CN114274508B

CN114274508B - Biological 3D printing system

Info

Publication number: CN114274508B
Application number: CN202111522749.9A
Authority: CN
Inventors: 张斌; 杨腾; 李琦; 罗熠晨; 张波; 马梁; 杨华勇
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2019-08-22
Filing date: 2019-08-22
Publication date: 2023-06-06
Anticipated expiration: 2039-08-22
Also published as: CN110450405A; CN110450405B; CN114274508A

Abstract

Biological 3D printing system, 3D printing system include extrusion type shower nozzle subassembly and objective table, and the objective table has the appearance chamber that matches with the printing household utensils. The invention has the advantages that: the system has the advantages that the plurality of spray head components can work cooperatively or sequentially, the printing modes are flexible and changeable, and the molding of a non-uniform mixed system of materials can be realized; setting a pre-printing area, cleaning and cleaning the nozzle tips of the nozzle assemblies, and guaranteeing stable output of materials in formal printing tasks; the peripheral surrounding temperature control and the bottom vacuum adsorption clamping of the printing vessel effectively ensure the quality of the formed living body structure and improve the survival rate of living body tissues.

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 suffer from various types of injuries to cause tissue defects or serious diseases to cause organ transplantation every year worldwide, and great tissue and organ repair demands are generated. Tissue organ transplantation is an extremely effective treatment method for the treatment of damaged massive soft tissues and internal organs of a human body. However, organ transplantation has difficulty in practical application due to the shortage of organ donor sources, immune rejection and other problems. 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 fabricated scaffold by some method. Then the constructed tissue substitute is planted into a patient after being cultured, and the original pathological tissue organ is replaced to restore the original body function so as to realize the treatment of diseases. The research and application of tissue engineering skin are effectively exemplified by the good development prospect of tissue engineering.

In recent years, 3D printing technology has been rapidly developed, and a new manufacturing mode is opened up for industrial manufacturing. In the biological field, techniques such as bioprinting, three-dimensional controlled organization of cells, etc. are also applied. The techniques have the capability of manipulating single cells or single component micro-sized droplets, can precisely 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 construction process of massive tissues and organs. Therefore, the development of the bio-printing technology is a necessary trend of future tissue engineering research. In a typical bioprinting apparatus, the most critical component is the forming head system.

In order to meet the manufacturing requirements of large-size complex tissue organs, especially for the tissue organs such as livers and the like with obvious unit structures, multiple materials are often required to be used in a combined mode. For example, when the skin is printed, the tissue such as blood vessels needs to be printed, and a single spray head is used for replacing the spray head for a long time, so that the efficiency is affected, and the hydrogel on the side just replaced by the spray head is solidified, and if a plurality of infusion channels of the same spray head are adopted, the problem of mixing materials at the spray head is caused; and can not print simultaneously, the efficiency is lower.

In the market, a single spray head takes envisionTec as an example, and each time a material is changed, the spray head is moved to a new spray head, then a vacuum adsorption mode is adopted for changing a cutter, so that the problems of long time and incapability of ensuring positioning accuracy exist. In addition, if a discrete hexagonal shape similar to a hepatocyte is printed, gaps exist between 6 blocks, and a long-time wiring can be realized; this severely limits the ability to print complex organs, with long printing times and low efficiency.

Disclosure of Invention

The invention aims to provide a multi-nozzle printing system which can work cooperatively by multiple nozzles 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 respective nozzles, a storage bucket and a temperature control module; the three-axial translation mechanism drives the spray head assembly to translate along the three axial directions (X axis, Y axis and Z axis), and comprises an X-axial translation unit, a Y-axial translation unit and a Z-axial translation unit, and the spray head assembly is arranged on the Z-axial translation unit. The spray head can move at any point of the XOY plane and can be lifted and lowered along the Z axial direction; the spray head component has independent functions of storing, extruding and printing; the object stage is used for receiving the material extruded by the nozzle assembly. The temperature control module keeps the temperature in the storage barrel, so that the material is kept at the temperature required during printing.

Multi-jet printing system

As a preferred scheme, a plurality of spray head assemblies are provided, each spray head assembly is provided with a respective spray head bracket, and the spray head bracket 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, and the spray head component is obliquely arranged. The inclination of the spray head components means that an included angle is formed between the spray head components and the Z axis, the spray nozzles are arranged obliquely downwards, and movement interference between storage tanks is avoided, so that a plurality of spray head components can work cooperatively at the same time.

As a preferable scheme, an angle adjusting mechanism is arranged between the fixing part and the mounting part of the spray head bracket. 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 with the mounting part, and the mounting part rotates relative to the fixing part, so that an included angle between the mounting part and the fixing part is adjusted, and the angle of the spray head assembly on the mounting 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 mechanism, way of tightening screw, etc.

Preferably, the cross section of the nozzle support is a right triangle, the surface of the bevel edge of the nozzle support is a mounting part, and the surface of one right-angle edge of the nozzle support is a fixing part. The nozzle assembly has a rotational degree of freedom within the mounting surface.

Preferably, at least one of the head assemblies has a rotation mechanism disposed between the mounting portion and the head assembly; the rotation freedom degree of the rotation mechanism is unified with the spray head assembly. The rotating mechanism takes the fixing part as a reference surface and drives the spray head assembly to rotate in the plane where the fixing part is located, so that the angle of the nozzles relative to the working platform and the relative angle among the 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 bracket. And applying an external force to the rotary seat, rotating the rotary seat to rotate around the rotary shaft, and further driving the spray head assembly to rotate to adjust the angle of the spray nozzle.

Preferably, the rotating mechanism is a mechanical turntable, the turntable is used as a rotating seat, and a locking screw or a locking bolt is arranged between the turntable and the spray head bracket. When the locking screw or the locking bolt is used for unlocking the turntable and the spray head support, the turntable can be rotated to adjust the angle of the spray nozzle. After the nozzle angle is adjusted, the turntable and the nozzle bracket are locked by a locking screw or a locking bolt, and the turntable and the nozzle are positioned.

Alternatively, the rotating shaft is connected to a rotating motor.

Preferably, the rotating mechanism is provided with one or more spray head assemblies; and, or, mounting one or more showerhead assemblies on each showerhead support; and/or, a plurality of spray head assemblies are arranged on each spray head support, and a respective rotating mechanism is arranged between each spray head assembly and each spray head support. 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 and can also be fixed positions.

The rotary mechanism is arranged, so that the spray head assembly has rotational freedom, and any angular displacement of the spray head tip can be realized in a travel range, and therefore, the relative positions among a plurality of spray head assemblies can be flexibly adjusted, and the common point of a plurality of spray heads becomes possible. The multiple nozzles are co-located, which may be that the multiple nozzles are aligned to the same designated point or area at the same time. Or at different times, the spray tip is aimed at the same point or area.

Triaxial translation mechanism

Preferably, each spray head assembly corresponds to a respective Z-axis translation unit; alternatively, at least two showerhead modules share a single 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 objective table guide rail matched with the objective table; 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; each spray head support corresponds to one Z-direction guide rail and/or a plurality of spray head supports share one Z-direction guide rail. That is, each of the head brackets may be mounted on a respective Z-rail, or a plurality of the head brackets may be mounted on a single Z-rail; alternatively, one nozzle holder corresponds to one Z-direction guide rail, and a plurality of nozzle holders share one Z-direction guide rail.

Preferably, the movable gantry is centered with the fixed gantry, a plurality of spray head components are arranged on the movable gantry, and a plurality of spray head components are arranged on the fixed gantry. The number of spray head assemblies on the moving gantry and the number of spray head assemblies on the fixed gantry may be the same or different.

Preferably, the showerhead assembly of the moving gantry and the showerhead assembly on the fixed gantry are symmetrical about a middle plane of the moving gantry and the fixed gantry.

As the preferable scheme, the movable gantry is provided with 3 spray head components, the fixed gantry is provided with 3 spray head components, the spray head components in the middle of the same gantry are fixedly connected with the spray head support, and the rest spray head components 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-direction guide rail is respectively provided with a first travel switch and a second travel switch, and a movement travel is arranged between the two travel switches. That is, the mobile gantry translates between the first travel switch and the second travel switch of its guide rail; the stage translates between a first travel switch and a second travel switch of its guide rail.

The triaxial translation mechanism can realize the migration of the position of any one spray head component at any point of a three-dimensional coordinate system.

Multi-nozzle co-dot printing

Preferably, the printing system has a co-point calibration sensor, and the print path start points of all the head assemblies are co-point when the nozzles of all the head assemblies touch the co-point sensor. The co-point calibration sensor is used to unify the coordinate system of all showerhead modules into the world coordinate system. The co-point calibration sensor is used to unify the coordinate system of all showerhead modules into the world coordinate system.

Preferably, the co-point calibration sensor comprises a calibration box 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; the point of the needle point triggering intersection of the nozzle is taken as the spray head assembly to reach the zero position. Each jet assembly starts with a null position for a print job.

Preferably, the first direction and the second direction are orthogonal. Preferably, the first direction is the X-axis and the second direction is the Y-axis; alternatively, the first direction is the Y-axis and the second direction is the X-axis.

Preferably, the first direction transmitter has a plurality, and each first direction transmitter has a corresponding first direction receiver; a plurality of second direction transmitters, each second direction transmitter having a respective first direction receiver; a plurality of path intersections in two directions are formed; one for each showerhead assembly. When calibrated, the null position is considered to be reached as long as the nozzle tip of the spray head assembly reaches within the calibration area of the co-sited calibration sensor. All of the head assemblies may reach the zero position simultaneously, and then all of the head assemblies may be performing different paths of print jobs in parallel at the same time, each head assembly completing a portion of the overall job. Alternatively, multiple nozzles can perform simultaneous co-printing on the same path, thereby enabling different biological materials on one print path.

Preprinting module

As the preferable scheme, the printing system is provided with a pre-printing module, the pre-printing module comprises a pre-printing base, a cleaning nozzle, a reflux groove, a hairbrush and a cutting line are arranged on the pre-printing base, the cleaning nozzle is positioned in the reflux groove, and the hairbrush is positioned beside the reflux groove. The cleaning nozzle sprays cleaning liquid for washing the spray head, and then the cleaning liquid is collected in the reflux groove and then discharged; the nozzle tip of the spray head assembly passes through a brush, and the brush wipes and cleans the nozzle tip; and then, extruding the material outwards by the nozzle assembly until the section of the extruded material is stable, cutting the material from the tip of the nozzle by the nozzle assembly through the cutting line, and moving the nozzle assembly to the objective table to perform a formal printing task.

The pre-printing module is provided with a pre-printing guide rail, and the pre-printing module is slidably matched with the pre-printing guide rail; the preprinting module has a motion driving mechanism. When the spray head assembly is pre-printed, the position of the spray head assembly is fixed, the pre-printing module moves to the lower side of the spray head assembly, after the pre-printing is finished, the pre-printing module withdraws from the spray head assembly, when the pre-printing module withdraws in sequence, the nozzle tip leaves the cleaning nozzle and contacts with the brush, and finally the cutting line cuts off the material at the nozzle tip, so that the pre-printing module finishes withdrawing. After the preprinting module is evacuated, the stage is moved under the showerhead assembly.

The preprinting module is set to clean the nozzle of the nozzle assembly, to eliminate the residual material during the last printing, and to print formally after the extruded material is stable.

Spray head assembly

As 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 preservation barrel cover and a heat preservation barrel bottom, the storage barrel is provided with a temperature control area which is wrapped by the heat preservation barrel cover and the heat preservation barrel bottom, the storage barrel between the temperature control area and the spray head is a heat preservation area, and the storage barrel in the heat preservation area is provided with a heat preservation sleeve; the heat preservation barrel cover and the heat preservation barrel bottom are connected in a sealing way 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 vat to control the temperature of the material in the storage vat.

Preferably, the temperature control module comprises an insulation layer and a water cooling plate, wherein the insulation layer is positioned between the bottom of the insulation barrel and the water cooling plate, the water cooling plate is connected with a spray head mounting piece, and the spray head mounting piece is connected with a spray head bracket or a rotating mechanism. Preferably, the spray head mounting member comprises a wing plate extending outwards from the outer edge of the water cooling plate, and screw holes are formed in the wing plate. The wing plate is fixed with the spray head bracket or the rotating seat through a screw or a bolt.

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 barrel is made of a heat-conducting medical metal material. For example, stainless steel is a common heat conducting medical metal material with good heat conductivity and good biocompatibility, and titanium alloy material is also used. The liquid heat transfer medium may be oil. The storage vat is lived to liquid medium parcel, and the precision of control by temperature change is high to the material difference in temperature in the storage vat is little, and material temperature uniformity is good.

Preferably, the plunger is connected to a pneumatic actuator. Pneumatic actuators, such as cylinders. 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 used for positioning and fixing the storage barrel.

In 3D printing of biological tissue, it is necessary to keep the material in a given temperature range for survival and propagation of biological components, and therefore, it is necessary to control and keep the temperature of the storage tank. 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 is slidably arranged 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 chamber or medium conduit, the medium chamber or medium conduit having a chamber medium chamber for receiving the print vessel, the medium chamber having a medium inlet and a medium outlet, the liquid medium having an operating temperature being fed into the medium chamber or medium conduit. That is, the liquid medium is sent to the medium cavity or the medium pipeline after reaching the designated temperature outside the medium cavity, and the heated place of the liquid medium can be an external medium container and a heater, such as an oil temperature machine. The medium with working temperature continuously circulates between the externally connected medium container and the medium cavity, the total amount of the liquid medium is large, compared with the precision of temperature control of a small amount of medium in the medium cavity, the precision is high, and the difficulty of temperature control is reduced.

Preferably, the medium chamber is a complete communication chamber.

Preferably, the print vessel is a circular vessel, the media cavity is a circular cavity, or the media cavity is a spiral pipe. The shape of the medium chamber may be such that it can be uniformly matched with the print vessel.

Clamp module

Preferably, the stage includes a jig module that holds the print vessel from the bottom.

Preferably, the fixture 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 printing, the printing vessel is required 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 is composed of a plurality of array units from inside to outside, the centers of all the array units are overlapped, and the outline enclosed 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, each array unit is provided with a respective valve assembly, and the valve assembly is arranged on a vacuum pipeline or between a vacuum pipeline and a vacuum air pump. For example, the print vessel is rectangular, then the array unit is a similar rectangle of the work platform. The micropores are arranged in the mode of arranging the array units, so that clamping of working platforms with different sizes can be realized.

Preferably, the printing vessel is a circular vessel, the micropores of the array units are enclosed into a circle, all the array units are arranged in concentric circles, and the most central array unit is a central micropore. All concentric circular arrays or one (or a plurality of) concentric circular arrays can be selectively opened according to the size of the printing vessel, so that the printing vessel is fixed.

Preferably, the center of the circle of the array unit is positioned at the center of the adsorption seat. The shape of the adsorption seat is not limited as long as the adsorption seat has a size to accommodate the array unit.

Multi-nozzle collaborative biological printing method

The invention provides a method for realizing multi-nozzle co-point printing by using the printer. The multi-nozzle collaborative biological printing method comprises the following steps: and placing the co-point calibration sensor at the path starting point of the print job, determining a spray head assembly needing to perform the print job, moving the spray head assembly to a zero position, and sequentially starting the print job from the zero position by the spray head assembly, or executing the same print path by all spray head assemblies performing the print job, and synchronously starting the print job from the zero position along the print path after all 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 point 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.

In the printing method aiming at the organization with multiple materials distributed at intervals or with several materials distributed alternately, as a preferable scheme, a plurality of printing materials are arranged in the same printing path, a nozzle assembly corresponding to the printing materials is selected as a nozzle assembly for performing a printing task, and a section of continuous path corresponding to each material is taken as a sub-path; taking any sub-path as a current task path, moving the co-point calibration sensor to the starting point of the current task path, enabling the current spray head assembly corresponding to the current task path to move to a zero position, and evacuating the co-point 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 current spray head assembly by the co-point calibration sensor and movement of the current spray head assembly along the current task path; repeating until all sub-paths are printed. The co-point calibration sensor is used for calibrating the starting point position of the current spray head assembly, so that continuous collaborative printing of multiple materials and multiple spray heads is realized, and printing of complex tissues of the multiple materials is possible.

Aiming at the situation that a certain material is used as a main printing material, but auxiliary materials are locally required to be added or compounded, as a preferable scheme, a spray head assembly corresponding to the printing material is selected as a spray head assembly for carrying out a printing task, a common point calibration sensor is arranged at the starting point of a printing path, all spray head assemblies for carrying out the printing task reach a zero position, the common point calibration sensor is removed, all spray head assemblies for carrying out the printing task synchronously move along the printing task path, and each spray head assembly extrudes materials in the task path corresponding to the material; and closing in the non-task path.

For example, when printing skin tissue, the main material is dermis layer material, but at the vascular site, the vascular material is extruded simultaneously with dermis layer material, or only vascular material is extruded, so as to realize the additive construction of tissue. After the printing of the vascular part is completed, the spray head component of the vascular material is closed, and the spray head component of the dermis layer material works. For another example, if a tissue is made of a basic material, but living cells are to be seeded on the basic material, then the nozzle assemblies of the basic material are operated along the printing path, and when the position where the living cells are to be seeded is reached, the nozzle assemblies corresponding to the living cell materials are also opened to fuse the living cells. It is also possible that multiple materials are combined on the same print path, where multiple nozzle assemblies are simultaneously turned on to perform a print job. It is also possible that the two sliced layers are of different materials, at this time, the nozzle assembly of the first sliced layer material is turned on, the nozzle assembly of the next sliced layer material is turned off, and after the current sliced layer printing task is completed, the nozzle assembly of the current sliced layer material is turned off; all the head assemblies are displaced to the height of the next slice, the head assembly of the next slice is used as the head assembly of the current slice, printing is started, and the printing is continuously performed 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 is provided with at least 3 axial translation degrees of freedom, certain spray head assemblies are additionally provided with rotation degrees of freedom (namely 4 degrees of freedom), the positions and angles of the spray head assemblies can be adjusted, the multiple 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 on nanoscale multi-cell unit components are avoided, and one-step forming is beneficial to the expression of unit functions; the efficiency of constructing large tissue structures and organs is improved from the unit level, and the quality of 3D printing biological tissues is improved from the functional level.

2. The multi-nozzle collaborative work can realize a plurality of feeding printing modes such as alternate printing of a plurality of materials layer by layer, non-uniform mixed printing of a plurality of materials on the same layer, printing of a single material, local composite additional materials of a main material and the like, the printing modes are flexible and changeable, the molding of a non-uniform mixed system of the materials can be realized, and an actual biological system can be simulated more truly.

3. Each spray head assembly can share a 3-axis translation mechanism, can also have independent freedom of movement, and multiple spray heads can synchronously perform respective printing tasks at different positions. For example, when printing livers, each jet prints one liver unit, or each jet prints a portion of a liver unit.

4. And a pre-printing area is arranged, the nozzle tips of the nozzle assemblies are cleaned, and stable output of materials in a formal printing task is ensured.

5. The printing vessel of the object stage utilizes peripheral surrounding type heat exchange to control the temperature, and the medium is continuously and circularly input into the medium cavity after being well controlled in the external medium container, so that the medium temperature is accurately controlled and the temperature is easy to control.

6. The printing vessel is clamped in a bottom adsorption mode, the number of the on valve assemblies is selected according to the size of the printing vessel, and stable and complete adsorption of the printing vessel is realized.

7. The outer periphery of the printing vessel is surrounded by temperature control and bottom vacuum adsorption and clamping, the temperature control and clamping phases are not mutually interfered, the printing vessel can be reliably adsorbed, the precision of a forming structure is improved, the requirement on the environmental temperature in biological printing is met, the quality of a formed living body structure is effectively ensured, and the survival rate of living body tissues is improved.

Drawings

Fig. 1 is an overall schematic of the present invention.

Fig. 2 is a schematic view of a fixed gantry load head assembly.

Fig. 3 is a schematic view of a loading head assembly on a movable gantry.

FIG. 4 is a schematic view of the spray head assembly mounted to a spray head bracket.

Fig. 5 is a schematic view of a swivel base provided on a shower head 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 view of the preprinting module mounted to a chassis.

FIG. 10 is a schematic view of the stage mounted on the stage rail.

FIG. 11 is a schematic diagram of a print vessel mated with a temperature control module, a clamp module.

Fig. 12 is a schematic diagram of a clamp module.

FIG. 13 is a schematic view of the carrier externally connected to the media container and vacuum air pump.

The marks in the figure are as follows: travel switch K, base 1, stage 5, co-point calibration sensor 6, print vessel 8, stationary gantry 21, moving gantry 22, x-axis guide 31, y-axis guide, Z-axis guide 33, storage bucket 41, head holder 42, temperature control module 43, nozzle 45, stage guide 51, temperature control module 52, chamber 53, suction mount 54, first direction emitter 61, first direction receiver 62, second direction emitter 63, second direction receiver 64, preprinting base 71, nozzle 72, reflow slot 73, brush 74, material bearing area 75, cut line 76, thermal bucket lid 431, thermal bucket bottom 432, water cooling plate 433, thermal layer 434, heating element 435, thermal jacket 436, head mount 437, locking screw 441, rotary mount 442, rotary shaft 443, medium inlet 521, medium outlet 522, microwell array 541, vacuum line 542, valve assembly 543, vacuum air pump 544, oil temperature machine 560.

Detailed Description

The construction and operation of the present invention will be described 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 nozzle assembly having respective nozzles 45, a storage tank 41, and a temperature control module 43, and a stage 5; and the three-axial translation mechanism drives the sprayer assembly to translate along the three axial directions (X-axis 31, Y-axis 32 and Z-axis 33), the three-axial 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 sprayer assembly is arranged on the Z-axis 33-direction translation unit. The spray head can move at any point of the XOY plane and can be lifted and lowered along the Z axis 33; the spray head component has independent functions of storing, extruding and printing; the stage 5 receives material extruded from the nozzle assembly. The temperature control module 43 maintains the temperature within the storage vat 41 to maintain the material at the desired temperature for printing. The biological printing system comprises a plurality of spray head assemblies, each spray head assembly comprises a respective spray head support 42, and the spray head support 42 is provided with a fixing 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, and the spray head component is obliquely arranged. The inclination of the spray head components means that the spray head components are intersected with the Z axis 33 to form an included angle, the spray nozzles 45 are arranged obliquely downwards, so that movement interference between the storage tanks 41 is avoided, and a plurality of spray head components can work cooperatively at the same time.

Material

The material referred to in this invention is a material or mixture for processing by a printer. When processed with the 3D printer of the present invention, some existing biomaterials may 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 materials for biological 3D printing, also referred to as "bio-inks". Although the material itself is a conventional material, printing can be performed using the printing apparatus and method to which the printing is distributed. The printed biological material has a three-dimensional space structure or a four-dimensional space, and can be provided with any through holes. Here, the through hole generally refers to a planar structure or a three-dimensional structure. For example, the holes may be in any shape, circular, rectangular, square, diamond, etc. in a plane. When the faces are in different dimensions, a three-dimensional shape is formed, each face or faces of the three-dimensional shape has a structure of holes, and the holes have a certain depth, wherein the holes can be communicated or not communicated or partially communicated, so that a channel penetrating the whole three-dimensional structure or part of the three-dimensional structure is formed. Such a structure is easy to realize with the printer of the present invention.

In some embodiments, the materials of the present invention may be mixed with stem cells for processing or printing, such that the material acts as a scaffold and the cells differentiate as an active cost, ultimately forming an active tissue. Of course, the scaffold structure may also be printed, and then the stem cells are allowed to fill the space of the scaffold, ultimately forming living tissue as well.

In summary, the printing of the new design of the present invention may print any suitable material.

In some embodiments, the storage tank 41 is a container for containing biological materials, and has good biocompatibility, and different storage tanks 41 may be used to contain the same materials. Alternatively, different materials or bio-inks may be contained in the reservoir 41, for example, reservoir a may contain one bio-material and reservoir B may contain another bio-material, the properties of the two materials not being the same, and the printing of complex biological tissues or organs may be achieved using the printing technique of the present invention. This is because a biological material or organ is not uniform in structure, but has differences in structure or biological properties. For example, mammalian skin materials have epidermis, dermis, the dermis has blood vessels and tissues connected to muscles, the structures of these different sites differ, the thickness differs, and the excess structure between tissues also differs, which also includes density, pore size, and the like. Thus, if printing by conventional printing is required, all structures or organizations are identical, while by the printing technique of the present invention, different structures of biological materials can be performed at once.

In some embodiments, as shown in FIG. 4, an angle adjustment mechanism is provided between the fixed portion and the mounting portion of the spray head bracket 42. The angle adjusting mechanism may be a wedge disposed between the spray head bracket 42 and the spray head assembly, or the fixing portion is hinged to the mounting portion, and the mounting portion rotates relative to the fixing portion, so as to adjust an included angle between the mounting portion and the fixing portion, and further adjust an angle of the spray head 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 mechanism, way of tightening screw, etc.

In some embodiments, as shown in fig. 4, the cross section of the nozzle 45 support is a right triangle, the surface of the hypotenuse of the nozzle 45 support is a mounting portion, and the surface of one of the right-angle sides of the nozzle 45 support is a fixing portion. The nozzle 45 assembly has a rotational degree of freedom within the mounting surface.

Rotary mechanism

In some embodiments, as shown in fig. 5, at least one of the showerhead assemblies has a rotation mechanism disposed between the mounting portion and the showerhead assembly; the rotation freedom degree of the rotation mechanism is unified with the spray head assembly. The rotating mechanism takes the fixing part as a reference surface and drives the spray head assembly to rotate in the plane where the fixing 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 seat 442, the rotation seat 442 being fixed to the showerhead assembly and the rotation shaft 443 being fixed to the mounting portion of the showerhead holder 42. External force is applied to the rotary base 442, and the rotary base rotates around the rotary shaft 443, so that the spray head assembly is driven to rotate, and the angle of the spray nozzle 45 is adjusted.

In some embodiments, the rotation mechanism is a mechanical dial that acts as a rotary seat 442 with a locking screw 441 or locking bolt disposed between the dial and the showerhead holder 42. When the locking screw 441 or the locking bolt is unlocked from the dial and the head holder 42, the dial may be rotated to adjust the angle of the nozzle 45. When the nozzle 45 is angularly adjusted, the dial and the head holder 42 are locked by the locking screw 441 or the locking bolt, and the dial and the nozzle 45 are positioned. Alternatively, the rotary shaft 443 is connected to a rotary motor.

In some embodiments, one or more spray head assemblies are mounted on the rotating mechanism; and, or, one or more showerhead assemblies mounted on each showerhead holder 42; and/or, a plurality of head assemblies are mounted on each head support 42, with a respective rotation mechanism disposed between each head assembly and the head support 42. Thus, the number of the spray heads can be flexibly expanded by mounting a plurality of spray head assemblies on the spray head support 42, and the expanded spray heads can have a rotational degree of freedom or a fixed position.

Triaxial translation mechanism

In some embodiments, each showerhead assembly corresponds to a respective Z-axis 33 translation unit; alternatively, at least two showerhead modules share a single Z-axis 33 translation unit.

As shown in fig. 2 and 3, the X-direction 31 translation mechanism includes a fixed gantry 21, a movable gantry 22, an X-direction 31 gantry rail engaged with the movable gantry 22, and an objective table 5 rail 51 engaged with the objective table 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; each of the head supports 42 may share a Z-rail 33 corresponding to one of the Z-rails 33 and/or the plurality of head supports 42 may share a Z-rail 33. That is, each head holder 42 may be mounted on a respective Z-rail 33, or a plurality of head holders 42 may be mounted on one Z-rail 33; alternatively, there is one head holder 42 corresponding to one Z-rail 33, and there are several head holders 42 sharing one Z-rail 33.

As shown in fig. 2 and 3, the movable gantry 22 and the fixed gantry 21 are centered, a plurality of spray head assemblies are provided on the movable gantry 22, and a plurality of spray head assemblies are provided on the fixed gantry 21. The number of head assemblies of the moving gantry 22 and the number of head assemblies of the fixed gantry 21 may be the same or different.

As shown in fig. 2 and 3, the head assembly of the moving gantry 22 and the head assembly on the fixed gantry 21 are symmetrical about 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 spray head assemblies, the fixed gantry 21 has 3 spray head assemblies, the spray head assemblies in the middle of the same gantry are fixedly connected with the spray head support 42, and the rest of the spray head assemblies are connected with the spray head support 42 through a rotating mechanism. Typically, 6 nozzle assemblies can satisfy most print jobs. However, when 6 head modules cannot satisfy a print job, it is possible to preferentially expand from the head modules on the outer side to expand the head modules on the outer side to two or more head modules sharing one head holder 42.

In still other embodiments, as shown in fig. 1, stage 5 rail 51 is located between moving gantry 22 and fixed gantry 21.

As shown in fig. 1, 2 and 3, each X-direction guide rail 31 has a first travel switch K and a second travel switch K, respectively, and a movement travel is provided between the two travel switches K. That is, the mobile gantry 22 translates between the first and second travel switches K and K of its guide rail; the stage 5 translates between a first travel switch K and a second travel switch K of its guide rail.

Spray head assembly

In some embodiments, the spray head assembly comprises a storage vat 41, a plunger matched with the storage vat 41, a temperature control module 43 and a spray nozzle 45, wherein the temperature control module 43 comprises a heat preservation barrel cover 431 and a heat preservation barrel bottom 432, the storage vat 41 is provided with a temperature control area which is wrapped by the heat preservation barrel cover 431 and the heat preservation barrel bottom 432, the storage vat 41 between the temperature control area and the spray head is a heat preservation area, and the storage vat 41 of the heat preservation area is provided with a heat preservation sleeve 436; the heat preservation barrel cover 431 and the heat preservation barrel bottom 432 are connected in a sealing mode 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 cavity or medium pipe, and the medium exchanges heat with the storage vat 41, so as to control the temperature of the material in the storage vat 41. Typically the medium of the spray head assembly is water. The heating element is an electric heating wire or a semiconductor sheet, etc.

The temperature control module 43 includes 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 nozzle mount 437, and the nozzle mount 437 is connected with the nozzle support 42 or a rotation mechanism. Preferably, the nozzle mount 437 includes a wing plate extending outwardly from the outer edge of the water cooling plate 433, with screw holes provided in the wing plate. The wings are secured to the spray head bracket 42 or swivel 442 by screws or bolts.

The medium chamber or medium conduit has 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 common heat conducting medical metal material with good heat conductivity and good biocompatibility, and titanium alloy material is also used. The liquid heat transfer medium may be oil. The liquid medium wraps the storage vat 41, the temperature control precision is high, the material temperature difference in the storage vat 41 is small, and the material temperature consistency is good.

The plunger is connected with the pneumatic actuating mechanism. Pneumatic actuators, such as cylinders. The nozzle 45 is a syringe needle.

The temperature control module 43 controls the temperature of the storage bucket 41 to keep the materials in the storage bucket 41 within a specified range. And, temperature control module 43 locates and secures storage vat 41.

In performing 3D printing of biological tissue, it is necessary to keep the material within a given temperature range for survival and reproduction of biological components, and therefore, it is necessary to control and keep the temperature of the tank 41. The showerhead assembly is a separate component in a 3D printing system.

Multi-nozzle co-dot printing

In some embodiments, as shown in fig. 7, the biological 3D printing system has a plurality of head assemblies and a co-point calibration sensor 6, and when the nozzles 45 of all the head assemblies touch the co-point sensor, the print path start points of all the head assemblies are co-point. The co-point calibration sensor 6 is used to unify the coordinate system of all showerhead modules into the world coordinate system. The co-point calibration sensor 6 is used to unify the coordinate system of all showerhead modules into the world coordinate system.

In some specific embodiments, as shown in fig. 7, the co-point calibration sensor 6 comprises 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 directional transmitter 61 to the first directional receiver 62 and the path from the second directional transmitter 63 to the second directional receiver 64 have intersections; the point of intersection of the needle tip trigger of the nozzle 45 is taken as the null point of the spray head assembly. Each jet assembly starts with a null position for a print job.

In some specific 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 emitters 61, each first direction emitter 61 having a respective corresponding first direction receiver 62; a plurality of second direction emitters 63, each second direction emitter 63 having a respective corresponding first direction receiver 62; a plurality of path intersections in two directions are formed; one for each showerhead assembly. In calibration, the null position is considered to be reached as long as the tip of the nozzle 45 of the spray head assembly reaches within the calibration area of the co-sited calibration sensor 6. All of the head assemblies may reach the zero position simultaneously, and then all of the head assemblies may be performing different paths of print jobs in parallel at the same time, each head assembly completing a portion of the overall job. Alternatively, multiple nozzles can perform simultaneous co-printing on the same path, thereby enabling different biological materials on one print path.

Preprinting module

As shown in fig. 8 and 9, the printing system is provided with a preprinting module, the preprinting module comprises a preprinting base 71, a cleaning nozzle 72, a reflux slot 73, a brush 74, a cutting line 76 and a material bearing area 75 are arranged on the preprinting base 71, the cleaning nozzle 72 is positioned in the reflux slot 73, and the brush 74 is positioned beside the reflux slot 73. The cleaning nozzle 72 sprays cleaning liquid for cleaning the spray head, and then the cleaning liquid is collected in the reflux groove 73 and then discharged; the tips of the nozzles 45 of the spray head assembly pass through a brush 74, and the brush 74 wipes the tips of the nozzles 45 clean; 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 at the tip end of the nozzle 45, and the nozzle 45 assembly moves to the object stage 5 to perform a formal printing task. The cutting wire 76 is a wire or other linear or filiform cutting element capable of cutting the 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, then the material is extruded in the material bearing area 75, and after the discharge flow of the nozzle 45 is stable, the nozzle 45 assembly passes through the cutting line.

The pre-printing module is provided with a pre-printing guide rail, and the pre-printing module is slidably matched with the pre-printing guide rail; the preprinting module has a motion driving mechanism. When the nozzle assembly is pre-printed, the position of the nozzle assembly is fixed, the pre-printing module moves to the lower part of the nozzle assembly, the pre-printing module withdraws from the nozzle assembly after the pre-printing is finished, the tip of the nozzle 45 leaves the cleaning nozzle 72 and contacts the hairbrush 74 when the pre-printing module withdraws in sequence, and finally the cutting line 76 cuts off the material at the tip of the nozzle 45, so that the pre-printing module finishes withdrawing. After the preprinting module is removed, the stage 5 is moved under the showerhead assembly.

The preprinting module is provided to clean the nozzle 45 of the nozzle assembly, remove the residual material from the last printing, and print formally after the extruded material is stable.

Object stage

As shown in fig. 9, the objective table 5 is a working platform for receiving materials from the nozzle assembly, realizing additive superposition and finally forming a 3D solid component; the stage 5 in the present invention is slidably mounted on the guide rail 51 of the stage 5.

In some embodiments, stage 5 of the biological 3D printing system includes a print vessel and a temperature control module 52, the temperature control module 52 wrapping around the periphery of the print vessel.

Temperature control module 52

The materials used by the biological 3D printing system are required to be kept in a specified temperature range, so that the material additive printing of the materials can be realized, and the survival rate of biological tissues can be improved.

In some embodiments, as shown in fig. 9, the temperature control module 52 includes a media cavity or media conduit having a receptacle 53 for receiving the print vessel 8, the media cavity having a media inlet 521 and a media outlet 522 into which a liquid media having an operating temperature is input. The medium cavity is a complete communicating cavity. The printing vessel is a circular vessel, the medium cavity is a circular cavity, or the medium cavity is a spiral pipeline. The shape of the medium chamber may be such that it can be uniformly matched with the print vessel.

In operation of the temperature control module 52, the liquid medium is delivered to the medium chamber or medium conduit after reaching a specified temperature outside the medium chamber, where the liquid medium is heated may be an external medium container and heater, such as an oil temperature machine 560. The medium with working temperature continuously circulates between the externally connected medium container and the medium cavity, the total amount of the liquid medium is large, compared with the precision of temperature control of a small amount of medium in the medium cavity, the precision is high, and the difficulty of temperature control is reduced.

Clamp module

In some embodiments, as shown in fig. 11, 12, the stage 5 includes a gripper module that secures the print vessel from the bottom.

The fixture module comprises an adsorption seat 54, a vacuum pipeline 542 and a vacuum air pump 544, wherein the adsorption seat 54 is provided with a micropore array 541, 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 work starts, the printing vessel is required 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 micropore 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 enclosed 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, adjacent micro-holes being communicated by a communication line, each array unit has a respective valve assembly 543, the valve assembly 543 being disposed on the vacuum line 542, or the valve assembly 543 being disposed between the vacuum line 542 and the vacuum air pump 544. For example, the print vessel is rectangular, then the array unit is a similar rectangle of the work platform. The micropores are arranged in the mode of arranging the array units, so that clamping of working platforms with different sizes can be realized.

The printing vessel is a circular vessel, the micropores of the array units are enclosed into a circle, all the array units are arranged in concentric circles, and the most central array unit is a central micropore. All concentric circular arrays or one (or a plurality of) concentric circular arrays can be selectively opened according to the size of the printing vessel, so that the printing vessel is fixed. Preferably, the center of the array unit is located at the center of the adsorption seat 54. The shape of the adsorption seat 54 is not limited as long as the adsorption seat 54 has a size to accommodate the array unit.

In some embodiments, the stage 5 has both the temperature control module 52 and the clamp module described above, as shown in fig. 10.

Taking the example of the co-dot printing of 6 different materials in the storage barrel 41 of the 6 spray head assemblies as an example, the working flow of the biological 3D printing system of the invention is described:

the coordinates of the spray heads are reset to zero before printing is started, the spray heads enter a cleaning area sequentially and stay on the cleaning liquid nozzles 45 to be washed by the cleaning liquid, and the surface is cleaned by passing through the wiping brush 74 sequentially along a fixed path. And the 6 execution sprayers are sequentially placed into the calibration module to carry out zero setting on the pose coordinates, the middle sprayers on one side of the fixed gantry 21 are used as references, the outer 4 sprayers rotate inwards by 45 degrees, and the drive motor moves the execution sprayers to form extrusion tail end co-points around the execution sprayers. And after the co-pointing is finished, each spray head drives synchronous translation and moves to a calibration module to detect the co-pointing error. If the error is out of the set range, 5 spray heads around the middle spray head on one side of the fixed gantry 21 are driven by the Y32 and Z axis 33 motors to finely adjust the positions of the spray heads, and the detection is performed again; if the error is within the set range, the next link is performed. The co-dot nozzle is moved to a pre-printing area for pre-working, for example, printing a rectangle and an arc, and after the quality of the extruded material is stable, the extruded material is moved through the cutting line 76, and the height of the cutting line 76 is set to be the same as the co-dot position of the nozzle in the horizontal direction, so that the cutting nozzle 45 is remained. The co-point spray head is moved into the working area vessel, and the formal extrusion printing is started. And after printing, the outer 4 spray head rotating motors return to the 0-degree position, and the coordinates of the 6 spray heads return to zero after the 6 spray heads sequentially execute cleaning operation.

The triaxial translation mechanism, objective table 5 and preprinting module etc. all set up on base 1, and base 1 can provide stable support to biological 3D printing system to and horizontal reference surface.

Multi-nozzle collaborative biological printing method

The invention provides a method for realizing multi-nozzle co-point printing by using the printer. The multi-nozzle collaborative biological printing method comprises the following steps: the co-point calibration sensor 6 is arranged at the path starting point of the printing task, the nozzle assembly which needs to carry out the printing task is determined, the nozzle assembly is moved to the zero position, the nozzle assembly starts the printing task from the zero position in sequence, or all the nozzle assemblies which carry out the printing task execute the same printing path, and after all the nozzle assemblies reach the zero position, the nozzle assemblies synchronously start the printing task from the zero position along the printing path.

In some embodiments, when the print job is started from a null position in sequence by the nozzle assembly, the print job is composed of a plurality of sub-paths, all of which intersect at a point, and the intersection point of the sub-paths serves as the null position of the printing system.

Aiming at the printing method of the organization with multiple materials distributed at intervals or with multiple materials distributed alternately, if multiple printing materials exist in the same printing path, selecting a nozzle assembly corresponding to the printing materials as a nozzle assembly for performing a printing task, wherein 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 co-point calibration sensor 6 to the starting point of the current task path, enabling the current spray head assembly corresponding to the current task path to move to a zero position, and evacuating the co-point 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 spray head assembly by the co-point calibration sensor 6 and movement of the current spray head assembly along the current task path; repeating until all sub-paths are printed. The co-point calibration sensor 6 is used for calibrating the starting point position of the current spray head assembly, so that continuous collaborative printing of multiple materials and multiple spray heads is realized, and printing of complex tissues of the multiple materials is possible.

Aiming at the situation that a certain material is used as a main printing material, but auxiliary materials are locally required to be added or compounded, a spray head assembly corresponding to the printing material is selected as a spray head assembly for performing a printing task, a co-point calibration sensor 6 is arranged at the starting point of a printing path, all spray head assemblies for performing the printing task reach zero positions, the co-point calibration sensor 6 is removed, all spray head assemblies for performing the printing task synchronously move along the printing task path, and each spray head assembly extrudes materials in the task path corresponding to the material; and closing in the non-task path.

The invention shown and described herein may be practiced without any of the elements, limitations 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 is therefore to be understood that while 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 documented herein are 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 any and all materials and information from any such articles, patents, patent applications, or other documents.

Claims

1. Biological 3D print system, its characterized in that: the 3D printing system comprises an extrusion type spray head assembly, an objective table, a co-point calibration sensor and a triaxial translation mechanism, wherein the objective table is provided with a containing cavity matched with a printing vessel; the object stage comprises a temperature control module, and the temperature control module wraps the bottom and the periphery of the printing vessel;

the plurality of the spray head assemblies are arranged, and when nozzles of all the spray head assemblies touch the common-point sensor, the printing path starting points of all the spray head 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 a part of the total tasks; or, the plurality of spray heads can synchronously and cooperatively print the same path, so that different biological materials can be arranged on one printing path;

at least one of the spray head assemblies is provided with a rotating mechanism, and the rotation freedom degree of the rotating mechanism is unified with that of the spray head assembly;

the co-point 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; taking the needle point triggering intersection point of the nozzle as a spray head component to reach a zero position;

The three-axial translation mechanism comprises an X-axial translation unit, a Y-axial translation unit and a Z-axial translation unit, the spray head assembly is arranged on the Z-axial translation unit, the spray head assembly comprises a spray head bracket, and the spray head bracket is provided with a fixing part connected with the Z-axial translation unit and an installation part connected with the spray head assembly; an angle adjusting mechanism is arranged between the fixing part and the mounting part of the spray head bracket;

each spray head assembly corresponds to a respective Z-axis translation unit;

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 objective table guide rail matched with the objective table; 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; each spray head support corresponds to one Z-direction guide rail and/or a plurality of spray head supports share one Z-direction guide rail; each spray head support is arranged on a Z-direction guide rail, or a plurality of spray head supports are arranged on a Z-direction guide rail; or, there is a shower nozzle support corresponding to a Z-direction guide rail, there are several shower nozzle supports that share a Z-direction guide rail at the same time;

A plurality of first direction transmitters, each first direction transmitter having a respective first direction receiver; a plurality of second direction transmitters, each second direction transmitter having a respective first direction receiver; a plurality of path intersections in two directions are formed; each intersection point corresponds to one spray head component; when calibrating, as long as the nozzle tip of the spray head assembly reaches the calibration area of the co-point calibration sensor, the zero position is considered to be reached; all the spray head components can reach zero position at the same time;

the temperature control module comprises a medium cavity or a medium pipeline, wherein the medium cavity or the medium pipeline is provided with a containing cavity for containing 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.

2. The biological 3D printing system of claim 1, wherein: the medium cavity is a complete communicating cavity.

3. The biological 3D printing system of claim 1, wherein: the printing vessel is a circular vessel, the medium cavity is a circular cavity, or the medium cavity is a spiral pipeline.

4. The biological 3D printing system of claim 1, wherein: the stage includes a clamp module that secures the print vessel from the bottom.

5. The biological 3D printing system of claim 4, wherein: the fixture 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.

6. The biological 3D printing system of claim 5, 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 enclosed 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, each array unit is provided with a respective valve assembly, and the valve assembly is arranged on a vacuum pipeline or between a vacuum pipeline and a vacuum air pump.

7. The biological 3D printing system of claim 5, wherein: the printing vessel is a circular vessel, the micropores of the array units are enclosed into a circle, all the array units are arranged in concentric circles, and the most central array unit is a central micropore.

8. The biological 3D printing system of claim 5, wherein: the center of the array unit is positioned at the center of the adsorption seat.