Field of technology

The present invention relates to a modular biophysical reactor, it falls within a field of the scientific research devices for experiments and tests and it is intended primarily for studying changes in properties of the biological materials in short or long-term cultivation under different physical conditions (temperature and pressure, various atmosphere composition, e.g. hypoxia, hyperoxia or carbon monoxide poisoning) and studies of the changes in the behaviour of the living organisms or small animals. Alternatively, the device can be used to verify a functionality of the technical devices or their components (tests of the components such as sensors, devices, and HW) under different pressure conditions and with different composition of the internal atmosphere.

Prior art

Overpressure or underpressure (decompression) vessels (hyperbaric chambers) are used in a number of technical, medical or scientific fields. They are usually designed for specific purposes such as testing of the instrumentation under overpressure and underpressure conditions, for medical purposes (mainly hyperbaric oxygen therapy), for pilots or astronauts training in weightlessness or for training athletes, and often for training and decompression rescue of divers.

Generally, a hyperbaric chamber is constructed in a form of the cylinder with pressure- adapted terminal, which may take the form of an entrance to such a chamber. The size of the chamber depends on its use, large chambers for dozens of patients, special purpose chambers as in the case of US20090038618A1 intended for the treatment of large farm animals up to single chambers are known. Various variants of small or single-person chambers for training, therapy or testing were most often patented. For example, a decompression chamber for divers is known from DE3732167. Another example is US5327904A describing a single-person chamber for a seated patient. The body of the chamber can be made of the metal or flexible materials depending on the required internal overpressure and it is assembled as one unit. An example of inflatable chamber is described in US20080006272A1, where the chamber is made of a flexible material and is reinforced with strips which also serve as a structural support.

A solution describing modular interior of the overpressure chamber is known from US6347628. The modularity lies in an internal airtight and pressure-resistant removable partition system, which allows the chamber to function as a single-person and, if necessary, a multi-person chamber can be created by removing this partition system. The external dimensions remain unchanged.

A fixed internal volume of the chamber is generally a major disadvantage of the known solutions. Another common disadvantage of the known solutions is their construction for a specific purpose with a number of technical and technological applications, which prevents their universal use in other experimental or test workplaces or adaptation of the chamber for another purpose. In addition to the large dimensions, which complicate transport and installation at the destination, the disadvantage is the high acquisition costs and the complexity of the technical background and operator training. Other known solutions are mostly devoted to a construction of the individual functional parts of the pressure chambers, e.g. CN200953821Y describes a method of heating the interior of the pressure vessel by means of a heating spiral.

Small overpressure or underpressure chambers and vessels, that can be used for various test and analytical methods, are known, including the field of medicine and biology, as for example, US20130145506A1, which describes a chamber for microscopic study of the samples wherein a microscope is located inside the pressure vessel and samples are inserted through a self-sealing window. JPH04184138 describes a pressure device with a small internal space for experiments at high pressures and temperatures. However, its design does not allow an insertion of the larger objects and control of the internal climate of the chamber. Furthermore, the solution described in CZ20118U1 is known, where a hypobaric and hyperbaric chamber is designed in a form of the non-metallic cylinder hermetically sealable on both sides, which is connected to a pump and a compressor and is connected to a control unit. This chamber is intended for experiments with small mammals examined by magnetic resonance imaging. It is generally a therapeutic pressure vessel in which high pressures and a large temperature range cannot be achieved and the temperature inside the chamber cannot be regulated. In addition, due to the non-metallic material used, it is not chemically and mechanically resistant, so that various aggressive gas mixtures and various types of interior exposure cannot be used in the experiments. A solution according to CZ305989B6 is known, disclosing a mobile hyperbaric mini-chamber, consisting of the container, the shell of which is adapted for hermetic closure by a lid using a locking mechanism, the chamber is equipped with sealable bushings to enable a connection with the internal space and provided with windows for monitoring the internal spaces.

It is an object of the present invention to provide a modular biophysical reactor which, with its modular construction, dimensions and operating parameters, overcomes the shortcomings of known solutions and is easily applicable to a wide range of experimental and test areas, especially in cell biophysics experiments, i.e. studies of the effect of the various physical conditions on cells, tissues and organisms.

Description of the invention

The modular biophysical reactor according to the present invention is a special pressure vessel which falls into the field of experimental and testing scientific research devices. It is intended primarily for a study of the changes in the properties of the biological (cells, tissues, animal models) or other materials during short-term or long-term cultivation in various physical conditions and various atmospheric compositions (e.g. induction of hypoxia or hyperoxia), temperature and ambient pressure. It can also be used to study changes in the behaviour of the living organisms or small animals. The invention can also be used to verify the functionality of technical devices or their components (testing of components such as sensors, devices, etc.) under various pressure conditions and with various compositions of the internal atmosphere. Its use is therefore partly similar to that of the hyperbaric chamber.

An essential feature of the invention is the construction of the reactor vessel from modules (parts or segments), while maintaining a hermetic tightness, which is a significant difference compared to conventional designs of closed vessels from one piece of material. According to the prior art search, such a concept has not yet been used. The advantage of the modular design is the effective change or adaptation of the structure or internal volume of the reactor by simply replacing, adding or removing another part. In the event of a fault or a change request, only the part is replaced and it is not necessary to manufacture the entire vessel again. The modular concept has another undeniable advantage and that is the reduced complexity of transport. In the case of large closed vessels of the hyperbaric chamber type, it is often necessary to make complicated construction modifications or to install the equipment before facility construction. In contrast, individual modules can be transported separately and assembled only at the final destination.

The modules are essentially hollow cylinders (chamber ring) with flanges for a firm mechanical connection using connecting means (e.g. rivets or bolts, preferably bolts) which ensure a firm mechanical connection of the modules and their mutual hermetical sealing. Other than cylindrical modules can be imagined (cube or prism), but the cylinder appears to be optimal in a number of aspects, e.g. overpressure or underpressure robustness, manufacturing processes, and others.

Several types of modules having different functions are provided. The flanges of the individual modules are complementary to each other, so that the modules can be connected in essentially any combination. A central module forms the main internal space of the reactor and can advantageously also be used for thermoregulation of the interior space of the reactor. A method of interior temperature regulation can be chosen according to requirements, conditions, material used, etc. An example can be water thermoregulation or thermoelectric temperature regulation using Peltier cells for heating or cooling through the module wall. The central module has an outer wall that is smooth or it is provided with surfaces for thermoelectric cells or with a channel for circulation of the tempering liquid.

An entry module with a hermetically sealable door serves to enter the internal space of the reactor according to the invention. The entry module comprises a connecting part with a flange for connection to the central module and the door. A construction of the door can be chosen according to the purpose of use, for example it can advantageously be provided with a toothed door fixation (the construction is known to a person skilled in the art). Then the door comprises its own toothed lid and a ring with teeth. Other mechanisms known to those skilled in the art can be selected for the door mechanism.

Further module is an extension module. The extension module may comprise ports for connecting sensors and media inputs. The ports are equipped with classic threads (metric M or imperial G) and can be hermetically sealed. The extension module can be connected to each end of the central module.

The rear part of the reactor according to the invention is terminated by a back module, which is essentially a lid which is firmly connectable to the flange of the previous module by suitable connecting means and can be hermetically sealed. The lid can be flat or arched (domed) and it can comprise additional ports for connecting internal and external spaces or it can be equipped with a window. The back module may optionally be provided with a second entry.

The reactor according to the invention can be oriented horizontally or vertically depending on the method of use.

A construction material of the modules is variable, depending on the purpose of use of the device. For example, light metallic or non-metallic materials (e.g. transparent etc.), such as aluminium, polyacrylate, polycarbonate, nylon, and others, can be used for normobaric experiments. The materials with high tensile and compressive strength, such as stainless steel, titanium, carbon fibre composite, and others, will be used for pressure (overpressure or underpressure) experiments. Another example can be the requirement for a toxic or corrosive environment of the internal atmosphere, when the material should have anti-corrosive properties. In case of minimizing the risk of bacterial contamination during cell cultivation, materials with natural antibacterial function (surface silver) or materials enabling the creation of highly smooth surfaces (below 0.5 pm) can be used. The modular concept also allows the creation of a device from two (or more) different construction materials, such as metal and transparent plastic. In one preferred embodiment, the central module or extension module is transparent. In this case, it is either made entirely of transparent material (such as polycarbonate, PC, PMMA (polymethyl methacrylate, plexiglass) or glass) or only the perimeter shell of the module is made of this transparent material and the flange of the module is made of another material (as well as other modules usually made of metal, e.g. steel). In another preferred embodiment, the back module may be transparent, in which case it is made of the above mentioned transparent materials.

Depending on the requirements for use, the entire structure can be supplemented with thermal, sound or radiation insulation. In the case of a construction made of metallic materials, the interior is electromagnetically shielded. The reactor may have various dimensions, the modules can be manufactured with diameters in sizes in the order of centimetres up to meters. The internal equipment of the reactor according to the invention is variable and depends on the intended use. The module with ports allows installation of the electrical devices, sensors, lighting, mechanical and electromechanical components, etc. in the reactor.

In the case of using the reactor for pressure purposes, the method of design and calculation of parameters (internal diameter, wall thickness, etc.) is governed by valid technical standards (e.g. technical standards CSN 69 0010 or CSN EN 13445) and is known to a person skilled in the art.

The advantages of the device according to the invention can be summarized as follows:

- the device according to the invention is composed of modules;

- the device according to the invention can be oriented horizontally or vertically;

- the device according to the invention can be operated under overpressure or underpressure;

- the device according to the invention can be assembled from standardized modules;

- the modules can be modified and other variants can be developed while maintaining connection compatibility;

- the device according to the invention made of a chemically resistant material can be operated with different internal atmospheric compositions;

- the modules can be manufactured from various construction materials;

- the device according to the invention can be assembled from one material or a combination of materials (e.g. metal and transparent plastic) and their properties can be modified depending on the requirements (e.g. pressure strength).

- the inner surface of the modules has a roughness below 0.5 pm for increased antibacterial protection;

- the devices according to the invention can be enlarged or reduced and small, medium or large devices (with diameter of centimetres to meters) can be manufactured;

- due to the modular design, the device according to the invention is better transportable and the assembly of the modular reactor of large diameter (e.g. hyperbaric chambers) in the interior of a building reduces the demands on construction work (often demolishing walls and windows).

The present invention provides the modular biophysical reactor as described herein and as defined in appended claims 1 to 12.

Brief of the

Specific embodiments of the invention are schematically illustrated in the accompanying figures: FIG. 1. Basic view of the reactor. A - side view from a side accessible to the user, door visible on the right, B - section, C - side view from the side of the holder by which the reactor is fixed to the instrument frame or wall.

FIG. 2. An exploded view of the reactor according to FIG. 1.

FIG. 3. Details of the modules: A - central module; embodiment with facets for thermoelectric cells, B - extension module in basic design, C - back module, D - entry module, E - extension module with ports, F - central module; embodiment with channel for circulation of the tempering liquid.

FIG. 4. Example of the changes in the scale.

FIG. 5. Example of the design of the reactor made of different materials (metal + transparent plastic).

FIG. 6. Exemplary embodiment - a prototype of the horizontal reactor.

FIG. 7. Illustration of the vertical reactor.

FIG. 8. Exemplary embodiment - a prototype of the vertical reactor.

The drawings, which illustrate the present invention and the examples of specific embodiments described below, in no way limit the scope of protection given in the claims, but merely clarify the essence of the invention.

Examples of the invention

Example 1

Reactor concept and description of the basic modules

The modular biophysical reactor is a special pressure vessel that comprises modules essentially in the shape of a hollow cylinder. The embodiment of the invention described in this example corresponds substantially to the schemes in FIGS. 1 to 3. The reactor comprises the central module 10 having a connecting flange 53 with holes 55 at each end which serves to interconnect the modules by suitable bolts 50. The extension module 20 is connected to the central module 10 on one side and the entry module 30 with an entry opening to the interior is connected on the other side. The other end of the extension module 20 is connected to the back module 40.

In this example, the extension module 20 serves to increase a volume of the internal space. The extension module 20 has the connecting flange 53 with the holes 55 at each end, which serves to interconnect the modules with suitable bolts 50. The extension module 20 can be manufactured in a variant 22 with ports 41, as shown in FIG. 3E.

The entry module 30 (see also FIG. 3 and 5) with entry opening used in this example serves as an entry into the interior of a closed pressure vessel. It comprises a connecting part 31 of the module with the flange 53 and a door 32. The door 32 comprises a toothed lid 33 and toothed ring 34 to enable rotary fixing of the lid 33. The lid 33 is provided with mountings 35 for the brackets 36 associated with the hinge 37. The process of closing the lid 33 is a conventional toothed fixation of the door, this construction is known to the persons skilled in the art. Individual modules have the connecting flanges 53 with the holes 55, which serve for connection of the modules with bolts 50. The shape of the flanges 53 and the number of the holes 55 for the bolts 50 are identical for all modules depicted in the example. Each module is provided on one connecting flange 53 with a groove 54 for the gasket to ensure hermetic sealing of the internal space of the device. The groove 54 may have e.g. semicircular or rectangular profile complementary to the profile of the gasket. The gasket is in the form of an o-ring. Material of the gasket depends on the intended use of the device, it can be made for example of rubber, inert silicone or materials capable of withstanding the action of oxygen. It is also possible to use flat permanent seal, wherein the groove 54 of the gasket may not be recessed. Method of designing a suitable groove and gasket for sealing the pressure vessel is known to the persons skilled in the art.

In the Example 1, the central module 10 is used as the central module in a variant for tempering the internal space with thermoelectric cells. On the outer surface of the module 10, facets 13 are formed for accommodating thermoelectric (Peltier) cells. Their area, number and way of attachment to the central module 10 depend on the requirements and the final design of the device. In this particular embodiment, there are 2 x 8, regularly spaced facets for the attachment of thermoelectric cells around the circumference of the module 10. Thermoelectric cells in conjunction with suitable control and measuring technology ensure a suitable internal space temperature. The proper control and measuring technology is known to a person skilled in the art. The thermoregulation of the interior space can be solved in other ways, for example, as shown in FIG. 3F, in the variant for tempering the interior with a liquid 11, where a meandering channel 14 for tempering liquid is placed on the outer surface of the module 10 instead of the facets for thermoelectric cells. Tempering liquid thermodynamically affects the temperature of the internal space of the reactor.

The back module 40 has holes for the bolts 50 on its edge, which have the same pitch as the holes in the connecting flange 53. In this example, ports 41 for communication between external and internal space are located in the back module 40 (see FIG. 3C). The ports 41 can be threaded, their location and size depend on the requirements and the final design.

Fasteners 52 for anchoring the body of the reactor to the skeleton of the instrumentation box are attached at appropriate places on the connecting flanges 53. The fasteners 52 also serve as a point of attachment of the holder 51 with the hinges 37 to the body of the central module 10.

The individual modules represent cylinders of various lengths, with an inner diameter of 160 mm and a wall thickness of 7 mm. The flanges 53 for connecting the modules exceed the outer diameter of the module body by 25 mm. The central module 10 with the facets 13 for Peltier cells is made in one piece as a single part, i.e. the facets are the integral parts of the module (see FIG. 1). The approximate size of one facet is 60 x 50 mm.

Similarly, the central module 11 with the channel 14 (see FIG. 3F) is made in one piece, and in addition it is provided with a casing which tightly seals the channel 14 for the tempering liquid. In an alternative embodiment, a tube (preferably made of copper) may be inserted into the channel 14 for conducting the tempering liquid. In another alternative embodiment, the tube for conducting the tempering liquid is wound on a smooth surface (without facets and channels) of the central module 10. In another variant, it is possible to use a heating cable wound around the central module 10 for thermoregulation.

The Example 1 describes the basic modules for building the modular biophysical reactor intended for the study of the changes of the properties of the biological materials during short or long term cultivation in different physical conditions and different atmospheric composition (e.g. inducing hypoxia or hyperoxia), temperature and internal pressure (overpressure and underpressure). It is clear that the modular nature of the reactor will allow to design other types of the modules with specific functions. Example 2

Possible scale changes

By changing a scale (scaling), it is possible to achieve variability of the device dimensions. Modules with a diameter of units of centimetres to meters can be manufactured. In FIG. 4, the central module 10 tempered with thermoelectric cells described in the present Example 1, with a diameter of 160 mm, and the central module 12 tempered with thermoelectric cells in the enlarged scale with diameter of 1 m are demonstrated for comparison. Comparing to the embodiment of the Example 1, the number of the facets for the placement of Peltier cells is changed (increased) in the central module 12. It is possible to change the scale of other modules in the same way, for example the extension module 22 with ports and its enlarged variant 23 are shown. The condition for scaling is to keep the same shape and dimension of flange 53 of all modules and the number of holes 55 for the connecting bolts 50. However, a reduction module can be manufactured for connecting modules of different diameters.

Example 3

Reactor orientation, different materials and their combinations

The device according to the invention described in the Example 1 is oriented horizontally. The prototype described in the Example 4 and shown in FIG. 6 was made for such a use. The concept of the invention allows the design and assembly of the device whose entry door and inner space will be oriented vertically as described in the Example 5 and shown in FIG. 7 and FIG. 8.

The device according to the invention described in the Examples 1, 4 and 5 is made of stainless steel AISI316L. It will be appreciated that the basic modules described in the Example 1 and shown in FIG. 3 may be made of other suitable materials depending on the requirements and the resulting design. FIG. 5 shows an example of the embodiment of the reactor made of different materials. Instead of the standard central module 10, a special central module 15 is used as the central part of the reactor, which is not made of steel and is not intended for interior temperature regulation, but it is made of flexible plastic or composite transparent material, preferably PMMA, PC, PVC-U, or glass. Alternatively, only the housing of the module 15 is made of the transparent material and the flange 53 is made of steel. In another embodiment, the entire back module 40 is made of the transparent material. The transparent material makes it possible to monitor the internal space during ongoing experiment, its external affecting (e.g. photodynamic therapy), or to ensure a view from the internal space (e.g. for a patient with claustrophobia).

Example 4

Example of reactor prototype design

To verify the concept and functionality of the reactor described in the Example 1, a prototype of the horizontal modular biophysical reactor was designed and manufactured. The production 3D model of the horizontal embodiment is identical to the model in FIG. 1. The prototype was designed to study changes in the properties of biological materials during short-term or long-term cultivation of the cell materials and tissues in different physical conditions and different atmospheric composition (e.g. induction of hypoxia or hyperoxia), temperature and internal pressure (overpressure and underpressure). The reactor was made of stainless steel AISI316L because to its good mechanical properties, biocompatibility, chemical stability and resistance.

Thanks to its small dimensions, the reactor is easy to move. The dimensions of the modules are as follows: All modules have an internal diameter of 160 mm. The central module 10 has a length of 200 mm, the extension module 20 without ports has a length of 80 mm. The entry module 30 has a length of 45 mm. The wall thickness is 7 mm. The internal volume is approximately 6.5 1, the volume of the working space is approximately 5 1, the diameter of the internal working surface is 160 mm, the maximum operating overpressure is 30 bar. The parameters and dimensions of the described example are designed for the insertion of 8 pieces of ordinary cultivation plastics of multiplate type (e.g. 6well) or 10 pieces of the Petri dish (D90) type. The surface 56 of the inner spaces was treated to have antibacterial effect, i.e. so that the surface roughness does not exceed 0.5 pm.

Depending on the experiment performed, sensors for measuring pressure, temperature, humidity, gas concentration, or fans, or LEDs can be placed into the reactor (using the ports in either the extension module 20 or the back module40). Example 5

Realization of the larger reactor

To verify the concept and functionality of the reactor described in the Example 1 and the concept of resizing according to the Example 3, a prototype of larger vertical reactor was designed and manufactured. The production 3D model of the vertical embodiment is shown in FIG. 7 and detail photographs of the prototype are presented in FIG. 8.

This prototype is intended primarily for the study of changes in the behaviour of the living organisms and small animals and also to verify the functionality of technical devices or their components (testing of components such as sensors, devices, and HW) under different pressure conditions and different internal atmospheres. Its use is therefore partly similar to the hyperbaric chamber.

The reactor was made of stainless steel AISI316L because of its good mechanical properties, biocompatibility, chemical stability and resistance.

The dimensions of the modules are as follows: All modules have an internal diameter of 270 mm. The central module 11 has a length of 175 mm, the extension module 22 with ports has a length of 60 mm. The entry module 30 has a height of 110 mm. The wall thickness is 10 mm.

The volume of the working space is approximately 20 1, the diameter of the inner working surface is 270 mm, the maximum operating overpressure is 20 bar.

The prototype has the central module 11 in a variant for tempering the interior with circulation of liquid, the extension module 22 comprises ports 41 for communication between internal and external spaces (gas inlet and outlet, sensors, electronics), the lid 33 and back (bottom) module 40 is equipped with window 57 for monitoring and noncontact influencing the contents of the internal spaces (e.g. magnetic stirrer or magnetic clutch). The surface 56 of the inner spaces is treated to have antibacterial effect, i.e. so that the surface roughness does not exceed 0.5 pm. Depending on the experiment performed, sensors for measuring pressure, temperature, humidity, gas concentration, or fans, or LEDs can be placed into the reactor (using the ports 41 of the extension module 22 or the back module 40). Industrial applicability

The modular biophysical reactor is a special pressure vessel, the use of which is partly similar to a hyperbaric chamber and falls into the field of experimental and testing scientific research equipment. It was designed primarily to study changes in biological (cells, tissues) or other materials during short-term or long-term exposure to various physical conditions and at various atmospheric compositions (e.g. induction of hypoxia or hyperoxia), temperature, and ambient pressure, and to study changes in the behaviour of living organisms or small animals. The reactor can be used to verify the functionality of the technical devices or their components (testing of components such as sensors, devices, and HW) under different pressure conditions and different inner atmospheres such as equipment for divers, small devices designed to operate in large hyperbaric chambers such as ECGs , oximeters and the like. By scaling up the parts of the reactor it is easy to manufacture a chamber usable for medical purposes (mainly hyperbaric oxygen therapy), for training pilots or astronauts in weightlessness or for training athletes, and for training and decompression rescue of divers.

List of reference numerals

10 Central module in a variant adapted for thermoregulation using thermoelectric cells

11 Central module in a variant adapted for thermoregulation using a liquid

12 Central module in a variant adapted for thermoregulation using thermoelectric cells with increased number of facets for thermoelectric cells

13 Facets for thermoelectric cells

14 Meandering channel for tempering liquid

15 Central module made of transparent material

20 Extension module

22 Extension module with ports

23 Extension module with ports with increased number of ports

30 Entry module with a door into internal space

31 Connecting part of the entry module

32 Door 33 Toothed entry lid

34 Toothed ring for rotary fixing of the entry lid

35 Mountings for brackets

36 Brackets

37 Hinge

40 Back module

41 Ports for communication between external and internal space

50 Connecting means (bolts) for connecting individual modules

51 Holder with hinges

52 Fasteners for anchoring the reactor body in the device rack

53 Connecting flange

54 Groove for a gasket

55 Holes for connecting means (bolts)

56 Internal surface

57 Window made of transparent material