Organ-like culture chip imaging detection device

Abstract

The utility model belongs to the field of medical instruments, and relates to an organ-like culture chip imaging detection device. The device comprises a placing platform, an imaging unit and a three-axis translation platform, the imaging unit is arranged below the placing platform; wherein the bottom surface or partial area of the bottom surface of the placing platform is of a transparent structure and is used for placing an organoid culture chip; wherein the imaging unit comprises an objective lens and is used for collecting an image of the organoid culture chip, and the position of the objective lens does not exceed the orthographic projection area range of the transparent structure on the horizontal plane where the objective lens is located; the imaging unit is mounted on the three-axis translation platform, and the three-axis translation platform is used for adjusting the imaging position of the imaging unit on the organoid culture chip. The device is suitable for real-time detection of organoid culture chips or culture vessels of various sizes / specifications after culture or drug sensitivity test.

Description

Technical Field

[0001] The utility model relates to the technical field of medical instruments, and in particular to an imaging detection device for organoid culture chip. Background Art

[0002] Organoids are three-dimensional in vitro cell cultures with multiple lineages and complex tertiary structures. Organoids are often derived from adult stem cells, pluripotent stem cells, and tumor stem cells. Organoids obtained through cell development can not only reconstruct the three-dimensional spatial structure of organs in real tissues, but also construct responsible cell lineage composition and microenvironment structure.

[0003] With the development of developmental biology and biotechnology, organoids in recent years have evolved from early single endothelial organoids to complex, multi-tissue, and highly structured miniature organ systems. More responsible organoid systems have more uses in application scenarios. In clinical application scenarios, complex organoid technology can provide more comprehensive disease models for patients with diseases such as tumors. By sampling cells from the patient's lesions, an organoid model with the same genetic background as the patient is constructed in vitro. The organoid model after in vitro expansion can replace the patient to test the therapeutic effects of different drugs, and select the best drug for the treatment of the patient. In the field of drug research and development, complex organoids can provide disease models with high tissue complexity, structures that are extremely similar to real tissues, and genetic backgrounds that are superior to those of experimental animals. They are used to screen drugs and improve the safety and success rate of drug research and development. In the field of regenerative medicine, complex human organoid technology can better simulate real human tissues, and is expected to construct human organ substitutes, thereby completing tissue or organ regeneration and ultimately solving the global shortage of donated organs.

[0004] Although complex organoid technology has brought huge opportunities in personalized medicine, drug development, and regenerative medicine, at the same time, the application of complex organoid technology still has certain limitations in terms of technical level. Since the use of this technology requires high-throughput organoid imaging and detection, on the detection end, due to the complex three-dimensional structure of organoids, a wide variety of cell types, and hydrogel encapsulation, it is difficult to use traditional two-dimensional imaging, biochemical testing, and sequencing methods to achieve high-throughput organoid detection. At the same time, both clinical requirements and drug development needs require parallel detection of organoids under different conditions. Only by achieving high-throughput detection of organoids can we truly push organoid technology into industrial transformation and help our country lead the world in organoid research, a new pillar of biomedicine. Utility Model Content

[0005] In response to the above defects or improvement needs of the prior art, the utility model provides an imaging detection device for organoid culture chips. The device is suitable for real-time detection of organoid culture chips or culture vessels of various sizes / specifications after culture or drug sensitivity testing by arranging an imaging unit under the placement platform. At the same time, the imaging unit is installed on a three-axis translation platform, which can achieve real-time imaging of the orientation compared to the traditional organoid culture that images and detects a single organoid culture chip of a single type. The device of the utility model solves the technical problem of real-time, convenient and efficient imaging during organoid culture.

[0006] To achieve the above-mentioned purpose, according to a first aspect of the utility model, there is provided an organoid culture chip imaging detection device, comprising: a placement platform, an imaging unit and a three-axis translation platform;

[0007] The imaging unit is arranged below the placement platform; wherein the bottom surface or a part of the bottom surface of the placement platform is a transparent structure for placing the organoid culture chip; wherein the imaging unit comprises an objective lens for collecting the image of the organoid culture chip, and the position of the objective lens does not exceed the orthographic projection area of ​​the transparent structure on the horizontal plane where the objective lens is located;

[0008] The imaging unit is mounted on the three-axis translation platform, and the three-axis translation platform is used to adjust the imaging position of the imaging unit on the organoid culture chip.

[0009] Furthermore, the imaging unit further comprises an optical path element, a reflector, a light source and a camera; wherein the light source is a visible light or a fluorescent excitation light source;

[0010] The reflector and the camera are arranged on the same straight line, and the angle formed by the objective lens and the mirror surface of the reflector and the angle formed by the mirror surface of the reflector and the camera are both 45 degrees, so that the image of the organoid culture chip reaches the reflector through the objective lens and is reflected to the camera.

[0011] Furthermore, the reflector is a 45-degree angle reflector.

[0012] Furthermore, the light sources are arranged on both sides of the objective lens opening.

[0013] Furthermore, the light source is arranged in the same plane and perpendicular to the imaging light path to form an auxiliary light path, and the fluorescent light path and the bright field light path are switched by horizontal translation perpendicular to the direction of the imaging light path; wherein the imaging light path is a straight light path where the reflector and the camera are located.

[0014] Furthermore, the placement platform is an assembleable transfer platform for placing at least one organoid culture chip.

[0015] Furthermore, the device also includes a device operation integrated unit; the three-axis translation platform is connected to the device operation integrated unit via a motor drive.

[0016] In general, the above technical solution conceived by the utility model has the following technical advantages compared with the prior art:

[0017] (1) The device provided by the utility model is suitable for real-time detection of organoid culture chips or culture vessels of various sizes / specifications after culture or drug sensitivity testing by arranging an imaging unit below the placement platform. At the same time, the imaging unit is installed on a three-axis translation platform, which can realize azimuth real-time imaging compared to the traditional organoid culture for imaging and detecting a single type of single organoid culture chip.

[0018] (2) The device of the present invention preferably uses dual-modality imaging of bright field and fluorescent field, and the imaging system can be programmed to move along the xyz axis for long-term real-time imaging of organoids. Compared with conventional organoid imaging equipment, imaging detection can achieve more convenient and efficient operation.

[0019] (3) The device of the present invention preferably adjusts the style of the placement platform for organoid culture to achieve simultaneous imaging and monitoring of multiple organoid culture chips or culture dishes, which can be expanded from one chip to six organoid culture chips or organoid dishes. Each unit can be imaged and monitored separately, and multiple organoid culture chips can also be connected in series for comparative imaging, thereby achieving integrated large-scale organoid culture chip imaging and detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a partial structural schematic diagram of the imaging and detection device of the organoid culture chip;

[0021] Figure 2 It is a schematic diagram of the imaging system of the organoid culture chip imaging and detection device;

[0022] Figure 3 This is a schematic diagram of the organoid culture chip imaging and detection device adapted to the organoid culture chip.

[0023] In all the drawings, the same reference numerals are used to represent the same elements or structures, wherein: 1-placing platform, 2-organoid culture chip, 3-transparent structure, 4-objective lens, 5-reflector, 6-imaging light path, 7-camera, 8-auxiliary light path, 9-illumination light source, 10-XYZ axis translation platform. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical scheme and advantages of the utility model clearer, the utility model is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the utility model and are not used to limit the utility model. In addition, the technical features involved in each embodiment of the utility model described below can be combined with each other as long as they do not conflict with each other. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the utility model.

[0025] The organoid culture chip imaging and detection device provided by the utility model is as follows: Figure 1 As shown, the device includes: a placement platform 1, an imaging unit and a three-axis translation platform 10.

[0026] The placement platform 1 can be adapted to at least one organoid culture chip 2 of different sizes and uses. The placement platform 1 is located above the entire device, and the bottom surface of the placement platform 1 or a part of the bottom surface area is a transparent structure 3.

[0027] The imaging unit is arranged below the placement platform 1, and the position of the component for collecting the organoid culture chip in the imaging unit does not exceed the range of the positive projection area of ​​the transparent structure 3 on the horizontal plane where the component is located. For example, when the component is an objective lens in an imaging optical path element, the objective lens is arranged on a parallel plane above the bottom surface of the placement platform, then when the light beam perpendicular to the placement platform passes vertically through the transparent structure, the projection area on the horizontal plane where the objective lens is located is the range of adjustment of the objective lens. In addition, when the objective lens is translated up and down in a direction perpendicular to the bottom surface, the plane where the objective lens is located will also change accordingly.

[0028] In addition, each component in the imaging unit is installed on a three-axis translation platform, which is used to adjust the imaging position of the imaging unit on the organoid culture chip through translation and focusing to achieve organoid imaging detection.

[0029] As an implementation mode of the utility model, the bottom surface or a part of the bottom surface of the placement platform 1 is a transparent structure 3 .

[0030] As an implementation mode of the utility model, the imaging unit includes an objective lens, a reflector, a camera and a light source, and the light source is a visible light or a fluorescent excitation light source;

[0031] like Figure 2 As shown, an objective lens 4 for imaging the organoid culture chip is contained below the imaging window 3. The objective lens can be controlled to move in the space vertically projected by the transparent structure 3. The objective lens 4 is connected to an optical path 6 through a reflector 5 inclined upward at a 45-degree angle below. The optical path 6 is used to align the objective lens 4 with a recording camera 7, so that the camera 7 can successfully record the imaging and detection signals.

[0032] In some embodiments, the reflector is a 45-degree angle reflector, the reflector and the camera are arranged on the same straight line, and the angle formed by the objective lens and the mirror surface of the reflector and the angle formed by the mirror surface of the reflector and the camera are both 45 degrees, so that the image of the organoid culture chip reaches the reflector through the objective lens and is reflected to the camera.

[0033] In some embodiments, illumination light sources 9 are arranged on the left and right sides of the opening of the objective lens 4, which can be used for bright field imaging or dark field imaging.

[0034] In some embodiments, a light source is arranged in the same plane and perpendicular to the imaging light path to form an auxiliary light path, which is horizontally translated perpendicular to the imaging light path. Figure 2 As shown, there is an auxiliary optical path 8 which can be moved by a motor in the middle of the optical path 6, which is used for switching between the fluorescent optical path and the bright field optical path. Among them, the imaging optical path is a straight optical path where the reflector and the camera are located.

[0035] As an embodiment of the present invention, the device further includes a device operation integrated unit; the three-axis translation platform 10 is connected to the device operation integrated unit via a motor drive, and is used for automated detection of the organoid culture chip.

[0036] Furthermore, each unit device in the device is connected to an external computer via a computer interface to achieve automated imaging and detection of the organoid culture chip.

[0037] As an embodiment of the present invention, the placement platform 1 is an adjustable / assembled transfer style to achieve simultaneous imaging and monitoring of multiple organoid culture chips or culture dishes. Figure 3 As shown, one organoid culture chip can be expanded to, for example, 6 organoid culture chips or organoid vessels. Each unit can be imaged and monitored individually, or multiple organoid culture chips can be connected in series for comparative imaging, thereby achieving integrated large-scale organoid culture chip imaging and detection.

[0038] Based on the method of using the device described in the above embodiment:

[0039] While the organoids are being cultured normally, the device turns on the imaging unit below the transparent structure, and uses an optical path on an xyz three-axis platform to support the entire structure of the imaging unit. A camera is connected to the end of the three-dimensionally movable optical path. Since the state of the organoid culture chip is being photographed and imaged, a conversion device is added to the optical path to achieve dual-modal imaging of fluorescence or bright field. The left and right ends of the objective lens edge of the shooting system are respectively equipped with a white light field for bright field imaging and a fluorescent light source for fluorescent imaging. The above components are controlled to move in the box through the xyz three-axis platform, thereby controlling the imaging range and autofocus.

[0040] The above device realizes full-process automated operation through the device's own or external computer.

[0041] The implementation methods of the present invention are provided for the purpose of illustration and description. Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present invention. Ordinary technicians in this field can change, modify, replace and transform the above embodiments within the scope of the present invention.

Claims

1. An organoid culture chip imaging detection device, characterized in that: include: Place the platform, imaging unit and three-axis translation platform; The imaging unit is arranged below the placement platform; wherein the bottom surface or a part of the bottom surface of the placement platform is a transparent structure for placing the organoid culture chip; wherein the imaging unit comprises an objective lens for collecting the image of the organoid culture chip, and the position of the objective lens does not exceed the orthographic projection area of ​​the transparent structure on the horizontal plane where the objective lens is located; The imaging unit is mounted on the three-axis translation platform, and the three-axis translation platform is used to adjust the imaging position of the imaging unit on the organoid culture chip.

2. The organoid culture chip imaging detection device according to claim 1, characterized in that: The imaging unit further comprises an optical path element, a reflector, a light source and a camera; wherein the light source is a visible light or a fluorescent excitation light source; The reflector and the camera are arranged on the same straight line, and the angle formed by the objective lens and the mirror surface of the reflector and the angle formed by the mirror surface of the reflector and the camera are both 45 degrees, so that the image of the organoid culture chip reaches the reflector through the objective lens and is reflected to the camera.

3. The organoid culture chip imaging detection device according to claim 2, characterized in that: The reflector is a 45-degree angle reflector.

4. The organoid culture chip imaging detection device according to claim 2, characterized in that: The light sources are arranged on both sides of the objective lens opening.

5. The organoid culture chip imaging detection device according to claim 2, characterized in that: The light source is arranged in the same plane and perpendicular to the imaging light path to form an auxiliary light path, and the fluorescent light path and the bright field light path are switched by horizontal translation perpendicular to the direction of the imaging light path; wherein the imaging light path is a straight light path where the reflector and the camera are located.

6. The organoid culture chip imaging detection device according to claim 1, characterized in that: The placement platform is an assembleable transfer platform used to place at least one organoid culture chip.

7. The organoid culture chip imaging detection device according to claim 1, characterized in that: The device also includes a device operation integrated unit; the three-axis translation platform is connected to the device operation integrated unit through motor drive.

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