CN111849778A - Cell culture device and system - Google Patents
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- CN111849778A CN111849778A CN201910357345.5A CN201910357345A CN111849778A CN 111849778 A CN111849778 A CN 111849778A CN 201910357345 A CN201910357345 A CN 201910357345A CN 111849778 A CN111849778 A CN 111849778A
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- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
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Abstract
The invention provides a cell culture device and a cell culture system, in particular to a cell culture device, which comprises a first chamber and a second chamber; and a mesh separating the first chamber and the second chamber. The invention also provides a cell culture system comprising the cell culture device. The cell culture device and the cell culture system can realize large-scale and stable cell culture.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to a cell culture device and system.
Background
Regenerative medicine is developed rapidly, and tissue and organ regeneration and repair with stem cells as seeds and tumor treatment with immune cells as carriers are the most rapid development directions of regenerative medicine. The automated culture and large-scale culture of regenerative medicine seed cells are bottlenecks which restrict the clinical application of cell medicines, and at present, a large amount of seed cells with good stability and uniformity are still difficult to obtain. In addition, lentivirus is the main gene editing vector in cell therapy at present, and how to produce lentivirus in large scale is also an important challenge at present.
Currently, in the field of cell culture, cell culture bags and hollow fibers are the main options for automated cell culture. However, when cells are cultured using a hollow fiber culture apparatus, the state of the cells cannot be observed in real time, the cell density is difficult to control reasonably, and the price is expensive. The cell culture bag is used for cell culture, the requirement of stabilizing cells in a microenvironment is difficult to meet, and the defects that the suspension cells are difficult to automate for liquid change and passage exist.
Therefore, those skilled in the art have made efforts to develop a cell culture apparatus which can stably culture cells in a large scale, and which is easy to use and low in cost.
Disclosure of Invention
The invention aims to provide a cell culture device and a cell culture system.
In a first aspect of the invention, there is provided a cell culture device comprising a first chamber and a second chamber; and a mesh separating the first chamber and the second chamber.
In another preferred example, the first chamber is configured to contain a cell culture fluid; the second chamber is configured to culture cells; the mesh is configured to block cells cultured in the second chamber from entering the first chamber.
In another preferred example, the first chamber is communicated with the outside through a first chamber inlet and a first chamber outlet; and/or the second chamber is communicated with the outside through a second chamber inlet and a second chamber outlet.
In another preferred embodiment, the cell culture apparatus comprises a closed body which is communicated with the outside only through the first chamber inlet, the first chamber outlet, the second chamber inlet and the second chamber outlet; the first and second chambers are located inside the body; the first and second chambers are separated by a mesh screen.
In another preferred example, the mesh screen is a molecular sieve made of a polymer material, which allows the culture solution to pass through freely, but does not allow the cells to pass through.
In another preferred example, the mesh size is 500 to 10000 meshes, preferably 3000 to 8000 meshes; more preferably 4000 to 6000 mesh.
In another preferred embodiment, the cell culture device is made of a biocompatible material.
In another preferred embodiment, the interior of the body of the cell culture apparatus is horizontally partitioned by the mesh screen and thereby forms the first chamber above the mesh screen and the second chamber below the mesh screen.
In another preferred embodiment, the mesh screen is pleated. A corrugated mesh may increase the area of fluid exchange between the first and second chambers.
In another preferred embodiment, the cell culture device has a connection mechanism configured to connect with another cell culture device; and when the two cell culture devices are connected, the first chambers of the two cell culture devices are communicated through a flow channel, and the second chambers of the two cell culture devices are communicated through another flow channel.
In another preferred example, one end of the cell culture apparatus has a convex portion, and the other end of the cell culture apparatus has a concave portion; wherein the convex portion of the cell culture apparatus is capable of mating with the concave portion of another cell culture apparatus to thereby enable connection of two or more cell culture apparatuses.
In another preferred example, the convex part is provided with a liquid flow channel communicated with the first chamber and a liquid flow channel communicated with the second chamber; the recess is provided with a flow passage communicating with the first chamber and a flow passage communicating with the second chamber.
In another preferred example, the top surface of the convex part is provided with a groove, and the groove is communicated with the liquid flow channel of the convex part; the liquid flow channel of the concave part protrudes out of the bottom surface of the concave part and can be matched with the groove.
In another preferred example, the flow channel entering and exiting from the first chamber and/or the flow channel entering and exiting from the second chamber is a graded distributed flow channel.
In a second aspect of the invention, there is provided a cell culture system comprising a cell culture unit comprising a cell culture device according to the first aspect of the invention.
In another preferred embodiment, the cell culture unit comprises a plurality of cell culture devices according to the first aspect of the invention, which are connected in series, wherein the first chambers of adjacent cell culture devices are connected by a flow channel, and the second chambers of adjacent cell culture devices are connected by a flow channel.
In another preferred embodiment, the cell culture unit comprises 2 to 200 cell culture devices according to the first aspect of the present invention, which are connected in series; preferably, 5 to 100 cell culture devices according to the first aspect of the invention are included in series.
In another preferred example, the cell culture system further comprises a feed liquid control unit, wherein the feed liquid control unit comprises a first feed liquid container and a second feed liquid container; the feed liquid inlet of the first feed liquid container is communicated with the first cavity outlet of the first cavity of the cell culture device, and the feed liquid outlet of the first feed liquid container is communicated with the first cavity inlet of the first cavity of the cell culture device, so that a first flow path is formed; and the feed liquid inlet of the second feed liquid container is communicated with the second cavity outlet of the second cavity of the cell culture device, and the feed liquid outlet of the second feed liquid container is communicated with the second cavity inlet of the second cavity of the cell culture device, so that a second flow path is formed.
In another preferred example, a pump for driving a liquid flow is provided in the first flow path and/or the second flow path.
In another preferred embodiment, a valve for controlling the flow of liquid is provided in the first flow path and/or the second flow path.
In another preferred example, the cell culture system comprises a cell culture unit and a feed liquid control unit which are separated from each other in space, and the cell culture unit is communicated with the feed liquid control unit through a pipeline.
In a further preferred embodiment, the cell culture unit has a temperature regulating mechanism which is provided for controlling the temperature within the cell culture unit.
In another preferred example, the feed liquid control unit is provided with a humidity adjusting mechanism, a temperature adjusting mechanism and a gas proportion adjusting mechanism; the humidity control mechanism is used for controlling the humidity in the feed liquid control unit; the temperature adjusting mechanism is used for controlling the temperature in the feed liquid control unit; the gas ratio adjustment mechanism is provided for adjusting the gas concentration ratio of oxygen, carbon dioxide, and/or nitrogen.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
FIG. 1 shows a schematic view of a cell culture apparatus according to a preferred embodiment of the present invention.
FIG. 2 shows a schematic diagram of the assembly structure of two cell culture devices according to the preferred embodiment of the present invention.
FIG. 3 is a schematic view showing the structure of a cell culture apparatus according to another preferred embodiment of the present invention.
FIG. 4 is an enlarged view showing the structure of the stepwise distributed flow channels of the cell culture apparatus according to the preferred embodiment of the present invention.
FIG. 5 shows the cell culture apparatus according to the alternative embodiment of the present invention in a ready-to-connect state.
FIG. 6 shows a schematic diagram of a cell culture system according to a preferred embodiment of the present invention.
Detailed Description
The present inventors have made extensive and intensive studies to obtain a cell culture apparatus and a cell culture system. The cell culture device of the invention is provided with a liquid flow system with an upper layer and a lower layer, and the middle parts of the liquid flow system are communicated with each other through a mesh screen membrane which does not allow cells to pass; the cell culture apparatus of the present invention can be freely assembled to be suitable for free-scale amplification and automated culture of cells.
It should be noted that in the description herein, the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, which are only for convenience of describing the present invention and simplifying the description, but do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
The main advantages of the invention are:
(1) the cell culture device is simultaneously suitable for culturing adherent cells and suspension cells, and can be used for co-culturing two or more cells.
(2) The invention can meet the requirement of adherent cells on a relatively stable microenvironment, and can also achieve the purpose of continuously replacing new and old culture solutions, and the cell culture unit and the gas-liquid exchange unit are separately arranged and are easier to control.
(3) The gas-liquid exchange mode adopts an open material liquid chamber to be directly arranged in the material liquid control device, and is technically easier to implement.
(4) The modular structure can realize the amplification of any integral multiple, is easy to adjust the cell density, obtains the optimal cell growth density requirement, and has obvious advantages compared with the fixed capacity of the existing automatic culture system.
(5) Can observe the cell state in real time, and is easier to control the cell state than a hollow fiber culture system.
(6) The device is also suitable for plasmid or virus transfection of cultured cells, and ensures the uniformity and the relative stability of a cell growth microenvironment during liquid change.
The present invention will be described in further detail with reference to the following examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
Example 1
As shown in fig. 1, the cell culture apparatus provided in this embodiment is a place where cells are cultured, and includes a first chamber 1 and a second chamber 2; and a mesh 3 separating the first chamber 1 and the second chamber 2. The first chamber 1 is provided for containing a cell culture fluid; the second chamber 2 is configured for culturing cells; the mesh 3 is arranged to block cells cultured in the second chamber 2 from entering the first chamber 1. The first chamber 1 is a space for containing a fresh culture solution or an exchanged culture solution, and the second chamber 2 is a space for the existence and growth of cells. The mesh 3 is located between the first chamber 1 and the second chamber 2 to separate the first chamber 1 and the second chamber 2, the fresh culture solution in the first chamber 1 enters the second chamber 2 through the pores of the mesh 3, and the cells in the second chamber 2 can hardly pass through the mesh 3 to enter the first chamber 1. Through the pore canal on the mesh screen 3, the first chamber 1 and the second chamber 2 can exchange liquid, supplement nutrients required by the cells in the second chamber 2, and take away metabolic waste of the cells, thereby ensuring the normal growth of the cells.
In this embodiment, the first chamber 1 is communicated with the outside through a first chamber inlet 11 and a first chamber outlet 12; the second chamber 2 communicates with the outside via a second chamber inlet 21 and a second chamber outlet 22. In this case, the cell culture apparatus of the present embodiment includes a sealed body communicating with the outside only through the first chamber inlet 11, the first chamber outlet 12, the second chamber inlet 21, and the second chamber outlet 22; the first chamber 1 and the second chamber 2 are located inside the body; the first chamber 1 and the second chamber 2 are separated by a mesh 3.
The size of the mesh screen 3 in the embodiment is 500 meshes to 10000 meshes, preferably 3000 meshes to 8000 meshes; more preferably 4000 to 6000 mesh.
In other embodiments, the mesh 3 may be a molecular sieve made of a polymer material, which allows the culture solution to pass through freely, but does not allow the cells to pass through.
As shown in FIG. 1, the inside of the body of the cell culture apparatus is horizontally partitioned by the mesh 3 and thereby the first chamber 1 located above the mesh 3 and the second chamber 2 located below the mesh 3 are formed.
In the large-scale cell culture process, the large-scale culture of cells can be realized by communicating a plurality of cell culture devices. As shown in fig. 1 and 2, the cell culture apparatus has a connection mechanism configured to connect with another cell culture apparatus; and when the two cell culture devices are connected, the first chambers 1 of the two cell culture devices are communicated through the flow channel, and the second chambers 2 of the two cell culture devices are communicated through the flow channel. In this embodiment, the connection mechanism includes a convex portion 41 provided at one end of the cell culture apparatus, and a concave portion 42 provided at the other end of the cell culture apparatus; as shown in FIG. 2, the convex portion 41 of the cell culture apparatus can be engaged with the concave portion 42 of another cell culture apparatus, thereby connecting two or more cell culture apparatuses.
Referring to fig. 1, one end of the convex portion 41 is provided with a liquid flow channel 111 communicating with the first chamber 1, and a liquid flow channel 211 communicating with the second chamber 2; the recess 42 is provided at one end with a flow channel 121 communicating with the first chamber 1 and a flow channel 221 communicating with the second chamber 2.
The openings of the liquid flow channel 111 and the liquid flow channel 211 on the top surface of the convex part 41 are in a groove structure, namely a groove 411; the openings of the liquid flow channel 121 and the liquid flow channel 221 at one end of the concave part 42 protrude from the bottom surface of the concave part 42 to form a protruding end 421, the protruding end 421 can be matched with the groove 411, and the protruding ends 421 can be correspondingly inserted into the groove 411 to form a sealing structure when being combined.
The cell culture apparatus provided in this embodiment is formed by using a biocompatible material, preferably a transparent material, as the material of all the components. The total volume of the cell culture apparatus body is usually 0.1 to 1L, preferably 0.3 to 0.5L. Wherein the volume of the first chamber is 0.05-0.5L, preferably 0.15-0.25L.
Example 2
The cell culture apparatus provided in this example has the same basic structure as that of example 1, except that the flow channel into and out of the first chamber 1 and the flow channel into and out of the second chamber 2 are graded and distributed flow channels. Referring to fig. 3 and 4, the end of the liquid flow channel 111, which communicates with the first chamber 1, is a stepped distributed liquid flow channel 5, and liquid flows into the first chamber 1 through a tree-shaped stepped distributed liquid flow channel, so that stable and uniform pressure of the liquid flow can be ensured. As shown in FIG. 4, the enlarged structure of the graded distribution type flow channel 5 is that the graded distribution type flow channel 5 is a tree-shaped branched flow channel through which the liquid can be gradually gathered or dispersed.
As shown in FIG. 3, in a preferred embodiment, the mesh in the cell culture apparatus of the present invention is corrugated, for example, may be corrugated. A corrugated mesh may increase the area of fluid exchange between the first and second chambers.
Example 3
The present embodiment provides a cell culture system, which comprises a cell culture unit 01, as shown in fig. 5 and 6, wherein the cell culture unit 01 comprises a plurality of cell culture devices of the present invention which are communicated in sequence, wherein the first chambers of adjacent cell culture devices are communicated through a flow channel, and the second chambers of adjacent cell culture devices are communicated through a flow channel. As shown in FIG. 5, 3 cell culture apparatuses according to the present invention are shown in a state to be connected.
As shown in fig. 6, the cell culture system further comprises a feed liquid control unit 02, wherein the feed liquid control unit 02 comprises a first feed liquid container 021 and a second feed liquid container 022; the feed liquid outlet 0211 of the first feed liquid container 021 is communicated with the first cavity chamber inlet of the first cavity chamber of the cell culture device, and the feed liquid inlet 0212 of the first feed liquid container 021 is communicated with the first cavity chamber outlet of the first cavity chamber of the cell culture device, so that a first flow path is formed; a second channel is formed by communicating a feed liquid outlet 0221 of the second feed liquid container 022 with a second chamber inlet of the second chamber of the cell culture apparatus, and communicating a feed liquid inlet 0222 of the second feed liquid container 022 with a second chamber outlet of the second chamber of the cell culture apparatus.
In this embodiment, a pump 04 for driving a liquid flow is provided in the first flow path and/or the second flow path; and a valve 05 to control the flow of liquid.
The first flow path is a culture solution flow path, which is a flow path of fresh culture solution or treated culture solution for recycling, and in the using process, the culture solution flows out from a solution outlet 0211 of the first solution container 021, enters the first chamber through a first chamber inlet of the first cell culture device in the cell culture unit 01 through a pipeline, sequentially flows through the first chambers of the cell culture devices in the cell culture unit 01, flows out of the cell culture unit 01 through a first chamber outlet of the last cell culture device, and circularly flows back to the first solution container 021 from a solution inlet 0212 of the first solution container 021 through a pipeline.
The second flow path is a cell fluid flow path which is a flow path of a cell fluid containing cells to be cultured, and is normally closed during the cell culture; when cell flow is desired, such as at the time of cell inoculation or at the end of cell culture harvest, the flow path is activated, and the cell fluid in the second chamber of each cell culture apparatus of the cell culture unit 01 flows out from the second chamber outlet of the last cell culture apparatus, enters the second feed liquid container 022 through the feed liquid inlet 0222 of the second feed liquid container 022, and in case circulation is desired, the cell fluid in the second feed liquid container 022 can flow out through the feed liquid outlet 0221 thereof, and enters the cell culture unit 01 through the second chamber inlet of the first cell culture apparatus, thereby forming a circulation loop.
The tubing used for each flow path in this embodiment may be conventional medical tubing.
In this embodiment, the first material liquid container 021 and the second material liquid container 022 may be provided with a pipeline for communication, and a valve 05 may be provided on the pipeline.
The cell culture system provided by the embodiment comprises a cell culture unit 01 and a feed liquid control unit 02 which are separated from each other in space, wherein the cell culture unit 01 is communicated with the feed liquid control unit 02 through a pipeline.
Generally, the cell culture unit 01 has a closed chamber structure and has a temperature control mechanism capable of controlling the temperature at which the cell culture unit is located to be the optimum temperature for cell culture.
Generally, the feed liquid control unit 02 is a closed cavity structure, and has a humidity adjusting mechanism, a temperature adjusting mechanism, and a gas proportion adjusting mechanism; the humidity control mechanism can control the humidity of the feed liquid control unit 02, for example, the humidity is controlled to be saturated; the temperature adjusting mechanism can control the temperature of the feed liquid control unit 02; the gas proportion adjusting mechanism is used for adjusting the gas concentration proportion of oxygen, carbon dioxide and nitrogen.
The first feed liquid container 021 and/or the second feed liquid container 022 of the feed liquid control unit 02 may be respectively provided with a cover which can be covered, and usually, the first feed liquid container 021 and/or the second feed liquid container 022 are opened to meet the requirement of gas exchange. The gas concentration ratio inside the liquid material control unit 02 is adjusted by the gas ratio adjusting mechanism, and the liquid in the first liquid material container 021 and the second liquid material container 022 inside the liquid control unit 02 can exchange gas through liquid-gas interfaces so as to meet the requirement of normal growth of cells.
Of course, the liquid in the first feed liquid container and/or the second feed liquid container of the cell culture system can be replaced as required during use.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Claims (10)
1. A cell culture device, comprising a first chamber and a second chamber; and a mesh separating the first chamber and the second chamber.
2. The cell culture assembly of claim 1 wherein the first chamber is configured to receive a cell culture fluid; the second chamber is configured to culture cells; the mesh is configured to block cells cultured in the second chamber from entering the first chamber.
3. The cell culture assembly of claim 1 wherein the first chamber is in communication with the ambient via a first chamber inlet and a first chamber outlet; and/or the second chamber is communicated with the outside through a second chamber inlet and a second chamber outlet.
4. The cell culture apparatus of claim 1, wherein the cell culture apparatus comprises a closed body communicating with the outside only through the first chamber inlet, the first chamber outlet, the second chamber inlet, and the second chamber outlet; the first and second chambers are located inside the body; the first and second chambers are separated by a mesh screen.
5. The cell culture apparatus of claim 1 wherein the interior of the body of the cell culture apparatus is horizontally partitioned by the mesh screen and thereby forms the first chamber above the mesh screen and the second chamber below the mesh screen.
6. The cell culture assembly of claim 1, wherein the cell culture assembly has an attachment mechanism configured to attach to another cell culture assembly; and when the two cell culture devices are connected, the first chambers of the two cell culture devices are communicated through a flow channel, and the second chambers of the two cell culture devices are communicated through another flow channel.
7. The cell culture apparatus according to claim 6, wherein one end of the cell culture apparatus has a convex portion and the other end of the cell culture apparatus has a concave portion; wherein the convex portion of the cell culture apparatus is capable of mating with the concave portion of another cell culture apparatus to thereby enable connection of two or more cell culture apparatuses.
8. A cell culture system comprising a cell culture unit comprising the cell culture apparatus of claim 1.
9. The cell culture system of claim 8, wherein the cell culture unit comprises a plurality of sequentially communicating cell culture devices of claim 1, wherein first chambers of adjacent cell culture devices are in communication via a flow channel and second chambers of adjacent cell culture devices are in communication via a flow channel.
10. The cell culture system of claim 9, further comprising a first feed solution container and a second feed solution container; the feed liquid inlet of the first feed liquid container is communicated with the first cavity outlet of the first cavity of the cell culture device, and the feed liquid outlet of the first feed liquid container is communicated with the first cavity inlet of the first cavity of the cell culture device, so that a first flow path is formed; and the feed liquid inlet of the second feed liquid container is communicated with the second cavity outlet of the second cavity of the cell culture device, and the feed liquid outlet of the second feed liquid container is communicated with the second cavity inlet of the second cavity of the cell culture device, so that a second flow path is formed.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115747060A (en) * | 2022-11-30 | 2023-03-07 | 苏州大学 | Universal organ chip module and three-dimensional multi-organ chip |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0155237A2 (en) * | 1984-03-15 | 1985-09-18 | MBR Bio Reactor AG | Process and apparatus for the culture of human, animal, plant and hybrid cells and microorganisms |
| CN1290744A (en) * | 1999-12-09 | 2001-04-11 | 中国科学院力学研究所 | Spacial dialyzing counterflow cell cultivator and cultivating method |
| US20030017142A1 (en) * | 1999-06-21 | 2003-01-23 | The General Hospital Corporation, A Massachusetts Corporation | Cell culture systems and methods for organ assist devices |
| JP2004147555A (en) * | 2002-10-30 | 2004-05-27 | Foundation For The Promotion Of Industrial Science | Cell culture apparatus, bioreactor and cell culture chamber |
| US20140308688A1 (en) * | 2011-12-08 | 2014-10-16 | Research Triangle Institute | Human emulated response with microfluidic enhanced systems |
| CN104893975A (en) * | 2015-05-28 | 2015-09-09 | 深圳富利鑫健康产业发展有限公司 | Both-chamber permselectivity cell culture device and application thereof |
| CN106544270A (en) * | 2016-12-06 | 2017-03-29 | 北京理工大学 | A kind of micro-fluidic chip and its cell culture processes for co-culture of cells |
| WO2018057769A1 (en) * | 2016-09-22 | 2018-03-29 | Corning Incorporated | Gravity flow cell culture devices, systems and methods of use thereof |
| CN108779421A (en) * | 2016-03-08 | 2018-11-09 | 国立研究开发法人产业技术综合研究所 | Cell culture apparatus and cell culture processes |
| CN109266548A (en) * | 2018-10-11 | 2019-01-25 | 广州洁特生物过滤股份有限公司 | A kind of dynamic cell culture device and cell culture system |
-
2019
- 2019-04-29 CN CN201910357345.5A patent/CN111849778B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0155237A2 (en) * | 1984-03-15 | 1985-09-18 | MBR Bio Reactor AG | Process and apparatus for the culture of human, animal, plant and hybrid cells and microorganisms |
| US20030017142A1 (en) * | 1999-06-21 | 2003-01-23 | The General Hospital Corporation, A Massachusetts Corporation | Cell culture systems and methods for organ assist devices |
| CN1290744A (en) * | 1999-12-09 | 2001-04-11 | 中国科学院力学研究所 | Spacial dialyzing counterflow cell cultivator and cultivating method |
| JP2004147555A (en) * | 2002-10-30 | 2004-05-27 | Foundation For The Promotion Of Industrial Science | Cell culture apparatus, bioreactor and cell culture chamber |
| US20140308688A1 (en) * | 2011-12-08 | 2014-10-16 | Research Triangle Institute | Human emulated response with microfluidic enhanced systems |
| CN104893975A (en) * | 2015-05-28 | 2015-09-09 | 深圳富利鑫健康产业发展有限公司 | Both-chamber permselectivity cell culture device and application thereof |
| CN108779421A (en) * | 2016-03-08 | 2018-11-09 | 国立研究开发法人产业技术综合研究所 | Cell culture apparatus and cell culture processes |
| WO2018057769A1 (en) * | 2016-09-22 | 2018-03-29 | Corning Incorporated | Gravity flow cell culture devices, systems and methods of use thereof |
| CN106544270A (en) * | 2016-12-06 | 2017-03-29 | 北京理工大学 | A kind of micro-fluidic chip and its cell culture processes for co-culture of cells |
| CN109266548A (en) * | 2018-10-11 | 2019-01-25 | 广州洁特生物过滤股份有限公司 | A kind of dynamic cell culture device and cell culture system |
Non-Patent Citations (1)
| Title |
|---|
| 陆鑫盛 上海：上海科学技术文献出版社: "气动自动化系统的优化设计", pages: 227 - 229 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115747060A (en) * | 2022-11-30 | 2023-03-07 | 苏州大学 | Universal organ chip module and three-dimensional multi-organ chip |
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