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Title:
PROCESS AND DEVICE FOR THE PRODUCTION OF CAPILLARIES, AND CAPILLARIES PRODUCED BY THE PROCESS
Document Type and Number:
WIPO Patent Application WO/2023/248132
Kind Code:
A1
Abstract:
The present invention relates to a process for producing capillaries formed for example by alginate salts. The process comprises exposing an aqueous solution of alginate salt to a direct current in an electrolytic cell comprising a positive central support electrode and a surrounding negative electrode, after which the central positive electrode with formed desired alginate deposit is introduced into a soluble hardening salt solution. The hardened deposit is subsequently separated from the positive central electrode. The invention also relates to a device for carrying out the process and a capillary produced by said process.

Inventors:
HALADA ŠTĚPÁN (CZ)
LÁZNIČKA VÁCLAV (CZ)
Application Number:
PCT/IB2023/056379
Publication Date:
December 28, 2023
Filing Date:
June 20, 2023
Export Citation:
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Assignee:
BTL HEALTHCARE TECH A S (CZ)
International Classes:
C25D9/02; C08J5/20; C08L5/04
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Claims:
CLAIMS cess for production of capillaries comprising the steps of: exposing a deposition compound solution to a direct current in an electrolytic cell comprising a central electrode (1) and a surrounding electrode (2) in order to form a deposit on the central electrode (1); introducing the deposit to a hardening salt solution in order to harden said deposit, thereby forming a capillary (3); and separating the capillary (3) from the central electrode (1); wherein the surrounding electrode (2) is positioned surrounding the central electrode (1) and the both the surrounding electrode (2) and the central electrode (1) are immersed in the deposition compound solution, or the surrounding electrode (2) forms at least part of a sheath of a deposition compound solution reservoir and the central electrode (1) is placed to the deposition compound solution.

2. The process for production of capillaries according to claim 1, wherein at least part of the sheath of the deposition compound solution reservoir is an inner layer of the sheath of the deposition compound solution reservoir.

3. The process for production of capillaries according to claim 1, wherein the deposition compound comprises a polymer.

4. The process for production of capillaries according to claim 3, wherein the deposition compound comprises a polysaccharide or a protein.

5. The process for production of capillaries according to claim 4, wherein the deposition compound comprises at least on of: alginic acid, carrageenan, pectin, cellulose, chitosan, xanthan, guar gum, hyaluronic acid, collagen, soy protein, gluten, gelatin, glycoprotein, proteoglycan, glycosaminoglycan, elastin, the salt and derivative thereof, or the mixture thereof.

6. The process for production of capillaries according to claim 3 to 5, wherein the deposition compound comprises a mixture of the alginic acid or its salt with at least one of: collagen, gelatin, glycoprotein, proteoglycan, glycosaminoglycan, elastin or hyaluronic acid.

7. The process for production of capillaries according to claim 1 comprising the steps of: exposing an aqueous solution of alginate salt to a direct current in an electrolytic cell comprising a positive central electrode (1) and a negative surrounding electrode (2) in order to form an alginate deposit on the positive central electrode (1); introducing the alginate deposit to a hardening salt solution in order to harden said alginate deposit, thereby forming an alginate capillary (3); and separating the alginate capillary (3) from the positive central electrode (1); wherein the negative surrounding electrode (2) is positioned surrounding the positive central electrode (1) and the both electrodes are immersed in the deposition compound solution, or the negative surrounding electrode (2) forms at least part of a sheath of alginate salt reservoir, and the positive central electrode (1) is placed to the alginate salt solution.

8. A capillary made by the process of claim 1.

9. An alginate capillary made by the process of claim 7.

10. A capillary comprising a mixture of the alginic acid or its salt with at least one of: collagen, gelatin, glycoprotein, proteoglycan, glycosaminoglycan, elastin or hyaluronic acid.

11. A device for production of capillaries comprising: an electrolytic cell comprising a central electrode (1) and a surrounding electrode (2) for formation of the deposit on the central electrode (1); a hardening tank (5) with a hardening salt solution for hardening said deposit, thereby forming a capillary (3); wherein the surrounding electrode (2) is positioned surrounding the central electrode (1) and the both electrodes are immersed in the deposition compound solution, or the surrounding electrode forms at least part of a sheath of a deposition compound reservoir and the central electrode (1) is placed to the deposition compound solution.

12. The device according to the claim 11, wherein the surrounding electrode (2) has a cylindrical, cubic shape, or a cuboid shape, or has a triangular, square or rectangular cross section.

13. The device according to the claim 11, wherein the central electrode (1) has a circular, triangular, square or rectangular cross section.

14. The device according to the claim 11, wherein the hardening solution comprises a source of positive crosslinking ions.

15. The device according to the claim 14, wherein the positive crosslinking ions comprise at least one of: H+, Ca2+, Ba2+, Cu2+, Cr2+, Zn2+, Fe2+, Mn2+, Al3+, or Fe3+.

17. The device according to the claim 11, further comprising: a central control unit; a DC power supply; and a measuring device comprising at least one of: a digital multimeter, a potentiometer, a potentiostat, or a timer.

Description:
PROCESS AND DEVICE FOR THE PRODUCTION OF CAPILLARIES, AND CAPILLARIES PRODUCED BY THE PROCESS FIELD OF THE INVENTION [1] The present invention relates to a process for the production of capillaries consisting for example of alginate salts. The capillaries are mainly used as diffusion capillaries. The diffusion capillaries are small tubes with porous walls. The pores limit the convective flow through the capillary walls due to their small sizes, but allow diffuse transport of the dissolved components if these components are smaller than the size of the pores. Diffuse transport can occur both from around the capillary inwards and vice versa. The direction is primarily given by the concentration gradient of the diffusing component. One of the possible applications of diffusion capillaries is the transport of nutrients to cell cultures, e.g. two dimensional or three dimensional cell cultures. [2] The invention also relates to a device for carrying out the above mentioned process and the capillaries produced by the process. BACKGROUND OF THE INVENTION [3] A technique of laser printing and a technique of using gelatin as a carrier material have been used for the production of capillaries, for example alginate capillaries. The laser printing technique is based on the laser-induced application of alginate to a positioning table located just above the level of the CaCl 2 hardening solution. This table moves in two horizontal axes during application and allows for the creation of alginate pseudo-2D geometries (the laser is stationary). The resolution of these geometries is affected by the size of the laser-generated alginate droplets. After creating the desired geometry, the applied alginate is hardened by immersing the stage in a hardening salt solution (vertical axis of the stage). After hardening, another layer of alginate may be applied to the layer already formed, after the height of the positioning table under the laser has been adjusted correctly. In the case of the technique using gelatin as a carrier material, the gelatin fiber is first drawn out by suitable means, for example using tweezers. After hardening, the gelatin fibers are soaked in an alginate solution. The alginate deposited on the gelatin fiber is then hardened by crosslinking in a calcium salt solution. In the case of both techniques, the obtained alginate capillaries are poorly geometrically defined, in particular in terms of their inner diameter, wall thickness and their uniformity along the entire length of the alginate capillaries. In the case of laser printing, this is due to the limited possibilities of the technique, which essentially makes it possible to obtain capillaries of very short length, for example about 8 mm, and very irregular shape, and in the case of the technique using gelatin as a carrier material, it is practically impossible to produce a carrier gelatin fiber having the desired diameter along its entire length. This insufficient reproducibility of said parameters of capillaries represents a disadvantage which significantly affects the applicability of such capillaries in their subsequent applications. [4] Methods of electrolytic deposition have also been disclosed within the state of the art, for example for the preparation of alginate capillaries. The process is based on exposition of the aqueous solution of alginate salt to a direct current provided by an electrolytic cell consisting of a positive and a negative electrode. The electrodes are made from metal wires and are placed into the solution of alginate salt. The alginate capillary is formed on the positive electrode. The disadvantage of this method is the inhomogeneous structure of formed capillaries, which impedes their use in practical applications. [5] For the abovementioned reasons, it is clear that there is currently a demand for devices and a processes for producing capillaries which do not suffer from the above- mentioned drawbacks, the process being efficient, economical, easy to implement, and which would provide the homogenous capillaries with the desired physicochemical properties. BRIEF SUMMARY OF THE INVENTION [6] The above mentioned disadvantages of said methods according to the state of the art may be eliminated by the novel device and process for production of capillaries according to the present invention, comprising exposing an deposition compound solution to a direct current in an electrolytic cell formed by a central electrode and a surrounding electrode. The central electrode may be positive and the surrounding electrode may be negative, or the central electrode may be negative and the surrounding electrode may be positive, based on properties and a charge of the deposition compound. For example in the case the alginic acid or its salt is used as the deposition compound, the central electrode is positive and the surrounding electrode is negative. [7] The deposit formed from the deposition compound on the central electrode, for example the alginate deposit may be then introduced into the solution of a soluble hardening salt, where the hardening ions are crosslinked into the deposit structure, and the hardened deposit may be subsequently separated from the positive central electrode. [8] The invention also relates to the device for carrying out the above mentioned process and the capillaries produced by the process. [9] A significant advantage of the process according to the invention is that by choosing the parameters used in its implementation, predetermined exact values of the shape and dimensions of the resulting capillary can be achieved. Thus, the length, internal cross-section and the shape of the alginate capillary, for example alginate capillary, may be predetermined by the appropriate choice of the length, the shape and the cross-section dimensions of the central electrode. The wall thickness of the capillary can be determined by interrupting the electrolytic process when the desired deposit thickness on the central electrode corresponding to the desired wall thickness of the capillary has been reached. The wall thickness is also affected by the set current and deposition time. The electric potential on the respective electrodes may be adjusted so that the current is constant throughout the deposition. The density of the deposit may be influenced by the electric potential applied between the two electrodes. The fact that the wall thickness of the capillary is the same along its entire length is ensured by the length dimension of the negative surrounding electrode, and the electrolytic effect which acts equally along the length of the deposit formation zone on the central electrode. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS [10] Fig.1 schematically shows a device comprising the electrodes for carrying out the process according to the invention [11] Fig.2 schematically illustrates the movement of ions in relation to the electrodes during the electrodeposition process of alginate deposition [12] Fig.3 shows the capillary with the capillary channel [13] Fig.4 schematically illustrates the movement of copper ions toward the negative electrode during the process of preparation of connectors by electroplating according to the invention [14] Fig.5 shows the capillary connected to connectors prepared by electroplating, the capillary channel is connected to connector channel. DETAILED DESCRIPTION OF THE INVENTION [15] The above mentioned disadvantages of said methods according to the state of the art may be eliminated by the novel process for production of capillaries 3 according to the present invention. [16] As may be seen in Fig.1, the electrolytic cell according to the invention may be formed by a central electrode 1 and a surrounding electrode 2. The central electrode 1 may be positive and the surrounding electrode 2 may be negative, or the central electrode 1 may be negative and the surrounding electrode 2 may be positive, based on properties and a charge of a deposition compound. For example in the case the alginic acid or its salt is used as the deposition compound, the central electrode 1 is positive and the surrounding electrode 2 is negative. [17] The reference electrode 4 may be used for measurement of electric potential between the central electrode 1 and the reference electrode 4 and for subsequent control of the electric current and the potential between the central electrode 1 and a surrounding electrode 2. The central electrode 1 serves as a deposition template using the deposition compound to form the capillary 3 on the central positive electrode 1. [18] The deposition compound may be negatively or positively charged material, e.g. polysaccharide or protein, or the salts, derivatives or mixtures thereof, or any other appropriate compound. The presence of carboxyl or hydroxyl groups helps to from crosslinked structure of the capillary. The polysaccharide may be for example carrageenan, pectin, cellulose, chitosan, xanthan, guar gum, hyaluronic acid, alginic acid and their salts and derivatives, such as for example carboxymethyl cellulose (CMC), carboxymethyl chitosan (CMCH), carboxymethyl xanthan. The alginic acid is a linear copolymer with homopolymeric D-mannuronic and L-guluronic acid blocks. As deposition compound may be used alginic acid or its salt, for example the salt of a metal and alginic acid, the water soluble salt of alginic acid, sodium or calcium salt of alginic acid. [19] The protein may be animal or vegetable protein, for example collagen, soy protein, gluten or gelatin. [20] Some deposition compounds, such as for example collagens, gelatin, glycoproteins, proteoglycans, glycosaminoglycans, elastin, hyaluronic acid, or other suitable deposition compounds, may be used, separately or in a mixture of deposition compounds, in order to promote adherence to the capillary and enhancement of the cell growth. [21] The deposition compounds may be used separately, or as a mixture of any of the above mentioned deposition compounds. As a mixture of deposition compounds may be used for example a mixture of the alginic acid or its salt with at least one of: collagen, gelatin, glycoprotein, proteoglycan, glycosaminoglycan, elastin or hyaluronic acid. [22] The mixture of deposition compounds may be used for example in their dissolved form as a mixed solution that may be used for deposition process. [23] The capillaries according to the invention may be formed under mild conditions, such as room temperature, neutral pH, and in the absence of any toxic substances. The capillaries may be consumable by for example human, mammal or other animal and available from non- animal sources. [24] Capillary alginate gels may be used for cultured meat production systems. They may provide contact guidance to the cells growth owing to the formation of aligned tissue along the length of self-assembled micro-capillaries. [25] Capillary material may be chemically functionalized to alter physicochemical and biological characteristics and properties. The ability to modify the properties of biomaterials is a highly compelling incentive for using capillaries in tissue engineering and regenerative medicine applications. [26] As cells do not have receptors able to recognize all materials, proliferation and differentiation of cells in the capillary environment may require signaling molecules and matrix interaction. The interaction of cells with biomaterials may be mediated through cellular receptors that recognize adhesion molecules at material surfaces. [27] Cell attachment peptides and other bioactive micro/macromolecules, such as arginylglycylaspartic acid (RGD), collagen, laminin, entactin, fibronectin, elastin or hyaluronic acid, may improve cellular adaptability to matrices. [28] Suitable cell lines that could be used for cultivation inside, outside or in the wall of capillary includes all mammalian cell lines, for example C2C12 cells, CHO-K1 cells, muscle cells, fibroblasts, myoblasts, adipocytes, macrophages, myosatellite cells, mesenchymal stem cells , induced pluripotent stem cells, embryonic stem cells, epithelial cells. Cell might be inserted as a monoclonal or polyclonal single-cell suspension, spheroids or on microcarriers. [29] The hardening tank 5 serves as a hardening reservoir for placement a hardening salt solution. The deposition compound solution of is exposed to a direct current in the electrolytic cell described above. The deposition compound solution may comprise any electrolyte, e.g. a polar solvent, such as water for dissolving the deposition compound. The deposition compound solution may aqueous solution. [30] In one aspect of the invention, the solution of alginate salt, for example the solution of sodium alginate in water, is exposed to a direct current in the electrolytic cell. The alginate is negatively charged in aqueous solution and due to the DC electric field migrates towards the positive central electrode 1, as shown in Fig.2, the positive sodium ions migrate towards the negative surrounding electrode 2. The alginate is not electroactive (not subjected to electrochemical transformations) and therefore accumulates on the positive central electrode 1 as a coating forming the capillary 3. [31] The resulting capillary 3 is depicted in Fig.3. The capillary 3 contains the capillary wall 6 and capillary channel 7. [32] The resulting capillary 3 may have an inner diameter equal, or substantially equal, to the outer diameter of positive central electrode 1. The thickness of the deposited layer depends on the applied potential, concentration of deposition compound in solution and electrodeposition duration. [33] The concentration of the deposition compound, for example alginate in the solution for electrodeposition may be in the range of 0.001% to 30% by weight, or in the range of 0.5% to 20%, or in the range of 1% to 10%. [34] The pH of the electrodeposition solution may be in the range of 2 to 10, or in the range of 3 to 9, or in the range of 6 to 8. [35] The capillary 3 formed due to the electrodeposition on the central electrode 1 may be transferred to the hardening solution, where the capillary 3 is hardened by crosslinking with any appropriate source of positive crosslinking ions, for example source of H + , Ca 2+ , Ba 2+ , Cu 2+ , Cr 2+ , Zn 2+ , Fe 2+ , Mn 2+ , Al 3+ , Fe 3+ . The source of positive crosslinking ion may be in the form of soluble salt. The source of positive crosslinking ions may be dissolved in a polar solvent, for example in water. The hardening solution may be formed for example of a solution of calcium chloride in water. [36] The concentration of the hardening salt in the hardening solution may be in the range of 0.001% to 50% by weight, or in the range of 0.5% to 20%, or in the range of 5% to 15%. [37] Instead of the hardening solution, a mixture of insoluble particles and a solvent may be used. The particles of insoluble compound may be for example calcium carbonate, magnesium chloride, magnesium carbonate, barium carbonate, ferrous carbonate, barium carbonate, or any other appropriate compound. The undissolved particles of insoluble compound, in this aspect of the invention, are dispersed in the solvent and dissociate in the area of the electrode, when the electric potential is applied to the electrolytic system. [38] The amount of insoluble hardening compound in the mixture with the solvent may be in the range of 0.001% to 50% by weight, or in the range of 0.5% to 20%, or in the range of 5% to 15%. [39] The hardening salt solution may be placed in the reservoir of the hardening salt solution formed by the hardening tank 5. The hardening tank 5 may be made of any appropriate material, for example glass, metal, e.g. stainless steel, or plastic materials, for example polypropylene, teflon, polystyrene, polyethylene, polyethylenethereftalate, HD/LD polyethylene, polyvinylchloride, acrylonitril butadien styrene, cycloolefin copolymers, high impact polystyrene, thermoplastic elastomer, polycarbonate, or polyoxymethylene. The hardening tank 5 may have a cylindrical shape, or any other appropriate shape. [40] The length of the capillary 3 prepared by the process according to the invention may be in the range of 1 mm to 10 m, or in the range of 2 mm to 1 m, or in the range of 5 mm to 20 cm. [41] The inner diameter of the capillary 3 prepared by the process according to the invention may be in the range of 50 µm to 10 cm, or in the range of 100 µm to 5 cm, or in the range of 1 mm to 1 cm. [42] The outer diameter of the capillary 3 prepared by the process according to the invention may be in the range of 51 µm to 11 cm, or in the range of 80 µm to 5 cm, or in the range of 100 µm to 5 mm. [43] The wall thickness of the capillary 3 prepared by the process according to the invention may be in the range of 1 µm to 10 mm, or in the range of 50 µm to 2 mm, or in the range of 100 µm to 0.8 mm. [44] The device for preparing the capillaries 3 may comprise a deposition compound solution reservoir. The device may comprise a hardening solution reservoir, for example formed by the hardening tank 5. [45] The surrounding electrode 2 may form at least part of a sheath of a deposition compound solution reservoir and the central electrode may be placed into deposition compound solution. [46] The at least part of the sheath of the deposition compound solution reservoir may be formed for example by an inner layer of the sheath of the deposition compound solution reservoir. [47] The device according to the invention may comprise more central electrodes 1 and surrounding electrodes 2 connected in parallel or in series according to a preset connection schema and purpose and settings of the processes, which may be for example the production of alginate capillaries 3 or another relevant electrodeponates, preparation of the connectors 8 for capillaries, etc. The arrangement of the electrodes in the device according to the invention may be with one surrounding electrode 2 and more central electrodes 1 placed in the deposition compound solution reservoir in the surrounding electrode 2. [48] The device for preparing the capillaries 3 may further comprise other components in order to supply electric current to the electrodes and to ensure the correct operation of the process. These components may be for example an electric current source, for example DC power supply, electric cables, wires, connectors, a setting and/or measuring device, for example formed by a digital multimeter, potentiometer, potentiostat, timer, central control unit and other optional appropriate components. [49] The central control unit may comprise a microprocessor, memory, including transitory or non-transitory memory, and software. The central control unit may control the duration of the electrolytic process, the electric current flow in the electrolytic system, the electric potential between the central electrode 1 and a surrounding electrode 2 based on measurement of the electric potential between the central electrode 1 and the reference electrode 4 and other variables. [50] The electrodes may be connected to a potentiostat, which may be connected to a computer with software that monitors and controls all functions of the system. [51] A commercially available device for setting and control of the electrolytic process may be used as well, for example “Gamry Reference 600” or any other appropriate commercially available device. [52] The electric current used in the deposition process may be in the range of 0.5 µA to 10 mA, or in the range of 10 µA to 5mA, or in the range of 0.1 mA to 1 mA. [53] The electric potential used in the deposition process may be in the range of 0.001 V to 20 V, or in the range of 1 V to 18V, or in the range of 1.2 V to 1.8 V. [54] The deposition time may be in the range of 0.001 min to 500 min, or in the range of 1 to 60 min, or in the range of 2 to 30 min. [55] The deposition rate may be in the range of 0.000005 mm/s to 0.1 mm/s, or in the range of 0.0001 mm/s to 0.01 mm/s, or in the range 0.0002 mm/s to 0.0003 mm/s. [56] The central electrode 1 serves for electrodeposition of the deposition compound, for example alginate. The central electrode 1 may have a diameter and shape equal, or substantially equal, to the desired inner diameter and shape of the deposited capillary 3 and a length at least equal to the length of the desired capillary 3. [57] The length of the central electrode 1 may be in the range of 1 mm to 10 m, or in the range of 2 mm to 1 m, or in the range of 5 mm to 20 cm. The length of central electrode 1 is considered to be the dimension in direction parallel to the central longitudinal axis of the central electrode 1. [58] The central electrode 1 may have a circular cross section or any other appropriate shape, for example triangular, square or rectangular cross section, or may be in any other appropriate shape. [59] The diameter of the central electrode 1 with a circular cross section may be in the range of 50 µm to 10 cm, or in the range of 100 µm to 5 cm, or in the range of 1 mm to 1 cm. In the case the central electrode 1 is in a shape other than in a shape with a circular cross section for example with triangular, square or rectangular cross section, the length of an edge of the shape may be in the range of 50 µm to 10 cm, or in the range of 100 µm to 5 cm, or in the range of 1 mm to 1 cm. [60] The central electrode 1 may be made of any appropriate electrically conductive material, for example metal, such as platinum, copper, silver, stainless steel and other metal materials. The central electrode 1 may be formed by a metal wire. [61] The surrounding electrode 2 may have a cylindrical shape including a bottom (lower base), wherein the surrounding electrode 2 may form at least part of a sheath of the deposition compound solution reservoir and the central electrode 1 may be placed into deposition compound solution. The at least part of the sheath of the deposition compound solution reservoir may be formed for example by an inner layer of the sheath of the deposition compound solution reservoir. The surrounding electrode 2 may form at least part of the sheath or inner surface of the of the deposition compound solution reservoir, as depicted in Fig.1. The deposition compound solution may comprise for example the solution of alginate. In another aspect of the invention, the surrounding electrode 2 may not form the at least part of sheath or inner surface of the deposition compound solution reservoir, for example the reservoir of alginate solution, and may instead be immersed in the solution of deposition compound and positioned to surround the central electrode 1. The surrounding electrode 2 may have a cylindrical shape without an upper and lower base (e.g. a hollow cylinder). The surrounding electrode 2 may have a cylindrical shape as mentioned, or may have any other appropriate shape, for example a cubic shape, cuboid shape, or a triangular, square or rectangular cross section, or any other appropriate shape. The surrounding electrode 2 may be in the form of a metal hollow cylinder. [62] The length of the surrounding electrode 2 may be in the range of 1 mm to 10 m, or in the range of 2 mm to 1 m, or in the range of 5 mm to 20 cm. The length of the surrounding electrode 2 is considered to be the dimension in direction parallel to the central longitudinal axis of the surrounding electrode 2. [63] The diameter of the surrounding electrode 2 may be in the range of 1 mm to 20 cm, or in the range of 2 mm to 10 cm, or in the range of 5 mm to 5 cm. [64] In the case wherein the surrounding electrode 2 has a shape other than a circular cross section, for example a triangular, square or rectangular cross section, the length of an edge of the surrounding electrode 2 may be in the range of 50 µm to 10 cm, or in the range of 100 µm to 5 cm, or in the range of 1 mm to 1 cm. [65] The wall thickness of the surrounding electrode 2 may be in the range of 20 µm to 1 cm or in the range of 100 µm to 500 µm, or in the range of 200 µm to 300 µm. [66] The surrounding electrode 2 may be made of any appropriate electrically conductive material, for example metal, such as platinum, copper, silver, stainless steel and other metal materials. [67] This advantageous arrangement of the central electrode 1 and surrounding electrode 2, wherein the surrounding electrode 2 is surrounding the central electrode 1, enables more homogenous distribution of dissociated ions of the deposition compound in the solution due to a more homogenous electrostatic field in the electrolyte, in comparison with the state of the art with two wire electrodes immersed in the solution of deposition compound, for example alginate. The process according to the invention provides a more homogenous structure of the deposited capillary 3. [68] The invention also relates to the capillary 3 produced by the above-mentioned process according to the invention. When the deposition is finished, the central electrode 1 and the deposited capillary 3 are introduced into a solution of hardening salt and the hardened deposit is subsequently separated from the central electrode 1. [69] The capillaries 3, for example alginate capillaries 3, prepared by the process according to the invention may undergo leaching of the positive crosslinking ions into the water or other solvent, where there is a lack of crosslinking ions. The proper storage and preservation of the capillaries 3 is desirable. A good option for storage of capillaries 3 is to store them in a solution of soluble salts of positive crosslinking ions. For example in the case of alginate capillaries 3 crosslinked with calcium ions, a solution of calcium chloride in water may be used for storage of the capillaries 3. The concentration of positive crosslinking cations may be in the range of 0.01 mmol/l to 1 mol/l, or in the range of 0.1 mmol/l to 0.5 mol/l, or in the range of 0.25 mmol/l to 100 mmol/l. [70] Separation of the hardened deposit from the central electrode 1 may be accomplished manually by separating the capillary 3 from the central electrode 1. For example a central electrode 1 made of platinum may have a smooth outer surface, in which case the deposit on the outer surface is easily separated. [71] A reference electrode 4 may be used within the system according to the invention. The reference electrode 4 may be inserted into the electrolytic system through the surrounding electrode 2 for voltage control between the central electrode 1 and the reference electrode 4. The reference electrode 4 may be connected to a potentiometer, configured to measure potential between the central electrode 1 and the reference electrode 4. The potential is a basic characteristic of the system, where applied voltage causes current flow. [72] A capillary 3 according to the invention may be used in many different aspects of industry. One possible use is in flow systems, for example as a capillary 3 through which a medium may diffuse around the capillary 3. Flow systems with capillaries 3 may be used for example for cell growth within biotechnological applications. Cells may be placed in the vicinity of the capillary 3, or cells may be placed on the capillary wall 6 or ingrown into the capillary wall 6. The medium may diffuse through the capillary wall 6 around the cells into the vicinity of capillary 3, or the cells may be placed around the capillary 3 and nutrients and gases, for example oxygen, may be delivered through the capillary wall 6. The capillary 3 may also be used to remove metabolites. The capillary 3, for example the alginate capillary 3 may be part of a hollow fiber system. Capillaries 3 may be used to form the hollow fibers. Cells may be placed inside the capillary 3 and a culture medium may diffuse through the capillary wall 6 to the inside of the capillary 3, where cells grow, proliferate or grow into a fiber structure or form other appropriate structures. [73] In one aspect of the invention, capillaries 3 according to the invention are connected to connectors 8, as shown in Fig.5. The usage of the connectors 8 is advantageous for example, when the capillaries 3 are used in flow systems, where it is important to provide reliable contact of the capillary 3 with a pump. The connectors 8 significantly facilitate the handling with the above mentioned flow systems, for example the connectors 8 facilitate handling with capillaries 3, improve the quality of flow properties through the capillary 3, the connection of the system to the medium, the insertion of cells into the system, etc., is improved. The connectors 8 may be prepared by electroplating of appropriate metal element, for example copper on the appropriate conductive material. The conductive material, for example stainless steel, or any other appropriate conductive material, may be immersed in an electroplating bath, for example a copper bath. The conductive material serves as the negative electrode 11 for deposition of electroplating ions. The negative electrode 11 may be for example in the form of needle, hollow cylinder or any other appropriate hollow form enabling forming the connector channel 9. The electroplating bath may comprise a salt of electroplating ions. The electroplating copper bath may comprise a copper salt, for example copper sulfate. The electroplating bath may comprise a solvent, for example water, and may further comprise other compounds, such as an acid, for example sulfuric acid, and ethanol. As the positive electrode 10, any appropriate conductive material may be used, for example a piece of copper wire may serve as the positive electrode 10. Using a direct current, the surface of the connector 8 is covered with a thin layer of electroplating ions, e.g. copper ions. The migration of positive copper ions towards the negative electrode 11 is depicted in Fig.4. [74] Part or all negative electrode11 may be covered with copper or other electroplating ions, and the electroplated parts of the negative electrode 11 may form connectors 8 for connection with alginate capillaries 3. [75] Fig.5 shows a capillary 3 connected to connectors 8 prepared by electroplating, the capillary channel 7 is connected to connector channel 9. [76] The process of preparing the connectors 8 by electroplating may be carried out before preparing the capillary 3 on the central electrode 1. The connectors 8, formed in the electroplating process, may be then connected to the central electrode 1 or deployed on the central electrode 1, which is serving for deposition and formation of the capillary 3 within the electrodeposition process. [77] When the central electrode 1 with the connectors 8 is connected to the electric field, the deposited electroplating ions, for example divalent copper ions are released and bind on the inner surface of the capillary 3, for example the alginate capillary 3, directly and thus ensure firm contact between the capillary wall 6 and the connector 8 itself. No strong bond is formed between the capillary wall 6 and the central electrode 1. The central electrode 1 may then be removed and a hollow space of the capillary 3 itself is created in its place forming the capillary channel 7. The result is the capillary 3 connected to connector 8, which is which facilitates its use. [78] The inner diameter of connector 8 may be in the range of 50 µm to 11 cm, or in the range of 100 µm to 5 cm, or in the range of 1 mm to 1 cm. [79] The outer diameter of connector 8 may be in the range of 150 µm to 13 cm, or in the range of 500 µm to 5 cm, or in the range of 1 mm to 1 cm. [80] The length of connector 8 may be in the range of 1 mm to 10 cm, or in the range of 0.5 cm to 8 cm, or in the range of 1cm to 3 cm. The length of connector 8 is considered to be the dimension in direction parallel to the central longitudinal axis of the connector 8. [81] A significant advantage of the method according to the invention is that by choosing the parameters used in its implementation, predetermined values of the resulting capillary 3, may be achieved. Thus, the internal diameter and shape of the capillary 3 is predetermined by the appropriate choice of the diameter and surface shape of the central electrode 1. The thickness of the alginate capillary wall 6 may be determined by interrupting the electrolytic process, when the thickness of the deposit on the central electrode 1 corresponding to the thickness of the capillary wall 6 has been reached, and may also affected by the set current and deposition time. The voltage may be adjusted so that the current is constant throughout the deposition. [82] The electrolytic system according to the invention may be set in chronopotentiometric mode, wherein chronopotentiometry is a galvanostatic method in which the current at the working central electrode 1 is held at a constant level for a given period of time. The working central electrode 1 potential and current are recorded as a function of time. [83] The density of this deposit may be influenced by the potential applied between the central electrode 1 and surrounding electrode 2. The thickness of the alginate capillary wall 6 may be determined by the length dimension of the central electrode 2 and may be the same along its entire length. [84] The important advantage of the novel process and device for production of capillaries 3 according to the present invention comprising arrangement of the central electrode 1 and a surrounding negative electrode 2 is that the process allows for production of more homogenous capillaries 3 in comparison with results of the processes and devices according to the state of the art. [85] The homogeneity of capillaries 3 may be characterized by the rate of diffusion through the capillary wall 6. According to the experiments, a homogeneous passage of fluorescently colored substances of different molecular sizes (fluorescein 300 Da, RNA 7200 Da) has been observed in the capillaries, for example the alginate capillaries 3 according to the invention. Based on the chosen deposition time and the applied voltage, it was possible to control the rate of passage of the active substances, which penetrated through the capillary pores in the homogeneously formed capillary wall 6. [86] In order to characterize, how large molecules may penetrate through the pores of the capillary walls 6, a solution of fluorescein (300 Da) may be used. The molar concentration may be in the range of 10 -2 to 10 -6 mol/l, or in the range of 10 -3 to 10 -5 mol/l. [87] Fluorescently labeled RNA (7200 Da) may be used for larger molecules, and the molar concentration may be in the range of 2∙10 −10 to 2∙10 -4 mol/l, or in the range of 2∙10 −9 to 2∙10 -5 mol/l. [88] The solution of fluorescently colored substance may be filled into a syringe connected to a piston pump, wherein a volumetric flow rate may be in the range of 0.5 μl/min to 500 μl/min, or in the range of 5 μl/min to 250 μl/min, or in the range of 20 μl/min to 100 μl/min. [89] The diffusion through the capillary wall 6 may be observed with a fluorescence microscope. [90] The diffusion coefficients, which characterize the diffusion rate of the capillaries, for example the alginate capillaries 3, may be in the range of 10 -17 m 2 /s to 10 -2 m 2 /s, or in the range of 10 -15 m 2 /s to 10 -5 m 2 /s, or in the range of 10 -10 m 2 /s to 10 -8 m 2 /s. [91] The greater thickness of the capillary 3 slows down the diffusion and therefore the transport of the fluorescently colored substance, for example fluorescein or RNA, across the capillary wall 6 is slower. The results captured in the photographs from the fluorescence microscope confirmed this assumption. The diffusion was lower for capillaries 3 made at higher voltages. The higher voltage used in the electrodeposition process may cause the formation of the capillaries 3 with the capillary walls 6 with higher density and smaller pores. [92] Image analysis of individual photo sequences from the fluorescence microscope may be performed, for example using Matlab software from MathWorks. This analysis may monitor the fluorescence intensity as a function of the spatial coordinate perpendicular to the capillary 3 itself. [93] Another parameter of the capillaries 3 according to the invention, corresponding to mechanical properties, is the strength of the material. This parameter may be important, for example when capillaries 3 are used in mechanically stressed systems, such as blood-vessels. The strength of the capillaries 3 may be measured on a rheometer. The capillaries 3 according to the invention had a significantly higher Young's modulus, in comparison with capillaries made according to state of the art processes, due to homogenous alginate deposition. The Young’s modulus of the capillaries 3 according to the invention may be in the range of 2 to 1000 kPa, or in the range of 5 to 800 kPa, or in the range of 10 to 500 kPa. [94] In to one innovative aspect of the invention, the electrolytic system, as depicted in Fig.1, was prepared. The system consisted of the positive central electrode 1 formed by a platinum wire and the stainless steel cylindrical negative surrounding electrode 2. The negative surrounding electrode 2 was forming a sheath of the alginate solution reservoir. The reference electrode 4 was inserted into the electrolytic system through the negative surrounding electrode 2. The system was connected to a commercially available potentiostat “Gamry Reference 600” for regulation and controlling the process. The process of alginate deposition was performed at neutral pH. A solution of sodium alginate with concentration 1.5 % by weight and a solution of calcium chloride with concentration 10% by weight were prepared.20 ml of the sodium alginate solution was poured into a cylindrical stainless steel negative surrounding electrode 2, with diameter 20.5 mm and length 90 mm.50 ml of calcium chloride solution was poured into a plastic hardening tank 5. The positive central electrode 1, comprising a platinum wire with a circular cross-section with a diameter of 500 µm and a smooth surface, was placed into the negative surrounding electrode 2 by immersion in a solution of sodium alginate so that its position corresponded to the central axis of the negative surrounding electrode 2. Subsequently, using the potentiostat “Gamry Reference 600”, deposition was started in the chronopotentiometric mode. The electrodeposition of the alginate on the positive central electrode 1 took place at a current load of 0.5 mA for 10 minutes. At the end of deposition, the positive central electrode 1 with the sodium alginate deposit was immersed into a hardening tank 5 with a calcium chloride solution by simple manipulation of the apparatus table, where it was left for two minutes. In this aspect of the invention, a layer of calcium alginate deposit with a thickness of 400 µm was formed on the positive central electrode 1, forming an alginate capillary 3 with an inner diameter of 500 µm, an outer diameter of 900 µm and a length of 5 cm. The alginate capillary 3 was then carefully withdrawn from the positive central electrode 1 by pulling in the longitudinal direction. [95] In other aspect of the invention, a connector 8 was prepared by copper electroplating on the stainless steel needle used as the negative electrode 11 for deposition of copper ions. The negative electrode 11 was immersed in a copper bath comprising 250 g of copper sulfate, 75 ml of sulfuric acid, 50 ml of ethanol and 1 l of distilled water. A piece of copper wire was used as the positive electrode 10. After using a direct current, the surface of the negative electrode 11 was covered with a thin layer of copper ions. [96] In one aspect of the invention, the homogeneity of alginate capillaries 3 was characterized by monitoring diffusion through the capillary wall 6. According to the experiments, a homogeneous passage of fluorescently colored substances of different molecular sizes (fluorescein 300 Da, RNA 7200 Da) through the capillary wall 6 was observed. Based on the chosen deposition time and the applied voltage, it was possible to control the rate of passage of the active substances, which penetrated through the alginate pores in the homogeneously formed capillary wall 6. In order to characterize how large molecules penetrate the pores of the walls of alginate capillaries 3, a solution of fluorescein (300 Da) with a molar concentration of 10 −4 mol/l was prepared. The same experiments were performed for larger molecules of fluorescently labeled RNA (7200 Da). A solution with a concentration of 2 ∙ 10 −7 mol/l was used. The solution was filled into a syringe, which was connected to a piston pump and set at a volumetric flow rate of 50 μl/min. The diffusion through capillary wall 6 was observed with a fluorescence microscope and a single photograph of the system was taken every 15 seconds for 30 minutes. [97] The greater thickness of the capillaries 3 slowed down the diffusion and therefore the transport of fluorescein and RNA across the capillary wall 6 was slower. The results captured in the photographs confirmed this assumption; the diffusion was weakened for capillaries 6 made at higher voltages. The higher voltage caused formation of capillaries 3 with higher density and smaller pores. [98] The image analysis of individual photo sequences was performed using Matlab software from MathWorks. This analysis monitors the fluorescence intensity as a function of the spatial coordinate perpendicular to the capillary itself. The image analysis confirmed a homogenous structure of the alginate capillaries according to the invention. [99] From the above mentioned, it is obvious, that the device and process according to the invention allow advantageous and efficient way of preparing the capillaries with homogeneous structure, as it was confirmed by experiments, for example by monitoring the diffusion through the capillary wall 6 using fluorescently colored substances observed in a fluorescence microscope.