Microfluidic chip for cell culture, comprising plurality of channels

Abstract

The present invention relates to a microfluidic chip for cell culture, comprising: an X-direction channel having at least a part extending in an X-direction; a Y-direction channel extending in a vertical direction across the X-direction channel; a Y-positive region channel formed to be in contact with the Y-direction channel in a Y-positive direction; a Y-negative region channel formed to be in contact with the Y-direction channel in a Y-negative direction; a Z-positive region channel formed to be in contact with the Y-direction channel in a Z direction; and a Y-positive direction reservoir surrounding the Y-positive region channel and in contact with the X-direction channel.

Description

Microfluidic chip for cell culture containing multiple channels

[0001] This application claims priority to Korean Patent Application No. 10-2024-0003794, filed January 9, 2024, the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a microfluidic chip for cell culture, wherein a plurality of channels can be in contact with a channel in which cells are cultured from various directions, thereby enabling observation of various cell reactions and facilitating easy conduct of experiments on cultured cells.

[0003] Biomaterials used in in vitro cell culture platforms must be transparent for imaging, biocompatible for cell culture, and have low swelling properties for operational flexibility and stability. Previously, thermoplastic polymers such as polystyrene or polymethyl methacrylate were commonly used as cell culture platforms, as they meet the basic requirements for in vitro cell culture platforms.

[0004] Meanwhile, a microfluidic chip, which is an example of a cell culture platform, includes a lower member and an upper member covering the lower member, and microchannels can be formed therein. Such a microfluidic chip is primarily made of a biocompatible material, and the lower member can be made of transparent glass or the like for cell analysis using a microscope or the like. Furthermore, the upper member can be made of a biocompatible silicone-derived material, such as polydimethylsiloxane (PDMS), capable of printing microchannels.

[0005] The object of the present invention is to provide a microfluidic chip for cell culture in which a plurality of channels can be in contact with a channel in which cells are cultured.

[0006] In order to solve the above problem, the present invention provides a microfluidic chip for cell culture, comprising an X-direction channel extending at least partly in the X direction, a Y-direction channel extending vertically across the X-direction channel, a Y-region channel formed to contact the Y-direction channel in the Y-region direction, a Y-subregion channel formed to contact the Y-direction channel in the Y-subdirection, a Z-region channel formed to contact the Y-direction channel in the Z direction, and a Y-region reserve surrounding the Y-region channel and contacting the X-direction channel.

[0007] In addition, the present invention provides a cell culture method using a microfluidic chip according to the present invention, comprising the steps of injecting hydrogel into the X-direction channel and the Y-direction channel, and injecting hydrogel or media into at least one of the Y-region channel, the Y-subregion channel, the Z-region channel, and the Y-region reserve.

[0008] The advantages of the present invention include the ability to provide a complex and diverse environment for cell culture, allowing for a multifaceted analysis of the impact on cell culture, since multiple channels can be connected to the cell culture channel. Furthermore, since pipettes and other devices can be easily accessed to cultured cells, cell experiments can also be conducted using these devices.

[0009] In addition, the chip according to the present invention can be manufactured using a material such as plastic, can be injection molded, and can be manufactured in a standardized structure, so it can be easily used.

[0010] Figure 1 shows an example of an implementation of the microfluidic chip of the present invention.

[0011] Figure 2 shows a bottom view of a microfluidic chip according to one embodiment of the present invention.

[0012] Figure 3 shows a front view of a microfluidic chip according to one embodiment of the present invention.

[0013] Figure 4 shows a bottom view for explaining a microfluidic chip according to one embodiment of the present invention.

[0014] Figure 5 shows a front view for explaining a microfluidic chip according to one embodiment of the present invention.

[0015] Figure 6 is a drawing for explaining a groove shape according to one embodiment of the present invention.

[0016] Figure 7 shows a bottom view for explaining a microfluidic chip according to one embodiment of the present invention.

[0017] Fig. 8 shows a cross-sectional view of the '+Y to -Y direction' of the Z-region channel for explaining a microfluidic chip according to one embodiment of the present invention.

[0018] Below, with reference to the attached drawings, embodiments of the present invention are described in detail to facilitate easy implementation by those skilled in the art. However, the present invention can be implemented in various different forms and is not limited to the embodiments described herein. In the drawings, irrelevant parts have been omitted for clarity, and similar reference numerals have been used throughout the specification to indicate similar elements.

[0019] Throughout this specification, when it is said that an element is "on" another element, this includes not only cases where the element is in contact with the other element, but also cases where another element exists between the two elements.

[0020] Throughout this specification, whenever a part is said to "include" a component, this means that it may include other components, but not to the exclusion of other components, unless otherwise stated.

[0021] Throughout this specification, references to “A and / or B” mean “A or B, or A and B.”

[0022] Throughout the present specification, each X, Y, Z direction and forward and reverse direction are used to describe the 3D structure of the microfluidic chip (4), and the directions are shown in FIGS. 4, 5, 7, and 8. However, the directions above may not necessarily mean directions that are 90 degrees apart from other directions, that is, X, Y, and Z directions that are generally known to those skilled in the art. For example, the X-direction channel (410) may not necessarily be formed at 90 degrees to the Y-direction, and other channels may also be applied by analogy.

[0023] Throughout this specification, the term "groove" is a term that includes a excavated groove structure. The groove structure of the present invention particularly includes a groove shape that narrows from a wide surface to a narrow surface (or, widens from a narrow surface to a wide surface; such as a trapezoidal shape). The groove structure used herein may be to prevent the solution between each channel from flowing into the other channel due to the Young-Laplace pressure. Here, the "Young-Laplace pressure" means an algebraic equation that describes the capillary pressure difference maintained at the interface between two static fluids, such as water and air, due to the surface tension or wall tension phenomenon.

[0024] In particular, the groove structure was designed using open microfluidic principles, and the surface was converted to hydrophilic through plasma treatment, enabling smooth fluid flow. This allows for precise control of surface tension and capillary action, enabling efficient management of the flow and separation of solutions between each channel. This method overcomes the structural limitations of conventional closed microfluidic systems and offers the ability to more flexibly and efficiently control fluid movement and interaction.

[0025] Hereinafter, implementation examples and embodiments of the present invention will be described in detail with reference to the attached drawings. However, the present invention may not be limited to these implementation examples and embodiments and drawings.

[0026] The present invention relates to a microfluidic chip (4) for cell culture including a plurality of channels, wherein the plurality of channels are in contact with the channel in which cells are cultured from various directions (Figs. 1 to 5).

[0027] In order to solve the technical problem that the present invention is trying to solve, the present invention

[0028] (1) An X-direction channel (410) extending at least partly in the X direction.

[0029] (2) Y-direction channel (420) crossing the above X-direction channel (410)

[0030] (3) Y-regular area channel (430) formed to contact the Y-direction channel (420) in the Y-regular direction.

[0031] (4) Y-region channel (440) formed to contact the Y-direction channel (420) in the Y-direction

[0032] (5) A Z-region channel (510) formed to fold in the Z direction on the Y-direction channel (420) above.

[0033] (7) It may include a Y-direction reserve (450) surrounding the Y-direction channel (430) and in contact with the X-direction channel (410).

[0034] According to one embodiment of the present invention, the X-direction channel (410) and the Y-direction channel (420) are channels in which cell culture is performed, and for convenience of explanation, the two channels are referred to as cell culture channels hereinafter.

[0035] Since the X-direction channel (410) can be in contact with the Y-direction reserve (450), and the Y-direction channel (420) can be in contact with the Y-region channel (430), the Y-subregion channel (440), and the Z-region channel (510), the cell culture channel can be in contact with up to four channels. This enables co-culture with various environments or cells.

[0036] In addition, the contact portion of the Y-direction channel (420) that is in contact with the Y-region channel (430) or the Y-subregion channel (440) may include a groove shape that becomes wider as it moves from the Y-direction channel (420) to another channel (Fig. 6). Although not necessarily due to the groove shape, even if a specific solution is injected into each channel, the solutions may be formed in layers at each contact portion of the Y-direction channel (420) without being mixed.

[0037] According to one embodiment of the present invention, the X-direction channel (410) may include a first passage part (1010) and a second passage part (1020) that are each connected to a Y-direction reserve (450) (Fig. 7). Here, the first passage part (1010) and the second passage part (1020) may each have one end connected to the X-direction channel (410) and the other end connected to the Y-direction reserve (450).

[0038] Additionally, the X-direction channel (410) and the Y-direction channel (420) can be formed to be connected to the bottom surface of the Y-direction reserve (450).

[0039] According to one embodiment of the present invention, the injection of the solution into the X-direction channel (410) is performed through the first passage (1010) or the second passage (1020), and the following can be satisfied so that no bubbles are generated in the solution into the X-direction channel (410). However, the present invention is not necessarily limited thereto.

[0040] (1) Solution injection into the X-direction channel (410) shall be performed through only one of the first passage (1010) or the second passage (1020).

[0041] (2) The solution shall flow along the wall of the Y-direction reserve (450) and be injected into the X-direction channel (410) through the first passage (1010) or the second passage (1020).

[0042] (3) Each end connected to the Y forward reserve (450) in the first passage (1010) and the second passage (1020) shall not be connected to each other.

[0043] Here, (1) and (3) are to prevent bubbles from forming between the solutions flowing in from various directions and meeting within the X-direction channel (410).

[0044] (2) This is to ensure that the injection of the solution is continuous and uninterrupted, so that air bubbles are not injected into each passage.

[0045] According to one embodiment of the present invention, the Y-region channel (430) is separated from the Z-region channel (510) by a partition wall, but may be formed to contact the upper portion in the Z-region direction. Through the above structure, the amount of solution injected into the Y-region channel (430) or the Z-region channel (510) can be controlled so that the solution injected into each channel can contact the solution in the other channel.

[0046] According to one embodiment of the present invention, the Z-region channel (510) is divided into an X-direction channel (410), a Y-region channel (430), and a Y-subregion channel (440) by a partition wall, and may be formed between the Y-region channel (430) and the Y-subregion channel (440). In addition, the Z-region channel (510) may include a groove shape that becomes narrower toward the Z-direction (FIG. 8). Through this, compared to the shape of a general straight passage, since the solution is continuously injected into the Z-region channel (510), it is possible to prevent bubbles from forming in the Z-region channel (510), for example, at the end of the channel in which the solution is injected.

[0047] According to one embodiment of the present invention, the microfluidic chip (4) may additionally include a Y-direction reserve (460) formed to contact the Y-region channel (440) from the upper part in the Z direction. The effect of this is the same as that of the solution in the Z-region channel (510) and the Z-direction reserve being in contact with each other as described above.

[0048] According to one embodiment of the present invention, the microfluidic chip (4) may further include a base portion at the bottom. This portion forms the bottom of the microfluidic chip (4), and prevents the solution injected into the channel from flowing out to the bottom. Alternatively, the base portion may be formed in a detachable form, thereby allowing cultured cells to access the bottom of the microfluidic chip (4).

[0049] According to one embodiment of the present invention, in order to culture cells in a cell culture channel, a hydrogel may be injected into the X-direction channel (410) and the Y-direction channel (420), and a hydrogel or media may be injected into at least one of the Y-region channel (430), the Y-subregion channel (440), the Z-region channel (510), and the Y-region reserve (450). In addition, a hydrogel or media may be optionally injected into the Y-subregion reserve (460).

[0050] [Explanation of symbols]

[0051] 4: Microfluidic chip

[0052] 410: X-direction channel

[0053] 420: Y-direction channel

[0054] 430: Y-area channel

[0055] 440: Y-area channel

[0056] 450: Y forward reserve

[0057] 460: Y-direction reserve

[0058] 510: Z-zone channel

[0059] 1010: Passage 1

[0060] 1020: Second passage

Claims

1. In a microfluidic chip for cell culture, An X-direction channel, at least part of which extends in the X direction; A Y-direction channel extending vertically across the above X-direction channel; A Y-region channel formed to contact the Y-direction channel in the Y-region direction; A Y-region channel formed to contact the Y-direction channel in the Y-direction; A Z-region channel formed to contact the Y-direction channel in the Z direction; and A Y-direction reserve surrounding the above Y-direction channel and in contact with the X-direction channel A microfluidic chip comprising:

2. In paragraph 1, A microfluidic chip, wherein the above Z-region channel is separated from the X-direction channel, the Y-region channel, and the Y-subregion channel by a partition wall, and is formed between the Y-region channel and the Y-subregion channel.

3. In paragraph 1, A microfluidic chip, wherein the contact portion of the Y-direction channel, which is in contact with the Y-region channel or the Y-subregion channel, respectively, includes a groove shape that widens as it moves from the Y-direction channel to another channel.

4. In paragraph 1, A microfluidic chip, wherein the X-direction channel includes a first passage section and a second passage section each communicating with the Y-direction reserve.

5. In paragraph 4, A microfluidic chip, wherein the first passage and the second passage are connected to the bottom surface of the Y-directional reserve.

6. In paragraph 4, A microfluidic chip, wherein the first passage and the second passage are not connected to each other.

7. In paragraph 1, A microfluidic chip, wherein the above Y-regular region channel is formed to contact the Y-regular reserve from the upper part in the Z direction.

8. In paragraph 1, A microfluidic chip, wherein the above Z-domain channel includes a groove shape that narrows toward the Z-direction.

9. In paragraph 1, The above microfluidic chip, A microfluidic chip further comprising a Y-direction reserve formed to contact the Y-region channel from above in the Z direction.

10. In paragraph 1, The above microfluidic chip, A microfluidic chip further comprising a base portion at the lowest portion.

11. A method for culturing cells using a microfluidic chip according to Article 1, A step of injecting hydrogel into the X-direction channel and the Y-direction channel; and A step of injecting a hydrogel or media into at least one of the Y-region channel, the Y-subregion channel, the Z-region channel, and the Y-direction reserve; A cell culture method comprising:

Images