In 2013 the Zelenograd Nanotechnology Centre (ZNTC) established an analytical laboratory in the premises of which innovative materials, technologies and equipment for biomedical applications are developed. This makes it possible for ZNTС to effectively promote a new promising area and successfully commercialise the applied research in the fields of medicine and biotechnology.
The ZNTС analytical laboratory is equipped with the up-to-date equipment that allows us to study the morphology and internal structure of the objects at the micro- and nanoscale levels. For research, modern high-resolution methods are used to get reliable information on the elemental and phase composition, morphological and crystallographic features of nanostructures. In addition, there is all the necessary equipment for the pilot production of medical devices.
The laboratory is part of a system of common use centres and is not only used by ZNTC’s portfolio companies but also provides research services to third parties.
Machines and equipment
The main tools for the study of the characteristics of nanoscale items in the laboratory are the scanning probe microscopes (SPM) Certus Optic I made by the Russian company Nano Scan Technology and Cypher ES of Asylum Research (USA). The laboratory staff have gained extensive experience in the study of biological cells, polymer molecules, nanoparticles, thin film coatings, semiconductors, dielectrics and piezoelectrics as well as other items and materials.
Certus Optic U is a scanning probe microscope (SPM) combined with the optical inverted microscope Olympus IX71. On the one hand, such integration facilitates the search for the research object on the sample surface; on the other, it makes it possible to study the surface beyond the resolving power of optical systems. The scanning base allows you to position a research object within a few fractions of a nanometre, and a scanning head allows accurate adjustment of the probe over the selected area. During the research a sample can be moved by a scanning base and a scanning head, both the head and base being constructed by the principle of parallel plate scanners thus eliminating the distortion typical of the piezo-tube systems.
The SPM Cypher in the expanded ES (Environmental Scanner) configuration allows you to implement a wide range of scanning probe microscopy methods in liquids and gases under controlled conditions with a resolution down to the atomic. The SPM is equipped with a sealed cell including cantilever and sample holders, in which liquids and gases including the aggressive and organic solvents, acids and alkalis pressurised to 34.5 kPa can be administered. It is possible to work with the microdroplet. There are several ports for the exchange of gases and liquids. Integrated temperature control helps stabilise the measurement conditions.
Certus Optic U and Cypher ES can operate in the atomic force microscopy, nanolithography and tunnelling microscopy modes including a number of special features, e.g. the atomic force cantilever research with increased stiffness at a frequency of 5 MHz for high precision imaging in Cypher ES.
The three-dimensional aerosol deposition system
One of the promising projects implemented in ZNTC using the laboratory capabilities is aimed at developing the three-dimensional aerosol spray coating system for various materials and objects. Three-dimensional aerosol spraying is a versatile technology that can be used for creating thin films and obtaining thick coatings. Compared with a vacuum sputtering, the following advantages can be offered:
•depositing non-metallic materials such as biocompatible polymers and photoresists;
•application of coating to objects and large areas;
•movement of the workpiece during spraying in two coordinates;
•use of simple technological modes (it does not require vacuum or high temperatures);
•low cost of equipment.
The technology can be applied in microelectronics, manufacture of medical devices and other areas for the application of functional, protective and decorative coatings. In particular, in microelectronics dimensional aerosol spraying has a potential for applying a photoresist on silicon wafers because in comparison with other technologies it provides a more uniform surface structure, absence of edge defects, effectively reaching the desired thickness, the ability to create uniform coatings on items with a challenging surface pattern, e.g. on the MEMS structures.
Currently, the start-up company NEOBIS (Nanoengineering of Organic and Biological Integrated Systems) develops the first Russian pilot three-dimensional aerosol spray plant in ZNTC. The technology has been successfully tested with the laboratory prototype Rainbow 2 created on the basis of 3D-printers.
The new unit will allow obtaining films characterised by high strength, uniform thickness and good adhesion to the substrate, on semiconductor wafers, polymeric materials and items of a complex shape. The technology allows you to apply both solutions and dispersions. There are two versions of the spray head, with a conventional needle and a pintle nozzle. NEOBIS professionals have developed a system that allows you to reduce the minimum droplet diameter from 20 µm to 1 µm (currently it passes patenting). Due to the use of the heated vacuum clamping table in combination with upper heating, film can be dried almost instantly which is important, for example, when photoresist is applied, as the substrate deformation is ruled out and the multilayer coating production time is reduced.
The plant will be operated from a PC with the ability to adjust about 30 process parameters including the solution characteristics and the parameters of movement of the head table, the parameters of spraying, pressure, heating etc. This will make it possible to select optimal treatment modes for various materials. The equipment can be characterised by ease of maintenance and operation, it is only necessary that it should be placed in a chemical cabinet or a laminar flow unit to protect the operator from the solution used.
"The developed plant is intended for laboratory research, experimental development and small-scale production", Roman Morozov, executive director at NEOBIS sayd. "The key competitive advantages over foreign counterparts include the significantly lower cost while demonstrating at least no worse performance as well as short delivery times, which is very important for the entities implementing projects in the framework of grants and various state programmes".
Adhesive homeostatic cellular scaffold for the accelerated tissue regeneration
The three-dimensional aerosol spray technology has successfully passed the practical test in several ZNTС projects, in particular in creating an adhesive homeostatic scaffold for the accelerated tissue regeneration.
Scaffold is an absorbent hemostatic agent that is used to seal wounds during the surgical operations involving lungs, liver and other organs. In addition to hemostasis, it should eventually be resorbed (dissolved) in the body, and ideally accelerate the regeneration of tissues. The homeostatic scaffold designed in ZNTC has all the above properties.
During the project implementation a unique process based on the interaction of nanoparticles and dispersion layering is developed. To prevent the destruction of the nanostructure of biopolymers only aqueous dispersions (ZNTC experts have executed applications for the Russian and international patents for the methods of preparing stable aqueous dispersions of biopolymers, such as collagen and chitosan) are used. Scaffold has a five-layer structure, and each layer of material is designed for a special function. On the outer layers the aerosol spraying method is used to create hemostatic and anti-adhesive coatings, the former has a good adhesion to the tissues of the body, and the latter prevents their fusion with each other.
"During the development, we took into account the fact that the cells interact effectively with only those objects that are significantly smaller than them; thus we should talk about nanoscale structures", R.Morozov noted. "The functional layers of the homeostatic scaffold contain the nanoscale fibres of collagen and chitosan; so unlike its foreign counterpart, our product cannot only be used to stop bleeding and resorbs in the body but also accelerates the tissue regeneration".
For the homeostatic scaffold produced is special inner packaging of a biocompatible plastic, which protects the outer nanostructured hemostatic layer from interaction with the packaging film and mechanical damage. All the major work designed to study biopolymers and obtain products prototypes is carried out in the analytical laboratory of ZNTC.
The partners of the project, which is supported by the Ministry of Industry and Trade of the Russian Federation, are the Samara State Medical University conducting animal studies and the Ivanovsky Research Institute of Virology of Russian Academy of Medical Sciences (Moscow) performing the research on cells.
Currently, the adhesive homeostatic scaffold for the accelerated tissue regeneration undergoes registration, after which pilot production will be set up.
***
ZNTC puts major emphasis on the developments for medicine and biology thus refuting the established thesis that Zelenograd is the city focusing only on the microelectronics industry. However, in the production of modern health care products the technologies, which are related to those used in electronics, are being more widely used; the new medical equipment is inconceivable without the latest achievements of the semiconductor industry.
The ZNTС analytical laboratory is equipped with the up-to-date equipment that allows us to study the morphology and internal structure of the objects at the micro- and nanoscale levels. For research, modern high-resolution methods are used to get reliable information on the elemental and phase composition, morphological and crystallographic features of nanostructures. In addition, there is all the necessary equipment for the pilot production of medical devices.
The laboratory is part of a system of common use centres and is not only used by ZNTC’s portfolio companies but also provides research services to third parties.
Machines and equipment
The main tools for the study of the characteristics of nanoscale items in the laboratory are the scanning probe microscopes (SPM) Certus Optic I made by the Russian company Nano Scan Technology and Cypher ES of Asylum Research (USA). The laboratory staff have gained extensive experience in the study of biological cells, polymer molecules, nanoparticles, thin film coatings, semiconductors, dielectrics and piezoelectrics as well as other items and materials.
Certus Optic U is a scanning probe microscope (SPM) combined with the optical inverted microscope Olympus IX71. On the one hand, such integration facilitates the search for the research object on the sample surface; on the other, it makes it possible to study the surface beyond the resolving power of optical systems. The scanning base allows you to position a research object within a few fractions of a nanometre, and a scanning head allows accurate adjustment of the probe over the selected area. During the research a sample can be moved by a scanning base and a scanning head, both the head and base being constructed by the principle of parallel plate scanners thus eliminating the distortion typical of the piezo-tube systems.
The SPM Cypher in the expanded ES (Environmental Scanner) configuration allows you to implement a wide range of scanning probe microscopy methods in liquids and gases under controlled conditions with a resolution down to the atomic. The SPM is equipped with a sealed cell including cantilever and sample holders, in which liquids and gases including the aggressive and organic solvents, acids and alkalis pressurised to 34.5 kPa can be administered. It is possible to work with the microdroplet. There are several ports for the exchange of gases and liquids. Integrated temperature control helps stabilise the measurement conditions.
Certus Optic U and Cypher ES can operate in the atomic force microscopy, nanolithography and tunnelling microscopy modes including a number of special features, e.g. the atomic force cantilever research with increased stiffness at a frequency of 5 MHz for high precision imaging in Cypher ES.
The three-dimensional aerosol deposition system
One of the promising projects implemented in ZNTC using the laboratory capabilities is aimed at developing the three-dimensional aerosol spray coating system for various materials and objects. Three-dimensional aerosol spraying is a versatile technology that can be used for creating thin films and obtaining thick coatings. Compared with a vacuum sputtering, the following advantages can be offered:
•depositing non-metallic materials such as biocompatible polymers and photoresists;
•application of coating to objects and large areas;
•movement of the workpiece during spraying in two coordinates;
•use of simple technological modes (it does not require vacuum or high temperatures);
•low cost of equipment.
The technology can be applied in microelectronics, manufacture of medical devices and other areas for the application of functional, protective and decorative coatings. In particular, in microelectronics dimensional aerosol spraying has a potential for applying a photoresist on silicon wafers because in comparison with other technologies it provides a more uniform surface structure, absence of edge defects, effectively reaching the desired thickness, the ability to create uniform coatings on items with a challenging surface pattern, e.g. on the MEMS structures.
Currently, the start-up company NEOBIS (Nanoengineering of Organic and Biological Integrated Systems) develops the first Russian pilot three-dimensional aerosol spray plant in ZNTC. The technology has been successfully tested with the laboratory prototype Rainbow 2 created on the basis of 3D-printers.
The new unit will allow obtaining films characterised by high strength, uniform thickness and good adhesion to the substrate, on semiconductor wafers, polymeric materials and items of a complex shape. The technology allows you to apply both solutions and dispersions. There are two versions of the spray head, with a conventional needle and a pintle nozzle. NEOBIS professionals have developed a system that allows you to reduce the minimum droplet diameter from 20 µm to 1 µm (currently it passes patenting). Due to the use of the heated vacuum clamping table in combination with upper heating, film can be dried almost instantly which is important, for example, when photoresist is applied, as the substrate deformation is ruled out and the multilayer coating production time is reduced.
The plant will be operated from a PC with the ability to adjust about 30 process parameters including the solution characteristics and the parameters of movement of the head table, the parameters of spraying, pressure, heating etc. This will make it possible to select optimal treatment modes for various materials. The equipment can be characterised by ease of maintenance and operation, it is only necessary that it should be placed in a chemical cabinet or a laminar flow unit to protect the operator from the solution used.
"The developed plant is intended for laboratory research, experimental development and small-scale production", Roman Morozov, executive director at NEOBIS sayd. "The key competitive advantages over foreign counterparts include the significantly lower cost while demonstrating at least no worse performance as well as short delivery times, which is very important for the entities implementing projects in the framework of grants and various state programmes".
Adhesive homeostatic cellular scaffold for the accelerated tissue regeneration
The three-dimensional aerosol spray technology has successfully passed the practical test in several ZNTС projects, in particular in creating an adhesive homeostatic scaffold for the accelerated tissue regeneration.
Scaffold is an absorbent hemostatic agent that is used to seal wounds during the surgical operations involving lungs, liver and other organs. In addition to hemostasis, it should eventually be resorbed (dissolved) in the body, and ideally accelerate the regeneration of tissues. The homeostatic scaffold designed in ZNTC has all the above properties.
During the project implementation a unique process based on the interaction of nanoparticles and dispersion layering is developed. To prevent the destruction of the nanostructure of biopolymers only aqueous dispersions (ZNTC experts have executed applications for the Russian and international patents for the methods of preparing stable aqueous dispersions of biopolymers, such as collagen and chitosan) are used. Scaffold has a five-layer structure, and each layer of material is designed for a special function. On the outer layers the aerosol spraying method is used to create hemostatic and anti-adhesive coatings, the former has a good adhesion to the tissues of the body, and the latter prevents their fusion with each other.
"During the development, we took into account the fact that the cells interact effectively with only those objects that are significantly smaller than them; thus we should talk about nanoscale structures", R.Morozov noted. "The functional layers of the homeostatic scaffold contain the nanoscale fibres of collagen and chitosan; so unlike its foreign counterpart, our product cannot only be used to stop bleeding and resorbs in the body but also accelerates the tissue regeneration".
For the homeostatic scaffold produced is special inner packaging of a biocompatible plastic, which protects the outer nanostructured hemostatic layer from interaction with the packaging film and mechanical damage. All the major work designed to study biopolymers and obtain products prototypes is carried out in the analytical laboratory of ZNTC.
The partners of the project, which is supported by the Ministry of Industry and Trade of the Russian Federation, are the Samara State Medical University conducting animal studies and the Ivanovsky Research Institute of Virology of Russian Academy of Medical Sciences (Moscow) performing the research on cells.
Currently, the adhesive homeostatic scaffold for the accelerated tissue regeneration undergoes registration, after which pilot production will be set up.
***
ZNTC puts major emphasis on the developments for medicine and biology thus refuting the established thesis that Zelenograd is the city focusing only on the microelectronics industry. However, in the production of modern health care products the technologies, which are related to those used in electronics, are being more widely used; the new medical equipment is inconceivable without the latest achievements of the semiconductor industry.
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