Organ-like culture monitoring device

By using resistance detection components in the organoid culture monitoring device to monitor the growth status of organoids in real time, the contamination problem caused by human intervention is solved and the accuracy of the analysis results is improved.

CN223422680UActive Publication Date: 2025-10-10GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH CHINESE ACADEMY OF SCIENCES
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Patent Information

Application Number
CN202422726824.9
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-11-08
Publication Date
2025-10-10
Estimated Expiration
2034-11-08

AI Technical Summary

Technical Problem

Existing technologies are prone to contamination of the growth environment due to human intervention during organoid culture monitoring, affecting the accuracy of analysis results.

Method used

A culture monitoring device comprising a base and a culture chip is used. The base is provided with a resistance detection component, and the culture chip is provided with a culture pool. Dynamic real-time monitoring is achieved by detecting the resistance changes of organoids in the culture pool, avoiding human intervention.

Benefits of technology

Dynamic real-time monitoring of the organoid growth environment is achieved, the accuracy of the analysis results is improved, and contamination of the growth environment is avoided.

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Abstract

The utility model belongs to the technical field of organoid culture, and particularly discloses an organoid culture monitoring device. According to the organ-like culture monitoring device, a culture chip is arranged on a resistance value detection assembly, an organ-like body and a culture medium are placed in a culture pool of the culture chip, the resistance value detection assembly is used for detecting the resistance value of the organ-like body in the culture pool, and the change of the resistance value can reflect the component change of the organ-like body in the culture process; the growth state of the cultured organoid is fed back through the resistance change curve, so that dynamic real-time monitoring of the cultured organoid is realized, the pollution of the organoid growth environment caused by human intervention is avoided, and the accuracy of an analysis result is improved; besides, the sample feeding plate is connected with the base to fix the culture chip above the resistance value detection assembly, the culture chip is prevented from moving to influence the monitoring result, and the distance between the base and the sample feeding plate is adjustable, so that the sample feeding plate and the culture chip as well as the culture chip and the resistance value detection assembly can be in close contact, and the accuracy of the monitoring result is ensured.
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Description

Technical Field

[0001] The utility model relates to the technical field of organoid culture, in particular to an organoid culture monitoring device. Background Art

[0002] Organoids are three-dimensional (3D) cell cultures that embody key features of the organs they represent. These in vitro culture systems comprise a self-renewing stem cell population that can differentiate into multiple organ-specific cell types, share a similar spatial organization with the corresponding organ, and can recapitulate some of its functions, thus providing a highly physiologically relevant system.

[0003] Because organoid development requires a long culture period, monitoring the organoid environment and growth process during the culture process is crucial. Existing techniques for monitoring organoid culture typically rely on static culture, where nutrients are manually supplied to the organoids. This process requires manual extraction of large amounts of data, processing and analysis, and then evaluation of the organoid's growth environment and status. Direct human intervention can easily contaminate the organoid's growth environment, leading to biased analysis results. Utility Model Content

[0004] The purpose of the utility model is to provide an organoid culture monitoring device to achieve dynamic real-time monitoring of cultured organoids, avoid contamination of the organoid growth environment caused by human intervention, and improve the accuracy of analysis results.

[0005] To achieve this purpose, the present invention adopts the following technical solutions:

[0006] A device for monitoring organoid culture, comprising:

[0007] A base, wherein a resistance detection component is provided on the base;

[0008] A culture chip is provided on the resistance detection component. The culture chip is provided with a culture pool, the culture pool is used to place organoids and culture medium, and the resistance detection component is used to detect the resistance of the organoids in the culture pool;

[0009] The sample injection plate is covered on the culture chip, the sample injection plate is detachably connected to the base, and the distance between the sample injection plate and the base is adjustable.

[0010] As an optional technical solution for the above-mentioned organoid culture monitoring device, the sample injection plate is provided with a liquid inlet tube and a liquid outlet tube, the culture chip is provided with a liquid inlet, a liquid outlet and a flow channel assembly, the flow channel assembly is connected to the culture tank, the liquid inlet and the liquid outlet are respectively connected to the flow channel assembly, the liquid inlet tube is inserted into the liquid inlet, and the liquid outlet tube is inserted into the liquid outlet.

[0011] As an optional technical solution for the above-mentioned organoid culture monitoring device, the liquid inlet tube and the liquid outlet tube are provided on the side of the sample injection plate facing the culture chip, and the sample injection plate is provided with a first through hole connected to the liquid inlet tube and a second through hole connected to the liquid outlet tube.

[0012] As an optional technical solution for the above-mentioned organoid culture monitoring device, a first boss and a second boss are provided on the side of the sample injection plate facing away from the culture chip, the liquid inlet tube is arranged corresponding to the first boss, the first through hole passes through the first boss, the liquid outlet tube is arranged corresponding to the second boss, and the second through hole passes through the second boss.

[0013] As an optional technical solution of the above-mentioned organoid culture monitoring device, a receiving groove is recessed on a side of the sample introduction plate facing the culture chip, and the receiving groove is used to receive the culture chip.

[0014] As an optional technical solution for the above-mentioned organoid culture monitoring device, a plurality of third bosses are provided on the base at circumferential intervals, the third bosses are in contact with the edge of the sample injection plate, a first connecting hole is provided at a position corresponding to the sample injection plate and the third bosses, a second connecting hole is provided on the third bosses, and a connecting piece passes through the first connecting hole and is connected to the second connecting hole.

[0015] As an optional technical solution for the above-mentioned organoid culture monitoring device, a plurality of fourth bosses are provided at circumferential intervals on the side of the sample introduction plate facing the culture chip, the fourth bosses are arranged in a one-to-one correspondence with the third bosses, the fourth bosses are pressed against the corresponding third bosses, and the first connecting hole passes through the fourth bosses.

[0016] As an optional technical solution of the above-mentioned organoid culture monitoring device, the second connecting hole is a threaded hole, the connecting member is a bolt, and the bolt is threadedly connected to the second connecting hole.

[0017] As an optional technical solution for the above-mentioned organoid culture monitoring device, a support boss is provided at a position on the base corresponding to the receiving groove, and the resistance detection component is arranged on the support boss. The area of ​​the support boss is larger than the area of ​​the culture chip and smaller than the area of ​​the notch of the receiving groove.

[0018] As an optional technical solution of the above-mentioned organoid culture monitoring device, the resistance detection component includes multiple resistance detection parts, and multiple culture pools are provided on the culture chip, and each culture pool is correspondingly provided with at least one resistance detection part.

[0019] Beneficial effects of the utility model:

[0020] The utility model provides an organoid culture monitoring device, in which a resistance detection component is arranged on a base, a culture chip is arranged on the resistance detection component, a culture pool of the culture chip is used to place organoids and culture medium, and the resistance detection component is used to detect the resistance of the organoid in the culture pool. The change in resistance can reflect the change in the composition of the organoid during the culture process, and the growth status of the cultured organoid is fed back through the resistance change curve to realize dynamic real-time monitoring of the cultured organoid, avoid contamination of the organoid growth environment caused by human intervention, and improve the accuracy of the analysis results; in addition, the sample plate is connected to the base to fix the culture chip above the resistance detection component to avoid the movement of the culture chip and affect the monitoring results. The distance between the base and the sample plate is adjustable, and the distance between the base and the sample plate can be adjusted according to actual installation requirements to ensure close contact between the sample plate and the culture chip, and between the culture chip and the resistance detection component, thereby ensuring the accuracy of the monitoring results. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the structure of the organoid culture monitoring device provided by an embodiment of the present invention;

[0022] Figure 2 This is a schematic diagram of the structure of the organoid culture monitoring device provided by an embodiment of the present invention;

[0023] Figure 3 This is a schematic diagram of the structure of the culture chip provided by an embodiment of the present utility model;

[0024] Figure 4 It is a cross-sectional view of the organoid culture monitoring device provided by an embodiment of the present utility model.

[0025] In the picture:

[0026] 1. Base; 2. Resistance detection component; 3. Culture chip; 4. Sample plate;

[0027] 11. Third boss; 12. Second connection hole; 13. Support boss;

[0028] 21. Resistance detection parts;

[0029] 31. Culture tank; 32. Liquid inlet; 33. Liquid outlet;

[0030] 41. Liquid inlet pipe; 42. Liquid outlet pipe; 43. First through hole; 44. Second through hole; 45. First boss; 46. Second boss; 47. Accommodating groove; 48. First connecting hole; 49. Fourth boss. DETAILED DESCRIPTION

[0031] The present invention will be further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are intended only to illustrate the present invention and are not intended to limit the present invention. It should also be noted that, for ease of description, the accompanying drawings only illustrate portions relevant to the present invention, not all of its components.

[0032] In the description of this utility model, unless otherwise specified or limited, the terms "connected," "connect," and "fixed" should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection or electrical connection; direct connection or indirect connection through an intermediate medium; internal communication between two components or interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in this utility model based on the specific circumstances.

[0033] In the present invention, unless otherwise expressly specified or limited, a first feature being "above" or "below" a second feature may include the first and second features being in direct contact, or may include the first and second features being in contact not directly but through another feature between them. Moreover, a first feature being "above," "above," and "above" a second feature may include the first feature being directly above or obliquely above the second feature, or may simply mean that the first feature is higher in level than the second feature. A first feature being "below," "below," and "below" a second feature may include the first feature being directly below or obliquely below the second feature, or may simply mean that the first feature is lower in level than the second feature.

[0034] In the description of this embodiment, the terms "upper," "lower," "right," and other orientations or positional relationships are based on the orientations or positional relationships shown in the accompanying drawings and are intended solely for ease of description and simplified operation. They do not indicate or imply that the devices or components referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first" and "second" are used solely for descriptive purposes and have no special meaning.

[0035] like Figure 1 、 Figure 2 and Figure 3As shown, this embodiment provides a culture monitoring device for organoids, which includes a base 1, a culture chip 3, and a sample injection plate 4. The base 1 is provided with a resistance detection component 2, the culture chip 3 is arranged on the resistance detection component 2, and the culture chip 3 is provided with a culture pool 31. The culture pool 31 is used to place organoids and culture medium. The resistance detection component 2 is used to detect the resistance of the organoids in the culture pool 31. The change in resistance can reflect the change in the composition of the organoids during the culture process. The growth status of the cultured organoids is fed back through the resistance change curve, realizing dynamic real-time monitoring of the cultured organoids, avoiding contamination of the organoid growth environment caused by human intervention, and improving the accuracy of the analysis results. The sample injection plate 4 is covered on the culture chip 3, and the sample injection plate 4 is detachably connected to the base 1, and the distance between the sample injection plate 4 and the base 1 is adjustable. The sample injection plate 4 is connected to the base 1 to fix the culture chip 3 above the resistance detection component 2 to prevent the culture chip 3 from moving and affecting the monitoring results. The distance between the base 1 and the sample injection plate 4 is adjustable. The distance between the base 1 and the sample injection plate 4 can be adjusted according to actual installation requirements to ensure close contact between the sample injection plate 4 and the culture chip 3, and between the culture chip 3 and the resistance detection component 2, thereby ensuring the accuracy of the monitoring results.

[0036] like Figure 2 、 Figure 3 and Figure 4 As shown, in some embodiments, the sample injection plate 4 is provided with a liquid inlet tube 41 and a liquid outlet tube 42, and the culture chip 3 is provided with a liquid inlet 32, a liquid outlet 33, and a flow channel assembly. The flow channel assembly is connected to the culture tank 31, and the liquid inlet 32 ​​and the liquid outlet 33 are respectively connected to the flow channel assembly. The liquid inlet tube 41 is inserted into the liquid inlet 32, and the liquid outlet tube 42 is inserted into the liquid outlet 33. Culture medium is perfused into the culture chip 3 through the liquid inlet tube 41 and the liquid inlet 32. After passing through the culture tank 31, the culture medium is discharged through the liquid outlet 33 and the liquid outlet tube 42, thereby realizing the supply and replacement of culture medium.

[0037] The liquid inlet 32 ​​and liquid outlet 33 of the culture chip 3 are typically disposed on the surface of the culture chip 3. Optionally, a liquid inlet pipe 41 and a liquid outlet pipe 42 are disposed on the side of the sample injection plate 4 facing the culture chip 3. The sample injection plate 4 is provided with a first through-hole 43 communicating with the liquid inlet pipe 41 and a second through-hole 44 communicating with the liquid outlet pipe 42. The culture medium enters the flow channel assembly through the first through-hole 43, the liquid inlet pipe 41, and the liquid inlet 32. After passing through the culture tank, the culture medium is discharged through the liquid outlet 33, the liquid outlet pipe 42, and the second through-hole 44. The liquid inlet pipe 41 and the liquid outlet pipe 42 are disposed on the side of the sample injection plate 4 facing the culture chip 3. When the sample injection plate 4 is mounted on the base 1, the liquid inlet pipe 41 can be plugged into the liquid inlet 32, and the liquid outlet pipe 42 can be plugged into the liquid outlet 33.

[0038] Furthermore, a first boss 45 and a second boss 46 are provided on the side of the sample injection plate 4 facing away from the culture chip 3. The liquid inlet tube 41 is provided corresponding to the first boss 45, and the first through hole 43 extends through the first boss 45. The liquid outlet tube 42 is provided corresponding to the second boss 46, and the second through hole 44 extends through the second boss 46. The first boss 45 and the second boss 46 facilitate connection with external pipelines to provide culture medium to the culture chip 3 and discharge culture medium from the culture chip 3.

[0039] In some other feasible embodiments, a liquid inlet tube 41 and a liquid outlet tube 42 are provided on the side of the sample injection plate 4 facing the culture chip 3, and a liquid inlet channel and a liquid outlet channel are provided on the sample injection plate 4, one end of the liquid inlet channel is connected to the liquid inlet tube 41, and the other end of the liquid inlet channel passes through the side of the sample injection plate 4, one end of the liquid outlet channel is connected to the liquid outlet tube 42, and the other end of the liquid outlet channel passes through the side of the sample injection plate 4.

[0040] In some embodiments, a receiving groove 47 is recessed on the side of the sample injection plate 4 facing the culture chip 3. The receiving groove 47 is used to receive the culture chip 3 so that the culture chip 3 will not be completely exposed to the external environment and the culture chip 3 is protected from damage.

[0041] The base 1 is provided with a plurality of third bosses 11 spaced circumferentially. The third bosses 11 contact the edge of the sample injection plate 4. A first connection hole 48 is provided at a position corresponding to the third bosses 11 on the sample injection plate 4. A second connection hole 12 is provided on the third bosses 11. A connector passes through the first connection hole 48 and connects to the second connection hole 12. The third bosses 11 are provided to support the sample injection plate 4, creating a certain gap between the sample injection plate 4 and the base 1 to facilitate adjustment of the pressure with which the sample injection plate 4 presses against the culture chip 3. The second connection hole 12 is provided on the third bosses 11 to reduce the thickness of the base 1 and achieve a stable connection between the sample injection plate 4 and the base 1.

[0042] In some other possible implementations, a third boss 11 is provided on the base 1 along the circumferential direction, and a plurality of second connection holes 12 are provided on the third boss 11 at intervals.

[0043] Optionally, a plurality of fourth bosses 49 are provided at circumferential intervals on the side of the sample injection plate 4 facing the culture chip 3. The fourth bosses 49 are arranged one-to-one in correspondence with the third bosses 11. The fourth bosses 49 are pressed against the corresponding third bosses 11. The first connecting hole 48 passes through the fourth bosses 49, which can increase the locking force between the sample injection plate 4 and the base 1.

[0044] The second connection hole 12 is a threaded hole, and the connecting member is a bolt, which is screwed to the second connection hole 12. A first connection hole 48 is formed on the upper surface of the sample injection plate 4 and is screwed to the second connection hole 12, which facilitates the connection and removal of the sample injection plate 4 and the base 1, and has a simple structure and low cost.

[0045] A support boss 13 is provided on the base 1 at a position corresponding to the receiving groove 47. The resistance detection assembly 2 is mounted on this support boss 13, providing support for the resistance detection assembly 2. The area of ​​the support boss 13 is larger than the area of ​​the culture chip 3 and smaller than the area of ​​the notch of the receiving groove 47. This ensures that the receiving groove 47 can accommodate the support boss 13 without interfering with the fourth boss 49, while still leaving sufficient space to support the culture chip 3. The height of the support boss 13 can be slightly higher than the third boss 11, but this is not specifically limited here.

[0046] When using the culture monitoring device, the culture chip 3 is first pre-fixed on the resistance detection component 2. The bonding method can be used, which is not specifically limited here. The organoid is then transplanted into the culture pool 31 of the culture chip 3, and the sample injection plate 4 is placed on the culture chip 3. The sample injection plate 4 and the base 1 are connected, and by adjusting the distance between the sample injection plate 4 and the base 1, the sample injection plate 4 presses the culture chip 3, and the culture chip 3 presses the resistance detection component 2. After the assembly is completed, the culture medium enters the culture chip 3 through the liquid inlet pipe 41 and the liquid inlet 32, flows through the culture pool 31, and is then discharged through the liquid outlet pipe 42 and the liquid outlet 33. At the same time, the resistance detection component 2 monitors the resistance changes of the organoids in the culture pool 31 to complete the monitoring of the growth status of the organoid culture process.

[0047] The resistance detection component 2 includes a plurality of resistance detection elements 21 , and a plurality of culture pools 31 are provided on the culture chip 3 . Each culture pool 31 is provided with at least one resistance detection element 21 to monitor the organoids in each culture pool 31 separately.

[0048] Optionally, resistance detection element 2 includes a detection electrode and a glass slide connected to the detection electrode. The specific structure is conventional and will not be described in detail here. The detection electrode can detect the resistance of the organoid in culture tank 31. Changes in the resistance reflect changes in the organoid's composition and, therefore, the growth status of the organoid.

[0049] The structure of the above-mentioned culture chip 3 is prior art and will not be described in detail here.

[0050] Obviously, the above-described embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention and are not intended to limit the manner in which the present invention is to be implemented. A person skilled in the art would be able to make various obvious changes, readjustments, and substitutions without departing from the scope of protection of the present invention. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. A device for monitoring organoid culture, characterized in that: include: A base (1), wherein a resistance detection component (2) is provided on the base (1); A culture chip (3) is arranged on the resistance detection component (2), the culture chip (3) is provided with a culture pool (31), the culture pool (31) is used to place organoids and culture medium, and the resistance detection component (2) is used to detect the resistance of the organoids in the culture pool (31); The sample injection plate (4) is covered on the culture chip (3); the sample injection plate (4) is detachably connected to the base (1), and the distance between the sample injection plate (4) and the base (1) is adjustable.

2. The organoid culture monitoring device according to claim 1, characterized in that: The sample injection plate (4) is provided with a liquid inlet pipe (41) and a liquid outlet pipe (42); the culture chip (3) is provided with a liquid inlet (32), a liquid outlet (33) and a flow channel assembly; the flow channel assembly is communicated with the culture pool (31); the liquid inlet (32) and the liquid outlet (33) are respectively communicated with the flow channel assembly; the liquid inlet pipe (41) is plugged into the liquid inlet (32); and the liquid outlet pipe (42) is plugged into the liquid outlet (33).

3. The organoid culture monitoring device according to claim 2, characterized in that: The sample injection plate (4) is provided with the liquid inlet pipe (41) and the liquid outlet pipe (42) on one side facing the culture chip (3), and the sample injection plate (4) is provided with a first through hole (43) communicating with the liquid inlet pipe (41) and a second through hole (44) communicating with the liquid outlet pipe (42).

4. The organoid culture monitoring device according to claim 3, characterized in that: The sample injection plate (4) is provided with a first boss (45) and a second boss (46) on a side facing away from the culture chip (3); the liquid inlet pipe (41) is arranged corresponding to the first boss (45); the first through hole (43) passes through the first boss (45); the liquid outlet pipe (42) is arranged corresponding to the second boss (46); the second through hole (44) passes through the second boss (46).

5. The organoid culture monitoring device according to claim 1, characterized in that: A receiving groove (47) is recessed on one side of the sample injection plate (4) facing the culture chip (3), and the receiving groove (47) is used to receive the culture chip (3).

6. The organoid culture monitoring device according to claim 5, characterized in that: A plurality of third bosses (11) are provided on the base (1) at intervals along the circumferential direction, the third bosses (11) are in contact with the edge of the injection plate (4), a first connecting hole (48) is provided at a position of the injection plate (4) corresponding to the third bosses (11), a second connecting hole (12) is provided on the third bosses (11), and a connecting piece is passed through the first connecting hole (48) and connected to the second connecting hole (12).

7. The organoid culture monitoring device according to claim 6, characterized in that: A plurality of fourth bosses (49) are provided at intervals along the circumferential direction on one side of the sample injection plate (4) facing the culture chip (3), and the fourth bosses (49) are arranged in a one-to-one correspondence with the third bosses (11). The fourth bosses (49) are pressed against the corresponding third bosses (11), and the first connecting hole (48) passes through the fourth bosses (49).

8. The organoid culture monitoring device according to claim 6, characterized in that: The second connecting hole (12) is a threaded hole, the connecting piece is a bolt, and the bolt is threadedly connected to the second connecting hole (12).

9. The organoid culture monitoring device according to claim 5, characterized in that: A supporting boss (13) is provided on the base (1) at a position corresponding to the receiving groove (47), and the resistance detection component (2) is arranged on the supporting boss (13). The area of ​​the supporting boss (13) is larger than the area of ​​the culture chip (3) and smaller than the area of ​​the notch of the receiving groove (47).

10. The organoid culture monitoring device according to claim 1, characterized in that: The resistance detection component (2) includes a plurality of resistance detection elements (21), and the culture chip (3) is provided with a plurality of culture pools (31), and each culture pool (31) is correspondingly provided with at least one resistance detection element (21).