Membrane chip for three-dimensional cell culture

By designing a membrane-based chip, the problems of high fluid requirements and large size caused by the simple structure of existing three-dimensional cell culture chips are solved, enabling efficient tissue and organ growth simulation and drug screening, reducing costs and improving detection efficiency.

CN116814422BActive Publication Date: 2026-04-07JIANGSU AVATARGET BIOTECHNOLOGY CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-08-05
Publication Date
2026-04-07

AI Technical Summary

Technical Problem

Existing three-dimensional cell culture chips have simple structures, resulting in high fluid requirements, large chip size, high manufacturing costs, and difficulty in simulating the microenvironment for tissue and organ growth.

Method used

The membrane chip design includes a sealing layer, a culture layer, and a connecting layer. The culture layer consists of alternating layers of sub-culture layers and separators. Each culture chamber is independently equipped with a fluid inlet, inlet channel, and outlet channel. The channel design is compact and consistent, and microfluidic technology is used to form a network to simulate the microenvironment for tissue and organ growth.

Benefits of technology

It achieves precise control in both time and space, improves the uniformity of the mixture, reduces labor costs, supports high-throughput, large-scale, and standardized testing, and has a compact structure that saves costs.

✦ Generated by Eureka AI based on patent content.

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Abstract

This invention provides a membrane-based chip for three-dimensional cell culture, comprising a sealing layer, a culture layer, and a connecting layer stacked sequentially. The culture layer includes multiple sub-culture layers and multiple separating layers stacked alternately. Each sub-culture layer has multiple culture chambers arranged sequentially in a symmetrical manner. Each culture chamber independently has a fluid inlet, an inlet channel, an outlet channel, and a fluid outlet. The inlet and outlet channels flow in the same direction as the overall arrangement of the culture chambers. The fluid inlet and outlet are respectively located at both ends of the arrangement direction of the culture chambers, forming a fluid inlet group and a fluid outlet group. The connecting layer has a fluid inlet group and a fluid outlet group at both ends, respectively connected to the corresponding fluid inlet group and fluid outlet group. This design can effectively simulate the microenvironment of tissue and organ growth, improve the uniformity of the mixture reaching the culture chambers, and make the membrane-based chip structure more compact.
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Description

Technical Field

[0001] This invention belongs to the fields of biological tissue engineering and biomedicine, and specifically relates to a membrane chip for three-dimensional cell culture. Background Technology

[0002] With the development of bioengineering and the expansion of its applications, the concept of cell culture has been broadened and developed, with three-dimensional cell culture receiving increasing attention. Three-dimensional cell culture refers to the co-culturing of cells with different material carriers possessing three-dimensional structures in vitro, allowing the cells to migrate and grow within the three-dimensional spatial structure of the carrier, forming a three-dimensional cell-carrier complex. Three-dimensional cell culture can more effectively support biological experiments and mitigate the limitations of the in vivo environment on cell culture. In related technologies, a culture system can be formed by injecting fluid into a culture chamber to cultivate three-dimensional cells. However, due to its simple structural design, this often results in high requirements for the fluid entering the chip, which significantly impacts experimental results. Furthermore, the non-compact structure of the related chips leads to large chip size and high manufacturing costs. Summary of the Invention

[0003] The present invention aims to solve at least one of the technical problems existing in the prior art, and to provide a membrane chip for three-dimensional cell culture.

[0004] The present invention provides a membrane chip for three-dimensional cell culture, the membrane chip comprising a sealing layer, a culture layer and a connecting layer stacked sequentially;

[0005] The culture layer includes multiple sub-culture layers and multiple separator layers arranged in alternating layers;

[0006] Each of the sub-culture layers is symmetrically provided with multiple culture chambers arranged in sequence, and each culture chamber is independently provided with a fluid inlet, an inlet channel, an outlet channel and a fluid outlet;

[0007] The inlet flow channel of each of the culture chambers flows in a direction consistent with the overall orientation of the arrangement of the plurality of culture chambers;

[0008] The outlet flow channel of each of the culture chambers flows in a direction consistent with the overall orientation of the arrangement of the plurality of culture chambers; and,

[0009] The fluid inlet and fluid outlet of each of the culture chambers are respectively disposed at both ends of the arrangement direction of the plurality of culture chambers, forming a fluid inlet group and a fluid outlet group;

[0010] The connecting layer is provided with a fluid inlet group and a fluid outlet group at both ends. The fluid inlet group is connected to the corresponding fluid inlet group, and the fluid outlet group is connected to the corresponding fluid outlet group.

[0011] Furthermore, the inlet and outlet channels of each culture chamber located on both sides of the partition layer are of the same length.

[0012] Furthermore, the inlet and outlet flow channels of each culture chamber located on the same side of the partition layer are of the same length.

[0013] Furthermore, the inlet channel and the outlet channel of each of the plurality of culture chambers are respectively disposed on both sides of the arrangement direction of the plurality of culture chambers.

[0014] Furthermore, in two adjacent sub-culture layers, the inlet and outlet channels of one sub-culture layer are arranged in a mirror image symmetrically with the inlet and outlet channels of the other sub-culture layer.

[0015] Furthermore, the inlet channel and the outlet channel of each culture chamber are respectively located on the side of the corresponding sub-culture layer facing the sealing layer.

[0016] Furthermore, the connecting layer is also provided with at least one observation hole that penetrates its thickness, and the position of the observation hole corresponds to the position of the culture chamber;

[0017] The membrane chip further includes at least one sealing element and at least one sealing cap, the sealing cap being disposed on the corresponding observation hole, and the sealing element being disposed between the corresponding sealing cap and the observation hole.

[0018] Furthermore, the sealing cap is detachably disposed in the observation hole.

[0019] Furthermore, at least one positioning hole is provided at the corresponding positions of the sealing layer, the culture layer, and the connecting layer.

[0020] Furthermore, the membrane chip also includes at least one connector located on the side of the connection layer opposite to the sealing layer, wherein,

[0021] The first end of the connector is connected to the fluid inlet group and the fluid outlet group, and the second end of the connector is used to connect to the culture system.

[0022] The membrane chip for three-dimensional cell culture of the present invention employs microfluidic technology, forming a network of microchannels on the membrane chip. This network consists of culture chambers within the membrane chip and fluid inlets, inlet channels, fluid outlets, and outlet channels connected to these chambers. This effectively simulates the microenvironment for tissue and organ growth, enabling more precise control in both time and space. It can be used for automated culture of tissue models and automated screening of drugs and cosmetics, further saving labor costs and achieving high-throughput, large-scale, and standardized detection.

[0023] Furthermore, in the membrane chip for three-dimensional cell culture of the present invention, the inlet channel of each culture chamber flows in a direction consistent with the overall arrangement direction of the plurality of culture chambers; the outlet channel of each culture chamber flows in a direction consistent with the overall arrangement direction of the plurality of culture chambers. When the inflowing fluid is a mixture, the longer channel can allow the mixture to be fully mixed, improving the uniformity of the mixture reaching the culture chamber. In addition, the fluid inlet and fluid outlet of each culture chamber can be respectively located at both ends of the arrangement direction of the plurality of culture chambers, forming a fluid inlet group and a fluid outlet group, thereby making the structure of the membrane chip more compact. Attached Figure Description

[0024] Figure 1 This is an exploded view of the film-type chip according to the first embodiment of the present invention;

[0025] Figure 2 This is a schematic diagram of the culture layer in the membrane chip according to the second embodiment of the present invention;

[0026] Figure 3 This is a schematic diagram of the structure of the first sub-culture layer in the culture layer of the third embodiment of the present invention;

[0027] Figure 4 This is a schematic diagram of the structure of the second sub-culture layer in the culture layer of the fourth embodiment of the present invention;

[0028] Figure 5 This is a schematic diagram of the interconnect layer in the film-type chip according to the fifth embodiment of the present invention. Detailed Implementation

[0029] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0030] like Figure 1 and Figure 2As shown, a membrane chip for three-dimensional cell culture includes a sealing layer A1, a culture layer A2, and a connecting layer A3 stacked sequentially. The sealing layer A1 and the connecting layer A3 can be die-cast or injection molded from highly transparent polymer materials such as polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS), and copolymers of cycloolefins (COC), or can be made from materials such as glass. The culture layer A2 includes multiple sub-culture layers and multiple separating layers stacked alternately. As an example, ... Figure 2 As shown, the culture layer A2 may include a first sub-culture layer B1, a separator layer B2, and a second sub-culture layer B3. The first sub-culture layer B1 and the second sub-culture layer B3 can be die-cast or injection molded from highly transparent polymer materials such as PMMA, PC, PS, and COC, or they can be made from materials such as glass. The separator layer B2 can be a porous membrane structure or a similar porous membrane structure; for example, the separator layer B2 can be a porous membrane structure made of materials such as PC, PET, PTFE, and NC. Of course, those skilled in the art can also select other materials to form the sealing layer A1, culture layer A2, and sealing layer A3 according to actual needs; this embodiment does not specifically limit this.

[0031] It should be understood that culture layer A2 may include not only two sub-culture layers (B1 / B3) and one separator layer B2, but also multiple sub-culture layers. For example, culture layer A2 may include three sub-culture layers and two separator layers. Of course, it may also include more sub-culture layers, with one (or more) separator layers placed between adjacent sub-culture layers.

[0032] For example, each of the sub-culture layers is symmetrically provided with three culture chambers arranged in sequence. Each culture chamber is independently provided with a fluid inlet, an inlet channel, an outlet channel, and a fluid outlet. The inlet channel of each culture chamber flows in the same direction as the overall arrangement direction of the plurality of culture chambers, and the outlet channel of each culture chamber flows in the same direction as the overall arrangement direction of the plurality of culture chambers.

[0033] Specifically, such as Figure 2 and Figure 3As shown, the first sub-culture layer B1 has three culture chambers (C1 / C2 / C3) arranged symmetrically in sequence. Culture chamber C1 corresponds to a fluid inlet C4, an inlet channel (the connecting pipe between culture chamber C1 and fluid inlet C4), a fluid outlet C9, and an outlet channel (the connecting pipe between culture chamber C1 and fluid outlet C9). Culture chamber C2 corresponds to a fluid inlet C5, an inlet channel (the connecting pipe between culture chamber C2 and fluid inlet C5), a fluid outlet C8, and an outlet channel (the connecting pipe between culture chamber C2 and fluid outlet C8). Culture chamber C3 corresponds to a fluid inlet C6, an inlet channel (the connecting pipe between culture chamber C3 and fluid inlet C6), a fluid outlet C7, and an outlet channel (the connecting pipe between culture chamber C3 and fluid outlet C7).

[0034] Specifically, such as Figure 2 and Figure 4 As shown, the second sub-culture layer B3 is symmetrically arranged with three culture chambers (D1 / D2 / D3). Culture chamber D1 corresponds to a fluid inlet D4, an inlet channel (the connecting pipe between culture chamber D1 and fluid inlet D4), a fluid outlet D12, and an outlet channel (the connecting pipe between culture chamber D1 and fluid outlet D12). Culture chamber D2 corresponds to a fluid inlet D5, an inlet channel (the connecting pipe between culture chamber D2 and fluid inlet D5), a fluid outlet D11, and an outlet channel (the connecting pipe between culture chamber D2 and fluid outlet D12). Culture chamber D3 corresponds to a fluid inlet D6, an inlet channel (the connecting pipe between culture chamber D3 and fluid inlet D6), a fluid outlet D10, and an outlet channel (the connecting pipe between culture chamber D3 and fluid outlet D10).

[0035] It should be understood that the first and second sub-culture layers can be designed with more culture chambers according to actual needs. Each culture chamber can also correspond to multiple fluid inlets, multiple inlet channels, multiple fluid outlets and multiple outlet channels. The specific number can be determined according to actual needs, and this embodiment does not impose any specific restrictions on this.

[0036] It should be noted that, when we say that the inlet flow channel of each culture chamber flows in the same direction as the overall arrangement of the plurality of culture chambers, it means that, for example... Figure 3 and Figure 4 As shown, the fluid direction of the three culture chambers on the first and second sub-culture layers is consistent, but each has a different degree of path curvature so that the flow channel length of each culture chamber is equal, ensuring that the pressure, flow velocity, shear force, etc. of each culture chamber are consistent.

[0037] As a concrete example, such as Figure 3 and Figure 4 As shown, the inlet and outlet channels can be waveforms, which can improve the compactness of the channels on the chip while ensuring the channel length. It should be noted that the waveform structure can be wavy or other shapes, such as S-shaped, etc., and this embodiment is not limited in this respect.

[0038] In a specific example, when the inflowing fluid is a mixture, a longer flow channel can also allow the mixture to be thoroughly mixed, improving the uniformity of the mixture reaching the culture chamber.

[0039] For example, such as Figure 3 and Figure 4 As shown, the fluid inlet and fluid outlet of each culture chamber are respectively located at both ends of the arrangement direction of the plurality of culture chambers, forming a fluid inlet group (composed of fluid inlets C4 / C5 / C6 / D4 / D5 / D6) and a fluid outlet group (composed of fluid outlets C7 / C8 / C9 / D10 / D11 / D12), that is, as Figure 3 and Figure 4 As shown, since the inlet and outlet channels are designed to be arranged along the length of the membrane chip, in addition to increasing the length of the channels, the fluid inlet group and the fluid outlet group can be distributed at both ends of the length of the membrane chip, thereby making the structure of the fluid inlet and the fluid outlet more compact.

[0040] Correspondingly, such as Figure 5 As shown, the two ends of the connecting layer A3 are provided with a fluid inlet group (composed of fluid inlets E4 / E5 / E6 / E7 / E8 / E9) and a fluid outlet group (composed of fluid outlets E10 / E11 / E12 / E13 / E14 / E15). The fluid inlet group is connected to the corresponding fluid inlet group, and the fluid outlet group is connected to the corresponding fluid outlet group.

[0041] Specifically, in practical applications, it should be combined with Figures 2 to 5 The external culture medium is introduced into the second sub-culture layer B3 through the fluid inlet (E4 / E5 / E6) in the connecting layer A3 and then into the fluid inlet (D4 / D5 / D6) in the second sub-culture layer B3. The medium flows into the culture chamber (D1 / D2 / D3) through each inlet channel to culture the tissues and organs within. Afterward, the culture medium flows into the fluid outlet (D10 / D11 / D12) through each outlet channel in the second sub-culture layer B3, and finally flows into the fluid outlet (E10 / E11 / E12) in the connecting layer A3 through this outlet to the external culture medium, thus completing the circulating perfusion culture of the tissues and organs within the culture chamber (D1 / D2 / D3).

[0042] Furthermore, when using the first sub-culture layer B1 for tissue and organ culture, a separator B2 is provided between the first sub-culture layer B1 and the second sub-culture layer B3. To ensure fluid flow, such as... Figure 4 As shown, the second sub-culture layer B3 is also provided with drainage inlets (D7 / D8 / D9) and drainage outlets (D12 / D13 / D14). In this way, the external culture medium is introduced into the second drainage inlets (D7 / D8 / D9) in the second sub-culture layer B3 through the fluid inlet (E7 / E8 / E9) in the connecting layer A3, and flows to the fluid inlet (C4 / C5 / C6) in the first sub-culture layer B1, and finally flows into the culture chamber (C1 / C2 / C3) through each inlet channel to culture the tissues and organs in the culture chamber. Subsequently, the culture medium flows into the fluid outlet (C7 / C8 / C9) through the outlet channels in the first sub-culture layer B1, and finally flows into the drainage outlet (D13 / D14 / D15) in the second sub-culture layer B3 through the fluid outlet (C7 / C8 / C9), and then through the fluid drainage outlet (E13 / E14 / E15) on the connecting layer A3 to the external culture medium, thereby completing the circulating perfusion culture of tissues and organs in the culture chamber (C1 / C2 / C3).

[0043] The membrane chip in this embodiment employs microfluidic technology, forming a network of microchannels on the membrane chip. This includes a culture chamber within the membrane chip, as well as fluid inlets, inlet channels, fluid outlets, and outlet channels connected to the culture chamber. This effectively simulates the microenvironment for tissue and organ growth, enabling more precise control in both time and space. It can be used for the automated culture of tissue and organ models and the automated screening of drugs and cosmetics, further saving labor costs and achieving high-throughput, large-scale, and standardized detection.

[0044] Furthermore, the inlet channel of each culture chamber flows in the same direction as the overall arrangement of the multiple culture chambers; the outlet channel of each culture chamber also flows in the same direction as the overall arrangement of the multiple culture chambers. When the inflowing fluid is a mixture, the longer channel allows for thorough mixing, improving the uniformity of the mixture reaching the culture chamber. If the inflowing fluid is a single fluid, additional components can be added to the fluid inlet to meet experimental needs, improving the ease of obtaining the mixed fluid and ensuring the uniformity of the mixed fluid reaching the culture chamber. Moreover, this arrangement of inlet and outlet channels allows the fluid inlet and outlet of each culture chamber to be located at opposite ends of the arrangement of the multiple culture chambers, resulting in a more compact membrane chip structure.

[0045] It should be noted that the positions of the inlet and outlet channels on each sub-culture layer are not limited. For example, the inlet and outlet channels on each sub-culture layer are located on the side of the corresponding sub-culture layer facing the sealing layer. That is, as... Figure 1 and Figure 2 The inlet and outlet channels are located on the lower surface of the corresponding sub-culture layers.

[0046] It should be further noted that there are no limitations on the size of each culture chamber. For example, the diameter of the culture chamber can be selected from 3mm to 25mm and the depth from 0.01mm to 5mm. The preferred diameter of this membrane chip is 13mm and the depth is 2mm.

[0047] Furthermore, no limitations are imposed on the dimensions of the fluid inlet, inlet channel, fluid outlet, and outlet channel mentioned above. For example, the fluid inlet diameter can be selected from 0.5mm to 2mm, the inlet and outlet channel widths from 0.1mm to 2mm, and the inlet and outlet channel depths from 0.01mm to 1mm. This chip preferably has a fluid inlet diameter of 1mm, an inlet and outlet channel width of 0.5mm, and an inlet and outlet channel depth of 0.5mm. Of course, those skilled in the art can design other dimensions for the fluid inlet, inlet channel, fluid outlet, and outlet channel according to actual needs, and this embodiment does not specifically limit these dimensions.

[0048] For example, in order to ensure that the inlet channel length of each culture chamber is the same and the outlet channel length of each culture chamber is the same, such as Figure 3 and Figure 4 As shown, taking the first sub-culture layer B1 as an example, the inlet channel farthest from the fluid inlet group (the inlet channel corresponding to culture chamber C3) is basically horizontal. The inlet channel closer to the fluid inlet group (the inlet channel corresponding to culture chamber C2) has a curved section. The inlet channel closest to the fluid inlet group (the inlet channel corresponding to culture chamber C1) also has a curved section, and its curvature is greater, in order to ensure that the overall length of each inlet channel is consistent.

[0049] For example, such as Figure 3 and Figure 4 As shown, the inlet and outlet channels of each culture chamber located on both sides of the partition layer B2 are of the same length. That is, as... Figure 3 and Figure 4 As shown, the inlet and outlet flow channels of the culture chambers on both sides of the separator B2 are of the same length. This ensures that the flux of gas or liquid flowing into the environment on both sides of the membrane is the same.

[0050] Furthermore, such as Figure 3 and Figure 4 As shown, the inlet and outlet flow channels of each culture chamber located on the same side of the partition layer are of the same length. That is, as... Figure 3 and Figure 4 As shown, the inlet and outlet flow channels for each culture chamber located below the separator B2 can be of the same length. Alternatively, the inlet and outlet flow channels for each culture chamber located above the separator B2 can be of the same length. Furthermore, the inlet and outlet flow channels for each culture chamber located below the separator B2 can also be of the same length. This ensures that the flux of inflowing gas or liquid is the same on the same side of the membrane, facilitating the consistent control of flow channel flux parameters during the culture process.

[0051] For example, such as Figure 3 and Figure 4 As shown, the inlet channel and the outlet channel of each of the plurality of culture chambers are respectively disposed on both sides of the arrangement direction of the plurality of culture chambers.

[0052] Specifically, such as Figure 3 As shown, the first sub-culture layer B1 is used as an example for explanation. The inlet channel of the first sub-culture layer B1 is located above the culture chambers (C1 / C2 / C3), and the outlet channel of the first sub-culture layer B1 is located below the culture chambers (C1 / C2 / C3).

[0053] For example, in two adjacent sub-culture layers, the inlet and outlet channels of one sub-culture layer are mirror-symmetrically arranged with the inlet and outlet channels of the other sub-culture layer. This facilitates the control of channel length (with identical channel lengths) when fabricating a film chip with this structure, reducing production difficulty.

[0054] Specifically, such as Figure 3 and Figure 4 As shown, the inlet channel in the first sub-culture layer B1 is located at the lower left of its culture chamber (C1 / C2 / C3), and the outlet channel in the first sub-culture layer B1 is located at the upper right of its culture chamber (C1 / C2 / C3). Correspondingly, the inlet channel in the second sub-culture layer B3 is located at the upper left of its culture chamber (D1 / D2 / D3), and the outlet channel in the second sub-culture layer B3 is located at the lower right of its culture chamber (D1 / D2 / D3).

[0055] For example, such as Figure 1As shown, the connecting layer A3 is further provided with three observation holes (E1 / E2 / E3) penetrating its thickness, and the positions of the three observation holes (E1 / E2 / E3) correspond to the positions of the culture chamber. The membrane chip also includes three sealing elements A4 and three sealing caps A6. The sealing caps A6 are placed over the corresponding observation holes (E1 / E2 / E3). Preferably, the sealing caps A6 should be detachably placed over the corresponding observation holes (E1 / E2 / E3). The sealing element A4 is disposed between the corresponding sealing cap A6 and the observation hole (E1 / E2 / E3). The sealing element A4 can be a sealing ring, such as a sealing ring made of elastic materials such as silicone, nitrile rubber, or polydimethylsiloxane (PDMS).

[0056] The membrane chip of this embodiment, with the observation hole provided on the connecting layer, can be used to add a paste-like, non-flowing compound into the culture chamber to detect the cultured organ tissue, and can also be conveniently removed for further detection such as sectioning and staining.

[0057] For example, such as Figure 1 As shown, the membrane chip also includes at least one connector A5, which is located on the side of the connecting layer A3 away from the sealing layer A1. The first end of the connector A5 is connected to the fluid inlet group and the fluid outlet group, and the second end of the connector A5 is used to connect to the external culture medium through an external piping system.

[0058] For example, such as Figure 1 , Figure 3 , Figure 4 and Figure 5 As shown, at least one positioning hole is provided at the corresponding positions of the sealing layer A1, the culture layer A2, and the connecting layer A3. Specifically, four symmetrically distributed positioning holes can be provided at the central position of the sealing layer A1, the culture layer A2, and the connecting layer A3. Through these positioning holes, the assembly of the membrane chip can be facilitated, thereby improving the assembly efficiency of the membrane chip.

[0059] It is understood that the above embodiments are merely exemplary implementations used to illustrate the principles of the present invention, and the present invention is not limited thereto. For those skilled in the art, various modifications and improvements can be made without departing from the spirit and essence of the present invention, and these modifications and improvements are also considered to be within the scope of protection of the present invention.

Claims

1. A membrane-based chip for three-dimensional cell culture, characterized in that, The membrane chip includes a sealing layer, a culture layer, and a connecting layer stacked sequentially. The culture layer includes multiple sub-culture layers and multiple separator layers arranged in alternating layers; Each of the sub-culture layers is symmetrically provided with multiple culture chambers arranged in sequence, and each culture chamber is independently provided with a fluid inlet, an inlet channel, an outlet channel and a fluid outlet; The overall orientation of the inlet flow channel of each of the culture chambers is consistent with the arrangement direction of the plurality of culture chambers; The outlet flow channel of each of the culture chambers is oriented in a manner consistent with the arrangement direction of the plurality of culture chambers; as well as, The fluid inlet and fluid outlet of each of the culture chambers are respectively disposed at both ends of the arrangement direction of the plurality of culture chambers, forming a fluid inlet group and a fluid outlet group; The connecting layer is provided with a fluid inlet group and a fluid outlet group at both ends. The fluid inlet group is connected to the corresponding fluid inlet group, and the fluid outlet group is connected to the corresponding fluid outlet group.

2. The film-type chip according to claim 1, characterized in that, The inlet and outlet channels of each culture chamber located on both sides of the partition layer are of the same length.

3. The film-type chip according to claim 1, characterized in that, The inlet and outlet flow channels of each culture chamber located on the same side of the partition layer are of the same length.

4. The film-type chip according to claim 1, characterized in that, The inlet channel and the outlet channel of each of the plurality of culture chambers are respectively disposed on both sides of the arrangement direction of the plurality of culture chambers.

5. The film-type chip according to claim 1, characterized in that, In two adjacent sub-culture layers, the inlet and outlet channels of one sub-culture layer are arranged in a mirror image symmetrically with the inlet and outlet channels of the other sub-culture layer.

6. The film-type chip according to any one of claims 1 to 5, characterized in that, The inlet and outlet channels of each culture chamber are located on the side of the corresponding sub-culture layer facing the sealing layer.

7. The film-type chip according to any one of claims 1 to 5, characterized in that, The connecting layer is also provided with at least one observation hole that penetrates its thickness, and the position of the observation hole corresponds to the position of the culture chamber; The membrane chip further includes at least one sealing element and at least one sealing cap, the sealing cap being disposed on the corresponding observation hole, and the sealing element being disposed between the corresponding sealing cap and the observation hole.

8. The film-type chip according to claim 7, characterized in that, The sealing cap is detachably installed in the observation hole.

9. The film-type chip according to any one of claims 1 to 5, characterized in that, At least one positioning hole is provided at the corresponding positions of the sealing layer, the culture layer, and the connecting layer.

10. The film-type chip according to any one of claims 1 to 5, characterized in that, The membrane chip further includes at least one connector, which is located on the side of the connection layer opposite to the sealing layer, wherein... The first end of the connector is connected to the fluid inlet group and the fluid outlet group, and the second end of the connector is used to connect to the culture system.

Citation Information

Patent Citations

  • Membrane-on-chip for three-dimensional cell culture

    CN218842192U