3D printer, extruder, injection moulding machine, compression moulding machine, method for 3D printing of a biological material and biological material produced using the method

公开(公告)号:
EP3653361B1
公开(公告)日:
2024-08-14
申请号:
EP2019181265
申请日:
2019-06-19
授权日:
2024-08-14
受理局:
欧洲专利局
专利类型:
授权发明
简单法律状态:
有效
法律状态/事件:
授权 | 权利转移
IPC分类号:
B29C64/112 | B29C64/124 | C08J3/24 | B29C48/00 | B29C45/00 | B29C43/00 | B33Y10/00 | B33Y30/00 | B33Y70/00 | A61L27/12 | A61L27/20 | A61L27/22 | A61L27/38 | A61L27/50
战略新兴产业分类:
前沿新材料
国民经济行业分类号:
C3523 | C3522
当前申请(专利权)人:
FRAUNHOFER-GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
原始申请(专利权)人:
FRAUNHOFER-GESELLSCHAFT ZUR FÖRDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
当前申请(专利权)人地址:
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工商统一社会信用代码:
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工商登记状态:
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工商注册地址:
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工商成立日期:
1949-01-01
工商企业类型:
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发明人:
SCHWARZ, DR. OLIVER | WENDLANDT, TIM
代理机构:
PFENNING, MEINIG & PARTNER MBB
代理人:
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摘要:
Es wird ein 3D-Drucker (1) bereitgestellt, der eine Kammer (2), eine Dosiereinheit (3) zum Inkontaktbringen von mindestens einem Enzym (5) mit einem in der Kammer befindlichen Material (10) und eine Steuerungseinheit enthält. Der 3D-Drucker (1) zeichnet sich dadurch aus, dass die Dosiereinheit (3) mindestens ein Enzym (5) enthält, das sich zur Katalyse einer kovalenten (chemischen) Verbindung von biologischem Material eignet und die Steuerungseinheit dazu konfiguriert ist, das Inkontaktbringen des mindestens einen Enzyms mit einem in der Kammer befindlichen biologischen Material (10) zu veranlassen. Über den erfindungsgemäßen 3D-Drucker können auf einfache und schnelle Art und Weise dreidimensionale biologische Materialien gedruckt werden, die gegenüber vergleichbaren biologischen Materialien verbesserte (biologische, chemische und mechanische) Eigenschaften aufweisen. Ein entsprechendes Verfahren zum 3D-Druck eines biologischen Materials wird vorgestellt und ein über das Verfahren herstellbares bzw. hergestelltes biologisches Material bereitgestellt.
技术问题语段:
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技术功效语段:
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权利要求:
1. A 3D printer (1), comprising: a) a chamber (2), optionally containing a biological material (6); b) a dosing unit (3) for bringing at least one enzyme (5) in contact with a material present in the chamber (2); and c) a control unit (4), characterized in that the dosing unit (3) contains at least one enzyme (5) suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material, and the control unit (4) is configured to prompt the process of bringing the at least one enzyme (5) in contact with a biological material present in the chamber (2). 2. The 3D printer (1) according to claim 1, characterized in that the chamber (2) i) comprises a temperature sensor (11) for measuring a temperature in the chamber (2); and/or ii) can be controlled in terms of the temperature, preferably to a temperature in the range of 30 to 60°C, particularly preferably to a temperature in the range of 30 to 50°C, the chamber (2) in particular comprising a heater (7); and/or iii) comprises a pressure sensor for measuring a pressure in the chamber (2); and/or iv) can be pressurized, preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, the chamber (2) in particular being connected to a compressed air source; and/or v) comprises an air moisture sensor for measuring an air moisture in the chamber (2); and/or vi) comprises a material moisture sensor for measuring a moisture of the material in the chamber (2), preferably a material moisture sensor based on an electrical resistance measurement; and/or vii) is settable to a certain moisture level, the chamber (2) in particular being connected to a water source or water vapor source; and/or viii) is suitable of being dehumidified, the chamber (2) in particular being connected to a condenser and/or a desiccant. 3. The 3D printer (1) according to any one of the preceding claims, characterized in that the dosing unit (3) i) is designed so as to be movable in the x direction, y direction and z direction, preferably by way of a Cartesian kinematic system, and particularly preferably is designed so as to be movable in the direction of a bottom (10) of the chamber (2); and/or ii) is connected to an electrical voltage source for delivering voltage to the dosing unit (3) and/or is connected to an ultrasound source, the voltage source and/or ultrasound source preferably being suitable for effectuating a release of the at least one enzyme (5) in biological cells, preferably by way of lysis of the biological cells; and/or iii) is fluidically connected to a reservoir which is suitable for adding a substance to the dosing unit (3), the substance preferably being suitable for effectuating a production and/or release of the at least one enzyme (5) in biological cells, preferably by way of a transport of the substance out of the biological cells and/or lysis of the biological cells; and/or iv) comprises a spray head in the direction of the chamber (2); and/or v) comprises a temperature sensor for measuring a temperature in the dosing unit (3); and/or vi) is controllable in terms of the temperature, preferably to a temperature of 1 to 20°C, preferably in the range of 2 to 10°C, particularly preferably in the range of 3°C to 5°C, the dosing unit (3) in particular comprising a cooling unit; and/or vii) comprises a pressure sensor for measuring a pressure in the dosing unit (3); and/or viii) is suitable of being pressurized, preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, the dosing unit (3) in particular being connected to a compressed air source; and/or ix) comprises an air moisture sensor for measuring an air moisture in the dosing unit (3); and/or x) is settable to a certain moisture level, the dosing unit (3) in particular being connected to a water source or water vapor source; and/or xi) comprises a pH meter; and/or xii) is connected to a UV/Vis spectrometer, which is suitable for measuring light absorption of a medium present in the interior of the dosing unit (3), the UV/Vis spectrometer preferably being configured to measure an absorption at a wavelength in the range of 240 to 750 nm, preferably 280 nm to 700 nm; and/or xiii) comprises a fill level sensor, which is suitable for measuring a volume of an enzyme solution in the dosing unit (3); and/or xiv) contains molecules which facilitate the covalent bonding of the biological material, preferably a molecule selected from the group consisting of enzyme substrates, enzyme cofactors, chemically activated molecules and mixtures thereof, the enzyme substrates in particular being selected from the group consisting of carbohydrates, proteins, peptides, nucleic acids, lipids, phenols, phenylpropanoids and mixtures thereof, optionally monomers, oligomers and/or polymers of these molecules, and/or the enzyme cofactor in particular being lysyl tyrosylquinone and/or the enzyme substrates in particular being chemically activated molecules; and/or xv) does not contain natural fibers, preferably does not contain biological material (6) that will covalently bond by a reaction catalyzed by the at least one enzyme (5); and/or xvi) does not contain hygroscopic mineral, and preferably does not contain hygroscopic material; and/or xvii) comprises a openable closure in the direction of the chamber (2), the control unit (4) preferably being configured to prompt the openable closure to be opened, particularly preferably based on a command of a user. 4. The 3D printer (1) according to any one of the preceding claims, characterized in that the at least one enzyme (5) i) is present in dissolved or solid form, preferably dissolved in an aqueous buffer solution or an aqueous fermentation medium or in the form of a solid powder; and/or ii) is contained in solid filaments and/or is immobilized in solid filaments; and/or iii) is contained in biological cells and/or is contained in the cell membrane of biological cells, the biological cells preferably being selected from the group consisting of prokaryotic cells, eukaryotic cells and mixtures thereof, particularly preferably selected from the group consisting of bacterial cells, archaean cells, fungal, plant and animal cells and mixtures thereof; and/or iv) is present in an interior of the dosing unit (3); and/or v) is present in the chamber (2); and/or vi) is immobilized on an outer wall of the dosing unit (3) which faces the chamber (2); and/or vii) is selected from the group consisting of laccases, tyrosinase, peroxidases, phenoloxidases, amino acid oxidases, transglutaminases and mixtures thereof. 5. The 3D printer (1) according to any one of the preceding claims, characterized in that the control unit (4) is configured i) to regulate a temperature of the chamber (2) and/or dosing unit (3), preferably to a temperature in the range of 30 to 60°C, particularly preferably of 30 to 50°C for the chamber (2) and/or to a temperature in the range of 1 to 20°C, preferably of 2 to 10°C, particularly preferably of 3 to 5°C for the dosing unit (3), in particular by controlling a heater (7) and/or cooling unit (8) of the chamber (2) and/or dosing unit (3); and/or ii) to regulate a pressure in the chamber (2) and/or dosing unit (3), preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, in particular by controlling a compressed air source connected to the chamber (2) and/or dosing unit (3); and/or iii) to regulate a moisture level in the chamber (2) and/or dosing unit (3), in particular via a water source or water vapor source connected to the chamber (2) and/or dosing unit (3); and/or iv) to determine the pH value of a medium in which the at least one enzyme (5) is present, in particular by way of a pH meter of the dosing unit (3); and/or v) to determine a concentration of the at least one enzyme (5) in a medium in which the at least one enzyme (5) is present, in particular by way of a UV spectrometer connected to the dosing unit (3); and/or vi) to determine a volume of an enzyme solution in the dosing unit (3), in particular by way of a fill level sensor contained in the dosing unit (3); and/or vii) to determine an exposure time of a biological material (6) present in the chamber (2) to the at least one enzyme (5). 6. The 3D printer (1) according to any one of the preceding claims, characterized in that it comprises an irradiation unit (9), which is suitable for irradiating electromagnetic radiation into the chamber (2), the irradiation unit (9) preferably being suitable for a) irradiating infrared light into the chamber (2), the irradiation unit (9) particularly preferably being selected from the group consisting of IR lamp, IR laser and combinations thereof; and/or b) irradiating UV light into the chamber (2), the irradiation unit (9) particularly preferably being selected from the group consisting of UV lamp, UV laser and combinations thereof, the control unit (4) being in particular configured to have the biological material irradiated at least regionally by way of the irradiation unit (9) for a certain time after the at least one enzyme (5) has been brought in contact with the biological material present in the chamber (2) so that the at least one enzyme (5) is activated or deactivated. 7. A method for 3D printing a biological material is, comprising the following steps: a) providing a biological material in a chamber (2) of a 3D printer (1), the chamber being suitable for receiving biological material; b) providing a dosing unit (3) suitable for bringing at least one enzyme (5) in contact with a material present in the chamber (2); and c) providing a control unit (4) in the 3D printer (1), characterized in that the dosing unit (3) is furnished with at least one enzyme (5) suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material, and the control unit (4) prompts the process of bringing the at least one enzyme (5) in contact with the biological material present in the chamber (2). 8. The method according to claim 7, characterized in that the chamber (2) i) comprises a temperature sensor for measuring a temperature in the chamber (2); and/or ii) is controlled in terms of the temperature, preferably to a temperature in the range of 30 to 60°C, particularly preferably is controlled to a temperature in the range of 30 to 50°C, in particular by way of a heater (7) contained in the chamber (2); and/or iii) comprises a pressure sensor for measuring a pressure in the chamber (2); and/or iv) is pressurized, preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, in particular by way of a compressed air source connected to the chamber (2); and/or v) comprises an air moisture sensor for measuring an air moisture in the chamber (2); and/or vi) comprises a material moisture sensor for measuring a moisture of the material in the chamber (2), preferably material moisture sensor based on an electrical resistance measurement; and/or vii) is set to a particular moisture level, in particular by way of a water source or water vapor source to which the chamber (2) is connected. 9. The method according to either claim 7 or 8, characterized in that the dosing unit (3) i) is moved in the x direction, y direction and z direction, preferably by way of a Cartesian kinematic system, and particularly preferably in the direction of a bottom (10) of the chamber (2); and/or ii) is connected to an electrical voltage source for delivering voltage to the dosing unit (3) and/or is connected to an ultrasound source, the voltage source and/or ultrasound source preferably being used to effectuate a release of the at least one enzyme (5) in biological cells, preferably by way of lysis of the biological cells; and/or iii) is fluidically connected to a reservoir which is suitable for adding a substance to the dosing unit (3), the substance preferably being suitable for effectuating a production and/or release of the at least one enzyme (5) in biological cells, preferably by way of a transport of the substance out of the biological cells and/or lysis of the biological cells; and/or iv) is equipped with a spray head in the direction of the chamber (2); and/or v) is equipped with a temperature sensor (12) for measuring a temperature in the dosing unit (3); and/or vi) is controllable or is controlled in terms of the temperature, preferably is controllable or is controlled to a temperature in the range of 1 to 20°C, preferably of 2 to 10°C, particularly preferably of 3 to 5°C, the dosing unit (3) in particular comprising a cooling unit; and/or vii) is equipped with a pressure sensor for measuring a pressure in the dosing unit (3); and/or viii) is suitable to be pressurized or is pressurized, preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, in particular by way of compressed air from a compressed air source to which the dosing unit (3) is connected or is being connected; and/or ix) is equipped with an air moisture sensor for measuring an air moisture in the dosing unit (3); and/or x) is settable or be set to a certain moisture level, the dosing unit (3) in particular by way of water and/or water vapor from a water source and/or water vapor source to which the dosing unit (3) is being connected; and/or xi) is equipped with a pH meter; and/or xii) is connected to a UV/Vis spectrometer and a measurement of a UV/Vis absorption of a medium present in the interior of the dosing unit (3) is carried out, an absorption being measured at a wavelength in the range of 240 nm to 750 nm, preferably 280 to 700 nm; and/or xiii) is equipped with a fill level sensor, which is suitable for measuring a volume of an enzyme solution in the dosing unit (3); and/or xiv) is furnished with molecules which facilitate the covalent bonding of the biological material, preferably a molecule selected from the group consisting of enzyme substrates, enzyme cofactors, chemically activated molecules and mixtures thereof, the enzyme substrates in particular being selected from carbohydrates, proteins, peptides, nucleic acids, lipids, phenols, phenylpropanoids and mixtures thereof, optionally monomers, oligomers and/or polymers of these molecules, the enzyme cofactor in particular being lysyl tyrosylquinone and/or the enzyme substrates in particular being chemically activated molecules; and/or xv) does not contain natural fibers, preferably does not contain biological material (6) that will covalently bond by a reaction catalyzed by the at least one enzyme (5); xvi) does not contain hygroscopic mineral, and preferably does not contain hygroscopic material; and/or xvii) comprises a openable closure in the direction of the chamber (2), the control unit (4) prompting the openable closure to be opened, particularly preferably based on a command of a user. 10. The method according to any one of claims 7 to 9, characterized in that the at least one enzyme (5) i) is present in dissolved or solid form, preferably dissolved in an aqueous buffer solution or an aqueous fermentation medium or in the form of a solid powder; and/or ii) is contained in solid filaments and/or is immobilized in solid filaments; and/or iii) is contained in biological cells and/or is contained in the cell membrane of biological cells, the biological cells preferably being selected from the group consisting of prokaryotic cells, eukaryotic cells and mixtures thereof, particularly preferably selected from the group consisting of bacterial cells, archaean cells, fungal, plant or animal cells and mixtures thereof; and/or iv) is provided in an interior of the dosing unit (3); and/or v) is provided in the chamber (2); and/or vi) is provided immobilized on an outer wall of the dosing unit (3) which faces the chamber (2); and/or vii) is selected from the group consisting of laccases, tyrosinase, peroxidases, phenoloxidases, amino acid oxidases, transglutaminases and mixtures thereof. 11. The method according to any one of claims 7 to 10, characterized in that the control unit (4) i) is used to regulate a temperature of the chamber (2) and/or dosing unit (3), preferably to a temperature in the range of 30 to 60°C, particularly preferably of 30 to 50°C for the chamber (2) and/or to a temperature in the range of 1 to 20°C, preferably of 2 to 10°C, particularly preferably of 3 to 5°C, for the dosing unit (3), in particular by controlling a heater (7) and/or cooling unit (8) of the chamber (2) and/or dosing unit (3); ii) is used to regulate a pressure in the chamber (2) and/or dosing unit (3), preferably to a pressure in the range of 0.1 to 20 bar, preferably 0.5 to 15 bar, particularly preferably 1 to 10 bar, in particular by controlling a compressed air source connected to the chamber (2) and/or dosing unit (3); and/or iii) is used to regulate a moisture level in the chamber (2) and/or dosing unit (3), in particular via a water source or water vapor source connected to the chamber (2) and/or dosing unit (3); and/or iv) is used to determine the pH value of a medium in which the at least one enzyme (5) is present, in particular by way of a pH meter of the dosing unit (3); and/or v) is used to determine a concentration of the at least one enzyme (5) in a medium in which the at least one enzyme (5) is present, in particular by way of a UV spectrometer connected to the dosing unit (3); and/or vi) is used to determine a volume of an enzyme solution in the dosing unit (3), in particular by way of a fill level sensor contained in the dosing unit (3); and/or vii) is used to determine an exposure time of a biological material (6) present in the chamber (2) to the at least one enzyme (5). 12. The method according to any one of claims 7 to 11, characterized in that the 3D printer (1) is equipped with an irradiation unit (9), which is suitable for irradiating electromagnetic radiation into the chamber (2), the irradiation unit (9) preferably being suitable for a) irradiating infrared light into the chamber (2), the irradiation unit (9) particularly preferably being selected from the group consisting of IR lamp, IR laser and combinations thereof; and/or b) irradiating UV light into the chamber (2), the irradiation unit (9) particularly preferably being selected from the group consisting of UV lamp, UV laser and combinations thereof, the biological material being irradiated at least regionally by way of the irradiation unit (9) for a certain time after the at least one enzyme (5) has been brought in contact with the biological material present in the chamber (2) so that at least one enzyme (5) is activated or deactivated. 13. An extruder, an injection molding machine or a compression molding machine, comprising: a) a chamber for receiving material, optionally containing a biological material; b) a dosing unit for bringing at least one enzyme in contact with a material present in the chamber; and c) a control unit, characterized in that the dosing unit contains at least one enzyme suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material, and the control unit is configured to prompt the process of bringing the at least one enzyme in contact with a biological material present in the chamber in such a manner that the total amount of enzyme is in a range of 0.001 wt.% to <0.01 wt.%, based on the total amount of biological material and enzyme in the chamber. 14. A method for extruding, for compression molding or for injection molding of a biological material, comprising the following steps: a) providing a biological material in a chamber of an extruder, of a compression molding machine or an injection molding machine, the chamber being suitable for receiving biological material; b) providing a dosing unit suitable for bringing at least one enzyme in contact with the biological material present in the chamber; and c) providing a control unit, characterized in that the dosing unit is furnished with at least one enzyme suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material, and the control unit prompts the process of bringing the at least one enzyme in contact with the biological material present in the chamber in such a manner that the total amount of enzyme is in a range of 0.001 wt.% to <0.01 wt.%, based on the total amount of biological material and enzyme in the chamber. 15. A biological material, produced by way of a method according to any one of claims 7 to 12 in which a plurality of layers of biological material were bonded to one another by enzyme action, characterized in that the biological material has a layer composition, the enzyme which is suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material being present between the layers of the bonded biological material, the total amount of the enzyme which is suitable for catalyzing a reaction suitable for effectuating a covalent bonding of biological material being in a range of 0.001 wt.% to <0.01 wt.%, based on the total amount of enzyme and biological material.
技术领域:
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背景技术:
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发明内容:
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具体实施方式:
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