CN112501019B - Multifunctional bioreactor - Google Patents

Multifunctional bioreactor Download PDF

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Publication number
CN112501019B
CN112501019B CN202011394956.6A CN202011394956A CN112501019B CN 112501019 B CN112501019 B CN 112501019B CN 202011394956 A CN202011394956 A CN 202011394956A CN 112501019 B CN112501019 B CN 112501019B
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culture
arm
module
fixing seat
cylinder
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CN112501019A (en
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钟华强
张传杰
袁玉宇
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Medprin Regenerative Medical Technologies Co Ltd
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Medprin Regenerative Medical Technologies Co Ltd
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    • 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
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • 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
    • C12M23/02—Form or structure of the vessel
    • C12M23/08—Flask, bottle or test tube
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    • 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
    • C12M23/40—Manifolds; Distribution pieces
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    • 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
    • C12M23/44—Multiple separable units; Modules
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    • 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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    • 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
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
    • 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
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
    • 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
    • C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/02—Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
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    • 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
    • C12M41/14—Incubators; Climatic chambers
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
    • C12M41/20—Heat exchange systems, e.g. heat jackets or outer envelopes the heat transfer medium being a gas
    • 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
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas

Abstract

The invention provides a multifunctional bioreactor. The utility model provides a multifunctional bioreactor, wherein, includes the main casing body, locates be used for carrying out the circulation culture device of circulation culture to the culture on the inside bottom surface of main casing body, locate be used for snatching on the inside top surface of main casing body the tissue tongs of culture in the circulation culture device, locate on the inside top surface of main casing body and the ring is located first bionical arm module, second bionical arm module, electric stimulation module and growth factor complementary module all around of tissue tongs, and locate environmental regulation and control module on the inside lateral wall of main casing body. The invention can carry out diversified culture on large tissues or complete organs and perfect the functions of the final large tissues or organs.

Description

Multifunctional bioreactor
Technical Field
The invention relates to the technical field of tissue engineering, in particular to a multifunctional bioreactor.
Background
In 2019, 4 months, a scientific research team of israel prints out the first whole heart of the world, which comprises cells, blood vessels, heart cavities and ventricles, through a 3D printing technology by using human tissues taken from a patient, and the heart is equivalent to the heart of a rabbit in size, can not pump blood at present, can only shrink, and further needs to be cultured in a later stage of a culture device, so that further experiments are carried out, and the heart functions of the rabbit are perfected.
The existing cell culture devices and bioreactors are mostly prepared for two-dimensional culture of common cells or culture of tissues with specific small sizes, such as stem cells, muscle tissues, blood vessels and the like, and specific culture means, such as addition of certain growth factors, certain mechanical stimulation and the like, are needed; however, if a complete organ is cultivated, the cultivation means to be considered will be more diversified, the cultivation period will be longer, and some problems may occur in the cultivation process and need to be adjusted in time, so it is necessary to develop a bioreactor with diversified cultivation means, and the function of the bioreactor can be flexibly adjusted in the cultivation process without modifying the structure.
Disclosure of Invention
In order to overcome the problem that the conventional cell culture device and bioreactor are prepared for two-dimensional culture of common cells or tissue culture with specific small size and cannot be applied to complete organ culture, the invention provides a multifunctional bioreactor. The invention can carry out diversified culture on large tissues or complete organs and perfect the functions of the final large tissues or organs.
In order to solve the technical problems, the invention adopts the following technical scheme: the utility model provides a multifunctional bioreactor, wherein, includes the main casing body, locates be used for carrying out the circulation culture device of circulation culture to the culture on the inside bottom surface of main casing body, locate be used for snatching on the inside top surface of main casing body the tissue tongs of culture in the circulation culture device, locate on the inside top surface of main casing body and the ring is located first bionical arm module, second bionical arm module, electric stimulation module and growth factor complementary module all around of tissue tongs, and locate environmental regulation and control module on the inside lateral wall of main casing body. The first bionic arm module and the second bionic arm module can perform different mechanical stimulation on the culture grabbed by the tissue grabber, can temporarily fix the culture grabbed by the tissue grabber, and can be used for removing the proliferation tissue on the culture; the electrical stimulation module can electrically stimulate the culture; the growth factor replenishment module may be positioned to replenish some growth factor as needed during the cultivation process. The environment regulation and control module provides a proper culture environment for the culture by optimizing the air in the main shell and regulating the temperature in the main shell. According to the invention, the culture function is modularized through the arrangement of the circulating culture device, the first bionic arm module, the second bionic arm module, the electric stimulation module and the growth factor supplementing module, a plurality of culture functions are simultaneously integrated, and a certain module can be flexibly replaced, so that a new culture function can be realized, and thus, the bioreactor is not required to be changed or redeveloped, a new culture requirement can be realized by only adjusting a certain part of structure, more diversified culture experiments can be further carried out, and the final large tissue or organ function is perfected.
Further, the first bionic arm module and the second bionic arm module are symmetrically arranged on two opposite sides of the tissue gripper, and the electric stimulation module and the growth factor supplementing module are symmetrically arranged on two opposite sides of the tissue gripper.
Further, the tissue gripper comprises an electric push rod arranged on the outer side face of the top of the main shell, one end of the tissue gripper is connected with the electric push rod through a first connecting block, the other end of the tissue gripper penetrates into a sliding bar in the main shell through a reserved hole in the side wall of the top of the main shell, a rotary cylinder connected with the other end of the sliding bar through a second connecting block, and a gripper connected to the rotary cylinder through a third connecting block. The slide bar can slide from top to bottom along with electric putter's motion, and revolving cylinder can drive the tongs and carry out 360 rotations to satisfy the cultivation demand at the different positions of culture, and the tongs can carry out the centre gripping to the culture, then follow the slide bar and slide and grasp whole culture from circulation culture apparatus, then cooperate other functional module to carry out some operations.
Further, the first bionic arm module comprises a first fixing seat fixedly connected to the inner wall of the top of the main shell, a first arm, a second arm, a micro cylinder, a finger fixing seat and fingers, wherein one end of the first arm is connected with the first fixing seat through a first gear motor, the other end of the second arm is connected with the second arm through a second gear motor, the cylinder barrel end of the micro cylinder is connected with the other end of the second arm through a third gear motor, the micro cylinder is fixed on the end face of one end of the micro cylinder through the cylinder fixing seat, and the fingers are symmetrically arranged on two sides of the other end of the finger fixing seat; the piston rod of the micro cylinder is connected with one end of the finger through a pull rod and can drive the finger to clamp or loosen; the structure of the second bionic arm module is the same as that of the first bionic arm module. The first arm and the second arm imitate human arms, the first gear motor and the second gear motor can rotate to swing up and down, and the micro cylinder can swing along with the rotation of the third gear motor to imitate the swing of human wrists.
Further, the electric stimulation module comprises a second fixing seat fixedly connected to the inner wall of the top of the main shell, a third arm, a fourth arm, an electric needle fixing seat and an electric needle, wherein one end of the third arm is connected with the second fixing seat through a fourth gear motor, one end of the fourth arm is connected with the other end of the third arm through a fifth gear motor, the electric needle fixing seat is connected with the other end of the fourth arm through a sixth gear motor, and the electric needle is arranged on the electric needle fixing seat, and can electrically stimulate a culture.
Further, the growth factor supplementing module comprises a third fixing seat fixedly connected to the inner wall of the top of the main shell, a fifth arm, a sixth arm and a needle cylinder fixing seat, wherein one end of the fifth arm is connected with the third fixing seat through a seventh gear motor, one end of the sixth arm is connected with the other end of the fifth arm through an eighth gear motor, the needle cylinder fixing seat is connected with the other end of the sixth arm through a ninth gear motor, and the needle cylinder is arranged on the needle cylinder fixing seat; one end of the needle cylinder, which is close to the needle cylinder fixing seat, is provided with a cylinder cover, and one end of the needle cylinder, which is far away from the needle cylinder fixing seat, is provided with a dispensing needle head through which growth factors are extruded. The needle cylinder fixing seat is provided with a through hole for a pipeline, one end of which is connected with the cylinder cover, and the other end of which is connected with equipment for providing production factors from the outside, to pass through.
Further, the circulation culture device comprises a culture pond, a liquid storage bottle and a peristaltic pump, wherein the culture pond is fixed under the tissue gripper through a support frame, the liquid storage bottle is arranged on one side of the culture pond, the peristaltic pump is arranged under the support frame, and the culture pond, the liquid storage bottle and the peristaltic pump are sequentially connected end to end through hoses to form a circulation loop. In this way, the culture can be dynamically cultivated in a culture tank and the medium is renewed.
Furthermore, the bottom surface of the culture pond is a gradient surface gradually decreasing from the periphery to the middle, so that the culture can be ensured to be kept at the middle position of the culture pond, and the tissue gripper can conveniently grasp the culture.
Further, at least one side wall of the culture pond and the main shell is made of transparent materials, so that the culture inside the culture pond can be conveniently observed.
Further, the environment control module comprises a filtering air inlet arranged on one inner side wall of the main shell, a temperature controller arranged on the other inner side wall of the main shell and a PTC heater arranged on the inner bottom surface of the main shell. The air inlet with the filter can filter and purify the air entering the inside of the main shell, and an oxygen adapting environment is provided for the inside of the main shell. The temperature controller and the PTC heater can be matched to control the temperature inside the main shell, and a proper temperature environment is provided for the culture process.
Compared with the prior art, the invention has the following beneficial effects:
the invention realizes the collection of a plurality of culture functions by simultaneously arranging the circulating culture device, the first bionic arm module, the second bionic arm module, the electric stimulation module and the growth factor supplementing module in one bioreactor, and can provide dynamic culture, mechanical stimulation, electric stimulation and positioning supplementation of growth factors for cultures. In addition, the invention carries out modularization treatment on the culture function, is beneficial to flexibly replacing or adding the function of a certain module in the culture process so as to meet new culture requirements, and can further carry out diversified culture on large tissues or complete organs and perfect the functions of the final large tissues or organs.
Drawings
Fig. 1 is a schematic view of the overall structure of the present invention.
Fig. 2 is a schematic view of the structure of the tissue gripper of the present invention.
Fig. 3 is a schematic structural diagram of a first bionic arm module/a second bionic arm module according to the present invention.
Fig. 4 is a schematic structural view of an electro-stimulation module in the present invention.
FIG. 5 is a schematic diagram of the structure of a growth factor supplement module according to the present invention.
FIG. 6 is a schematic view showing the internal structure of the culture pond according to the present invention.
Detailed Description
The drawings are for illustrative purposes only and are not to be construed as limiting the present patent; for the purpose of better illustrating the embodiments, certain elements of the drawings may be omitted, enlarged or reduced and do not represent the actual product dimensions; it will be appreciated by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted. The positional relationship depicted in the drawings is for illustrative purposes only and is not to be construed as limiting the present patent.
As shown in fig. 1, a multifunctional bioreactor comprises a main casing 1, a circulating culture device arranged on the inner bottom surface of the main casing 1 and used for circulating culture of a culture, a tissue gripper 2 arranged on the inner top surface of the main casing 1 and used for gripping the culture in the circulating culture device, a first bionic arm module 3, a second bionic arm module 4, an electric stimulation module 5 and a growth factor supplementing module 6 arranged on the inner top surface of the main casing 1 and around the tissue gripper 2, and an environment regulating module arranged on the inner side wall of the main casing 1. The first bionic arm module 3 and the second bionic arm module 4 can perform different mechanical stimulation on the culture grabbed by the tissue grabber 2, can temporarily fix the culture grabbed by the tissue grabber 2, and can be used for removing the proliferation tissue on the culture; the electrical stimulation module 5 may electrically stimulate the culture; the growth factor replenishment module 6 may be positioned to replenish some growth factor as needed during the cultivation process. The environment control module provides a proper culture environment for the culture by optimizing the air in the main housing 1 and controlling the temperature in the main housing 1. According to the invention, the culture function is modularized through the arrangement of the circulating culture device, the first bionic arm module 3, the second bionic arm module 4, the electric stimulation module 5 and the growth factor supplementing module 6, a plurality of culture functions are simultaneously integrated, a certain module can be flexibly replaced, and a new culture function can be realized, so that the bioreactor is not required to be changed or redeveloped, and the new culture requirement can be realized by only adjusting a certain part of structure, so that more diversified culture experiments can be carried out, and the final large tissue or organ function is perfected.
As shown in fig. 1, the first bionic arm module 3 and the second bionic arm module 4 are symmetrically disposed on two opposite sides of the tissue gripper 2, and the electrical stimulation module 5 and the growth factor supplementing module 6 are symmetrically disposed on two opposite sides of the tissue gripper 2.
As shown in fig. 2, the tissue gripper 2 includes an electric push rod 201 disposed on the outer side surface of the top of the main housing 1, a sliding bar 203 having one end connected to the electric push rod 201 via a first connection block 202 and the other end penetrating into the main housing 1 via a preformed hole on the side wall of the top of the main housing 1, a rotary cylinder 205 connected to the other end of the sliding bar 203 via a second connection block 204, and a gripper 207 connected to the rotary cylinder 205 via a third connection block 206. The sliding bar 203 can slide up and down along with the movement of the electric push rod 201, the rotary air cylinder 205 can drive the gripper 207 to rotate 360 degrees so as to meet the culture requirements of different parts of a culture, the gripper 207 can clamp the culture, then the whole culture is grabbed from the circulating culture device along with the sliding bar 203, and then the whole culture is matched with other functional modules to perform some operations.
As shown in fig. 3, the first bionic arm module 3 includes a first fixing base 301 fixedly connected to the inner wall of the top of the main housing 1, a first arm 303, one end of which is connected to the first fixing base 301 through a first gear motor 302, a second arm 305, one end of which is connected to the other end of the first arm 303 through a second gear motor 304, a micro cylinder 307, the cylinder end of which is connected to the other end of the second arm 305 through a third gear motor 306, a finger fixing base 309, which fixes the micro cylinder 307 on the end surface of one end of the finger fixing base 309 through a cylinder fixing base 308, and fingers 3010 symmetrically arranged on two sides of the other end of the finger fixing base 309; the piston rod of the micro air cylinder 307 is connected with one end of the finger 3010 through a pull rod 3011 and can drive the finger 3010 to clamp or loosen; the structure of the second bionic arm module 4 is the same as that of the first bionic arm module 3. The first arm 303 and the second arm 305 are arms simulating a human, and can swing up and down by the rotation of the first gear motor 302 and the second gear motor 304, and the micro cylinder 307 can swing along with the rotation of the third gear motor 306, simulating the swing of the human wrist.
As shown in fig. 4, the electrical stimulation module 5 includes a second fixing base 501 fixedly connected to the inner wall of the top of the main housing 1, a third arm 503, one end of which is connected to the second fixing base 501 through a fourth gear motor 502, a fourth arm 505, one end of which is connected to the other end of the third arm 503 through a fifth gear motor 504, an electrical needle fixing base 507, which is connected to the other end of the fourth arm 505 through a sixth gear motor 506, and an electrical needle 508 provided on the electrical needle fixing base 507, where the electrical needle 508 can electrically stimulate the culture.
As shown in fig. 5, the growth factor supplementing module 6 includes a third fixing base 601 fixedly connected to the inner wall of the top of the main casing 1, a fifth arm 603 having one end connected to the third fixing base 601 through a seventh gear motor 602, a sixth arm 605 having one end connected to the other end of the fifth arm 603 through an eighth gear motor 604, a syringe fixing base 607 connected to the other end of the sixth arm 605 through a ninth gear motor 606, and a syringe 608 disposed on the syringe fixing base 607; one end of the syringe 608, which is close to the syringe fixing base 607, is provided with a cap 609, one end of the syringe 608, which is far away from the syringe fixing base 607, is provided with a dispensing needle 6010, and the growth factors are extruded through the dispensing needle 6010. The cylinder fixing base 607 is provided with a through hole 6011 for a pipeline with one end connected to the cylinder cover 609 and the other end connected with equipment for providing production factors from outside to pass through.
As shown in fig. 1, the circulation culture device comprises a culture pond 8 fixed under the tissue gripper 2 through a support frame 7, a liquid storage bottle 9 arranged on one side of the culture pond 8 and a peristaltic pump 10 arranged under the support frame 7, wherein the culture pond 8, the liquid storage bottle 9 and the peristaltic pump 10 are sequentially connected end to end through a hose 11 to form a circulation loop. In this way, the culture can be dynamically cultivated in the culture tank 8 and the medium is renewed.
As shown in FIG. 6, the bottom surface of the culture pond 8 is a gradient surface 801 gradually decreasing from the periphery to the middle, so that the culture can be ensured to be kept at the middle position of the culture pond 8, and the tissue gripper 2 can conveniently grip the culture.
In this embodiment, at least one side wall of the culture pond 8 and the main housing 1 is made of transparent material, so as to facilitate observation of the culture in the culture pond 8.
As shown in fig. 1, the environmental conditioning module includes a filtered air inlet 12 provided on one inner side wall of the main housing 1, a temperature controller 13 provided on the other inner side wall of the main housing 1, and a PTC heater 14 provided on the inner bottom surface of the main housing 1. The filtered air inlet 12 can filter and purify air entering the interior of the main housing 1 to provide an oxygen-suitable environment for the interior of the main housing 1. The temperature controller 13 and the PTC heater 14 can be matched to control the temperature inside the main shell 1, so as to provide a proper temperature environment for the cultivation process.
The working procedure of this embodiment is as follows: firstly, the temperature controller 13 is started, the PTC heater 14 starts to heat, the air inlet 12 with the filter starts to air, after the inside of the shell is heated to a proper temperature and an oxygen-adapting environment, the liquid storage bottle 9 is filled with culture medium, the culture pond 8 is internally provided with culture tissue, the peristaltic pump 10 is started, and the culture medium flows through the hose 11 to enter the culture pond 8 to start circulating culture. Taking the example of the heart which can shrink mentioned in the background art, after a period of cultivation, the shrinkage frequency of different positions of heart tissue is found to be inconsistent, after preliminary analysis, the assumption is that the printing material is uneven in the printing process, so that the cell density of the left atrium position is high, the cell density of the right atrium position is low, and therefore the shrinkage frequency of the left atrium position is high, and the shrinkage frequency of the right atrium position is low. The solution is that the electric push rod 201 moves downwards, the sliding rod 203 drives the grip 207 to move downwards to grip heart tissue, after the gripping is completed, the electric push rod 201 moves upwards, the sliding rod 203 drives the grip 207 to move upwards to grip heart tissue to be positioned above the culture pond 8, the fourth gear motor 502 rotates anticlockwise, the third arm 503 is close to heart tissue, the fifth gear motor 504 rotates clockwise, the third arm 503 and the fourth arm 505 are collinear, the sixth gear motor 506 rotates clockwise to drive the electric needle 508 to be positioned on the left atrium, the electric needle 508 slowly contacts the outer surface of the left atrium, and the electric needle 508 inputs gentle electrocardio frequency to reduce the contraction frequency of the left atrium, the fifth arm 603 and the sixth arm 605 of the growth factor supplementing module 6 also cooperatively move through the seventh gear motor 602, the eighth gear motor 604 and the ninth gear motor 606 to enable the dispensing needle 6010 to come into the right atrium, the syringe 608 is preloaded with a cardiac cell mixed liquid with growth factors, a pipeline connected with the syringe 608 cover starts ventilation, a part of the cardiac cell mixed liquid with growth factors is injected into the right atrium, after the injection is completed, the eighth gear motor 604 rotates to enable the dispensing needle 6010 to withdraw, the rotary cylinder 205 starts ventilation to rotate, the gripper 207 drives cardiac tissue to rotate, the surface of the right atrium comes near the electric stimulation module 5, meanwhile, the electric needle 508 comes into the right atrium position and slowly contacts the outer surface of the right atrium, the electric needle 508 inputs a gentle electrocardio frequency, so that the contraction frequency of the right atrium rises and keeps consistent with the contraction frequency of the left atrium. If the gripper 207 is found to block some parts of the heart tissue, the electric stimulation module 5 and the growth factor supplementing module 6 cannot operate, the first bionic arm module 3 and the second bionic arm module 4 come near the heart tissue, the micro-cylinder 307 is ventilated to drive the pull rod 3011, so that the two fingers 3010 clamp the heart tissue, the heart tissue is temporarily fixed, the rotary cylinder 205 drives the gripper 207 to adjust the angle, the heart tissue is grabbed again, and then the above operation is performed.
After a period of incubation, if some proliferation tissues appear in the heart tissue, the operation of the tissue gripper 2 can be repeated, the first bionic arm module 3 reaches the vicinity of the heart tissue, two fingers 3010 are inserted into the heart tissue, so that the micro air cylinder 307 is ventilated to drive the pull rod 3011, the two fingers 3010 clamp the proliferation tissues to pull the proliferation tissues outwards, in addition, the two fingers 3010 can clamp and stimulate the heart tissue, and a mechanical experiment is simulated.
In addition, because the culture time of the whole organ is long, results beyond experimental design or new culture requirements can be generated in the culture process, the culture function is modularized, the function of a certain module can be flexibly replaced or added to meet the new culture requirements, thus the bioreactor is not required to be changed or redeveloped, the new culture requirements can be realized by only adjusting a certain part of structure, further more diversified culture experiments can be carried out, and the final large tissue or organ functions are perfected.
It is to be understood that the above examples of the present invention are provided for clarity of illustration only and are not limiting of the embodiments of the present invention. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are desired to be protected by the following claims.

Claims (10)

1. The multifunctional bioreactor is characterized by comprising a main shell (1), a circulating culture device, a tissue gripper (2) and an environment regulation module, wherein the circulating culture device is arranged on the inner bottom surface of the main shell (1) and used for circularly culturing a culture, the tissue gripper (2) is arranged on the inner top surface of the main shell (1) and used for gripping the culture in the circulating culture device, the first bionic arm module (3), the second bionic arm module (4), the electric stimulation module (5) and the growth factor supplementing module (6) are arranged on the inner top surface of the main shell (1) and are annularly arranged around the tissue gripper (2), and the environment regulation module is arranged on the inner side wall of the main shell (1);
the circulating culture device comprises a culture pond (8), a liquid storage bottle (9) and a peristaltic pump (10), wherein the culture pond (8), the liquid storage bottle (9) and the peristaltic pump (10) are sequentially connected end to end through a hose (11) to form a circulating loop.
2. The multifunctional bioreactor according to claim 1, wherein the first bionic arm module (3) and the second bionic arm module (4) are symmetrically arranged on two opposite sides of the tissue gripper (2), and the electrical stimulation module (5) and the growth factor supplementing module (6) are symmetrically arranged on two opposite sides of the tissue gripper (2).
3. The multifunctional bioreactor according to claim 1 or 2, wherein the tissue gripper (2) comprises an electric push rod (201) arranged on the outer side surface of the top of the main shell (1), a sliding bar (203) with one end connected with the electric push rod (201) through a first connecting block (202) and the other end penetrating into the main shell (1) through a reserved hole on the side wall of the top of the main shell (1), a rotary cylinder (205) connected with the other end of the sliding bar (203) through a second connecting block (204), and a gripper (207) connected with the rotary cylinder (205) through a third connecting block (206).
4. The multifunctional bioreactor according to claim 1 or 2, wherein the first bionic arm module (3) comprises a first fixing seat (301) fixedly connected to the inner wall of the top of the main shell (1), a first arm (303) with one end connected with the first fixing seat (301) through a first gear motor (302), a second arm (305) with one end connected with the other end of the first arm (303) through a second gear motor (304), a micro cylinder (307) with a cylinder end connected with the other end of the second arm (305) through a third gear motor (306), a finger fixing seat (309) for fixing the micro cylinder (307) on one end face of the finger fixing seat through a cylinder fixing seat (308), and fingers (3010) symmetrically arranged on two sides of the other end of the finger fixing seat (309); the piston rod of the micro cylinder (307) is connected with one end of the finger (3010) through a pull rod (3011) and can drive the finger (3010) to clamp or loosen; the structure of the second bionic arm module (4) is the same as that of the first bionic arm module (3).
5. The multifunctional bioreactor according to claim 1 or 2, wherein the electric stimulation module (5) comprises a second fixing seat (501) fixedly connected to the inner wall of the top of the main shell (1), a third arm (503) with one end connected with the second fixing seat (501) through a fourth gear motor (502), a fourth arm (505) with one end connected with the other end of the third arm (503) through a fifth gear motor (504), an electric needle fixing seat (507) with the other end connected with the fourth arm (505) through a sixth gear motor (506), and an electric needle (508) arranged on the electric needle fixing seat (507).
6. The multifunctional bioreactor according to claim 1 or 2, characterized in that the growth factor supplementing module (6) comprises a third fixing base (601) fixedly connected to the top inner wall of the main housing (1), a fifth arm (603) with one end connected with the third fixing base (601) through a seventh gear motor (602), a sixth arm (605) with one end connected with the other end of the fifth arm (603) through an eighth gear motor (604), a syringe fixing base (607) with the other end connected with the sixth arm (605) through a ninth gear motor (606), and a syringe (608) arranged on the syringe fixing base (607); one end of the needle cylinder (608) close to the needle cylinder fixing seat (607) is provided with a cylinder cover (609), one end of the needle cylinder (608) far away from the needle cylinder fixing seat (607) is provided with a dispensing needle head (6010), and the needle cylinder fixing seat (607) is provided with a through hole (6011) for one end to be connected with a pipeline connected with equipment for providing production factors on the other end of the cylinder cover (609) and the outside to pass through.
7. The multifunctional bioreactor according to claim 1 or 2, characterized in that the circulating culture apparatus comprises a culture pond (8) fixed under the tissue gripper (2) through a support frame (7), a liquid storage bottle (9) arranged at one side of the culture pond (8), and a peristaltic pump (10) arranged under the support frame (7).
8. The multifunctional bioreactor according to claim 7, characterized in that the bottom surface of the culture tank (8) is a gradient surface (801) gradually decreasing from the periphery to the middle.
9. The multifunctional bioreactor according to claim 7, characterized in that at least one side wall of the culture tank (8) and the main housing (1) is made of transparent material.
10. The multifunctional bioreactor according to claim 1 or 2, characterized in that the environmental conditioning module comprises a filtered air inlet (12) provided on one inner side wall of the main housing (1), a temperature controller (13) provided on the other inner side wall of the main housing (1), and a PTC heater (14) provided on the inner bottom surface of the main housing (1).
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