CN216445380U - Organoid culture chip - Google Patents

Abstract

The embodiment of the utility model provides an organoid culture chip. The organoid culture chip includes: a body; a plurality of culture wells disposed on an upper surface of the body, the plurality of culture wells being in series communication through a first channel to form a set of culture wells; the co-culture holes are arranged on the upper surface of the body, the co-culture holes correspond to the culture holes one by one, each culture hole is communicated to the corresponding co-culture hole through a second channel, and the first channel is higher than the second channel. By adopting the organoid culture chip of the embodiment of the utility model, the main body has high flux, and the overall size, the size of the culture holes and the number of the culture holes can be flexibly designed. Meanwhile, on one hand, the method can meet the requirement of co-culture and maintain micro-fluidic; on the other hand, the cultured organoids have good consistency, and are beneficial to experimental research such as drug screening and the like. In addition, the structural design of the organoid culture chip is not complicated, and the manufacturing cost and the cost are relatively low.

Description

Organoid culture chip

Technical Field

The utility model relates to the technical field of cells, in particular to an organoid culture chip.

Background

Organoids are of great value for many studies in biology, disease pathology, regenerative mechanisms, precision medicine, and drug screening. By means of the organoid, the human body can be helped to overcome many biological and medical research problems more efficiently and safely.

In recent years, with the increasing importance of organoids in research, organoid culture techniques have been developed. At present, when many people culture organoids, the used culture plate (or called as a chip) has a simple structure, on one hand, co-culture cannot be realized, and batch culture on the basis of microfluidics cannot be met; on the other hand, the cultured organoids have poor consistency, which is not beneficial to the comparison of the subsequent experimental results.

SUMMERY OF THE UTILITY MODEL

To at least partially solve the problems of the prior art, embodiments of the present invention provide an organoid culture chip. The organoid culture chip includes: a body; a plurality of culture wells disposed on an upper surface of the body, the plurality of culture wells being in series communication through a first channel to form a set of culture wells; the co-culture holes are arranged on the upper surface of the body, the co-culture holes correspond to the culture holes one by one, each culture hole is communicated to the corresponding co-culture hole through a second channel, and the first channel is higher than the second channel.

Illustratively, the bottom of each of the plurality of culture wells is provided with a plurality of culture recesses that are recessed downward.

Illustratively, each of the plurality of culture recesses is contiguous with its neighboring culture recess.

Illustratively, each of the plurality of culture recesses is hemispherical.

Illustratively, the organoid culture chip further comprises a cover covering the non-end culture wells and the plurality of co-culture wells in the culture well group.

Illustratively, a plurality of culture hole plugs and a plurality of co-culture hole plugs are arranged on the lower surface of the cover body, the culture hole plugs plug the culture holes at the non-end part in a one-to-one correspondence manner, and the co-culture hole plugs plug the co-culture holes in a one-to-one correspondence manner.

Illustratively, the body has a plate shape, and a plurality of cylindrical portions extend upward from an upper surface of the body, and spaces inside the plurality of cylindrical portions form the plurality of culture wells and the plurality of co-culture wells.

Illustratively, the plurality of culture wells within the set of culture wells are arranged in rows along a lateral direction.

Illustratively, the body is provided with a plurality of culture hole groups, adjacent culture hole groups are not communicated with each other, the plurality of culture holes in each culture hole group are respectively arranged along the longitudinal direction with the corresponding co-culture holes, and the plurality of co-culture holes corresponding to each culture hole group are arranged along the transverse direction to form a co-culture hole group.

Illustratively, the culture well groups and the co-culture well groups are arranged alternately along the longitudinal direction.

By adopting the organoid culture chip of the embodiment of the utility model, the main body has high flux, and the overall size, the size of the culture holes and the number of the culture holes can be flexibly designed. Meanwhile, on one hand, the method can meet the requirement of co-culture and maintain micro-fluidic; on the other hand, the cultured organoids have good consistency, and are beneficial to experimental research such as drug screening and the like. In addition, the structural design of the organoid culture chip is not complicated, and the manufacturing cost and the cost are relatively low.

A series of concepts in a simplified form are introduced in the disclosure, which will be described in further detail in the detailed description section. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

The advantages and features of the present invention are described in detail below with reference to the accompanying drawings.

Drawings

The following drawings of the utility model are included to provide a further understanding of the utility model. The drawings illustrate embodiments of the utility model and, together with the description, serve to explain the principles of the utility model. In the drawings, there is shown in the drawings,

FIG. 1 is a perspective view of an organoid culture chip according to an exemplary embodiment of the present invention;

FIG. 2 is a perspective view of the organoid culture chip shown in FIG. 1 with the cover removed;

FIG. 3 is a top view of the organoid culture chip shown in FIG. 2;

FIG. 4 is an enlarged partial view of the organoid culture chip shown in FIG. 3;

FIG. 5 is an angled side view of the organoid culture chip shown in FIG. 2;

FIG. 6 is a side view of another angle of the organoid culture chip shown in FIG. 2;

FIG. 7 is a diagram illustrating a state of use of an organoid culture chip according to an exemplary embodiment of the present invention;

FIG. 8 is an angled perspective view of the cover shown in FIG. 1; and

fig. 9 is a perspective view of another angle of the cover shown in fig. 8.

Wherein the figures include the following reference numerals:

100. a body; 110. a cylindrical portion; 200. a culture well; 210. a culture recess; 300. co-culturing holes; 410. a first channel; 420. a second channel; 500. a cover body; 510. a culture well plug; 520. co-culture hole plugging; 530. a top plate; 540. a side plate; 550. opening the gap; 610. gelling; 620. and (4) a culture solution.

Detailed Description

In the following description, numerous details are provided to provide a thorough understanding of the present invention. One skilled in the art, however, will understand that the following description merely illustrates a preferred embodiment of the utility model and that the utility model may be practiced without one or more of these details. In other instances, well known features have not been described in detail so as not to obscure the utility model.

The embodiment of the utility model provides an organoid culture chip. Organoid culture chips can be used to culture cells, including but not limited to organoid cells, other cells or tissues affecting organoids, and the like. For clarity and simplicity of description, the transverse direction X-X, the longitudinal direction Y-Y and the vertical direction Z-Z are defined. The transverse direction X-X, the longitudinal direction Y-Y and the vertical direction Z-Z may be mutually perpendicular. The vertical direction Z-Z is generally the height direction of the organoid culture chip. The transverse direction X-X generally refers to the length direction of the organoid culture chip. The longitudinal direction Y-Y generally refers to the width direction of the organoid culture chip.

As shown in FIG. 2, the organoid culture chip may include a body 100, culture wells 200, and co-culture wells 300.

The structure of the body 100 may be any, including but not limited to a plate shape as shown in the figures, and may be, for example, a column shape or the like.

The number of the culture wells 200 may be plural. The plurality of culture wells 200 may be provided on the upper surface of the body 100 by welding, adhesion, molding, or the like. The plurality of culture wells 200 may be identical or different in structure. The number of the co-culture wells 300 may be plural. The plurality of co-culture wells 300 may correspond one-to-one to the plurality of culture wells 200. That is, the number of co-culture wells 300 and the number of culture wells 200 may be the same. The plurality of co-culture wells 300 may be identical or different in structure. The structure of the co-culture well 300 may be the same as or different from that of the culture well 200. The copending holes 300 may be provided on the upper surface of the body 100 by welding, bonding, or molding. Here and hereinafter, the terms of orientation "upper" and "lower" are used to refer to opposite ends along the vertical direction Z-Z, and in the angle shown in fig. 2, "upper" refers to the side near the upper right, and "lower" refers to the side near the lower left. Illustratively, the body 100 may have a plate shape. A plurality of cylindrical portions 110 extend upward from the upper surface of the body 100. The space in the plurality of cylindrical parts 110 may form a plurality of culture wells 200 and a plurality of co-culture wells 300. Through the arrangement, the organoid culture chip has the advantages of simple structure, less raw material consumption and low manufacturing cost. In other embodiments not shown, a plurality of grooves may extend downwardly from the upper surface of the body 100. The space within the recess may form a plurality of culture wells 200 and a plurality of co-culture wells 300.

Multiple culture wells 200 may be in series communication through a first channel 410 to form a set of culture wells. The number of culture well groups may be arbitrary. In embodiments where the number of culture well groups comprises a plurality, the configuration of the plurality of culture well groups may be the same or different. Illustratively, the first channel 410 may be located at a middle position of the culture well 200 or at a position closer to the aperture of the culture well 200 along the vertical direction Z-Z. In actual use, referring to fig. 7, the bottom of the culture well 200 needs to be laid with a gel 610. The height of the first channel 410 may be determined according to the height at which the gel 610 is laid, as long as it is ensured that the height of the first channel 410 is higher than the height at which the gel 610 is laid.

Each of the co-culture wells 300 may correspond to one of the culture wells 200, and communicate with each other through the second channel 420. Wherein, in the vertical direction Z-Z, the first channel 410 may be higher than the second channel 420. Illustratively, the second channel 420 may be located at a position intermediate to the culture well 200 and the co-culture well 300 or at a position closer to the bottom of the culture well 200 and the co-culture well 300 along the vertical direction Z-Z.

The organoid culture chip provided by the embodiment of the present invention may add organoid cells to the bottom of the culture well 200, and add other cells or tissues affecting organoids to the bottom of the culture well 200. Thus, referring to fig. 5 in combination, through the second channel 420, other cells or tissues affecting organoids within the co-culture well 300 can be allowed to release factors, thereby affecting organoid cells within the culture well 200, and also allowing the two parts to grow in an environment independent of each other, thereby allowing co-culture. Organoid culture chips can be used in a variety of co-culture scenarios. Illustratively, islet cells and pancreas can be co-cultured to achieve a common microenvironment system, promote secretion of factors, allow organoids to grow well and quickly, and save costs. Alternatively, normal cells and cancer cells may be co-cultured to perform a death detection assay for each of the different cells. The co-culture time is the same, the environment is the same, and the co-culture time and the environment are not influenced mutually, so that the stability is better. Therefore, the co-culture can not only save the cost, but also be used as a control to ensure the accuracy of the experiment.

Referring to fig. 7 in combination, in order to create a normal growth environment for organoid cells, a gel 610 may be laid down to the bottom of the culture well 200. Specifically, organoid cells form a three-dimensional structure after growth and division, and gel 610 can mimic the environment in a living body and allow the three-dimensional structure to exist therein. The cells in the culture well 200 may pass through the gel 610 and fall to the bottom of the culture well 200. To provide nutrients to the organoid cells and other cells or tissues affecting the organoid, culture fluid 620 may be injected into each of culture well 200 and co-culture well 300. The culture liquid 620 may remain above the gel 610 within the culture well 200.

Referring to fig. 6 in combination, in the culture well 200, after the height of the culture liquid 620 reaches the height of the first channel 410, the culture liquid 620 may flow into the adjacent culture well 200 through the first channel 410, and thus into all the culture wells 200 in the culture well group. Thus, a microfluidic culture medium environment is constructed. The micro-fluidic culture solution environment can not only control the culture conditions in vitro, but also control the flow rate of the culture solution, thereby deeply simulating the microenvironment in vivo. The micro-fluidic arrangement can promote the rapid generation and transformation of organoids, and can realize the periodic culture, reduce the liquid changing operation and liberate experimenters. Through microfluidic operation, fresh culture solution can be replaced all the time on the premise of low consumption. Therefore, the labor cost of the experiment can be reduced.

By adopting the organoid culture chip of the embodiment of the present invention, the main body has a high flux, and the overall size, the size of the culture wells 200, and the number of the culture wells 200 can be flexibly designed. Meanwhile, on one hand, the co-culture can be met, and the micro-fluidic control is maintained; on the other hand, the cultured organoids have good consistency, and are beneficial to experimental research such as drug screening and the like. In addition, the structural design of the organoid culture chip is not complicated, and the manufacturing cost and the cost are relatively low.

Illustratively, as shown in FIGS. 3 to 4 and 7, the bottom of each of the plurality of culture wells 200 may be provided with a culture recess 210 that is recessed downward. The number of the culture recesses 210 may be plural, including but not limited to 9 shown in the drawing. The plurality of culture recesses 210 may be identical in structure or different in structure. Preferably, each of the plurality of culture recesses 210 may have a hemispherical shape. The culture recess 210 having a hemispherical shape is easy to process, so that the manufacturing cost can be reduced. Organoid cells can fall into culture recess 210. By providing the culture recess 210, adherent culture or pellet culture can be facilitated.

Further, as shown in FIGS. 2 to 3, each of the plurality of culture recesses 210 is adjacent to its adjacent culture recess 210 as viewed downward in the vertical direction Z-Z. In embodiments where each of the plurality of culture recesses 210 is hemispherical, the mutual abutment refers to mutual tangency. By making the culture recesses 210 adjacent to each other, the number of cells in each culture recess 210 can be consistent, and the consistency of the cultured organoids is good, so that more accurate basis can be provided for comparison of subsequent experimental results.

Illustratively, as shown in FIGS. 1 and 8-9, the organoid culture chip may further include a cover 500. The culture well group may have culture wells 200 in both ends, and culture wells 200 in the non-end portion between the two end portions. The cover 500 may cover the culture well 200 and the plurality of co-culture wells 300 at the non-end portion of the culture well group. Illustratively, the cover 500 may be provided with a notch 550. The cutout 550 may expose an end culture well 200 in a set of culture wells. Thus, the culture medium 620 can be injected into the culture well 200 at one end (for example, the left end) of the culture well group. The culture liquid 620 may flow into the adjacent culture well 200 through the first channel 410, and thus into all the culture wells 200 in the culture well group. Finally, the culture solution 620 can be aspirated from the culture well 200 at the other end (e.g., the right end) of the culture well group, thereby forming the microfluidic environment. Therefore, the structure is simple and the cost is low. In addition, the cover 500 can cover the organoid cells and other cells or tissues affecting the organoid, thereby preventing the organoid cells and other cells or tissues from being affected by the outside and ensuring the stability of the culture environment.

Further, as shown in fig. 9, a plurality of culture well plugs 510 and a plurality of co-culture well plugs 520 extending downward may be provided on the lower surface of the cover 500. The plurality of culture well plugs 510 may plug the non-end culture wells 200 in a one-to-one correspondence. The plurality of co-culture hole plugs 520 may plug the plurality of co-culture holes 300 in a one-to-one correspondence. This arrangement can improve the sealing property of the cover 500 and further ensure the stability of the culture environment.

Illustratively, as shown in fig. 8-9, the cover 500 may include a top panel 530 and side panels 540. The side plates 540 may be connected to edges of the top plate 530 and extend downward from the edges of the top plate 530. The side plate 540 may surround the culture well 200 and the plurality of co-culture wells 300 in the non-end portion of the culture well group covered with the cover 500. This arrangement can improve the sealing property of the cover 500 and further ensure the stability of the culture environment.

The plurality of culture wells 200 within a culture well group may be arranged in any suitable shape, including but not limited to a straight line, a curved line, a polyline, or the like. Illustratively, as shown in FIGS. 2-3, a plurality of culture wells 200 within a set of culture wells may be arranged in rows along the lateral direction X-X. Thus, the culture well group has a simple structure and low manufacturing cost.

Further, as shown in FIGS. 2-3, a plurality of culture well groups may be provided on the body 100. The adjacent culture well groups are not communicated with each other. The plurality of culture wells 200 in each culture well group are arranged along the longitudinal direction Y-Y with their corresponding co-culture wells 300, respectively. The plurality of co-culture wells 300 for each set of culture wells may be arranged along the transverse direction X-X to form a set of co-culture wells. Thus, the culture well group and the co-culture well group have simple structures and low manufacturing cost. In addition, the number of the culture wells 200 and the co-culture wells 300 is large, which facilitates high-throughput culture.

Further, the culture well groups and co-culture well groups may be arranged alternately along the longitudinal direction Y-Y. In the example shown in the figure, the culture well group and co-culture well group total 6 rows. Wherein the culture well groups are arranged in the 1 st, 3 rd and 5 th rows, and the co-culture well groups are arranged in the 2 nd, 4 th and 6 th rows. However, in practical use, the arrangement of the culture well groups and co-culture well groups may be arbitrary as long as the alternate arrangement is satisfied. With this arrangement, it is convenient to distinguish the culture well 200 from the co-culture well 300, thereby reducing the possibility of occurrence of erroneous operation.

In the description of the present invention, it is to be understood that the directions or positional relationships indicated by the directional terms such as "front", "rear", "upper", "lower", "left", "right", "lateral", "vertical", "horizontal" and "top", "bottom", etc., are generally based on the directions or positional relationships shown in the drawings, and are only for convenience of describing the present invention and simplifying the description, and in the case of not making a reverse explanation, these directional terms do not indicate and imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore, should not be construed as limiting the scope of the present invention; the terms "inner" and "outer" refer to the interior and exterior relative to the contours of the components themselves.

For ease of description, relative terms of regions such as "above … …", "above … …", "on … …", "above", etc. may be used herein to describe the regional positional relationship of one or more components or features to other components or features shown in the figures. It is to be understood that the relative terms of the regions are intended to encompass not only the orientation of the element as depicted in the figures, but also different orientations in use or operation. For example, if an element in the drawings is turned over in its entirety, the articles "over" or "on" other elements or features will include the articles "under" or "beneath" the other elements or features. Thus, the exemplary term "above … …" can include both an orientation of "above … …" and "below … …". Further, these components or features may also be positioned at various other angles (e.g., rotated 90 degrees or other angles), all of which are intended to be encompassed herein.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, elements, components, and/or combinations thereof, unless the context clearly indicates otherwise.

It should be noted that the terms "first," "second," and the like in the description and claims of this application and in the drawings described above are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in sequences other than those illustrated or described herein.

The present invention has been illustrated by the above embodiments, but it should be understood that the above embodiments are for illustrative and descriptive purposes only and are not intended to limit the utility model to the scope of the described embodiments. Furthermore, it will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that many variations and modifications may be made in accordance with the teachings of the present invention, which variations and modifications are within the scope of the present invention as claimed. The scope of the utility model is defined by the appended claims and equivalents thereof.

Claims (10)

1. An organoid culture chip, comprising:

a body;

a plurality of culture wells disposed on an upper surface of the body, the plurality of culture wells being in series communication through a first channel to form a set of culture wells; and

the culture device comprises a body, a plurality of co-culture holes arranged on the upper surface of the body, a plurality of culture holes which are in one-to-one correspondence with the co-culture holes, and each culture hole is communicated to the corresponding co-culture hole through a second channel, wherein the first channel is higher than the second channel.

2. The organoid culture chip of claim 1, wherein the bottom of each of said plurality of culture wells is provided with a plurality of culture recesses recessed downward.

3. The organoid culture chip of claim 2 wherein each of said plurality of culture recesses is contiguous with its adjacent culture recess.

4. The organoid culture chip of claim 2 wherein each of said plurality of culture recesses is hemispherical.

5. The organoid culture chip of claim 1, further comprising a cover covering the non-end culture wells and the plurality of co-culture wells in the set of culture wells.

6. The organoid culture chip of claim 5, wherein a plurality of culture hole plugs extending downward and a plurality of co-culture hole plugs are provided on the lower surface of the cover, the plurality of culture hole plugs plugging the non-end culture holes in a one-to-one correspondence, and the plurality of co-culture hole plugs plugging the plurality of co-culture holes in a one-to-one correspondence.

7. The organoid culture chip of claim 1, wherein the body has a plate shape, a plurality of cylindrical portions extend upward from an upper surface of the body, and spaces in the plurality of cylindrical portions form the plurality of culture wells and the plurality of co-culture wells.

8. The organoid culture chip of claim 1 wherein said plurality of culture wells in said set of culture wells are arranged in a row along a lateral direction.

9. The organoid culture chip of claim 8, wherein the body has a plurality of culture well groups, adjacent culture well groups are not connected to each other, the plurality of culture wells in each culture well group are arranged with their corresponding co-culture wells along the longitudinal direction, and the plurality of co-culture wells in each culture well group are arranged along the transverse direction to form a co-culture well group.

10. The organoid culture chip of claim 9, wherein along the longitudinal direction, the sets of culture wells and the sets of co-culture wells are arranged alternately.

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