Institute of Chromatography “EcoNova”, Ltd. was set up in Novosibirsk as an enterprise to do innovation business.
A special place among its science-intensive products belongs to MiLiChrome© Рђ-02, the microcolumn liquid chromatograph, which is a unique expert-class instrument for conducting chemical analyses. As far back as 1985 researchers from a number of Institutes at the Siberian division of the Russian Academy of Sciences, who now constitute the core of the EcoNova staff, were awarded the USSR State Prize in Science and Engineering for developing the previous generations of such instruments.
During those years the very structure of the Soviet economy was spurring up the development of the analytical chemistry in rather narrow fields: analyzing inorganic matters (minerals, metals and alloys, fertilizers, construction materials) as well as analyzing simple organic matters (fuel hydrocarbons, monomers of plastics) and just a few complex organic ones (drugs, dyes, pesticides, explosives). The “gross” approach practically failed to stimulate development of the hi-tech chemical production and, as a result, the USSR never had high-quality and different plastics, many needed drugs and dyes, competitive color photomaterials, etc. while the analytical chemistry of complex organic molecules remained a purely academic discipline. The instrument-making industry was producing only what was ordered: general laboratory equipment and instruments for inorganic analyses. The only exception was the analytical chemistry of volatile mixtures that the petrochemical industry needed: obtaining motor fuels from oil required the use of the gas chromatography method.
In the 1980s the High Performance Liquid Chromatography (HPLC) in the post-industrial economies became a strategic priority getting equal in its importance to research studies of computer technologies, space and medicine. The intensive development of HPLC made it a universal instrumental method of the analytical chemistry. For example, under the pharmacopeial standards of the U.S., Great Britain and United Europe HPLC is used to control quality of over 65% of drug substances.
The priority importance of HPLC is implied not only by imperatives of the innovation development but also by radical changes in notions of chemically dangerous substances and chemical security. Today, they are regarded as being not just the toxic ones that get to the environment as a result of accidents, disasters, subversive activity or industrial harmful discharges. A person comes across potentially as well as actually dangerous substances practically everywhere: in drugs, food, household chemical goods, perfume, tap water, etc. Unfortunately, Russia finds itself among countries that are least protected against new kinds of the chemical danger.
This is the result of the sharply increased volumes of imported (as a rule, in small lots) food raw materials, foodstuffs and drugs as well as of the changed structure of the domestic production with the non-state, private sector now being favored. Imported shipments of foodstuffs and drugs have become quite profitable and, as a consequence, turned into a criminal business, while the system of quality (and safety) control has been corrupted. As soon as the state functions like setting norms (regulation), affirming their observance (certification) and control of already certified products (supervision) have been concentrated in a single structure (the Ministry of Health), it has started to actively develop profitable (requiring payments) directions of its operations and to reduce to a minimum the ones, which require expenditure (budgeted). In this case those are the norm-setting and supervision functions. However, profit-bringing licensing, certification, accreditation and attestation evolve only until they are not forced out by falsification (counterfeit) that is an even more profitable business. With the absence of proper regulation and supervision it is obviously just a matter of time.
In the Soviet times it was much simpler to solve the problem of controlling quality of, say, drugs because most of ready-for-use drug dosage forms were produced from substances synthesized at domestic plants under well-known and perfectly adjusted technologies. The regulation of admixtures was done with specifics of these technologies being taken into consideration and precisely those admixtures that might be expected to appear were put under control. But then the situation changed drastically. Practically all pharmaceutical plants in the Russian Federation stopped producing substances as making ready-for-use drug dosage forms was reoriented to cheap imported substances made under unknown technologies. And this means that the nature of admixtures that possibly accompany them is unknown as well. Who can guarantee that the purchased drug cures, not cripples us? The situation is about the same in the market of foodstuffs, the market of household chemical goods. In the past, with a limited number of importers the state monopoly on imports made it possible for a few well-equipped laboratories to thoroughly control shipped-in foodstuffs and drugs. But today their capabilities are obviously insufficient. Instead of setting a network of such strong laboratories the Ministry of Health went the other way: the Ministry sharply reduced the number of controlled indexes, thus, making the control itself quite feasible for its numerous but weak laboratories. As a result, a number of harmful substances to be controlled in foodstuffs and drugs in Russia is by hundreds of times smaller than in developed countries (particularly, in the U.S.). For example, only 9 organic substances are obligatorily controlled in tap water, although the existing regulations are supposed to embrace 702 of them; however, the remaining 693 substances are controlled just in concrete water supply systems and only in cases, when they have already been discovered there. “Lowering the bar”, i.e. the simplification of methods to analyze foodstuffs and objects of the environment turned Russia in a country open to import shipments of low-quality, falsified and chemically dangerous goods and technologies. Maybe, precisely there lies the real reason for the extremely poor “health of the nation” that we keep hearing about all the time?
It is obvious that the more chemically dangerous substances are controlled, the stronger the security is. But the increase in a number of regulations assumes the availability of the whole corps of highly qualified analytical chemists that the country lacks anyway. In the new economic realities the only way out seems to be in using high-performance, universal and very much automated analyzers. Such, in fact, is the MiLiChrome A-02 chromatograph. EcoNova started making it as far back as the early 1990s. Works on making it were done both in Russia and Germany, at the company Dr. Ing. Herbert Knauer GmbH, Wissenschaftliche Geraetebau. They were completed in 1995 and all author's rights remained with EcoNova. The partner received an exclusive right to sell the chromatograph outside Russia.
If EcoNova made just the instrument itself, then, however good it would be, the company with its limited financial resources could hardly hope for a success in a severely competitive market. But EcoNova also worked out a comprehensive method backup that makes it possible to use the chromatograph for accomplishing a great many analytical tasks. Precisely the combination of the original and efficient structure with the large package of no less original and efficient analyzing methods puts MiLiChrome A-02 in the same rank with the best models developed by recognized world trendsetters in instrument-making.
The use of MiLiChrome A-02 makes it possible to qualitatively change the very principles of organizing multi-purpose analytical laboratories at state controlling and expert offices as well as in industries, medicine, scientific organizations, etc. The main point is that just the one method, HPLC, is applied in cases, when a lot of others have had to be applied before.
Multi-purpose analytical laboratories that use the one universal method and same-type equipment have obvious advantages of the organizational and economic nature: problems of making equipment complete, of repairing and checking it are solved in a simpler way; a capability to quickly switch from one type of analyses to the other ones considerably raises the efficiency of both multiple and single analyses; a range of auxiliary reagents is significantly cut down; personnel training becomes easier, a number of overworked chemical analysts is reduced several times as much; the procedure of attesting methods of analyses becomes much easier and time needed for mastering them is reduced; there is a real opportunity to set up a network of standard analytical laboratories and single systems of analytical control inside any department.
HPLC is used most widely in the following areas of chemical analyses (subjects of analysis are boldfaced, if the use of HPLC is practically beyond comparison):
- Foodstuff quality control – tonic and flavoring additives, aldehydes, ketones, vitamins, sugars, dyes, preservatives, hormonal agents, antibiotics, triazine, carbamate and other pesticides, mycotoxins, nitrosoamines, polycyclic aromatic hydrocarbons, etc.
- Environment protection – phenols, organic nitrocompounds, mono- and polycyclic aromatic hydrocarbons, a number of pesticides, main anions and cations.
- Criminalistics – narcotics, organic explosives and dyes, strong pharmaceuticals.
- Pharmaceutical industry – steroid hormones, practically all products of organic synthesis, antibiotics, polymeric agents, vitamins, albumen agents.
- Medicine – abovementioned biochemical and pharmaceutical substances as well as their metabolites in biologic liquids (aminoacids, purines and pyrimidines, steroid hormones, lipids) when diagnosing diseases and determining pace of excreting pharmaceuticals from organism so as to set individual dosage.
- Agriculture – determining presence of nitrate and phosphate in soils so as to set needed amount of fertilizers; determinig nutritive value of forage (aminoacids and vitamins), analyzing pesticides in soil, water and agricultural products.
- Biochemistry, bioorganic chemistry, genetic engineering, biotechnology – sugars, lipids, steroids, albumens, aminoacids, nucleosides and their derivatives, vitamins, peptides, oligonucleotides, porthyrins, etc.
- Organic chemistry – all enduring products of organic synthesis, dyes, thermolabile compounds, low-volatile compounds); inorganic chemistry (practically all soluble compounds in the form of ions and complex compounds).
Typical major tasks that are accomplished most effectively with the use of MiLiChrome A-02 are as follows:
- control over quality and safety of foodstuffs, liquors and soft drinks, tap water, household chemical goods, perfume, at all stages of their production;
- determining the nature of pollution at sites of man-caused accidents or emergencies;
- discovery and analysis of narcotics as well as strong, poisonous and explosive substances;
- determining presence of harmful substances (polycycling and other aromatic hydrocarbons, phenols, pesticides, organic dyes, ions of heavy metals, alkali and earth metals) in liquid flows, air emissions and solid waste at enterprises and in living organisms;
- monitoring processes of organic synthesis, oil refining and coal processing, biochemical and microbiological production;
- analyzing quality of soils in terms of fertilizing, presence of pesticides and herbicides in soil, water and products; analyzing nutritive value of forage;
- complex research analytical tasks;
- getting micro-quantity of ultra-pure substance.
The constructive peculiarities of the instrument make it possible to avoid the necessity of long and laborious adjustment. The instrument is ready for operation in just 20 minutes after being unpacked. Its compactness (it weighs 17 kilos), the dimensions, which are similar to the ones of a sewing machine, vibrostability, complete operation through either a desk or laptop computer with minimal hardware resources allow to easily transport the instrument to conduct field analyses. Consuming minimum organic solvents MiLiChrome A-02 does not need any specially prepared premises for its use. And the last but not the least feature is that with an average 24-hour load MiLiChrome A-02 lets save over 5.000 dollars a year on spent materials only.
Costing considerably less than similar foreign instruments MiLiChrome A-02 is in no way inferior to them by its analytical potential: the typical sensitivity of analysis by concentration is 0.1 to 1 mg/l and 1 to10 ng by the amount of substance; the typical number of substances being found in one sample comes to between 25 and 30; time spent on analyzing is approximately 1 minute per one substance; it does up to 200 analyses in a fully automatic regime. The software includes all generally accepted functions for identifying substances, determining their quantity and compiling a summary document. On the one hand, a friendly interface ensures a maximum simplicity of procedure for its operator (he/she just needs to fill up a logbook for samples to be analyzed, to put test tubes with samples into the autobatcher and prepare eluents); on the other hand, with respect to analyzing methods operators are provided with a maximum freedom and flexibility in choosing operation regimes.
The unique peculiarity of MiLiChrome A-02 is the constructively built-in reducibility of results (“sameness”) received with instruments that were made in different years. This allows to reliably interpret these results without a preliminary calibration through standard models. Therefore, there are a lot of possibilities to apply universal methods on a mass scale (for example, for analyzing drugs as well as strong, narcotic and psychotropic substances).
The mechanical joints of MiLiChrome A-02 are made at the Berdsky electromechanical plant (BEMZ JSC) that has gained a big experience in making sensitive navigation machinery for military purposes; components that are used in the instrument (electronic components, plastics, capillaries, etc.) are the best available in the world market. The final assembly, adjustment and testing of each instrument are done at EcoNova; after that an independent metrological testing is done. Servicing and personnel training are arranged by EcoNova as well. During the warranty period servicing is carried out directly at customer's premises. After the warranty period expires, the servicing is done either under separate contracts or after works are completed. Thus, developers of MiLiChrome A-02 take upon themselves all the responsibility for each and every instrument.
Among today's users of the instrument are forensic medical examination laboratories, control-and-analysis laboratories, the Scientific Research Institute of Pharmacology, the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, other scientific research institutes, universities and colleges, pharmacological enterprises, state agencies of standardization and metrology, RAO UES, the State Customs Committee, the Federal Security Service of the Russian Federation, Ukraine's Ministry of Internal Affairs, customers from Germany, the U.S. and other countries.
At present, there are about 100,000 chromatographs in the U.S. (one instrument for every 2,500 people), while in the whole territory of the former USSR there are less than 10,000 chromatographs. Starting in 2004 all Russian enterprises producing pharmaceuticals should have switched to a new standard that provides for an entry control of all shipped substances, a stage-by-stage control of production and pre-exit certification. In fact, this means that every pharmaceutical plant should acquire from 2 to 3 chromatographs as a minimum.
EcoNova is successfully realizing the model of dividing commercial risks between the State, small-scale innovation enterprises and academic institutions. As a result, new generations of analytical instruments are being developed and MiLiChrome A-02, which has been given high marks, is about to move to the world market. It is worth noting that China alone is buying over 3,000 chromatographs a year. And with a state support the Novosibirsk region is quite capable of taking over one fifth of this market. The further advance of EcoNova' products results in jobs for highly qualified specialists and spurs up development of technopark zones around the Siberian division of the Russian Academy of Sciences.