A microscope inspection device
By integrating a multi-channel light source and an automatic optical path switching microscope detection device, the problems of complex operation and dust accumulation in 3D biological tissue detection have been solved, achieving efficient and accurate automatic detection results.
Patent Information
- Application Number
- CN202310070470.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-01-20
- Publication Date
- 2025-10-31
- Estimated Expiration
- 2043-01-20
AI Technical Summary
Existing microscope equipment is complex to operate in 3D biological tissue detection, requiring manual switching of light sources and objectives, resulting in low detection efficiency and easy dust accumulation, which affects the imaging effect.
A microscope inspection device was designed, which integrates a multi-channel light source assembly, objective lens mechanism, fluorescence mechanism and imaging mechanism. The control system automatically switches the light source and optical path, and the shielding mechanism protects the optical components, simplifying operation and improving inspection efficiency and accuracy.
It enables efficient and automated detection of 3D biological tissues, simplifies the operation process, improves detection efficiency and imaging accuracy, and reduces the probability of dust accumulation on optical components.
Smart Images

Figure CN116794000B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of imaging device technology, and in particular to a microscope inspection device. Background Technology
[0002] Significant breakthroughs have been made in cell biology within life sciences. However, the observation of 3D biological tissue cultures, particularly the segmentation, counting, and localization of organoid cells, still largely relies on manual methods. The introduction of artificial intelligence technology can significantly improve observation efficiency. Compared to 2D environments, the difficulty in observing biological tissues in 3D lies in the numerous adverse effects that their free-growing environment can have on imaging results, such as occlusion and overlap, out-of-focus, heterogeneous cell sizes, poor lighting, excessive cell density, and sparse cell count.
[0003] Detection of 3D biological tissues includes in vivo observation and breakpoint observation. In vivo observation focuses on morphological observation using bright-field and symmetrical lighting, while breakpoint observation focuses on detecting various indicators using fluorescence. Currently, there is a severe lack of detection methods for 3D biological tissues, and optical and electrochemical techniques capable of real-time detection of various indicators in living organisms are still insufficient. Summary of the Invention
[0004] This application provides a microscope inspection device that can solve the problem of inconvenience in microscope inspection for 3D biological tissue inspection.
[0005] This application provides a microscope inspection device, characterized in that it is used for inspecting 3D biological tissues, comprising:
[0006] The material stage has a sample area;
[0007] A multi-channel light source assembly is disposed on one side of the material stage corresponding to the sample area, and is capable of emitting preset light to the sample area;
[0008] The objective lens mechanism is located on the side of the stage away from the multi-channel light source assembly, corresponding to the sample area, and has a working state and a dormant state.
[0009] The shielding mechanism includes a shielding member and a shielding drive mechanism. The shielding drive mechanism is connected to the shielding member. In the use state, the shielding drive mechanism is used to drive the shielding member to avoid the optical path between the objective lens mechanism and the sample area. In the dormant state, the shielding drive mechanism is used to drive the shielding member to shield the objective lens mechanism.
[0010] An imaging mechanism, configured corresponding to the objective lens mechanism, is provided to receive light passing through the objective lens mechanism; and
[0011] A fluorescence mechanism includes a fluorescence driving component and a fluorescence excitation component. The fluorescence driving component is connected to the fluorescence excitation component to drive the fluorescence excitation component to switch between a first state and a second state when the objective mechanism is in use. In the first state, the fluorescence excitation component avoids the optical path between the objective mechanism and the imaging mechanism, and the preset light passing through the sample area reaches the imaging mechanism via the objective mechanism. In the second state, the fluorescence excitation component is located on the optical path between the objective mechanism and the imaging mechanism, and the excitation light emitted from the fluorescence excitation component passes through the objective mechanism to reach the sample area. The fluorescence generated by the excitation light on the sample in the sample area passes sequentially through the objective mechanism and the fluorescence excitation component to reach the imaging mechanism.
[0012] In some exemplary embodiments, with the direction of the multi-channel light source assembly toward the objective lens mechanism as the first direction, the fluorescence driving assembly drives the fluorescence excitation assembly to move in a preset direction that forms an angle with the first direction, so as to drive the fluorescence excitation assembly to switch between the first state and the second state.
[0013] The light rays passing through the objective lens mechanism are received by the imaging mechanism at an angle to the first direction.
[0014] In some exemplary embodiments, the imaging mechanism includes:
[0015] The camera and the objective lens mechanism are located on the same side of the loading stage;
[0016] An imaging reflector is provided corresponding to the objective lens mechanism and the camera to receive light passing through the objective lens mechanism along the first direction and reflect the light to be projected onto the camera along the second direction, wherein the second direction forms an angle with the first direction and the second direction is the preset direction.
[0017] In some exemplary embodiments, the microscope inspection device further includes:
[0018] An auxiliary reflective element is disposed in the first direction corresponding to the objective lens mechanism to receive light passing through the objective lens mechanism and reflect the light to be projected along the second direction;
[0019] The imaging mechanism includes:
[0020] The camera and the objective lens mechanism are located on the same side of the loading stage.
[0021] An imaging reflector is disposed in the second direction corresponding to the auxiliary reflector to receive the light reflected by the auxiliary reflector and reflect the light to be projected onto the camera along a third direction. The first direction, the second direction, and the third direction are at angles to each other, and the third direction is the preset direction.
[0022] In some exemplary embodiments, the fluorescence excitation component includes:
[0023] An excitation light source is used to emit the excitation light;
[0024] An excitation block is connected to the fluorescence driving assembly and to the excitation light source. In the second state, the excitation block is located in the optical path between the objective lens mechanism and the imaging mechanism, so that the excitation light reaches the objective lens mechanism via the excitation block, and the fluorescence reaches the imaging mechanism via the excitation block.
[0025] In some exemplary embodiments, the fluorescence excitation assembly includes a plurality of excitation light sources, and the excitation light emitted by the plurality of excitation light sources has a different wavelength;
[0026] The fluorescence excitation assembly includes multiple excitation blocks corresponding one-to-one with the multiple excitation light sources. The excitation light emitted by each excitation light source is emitted through the corresponding excitation block. In the second state, one of the excitation blocks corresponds to the objective lens mechanism and the imaging mechanism; or...
[0027] The fluorescence excitation assembly includes an excitation block connected to a plurality of the excitation light sources, wherein the excitation light emitted by each of the excitation light sources is emitted through the excitation block; or,
[0028] The plurality of excitation light sources are arranged side by side along the direction in which the fluorescence driving component drives the fluorescence excitation component to move.
[0029] In some exemplary embodiments, the preset light includes bright field light or phase contrast light.
[0030] In some exemplary embodiments, the microscope inspection device further includes:
[0031] Mounting frame, wherein the material carrier is disposed on the mounting frame;
[0032] An objective lens driving mechanism is disposed on the mounting bracket and connected to the objective lens mechanism to drive the objective lens mechanism relative to the material stage in a first direction, thereby driving the objective lens mechanism to switch between the use state and the sleep state. The first direction is the direction in which the multi-channel light source assembly faces the objective lens mechanism.
[0033] In some exemplary embodiments, the shielding member includes two shielding plates and is located on the same side of the stage as the objective lens mechanism; the shielding drive mechanism is located on the mounting bracket and connected to the two shielding plates; in the use state, the shielding drive mechanism is used to drive the two shielding plates away from each other in a direction forming an angle with the first direction to avoid the optical path between the objective lens mechanism and the sample area; in the dormant state, the shielding drive mechanism is used to drive the shielding member to shield the objective lens mechanism.
[0034] In some exemplary embodiments, the objective lens mechanism includes: a plurality of objectives and an objective lens switcher connected to the plurality of objectives to switch one of the objectives toward the sample area; the microscope inspection device further includes a mounting frame and a material drive assembly disposed on the mounting frame and connected to the material stage to drive the material stage to move so that one of the areas to be inspected in the sample area corresponds to the objective lens.
[0035] The microscope inspection device based on the embodiments of this application has at least the following beneficial effects:
[0036] The microscope inspection device of this application integrates multiple light sources, which can switch the required light to inspect the sample according to the inspection needs, resulting in high inspection efficiency. By integrating multiple light sources, it is possible to observe 3D biological tissue culture, such as the segmentation, counting, and localization of organoid cells, and to achieve high-throughput cell imaging analysis and intelligent delineation of cell edges.
[0037] By setting the preset light emitted by the multi-channel light source component and the excitation light emitted by the fluorescence excitation component to be projected onto the sample area from two opposite directions, it is convenient to adjust the positions of the multi-channel light source component, the fluorescence excitation component and the objective lens mechanism, which helps to shorten the optical path and improve the accuracy of the detection results.
[0038] By setting the fluorescence driving component to switch between the first and second states, different optical paths can be switched, eliminating the need for human observation of whether the light source is in place or for manual adjustment of the light source position. Furthermore, the relevant detection structures for different light sources are all integrated into the microscope detection device of this application, eliminating the need for assembly and adjustment of the relevant detection structures during use, making operation convenient and efficient.
[0039] Dust accumulation on the surface of any element used to transmit light can affect the imaging effect of the sample. This application designs the placement of the objective lens mechanism, fluorescence mechanism, and imaging mechanism to make the entire structure compact, thereby enabling the objective lens mechanism, fluorescence mechanism, and imaging mechanism to be protected by a shielding mechanism. In the dormant state, this reduces the probability of dust accumulation on the surface of the objective lens mechanism, fluorescence mechanism, and imaging mechanism, and improves the imaging effect. Attached Figure Description
[0040] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0041] Figure 1 This is a three-dimensional structural schematic diagram of a microscope inspection device according to an embodiment of this application;
[0042] Figure 2 This is an exploded structural diagram of a microscope inspection device according to an embodiment of this application;
[0043] Figure 3 This is a flowchart of the detection process of a microscope detection device according to an embodiment of this application;
[0044] Figure 4 This is a three-dimensional structural diagram of a microscope inspection device including an auxiliary reflective element according to an embodiment of this application;
[0045] Figure 5 This is an exploded view of a microscope inspection device including an auxiliary reflective element according to an embodiment of this application.
[0046] Figure 6 This is a three-dimensional structural diagram of the installation of a fluorescence excitation component when the excitation light is emitted from the excitation block in a second direction according to an embodiment of this application.
[0047] Figure 7 This is a top view schematic diagram of the installation structure of the fluorescence excitation component when the excitation light is emitted from the excitation block in a second direction according to an embodiment of this application;
[0048] Figure 8 This is a three-dimensional structural diagram of the installation of a fluorescence excitation component when the excitation light is emitted from the excitation block along a first direction, according to one embodiment of this application.
[0049] Figure 9 This is a three-dimensional structural diagram of a plurality of excitation light sources connected to the same excitation block according to an embodiment of this application;
[0050] Figure 10 This is a three-dimensional structural diagram of multiple excitation light sources connected to the same excitation block according to another embodiment of this application;
[0051] Figure 11 This is a schematic diagram of the imaging mechanism in use according to an embodiment of this application;
[0052] Figure 12This is a schematic diagram of the shielding mechanism provided on the mounting frame according to one embodiment of this application.
[0053] Figure label:
[0054] 1. Microscope inspection device;
[0055] 100. Material loading stage; 101. Sample area;
[0056] 200. Multi-channel light source assembly; 210. Light source; 220. Phase plate housing; 230. Condenser lens; 240. Phase plate switching component;
[0057] 300. Objective lens mechanism; 310. Objective lens; 320. Objective lens switcher;
[0058] 400, Imaging mechanism; 410, Camera; 420, Imaging reflector; 430, Camera adapter; 401, Auxiliary reflector; 400a, First light-transmitting area; 401a, Second light-transmitting area; 401b, Third light-transmitting area;
[0059] 500, Fluorescent mechanism; 510, Fluorescent driving assembly; 511, First drive motor; 512, First lead screw; 513, First mounting plate; 513a, First clearance hole; 514, First guide rail; 515, First slider;
[0060] 520. Fluorescence excitation assembly; 521. Excitation source; 522. Excitation block;
[0061] 600. Mounting bracket;
[0062] 700. Objective lens drive mechanism;
[0063] 800, shielding mechanism; 810, shielding component; 811, shielding plate; 820, shielding drive mechanism; 821, second drive motor; 822, drive component; 823, driven component; 824, synchronizing component; 8241, first straight section; 8242, second straight section; 825, first slider; 825a, first clearance area; 826, second slider; 830, shielding frame; 830a, hollow area;
[0064] 900. Material loading drive assembly;
[0065] A. First direction; B. Second direction; C. Third direction; X. Preset direction. Detailed Implementation
[0066] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.
[0067] The inventors discovered that establishing a comprehensive technical standard system for the observation and detection of 3D biological tissues is crucial for further advancement in related research and the development of the 3D biological tissue industry. In 3D biological tissue detection, microscopes can be used to detect the activity and size of 3D biological tissues. However, microscopes require numerous auxiliary devices to achieve their observation functions, such as bright-field lamps, fluorescent lamps, and cameras, making operation complex. When manually operating a microscope, prolonged observation through the eyepiece can easily cause eye strain, and some excitation light during fluorescence observation is harmful to the eyes. Manually operating a microscope requires switching objectives, focusing, and performing various actions, which is time-consuming and requires specialized training. Furthermore, the objectives lack adequate protection when not in use, leading to dust accumulation over time and necessitating frequent maintenance.
[0068] To address the aforementioned issues, this application provides a microscope detection device for 3D biological tissue detection, which evaluates key parameters such as 3D biological tissue activity and size. This improves the effectiveness and timeliness of 3D biological tissue detection and helps shorten the overall 3D biological tissue detection process.
[0069] like Figure 1 and Figure 2 The diagram shown is a schematic diagram of the structure of a microscope inspection device 10 according to an embodiment of this application. The microscope inspection device 10 includes a stage 100, a multi-channel light source assembly 200, an objective lens mechanism 300, an imaging mechanism 400, and a fluorescence mechanism 500.
[0070] The stage 100 has a sample area 101 through which light can pass. For example, the sample area 101 may be equipped with a light-transmitting element or have a light-transmitting hole. During testing, the sample to be tested is placed on the stage 100 and positioned corresponding to the sample area 101 so that light entering and exiting the sample area 101 can reach the sample. The sample to be tested may include organoid cells or microorganisms.
[0071] A multi-channel light source assembly 200 is disposed on one side of the stage 100 corresponding to the sample area 101, and is capable of emitting preset light into the sample area 101. An objective lens mechanism 300 is disposed on the side of the stage 100 opposite to the multi-channel light source assembly 200, corresponding to the sample area 101. The objective lens mechanism 300 has a working state and a dormant state. In the working state, the objective lens mechanism 300 can be used to magnify the image formed by the light entering and exiting the sample area 101. In the dormant state, the objective lens mechanism 300 cannot allow light entering or exiting the sample area 101 to pass through, or the objective lens mechanism 300 cannot allow light entering or exiting the sample area 101 to pass through due to obstruction by other structural components. An imaging mechanism 400 is disposed corresponding to the objective lens mechanism 300 to receive the light passing through the objective lens mechanism 300.
[0072] The fluorescence mechanism 500 includes a fluorescence driving component 510 and a fluorescence excitation component 520. The fluorescence driving component 510 is connected to the fluorescence excitation component 520 to drive the fluorescence excitation component 520 to switch between a first state and a second state when the objective lens mechanism 300 is in use. In the first state, the fluorescence excitation component 520 avoids the optical path between the objective lens mechanism 300 and the imaging mechanism 400, and the preset light passing through the sample area 101 reaches the imaging mechanism 400 via the objective lens mechanism 300. In the second state, the fluorescence excitation component 520 is located in the optical path between the objective lens mechanism 300 and the imaging mechanism 400. The excitation light emitted from the fluorescence excitation component 520 passes through the objective lens mechanism 300 and reaches the sample area 101, and the dye of the sample to be tested in the sample area 101 is excited by the excitation light to generate fluorescence. The fluorescence sequentially passes through the objective lens mechanism 300 and the fluorescence excitation component 520 to reach the imaging mechanism 400.
[0073] like Figure 3 As shown, when a preset light source is needed to illuminate the sample for detection, the fluorescence driving component 510 drives the fluorescence excitation component 520 in a first state to prevent the fluorescence excitation component 520 from obstructing the propagation of light between the objective lens mechanism 300 and the imaging mechanism 400. The multi-channel light source component 200 is activated to emit the preset light source into the sample area 101. The preset light source passes through the sample to be detected in the sample area 101 and reaches the objective lens mechanism 300. The objective lens mechanism 300 magnifies the image of the sample to be detected, and the imaging mechanism 400 receives the magnified image from the objective lens mechanism 300 to obtain relevant detection parameters of the sample to be detected.
[0074] Optionally, the preset light source includes bright-field (BF) light or phase-contrast light. Bright-field light forms an image by mapping when it passes through the sample to be tested; phase-contrast light provides an image by presenting an intensity distribution through optical phase delay when it passes through the sample to be tested.
[0075] The multi-channel top light source assembly 200 includes a top light source 210, a phase plate, a phase plate housing 220, a condenser lens 230, and a phase plate switching component 240. The top light source 210 is connected to the phase plate housing 220, and the condenser lens 230 is connected to the end of the phase plate housing 220 opposite to the top light source 210. The phase plate is installed in the internal space of the phase plate housing 220 and has a bright field channel and a phase contrast channel. The phase plate switching component 240 extends into the internal space of the phase plate housing 220 and connects to the phase plate, acting on the phase plate to align the bright field channel or the phase contrast channel with the top light source 210. When the bright field channel aligns with the top light source 210, the light emitted by the top light source 210 passes through the bright field channel to the condenser lens 230, and is focused by the condenser lens 230 before being emitted, thus forming bright field light. When the phase contrast channel corresponds to the top light source 210, the light emitted by the top light source 210 passes through the phase contrast channel to the condenser lens 230, and is focused by the condenser lens 230 before being emitted, thus forming phase contrast light.
[0076] like Figure 3 As shown, when excitation light needs to be applied to the sample for detection, the multi-channel light source assembly 200 stops emitting preset light, and the fluorescence driving assembly 510 drives the fluorescence excitation assembly 520 to the second state, allowing light between the objective lens mechanism 300 and the imaging mechanism 400 to also pass through the fluorescence excitation assembly 520. The fluorescence excitation assembly 520 is activated to emit excitation light to the objective lens mechanism 300. The excitation light passes through the objective lens mechanism 300 and reaches the sample to be detected. The sample is excited by the excitation light to produce fluorescence, which is then projected back to the objective lens mechanism 300. The objective lens mechanism 300 magnifies the fluorescence image of the sample, and the imaging mechanism 400 receives the magnified fluorescence image from the objective lens mechanism 300 to obtain relevant detection parameters of the sample.
[0077] The multi-channel light source assembly 200, fluorescence driving assembly 510, and fluorescence excitation assembly 520 are all connected to the control system. The control system controls the fluorescence excitation assembly 520 to switch between a first state and a second state. The control system also controls the multi-channel light source assembly 200 to emit preset light and controls the type of preset light emitted by the multi-channel light source assembly 200. Furthermore, the control system controls the fluorescence excitation assembly 520 to emit excitation light. By flexibly switching between the preset light and the excitation light through the control system for relevant detection, there is no need for human observation of whether the light source is in place, nor is there a need for manual adjustment of the light source position. The imaging mechanism 400 is connected to the display structure, which receives and displays the image of the sample to be detected sent by the imaging mechanism 400 for real-time observation of the sample. Optionally, the control system and the display structure can be integrated into a terminal device for operation. For example, the terminal device includes a computer, a touch panel, etc.
[0078] With the direction of the multi-channel light source assembly 200 toward the objective lens mechanism 300 as the first direction A, the light entering and exiting the objective lens mechanism 300 propagates along the first direction A. For example, if the first direction A is vertical and the sample to be tested is plate-shaped, the plate surface of the sample to be tested is placed on the stage 100 perpendicular to the first direction A during testing; or, the first direction A can be set to an angle with the vertical direction, and during testing, the plate surface of the sample to be tested is perpendicular to the first direction A and fixed to the stage 100.
[0079] Optionally, the fluorescence driving component 510 drives the fluorescence excitation component 520 to move in a preset direction X at an angle to the first direction A, so as to drive the fluorescence excitation component 520 to switch between a first state and a second state, so that the fluorescence driving component 510 can smoothly move the fluorescence excitation component 520 in and out of the optical path between the objective lens mechanism 300 and the imaging mechanism 400.
[0080] In this configuration, the light rays passing through the objective lens mechanism 300 are received by the imaging mechanism 400 at an angle to the first direction A. This allows for proper positioning of the imaging mechanism 400, resulting in a compact overall structure. It also facilitates adjusting the optical path of the light rays passing through the objective lens mechanism 300 to the imaging mechanism 400 within a suitable range, thereby improving detection accuracy. Optionally, such as... Figure 1 and Figure 4 As shown, the imaging mechanism 400 and the objective lens mechanism 300 are located on the same side of the loading stage 100.
[0081] The imaging mechanism 400 includes a camera 410 and an imaging reflector 420. One end of the imaging reflector 420 is connected to the camera 410, and the other end forms a first light-transmitting area 400a for light to enter and exit. Optionally, the imaging reflector 420 includes a first housing and an imaging mirror. The imaging mirror is disposed inside the first housing, and the first light-transmitting area 400a is formed in the first housing. The imaging mechanism 400 also includes a camera adapter 430, which is connected between the camera 410 and the imaging reflector 420. Specifically, the camera adapter 430 is connected to the first housing to project light passing through the imaging reflector 420 onto the camera 410.
[0082] Optionally, such as Figure 1 and Figure 2As shown, one end of the imaging reflector 420 is positioned corresponding to the camera 410, and the other end is positioned corresponding to the objective lens mechanism 300 (specifically, the first light-transmitting area 400a corresponds to the objective lens mechanism 300). It receives light passing through the objective lens mechanism 300 along the first direction A and reflects the light to be projected onto the camera 410 along the second direction B. The second direction B forms an angle with the first direction A, making the entire optical path of the light passing through the objective lens mechanism 300 to the camera 410 simple and reducing the loss during the light propagation process. In addition, the light passing through the objective lens mechanism 300 is reflected to the camera 410 only once by the imaging reflector 420, which can reduce the shadows around the image and improve the imaging effect.
[0083] Optionally, the second direction B is a preset direction X. The direction in which the fluorescence driving component 510 drives the fluorescence excitation component 520 to switch from the first state to the second state is direction M1. The light reflected by the imaging reflector 420 is projected onto the camera 410 along direction M2. Directions M1 and M2 are opposite to each other so as to arrange the installation positions of the camera 410 and the fluorescence excitation component 520 and enable the fluorescence excitation component 520 to move smoothly.
[0084] like Figure 4 and Figure 5 As shown, the microscope inspection device 10 also includes an auxiliary reflector 401. The auxiliary reflector 401 is disposed in the first direction A corresponding to the objective lens mechanism 300 to receive light passing through the objective lens mechanism 300 and reflect the light to be projected along the second direction B. The imaging reflector 420 is disposed in the second direction B corresponding to the auxiliary reflector 401 to receive light reflected by the auxiliary reflector 401 and reflect the light to be projected onto the camera 410 along the third direction C. The first direction A, the second direction B and the third direction C are at angles to each other, and the third direction C is a preset direction X.
[0085] Optionally, the auxiliary reflector 401 includes a second housing and an auxiliary reflector, such as Figure 5 As shown, the second housing has a second light-transmitting area 401a and a third light-transmitting area 401b for light to enter and exit. The second light-transmitting area 401a corresponds to the objective lens mechanism 300, and the third light-transmitting area 401b corresponds to the imaging reflector 420. An auxiliary reflector is disposed in the internal space of the second housing. Light rays passing through the objective lens mechanism 300 along the first direction A pass through the second light-transmitting area 401a and are projected onto the auxiliary reflector. After being reflected by the auxiliary reflector, the light rays exit from the third light-transmitting area 401b along the second direction B and are projected onto the imaging reflector 420. Furthermore, the first direction A, the preset direction X, and the third direction C are perpendicular to each other.
[0086] The fluorescence excitation assembly 520 includes an excitation light source 521 and an excitation block 522. The excitation light source 521 is used to emit excitation light and is connected to a control system. The control system is used to control the state of laser emission by the excitation light source 521. The excitation light source 521 is connected to the excitation block 522, and the excitation block 522 is connected to the fluorescence driving assembly 510. The fluorescence driving assembly 510 drives the excitation block 522 to move in a preset direction X, and drives the excitation light source 521 to move together.
[0087] In the second state, the fluorescence driving component 510 drives the excitation block 522 to move to the optical path between the objective lens mechanism 300 and the imaging mechanism 400, so that the excitation light reaches the objective lens mechanism 300 via the excitation block 522, and the fluorescence reaches the imaging mechanism 400 via the excitation block 522. Specifically, the excitation block 522 includes a mounting housing, and a collimating lens group, an excitation light filter, and a dichroic mirror disposed inside the mounting housing. The light emitted by the excitation source 521 is collimated by the collimating lens group to form collimated excitation light. The collimated excitation light is filtered by the excitation light filter (only light of a preset wavelength can pass through the excitation light filter), and then projected onto the dichroic mirror. After being emitted by the dichroic mirror, it passes through the objective lens mechanism 300 to reach the sample area 101. The dye on the sample in the sample area 101 generates fluorescence under the excitation of the filtered collimated excitation light. The fluorescence is magnified by the objective lens mechanism 300, emitted by the dichroic mirror, and filtered by the excitation light filter before reaching the imaging mechanism 400.
[0088] The microscope inspection device 10 also includes a mounting bracket 600, on which the fluorescence driving assembly 510 is mounted. Optionally, as... Figure 6 and Figure 7 As shown, the fluorescence driving assembly 510 includes a first driving motor 511, a first lead screw 512, a first mounting plate 513, a first guide rail 514, and a first slider 515. The fluorescence excitation assembly 520 is mounted on the first slider 515. The first slider 515 is connected to the first lead screw 512 and slidably mounted on the first guide rail 514. The first guide rail 514 is mounted on the first mounting plate 513. The first mounting plate 513 is mounted on the mounting bracket 600. The first lead screw 512 is connected to the driving end of the first driving motor 511. The first driving motor 511 is connected to the control system. The control system controls the first driving motor 511 to operate, driving the first lead screw 512 to rotate, thereby driving the first slider 515 to move along the preset direction X on the first guide rail 514, thereby driving the fluorescence excitation assembly 520 to move in the first direction A.
[0089] like Figure 1 As shown, when the imaging reflector 420 is set to correspond to the objective lens mechanism 300 and the camera 410, in the second state, the excitation block 522 corresponds to the imaging reflector 420, and light enters and exits the excitation block 522 along the first direction A. At this time, as... Figure 8 and Figure 9 As shown, the excitation light source 521 can be disposed on one side of the excitation block 522 along the third direction C. Further, in the third direction C, the excitation light source 521 is disposed on the side of the excitation block 522 away from the objective lens mechanism 300.
[0090] like Figure 4 As shown, when the imaging reflector 420 is set to correspond to the auxiliary reflector 401 in the second direction B, in the second state, the excitation block 522 corresponds to the auxiliary reflector 401, and light enters and exits the excitation block 522 along the second direction B. At this time, as... Figure 6 and Figure 7 As shown, the excitation light source 521 can be disposed on one side of the excitation block 522 along the first direction A, and the first mounting plate 513 avoids the optical path between the imaging reflector 420 and the auxiliary reflector 401. Optionally, the first mounting plate 513 is provided with a first clearance hole 513a, through which the optical path between the imaging reflector 420 and the auxiliary reflector 401 passes, thereby improving the structural strength of the first mounting plate 513 and thus improving the installation stability of the fluorescence mechanism 500. In the first state, the excitation block 522 avoids the first clearance hole 513a; in the second state, the excitation block 522 corresponds to the clearance hole, so that the light passing through the first clearance hole 513a can also pass through the excitation block 522.
[0091] The fluorescence excitation assembly 520 includes multiple excitation light sources 521, and the excitation light emitted by the multiple excitation light sources 521 has a different wavelength. For example, the excitation light includes red light, blue light, green light, or yellow light, which will correspondingly excite the sample to be tested to produce red fluorescence, blue fluorescence, green fluorescence, or yellow fluorescence. This application does not limit the number of excitation light sources 521 or the type of excitation light, and the specific selection can be made according to actual needs.
[0092] Optionally, such as Figures 6 to 8 As shown, the fluorescence excitation assembly 520 includes multiple excitation blocks 522 corresponding to multiple excitation light sources 521. The excitation light emitted by each excitation light source 521 is emitted through the corresponding excitation block 522. In the second state, one of the excitation blocks 522 corresponds to the objective lens mechanism 300 and the imaging mechanism 400.
[0093] Optionally, such as Figure 9 Figure 10 As shown, the fluorescence excitation assembly 520 includes an excitation block 522 connected to a plurality of excitation light sources 521, and the excitation light emitted by each excitation light source 521 is emitted through the excitation block 522. Further, the plurality of excitation light sources 521 are disposed on the same side of the excitation block 522.
[0094] Multiple excitation light sources 521 are arranged side by side along the direction (i.e., the preset direction X) in which the fluorescence driving component 510 drives the fluorescence excitation component 520 to move, so as to orderly arrange the positions of multiple excitation light sources 521 and excitation block 522, thereby facilitating the smooth switching of the fluorescence excitation component 520 between the first state and the second state.
[0095] The microscope inspection device 10 also includes an objective lens drive mechanism 700, which is mounted on the mounting bracket 600 and connected to the objective lens mechanism 300. The objective lens drive mechanism 700 drives the objective lens mechanism 300 to move away from or closer to the stage 100 in the first direction A, thereby adjusting the distance between the objective lens mechanism 300 and the sample area 101 in the first direction A to ensure a clear image. Optionally, the objective lens drive mechanism 700 is a sliding stage mechanism, with its drive end connected to the objective lens mechanism 300 to move the objective lens mechanism 300 in the first direction A. Of course, in other embodiments, the objective lens drive mechanism 700 can also have other structures, capable of moving the objective lens mechanism 300 in the first direction A and in a direction perpendicular to the first direction A, flexibly adjusting the position of the objective lens mechanism 300 so that the objective lens mechanism 300 corresponds to a portion of the sample area 101 in a plane perpendicular to the first direction A.
[0096] The objective lens drive mechanism 700 drives the objective lens mechanism 300 to move in the first direction A to switch between a working state and a dormant state. In the working state, the objective lens mechanism 300 is adjustable under the drive of the objective lens drive mechanism 700. In the dormant state, the objective lens mechanism 300 remains unchanged, and the distance between the objective lens mechanism 300 and the sample area 101 in the first direction A is a preset distance.
[0097] The microscope inspection device 10 also includes a shielding mechanism 800, which includes a shielding member 810 and a shielding drive mechanism 820. Optionally, the shielding drive mechanism 820 is mounted on the mounting bracket 600. The shielding drive mechanism 820 is connected to the shielding member 810. In the working state, the shielding drive mechanism 820 drives the shielding member 810 to avoid the optical path between the objective lens mechanism 300 and the sample area 101. In the dormant state, the shielding drive mechanism 820 drives the shielding member 810 to shield the objective lens mechanism 300, thereby protecting the objective lens mechanism 300 and the structural components located below the shielding member 810 and preventing dust accumulation. The shielding member 810 and the objective lens mechanism 300 are located on the same side of the stage 100. In the dormant state, along the first direction A, the distance from the shielding member 810 to the sample area 101 is less than the distance from the objective lens mechanism 300 to the sample area 101, so that the shielding member 810 is adjacent to the objective lens mechanism 300 to prevent dust from falling onto the objective lens mechanism 300. For example, the first direction A is a vertical direction. Dust accumulation on the surface of any element used to transmit light can affect the imaging effect of the sample. This application designs the placement of the objective lens mechanism 300 and the excitation block 522, and combines the imaging reflector 420 and the auxiliary reflector 401 to change the direction of light propagation, making the entire structure compact. This allows the shielding mechanism 800 to protect the objective lens mechanism 300, the excitation block 522, the imaging reflector 420, and the auxiliary reflector 401, thereby improving the imaging effect. Furthermore, when the position of the objective lens mechanism 300 is adjustable, the objective lens mechanism 300 can be adjusted to be closer to the excitation block 522, the imaging reflector 420, and the auxiliary reflector 401 in the first direction A during the dormant state, thereby reducing the probability of dust accumulation on the surface of the aforementioned optical devices.
[0098] The shielding member 810 includes two shielding plates 811. A shielding drive mechanism 820 drives the two shielding plates 811 to move away from each other in a direction forming an angle with the first direction A, thereby avoiding the optical path between the objective lens mechanism 300 and the sample area 101, allowing light entering and exiting the sample area 101 to pass through the objective lens mechanism 300. Optionally, the shielding plate 811 surface is perpendicular to the first direction A, and the shielding drive mechanism 820 drives the two shielding plates 811 to move away from each other in a direction perpendicular to the first direction A, thereby exposing the objective lens mechanism 300 and allowing the objective lens mechanism 300 to move smoothly in the first direction A, enabling the objective lens mechanism 300 to switch between a use state and a sleep state.
[0099] like Figure 11As shown, the shielding mechanism 800 also includes a shielding frame 830, which has a corresponding cutout area 830a of the objective lens mechanism 300. When the objective lens mechanism 300 moves in the first direction A under the drive of the objective lens drive mechanism 700, it can pass through the cutout area 830a to move away from or towards the sample area 101. The portion of the shielding frame 830 forming the cutout area 830a has a groove, and two shielding plates 811 are slidably disposed in the groove and can slide away from or towards each other under the drive of the shielding drive mechanism 820. Optionally, the shielding drive mechanism 820 is disposed on the shielding frame 830, and the shielding frame 830 is disposed on the mounting bracket 600.
[0100] Optionally, such as Figure 12 As shown, the blocking drive mechanism 820 includes a second drive motor 821, a drive member 822, a driven member 823, and a synchronizing member 824. The second drive motor 821 is mounted on the blocking frame 830 and connected to the drive member 822. The drive member 822 and the driven member 823 are parallel in axis and form an angle with or are positioned along the first direction A and the plane containing the second direction B. The synchronizing member 824 is connected to the periphery of both the drive member 822 and the driven member 823. In a direction perpendicular to the axis of the drive member 822, the synchronizing member 824 includes a first straight section 8241 located on one side of the drive member 822 and the driven member 823, and a second straight section 8242 located on the other side of the drive member 822 and the driven member 823. One blocking plate 811 is connected to the first straight section 8241, and the other blocking plate 811 is connected to the second straight section 8242. The second drive motor 821 is controlled to rotate the drive member 822, thereby causing the drive member 822 to move (the first straight segment 8241 and the second straight segment 8242 move in opposite directions), which in turn causes the driven member 823 to rotate. Thus, under the action of the synchronizing member 824, the two baffles 811 can move away from each other or move closer to each other. For example, when the second drive motor 821 controls the drive member 822 to rotate clockwise, the two baffles 811 move away from each other in the second direction; when the second drive motor 821 controls the drive member 822 to rotate counterclockwise, the two baffles 811 move closer to each other in the second direction.
[0101] The blocking drive mechanism 820 also includes a first slider 825 and a second slider 826. One blocking plate 811 is connected to the first straight segment 8241 via the first slider 825, and the other blocking plate 811 is connected to the second straight segment 8242 via the second slider 826. Further, when the axes of both the driving member 822 and the driven member 823 form an angle with the plane containing the first direction A and the second direction B, the first slider 825 has a first clearance area 825a to avoid the second straight segment 8242, and / or the second slider 826 has a second clearance area to avoid the first straight segment 8241. This allows the first slider 825 and the second slider 826 to move smoothly under the drive of the synchronizing member 824. For example, when the driving member 822, the driven member 823, and the synchronizing member 824 are all located on the side of the shielding frame 830 away from the sample area 101, in the first direction A, the distance from the first straight segment 8241 to the shielding frame 830 is greater than the distance from the second straight segment 8242 to the shielding frame 830. In this case, the first slider 825 is provided with a first clearance area 825a to avoid the second straight segment 8242. Preferably, the axial directions of both the driving member 822 and the driven member 823 are both arranged along the third direction C. In the first direction A, the first straight segment 8241 is located on one side of both the driving member 822 and the driven member 823, and the second straight segment 8242 is located on the other side of both the driving member 822 and the driven member 823, making the overall structure of the shielding driving mechanism 820 compact.
[0102] Optionally, the driving component 822 is a driving wheel, the driven component 823 is a driven wheel, and the synchronizing component 824 is a timing belt, which is sleeved around the driving wheel and the driven wheel. Alternatively, the driving component 822 is a driving gear, the driven component 823 is a driven gear, the first straight section 8241 is a first rack, and the second straight section 8242 is a second rack. The first rack is located on one side of the driving gear and the driven gear and meshes with both of them, while the second rack is located on the other side of the driving gear and the driven gear and meshes with both of them. Both the first rack and the second rack are slidably mounted on the shielding frame 830. This application does not limit the structure of the shielding driving mechanism 820; it can be selected according to actual needs. Any shielding driving mechanism 820 that can drive the shielding component 810 to shield the objective lens mechanism 300 and expose the objective lens mechanism 300 is applicable to this application.
[0103] The objective lens mechanism 300 includes multiple objective lenses 310 and an objective lens switcher 320. The objective lens switcher 320 is connected to the multiple objective lenses 310 to switch the orientation of one of the objective lenses 310 toward the sample area 101. Each objective lens 310 has a different magnification. In use, the objective lens 310 with the required magnification can be switched to face the sample area 101 according to actual needs. Optionally, the multiple objective lenses 310 are arranged in a circle with the direction of the first direction A as the rotation center. The objective lens switcher 320 can drive the multiple objective lenses 310 to rotate around the rotation center to switch the orientation of one of the objective lenses 310 toward the sample area 101. This application does not limit the structure of the objective lens switcher 320; it can be selected according to actual needs, as long as it can achieve the switching of the orientation of each objective lens 310 toward the sample area 101.
[0104] During testing, depending on different testing requirements, the objective lens 310 needs to be adjusted to correspond with multiple areas of the sample area 101 in order to acquire images of multiple areas of the sample to be tested in the sample area 101. At this time, at least one of the objective lens mechanism 300 and the sample to be tested can be moved so that the objective lens 310 can acquire images of the sample to be tested in different areas.
[0105] The microscope inspection device 10 also includes a material drive assembly 900, which is mounted on the mounting frame 600 and connected to the stage 100 to drive the stage 100 and the sample to be inspected to move, so that one of the areas to be inspected in the sample area 101 corresponds to the objective lens 310. Optionally, the material drive assembly 900 is used to drive the stage 100 to move in a plane perpendicular to the first direction A, so as to quickly adjust the correspondence between each area to be inspected in the sample area 101 and the objective lens 310. This application does not limit the structure of the material drive assembly 900, and it can be selected according to actual needs, as long as it can drive the stage 100 and the sample to be inspected to move in a plane perpendicular to the first direction A. However, it should be noted that the material drive assembly 900 should avoid the optical path between the sample area 101 and the objective lens mechanism 300 to prevent the material drive assembly 900 from obstructing the movement of the objective lens mechanism 300 relative to the sample area 101.
[0106] Optionally, the material drive assembly 900, objective lens switcher 320, occlusion drive mechanism 820 and imaging drive mechanism 700 are all connected to the control system, and the control system controls the operation of the material drive assembly 900, objective lens switcher 320, occlusion drive mechanism 820 and imaging drive mechanism 700 respectively to improve detection efficiency.
[0107] The microscope inspection device 10 also includes an imaging analysis mechanism electrically connected to the camera 410 to receive and analyze image information of the sample to be inspected transmitted by the camera 410. For example, the imaging analysis mechanism analyzes the image information of the sample to be inspected, including segmentation, counting, and localization of 3D biological tissues, enabling high-throughput operation and observation, thereby performing imaging analysis and intelligent edge delineation of 3D biological tissues. The imaging analysis mechanism is also electrically connected to a display structure to send the analysis results to the display structure for display.
[0108] In the accompanying drawings of this embodiment, the same or similar reference numerals correspond to the same or similar components. In the description of this application, it should be understood that if terms such as "upper," "lower," "left," and "right" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, they are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the terms used to describe positional relationships in the accompanying drawings are only for illustrative purposes and should not be construed as limiting this patent. For those skilled in the art, the specific meaning of the above terms can be understood according to the specific circumstances.
[0109] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.
Claims
1. A microscope inspection device, characterized in that, Used for the detection of 3D biological tissues, including: The material stage has a sample area; A multi-channel light source assembly is disposed on one side of the material stage corresponding to the sample area, and is capable of emitting preset light to the sample area; The objective lens mechanism is located on the side of the stage away from the multi-channel light source assembly, corresponding to the sample area, and has a working state and a dormant state. The shielding mechanism includes a shielding member and a shielding drive mechanism. The shielding drive mechanism is connected to the shielding member. In the use state, the shielding drive mechanism is used to drive the shielding member to avoid the optical path between the objective lens mechanism and the sample area. In the dormant state, the shielding drive mechanism is used to drive the shielding member to shield the objective lens mechanism. An imaging mechanism, configured corresponding to the objective lens mechanism, is provided to receive light passing through the objective lens mechanism; and A fluorescence mechanism includes a fluorescence driving component and a fluorescence excitation component. The fluorescence excitation component, the imaging mechanism, and the objective lens mechanism are located on the same side of the stage. The fluorescence excitation component includes an excitation light source and an excitation block. The excitation block is connected to the excitation light source, and the fluorescence driving component is connected to the excitation block to drive the fluorescence excitation component to switch between a first state and a second state when the objective lens mechanism is in use. In the first state, the fluorescence excitation component avoids the optical path between the objective lens mechanism and the imaging mechanism, and the preset light rays passing through the sample area reach the imaging mechanism via the objective lens mechanism. In the second state, the fluorescence excitation component is located on the optical path between the objective lens mechanism and the imaging mechanism, and the excitation light emitted from the fluorescence excitation component passes through the objective lens mechanism to reach the sample area. The fluorescence generated by the excitation light on the sample in the sample area passes sequentially through the objective lens mechanism and the fluorescence excitation component to reach the imaging mechanism. With the direction of the multi-channel light source assembly toward the objective lens mechanism as the first direction, the fluorescence driving assembly drives the fluorescence excitation assembly to move in a preset direction that forms an angle with the first direction, so as to drive the fluorescence excitation assembly to switch between the first state and the second state; The light rays passing through the objective lens mechanism are received by the imaging mechanism at an angle to the first direction.
2. The microscope inspection device according to claim 1, characterized in that, The imaging mechanism includes: The camera and the objective lens mechanism are located on the same side of the loading stage; An imaging reflector is provided corresponding to the objective lens mechanism and the camera to receive light passing through the objective lens mechanism along the first direction and reflect the light to be projected onto the camera along the second direction, wherein the second direction forms an angle with the first direction and the second direction is the preset direction.
3. The microscope inspection device according to claim 1, characterized in that, The microscope inspection device also includes: An auxiliary reflective element is disposed in the first direction corresponding to the objective lens mechanism to receive light passing through the objective lens mechanism and reflect the light to be projected along the second direction; The imaging mechanism includes: The camera and the objective lens mechanism are located on the same side of the loading stage. An imaging reflector is disposed in the second direction corresponding to the auxiliary reflector to receive the light reflected by the auxiliary reflector and reflect the light to be projected onto the camera along a third direction. The first direction, the second direction, and the third direction are at angles to each other, and the third direction is the preset direction.
4. The microscope inspection device according to claim 1, characterized in that, In the second state, the excitation block is located in the optical path between the objective lens mechanism and the imaging mechanism, so that the excitation light reaches the objective lens mechanism via the excitation block, and the fluorescence reaches the imaging mechanism via the excitation block.
5. The microscope inspection device according to claim 4, characterized in that, The fluorescence excitation component includes a plurality of excitation light sources, and the wavelengths of the excitation light emitted by the plurality of excitation light sources are different. The fluorescence excitation assembly includes multiple excitation blocks corresponding one-to-one with the multiple excitation light sources. The excitation light emitted by each excitation light source is emitted through the corresponding excitation block. In the second state, one of the excitation blocks corresponds to the objective lens mechanism and the imaging mechanism; or... The fluorescence excitation assembly includes an excitation block connected to a plurality of excitation light sources, wherein the excitation light emitted by each excitation light source is emitted through the excitation block; or, The plurality of excitation light sources are arranged side by side along the direction in which the fluorescence driving component drives the fluorescence excitation component to move.
6. The microscope inspection device according to claim 1, characterized in that, The preset light includes bright field light or contrasting light.
7. The microscope inspection device according to claim 1, characterized in that, The microscope inspection device also includes: Mounting frame, wherein the material carrier is disposed on the mounting frame; An objective lens driving mechanism is disposed on the mounting bracket and connected to the objective lens mechanism to drive the objective lens mechanism relative to the material stage in a first direction, thereby driving the objective lens mechanism to switch between the use state and the sleep state. The first direction is the direction in which the multi-channel light source assembly faces the objective lens mechanism.
8. The microscope inspection device according to claim 7, characterized in that, The shielding component includes two shielding plates, which are located on the same side of the stage as the objective lens mechanism. The shielding drive mechanism is located on the mounting bracket and connected to the two shielding plates. In the use state, the shielding drive mechanism drives the two shielding plates to move away from each other in a direction that forms an angle with the first direction, so as to avoid the optical path between the objective lens mechanism and the sample area. In the dormant state, the shielding drive mechanism drives the shielding component to shield the objective lens mechanism.
9. The microscope inspection device according to claim 1, characterized in that, The objective lens mechanism includes: a plurality of objectives and an objective lens switcher, the objective lens switcher being connected to the plurality of objectives to switch one of the objectives toward the sample area; The microscope inspection device further includes a mounting frame and a material driving assembly. The material driving assembly is located on the mounting frame and connected to the material stage to drive the material stage to move so that one of the areas to be inspected in the sample area corresponds to the objective lens.
Citation Information
Patent Citations
Microscope detection device
CN219625358U