CN201268704Y - Dynamic bionic pulsating movement bioreactor - Google Patents
Dynamic bionic pulsating movement bioreactor Download PDFInfo
- Publication number
- CN201268704Y CN201268704Y CNU2008202216284U CN200820221628U CN201268704Y CN 201268704 Y CN201268704 Y CN 201268704Y CN U2008202216284 U CNU2008202216284 U CN U2008202216284U CN 200820221628 U CN200820221628 U CN 200820221628U CN 201268704 Y CN201268704 Y CN 201268704Y
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- dynamic
- bionical
- bioreactor
- culture chamber
- pressure
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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
- 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
- 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
Abstract
The utility model relates to a dynamic bionics pulse bioreactor which comprises a simulation heart compressor; a check valve is arranged on the input end of the simulation heart compressor, and a cultivation chamber is connected with the output end of the simulation heart compressor; the check valve is connected with first cell returning liquid and second cell returning liquid, the first cell returning liquid is provided with a protection gas interface and a pH meter, the second cell returning liquid is provided with a filtration gauze pad which is communicated with a pressure -difference regulator by an electric valve connected with a pipeline, the pressure-difference regulator is connected with the cultivation chamber by the pipeline, tissue engineering cardiac valves or blood vessels are arranged in the cultivation chamber, a pressure sensor is arranged above the cultivation chamber, a special camera with an image collector is arranged in the horizontal direction of the cultivation chamber, the pressure sensor is connected with a data collector, the data collector and the special camera with an image collector are respectively connected with a computer, and the computer is communicated with the electric valve by a control signal wire. The utility model can analyze and simulate the human body blood circulation system, cultivate the condition for cell growth and store relative data.
Description
Technical field
The utility model relates to a kind of bio-reactor, and particularly a kind of dynamic bionical impulsive motion bioreactor that is used for the artificial heart blood circulation is to substitute present static bio-reactor.
Background technology
This new installation with innovative technology of bio-reactor has been obtained success in the biomaterial industrialization.Bio-reactor is the key equipment in the biomaterial course of processing.Since nearly over half a century, because the broad research to bio-reactor is used, existing many products, but in the majority with static state, according to the research and development that deepens continuously, the existing external pulsation reactor of development voluntarily is applied to TEHV and answers power apparatus, the haemodynamics of basic energy simple analog intracorporeal heart valve, be used for the research of TEHV pre-adaptation, this device adopts exotic materials to design and produce external pulsation reactor and pre-adaptation stress culture systems voluntarily according to fluid mechanics principle; Place reactor to turn round bioprosthetic valves, observe the working order of bioprosthetic valves and the stability of system.Make support to take off the cell porcine aortic valve, the new born bovine aortic endothelial cell is made seed cell and is made up the organizational project heart valve leaflet, behind the static cultivation 4d, insert and carry out pre-adaptation in the reactor and handle 24h (flow transfers to 400ml/min by 30ml/min, frequency 30 times/min), observe the endotheliocyte residual condition, and compare with the valve of static cultivation.The result shows: this device can produce the pulsation liquid flow, the bioprosthetic valves works better, and running 7d, system state is stable.Static cultivation successfully makes up TEHV, and endotheliocyte and lobe leaf support stick closely, forms the monolayer cell layer along the lobe leaf surface, and growth conditions is good; The lobe leaf endotheliocyte part of dynamically cultivating is washed away to come off, and residual sticking of small part cell (6.26%) only arranged.
Above-mentioned impulsive motion bioreactor has the following disadvantages:
(1) do not have unit clamp, valve or blood vessel are difficult for fixing;
(2) no viewing window is unfavorable for the observation of TEHV or blood vessel;
(3) nonelastic load, the pressure of the pulsation liquid flow that produces rises, descends too fast, surging force is too big, bigger for the damage of biologic bracket material especially lobe leaf, blood pressure and blood flow that can not the human simulation human body very easily come off seed cell, are unfavorable for sticking of seed cell, growth, the keeping of differentiation and phenotype and function.
(4) level of automation is not enough, and demonstration that can not be real-time is analyzed, and adjusts and write down each parameter of culture environment in the impulsive motion bioreactor.
(5) culture chamber mostly is glass or organic plastics, is unfavorable for sterilization and repeated use.
Summary of the invention
Impulsive motion bioreactor is not quite similar in the research of every field, different different according to the biological material category of research with research purpose, requirement to device is also different, the purpose of this utility model is, a kind of dynamic bionical biological pulsation reactor is provided, this dynamic biological pulsation reactor can human simulation human heart blood circulation, especially the human simulation of blood pressure and blood flow, and can provide culture environment each related data in real time, reduce the pulsation liquid flow to the impact injury of biologic bracket material especially lobe leaf and the impact of seed cell, improve the surviving rate of TEHV seed cell in external structure, adherence rate, promote the differentiation of seed cell (stem cell), keep the normal phenotype of seed cell, function.
In order to realize above-mentioned task, the utility model is taked following technical solution:
A kind of dynamic bionical impulsive motion bioreactor is characterized in that, comprises a simulation heart compressor, and the input terminus of this pseudocardia compressor is equipped with vacuum breaker, and output terminal is connected with culture chamber; Vacuum breaker is connected in series with the first return-enclosure liquid and the second return-enclosure liquid by pipeline, the first return-enclosure liquid is provided with the shielding gas interface and the Ph value detects meter, on the second return-enclosure liquid filtration gauze pad is installed, filtering gauze pad is communicated with differential pressure regulator by the electrically operated valve that connects on the pipeline, differential pressure regulator is connected with culture chamber by pipeline, biovalve is arranged in the culture chamber, there is pressure transmitter the culture chamber top, the horizontal direction of culture chamber is provided with the special-purpose camera that has image acquisition device, wherein, pressure transmitter is connected with data acquisition unit; Data acquisition unit, the special-purpose camera that has an image acquisition device are connected with computer respectively, and computer is communicated with electrically operated valve by control signal wire.
Other characteristics of the present utility model are:
Described biovalve is installed on the biovalve unit clamp; The described special-purpose camera that has image acquisition device has sleeve on every side, and the image acquisition device front is equipped with transparent glass, between transparent glass and the sleeve sealing-ring is housed.
Described differential pressure regulator comprises the soft load of an energy human simulation blood vessel, soft load is to be made by the very little rubber hose of elasticity, this soft load is installed in the folding capsule of bellows, and soft load is among the encirclement of the hydraulic pressure body in the folding capsule of bellows all the time, and is subjected to uniform pressure; The folding capsule periphery of bellows is coated by housing, on the folding capsule of bellows adjustable spring is installed, and is connected with leading screw on the adjustable spring, and handle is housed on the leading screw.
Dynamic bionical impulsive motion bioreactor of the present utility model, can analyze, the condition of the human simulation blood of human body recycle system and culturing cell growth, can effectively control the mean pressure and the differential pressure thereof of nutrient solution, and the rising and the downcurve of pressure approach human body, and these parameters can be regulated as required at any time, accurate dynamic shows the parameters such as pressure curve of nutrient solution in the dynamic biological pulsation reactor in real time, and has as required related data such as is stored at function.
Description of drawings
Fig. 1 is a dynamic bionical impulsive motion bioreactor structural representation of the present utility model;
Fig. 2 is a biovalve unit clamp structural representation;
Fig. 3 is the structural representation of reaction chamber in the impulsive motion bioreactor;
Fig. 4 is the differential pressure regulator structural representation;
The utility model is described in further detail below in conjunction with accompanying drawing.
Embodiment
Adherence rate for cell seed cell in the process of external structure of improving TEHV or engineering blood vessel, surviving rate, promotion is as the directional induction differentiation differentiation of the stem cell of seed cell, keep the structure of seed cell, phenotype and function, reduce the pulsation liquid flow to the impact injury of biologic bracket material especially lobe leaf and the impact of seed cell, improve the TEHV of structure and the success ratio and the quality of engineering blood vessel, structure can be used for clinical organizational project valve and blood vessel, the applicant begins to develop the dynamic biological pulsation reactor of the human simulation blood of human body recycle system already, to substitute present static bio-reactor.
Condition by analysis, the human simulation blood of human body recycle system and culturing cell growth, not only require the effectively mean pressure and the differential pressure thereof of control nutrient solution, and the rising of pressure and downcurve approach human body, and require these parameters to regulate at any time as required; For each parts disinfection easily of guaranteeing at every turn nutrient solution in the whole device to be flow through etc., in design, necessarily require on structure and material, to realize miniaturization and modularization again.
Consider above principal element, the dynamic bionical impulsive motion bioreactor structure principle chart of the utility model design is referring to Fig. 1, this dynamic bionical impulsive motion bioreactor comprises a simulation heart compressor 1, and the input terminus of this pseudocardia compressor 1 is equipped with vacuum breaker 2, and output terminal is connected with culture chamber 14; Vacuum breaker 2 is connected in series with the first return-enclosure liquid 3 by pipeline and the second return-enclosure liquid, 4, the first return-enclosure liquid 3 are provided with shielding gas interface 6 and the Ph value detects meter 7, and the shielding gas that shielding gas interface 6 feeds is selected 5% CO
2With 95% the mixed gas that Air constituted.Be equipped with on the second return-enclosure liquid 4 and filter gauze pad 5, filtering gauze pad 5 is connected with differential pressure regulator 8 by the electrically operated valve 9 that connects on the pipeline, differential pressure regulator 8 is connected with culture chamber 14 by pipeline, biovalve 15 is arranged in the culture chamber 14, there is pressure transmitter 13 culture chamber 14 tops, the horizontal direction of culture chamber 14 is provided with the special-purpose camera 12 that has image acquisition device, wherein, pressure transmitter 13 is connected with data acquisition unit 11, this data acquisition unit 11 links to each other with computer 10, the special-purpose camera 12 that has image acquisition device also is connected with computer 10, and computer 10 is communicated with electrically operated valve 9 by control signal wire.
Be provided with software in the computer 10, software is the computer program that utilizes the VC++ establishment, friendly interface, easy to operate, accurate dynamic shows the parameter such as pressure curve of nutrient solution in the dynamic biological pulsation reactor and has as required related data such as is stored at function in real time.
The major function that first, second backflash 3,4 and the pH value that inserts detect meter 7 is to carry out froth breaking and in the stream time that reaches a week some parameter such as pH value of its nutrient solution shown and adjustment etc. by the 5 pairs of nutrient solutions of filtration gauze pad that are provided with.
Above-mentioned biovalve 15 is installed on the biovalve unit clamp 16.Biovalve unit clamp 16 can realize carrying out on request the loading and unloading of heart valve 15 easily by means of guide rod 26; Biovalve unit clamp 16 comprises the litter that has bolt 21 of pair of parallel, the two ends of litter 21 respectively are equipped with the hollow round platform of taper that a pair of internal diameter equates, this forms forward and backward anchor clamps to the hollow round platform of taper at litter 21 two ends, front jig is made up of external hollow round platform 22 and interior hollow round platform 23, rear jig is made up of external hollow round platform 25 and interior hollow round platform 24, front jig and rear jig are installed in the outside of two tack bolts 27 on the litter 21, by holding bolt 28 location of outermost on the litter 21; Pass a guide rod 26 in front jig and the rear jig, the diameter of this guide rod 26 is smaller or equal to the internal diameter of hollow round platform, and a cone cassette tape is arranged on the diameter, the outer side of the external hollow round platform 22 of front jig and the external hollow round platform 25 of rear jig is bossed annulus cassette tape respectively, and the height of its projection is 0.5mm～0.6mm.The external hollow round platform 22 of front jig and the diameter of interior hollow round platform 23 are greater than the external hollow round platform 25 of rear jig and the diameter of interior hollow round platform 24 (promptly increasing the bolt plane), so that whole cardiovascular (heart valve) anchor clamps are fixed in the culture chamber 15.
The special-purpose camera 12 that has image acquisition device has sleeve 19 on every side, and special-purpose camera 12 fronts that have image acquisition device are equipped with transparent glass 17, between transparent glass 17 and the sleeve 19 sealing-ring 18 are housed.But the upgrowth situation of transparent glass 17 cell on direct viewing Sheng Wu Vital-fixture film 15, special-purpose camera 12 that can also be by having image acquisition device is presented at the situation during cell cultures on the biovalve on the display screen of computer 10, perhaps it is retained in the computer 10, convenience compares the upgrowth situation of biovalve in the future.
Differential pressure regulator 8 comprises the soft load 41 of a simulated blood vessel, and this soft load 41 is installed in the folding capsule 43 of bellows, and soft load 41 is among the encirclement of the hydraulic pressure body in the folding capsule 43 of bellows all the time, thereby is subjected to uniform pressure; Folding capsule 43 peripheries of bellows are coated by housing 42, on the folding capsule 42 of bellows adjustable spring 44 are installed, and are connected with leading screw 45 on the adjustable spring 44, and handle 46 is housed on the leading screw 45.
The principle of work of differential pressure regulator 8 is: soft load 41 is to be made by the very strong medical rubber hose of elasticity.Because increasing degree with soft load 41 volumetrical, the highly compressed height is inversely proportional to substantially, the degree that causes soft load 41 volumes to increase after the nutrient solution swash of wave is come has each time determined the rising amplitude of high terminal pressure, and soft load 41 volumes increase how much depend on it around the hydraulic pressure body to its applied pressure, so just can regulate the pressure of 44 pairs of hydraulic pressure bodies of adjustable spring by handle 46 rotational lead screws 45, and this pressure is transmitted and evenly impose on soft load 41, thereby effectively realize adjusting and control to differential pressure by the hydraulic pressure body.
Electrically operated valve 9 is the topworkies in the closed loop control system formed of computer 10 and pressure transmitter 13, its major function is the mean pressure curve that designs in computer 10 in advance according to people, the function that realizes regulating mean pressure by the aperture of automatic adjusting electrically operated valve 9.
The ultimate principle of dynamic bionical impulsive motion bioreactor anthropomorphic dummy's of the present utility model blood circulation pressure and other parameters is: the suitable differential pressure curve of regulating by differential pressure regulator that on the basis of the constant pressure curve of realizing by closed loop control system, superposes again, just can realize the pressure curve of anthropomorphic dummy's heart and blood circulation system.Require its pressure between 70～110mmHg, to change in a certain period of biological example valve (heart valve) cell growth with sinusoidal rule, then electrically operated valve 9 is adjusted to 90mmHg according to the instruction of computer 10 automatically with constant pressure, and the sinusoidal pressure curve that is superimposed with amplitude that differential pressure regulator regulates out then and is 20mmHg then can be realized.
Claims (6)
1. a dynamic bionical impulsive motion bioreactor is characterized in that, comprises a simulation heart compressor (1), and the input terminus of this pseudocardia compressor (1) is equipped with vacuum breaker (2), and output terminal is connected with culture chamber (14); Vacuum breaker (2) is connected in series with the first return-enclosure liquid (3) and the second return-enclosure liquid (4) by pipeline, the first return-enclosure liquid (3) is provided with shielding gas interface (6) and the Ph value detects meter (7), be equipped with on the second return-enclosure liquid (4) and filter gauze pad (5), filtering gauze pad (5) is communicated with differential pressure regulator (8) by the electrically operated valve (9) that connects on the pipeline, differential pressure regulator (8) is connected with culture chamber (14) by pipeline, biovalve (15) is arranged in the culture chamber (14), there is pressure transmitter (13) culture chamber (14) top, the horizontal direction of culture chamber (14) is provided with the special-purpose camera (12) that has image acquisition device, wherein, pressure transmitter (13) is connected with data acquisition unit (11); Data acquisition unit (11), the special-purpose camera (12) that has an image acquisition device are connected with computer (10) respectively, and computer (10) is communicated with electrically operated valve (9) by control signal wire.
2. dynamic bionical impulsive motion bioreactor as claimed in claim 1 is characterized in that described biovalve (15) is installed on the biovalve unit clamp (16).
3. dynamic bionical impulsive motion bioreactor as claimed in claim 1, it is characterized in that, described special-purpose camera and image acquisition device (12) have sleeve (19) on every side, special-purpose camera and image acquisition device (12) front are equipped with transparent glass (17), between transparent glass (17) and the sleeve (19) sealing-ring (18) are housed.
4. dynamic bionical impulsive motion bioreactor as claimed in claim 1, it is characterized in that, described differential pressure regulator (8) comprises the soft load (41) of a simulated blood vessel, this soft load (41) is installed in the folding capsule (43) of bellows, soft load (41) is among the encirclement of the hydraulic pressure body in the folding capsule (43) of bellows all the time, and is subjected to uniform pressure; Bellows fold capsule (43) periphery and are coated by housing (42), and bellows fold adjustable spring (44) is installed on the capsule (42), are connected with leading screw (45) on the adjustable spring (44), and handle (46) is housed on the leading screw (45).
5. dynamic bionical impulsive motion bioreactor as claimed in claim 4 is characterized in that, described soft load (41) is to be made by the very strong medical rubber hose of elasticity.
6. dynamic bionical impulsive motion bioreactor as claimed in claim 1 is characterized in that, the shielding gas that described shielding gas interface 6 feeds is selected 5% CO
2Mixed gas with 95% Air.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2008202216284U CN201268704Y (en) | 2008-09-26 | 2008-09-26 | Dynamic bionic pulsating movement bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2008202216284U CN201268704Y (en) | 2008-09-26 | 2008-09-26 | Dynamic bionic pulsating movement bioreactor |
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| CN201268704Y true CN201268704Y (en) | 2009-07-08 |
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| CNU2008202216284U Expired - Fee Related CN201268704Y (en) | 2008-09-26 | 2008-09-26 | Dynamic bionic pulsating movement bioreactor |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102415919A (en) * | 2011-11-15 | 2012-04-18 | 微创医疗器械(上海)有限公司 | Steady flow field equipment for modifying artificial biologic valve and method thereof |
| CN102430150A (en) * | 2011-11-04 | 2012-05-02 | 微创医疗器械(上海)有限公司 | Sizing equipment and method for pulse fluid assisted fixed artificial bioprosthetic valve |
| CN103300943A (en) * | 2013-05-16 | 2013-09-18 | 金仕生物科技（常熟）有限公司 | Cardiac valve detecting device |
| EP2846633A4 (en) * | 2012-04-02 | 2016-03-23 | Childrens Mercy Hospital | Disposable single use self-contained cyclic pressure and flow bioreactor system |
| CN110066786A (en) * | 2019-05-15 | 2019-07-30 | 刘宝全 | A method of enhancing stem cell blood adaptability |
| CN110974318A (en) * | 2019-11-25 | 2020-04-10 | 西安马克医疗科技有限公司 | External simulation device and simulation system for transcatheter aortic valve replacement |
| CN111925939A (en) * | 2020-09-08 | 2020-11-13 | 华中科技大学同济医学院附属协和医院 | Dynamic pressurized tissue engineering valve cell inoculator and use method thereof |
| CN117705560A (en) * | 2024-02-06 | 2024-03-15 | 圣塔菲医疗科技(常州)有限公司 | Real-time abrasion test device for cardiovascular implant |
| CN117705560B (en) * | 2024-02-06 | 2024-04-19 | 圣塔菲医疗科技(常州)有限公司 | Real-time abrasion test device for cardiovascular implant |
-
2008
- 2008-09-26 CN CNU2008202216284U patent/CN201268704Y/en not_active Expired - Fee Related
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102430150A (en) * | 2011-11-04 | 2012-05-02 | 微创医疗器械(上海)有限公司 | Sizing equipment and method for pulse fluid assisted fixed artificial bioprosthetic valve |
| CN102415919A (en) * | 2011-11-15 | 2012-04-18 | 微创医疗器械(上海)有限公司 | Steady flow field equipment for modifying artificial biologic valve and method thereof |
| CN102415919B (en) * | 2011-11-15 | 2014-03-19 | 上海微创医疗器械（集团）有限公司 | Steady flow field equipment for modifying artificial biologic valve and method thereof |
| EP2846633A4 (en) * | 2012-04-02 | 2016-03-23 | Childrens Mercy Hospital | Disposable single use self-contained cyclic pressure and flow bioreactor system |
| CN103300943A (en) * | 2013-05-16 | 2013-09-18 | 金仕生物科技（常熟）有限公司 | Cardiac valve detecting device |
| CN103300943B (en) * | 2013-05-16 | 2015-08-19 | 金仕生物科技（常熟）有限公司 | Cardiac valve checkout gear |
| CN110066786A (en) * | 2019-05-15 | 2019-07-30 | 刘宝全 | A method of enhancing stem cell blood adaptability |
| CN110974318A (en) * | 2019-11-25 | 2020-04-10 | 西安马克医疗科技有限公司 | External simulation device and simulation system for transcatheter aortic valve replacement |
| CN111925939A (en) * | 2020-09-08 | 2020-11-13 | 华中科技大学同济医学院附属协和医院 | Dynamic pressurized tissue engineering valve cell inoculator and use method thereof |
| CN111925939B (en) * | 2020-09-08 | 2023-07-04 | 华中科技大学同济医学院附属协和医院 | Application method of dynamic pressurization tissue engineering valve cell inoculator |
| CN117705560A (en) * | 2024-02-06 | 2024-03-15 | 圣塔菲医疗科技(常州)有限公司 | Real-time abrasion test device for cardiovascular implant |
| CN117705560B (en) * | 2024-02-06 | 2024-04-19 | 圣塔菲医疗科技(常州)有限公司 | Real-time abrasion test device for cardiovascular implant |
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Granted publication date: 20090708 Termination date: 20110926 |