A fully automatic double reflection microscopic detection observation device and method

Abstract

A fully automatic double reflection microscopic detection observation device and method, relating to the field of intelligent control. The invention solves the problem that the observation method in the prior art is to observe the culture dish by single reflection and side transmission, and can only observe limited positions without the function of accurately analyzing the results. The device includes: an upper observation module for collecting image information in the upward direction; an intermediate receiving module for connecting the upper observation module and the lower observation module; a lower observation module for collecting image information in the downward direction; a top Z-axis focusing function module for determining whether the image in the upper optical module is clear when the microscope head moves upward; a bottom Z-axis focusing function module for determining whether the image information in the lower optical module collected when the microscope head moves downward is clear; a main control center for analyzing and processing images at different positions obtained by the upper optical module and the lower optical module. It is suitable for use in hospitals, laboratories, and the vaccine industry.

Description

Technical Field

[0001] The invention relates to the field of intelligent control technology, and in particular to a fully automatic double reflection microscopic detection and observation device and method. Background Art

[0002] Double reflection observation has high clarity, strong adaptability, and a large observation area, which improves the accuracy of cell culture results to a certain extent. The reflected light source forms reflected light on the liquid surface in the culture dish and is introduced into the microscope imaging lens to assist imaging. The brightness and clarity of the image can be adjusted by adjusting the brightness of the light source and the angle between the light source and the microscope imaging lens. Images formed by brightness and angles within a certain range can be compared. The parameters of the light source in each light-sensing environment are determined according to the clarity of the observed image sample.

[0003] The traditional observation method is to observe the culture dish by single reflection and side transmission, which can only observe limited positions and does not have the function of accurately analyzing the results. Summary of the invention

[0004] The present invention aims to solve the problem that the observation method in the prior art is to observe the culture dish by single reflection and side transmission, which can only observe limited positions and has no function of accurately analyzing the results.

[0005] To solve the above technical problems, the present invention is achieved through the following technical solutions:

[0006] Solution 1: The present invention proposes that the device includes an upper observation module, an intermediate receiving module, a lower observation module, and an optical module;

[0007] The upper observation module includes a circuit control module, an upper optical module, an upper X-axis module, a main control center, a top automatic control module, and an upper Y-axis module;

[0008] The intermediate receiving module includes an upper supporting plate, a supporting plate, a tray, an upper sealing plate, a lower supporting plate, and a lower sealing plate;

[0009] The lower observation device module includes a lower X-axis module, a lower optical module, casters, and a lower Y-axis module;

[0010] The optical module includes a lower light source fixing ring, a light source, a camera, a lower light source adjustment block, a lower lens fixing ring, and a microscope lens;

[0011] The upper observation module is connected to the middle receiving module by means of threads, and the lower observation module is connected to the middle receiving module by means of threads, so as to support the upper observation module and the middle receiving module;

[0012] The circuit control module is fixed on the inner wall of the upper observation module by means of threads, and the circuit control module controls the movement of the top control module to control the movement of the upper optical module to realize image acquisition;

[0013] The upper Y-axis module is fixed to the upper support plate of the upper observation module by means of threads, and is used to drive the upper X-axis module, the top automatic control module and the upper optical module to move along the Y-axis direction, and collect images for observation through the upper optical module;

[0014] The lower X-axis module is fixed on the bottom plate of the lower observation module by means of threads, driving the lower Y-axis module and the lower optical module to collect images for observation along the X-axis movement. The lower Y-axis module is fixed on the flat plate by means of threads, and then fixed on the slider of the lower X-axis module by means of threads, and moves along the Y-axis direction to collect images for observation through the lower optical module;

[0015] The camera is connected to the microscope head through an external thread, the lower lens fixing ring is fixed to the microscope head through a top screw and a thread, the lower light source fixing ring is fixed to the lower light source adjustment block through a thread, the lower light source adjustment block is connected to the lower lens fixing ring, and the screws on both sides of the lower light source adjustment block are adjusted by loosening and tightening the angle to adjust the angle between the light source and the lens to achieve the adjustment of image clarity; the light source is fixed to the lower light source fixing ring through a top screw and a thread, the image is adjusted by adjusting the upper and lower position of the light source by the tightness of the top screw, and the observed image is adjusted by adjusting the tightness of the screw.

[0016] Furthermore, a preferred embodiment is provided, wherein the upper observation module and the lower observation module are symmetrically arranged.

[0017] Further, a preferred embodiment is provided, wherein the device further comprises a bottom Z-axis focusing module, wherein the bottom Z-axis focusing module comprises a bottom lifting block, a bottom lifting screw, and a Z-axis module under a bottom optical system fixing block;

[0018] The bottom lifting screw is connected to the bottom lifting block and the lower Z-axis module by means of a thread, and the bottom optical system fixing block is driven to move up and down by the rotation of the screw.

[0019] Further, a preferred embodiment is provided, wherein the device further comprises a top Z-axis focusing function module, wherein the top Z-axis focusing function module comprises a top lifting block, a top lifting screw, a top optical system fixing block, and an upper Z-axis module;

[0020] The upper Z-axis module is fixed to the support frame by means of threads, and the top lifting block is fixed to the slider of the upper Z-axis module by means of threads. The top lifting screw is connected to the bearing seat and the synchronous pulley up and down, and is connected to the top lifting block by means of threads. The top lifting screw rotates through the threaded fixing method to drive the top optical system fixing block to move up and down, that is, the upper optical module moves up and down to adjust the focal length of the optical system to obtain a clear image.

[0021] Furthermore, a preferred embodiment is provided, wherein the device further comprises 6 motors, all of which are fixed to respective motor support frames by means of threads.

[0022] Furthermore, a preferred embodiment is provided, wherein the lower support plate in the intermediate receiving module is the top plate of the lower observation module, the support column in the intermediate receiving module is fixed above it by means of threads, and the support column fixes the upper support plate of the upper observation module together by means of threads.

[0023] Furthermore, a preferred embodiment is provided, in which a groove is provided on the inner side of the mating surface between the support column and the upper support plate, and the groove slides the upper sealing plate into the upper observation main module.

[0024] Furthermore, a preferred embodiment is provided, wherein the tray is fixed to the lower support plate by means of threads, and a groove is provided at the bottom of the tray.

[0025] Furthermore, a preferred embodiment is provided, wherein the light source and the microscope lens form an angle between 10° and 45°.

[0026] Solution 2: A fully automatic double reflection microscopic detection and observation method, which is implemented based on the device described in Solution 1, and comprises:

[0027] S1. Place the cell factory on the tray, select the fully automatic one-key operation in the main control center, and automatically scan the entire upper and lower planes, use the camera to take fixed-point photos and save the pictures;

[0028] S2. Place the cell factory on the tray, select manual control in the main control center, select the autofocus function to find a clear image; observe the culture status through manual translation, select representative points and use the camera to take pictures.

[0029] S3, compare and analyze the pictures saved by the fixed-point photography in S1 with the pictures saved by the representative points selected in S2, and complete the fully automatic double reflection microscopic detection and observation.

[0030] The present invention is beneficial in that:

[0031] The fully automatic double reflection microscopic detection observation device of the present invention can perform observations in two directions, upper and lower, and can perform all-round observations on the entire plane, thereby greatly increasing the observation area and the accuracy of the culture results.

[0032] The double reflection observation technology of the present invention has high definition and high flexibility, can accurately observe various forms of cells and bacteria and viruses, and reduce the possibility of misjudgment of culture results.

[0033] The fully automated device of the present invention reduces the manual operation process, reduces the risk of human error, and improves the reliability of the observation results. At the same time, the automated system speeds up the overall observation process and improves work efficiency.

[0034] Changing the servo closed-loop system described in the present invention to a step open-loop system is beneficial to providing favorable conditions for updating new functions of the control system and reducing costs.

[0035] The fully automatic double reflection microscopic observation device of the present invention is equipped with advanced image processing and data analysis functions, which can quickly observe the results and generate detailed reports, making it convenient for on-site observation and analysis personnel to conduct specific analysis.

[0036] The fully automatic double reflection microscopic observation device of the present invention provides a more accurate and convenient solution for cell culture, and helps to improve the error rate of pharmaceutical and vaccine production.

[0037] The present invention is also applicable to hospitals, research institutes, laboratories, and vaccine industries. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is a schematic structural diagram of a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0039] Figure 2 This is a schematic diagram of the structure of the upper observation device module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0040] Figure 3 This is a schematic diagram of the structure of an intermediate receiving module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0041] Figure 4 This is a schematic diagram of the structure of the lower observation device module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0042] Figure 5 This is a schematic diagram of the bottom structure of the lower observation device module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0043] Figure 6This is a schematic structural diagram of a bottom Z-peripheral focusing function module in a fully automatic double-reflection microscopic detection and observation device described in Implementation Example 1.

[0044] Figure 7 This is a schematic diagram of the structure of an optical module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0045] Figure 8 This is a schematic diagram of the structure of a top Z-axis focusing function module in a fully automatic double reflection microscopic detection and observation device described in Implementation Example 1.

[0046] Fig. 9 This is a flow chart of a fully automatic double reflection microscopy detection and observation method described in Implementation Example 10.

[0047] Fig.10 This is a schematic diagram of comparing and analyzing the pictures saved by the fixed-point photography described in Implementation Example 11 and the pictures saved by selecting representative points 2.

[0048] (a) is a schematic diagram of the bottom layer, (b) is a schematic diagram of the bottom two layers, (c) is a schematic diagram of the bottom three layers, (d) is a schematic diagram of the top two layers, and (e) is a schematic diagram of the top layer.

[0049] In the figure, an upper observation general module 1, an intermediate receiving module 2, a lower observation general module 3, a circuit control module 4, an upper optical module 5, an upper X-axis module 6, a main control center 7, a top automatic control module 8, an upper Y-axis module 9, an upper support plate 10, a support plate, a tray, an upper sealing plate 13, a lower support plate 14, a lower sealing plate 15, a lower X-axis module 16, a lower optical module 17, casters 18, a lower Y-axis module 19, a stepper motor 20, a bottom lifting block 21, a bottom lifting screw rod 22, a bottom optical system fixing block 23, a lower Z-axis module 24, a lower light source fixing ring 25, a light source 26, a camera 27, a lower light source adjustment block 28, a lower lens fixing ring 29, a microscope lens 30, a top lifting block 31, a top lifting screw rod 32, a top optical system fixing block 33, and an upper Z-axis module 34. DETAILED DESCRIPTION

[0050] In order to make the purpose, technical solutions and advantages of the implementation methods of the present application clearer, the technical solutions in the implementation methods of the present application will be clearly and completely described below in conjunction with the drawings in the implementation methods of the present application. Obviously, the described implementation methods are only part of the implementation methods of the present application, not all of the implementation methods.

[0051] Embodiment 1: This embodiment provides a fully automatic double reflection microscopic detection observation device, which includes an upper observation module 1, an intermediate receiving module 2, a lower observation module 3, and an optical module;

[0052] The upper observation module 1 includes a circuit control module 4, an upper optical module 5, an upper X-axis module 6, a main control center 7, a top automatic control module 8, and an upper Y-axis module 9;

[0053] The intermediate receiving module 2 includes an upper support plate 10, a support plate 11, a tray 12, an upper sealing plate 13, a lower support plate 14, and a lower sealing plate 15;

[0054] The lower observation device module 3 includes a lower X-axis module 16, a lower optical module 17, casters 18, and a lower Y-axis module 19;

[0055] The optical module includes a lower light source fixing ring 25, a light source 26, a camera 27, a lower light source adjustment block 28, a lower lens fixing ring 29, and a microscope lens 30;

[0056] The upper observation module 1 is connected to the middle receiving module 2 by means of threads, and the lower observation module 3 is connected to the middle receiving module 2 by means of threads, so as to support the upper observation module 1 and the middle receiving module 2;

[0057] The circuit control module 4 is fixed on the inner wall of the upper observation module 1 by means of threads, and the circuit control module 4 controls the movement of the top control module 8 to control the movement of the upper optical module 5 to realize the acquisition of images;

[0058] The upper Y-axis module 9 is fixed to the upper support plate 10 of the upper observation module 1 by means of threads, and is used to drive the upper X-axis module 6, the top automatic control module 8 and the upper optical module 5 to move along the y-axis direction, and collect images for observation through the upper optical module 5;

[0059] The lower X-axis module 16 is fixed to the bottom plate of the lower observation module 3 by means of threads, driving the lower Y-axis module 19 and the lower optical module 17 to collect images for observation along the X-axis direction. The lower Y-axis module 19 is fixed to the flat plate by means of threads, and then fixed to the slider of the lower X-axis module 16 by means of threads, and moves along the Y-axis direction to collect images for observation through the lower optical module 17;

[0060] The camera 27 is connected to the microscope lens 30 by means of external threads, the lower lens fixing ring 29 is fixed to the microscope lens 30 by means of top screws and threads, the lower light source fixing ring 25 is fixed to the lower light source adjustment block 28 by means of threads, the lower light source adjustment block 28 is connected to the lower lens fixing ring 29, and the screws on both sides of the lower light source adjustment block 28 are adjusted by loosening and tightening the angle to adjust the angle between the light source and the lens to achieve the adjustment of the image clarity; the light source 26 is fixed to the lower light source fixing ring 25 by means of top screws and threads, the image is adjusted by adjusting the upper and lower position of the light source 26 by the tightness of the top screw, and the observed image is adjusted by adjusting the tightness of the screws.

[0061] Embodiment 2: This embodiment further limits the fully automatic double reflection microscopic detection and observation device described in Embodiment 1, and the upper observation module 1 and the lower observation module 3 are symmetrically arranged.

[0062] Embodiment 3. This embodiment is a further limitation of the fully automatic double reflection microscopic detection and observation device described in Embodiment 1. The device further includes a bottom Z-axis focusing module, and the bottom Z-axis focusing module includes a bottom lifting block 21, a bottom lifting screw 22, a bottom optical system fixing block 23, and a lower Z-axis module 24.

[0063] The bottom lifting screw 22 is connected to the bottom lifting block 21 and the lower Z-axis module 24 by means of threads, and the bottom optical system fixing block 23 is driven to move up and down by the rotation of the screw.

[0064] Embodiment 4. This embodiment is a further limitation of the fully automatic double reflection microscopic detection and observation device described in Embodiment 1. The device further includes a top Z-axis focusing function module, and the top Z-axis focusing function module includes a top lifting block 31, a top lifting screw 32, a top optical system fixing block 33, and an upper Z-axis module 34.

[0065] The upper Z-axis module 34 is fixed to the support frame by means of threads, the top lifting block 31 is fixed to the slider of the upper Z-axis module 34 by means of threads, the top lifting screw 32 is connected to the bearing seat and the synchronous pulley up and down, and is connected to the top lifting block 31 by means of threads, and the top optical system fixing block 33 is driven up and down by the rotation of the top lifting screw 32 through the threaded fixing method, that is, the upper optical module 5 moves up and down to adjust the focal length of the optical system to obtain a clear image.

[0066] Embodiment 5: This embodiment further limits the fully automatic double reflection microscopic detection and observation device described in Embodiment 1. The device further includes 6 motors 20, which are all fixed on each motor support frame by means of threads.

[0067] Embodiment 6. This embodiment is a further limitation of the fully automatic double reflection microscopic detection and observation device described in embodiment 1. The lower support plate 14 in the intermediate receiving module 2 is the top plate of the lower observation total module 3. The support column 11 in the intermediate receiving module 2 is fixed above it by means of threads, and the support column 11 fixes the upper support plate 10 of the upper observation total module 1 together by means of threads.

[0068] Embodiment 7. This embodiment further limits the fully automatic double reflection microscopic detection and observation device described in embodiment 1. A groove is provided on the inner side of the mating surface between the support column 11 and the upper support plate (10), and the groove slides the upper sealing plate 13 into the upper observation module 1.

[0069] Embodiment 8: This embodiment further limits the fully automatic double reflection microscopic detection and observation device described in Embodiment 1. The tray 12 is fixed to the lower support plate 14 by means of threads, and a groove is provided at the bottom of the tray 12.

[0070] Embodiment 9: This embodiment further limits the fully automatic double reflection microscopic detection and observation device described in Embodiment 8, wherein the light source 26 and the microscope lens 30 form an angle within a range of 10° to 45°.

[0071] Embodiment 10: This embodiment proposes a fully automatic double reflection microscopic detection observation method, which is implemented based on the device described in embodiment 1, and includes:

[0072] S1. Place the cell factory on the tray 12, select the fully automatic one-key operation in the main control center 7, and automatically scan the entire upper and lower planes, use the camera 27 to take fixed-point photos and save the pictures;

[0073] S2, place the cell factory on the tray 12, select the manual control operation in the main control center 7, select the auto focus function to find a clear image; observe the culture status through manual operation translation, select representative points and use the camera 27 to take pictures,

[0074] S3, compare and analyze the pictures saved by the fixed-point photography in S1 with the pictures saved by the representative points selected in S2, and complete the fully automatic double reflection microscopic detection and observation.

[0075] Implementation eleven: This implementation provides an example, which is used to explain the above implementations one to ten. The specific example is as follows:

[0076] See also Figures 1 to 10 To explain this embodiment, first, the stepper motor 20 moves the lower optical module 17 to a position where a clearer image can be seen through a belt, and then controls it. The main control center 7 selects the full automatic mode or the manual mode, and the software controls the operation of the X, Y, and Z axes of the lower X-axis module 6, the lower Y-axis module 9, and the lower Z-axis module 24.

[0077] Figure 1 In the figure, the upper observation module 1 is connected to the middle receiving module 2 by means of threads, and the middle receiving module supports the upper observation module 1. The lower observation module 3 plays a general supporting role at the bottom of the two modules, and is also connected to the middle receiving module 2 by means of threads. The three are connected one by one by means of threads and support each other.

[0078] Figure 2In the figure, the circuit control module 4 is fixed on the inner wall of the upper observation module 1 by threading, and controls the entire instrument. The upper Y-axis module 9 is fixed on the upper support plate 10 of the upper observation module 1 by threading, and drives the upper X-axis module 6, the top automatic control module 8 and the upper optical module 5 to move along the y-axis direction, and collects images through the upper optical module 5 for observation.

[0079] Among them, the upper X-axis module 6 is fixed on a plane support plate by a threaded method, and the plane support plate is fixed on the slider of the upper Y-axis module 9 by a threaded method. The upper optical module 5 is controlled by the top automatic control module 8 to move along the upper X-axis module 6 along the X-axis direction to collect images for observation through the upper optical module 5. The top automatic control module 8 is fixed on the upper X-axis module (6 by a threaded method, and the upper optical module (5 is fixed by a threaded method. The top control module 8 is controlled by the circuit control module 4 to move so as to control the movement of the upper optical module 5 to realize the image collection. Finally, the main control center 7 is screwed with its own thread, and the main control center 7 is fixed to the inner wall of the shell by locking the screws.

[0080] Figure 3 In the figure, the lower support plate 14 is the top plate of the lower observation module 3, and the support column 11 in the intermediate receiving module 2 is fixed thereon by means of threads, and the support column 11 also fixes the upper support plate 10 on the bottom plate of the upper observation module 1 by means of threads, so as to form a supporting whole. The support column 11 is hollow inside, and the line transmission of the upper observation module 1 and the lower observation module 3 is docked through the inside. The tray 12 is the tray of the cell culture dish, and is also fixed to the lower support plate 14 by means of threads. The bottom of the tray 12 has a groove, which can just slide the lower sealing plate 15 into the channel to isolate the lower observation module 3 from the outside, and can block the entry of corrosive gases and liquids when the instrument stops using and is disinfected. The inner side of the docking surface between the support column 11 and the upper support plate (10) also has a groove, which can just slide the upper sealing plate 13 into the channel to isolate the upper observation module 1 from the outside, and also block the entry of corrosive gases and liquids.

[0081] Figure 4 In the figure, the caster 18 is fixed to the bottom plate of the lower observation module 3 by means of threads, and plays the role of moving the entire instrument. The lower X-axis module 16 is fixed to the bottom plate of the lower observation module 3 by means of threads, driving the lower Y-axis module 19 and the lower optical module 17 to move along the X direction to collect images for observation. The lower Y-axis module 19 is fixed to the flat plate by means of threads, and then fixed to the slider of the lower X-axis module 16 by means of threads, and moves along the Y-axis direction to collect images for observation through the lower optical module 17.

[0082] Figure 5In this embodiment, there are a total of 6 motors 20, all of which are fixed on each motor support frame by threading.

[0083] Figure 6 In the figure, the lower Z-axis module 24 is fixed on the support frame by means of threads, which guides the lower optical module 17 to move along the Z-axis. The bottom lifting block 21 is fixed on the slider of the lower Z-axis module 24 by means of threads, and the upper and lower parts are connected to the bearing seat and the synchronous pulley. The bottom optical system 23 fixing block is fixed on the bottom lifting block 21 by means of threads. The bottom lifting block 21 drives the lower optical module 17 to move along the Z-axis to adjust the focal length of the optical system so that a clear image can be obtained.

[0084] Figure 7 In the embodiment, the camera 27 is connected to the microscope lens 30 by means of external threads, and the lower lens fixing ring 29 is fixed to the microscope lens 30 by means of top screws and threads, and the position can be adjusted up and down by loosening the top screws to adjust the optical effect, which is very important for clear image acquisition. The lower light source fixing ring 25 is fixed to the lower light source adjustment block 28 by means of threads, and is connected to the lower lens fixing ring 29 in the same way, and the screws on both sides of the lower light source adjustment block 28 can adjust the angle between the light source and the lens by loosening and tightening to adjust the image clarity. The light source 26 is fixed to the lower light source fixing ring 25 by means of top screws and threads, and the position of the light source 26 can also be adjusted by loosening and tightening the top screws to adjust the image clarity. All the screws of this module can be adjusted to adjust the image clarity by adjusting the tightness. It is very important to obtain a clear image.

[0085] Figure 8 In the figure, the upper Z-axis module 34 is fixed on the support frame by means of threads, the top lifting block 31 is fixed on the slider of the upper Z-axis module 34 by means of threads, the top lifting screw 32 is connected to the bearing seat and the synchronous pulley up and down, and is connected to the top lifting block 31 by means of threads in the middle. The top lifting screw 32 rotates and drives the top optical system fixing block 33 to move up and down through the threaded fixing method, so that the upper optical module 5 moves up and down to adjust the focal length of the optical system to obtain a clear image.

[0086] The upper and lower ends of the bottom lifting screw 22 are fixed on the bottom Z-axis focusing function module fixing plate through bearings. The stepper motor 20 fine-tunes and drives the bottom lifting screw 22 to rotate through the synchronous belt.

[0087] The bottom lifting screw 22 is connected with the bottom lifting block 21 and the lower Z-axis module 24 by means of threads, and the bottom optical system 23 fixing block is driven to move up and down by the rotation of the screw.

[0088] The bottom optical system 23 fixing block is connected to the bottom lifting block 21 by means of threads, thereby controlling the up and down movement of the lower optical module 17.

[0089] The lower light source fixing ring 25 and the lower lens fixing ring 29 are both fixed at corresponding positions by means of threads and top screws, and can be moved up and down to be adjusted in coordination with the formed image.

[0090] The lower light source adjustment block 28 is connected with the lower light source fixing ring 25 and the lower lens fixing ring 29 by screw threads.

[0091] First, let the light source 26 and the microscope lens 30 form any degree in the range of 10° to 45°, and display a relatively clear image on the main control center 7. Then adjust the angle to evenly cover the entire display interface, and then adjust the stepper motor 20 to fine-tune the movement of the microscope lens 30 up and down until the image is clear. The main control center 7 controls the software to make the camera 27 take fixed-point photos and save them. Because the bottom can scan three layers, each cross-layer observation must be controlled by the main control center 7 to control the stepper motor 20 to operate the lower optical module 17 until a clear image is displayed.

[0092] When the operation is finished and the machine is shut down, the lower optical module 17 is moved to the bottom by the stepper motor 20 so that the lower sealing plate 15 can be closed without interference.

[0093] First, the main control center 7 switches and operates the upper optical module 5 to observe the culture status of the upper two layers of the cell factory.

[0094] The top lifting screw 32 is fixed together with the top Z-axis focusing function module through the upper and lower bearing fixing seats.

[0095] The stepper motor 20 drives the top lifting screw 32 to rotate through the synchronous belt

[0096] The top lifting block 31 is connected to the rotating bearing seat 32 on the top lifting screw rod by means of threads.

[0097] The top optical system fixing block 33 is connected to the top lifting block 27 by means of threads.

[0098] The main control center 7 controls the stepper motor 20 to control the upper X-axis module 6, the upper Y-axis module 9, and the upper Z-axis module 34 so that the optical module 5 can move in three directions: X, Y, and Z.

[0099] The method for observing the first layer at the top is the same as that for observing the bottom plane. After the upper optical module 5 observes the top layer, it slowly moves downward through the stepper motor 20, and moves the stepper motor 20 in the X and Y directions to the center of the top corner of the cell factory for fixed-point observation. Before each fixed-point observation, the up and down movement must be repeated to avoid the corners.

[0100] The images at different positions are obtained by the upper optical module 5 and the lower optical module 17, and then the main control center 7 software is used to analyze and process the images to obtain the results.

[0101] After the device is built, the object is fixed and scanned, and then compared with the standard pictures, and finally analyzed and judged. By comparing the collected pictures with the standard pictures, the device meets the standards. In addition, the LED light source of this embodiment can be changed to a ring light source.

[0102] The fully automatic cell factory in-situ observation device in this embodiment involves multiple fields and is applicable to the vaccine industry, cell and gene therapy, and stem cell fields. This technology achieves multi-layer, comprehensive, rapid and clear observation of 40-layer cell factory culture dishes through unique lens and light source design and precise automatic control.

[0103] The side observation technology is a method of directly penetrating the culture dish to provide light source to the lens. The light source and the lens are in a straight line. With the help of the robotic arm, the optical axis can be adjusted to the angle of the culture dish to observe the cell culture status within 10-15mm from the edge of each layer of the 40-layer culture dish. The fully automatic microscopic imaging observation technology can be controlled by advanced software to perform scanning observation and take pictures of the entire layer of cell culture dishes, identify the cell culture status pictures of the bottom three layers, and analyze the overall cell culture status in combination with side observation.

[0104] The implementation steps are:

[0105] Sample preparation: Spread the liquid in the culture dish evenly on each layer so that the liquid level of each layer is roughly the same.

[0106] Focus adjustment: Adjust the focus through the control system until a relatively clear image can be seen.

[0107] Light source adjustment: Keep the focal length unchanged, adjust the light source up and down until a clear image is presented and fix the light source position.

[0108] Scanning and observation and analysis: The software controls the lens to move in parallel, and fixed-point photography is performed to observe and analyze all photos and evaluate the culture status.

[0109] Thus, the data is comprehensive: comprehensive coverage scanning observation, random photography, and improved data collection efficiency; strong matching: suitable for culture dishes of all layers. High precision: using servo system, high motion precision. High degree of automation: with one-button operation and manual operation, it can adapt to different needs and greatly improve work efficiency.

[0110] In this embodiment, the ring light source is adjusted up and down to evenly illuminate the light reflected from the liquid surface in the culture dish to provide light source for the lens. It is also suitable for adjustable light source angles and is suitable for various occasions. The light source and the lens are aligned with each other and penetrate the culture dish at an angle. The size of the observed area depends on the height of each layer. The clarity is adjusted by adjusting the angle between the optical axis and the culture dish and the distance between the lens and the culture dish. It is conducive to imaging the complete cell structure clearly, which is conducive to observation and analysis. The whole machine adopts a servo motor with an encoder and a collective controller, and the entire working stroke is closed-loop controlled. It achieves low-cost open-loop control, and various functions can be added later to meet more needs.

[0111] The device described in this embodiment is made of mirror stainless steel as a whole, and the stainless steel material has low activity. The role of the open-loop stepping control system is to reduce costs, and subsequent secondary development can continue on the original basis to better meet market demand.

[0112] Modular design reduces the size of the equipment, reduces the complexity of the structure, and facilitates maintenance. Automated equipment reduces manual operation and improves work efficiency. Reduces manual errors, saves labor and time, and improves production efficiency. Simplifies operation. Equipped with advanced data processing software, it can automatically analyze and manage test results. Provides comprehensive images to help operators analyze and summarize, and is used for subsequent production data storage.

[0113] The device and method described in this embodiment are applicable to a variety of fields, including hospitals, research institutes, laboratories, vaccine companies, etc. It can improve the overall cell gene culture level and the progress of biomedical engineering. It can provide high-precision, multi-magnification cell culture image data to provide reliable data support for production personnel. It can promote the development of allergen-related research and explore new allergy mechanisms and treatment methods. It can promote the development of vaccine industry and stem cell industries and explore new biomedical processes.

[0114] By designing a cell factory microscopic observation device, we aim to achieve more efficient, accurate and comprehensive cell culture observation, meet the needs of vaccine production and scientific research, and improve the development of biomedicine.

[0115] Those skilled in the art will appreciate that the above are only preferred embodiments of the present invention, and the various embodiments of the present disclosure and / or the features described in the claims may be combined or combined in various ways, even if such combinations or combinations are not explicitly described in the present disclosure. It is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art may still modify the technical solutions described in the aforementioned embodiments, or perform equivalent substitutions on some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

[0116] Although preferred embodiments of the present invention have been described, additional changes and modifications may be made to these embodiments by those skilled in the art once the basic inventive concepts are known. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention. Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A fully automatic double reflection microscopic detection and observation device, characterized in that: The device comprises an upper observation module (1), an intermediate receiving module (2), a lower observation module (3), and an optical module; The upper observation module (1) comprises a circuit control module (4), an upper optical module (5), an upper X-axis module (6), a main control center (7), a top automatic control module (8), and an upper Y-axis module (9); The intermediate receiving module (2) comprises an upper supporting plate (10), a supporting column (11), a tray (12), an upper sealing plate (13), a lower supporting plate (14), and a lower sealing plate (15); The lower observation module (3) comprises a lower X-axis module (16), a lower optical module (17), casters (18), and a lower Y-axis module (19); The optical module comprises a lower light source fixing ring (25), a light source (26), a camera (27), a lower light source adjustment block (28), a lower lens fixing ring (29), and a microscope lens (30); The upper observation main module (1) is connected to the middle receiving module (2) by means of threads, and the lower observation main module (3) is connected to the middle receiving module (2) by means of threads, so as to support the upper observation main module (1) and the middle receiving module (2); The circuit control module (4) is fixed to the inner wall of the upper observation main module (1) by means of threads, and the circuit control module (4) controls the movement of the top automatic control module (8) to control the movement of the upper optical module (5) to achieve image acquisition; The upper Y-axis module (9) is fixed to the upper support plate (10) of the upper observation main module (1) by means of threads, and is used to drive the upper X-axis module (6), the top automatic control module (8) and the upper optical module (5) to move along the Y-axis direction, and collect images through the upper optical module (5) for observation; The lower X-axis module (16) is fixed to the bottom plate of the lower observation module (3) by means of threads, driving the lower Y-axis module (19) and the lower optical module (17) to move along the X direction to collect images for observation; the lower Y-axis module (19) is fixed to the flat plate by means of threads, and then fixed to the slider of the lower X-axis module (16) by means of threads, and moves along the Y-axis direction to collect images for observation through the lower optical module (17); The camera (27) is connected to the microscope lens (30) by means of external threads, the lower lens fixing ring (29) is fixed to the microscope lens (30) by means of top screws and threads, the lower light source fixing ring (25) is fixed to the lower light source adjustment block (28) by means of threads, the lower light source adjustment block (28) is connected to the lower lens fixing ring (29), and the screws on both sides of the lower light source adjustment block (28) are adjusted by looseness and tightness to adjust the angle between the light source and the lens to achieve the adjustment of the image clarity; the light source (26) is fixed to the lower light source fixing ring (25) by means of top screws and threads, the image is adjusted by adjusting the tightness of the top screws to adjust the upper and lower positions of the light source (26), and the observed image is adjusted by adjusting the tightness of the screws.

2. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The upper observation module (1) and the lower observation module (3) are symmetrically arranged.

3. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The device also includes a bottom Z-axis focusing module, which includes a bottom lifting block (21), a bottom lifting screw (22), a bottom optical system fixing block (23), and a lower Z-axis module (24); The bottom lifting screw (22) is connected to the bottom lifting block (21) and the lower Z-axis module (24) by means of threads, and the bottom optical system fixing block (23) is driven to move up and down by the rotation of the screw.

4. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The device also includes a top Z-axis focusing function module, which includes a top lifting block (31), a top lifting screw (32), a top optical system fixing block (33), and an upper Z-axis module (34); The upper Z-axis module (34) is fixed to the support frame by means of threads, the top lifting block (31) is fixed to the slider of the upper Z-axis module (34) by means of threads, the top lifting screw (32) is connected to the bearing seat and the synchronous pulley up and down, and is connected to the top lifting block (31) by means of threads, and the top lifting screw (32) is rotated by means of threads to drive the top optical system fixing block (33) to move up and down, that is, the upper optical module (5) moves up and down to adjust the focal length of the optical system to obtain a clear image.

5. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The device also includes 6 motors (20), which are all fixed on the motor support frames by means of threads.

6. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The lower support plate (14) in the intermediate receiving module (2) is the top plate of the lower observation module (3), and the support column (11) in the intermediate receiving module (2) is fixed on top of it by means of threads, and the support column (11) is fixed together with the upper support plate (10) of the upper observation module (1) by means of threads.

7. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: A groove is provided on the inner side of the butt joint surface between the support column (11) and the upper support plate (10), and the groove allows the upper sealing plate (13) to slide into the upper observation main module (1).

8. The fully automatic double reflection microscopic detection and observation device according to claim 1, characterized in that: The tray (12) is fixed to the lower support plate (14) by means of threads, and a groove is provided at the bottom of the tray (12).

9. The fully automatic double reflection microscopic detection and observation device according to claim 8, characterized in that: The light source (26) and the microscope lens (30) form an angle of any degree within the range of 10° to 45°.

10. A fully automatic double reflection microscopic detection observation method, characterized in that: The method is implemented based on the device according to claim 1, and the method includes: S1. Place the cell factory on the tray (12), select the fully automatic one-key operation in the main control center (7), and automatically scan the entire upper and lower planes, use the camera (27) to take fixed-point photos and save the pictures; S2. Place the cell factory on the tray (12), select the manual control operation in the main control center (7), select the autofocus function to find a clear image; observe the culture status through manual translation, select representative points and use the camera (27) to take pictures, S3, compare and analyze the pictures saved by the fixed-point photography in S1 with the pictures saved by the representative points selected in S2, and complete the fully automatic double reflection microscopic detection and observation.

Images