A microfluidic chip for cell culture

Abstract

The utility model belongs to cell culture technical field, concretely relates to a kind of microfluidic chip for cell culture, including at least three fluid channels, each fluid channel includes the communication section in the middle, and the partition section being set at the two sides of communication section;The communication section between adjacent fluid channels is separated by controllable on-off isolation column array structure;Column array structure includes one or more column array units.By membraneless design, fluid mechanics control and high-throughput cell culture method, more simple, flexible and efficient solution is provided.

Description

Technical Field

[0001] This invention belongs to the field of cell culture technology, specifically relating to a microfluidic chip for cell culture. Background Technology

[0002] Traditional two-dimensional (2D) cell culture methods cannot simulate the real structure and cellular composition within human organs, lacking the spatial organization of cells in vivo, thus failing to effectively reproduce the characteristics and functions of real tissues and organs. Although animal models have certain advantages over 2D cell models, they are costly, have low throughput, and raise ethical concerns. Furthermore, due to species differences, animal models often fail to accurately simulate human conditions.

[0003] Microfluidic chip technology combines innovative achievements from multiple fields such as chemistry, fluid physics, microelectronics, new materials technology, biology, and biomedical engineering. It enables the simulation of the in vivo environment on a chip, constructing more biomimetic microenvironments, and thus facilitating the culture and research of cell or organ models. Different cells in the human body possess natural physiological configurations, interacting and regulating each other through contact or non-contact methods. Microfluidic chips typically use porous membranes to simulate these intercellular interface structures, reproducing the types and arrangements of cells in the human body by culturing different cells on both sides of the membrane.

[0004] However, there are some technical challenges in using porous membranes: on the one hand, the material properties and biocompatibility of the membranes are required to be high, and different types of cells require the selection of porous membranes with appropriate pore sizes to ensure their biocompatibility with all cells; on the other hand, the way the membranes are integrated into the chip is quite complex, which increases the difficulty of design and operation.

[0005] In view of the above, this utility model is hereby proposed. Utility Model Content

[0006] To address the aforementioned technical problems in the existing technology, this utility model provides a microfluidic chip for cell culture, which offers a simpler, more flexible, and more efficient solution through membrane-free design, fluid dynamics control, and patterned cell culture methods.

[0007] To achieve the above objectives, the technical solution of this utility model is as follows:

[0008] A microfluidic chip for cell culture includes at least three fluid channels, each fluid channel including a central connecting segment and separating segments disposed on both sides of the connecting segment; the connecting segments of adjacent fluid channels are controllably separated by a columnar array structure; the columnar array structure includes one or more columnar array units.

[0009] Furthermore, when the columnar array structure includes multiple columnar array units, the columnar protrusions in adjacent columnar array units are arranged alternately.

[0010] Furthermore, the cross-section of the columnar array unit is polygonal or circular.

[0011] Furthermore, when there are three fluid channels, the three fluid channels are set up in parallel.

[0012] Furthermore, when there are four fluid channels, three of them are curved and distributed in a circular array; the other fluid channel is located at the center of the three fluid channels and separates them.

[0013] Furthermore, each of the three fluid channels in the circular array has two or three liquid inlets / outlets.

[0014] Furthermore, the microfluidic chip is characterized by including an upper substrate, an intermediate substrate, and a lower substrate arranged sequentially from top to bottom, with the fluid channels all disposed on the intermediate substrate.

[0015] Furthermore, the upper substrate is provided with a plurality of through holes, which are respectively connected to different fluid channels.

[0016] Furthermore, the upper substrate, the middle plate, and the lower substrate are fixed by means of bonding, hot pressing, or screws.

[0017] Furthermore, the upper substrate is rectangular or hexagonal, and the shapes of the middle plate and the lower substrate correspond to those of the upper substrate.

[0018] The microfluidic chip for cell culture provided by this invention offers a simpler, more flexible, and more efficient solution through its membrane-free design, fluid dynamics control, and high-throughput cell culture methods. It not only simplifies the complexity of traditional methods in structure but also more closely approximates the physiological environment in cell culture and model construction, possessing broad application potential and practical value. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the microfluidic chip provided in Example 1;

[0020] Figure 2 for Figure 1 The diagram shows the exploded structure of the microfluidic chip.

[0021] Figure 3 for Figure 1 The diagram shows the structure of the intermediate board in the microfluidic chip.

[0022] Figure 4A top view of the rectangular columnar array structure of the microfluidic chip provided in Embodiment 1;

[0023] Figure 5 This is a top view of the circular columnar array structure of the microfluidic chip provided in Embodiment 2;

[0024] Figure 6 This is a schematic diagram of the microfluidic chip provided in Example 3;

[0025] Figure 7 This is a schematic diagram of the intermediate board of the microfluidic chip provided in Embodiment 3;

[0026] Figure 8 This is a schematic diagram of the microfluidic chip provided in Example 4;

[0027] Figure 9 This is a schematic diagram of the intermediate board of the microfluidic chip provided in Embodiment 4;

[0028] Explanation of reference numerals in the attached drawings: 1. Columnar array structure; 2. Entrance / exit; 3. Upper substrate; 4. Middle plate; 5. Lower substrate; 6. Separating section; 7. Connecting section; 8. Through hole. Detailed Implementation

[0029] The technical solution of this utility model will be clearly described below with reference to the accompanying drawings. Obviously, the described embodiments are not all embodiments of this utility model. All other embodiments obtained by those skilled in the art without creative effort are within the protection scope of this utility model.

[0030] It should be noted that, unless otherwise specifically stated, the relative arrangement and numerical expressions of the components and steps described in these embodiments should not be construed as limiting the scope of this utility model.

[0031] The following description of exemplary embodiments is merely illustrative and is not intended to limit the present invention or its application or use in any way. Techniques, methods, and apparatus known to those skilled in the art may not be discussed in detail herein, but where applicable, such techniques, methods, and apparatus should be considered part of this specification.

[0032] Example 1

[0033] This embodiment provides a microfluidic chip for cell culture, such as... Figure 1 and Figure 2 As shown, the microfluidic chip includes an upper substrate 3, a middle plate 4 and a lower substrate 5 arranged sequentially from top to bottom, and is assembled into a sealed space by hot pressing.

[0034] The upper substrate 3 is a transparent rectangular sheet with six through holes 8. The through holes 8 allow fluid to flow from the outside into the interior of the microfluidic chip, and the through holes 8 are connected to the inlet and outlet 2 on the middle plate 4.

[0035] like Figure 3 As shown, the intermediate plate 4 is provided with 3 fluid channels, which are arranged in parallel. Each fluid channel includes a middle connecting section 7 and a dividing section 6 on both sides of the connecting section 7. Each dividing section 6 is provided with an inlet / outlet 2 for liquid to drip in at one end. Adjacent connecting sections 7 are separated by a columnar array structure 1 that can be controlled to open and close.

[0036] Each columnar array structure 1 includes two columnar array units, with the columnar protrusions in the two columnar array units arranged alternately. The cross-section of the columnar array unit is polygonal; see reference. Figure 4 In this embodiment, the columnar protrusions are rectangular protrusions, and the cross-section of the columnar array is rectangular. In other embodiments, each columnar array structure 1 may further include one columnar array unit or three or more columnar array units, and the rectangular protrusions may also be replaced with circular protrusions.

[0037] In the isolated state, the rectangular columnar array separates the connecting segments 7 of different channels, simulating the environment for patterned cell culture. The use of a rectangular columnar array to separate the connecting segments 7 of the channels ensures effective fluid diversion within different channels for cell culture. Specifically, the rectangular columnar array provides multiple isolation points, promoting cell culture through different channels and avoiding direct contact or interference, thus simulating the natural distribution and tissue function of cells in the human body. When the rectangular array is in the connected state, cells can flow between the fluid channels through the rectangular columnar array, helping to create a suitable environment for cell growth within the chip, while avoiding the complexity and potential problems of using porous membranes in traditional methods.

[0038] Example 2

[0039] This embodiment provides a microfluidic chip for cell culture. The microfluidic chip includes an upper substrate 3, a middle plate 4 and a lower substrate 5 arranged sequentially from top to bottom, and is assembled into a closed space by bonding and fixing.

[0040] The upper substrate 3 is a transparent rectangular sheet with six through holes 8. The through holes 8 allow fluid to flow from the outside into the interior of the microfluidic chip, and the through holes 8 are connected to the inlet and outlet 2 on the middle plate 4.

[0041] like Figure 3As shown, the intermediate plate 4 is provided with 3 fluid channels, which are arranged in parallel. Each fluid channel includes a middle connecting section 7 and a dividing section 6 on both sides of the connecting section 7. Each dividing section 6 is provided with an inlet / outlet 2 for liquid to drip in at one end. Adjacent connecting sections 7 are separated by a columnar array structure 1 that can be controlled to open and close.

[0042] Each columnar array structure 1 includes two columnar array units, with the columnar protrusions in the two columnar array units arranged alternately. The cross-section of the columnar array unit is circular; see reference. Figure 5 In this embodiment, the columnar protrusions are circular. The circular columnar array is arranged in a linear pattern, and the columnar units are arranged relatively evenly to form a regular array. A certain gap is left between adjacent columnar units to allow fluid flow and to enable cells to be effectively captured. Through interaction with the fluid, the columnar units can guide cells to remain in the concave areas of the array, thereby achieving array-based cell culture.

[0043] In the isolated state, the circular columnar array separates the connecting segments 7 of different channels, simulating the environment for patterned cell culture. The use of a circular columnar array to separate the connecting segments 7 of the channels ensures effective fluid diversion within different channels for cell culture. Specifically, the circular columnar array provides multiple isolation points, promoting cell culture through different channels and avoiding direct contact or interference, thus mimicking the natural distribution and tissue function of cells in the human body. When the circular array is connected, cells can flow between the fluid channels through the circular columnar array, helping to create a suitable environment for cell growth within the chip, while avoiding the complexity and potential problems of using porous membranes in traditional methods.

[0044] Example 3

[0045] See Figure 6 This embodiment provides a microfluidic chip for cell culture. The microfluidic chip consists of an upper substrate 3, a middle plate 4, and a lower substrate 5, which are arranged sequentially from top to bottom and assembled into a sealed space by bonding.

[0046] The upper substrate 3 is a transparent hexagonal sheet with nine through holes 8. The through holes 8 allow fluid to flow from the outside into the interior of the microfluidic chip, and the through holes 8 are connected to the inlet and outlet 2 on the middle plate 4.

[0047] like Figure 7 As shown, the intermediate plate 4 has four fluid channels extending outward from the center of the hexagon and connecting with the central area. Each fluid channel includes a central connecting section 7 and two dividing sections 6 on both sides of the connecting section 7. Each dividing section 6 has an inlet / outlet 2 for liquid dripping at one end. Adjacent connecting sections 7 are separated by a columnar array structure 1 that can be controlled to open and close.

[0048] Each columnar array structure 1 includes two columnar array units, with the columnar protrusions in the two columnar array units arranged alternately. The cross-section of the columnar array unit is polygonal. In this embodiment, the columnar protrusions are rectangular protrusions, and the cross-section of the columnar array is rectangular.

[0049] Setting up four fluid channels provides greater flexibility in fluid control. Each channel can independently adjust its flow rate and direction, allowing for precise control of the fluid environment within each channel. This is highly advantageous in experiments requiring delicate manipulation, especially when experiments involve cell migration, diffusion, or other biological processes.

[0050] The fluid channel also includes a gel barrier channel located between different cell culture channels. By filling it with a biocompatible gel material, physical isolation and molecular diffusion exchange between cells are achieved. The shape and position of the gel barrier channel are determined by the columnar array structure 1, which is used to support the gel material and prevent it from collapsing after formation.

[0051] The gel barrier channels formed by the columnar array units have selective permeability, which can isolate different fluid channels, prevent direct mixing of liquids, achieve selective connection between fluid channels, and provide stable growth support for cells without the need for additional porous membranes.

[0052] Example 4

[0053] See Figure 8 This embodiment provides a microfluidic chip for cell culture. The microfluidic chip consists of an upper substrate 3, a middle plate 4, and a lower substrate 5, which are arranged sequentially from top to bottom and assembled into a sealed space by bonding.

[0054] The upper substrate 3 is a transparent hexagonal sheet with 13 through holes 8. The through holes 8 allow fluid to flow from the outside into the interior of the microfluidic chip, and the through holes 8 are connected to the inlet and outlet 2 on the middle plate 4.

[0055] like Figure 9 As shown, the intermediate plate has four fluid channels extending outward from the center of the hexagon and connecting with the central area. Each fluid channel includes a central connecting section 7 and two dividing sections 6 on both sides of the connecting section 7. Each dividing section has an inlet / outlet 2 for liquid dripping at one end. Adjacent connecting sections 7 are separated by a columnar array structure 1 that can be controlled to open and close.

[0056] Each columnar array structure 1 includes two columnar array units, with the columnar protrusions in the two columnar array units arranged alternately, and the cross-section of the columnar array unit is circular; in this embodiment, the columnar protrusions are circular protrusions.

[0057] Liquid can be directly introduced into the intermediate fluid channel through the through-hole 8. Each channel can be used to introduce different reagents, drugs, or cell suspensions through the through-hole 8 on the upper substrate 3 for experiments such as cell culture, drug screening, and gene analysis. By independently controlling each fluid channel, it is possible to ensure that different reagents do not interfere with each other and to make effective comparisons under different experimental conditions.

[0058] In summary, this utility model has the following advantages:

[0059] 1. Multiple cell types can be cultured in different channels to construct complex non-contact barrier organoid models, simulating the interaction between different organs in the human body and improving the realism and reliability of the model;

[0060] 2. By utilizing the microscopic liquid laminar flow phenomenon and precisely controlling the flow rate and direction of the fluid, the patterned positioning and seeding of cells within the chip can be achieved, accurately simulating the natural arrangement and distribution of cells in the human body and improving the simulation accuracy of the co-culture model;

[0061] 3. By controlling the crossflow of liquids in different fluid channels, the effective diffusion and exchange of cytokines and nutrients can be achieved, promoting signal transduction and mutual regulation between different cell types, simulating the complex biochemical environment in vivo, and enhancing the functionality and complexity of the co-culture model.

[0062] The above specific embodiments are only used to illustrate the technical solution of this utility model and are not intended to limit it. Although this utility model has been described in detail with reference to examples, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solution of this utility model without departing from the scope of the technical solution of this utility model, and all such modifications or substitutions should be covered within the scope of the claims of this utility model.

Claims

1. A microfluidic chip for cell culture, characterized in that, It includes at least three fluid channels, each fluid channel including a central connecting section and dividing sections on both sides of the connecting section; the connecting sections of adjacent fluid channels are separated by a columnar array structure that can be controlled to open and close; the columnar array structure includes one or more columnar array units; When the columnar array structure includes multiple columnar array units, the columnar protrusions in adjacent columnar array units are staggered; the cross-section of the columnar array unit is polygonal or circular; when the number of fluid channels is three, the three fluid channels are arranged in parallel. When there are four fluid channels, three of them are curved and distributed in a circular array; the other fluid channel is located in the center of the three fluid channels and separates them.

2. The microfluidic chip according to claim 1, characterized in that, Each of the three fluid channels in the circular array has two or three liquid inlets / outlets.

3. The microfluidic chip according to any one of claims 1 to 2, characterized in that, The microfluidic chip also includes an upper substrate, an intermediate substrate, and a lower substrate arranged sequentially from top to bottom, with the fluid channels all disposed on the intermediate substrate.

4. The microfluidic chip according to claim 3, characterized in that, The upper substrate is provided with a plurality of through holes, which are respectively connected to different fluid channels.

5. The microfluidic chip according to claim 3, characterized in that, The upper substrate, middle plate, and lower substrate are fixed by bonding, hot pressing, or screws.

6. The microfluidic chip according to claim 3, characterized in that, The upper substrate is rectangular or hexagonal, and the shapes of the middle plate and the lower substrate correspond to those of the upper substrate.

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