Biosensor Academy: the success story is just beginning
Testing of nanosensitiesTigran Oganesyan, "Expert", May 5, 2008
At the beginning of 2002, Igor Yaminsky, professor of the Department of Polymer and Crystal Physics of the Faculty of Physics of Moscow State University and, concurrently, the Department of High Molecular Polymers of the Faculty of Chemistry, came up with an interesting idea – to create a joint group of probe microscopy of the Chemical and Physical Faculty.
Announcements about the recruitment of a new group of students were posted in the academic buildings of both faculties, however, to the great surprise of the professor, no one responded to the call. After some time, he made a second advertising attempt – the result was zero again.
In an interview with the correspondent of the "Expert" Igor Yaminsky described the further development of events as follows: "To be honest, I was simply amazed by the indifference of the students: it seemed to me naively that probe microscopy was a very promising and good direction! What can I say, if I repeated this experiment now, I am sure that the harvest of those wishing would be abundant. However, just six years ago, the topic of probe microscopy and nanotechnology sounded much weaker… In general, after such a double puncture, my colleagues and I finally realized that something urgently needed to be changed in our advertising campaign. And, having made the necessary correction for the trends of the time at that time, in the latest version we wrote that we were looking for students to develop nanotechnological Internet equipment. The essence of the proposal from this amendment has not changed much, because our devices are really integrated into a single network – they can be controlled from any remote computer. In particular, this scheme was implemented in a special student workshop – when getting acquainted with the basics of the functioning of probe microscopes, students could do all the work and take measurements from remote computers. Therefore, formally, having thrown the "Internet fishing rod" for the third attempt, we were not trying to deceive anyone at all."
The new advertising move worked with a bang: the united group was finally created. Two years later, in 2004, having thoroughly trained young adherents of probe microscopy with an Internet bias, Professor Yaminsky came up with a tricky problem that, as he believed, would occupy their inquisitive minds for a long time. The task was as follows: to make measuring weights based on an atomic force microscope (AFM) in order to weigh a bacterial cell on them (the average mass of a bacterial cell is about 10-14 g).
Only a little more than a month has passed since the task was set, when a second-year student of the Faculty of Physics, Gleb Kiselyov, came to the supervisor. Professor Yaminsky once again experienced strong emotions, however, now of a positive nature: "I must honestly admit, it was only then that I realized that this idea could really be successfully implemented in practice. Gleb Kiselyov showed me in every detail how he managed to weigh the bacterium, how he glued small polystyrene balls weighing nine nanograms and ten microns in diameter in order to calibrate the scales, how he fixed these balls one by one and noted changes in the resonant frequency of the cantilever (an ultra-sensitive sensor of an atomic force microscope) and so on. In fact, he got a real working device! And after a while, Gleb went and mastered the lathe milling machine and himself turned out the main core for the liquid chamber of the biosensor. A huge talent! Now Gleb is already a candidate of physical and mathematical sciences - he completed postgraduate studies in two years instead of three."
In the same year 2004, the head of the Fund for the Promotion of Small Forms of Enterprises in the Scientific and Technical Field (MFPNTS) Ivan Bortnik announced the launch of a special program "Start", a competition of innovative projects. Having learned about the competition, the wards of Professor Yaminsky decided to take an active part in it – four of his teams went to defend their original ideas in front of an authoritative jury. It turned out that the senior, postgraduate, teams did not pass this selection, and the student project of Gleb Kiselyov, who presented his idea of "atomic scales", received the unanimous support of professional experts.
In addition to Gleb, two other students participated in the presentation, one of whom, a student of the chemical faculty of Moscow State University, Pyotr Gorelkin, who joined the Joint Group of Professor Yaminsky a year later Kiselyov, later became his closest assistant and accomplice in the innovation field.
Academy of BiosensorsHaving approved the idea, the fund's experts at the same time put forward a strict condition: in order to receive further financing, Kiselev and Co. need to create a new enterprise.
Here we need to make a small digression to clarify the most important role in the described story of Igor Yaminsky.
The fact is that, in addition to the fact that he leads a double scientific life (working at the physics and chemistry faculty of Moscow State University), Professor Yaminsky is one of the oldest private entrepreneurs in Russia in the scientific and technological field. On September 12, 1990, just a month after the adoption of the law on small enterprises, in the Central Administrative District of Moscow, he officially registered the company "Center for Advanced Technologies", a single-profile enterprise whose main task was the development and creation of devices and methods of scanning probe microscopy. In the same year, the company produced its first product – the scanning tunneling microscope "Scan", and since 1993, the development of a new series of atomic force and tunneling microscopes "FemtoScan" (the first such microscope was launched four years later). In 2002, the center's products won the INTAS competition for international projects in the field of nanotechnology, and FemtoScan software is now considered one of the best in the world in its field and works at universities and research centers in Russia, the United States, Great Britain, Germany, France, Japan, South Korea, Finland, etc.
After the victory of his young student's project at the competition announced by the Bortnik Foundation, Igor Yaminsky came to the conclusion that a separate scientific and production direction - biosensory – should be allocated for its development. In 2005, with his blessing, a new company was established, certified as an innovative enterprise. Gleb Kiselyov, a student, was appointed Director General.
The "senior investor", as Igor Yaminsky and his center are called by young innovators, came up with a spectacular name for the new company – LLC "Academy of Biosensors". To clarify exactly what Professor Yaminsky meant by enrolling his students in the "academicians" in advance, we did not succeed, Gleb Kiselyov himself honestly admitted that he was not enthusiastic about such a bright sign on the doors of his brainchild, but he did not argue with the supervisor.
At the first stage, the MFPNTS Assistance Fund allocated 750 thousand rubles for the project, and already from the second stage, a parity financing scheme was launched: the Academy of Biosensors received half of the total amount of 3 million rubles from the fund, and another 1.5 million was invested in the case of the "senior investor", the Center for Advanced Technologies.
Thanks to these means, Kiselyov and Gorelkin gradually brought to mind the basic modification of their device: Gleb was the main theorist and creative, and Peter was the main experimenter-tester. As a result, the Academy of Biosensors managed to create for the first time in Russia a prototype of a precision cantilever analyzer – the Atomic Scales device.
Microcantilever systems are solid–phase converters of biochemical reactions occurring on their surface into an analytical signal. Cantilever sensors make it possible to measure the mass of micro-objects up to 10-18 g (the mass of the virus) and measure the forces of intermolecular interaction in ultrathin bioreceptor films. In other words, they combine the functions of biological and chemical nanosensors. A useful signal when binding the substance being determined to the membrane receptor is the degree of its deformation, which is determined using a precision laser-optical system.
It is important to note that the cantilever analyzer has a special energy filter, thanks to which it is able to distinguish specific molecules of the analyzed substance from non-specific ones that reacted with its receptor, and can detect several types of biomarkers at once.
The very idea of creating a device for recording ultra−small amounts of matter in gases and liquids based on probe microscopy technologies was born back in the 90s of the last century – in the homeland of the AFM (as well as its predecessor, the scanning tunneling microscope, STM), in Switzerland, in the laboratory of the Zurich division of IBM Corporation. To date, a number of nanotechnology sensor analyzers have already been created abroad, which are used as liquid chromatographs, gas analyzers and biosensors. The closest analogue of the device developed by the Academy of Biosensors is the Cantisens device, manufactured by the Swiss company Concentris. The products of the Danish company Cantion – Canti Lab 4 also deserve special mention (although Cantion does not produce complex devices themselves, but only makes cantilever analyzers). Oddly enough, there are no other potential competitors for the Russian analyzer abroad today (another company, the American Protiveris, which produced the VeriScan 3000 device, recently quietly rested in bose).
At the same time, both Cantisens and Canti Lab 4, unlike the device of Russian developers, are still mainly focused on solving fundamental scientific problems and are intended exclusively for research laboratories, and not for mass production. In addition, "Atomic scales" are significantly cheaper than foreign analogues: the same Swiss Cantisens is sold on the market for 250 thousand euros, while the current price of the device from Russian manufacturers is only 750 thousand rubles (about 20 thousand euros). Commenting on such a price spread, Pyotr Gorelkin explained that "unlike our foreign colleagues who offer special, very expensive cantilevers in a set, we use conventional silicon consoles, and we have also developed a much simpler and more convenient system for entering samples into the device – either through static pumps or through micro-nozzles." Another significant advantage of "Atomic Scales" is the possibility of remote monitoring of the measurement process via a local network or the Internet. Concentris does not yet have software protocols that would allow remote monitoring, while the Academy of Biosensors together with the "senior investor" have developed a very original software, a kind of simplified version of the software used in atomic force microscopy.
"Bedside" diagnosticsKiselyov and Gorelkin conducted a large series of test experiments on the recognition of various substances on Atomic Scales.
In particular, high-precision analyzers of heavy metal ions, odorous organic thiols, horseradish peroxidase and morphine were created on the basis of the device.
"In principle, our device can be specially configured to detect almost any chemical substance: the same enzyme immunoassay, actively used by us, works to determine literally a million different substances, – emphasizes Gleb Kiselyov. – And our detector can work with all the “chemistry” that is used in other methods. In fact, the device is practically universal in this sense."
Applications of such analyzers can be found in a variety of ways. As noted by Igor Yaminsky, "it is possible to make chemical sensors in factories, quickly detect gas leaks in apartments, it is possible to use them to make early detection of the first symptoms of toxic chemicals in public places and on transport: airports, planes, trains, and so on. Finally, they are perfectly adapted to determine the purity of drinking water or the degree of its contamination with various reagents." However, the most promising and important direction, according to him, can and should be medical. Kiselyov and Gorelkin focused their attention on the development of biosensors, more precisely on drug diagnostics.
So, according to Pyotr Gorelkin, "the morphine test was needed primarily as a trial experiment to determine medicinal substances, since morphine is an analogue of a drug. According to the same scheme, you can do a test control of other drugs." Gleb Kiselyov continues: "We are particularly counting on the medical use of the device, primarily for bedside online diagnostics (monitoring) of patients. Analysis of the state of wastewater, atmospheric composition, and so on is all good, of course, but there are other proven methods of online analysis. But in medicine, such online control has not yet been created. Moreover, we will not even need to explain to doctors for a long time what our device may be useful for – it is quite enough just to show its round-the-clock efficiency and effectiveness. If we bring it to mind, many medical institutions will be happy to buy it from us."
Of course, "there are enough opponents of our idea in domestic medicine – the level of resistance to the practical implementation of a new device is quite high, and we are often told that getting into medicine is a deliberately disastrous idea, they say, you can only break your forehead there," continues Pyotr Gorelkin. "But we are not going to go ahead – we are counting on assistants in this matter, on various support centers and funds, on personal contacts with interested persons and institutions." Recently, he himself met at the Ministry of Health of the Russian Federation with the chief laboratory assistant Vladimir Dolgov, who is actually in charge of all clinical diagnostics in Russia. In addition, young bio-innovators held a special presentation of their device for officials of the Ministry of Health. Last year, Gorelkin made a separate report about him at a conference held at the First Medical Institute. "Everyone was very interested in our device then," he says. – Today, the issue of operational control of the patient's condition during his treatment is very acute, the main problem is not even in establishing a diagnosis, but in monitoring the quality of the treatment course: what is the concentration level of drugs in the blood, cholesterol and other hormones. And a very recent example: At the World of Biotechnology exhibition, held in March 2008 in Moscow, doctors from the Burdenko Institute of Neurosurgery approached us – they were very interested in a sensor that could determine the level of a special hormone responsible for the occurrence of stroke in people in real time."
As for Gleb Kiselyov, he is going to work at the Center of Obstetrics and Gynecology with Academician Sukhoi, who shows great interest in the development of new sensory methods of clinical diagnostics.
Our company – me and PetyaIn 2007, the Kiselyov-Gorelkin project "Production of the universal biochemical analyzer "Atomic Scales"" became the winner of the Competition of Russian innovations, organized by our magazine for many years, in the nomination "Best Innovative Project".
Thanks to this victory, it was possible to establish close contacts with the Moscow Agency for the Development of Innovative Entrepreneurship (NP ARIP), established at the end of 2006 on the initiative of the Department of Support and Development of Small Entrepreneurship of the city of Moscow. The General Director of the agency Alexey Kostrov promised personal assistance to the Academy of Biosensors in obtaining a special grant from the department and assistance in writing an adequate feasibility study of the project. According to Gleb Kiselyov, ARIP is not only ready to provide this subsidy, but also offers assistance in further promoting the project, in particular in its support in terms of intellectual property formation, in providing advice on various strategic issues.
Another potential source of replenishment of the budget of a young firm is of foreign origin. This is a NATO grant provided within the framework of the special Science for Piece program ("Science for Peace"). The application for this grant for the development of a remote control system for cantilever sensors successfully overcame the first round of the competition, and Kiselyov and Gorelkin expect that they will be able to pass the "NATO cordons" to the end and get hold of 250 thousand euros allocated for scientific research.
An interesting offer from abroad has recently been received from the French: within the framework of a special program, the French Embassy selected 10 best young Russian companies, and the Academy of Biosensors was on this elite list. Pyotr Gorelkin was invited as part of the Russian delegation to visit two national biotechnoparks of France (in Grenoble and Lille). During the trip, the French actively probed the ground for the possible creation of a branch of a Russian company to work in the European market, offering very preferential conditions (such a branch will be exempt from all French taxes for five years, rental rates with full infrastructure are about 100 euros per square meter per year, etc.). As Igor Yaminsky says"we are considering this opportunity very seriously, but first we need to strengthen ourselves in the Russian market."
Kiselyov and Gorelkin, as well as their "senior investor" Igor Yaminsky, associate certain hopes today with a large-scale financing program announced by the Russian Nanotechnology Corporation. Having been part of the Russian delegation at the recent nanotechnology exhibition in Japan, Mr. Yaminsky took advantage of the favorable opportunity to finally get to know the CEO of Rosnanotech Leonid Melamed personally. According to Yaminsky, he managed to talk to the "chief Russian nanotechnologist" face-to-face for an hour and tell him both about the activities of his company (the Center for Advanced Technologies) and about the developments of young wards from the Academy of Biosensors.
How much money does Kiselyov and K o need in total for the effective promotion of their offspring? Gleb himself estimates that it takes about 15 million rubles to fine-tune the instrument base and the firm's final transition to free navigation. According to him, "from a purely scientific point of view, almost everything has already been done by us. Figuratively speaking, if everything is made “on plasticine”, the device will work normally. Today we face two key tasks – the technological refinement of the device for purely medical purposes and the development of “chemistry” for a specific task. For example, if we are asked to make a special sensor for the definition of a particular hormone, it will take some time, money, it will be necessary to conduct a separate R&D. But today, in fact, our entire company is myself and Petya Gorelkin. Of course, it will be difficult for us to do this together. But, on the other hand, until quite recently, the task of creating our device itself seemed almost impossible to me."
Portal "Eternal youth" www.vechnayamolodost.ru
05.05.2008