Full-automatic organoid imaging analyzer

Abstract

The utility model relates to the technical field of fluorescence imaging, in particular to a full-automatic organ-like imaging analyzer which comprises a bottom frame, an objective table, a bright field light source, an objective lens, a concentrator, a fluorescence module, a large-target-surface camera, a light splitting color filter, a power supply and a cooling fan, the surface of the bottom frame is connected with a shell, and the outer surface of the bottom frame is provided with a wiring port. A supporting plate is fixedly connected to the surface of the bottom frame, a second sliding plate is slidably connected to the surface of the supporting plate, and a first sliding plate is slidably connected to the surface of the second sliding plate. According to the utility model, full-hole in-situ imaging and analysis functions are realized, full-hole or partial-view imaging scanning and automatic splicing can be carried out aiming at a U-shaped bottom, a conventional culture plate and an organ chip culture plate, spliced images of different focal planes can be automatically obtained, and an image in which all organs are clear is finally obtained through a depth-of-field fusion technology. And the change process of indexes such as the number and the total area of the organoids under different processing conditions is further obtained.

Description

Technical Field

[0001] This utility model relates to the field of microscopic phase difference and fluorescence imaging technology, specifically a fully automated organoid imaging analyzer. Background Technology

[0002] The fully automated organoid imaging analyzer is an analytical instrument used in scientific fields such as oncology, immunology, neurobiology, drug screening, and traditional Chinese medicine research. It mainly achieves observation and analysis through a microscope.

[0003] Existing organoid imaging analyzers are heavy, complex to use, and cannot automatically focus or stitch images. They also have limited observation methods and cannot be adapted to various adapters such as multi-well plates for rapid and stable testing. Utility Model Content

[0004] The purpose of this invention is to provide a fully automated organoid imaging analyzer to solve the problems mentioned in the background art, such as heavy structure, complex use, inability to automatically focus and stitch images, limited observation methods, lack of darkroom imaging, and inability to adapt to various adapters such as multi-well plates for rapid and stable detection.

[0005] To achieve the above objectives, this utility model provides the following technical solution: a fully automated organoid imaging analyzer, comprising a base frame, a stage, a bright-field light source, an objective lens, a hub, a fluorescence module, a large-target camera, a spectrophotometer, a power supply, and a cooling fan. A housing is connected to the surface of the base frame, and wiring ports are provided on the outer surface of the base frame. A support plate is fixedly connected to the surface of the base frame, and a second sliding plate is slidably connected to the surface of the support plate. A first sliding plate is slidably connected to the surface of the second sliding plate, and a stage is slidably connected to the surface of the first sliding plate. An in / out chamber motor is provided on the surface of the stage. A support frame is fixedly connected to the surface of the base frame, and a bright field light source is provided on the surface of the support frame. A control motor is provided on the surface of the second slide plate, and a motor is provided on the surface of the first slide plate. A hub and an adjustment shaft are fixedly connected to the surface of the base frame. A control frame is slidably connected to the surface of the adjustment shaft. An objective lens is connected to the surface of the control frame. A fluorescence module is slidably connected to the surface of the adjustment shaft. A violet light source, a blue light source, and a large target camera are provided on the surface of the fluorescence module. A drive motor is provided on the surface of the adjustment shaft, and a spectrophotometer is provided on the surface of the fluorescence module.

[0006] Preferably, the outer shell adopts an arc-shaped structure with an arc in the middle, and the lower left side of the outer shell has a red, green and orange indicator light strip to facilitate the indication of the working status of the instrument and the experimental progress.

[0007] Preferably, the surface of the wiring port is provided with a power interface and an imaging interface, the second slide plate acts on the base frame above the support plate, the second slide plate is slidably connected to the support plate through a control motor, the first slide plate is slidably connected to the second slide plate through a motor, and the loading platform is slidably connected to the first slide plate through an in-and-out motor.

[0008] Preferably, the stage is plate-shaped, and a through groove is provided through the middle of the stage. The through groove has a U-shaped bottom and supports the placement and connection of conventional 6, 12, 24, 48, 96, and 384-well culture plates and organ-on-a-chip culture plates. The through groove is positioned below a bright field light source, and a baffle is provided below the bright field light source.

[0009] Preferably, the objective lens acts below the stage via an adjustment shaft and a control frame, and the objective lens and the control frame are fixed together by bolts.

[0010] Preferably, the violet light source, blue light source, green light source, and large target camera are powered by a hub, the violet light source, blue light source, and green light source act on two adjacent sides of the fluorescence module, and the large target camera acts below the blue light source.

[0011] Preferably, the control frame is slidably connected to the drive motor and the adjustment shaft, and the fluorescent module has a slanted groove in the middle, through which the spectrophotometer acts on the surface of the fluorescent module.

[0012] Compared with the prior art, the beneficial effects of this utility model are:

[0013] 1. This instrument enables in-situ imaging and analysis of all wells. No special treatment is required for cultured cell spheres or organoids; it can perform whole-well imaging scanning, image stitching, counting, and analysis simultaneously. Utilizing a large-area camera, a single image size under a 10X objective is 2.235 × 1.397 mm. Only 15 images are needed for stitching together a standard 96-well plate. It supports various consumables, including U-shaped bottom plates and standard 6, 12, 24, 48, 96, and 384-well culture plates, organ-on-a-chip culture plates, cell counting plates, culture dishes, and culture flasks. The instrument can perform whole-well or partial-field imaging scanning and automatic stitching, automatically obtaining stitched images from different focal planes. Through depth-of-field fusion technology, a single image with clear images of all organoids is obtained, allowing for the observation of changes in the number, total area, and other indicators of organoids under different treatment conditions.

[0014] 2. It adopts a box-type design with its own darkroom environment, eliminating the need for a separate darkroom space. Ordinary laboratory tables can be used normally, and it is not affected by external light, resulting in clearer fluorescence.

[0015] 3. Compact size: Compared with ordinary microscopes and large high-content equipment, it is easy to move. Ordinary experimental personnel can move it easily without special calibration and professional adjustment after moving it, making it more convenient to use. Simple design: Compared with ordinary microscopes and high-content equipment, the optical path is simple, the fluorescence is brighter under the same conditions, and it avoids photodamage to organoids caused by strong excitation light, which is more conducive to organoid experiments.

[0016] 4. It adopts a closed design and can be placed directly in the cell culture room. Compared with ordinary microscopes, it is more convenient for disinfection. It is suitable for ultraviolet disinfection and alcohol disinfection. The surface is smooth, and alcohol surface disinfection is more convenient and more thorough.

[0017] 5. It adopts a high-contrast phase difference design, which achieves a high-contrast phase difference effect through the deflection design of the light source and condenser lens optical path. The optical path is simple and easy to maintain.

[0018] 6. Supports automatic focusing and automatic image stitching. The perforated plate supports automatic edge trimming. No specific settings are required from the user, making it easy to operate. Attached Figure Description

[0019] Figure 1 This is a three-dimensional front view of the structure of this utility model;

[0020] Figure 2 This is a three-dimensional rear view of the structure of this utility model;

[0021] Figure 3 This is a three-dimensional structural diagram of the base frame of this utility model;

[0022] Figure 4 This is a partial three-dimensional schematic diagram of the base frame of this utility model;

[0023] Figure 5 This is a partial three-dimensional schematic diagram of the connection structure between the support frame and the bright field light source of this utility model;

[0024] Figure 6 This is a three-dimensional schematic diagram of the structure of the adjusting shaft of this utility model;

[0025] Figure 7 This is a side perspective three-dimensional schematic diagram of the structure of the adjusting shaft of this utility model.

[0026] In the diagram: 1. Base frame; 2. Outer shell; 3. Wiring port; 4. Support plate; 5. First slide plate; 6. Second slide plate; 7. Stage; 8. Support frame; 9. Bright field light source; 10. In / out chamber motor; 11. Control motor; 12. Objective lens; 13. Hub; 14. Adjustment shaft; 15. Control frame; 16. Fluorescent module; 17. Ultraviolet light source; 18. Blue light source; 19. Large target camera; 20. Drive motor; 21. Green light source; 22. Objective lens changing window. Detailed Implementation

[0027] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0028] Please see Figure 1-7 One embodiment provided by this utility model:

[0029] The fully automated organoid imaging analyzer includes a base frame 1, a stage 7, a bright-field light source 9, an objective lens 12, a hub 13, a fluorescence module 16, a large-area camera 19, a spectrophotometer, a power supply, and a cooling fan. A housing 2 is connected to the surface of the base frame 1. A wiring port 3 is provided on the outer surface of the base frame 1. A support plate 4 is fixedly connected to the surface of the base frame 1. A second slide plate 6 is slidably connected to the surface of the support plate 4. A first slide plate 5 is slidably connected to the surface of the second slide plate 6. The stage 7 is slidably connected to the surface of the stage 7. An in / out motor 10 is provided on the surface of the stage 7. A support frame 8 is fixedly connected to the surface of the base frame 1. A bright-field light source 9 is provided on the surface of the support frame 8. A control motor 13 is provided on the surface of the second slide plate 6. The first slide plate... A motor is mounted on the surface of the base frame 5. A hub 13 and an adjustment shaft 14 are fixedly connected to the surface of the base frame 1. A control frame 15 is slidably connected to the surface of the adjustment shaft 14. An objective lens 12 is connected to the surface of the control frame 15. A fluorescence module 16 is slidably connected to the surface of the adjustment shaft 14. A violet light source 17, a blue light source 18, a green light source 21, and a large target camera 19 are mounted on the surface of the fluorescence module 16. A drive motor 20 is mounted on the surface of the adjustment shaft 14. A spectrophotometer is mounted on the surface of the fluorescence module 16. Through the connection between the base frame 1 and the support frame 8, the position of the bright field light source 9 is supported by the support frame 8. Under the action of the stage 7 and the objective lens 12, the imaging operation effect of the test sample on the stage 7 is achieved.

[0030] Furthermore, the outer shell 2 adopts an arc-shaped structure with a curved center. A red, green, and orange indicator light strip is located on the lower left side of the outer shell 2, facilitating the indication of the instrument's working status and experimental progress. Through the outer shell 2, the base frame 1 is sealed and controlled, providing a self-contained darkroom environment. No separate darkroom space is required; a standard laboratory bench can be used normally. It is unaffected by external light, resulting in clearer fluorescence. The top of the outer shell 2 is compatible with a 15.6-inch computer, and its height is ergonomically designed for easy operation. Its compact size and easy portability allow it to hold cell culture plates.

[0031] Furthermore, the surface of the wiring port 3 is provided with a power interface and an imaging interface. The second slide plate 6 is supported above the base frame 1 by the support plate 4. The second slide plate 6 is slidably connected to the support plate 4 by the control motor 11. The first slide plate 5 is slidably connected to the second slide plate 6 by the motor. The platform 7 is slidably connected to the first slide plate 5 by the in-and-out motor 10. Through the function of the wiring port 3, the power supply and imaging operation of the equipment are achieved. Under the action of the support plate 4, the position of the second slide plate 6 and the first slide plate 5 is supported. Under the action of the in-and-out motor 10, the control motor 11 and the motor, the sliding control effect of the second slide plate 6, the first slide plate 5 and the platform 7 is achieved.

[0032] Furthermore, the stage 7 is plate-shaped, and a through groove is provided through the middle of the stage 7. The through groove supports the placement and connection of cell counting plates, glass slides, culture dishes, and culture flasks. The position of the through groove is below the bright field light source 9, and a baffle is provided below the bright field light source 9. Through the function of the through groove on the stage 7, it is convenient to place U-shaped bottom and conventional 6, 12, 24, 48, 96, 384-well culture plates and organ-on-a-chip culture plates, cell counting plates, glass slides, culture dishes, and culture flasks. Under the action of the inlet / outlet motor 10, the sample can be automatically fed into and out of the chamber.

[0033] Furthermore, the objective lens 12 acts below the stage 7 via the adjustment shaft 14 and the control frame 15. The objective lens 12 and the control frame 15 are fixed by bolts. Through the connection between the objective lens 12 and the control frame 15, and the sliding connection between the control frame 15 and the adjustment shaft 14, the position of the objective lens 12 can be adjusted. Moreover, the objective lens 12 is detachable from the control frame 15, making it convenient to replace it with different models.

[0034] Furthermore, the violet light source 17, blue light source 18, green light source 21, and large target camera 19 are powered by the hub 13. The violet light source 17, blue light source 18, and green light source 21 act on the two adjacent sides of the fluorescence module 16, and the large target camera 19 acts below the blue light source 18. Through the connection between the fluorescence module 16 and the violet light source 17, and the connection between the blue light source 18 and the fluorescence module 16, the fluorescence light source is automatically switched by software control under the action of the spectrophotometer. With the large target camera 19, the sample is imaged.

[0035] Furthermore, the control frame 15 is slidably connected to the adjustment shaft 14 via the drive motor 20. The fluorescent module 16 has an inclined groove in the middle. The spectrophotometer acts on the surface of the fluorescent module 16 through the inclined groove. Under the action of the drive motor 20, the position of the control frame 15 on the adjustment shaft 14 is adjusted, thereby controlling the position of the objective lens 12 and achieving its automatic focusing effect.

[0036] Working principle: Under the action of the in-and-out motor 10, the control motor 11, and the motor, the sliding control effect of the second slide plate 6, the first slide plate 5, and the stage 7 is achieved. Under the action of the in-and-out motor 10 and the stage 7, the position of the stage 7 on the first slide plate 6 can be adjusted, which facilitates the placement of samples and enables them to automatically enter and exit the chamber. Under the action of the bright field light source 9 and the objective lens 12, through the connection between the objective lens 12 and the control frame 15, and under the action of the drive motor 20, the stage 7 is used to achieve automatic focusing and imaging at multiple positions. Under the action of the bright field light source 9, the violet light source 17, the blue light source 18, and the green light source 21, through the action of the spectrophotometer on the fluorescence module 16, the switching effect of the fluorescence light source is achieved.

[0037] It will be apparent to those skilled in the art that this invention is not limited to the details of the exemplary embodiments described above, and that it can be implemented in other specific forms without departing from the spirit or essential characteristics of this invention. Therefore, the embodiments should be considered illustrative and non-limiting in all respects, and the scope of this invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within this invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

Claims

1. A fully automated organoid imaging analyzer comprising a base frame (1), a stage (7), a brightfield light source (9), an objective lens (12), a hub (13), a fluorescence module (16), a large target area camera (19), a light splitting filter, a power supply and a cooling fan, characterized in that: The base frame (1) is connected to a housing (2). The outer surface of the base frame (1) is provided with a wiring port (3). The base frame (1) is fixedly connected to a support plate (4). The support plate (4) is slidably connected to a second slide plate (6). The second slide plate (6) is slidably connected to a first slide plate (5). The first slide plate (5) is slidably connected to a platform (7). The platform (7) is provided with an in-and-out motor (10). The base frame (1) is fixedly connected to a support frame (8). The support frame (8) is provided with a bright field light source (9). The second slide plate (6) is provided with a control motor ( ). 11), a motor is provided on the surface of the first slide (5), a hub (13) and an adjustment shaft (14) are fixedly connected to the surface of the base frame (1), a control frame (15) is slidably connected to the surface of the adjustment shaft (14), an objective lens (12) is connected to the surface of the control frame (15), a fluorescence module (16) is slidably connected to the surface of the adjustment shaft (14), a violet light source (17), a blue light source (18), a green light source (21) and a large target camera (19) are provided on the surface of the fluorescence module (16), a drive motor (20) is provided on the surface of the adjustment shaft (14), and a spectrophotometer is provided on the surface of the fluorescence module (16).

2. The fully automated organoid imager of claim 1, wherein: The outer shell (2) adopts an arc-shaped structure and has an arc in the middle. The lower left side of the outer shell (2) has a red, green and orange indicator light strip.

3. The fully automated organoid imager of claim 1, wherein: The surface of the wiring port (3) is provided with a power interface and an imaging interface. The second slide plate (6) acts on the base frame (1) through the support plate (4). The second slide plate (6) is slidably connected to the support plate (4) through the control motor (11). The first slide plate (5) is slidably connected to the second slide plate (6) through the motor. The platform (7) is slidably connected to the first slide plate (5) through the in-and-out motor (10).

4. The fully automated organoid imager of claim 1, wherein: The stage (7) is plate-shaped, and a through groove is provided in the middle of the stage (7). The through groove has a U-shaped bottom and supports the placement and connection of glass slides, culture dishes and culture bottles for conventional 6, 12, 24, 48, 96 and 384-well culture plates and organ chip culture plates. The through groove is located below the bright field light source (9), and a baffle is provided below the bright field light source (9).

5. The fully automated organoid imager of claim 1, wherein: The objective lens (12) is positioned below the stage (7) via the adjustment shaft (14) and the control frame (15), and the objective lens (12) and the control frame (15) are fixed together by bolts.

6. The fully automated organoid imaging analyzer according to claim 1, characterized in that: The violet light source (17), blue light source (18), green light source (21) and large target camera (19) are powered by a hub (13). The violet light source (17), blue light source (18) and green light source (21) act on two adjacent sides of the fluorescent module (16), and the large target camera (19) acts below the blue light source (18).

7. The fully automated organoid imager of claim 1, wherein: The control frame (15) is slidably connected to the drive motor (20) and the adjustment shaft (14). The fluorescent module (16) has a slanted groove in the middle, and the spectrophotometer acts on the surface of the fluorescent module (16) through the slanted groove.

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