"You can measure the mass of the virus": a Russian physicist on a new domestic ultra-precise mass spectrometer

— Earlier, you patented a new ultra-precise mass spectrometer with electron shock ionization based on a multi-electrode harmonized Kingdon trap. Could you explain how the mass spectrometer you developed works and how it differs from others?

- Mass spectrometers are very different, but in general they are all designed to determine the composition of mixtures of various substances. You can find out the composition by determining the weight of the molecules that make up the mixture - the atoms and molecules of each substance or compound have their exact weight. The process of "weighing" the molecules of the sample under study using a mass spectrometer can be organized in different ways.

However, in any case, atoms or molecules must first be ionized. In the simplest case, this means "tearing off" an electron from them - then they will have an electric charge. Charged particles interact with an electric and magnetic field, and the behavior of ionized molecules (ions) will depend on their mass. If the mass is measured accurately, the molecule can be identified from it.

Mass spectrometers differ in how molecules are ionized and how mass information is extracted. For example, when particles interact with an electric field, they acquire different speeds depending on the mass. In this case, it is possible for all particles to measure the time of flight from one point to another and determine the speed at which they fly, and, knowing it, calculate the mass. But this is just one of many methods.

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Our appliance is an electrostatic trap. The field in it creates two reflective elements, or mirrors, between which ions fly - we want to know their mass. The particles are reflected from one and the other mirror, and this is how we measure the frequency of oscillations (movements) of these ions. This quantity contains the information we are interested in about the mass: the lower the frequency, the greater the mass.

We call such a device a "trap" because ions are trapped inside it. Imagine a can of cola, in which two holes are drilled from the ends and a wire is inserted into them, passing through the entire can. If the bank is grounded, and a constant negative voltage is applied to the wire, then the ions inside will not be able to fall either on the surface of the can or on the wire. This is forbidden by the laws of physics. They will somehow hang out in the jar and circle near the wire for a long time. This is how the Kingdon trap, invented back in 1923, is the prototype of ours.

American physicist Randall Knight proposed to change the shape of the can in such a way that it was possible to determine their mass by the frequency of oscillations of ions along the wire. Later, the Russian physicist Alexander Makarov embodied this idea in a mass spectrometer called "Orbitrep". And Professor of St. Petersburg State Polytechnic University Yuri Golikov further modernized the method of confinement of Kingdon ions and proposed to use not one electrode, but several. There are four electrodes in our mass spectrometer.

Such a multi-electrode trap has an important advantage over a single-electrode trap - you can create ions right inside the trap and hold them for a long time. For example, run a gas there and ionize it with electrons. If there is only one electrode in the trap, then ions have to be introduced from the outside. This means that it is necessary to create and accumulate them somewhere outside - this process takes place in another, external trap. Then a separate step is required when they are thrown into the main one. As a result, the device becomes more complex and cumbersome. Although this difference does not affect the accuracy of measurements.

— In what areas is the mass spectroscopy method predominantly in demand?

- Initially, mass spectrometers were proposed in order to understand how transformations occur in chemical reactions. Soon, with the help of such devices, isotopes were discovered - varieties of atoms that are chemically identical, but differ in mass due to the different number of neutrons in the nucleus. Now, in each field of application, specialized mass spectrometers are used - there are even those that can measure the mass of the virus, and it is tens of millions of times heavier than a hydrogen atom.

Of the modern applications of such devices, it is impossible not to mention medical ones. For example, they are used in neonatal screening - the newborn is examined for the presence of hereditary diseases that pose a serious threat to life.

Mass spectrometers in this case measure the concentration in the blood of metabolites - products that, in case of metabolic disorders, are produced in excess or in deficiency. This anomaly is directly related to genetic disorders.

Mass spectrometers are also used to identify non-antibiotic pathogenic bacteria. Previously, in order to find out the type of bacterium, it was placed in a special nutrient medium, and doctors tested its resistance to drugs. Now it is possible to "identify" this bacterium on a mass spectrometer and correlate it with a class of previously accumulated data. At the same time, it is not the bacterium itself that is weighed, but proteins from its so-called ribosomal complex, which is different for each strain. In our laboratory, we have developed a similar method for determining strains of the COVID-19 virus by its proteins.

• A tokamak designed for controlled thermonuclear fusion
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Mass spectrometry is also used in proteomics. The concentrations of proteins in physiological fluids are measured: blood, tears, saliva, etc. The fact is that in the presence of a disease, protein concentrations change, and by comparing their levels in healthy and sick people, the disease can be diagnosed. For example, during the COVID-19 pandemic, my colleagues and I developed a mass spectrometric method that can determine the probability of survival of a patient.

There are many other applications of mass spectrometry in medicine. For example, thanks to the analysis of proteins in the blood, we at Skoltech have learned to predict whether dementia will turn into Alzheimer's disease.

Mass spectrometry helps to make industrially relevant decisions. In particular, Skoltech is working on its applications in metallurgy, oil production and in the problems of thermonuclear fusion - we are talking about determining the composition of heavy oils, the gas phase over molten metal in production and the concentrations of various isotopes of hydrogen and helium on tokamaks.

A separate topic is mass spectrometry for space. Initially, we at Skoltech developed our device specifically for space research.

As we know, as a result of the space race between the USSR and the USA in the XX century, a lot of lunar soil (regolith) from the equatorial regions of the Moon was delivered to Earth. Now its composition is known, but scientists are interested in the composition of the soil at the lunar poles, in craters, where there is reason to look for water and primitive organic matter from comets. It can be recognized by sending a mass spectrometer to the moon.

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—How does the spectrometer developed by you differ from analogues currently presented in the domestic and world markets? Does it have any other characteristics besides accuracy?

"Many mass spectrometers are very large and weigh about a ton. Our device is very small, desktop, but nevertheless very accurate. He, of course, will not be able to conduct a subtle analysis of oil, but such a task is not set before him. It is more likely to compete with the previously mentioned Orbitrap mass spectrometer.

In addition to the accuracy of mass measurements, mass spectrometers have two other important characteristics. The first is resolution, that is, how well the device is able to distinguish ions with very close masses. The second is the dynamic range of concentrations, that is, how much the concentrations of two substances in the analyzed mixture can differ. For example, the ratio of helium-4 and helium-3 on the Earth's surface in seismically inactive areas is known - 1:10000000 - and it is necessary to compare it with the ratio of these isotopes near faults in the earth's crust, where they try to predict seismic activity. In this case, the dynamic range must be at least 10 million. The dynamic range of our device is higher than that of Orbitrep.

— Work on your mass spectrometer has been going on for many years. What difficulties did you encounter when creating the device?

- The work continues now, and difficulties continue to arise. For example, the measured frequency of ion oscillations in an electric field depends on the potential (a scalar quantity equal to the ratio of the potential energy of the charge in the field to this charge. - RT), which we apply to the internal electrodes ("wires"), and it must be maintained with very high accuracy. It is very difficult to manufacture such DC voltage sources. Initially, we found such a device in Japan, but now we have ordered a replacement from domestic manufacturers. Moreover, we are gradually switching to Russian electronics, previously there were American units in our device.

Another difficulty lies in the fact that for the manufacture of the device and parts for it, we use high-precision equipment - five-axis machines with almost micron accuracy, of which there are very few in our country. We tried to make parts using 3D printing, but we did not get the required quality.

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- Does your development now have prospects to enter serial production? Are industrial enterprises interested in it?

- Yes, of course, they are interested. We have already received a response from Rosatom and Rostec. There is great interest in our development from our Chinese colleagues - we plan to create a joint laboratory. Our mass spectrometer is of interest to chemists, pharmacists and specialists from other fields where the device can be useful.

- What is the current situation with the production of high-precision equipment? Earlier it was reported that at the beginning of 2022, the American manufacturer of laboratory equipment Thermo Fisher, which left Russia, occupied 30% of the Russian market. Why was there no or little laboratory equipment produced in Russia? What was the situation with this during the Soviet era?

—When I was a student, we worked only on domestic devices and did not even know about imported equipment. Chemical, medical and isotope mass spectrometers were produced in our country. In the 90s, the government decided to purchase equipment from Western countries - Japan, Germany, and the USA. This is how domestic instrumentation was ruined.

In fact, we can create everything ourselves, since almost all innovative ideas in the field of modern mass spectrometry are Russian. Now in our country they are again engaged in the development of such high-precision domestic equipment. Thus, the Russian companies "Chromatek" and "Interlab" produce simple mass spectrometers, which - in their class - are not inferior to imported ones.

• The first director of the Vernadsky Institute of Geochemistry and Analytical Chemistry, Academician of the USSR Academy of Sciences Alexander Vinogradov and a researcher at the laboratory at the mass spectrometer
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The national school of mass spectrometry has been preserved and knowledge is being passed on to a new generation of researchers. Most of the participants in our project are young scientists.

- Earlier in Russia, a program for import substitution of laboratory equipment was also announced. Scientists have compiled a list of about a hundred types of devices. Is there really a shortage of such equipment now?

- There is undoubtedly a shortage of equipment. The import of devices from China, which has intensified recently, is not a way out. Because Chinese equipment is a copy of Western, but of lower quality. In general, it works, but I would still like us to have our own developments in this area. We have the competencies for this, and they need to be developed, this is not an area where you can save.