CN103131635B - Cavity-type dynamic-filling bioreaction device - Google Patents
Cavity-type dynamic-filling bioreaction device Download PDFInfo
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- CN103131635B CN103131635B CN201110382573.1A CN201110382573A CN103131635B CN 103131635 B CN103131635 B CN 103131635B CN 201110382573 A CN201110382573 A CN 201110382573A CN 103131635 B CN103131635 B CN 103131635B
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- nutrient solution
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- 239000000523 sample Substances 0.000 claims abstract description 46
- 235000015097 nutrients Nutrition 0.000 claims abstract description 29
- 239000012472 biological sample Substances 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 239000007788 liquid Substances 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 230000008676 import Effects 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 5
- 238000010030 laminating Methods 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 22
- 230000002572 peristaltic effect Effects 0.000 description 13
- 230000008859 change Effects 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 239000007789 gas Substances 0.000 description 6
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- 235000016709 nutrition Nutrition 0.000 description 5
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- 238000000034 method Methods 0.000 description 4
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- 229920001296 polysiloxane Polymers 0.000 description 3
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229940088623 biologically active substance Drugs 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
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- 231100000956 nontoxicity Toxicity 0.000 description 2
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- 230000008439 repair process Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
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- 235000019046 balanced nutrition Nutrition 0.000 description 1
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- 238000004113 cell culture Methods 0.000 description 1
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- 235000003170 nutritional factors Nutrition 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention provides a cavity-type dynamic-filling bioreaction device comprising a biological sample culture component, a nutrient solution flowing pipe and a power pump component. The biological sample culture component is provided with an in-out port communicated with the nutrient solution flowing pipe. The biological sample culture component comprises an upper cover body, a container body and a sample bearing frame, wherein the upper cover body is connected with the container body, a supporting ring is arranged on the inner wall of the container body, the sample bearing frame is arranged on the supporting ring, a supporting block is arranged on the inner side of the sample bearing frame, a sample bearing plate is arranged in a cavity formed by the supporting block and the sample bearing frame, and culture through holes are longitudinally formed in the sample bearing plate. The nutrient solution flowing pipe comprises an output pipe and an input pipe, wherein the output pipe and the input pipe are respectively connected with the power pump component.
Description
Technical field
The present invention relates to be applied in the device of culture sample in the field such as plant, animal and human body tissue engineering, relate in particular to a kind of by continuing dynamically to supply with nutrition and regulate the stimulation of mechanics and biologically active substance to reach to promote cell and the propagation of tissue and the cavity type of differentiation dynamically to pour into biological tissue's reaction unit.
Background technology
Organizational project combines cytobiology and engineering science principle, and anatomical structure and the physiological function of research normal cell, tissue or organ, so as to producing the artificial substituting product of the structure and function that can improve, repair or rebuild damaged tissue.Its mode is to obtain a small amount of tissue from body, through separating and amplification and obtain seed cell, be inoculated in biological support, breed and induction is differentiated to form organizational project member by vitro culture, then for repair and reconstruction, recovery organization and the organ shape and function at disease damage position.
In organizational project development, for solving shortage and the Industrialization of tissue or the required donor material of organ transfer operation, bio-reactor arises at the historic moment.Cultivate from initial Petri dish static cultivation dynamic 3 D input type perfusion finally, the form of bio-reactor and function are in continuous variation, but the subject matter that they exist is not that cell skewness in biological support has particular requirement to support shape exactly, and the low shortcoming of they ubiquity production capacities.
Chinese patent CN 1352240A has disclosed the device that a kind of cell with twoport culturing bottle and organizational project are cultivated.It comprises and in incubator, is equipped with well heater and the sensor that temperature is connected with gas flow control device, with temperature control damper.Gas inlet is arranged at incubator top, and on it, the gas pipeline in incubator is inserted in fixing one end, and the other end is communicated with gas cylinder by a gas meter; Also comprise the bed that rolls, on it, put rolling culturing bottle, its lower peace one driving mechanism of more than 2 both ends open, driving mechanism is connected with motor.
Chinese patent CN 1542121A has disclosed a kind of dynamic 3 D input type tissue reaction device, comprise one can be for cell is inoculated in to the incubator on the biological support body with centre channel.And further comprise that at least one matches with the centre channel of biological support body and stretches into the conduit of this centre channel and a circulation infusion set being connected with this conduit.This incubator is provided with an input aperture and a delivery port, and conduit is connected with circulation infusion set by this input aperture.
Although existing bio-reactor can provide dimensional culture environment to the cell on the biological support of organizational project, but cannot make cell be evenly distributed in biological support, in the time building cell-biological support complex body of different size, need to again customize reactor and only can build cell-biological support complex body of hollow, these unfavorable factors all limited tissue engineering product a large amount of productions.
Summary of the invention
The present invention is according to the deficiencies in the prior art part, provide a kind of cavity type dynamically to pour into biological reaction apparatus, can promote the propagation of cell and tissue and differentiation and formative tissue engineering component by regulating flow, stress, nutrition and the activity substance content of cell culture fluid in device, reaching.
To achieve these goals, provide a kind of cavity type dynamically to pour into biological reaction apparatus, it is characterized in that, comprise biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts, described biological sample is cultivated parts and is provided with the import and export that are connected with the mobile pipe fitting of nutrient solution; Described biological sample is cultivated parts and is comprised upper cover body, container body and put sample carrier, upper cover body is connected with container body, container body inwall is provided with support ring, the described sample carrier of putting is arranged on support ring, the inner side of putting sample carrier is provided with back-up block, being provided with and holding model by back-up block with in putting the cavity that sample carrier forms, described in hold model and be provided with cultivation through hole, cultivate through hole and be longitudinally arranged on and hold in model.The mobile pipe fitting of described nutrient solution comprises output tube and input tube, and described output tube is connected with power-driven pump parts respectively with input tube, and described output tube is provided with strainer.
Upper cover body is connected by thread helix with container body, can ensure good sealing property.Upper cover body, container body and put sample carrier and can all use inorganic, the organic or metallic substance of nontoxicity to make, its shape can be rectangle, semisphere, the shape such as cylindrical.Upper cover body, container body and the shape of putting sample carrier are mated mutually.
In the above-mentioned reaction unit providing, wherein said biological sample is cultivated on parts and is also provided with gaseous interchange mouth, and described gaseous interchange mouth is provided with gaseous interchange regulated valve and strainer, and described strainer is arranged on the exit of gaseous interchange regulated valve.In the above-mentioned reaction unit providing, on wherein said output tube, also have T-valve, one end of described T-valve is connected with output tube, and the other end is connected with power-driven pump parts.Change stress and oxygen atmosphere by adjustments of gas interchange valve and peristaltic pump, equally also can change by T-valve nutrition and the induced environment of nutrient solution, affect growth and the differentiation of cell and tissue.
In the above-mentioned reaction unit providing, the diameter of wherein said import and export and gaseous interchange mouth is 2 ~ 100 millimeters.Be made up of polyethylene and medical silica-gel with importing and exporting the input tube and the output tube that are connected, diameter matches with the diameter of input aperture and delivery port respectively, and its length is between 20 ~ 10000 millimeters.
In the above-mentioned reaction unit providing, between wherein said upper cover body and container body, be provided with silica gel sealing pad.
In the above-mentioned reaction unit providing, the wherein said sample carrier of putting is provided with draw ring, the two ends of draw ring with put sample carrier and be connected.
In the above-mentioned reaction unit providing, wherein said bottom of putting sample carrier is provided with projection, and the groove arranging on described projection and described support ring matches.Projection is embedded in groove, can prevent from putting sample carrier and rotate in container body.
In the above-mentioned reaction unit providing, the wherein said sidewall of putting sample carrier is provided with extension stopper, and the inwall that sample carrier is put in the laminating of extension stopper upwards extends.
In the above-mentioned reaction unit providing, the wherein said model that holds is provided with spreader plate, separating liquid groove on spreader plate, and described splitter box is provided with and leads to the flow channel for liquids that holds model bottom.Flow channel for liquids can be arranged on the surface of splitter box, also can be arranged on the inside of holding model, can guarantee that nutrient solution is evenly diverted in each culture sample.Hold the thickness of model and spreader plate between 2 ~ 200 millimeters.
In the above-mentioned reaction unit providing, wherein said power-driven pump parts are peristaltic pump.Forms circulation by peristaltic pump eccentric wheel extruding silicone tube power-assist nutrient solution, can according to how many adjustment flows of fill orifice, also can the direct motion of peristaltic pump or the flow direction of the loading change nutrient solution that drives in the wrong direction.
Cavity type provided by the invention dynamically pour into biological reaction apparatus can be under multiple environment culturing cell and tissue, and can to the organizational project member of different shape and different quantities carry out in same time and equivalent environment, cultivate, in culturing process, can change as required nutrient environment, add biologically active substance, and change cultivation ambient stress and change oxygen environment.
Brief description of the drawings
Fig. 1 is the structural representation that cavity type of the present invention dynamically pours into biological reaction apparatus.
Fig. 2 is the sectional view that in the present invention, biological sample is cultivated parts.
Fig. 3 is the sectional view of the mid-sample carrier of the present invention.
Fig. 4 is the schematic diagram that holds model in the present invention.
Fig. 5 is the schematic diagram of spreader plate in the present invention.
Embodiment
The invention provides a kind of cavity type and dynamically pour into biological tissue's reaction unit, promote the propagation of cell and tissue and differentiation and formative tissue engineering component by regulating flow, stress and nutrition and the activity substance content of cell culture fluid in device, reaching.
The dynamic perfused tissue reaction unit of cavity type of the present invention is the principle of utilizing blood circulation of human body, the method that adopts dynamic liquid perfusion to cultivate, make the cell of different cell-biological support complex bodys inside in and same chamber inner at cultivated each cell-biological support complex body can obtain all the time enough and balanced nutrition, make it better carry out division growth, there is the tissue of good function or the surrogate of organ thereby form.
Come by the following examples the present invention to be described in further details, to better understand the content of the invention, but embodiment does not limit the protection domain of the invention.
Cavity type provided by the invention dynamically pours into biological reaction apparatus and comprises biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts three parts.
Biological sample is cultivated parts and is comprised upper cover body 1, container body 13 and put sample carrier 23.Upper cover body 1 is provided with the import being connected with the mobile pipe fitting of nutrient solution, and container body 13 is provided with the outlet being connected with the mobile pipe fitting of nutrient solution.The diameter of import and export and gaseous interchange mouth is between 2 ~ 100 millimeters.Upper cover body 1 is connected by thread helix with container body 13, wherein between upper cover body 1 and container body 13, is provided with the silica gel sealing pad 7 for sealing.
On container body 13 inwalls, be provided with support ring 10, make to put sample carrier 23 can frame on support ring 10.Put sample carrier upside and establish the back-up block 15 extending internally.Being provided with and holding model 22 by back-up block 15 with in putting the cavity that sample carrier 23 forms.On sample carrier 23, be provided with draw ring 8 putting, the two ends of draw ring 8 with put sample carrier 23 and be connected, be convenient to put taking of sample carrier 23.Be provided with projection 11 in the bottom of putting sample carrier 23, projection 11 matches with the groove being arranged on support ring, can prevent from putting sample carrier 23 in the interior rotation of container body 13.On the sidewall of putting sample carrier 23, be provided with and extend stopper 4, the inwall that sample carrier 4 is put in 4 laminatings of extension stopper upwards extends, and that extends the inner nutrient solution of the anti-locking apparatus of stopper 4 routs up reaction unit because rocking.
According to the requirement of cultivating, be provided with and need the cultivation of quantity through hole 25 holding on model 22, cultivate through hole 25 and be longitudinally arranged on and hold in model 22.Cultivate the sample of placing and can fix cultivation in through hole 25, nutrient solution can be arbitrarily by cultivating through hole 25.
On model 22, be provided with spreader plate 9, smaller the holding on model 22 of shape of spreader plate 9 holding.Separating liquid groove 213 on spreader plate 9, splitter box 213 is provided with and leads to the flow channel for liquids 214 that holds model 22 bottoms.Flow channel for liquids 214 can be arranged on the surface of splitter box 213, also can be arranged on the inside of holding model 9.These grooves and runner can guarantee that the nutrient solution after injection device is evenly diverted in each culture sample.
Cultivate on parts and be also provided with gaseous interchange mouth at biological sample, gaseous interchange mouth selects excellent being arranged in upper cover body 1.Gaseous interchange mouth is provided with gaseous interchange variable valve 311 and strainer 310, and strainer 310 is arranged on the exit of gaseous interchange variable valve 311, and strainer 310 can reduce bacterium in scavenging period and enter in cultivation parts.
Upper cover body 1, container body 13 and put sample carrier 23 and can all use inorganic, the organic or metallic substance of nontoxicity to make, its shape can be rectangle, semisphere, the shape such as cylindrical.Upper cover body, container body and the shape of putting sample carrier are mated mutually.
The mobile pipe fitting of nutrient solution comprises output tube 16 and input tube 20, and output tube 16 is connected with power-driven pump parts respectively with input tube 20.Input tube 20 and output tube 16 are provided with the accessories such as strainer 18, T-valve 19, silica gel extruded tube 24, and it adopts telescoping to connect, and are convenient to replacing, clean filter and load nutrient solution.Select one end of T-valve 24 to be connected with output tube, the other end is connected with power-driven pump parts, can help to load sampling observation sampling in nutritional factor or culturing process.Silica gel extruded tube has ventilation property, can complete gaseous interchange with the external world.The nutrient solution of strainer 18 filtered and recycled, can stop cell and other tangible materials of being scattered to be input in the middle of multiporous biological support.
Power-driven pump parts are selected peristaltic pump 17, by peristaltic pump eccentric wheel extruding silicone tube, nutrient solution are circulated.Can be according to the number adjustment flow of fill orifice, its flow is controlled between 0.01 ~ 50ml/h.Nutrition supplying amount and the stress of sample be can also change by peristaltic pump, propagation and the differentiation of cell and tissue affected.Peristaltic pump extruding silicone tube can direct motion or is driven in the wrong direction and load nutrient solution, and nutrient solution is flowed according to practical situation.
While using cavity type of the present invention dynamically to pour into biological tissue's reaction unit, need to carry out sterilization to the whole system except peristaltic pump.Be connected successively with the order of out splice going splice 14 according to input adapter 3, input tube 20, crossover sub 21, silica gel silica gel extruded tube 24, peristaltic pump 17, T-valve 19, strainer 18, output tube 16.When starting after peristaltic pump 17, nutrient solution enters biological sample by peristaltic pump 17, input tube 20 and cultivates parts.Under action of gravity, nutrient solution flows to the cultivation through hole 25 holding on model 22 holding to be uniformly distributed on model 9.Flow through after the culture of cultivating in through hole 25, flow to the bottom of biological sample cultivation parts, and flow out biological sample cultivation parts by out splice going splice 14, flowing by peristaltic pump 17 recirculation nutrient solutions.
Cavity type provided by the invention dynamically pours into biological reaction apparatus can be for the combined enclosed environment of cells in vitro cultivation or tissue construction, and culture apparatus of the present invention can be in common cell cultures indoor carrying out, can carry out the structure of homogeneous cell-biological support complex body of one or more, identical or different specification simultaneously, have and use simple and easy, controlled, efficient, voluminous, homogeneous and effectively avoid the advantages such as pollution that operating process causes.
Above specific embodiments of the invention be have been described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and alternative also all among category of the present invention.Therefore, equalization conversion and the amendment done without departing from the spirit and scope of the invention, all should contain within the scope of the invention.
Claims (10)
1. cavity type dynamically pours into a biological reaction apparatus, it is characterized in that, comprises biological sample cultivation parts, the mobile pipe fitting of nutrient solution and power-driven pump parts, and described biological sample is cultivated parts and is provided with the import and export that are connected with the mobile pipe fitting of nutrient solution;
Described biological sample is cultivated parts and is comprised upper cover body, container body and put sample carrier, upper cover body is connected with container body, container body inwall is provided with support ring, the described sample carrier of putting is arranged on support ring, the inner side of putting sample carrier is provided with back-up block, being provided with and holding model by back-up block with in putting the cavity that sample carrier forms, described in hold model and be provided with cultivation through hole, cultivate through hole and be longitudinally arranged on and hold in model;
The mobile pipe fitting of described nutrient solution comprises output tube and input tube, and described output tube is connected with power-driven pump parts respectively with input tube.
2. reaction unit according to claim 1, it is characterized in that, described biological sample is cultivated on parts and is also provided with gaseous interchange mouth, and described gaseous interchange mouth is provided with gaseous interchange regulated valve and strainer, and described strainer is arranged on the exit of gaseous interchange regulated valve.
3. reaction unit according to claim 1 and 2, is characterized in that, also has strainer on described output tube.
4. reaction unit according to claim 1, is characterized in that, described upper cover body is connected by thread helix with container body.
5. reaction unit according to claim 1, is characterized in that, is provided with silica gel sealing pad between described upper cover body and container body.
6. reaction unit according to claim 1, is characterized in that, described in put sample carrier and be provided with draw ring, the two ends of draw ring with put sample carrier and be connected.
7. reaction unit according to claim 1, is characterized in that, described in put sample carrier bottom be provided with projection, the groove arranging on described projection and described support ring matches.
8. reaction unit according to claim 1, is characterized in that, described in put sample carrier sidewall be provided with extension stopper, extend the inwall that stopper laminating puts sample carrier and upwards extend.
9. reaction unit according to claim 1, is characterized in that, described in hold model and be provided with spreader plate, on spreader plate, have separating liquid groove, described splitter box is provided with and leads to the flow channel for liquids that holds model bottom.
10. reaction unit according to claim 1, is characterized in that, also has T-valve on described output tube, and one end of described T-valve is connected with output tube, and the other end is connected with power-driven pump parts.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110382573.1A CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110382573.1A CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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| CN103131635A CN103131635A (en) | 2013-06-05 |
| CN103131635B true CN103131635B (en) | 2014-08-13 |
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| CN201110382573.1A Expired - Fee Related CN103131635B (en) | 2011-11-28 | 2011-11-28 | Cavity-type dynamic-filling bioreaction device |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104893973A (en) * | 2015-03-17 | 2015-09-09 | 成都军区昆明总医院 | Dynamic perfusion culture system for promoting tissue engineering products to be vascularized in vitro |
| CN104962456B (en) * | 2015-07-16 | 2017-04-05 | 中国海洋大学 | A kind of recovering device of utilization microbubble recoil concentration raceway pond microalgae cell |
| CN106010966B (en) * | 2016-06-08 | 2019-03-15 | 中山大学附属第一医院 | Multidirectional tissue engineering porous material perfusion system |
| KR102580754B1 (en) * | 2016-08-21 | 2023-09-19 | 아드바 바이오테크놀로지 리미티드 | Bioreactor and methods of use thereof |
| CN108315256B (en) * | 2018-04-26 | 2024-04-09 | 上海久博生物工程有限公司 | Active aeration component, active aeration bioreactor and cell culture device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2356041Y (en) * | 1998-12-26 | 1999-12-29 | 王朝华 | Large scale continuous cultivating device for microorganism and animal and vegetable cell |
| CN1542121A (en) * | 2003-04-29 | 2004-11-03 | 卢建熙 | 3D dynamic input type tissue reaction device |
-
2011
- 2011-11-28 CN CN201110382573.1A patent/CN103131635B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2356041Y (en) * | 1998-12-26 | 1999-12-29 | 王朝华 | Large scale continuous cultivating device for microorganism and animal and vegetable cell |
| CN1542121A (en) * | 2003-04-29 | 2004-11-03 | 卢建熙 | 3D dynamic input type tissue reaction device |
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