CN110373324A - Collect the device of biopsy 3D printing and histocyte culture function integration - Google Patents
Collect the device of biopsy 3D printing and histocyte culture function integration Download PDFInfo
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- CN110373324A CN110373324A CN201910692330.4A CN201910692330A CN110373324A CN 110373324 A CN110373324 A CN 110373324A CN 201910692330 A CN201910692330 A CN 201910692330A CN 110373324 A CN110373324 A CN 110373324A
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/30—Auxiliary operations or equipment
- B29C64/379—Handling of additively manufactured objects, e.g. using robots
-
- 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
-
- 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
- B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/48—Holding appliances; Racks; Supports
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C—CHEMISTRY; METALLURGY
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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Abstract
A kind of device collecting biopsy 3D printing and histocyte culture function integration, bionical organizational project incubator is equipped with inlet and liquid outlet, the intracavitary hoistable platform for being equipped with carrying printing tissue of the incubator, 3D printing equipment is located on incubator, each mechanical arm free end of printing device is respectively equipped with printing head, inner screw sheath is fixed in hoistable platform lower end, inner screw sheath is slidably matched with the sealing element in the axis hole of incubator bottom, driving motor is located at below incubator, driving motor shaft is cooperated by screw rod and inner screw sheath, directive slide track is equipped in incubator, hoistable platform is slidably matched with directive slide track, the 3D printing equipment, driving motor, warmer is controlled by computer software control system, driving motor computer software control system control driving hoistable platform in 3D printing during gradually under Drop makes the tissue green body decline of printing immerse the culture solution in incubator, and printing plane is allowed to be maintained at culture solution ullage.
Description
Technical field
The present invention relates to bioengineered tissue preparation facilities field, in particular to a kind of collection biopsy 3D printing and group
Knit the device of cell culture function integration.
Background technique
Biological 3D printing is a kind of engineering tissue construction method with applications well prospect, with next life in recent years
Continuous improvement of the fast development and people of object 3D printing technique to accurate medical demands, biological 3D printing is with its exclusive
Property feature, gets more and more extensive concerning of people.3D printing technique is included in the emphasis of technology development by China at present.
Since biological 3D printing technique has the characteristics that containing cell printing, can only only it use cytocompatibility degree higher solid
Chemical industry skill, what is mainly used at present is ultraviolet light curing molding technology.Since the penetrability of ultraviolet light is poor, the printing of photocuring
Journey need carry out periodical thin layer printing, curing molding；Photopolymerization reaction has longer time hysteresis quality simultaneously, results in
The time of printing large volume complex organization is often up to even a couple of days a few hours.Therefore, in prolonged print procedure, cell
It in starvation, results in cell and a series of pathological changes such as autophagy, apoptosis occurs, cause biology in the tissue of printing living
Property is poor, it is difficult to survive.To solve the above problems, at present frequently with method be low temperature printing, that is, reduce printing cabin temperature
Degree slows down the metabolism of cell, can reduce the death rate of cell to a certain extent to 4-10 DEG C.But low temperature often results in
Cell mitochondrial damage causes the activity of cell to be still difficult to maintain higher level, cannot achieve the biological 3D printing of high activity,
Seriously limit the clinical application of biological 3D printing.
Summary of the invention
An object of the present invention be in view of the deficienciess of the prior art, provide a kind of collection biopsy 3D printing and
The device of histocyte culture function integration, it is set by the way that biological 3D printer is arranged on bionical organizational project incubator
It is standby, the hoistable platform of setting carrying printing tissue in bionical organizational project incubator, make during 3D printing gradually at
Type organizer can decline with hoistable platform, be immersed in culture solution obtain nutrition supply in time, realize environment in print procedure
Temperature is maintained at 37 DEG C of high activities to guarantee printing cell, guarantees the long-term surviving and biological function of 3D printing biological tissue.
It is another object of the present invention in view of the deficienciess of the prior art, providing a kind of using described in claim 1
The organizational project culture systems of integrated apparatus, it can regulate and control the nutrition supply of Cyclic culture liquid, be formed in stable bionical mould
Biopsy 3D printing is carried out in near-ring border.
The external bionical culture of biological tissue refers to that the tissue engineering tissue by application tissue engineering technique building is placed in mould
It is cultivated under the condition of in vitro culture of quasi- body physiological environment, to promote tissue engineering tissue structure and function mature, is led to
It is often that bionical culture is realized by bionical organizational project incubator.
An object of the present invention is achieved in that a kind of collection biopsy 3D printing and histocyte culture function
Integrated device, including bionical organizational project incubator, 3D printing equipment, driving motor, the bionical organizational project culture
Device is equipped with the inlet and liquid outlet of culture solution, the intracavitary liter for being equipped with carrying printing tissue of the bionical organizational project incubator
Platform drops, and 3D printing equipment is mounted on organizational project incubator upper end, and multiple mechanical arms of the 3D printing equipment protrude into group
Weaver's journey incubator is intracavitary, and the free end of each mechanical arm is respectively equipped with printing head, and the lifting of the carrying printing tissue is flat
Platform lower end is fixedly connected with an inner screw sheath, and the inner screw sheath extends downwardly the axis hole of organizational project incubator bottom setting, and
It is slidably matched with the sealing element formation being arranged in axis hole, the driving motor is located at below organizational project incubator, driving motor
Shaft be threadedly engaged by screw rod and inner screw sheath, directive slide track is equipped on the inside of the cavity wall of the organizational project incubator, is held
The hoistable platform for carrying printing tissue passes through the guide groove being equipped with and directive slide track is slidably matched and forms circumferential limit.The 3D is beaten
Printing apparatus, driving motor are controlled by computer software control system, and the computer software control system is beaten for controlling 3D
Printing apparatus printing has the tissue green body of living biological cell, for controlling the hoistable platform of driving motor driving carrying printing tissue
Gradually decline during 3D printing, makes to print plane and remain at the ullage of culture solution, and the tissue green body printed
It is cultivated in the culture solution immersed in bionical organizational project incubator with hoistable platform decline.3D printing equipment is soft in computer
Under the control of part control system, the carrying by the printing head of multiple mechanical arm free ends, in bionical organizational project incubator
Print and carry out tissue printing on the hoistable platform of tissue, driving motor under the control of computer software control system, with print into
Degree driving hoistable platform gradually declines, and the tissue of printing shaping is made gradually to immerse the culture solution in bionical organizational project incubator
In, and printing plane is allowed to be kept above about 500 μm of culture solution liquid level, the tissue of printing shaping can be made to be immersed in culture solution in time
In obtain nutrition supply, improve the high activity of cell, guarantee the long-term surviving and biological function of 3D printing biological tissue.
On multiple respectively arranged printing heads of mechanical arm, some is equipped with ultraviolet source, and some is equipped with heating device, has
Be equipped with ultraviolet source and heating device, be respectively used to the solidification of the bio-ink plasticity of printing or etching removal printing casting mold
Agent.
The intracavitary of the bionical organizational project incubator is equipped with chlorination equipment.Make 3D printing can in gnotobasis into
Row.
The sealing element uses oil sealing or mechanical seal.Not only it can prevent culture solution from leaking out, but also can guarantee that inner screw sheath turns
Dynamic and lifting.
The hoistable platform of the carrying printing tissue is equipped with several through-holes up and down, for passing through for culture solution.
Printing tissue carrier is mounted on the hoistable platform of the carrying printing tissue.In printing tissue carrier
On carry out tissue printing, can be woven on hoistable platform and slide to avoid printing group, cause printing error, guarantee that tissue is printed as
Function.
The inlet upstream of the bionical organizational project incubator is equipped with a warmer, and warmer is by computer software control
System control.Make to enter culture solution in bionical organizational project incubator and be maintained at 37 DEG C, realizes printing tissue in time at 37 DEG C
Environment temperature is cultivated, and the high activity of cell is improved.
The driving motor is stepper motor.Be conducive to control the decline precision in hoistable platform, guarantee that printing plane exists
Higher than about 500 μm of culture solution liquid level, and can gradually decline with printing progress.
It is another object of the present invention to what is be achieved:
A kind of organizational project culture systems using integrated apparatus described in claim 1, it is characterised in that: including claim
Collection biopsy 3D printing described in 1 and histocyte culture function integration device, the collection biopsy 3D printing
It is exchanged by circulating perfusion device with culture solution gas/liquid and liquid liquid with the inlet of histocyte culture function integration device
The Cyclic culture liquid outlet connection of device, the collection biopsy 3D printing and histocyte culture function integration device go out
Liquid mouth is connect by biochemical composition detection unit with the Cyclic culture liquid entrance of culture solution gas/liquid and liquid liquid exchanger, the training
The fresh medium import of nutrient solution gas/liquid and liquid liquid exchanger is connect with the downstream of an expansion pump, the upstream end of the expansion pump
It is connect with a fresh medium storage bottle, the culture solution gas/liquid connects storage through solenoid valve with the gas feed of liquid liquid exchanger
The gas vent of gas cylinder, culture solution gas/liquid and liquid liquid exchanger communicates with the outside world, the downstream of the circulating perfusion device with
Warmer, the collection life are set between collection biopsy 3D printing and the inlet of histocyte culture function integration device
The 3D printing equipment of the 3D printing of object living tissue and histocyte culture function integration device, driving motor, biochemical composition detection
Unit, circulating perfusion device, expansion pump, solenoid valve, warmer are controlled by computer software control system, and the 3D printing is set
Standby that tissue printing is carried out under the control of computer software control system, the driving motor is controlled in computer software control system
The hoistable platform of lower driving carrying printing tissue gradually declines with print progress, and the circulating perfusion device is in computer software control
The speed of the lower control perfusion of system control processed, the biochemical composition detection unit are used to monitor in real time pH, the oxygen of Cyclic culture liquid
Partial pressure, sugared ingredient, and Real-time Feedback is to computer software control system, computer software control network analysis acquisition it is biochemical at
Divide output signal after the information of detection unit to control expansion pump, electromagnetic valve work, regulates and controls the nutrition supply of Cyclic culture liquid, it is described
Warmer control loop culture-liquid temp under the control of computer software control system, is consequently formed human simulation environment and is given birth to
The 3D printing of object living tissue and histocyte culture.The system can make to collect biopsy 3D printing and histocyte culture function
During 3D printing, the Cyclic culture liquid provided by perfusion provides printing tissue cultivate nutrition in time integrated apparatus,
And printing, the pH of culture environment, partial pressure of oxygen, sugared ingredient are monitored by biochemical composition detection unit, by collecting
Information regulate and control the nutrition supply of Cyclic culture liquid in time, realize feedback-intelligence adjusting-culture solution update.And the circulation fills
It flows and is set between the downstream of device and collection biopsy 3D printing and the inlet of histocyte culture function integration device
Warmer is set, the Cyclic culture liquid entered in integrated apparatus can be made to be able to maintain that 37 DEG C of temperature.It thus is biology group living
It knits 3D printing and stable human simulation environment is provided, improve the high activity of biopsy and histocyte culture, guarantee that 3D is beaten
Print the long-term surviving and biological function of biological tissue.
And biochemical composition detection unit is placed in collection biopsy 3D printing and histocyte culture function integration device
Liquid outlet downstream, the indexs such as pH, partial pressure of oxygen, sugared ingredient in the Cyclic culture liquid that flows out can be monitored after cultivating in real time, be Xiang Pei
Nutrient solution gas/liquid and liquid liquid exchanger supply fresh medium and O2 、CO2 、N2Amount provide foundation, thereby guarantee that through culture solution
The circulation that gas/liquid and liquid liquid exchanger are conveyed to collection biopsy 3D printing and histocyte culture function integration device
The nutritional sufficiency of culture solution.
The circulating perfusion device uses expansion pump driven by stepper motors, and expansion pump uses stretching with fold cavity wall
Contracting variable displacement pump capsule, the contraction and diastole of Telescopic variable volume formula pump capsule can make Cyclic culture liquid generate pulsed liquid stream.
The invention has the benefit that by integrating biological 3D printing equipment and bionical organizational project incubator,
It is controlled by computer software control system, the hoistable platform of the carrying printing tissue in bionical organizational project incubator is enterprising
Row 3D printing living cells biological tissue can make printing by carrying out the circulation perfusion of Cyclic culture liquid in print procedure
Cell obtains good nutrition supply and mass exchange in printing link in time, realizes the bionic optimization of printing environment, maximum
The biological activity of the guarantee printing tissue of limit.The Cyclic culture liquid for providing 37 DEG C by warmer simultaneously, solves tradition
Low temperature printing technology cause cell activity decline the problem of, make print cell activity be greatly improved, to realize
The long-term surviving of cell in print procedure.
Have the characteristics that certain hysteresis quality for the curing molding of 3D printing bio-ink, is beaten with hoistable platform carrying
Tissue is printed, the height at printing interface is controlled by computer software control system, guarantees that printing interface is in always and is higher than circulation
The height of culture solution liquid level 500um, that is, ensure that histiocytic nutrition supply, and not influence the molding of bio-ink, realize
The unification of the stability and high activity of print structure.
Present invention will be further explained below with reference to the attached drawings and examples.
Detailed description of the invention
Fig. 1 is the schematic diagram of the bionical organizational project incubator with biological 3D printing function of the invention；
Fig. 2 is the schematic diagram of the bionical organizational project culture systems with biological 3D printing function of the invention.
Specific embodiment
Referring to Fig. 1, a kind of device collecting biopsy 3D printing and histocyte culture function integration, including it is bionical
Organizational project incubator 1,3D printing equipment, driving motor 3-3.The driving motor 3-3 is stepper motor.The bionical tissue
Engineering incubator 1 is the container equipped with inner cavity, which is equipped with the inlet 1-2 and liquid out of culture solution
Mouth 1-1, wherein the position of liquid outlet 1-1 is higher than inlet 1-2, and Cyclic culture liquid can be made to keep the liquid level of setting.Institute
The intracavitary hoistable platform 2 for being equipped with carrying printing tissue of bionical organizational project incubator 1 is stated, 3D printing equipment is fixed on group
On the cover board of 1 upper end of weaver's journey incubator.Multiple mechanical arms 8 of the 3D printing equipment protrude into 1 chamber of organizational project incubator
Interior, the free end of each mechanical arm 8 is respectively equipped with printing head 7, and printing head 7 includes the spray head for printing bio-ink,
For the spray head of print carriage material, for printing the spray head of cast agent.These printing heads are equipped with ultraviolet source, and some is equipped with
Heating device, some are equipped with ultraviolet source and heating device, these ultraviolet sources, heating device can be respectively used to the life to printing
The solidification of object ink plasticity or etching removal printing cast agent.2 lower end of hoistable platform of the carrying printing tissue is fixedly connected with one
Inner screw sheath 3-2, inner screw sheath 3-2 and hoistable platform 2 are integrally machined molding or are weldingly fixed on 2 lower end of hoistable platform,
Screw can be used to be fixedly connected with hoistable platform 2, the inner screw sheath 3-2 extends downwardly the setting of 1 bottom of organizational project incubator
Axis hole, and be arranged in axis hole sealing element 4 formation be slidably matched.The sealing element 4 uses oil sealing or mechanical seal, this reality
It applies example to be sealed using oil sealing, can prevent the Cyclic culture liquid contained in organizational project incubator 1 from leaking and making interior spiral shell
Line set 3-2 is moved up and down relative to oil sealing.The driving motor 3-3 is located at 1 lower section of organizational project incubator, driving motor 3-3
Shaft be threadedly engaged by screw rod 3-1 and inner screw sheath 3-2, the shaft of the screw rod 3-1 and driving motor 3-3 is circumferentially fixed
The extended segment stretched out outside driving motor 3-3 shaft can also be processed into screw rod by connection.The chamber of the organizational project incubator 1
Directive slide track 6 is equipped on the inside of wall, the hoistable platform 2 of carrying printing tissue passes through the guide groove being equipped with and matches with the sliding of directive slide track 6
Circumferential limit is closed and formed, bolt and nut mechanism is consequently formed, under the driving of driving motor 3-3, screw rod 3-1 rotation makes interior spiral shell
Line set 3-2 is linearly moved, and the hoistable platform 2 of carrying printing tissue is driven to rise or fall.The liter of the carrying printing tissue
It drops platform 2 and is equipped with several through-holes up and down, for passing through for culture solution.Liter of the present embodiment in the carrying printing tissue
It is mounted with printing tissue carrier 13 on drop platform 2, prints tissue carrier 13 by screw or pin shaft and is fixed on lifting
2 upper end of platform can be displaced under culture solution buoyancy to avoid printing tissue carrier 13, cause printing error.3D
It is printed upon and starts to carry out in the groove of tissue carrier 13, the groove being equipped with using printing tissue carrier 13 limits printing tissue
Position prevents printing tissue biases.The present embodiment is equipped with a warmer in the upstream inlet 1-2 of bionical organizational project incubator 1
20, which can be used the electricity heating device of infusion, and the feed liquor delivery pipe of Cyclic culture liquid is allowed to pass through from warmer 20,
The temperature of Cyclic culture liquid can be maintained 37 DEG C, eliminate the disadvantage that Conventional cryogenic printing technology causes cell activity to decline
End.The 3D printing equipment, driving motor 3-3, warmer 20 connect (not shown) with computer by data line, by calculating
The control of machine software control system.The computer software control system has living biological cell for controlling the printing of 3D printing equipment
Tissue green body；It is also used for controlling the hoistable platform 2 of driving motor 3-3 driving carrying printing tissue during 3D printing gradually
Decline makes to print the ullage that plane remains at culture solution, and the tissue green body printed declines in time with hoistable platform 2
It is cultivated in the culture solution immersed in bionical organizational project incubator 1；And for controlling 20 temperature of warmer, make from heating
The temperature for the Cyclic culture liquid that device 20 passes through can maintain 37 DEG C.The intracavitary of bionical organizational project incubator 1 can also set
Set chlorination equipment 5.Ultraviolet disinfection device can be used in the chlorination equipment 5, bionical organizational project can be made to train by chlorination equipment 5
It supports 1 inner cavity of device and forms gnotobasis, print procedure is avoided to cause germ contamination.
The present apparatus is when carrying out biopsy 3D printing, by computer software control system according to the biology group living of foundation
3D model is knitted, control 3D printing equipment is enterprising in the hoistable platform 2 of the intracavitary carrying printing tissue of bionical organizational project incubator 1
Row 3D printing controls perfusion into bionical 1 chamber of organizational project incubator by computer software control system before 3D printing printing
Interior Cyclic culture liquid measure, after 3D printing starts, as printing tissue 12 gradually increases, driving motor 3-3 is in computer software
Control system controls lower driving hoistable platform 2 and is gradually reduced, allow the printing tissue 12 of printing shaping with the decline of hoistable platform 2 by
It gradually immerses in culture solution and is cultivated in time, and make to print printing plane of the tissue 12 in print procedure and remain to be higher than
It 500 μm of culture solution liquid level, avoids printing plane in print procedure from being flooded in culture solution, guarantees that print procedure is normally carried out, directly
To printing tissue 12, finally printing is completed, and printing tissue 12 after the completion, which is just totally immersed into culture solution, to be cultivated.
Referring to Fig. 1, Fig. 2, a kind of organizational project culture systems using integrated apparatus described in claim 1, including power
Benefit require 1 described in the 3D printing of collection biopsy and histocyte culture function integration device, the collection biopsy
The inlet of the organizational project incubator 1 of 3D printing and histocyte culture function integration device passes through circulating perfusion device 11
It exports and connects with the Cyclic culture liquid of culture solution gas/liquid and liquid liquid exchanger 9, the upstream end of the circulating perfusion device 11 is logical
Cross the Cyclic culture liquid outlet that perfusion tube 22 connects culture solution gas/liquid and liquid liquid exchanger 9, the downstream of circulating perfusion device 11
End connects the inlet of organizational project incubator 1 by perfusion tube 14.The circulating perfusion device 11 is used and is driven by stepper motor
Dynamic expansion pump, the expansion pump use the Telescopic variable volume formula with fold cavity wall to pump capsule, and Telescopic variable volume formula pumps the contraction of capsule and relaxes
Opening can make Cyclic culture liquid generate pulsed liquid stream；Certainly, the circulating perfusion device 11 can also be used peristaltic pump and realize filling
Stream is only shunk using peristaltic pump simulated blood vessel and the effect of diastole is not as good as expansion pump.The collection biopsy 3D printing and
The liquid outlet of the organizational project incubator 1 of histocyte culture function integration device passes through biochemical composition detection unit 10 and training
Nutrient solution gas/liquid is connected with the Cyclic culture liquid entrance of liquid liquid exchanger 9.The upstream end of the biochemical composition detection unit 10 is logical
The liquid outlet that perfusion tube 23 connects organizational project incubator 1 is crossed, the downstream of the biochemical composition detection unit 10 passes through infusion
The Cyclic culture liquid entrance of pipe 24 connection culture solution gas/liquid and liquid liquid exchanger 9.The culture solution gas/liquid and liquid liquid exchange
The fresh medium import of device 9 is connect by perfusion tube 21 with the downstream of an expansion pump 15, and the upstream end of the expansion pump 15 is logical
Perfusion tube 26 is crossed to connect with the outlet of a fresh medium storage bottle 16, the culture solution gas/liquid and liquid liquid exchanger 9 it is new
Fresh culture solution outlet is connect by perfusion tube 25 with the import of fresh medium storage bottle 16, the culture solution gas/liquid and liquid liquid
The gas feed of exchanger 9 connects storage cylinder 17, culture solution gas/liquid and liquid liquid exchanger 9 through solenoid valve 18 by air supply pipe 19
Gas vent communicate with the outside world.The downstream of the circulating perfusion device 11 and collection biopsy 3D printing and histocyte
It cultivates and warmer 20 is set between the inlet of the organizational project incubator 1 of function integration device, make circulating perfusion device 11
The perfusion tube 14 of inlet of downstream connection organizational project incubator 1 pass through from warmer 20, can will be out of perfusion tube
The Cyclic culture liquid of process is warmed to 37 DEG C and enters back into organizational project incubator 1, creates one for histocyte culture and is suitble to
Environment temperature guarantee the long-term surviving and biological function of 3D printing biological tissue to improve cell high activity.The collection biology
The 3D printing equipment of living tissue 3D printing and histocyte culture function integration device, driving motor 3-3, biochemical composition detection
Unit 10, circulating perfusion device 11, expansion pump 15, solenoid valve 18, warmer 20 are controlled (not by computer software control system
Diagram).3D printing equipment is set to carry out tissue printing under the control of computer software control system；Driving motor 3-3 is in computer
The hoistable platform 2 of the lower driving carrying printing tissue of software control system control gradually declines with print progress, allows and has printed
Tissue green body, which timely enters, to be obtained obtaining nutrition in the Cyclic culture liquid in organizational project incubator 1, is cultivated；And it recycles and fills
The speed that device 11 controls perfusion under the control of computer software control system is flowed, keeps recycling training in organizational project incubator 1
The liquid level of nutrient solution；The biochemical composition detection unit 10 be used to monitor in real time the pH of Cyclic culture liquid, partial pressure of oxygen, sugar at
Point, and Real-time Feedback is examined to computer software control system by the biochemical composition that computer software control network analysis acquires
Output signal controls expansion pump 15, the work of solenoid valve 18 after surveying the information of unit, exchanges in time to culture solution gas/liquid and liquid liquid
Fresh medium and required O are supplemented in device 92 、CO2 、N2, regulate and control the nutrition supply of Cyclic culture liquid；The warmer 20 exists
Computer software control system controls lower control loop culture-liquid temp, protects the Cyclic culture liquid temperature passed through from warmer 20
It holds and is entered back into organizational project incubator 1 at 37 DEG C；Human simulation environment is consequently formed and carries out biopsy 3D printing and group
Knit the organizational project culture systems for integrating biopsy 3D printing and histocyte culture function of cell culture.This skill
Culture solution gas/liquid and liquid liquid exchanger 9 in art scheme use Authorization Notice No. for the organizational project group of 101486967 B of CN
The culture solution gas/liquid and liquid liquid exchanger for knitting bionic cultivation, can make Cyclic culture liquid be always maintained at sufficient nutrition, moreover it is possible to
The dosage of fresh medium is reduced, the cost of biopsy 3D printing and histocyte culture is reduced.
The apparatus and system of collection biopsy 3D printing and histocyte culture function integration of the invention is worked
Journey has the following steps by taking the institutional framework at 3D printing shin bone epiphysis end as an example:
1, biomedical information acquisition and modeling:
1) acquisition needs to print the biological information with cartilage-bone-to-bone marrow composite construction shin bone epiphysis end, by optimizing bone knot
Structure image collecting method learns three-dimensional cross-sectional reconstruction technique, the epiphysis of personalization acquisition people's tibial plateau with perfusion casting mold and group
The internal structure external structure at end and the three-dimensional data of blood circulation pipe network；
2) biological information of acquisition is inputted into computer software, actual tissue appearance and microenvironment is expressed as bionical more materials
Material, multiple dimensioned geometrical model, establish bionical cartilage-bone-to-bone marrow and its capilary three-dimensional mathematical model, the geometrical model of foundation
Including nutrition pore region, the vascular wall area, lumen of vessels among cartilaginous areas, dense bone region, cancellous bone region, cancellous bone
Region, the outer auxiliary plastic region of tissue.
2, biometric print material is configured
Various cells needed for preparing building cartilage-bone-to-bone marrow complex tissue are prepared and are applicable in building cartilage-bone-to-bone marrow complex group
The liquid curable hydrogel material carrier for knitting required various cells, will be each needed for building cartilage-bone-to-bone marrow complex tissue
Kind cell is inoculated in corresponding liquid curable hydrogel material carrier respectively by the density of setting, is prepared celliferous various
Bio-ink, meanwhile, it is formulated for the hard material in the printing dense bone region of cartilage-bone-to-bone marrow complex tissue, and prepare and use
In the first cast agent for assisting plastic region outside printing tissue, it is formulated for the of the nutrition pore region among printing cancellous bone
Two cast agents are formulated for the third cast agent of printing blood vessel cavity region.
3,3D printing bone tissue green body:
Prepare before printing: the equipment such as bionical organizational project incubator 1, biochemical monitoring unit 10, circulating perfusion device 11 are carried out
Oxirane disinfection loads in fresh medium storage bottle 16 and contains 10% fetal calf serum, the complete culture of 1% blueness/streptomysin
Base.Ultraviolet disinfection 1h is carried out to bionical 1 place environment of organizational project incubator.Computer is opened, the number established before being loaded into
Learn geometrical model；
The cast agent of preparation, hard material and celliferous bio-ink are respectively loaded on to each feed bin of biological 3D printing equipment
In, carrying of the 3D printing equipment in bionical organizational project incubator 1 is controlled by computer software control system and prints tissue
Hoistable platform 2 on, according to setting print routine carry out 3D printing, multiple spray heads of biological 3D printing equipment are according to setting
Print routine sprays in turn or squeezes out liquid and carries out 3D printing, and the liquid for spraying or squeezing out solidifies under the conditions of corresponding respectively,
Wherein, plastic region is assisted with outside the first cast agent printing tissue, with the nutrition hole among the second cast agent printing cancellous bone
Region, prints blood vessel cavity region with third cast agent, prints cartilage-bone-to-bone marrow complex group with the bio-ink containing cartilage cell
The cartilaginous areas knitted prints cartilage-bone-to-bone marrow complex tissue pine with the bio-ink containing osteoblast and mescenchymal stem cell
Matter bone region prints vascular wall area with the bio-ink containing vascular endothelial cell, multiple with hard material printing cartilage-bone-to-bone marrow
It is combined the dense bone region knitted, forms cartilage-bone-to-bone marrow complex tissue green body.
The printing head 7 of 8 free end of each mechanical arm of 3D printing equipment, according to the geometrical model of foundation in computer
Alternating prints each print area under the control of software control system.
In print procedure, driving motor 3-3 is flat with printing progress driving lifting under the control of computer software control system
Platform 2 gradually declines, and immerses the tissue of printing shaping gradually in the Cyclic culture liquid in bionical organizational project incubator 1, and allow
Printing plane is kept above about 500 μm of culture solution liquid level, is immersed in the tissue of printing shaping in culture solution in time and obtains nutrition
Supply improves the high activity of cell, guarantees the long-term surviving and biological function of 3D printing biological tissue, and enables printing head 7
It is enough to continue to be printed in printing plane, allow printing plane not generate interference with culture solution.Meanwhile warmer 20 is in computer
The Cyclic culture liquid flowed through is heated under software control system control, makes to enter following in bionical organizational project incubator 1
Ring culture solution maintains 37 DEG C, for improving the activity of printing cell.And keep celliferous bio-ink purple in 365nm wavelength
Solidify under outer light action, solidifies cast agent at a temperature of 37 DEG C or under thrombin action.
4, etching molding:
After organizing green body solidification, classification etching is carried out to the cast agent in each region, is distinguished in different phase using different means
Removal for aid in tissue plasticity the first cast agent, for molding second cast agent of nutrition hole and for lumen of vessels at
The third cast agent of type obtains cartilage-bone-to-bone marrow complex tissue of rete vasculosum and nutrition hole.For example, 2 after the completion of printing
Hour, the first cast agent that plastic region is assisted outside tissue is dispelled by the ultraviolet degradation of 254nm, then by cooling to 25
The second cast agent 22 for DEG C dispelling nutrition pore region, such as n-isopropyl acrylamide, to form nutrition hole；Using 2-4
The process its cell growth and merged, is added fibrinolysin in culture solution or the third casting mold of blood vessel cavity region is dispelled in ladder cooling
Agent forms rete vasculosum.
5, in vitro culture:
It allows the shin bone epiphysis end green body of printing shaping to be submerged in the culture solution in organizational project incubator 1, is followed using culture solution
Ring perfusion is cultivated, and is supervised by biochemical composition detection unit 10 to the pH of Cyclic culture liquid, partial pressure of oxygen, sugared ingredient
Control controls expansion pump 15,18 work of solenoid valve after the analysis of computer software control system by collected information as needed
Make, supplements fresh medium and O to culture solution gas/liquid and liquid liquid exchanger 9 in time2 、CO2 、N2, and control loop perfusion fills
11 regulation Cyclic culture flow velocities are set, sufficient nutrition supply is provided for tissue cultures, realizes feedback-intelligence adjusting-culture solution
It updates, guarantees the nutrition of Cyclic culture liquid, while Cyclic culture liquid being made to keep 37 DEG C of temperature, provide one more for tissue cultures
Add the environment of suitable cell survival, breeding, improve cell activity, continuously recycled perfusion culture 60 days, realizes shin bone epiphysis end
The pre- maturation of tissue.Thereby guarantee that the long-term surviving and biological function of 3D printing biological tissue.
Claims (10)
1. a kind of device for collecting biopsy 3D printing and histocyte culture function integration, it is characterised in that: including imitative
Raw organizational project incubator, 3D printing equipment, driving motor, the bionical organizational project incubator are equipped with the inlet of culture solution
And liquid outlet, the intracavitary hoistable platform for being equipped with carrying printing tissue of the bionical organizational project incubator, 3D printing equipment peace
Mounted in organizational project incubator upper end, it is intracavitary that multiple mechanical arms of the 3D printing equipment protrude into organizational project incubator, respectively
The free end of mechanical arm is respectively equipped with printing head, and the hoistable platform lower end of the carrying printing tissue is fixedly connected with spiral shell in one
Line set, the inner screw sheath extend downwardly the axis hole of organizational project incubator bottom setting, and with the sealing element that is arranged in axis hole
Formation is slidably matched, and the driving motor is located at below organizational project incubator, and the shaft of driving motor passes through screw rod and interior spiral shell
The cooperation of line external threading, the cavity wall inside of the organizational project incubator are equipped with directive slide track, the hoistable platform of carrying printing tissue
It is slidably matched by the guide groove and directive slide track that are equipped with and forms circumferential limit, the 3D printing equipment, driving motor, heating
Device is controlled by computer software control system, and the computer software control system has for controlling the printing of 3D printing equipment
The tissue green body of living biological cell, for controlling the hoistable platform of driving motor driving carrying printing tissue during 3D printing
Gradually decline, makes to print the ullage that plane remains at culture solution, and the tissue green body printed declines with hoistable platform
It is cultivated in the culture solution immersed in bionical organizational project incubator.
2. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: on multiple respectively arranged printing heads of mechanical arm, some is equipped with ultraviolet source, and some is equipped with heating device,
Some is equipped with ultraviolet source and heating device, is respectively used to the solidification of bio-ink plasticity or etching removal printing casting mold to printing
Agent.
3. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: the intracavitary of the bionical organizational project incubator is equipped with chlorination equipment.
4. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: the sealing element uses oil sealing or mechanical seal.
5. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: the hoistable platform of the carrying printing tissue is equipped with several through-holes up and down, for passing through for culture solution.
6. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
It is characterized in that: being mounted with printing tissue carrier on the hoistable platform of the carrying printing tissue.
7. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: the inlet upstream of the bionical organizational project incubator is equipped with a warmer, and warmer is by computer software control
System control processed.
8. the device of collection biopsy 3D printing and histocyte culture function integration according to claim 1,
Be characterized in that: the driving motor is stepper motor.
9. a kind of organizational project culture systems using integrated apparatus described in claim 1, it is characterised in that: wanted including right
Collection biopsy 3D printing described in asking 1 and histocyte culture function integration device, the collection biopsy 3D are beaten
The inlet of print and histocyte culture function integration device is handed over by circulating perfusion device and culture solution gas/liquid and liquid liquid
The Cyclic culture liquid outlet connection of parallel operation, the collection biopsy 3D printing and histocyte culture function integration device
Liquid outlet is connect by biochemical composition detection unit with the Cyclic culture liquid entrance of culture solution gas/liquid and liquid liquid exchanger, described
The fresh medium import of culture solution gas/liquid and liquid liquid exchanger is connect with the downstream of an expansion pump, the upstream of the expansion pump
End is connect with a fresh medium storage bottle, and the culture solution gas/liquid is connected with the gas feed of liquid liquid exchanger through solenoid valve
The gas vent of storage cylinder, culture solution gas/liquid and liquid liquid exchanger communicates with the outside world, the downstream of the circulating perfusion device
Warmer, the collection are set between collection biopsy 3D printing and the inlet of histocyte culture function integration device
The 3D printing equipment of biopsy 3D printing and histocyte culture function integration device, driving motor, biochemical composition inspection
It surveys unit, circulating perfusion device, expansion pump, solenoid valve, warmer to be controlled by computer software control system, the 3D printing
Equipment carries out tissue printing under the control of computer software control system, and the driving motor is in computer software control system control
The hoistable platform of the lower driving carrying printing tissue of system gradually declines with print progress, and the circulating perfusion device is in computer software
The speed of the lower control perfusion of control system control, the biochemical composition detection unit be used to monitor in real time Cyclic culture liquid pH,
Partial pressure of oxygen, sugared ingredient, and the biochemistry that Real-time Feedback is acquired to computer software control system, computer software control network analysis
Output signal controls expansion pump, electromagnetic valve work after the information of composition detection unit, regulates and controls the nutrition supply of Cyclic culture liquid, institute
Warmer control loop culture-liquid temp under the control of computer software control system is stated, the progress of human simulation environment is consequently formed
Biopsy 3D printing and histocyte culture.
10. organizational project culture systems according to claim 9, it is characterised in that: the circulating perfusion device use by
Stepper motor driven expansion pump, expansion pump use the Telescopic variable volume formula with fold cavity wall to pump capsule, and Telescopic variable volume formula pumps capsule
Contraction and diastole can make Cyclic culture liquid generate pulsed liquid stream.
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| CN201910692330.4A CN110373324A (en) | 2019-07-30 | 2019-07-30 | Collect the device of biopsy 3D printing and histocyte culture function integration |
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| CN201910692330.4A CN110373324A (en) | 2019-07-30 | 2019-07-30 | Collect the device of biopsy 3D printing and histocyte culture function integration |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113180879A (en) * | 2021-05-24 | 2021-07-30 | 上海大学 | Biological tissue preparation system and method |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN201395599Y (en) * | 2009-05-22 | 2010-02-03 | 广州迈普再生医学科技有限公司 | Bioreactor and biological printing system |
| CN101486968B (en) * | 2009-02-13 | 2011-11-09 | 中国人民解放军第三军医大学第一附属医院 | Intellectualized bionic cultivation apparatus for tissue engineering tissue |
| CN103589808A (en) * | 2013-11-11 | 2014-02-19 | 中国人民解放军第三军医大学第一附属医院 | Automatic control method and system for pH/oxygen partial pressure/partial pressure of carbon dioxide of cell and tissue culture solution |
| CN203548137U (en) * | 2013-11-12 | 2014-04-16 | 中国人民解放军第三军医大学第一附属医院 | Solution feed pump for bionic culture in tissue engineering |
| CN104726332A (en) * | 2015-03-05 | 2015-06-24 | 西安交通大学 | Brain-like tissue in-vitro printing and culture system and brain-like tissue in-vitro printing and culture method |
| CN104758085A (en) * | 2014-12-26 | 2015-07-08 | 南京师范大学 | Three dimensional biology printing device and method |
| CN105524831A (en) * | 2015-12-29 | 2016-04-27 | 西安交通大学 | An ultra-clean high-stability biological 3D printing-culturing integrated system and a method therefor |
| CN105754857A (en) * | 2016-04-20 | 2016-07-13 | 清华大学深圳研究生院 | Three-dimensional capillary network biochip manufacturing method |
| CN104490489B (en) * | 2014-12-02 | 2017-02-01 | 淮安皓运生物科技有限公司 | Method for preparing tissue engineering blood vessel based on 3D bioprinting technology |
| CN106754356A (en) * | 2016-11-30 | 2017-05-31 | 广州迈普再生医学科技有限公司 | Three-dimensional perfused culture system and the histoorgan of 3D printing |
| US20190177676A1 (en) * | 2017-12-12 | 2019-06-13 | Chun To Chow | Apparatus and method for three-dimensional (3d) printing / bio-printing |
-
2019
- 2019-07-30 CN CN201910692330.4A patent/CN110373324A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101486968B (en) * | 2009-02-13 | 2011-11-09 | 中国人民解放军第三军医大学第一附属医院 | Intellectualized bionic cultivation apparatus for tissue engineering tissue |
| CN201395599Y (en) * | 2009-05-22 | 2010-02-03 | 广州迈普再生医学科技有限公司 | Bioreactor and biological printing system |
| CN103589808A (en) * | 2013-11-11 | 2014-02-19 | 中国人民解放军第三军医大学第一附属医院 | Automatic control method and system for pH/oxygen partial pressure/partial pressure of carbon dioxide of cell and tissue culture solution |
| CN203548137U (en) * | 2013-11-12 | 2014-04-16 | 中国人民解放军第三军医大学第一附属医院 | Solution feed pump for bionic culture in tissue engineering |
| CN104490489B (en) * | 2014-12-02 | 2017-02-01 | 淮安皓运生物科技有限公司 | Method for preparing tissue engineering blood vessel based on 3D bioprinting technology |
| CN104758085A (en) * | 2014-12-26 | 2015-07-08 | 南京师范大学 | Three dimensional biology printing device and method |
| CN104726332A (en) * | 2015-03-05 | 2015-06-24 | 西安交通大学 | Brain-like tissue in-vitro printing and culture system and brain-like tissue in-vitro printing and culture method |
| CN105524831A (en) * | 2015-12-29 | 2016-04-27 | 西安交通大学 | An ultra-clean high-stability biological 3D printing-culturing integrated system and a method therefor |
| CN105754857A (en) * | 2016-04-20 | 2016-07-13 | 清华大学深圳研究生院 | Three-dimensional capillary network biochip manufacturing method |
| CN106754356A (en) * | 2016-11-30 | 2017-05-31 | 广州迈普再生医学科技有限公司 | Three-dimensional perfused culture system and the histoorgan of 3D printing |
| US20190177676A1 (en) * | 2017-12-12 | 2019-06-13 | Chun To Chow | Apparatus and method for three-dimensional (3d) printing / bio-printing |
Non-Patent Citations (1)
| Title |
|---|
| LESTER J. SMITH等: "FABRICA: A Bioreactor Platform for Printing, Perfusing, Observing, & Stimulating 3D Tissues", 《SCIENTIFIC REPORTS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113180879A (en) * | 2021-05-24 | 2021-07-30 | 上海大学 | Biological tissue preparation system and method |
| CN113180879B (en) * | 2021-05-24 | 2023-12-22 | 上海大学 | Biological tissue preparation system and method |
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