INNOVATION AND NANOTECHNOLOGIES: in agriculture, food sector and medicine

Cluster passport: development and use of ecologically safe new generation nano-disinfectants based on additives of oligodynamic metals (nanosilver, nanocopper, nanogold etc.) in colloid solutions based on natural biopolymers (chitosan, dextran etc.), high-molecular compounds (PEG, PVS) in particular in veterinary to substitute chemical disinfectants which have strong biocide properties local in time and spaced (formaldehyde, chlorine and iodine compounds, ozone, alkali etc.) but also high toxicity.

Treatment of food products with non-concentrated ecologically safe ‘eatable’ nano-disinfectants for prolongation of food products shelf-life without the necessity to remove disinfectants before consumption.

Introduction of innovative environmentally friendly nano agroadditives for plants and vegetables growth stimulation without contamination of agricultural soils.

Heads:

Doctor of Physico-Mathematical Sciences, Corresponding Member of NASU, Leonid Sukhodub, Sumy State University, Medical Institute

Doctor of Biological Sciences, Professor, Corresponding Member of NASU, Mykola Spivak, Institute of Microbiology and Virology of NASU

Senior researcher, Candidate of Technical Sciences, Lyudmyla Kisterska, Institute of Superhard Materials of NASU

Legal addresses:

1. Sumy   State   University,   Medical   Insitute, 2b, Rimsky-Korsakov St., Sumy, 40007, Ukraine.
2. Institute of Microbiology and Virology of NASU, 154, Zabolotnoho St., Kyiv, 03680, Ukraine.
3. V. Bakul Institute of Superhard Materials, 2, Avtozavodska St., Kyiv, 04074, Ukraine.

Co-authors: Doctor of Biological Sciences O. Demchenko, Head of biotechnologies section; senior researcher, Candidate of Biological Sciences S. Shandrenko, Head of Metabolism Regulation Department, O. Palladin Institute of Biochemistry; Doctor of Technical Sciences O. Tretiak, Director of Institute of High Technologies, T. Shevchenko Kyiv National University; Doctor of Medical Sciences O. Surmasheva, Head of laboratory of sanitary microbiology, O. Marzeev Institute of Hygiene and Medical Ecology; senior researcher, Candidate of Technical Sciences Y. Dashkovskyy, Head of problem-oriented research laboratory, National University of Food Technologies of MESYSU; lead researcher of Institute of Applied Physics D. Chivanov, Sumy National Agrarian University (SNAU); State Institute of Mineral Fertilizers and Pigments; Institute of Aviculture (Kharkiv).

Contact e-mails: n.spivak@rambler.ru, kluda@ymail.com, l_sukhodub@yahoo.com, n.zholobak@gmail.com

Why Sumy State University and Institute of Applied Physics of NASU?

In Sumy State University on the basis of the Department of Biochemistry and Pharmacology the new department – Department of Biophysics, Biochemistry, Pharmacology and Biomolecular Engineering (BBPBI) was created one year ago. The Department was headed by Professor L. Sukhodub, a Corresponding Member of NASU, who has been for 20 years heading the section of biophysics and mass-spectrometry of the Institute of Applied Physics of NASU, and now occupies the position of senior researcher of this section (as his second employment).

BBPBI Department staff: 2 professors, 5 Associate Professors, 1 senior teacher, 1 assistant, 1 laboratory head and auxiliary personnel. Head of the Department – the Corresponding Member of NASU, Doctor of Physico-Mathematical Sciences, Professor Leonid Sukhodub. Prof. Sukhodub graduated from Kharkiv Polytechnical Institute with the specialization “Metalls physics”, then gained his science degree of candidate of physico-mathematical sciences in the “Molecular physics” and scientific degree of Doctor of Physico-Mathematical Sciences in specialization “Biophysics”. He worked as a junior researcher, then researcher, head of Department of Molecular Biophysics at B. Verkin Physico-Technical Institute of Low Temperatures of NASU and now heads the Department of Mass-Spectrometry and Biophysics of the Institute of Applied Physics of NASU. Prof. Sukhodub is the author of 185 peer-reviewed scholar papers, 2 monographs, more than 120 conference reports theses. Prof. Sukhodub heads the section “Applied biophysics” in the National biophysics association and is a member of a board of the National mass-spectrometry association. Under his supervision 13 dissertations of Candidates of Sciences were defended, and now Prof. Sukhodub supervises 3 post-graduate students’ scientific work. Prof. Sukhodub is a very active worker of education. For few years he has been lecturing on the modern instrumental methods in physics and biophysics research for students of Sumy State University. In 2002-2003 L. Sukhodub worked in the University of Münster (Germany) within framework of DFG-Mercator grant. In 2005 Prof. Sukhodub was invited to the Technical University of Dresden (Germany) to deliver lectures for students and post-graduates on the modern mass-spectrometry and other instrumental methods in biomaterials research.

Among a few priority directions of the newly established department there are such which are related to further development of advanced technologies on the basis of modern instrumental methods of contemporary nanoagrochemistry.

• On-line tracing (quantitative) of lipometabolism condition in cells of agricultural products using soft ionizing mass-spectrometry and accelerating mass-spectrometry;
• Development of express diagnostics of animals diseases (in particular, Marek’s disease of chickens) grounding on quantitative and qualitative indicators of total lipid fraction of blood;
• Development of biomimetic technologies of incubator chicken eggs using nanocomposites of chitosan and photocatalytic particles of titan dioxide TiO2 («nanoTi_ARTICLE») and formula for directed construction of defense coating for eggs – “artificial cuticle” (“ARTIficial cutiCLE” «ARTICLE»).

For these and others nanotechnological research activities the Sumy State University has the strong experimental resources:

a) Department of Biophysics, Biochemistry, Pharmacology and Biomolecular Engineering (prof. L. Sukhodub):

• Laboratory for synthesis of nanostructured biomaterials and coatings;
• Diffractometer DRON3-07;
• X-ray-fluorescent spectrometer ElvaX-light.

b) Department of Pathophysiology (prof. O. Ataman):

• Polymerase chain reaction with RFLP analysis;
  c) Department of Nanoelectronics (Professor O.
  Pohrebniak):
• Vacuum system for magnetic dispersion (VSA-
  350-02);
• Scanning electronic microscope SEM-102E;
• Transmission microscope TEM-100K.

Institute of Applied Physics (IAP) was created on the basis of the Sumy branch of the Institute of Metallophysics in compliance with the NASU Presidium’s decree of 21 November 1991 No 299 with an objective to deepen and broaden fundamental and applied research in the field of nuclear technologies. The establishment of the Institute was initiated by current director of the IAP, member of NASU, V. Storizhko with a group of his colleagues from the National scientific center “Kharkiv physic-technical institute” of NASU. This idea to establish the first in the Sumy region academic institute was from the very beginning supported by the President of NASU, member of NASU B. Paton and by the first vice-president of NASU, member of NASU V. Bariakhtar. IAP of NASU is a part of nuclear physics and energetics section of NASU.

Main directions of Institute of Applied Physics of NASU research activity are:

1. Study of processes of ion and low-energy electrons interaction with the matter;
2. Development of nuclear physic methods with submicron resolution and electrostatic accelerators;
3. Molecular radiological biophysics;
4. Designing instruments for science and education.

The Institute has the unique experimental base:

1. Microanalytical complex: channel of ionluminescence; channel of nuclear reactions; channel of scanning nuclear microprobe; channel of Reserfordian reverse dispersion with high resolution, equipped with magnet spectrometer; channel of recoil nuclei with high resolution, equipped with electrostatic spectrometer; analytical channel for research of hydrogen and helium in materials.
2. MeV scanning ion microprobe for determining the map of micro admixtures distribution in the subcoating layer of research samples using nondestruction methods of analysis.
3. Center for collective use basing on accelerating mass-spectrometer Tandetron 1.0 MV model 4110Bo-AMS, produced by HVEE (Netherlands) in 2009.
4. A set of equipment serving the needs of ion accelerators and ion-radiatioin modification of materials: source with volume-plasma generation of negative ions (non-caecium source); high-dosage implanter with mass separation of ions; test bench for research of high intensity ion-sources; apparatus for high-frequency magnetrone dispersion; electroradiation apparatus; high vacuum apparatus for measuring parameters of gas field source of needlecapillary type with cooling emitter to the temperature of liquid nitrogen; vacuum bench of gas field ion source working at room temperature.
5. Laboratory of spectral analysis using atom absorption spectrometry with electrothermic atomization in graphite furnace, atom-absorption spectrometry in flame, atom-emitting spectrometry in flame, molecular spectrometry, traditional “wet chemistry”.
6. FAB mass- spectrometer, PDMS massspectrometer, scanning electronic microscope.
7. Laser isotope mass-spectrometer with coordination-sensitive detector.
8. Specialized GRID-cluster for computer modelling of radiation defects of reactor materials.

This resource base for experiments allows for multidisciplinary applied research and studies in the field of nuclear nanotechnologies, development of research in the field of nuclear medicine (including new highly efficient nuclear methods for early diagnostics and therapy of oncological and cardiovascular diseases); nuclear forensics. The Institute have more than 230 workers, 116 of them are involved in research activities, among them 1 member of NASU, 3 Corresponding Members of NASU, 12 Doctors of Sciences and 36 Candidates of Sciences. The Institute is comprised of 6 departments.

Department of Biophysics and Mass-Spectrometry (Head of the Department – Candidate
of Physico-Mathematical Sciences S. Danylchenko). Activity directions:

1. Radiological biophysics.
2. Fundamental and experimental researches of thermodynamic stability of biological clusters – main structural elements of DNA and RNA.
3. Study of ionization processes in massspectrometry methods.
4. Research of adducts of some medical preparations and DNA and their components.

The Institute has broad international contacts. For example, the IAP of NASU actively collaborated with the European Center of Nuclear Research (CERN, Geneva, Switzerland), actively participates in theoretical research of antiproton beam of accumulating circle cooling within the FAIR project of the European Research Center of Ions and Antiprotons, cooperates with MAGATE (Austria) within projects titled “Use of nuclear-physical methods for characterization and preservation of culture heritage artifacts in the European region” and “Microanalytical methods of nuclear spectrometry for monitoring of environment and for material science”. The Institute also established relations with United Institute of Nuclear Research (Dubna, Russian Federation) regarding issues of electrostatic acceleration and beam technologies. The Memorandum on cooperation was signed between the Institute and the Ukrainian science and technology center regarding cooperation aimed at research and improvement of long-term Institute’s sustainability.

Cluster’s activity will be aimed at solving the following problems:

1. Introduction of new methods of food products and veterinary complexes treatment with ecologically safe new generation nano-disinfectants and use of innovation methods for control of food products safety and quality at all levels of the food chain.
2. Prevention of human diseases of alimentary genesis and improvement of people’s immunity by introduction of nanotechnological modificators and oligodymanic metals to the food chain.
3. Improvement of legislative base in the field of food safety and in particular that regarding safe use of nanomaterials in line with EU norms.
4. Improving culture of fertilizers application, processing, packaging and consumption of food products.
5. Development of theoretical foundations of design and production methods of artificial protective coatings (artificial nano-cuticle; NanoARTICLE; NanoARTIficial_cutiCLE) on the basis of natural biopolymers (chitosan, dextran etc.), high-molecular substances (polyethylene glycol, PVS) and bioactive photocatalytic nanoparticles of metals and their oxides (TiO2, Fe2O3, Zn, Zr, Al, Cu compounds) along with bio- and immunostimulators of natural origin for protection of incubatory chicken eggs and for improvement of chicken embryos metabolism.
6. Study of chemical composition of source substances (mostly glycoproteins) influence on crystal structure of calcite (CaCO3) composites with the objective to obtain coatings of “artificial cuticle” type with regulated indicators of gas permeability and velocity of biologically active substances release facilitating development of an embryo during incubation.
7. Use of photocatalytic destruction in presence of ultra- and nano-dispersed particles of titan oxide, iron and other metals and their oxides for production of construction materials with biocide properties.

Suggested innovations:

1. Elimination of wide spectrum of causative infectious agents which live in the environment using ecologically safe new generation nano-disinfectants produced on the basis of oligodymanic metals additives (nanosilver, nanocopper, nanogold etc.) in colloid solutions on the basis of natural biopolymers (chitosan, dextran etc.), high-molecular substances (PEG, PVS), in particular in veterinary to replace chemical disinfectants which have powerful biocide properties localized in space and time (formaldehyde, chlorine, iodine substances, ozone, alkali etc.) but also high toxicity.
2. Treatment of food products with nonconcentrated ecologically safe “edible” nanodisinfectants – nano-suspensions of sliver and composite colloid solutions of nanometals based on liquid polysaccharides in order to extend food products shelf life without necessity to remove disinfection products before consumption.
3. Modification of packaging materials for food products with new generation biocide nano-additives allowing to increase ecological safety and shelf life of food products by few times without change in traditional methods of packaging materials production.
4. Introduction of innovative nano-additives for agriculture in order to stimulate growth of plants and vegetables without contamination of agricultural soils.

Why section of interferon and immunomodulators of IMV of NASU?

Main directions of the section’s activity are:

• Identification of fundamental basics of physiological role of interferon system and immunoregulatory cytokines in normal and pathological conditions (infectious inflammatory disease of bacterial, viral or composite bacterialviral genesis and also of pre-tumor and tumor disease, induced by carcinogenic viruses);
• Development of scientifically substantiated approaches towards optimization production technologies of new interferonogenes and antivirus preparations based on derivatives and analogues of amixin and of molecular complexes of onechain RNA in combination with monodimensional synthetic intercalators;
• Identification of immunomodulatory properties of new probiotics and prebiotics preparations created on the basis of Lactobacterium and its derivatives; lectins of bacterial and plant origin; synthetic muramodipepids etc.
• Development of new biotechnological foundations for construction of test-systems for identification of viral and bacterial infections’ causative agents on the basis of recombinant proteins of human and animals viruses.

In the Section of interferon and immunomodulators the new direction in interferonology was for the first time theoretically substantiated, experimentally proved and clinically approved – namely identification of antibacterial efficiency of interferon preparation under bacterial infections (sepsis, pyoseptic processes, salmonellosis, toxicoinfectious shock etc.). We formulated the notion of interferon system and identified direct and reverse connections between this system and immune and neuroendocrine systems of an organism. Researchers of the Section developed a methodology of identification of interferon status of an organism and this allows for determining the role and place of interferon system on the level of population.

Researches made during last 5 years established fundamental foundations of interferon system functioning under pre-tumor and tumor diseases, caused by carcinogenic papilloma viruses; allowed to develop new approach to purposeful stimulation of interferon generation based on the original concept of directed construction of substances – inductors of interferon; brought new information about general architecture and morphogenesis of complex human and animals viruses ascribed to one taxon and this is related to understanding of fundamental virology problems as regards evolution of phyto- and animal pathogenic rhabdoviruses. Using modern methods of immune biotechnologies researchers of the Section obtained first and second generations interferon preparations as well as prospective interferon inductors. Individual indications and contraindications for clinical use of interferon and its inductors under viral, bacterial and other pathogenic processes were identified.

The section has fruitful cooperation with a number of laboratories from the USA, Canada, Russia, Israel, Iran, Slovakia and other countries. The employees of the section defended 7 Doctoral and 22 candidate dissertations, published 10 monographs, 4 practical handbooks, 4 methodology recommendations for Ministry of Health of USSR and Ukraine, published the first in Ukraine “Basic Virology” textbook, have 68 copyrights and patents of USSR, Ukraine and Russia. The section developed a technology to produce preparation of α-interferon and γ-interferon (such as animaferon, splenoferon, diaferon). These results were distinguished with the State award of Ukraine in the field of science and technics (2005), with D. Zabolotbny award of NASU (2001), I. Mechnikov award of NASU (2004), I. Pavlov silver medal (Russia, 2002), golden medal of World Organization of Intellectual Property (Switzerland, 2002), Honorary diploma of Kyiv City mayor (2003) and diploma of Verkhovna Rada of Ukraine (2007) , O. Bogomolets award of NASU, O. Palladin award and with three awards of President of Ukraine for young scientists.

Why V. Bakul Institute of Superhard Materials?

V. Bakul Institute of Superhard Materials (ISM) of NASU celebrated its 50th anniversary in 2011. ISM was created in 1961 by the government decree under auspices of State Plan of Ukrainian SSR. In 1972 the ISM was transferred to the structure of the Academy of Sciences of Ukrainian SSR. In the very short terms personnel of the Institute using the laboratories of the Institute of High Pressure Physics of Academy of Sciences of USSR developed the technologies for industry-scale production of synthetic diamonds and organized the production of synthetic diamonds and instruments from them. In 1960s-1970s highly efficient instruments made of superhard materials were introduced in thousands of industrial enterprises of different fields in USSR and other socialistic countries.

In the short period of time the ISM became one the world’s leading centers in material science in the fields of extra high pressures and extra high temperatures. The ISM staff deservedly occupies one of the most prominent positions in the world regarding development of fundamental researches in physicalchemical grounds for the synthesis of superhard materials, development of methods of studying their internal structure and set of physical and chemical properties.

V. Bakul ISM of NASU cooperates with research and production centers of superhard and nanomaterials in many foreign countries including USA, Japan, Germany, UK, RSA, China, Poland, Israel and others. Products with ISM trademark are widely known in the world; there is licensed production of ISM products in Ukraine, Belarus, Russia, Bulgaria, Serbia, Hungary, Germany, China, South Korea and other countries.
The Institute is comprised of 12 main scientific departments, 1 research laboratory and 4 auxiliary departments and an administrative section. 406 people work in the Institute, among them 206 researchers including 84 Candidates of Sciences, 32 Doctors of sciences, 2 members of NASU and 5 Corresponding Members of NASU.

Some of research results of the ISM are of world-class in material science for example such as synthesis of high-purity monocrystals of diamonds of big size and perfect structure (1993, Patent of Ukrain No2), production of different color diamonds (2006); synthesis of superconductive magnesium diboride with high level mechanical properties for use in construction (2006); development of constructions for movable endoprostheses of joints on the basis of artificial sapphires, titan-silicon alloys, aluminum and zirconium oxides (2008-2011) Since 2006 the ISM has been successfully developing ecologically safe nanotechnologies of industrial production of colloid nanometal solutions in liquid mediums such as natural biopolymers (chitosan, dextran), high-molecular substances (PEG, PVS), glycerine, natural and artificial oils etc. These provide master-butches for creation of new generation nanodisinfectants which would easily modify products of personal hygiene, pharmacological preparations, food products and packaging materials.

Center for collective use of devices “Analytical center of research and nano-diagnostics of superhard material” functions within the ISM. Since the establishment of the Institute more than 8 thousand articles have been published by its staff, the Institute has more than 3000 of copyrights and patents, 20 licenses. For the last decade the ISM have taken out 335 patents and carried out seven license agreements. The Institute became a coordinator of the European program START that united centers of perfection in the field of material science from France, Poland and other EU countries.

The Institute suggests development and introduction into nutrition of ion-plasma nanodispersion of metals and production of high efficiency industrial equipment for production of concentrated nanoadditves in the wide range of mediums – natural biopolymers (chitosan, dextran etc.), high molecular substnces (PEG, PVS), polysaccharides, food glycerine etc.

The essence of the problem

Production of high concentration suspensions of nano-structure material on the basis of organic and non-organic liquids (so called “master-butches”) which are added to numerous products of disinfection, personal hygiene products, pharmacology products, food products and drinks in order to improve their consumption properties has become a very important and independent area of nanotechnologies research in the world. Of particular prospect is production of oligodynamic metals (Au, Ag, Pt, Fe, Cu) concentrated nanosuspensions in liquids which are the most frequently used ingredients in modern home chemical products, products of personal hygiene and food products and easily get mixed up with them without need to change the traditional production. Use of nanomaterials most frequently demands their dissolution in different liquids in order to inject a homogenous solution to the final product. For example, an important way of using nano-additives in medicine is a delivery through dissolution of active nanoparticles in organic liquid mediums. Since most of nanomaterial solutions are thermodynamically unstable, they quickly agglomerate and coagulate and that makes them non-effective for practical use. Most of metal nanoparticles produced on industrial scale in the form of nanopowder and thus they demand multistage processes of colloid chemistry for transforming them into liquid solutions: moistening nanopowders with liquids, destruction of agglomerates using different technologies and their stabilization in solutions in non-coagulated form by adding of special dissoluble agents.

The Institute of Superhard Materials developed an efficient single stage method for production of high concentration colloid solutions (suspensions) of nanometals using water-soluble and water insoluble liquid mediums where plasma beam in vacuum disperses metals and in the same cycle implants nanoparticles to vacuum cleaned liquids. Therefore, both in Ukraine and in the world complex “wet-dry” technologies which utilize productive physical methods of metal dispersion along with engineering solutions for implanting metal nanoparticles into liquid mediums in one technological cycle became the most important practical method for production of metal nanoparticles solutions in the wide spectrum of liquids (master-butches). In Ukraine the “Rubin” company from Kharkiv, which owns numerous Ukrainian patents in nanotechnologies using silver nanoparticles, is an industrial manufacturer of commercialized silver nanocoatings produced using gas-core synthesis technology. In E.O. Paton Electric-Welding Institute an industrial technology of obtaining nanoparticles for magnetic liquids through electron beam evaporation and condensation in vacuum was developed.

During 2007-2011 within grants of NASU V. Bakul Institute of Superhard Materials together with E.O. Paton Electric-Welding Institute developed the new technologies of metallocolloids production. Under supervision of NASU academicians M. Novikov and D. Dudko a technology and equipment for ecologically safe single stage plasma nano-dispersion of metals in vacuum with implanting them into liquid media in a single technological cycle were developed.

This technology in particular was practically used for production of high concentration nanosuspensions of silver in liquid water-soluble mediums for nanomodification of new generation bactericides for disinfection of contact surfaces, tissues, filters and so on.

What do we suggest?

Introduction of complex “wet-dry” technology of localized ion-plasma nano-dispersion of electroconductive materials in the V. Bakul IMS of NASU and run of pilot production plant for production of concentrated (up to 1000 mg per liter) nanosuspensions of metals (Ag, Cu, Fe, Mo, Pt, Pd, Au etc.) and for production of concentrated nano-additives in the wide range of liquid medium such as natural biopolymers (chitosan, dextran), high molecular substances (PEG, PVS), polysaccharides, food glycerine with output rate up to 10,000 liter per year. Control over size, form, distributioin of produced nanoparticles as well as high productivity of dispersion (at least ten times higher than of known methods of wet synthesis of nanoparticles) allows to develop an industrial technology of nanometal colloids mass production with predetermined properties and concentration.

Possible fields for application of research results:

1. Nanomodification of polymer packaging materials in order to add bactericide properties to them and for extension of food products shelf life.
2. Nanomodification of water and air conditioning systems in order to add bactericide properties to them and for use in veterinary complexes, in food sector enterprises, in public catering enterprises;
3. Development of new generation environmentally friendly nano disinfectants for agriculture, grain, milk and meat processing;
4. Development of nanothechnological instruments for plants and veterinary complexes protection;
5. Development of nanosuspensions of silver and composite colloid nanometals solutions on the basis of liquid polysaccharides for low-concentration ecologically safe “edible” nano disinfectants inclusion to food products.

The most important commercial results are:

1. Affordable nanocolloids on the basis of liquids preferred by customer companies: these nanocolloids require neither complicated methods of mixing with end products nor changes in traditional production technologies;
2. Investment offers packets for organizations interested in purchasing nanoproducts and equipment for embedding it in their own production structure.

Cluster 8 include:

A. Research institutions of NAASU and NASU:

1. Sumy State University (Sumy).
2. Institute of Applied Physics of NASU (Sumy).
3. D. K. Zabolotnyy Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine.
4. V. Bakul Institute for Superhard Materials of NASU.
5. O. O. Ovcharenko Institute of Biocolloid Chemistry of NASU.
6. Institute of Scintillation Materials of NASU.
7. O. V. Bogatskyy Institute of Physical Chemistry of NASU.
8. Bila Tserkva National Agrarian University (Bila Tserkva).
9. Science and Research Institution “State Center of Innovative Biotechnologies”.
10. O. O. Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine (Kyiv).
11. O. M. Marzeev Institute of Hygiene and Medical Ecology of National Academy of Medical Sciences of Ukraine (NAMSU).

B. Business enterprises (SME’s, private companies):

1. “Diaprofmed” research and production enterprise.
2. “Intervetmed” Ltd.
3. “Nanotechmed” Ltd.
4. Joint enterprise “Marketing of Superhard Materials”.