WO2017113156A1 - 生物打印机打印模块及生物打印机 - Google Patents

生物打印机打印模块及生物打印机 Download PDF

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Publication number
WO2017113156A1
WO2017113156A1 PCT/CN2015/099795 CN2015099795W WO2017113156A1 WO 2017113156 A1 WO2017113156 A1 WO 2017113156A1 CN 2015099795 W CN2015099795 W CN 2015099795W WO 2017113156 A1 WO2017113156 A1 WO 2017113156A1
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WO
WIPO (PCT)
Prior art keywords
nutrient solution
rotating rod
printing module
bioprinter
module according
Prior art date
Application number
PCT/CN2015/099795
Other languages
English (en)
French (fr)
Inventor
温学敏
李意军
Original Assignee
四川蓝光英诺生物科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by 四川蓝光英诺生物科技股份有限公司 filed Critical 四川蓝光英诺生物科技股份有限公司
Priority to PCT/CN2015/099795 priority Critical patent/WO2017113156A1/zh
Priority to US16/067,570 priority patent/US20190010447A1/en
Priority to EP15911785.2A priority patent/EP3398774B1/en
Publication of WO2017113156A1 publication Critical patent/WO2017113156A1/zh

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00Apparatus for additive manufacturing; Details thereof or accessories therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0062General methods for three-dimensional culture
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • A61F2/062Apparatus for the production of blood vessels made from natural tissue or with layers of living cells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/245Platforms or substrates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y40/00Auxiliary operations or equipment, e.g. for material handling
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00Data acquisition or data processing for additive manufacturing
    • B33Y50/02Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00Tissue, human, animal or plant cell, or virus culture apparatus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • A61F2002/30985Designing or manufacturing processes using three dimensional printing [3DP]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001Designing or manufacturing processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/227Driving means
    • B29C64/241Driving means for rotary motion
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/40Manifolds; Distribution pieces

Definitions

  • the present invention relates to the field of bioprinting technology, and in particular, to a bioprinter printing module and a bioprinter.
  • Biological 3D printing refers to the printing of biological materials (including natural biological materials, synthetic biological materials or cell solutions) into a three-dimensional structure of design through the principle and method of 3D printing, which is different from ordinary 3D printing technology and production of biological 3D printing technology.
  • Biological tissues or organs also have certain biological functions, which need to provide conditions for the further growth of cells and tissues. It is precisely because of the above characteristics that biological 3D printing technology is developing and facing many specific technical problems.
  • cell 3D printing technology the technology of using cells as printing materials is called cell 3D printing technology. People can use cell and biocompatible materials to make bio ink, move the nozzle and spray the bio ink, and control it through the program. The nozzle moves to print the bio-ink according to a preset target to be printed according to the three-dimensional digital model of the object.
  • bio-3D printing methods are commonly used to make cavity active tissues such as artificial blood vessels, which provides a way to treat many vascular diseases.
  • the printer for printing blood vessels in the prior art includes a rotating rod and a printing nozzle.
  • the length and size of the rotating rod are designed according to the shape and size of the blood vessel to be printed.
  • One end of the rotating rod is supported by the bracket and driven by the motor, and the other end is suspended.
  • the print head is located above the rotating rod and is movable relative to the surface of the rotating rod. During operation, the print head sprays bio-ink onto the surface of the rotating rod to form biological vascular tissue.
  • the rotating rod with vascular tissue is removed and placed in a biological incubator, and various growth factors and differentiation-promoting factors are added. Accelerate the vascular tissue structure and various physiological functions to mature and obtain the required blood vessels.
  • a first aspect of the present invention provides a bioprinter printing module, comprising: a support member and a rotary lever provided with a nutrient supply interface, the rotary lever being rotatably supported on the support member
  • the surface of the rotating rod is for receiving the biological ink provided by the printing nozzle
  • the rotating rod comprises a hollow pipe section having a central through hole
  • the pipe wall of the hollow pipe section is provided with a permeating hole communicating with the central through hole
  • the nutrient solution supply interface communicates with a central through hole of the rotating rod to introduce an external nutrient solution into the rotating rod.
  • the support member includes a support portion and a nutrient solution delivery portion
  • the nutrient solution supply interface is disposed in a circumferential direction of the rotating rod
  • the rotating rod is rotatably supported on the support portion
  • the nutrient solution conveying portion is sleeved on the rotating rod and has a conveying portion interface
  • the nutrient liquid conveying portion is provided with a conversion cavity that is in communication with the conveying portion and surrounds the rotating rod in a circumferential direction.
  • the nutrient solution supply interface communicates with the central through hole and the conversion cavity.
  • a sealing device is further provided, the sealing device being disposed between the nutrient solution conveying portion and the rotating rod.
  • a nutrient solution tank for supplying nutrient solution to the rotating rod, the nutrient solution tank having a tank interface, the tank interface being connected to the conveying portion by a nutrient solution conveying device, the nutrient solution
  • the conveying device is configured to control the nutrient solution in the nutrient solution tank to enter the rotating rod.
  • the nutrient solution delivery device is further configured to control the flow rate and flow of the nutrient solution
  • the bio-printer module further includes a nutrient solution control device connected in series with the nutrient solution delivery device, the slot interface and the delivery portion interface are connected by the nutrient solution delivery device and the nutrient solution control device, The nutrient solution control device is used to control the flow rate and flow rate of the nutrient solution.
  • a temperature detecting means for detecting the temperature of the nutrient solution or a nutrient solution temperature controlling means for controlling the temperature of the nutrient solution is further included.
  • the nutrient solution temperature control device includes: a semiconductor refrigerating sheet, a temperature controller, and a heat dissipating device, wherein the semiconductor refrigerating sheet is disposed at a bottom of the nutrient solution tank for controlling under the control of the temperature controller
  • the nutrient solution tank is heated or cooled
  • the semiconductor refrigeration sheet has a temperature control end and a non-temperature control end, the temperature control end is disposed toward the nutrient solution tank, and the non-temperature control end is disposed toward the heat dissipation device .
  • a heat conducting plate or a heat equalizing plate is disposed between the nutrient solution tank and the semiconductor refrigeration sheet.
  • the rotating rod further includes a transfer section, the nutrient supply interface is disposed on the transfer section, and the transfer section is detachably coaxially disposed at an end of the hollow pipe section.
  • the adapter segment is rotatably supported on the support member, and the adapter segment can be driven to drive the hollow tube segment to rotate.
  • a connector is further included, and the transition section is connected to an end of the hollow pipe section through the connector.
  • the connector is a threaded connector.
  • a hollow portion communicating with the nutrient solution supply interface is disposed in the transfer section, and the hollow portion communicates with a central through hole of the hollow pipe segment to introduce nutrient solution into the hollow portion through the hollow portion Hollow pipe section.
  • the transfer section is sealingly connected to an end of the hollow pipe section.
  • a servo motor is further included, the servo motor being arranged in parallel with the rotating rod, and the servo motor and the rotating rod are connected by a timing pulley and a timing belt.
  • a second aspect of the present invention provides a bioprinter comprising the printing module described in the above embodiments.
  • the bioprinter printing module of the present invention is rotated in the
  • the nutrient supply interface and the permeation hole are arranged on the rotating rod, and the external nutrient solution can be introduced into the rotating rod through the nutrient supply interface during the printing process, and then exuded from the permeation hole to supply the cells and the biological tubular tissue on the rotating rod.
  • the external nutrient solution can be introduced into the rotating rod through the nutrient supply interface during the printing process, and then exuded from the permeation hole to supply the cells and the biological tubular tissue on the rotating rod.
  • FIG. 1 is a three-dimensional structural diagram of an embodiment of a bioprinter printing module of the present invention
  • FIG. 2 is a top plan view of the bioprinter printing module of FIG. 1;
  • Figure 3 is a cross-sectional view of the bioprinter print module of Figure 2 taken along line A-A;
  • FIG. 4 is a partial enlarged view B of the bioprinter printing module shown in FIG. 2.
  • the present invention provides a bioprinter printing module, as shown in FIGS. 1 to 4, comprising: a support member and a rotating rod provided with a nutrient supply interface 14, the rotating rod being rotatably supported on the support member, the rotating rod
  • the surface is for receiving the biological ink provided by the printing nozzle
  • the rotating rod comprises a hollow tube section 22 having a central through hole
  • the tube wall of the hollow tube section 22 is provided with a permeation hole 26 communicating with the central through hole, the nutrient supply interface and The central through hole of the rotating rod communicates to introduce the external nutrient solution into the rotating rod.
  • the biological tubular tissue can be a blood vessel.
  • the nutrient solution can be used in a single-use manner as needed, and biosafety can be improved.
  • the bioprinter printing module of the embodiment of the invention can introduce the external nutrient solution into the inside of the rotating rod through the nutrient solution supply interface 14 during the printing process, and then ooze out from the permeation hole 26 to supply the cells and the biological tubular tissue on the rotating rod. In order to protect cells and biological tubular tissues, thereby improving cell survival and biological functions.
  • the rotating rod in this embodiment may include only the hollow pipe section 22, or only one end of the hollow pipe section 22 may be provided with a transfer section, or the structure shown in FIG. 3 may be adopted, that is, the rotating rod includes a hollow pipe section. 22 and a transfer section 15 and a transfer section 24 connected at both ends of the hollow pipe section 22, the transfer section 15 and the transfer section 24 are a first rotary adapter and a second rotary adapter, respectively.
  • the embodiments given below is described by taking a rotating rod of the composition shown in FIG. 3 as an example.
  • the nutrient solution can be introduced from the end of the rotating rod through the conveying pipe.
  • the central through hole inside the rotating rod needs to be penetrated in the axial direction, and a dynamic and static conversion joint is needed at the connection between the conveying pipe and the rotating rod.
  • the nutrient solution supply interface 14 is provided in the circumferential direction of the rotary lever.
  • the rotating rod includes a hollow pipe section 22 and a transition section 15 and a transition section 24 connected at both ends of the hollow pipe section 22, and the transition section 15 and the transition section 24 are a first rotation adapter and a second rotation, respectively. adapter.
  • the nutrient solution supply interface 14 is disposed in the circumferential direction of the first rotation adapter and the second rotation adapter, and the two nutrient solution delivery portions 19 are respectively sleeved on the first rotation adapter and the second rotation adapter and have a conveying interface Referring to the enlarged view B shown in FIG.
  • the nutrient solution conveying portion 19 is provided with a conversion cavity 25 which is in communication with the conveying portion and which surrounds the rotating rod in the circumferential direction for the flow of the nutrient solution and the nutrient supply interface.
  • 14 connects the central through hole and the conversion cavity 25.
  • the conversion cavity 25 is opened along the axis of the inner portion of the inner hole of the nutrient solution delivery portion 19 and surrounds the corresponding rotary adapter in the circumferential direction.
  • the conversion cavity 25 is a cylindrical cavity. .
  • the first rotary adapter and the second rotary adapter are each connected to the nutrient supply interface 14 from an end adjacent to the hollow tube section 22.
  • the hollow portion communicates with the central through hole of the hollow pipe section 22 to introduce the nutrient solution into the hollow pipe section 22 through the hollow portion.
  • the nutrient solution supply interface 14 is a hole that is radially opened on the outer wall of the first and second rotary adapters.
  • the embodiment in which the nutrient solution supply interface 14 is disposed in the circumferential direction of the rotating rod allows the nutrient solution supply interface 14 to be immersed in the nutrient solution filled in the conversion cavity 25 at any time, thereby solving the movement of the nutrient solution from the fixed structure into the moving structure.
  • the technical problem is also that a part of the nutrient solution can be stored in advance in the conversion cavity 25, thereby making the supply of the nutrient solution more stable.
  • the support member may include a support portion and a nutrient solution delivery portion 19, the first rotation adapter and the second rotation adapter being rotatably supported on the support portion, and the support portion and the nutrient solution delivery portion 19 may be designed
  • the support portion and the nutrient solution delivery portion 19 may be designed
  • the monolithic structure has no limitation on the positional relationship between the support portion and the nutrient solution transporting portion 19 along the axis of the rotating rod.
  • the support portions are respectively a first abutment 17 and a second abutment 23 fixed to the mounting plate 1, the first abutment 17 supporting the first rotary adapter through the bearing 18, and the second abutment 23 passing
  • the bearing supports the second rotary adapter, and the use of the double-sided support structure improves the rotational stability of the rotating rod.
  • a sealing device such as a sealing ring 20 is provided between the second rotary adapters, specifically an O-ring.
  • a sealing ring 20 is respectively disposed on both sides of the conversion cavity 25 to achieve a better sealing effect.
  • the nutrient solution is introduced from the circumferential direction of the transfer section can make the setting of the seal ring easier.
  • a sealing connection should also be made between the adapter section and the end of the hollow tubular section 22.
  • the bioprinter printing module further includes a nutrient solution tank 11 for supplying nutrient solution to the rotating rod, the nutrient solution tank 11 having a tank interface.
  • the tank interface is coupled to the delivery portion via a nutrient solution delivery device for controlling the nutrient solution in the nutrient solution tank 11 to smoothly enter the rotating rod.
  • a pump can be placed between the tank interface and the delivery interface to facilitate the flow of nutrient solution.
  • the nutrient solution conveying device can also control the flow rate and flow rate of the nutrient solution, and specifically, a circulating pump with adjustable flow rate can be used, for example, a peristaltic pump or a gear pump.
  • the bio-printer printing module further includes a nutrient solution control device connected in series with the nutrient solution delivery device, the slot interface and the delivery portion interface are connected by the nutrient solution delivery device and the nutrient solution control device, and the nutrient solution control device is used for controlling The flow rate and flow rate of the nutrient solution.
  • a circulation pump with a flow regulator for example, use a circulation pump with a flow regulator.
  • the temperature control capability of the rotating rod can be adjusted indirectly during the printing process by adjusting the flow rate and flow rate of the nutrient solution, which provides a basis for cooling and heating of high temperature printing or mass printing. During the rotation of the rotating rod, it is possible to decide whether to open the nutrient solution cycle as needed.
  • the transport unit interface on the nutrient solution transport unit 19 includes a first pipe joint 5 provided on the left side (based on the direction of Fig. 3) on the nutrient solution transport unit 19, and a nutrient solution provided on the right side.
  • the tank interface on the nutrient solution tank 11 includes a third pipe joint 7 and a fourth pipe joint 8 which are provided on the nutrient solution tank 11.
  • the circulation pump may be disposed between the first pipe joint 5 and the fourth pipe joint 8, or between the second pipe joint 6 and the third pipe joint 7, for promoting the flow of the nutrient solution, and the flow path of the nutrient solution will be It is described in the following description of the working principle of the printer, and will not be described in detail here.
  • the first pipe joint 5, the second pipe joint 6, the third pipe joint 7, the fourth pipe joint 8, and the fifth pipe joint 9 disposed on the side of the water-cooling plate 12 are considered from the viewpoint of convenience and aesthetics of the piping layout.
  • the sixth pipe joint 10 is disposed on the same side of the printer.
  • the nutrient solution provided needs to be kept within a certain temperature range, and a temperature detecting component for detecting the temperature of the nutrient solution can also be provided for this purpose.
  • a temperature detecting component is provided at the outlet of the circulation pump for obtaining the outlet temperature of the circulation pump, and combined with the circulation time of the nutrient solution, the nutrient solution in the rotating rod can be comprehensively determined whether the nutrient solution in the rotating rod meets the need. temperature.
  • the temperature detecting device may be disposed in the conversion cavity 25 or in the nutrient solution tank 11 or the like.
  • the printer further includes a nutrient solution temperature control device for controlling the temperature of the nutrient solution.
  • the nutrient solution temperature control device includes: at least one semiconductor refrigerating sheet 13, a temperature controller and a heat sink, and at least one semiconductor refrigerating sheet 13 is disposed outside the nutrient solution tank 11 for control of the temperature controller. Heat or cool down.
  • the provision of a plurality of semiconductor refrigerating sheets 13 can effectively increase the power of cooling or heating, and can also achieve the effect of redundant backup. More preferably, a gap may be provided between the adjacent two semiconductor refrigerating sheets 13 to facilitate the installation and wiring of the semiconductor refrigerating sheet 13, and the wiring may be placed in the gap to provide protection.
  • the semiconductor refrigerating sheet 13 has a temperature control end and a non-temperature control end, and the temperature control end is disposed toward the nutrient solution tank 11 to achieve the purpose of controlling the temperature of the nutrient solution tank 11 and controlling the temperature of the nutrient solution in the nutrient solution tank 11,
  • the temperature control end is set toward the heat sink.
  • the nutrient solution tank 11 is located directly below the rotating rod, scattered
  • the heat device comprises a water-cooling plate 12, and the semiconductor refrigeration sheet 13 is disposed under the nutrient solution tank 11 for automatically changing the working mode, including the heating or cooling mode, by the program under the control of the external temperature controller; the water-cooling plate 12 is set in the semiconductor refrigeration
  • the sheet 13 is fixed on the mounting plate 1 for carrying away heat generated during operation of the semiconductor refrigerating sheet 13, wherein the water-cooling plate 12 can also be replaced by other heat dissipating means, such as fan cooling.
  • a heat conducting plate or a heat equalizing plate having a size larger than the bottom area of the trough body is designed under the rectangular nutrient solution tank 11, and on the one hand, the heat generated by the semiconductor refrigerating sheet 13 can be uniformly directed to the nutrient solution tank.
  • the semiconductor refrigerating sheet 13 can be sandwiched between the base and the water-cooling plate 12, and the fixing of the water-cooling plate 12 can be achieved by providing bolts around the base.
  • a plurality of semiconductor cooling fins 13 can be arranged side by side.
  • the semiconductor refrigerating sheet 13 is generally square, in order to uniformly heat the rectangular nutrient solution tank 11, two semiconductor refrigerating sheets 13 may be arranged side by side.
  • the side of the water-cooling plate 12 is provided with a fifth pipe joint 9 and a sixth pipe joint 10, and the fifth pipe joint 9 and the sixth pipe joint 10 are respectively connected to the water inlet of the external water-cooling circulation system. And the water outlet for taking away the heat generated when the semiconductor refrigeration sheet 13 works.
  • the temperature control system When the heating is required, the temperature control system is in a heating state, at which time the temperature control end of the semiconductor refrigerating sheet 13 is a hot surface, and the heat generated by the heating is transmitted to the nutrient solution in the nutrient solution tank 11 to accelerate the temperature of the nutrient solution. purpose.
  • the temperature-controlled end of the semiconductor refrigerating sheet 13 becomes a cold surface to absorb the heat of the nutrient solution in the nutrient solution tank 11, thereby achieving the purpose of cooling the nutrient solution, and at the same time, the non-temperature-controlled end of the semiconductor is changed.
  • the heating surface transfers heat to the water-cooling plate 12 to reduce the temperature difference between the cold and hot surfaces of the semiconductor refrigerating sheet 13 and increase the cooling effect.
  • the rotating rod includes at least one transfer section in addition to the hollow pipe section 22 (the transfer sections 15 and 24 in Fig. 3 are the first rotary adapter and the first a two-rotation adapter), the nutrient solution supply interface 14 is disposed on the transfer sections 15 and 24, and the transfer section is detachably coaxially disposed at an end of the hollow pipe section 22, and is rotatably supported on the support member, It is driven to drive the hollow tube section 22 to rotate, thereby cooperating with the print head to achieve printing of biological tubular tissue or other active tissue of the cavity.
  • the transfer sections 15 and 24 in Fig. 3 are the first rotary adapter and the first a two-rotation adapter
  • the bioprinter printing module of this embodiment avoids the structure of directly supporting the end of the rotating rod in the prior art by designing the rotating rod as a segmented detachable structure and supporting the transfer section by the supporting member.
  • the utility model can conveniently remove the rotating rod after the biological tubular tissue is printed, without disassembling the supporting member, and also conveniently installing the rotating rod in the next printing, so that the loading and unloading is convenient, thereby saving printing time and easily ensuring the printer. Installation accuracy.
  • it is convenient to replace the rotary rods of different specifications to print different biological tubular tissues by simply replacing the interface between the hollow tube segments and the transfer segments.
  • the transfer portion 15 is a first rotary adapter
  • the transfer portion 24 is a second rotary adapter, respectively detachably
  • the shaft is disposed at two ends of the hollow pipe section 22, and the support member supports the two transfer segments to indirectly support the rotating rod, and driving one of the transfer segments or driving the two transfer segments at the same time can drive
  • the hollow tube section 22 rotates to cooperate with the movement of at least one of the printing heads in the three directions of X, Y and Z, so that the biological ink ejected from the printing head adheres to the outer surface of the hollow tube section 22 according to a predetermined trajectory. , thereby enabling the printing of biological tubular tissue.
  • the rotation can be made.
  • the hollow tube section 22 can be separated from the transfer section to be disassembled, placed in a biological incubator, and various growth factors and differentiation-promoting factors are added to accelerate the biological tubular structure and various physiological functions. Mature to obtain the desired biological tubular tissue.
  • the hollow tube section 22 corresponding to the diameter of the biological tubular tissue is mounted to the transfer section.
  • the printer further includes two connectors 21 through which the first rotary adapter and the second rotary adapter respectively pass A connector 21 is attached to both ends of the hollow tubular section 22.
  • the connector 21 is a threaded connector, that is, a threaded hole is formed in the connector 21, and the two axial sections of the threaded hole are respectively adapted to the diameters of the rotary adapter and the hollow pipe section 22, and the threaded holes are matched with the rotary adapter.
  • the axial length of the smaller hole diameter of the threaded hole that cooperates with the hollow pipe section 22 is provided with a margin; and an external thread is provided at the connecting section of the first rotary adapter and the second rotary adapter and the hollow pipe section 22,
  • the detachable connection can be achieved by the cooperation of internal and external threads.
  • the two connectors 21 are provided.
  • the hollow tube section 22 can be removed by moving to both ends respectively; when the biological tubular structure needs to be printed, the hollow tube section 22 is butted between the first rotation adapter and the second rotation adapter, and then the two connections are rotated.
  • the two connectors 21 are respectively moved in the middle, so that the hollow pipe section 22 can be installed, and the threaded connector can be locked.
  • the hollow tube section 22 can be selected from different sizes ranging from 1.5 mm to 10 mm depending on the application of printing different sizes of biological tubular tissue.
  • only the hollow tube segments 22 and the threaded connectors can be replaced on the basis of the printer. The realization does not require the design of the support structure to be changed as in the prior art structure, thereby improving the versatility and flexibility of use of the printer.
  • the hollow tubular section 22 is directly connected to the end of the transition section.
  • the transfer section and the hollow pipe section can be directly connected by a thread.
  • a sliding slot may be radially opened at an end of the first rotary adapter and the second rotary adapter adjacent to the hollow pipe segment, and the sliding slot extends to the axial center of the rotating rod, and Both ends of the hollow pipe section are provided with an overhanging portion adapted to the sliding groove, and the outer protruding portion only needs to be embedded from the open end of the sliding groove, and then fixed by a pin or other fasteners. .
  • the transfer section in order to avoid leakage of the nutrient solution during transportation, it is preferable to seal the transfer section to the end of the hollow pipe section 22.
  • the screw connector is tightened to seal between the two rotary adapters and the hollow tubular section 22. The gap transmits the rotational power to the hollow tube section 22.
  • the printer drives the rotating rod through the servo motor 2, and the servo motor 2 moves in conjunction with the external printing head under the control of the control system to form a spiral on the hollow tube section 22. Cavity structure.
  • the use of the servo motor 2 can more precisely control the rotational speed of the rotating rod, thereby improving the position control of the rotating rod, and thus can control the joint movement with the printing head.
  • the servo motor 2 is arranged in parallel with the rotating rod on the mounting plate 1.
  • the servo motor 2 and the first rotating adapter are connected by the timing pulley 3 and the timing belt for transmitting the power of the servo motor 2 to the first rotation adapter, the belt transmission
  • the method is conducive to the overall structural arrangement.
  • the servo motor 2 is connected to the driving wheel of the timing pulley 3, and the first rotation adapter is connected to the driven wheel of the timing pulley 3, for example, by means of a key connection or a fastener connection.
  • the timing pulley 3 adjusts the tensioning force by the tension adjuster 4, so that the servo motor 2 can perform position control by the timing pulley 3 with a certain speed ratio more accurately.
  • the belt drive method does not require lubrication, which can avoid the contamination of the biological tubular tissue during the printing process, thereby ensuring the safety of the artificial biological tubular tissue. In the case of being able to isolate the contamination of the lubricating oil, gear transmission or chain transmission can also be used.
  • the first rotation adapter is used as the active end
  • the second rotation adapter is used as the driven end
  • the first rotary adapter is mounted on the first mount 17 by two bearings 18 to make the support force more stable and to be thrust on both sides by the end cap 16 and the nutrient solution transport portion 19.
  • the connection between the driven end and the active end can be in the same form, and the structure can be adjusted according to requirements.
  • the first holder 17 and the second holder 23 outside the two nutrient solution conveying portions 19 so that the support points are as close as possible to the ends of the shaft. Moreover, all the components related to the rotating rod in the printer are mounted on the same mounting plate 1, which can improve the stability of the overall performance.
  • the nutrient solution is charged into the nutrient solution tank 11, the temperature control temperature is set, and the nutrient solution circulation pump is turned on, and the nutrient solution enters the inlet of the circulation pump from the fourth pipe joint 8 and passes through the pressurized nutrient solution and then enters from the outlet of the circulation pump.
  • the conversion cavity 25 of the nutrient delivery portion 19 is filled with the conversion cavity 25, and then enters the hollow portion of the first rotary adapter from the nutrient supply interface 14 to flow into the hollow tube section 22, and the nutrient solution can be
  • the permeation hole 26 in the wall of the empty pipe section 22 oozes outward, and the nutrient solution which does not penetrate outward from the permeation hole 26 continues to flow to the nutrient solution conveying portion of the driven end, and flows out to the second method in the opposite manner to the inflow process.
  • the pipe joint 6, the second pipe joint 6 is connected to the third pipe joint 7 on the nutrient solution tank 11, so that the nutrient solution is returned to the nutrient solution tank 11 at a suitable temperature, and is circulated accordingly.
  • the present invention also provides a bioprinter comprising the printing module of the above embodiment, the printing module being capable of cooperating with a printing nozzle on the printer to effect printing of biological tubular tissue or other active tissue of the cavity.
  • the print module is horizontally mounted and placed at 90 degrees with the print head to enable lateral bio-tubular tissue printing.
  • the bio-printer can improve the convenience of the printer and shorten the printing time because of the convenient disassembly of the printing module; and because the nutrient solution can be supplied to the cells during the printing process, the biological tubular tissue produced by the printer or Other cavity active tissues are capable of maintaining high activity and long life.

Abstract

提供了一种生物打印机打印模块及生物打印机,打印模块包括:支撑部件和设有营养液供应接口(14)的旋转杆,旋转杆可转动地支撑于支撑部件上,旋转杆的表面用于接收打印喷头提供的生物墨汁,旋转杆包括具有中央通孔的中空管段(22),且中空管段(22)的管壁上设有与中央通孔连通的渗透孔(26),营养液供应接口与旋转杆的中央通孔连通以将外部的营养液导入旋转杆。上述打印模块能够在打印过程中将外界的营养液通过营养液供应接口导入旋转杆内部,再从渗透孔中渗出以供给旋转杆上的细胞和生物管状组织,从而提高细胞的存活率和生物学功能。

Description

生物打印机打印模块及生物打印机 技术领域
本发明涉及生物打印技术领域,尤其涉及一种生物打印机打印模块及生物打印机。
背景技术
生物3D打印是指通过3D打印的原理和方法,将生物材料(包括天然生物材料、合成生物材料或细胞溶液)打印成为设计的三维结构体,区别于普通的3D打印技术,生物3D打印技术生产的生物组织或器官还具有一定的生物学功能,需为细胞和组织的进一步生长提供条件,正是由于上述特性,生物3D打印技术在发展中,面临着很多特定的技术问题。
其中,在生物3D打印领域,将细胞作为打印材料的技术称为细胞3D打印技术,人们可以利用细胞和生物相容性材料制成生物墨汁,使喷头移动并将生物墨汁喷出,通过程序控制喷头运动,将生物墨汁按照预设的目标打印,以按照物体的三维数字模型打印成型。在医疗领域中,常用生物3D打印的方法制作腔体活性组织如人工血管,这为治疗很多血管类疾病提供了途径。
现有技术中用于打印血管的打印机,包括旋转杆和打印喷头,旋转杆的长度和大小根据需要打印的血管形状和大小进行设计,旋转杆的一端通过支架支撑并由电机驱动,另一端悬空,打印喷头位于旋转杆上方,且能相对于旋转杆的表面移动。工作时打印喷头将生物墨汁喷射到旋转杆的表面上以形成生物血管组织,打印完毕后,将带有血管组织的旋转杆取下放入生物培养箱内,加入各种生长因子和促分化因子,加速血管组织结构和各种生理功能发育成熟,得到需要的血管。
但是此种方案在打印喷头将细胞喷射到旋转杆上形成生物血管组织以后、直至整个打印过程结束的这段时间内,位于旋转杆上 的细胞和生物血管组织缺乏外界营养供给,其细胞存活和生物学功能实现都将受到影响。可见,对于生物3D打印,营养供给是必不可少的重要环节,而如何向动态的旋转杆上的载体提供营养液,则一直是本领域难以解决的技术难题。
发明内容
本发明的目的是提出一种生物打印机打印模块及生物打印机,能够在打印过程中将外界的营养液供给旋转杆上的细胞和生物管状组织。
为实现上述目的,本发明第一方面提供了一种生物打印机打印模块,包括:支撑部件和设有营养液供应接口的旋转杆,所述旋转杆可转动地支撑于所述支撑部件上,所述旋转杆的表面用于接收打印喷头提供的生物墨汁,所述旋转杆包括具有中央通孔的中空管段,且中空管段的管壁上设有与所述中央通孔连通的渗透孔,所述营养液供应接口与所述旋转杆的中央通孔连通以将外部的营养液导入所述旋转杆。
进一步地,所述支撑部件包括支撑部和营养液输送部,所述营养液供应接口设在所述旋转杆的圆周方向上,所述旋转杆可转动地支撑于所述支撑部上,所述营养液输送部套设在所述旋转杆上并具有输送部接口,所述营养液输送部内设有与所述输送部接口连通的、在圆周方向上包围所述旋转杆的转换空腔,所述营养液供应接口连通所述中央通孔与所述转换空腔。
进一步地,还包括密封装置,所述密封装置设在所述营养液输送部与所述旋转杆之间。
进一步地,还包括用于向所述旋转杆提供营养液的营养液槽,所述营养液槽具有槽接口,所述槽接口与所述输送部接口通过营养液输送装置连接,所述营养液输送装置用于控制所述营养液槽内的营养液进入所述旋转杆。
进一步地,所述营养液输送装置还用于控制营养液的流速和流 量;或者所述生物打印机打印模块还包括与所述营养液输送装置串联的营养液控制装置,所述槽接口与所述输送部接口通过营养液输送装置和所述营养液控制装置连接,所述营养液控制装置用于控制营养液的流速和流量。
进一步地,还包括用于检测营养液温度的温度检测部件或用于控制营养液温度的营养液温控装置。
进一步地,所述营养液温控装置包括:半导体制冷片、温度控制器和散热装置,所述半导体制冷片设置于所述营养液槽的底部,用于在所述温度控制器的控制下对所述营养液槽进行加热或冷却,所述半导体制冷片具有控温端和非控温端,所述控温端朝向所述营养液槽设置,所述非控温端朝向所述散热装置设置。
进一步地,所述营养液槽与所述半导体制冷片之间设有导热板或均热板。
进一步地,所述旋转杆还包括转接段,所述营养液供应接口设置在所述转接段上,所述转接段可拆卸地同轴设在所述中空管段的端部,所述转接段可转动地支撑于所述支撑部件上,所述转接段能够被驱动以带动所述中空管段旋转。
进一步地,还包括连接器,所述转接段通过所述连接器与所述中空管段的端部连接。
进一步地,所述连接器为螺纹连接器。
进一步地,所述转接段内设有与所述营养液供应接口连通的中空部,所述中空部与所述中空管段的中央通孔连通以通过所述中空部将营养液导入所述中空管段。
进一步地,所述转接段与所述中空管段的端部密封连接。
进一步地,还包括伺服电机,所述伺服电机与所述旋转杆平行布置,所述伺服电机与所述旋转杆通过同步带轮和同步带连接。
为实现上述目的,本发明第二方面提供了一种生物打印机,包括上述实施例所述的打印模块。
基于上述技术方案,本发明的生物打印机打印模块,通过在旋 转杆上设置营养液供应接口和渗透孔,能够在打印过程中将外界的营养液通过营养液供应接口导入旋转杆内部,再从渗透孔渗出以供给旋转杆上的细胞和生物管状组织,从而对细胞和生物管状组织形成保护,进而提高细胞的存活率和生物学功能。
附图说明
此处所说明的附图用来提供对本发明的进一步理解,构成本申请的一部分,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。在附图中:
图1本发明生物打印机打印模块的一个实施例的三维结构示意图;
图2为图1所示生物打印机打印模块的俯视图;
图3为图2所示生物打印机打印模块的A-A剖视图;
图4为图2所示生物打印机打印模块的局部放大图B。
附图标记说明
1-安装板;2-伺服电机;3-同步带轮;4-张紧调节器;5-第一管接头;6-第二管接头;7-第三管接头;8-第四管接头;9-第五管接头;10-第六管接头;11-营养液槽;12-水冷板;13-半导体制冷片;14-营养液供应接口;15-转接段;16-端盖;17-第一支座;18-轴承;19-营养液输送部;20-密封圈;21-连接器;22-中空管段;23-第二支座;24-转接段;25-转换空腔;26-渗透孔。
具体实施方式
以下详细说明本发明。在以下段落中,更为详细地限定了实施例的不同方面。如此限定的各方面可与任何其他的一个方面或多个方面组合,除非明确指出不可组合。尤其是,被认为是优选的或有利的任何特征可与其他一个或多个被认为是优选的或有利的特征。
本发明中出现的“第一”、“第二”等用语仅是为了方便描述,以区分具有相同名称的不同组成部件,并不表示先后或主次关系。
在本发明的描述中,需要理解的是,术语“上”、“下”、“前”、“后”、“左”和“右”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本发明,而不是指示或暗示所指的装置必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本发明保护范围的限制。
本发明提供了一种生物打印机打印模块,如图1至图4所示,包括:支撑部件和设有营养液供应接口14的旋转杆,旋转杆可转动地支撑于支撑部件上,旋转杆的表面用于接收打印喷头提供的生物墨汁,旋转杆包括具有中央通孔的中空管段22,且中空管段22的管壁上设有与中央通孔连通的渗透孔26,营养液供应接口与旋转杆的中央通孔连通以将外部的营养液导入旋转杆。
而且,通过调节旋转杆上渗透孔26的分布及尺寸,可以适应不同厚度、长度和性质的生物管状组织打印的需要。例如:生物管状组织可以是血管。另外,营养液根据需要,可以采用一次性使用的方式,能够提高生物安全性。
本发明实施例的生物打印机打印模块,能够在打印过程中将外界的营养液通过营养液供应接口14导入旋转杆内部,再从渗透孔26中渗出以供给旋转杆上的细胞和生物管状组织,从而对细胞和生物管状组织形成保护,进而提高细胞的存活率和生物学功能。
该实施例中的旋转杆可只包括中空管段22,或者只在中空管段22的一端设有转接段,也可以采取图3所示的结构,即旋转杆包括中空管段22和连接在中空管段22两端的转接段15和转接段24,转接段15和转接段24分别为第一旋转适配器和第二旋转适配器。下面给出的各个实施例均以图3所示组成结构的旋转杆为例进行说明。
为了将营养液从固定结构引导至转动的旋转杆内部,至少可以采用两种类型的导入方式:
其一,可以从旋转杆的端部通过输送管导入营养液,这种情况下需要将旋转杆内部的中央通孔沿轴向贯通,并需要在输送管与旋转杆的连接处设置动静转换接头。
其二,营养液供应接口14设在旋转杆的圆周方向上。具体地,旋转杆包括中空管段22和连接在中空管段22两端的转接段15和转接段24,转接段15和转接段24分别为第一旋转适配器和第二旋转适配器。相应地,营养液供应接口14设在第一旋转适配器和第二旋转适配器的圆周方向上,两个营养液输送部19分别套设在第一旋转适配器和第二旋转适配器上并具有输送部接口,参见图4所示的放大图B,营养液输送部19内设有与输送部接口连通的、在圆周方向上包围旋转杆的转换空腔25,用于营养液的流动,营养液供应接口14连通中央通孔与转换空腔25。对于一种具体的结构,转换空腔25在营养液输送部19内孔的中间段沿自身轴线开设,且在圆周方向上包围对应的旋转适配器,优选地,转换空腔25为圆柱形空腔。
为了使营养液能够从营养液供应接口14流入中空管段22的中央通孔,第一旋转适配器和第二旋转适配器从靠近中空管段22的一端起均设有与营养液供应接口14连通的中空部,中空部与中空管段22的中央通孔连通,以通过中空部将营养液导入中空管段22。优选地,营养液供应接口14为在第一旋转适配器和第二旋转适配器的外壁上沿径向开设的孔。
营养液供应接口14设在旋转杆圆周方向上的实施例可以使营养液供应接口14在任何时刻都浸泡在充满于转换空腔25内的营养液中,解决了营养液从固定结构进入运动结构的技术难题,而且还能够在转换空腔25内提前存储一部分营养液,从而使营养液的供应更加稳定。
在该实施例中,支撑部件可以包括支撑部和营养液输送部19,第一旋转适配器和第二旋转适配器可转动地支撑于支撑部上,支撑部和营养液输送部19之间既可以设计为独立的结构,也可设计为 整体式的结构,这里对支撑部与营养液输送部19沿旋转杆轴线的位置关系没有限制。在图3中,支撑部分别为固定在安装板1上的第一支座17和第二支座23,第一支座17通过轴承18对第一旋转适配器进行支撑,第二支座23通过轴承对第二旋转适配器进行支撑,双侧支撑结构的采用,提高了旋转杆的转动平稳性。
进一步地,为了防止营养液从营养液输送部19与第一旋转适配器或第二旋转适配器之间的间隙泄漏,在营养液输送部19与第一旋转适配器之间,以及营养液输送部19与第二旋转适配器之间设置密封装置,例如密封圈20,具体可为O型密封圈。优选地,在转换空腔25的两侧分别设置至少一个密封圈20可以达到较好的密封效果。从转接段的周向导入营养液的实施例能够使密封圈的设置更加容易。而且,转接段与中空管段22的端部之间也应该进行密封连接。
为了在打印过程中为生物管状组织提供营养液,生物打印机打印模块还包括用于向旋转杆提供营养液的营养液槽11,营养液槽11具有槽接口。在一个实施例中,槽接口与输送部接口通过营养液输送装置连接,营养液输送装置用于控制营养液槽11内的营养液顺利地进入旋转杆。例如,可在槽接口与输送部接口之间设置泵,以促进营养液的流动。进一步地,营养液输送装置还能控制营养液的流速和流量,具体可采用流量可调的循环泵,例如可以为蠕动泵或齿轮泵等。
在另一个实施例中,生物打印机打印模块还包括与营养液输送装置串联的营养液控制装置,槽接口与输送部接口通过营养液输送装置和营养液控制装置连接,营养液控制装置用于控制营养液的流速和流量。例如,将循环泵与流量调节阀配合使用。
对于这两种实施例,在打印过程中,通过调整营养液的流速和流量,还可以间接的调节旋转杆的温控能力,为高温打印或大量打印的冷却和加热提供了基础。在旋转杆旋转的过程中,可根据需要决定是否打开营养液循环。
下面将给出一种在营养液槽11和营养液输送部19上设置各接口的具体方式。如图1所示,营养液输送部19上的输送部接口包括:设在左侧(以图3的方向为基准)营养液输送部19上的第一管接头5以及设在右侧营养液输送部19上的第二管接头6。营养液槽11上的槽接口包括:设在营养液槽11上的第三管接头7和第四管接头8。循环泵可以设在第一管接头5与第四管接头8之间,或者设在第二管接头6与第三管接头7之间,用于促进营养液的流动,营养液的流动路径将在后续描述打印机的工作原理时描述,这里暂不详述。从管路布局的方便及美观度考虑,将第一管接头5、第二管接头6、第三管接头7、第四管接头8、以及设置于水冷板12的侧面的第五管接头9和第六管接头10布置在打印机的同一侧。
为了保证打印过程中生物细胞的活性,提供的营养液需要保持在一定的温度范围内,为此还可以设置用于检测营养液温度的温度检测部件。在一种可实现的实施例中,在循环泵的出口设有温度检测部件,用于获得循环泵的出口温度,再结合营养液的循环时间就能综合判断旋转杆中的营养液是否达到需要的温度。另外,温度检测装置还可以设置在转换空腔25内或者营养液槽11内等位置。
在本发明的一个实施例中,打印机还包括用于控制营养液温度的营养液温控装置。如图3所示,营养液温控装置包括:至少一个半导体制冷片13、温度控制器和散热装置,至少一个半导体制冷片13设置于营养液槽11的外侧,用于在温度控制器的控制下进行加热或冷却。设置多个半导体制冷片13能够有效地提升制冷或加热的功率,还能起到冗余备份的效果。更优地,相邻的两个半导体制冷片13之间可以设置间隙,以方便半导体制冷片13安装和接线,将接线置于间隙内还能起到保护作用。其中,半导体制冷片13具有控温端和非控温端,控温端朝向营养液槽11设置,以实现控制营养液槽11的温度进而控制营养液槽11内的营养液温度的目的,非控温端朝向散热装置设置。
在具体的结构设计中,营养液槽11位于旋转杆的正下方,散 热装置包括水冷板12,半导体制冷片13设在营养液槽11下方,用于在外部温度控制器的控制下通过程序自动的改变工作模式,包括加热或制冷模式;水冷板12设在半导体制冷片13的下方,且固定在安装板1上,用于带走半导体制冷片13工作时产生的热量,其中,水冷板12也可以用其它的散热装置代替,例如风扇冷却等。
为了方便半导体制冷片13的固定,在矩形营养液槽11的下方设计一个尺寸大于槽体底面积的导热板或均热板,一方面可以将半导体制冷片13产生的热量均匀地向营养液槽11传递,另一方面还可以将半导体制冷片13夹在底座与水冷板12之间,并通过在底座的四周设置螺栓以实现和水冷板12的固定。可以并排设置多块半导体制冷片13。例如由于半导体制冷片13一般为正方形,为了能够对矩形营养液槽11均匀地加热,可以采用两块半导体制冷片13并排设置。如图1和图2所示,水冷板12的侧面设有第五管接头9和第六管接头10,第五管接头9和第六管接头10分别连接外置的水冷循环系统的进水口和出水口,用来带走半导体制冷片13工作时产生的热量。
当需要加热时,温控系统处于加热状态,此时半导体制冷片13的控温端为热面,并将加热产生的热量传递给营养液槽11中的营养液,实现对营养液进行升温的目的。反之,当需要冷却时,半导体制冷片13的控温端变成冷面,来吸收营养液槽11中营养液的热量,实现对营养液进行降温的目的,同时,半导体的非控温端变成热面,把热量传递给水冷板12,以便缩小半导体制冷片13冷热面的温差,增加制冷效果。
现有技术中的打印机还存在另外一个缺点,在每次打印完毕后,将将旋转杆卸下时都需要将端部的支撑结构一起拆下,使得拆装过程较为繁琐,且难以保证每次安装的精度一致;而且当需要打印不同直径的生物管状组织时,就需要更换为相应直径的旋转杆,使得支撑结构也需要重新设计,使该打印机的通用性和适应性较差。
为了解决这一问题,在本发明改进的实施例中,旋转杆除了包括中空管段22,还包括至少一个转接段(图3中转接段15和24分别为第一旋转适配器和第二旋转适配器),营养液供应接口14设置在转接段15和24上,转接段可拆卸地同轴设在中空管段22的端部,并且可转动地支撑于支撑部件上,能够被驱动以带动中空管段22旋转,从而与打印喷头配合实现生物管状组织或者其它腔体活性组织的打印。
该实施例的生物打印机打印模块,通过将旋转杆设计为分段可拆卸的结构,并由支撑部件对转接段进行支撑,避免了现有技术中直接对旋转杆的端部进行支撑的结构,能够在生物管状组织打印完毕后方便地将旋转杆拆下,不需要拆卸支撑部件,同样在下次打印时也可方便安装旋转杆,使得装卸较为便捷,从而可以节约打印时间,而且容易保证打印机的安装精度。另外,在需要打印不同直径的生物管状组织时,只需简单更换中空管段与转接段的接口,即可方便地更换不同规格的旋转杆来打印不同的生物管状组织。
在一种结构形式中,只采用一个转接段,该转接段连接在中空管段的一端,另一端悬空,当需要拆装旋转杆时,只需要断开或连接中空管段和转接段两者之间的接口部分,不涉及支撑结构的拆装。
在另一种结构形式中,采用两个转接段,在图3所示的实施例中,转接段15为第一旋转适配器,转接段24为第二旋转适配器,分别可拆卸地同轴设在中空管段22的两端,支撑部件对两个转接段进行支撑,从而间接地实现对旋转杆的支撑,驱动其中一个转接段或者同时驱动两个转接段就能带动中空管段22旋转,从而与打印喷头在X、Y和Z三个方向至少之一的运动相配合,使得打印喷头喷出的生物墨汁按照预定的轨迹附着在中空管段22的外表面,从而实现生物管状组织的打印。
对于采用两个转接段的实施例,由于生物管状组织在打印时以旋转杆为基体,而且旋转杆采用两端支撑的形式,可以使得转动较 为平稳,因而在打印较长的生物管状组织时,能够获得较高的精度,尽量减少由于重力作用而使旋转杆发生变形,从而影响生物墨汁预设的运动轨迹。在打印完毕后,可以将中空管段22与转接段相分离以实现拆卸,并放入生物培养箱内,加入各种生长因子和促分化因子,加速生物管状组织结构和各种生理功能发育成熟,以得到需要的生物管状组织。当需要再次打印时,再将与生物管状组织直径对应的中空管段22安装到转接段上。
下面的各种实施例将以采用两个转接段的打印机实现生物管状组织打印为例进行说明。
为了实现中空管段22与转接段之间的可拆卸连接,在一种实现形式中,参见图3,该打印机还包括两个连接器21,第一旋转适配器和第二旋转适配器分别通过一个连接器21连接在中空管段22的两端。优选地,连接器21为螺纹连接器,即在连接器21上开设螺纹孔,螺纹孔的轴向两段分别与旋转适配器和中空管段22的直径相适应,与旋转适配器配合的螺纹孔或与中空管段22配合的螺纹孔中孔径较小者的轴向长度设有余量;而且在第一旋转适配器和第二旋转适配器与中空管段22的连接段设置外螺纹,通过内外螺纹的配合即可实现可拆卸连接。
当生物管状组织打印完毕需要拆下中空管段22时,仅需要旋转两个连接器21,例如,在与旋转适配器配合的螺纹孔的轴向长度设有余量时使两个连接器21分别向两端移动,即可将中空管段22拆下;当需要打印生物管状组织时,将中空管段22对接在第一旋转适配器和第二旋转适配器之间,再旋转两个连接器21,例如,在与旋转适配器配合的螺纹孔的轴向长度设有余量时使两个连接器21分别向中间移动,即可实现中空管段22的安装,将螺纹连接器锁紧后,可以将外部的旋转动力通过第一旋转适配器或第二旋转适配器传递至中空管段22。可以看出,采用螺纹连接器的方式使得拆装较为方便,不会涉及到两端的支撑结构,从而能够保证打印机的安装精度,确保中空管段22安装完毕后,旋转时的跳动符合要求, 进而使生物墨汁在旋转杆表面形成的轨迹更加精确,以保证人工生物管状组织内部结构的排布更符合需求。
另外,中空管段22可根据打印不同大小生物管状组织的用途,选择直径从1.5mm到10mm的不同的规格。同时,也可以制作一系列与生物管状组织直径相配套的螺纹连接器,在打印不同直径的生物管状组织时,可以在该打印机的基础上,只更换中空管段22和螺纹连接器即可实现,不用像现有技术中的结构需要改变支撑结构的设计,从而提高了打印机的通用性和使用灵活性。
除了采用螺纹连接器,本领域技术人员也可以采用卡扣或者卡箍或者法兰盘类型的结构实现可拆卸连接。
在另一种实现形式中,中空管段22与转接段的端部直接连接。这里将举例给出几种可供参考的结构形式。其一,若只采用一个转接段,则可将转接段与中空管段设计通过螺纹直接连接的结构。其二,若采用两个转接段,可在第一旋转适配器和第二旋转适配器靠近中空管段的一端沿径向开设有滑槽,滑槽延伸至旋转杆的轴心线处,且中空管段的两端均设有与滑槽相适配的外伸部,在安装时仅需要从滑槽的开放端将外伸部嵌入,然后再通过销轴或其它紧固件进行固定。
对于上述各实施例,为了尽量避免营养液在输送过程中发生泄漏,最好将转接段与中空管段22的端部密封连接。对于通过螺纹连接器将第一旋转适配器和第二旋转适配器与中空管段22连接的实施例,将螺纹连接器旋紧后,即可密封两个旋转适配器与中空管段22之间的缝隙,并将旋转动力传递至中空管段22。
在本发明的再一个实施例中,打印机通过伺服电机2来驱动旋转杆,伺服电机2在控制系统的控制下,与外部的打印喷头联合运动,在中空管段22上螺旋形成所需要的腔体结构。伺服电机2的采用能够较为精确地控制旋转杆的转速,从而提高对旋转杆进行位置控制的能力,进而能够控制与打印喷头进行联合运动。
在一个优选的实施例中,为了节省空间,如图2所示的俯视图, 伺服电机2与旋转杆平行布置在安装板1上,伺服电机2与笫一旋转适配器通过同步带轮3和同步带连接,用于将伺服电机2的动力传递至笫一旋转适配器,带传动的方式利于整体结构布置。其中,伺服电机2与同步带轮3的主动轮连接,第一旋转适配器与同步带轮3的从动轮连接,例如:可以采用键连接或者紧固件连接等方式。同步带轮3通过张紧调节器4来调节张紧力,这样伺服电机2就可以较为精确地通过同步带轮3按照一定速比进行位置控制。采用带传动的方式不需要进行润滑,可以避免生物管状组织在打印过程中受到润滑油的污染,从而保证人工生物管状组织使用的安全性。在能够隔离润滑油污染的情况下,也可以采用齿轮传动或者链传动的方式。
对于该实施例中的动力传递方式,参考图3,第一旋转适配器作为主动端,第二旋转适配器作为从动端,设置在主动端的第一支座17与设置在从动端的第二支座23在安装调试中要保证安装于其上的两个营养液输送部19同轴,以保证旋转杆在旋转过程中的跳动尽量小。更进一步地,第一旋转适配器通过两个轴承18安装于第一支座17上,以使支撑力更加稳定,并通过端盖16和营养液输送部19在两侧进行止推。从动端与主动端的连接方式可采用相同的形式,在结构上可以根据需求进行调整。为了达到较好的支撑刚度,最好将第一支座17和第二支座23设在两个营养液输送部19的外侧,以使支撑点尽量靠近轴的端部。而且该打印机中所有与旋转杆相关的组件均安装在同一安装板1上,能够提高整体性能的稳定性。
为了使本领域技术人员清楚地了解本发明腔体活性组织的打印机的工作原理,下面将结合图1至图3所示的具体实施例,对其工作过程进行详细阐述。
将营养液装入营养液槽11中,设置温控温度,同时打开营养液循环泵,营养液从第四管接头8进入循环泵的进口,经过加压的营养液再从循环泵的出口进入第一管接头5,从而流入主动端的营 养液输送部19的转换空腔25内,并充满转换空腔25,再由营养液供应接口14进入第一旋转适配器的中空部,进而流动到中空管段22的内部,营养液可由中空管段22管壁上的渗透孔26向外渗出,未从渗透孔26向外渗透的营养液继续流动至从动端的营养液输送部,经过与流入过程相反的方法,流出至第二管接头6,第二管接头6与营养液槽11上的第三管接头7相连接,从而使营养液回到营养液槽11中保持适宜的温度,依此循环。当然,也可以选择使营养液通过第二管接头6进入而从第一管接头5流出,此时循环泵的输送方向也需要相应地进行切换。
通过检测外置循环泵出口处的温度以及循环时间,可以推测当前旋转杆内营养液是否达到设定温度。当达到设定温度时,伺服电机2在控制系统的控制下,通过同步带轮3控制旋转杆旋转,从而与外部的打印喷头联合运动,在旋转杆上螺旋形成所需要的腔体结构,在打印的过程中,营养液从旋转杆的渗透孔26渗出为细胞提供营养。另外,本发明还提供了一种生物打印机,包括上述实施例所述的打印模块,该打印模块能够与打印机上的打印喷头相配合从而实现生物管状组织或者其它腔体活性组织的打印。在使用时,将打印模块水平安装,与打印喷头构成90度安放,可实现横向生物管状组织的打印。此种生物打印机由于采用了拆卸方便的打印模块,因而能够提高打印机使用的便捷性,并缩短打印时间;而且由于在打印过程中可以给细胞提供营养液,使得此种打印机制作的生物管状组织或其它腔体活性组织能够保持较高的活性和较长的寿命。
以上对本发明所提供的一种生物打印机打印模块及生物打印机进行了详细介绍。本文中应用了具体的实施例对本发明的原理及实施方式进行了阐述,以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也落入本发明权利要求的保护范围内。

Claims (15)

  1. 一种生物打印机打印模块,其特征在于,包括:支撑部件和设有营养液供应接口(14)的旋转杆,所述旋转杆可转动地支撑于所述支撑部件上,所述旋转杆的表面用于接收打印喷头提供的生物墨汁,所述旋转杆包括具有中央通孔的中空管段(22),且中空管段(22)的管壁上设有与所述中央通孔连通的渗透孔(26),所述营养液供应接口与所述旋转杆的中央通孔连通以将外部的营养液导入所述旋转杆。
  2. 根据权利要求1所述的生物打印机打印模块,其特征在于,所述支撑部件包括支撑部和营养液输送部(19),所述营养液供应接口(14)设在所述旋转杆的圆周方向上,所述旋转杆可转动地支撑于所述支撑部上,所述营养液输送部(19)套设在所述旋转杆上并具有输送部接口,所述营养液输送部(19)内设有与所述输送部接口连通的、在圆周方向上包围所述旋转杆的转换空腔(25),所述营养液供应接口(14)连通所述中央通孔与所述转换空腔(25)。
  3. 根据权利要求2所述的生物打印机打印模块,其特征在于,还包括密封装置,所述密封装置设在所述营养液输送部(19)与所述旋转杆之间。
  4. 根据权利要求2所述的生物打印机打印模块,其特征在于,还包括用于向所述旋转杆提供营养液的营养液槽(11),所述营养液槽(11)具有槽接口,所述槽接口与所述输送部接口通过营养液输送装置连接,所述营养液输送装置用于控制所述营养液槽(11)内的营养液进入所述旋转杆。
  5. 根据权利要求4所述的生物打印机打印模块,其特征在于,所述营养液输送装置还用于控制营养液的流速和流量;或者所述生物打印机打印模块还包括与所述营养液输送装置串联的营养液控制装置,所述槽接口与所述输送部接口通过所述营养液输送装置和所述营养液控制装置连接,所述营养液控制装置用于控制营养液的 流速和流量。
  6. 根据权利要求4所述的生物打印机打印模块,其特征在于,还包括用于检测营养液温度的温度检测部件或用于控制营养液温度的营养液温控装置。
  7. 根据权利要求6所述的生物打印机打印模块,其特征在于,所述营养液温控装置包括:半导体制冷片(13)、温度控制器和散热装置,所述半导体制冷片(13)设置于所述营养液槽(11)的底部,用于在所述温度控制器的控制下对所述营养液槽(11)进行加热或冷却,所述半导体制冷片(13)具有控温端和非控温端,所述控温端朝向所述营养液槽(11)设置,所述非控温端朝向所述散热装置设置。
  8. 根据权利要求7所述的生物打印机打印模块,其特征在于,所述营养液槽(11)与所述半导体制冷片(13)之间设有导热板或均热板。
  9. 根据权利要求1所述的生物打印机打印模块,其特征在于,所述旋转杆还包括转接段(15;24),所述营养液供应接口(14)设置在所述转接段(15;24)上,所述转接段(15;24)可拆卸地同轴设在所述中空管段(22)的端部,所述转接段(15;24)可转动地支撑于所述支撑部件上,所述转接段(15;24)能够被驱动以带动所述中空管段(22)旋转。
  10. 根据权利要求9所述的生物打印机打印模块,其特征在于,还包括连接器(21),所述转接段(15;24)通过所述连接器(21)与所述中空管段(22)的端部连接。
  11. 根据权利要求10所述的生物打印机打印模块,其特征在于,所述连接器(21)为螺纹连接器。
  12. 根据权利要求9所述的生物打印机打印模块,其特征在于,所述转接段(15;24)内设有与所述营养液供应接口(14)连通的中空部,所述中空部与所述中空管段(22)的中央通孔连通以通过所述中空部将营养液导入所述中空管段(22)。
  13. 根据权利要求9所述的生物打印机打印模块,其特征在于,所述转接段(15;24)与所述中空管段(22)的端部密封连接。
  14. 根据权利要求1所述的生物打印机打印模块,其特征在于,还包括伺服电机(2),所述伺服电机(2)与所述旋转杆平行布置,所述伺服电机(2)与所述旋转杆通过同步带轮(3)和同步带连接。
  15. 一种生物打印机,其特征在于,包括权利要求1所述的打印模块。
PCT/CN2015/099795 2015-12-30 2015-12-30 生物打印机打印模块及生物打印机 WO2017113156A1 (zh)

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