Does Russia not need biosensors?
Russian scientists can do betterMarina Muravyeva
Photo: Dmitry Europin
STRF.ruScientists of the Chemical Faculty of Lomonosov Moscow State University have developed highly sensitive biosensors for the determination of glucose, lactate, hydrogen peroxide and other compounds.
These devices are significantly superior in their capabilities to foreign analogues, and they can be used almost everywhere: from medicine to industrial ecology. At the IX International Forum "High Technologies of the XX-I century" Arkady Karjakin's laboratory received a bronze statuette "St. George" for the development of biosensors
The development of biosensors is primarily associated with clinical diagnostics, namely non-invasive methods that allow the analysis of the main components of metabolism without blood sampling. Biosensors with their high sensitivity and selectivity should play a key role in this direction. In addition, they can be actively used in the food industry – to analyze the freshness and quality of products, control various fermentations, for example, in brewing and winemaking, as well as the content of artificial food additives.
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A biosensor is a device consisting of a signal converter (transducer) and a certain recognition element. At the first stage, the bioelement "recognizes" a substance specific to it from a multicomponent mixture. At the second stage, information about the course of a biochemical reaction is converted into the form of an electrochemical or, for example, an optical signal. This stage is key in the biosensor operation.
The most sensitiveThey have been working on the creation of biosensors in the laboratory of electrochemical Methods of the Chemical Faculty of Moscow State University under the guidance of Professor Arkady Karyakin since the mid-1990s.
During the research, which during this time was carried out with the support of the RFBR, the Bortnik Foundation, Rosnauki (Federal Research and Development Center and Federal Target Program "Research and Development") and other organizations, including foreign ones, scientists managed to make the most sensitive sensor. Combining scientific approaches to create the most efficient hydrogen peroxide signal converter and the most optimal immobilization (binding) of the enzyme on the surface of the transducer, it was possible to develop a glucose biosensor, which today has record analytical characteristics: it allows analyzing glucose in the flow-injection system up to a concentration of 10-7 M with a sensitivity of 0.05 A M -1 cm–2. This sensor exceeds the existing analogues in sensitivity by two or three orders of magnitude. In addition, the scientists managed to achieve another result: using the method they developed, the electrodes of the device can be both in the most stable (for a year) and in the most active state – they can withstand up to a thousand measurements.
"The development of glucose sensors is an extremely urgent task,– Arkady Karyakin comments. – Diabetes mellitus affects up to eight percent of the total population in developed countries, and up to ten percent in developing countries. These people need to measure their blood sugar levels every day, sometimes several times a day. It is not possible to do this effectively by physical methods. The walls of the vessels are lined with polysaccharides, which are very much even compared to the huge glucose content in the blood. The biosensor is highly selective, and it does not need to be heated like chemical sensors that start working only after heating (from 100 to 500 degrees). So the advantages of biosensors in this case are obvious. In addition, they can be used to determine blood glucose levels in the most patient-friendly conditions."
The simplest glucose biosensors have long been sold in pharmacies (since the end of the last century). For the analysis of glucose in the blood, such sensitive sensors are not required, which were developed at the MSU Chemical Faculty. But in the future, with the development of non–invasive diagnostic methods, such biosensors will become indispensable. In addition, diagnostics can be carried out by implanting a sensor inside a blood vessel to continuously monitor key blood components. In this regard, more and more attention is being paid to the miniaturization of biosensors.
Instead of kvass – sodaIn addition to glucose sensors, Arkady Karyakin's laboratory has also developed biosensors for the determination of lactate, ethanol and several other substances in biological media and food.
A special enzyme is introduced into the composition of one of the electrodes, which selectively catalyzes the oxidation of the substrate with oxygen in the air – a substance whose concentration must be measured. At the same time, peroxide is released, by determining the concentration of which, you can find out the content of the substrate itself – for example, lactate (glucose is determined by the same principle).
To confirm the suitability of the developed biosensors, scientists analyzed various products and beverages, for example, evaluated the quality of several varieties of kvass. This drink is known to be prepared by fermentation, during which lactic acid (lactate) appears. During the experiment, it turned out that kvass of one of the advertised brands, which is positioned as a natural product, does not contain lactate. That is, in fact, the drink is a kind of Coca-Cola. This is the simplest example of how any consumer can find out about the quality of the purchased product using a biosensor. A similar experiment was conducted with grape wines. Certain concentrations of sugars are characteristic of natural ones. In the surrogates, their proportions are broken, and the manufacturers mask the taste flaws by sweetening the drink, which is easy to determine with the help of biosensors.
To carry out the analysis, the object under study is needed – a drop of liquid (biological or some kind of drink), in which the content of the desired substance is determined. The method is so selective that it allows you to recognize a compound in an environment of any composition and any concentration. In fact, the basis of the method is the electrochemical determination of hydrogen peroxide, but the tasks may be different. For this, platinum electrodes are usually used, which are considered the most effective, but expensive. Scientists of the Chemical Faculty replaced them with cheap analogues based on the usual iron compound – Prussian blue. The advantage is not only in price, but also a thousand times higher efficiency and selectivity of action. In addition, the shelf life of such electrodes is practically unlimited.
For the analysis, of course, additional equipment will be needed, mainly typical: a potentiostat (like a pH meter, but somewhat more complicated), and for the automation of the process - a peristaltic pump and a flow cell, which was developed at the Chemical Faculty.
Not with blood, but with sweatCurrently, Arkady Karyakin's laboratory and the Institute of Physical Education and Sports have launched a joint project funded by Rosnauka (the project "Highly effective biosensor for non-invasive assessment of human stress conditions").
How athletes perceive the load is judged by blood samples for glucose and lactate. Considering that the procedure has to be carried out quite often, there is little pleasant in this. The sensors developed at the Chemical Faculty are highly specific and selective, and according to preliminary data, they are able to determine the concentration of glucose and lactate not by blood, but by sweat.
In the future, it is planned to create a special device that allows, depending on the personal parameters of athletes, to dose their individual load. This is extremely important, since coaches cannot know the characteristics of the body of their wards, so they work with them according to a general schedule, which does not always lead to the desired results. As an example, Arkady Karjakin cites the story of the sporting success of Manuela Di Centa, who at the beginning of her career did not promise outstanding results. And after some time, I was able to unexpectedly become a leader for many. It turned out that she managed to achieve this thanks to training with oxygen sensors on her muscles. The trainer individually selected the load based on the oxygen consumption of the muscles. And, most likely, thanks to this technique, the athlete dramatically raised her status and became an unattainable Olympic champion.
Another area of research in Arkady Karyakin's laboratory is related to the determination of hydrogen peroxide in exhaled air condensate as a marker of certain inflammatory processes in the lungs. "We conducted joint experiments with the Institute of Pulmonology under the leadership of Academician of the Russian Academy of Medical Sciences Alexander Chuchalin, studied the possibilities of diagnosing lung diseases using biosensors," says Arkady Karyakin. – The fact is that in half of cases, the wrong diagnosis is made by traditional methods: two out of three patients receive the wrong treatment. In addition, the diagnostic methods are very painful."
Scientists intend to develop a system for therapists and pulmonologists that allows to effectively and painlessly clarify diagnoses and monitor the course of treatment. For this purpose, a special sensor and a flow system will be used, which will allow the analysis of samples of exhaled air condensate by the express method - in less than a minute.
There is a struggle for every articleScientists of the Laboratory of Electrochemical Methods of the Chemical Faculty of Moscow State University publish the results of their research in leading foreign scientific publications.
The most prestigious scientific journal of chemistry "Angewandte Chemie", which surpasses the "Journal of the American Chemical Society" in citation, published an article by Moscow chemists, which claims that scientists have created a record-breaking electrochemical sensor for the determination of hydrogen peroxide. Another authoritative journal, the American Analytical Chemistry, published an article about the most sensitive glucose biosensor. What Moscow scientists do is highly respected in the West, especially their fundamental research.
Scientists of the laboratory of electrochemical methods are actively quoted, in particular, Arkady Karyakin has at least 300 citations per year, and the total personal CI index has exceeded two thousand (this is one of the best results among young scientists of the Chemical Faculty of Moscow State University). In addition, Arkady Karyakin is the only Russian member of the editorial boards of leading foreign journals such as Electroanalysis, Electrochemistry Communications, Talanta and others.
Professor Karjakin does not share the opinion prevailing in the scientific community that Russian scientists are being harassed and are not given the opportunity to be published in foreign journals. "Naturally, it is easier for Americans to be published in American magazines, just as it is easier for Russians to be published in domestic ones," says Arkady Karyakin. – Personally, I have always had difficulties with a foreign language. Nevertheless, I am now a member of the editorial boards of foreign journals. When I published my first article in Analytical Chemistry, one of the referees wrote that my English was not good, but the research was interesting, and it was up to the editors to correct the language."
Of course, there are cases when a really worthy study receives a negative review from several reviewers, Arkady Karyakin admits. In such cases, it is necessary to defend the right of publication from the editorial board. Joe Wang, editor–in-chief of Electroanalysis magazine, likes to repeat that every article is a struggle. And if you do not participate in it, then it is in vain to expect victory. These words belong to a successful scientist who founded his own journal.
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The biosenser market, which has been developing since the late 1980s, is constantly growing. In 1995, it was already half a billion dollars, now it exceeds 12 billion dollars a year. To date, the best-selling biosensors are for determining glucose levels. In many ways, they determine the market – sales from other tests account for less than 10 percent of total revenue.
In the field of sensors, the Laboratory of electrochemical methods of Moscow State University occupies a leading position at the world level. Some European partners have switched to their scientific approaches in biosensor technologies. For example, the laboratory of the University of Rome Tor Vergata (University of Rome Tor Vergata) became the followers of Moscow scientists, completely reorienting the fundamental part of the work on the methods developed at the Chemical Faculty.
The next stage to be passed by the scientists of the laboratory of electrochemical methods is an innovative one. They have already started working in this direction – they have created a small enterprise (within the framework of the "Start" project of the Bortnik Foundation), mastered the technology for manufacturing electrodes by a method called screen printing in the West, and "screen printing" in Russia.
"We can make the final product," says Arkady Karjakin. – In general, we do not depend on anyone, we are able to carry out the entire technological process ourselves, only polymers and paints have to be bought."
In a day, about a thousand electrodes can be made, which, according to the original technology of Moscow chemists, are modified into biosensors. The cost of one electrode is about ten rubles, the selling price could reach 20-30 rubles, for comparison – foreign analogues cost about two euros (almost 90 rubles). But so far, the production of biosensors in Karyakin's laboratory has not been put on a commercial basis – the electrodes are made free of charge for the scientific purposes of the laboratory and partners.
In order to mass produce sensors in Russia to detect, for example, glucose, full automation of this process is required. And this requires significant investments. This issue should be regulated at the state level, Arkady Karyakin believes. Otherwise, having its own developments that are significantly superior to foreign analogues, Russia will depend on imports.
"The importance of biosensors is not well understood in our country yet,– Arkady Karyakin notes. – Cheap, simple and selective analyses that can be carried out using biosensors are still underestimated. Let's say in Japan, one of the fathers of biosensors, Isao Karube, was able to convince his fellow citizens of the benefits of biosensors so much that without the use of sensors, people did not buy products in the store. They even made something like a knife, which had a built-in sensor that allows you to determine the freshness of fish. There was actually a state program, funding was allocated for the development of biosensors. It is difficult to say whether there will be any purposeful policy in this direction in Russia."
Nevertheless, Arkady Karjakin's laboratory does not lose hope. Or rather, they put them on the youth. Students and postgraduates have a huge interest in this topic. And biosensorics, by definition, cannot fail to develop. The only question is the pace.
Portal "Eternal youth" www.vechnayamolodost.ru15.04.2009