Organ-like culture monitoring device

Abstract

The invention 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.

Description

Technical Field

[0001] The present invention relates to the technical field of organoid culture, and in particular to a culture monitoring device for organoids. Background Art

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

[0003] Since the development of organoids requires a long culture period, it is crucial to monitor the environment and growth process of organoids during the culture process. In the prior art, in the process of monitoring organoid culture, a static culture that usually uses artificial nutrition to supplement the organoids is required. During the culture process, a large amount of data needs to be manually extracted, processed and analyzed, and then the growth environment and status of the organoids are evaluated. Direct human intervention can easily cause pollution to the growth environment of the organoids, resulting in deviations in the analysis results. Summary of the invention

[0004] The purpose of the present invention 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 object, the present invention adopts the following technical solutions:

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

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

[0008] A culture chip is arranged on the resistance detection component, the culture chip is provided with a culture pool, the culture pool is used to place the organoid and the culture medium, and the resistance detection component is used to detect the resistance of the organoid 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 of 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 one side of the sample introduction plate facing the culture chip, the fourth bosses are arranged one-to-one in 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 piece 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 supporting boss is provided at a position on the base corresponding to the receiving groove, and the resistance detection component is arranged on the supporting boss. The area of ​​the supporting 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 a plurality of resistance detection elements, a plurality of culture pools are provided on the culture chip, and at least one resistance detection element is correspondingly arranged for each culture pool.

[0019] Beneficial effects of the present invention:

[0020] The organoid culture monitoring device provided by the present invention has a resistance detection component arranged on a base, a culture chip arranged on the resistance detection component, a culture pool of the culture chip for placing organoids and culture medium, and the resistance detection component for detecting 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 state 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 result; in addition, the sample injection 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 result, and the distance between the base and the sample injection plate is adjustable, and the distance between the base and the sample injection plate can be adjusted according to the actual installation requirements, so that the sample injection plate and the culture chip, and the culture chip and the resistance detection component can be in close contact, thereby ensuring the accuracy of the monitoring result. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a schematic diagram of the structure of an organoid culture monitoring device provided in an embodiment of the present invention;

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

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

[0024] Figure 4 4 is a cross-sectional view of an organoid culture monitoring device provided in an embodiment of the present invention.

[0025] In the figure:

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

[0027] 11. third boss; 12. second connection hole; 13. supporting boss;

[0028] 21. Resistance detection parts;

[0029] 31. Cultivation 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 in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention. It should also be noted that, for ease of description, only parts related to the present invention, rather than all structures, are shown in the accompanying drawings.

[0032] In the description of the present invention, unless otherwise clearly specified and limited, the terms "connected", "connected", and "fixed" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

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

[0034] In the description of this embodiment, the terms "upper", "lower", "right", etc., directions or positional relationships are based on the directions or positional relationships shown in the drawings, and are only for the convenience of description and simplification of operation, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are only used to distinguish in the description 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. A resistance detection component 2 is provided on the base 1, and the culture chip 3 is arranged on the resistance detection component 2. A culture pool 31 is provided on the culture chip 3. 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 state of the cultured organoids is fed back through the resistance change curve to achieve dynamic real-time monitoring of the cultured organoids, avoid contamination of the organoid growth environment caused by human intervention, and improve 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 pipe 41 and a liquid outlet pipe 42, the culture chip 3 is provided with a liquid inlet port 32, a liquid outlet port 33 and a flow channel assembly, the flow channel assembly is connected to the culture tank 31, the liquid inlet port 32 and the liquid outlet port 33 are respectively connected to the flow channel assembly, the liquid inlet pipe 41 is plugged into the liquid inlet port 32, and the liquid outlet pipe 42 is plugged into the liquid outlet port 33. The culture medium is perfused into the culture chip 3 through the liquid inlet pipe 41 and the liquid inlet port 32, and the culture medium is discharged through the liquid outlet port 33 and the liquid outlet pipe 42 after passing through the culture tank 31, so as to realize the supply and replacement of the culture medium.

[0037] The liquid inlet 32 ​​and the liquid outlet 33 of the culture chip 3 are usually arranged on the surface of the culture chip 3. Optionally, a liquid inlet pipe 41 and a liquid outlet pipe 42 are arranged 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 connected to the liquid inlet pipe 41 and a second through hole 44 connected to 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 31, 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 arranged on the side of the sample injection plate 4 facing the culture chip 3. When the sample injection plate 4 is installed 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 pipe 41 is provided corresponding to the first boss 45, the first through hole 43 penetrates the first boss 45, the liquid outlet pipe 42 is provided corresponding to the second boss 46, and the second through hole 44 penetrates the second boss 46. The first boss 45 and the second boss 46 are provided to facilitate connection with external pipelines, so as to realize supplying culture medium to the culture chip 3 and discharging culture medium in 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 one side of the sample injection plate 4 facing the culture chip 3. The receiving groove 47 is used to receive the culture chip 3. The culture chip 3 will not be completely exposed to the external environment, thus protecting the culture chip 3 from damage.

[0041] A plurality of third bosses 11 are provided at intervals along the circumference of the base 1. The third bosses 11 are in contact with the edge of the sample injection plate 4. A first connection hole 48 is provided at a position corresponding to the sample injection plate 4 and the third bosses 11. A second connection hole 12 is provided on the third boss 11. The connector passes through the first connection hole 48 and is connected to the second connection hole 12. The third boss 11 is provided to support the sample injection plate 4 so that there is a certain gap between the sample injection plate 4 and the base 1, so as to adjust the pressure of the sample injection plate 4 pressing the culture chip 3. The second connection hole 12 is provided on the third boss 11, which can reduce the thickness of the base 1 and also realize the stable connection between the sample injection plate 4 and the base 1.

[0042] In some other practicable embodiments, a third boss 11 is circumferentially provided on the base 1 , and a plurality of second connection holes 12 are spaced apart on the third boss 11 .

[0043] Optionally, a plurality of fourth bosses 49 are circumferentially spaced apart on one side of the sample injection plate 4 facing the culture chip 3, and the fourth bosses 49 are arranged one-to-one corresponding to the third bosses 11. The fourth bosses 49 are pressed against the corresponding third bosses 11, and the first connecting holes 48 pass 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 connection piece is a bolt, which is screwed to the second connection hole 12. The first connection hole 48 is drilled on the upper surface of the sample injection plate 4, and then screwed to the second connection hole 12, which facilitates the connection and disassembly 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 at a position on the base 1 corresponding to the receiving groove 47, and the resistance detection component 2 is arranged on the support boss 13 to provide support for the installation of the resistance detection component 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, so that the receiving groove 47 can accommodate the support boss 13, the support boss 13 and the fourth boss 49 will not interfere with each other, and at the same time there is enough space to support the culture chip 3. The support boss 13 can be slightly higher than the height of the third boss 11, which 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, which can be bonded, and is not specifically limited here. Then the organoid is transplanted into the culture pool 31 of the culture chip 3, the sample injection plate 4 is covered on the culture chip 3, the sample injection plate 4 and the base 1 are connected, and the sample injection plate 4 is pressed against the culture chip 3 by adjusting the distance between the sample injection plate 4 and the base 1, and the culture chip 3 is pressed against 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 port 32, flows through the culture pool 31, and is then discharged through the liquid outlet pipe 42 and the liquid outlet port 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 . 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 respectively.

[0048] Optionally, the resistance detection member 21 includes a detection electrode and a glass slide connected to the detection electrode. The specific structure is prior art and will not be described in detail here. The detection electrode can obtain the resistance value of the organoid in the culture tank 31, and the change in the resistance value reflects the change in the composition of the organoid, thereby reflecting 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 embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, various obvious changes, readjustments and substitutions can be made without departing from the protection scope of the present invention. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A culture monitoring device for organoids, 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); a culture pool (31) is provided on the culture chip (3); 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 port (32), a liquid outlet port (33) and a flow channel component; the flow channel component is connected to the culture pool (31); the liquid inlet port (32) and the liquid outlet port (33) are respectively connected to the flow channel component; the liquid inlet pipe (41) is plugged into the liquid inlet port (32); and the liquid outlet pipe (42) is plugged into the liquid outlet port (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 tube (41) and the liquid outlet tube (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 tube (41) and a second through hole (44) communicating with the liquid outlet tube (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); and 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 arranged 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 arranged at a position corresponding to the injection plate (4) and the third bosses (11), a second connecting hole (12) is arranged on the third boss (11), and a connecting piece passes through the first connecting hole (48) and is 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); 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); 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, and the connecting piece is a bolt, which is threadedly connected to the second connecting hole (12).

9. The organoid culture monitoring device according to claim 5, characterized in that: A support 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 support boss (13). 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).

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

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