CN114274508A - Biological 3D printing system - Google Patents

Biological 3D printing system Download PDF

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Publication number
CN114274508A
CN114274508A CN202111522749.9A CN202111522749A CN114274508A CN 114274508 A CN114274508 A CN 114274508A CN 202111522749 A CN202111522749 A CN 202111522749A CN 114274508 A CN114274508 A CN 114274508A
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CN
China
Prior art keywords
printing
spray head
medium
nozzle
biological
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Granted
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CN202111522749.9A
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Chinese (zh)
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CN114274508B (en
Inventor
张斌
杨腾
李琦
罗熠晨
张波
马梁
杨华勇
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Zhejiang University ZJU
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Zhejiang University ZJU
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    • 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
    • B29C64/112Processes 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
    • 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
    • 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
    • B29C64/205Means for applying layers
    • B29C64/209Heads; Nozzles
    • 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
    • B33Y10/00Processes of additive manufacturing
    • 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
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P10/00Technologies related to metal processing
    • Y02P10/25Process efficiency

Abstract

Biological 3D printing system, 3D printing system include the shower nozzle subassembly and the objective table of extruding the formula, and the objective table has the appearance chamber that matches with printing household utensils. The invention has the advantages that: the system is provided with a plurality of spray head assemblies which can work cooperatively or sequentially, the printing mode is flexible and changeable, and the non-uniform mixed system forming of materials can be realized; setting a pre-printing area, cleaning and cleaning the tip of a nozzle assembly, and ensuring stable output of materials in a formal printing task; the peripheral type of the printing vessel is surrounded by temperature control and vacuum adsorption clamping at the bottom, so that the quality of the formed living body structure is effectively guaranteed, and the survival rate of living body tissues is improved.

Description

Biological 3D printing system
Technical Field
The invention relates to the technical field of biological 3D printing in tissue engineering, in particular to a biological 3D printing system of high-precision biological printing equipment.
Background
An extremely large number of people worldwide suffer various types of injuries every year, resulting in tissue defects, or serious diseases that require organ transplantation, creating a huge tissue and organ repair need. Tissue organ transplantation is an extremely effective treatment for the treatment of large damaged soft tissues and internal organs of the human body. However, the practical application of organ transplantation therapy has difficulty due to the shortage of organ donor sources and the problems of immunological rejection. The proposal of tissue engineering opens up a new way for solving the problems. Tissue engineering is the construction of functional tissue substitutes by attaching living cells to a biomaterial matrix or prepared scaffolds by some method. Then the constructed tissue substitute is cultured and implanted into the body of a patient to replace the original pathological tissue organ to recover the original body function so as to realize the treatment of the disease. The research and application of the tissue engineering skin are effective exemplifications about good development prospect of the tissue engineering.
In recent years, the rapid development of 3D printing technology opens up a new manufacturing and production model for industrial manufacturing. In the biological field, techniques such as bioprinting and three-dimensional controlled organization of cells are also applied. The technologies have the capability of operating single cells or single-component micro-size liquid drops, can accurately control the spatial position and distribution of an operation object, and have great significance for realizing the spatial position deposition of different cells and biological materials in the process of constructing large tissues and organs. Therefore, the development of bioprinting technology is a necessary trend for future tissue engineering research. In a typical bioprinting apparatus, the most critical component is the shaped jet system.
In order to meet the manufacturing requirements of large-size complex tissue organs, particularly for tissue organs with obvious unit structures such as livers and the like, multiple materials are often required to be compounded and used. For example, when the skin is printed, tissues such as blood vessels and the like need to be printed, if a single spray head is used, a process of replacing the spray head for a long time is needed, so that the efficiency is influenced, the hydrogel on the side where the spray head is just replaced is possibly solidified, and if a plurality of infusion channels of the same spray head are adopted, the problem of material mixing at the spray head is caused; and cannot print simultaneously, and the efficiency is lower.
Single shower nozzle in the market takes envisionTec as an example, and the shower nozzle all will be removed to new shower nozzle department to trade the material each time, then adopts the mode tool changing of vacuum adsorption, has the problem that the time is long, positioning accuracy can't guarantee. In addition, if a discrete hexagonal shape similar to a hepatocyte is printed, 6 pieces have gaps between them, and there is a long time for routing; this severely limited the ability to print complex organs, with lengthy printing times and inefficiencies.
Disclosure of Invention
The invention aims to provide a multi-nozzle printing system which can work in a multi-nozzle cooperation mode and improve the printing capacity and efficiency of complex organs.
The biological 3D printing system comprises an extrusion type spray head assembly and an objective table, wherein the spray head assembly is provided with a respective nozzle, a storage barrel and a temperature control module; the three-axis translation mechanism drives the spray head assembly to translate along three axes (an X axis, a Y axis and a Z axis), the three-axis translation mechanism comprises an X axis translation unit, a Y axis translation unit and a Z axis translation unit, and the spray head assembly is installed on the Z axis translation unit. The spray head can move at any point of the XOY plane and can lift along the Z-axis direction; the spray head assembly has independent storage, extrusion and printing functions; the object stage is used for receiving the material extruded by the spray head component. The temperature control module keeps the temperature in the storage vat, so that the materials are kept at the temperature required by printing.
Multi-nozzle printing system
Preferably, the spray head assembly is provided with a plurality of spray head assemblies, each spray head assembly is provided with a respective spray head support, and each spray head support is provided with a fixing part connected with the Z-axis translation unit and a mounting part connected with the spray head assembly; the fixed part and the installation part are inclined angles, and the spray head assembly is arranged in an inclined mode. The slope of shower nozzle subassembly indicates to be the contained angle with the Z axle alternately, and the nozzle sets up to one side down, avoids taking place the motion between the storage vat to interfere, makes a plurality of shower nozzle subassemblies can collaborative work simultaneously.
Preferably, an angle adjusting mechanism is arranged between the fixing part and the mounting part of the spray head support. The angle adjusting mechanism can be a wedge block arranged between the spray head support and the spray head assembly, or the fixing part is hinged to the installation part, and the installation part rotates relative to the fixing part, so that an included angle between the installation part and the fixing part is adjusted, and further the angle of the spray head assembly on the installation part relative to the Z axis is adjusted. When the specified angle is reached, the position between the fixing part and the mounting part is locked. The locking mode adopts the prior art, such as: ratchet-pawl mechanisms, the manner of tightening screws, etc.
Preferably, the cross section of the nozzle support is in the shape of a right triangle, the surface of the hypotenuse of the nozzle support is an installation part, and the surface of one of the right-angle sides of the nozzle support is a fixing part. The nozzle assembly may have rotational freedom in the mounting face.
Preferably, at least one spray head assembly is provided with a rotating mechanism, and the rotating mechanism is arranged between the mounting part and the spray head assembly; the rotational degree of freedom of the rotating mechanism is unified with the spray head assembly. The rotating mechanism takes the fixed part as a datum plane and drives the spray head assembly to rotate in a plane where the fixed part is located, so that the angle of the spray nozzles relative to the working platform and the relative angle among the spray nozzles are adjusted.
Preferably, the rotating mechanism comprises a rotating shaft and a rotating seat, the rotating seat is fixed with the spray head assembly, and the rotating shaft is fixed with the mounting part of the spray head support. External force is applied to the rotating seat, and the rotating seat rotates around the rotating shaft, so that the spray head assembly is driven to rotate, and the angle of the spray nozzle is adjusted.
Preferably, the rotating mechanism is a mechanical rotating disc, the rotating disc is used as a rotating seat, and a locking screw or a locking bolt is arranged between the rotating disc and the spray head support. When the locking screw or the locking bolt does not lock the rotary disc and the spray head bracket, the rotary disc can be rotated to adjust the angle of the spray nozzle. After the angle of the nozzle is adjusted, the rotating disc and the nozzle support are locked by a locking screw or a locking bolt, and the rotating disc and the nozzle are positioned.
Alternatively, the rotating shaft is connected to a rotating motor.
Preferably, one or more spray head assemblies are arranged on the rotating mechanism; and/or one or more spray head components are arranged on each spray head bracket; and/or a plurality of spray head assemblies are arranged on each spray head bracket, and a respective rotating mechanism is arranged between each spray head assembly and each spray head bracket. Therefore, the purpose of flexibly expanding the number of the spray heads can be achieved by installing a plurality of spray head components on the spray head support, and the expanded spray heads can have rotational freedom degrees and can also be fixed in position.
The arrangement of the rotating mechanism enables the spray head assembly to have rotational freedom, and any angular displacement of the spray head tip can be realized within a stroke range, so that the relative positions of the plurality of spray head assemblies can be flexibly adjusted, and the multipoint concurrent connection of the plurality of spray heads becomes possible. Multiple jets may be co-located such that multiple jets are aimed at the same designated point or area at the same time. Or at different times, the tips of the jets may be aimed at the same point or region.
Triaxial translation mechanism
Preferably, each spray head assembly corresponds to a respective Z-axis translation unit; alternatively, at least two showerhead assemblies share a Z-axis translation unit.
Preferably, the X-direction translation mechanism comprises a fixed gantry, a movable gantry, an X-direction gantry guide rail matched with the movable gantry and an object stage guide rail matched with the object stage; the fixed gantry and the movable gantry are respectively provided with a Y-direction guide rail and a Z-direction guide rail, the Z-direction guide rail is slidably arranged on the Y-direction guide rail, and the spray head bracket is slidably arranged on the Z-direction guide rail; and one Z-direction guide rail corresponding to each spray head bracket and/or one Z-direction guide rail shared by a plurality of spray head brackets. That is, each of the head holders may be mounted on a respective Z-guide, or a plurality of head holders may be mounted on one Z-guide; or one spray head bracket corresponds to one Z-direction guide rail, and simultaneously, a plurality of spray head brackets share one Z-direction guide rail.
Preferably, the movable gantry and the fixed gantry are aligned, the movable gantry is provided with a plurality of spray head assemblies, and the fixed gantry is provided with a plurality of spray head assemblies. The number of the spray head assemblies of the movable gantry and the number of the spray head assemblies on the fixed gantry can be the same or different.
Preferably, the spray head assembly on the moving gantry and the spray head assembly on the fixed gantry are symmetrical about the middle plane of the moving gantry and the fixed gantry.
As the preferred scheme, the movable gantry is provided with 3 spray head assemblies, the fixed gantry is provided with 3 spray head assemblies, the spray head assemblies in the middle of the spray head assemblies of the same gantry are fixedly connected with a spray head support, and the other spray head assemblies are connected with the spray head support through a rotating mechanism.
Preferably, the stage rail is located between the moving gantry and the fixed gantry.
Preferably, each X-directional guide rail is respectively provided with a first travel switch and a second travel switch, and a movement travel is formed between the two travel switches. That is, the mobile gantry translates between the first and second travel switches of its guide rail; the stage translates between the first and second travel switches of its guide rail.
The triaxial translation mechanism can realize the position migration of any one spray head assembly at any point of the three-dimensional coordinate system.
Multi-nozzle common-point printing
Preferably, the printing system has a common-point calibration sensor, and when the nozzles of all the nozzle assemblies touch the common-point sensor, the printing paths of all the nozzle assemblies start to be common with each other. The coordinate systems of all showerhead modules are unified into a world coordinate system with a common point calibration sensor. The coordinate systems of all showerhead modules are unified into a world coordinate system with a common point calibration sensor.
Preferably, the concurrent calibration sensor comprises a calibration box, and the calibration box is provided with a first direction transmitter, a first direction receiver, a second direction transmitter and a second direction receiver; the path from the first direction transmitter to the first direction receiver and the path from the second direction transmitter to the second direction receiver have an intersection point; and triggering the intersection point by using the needle point of the nozzle as a spray head assembly to reach the zero position. Each head assembly performs a print job starting from a zero position.
Preferably, the first direction and the second direction are orthogonal. Preferably, the first direction is the X-axis direction and the second direction is the Y-axis direction; alternatively, the first direction is the Y-axis direction and the second direction is the X-axis direction.
Preferably, there are a plurality of first direction transmitters, each first direction transmitter having a corresponding first direction receiver; the number of the second directional transmitters is multiple, and each second directional transmitter is provided with a corresponding first directional receiver; the path intersection points in two directions are multiple; each intersection corresponds to a showerhead assembly. In calibration, a null position is assumed to be reached as long as the nozzle tips of the spray head assembly reach within the calibration area of the concurrent calibration sensor. All the spray head assemblies can reach the zero position at the same time, so that all the spray head assemblies can perform printing tasks with different forces in parallel in the same time, and each spray head assembly completes one part of the total task. Or a plurality of nozzles can synchronously and cooperatively print the same road strength, so that different biological materials can be printed on one printing path.
Preprinting module
Preferably, the printing system is provided with a preprinting module, the preprinting module comprises a preprinting base, a cleaning nozzle, a backflow groove, a brush and a cutting line are arranged on the preprinting base, the cleaning nozzle is located in the backflow groove, and the brush is located beside the backflow groove. The cleaning nozzle sprays cleaning fluid for cleaning the spray head, and then the cleaning fluid is collected in the reflux tank and then discharged; the tip end of the nozzle of the spray head assembly passes through the hairbrush, and the hairbrush wipes and cleans the tip end of the nozzle; and then, extruding the material outwards by the nozzle assembly until the section of the extruded material is stable, cutting the material discharged from the nozzle tip by the nozzle assembly through a cutting line, and moving the nozzle assembly to an objective table to carry out formal printing task.
According to the preferable scheme, the pre-printing module is provided with a pre-printing guide rail, and the pre-printing module can be matched with the pre-printing guide rail in a sliding manner; the pre-print module has a motion drive mechanism. When the nozzle assembly is pre-printed, the position of the nozzle assembly can be fixed, the pre-printing module moves to the position below the nozzle assembly, the pre-printing module withdraws from the nozzle assembly after the pre-printing is finished, the tip of the nozzle leaves the cleaning nozzle and contacts with the hairbrush after the tip of the nozzle leaves the cleaning nozzle during the withdrawal sequence of the pre-printing module, the material at the tip of the nozzle is cut off by the cutting line, and the pre-printing module withdraws. After the pre-print module is withdrawn, the stage moves below the nozzle assembly.
The pre-printing module is arranged for cleaning a nozzle of the spray head assembly, removing residual materials during last printing and performing formal printing after extruded materials are stable.
Spray head assembly
According to a preferable scheme, the spray head assembly comprises a storage barrel, a plunger matched with the storage barrel, a temperature control module and a spray nozzle, wherein the temperature control module comprises a heat-insulation barrel cover and a heat-insulation barrel bottom; the heat-insulating barrel cover and the heat-insulating barrel bottom are hermetically connected to form a medium cavity or a medium pipeline, and the medium cavity or the medium pipeline is provided with a heating element. The heating element heats the medium in the medium cavity or the medium pipeline, and the medium exchanges heat with the storage bucket to control the temperature of the material in the storage bucket.
Preferably, the temperature control module comprises a heat preservation layer and a water cooling plate, the heat preservation layer is located between the bottom of the heat preservation barrel and the water cooling plate, the water cooling plate is connected with the spray nozzle mounting piece, and the spray nozzle mounting piece is connected with the spray nozzle support or the rotating mechanism. Preferably, the nozzle mounting member includes a wing plate extending outwardly from an outer edge of the water-cooled plate, the wing plate being provided with a screw hole. The wing plate is fixed with the spray head bracket or the rotating seat through screws or bolts.
Preferably, the medium cavity or the medium pipeline is provided with a medium inlet and a medium outlet, the medium is a liquid heat-conducting medium, and the storage vat is made of a heat-conducting medical metal material. For example, stainless steel is a commonly used heat-conducting medical metal material with good heat conductivity and good biocompatibility, and a titanium alloy material is also used. The liquid heat transfer medium may be oil. The liquid medium wraps the storage barrel, the temperature control precision is high, the temperature difference of materials in the storage barrel is small, and the consistency of the temperature of the materials is good.
Preferably, the plunger is connected to a pneumatic actuator. A pneumatic actuator, such as a cylinder. The nozzle is a syringe needle.
The temperature control module controls the temperature of the storage barrel and keeps the materials in the storage barrel within a specified range. And, the temperature control module is fixed a position and is fixed the storage vat.
When biological tissue 3D printing is carried out, materials need to be kept in a given temperature range so as to facilitate living and propagation of biological components, and therefore, the storage barrel needs to be subjected to temperature control and heat preservation. The showerhead assembly is a separate component in a 3D printing system.
Object stage
The objective table is a working platform for receiving materials from the spray head assembly, realizing additive superposition and finally forming a 3D solid component; the object stage of the invention is slidably mounted on the object stage guide rail.
Preferably, the object stage comprises a printing vessel and a temperature control module, and the temperature control module wraps the periphery of the printing vessel.
Temperature control module
Preferably, the temperature control module comprises a medium cavity or a medium pipeline, the medium cavity or the medium pipeline is provided with a cavity for accommodating the printing vessel and is provided with a medium inlet and a medium outlet, and the liquid medium with the working temperature is input into the medium cavity or the medium pipeline. That is, the liquid medium reaches a specified temperature outside the medium chamber and then is sent into the medium chamber or the medium pipeline, and the place where the liquid medium is heated can be an external medium container and a heater, such as an oil temperature machine. The medium with the working temperature continuously circulates between the externally connected medium container and the medium cavity, the total amount of the liquid medium is large, and compared with the method that the temperature control is only performed on a small amount of medium in the medium cavity, the precision is high, and the difficulty of the temperature control is reduced.
Preferably, the medium chamber is a complete communicating chamber.
Preferably, the printing vessel is a circular vessel and the media chamber is a circular chamber, or the media chamber is a spiral conduit. The shape of the media chamber may be any shape that can be uniformly matched to the print vessel.
Clamp module
Preferably, the object table comprises a gripper module, which holds the printing vessel from the bottom.
Preferably, the clamp module comprises an adsorption seat, a vacuum pipeline and a vacuum air pump, wherein the adsorption seat is provided with a micropore array, the micropore array is communicated with the vacuum pipeline, and the vacuum pipeline is connected with the vacuum air pump. Before the printing work begins, the printing vessel needs to be clamped and fixed, the printing vessel is placed on the adsorption seat, the vacuum air pump is started, negative pressure is formed between the adsorption seat and the printing vessel under the action of the micropore array and the vacuum pipeline, and the printing vessel is fixed.
Preferably, the micropore array consists of a plurality of array units from inside to outside, the centers of all the array units are overlapped, and the contour surrounded by each array unit is the same as or similar to the shape of the working platform; each array unit is provided with 1 or more micropores, adjacent micropores are communicated through a communication pipeline, and each array unit is provided with a respective valve assembly which is arranged on the vacuum pipeline or between the vacuum pipeline and the vacuum air pump. For example, where the print vessel is rectangular, then the array elements are similar rectangles of the work platform. The micropores are arranged in the form of the array units, so that the working platforms with different sizes can be clamped.
Preferably, the printing utensil is a circular utensil, the micropores of the array units enclose a circle, all the array units are arranged in concentric circles, and the centremost array unit is a central micropore. All the concentric circular arrays or one (or a plurality) of the concentric circular arrays can be selectively opened according to the size of the printing vessel, and the printing vessel can be fixed.
Preferably, the center of the array unit is located at the center of the adsorption seat. The suction base may have a size to accommodate the array unit, and the shape of the suction base is not limited.
Multi-nozzle cooperative biological printing method
The invention provides a method for realizing multi-nozzle co-dot printing by using the printer. The multi-nozzle collaborative biological printing method executes the following operations: the method comprises the steps of placing a concurrent calibration sensor at the starting point of a path of a printing task, determining a spray head assembly needing to perform the printing task, moving the spray head assembly to a zero position, and starting the printing task from the zero position by the spray head assembly in sequence, or executing the same printing path by all the spray head assemblies carrying out the printing task, and synchronously starting the printing task from the zero position along the printing path after all the spray head assemblies reach the zero position.
Preferably, the print job is composed of a plurality of sub-paths, all of which intersect at a point, and the distance between the origin of the coordinate system and the intersection is obtained. Or the printing task is composed of a plurality of sub-paths, the sub-paths are mutually independent, the starting point position of each sub-path is obtained, the nozzle assemblies respectively execute the sub-path printing task, and the nozzle assemblies work simultaneously.
Aiming at a printing method of an organization with multiple materials distributed at intervals or several materials distributed alternately, as a preferred scheme, multiple printing materials are arranged in the same printing path, a spray head assembly corresponding to the printing materials is selected as a spray head assembly for printing tasks, and a section of continuous path corresponding to each material is used as a sub-path; taking any sub path as a current task path, moving the concurrent calibration sensor to the starting point of the current task path, moving the current spray head assembly corresponding to the current task path to a zero position, and withdrawing the concurrent calibration sensor; the current spray head assembly moves along the current task path; after the current task path is completed, selecting the next path as the current path, and repeating zero calibration of the concurrent calibration sensor on the current sprayer assembly and movement of the current sprayer assembly along the current task path; and repeating until all the sub-paths are printed completely. The starting point position calibration of the current spray head assembly is realized by using the concurrent calibration sensor, so that the continuous cooperative printing of multiple materials and multiple spray heads is realized, and the printing of the complex organization of the multiple materials becomes possible.
Aiming at the situation that a certain material is used as a main printing material, but an auxiliary material needs to be added or compounded locally, as a preferred scheme, a nozzle assembly corresponding to the printing material is selected as a nozzle assembly for printing tasks, a common-point calibration sensor is arranged at the starting point of a printing path, all nozzle assemblies for printing tasks reach zero positions, the common-point calibration sensor is withdrawn, all nozzle assemblies for printing tasks synchronously move along the printing task path, and each nozzle assembly extrudes the material in a task path corresponding to the material; and closing in the non-task path.
For example, when skin tissue is printed, the main material is a dermis layer material, but in a part with blood vessels, the blood vessel material and the dermis layer material are extruded simultaneously, or only the blood vessel material is extruded, so that the additive construction of the tissue is realized. After the blood vessel part is printed, the nozzle component of the blood vessel material is closed, and the nozzle component of the dermis layer material works. For another example, if a tissue is composed of a base material but living cells need to be seeded on the base material, the nozzle assembly of the base material is operated along the printing path, and when the position where living cells need to be seeded is reached, the corresponding nozzle assembly of the living cell material is also opened to fuse the living cells. It is also possible that multiple materials are combined in the same print path, and multiple nozzle assemblies are simultaneously activated to perform the print job. It is also possible that the two slicing layers are made of different materials, at this time, the spray head component of the first slicing layer material is turned on, the spray head component of the next slicing layer material is turned off, and after the printing task of the current slicing layer is completed, the spray head component of the current slicing layer material is turned off; and all the spray head assemblies are shifted to the height of the next slice layer, the spray head assembly of the next slice layer material is used as the spray head assembly of the current slice layer material, the printing is started, and the process is continuously carried out until the printing task is finished, and the like.
The invention has the advantages that:
1. the system is provided with a plurality of spray head assemblies, each spray head assembly at least has 3 axial translation degrees of freedom, some spray head assemblies also increase the rotational degrees of freedom (namely 4 degrees of freedom), the positions and the angles of the spray head assemblies can be adjusted, the plurality of spray head assemblies can work cooperatively or sequentially, multi-path and multi-material printing can be realized in one printing task, repeated calibration and cyclic printing processing of nanoscale multi-cell unit components are avoided, and one-step forming is favorable for expressing the functions of the units; the efficiency of constructing large tissue structures and organs is improved from the unit level, and the quality of 3D printed biological tissues is improved from the functional level.
2. The multi-nozzle cooperative work can realize multiple feeding printing modes such as multiple material layer-by-layer alternate printing, multiple material same-layer non-uniform mixed printing, single material printing, main material local composite additional material and the like, the printing modes are flexible and changeable, the non-uniform mixed system forming of materials can be realized, and the actual biological system can be simulated more truly.
3. Each spray head assembly can share a 3-axis translation mechanism and can also have independent freedom of movement, and multiple spray heads can synchronously perform respective printing tasks at different positions. For example, when printing a liver, each printhead prints one liver cell, or each printhead prints a portion of a liver cell.
4. And a pre-printing area is arranged, the tip of a nozzle of the spray head assembly is cleaned and cleaned, and stable output of materials in a formal printing task is guaranteed.
5. The printing utensil of the objective table utilizes the peripheral surrounding type heat exchange to carry out temperature control, the medium is continuously and circularly input into the medium cavity after the temperature of the medium is well controlled in the external medium container, the temperature control of the medium is accurate, and the temperature control is easy.
6. The printing vessel is clamped in a bottom adsorption mode, the number of the valve components is selected to be switched on according to the size of the printing vessel, and the printing vessel is stably and completely adsorbed.
7. Temperature control and bottom vacuum adsorption clamping are encircleed to the peripheral formula of printing household utensils, and temperature control and clamping stationary phase mutual noninterference can reliably adsorb printing household utensils, improve the precision of shaping structure, compromise the demand to ambient temperature in the biological printing simultaneously, effectively ensure the quality of shaping living body structure, improve the survival rate of living body tissue.
Drawings
Fig. 1 is an overall schematic view of the present invention.
FIG. 2 is a schematic view of a spray head assembly loaded on a fixed gantry.
FIG. 3 is a schematic view of the spray head assembly loaded on the movable gantry.
FIG. 4 is a schematic view of the showerhead assembly mounted to a showerhead holder.
FIG. 5 is a schematic view of a spin base provided on the showerhead holder.
Fig. 6 is a schematic view of a showerhead assembly.
FIG. 7 is a schematic diagram of a co-point calibration sensor.
FIG. 8 is a schematic diagram of a preprinting module.
FIG. 9 is a schematic illustration of a pre-print module position mounted to a base.
Fig. 10 is a schematic view of the stage mounted on the stage rail.
FIG. 11 is a schematic diagram of a printing vessel in cooperation with a temperature control module and a gripper module.
Figure 12 is a schematic diagram of a gripper module.
FIG. 13 is a schematic view of the stage with a media container and vacuum pump attached.
The labels in the figure are: a travel switch K, a base 1, an object stage 5, a concurrent calibration sensor 6, a printing vessel 8, a fixed gantry 21, a movable gantry 22, an X-axis guide rail 31, a Y-axis guide rail, a Z-axis guide rail 33, a storage tank 41, a spray head bracket 42, a temperature control module 43, a spray nozzle 45, an object stage guide rail 51, a temperature control module 52, a cavity 53, a suction seat 54, a first direction emitter 61, a first direction receiver 62, a second direction emitter 63, a second direction receiver 64, a preprinting base 71, a spray nozzle 72, a reflux groove 73, a brush 74, a material bearing area 75, a cutting line 76, a heat preservation barrel cover 431, a heat preservation barrel bottom 432, a water cooling plate 433, a heat preservation layer 434, a heating element 435, a heat preservation sleeve 436, a spray head mounting part 437, a locking screw 441, a rotary seat 442, a rotary shaft, a medium inlet 521, a medium outlet 522, a micropore array 541, a vacuum pipeline 542, 543, vacuum air pump 544 and oil temperature machine 560
Detailed Description
The structure and operation of the invention are explained in detail with reference to the accompanying drawings.
Multi-nozzle biological 3D printing system
As shown in fig. 1, the multi-nozzle biological 3D printing system of the present invention includes an extrusion-type nozzle assembly and a stage 5, wherein the nozzle assembly has a respective nozzle 45, a storage tank 41 and a temperature control module 43; the three-axis translation mechanism drives the spray head assembly to translate along three axes (an X axis 31, a Y axis 32 and a Z axis 33), the three-axis translation mechanism comprises an X axis 31 direction translation unit, a Y axis 32 direction translation unit and a Z axis 33 direction translation unit, and the spray head assembly is installed on the Z axis 33 direction translation unit. The spray head can move at any point of the XOY plane and can lift along the Z-axis 33; the spray head assembly has independent storage, extrusion and printing functions; the object stage 5 is used for receiving the material extruded by the spray head component. The temperature control module 43 maintains the temperature in the storage tank 41, so that the material is maintained at the temperature required for printing. The biological printing system is provided with a plurality of spray head assemblies, each spray head assembly is provided with a respective spray head bracket 42, and each spray head bracket 42 is provided with a fixed part connected with the Z-axis 33-direction translation unit and a mounting part connected with the spray head assembly; the fixed part and the installation part are inclined angles, and the spray head assembly is arranged in an inclined mode. The slope of shower nozzle subassembly indicates to intersect with Z axle 33 and is the contained angle, and nozzle 45 sets up downwards to one side, avoids taking place the motion between storage vat 41 and interferes, makes a plurality of shower nozzle subassemblies can collaborative work simultaneously.
Material(s)
In the present invention, the material refers to a material or a mixture for processing by a printer. When processed with the 3D printer of the present invention, some of the existing biomaterials can be used for printing. For example, many materials include natural polymers: collagen, silk fibers, gelatin, alginate and synthetic polymers: polyethylene glycol (PEG) or any combination thereof may be used in the printer of the present invention for processing. These are also referred to as "bio-inks" as materials for bio-3D printing. Although the material itself is conventional, it can be printed using the printing apparatus and method disclosed. The printed biological material has a three-dimensional structure or a four-dimensional structure, and any through hole can be arranged. The through-hole is generally a planar structure or a three-dimensional structure. For example, there is a hole in a plane, and the shape of the hole may be any shape, circular, rectangular, square, diamond, etc. When the plurality of surfaces are in different dimensions, a three-dimensional shape is formed, each surface or a plurality of surfaces of the three-dimensional shape are provided with holes, and the holes have certain depths, wherein the holes can be communicated or not communicated or partially communicated, so that a channel penetrating through the whole three-dimensional structure or part of the three-dimensional structure is formed. Such a configuration is easily realized by the printer of the present invention.
In some embodiments, the material of the present invention may be processed or printed in combination with stem cells, such that the material serves as a scaffold and the cells can be differentiated as an active agent, ultimately forming viable tissue. Of course, it is also possible to print the scaffold structure and then allow the stem cells to fill the space of the scaffold, eventually also forming living tissue.
In general, the newly designed printing of the present invention can print any suitable material.
In some embodiments, the storage barrels 41 are containers for biological materials, and have good biocompatibility, and different storage barrels 41 can be used for holding the same materials. Optionally, different materials or bio-inks can be contained in the storage vat 41, for example, the storage vat a contains one bio-material, the storage vat B contains another bio-material, and the properties of the two materials are not the same. This is because a biological material or organ is not uniform in structure but has a difference in structural or biological properties. For example, mammalian skin materials, including epidermis, dermis, which has blood vessels and tissues connected to muscles, have different structures at different parts, different thicknesses, and different transition structures between the tissues, and such differences include density, pore size, and the like. Thus, if printing by conventional printing is required, all structures or tissues are the same, and by the printing technique of the present invention, biomaterials of different structures can be processed at once.
In some embodiments, as shown in FIG. 4, there is an angle adjustment mechanism between the fixed portion and the mounting portion of the head holder 42. The angle adjustment mechanism may be a wedge disposed between the nozzle support 42 and the nozzle assembly, or the fixed portion may be hinged to the mounting portion, and the mounting portion may rotate relative to the fixed portion to adjust the included angle between the mounting portion and the fixed portion, and thereby adjust the angle of the nozzle assembly on the mounting portion relative to the Z-axis 33. When the specified angle is reached, the position between the fixing part and the mounting part is locked. The locking mode adopts the prior art, such as: ratchet-pawl mechanisms, the manner of tightening screws, etc.
In some specific embodiments, as shown in fig. 4, the cross section of the nozzle 45 holder is a right triangle, the surface of the hypotenuse of the nozzle 45 holder is the mounting portion, and the surface of one of the legs of the nozzle 45 is the fixing portion. The nozzle 45 is assembled to have rotational freedom in the mounting plane.
Rotating mechanism
The arrangement of the rotating mechanism enables the spray head assembly to have rotational freedom, and any angular displacement of the spray head tip can be realized within a stroke range, so that the relative positions of the plurality of spray head assemblies can be flexibly adjusted, and the multipoint concurrent connection of the plurality of spray heads becomes possible. Multiple jets may be co-located such that multiple jets are aimed at the same designated point or area at the same time. Or at different times, the tips of the jets may be aimed at the same point or region.
In some embodiments, as shown in fig. 5, at least one of the showerhead modules has a rotation mechanism disposed between the mounting portion and the showerhead module; the rotational degree of freedom of the rotating mechanism is unified with the spray head assembly. The rotating mechanism takes the fixed part as a reference surface and drives the spray head assembly to rotate in a plane where the fixed part is located, so that the angle of the spray nozzles 45 relative to the working platform and the relative angle between the spray nozzles 45 are adjusted.
In some embodiments, the rotation mechanism includes a rotation shaft 443 and a rotation base 442, the rotation base 442 is fixed to the head assembly, and the rotation shaft 443 is fixed to the mounting portion of the head holder 42. An external force is applied to the rotary base 442 to rotate around the rotary shaft 443, so as to drive the nozzle assembly to rotate and adjust the angle of the nozzle 45.
In some embodiments, the rotation mechanism is a mechanical rotary plate, which serves as the rotary base 442, and a locking screw 441 or a locking bolt is disposed between the rotary plate and the nozzle holder 42. When the locking screw 441 or the locking bolt does not lock the turntable and the nozzle holder 42, the turntable can be rotated to adjust the angle of the nozzle 45. When the angle of the nozzle 45 is adjusted, the turntable and the head holder 42 are locked by the locking screw 441 or the locking bolt, and the turntable and the nozzle 45 are positioned. Alternatively, the rotation shaft 443 is connected to a rotary motor.
In some embodiments, the rotating mechanism has one or more showerhead assemblies mounted thereon; and/or one or more showerhead modules are mounted on each showerhead support 42; and/or, each spray head support 42 is provided with a plurality of spray head assemblies, and a respective rotating mechanism is arranged between each spray head assembly and the spray head support 42. Thus, the number of spray heads can be flexibly expanded by installing a plurality of spray head assemblies on the spray head holder 42, and the expanded spray heads can have a rotational degree of freedom or can be fixed in position.
Triaxial translation mechanism
The triaxial translation mechanism can realize the position migration of any one spray head assembly at any point of the three-dimensional coordinate system.
In some specific forms, each showerhead assembly corresponds to a respective Z-axis 33 translation unit; alternatively, at least two showerhead assemblies share a Z-axis 33 translation unit.
As shown in fig. 2 and 3, the X-direction 31 translation mechanism includes a fixed gantry 21, a moving gantry 22, an X-direction 31 gantry guide rail cooperating with the moving gantry 22 and a stage 5 guide rail 51 cooperating with the stage 5; the fixed gantry 21 and the movable gantry 22 are respectively provided with a Y-direction guide rail 32 and a Z-direction guide rail 33, the Z-direction guide rail 33 is slidably arranged on the Y-direction guide rail 32, and the spray head bracket 42 is slidably arranged on the Z-direction guide rail 33; one Z-rail 33 for each showerhead holder 42 and/or one Z-rail 33 for a plurality of showerhead holders 42. That is, each head support 42 may be mounted on a respective Z-rail 33, or a plurality of head supports 42 may be mounted on a single Z-rail 33; alternatively, there may be one head holder 42 for each Z-guide 33, and several head holders 42 may share one Z-guide 33.
As shown in fig. 2 and 3, the movable gantry 22 and the fixed gantry 21 are aligned, a plurality of nozzle assemblies are arranged on the movable gantry 22, and a plurality of nozzle assemblies are arranged on the fixed gantry 21. The number of showerhead modules on the moving gantry 22 and the number of showerhead modules on the fixed gantry 21 may be the same or different.
As shown in fig. 2 and 3, the showerhead modules on the moving gantry 22 and the fixed gantry 21 are symmetrical with respect to the middle plane of the moving gantry 22 and the fixed gantry 21.
As shown in fig. 2 and 3, the movable gantry 22 has 3 nozzle assemblies, the fixed gantry 21 has 3 nozzle assemblies, the nozzle assemblies in the middle of the same gantry are fixedly connected with the nozzle support 42, and the rest of the nozzle assemblies are connected with the nozzle support 42 through the rotating mechanism. Generally, 6 jet assemblies can satisfy most print jobs. However, when 6 head modules cannot satisfy a print job, the head modules located outside may be preferentially expanded so that two or more head modules share one head holder 42.
In still other embodiments, as shown in fig. 1, the stage 5 guide 51 is located between the moving gantry 22 and the fixed gantry 21.
As shown in fig. 1, 2 and 3, each X-directional guide rail 31 has a first travel switch K and a second travel switch K, respectively, and a movement stroke is formed between the two travel switches K. That is, the mobile gantry 22 translates between the first and second travel switches K of its guide rails; the object table 5 translates between the first and second travel switches K of its guide.
Spray head assembly
In some embodiments, the spray head assembly includes a storage barrel 41, a plunger matched with the storage barrel 41, a temperature control module 43 and a spray nozzle 45, the temperature control module 43 includes a heat-insulating barrel cover 431 and a heat-insulating barrel bottom 432, the storage barrel 41 has a temperature control area wrapped by the heat-insulating barrel cover 431 and the heat-insulating barrel bottom 432, the storage barrel 41 between the temperature control area and the spray head is a heat-insulating area, and the storage barrel 41 in the heat-insulating area is provided with a heat-insulating sleeve 436; the heat-insulating barrel cover 431 and the heat-insulating barrel bottom 432 are hermetically connected to form a medium cavity or a medium pipeline, and the medium cavity or the medium pipeline is provided with a heating element 435. The heating element 435 heats the medium in the medium chamber or medium pipeline, and the medium exchanges heat with the storage bucket 41 to control the temperature of the material in the storage bucket 41. Typically the medium of the spray head assembly is water. The heating member is a heating wire or a semiconductor wafer or the like.
The temperature control module 43 comprises a heat insulation layer 434 and a water cooling plate, the heat insulation layer 434 is located between the heat insulation barrel bottom 432 and the water cooling plate, the water cooling plate is connected with a spray head mounting part 437, and the spray head mounting part 437 is connected with the spray head bracket 42 or the rotating mechanism. Preferably, the shower head mounting member 437 includes a wing plate extending outwardly from the outer edge of the water cooling plate 433, with a screw hole formed in the wing plate. The wings are fixed to the head holder 42 or the rotary base 442 by screws or bolts.
The medium cavity or the medium pipeline is provided with a medium inlet 521 and a medium outlet 522, the medium is a liquid heat-conducting medium, and the storage vat 41 is made of a heat-conducting medical metal material. For example, stainless steel is a commonly used heat-conducting medical metal material with good heat conductivity and good biocompatibility, and a titanium alloy material is also used. The liquid heat transfer medium may be oil. The liquid medium wraps the storage barrel 41, the temperature control precision is high, the temperature difference of materials in the storage barrel 41 is small, and the consistency of the temperature of the materials is good.
The plunger is connected with the pneumatic actuator. A pneumatic actuator, such as a cylinder. The nozzle 45 is a syringe needle.
The temperature control module 43 controls the temperature of the storage tank 41 to keep the material in the storage tank 41 within a specified range. And, the temperature control module 43 positions and fixes the storage vat 41.
When 3D printing is performed on biological tissues, the materials need to be kept in a given temperature range for living and breeding of biological components, and therefore, the storage barrel 41 needs to be subjected to temperature control and heat preservation. The showerhead assembly is a separate component in a 3D printing system.
Multi-nozzle common-point printing
In some embodiments, as shown in fig. 7, a biological 3D printing system has multiple jetting head assemblies and a common point calibration sensor 6, and when the nozzles 45 of all the jetting head assemblies touch the common point sensor, the printing path force starting points of all the jetting head assemblies are common. The coordinate system of all the showerhead modules is unified into the world coordinate system with a common point calibration sensor 6. The coordinate system of all the showerhead modules is unified into the world coordinate system with a common point calibration sensor 6.
In some specific embodiments, as shown in fig. 7, the concurrent calibration sensor 6 includes a calibration box provided with a first direction transmitter 61, a first direction receiver 62, a second direction transmitter 63, and a second direction receiver 64; the path from the first direction transmitter 61 to the first direction receiver 62 and the path from the second direction transmitter 63 to the second direction receiver 64 have an intersection; the point of intersection of the tip trigger of nozzle 45 is used as the spray head assembly to reach zero. Each head assembly performs a print job starting from a zero position.
In some embodiments, the first direction and the second direction are orthogonal. For example, the first direction is the X-axis 31, and the second direction is the Y-axis 32; alternatively, the first direction is the Y-axis 32 direction and the second direction is the X-axis 31 direction.
In some embodiments, there are a plurality of first direction transmitters 61, and each first direction transmitter 61 has a corresponding first direction receiver 62; a plurality of second directional transmitters 63, each second directional transmitter 63 having a respective corresponding first directional receiver 62; the path intersection points in two directions are multiple; each intersection corresponds to a showerhead assembly. In calibration, the null position is assumed to be reached whenever the tip of the nozzle 45 of the spray head assembly reaches within the calibration area of the co-point calibration sensor 6. All the spray head assemblies can reach the zero position at the same time, so that all the spray head assemblies can perform printing tasks with different forces in parallel in the same time, and each spray head assembly completes one part of the total task. Or a plurality of nozzles can synchronously and cooperatively print the same road strength, so that different biological materials can be printed on one printing path.
Preprinting module
As shown in fig. 8 and 9, the printing system has a pre-printing module, the pre-printing module includes a pre-printing base 71, a cleaning nozzle 72, a return groove 73, a brush 74, a cutting line 76 and a material carrying area 75 are disposed on the pre-printing base 71, the cleaning nozzle 72 is disposed in the return groove 73, and the brush 74 is disposed beside the return groove 73. The cleaning nozzle 72 sprays cleaning liquid for cleaning the spray head, and then the cleaning liquid is collected in the return tank 73 and discharged; the tip of the nozzle 45 of the spray head assembly passes through the brush 74, and the brush 74 wipes and cleans the tip of the nozzle 45; and then, the nozzle assembly extrudes the material outwards until the section of the extruded material is stable, the nozzle assembly passes through the cutting line 76, the cutting line 76 cuts off the material discharged from the tip of the nozzle 45, and the nozzle 45 assembly moves to the objective table 5 to carry out formal printing tasks. The cutting wire 76 is a wire filament or other wire-like or wire-like cutting member capable of severing material at the tip of the nozzle 45.
The material bearing area 75 is located between the brush 74 and the cutting line 76, the nozzle 45 is cleaned by the cleaning nozzle 45 and the brush 74, and then the material is extruded out of the material bearing area 75, and after the discharging flow of the nozzle 45 is stable, the nozzle 45 assembly passes through the cutting line.
According to the preferable scheme, the pre-printing module is provided with a pre-printing guide rail, and the pre-printing module can be matched with the pre-printing guide rail in a sliding manner; the pre-print module has a motion drive mechanism. When the nozzle assembly is used for preprinting, the position of the nozzle assembly can be fixed, the preprinting module moves to the position below the nozzle assembly, after the preprinting is finished, the preprinting module is withdrawn from the nozzle assembly, when the preprinting module is withdrawn in sequence, the tip of the nozzle 45 leaves the cleaning nozzle 72 and then contacts the brush 74, finally the cutting line 76 cuts off the material at the tip of the nozzle 45, and the preprinting module is withdrawn. After the pre-print module is removed, the stage 5 is moved under the head assembly.
The pre-printing module is provided to clean the nozzle 45 of the head assembly, remove the residual material during the previous printing, and perform formal printing after the extruded material is stabilized.
Object stage
As shown in fig. 9, the stage 5 is a working platform for receiving the materials from the nozzle assembly, implementing additive stacking, and finally forming a 3D solid member; the stage 5 of the present invention is slidably mounted on the rail 51 of the stage 5.
In some embodiments, stage 5 of the biological 3D printing system comprises a printing vessel and a temperature control module 52, the temperature control module 52 wrapping around the periphery of the printing vessel.
Temperature control module 52
The material used by the biological 3D printing system needs to be maintained within a specified temperature range to enable additive printing of the material and to increase the survival rate of the biological tissue.
In some embodiments, as shown in fig. 9, the temperature control module 52 comprises a media chamber or media conduit having a cavity 53 accommodating the printing vessel 8, the media chamber having a media inlet 521 and a media outlet 522, a liquid medium having an operating temperature being fed into the media chamber or media conduit. The medium cavity is a complete communicating cavity. The printing vessel is a circular vessel and the medium cavity is a circular cavity, or the medium cavity is a spiral pipeline. The shape of the media chamber may be any shape that can be uniformly matched to the print vessel.
When the temperature control module 52 is operated, the liquid medium reaches a predetermined temperature outside the medium chamber and is then fed into the medium chamber or the medium pipe, and the place where the liquid medium is heated may be an external medium container and a heater, such as the oil temperature machine 560. The medium with the working temperature continuously circulates between the externally connected medium container and the medium cavity, the total amount of the liquid medium is large, and compared with the method that the temperature control is only performed on a small amount of medium in the medium cavity, the precision is high, and the difficulty of the temperature control is reduced.
Clamp module
In some embodiments, as shown in fig. 11, 12, the stage 5 includes a gripper module that holds the printing vessel from the bottom.
The clamp module comprises an adsorption seat 54, a vacuum pipeline 542 and a vacuum air pump 544, wherein a micropore array 541 is arranged on the adsorption seat 54, the micropore array 541 is communicated with the vacuum pipeline 542, and the vacuum pipeline 542 is connected with the vacuum air pump 544. Before the printing operation starts, the printing vessel needs to be clamped and fixed, the printing vessel is placed on the adsorption seat 54, the vacuum air pump 544 is started, negative pressure is formed between the adsorption seat 54 and the printing vessel under the action of the micropore array 541 and the vacuum pipeline 542, and the printing vessel is fixed.
The micro-pore array 541 is composed of a plurality of array units from inside to outside, the centers of all the array units are overlapped, and the outline surrounded by each array unit is the same as or similar to the shape of the working platform; each array unit has 1 or more micro-holes, the adjacent micro-holes are communicated through a communication pipeline, each array unit has a respective valve assembly 543, the valve assembly 543 is arranged on the vacuum pipeline 542, or the valve assembly 543 is arranged between the vacuum pipeline 542 and the vacuum air pump 544. For example, where the print vessel is rectangular, then the array elements are similar rectangles of the work platform. The micropores are arranged in the form of the array units, so that the working platforms with different sizes can be clamped.
The printing utensil is a circular utensil, the micropores of the array units enclose a circle, all the array units are arranged in a concentric circle, and the most central array unit is a central micropore. All the concentric circular arrays or one (or a plurality) of the concentric circular arrays can be selectively opened according to the size of the printing vessel, and the printing vessel can be fixed. Preferably, the center of the array unit is located at the center of the suction seat 54. The suction holder 54 may have a size to accommodate the array unit, and the shape of the suction holder 54 is not limited.
In some embodiments, the stage 5 has both the temperature control module 52 and the clamp module described above, as shown in fig. 10.
The working process of the biological 3D printing system of the present invention is described by taking the co-printing of 6 different materials built in the storage vat 41 of 6 nozzle assemblies as an example:
and 6 executing spray heads return to zero coordinates before printing, sequentially enter a cleaning area, stay on the cleaning liquid nozzles 45 to wash the cleaning liquid, and sequentially pass through the cleaning brush 74 along a fixed path to clean the surface. The 6 execution nozzles are sequentially placed in the calibration module to perform respective pose coordinate zero setting, the middle nozzle on one side of the fixed gantry 21 is taken as a reference, the 4 nozzle rotating motors on the outer side rotate inwards by 45 degrees, and the driving motors move the respective execution nozzles to form extrusion tail end common points around the execution nozzles. And after the concurrent point is finished, each sprayer drives to synchronously translate, and moves to the calibration module to detect the concurrent point error. If the error is out of the set range, finely adjusting the self positions of 5 nozzles around the middle nozzle at one side of the fixed gantry 21 under the drive of respective Y32 and Z-axis 33 motors, and detecting again; if the error is within the set range, the next step is performed. The co-point nozzle is moved to a pre-printing area for pre-working, for example, printing a rectangle or an arc, and after the extruded material has stabilized quality, the co-point nozzle is moved across a cutting line 76, and the height of the cutting line 76 is set to be the same as the height of the co-point position of the nozzle in the horizontal direction, so as to cut off the residue at the nozzle 45. And the concurrent nozzle system moves into a vessel in a working area to start formal extrusion printing. After printing is finished, the rotating motors of the 4 spray heads on the outer side return to 0-degree positions, and the 6 spray heads sequentially execute cleaning operation and then return to zero coordinates.
Triaxial translation mechanism, objective table 5 and print module etc. in advance all set up on base 1, and base 1 can provide stable support to and the horizontally reference surface for biological 3D printing system.
Multi-nozzle cooperative biological printing method
The invention provides a method for realizing multi-nozzle co-dot printing by using the printer. The multi-nozzle collaborative biological printing method executes the following operations: the common point calibration sensor 6 is arranged at the starting point of a path of a printing task, a spray head assembly needing to be subjected to the printing task is determined, the spray head assembly is moved to a zero position, the spray head assembly sequentially starts the printing task from the zero position, or all the spray head assemblies carrying out the printing task execute the same printing path, and the printing task is synchronously started from the zero position along the printing path after all the spray head assemblies reach the zero position.
In some embodiments, when the printhead assembly begins a print job sequentially from a null position, the print job is comprised of a plurality of sub-paths, all of the sub-paths intersect at a point, and the intersection of the sub-paths serves as the null position of the printing system.
Aiming at a printing method of an organization with multiple materials distributed at intervals or several materials distributed alternately, if multiple printing materials exist in the same printing path, a spray head component corresponding to the printing materials is selected as a spray head component for printing tasks, and a section of continuous path corresponding to each material is used as a sub-path; taking any sub path as a current task path, moving the concurrent calibration sensor 6 to the starting point of the current task path, moving the current spray head assembly corresponding to the current task path to a zero position, and withdrawing the concurrent calibration sensor 6; the current spray head assembly moves along the current task path; after the current task path is completed, selecting the next path as the current path, and repeating zero calibration of the current sprayer assembly by the concurrent calibration sensor 6 and movement of the current sprayer assembly along the current task path; and repeating until all the sub-paths are printed completely. The starting point position calibration of the current spray head assembly is realized by the common-point calibration sensor 6, so that the continuous cooperative printing of multiple materials and multiple spray heads is realized, and the printing of the complex organization of the multiple materials becomes possible.
Aiming at the condition that a certain material is used as a main printing material, but an auxiliary material needs to be added or compounded locally, a nozzle assembly corresponding to the printing material is selected as a nozzle assembly for printing tasks, a common-point calibration sensor 6 is arranged at the starting point of a printing path, all nozzle assemblies for printing tasks reach zero positions, the common-point calibration sensor 6 is withdrawn, all nozzle assemblies for printing tasks synchronously move along the printing task path, and each nozzle assembly extrudes the material in a task path corresponding to the material; and closing in the non-task path.
For example, when skin tissue is printed, the main material is a dermis layer material, but in a part with blood vessels, the blood vessel material and the dermis layer material are extruded simultaneously, or only the blood vessel material is extruded, so that the additive construction of the tissue is realized. After the blood vessel part is printed, the nozzle component of the blood vessel material is closed, and the nozzle component of the dermis layer material works. For another example, if a tissue is composed of a base material but living cells need to be seeded on the base material, the nozzle assembly of the base material is operated along the printing path, and when the position where living cells need to be seeded is reached, the corresponding nozzle assembly of the living cell material is also opened to fuse the living cells. It is also possible that multiple materials are combined in the same print path, and multiple nozzle assemblies are simultaneously activated to perform the print job. It is also possible that the two slicing layers are made of different materials, at this time, the spray head component of the first slicing layer material is turned on, the spray head component of the next slicing layer material is turned off, and after the printing task of the current slicing layer is completed, the spray head component of the current slicing layer material is turned off; and all the spray head assemblies are shifted to the height of the next slice layer, the spray head assembly of the next slice layer material is used as the spray head assembly of the current slice layer material, the printing is started, and the process is continuously carried out until the printing task is finished, and the like.
The invention shown and described herein may be practiced in the absence of any element or elements, limitation or limitations, which is specifically disclosed herein. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, and it is recognized that various modifications are possible within the scope of the invention. It should therefore be understood that although the present invention has been specifically disclosed by various embodiments and optional features, modification and variation of the concepts herein described may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
The contents of the articles, patents, patent applications, and all other documents and electronically available information described or cited herein are hereby incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. Applicants reserve the right to incorporate into this application any and all materials and information from any such articles, patents, patent applications, or other documents.

Claims (10)

1. Biological 3D printing system, its characterized in that: the 3D printing system comprises an extrusion type spray head assembly, an objective table, a concurrent calibration sensor and a triaxial translation mechanism, wherein the objective table is provided with a containing cavity matched with a printing vessel; the objective table comprises a temperature control module, and the temperature control module wraps the bottom and the periphery of the printing vessel;
when the nozzles of all the nozzle assemblies touch the common-point sensor, the initial points of the printing paths of all the nozzle assemblies are in common-point; all the spray head assemblies can perform printing tasks of different paths in parallel at the same time, and each spray head assembly completes one part of the total task; or a plurality of spray heads can synchronously and cooperatively print the same path, so that different biological materials can be printed on one printing path;
at least one spray head assembly is provided with a rotating mechanism, and the rotational freedom degree of the rotating mechanism is unified with the spray head assembly;
the concurrent calibration sensor comprises a calibration box, wherein the calibration box is provided with a first direction transmitter, a first direction receiver, a second direction transmitter and a second direction receiver; the path from the first direction transmitter to the first direction receiver and the path from the second direction transmitter to the second direction receiver have an intersection point; and triggering the intersection point by using the needle point of the nozzle as a spray head assembly to reach the zero position.
2. The biological 3D printing system of claim 1, wherein: the temperature control module comprises a medium cavity or a medium pipeline, the medium cavity or the medium pipeline is provided with a cavity for accommodating the printing vessel, the medium cavity is provided with a medium inlet and a medium outlet, and liquid medium with working temperature is input into the medium cavity or the medium pipeline.
3. The biological 3D printing system of claim 2, wherein: the medium cavity is a complete communicating cavity.
4. The biological 3D printing system of claim 2, wherein: the printing vessel is a circular vessel and the medium cavity is a circular cavity, or the medium cavity is a spiral pipeline.
5. The biological 3D printing system of claim 1, wherein: the stage includes a clamp module that secures the printing vessel from the bottom.
6. The biological 3D printing system of claim 5, wherein: the clamp module comprises an adsorption seat, a vacuum pipeline and a vacuum air pump, wherein a micropore array is arranged on the adsorption seat and communicated with the vacuum pipeline, and the vacuum pipeline is connected with the vacuum air pump.
7. The biological 3D printing system of claim 6, wherein: the micropore array consists of a plurality of array units from inside to outside, the centers of all the array units are overlapped, and the outline surrounded by each array unit is the same as or similar to the shape of the working platform; each array unit is provided with 1 or more micropores, adjacent micropores are communicated through a communication pipeline, and each array unit is provided with a respective valve assembly which is arranged on the vacuum pipeline or between the vacuum pipeline and the vacuum air pump.
8. The biological 3D printing system of claim 6, wherein: the printing utensil is a circular utensil, the micropores of the array units enclose a circle, all the array units are arranged in a concentric circle, and the most central array unit is a central micropore.
9. The biological 3D printing system of claim 6, wherein: the circle center of the array unit is positioned at the center of the adsorption seat.
10. The biological 3D printing system of claim 6, wherein: the objective table comprises a temperature control module, the temperature control module comprises a medium cavity or a medium pipeline, the medium cavity or the medium pipeline is provided with a cavity medium cavity for accommodating a printing vessel and a medium inlet and a medium outlet, and a liquid medium with working temperature is input into the medium cavity or the medium pipeline; the gripper module holds the printing vessel from the bottom.
CN202111522749.9A 2019-08-22 2019-08-22 Biological 3D printing system Active CN114274508B (en)

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CN201910777769.7A CN110450405B (en) 2019-08-22 2019-08-22 Multi-nozzle cooperative biological printing method
CN202111522749.9A CN114274508B (en) 2019-08-22 2019-08-22 Biological 3D printing system

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