17 December 2021

Intravenous cytometer

Scientists have found an effective method of searching for cancer cells in the blood

RIA News

The parameters of laser radiation at which melanoma cells heat up and generate ultrasonic signals have been established by scientists at Saratov State University. This information will be used to create a photoacoustic cytometer, which in a few minutes will be able to "view" a significant amount of blood in the patient's body and detect cancer cells in it at an early stage of the disease without taking tests. The results of the study are published in Scientific Reports (Kozlova et al., Dynamic blood flow phantom for in vivo liquid biopsy standardization).

According to scientists of the Saratov National Research State University named after N.G. Chernyshevsky, mortality from oncological diseases in about 90 percent of cases is associated with the formation of metastases, when cancer cells from the primary tumor penetrate into the lymphatic and blood vessels and then spread by flows of biological fluids throughout the body.

Primary tumors in many cases are successfully surgically removed and non-metastatic cancer can be cured. However, metastatic cancer, in which numerous metastases develop in various organs, is difficult to treat. In such a situation, it is important to detect circulating tumor cells in the patient's blood as early as possible, when treatment is still effective.

The method of flow cytometry allows you to examine blood by light scattering and fluorescence signals. A test tube with blood is placed in a conventional flow cytometer, and the device separates its cells so that they pass one by one through a thin tube, illuminates them with a laser and measures how they glow and how they scatter laser light. This allows you to determine how many and which cells are found in the blood, and helps the doctor to make a diagnosis.

Scientists of the Saratov National Research State University named after N.G. Chernyshevsky are developing a photoacoustic cytometer to search for melanoma cells in the blood, said Olga Inozemtseva, senior researcher at the Biomedical Photoacoustics Laboratory of the University's Scientific Medical Center.

"Our cytometer, instead of a tube with separate, well-separated cells, works directly in a large vessel on the back of the hand, where a large flow of cells rushes at high speed. In order to "see" foreign objects of interest to us in the blood, for example, circulating tumor cells, we use photoacoustics technology that combines a medical laser (a similar one is used, for example, for laser hair removal) and an ultrasound installation."

If the cells absorb radiation at the laser wavelength, they heat up, thermal expansion of the material occurs and a sound very similar to the signal used in medical ultrasound installations occurs. Experts investigated at what laser parameters melanoma cells begin to heat up effectively and generate ultrasonic signals. It turned out that the signal level strongly depends on the conditions and stage of growth of cancer cells.

Based on the results obtained, scientists have developed artificial "cancer" cells – phantoms that begin to "sound" at the same parameters and generally behave like cancer cells. But, unlike them, these phantoms retain the same signal all the time, which allows you to transfer the results of measurements from one installation to another and use them as a signal reference.

"We have manufactured a system that includes model objects based on silicon dioxide and layer-by-layer (LbL) capsules containing hemoglobin molecules or natural melanin particles, depending on the required properties. We wanted to make them not only similar to real objects in size and shape, but also to simulate their optical properties and, in part, chemical compounds so that they could be detected using various analysis methods," Olga Inozemtseva said.

Artificial "cancer" cells are completely biocompatible, researchers can inject them into the bloodstream of laboratory mice and "see" them with the help of a photoacoustic flow cytometer being developed.

At the moment, researchers are finalizing photoacoustic flow cytometers and clarifying the parameters of an experimental model that will allow the transfer of measurement technology from animals to humans.

"Our phantoms allow us to move from single natural cancer cells circulating in the blood to tens of thousands of artificial ones, and thus gain the amount of information necessary to create a database of cell responses," Olga Inozemtseva noted.

This will allow you to build a cytometer that can work not with a blood sampling tube, where literally a few cancer cells get, but in 15 minutes without taking blood, "view" a significant part of the blood circulating in the human body. This will significantly increase the probability of detecting a cancer cell at an early stage of the development of the disease, track how their number changes during the treatment of patients with melanoma and, if necessary, adjust treatment.

"The phantoms created by other researchers differ significantly in parameters from real cancer cells. They allow you to detect yourself, calibrate the device, but do not allow you to transfer the parameters of the experimental model from an animal to a human. To do this, we needed phantoms developed by us," the author of the study stressed.

In the near future, scientists will create a model to search for cancer cells directly in human blood with safe laser parameters.

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