CN114250149A - Stress bioreactor for tissue organ culture and culture robot - Google Patents
Stress bioreactor for tissue organ culture and culture robot Download PDFInfo
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- CN114250149A CN114250149A CN202111648363.2A CN202111648363A CN114250149A CN 114250149 A CN114250149 A CN 114250149A CN 202111648363 A CN202111648363 A CN 202111648363A CN 114250149 A CN114250149 A CN 114250149A
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- 210000000056 organ Anatomy 0.000 title claims abstract description 93
- 230000007246 mechanism Effects 0.000 claims abstract description 34
- 238000007789 sealing Methods 0.000 claims description 33
- 238000006073 displacement reaction Methods 0.000 claims description 13
- 230000005540 biological transmission Effects 0.000 claims description 12
- 230000000638 stimulation Effects 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000002572 peristaltic effect Effects 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 239000012531 culture fluid Substances 0.000 claims description 4
- 230000008602 contraction Effects 0.000 claims description 3
- 239000013013 elastic material Substances 0.000 claims description 3
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/58—Reaction vessels connected in series or in parallel
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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
- 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
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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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/46—Means for fastening
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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
- 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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- 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
- C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
- C12M37/04—Seals
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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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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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
- C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
Abstract
The invention relates to a stress bioreactor and a culture robot for tissue organ culture, which are characterized in that: including drive arrangement (1) and a plurality of culture room (9) of parallel arrangement, be equipped with in every culture room (9) and remove anchor clamps (7) and mounting fixture (8), artifical tissue or organ (10) both ends are held remove anchor clamps (7) with between mounting fixture (8), drive arrangement (1) pass through drive mechanism and connect in every culture room (9) remove anchor clamps (7), thereby drive remove anchor clamps (7) and carry artificial tissue or organ (10) reciprocating stretching motion. The invention adopts the parallel design of multiple culture chambers, can independently culture a plurality of artificial tissues or organs at the same time without mutual interference, and greatly improves the use efficiency of the machine and the culture efficiency of the artificial tissues or organs. More culture chambers can be further expanded by lengthening the cross beams and modularly splicing the base.
Description
Technical Field
The invention relates to a biological tissue engineering culture device, in particular to a stress bioreactor for tissue organ culture, a tissue organ culture robot and a control method thereof.
Background
At present, the bottleneck of insufficient mechanical property and biological function exists in the artificial tissue or organ constructed by using the tissue engineering method, and the clinical application of the artificial tissue or organ is restricted. One of the important causes of this phenomenon is the lack of mechanical stimulation of the artificial tissue or organ during in vitro culture. Therefore, bioreactor devices that provide tissue-specific mechanical stimulation during in vitro culture of artificial tissues or organs are of particular importance.
The device in the prior art mostly adopts the design that 1 driving device corresponds to 1 culture bin, but when tissue organ culture is carried out, a large number of tissues are often required to be cultured simultaneously, so that a plurality of devices are required to be equipped, the culture cost is high, and the devices are wasted.
At present, for mechanical stimulation equipment, the mechanical stimulation time for artificial tissues or organs is generally about 1-8h every day, the rest time is not required to be subjected to mechanical stimulation, but a culture room and a driving device are difficult to disassemble and assemble, so that the utilization rate of the equipment is very low.
The pollution prevention of the bioreactor is the important factor in the product design, and the good sealing effect can prevent the substances in the culture chamber from contacting with the outside, thereby ensuring that the artificial tissues or organs do not generate bacterial pollution in the in-vitro culture process for 1 to 4 months or more.
Disclosure of Invention
The invention designs a stress bioreactor and a culture robot for tissue organ culture, which solve the technical problems that: (1) the prior art can not realize that one driving device can culture a plurality of culture chambers simultaneously; (2) the culture chamber and the driving device are not easy to disassemble; (3) the culture chamber in the prior art has poor sealing effect and is easy to cause bacterial pollution.
In order to solve the technical problems, the invention adopts the following scheme:
a stress bioreactor for tissue organ culture and a culture robot comprise a driving device and a plurality of culture chambers which are arranged in parallel, wherein a movable clamp and a fixed clamp are arranged in each culture chamber, two ends of an artificial tissue or organ are clamped between the movable clamp and the fixed clamp, and the driving device is connected with the movable clamp in each culture chamber through a transmission mechanism so as to drive the artificial tissue or organ clamped by the movable clamp to do reciprocating stretching motion.
Preferably, the transmission mechanism comprises a connecting shaft, a beam and a plurality of push-pull rods, one end of the connecting shaft is connected with the driving device, the other end of the connecting shaft is connected with the beam, the beam is vertically connected with one ends of the push-pull rods, and the other ends of the push-pull rods penetrate through a through hole of the culture chamber and are connected with the movable clamp.
Preferably, each culture chamber is fixed on the base, each culture chamber is detachably connected with the base through a second dismounting and connecting mechanism, the beam is detachably connected with each push-pull rod through a first dismounting and connecting mechanism, and the first dismounting and connecting mechanism and the second dismounting and connecting mechanism are matched with each other to realize quick dismounting and replacement of the culture chambers.
Preferably, the sealing sleeve is made of elastic materials and comprises a sealing ring thick end and a sealing ring thin end, and the inner diameter of the sealing ring thin end is smaller than that of the push-pull rod, so that the sealing ring thin end can be tightly hooped on the push-pull rod through elastic contraction to keep the relative position and form a sealing structure; the thick end of the sealing ring is tightly pressed and sealed with the box body of the culture chamber through a guide sleeve with threads; when the push-pull rod is conveyed in a reciprocating mode, the sealing sleeves are folded or unfolded in a fold mode.
Preferably, the culture chamber is provided with a liquid outlet, a liquid inlet and a valve, and the culture solution circularly flows in the culture chamber through a peristaltic pump and a pipeline.
Preferably, a mechanical sensor is arranged on the connecting shaft, and the mechanical sensor is used for measuring the tension and feeding the tension back to the driving device to realize controllable mechanical stimulation of the artificial tissue or organ; or a displacement sensor is arranged in the driving device, and the displacement of the cross beam is accurately controlled through the displacement sensor, so that the deformation of the artificial tissue or organ is controlled.
Preferably, the driving device is a cylinder or an oil cylinder, and the cylinder or the oil cylinder is connected with the connecting shaft and enables the connecting shaft to reciprocate.
Preferably, the driving device is a motor and a screw rod, two ends of the screw rod are fixed between the first positioning plate and the second positioning plate, the motor is connected with the screw rod, the motor can move axially along the screw rod during working, the motor is fixedly connected with the first end of the connecting shaft, and the connecting shaft can reciprocate when the motor moves.
Preferably, the moving jig has two connecting portions: a first connection portion and a second connection portion; the first connecting part is connected with the other end of the push-pull rod, the first connecting part is provided with a horizontal hole and a vertical hole, the horizontal hole and the vertical hole are communicated with each other, the other end of the push-pull rod is provided with a vertical hole, the other end of the push-pull rod is inserted into the first connecting part through the horizontal hole of the first connecting part and enables the vertical hole of the push-pull rod to be communicated with the vertical hole of the first connecting part, the first vertical locking part is inserted into the vertical hole of the push-pull rod and the vertical hole of the first connecting part to lock the push-pull rod and the movable clamp, unlocking can be realized only by pulling out the first vertical locking part, quick locking and unlocking of the first connecting part and the first vertical locking part are realized, and the locking effect is firm;
the second connecting part comprises a movable part and a fixed part, wherein the movable part comprises a first clamping sheet and a first locking unit, and correspondingly, the fixed part comprises a second clamping sheet and a second locking unit; when the moving part moves in the vertical direction, the second clamping piece and the first clamping piece are matched with each other to clamp, fix or release the artificial tissue or organ; the first screw rod passes through the second locking unit and is in threaded connection with the first locking unit, and the movable part can be moved up and down by screwing the first screw rod so as to clamp or release the artificial tissue or organ, so that the artificial tissue or organ can be clamped or taken out.
A control method of a stress bioreactor for tissue organ culture comprises the following steps: when the number of times the artificial tissue or organ needs to be stretched per unit time is increased or decreased; or/and when the artificial tissue or organ needs to adjust the stress; or/and when the artificial tissue or organ needs to adjust the stretching displacement; or/and when the culture fluid pressure in the culture chamber of the artificial tissue or organ is required to be increased or decreased; the control unit realizes adjustment by controlling the peristaltic pump and the driving device so as to ensure that the growth adjustment of the artificial tissue or organ is optimal.
Compared with the prior art, the stress bioreactor and the culture robot for tissue organ culture have the following beneficial effects:
(1) the invention adopts the parallel design of multiple culture chambers, can independently culture a plurality of artificial tissues or organs at the same time without mutual interference, and greatly improves the use efficiency of the machine and the culture efficiency of the artificial tissues or organs. More culture chambers can be further expanded by lengthening the cross beams and modularly splicing the base.
(2) According to the rapid disassembly and assembly design of the culture chambers, after the first group of culture chambers finish mechanical stimulation, the first group of culture chambers can be disassembled rapidly, and the second group of culture chambers are installed to continue mechanical stimulation. Therefore, one driving equipment host can perform mechanical stimulation on a plurality of culture rooms in one day, and the use efficiency of the equipment is greatly improved.
(3) The conical sealing ring structure can ensure a good sealing structure, the sealing performance cannot be damaged when the push handrail moves in a reciprocating mode, the push handrail can be quickly disassembled and assembled, only one end of the guide sleeve with the threads is required to be disassembled, and the operation is convenient.
(4) The invention can adjust the stretching frequency and the culture fluid pressure according to the needs of the artificial tissues or organs, and provides better environment and conditions for the growth of the artificial tissues or organs.
(5) According to the invention, the push-pull rod and the movable clamp are locked by the movable clamp through the first vertical locking piece, and the first vertical locking piece is only pulled out for unlocking, so that the quick locking and unlocking of the push-pull rod and the movable clamp are realized, and the locking effect is firm. And the movable clamp can enable the movable part to move up and down by screwing the first screw rod so as to clamp or release the artificial tissue or organ, so that the artificial tissue or organ can be clamped or taken out, the operation is convenient, and the pollution risk is reduced.
Drawings
FIG. 1: the invention is used for the three-dimensional structure sketch map of the stress bioreactor of tissue organ culture;
FIG. 2: two ends of a push-pull rod are connected schematically;
FIG. 3: the push-pull rod and the sealing ring are connected schematically;
FIG. 4: the structure of the sealing ring is shown schematically;
FIG. 5: the invention discloses a first structural schematic diagram of a driving device;
FIG. 6: schematic connection of the culture chambers of the present invention;
FIG. 7: the invention discloses a control schematic diagram of a culture robot.
Description of reference numerals:
1-a drive device; 2-a mechanical sensor; 3, connecting the shaft; 4, a cross beam; 5-a first detachable connecting mechanism; 6, a push-pull rod; 7, moving the clamp; 8, fixing a clamp; 9-culture room; 10-an artificial tissue or organ; 11-the thick end of the sealing ring; 12-thin end of sealing ring; 13-a guide sleeve; 14, a motor; 15-a screw rod; 16-a first positioning plate; 17-a second positioning plate; 18-a liquid outlet; 19-liquid inlet; 20-a base; 21-a second disconnect coupling mechanism; 22-a displacement sensor; 23-a first screw; 24 — a first vertical locking member; 25-a movable member; 26 — a second vertical locking portion; 27-connecting the second end of the shaft; 28-biting teeth.
Detailed Description
The invention is further described below with reference to fig. 1 to 7:
as shown in figure 1, a stress bioreactor and a culture robot for tissue organ culture, which comprises a driving device 1 and a plurality of culture chambers 9 arranged in parallel, wherein each culture chamber 9 is provided with a movable clamp 7 and a fixed clamp 8, two ends of an artificial tissue or organ 10 are clamped between the movable clamp 7 and the fixed clamp 8, and the driving device 1 is connected with the movable clamp 7 in each culture chamber 9 through a transmission mechanism, so that the artificial tissue or organ 10 clamped by the movable clamp 7 is driven to do reciprocating stretching motion.
Every is cultivateed room 9 and fixes on base 20, and every is cultivateed room 9 and is realized dismantling through second dismantlement coupling mechanism 21 and base 20 and be connected, and crossbeam 4 and every push-and-pull rod 6 realize dismantling through first dismantlement coupling mechanism 5 and dismantle coupling mechanism 5 and mutually support with second dismantlement coupling mechanism 21 and realize dismantling fast and the replacement of cultivateing room 9. The first detachable connecting mechanism 5 comprises a second vertical locking portion 26 and a connecting shaft second end portion 27, the connecting shaft second end portion 27 is provided with a through hole, the end portion of the push-pull rod 6 is correspondingly provided with a through hole, and the second vertical locking portion 26 penetrates through the through hole of the connecting shaft second end portion 27 and the through hole of the push-pull rod 6 to rapidly connect the two.
The connecting shaft 3 is provided with a mechanical sensor 2, and the mechanical sensor 2 measures the tension and feeds the tension back to the driving device 1 to realize controllable mechanical stimulation of the artificial tissue or organ; or, the driving device 1 is provided with a displacement sensor 22, and the displacement of the beam 4 is accurately controlled through the displacement sensor 22, so that the deformation of the artificial tissue or organ is controlled.
As shown in fig. 2 and 3, the transmission mechanism includes a connecting shaft 3, a beam 4, and a plurality of push-pull rods 6, one end of the connecting shaft 3 is connected to the driving device 1, the other end of the connecting shaft 3 is connected to the beam 4, the beam 4 is vertically connected to one end of the plurality of push-pull rods 6, and the other end of the plurality of push-pull rods 6 passes through a through hole of a culture chamber 9 and is connected to the movable clamp 7.
The moving jig 7 has two connecting portions: a first connection portion and a second connection portion. The first connecting portion is connected with the other end of the push-pull rod 6, the first connecting portion is provided with a horizontal hole and a vertical hole, the horizontal hole and the vertical hole are communicated with each other, the other end of the push-pull rod 6 is provided with a vertical hole, the other end of the push-pull rod 6 is inserted into the first connecting portion through the horizontal hole of the first connecting portion, the vertical hole of the push-pull rod 6 is communicated with the vertical hole of the first connecting portion, the first vertical locking piece 24 is inserted into the vertical hole of the push-pull rod 6 and the vertical hole of the first connecting portion to lock the push-pull rod 6 and the movable clamp 7, unlocking can be achieved only by pulling out the first vertical locking piece 24, rapid locking and unlocking of the first connecting portion and the movable clamp are achieved, and the locking effect is firm.
The second connecting portion includes a movable member 25 and a fixed member, wherein the movable member 25 includes a first clamping piece and a first locking unit, and correspondingly, the fixed member includes a second clamping piece and a second locking unit; when the moving member 25 moves in the vertical direction, the second clamping piece and the first clamping piece are matched with each other to clamp, fix or release the artificial tissue or organ 10; the first screw 23 penetrates through the second locking unit and is in threaded connection with the first locking unit, and the movable piece 25 can be moved up and down by screwing the first screw 23 so as to clamp or release the artificial tissue or organ 10, so that the artificial tissue or organ 10 can be clamped or taken out.
The above-described structure of the movable jig is to facilitate installation of the artificial tissue or organ 10 because the internal space of the culture chamber 9 is relatively small. The right hand uses forceps to clamp the artificial tissue or organ 10 and place the artificial tissue or organ 10 on the first holding sheet of the clamp, and the artificial tissue or organ 10 can be released or clamped by screwing the first screw 23. Thus, the human hand does not reach deep into the inner space of the cultivation room 9, the operation is facilitated and the risk of contamination is reduced.
The first holding piece is provided with teeth 28 to increase the firmness of holding the artificial tissue or organ 10.
As shown in fig. 4, the device further comprises a sealing sleeve made of an elastic material, wherein the sealing sleeve comprises a sealing ring thick end 11 and a sealing ring thin end 12, and the inner diameter of the sealing ring thin end 12 is smaller than that of the push-pull rod 6, so that the sealing ring thin end 12 can be tightly hooped on the push-pull rod 6 by elastic contraction to keep the relative position and form a sealing structure; the thick end 11 of the sealing ring is tightly pressed and sealed with the box body of the culture chamber 9 through a guide sleeve 13 with threads; the gland folds or unfolds as the push-pull rod 6 is transported back and forth.
As shown in fig. 5, the first embodiment of the driving device 1 is a motor 14 and a screw rod 15, two ends of the screw rod 15 are fixed between a first positioning plate 16 and a second positioning plate 17, the motor 14 is connected with the screw rod 15, the motor 14 can move along the axial direction of the screw rod 15 when working, the motor 14 is fixedly connected with the end of the connecting shaft 3, and the connecting shaft 3 is also reciprocated when the motor 14 moves.
The second embodiment of the driving device 1 is a cylinder or an oil cylinder which is connected with the connecting shaft 3 and makes the connecting shaft 3 reciprocate.
As shown in FIG. 6, the culture chamber 9 is provided with a liquid outlet 18, a liquid inlet 19 and a valve, and the culture solution is circulated in the culture chamber 9 by a peristaltic pump and a pipeline.
During perfusion, the valve of the liquid outlet is closed, and the air in the culture chamber 9 is compressed by the liquid flowing into the culture chamber continuously, so that the hydraulic stimulation to the tissue in the culture chamber 9 can be further realized.
The invention relates to a control method of a stress bioreactor for tissue organ culture, which comprises the following steps: when the number of times of stretching the artificial tissue or organ 10 per unit time is required to be increased or decreased and the pressure of the culture fluid in the culture chamber 9 is required to be increased or decreased, the control unit realizes adjustment by controlling the peristaltic pump and the driving device to ensure optimal growth adjustment of the artificial tissue or organ 10.
As shown in FIG. 7, a tissue organ culture robot which can realize automatic stretching of organ tissues in different culture rooms and stretch them a set number of times. After the stretching times are completed, the transmission mechanism in the culture chamber can be automatically disconnected, so that the stretching of the tissue organ in other culture chambers is not influenced.
In particular to a tissue organ culture robot, which comprises a control unit, a driving device 1 and a plurality of culture chambers 9 arranged in parallel, wherein each culture chamber 9 is provided with a movable clamp 7 and a fixed clamp 8, two ends of an artificial tissue or organ 10 are clamped between the movable clamp 7 and the fixed clamp 8, the driving device 1 is connected with the movable clamp 7 in each culture chamber 9 through a transmission mechanism, thereby driving the artificial tissue or organ 10 clamped by the movable clamp 7 to do reciprocating stretching motion, the stretching times of the artificial tissue or organ in each culture chamber can be the same or different, when the stretching quantity in one or more culture chambers reaches a preset value, the control unit activates the magnetic unlocking mechanism, and the magnetic unlocking mechanism disconnects the corresponding transmission mechanism, so that the stretching work in the culture chamber is ensured not to be carried out any more, and the normal stretching of the tissues and organs of other culture chambers is not interfered.
The magnetic unlocking structure comprises an electromagnet and a second vertical locking part 26 which can be magnetically induced, the electromagnet is positioned above or below the second vertical locking part 26, when the electromagnet generates magnetic force, the second vertical locking part 26 moves vertically to be away from the through hole of the second end part 27 of the connecting shaft or/and the through hole of the push-pull rod 6, and the reciprocating motion of the connecting shaft 3 is not transmitted to the moving clamp 7 in the culture chamber. The transmission mechanism is disconnected in various types, and a person skilled in the art can select different automatic unlocking mechanisms to lock or unlock at selectable positions of the whole transmission mechanism.
The second vertical locking portion 26 is also connected to a return spring which will return the second vertical locking portion 26 to the through hole of the second end 27 of the connecting shaft and the through hole of the push-pull rod 6 when the electromagnet is de-energized and no magnetic force is generated.
The invention is described above with reference to the accompanying drawings, it is obvious that the implementation of the invention is not limited in the above manner, and it is within the scope of the invention to adopt various modifications of the inventive method concept and solution, or to apply the inventive concept and solution directly to other applications without modification.
Claims (13)
1. A stress bioreactor for tissue organ culture, characterized by: including drive arrangement (1) and a plurality of culture room (9) of parallel arrangement, be equipped with in every culture room (9) and remove anchor clamps (7) and mounting fixture (8), artifical tissue or organ (10) both ends are held remove anchor clamps (7) with between mounting fixture (8), drive arrangement (1) pass through drive mechanism and connect in every culture room (9) remove anchor clamps (7), thereby drive remove anchor clamps (7) and carry artifical tissue or organ (10) reciprocating stretching motion.
2. Stress-bioreactor for tissue organ culture according to claim 1, characterized in that: the transmission mechanism comprises a connecting shaft (3), a cross beam (4) and a plurality of push-pull rods (6), one end of the connecting shaft (3) is connected with the driving device (1), the other end of the connecting shaft (3) is connected with the cross beam (4), the cross beam (4) is vertically connected with one ends of the plurality of push-pull rods (6), and the other ends of the plurality of push-pull rods (6) penetrate through a through hole of the culture chamber (9) to be connected with the movable clamp (7).
3. Stress-bioreactor for tissue organ culture according to claim 1 or 2, characterized in that: each culture chamber (9) is fixed on a base (20), each culture chamber (9) is detachably connected with the base (20) through a second detachable connecting mechanism (21), the beam (4) is detachably connected with each push-pull rod (6) through a first detachable connecting mechanism (5), and the first detachable connecting mechanism (5) is matched with the second detachable connecting mechanism (21) to realize quick detachment and replacement of the culture chambers (9).
4. The stress bioreactor for tissue organ culture according to claim 3, characterized in that: the sealing sleeve is made of elastic materials and comprises a sealing ring thick end (11) and a sealing ring thin end (12), and the inner diameter of the sealing ring thin end (12) is smaller than that of the push-pull rod (6), so that the sealing ring thin end (12) can be tightly hooped on the push-pull rod (6) through elastic contraction to keep the relative position and form a sealing structure; the thick end (11) of the sealing ring is tightly pressed and sealed with the box body of the culture chamber (9) through a guide sleeve (13) with threads; when the push-pull rod (6) is conveyed in a reciprocating mode, the sealing sleeves are folded or unfolded in a fold mode.
5. Stress-bioreactor for tissue organ culture according to claim 1, 2 or 4, characterized in that: the culture chamber (9) is provided with a liquid outlet (18), a liquid inlet (19) and a valve, and the culture solution circularly flows in the culture chamber (9) through a peristaltic pump and a pipeline.
6. Stress-bioreactor for tissue organ culture according to claim 2, characterized in that:
the connecting shaft (3) is provided with a mechanical sensor (2), and the mechanical sensor (2) is used for measuring the tension and feeding the tension back to the driving device (1) to realize controllable mechanical stimulation of the artificial tissue or organ;
or a displacement sensor (22) is arranged in the driving device (1), and the displacement of the cross beam (4) is accurately controlled through the displacement sensor (22), so that the deformation of the artificial tissue or organ is controlled.
7. Stress-bioreactor for tissue organ culture according to claim 2, characterized in that: the driving device (1) is an air cylinder or an oil cylinder, and the air cylinder or the oil cylinder is connected with the connecting shaft (3) and enables the connecting shaft (3) to reciprocate.
8. Stress-bioreactor for tissue organ culture according to claim 2, characterized in that: drive arrangement (1) is motor (14) and lead screw (15), lead screw (15) both ends are fixed between first locating plate (16) and second locating plate (17), motor (14) with lead screw (15) are connected, motor (14) during operation can along the axial displacement of lead screw (15), motor (14) with connecting axle (3) tip fixed connection, also make during motor (14) remove connecting axle (3) reciprocating motion.
9. Stress-bioreactor for tissue organ culture according to claim 2, characterized in that: the movable clamp (7) has two connecting parts: a first connection portion and a second connection portion;
the first connecting portion is connected with the other end of the push-pull rod (6), the first connecting portion is provided with a horizontal hole and a vertical hole, the horizontal hole and the vertical hole are communicated with each other, the other end of the push-pull rod (6) is provided with a vertical hole, the other end of the push-pull rod (6) is inserted into the first connecting portion through the horizontal hole of the first connecting portion, the vertical hole of the push-pull rod (6) is communicated with the vertical hole of the first connecting portion, a first vertical locking piece (24) is inserted into the vertical hole of the push-pull rod (6) and the vertical hole of the first connecting portion to lock the push-pull rod (6) and the movable clamp (7), unlocking can be achieved only by pulling out the first vertical locking piece (24), quick locking and unlocking of the first vertical locking piece and the first vertical locking piece are achieved, and the locking effect is firm;
the second connecting part comprises a movable part (25) and a fixed part, wherein the movable part (25) comprises a first clamping sheet and a first locking unit, and correspondingly, the fixed part comprises a second clamping sheet and a second locking unit; when the moving piece (25) moves in the vertical direction, the second clamping piece and the first clamping piece are matched with each other to clamp, fix or release the artificial tissue or organ (10); the first screw rod (23) penetrates through the second locking unit to be in threaded connection with the first locking unit, and the movable piece (25) can move up and down by screwing the first screw rod (23) so as to clamp or release the artificial tissue or organ (10), so that the artificial tissue or organ (10) can be clamped or taken out.
10. A method of controlling a stress bioreactor for tissue organ culture according to any one of claims 1-9, comprising the steps of:
when the artificial tissue or organ (10) needs to be stretched more or less per unit time;
or/and when the artificial tissue or organ (10) needs to adjust the stress magnitude;
or/and when the artificial tissue or organ (10) needs to adjust the stretching displacement;
or/and when the artificial tissue or organ (10) requires a culture fluid pressure in the culture chamber (9) to be increased or decreased;
the control unit realizes adjustment by controlling the peristaltic pump and the driving device so as to ensure that the growth of the artificial tissue or organ (10) is adjusted optimally.
11. A tissue organ culture robot, characterized in that: the device comprises a control unit, a magnetic release lock structure, a driving device and a plurality of culture chambers which are arranged in parallel, wherein a movable clamp and a fixed clamp are arranged in each culture chamber, two ends of an artificial tissue or organ are clamped between the movable clamp and the fixed clamp, the driving device is connected with the movable clamp in each culture chamber through a transmission mechanism so as to drive the artificial tissue or organ clamped by the movable clamp to do reciprocating stretching motion, the stretching times of the artificial tissue or organ in each culture chamber are the same or different, when the stretching number in one or more culture chambers reaches a preset value, the control unit activates the magnetic release lock mechanism, and the magnetic release lock mechanism disconnects the corresponding transmission mechanism, so that the stretching work in the culture chamber is ensured not to be carried out any more, and the normal stretching of the tissue or organ of other culture chambers is not interfered.
12. The tissue organ culture robot of claim 11, wherein: the magnetic unlocking structure comprises an electromagnet and a second vertical locking part which can be magnetically induced, the electromagnet is positioned above or below the second vertical locking part, when the electromagnet generates magnetic force, the second vertical locking part vertically moves to be away from the through hole at the second end part of the connecting shaft or/and the through hole of the push-pull rod, and the reciprocating motion of the connecting shaft is not transmitted to the moving clamp in the culture chamber.
13. The tissue organ culture robot of claim 11, wherein: the second vertical locking part is also connected with a return spring, and when the electromagnet is not powered off and does not generate magnetic force, the return spring enables the second vertical locking part to return to the through hole at the second end part of the connecting shaft and the through hole of the push-pull rod again.
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