WO2022222789A1 - 生物微球打印机 - Google Patents

生物微球打印机 Download PDF

Info

Publication number
WO2022222789A1
WO2022222789A1 PCT/CN2022/086339 CN2022086339W WO2022222789A1 WO 2022222789 A1 WO2022222789 A1 WO 2022222789A1 CN 2022086339 W CN2022086339 W CN 2022086339W WO 2022222789 A1 WO2022222789 A1 WO 2022222789A1
Authority
WO
WIPO (PCT)
Prior art keywords
microsphere
biological
flow tube
module
printing
Prior art date
Application number
PCT/CN2022/086339
Other languages
English (en)
French (fr)
Inventor
马少华
曹远雄
徐冰
赵浩然
王子天
Original Assignee
清华大学深圳国际研究生院
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.)
Filing date
Publication date
Application filed by 清华大学深圳国际研究生院 filed Critical 清华大学深圳国际研究生院
Publication of WO2022222789A1 publication Critical patent/WO2022222789A1/zh

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive 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
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body
    • A61M35/20—Non-portable devices, e.g. spraying booths
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive 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
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B29C64/112—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using individual droplets, e.g. from jetting heads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive 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
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205—Means for applying layers
    • B29C64/209—Heads; Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive 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
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/295—Heating elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE 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
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS 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
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus

Definitions

  • the invention relates to the technical field of biological manufacturing, in particular to a biological microsphere printer.
  • the present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a biological microsphere printer with high printing precision.
  • the biological microsphere printer includes: a preparation module, including a water-phase liquid supply device, an oil-phase liquid supply device and a mixer, the water-phase liquid supply device and the oil-phase liquid supply device are both connected with the The mixer is connected, the water phase feeder delivers the water phase material to the mixer, the oil phase feeder delivers the oil phase material to the mixer, and the mixer is used to make the the water-phase material and the oil-phase material are contacted and mixed to form the micro-droplets; a curing module is connected with the mixer, and the curing module is used for receiving the micro-droplets and making the micro-droplets The droplets are solidified to form the biological microspheres; a printing module includes a printing head and a displacement mechanism, the printing head is connected with the displacement mechanism, the printing head is connected with the curing module, and the displacement mechanism is used to drive the the print head moves, the print head is used to receive the biological microspheres and transport the biological microspheres to the area to be printed; a scanning module is used to collect
  • the biological microsphere printer according to the embodiment of the present invention has at least the following beneficial effects: scanning and identifying the area to be printed by the scanning module, and then accurately printing each biological microsphere to a suitable location according to the analysis result of the image information by the control module In order to repair the wound, the biological microsphere printer has high printing accuracy.
  • the mixer includes: a three-way pipe, including two first input parts and a first output part, the first input part and the first output part communicate with each other; a switching valve , including a valve body and a valve core, the valve core is located inside the valve body, the valve body has a plurality of second input parts and a second output part, the second input part has a water phase input port, The second output part has a water-phase output port, there are a plurality of the water-phase liquid supply devices, each of the water-phase liquid supply devices is respectively connected with one of the second input parts, and the valve core has a valve an inner channel, the valve core can be rotated relative to the valve body, so that the water-phase output port and one of the water-phase input ports are communicated through the valve inner channel; one of the first input parts is connected to The second output part is connected, the other first input part is connected with the oil phase liquid supply device, and the first output part is connected with the curing module.
  • a switching valve including a valve body and a valve core
  • the printing module further includes an air source, the air source is connected to the print head, and the air source supplies air to the print head, so that the Biological microspheres are ejected from the print head.
  • the print head includes: a microsphere flow tube, one end of which is connected to the curing module, the microsphere flow tube is for the flow of the biological microspheres; a gas flow tube, the microspheres flow One end of the pipe is connected with the side of the gas flow pipe, so that the lumen of the gas flow pipe is communicated with the lumen of the microsphere flow pipe, and one end of the gas flow pipe is connected with the gas source,
  • the gas source is used for supplying gas in the gas flow pipe, so that the biological microspheres are ejected from the other end of the gas flow pipe.
  • the print head includes: a microsphere flow pipe, one end of which is connected to the curing module, the microsphere flow pipe is for the flow of the biological microspheres; a gas flow pipe, the gas flow pipe One end of the gas flow tube is connected to the side of the microsphere flow tube, so that the lumen of the gas flow tube is communicated with the lumen of the microsphere flow tube, and the other end of the gas flow tube is connected to the gas source , the gas source is used for supplying gas in the gas flow pipe, so that the biological microspheres are ejected from the end of the microsphere flow pipe away from the curing module.
  • the print head includes: a microsphere flow pipe, one end of which is connected to the curing module, the microsphere flow pipe is for the flow of the biological microspheres; a gas flow pipe, one end of which is connected to the gas flow pipe source connection; a fixed block with a first flow channel and a second flow channel inside, a first insertion port, a second insertion port and a printing port are opened on the outer surface of the fixed block, the first insertion port and the printing port are respectively communicated with both ends of the first flow channel, one end of the second flow channel is communicated with the side of the first flow channel, and the other end of the second flow channel is communicated with the second insertion port ;
  • the end of the gas flow tube away from the gas source is inserted into the fixing block from the first insertion port, so that the lumen of the gas flow tube communicates with the first flow channel, and the microspheres
  • One end of the flow tube is inserted into the fixing block from the second insertion port, so that the cavity of the microsphere
  • the microsphere flow tube, the gas flow tube, the first flow channel, the second flow channel, the first insertion port, the second insertion port, and the Each of the printing ports is provided with multiple ones, and one of the first flow channels and one of the second flow channels are communicated to form a printing cavity, and the adjacent printing cavities are separated from each other.
  • the print head comprises: a microsphere flow tube, one end of which is connected to the curing module, the microsphere flow tube is for the flow of the biological microspheres, and the other end of the microsphere flow tube is used for the flow of the biological microspheres.
  • One end is an ejection end, and the biological microspheres are ejected from the microsphere flow tube through the ejection end; there are two gas flow tubes, and the gas flow tubes are opposite to the microsphere flow tubes.
  • the curing module includes a water bath heater, and the water bath heater includes: a box body with a heating cavity inside; a heat transfer liquid accommodated in the heating cavity; The box is connected, and the heating element is used for heating the heat-conducting fluid; a curing tube, the lumen of the curing tube is for the flow of the biological microspheres, and a part of the curing tube is immersed in the heat-conducting fluid.
  • the printing module further includes a color sensor, the color sensor is electrically connected to the control module, and the color sensor is used for identifying the color of the biological microspheres in the printing head and The color information of the biological microspheres is transmitted to the control module, and the control module can drive the displacement mechanism according to the color information.
  • Fig. 1 is the overall schematic diagram of the biological microsphere printer
  • 2 is a simplified schematic diagram of the connection mode of the water-phase liquid supply device, the oil-phase liquid supply device and the mixer in some embodiments;
  • FIG. 3 is a schematic diagram of the principle of a switching valve in some embodiments.
  • FIG. 4 is a schematic diagram of a first setting mode of the print head
  • FIG. 5 is a schematic diagram of a second setting mode of the print head
  • FIG. 6 is a schematic diagram of a third setting mode of the print head
  • FIG. 7 is a schematic diagram of a fourth setting mode of the print head
  • FIG. 8 is a schematic diagram of an assembly method of the print head in FIG. 7;
  • FIG. 9 is a schematic diagram of a fourth setting mode of the print head.
  • FIG. 10 is a simplified schematic diagram of a maturation module in some embodiments.
  • the azimuth description such as the azimuth or position relationship indicated by up, down, front, rear, left, right, etc.
  • the azimuth description is based on the azimuth or position relationship shown in the drawings, only In order to facilitate the description of the present invention and simplify the description, it is not indicated or implied that the indicated device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore should not be construed as limiting the present invention.
  • the invention provides a biological microsphere printer.
  • the biological microsphere printer is used to print biological microspheres to the area to be printed to repair wounds, such as skin wounds and muscle injuries.
  • the to-be-printed area can be the affected area of human organs or tissues. damaged area.
  • Biological microspheres include water-phase materials and repair cells.
  • the water-phase materials can be hydrogel, matrigel, etc.
  • the hydrogel solution can be converted from a liquid state to a gel state (solid state), and the repair cells are based on the type of the target to be repaired. Can be set to muscle cells, stem cells, liver cells, etc.
  • the production of biological microspheres also requires oil-phase materials (such as bio-fluorine oil), and the oil-phase materials themselves are not used as components to constitute the biological microspheres; oil-phase materials and water-phase materials are immiscible with each other, based on oil-phase materials and water-phase materials
  • oil-phase materials and water-phase materials are immiscible with each other, based on oil-phase materials and water-phase materials
  • the specific principle of how to form the microdroplets belongs to the well-known technology in the art, and will not be discussed in detail here. Repair cells can be premixed in the aqueous phase material. After the microdroplets are solidified and formed, biological microspheres are formed, and the microdroplets are solid
  • the biological microsphere printer of the present invention includes a preparation module 101 , a curing module 102 , a printing module 103 , a scanning module 104 and a control module 105 .
  • the preparation module 101 includes a water-phase liquid supply device 106, an oil-phase liquid supply device 107, and a mixer 206. Both the water-phase liquid supply device 106 and the oil-phase liquid supply device 107 are connected to the mixer 206, and the water The phase liquid feeder 106 delivers the water phase material 201 to the mixer 206 (the delivered water phase material 201 has already been mixed with repair cells 203), and the oil phase liquid supplier 107 delivers the oil phase material 202 to the mixer 206, and the water phase material 201 and oil phase material 202 are contacted and mixed in mixer 206 to form droplets 108 .
  • the water-phase liquid supplier 106 may include a syringe pump, and the syringe pump itself has a cavity for storing liquid, so the water-phase liquid supplier 106 may not need to be additionally provided with a storage device for the water-phase material 201 . container.
  • the pump of the water-phase liquid supplier 106 may be set to other types of pumps, such as a plunger pump, a peristaltic pump, etc.
  • a liquid storage container needs to be set in the water-phase liquid supplier 106; to Taking the plunger pump as an example, the plunger pump draws the water-phase material 201 from the liquid storage container, and then pumps the water-phase material 201 to the mixer 206 .
  • the specific arrangement of the oil-phase liquid supply device 107 is similar to that of the water-phase liquid supply device 106, and the description is not repeated here.
  • the flow ratio between the water phase material 201 and the oil phase material 202 flowing into the tee pipe 205 can be adjusted, thereby adjusting the adjacent microdroplets 108 (or adjacent biological microspheres 109 ). ), and adjust the diameter of the microdroplets 108 (or biological microspheres 109).
  • the mixer 206 may specifically include a three-way pipe 205, and the three-way pipe 205 includes two first input parts 207 and a first output part 208, and the first input part 207 and the first output
  • the two first input parts 207 are connected to the water phase liquid supply device 106 and the oil phase liquid supply device 107 respectively, and the first output part 208 is connected to the curing module 102 through pipe fittings to realize the transportation of micro droplets 108 .
  • the water phase material 201 and the oil phase material 202 are mixed in the tee pipe 205, and the oil phase material 202 and the microdroplets 108 formed after mixing (the microdroplets 108 are dispersed in the oil phase material 202) are transported to the aging module 102.
  • the microdroplets 108 enter the curing module 102 and then solidify to form biological microspheres 109 .
  • the water phase material 201 is set as matrigel
  • the curing module 102 includes a water bath heater 1006
  • the microdroplets 108 are heated to a certain temperature in a water bath and then gelled and solidified to form biological microspheres 109 .
  • the solidification of the micro-droplets 108 by heating is relatively simple and the cost is low; and the use of water bath heating can ensure that the micro-droplets 108 are heated evenly, thereby ensuring the molding effect.
  • the water bath heater 1006 includes a box body 1001, a curing tube 1002, a heat transfer fluid 1003 and a heating element 1004; the inside of the box body 1001 has a heating cavity 1005, the heat transfer fluid 1003 is accommodated in the heating cavity 1005, and the heating element 1004 is connected to the heating element 1004.
  • the box 1001 is connected (the heating element 1004 can be installed on the outer wall of the box 1001 ), and a part of the curing tube 1002 is immersed in the thermal fluid 1003 .
  • One end of the curing tube 1002 is connected to the preparation module 101, and the other end is connected to the printing module 103.
  • the microdroplets 108 from the preparation module 101 flow along the lumen of the curing tube 1002 to the printing module 103, and the microdroplets 108 pass through the thermal fluid during the flow. 1003 heating and gradually forming.
  • the control module 105 can be set as a computer, and the printing module 103 and the scanning module 104 are both electrically connected to the control module 105 (specifically, the electrical connection can be achieved through a communication cable).
  • the printing module 103 includes a print head 110 and a displacement mechanism.
  • the print head 110 is connected to the displacement mechanism.
  • the displacement mechanism is not specifically shown in the figure.
  • the displacement mechanism can be specifically set as a multi-axis robotic arm or a multi-axis displacement platform.
  • the head 110 moves.
  • the scanning module 104 includes a camera, and the camera can collect image information of the area to be printed and send it to the control module 105 .
  • the control module 105 performs three-dimensional modeling of the to-be-printed area according to the received image information of the to-be-printed area, and then the control module divides the three-dimensional model, converts it into a three-dimensional structure composed of biological microspheres 109, and then extracts each The center coordinates of the biological microspheres 109 are transmitted to the control system.
  • the control module 105 controls the movement of the displacement mechanism according to the printing position, and the print head 110 moves to an appropriate position under the drive of the displacement mechanism; after the print head 110 moves to the appropriate position, the control module 105 controls the printing The head 110 is opened, and the biological microspheres 109 are ejected.
  • the biological microsphere printer provided by the present invention scans and identifies the area to be printed by the scanning module 104, and then accurately prints each biological microsphere 109 to a suitable position according to the analysis result of the image information by the control module 105 to repair the wound , the printing precision of the biological microsphere printer is high.
  • the mixer 206 further includes a switching valve 204, the switching valve 204 includes a valve body 301 and a valve core 302, and the valve body 301 has a second output part 307 and a plurality of second inputs Part 306, the second input part 306 has a water phase input port 304, and the second output part 307 has a water phase output port 303.
  • a plurality of water-phase liquid feeders 106 are provided, and the water-phase materials 201 in the water-phase liquid feeders 106 are of the same type, but the repair cells 203 mixed with the water-phase materials 201 are different in each water-phase liquid feeder 106 .
  • the water phase material 201 and the oil phase material 202 in different water phase liquid supply devices 106 can be mixed to finally obtain different types of biological microspheres 109.
  • the advantage of this setting is that multiple types of biological microspheres 109 can be printed by one printer without stopping the operation of the machine and changing materials in the middle.
  • the general working principle of the switching valve 204 can refer to FIG. 3 .
  • the second input parts 306 correspond to the water-phase liquid supply devices 106 one-to-one.
  • One water-phase liquid supply device 106 is connected to a second input part 306 through a pipe fitting, and a second input part 306 is The input part 306 is only connected to one water-phase liquid supply device 106 ; the second output part is connected to one of the first input parts 207 of the three-way pipe 205 .
  • the valve core 302 is located inside the valve body 301, and the valve core 302 has an inner valve channel 305.
  • the valve core 302 can rotate relative to the valve body 301, so that the water phase output port 303 and different water phase input ports 304 pass through the valve inner channel 305 Connected.
  • the printing module 103 further includes an air source, and the air source can be specifically set as an air compressor.
  • the air source is connected to the print head 110 through a hose, and the air source supplies air to the print head 110 so that the print head 110
  • the biological microspheres 109 in the middle are ejected from the print head 110; and the oil phase material 202 ejected together with the biological microspheres 109 can volatilize rapidly under the action of high-speed airflow.
  • the biological microspheres 109 are ejected by gas, and the print head 110 can keep a certain distance from the area to be printed, that is, non-contact printing can be realized.
  • jet printing is beneficial to improve the versatility of the printer.
  • the print head 110 includes a microsphere flow tube 402 and a gas flow tube 401.
  • the microsphere flow tube 402 is arranged horizontally, and the gas flow tube 401 is arranged vertically.
  • One end of the microsphere flow tube 402 is connected to the curing module. 102 is connected, the other end of the microsphere flow tube 402 is connected with the side of the gas flow tube 401, and the lumen of the gas flow tube 401 is communicated with the lumen of the microsphere flow tube 402; one end of the gas flow tube 401 is connected with the gas source .
  • the second setting method can refer to Fig. 5.
  • This setting method is similar to the first setting method. The difference is that the microsphere flow tube 402 is arranged vertically, the gas flow tube 401 is arranged horizontally, and one end of the gas flow tube 401 flows with the microspheres. The side of the tube 402 is connected.
  • the biological microspheres 109 and the oil phase material 202 cannot easily leave the microsphere flow tube 402 due to their own gravity; when the gas flows into the microsphere flow tube 402 , the gas will squeeze out the biological microspheres 109 and part of the oil phase material 202 , and the biological microspheres 109 will be ejected from the end of the microsphere flow pipe which is far away from the curing module.
  • This setup is also simpler and easier to control.
  • the print head 110 includes a microsphere flow tube 402 and two gas flow tubes 401 .
  • the biological microspheres 109 are ejected from the end of the microsphere flow tube 402 away from the curing module 102 , and the microspheres flow.
  • the end of the pipe 402 away from the curing module 102 is the ejection end 601.
  • the two gas flow pipes 401 are symmetrically arranged based on the microsphere flow pipe 402; The sides of the microsphere flow tube 402 are connected, the other end of the gas flow tube 401 extends away from the ejection end 601 , and the ends of the two gas flow tubes 401 away from the microsphere flow tube 402 are connected to the gas source.
  • the gas will enter the microsphere flow tube 402 from the two gas flow tubes 401 .
  • the lateral distribution of the force exerted by the two gases on the biological microspheres 109 The forces cancel each other out, therefore, the biological microspheres 109 can be ejected relatively straightly along the axis of the microsphere flow tube 402 to the area to be printed, which is beneficial to reduce the error between the actual landing point and the theoretical landing point of the biological microspheres 109, and improve the Printing accuracy.
  • the print head 110 includes a microsphere flow tube 402, a gas flow tube 401 and a fixed block 701.
  • the microsphere flow tube 402 and The gas flow tubes 401 are not directly connected, but are connected through the fixed block 701 .
  • the inside of the fixed block 701 has a first flow channel 702 and a second flow channel 703 that communicate with each other.
  • the outer surface of the fixed block 701 is provided with a first insertion port 705, a second insertion port 707 and a printing port 706.
  • the first insertion port 705 and The printing ports 706 are respectively communicated with both ends of the first flow channel 702 , one end of the second flow channel 703 is communicated with the side of the first flow channel 702 , and the other end of the second flow channel 703 is communicated with the second insertion port 707 .
  • One end of the gas flow tube 401 is connected to the gas source, and the other end of the gas flow tube 401 is inserted into the fixing block 701 from the first insertion port 705, so that the lumen of the gas flow tube 401 is communicated with the first flow channel 702, and the microspheres flow
  • One end of the tube 402 is inserted into the fixing block 701 from the second insertion port 707 , so that the lumen of the microsphere flow tube 402 communicates with the second flow channel 703 , and the printing port 706 is for ejecting the biological microspheres 109 .
  • the advantage of this arrangement is that the print head 110 can be formed by assembling components with relatively simple shapes, and there is no need to arrange components with complex shapes; Instead of replacing the entire printhead 110 directly, the damaged parts can be replaced, which is beneficial for saving maintenance costs.
  • the microsphere flow tube 402 which is similar to the fourth setting method, except that the microsphere flow tube 402, the gas flow tube 401, the first flow channel 702, the second flow channel 703, the first insert There are multiple ports 705 , second insertion ports 707 and printing ports 706 .
  • the first flow channel 702 and the second flow channel 703 communicate with each other to form a printing cavity 704 , and adjacent printing cavities 704 are separated from each other.
  • the biological microspheres 109 ejected from different printing ports 706 can be different, so that different printing ports 706 are facing the target printing position so that different biological microspheres 109 can be printed on different printing points.
  • the biological microspheres 109 ejected from different printing ports 706 are of the same type, and when there is a large area in the to-be-printed area and the same type of biological microspheres 109 is required, this setting can improve the printing efficiency.
  • the printing module 103 and the curing module 102 are connected through a pipe fitting, that is, different types of biological microspheres 109 enter the printing module 103 through the same pipeline;
  • the function of transferring different kinds of biological microspheres 109 to different microsphere flow tubes 402 can also be realized by the switching valve 204 (an additional switching valve 204 is provided in the printing module 103 ).
  • the control module 105 is electrically connected to the preparation module 101, and the control module 105 can record the working state of the switching valve 204 in the preparation module 101, the infusion rate of the water-phase liquid supply device 106 and the infusion rate of the oil-phase liquid supply device 107, and calculate a certain The type of the biological microspheres 109 that will be transferred to the print head 110 at a point in time, according to the type of the biological microspheres 109 , the state of the switching valve 204 in the printing module 103 can be adjusted to achieve a specific biological microspheres 109 Transfer to a specific microsphere flow tube 402.
  • the control module 105 further includes a color sensor 403, the color sensor 403 is electrically connected to the control module 105, and the color sensor 403 is used to identify the color of the biological microspheres 109 in the print head 110 and send the biological micro
  • the color information of the ball 109 is transmitted to the control module 105, and the control module 105 can drive the displacement mechanism according to the color information.
  • the biological microsphere printer can print different biological microspheres 109 for the convenience of distinguishing. Different biological microspheres 109 can be dyed with different colors in order to print different biological microspheres 109 on suitable positions.
  • the dyeing operation may specifically be: adding a non-cytotoxic dye to the water-phase material 201 in the water-phase liquid supplier 106 to realize dyeing.
  • the control module 105 can determine the type of the biological microspheres 109 to be ejected according to the color of the biological microspheres 109, and drive the displacement mechanism to move the print head according to the type of the biological microspheres 109. Move to a suitable location.
  • the color sensor 403 is provided, the gas flow tube 401 and the microsphere flow tube 402 are set as transparent tubes. If the print head 110 further includes the fixing block 701 , the fixing block 701 also needs to be set to be transparent.

Landscapes

  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Manufacturing & Machinery (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Mechanical Engineering (AREA)
  • Optics & Photonics (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)

Abstract

本发明提供了一种生物微球打印机。生物微球打印机包括制备模块、熟化模块、打印模块、扫描模块和控制模块；制备模块用于制备微液滴，微液滴在熟化模块中固化成型以形成生物微球；打印模块包括打印头和位移机构，扫描模块采集待打印区域的图像信息，控制模块根据扫描模块采集的图像信息启闭打印头和驱动位移机构。本发明提供的生物微球打印机，通过扫描模块对待打印区域进行扫描和识别，然后根据控制模块对图像信息的分析结果将每一生物微球准确地打印至合适的位置上以修复创伤，该生物微球打印机的打印精度高。

Description

生物微球打印机 技术领域
本发明涉及生物制造技术领域，尤其涉及一种生物微球打印机。
背景技术
目前有一种利用生物微球的创伤修复技术，将含有特定细胞的生物微球覆盖创伤处，部分技术人员或医疗人员会利用一些3D打印设备将成型的生物微球打印到创伤处。相对于微球本身的尺寸，伤口面积较大，创伤修复通常需要根据伤口的形状将多个微球排列或堆叠在伤口处。现有的这些打印设备打印精度不高，无法准确地将单个生物微球打印至合适位置上，影响了创伤修复效果。
发明内容
本发明旨在至少解决现有技术中存在的技术问题之一。为此，本发明提出一种生物微球打印机，该生物微球打印机打印精度高。
根据本发明实施例的生物微球打印机，包括：制备模块，包括水相供液器、油相供液器和混合器，所述水相供液器和所述油相供液器均与所述混合器连接，所述水相供液器向所述混合器输送所述水相材料，所述油相供液器向所述混合器输送所述油相材料，所述混合器用于使所述水相材料和所述油相材料接触并混合以形成所述微液滴；熟化模块，与所述混合器连接，所述熟化模块用于接收所述微液滴，并使所述微液滴固化以形成所述生物微球；打印模块，包括打印头和位移机构，所述打印头与所述位移机构连接，所述打印头与所述熟化模块连接，所述位移机构用于驱动所述打印头移动，所述打印头用于接收所述生物微球并将所述生物微球输送至所述待打印区域；扫描模块，用于采集所述待打印区域的图像信息；控制模块，所述控制模块与所述扫描模块电连接，所述控制模块与所述打印模块电连接，所述控制模块用于接收所述图像信息，并根据所述图像信息启闭所述打印头和移动所述打印头。
根据本发明实施例的生物微球打印机，至少具有如下有益效果：通过扫描模块对待打印区域进行扫描和识别，然后根据控制模块对图像信息的分析结果将每一生物微球准确地打印至合适的位置上以修复创伤，该生物微球打印机的打印精度高。
根据本发明的一些实施例，所述混合器包括：三通管，包括两个第一输入部和一个第一输出部，所述第一输入部与所述第一输出部相互连通；切换阀，包括阀体和阀芯，所述阀芯位于所述阀体的内部，所述阀体具有多个第二输入部和一个第二输出部，所述第二输入部具有水相输入口，所述第二输出部具有水相输出口，所述水相供液器设置有多个，每一所述水相供液器分别与一个所述第二输入部连接，所述阀芯具有阀内通道，所述阀芯能够相对于所述阀体转动，以使所述水相输出口和其中一个所述水相输入口通过所述阀内通道连通；其中一个所述第一输入部与所述第二输出部连接，另一个所述第一输入部与所述油相供液器连接，所述第一输出部与所述熟化模块连接。
根据本发明的一些实施例，所述打印模块还包括气源，所述气源与所述打印头连接，所述气源为所述打印头供气，以使所述打印头中的所述生物微球从所述打印头中喷出。
根据本发明的一些实施例，所述打印头包括：微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；气体流动管，所述微球流动管的一端与所述气体流动管的侧部连接，以使所述气体流动管的管腔与所述微球流动管的管腔连通，所述气体流动管的一端与所述气源连接，所述气源用于为所述气体流动管内供气，以使所述生物微球从所述气体流动管的另一端喷出。
根据本发明的一些实施例，所述打印头包括：微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；气体流动管，所述气体流动管的一端与所述微球流动管的侧部连接，以使所述气体流动管的管腔和所述微球流动管的管腔连通，所述气体流动管的另一端与所述气源连接，所述气源用于为所述气体流动管内供气，以使所述生物微球从所述微球流动管远离所述熟化模块的一端喷出。
根据本发明的一些实施例，所述打印头包括：微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；气体流动管，一端与所述气源连接；固定块，内部具有第一流动通道和第二流动通道，所述固定块的外表开设有第一插入口、第二插入口和打印口，所述第一插入口和所述打印口分别与所述第一流动通道的两端连通，所述第二流动通道的一端与所述第一流动通道的侧部连通，所述第二流动通道的另一端与所述第二插入口连通；所述气体流动管远离所述气源的一端从所述第一插入口插入所述固定块中，以使所述气体流动管的管腔与所述第一流动通道连通，所述微球流动管的一端从所述第二插入口插入所述固定块中，以使所述微球流动管的官腔与所述第二流动通道连通，所述打印口供所述生物微球喷出。
根据本发明的一些实施例，所述微球流动管、所述气体流动管、所述第一流动通道、所 述第二流动通道、所述第一插入口、所述第二插入口和所述打印口均设置有多个，一个所述第一流动通道和一个所述第二流动通道连通以形成打印腔，相邻的所述打印腔相互分隔。
根据本发明的一些实施例，所述打印头包括：微球流动管，其一端与所述熟化模块连接，所述微球流动管供所述生物微球流动，所述微球流动管的另一端为喷出端，所述生物微球通过所述喷出端从所述微球流动管中喷出；气体流动管，设置有两个，所述气体流动管相对于所述微球流动管倾斜设置，且两个所述气体流动管基于所述微球流动管对称设置，所述气体流动管的一端与所述微球流动管的侧部连接，以使所述微球流动管的管腔与所述微球流动管的管腔连通，所述气体流动管的另一端，朝远离所述喷出端延伸，两个所述气体流动管远离所述微球流动管的一端均与所述气源连接。
根据本发明的一些实施例，所述熟化模块包括水浴加热器，所述水浴加热器包括：箱体，内部具有加热腔；导热液，容置在所述加热腔中；加热件，与所述箱体连接，所述加热件用于加热所述导热液；熟化管，所述熟化管的管腔供所述生物微球流动，所述熟化管的一部分浸泡在所述导热液中。
根据本发明的一些实施例，所述打印模块还包括颜色传感器，所述颜色传感器与所述控制模块电连接，所述颜色传感器用于识别所述打印头内的所述生物微球的颜色并将所述生物微球的颜色信息传递至所述控制模块，所述控制模块能够根据所述颜色信息驱动所述位移机构。
本发明的附加方面和优点将在下面的描述中部分给出，部分将从下面的描述中变得明显，或通过本发明的实践了解到。
附图说明
下面结合附图和实施例对本发明做进一步的说明，其中：
图1为生物微球打印机的整体示意图；
图2为一些实施例中水相供液器、油相供液器和混合器的连接方式简化示意图；
图3为一些实施例中切换阀的原理示意图；
图4为打印头的第一种设置方式的示意图；
图5为打印头的第二种设置方式的示意图；
图6为打印头的第三种设置方式的示意图；
图7为打印头的第四种设置方式的示意图；
图8为图7中的打印头的组装方式示意图；
图9为打印头的第四种设置方式的示意图；
图10为一些实施例中熟化模块的简化示意图。
附图标记：101-制备模块，102-熟化模块，103-打印模块，104-扫描模块，105-控制模块，106-水相供液器，107-油相供液器，108-微液滴，109-生物微球，110-打印头，201-水相材料，202-油相材料，203-修复细胞，204-切换阀，205-三通管，206-混合器，207-第一输入部，208-第一输出部，301-阀体，302-阀芯，303-水相输出口，304-水相输入口，305-阀内通道，306-第二输入部，307-第二输出部，401-气体流动管，402-微球流动管，403-颜色传感器，601-喷出端，701-固定块，702-第一流动通道，703-第二流动通道，704-打印腔，705-第一插入口，706-打印口，707-第二插入口，1001-箱体，1002-熟化管，1003-导热液，1004-加热件，1005-加热腔，1006-水浴加热器。
具体实施方式
下面详细描述本发明的实施例，所述实施例的示例在附图中示出，其中自始至终相同或类似的标号表示相同或类似的元件或具有相同或类似功能的元件。下面通过参考附图描述的实施例是示例性的，仅用于解释本发明，而不能理解为对本发明的限制。
在本发明的描述中，需要理解的是，涉及到方位描述，例如上、下、前、后、左、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和简化描述，而不是指示或暗示所指的装置或元件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的限制。
在本发明的描述中，若干的含义是一个以上，多个的含义是两个以上，大于、小于、超过等理解为不包括本数，以上、以下、以内等理解为包括本数。如果有描述到第一、第二只是用于区分技术特征为目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量或者隐含指明所指示的技术特征的先后关系。
本发明的描述中，除非另有明确的限定，设置、安装、连接等词语应做广义理解，所属技术领域技术人员可以结合技术方案的具体内容合理确定上述词语在本发明中的具体含义。
本发明的描述中，参考术语“一个实施例”、“一些实施例”、“示意性实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不一定指的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
本发明提供了一种生物微球打印机，生物微球打印机用于将生物微球打印至待打印区域，以修复创伤，例如修复皮肤伤口、肌肉损伤，待打印区域可以是人体器官或组织的受损区域。生物微球包括水相材料和修复细胞，水相材料具体可以是水凝胶、基质胶等，水凝胶溶液可以从液态转化为凝胶态(固态)，修复细胞根据待修复的目标的种类可以设置为肌肉细胞、干细胞、肝脏细胞等。生物微球的制作还需要油相材料(例如生物氟油)，油相材料本身不作为构成生物微球的成分；油相材料与水相材料互不相溶，基于油相材料和水相材料两者的表面张力和液体黏度的差异，油相材料和水相材料在管道的交叉点相遇后，水相材料在油相材料的剪切和挤压作用下被夹断，从而形成水相材料的微液滴。如何形成微液滴的具体原理属于本领域的公知技术，此处不详细论述。修复细胞可以预先混合在水相材料中。微液滴固化成型后形成生物微球，微液滴在适当的温度、光照、离子或酶的作用下固化成生物微球。
参照图1，本发明的生物微球打印机包括制备模块101、熟化模块102、打印模块103、扫描模块104和控制模块105。
参照图1和图2，制备模块101包括水相供液器106、油相供液器107和混合器206，水相供液器106和油相供液器107均与混合器206连接，水相供液器106向混合器206输送水相材料201(被输送的水相材料201中已混合有修复细胞203)，油相供液器107向混合器206输送油相材料202，水相材料201和油相材料202在混合器206中接触、混合，从而形成微液滴108。
参照图1，在一些实施例中，水相供液器106可包括注射泵，注射泵本身具有储液的腔体，因此水相供液器106可以不需要再额外设置储存水相材料201的容器。在另一些实施例中，水相供液器106的泵可以设置为其他类型的泵，例如柱塞泵、蠕动泵等，对应地，水相供液器106中还需要设置储液容器；以柱塞泵为例，柱塞泵从储液容器中抽取水相材料201，然后将水相材料201泵送至混合器206。油相供液器107的具体设置与水相供液器106类似，此处不重复描述。此外，通过调整泵的输送速率可以调整流入三通管205中的水相材料201和油相材料202的之间流量比例，从而调整相邻的微液滴108(或相邻的生物微球109)的间隔，以及调整微液滴108(或生物微球109)的直径。
参照图1，在一些实施例中，混合器206具体可以包括三通管205，三通管205包括两个第一输入部207和一个第一输出部208，第一输入部207和第一输出部208连通，两个第一输入部207分别与水相供液器106、油相供液器107连接，第一输出部208与熟化模块102通过管件进行连接，以实现微液滴108的输送。水相材料201和油相材料202在三通管205内混合，油相材料202与混合后形成的微液滴108(微液滴108分散于油相材料202中)被 输送至熟化模块102。
微液滴108进入熟化模块102后固化以形成生物微球109。参照图10，在一些实施例中，水相材料201设置为基质胶，熟化模块102包括水浴加热器1006，微液滴108经水浴加热至一定温度后成胶固化，形成生物微球109。通过加热的方式实现微液滴108的固化较为简单，成本较低；而采用水浴加热能够保证微液滴108受热均匀，从而保证成型效果。参照图10，水浴加热器1006包括箱体1001、熟化管1002、导热液1003和加热件1004；箱体1001的内部具有加热腔1005，导热液1003容置在加热腔1005中，加热件1004与箱体1001连接(加热件1004可以安装于箱体1001的外壁上)，熟化管1002的一部分浸泡在导热液1003中。熟化管1002的一端与制备模块101连接，另一端与打印模块103连接，来自制备模块101的微液滴108沿熟化管1002的管腔流动至打印模块103，微液滴108流动途中经过导热液1003的加热而逐渐成型。
参照图1，控制模块105可以设置为计算机，打印模块103和扫描模块104均与控制模块105电连接(具体可以通过通讯线缆实现电连接)。打印模块103包括打印头110和位移机构，打印头110与位移机构连接，位移机构图中未具体示出，位移机构具体可以设置为多轴机械臂或多轴位移平台，位移机构用于驱动打印头110移动。扫描模块104包括摄像头，摄像头能够采集待打印区域的图像信息并输送至控制模块105。控制模块105根据接收到待打印区域的图像信息进行待打印区域的三维建模，然后控制模块对三维模型进行切分处理，将其转化成由生物微球109组成的三维结构，然后提取每一生物微球109中心坐标并传至控制系统中。得到生物微球109的打印位置后，控制模块105根据打印位置控制位移机构运动，打印头110在位移机构的驱动下移动至合适的位置；打印头110移动至合适位置后，控制模块105控制打印头110开启，生物微球109被打出。
本发明提供的生物微球打印机，通过扫描模块104对待打印区域进行扫描和识别，然后根据控制模块105对图像信息的分析结果将每一生物微球109准确地打印至合适的位置上以修复创伤，该生物微球打印机的打印精度高。
参照图2和图3，在一些实施例中，混合器206还包括切换阀204，切换阀204包括阀体301和阀芯302，阀体301具有一个第二输出部307和多个第二输入部306，第二输入部306具有水相输入口304，第二输出部307具有水相输出口303。水相供液器106设置有多个，水相供液器106中的水相材料201种类相同，但每个水相供液器106中，水相材料201混有的修复细胞203种类不同。通过切换阀204的切换，将不同的水相供液器106中的水相材料201与油相材料202混合最终可以得到不同种类的生物微球109。这样设置的好处在于，可以在 中途不需要暂停机器的运作和更换材料的情况下，利用一个打印机打印多种类型的生物微球109。
切换阀204的大致工作原理可参考图3，第二输入部306与水相供液器106一一对应，一个水相供液器106通过管件与一个第二输入部306连接，且一个第二输入部306仅与一个水相供液器106连接；第二输出部则与三通管205的其中一个第一输入部207连接。阀芯302位于阀体301的内部，阀芯302内部具有阀内通道305，阀芯302能够相对阀体301转动，以使水相输出口303与不同的水相输入口304通过阀内通道305连通。
在一些实施例中，打印模块103还包括气源，气源具体可以设置为空气压缩机，气源与打印头110通过软管进行连接，气源为打印头110供气，以使打印头110中的生物微球109从打印头110中喷出；而随生物微球109一同喷出的油相材料202可以在高速的气流作用下快速挥发。利用气体将生物微球109喷出，打印头110可以与待打印区域保持一定距离，即可以实现无接触式打印。无接触式的打印适用场景相对更多，喷气式的打印有利于提高打印机的通用性。
下面介绍几种打印头110的具体设置方式。
第一种设置方式可参考图4，打印头110包括微球流动管402和气体流动管401，微球流动管402横向设置，气体流动管401纵向设置，微球流动管402的一端与熟化模块102连接，微球流动管402的另一端与气体流动管401的侧部连接，且气体流动管401的管腔与微球流动管402的管腔连通；气体流动管401的一端与气源连接。在水相供液器106和油相供液器107的输送作用下，微球流动管402内流动的生物微球109被推至气体流动管401中，随后生物微球109被气流推动而从气体流动管401未与气源连接的一端喷出。这种设置方式相对较为简单，且易于控制。
第二种设置方式可参考图5，这种设置方式与第一种设置方式类似，区别在于，微球流动管402纵向设置，气体流动管401横向设置，气体流动管401的一端与微球流动管402的侧部连接。由于微球流动管402的实际管径较小，在液体表面张力的作用下，生物微球109和油相材料202不易因自身重力离开微球流动管402；当气体流入微球流动管402后，气体会挤出生物微球109和部分油相材料202，生物微球109从微球流动管的远离熟化模块的一端喷出。这种设置方式同样较为简单且易于控制。
第三种设置方式可参考图6，打印头110包括一个微球流动管402和两个气体流动管401，生物微球109从微球流动管402远离熟化模块102的一端喷出，微球流动管402远离熟化模块102这一端为喷出端601，两个气体流动管401基于微球流动管402对称设置；气体流动 管401相对于微球流动管402倾斜设置，气体流动管401的一端与微球流动管402的侧部连接，气体流动管401的另一端朝远离喷出端601的方向延伸，两个气体流动管401远离微球流动管402的一端与气源连接。在这种设置方式下，气体会从两个气体流动管401进入微球流动管402中，基于气体流动管401的对称设置，两股气体施加在生物微球109上的作用力的侧向分力相互抵消，因此，生物微球109能够沿微球流动管402的轴线较为笔直地喷出至待打印区域，这有利于减小生物微球109的实际落点与理论落点的误差，提高打印精度。
第四种设置方式可参照图7和图8，这种设置方式与上述三种方式均不同，打印头110包括微球流动管402、气体流动管401和固定块701，微球流动管402和气体流动管401不直接连接，而是通过固定块701连接。固定块701的内部具有相互连通的第一流动通道702和第二流动通道703，固定块701的外表开设有第一插入口705、第二插入口707和打印口706，第一插入口705和打印口706分别与第一流动通道702的两端连通，第二流动通道703的一端与第一流动通道702的侧部连通，第二流动通道703的另一端与第二插入口707连通。气体流动管401的一端与气源连接，气体流动管401的另一端从第一插入口705插入固定块701中，以使气体流动管401的管腔与第一流动通道702连通，微球流动管402的一端从第二插入口707插入固定块701中，以使微球流动管402的管腔与第二流动通道703连通，打印口706则供生物微球109喷出。这种设置方式的好处在于，打印头110可以由形状相对简单的部件相互组装形成，不需要设置形状复杂的部件；此外，由于打印头110由多个部件组装而成，当某一部件损坏时可以更换损坏部件而不是直接更换整个打印头110，这样有利于节约维修成本。
第五种设置方式可参照图9，该设置方式与第四种设置方式类似，区别在于，微球流动管402、气体流动管401、第一流动通道702、第二流动通道703、第一插入口705、第二插入口707和打印口706均设置有多个，第一流动通道702和第二流动通道703连通以形成打印腔704，相邻的打印腔704相互分隔。这种设置方式下，从不同的打印口706中喷出的生物微球109可以不同，使不同的打印口706正对目标打印位置便可将不同的生物微球109打印至不同的打印点上；又或者，不同的打印口706中喷出的生物微球109种类相同，在待打印区域有较大面积需要同种类的生物微球109时，这样设置可以提高打印效率。
需要说明的是，参考图1，打印模块103和熟化模块102之间通过一个管件进行连接，即不同种类的生物微球109均通过相同的管路进入打印模块103；将一个管路中的不同种类的生物微球109转移至不同的微球流动管402的功能，同样可以通过切换阀204实现(在打印模块103中额外设置一个切换阀204)。控制模块105与制备模块101电连接，控制模块 105可记录制备模块101中的切换阀204的工作状态、水相供液器106的输液速率和油相供液器107的输液速率，推算出某一时间点上即将转移至打印头110的那一个生物微球109的种类，根据这一个生物微球109的种类，可以调整打印模块103中的切换阀204的状态，实现特定的生物微球109转移至特定的微球流动管402。
参照图4，在一些实施例中，控制模块105还包括颜色传感器403，颜色传感器403与控制模块105电连接，颜色传感器403用于识别打印头110内的生物微球109的颜色并将生物微球109的颜色信息传递至控制模块105，控制模块105能够根据颜色信息驱动位移机构。上文已提及，在水相供液器106设置有多个，且不同的水相供液器106中的修复细胞203不同，生物微球打印机可以打印不同的生物微球109，为便于区分不同的生物微球109以便将不同的生物微球109打印至合适的位置上，可以使不同的生物微球109染上不同的颜色。染色的操作具体可以是，向水相供液器106中的水相材料201添加无细胞毒性的染料实现染色。颜色传感器403识别生物微球109的颜色后，控制模块105可以根据生物微球109的颜色确定将要喷出的生物微球109的种类，并根据生物微球109的种类，驱动位移机构将打印头移动至合适的位置。而设置有颜色传感器403的情况下，气体流动管401和微球流动管402设置为透明的管件，若打印头110还包括固定块701，固定块701也需要设置为透明的。
上面结合附图对本发明实施例作了详细说明，但是本发明不限于上述实施例，在所属技术领域普通技术人员所具备的知识范围内，还可以在不脱离本发明宗旨的前提下作出各种变化。此外，在不冲突的情况下，本发明的实施例及实施例中的特征可以相互组合。

Claims (10)

  1. 生物微球打印机，用于将生物微球打印至待打印区域，所述生物微球包括水相材料和修复细胞，所述修复细胞混合在所述水相材料中，所述水相材料与油相材料混合后，所述水相材料被所述油相材料剪切和挤压以形成所述水相材料的微液滴，所述微液滴固化形成所述生物微球，其特征在于，包括：
    制备模块，包括水相供液器、油相供液器和混合器，所述水相供液器和所述油相供液器均与所述混合器连接，所述水相供液器向所述混合器输送所述水相材料，所述油相供液器向所述混合器输送所述油相材料，所述混合器用于使所述水相材料和所述油相材料接触并混合以形成所述微液滴；
    熟化模块，与所述混合器连接，所述熟化模块用于接收所述微液滴，并使所述微液滴固化以形成所述生物微球；
    打印模块，包括打印头和位移机构，所述打印头与所述位移机构连接，所述打印头与所述熟化模块连接，所述位移机构用于驱动所述打印头移动，所述打印头用于接收所述生物微球并将所述生物微球输送至所述待打印区域；
    扫描模块，用于采集所述待打印区域的图像信息；
    控制模块，所述控制模块与所述扫描模块电连接，所述控制模块与所述打印模块电连接，所述控制模块用于接收所述图像信息，并根据所述图像信息启闭所述打印头和驱动所述位移机构。
  2. 根据权利要求1所述的生物微球打印机，其特征在于，所述混合器包括：
    三通管，包括两个第一输入部和一个第一输出部，所述第一输入部与所述第一输出部相互连通；
    切换阀，包括阀体和阀芯，所述阀芯位于所述阀体的内部，所述阀体具有多个第二输入部和一个第二输出部，所述第二输入部具有水相输入口，所述第二输出部具有水相输出口，所述水相供液器设置有多个，每一所述水相供液器分别与一个所述第二输入部连接，所述阀芯具有阀内通道，所述阀芯能够相对于所述阀体转动，以使所述水相输出口和其中一个所述水相输入口通过所述阀内通道连通；
    其中一个所述第一输入部与所述第二输出部连接，另一个所述第一输入部与所述油相供液器连接，所述第一输出部与所述熟化模块连接。
  3. 根据权利要求1或2所述的生物微球打印机，其特征在于，所述打印模块还包括气源， 所述气源与所述打印头连接，所述气源为所述打印头供气，以使所述打印头中的所述生物微球从所述打印头中喷出。
  4. 根据权利要求3所述的生物微球打印机，其特征在于，所述打印头包括：
    微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；
    气体流动管，所述微球流动管的一端与所述气体流动管的侧部连接，以使所述气体流动管的管腔与所述微球流动管的管腔连通，所述气体流动管的一端与所述气源连接，所述气源用于为所述气体流动管内供气，以使所述生物微球从所述气体流动管的另一端喷出。
  5. 根据权利要求3所述的生物微球打印机，其特征在于，所述打印头包括：
    微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；
    气体流动管，所述气体流动管的一端与所述微球流动管的侧部连接，以使所述气体流动管的管腔和所述微球流动管的管腔连通，所述气体流动管的另一端与所述气源连接，所述气源用于为所述气体流动管内供气，以使所述生物微球从所述微球流动管远离所述熟化模块的一端喷出。
  6. 根据权利要求3所述的生物微球打印机，其特征在于，所述打印头包括：
    微球流动管，一端与所述熟化模块连接，所述微球流动管供所述生物微球流动；
    气体流动管，一端与所述气源连接；
    固定块，内部具有第一流动通道和第二流动通道，所述固定块的外表开设有第一插入口、第二插入口和打印口，所述第一插入口和所述打印口分别与所述第一流动通道的两端连通，所述第二流动通道的一端与所述第一流动通道的侧部连通，所述第二流动通道的另一端与所述第二插入口连通；
    所述气体流动管远离所述气源的一端从所述第一插入口插入所述固定块中，以使所述气体流动管的管腔与所述第一流动通道连通，所述微球流动管的一端从所述第二插入口插入所述固定块中，以使所述微球流动管的官腔与所述第二流动通道连通，所述打印口供所述生物微球喷出。
  7. 根据权利要求6所述的生物微球打印机，其特征在于，所述微球流动管、所述气体流动管、所述第一流动通道、所述第二流动通道、所述第一插入口、所述第二插入口和所述打印口均设置有多个，一个所述第一流动通道和一个所述第二流动通道连通以形成打印腔，相邻的所述打印腔相互分隔。
  8. 根据权利要求3所述的生物微球打印机，其特征在于，所述打印头包括：
    微球流动管，其一端与所述熟化模块连接，所述微球流动管供所述生物微球流动，所述 微球流动管的另一端为喷出端，所述生物微球通过所述喷出端从所述微球流动管中喷出；
    气体流动管，设置有两个，所述气体流动管相对于所述微球流动管倾斜设置，且两个所述气体流动管基于所述微球流动管对称设置，所述气体流动管的一端与所述微球流动管的侧部连接，以使所述微球流动管的管腔与所述微球流动管的管腔连通，所述气体流动管的另一端，朝远离所述喷出端延伸，两个所述气体流动管远离所述微球流动管的一端均与所述气源连接。
  9. 根据权利要求1所述的生物微球打印机，其特征在于，所述熟化模块包括水浴加热器，所述水浴加热器包括：
    箱体，内部具有加热腔；
    导热液，容置在所述加热腔中；
    加热件，与所述箱体连接，所述加热件用于加热所述导热液；
    熟化管，所述熟化管的管腔供所述生物微球流动，所述熟化管的一部分浸泡在所述导热液中。
  10. 根据权利要求1所述的生物微球打印机，其特征在于，所述打印模块还包括颜色传感器，所述颜色传感器与所述控制模块电连接，所述颜色传感器用于识别所述打印头内的所述生物微球的颜色并将所述生物微球的颜色信息传递至所述控制模块，所述控制模块能够根据所述颜色信息驱动所述位移机构。
PCT/CN2022/086339 2021-04-20 2022-04-12 生物微球打印机 WO2022222789A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110433571.4 2021-04-20
CN202110433571.4A CN113246467B (zh) 2021-04-20 2021-04-20 生物微球打印机

Publications (1)

Publication Number Publication Date
WO2022222789A1 true WO2022222789A1 (zh) 2022-10-27

Family

ID=77221267

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/086339 WO2022222789A1 (zh) 2021-04-20 2022-04-12 生物微球打印机

Country Status (2)

Country Link
CN (1) CN113246467B (zh)
WO (1) WO2022222789A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113246467B (zh) * 2021-04-20 2023-02-24 清华大学深圳国际研究生院 生物微球打印机

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106073788A (zh) * 2016-07-19 2016-11-09 杭州捷诺飞生物科技有限公司 基于oct的原位三维打印皮肤修复设备及其实现方法
US20170001439A1 (en) * 2014-01-24 2017-01-05 Eth Zurich Acoustophoretic printing apparatus and method
CN109203451A (zh) * 2018-09-07 2019-01-15 中国石油大学(华东) 一种基于气流传送的生物打印新方法
CN109822898A (zh) * 2019-03-18 2019-05-31 清华大学 一种用于生物3d打印机的微喷头装置及其应用
CN110042077A (zh) * 2019-04-22 2019-07-23 清华-伯克利深圳学院筹备办公室 一种类器官球体的高通量培养方法
CN110815824A (zh) * 2019-11-15 2020-02-21 清华-伯克利深圳学院筹备办公室 一种3d打印装置及3d打印系统
CN113246467A (zh) * 2021-04-20 2021-08-13 清华大学深圳国际研究生院 生物微球打印机

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103382438A (zh) * 2013-06-24 2013-11-06 清华大学 具搅拌功能的生物喷墨打印装置及打印方法
TWI491495B (zh) * 2013-12-13 2015-07-11 三緯國際立體列印科技股份有限公司 列印頭模組
CN105415688B (zh) * 2015-12-22 2017-10-20 珠海天威飞马打印耗材有限公司 三维打印机和三维打印方法
US10969350B2 (en) * 2017-05-22 2021-04-06 Arizona Board Of Regents On Behalf Of Arizona Stat Metal electrode based 3D printed device for tuning microfluidic droplet generation frequency and synchronizing phase for serial femtosecond crystallography
CN107471646B (zh) * 2017-10-16 2021-07-27 荆门米丰信息科技有限公司 一种用于彩色物体成型的三维打印机及其打印方法
CN111002427B (zh) * 2019-12-18 2020-09-22 南京理工大学 一种基于光固化技术的叠层式陶瓷基复合材料3d打印成型装置和方法
CN111605186A (zh) * 2020-06-17 2020-09-01 中国人民解放军总医院 一种喷墨打印凝胶微球的装置以及打印方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170001439A1 (en) * 2014-01-24 2017-01-05 Eth Zurich Acoustophoretic printing apparatus and method
CN106073788A (zh) * 2016-07-19 2016-11-09 杭州捷诺飞生物科技有限公司 基于oct的原位三维打印皮肤修复设备及其实现方法
CN109203451A (zh) * 2018-09-07 2019-01-15 中国石油大学(华东) 一种基于气流传送的生物打印新方法
CN109822898A (zh) * 2019-03-18 2019-05-31 清华大学 一种用于生物3d打印机的微喷头装置及其应用
CN110042077A (zh) * 2019-04-22 2019-07-23 清华-伯克利深圳学院筹备办公室 一种类器官球体的高通量培养方法
CN110815824A (zh) * 2019-11-15 2020-02-21 清华-伯克利深圳学院筹备办公室 一种3d打印装置及3d打印系统
CN113246467A (zh) * 2021-04-20 2021-08-13 清华大学深圳国际研究生院 生物微球打印机

Also Published As

Publication number Publication date
CN113246467B (zh) 2023-02-24
CN113246467A (zh) 2021-08-13

Similar Documents

Publication Publication Date Title
WO2022222789A1 (zh) 生物微球打印机
CN104708821A (zh) 一种用于组织/器官芯片集成制造的三维打印方法及装置
CN110039774B (zh) 3d打印机及其打印方法
CN101602284A (zh) 用于印刷透镜模具的粘度控制和着色剂循环
WO2024017118A1 (zh) 细胞球体制备装置及制备方法
CN110280716A (zh) 一种喷墨装置及3d打印设备
CN110435148A (zh) 一种基于液体瞬间固化的空间性能组合3d打印设备及方法
CN220008646U (zh) 一种风扇叶模具
CN109533700A (zh) 一种智能检测预警的中药材贮藏系统
CN105974970B (zh) 温等静压机工作容器与载热介质温度同步系统
CN218084188U (zh) 一种双喷头3d打印机
CN206899996U (zh) 具有加热功能的喷墨打印喷头及喷墨打印设备
CN215242567U (zh) 一种单阀咀
CN209109193U (zh) 一种液滴包含物的提取装置
CN210473635U (zh) 一种溶液调配装置
CN112874166B (zh) 一种具有询问型均墨结构的打印机
CN209307247U (zh) 一种可搅拌的有机肥蒸汽发酵罐
CN106738882A (zh) 一种节能型3d打印设备
CN106042261A (zh) 一种列排式反应注射成型机组
CN112169016B (zh) 微球打印装置
CN210758971U (zh) 一种用于针阀式热流道系统的平衡进胶结构
JP6795729B1 (ja) 供給チューブ
CN221562128U (zh) 一种液态硅胶模具冷却嘴装置
CN206287510U (zh) 一种多彩fdm打印机喷头装置
CN104044264A (zh) 一种多层共挤膜生产装置

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22790898

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22790898

Country of ref document: EP

Kind code of ref document: A1