CN106725999A - The anti-blocking multicellular organism increasing material manufacturing method and device of high-precision ultrasound - Google Patents
The anti-blocking multicellular organism increasing material manufacturing method and device of high-precision ultrasound Download PDFInfo
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- CN106725999A CN106725999A CN201710027539.XA CN201710027539A CN106725999A CN 106725999 A CN106725999 A CN 106725999A CN 201710027539 A CN201710027539 A CN 201710027539A CN 106725999 A CN106725999 A CN 106725999A
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- shower nozzle
- storage compartment
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- stairstepping
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Manufacturing & Machinery (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Special Spraying Apparatus (AREA)
Abstract
The present invention relates to a kind of anti-blocking multicellular organism increasing material manufacturing method and device of high-precision ultrasound, belong to biological increases material manufacturing technology field.Triaxial movement platform is arranged on the underface of transverse movement axle, and many nozzle components are arranged on transverse movement axle；Driven by piezoelectric type and ultrasonic assistive technologies spray many material many cells, and use micron order nozzle and ultrasonic spray nozzle device combination ultrasonic wave anti-blocking method, realize that outside hydrogel is converted to colloidal sol shape, cell is accurately positioned deposition by micron order nozzle, realize many materials, many cells, high activity precise Printing labyrinth organ.The printing precision is caused to reduce by enlarged nozzle diameter to prevent shower nozzle from blocking present invention, avoiding conventional cell printer, overcome many Material cladding printings of many cells and the limitation of unicellular precise Printing, the low problem of cell survival rate during many file printings of many cells is solved, the three-dimensional integration printing of complex biological organ-tissue is realized.
Description
Technical field
The present invention relates to biological increases material manufacturing technology field, and in particular to the three dimensional structure of many material many cells increasing material manufacturings
The method and device of increasing material manufacturing.
Background technology
The bio-ink that Organ printing is made with stem cell differentiation produces organ as raw material using increasing material manufacturing principle
Biometric print method.Organ is made up of complicated blood vessel network, tissue, muscle, nerve etc., it is desirable to which printer is necessary
Possesses the ability of many material many cells printings；Organ has closely tissue in itself, and substantial amounts of capillary causes iuntercellular
Spacing very little, it is desirable to which printer being capable of high accuracy deposition of cells and precise Printing biomaterial；During cell printing, general meeting
Reduce spray nozzle diameter and meet and cell is accurately positioned, easy nozzle is blocked, therefore it is required that printer have it is anti-blocking
Plug device or method.
At present, if Organ printing owner is printed using the big nozzle cellule tissue of big shower nozzle, the droplet size for being sprayed
It is larger, it is impossible to ensure that once injection prints cell quantity, cause cell printing chaotic, tissue generation intersects serious, it is impossible to press
Respective organization is generated according to predetermined space；This kind of printer is in order to ensure printing precision, and print speed is typically all relatively low, it is impossible to and
When supply cell nutrients, cell survival rate is not high；Meanwhile, this kind of printer does not account for nutrient supply after Organ printing is completed
The design of class blood vessel structure, cell survival rate is not high.
The content of the invention
The present invention provides a kind of anti-blocking multicellular organism increasing material manufacturing method and device of high-precision ultrasound, is beaten with solving organ
The problem that cellular localization present in print process is inaccurate, survival rate is low, shower nozzle is blocked, printing effect is low.
The present invention is adopted the technical scheme that：Comprise the following steps：
1) start printing before, printing equipment is put into disinfection cabinet or sterilization tank 15min, be finally putting into sterility test room or
Person's sterility test case etc. is to be printed；
2) biological solution containing various cells is injected into the storage compartment one being connected with shower nozzle one, strong is applied to shower nozzle
Degree 20mw/cm2, the ultrasonic wave of frequency 200KHz, the unlatching Piexoelectric actuator of shower nozzle one and the pneumatic means of storage compartment one, piezoelectricity drive
Dynamic device is with ultrasonic waveform into combination flooding power, and drop ejection efficiency is higher；
3) high-strength composite hydrogel is injected into in the nozzle specially used storage compartment two being connected of printing blood vessel, opens storage compartment
Two pneumatic means, wait to be printed；
4) printed polyethylene (PE) the organ base with 80% porosity, the bottom are placed on substrate
Seat is customized according to organ bottom size, it is easy to absorption of the organ bottom cell to nutrient in print procedure；
5) threedimensional model of biologic-organ to be printed is obtained, then the threedimensional model is divided into some two-dimentional aspects, then cut
Piece is layered as STL formatted files, and then the two-dimentional plane data is imported into Labview pc control procedures, control
Program controls the drive device of each shower nozzle one and shower nozzle two according to two-dimentional plane data, storage compartment one and storage compartment two it is pneumatic
Device；
6) Labview host computer procedures control shower nozzle to move to current position to be printed according to two-dimentional plane data, start
Printing ground floor, is provided with the triaxial movement platform movement of grating scale, and pneumatic means applies instantaneous pressure, pressure value to storage compartment
It is 0.6mpa, pressure time is 980ms, and the biological solution in storage compartment one flows to shower nozzle one, and Piexoelectric actuator is to shower nozzle one
Apply pressure, low-intensity ultrasonic disperses the cell that extruding is assembled, prevents each spray nozzle clogging of shower nozzle one, completes injection single
Cell, changes permeability of cell membrane, and cell is vibrant, and survival rate is high；
7) repeat step 6), when printing blood vessel is needed, Labview host computer procedures are beaten according to the control of two-dimentional plane data
Print blood vessel is nozzle specially used to move to current print position, and pneumatic means applies continuous 0.3mpa, hydrogel to storage compartment two
Flow direction printing blood vessel is nozzle specially used, empty class blood vessel structure in jet printing, is that later stage organ culture supplies nutrients passage；
8) repeat step 6), 7) untill all two-dimentional aspect printings are completed, obtain biologic-organ.
The driving voltage of shower nozzle of the present invention is that shower nozzle sprays spray rate and is after 60-130V, Piezoelectric Driving and ULTRASONIC COMPLEX
100Hz—90KHz。
A kind of anti-blocking multicellular organism increasing material manufacturing device of high-precision ultrasound, triaxial movement platform is arranged on transverse movement axle
Underface, many nozzle components be arranged on transverse movement axle on；
The structure of triaxial movement platform of the present invention is：Z axis leading screw block is installed by guide pillar one and high-accuracy leading screw one
On triaxial movement platform pedestal, high-accuracy leading screw one is connected by triaxial movement platform pedestal with servomotor three, three axles fortune
Shower nozzle entrance is provided with moving platform pedestal top board, Z axis platform is arranged on Z axis leading screw block by Z axis stage+module seat, organ training
Support vessel to be arranged on substrate installing plate by substrate, substrate installing plate is arranged on servo by guide pillar two and high-accuracy leading screw two
On motor one, servomotor one is arranged on the installing plate of servomotor one by the mounting seat of servomotor one, and servomotor one is pacified
Dress plate passes through, and the mounting seat of servomotor one is arranged on guide rail slide block one, and guide rail slide block one is arranged on Z axis by line slideway one
On platform, guide rail slide block one is connected by connecting plate one with feed screw nut, and feed screw nut is by high-accuracy leading screw three and servo electricity
Machine two is connected, and servomotor two is arranged on Z axis platform by the installing plate of servomotor two, and the installing plate of servomotor two is by watching
The mounting seat of motor two is taken to be fastened on Z axis platform；
The structure of transverse movement axle of the present invention is：Support is arranged on base, and line slideway two is fixed by screw
On support, the two ends of high-accuracy leading screw four are connected on servomotor four and the installing plate of high-accuracy leading screw four, servomotor
4 years rack-mount by the installing plate of servomotor four, and the installing plate of servomotor four is pacified by the mounting seat of servomotor four
On support, nozzle component mounting hole is provided with nozzle component mounting seat, nozzle component mounting seat is pacified by guide rail slide block two
On line slideway two；
The structure of many nozzle components of the present invention is：Line slideway three is arranged on shower nozzle by the screw hole of line slideway three
On unit installing board, cylinder mount plate is arranged on nozzle component base plate, and blood vessel shower nozzle is arranged on shower nozzle retainer plate, micron
Level syringe needle is connected with syringe, and ultrasonic transducer is arranged on syringe, and syringe is connected with stairstepping shower nozzle, and piezoelectric ceramics rod is installed
On stairstepping shower nozzle, compressed air inlet is managed by aseptic compression screen pack Pipe installing in stairstepping storage compartment, feed liquor
Pipe is connected by shockproof flexible pipe installed in the side of stairstepping storage compartment, stairstepping storage compartment with stairstepping shower nozzle, stairstepping spray
Head is arranged on shower nozzle retainer plate, and stairstepping storage compartment is arranged on storage compartment's retainer plate, and storage compartment's retainer plate passes through storage compartment
Retainer plate attachment screw is fixed on guide rail slide block three, and shower nozzle retainer plate is fixed on connecting plate by shower nozzle retainer plate attachment screw
On two, hydraulic cylinder is connected on connecting plate two by hydraulic cylinder push rod, and the two ends of connecting plate two connect guide rail slide block three respectively, ultrasound
Wave transducer is connected by power line with ultrasonic power, and circular diaphragm is placed on the inside of stairstepping shower nozzle, aseptic compressed
Filter screen is placed in aseptic compression screen pack pipeline, and electromagnetic switch valve one is placed on feed tube, and electromagnetic switch valve two is placed on
On shockproof flexible pipe, feed room is connected by feeder sleeve with feed tube；
The structure of blood vessel shower nozzle of the present invention is：Middle mandrel is arranged in stairstepping blood vessel shower nozzle inner top, with circle
Cylindricality shower nozzle forms coaxial angiocarpy print components, and electromagnetic switch valve three is arranged on shockproof flexible pipe two, and electromagnetic switch valve four is pacified
On feed tube two, compressed air inlet pipe two is by aseptic compressed inside aseptic compression screen pack pipeline two
Filter screen two is connected in stairstepping storage compartment two, and feed room two is connected by feeder sleeve two with feed tube two；
The internal diameter of micron order syringe needle 306 of the present invention is 9 μm -120 μm.
The present invention has advantages below：
Using piezoelectricity and ultrasonic assistant composite flooding shower nozzle regulation device, membrane passage and increase can be increased
The vigor of cell, printing cell survival rate is higher, and low-intensity ultrasonic can also be by the hydrogel of current package cell by gel
State not exclusively changes to collosol state, waits after disengaging spray nozzle and returns to original gel state, plays support thin
The effect of born of the same parents, effectively have adjusted in cellular biological material print procedure because outside water-setting adhesiveness is high or coagulation grade
The problem that spray nozzle is blocked caused by height, spray nozzle blocking probability reduces 35%.
Using many nozzle printing methods, after reducing spray nozzle blocking probability, sprayed using 9 microns of more small shower nozzles
Mouth, printed droplets are several picoliters, it is possible to prevente effectively from causing the tissue of generation during Organ printing due to cell deposition confusion
Intersect the chaotic phenomenon of serious and blood flow paths, cell high accuracy can be deposited in the organ space specified.
Stairstepping blood vessel nozzle component is employed, the nutriment service duct of later stage organ culture, Ke Yiti is efficiently solved
The survival rate of cell high, makes Organ printing survival rate bigger, while using retainer plate grip device, can easily load and unload shower nozzle
And storage compartment, it is easy to ultrasonic wave up-down vibration, interchangeability is high, easy to setup, can continue to expand the quantity of integrated shower nozzle, easily
In the printing demand for realizing various organs.
Brief description of the drawings
Fig. 1 is structural representation of the invention；
Fig. 2 a are the structural representations of triaxial movement platform of the present invention；
Fig. 2 b are the upward views of triaxial movement platform of the present invention；
Fig. 2 c are triaxial movement platform explosive views of the present invention；
Fig. 3 is the structural representation of transverse movement shaft assembly of the present invention；
Fig. 4 a are the structural representations of many nozzle components of the invention；
Fig. 4 b are single spraying head driving apparatus structural representations in many nozzle components of the invention；
Fig. 4 c are single spraying head installation drawings of the present invention；
Fig. 4 d are single spraying fixture head figures of the present invention；
Fig. 4 e are many shower head principle figures of stairstepping of the present invention；
Fig. 4 f are blood vessel shower head principle figures of the present invention；
In figure：1 triaxial movement platform；2 transverse movement axles；Nozzle component more than 3；101 triaxial movement platform pedestals；102Z axles
Platform；103 servomotors one；104 organ culture vessel；105 shower nozzle entrances；106 guide pillars one；107 high-accuracy leading screws one；108
Servomotor two；109Z axial filament thick stick blocks；110 servomotors three；111 guide rail slide blocks one；The mounting seat of 112 servomotor two；113 watch
Take the installing plate of motor two；The mounting seat of 114 servomotor one；The installing plate of 115 servomotor one；116 connecting plates one；117 leading screw spiral shells
It is female；118 substrates；119 substrate installing plates；120 high-accuracy leading screws two；121 guide pillars two；122 high-accuracy leading screws three；123Z shaft platforms
Mounting seat；124 line slideways one；201 bases；202 supports；203 line slideways two；204 servomotors four；205 servomotors
Four mounting seats；The installing plate of 206 servomotor four；207 guide rail slide blocks two；208 nozzle component mounting seats；209 nozzle components are installed
Hole；The installing plate of 210 high-accuracy leading screw four；211 high-accuracy leading screws four；301 line slideways three；The screw hole of 302 line slideway three；
303 cylinder mount plates；304 blood vessel shower nozzles；305 nozzle component base plates；306 micron order syringe needles；307 syringes；308 stairsteppings spray
Head；309 piezoelectric ceramics rods；310 compressed air inlet pipes one；311 aseptic compression screen pack pipelines one；312 feed tubes one；313
Stairstepping storage compartment one；314 shockproof flexible pipes one；315 ultrasonic transducers；316 connecting plates two；317 shower nozzle retainer plates connect spiral shell
Nail；318 hydraulic cylinder push rods；319 hydraulic cylinders；320 shower nozzle retainer plates；321 storage compartment's retainer plate attachment screws；322 storage compartments consolidate
Fixed circle；323 guide rail slide blocks three；324 power lines；325 ultrasonic powers；326 circular diaphragms；327 aseptic compression screen packs one；
328 electromagnetic switch valves one；329 feed rooms one；330 feeder sleeves one；331 electromagnetic switch valves two；Mandrel in 30401；30402 ladders
Shape blood vessel shower nozzle；30403 electromagnetic switch valves three；30404 compressed air inlet pipes two；30405 aseptic compression screen packs two；
30406 aseptic compression screen pack pipelines two；30407 electromagnetic switch valves four；30408 feed rooms two；30409 feeder sleeves two；
30410 feed tubes two；30411 stairstepping storage compartments two；30412 shockproof flexible pipes two.
Specific embodiment
Comprise the following steps：
1) start printing before, printing equipment is put into disinfection cabinet or sterilization tank 15min, be finally putting into sterility test room or
Person's sterility test case etc. is to be printed；
2) biological solution containing various cells is injected into the storage compartment one being connected with shower nozzle one, strong is applied to shower nozzle
Degree 20mw/cm2, the ultrasonic wave of frequency 200KHz, the unlatching Piexoelectric actuator of shower nozzle one and the pneumatic means of storage compartment one, piezoelectricity drive
Dynamic device is with ultrasonic waveform into combination flooding power, and drop ejection efficiency is higher；
3) high-strength composite hydrogel is injected into in the nozzle specially used storage compartment two being connected of printing blood vessel, opens storage compartment
Two pneumatic means, wait to be printed；
4) printed polyethylene (PE) the organ base with 80% porosity, the bottom are placed on substrate
Seat is customized according to organ bottom size, it is easy to absorption of the organ bottom cell to nutrient in print procedure；
5) threedimensional model of biologic-organ to be printed is obtained, then the threedimensional model is divided into some two-dimentional aspects, then cut
Piece is layered as STL formatted files, and then the two-dimentional plane data is imported into Labview pc control procedures, control
Program controls the drive device of each shower nozzle one and shower nozzle two according to two-dimentional plane data, storage compartment one and storage compartment two it is pneumatic
Device；
6) Labview host computer procedures control shower nozzle to move to current position to be printed according to two-dimentional plane data, start
Printing ground floor, is provided with the triaxial movement platform movement of grating scale, and pneumatic means applies instantaneous pressure, pressure value to storage compartment
It is 0.6mpa, pressure time is 980ms, and the biological solution in storage compartment one flows to shower nozzle one, and Piexoelectric actuator is to shower nozzle one
Apply pressure, low-intensity ultrasonic disperses the cell that extruding is assembled, prevents each spray nozzle clogging of shower nozzle one, completes injection single
Cell, changes permeability of cell membrane, and cell is vibrant, and survival rate is high；
7) repeat step 6), when printing blood vessel is needed, Labview host computer procedures are beaten according to the control of two-dimentional plane data
Print blood vessel is nozzle specially used to move to current print position, and pneumatic means applies continuous 0.3mpa, hydrogel to storage compartment two
Flow direction printing blood vessel is nozzle specially used, empty class blood vessel structure in jet printing, is that later stage organ culture supplies nutrients passage；
8) repeat step 6), 7) untill all two-dimentional aspect printings are completed, obtain biologic-organ.
The driving voltage of shower nozzle of the present invention is that shower nozzle sprays spray rate and is after 60-130V, Piezoelectric Driving and ULTRASONIC COMPLEX
100Hz—90KHz。
A kind of anti-blocking multicellular organism increasing material manufacturing device of high-precision ultrasound, triaxial movement platform 1 is arranged on transverse movement
The underface of axle 2, many nozzle components 3 are arranged on transverse movement axle 2；
The structure of triaxial movement platform of the present invention 1 is：Z axis leading screw block 109 passes through guide pillar 1 and high-accuracy leading screw
One 107 are arranged on triaxial movement platform pedestal 101, and high-accuracy leading screw 1 passes through triaxial movement platform pedestal 101 and servo
Motor 3 110 is connected, and shower nozzle entrance 105 is provided with triaxial movement platform pedestal top board, and Z axis platform is by Z axis stage+module seat
123 are arranged on Z axis leading screw block, and organ culture vessel 104 are arranged on substrate installing plate 119 by substrate 118, and substrate is installed
Plate 119 is arranged on servomotor 1 by guide pillar 2 121 and high-accuracy leading screw 2 120, and servomotor 1 is by watching
Take the mounting seat 114 of motor one to be arranged on the installing plate of servomotor one, the installing plate 115 of servomotor one passes through, servomotor one
Mounting seat 114 is arranged on guide rail slide block 1, and guide rail slide block 1 is arranged on Z axis platform 102 by line slideway 1
On, guide rail slide block 1 is connected by connecting plate 1 with feed screw nut 117, and feed screw nut 117 passes through high-accuracy leading screw three
122 are connected with servomotor 2 108, and servomotor 2 108 is arranged on Z axis platform 102 by the installing plate 113 of servomotor two
On, the installing plate 113 of servomotor two is fastened on Z axis platform by the mounting seat 112 of servomotor two；
The structure of transverse movement axle of the present invention is：Support 202 is arranged on base 201, and line slideway 2 203 passes through
Screw is fixed on support 202, and the two ends of high-accuracy leading screw 4 211 are connected to servomotor 4 204 and high-accuracy leading screw four
On installing plate 210, servomotor is arranged on support 202 for 4 years by the installing plate 206 of servomotor four, servomotor four
Installing plate 206 is arranged on support 202 by the mounting seat 205 of servomotor four, and jet head sets are provided with nozzle component mounting seat 208
Part mounting hole 209, nozzle component mounting seat 208 is arranged on line slideway 2 203 by guide rail slide block 2 207；
The structure of many nozzle components 3 of the present invention is：Line slideway 3 301 is pacified by the screw hole 302 of line slideway three
On nozzle component installing plate 305, cylinder mount plate 303 is arranged on nozzle component base plate 305, and blood vessel shower nozzle 304 is pacified
On shower nozzle retainer plate 320, micron order syringe needle 306 is connected with syringe 307, and ultrasonic transducer 315 is arranged on syringe 307
On, syringe 307 is connected with stairstepping shower nozzle 308, and piezoelectric ceramics rod 309 is arranged on stairstepping shower nozzle 308, compressed air inlet
Pipe 310 is arranged in stairstepping storage compartment 313 by aseptic compression screen pack pipeline 311, and feed tube 312 is stored up installed in stairstepping
Expect the side of room 313, stairstepping storage compartment 313 is connected by shockproof flexible pipe 314 with stairstepping shower nozzle 308, stairstepping shower nozzle 308
On shower nozzle retainer plate 320, stairstepping storage compartment 313 is arranged on storage compartment's retainer plate 322, storage compartment's retainer plate 322
It is fixed on guide rail slide block 3 323 by storage compartment retainer plate attachment screw 321, shower nozzle retainer plate 320 passes through shower nozzle retainer plate
Attachment screw 317 is fixed on connecting plate 2 316, and hydraulic cylinder 319 is connected on connecting plate 2 316 by hydraulic cylinder push rod 318,
The two ends of connecting plate 2 316 connect guide rail slide block 3 323 respectively, and ultrasonic transducer 315 passes through power line 324 and ultrasonic power
325 are connected, and circular diaphragm 326 is placed on the inside of stairstepping shower nozzle 308, and aseptic compression screen pack 327 is placed on aseptic compression
In screen pack pipeline 311, electromagnetic switch valve 1 is placed on feed tube 312, and electromagnetic switch valve 2 331 is placed on shockproof soft
On pipe 314, feed room 329 is connected by 330 feeder sleeves with feed tube；
The structure of blood vessel shower nozzle 304 of the present invention is：Middle mandrel 30401 is arranged in stairstepping blood vessel shower nozzle 30402
On portion's top board, coaxial angiocarpy print components are formed with cylindrical shower nozzle 30402, electromagnetic switch valve 3 30403 is arranged on shockproof
On flexible pipe 2 30412, electromagnetic switch valve 4 30407 is arranged on feed tube 2 30410, and compressed air inlet pipe 2 30404 leads to
The aseptic compression screen pack 2 30405 crossed inside aseptic compression screen pack pipeline 2 30406 is connected to stairstepping storing
On room 2 30411, feed room 2 30408 is connected by feeder sleeve 2 30409 with feed tube 2 30410；
The internal diameter of micron order syringe needle 306 of the present invention is 9 μm -120 μm.
Below using the anti-blocking multicellular organism increasing material manufacturing device of high-precision ultrasound come further the method for the invention.
Start printing before, printing equipment is put into disinfection cabinet or sterilization tank 15min, be finally putting into sterility test room or
Sterility test case etc. is to be printed；
Open electromagnetic switch valve 1 and close electromagnetic switch valve 2 331, by the feed containing various cellular biological materials
Room 1 enters into each stairstepping and stores up under the driving of pneumatic means by feeder sleeve 1 and the feed tube 1 opened
Material room 1, when being filled into 2/3 position to stairstepping storage compartment 1, closes electromagnetic switch valve 1 and stops feed；Beat
Open electromagnetic switch valve 4 30407 and close electromagnetic switch valve 3 30403, by containing by modified high-strength composite hydrogel
Feed room 2 30408 enters into rank under the driving of pneumatic means by feeder sleeve 2 30409 and the feed tube 2 30410 opened
Trapezoidal storage compartment 2 30411, when being filled into 2/3 position to stairstepping storage compartment 2 30411, closes electromagnetic switch valve four
30407 stop feed；
Printed polyethylene (PE) the organ base with 80% porosity, the base are placed on substrate
Customized according to organ bottom size, it is easy to absorption of the organ bottom cell to nutrient in print procedure；
The threedimensional model of biologic-organ to be printed is obtained, then the threedimensional model is divided into some two-dimentional aspects, then cut into slices
STL formatted files are layered as, then the two-dimentional plane data is imported into Labview pc control procedures, control journey
Sequence according to two-dimentional plane data control equipped with grating scale triaxial movement platform 1, and each shower nozzle drive device and storing
The pneumatic means of room；
Labview host computer procedures control stairstepping shower nozzle to move to the top of shower nozzle entrance 105 according to two-dimentional plane data,
Then hydraulic cylinder 319 promotes connecting plate 2 316 to drive and is separately mounted on shower nozzle retainer plate 320 and storage compartment's retainer plate 322
Stairstepping shower nozzle 308 and stairstepping storage compartment 1 move downward, after stairstepping spray nozzle reaches specified location, hydraulic pressure
Cylinder 319 stops propulsion, and the convert rotational motion of servomotor 3 110 drives the straight line fortune of Z axis platform into high-accuracy leading screw 1
It is dynamic, rise certain altitude, when keeping 1mm height to stairstepping spray nozzle and the bottom of organ culture vessel 104, by grating
The feedback signal of chi, Labview host computers treatment stops servomotor 3 110 and rotates；
Start to print ground floor, open electromagnetic switch valve 2 331, pneumatic means applies wink to stairstepping storage compartment 1
When pressure, pressure value is 0.6mpa, and pressure time is 980ms, and droplet size is 45 picoliters, in stairstepping storage compartment 1
Biological solution is flowed in stairstepping shower nozzle 308 by shockproof flexible pipe 1, opens ultrasonic power 325, and intensity is applied to shower nozzle
20mw/cm2, the ultrasonic wave of frequency 200KHz, while opening each Piexoelectric actuator of stairstepping shower nozzle 308 to stairstepping shower nozzle
308 apply pressure, open the pneumatic means of stairstepping storage compartment 2 30411, and Labview host computer procedures receive print signal
After, Piexoelectric actuator and ultrasonic wave added device apply high-frequency drive power to stairstepping shower nozzle 308, and injection drop is only 8-
10 picoliters, the triaxial movement platform 1 for being then provided with grating scale by PMAC motion control card controls is moved, and low-intensity ultrasonic can
To destroy the cell of extruding aggregation, disperse it, complete injection individual cells, after the completion of ground floor, start next layer of printing, watch
The linear motion that the convert rotational motion of motor 3 110 drives Z axis platform into high-accuracy leading screw 1 is taken, declines a thickness, opened
The printing of next layer of beginning；
When printing blood vessel is needed, Labview host computer procedures close electromagnetic switch valve according to the control of two-dimentional plane data
2 331, current stairstepping shower nozzle 308 is moved upwards under the control of hydraulic cylinder 319, is then watched by PMAC motion control card controls
Take many nozzle components 3 of the rotational movement of motor 4 205 to move, stop when reaching shower nozzle 105 surface of entrance to blood vessel shower nozzle 304
Only move, then hydraulic cylinder 319 promotes connecting plate 2 316 to drive and is separately mounted to shower nozzle retainer plate 320 and storage compartment's retainer plate
Stairstepping blood vessel shower nozzle 30402 and stairstepping storage compartment 2 30411 on 322 are moved downward, and open electromagnetic switch valve 3 30403
With the pneumatic means in stairstepping storage compartment 2 30411, pneumatic means is to the applying of stairstepping storage compartment 2 30411 continuous
0.3mpa, hydrogel flows to stairstepping blood vessel shower nozzle 30402 by shockproof flexible pipe 2 30412, due to stairstepping blood vessel shower nozzle
30402 closing, stairstepping storage compartment 2 30411 continue to pressure downstairs shape blood vessel shower nozzle 30402 eject it is hollow
Class blood vessel structure, be that later stage organ culture supplies nutrients passage；
Correlation step is repeated, untill all two-dimentional aspect printings are completed, biologic-organ is obtained.
Claims (8)
1. a kind of anti-blocking multicellular organism increasing material manufacturing method of high-precision ultrasound, it is characterised in that comprise the following steps：
1) before starting printing, printing equipment is put into disinfection cabinet or sterilization tank 15min, is finally putting into sterility test room or nothing
Bacterium chamber etc. is to be printed；
2) biological solution containing various cells is injected into the storage compartment one being connected with shower nozzle one, intensity is applied to shower nozzle
20mw/cm2, the ultrasonic wave of frequency 200KHz, the unlatching Piexoelectric actuator of shower nozzle one and the pneumatic means of storage compartment one, Piezoelectric Driving
Device is with ultrasonic waveform into combination flooding power, and drop ejection efficiency is higher；
3) high-strength composite hydrogel is injected into in the nozzle specially used storage compartment two being connected of printing blood vessel, opens the gas of storage compartment two
Dynamic device, waits to be printed；
4) printed polyethylene (PE) the organ base with 80% porosity, the base root are placed on substrate
Customized according to organ bottom size, it is easy to absorption of the organ bottom cell to nutrient in print procedure；
5) obtain the threedimensional model of biologic-organ to be printed, then the threedimensional model is divided into some two-dimentional aspects, then cut into slices point
Layer is STL formatted files, then the two-dimentional plane data is imported into Labview pc control procedures, control program
The pneumatic dress of the drive device of each shower nozzle one and shower nozzle two, storage compartment one and storage compartment two is controlled according to two-dimentional plane data
Put；
6) Labview host computer procedures control shower nozzle to move to current position to be printed according to two-dimentional plane data, start printing
Ground floor, is provided with the triaxial movement platform movement of grating scale, and pneumatic means applies instantaneous pressure to storage compartment, and pressure value is
0.6mpa, pressure time is 980ms, and the biological solution in storage compartment one flows to shower nozzle one, and Piexoelectric actuator is applied to shower nozzle one
Plus-pressure, low-intensity ultrasonic disperses the cell that extruding is assembled, and prevents each spray nozzle clogging of shower nozzle one, completes injection single thin
Born of the same parents, change permeability of cell membrane, and cell is vibrant, and survival rate is high；
7) repeat step 6), when printing blood vessel is needed, Labview host computer procedures are according to two-dimentional plane data control printing blood
Pipe is nozzle specially used to move to current print position, and pneumatic means applies continuous 0.3mpa, hydrogel flow direction to storage compartment two
Printing blood vessel is nozzle specially used, empty class blood vessel structure in jet printing, is that later stage organ culture supplies nutrients passage；
8) repeat step 6), 7) untill all two-dimentional aspect printings are completed, obtain biologic-organ.
2. a kind of anti-blocking multicellular organism increasing material manufacturing method of high-precision ultrasound according to claim 1, its feature exists
In the driving voltage of shower nozzle is 60-130V, and shower nozzle injection spray rate is 100Hz-90KHz after Piezoelectric Driving and ULTRASONIC COMPLEX.
3. the anti-blocking multicellular organism increasing material manufacturing device of a kind of high-precision ultrasound, it is characterised in that：Triaxial movement platform is arranged on
The underface of transverse movement axle, many nozzle components are arranged on transverse movement axle.
4. the anti-blocking multicellular organism increasing material manufacturing device of a kind of high-precision ultrasound according to claim 3, it is characterised in that
The structure of the triaxial movement platform is：Z axis leading screw block is arranged on triaxial movement platform by guide pillar one and high-accuracy leading screw one
On pedestal, high-accuracy leading screw one is connected by triaxial movement platform pedestal with servomotor three, triaxial movement platform pedestal top board
On be provided with shower nozzle entrance, Z axis platform is arranged on Z axis leading screw block by Z axis stage+module seat, and organ culture vessel pass through substrate
On substrate installing plate, substrate installing plate is arranged on servomotor one by guide pillar two and high-accuracy leading screw two, servo
Motor one is arranged on the installing plate of servomotor one by the mounting seat of servomotor one, and the installing plate of servomotor one passes through, servo
The mounting seat of motor one is arranged on guide rail slide block one, and guide rail slide block one is arranged on Z axis platform by line slideway one, and guide rail is slided
Block one is connected by connecting plate one with feed screw nut, and feed screw nut is connected by high-accuracy leading screw three with servomotor two, servo
Motor two is arranged on Z axis platform by the installing plate of servomotor two, and the installing plate of servomotor two is installed by servomotor two
Seat is fastened on Z axis platform.
5. a kind of anti-blocking multicellular organism increasing material manufacturing device of high-precision ultrasound according to claim 3, its feature exists
In the structure of the transverse movement axle is：Support is arranged on base, and line slideway two is fixed by screws on support, high
The two ends of precision lead screw four are connected on servomotor four and the installing plate of high-accuracy leading screw four, and servomotor passes through servo in 4 years
The installing plate of motor four is rack-mount, and the installing plate of servomotor four is rack-mount by the mounting seat of servomotor four, spray
Nozzle component mounting hole is provided with head assembly mounting seat, nozzle component mounting seat is arranged on line slideway two by guide rail slide block two
On.
6. the anti-blocking multicellular organism increasing material manufacturing device of a kind of high-precision ultrasound according to claim 3, it is characterised in that
The structure of many nozzle components is：Line slideway three is arranged on nozzle component installing plate by the screw hole of line slideway three,
Cylinder mount plate is arranged on nozzle component base plate, and blood vessel shower nozzle is arranged on shower nozzle retainer plate, micron order syringe needle and syringe
Connection, ultrasonic transducer is arranged on syringe, and syringe is connected with stairstepping shower nozzle, and piezoelectric ceramics rod is arranged on stairstepping shower nozzle
On, by aseptic compression screen pack Pipe installing in stairstepping storage compartment, feed tube is arranged on ladder to compressed air inlet pipe
The side of shape storage compartment, stairstepping storage compartment is connected by shockproof flexible pipe with stairstepping shower nozzle, and stairstepping shower nozzle is arranged on shower nozzle
On retainer plate, stairstepping storage compartment is arranged on storage compartment's retainer plate, and storage compartment's retainer plate connects spiral shell by storage compartment's retainer plate
Nail is fixed on guide rail slide block three, and shower nozzle retainer plate is fixed on connecting plate two by shower nozzle retainer plate attachment screw, hydraulic cylinder
It is connected on connecting plate two by hydraulic cylinder push rod, the two ends of connecting plate two connect guide rail slide block three respectively, ultrasonic transducer leads to
Cross power line to be connected with ultrasonic power, circular diaphragm is placed on the inside of stairstepping shower nozzle, aseptic compression screen pack is placed on
In aseptic compression screen pack pipeline, electromagnetic switch valve one is placed on feed tube, and electromagnetic switch valve two is placed on shockproof flexible pipe,
Feed room is connected by feeder sleeve with feed tube.
7. the anti-blocking multicellular organism increasing material manufacturing device of a kind of high-precision ultrasound according to claim 6, it is characterised in that
The structure of the blood vessel shower nozzle is：Middle mandrel is arranged in stairstepping blood vessel shower nozzle inner top, is formed together with cylindrical shower nozzle
Axle center blood vessel print components, electromagnetic switch valve three is arranged on shockproof flexible pipe two, and electromagnetic switch valve four is arranged on feed tube two,
Compressed air inlet pipe two is connected to rank by the aseptic compression screen pack two inside aseptic compression screen pack pipeline two
In trapezoidal storage compartment two, feed room two is connected by feeder sleeve two with feed tube two.
8. a kind of anti-blocking multicellular organism increasing material manufacturing device of high-precision ultrasound according to claim 6, its feature exists
In the internal diameter of the micron order syringe needle is 9 μm -120 μm.
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