Cell culture device capable of synchronous culture medium replacement

Abstract

The present invention relates to the technical field of microbial culture, and discloses a cell culture device capable of synchronously replacing culture medium, comprising: a box body, comprising a plate body and a surrounding plate, wherein the surrounding plate and the upper surface of the plate body form a main pool capable of accommodating culture medium; a base hole, which is opened on the upper plate surface of the plate body, and the base holes include a plurality of base holes, which are arranged in a matrix; a filter cartridge, wherein a filter cartridge is provided above each base hole, and a downstream flow gap is provided on the cartridge wall of the filter cartridge on at least the downstream side; a sinking cavity is provided on the upper plate surface of the plate body on the upstream side of each base hole, and an upstream hole wall is defined between the sinking cavity and the base hole, and a first upstream flow gap is provided on the upstream hole wall; a water dam is provided between each two adjacent filter cartridges, and adjacent rows of water dams and filter cartridges separate the main pool into pool units, and each row of water dams enables the culture medium in the pool unit to actively flow to the sinking cavity and enter the base hole through the first upstream flow gap.

Description

Technical Field

[0001] The present invention relates to the technical field of microbial culture, in particular to a cell culture device capable of synchronously replacing culture medium. Background Art

[0002] As is known to all, a typical device capable of culturing a large number of cells simultaneously is a well plate (or microwell plate). Specifically, the well plate comprises a plate body and a large number of base wells provided on the plate body. Culture medium is injected into each base well, and cells to be cultured are implanted into the base wells. Thus, a large number of cells can be cultured simultaneously using the numerous base wells of the well plate.

[0003] The above-mentioned well plates in the prior art have the following drawbacks for culturing cells: the wells are independent of each other. When the culture medium needs to be replaced, a device with multiple needles arranged in a consistent pattern must be used to simultaneously aspirate and inject the culture medium into each well. Otherwise, a single needle must be used to aspirate and inject the culture medium into each well in sequence. Therefore, the well plates with the above-mentioned structure require specialized and expensive equipment to complete the culture medium replacement, and the well plates must be placed in the environment where the equipment is located. In addition, in some cases, for example, if the cells are small in size, when the culture medium is replaced by aspiration using a needle, the cells may be simultaneously sucked into the needle, resulting in the undesirable removal of the cells.

[0004] To overcome these drawbacks, a well plate has emerged in the prior art for facilitating culture medium replacement (or transfer). Specifically, this well plate improves upon conventional well plates by connecting each matrix-arranged column (row) of wells via a fluid channel. Specifically, a fluid channel connecting two adjacent wells in each column (row) is machined between them. This allows medium removal by aspirating from the rear of each column (row) or by tilting the well plate to direct medium from each well toward the rear. Furthermore, medium replacement can be achieved by injecting medium into the wells at the head, gradually dispensing it into each well.

[0005] However, the improved well plates in the prior art still have the following defects during use: when removing culture medium using fluid channels and injecting culture medium into base wells, cells in some base wells may be transferred to other base wells along with the culture medium, or even flow out of the plate wells along with the culture medium, resulting in undesirable removal of cells. Summary of the Invention

[0006] In view of the above technical problems existing in the prior art, the present invention provides a cell culture device capable of synchronously replacing culture medium.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0008] A cell culture device capable of synchronously replacing culture medium, comprising:

[0009] The box body comprises a rectangular plate body and a surrounding plate arranged around the side of the plate body, wherein the surrounding plate and the upper surface of the plate body form a main pool capable of accommodating culture medium;

[0010] Basal holes are provided on the upper surface of the plate body, and the basal holes include a plurality of basal holes, and the basal holes are arranged in a matrix so that the culture medium flows along the row arrangement direction of the basal holes;

[0011] A filter cartridge is provided above each base hole, and a downstream flow gap is provided on at least the downstream side of the filter cartridge wall; wherein:

[0012] A sinking cavity is formed on the upper plate surface of the plate body on the upstream side of each base hole, an upstream hole wall is defined between the sinking cavity and the base hole, and a first upstream flow gap is formed on the upstream hole wall;

[0013] A water dam is provided between each adjacent two filter cartridges in each row of the filter cartridges. The water dams and filter cartridges in adjacent rows separate the main pool into pool units. The water dams in each row allow the culture medium in the pool unit to actively flow toward the sinking cavity and enter the base hole through the first upstream flow gap.

[0014] Preferably, the flow cross-section defined by the downstream flow gap allowing the medium to pass through is larger than the flow cross-section defined by the first upstream flow gap allowing the medium to pass through.

[0015] Preferably, a second upstream flow gap is provided on the upstream wall of the filter cartridge, and the flow cross-section defined by the second upstream flow gap allowing the culture medium to pass through is smaller than the flow cross-section defined by the first upstream flow gap allowing the culture medium to pass through.

[0016] Preferably, the sum of the flow cross-sections of the first upstream flow gap and the second upstream flow gap is smaller than the flow cross-section of the downstream flow gap.

[0017] Preferably, the width of the first upstream flow gap gradually increases from top to bottom, and the lower end of the first upstream flow gap is configured as a blunted arc portion.

[0018] Preferably, the height of the water retaining dam in each row is higher than the height of the filter cartridges in the row.

[0019] Preferably, the matrix-arranged water retaining dams and the matrix-arranged filter cartridges are integrally formed from plastic material by injection molding or laser etching.

[0020] Preferably, the cell culture device capable of synchronously replacing culture medium further comprises a transferable component, wherein the transferable component comprises a mesh body and a plurality of culture baskets, wherein the mesh body is used to be attached to the upper surface of the plate body, and the mesh body has hollow portions corresponding one to one with the base holes, and the culture baskets are arranged correspondingly below the hollow portions and attached to the mesh body, and the culture baskets extend into the base holes, and the cells are located in the culture baskets.

[0021] Preferably, a liquid inlet interface and a liquid outlet interface are respectively arranged on the two opposite enclosures.

[0022] Preferably, the upper portion of the box body is detachably covered with a transparent cover.

[0023] Compared with the prior art, the cell culture device capable of synchronously replacing culture medium provided by the present invention has the following beneficial effects:

[0024] By arranging intercepting components that alternately arrange water dams and filter cartridges in the main pool of the box body, and by arranging a sinking cavity upstream of each base hole, and opening a downstream slit on the downstream wall of the filter cartridge and an upstream slit on the upstream wall of the base hole, the culture medium is forced to flow downward preferentially and enter the base hole, thereby significantly improving the replacement efficiency of the culture medium around the cells without causing undesirable migration of the cells.

[0025] This disclosure is an overview of various implementations or examples of the technology, and is not a comprehensive disclosure of the full scope or all features of the disclosed technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In the drawings, which are not necessarily drawn to scale, the same reference numerals may describe similar components in different views. The same reference numerals with letter suffixes or different letter suffixes may represent different instances of similar components. The accompanying drawings generally illustrate various embodiments by way of example and not limitation, and together with the description and claims, serve to illustrate the embodiments of the invention. Where appropriate, the same reference numerals are used throughout the drawings to refer to the same or similar parts. Such embodiments are illustrative and are not intended to be exhaustive or exclusive of the embodiments of the present apparatus or method.

[0027] Figure 1 This is a top view of the cell culture device capable of synchronously replacing culture medium provided by the present invention.

[0028] Figure 2 for Figure 1 An enlarged view of detail B.

[0029] Figure 3 for Figure 1 AA section view.

[0030] Figure 4 for Figure 3 An enlarged view of a portion C.

[0031] Reference numerals:

[0032] 10-Box body; 20-Plate body; 21-Base hole; 22-Upstream hole wall; 23-Sinking cavity; 31-Rear panel; 32-Front panel; 33-Side panel; 34-Main pool; 35-Pool unit; 40-Filter cartridge; 50-Water retaining dam; 61-Downstream flow gap; 62-First upstream flow gap; 63-Second upstream flow gap; 71-Liquid inlet interface; 72-Liquid outlet interface; 80-Transparent cover; 90-Transferable component; 91-Mesh body; 92-Culture basket. DETAILED DESCRIPTION

[0033] Unless otherwise defined, the technical or scientific terms used in the present invention shall have the usual meanings understood by persons of ordinary skill in the field to which the present invention belongs. The words "first", "second" and similar terms used in the present invention do not indicate any order, quantity or importance, but are only used to distinguish different components. Words such as "include" or "comprise" mean that the elements or objects preceding the word include the elements or objects listed after the word and their equivalents, without excluding other elements or objects. Words such as "connect" or "connected" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative positional relationships. When the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0034] In order to keep the following description of the embodiments of the present invention clear and concise, detailed descriptions of known functions and known components are omitted.

[0035] like Figures 1 to 4 As shown, the present invention discloses a cell culture device, which can culture a large number of cells simultaneously by configuring a plurality of base holes 21. The culture device includes: a box body 10, a transferable component 90, an intercepting component and a transparent cover 80.

[0036] The box body 10 includes a rectangular plate body 20, and a front panel 32, a rear panel 31, and two side panels 33 arranged around the four sides of the plate body 20. The front panel 32, the rear panel 31, the two side panels 33, and the upper surface of the plate body 20 together form a main pool 34 for accommodating culture medium. The rear panel 31 (or upstream panel) is provided with a liquid inlet port 71 that communicates with the main pool 34, and the front panel 32 (or downstream panel) is provided with a liquid outlet port 72 that communicates with the main pool 34. When the culture medium needs to be replaced, the new culture medium enters the main pool 34 through the liquid inlet port 71, then flows through the main pool 34 and out of the liquid outlet port 72.

[0037] The plate body 20 can be made of a biocompatible material, for example, a biocompatible high molecular polymer by injection molding, or can be made of a biocompatible alloy material, for example, a titanium alloy. Preferably, the plate body 20 is made of a biocompatible high molecular polymer by injection molding.

[0038] The upper surface of the plate body 20 is defined by numerous basal holes 21, arranged in a matrix of multiple rows and columns. These basal holes 21 are arranged in rows in the direction of the front and rear panels 32 and 31, and new culture medium passes through each row of basal holes 21 in sequence. A sinking cavity 23 is defined in the upper surface of the plate body 20 upstream of each basal hole 21 in each row. This sinking cavity 23 does not extend through the basal hole 21, but rather, together with the basal hole 21, defines an upstream hole wall 22. The basal holes 21 and sinking cavity 23 can be integrally injection-molded with the plate body 20, or they can be engraved.

[0039] A plurality of first upstream flow slits 62 are formed on the upstream pore wall 22 of the base pore 21, allowing culture medium entering the sinking cavity 23 to enter the base pore 21 through the first upstream flow slits 62. Preferably, the first upstream flow slits 62 are formed by engraving. Preferably, the width of the first upstream flow slits 62 gradually increases from top to bottom, making it easier for culture medium to enter the bottom of the base pore 21 from the lower portion of the upstream pore wall 22. More preferably, the lower end of the first upstream flow slit 62 is processed into an arc-shaped passivation portion to prevent this area from being blocked by impurities.

[0040] The interception component includes a plurality of filter cartridges 40 and water dams 50. Each base hole 21 is provided with a filter cartridge 40. Thus, the filter cartridges 40 are arranged in a matrix in multiple rows and columns. A water dam 50 is arranged between each adjacent filter cartridge 40 in each row. Thus, the filter cartridges 40 and water dams 50 in each row are arranged alternately. Moreover, pool units 35 are defined between each adjacent row of filter cartridges 40 and water dams 50. Thus, the main pool 34 is divided into multiple pool units 35 arranged along the flow direction of the culture medium. When the culture medium needs to be replaced, the filter cartridges 40 and water dams 50 in the same row have an interception effect on the culture medium upstream thereof, forcing the culture medium to enter the sinking cavity 23 corresponding to each base hole 21 and enter the base hole 21 through the first upstream flow gap 62 of the upstream hole wall 22 for replacing the culture medium in the base hole 21.

[0041] Each filter cartridge 40 has a plurality of downstream flow slots 61 formed on its downstream wall. Apparently, the height of these downstream flow slots 61 is higher than that of the first upstream flow slots 62. This allows the culture medium that enters the base pore 21 through the first upstream flow slots 62 to move upward and then flow out of the downstream flow slots 61. However, the cells in the base pore 21 are intercepted by the filter cartridge 40 wall, preventing unwanted migration. Thus, without causing unwanted cell migration, the replacement rate of the culture medium in the base pore 21 is significantly increased. Preferably, the matrix-arranged filter cartridges 40 and the matrix-arranged water retaining dams 50 are integrally injection-molded from a plastic material. Thus, the intercepting components can be detachably mounted in the main sump 34, which facilitates cleaning of the main sump 34 of the cartridge body 10.

[0042] The transferable component 90 comprises a mesh body 91 and a plurality of culture baskets 92 arranged in a matrix and attached to the bottom of the mesh body 91. The mesh body 91 is attached to the upper surface of the plate 20 and has hollow portions corresponding to the basal holes 21. The culture baskets 92 are attached to the bottom of the hollow portions. Thus, the culture baskets 92 are positioned within the basal holes 21, and cells are cultured in the culture baskets 92. When it is necessary to transfer the cells in each basal hole 21 en masse, the intercepting component is first removed. Then, the transferable component 90 can be transferred to achieve the transfer of the cells en masse.

[0043] The transparent cover 80 is used to cover the box body 10 and is located above each basal well 21. The transparent cover 80 can be made of inorganic glass or organic glass. The transparent cover 80 can block interference from external air and impurities and facilitate observation of the growth of cells in each basal well 21.

[0044] In some preferred embodiments, a plurality of second upstream flow slits 63 are provided on the wall of the upstream side of each filter cartridge 40, so that a portion of the upstream culture medium enters the lower middle portion of the base hole 21 through the sinking cavity 23 and the first upstream flow slits 62, while another portion passes through the area above the base hole 21 through the second upstream flow slits 63 to replace the culture medium above the base hole 21.

[0045] In some preferred embodiments, the flow cross-section defined by all the first upstream flow gaps 62 allowing the culture medium to pass through is larger than the flow cross-section defined by all the second upstream flow gaps 63 allowing the culture medium to pass through, which allows more culture medium to enter the base pore 21 through the first upstream flow gaps 62, thereby allowing the culture medium around the cells to be replaced more efficiently.

[0046] In some preferred embodiments, the sum of the flow cross-sections of all first upstream flow gaps 62 and all second upstream flow gaps 63 is smaller than the flow cross-sections of all downstream flow gaps 61. In this way, when replacing the culture medium, the liquid level of the culture medium in the filter cartridge 40 is always lower than the liquid level of the culture medium upstream of the flow cartridge, thereby further improving the replacement efficiency of the culture medium in the base hole 21 and above it.

[0047] In some preferred embodiments, the height of the dam 50 is higher than that of the filter cartridge 40 , so that the culture medium in each pool unit 35 flows to the next pool unit 35 only through the base hole 21 .

[0048] The above-mentioned culture device disclosed in the present invention has at least the following advantages:

[0049] By arranging intercepting components in which water dams 50 and filter cartridges 40 are alternately arranged in the main pool 34 of the box body 10, and by arranging a sinking cavity 23 upstream of each base hole 21, and opening a downstream slit on the downstream wall of the filter cartridge 40 and an upstream slit on the upstream wall 22 of the base hole 21, the culture medium is forced to flow downward preferentially and enter the base hole 21, thereby significantly improving the replacement efficiency of the culture medium around the cells without causing undesirable migration of the cells.

[0050] Furthermore, although exemplary embodiments have been described herein, the scope of the present invention includes any and all embodiments based on the present invention with equivalent elements, modifications, omissions, combinations (e.g., solutions that intersect various embodiments), adaptations, or changes. The elements of the claims are to be interpreted broadly based on the language employed in the claims and are not limited to the examples described in this specification or during the prosecution of this application, which examples are to be construed as non-exclusive. Therefore, it is intended that this specification and examples be considered merely as examples, with the true scope and spirit being indicated by the following claims and their full scope of equivalents.

[0051] The above description is intended to be illustrative and not restrictive. For example, the above examples (or one or more versions thereof) may be used in combination with each other. For example, a person of ordinary skill in the art may use other embodiments when reading the above description. In addition, in the above detailed description, various features may be grouped together to simplify the invention. This should not be interpreted as an intention that a disclosed feature that is not claimed for protection is essential to any claim. On the contrary, the subject matter of the present invention may have less than all the features of a particular disclosed embodiment. Therefore, the following claims are incorporated into the detailed description as examples or embodiments, with each claim independently serving as a separate embodiment, and it is contemplated that these embodiments may be combined with each other in various combinations or arrangements. The scope of the invention should be determined with reference to the appended claims and the full scope of equivalents to which such claims are entitled.

[0052] The above embodiments are merely exemplary embodiments of the present invention and are not intended to limit the scope of the present invention. The scope of protection of the present invention is defined by the claims. Those skilled in the art may make various modifications or equivalent substitutions to the present invention within the spirit and scope of protection of the present invention, and such modifications or equivalent substitutions shall also be deemed to fall within the scope of protection of the present invention.

Claims

1. A cell culture device capable of synchronously replacing culture medium, characterized in that: include: The box body comprises a rectangular plate body and a surrounding plate arranged around the side of the plate body, wherein the surrounding plate and the upper surface of the plate body form a main pool capable of accommodating culture medium; Basal holes are provided on the upper surface of the plate body, and the basal holes include a plurality of basal holes, and the basal holes are arranged in a matrix so that the culture medium flows along the row arrangement direction of the basal holes; A filter cartridge is provided above each base hole, and a downstream flow gap is provided on at least the downstream side of the filter cartridge wall; wherein: A sinking cavity is formed on the upper plate surface of the plate body on the upstream side of each base hole, an upstream hole wall is defined between the sinking cavity and the base hole, and a first upstream flow gap is formed on the upstream hole wall; A water dam is provided between each adjacent two filter cartridges in each row of the filter cartridges. The water dams and filter cartridges in adjacent rows separate the main pool into pool units. The water dams in each row allow the culture medium in the pool unit to actively flow toward the sinking cavity and enter the base hole through the first upstream flow gap.

2. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: The flow cross section defined by the downstream flow gap and allowing the medium to pass through is larger than the flow cross section defined by the first upstream flow gap and allowing the medium to pass through.

3. The cell culture device capable of synchronously replacing culture medium according to claim 2, characterized in that: A second upstream flow gap is provided on the upstream wall of the filter cartridge, and the flow cross-section defined by the second upstream flow gap allowing the culture medium to pass through is smaller than the flow cross-section defined by the first upstream flow gap allowing the culture medium to pass through.

4. The cell culture device capable of synchronously replacing culture medium according to claim 3, characterized in that: The sum of the flow cross-sections of the first upstream flow gap and the second upstream flow gap is smaller than the flow cross-section of the downstream flow gap.

5. The cell culture device capable of synchronously replacing culture medium according to claim 2, characterized in that: The width of the first upstream flow gap gradually increases from top to bottom, and the lower end of the first upstream flow gap is configured as a blunted arc portion.

6. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: The height of the water retaining dam in each row is higher than the height of the filter cartridges in the row.

7. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: The matrix-arranged water retaining dams and the matrix-arranged filter cartridges are integrally formed from plastic material through injection molding or laser etching technology.

8. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: The cell culture device capable of synchronously replacing culture medium further includes a transferable component, which includes a mesh body and a plurality of culture baskets. The mesh body is used to be attached to the upper surface of the plate body. The mesh body has hollow portions corresponding one to one with the base holes. The culture baskets are arranged correspondingly below the hollow portions and attached to the mesh body. The culture baskets extend into the base holes, and the cells are located in the culture baskets.

9. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: A liquid inlet interface and a liquid outlet interface are respectively arranged on the two opposite enclosures.

10. The cell culture device capable of synchronously replacing culture medium according to claim 1, characterized in that: The upper portion of the box body is detachably covered with a transparent cover.

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