer of cells of the blood vessel where the blood was circulating. Through microchannels, it was possible to bring harmful bacteria or drug molecules and monitor what was happening.

There are already chips that mimic the work of the kidney, liver, intestines, and heart. Next up is the brain. It is protected by the blood-brain barrier, through which many drugs do not penetrate. The new technology will help determine how effective a particular drug is in such a situation.

In the future, scientists want to create a whole organism-on-a-chip, reproducing the system of all vital organs. For example, the American agency DARPA has already assembled ten microphysiological models on one device.

Russian laboratory-on-a-chip

In Russia, breakthrough technology is being successfully developed at the Scientific and educational center "Functional Micro/Nanosystems" (REC FMN) of Bauman Moscow State Technical University. Over the past five years, several know-how have emerged that have made it possible to make chips from silicon, polymer and glass, as well as to manufacture microfluidic fluid flow sensors.

"Imagine a miniature heater that dissipates very little (less than 100 milliwatts) of heat. You feed the liquid into the microchannel. Naturally, the liquid carries away the heat. Next to such a heater, temperature sensors are installed directly in the microchannel on both sides. Now we know in which direction the heat is moving and at what speed. Now the accuracy is no worse than 92 percent, the result is at the world level. And considering that all technologies are borrowed from microelectronics, the device is easily scaled for multichannel laboratories-on-a-chip and organisms-on—a-chip," says Ilya Rodionov, Director of the REC.

Engineers have developed chips with complex microchannel circuits and a whole series of different biosensors, mainly optical, analyzing radiation to detect even very small concentrations of various biological objects. The next step is a chip made of materials resistant to aggressive environments to work with bacteria and viruses. The effectiveness of the new method, which has no microfluidic analogues in the world today, exceeds 80 percent.


Russian scientists have also taken up the creation of a brain-on-a-chip. There is no way to do without interdisciplinary cooperation, implemented today within the framework of the federal program "Priority-2030" and the strategic project Bauman DeepTech. The staff of the scientific and educational center has already established contact with the Faculty of Biomedical Engineering of MSTU, as well as the Scientific Center of Neurology.

"Biologists can grow cell cultures, and we can make chips. We complement each other very successfully," said Vitaly Ryzhkov, a leading researcher of the REC in the direction of "Bionanotechnology and microfluidics".

First you need to populate brain cells on the chip and organize their interaction.

"We need five to seven bioreactors, where cells characteristic of a particular part of the human brain are grown. Next, it is necessary to create a microfluidic system with a membrane structure in order to supply nutrients, as it happens in our head through the blood. We will connect these bioreactors with very thin channels that mimic the capillary system. This will open the way for pioneering research," Ilya Rodionov notes.

Even if we simulate the work of one structure of the human brain, for example, the blood-brain barrier, it is already possible to study the metabolic processes in this structure, how it participates in metabolism and modification.

"At water treatment plants, crayfish are used to assess water quality, which, as is known, prefer reservoirs with very clean water. If they do not take root, then it is necessary to take measures. In the laboratory-on-a—chip, the same principle, only instead of cancers, there are living human cells," explains Vitaly Ryzhkov.

Brain cells can be obtained by biopsy or autopsy, as well as grown from stem cells. However, a number of problems have to be solved.

"For example, we have grown 20 by 20 micron balls from brain cells, the so-called organoids. They live while they are washed with a solution that supplies nutrients and removes metabolic products. But when the organoids increase to 50 by 50 microns, the cells deep inside do not receive nutrition and poison the surrounding cells with toxins," the researcher clarifies.

The REC FMN has developed technologies for the manufacture of rigid and elastic microfluidic chips ready for colonization with living cells. The next two to three years will be spent on modeling either the blood-brain barrier or the hematolycoietic barrier, which is much less studied (it separates the cerebrospinal fluid from the blood).

Now it is difficult to assess how effective the search for drugs with the help of an organism-on-a-chip will be, because such systems do not yet exist. However, in ten years they will appear.

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