A sample high-throughput automatic detection device

Abstract

The utility model relates to biological detection technical field, concretely relates to a kind of sample high flux automatic detection equipment, including constant temperature storage bin, automatic stage, micro main body, multimode imaging device, sample transfer device and control system, micro main body is set on the upper side of automatic stage, multimode imaging device is set in the rear of micro main body, and with multimode imaging device integration in same imaging light path;Multimode imaging device includes hyperspectral imaging module and super high magnification imaging module, to realize the synchronous acquisition of the spectral information and cell internal structure high-definition morphological information of the same sample area;Control system controls sample transfer device to take out sample slide from constant temperature storage bin, and it is transported to automatic stage to carry out multimode imaging, and after imaging, the whole process of being sent back constant temperature storage bin.The utility model solves the technical problem that traditional single-function equipment needs multiple sample changes, and data is difficult to associate.

Description

Technical Field

[0001] This utility model relates to the field of biological detection technology, specifically to a high-throughput automatic sample detection device. Background Technology

[0002] In cell biology research and clinical pathology diagnosis, immunofluorescence staining technology is widely used for the specific labeling and visualization analysis of specific cellular structures or biomolecules. With the deepening of research in areas such as multi-target joint detection and tumor microenvironment analysis, the demand for simultaneously identifying multiple fluorescent markers is increasing. Traditional fluorescence microscopy relies on a filter wheel to switch between different wavelengths for multi-channel imaging, but its spectral resolution is limited, making it difficult to effectively distinguish fluorescent dyes with overlapping emission spectra, easily leading to signal crosstalk and affecting quantitative accuracy.

[0003] Hyperspectral imaging, as an advanced detection method integrating spatial imaging and continuous spectral analysis, can simultaneously acquire spatial image information of the observed target and provide a continuous spectral curve for each pixel in the image, achieving "image-spectrum integration" detection. This technology can solve the core pain points of fluorescence microscopy imaging. Through spectral unmixing algorithms, it can effectively separate multiple co-located fluorescence signals, significantly improving the specificity and information dimension of multi-label detection, thus showing great potential in fields such as cell biology and digital pathology.

[0004] Currently, in the fields of biomedical testing, pathological analysis, and scientific research, high-throughput, multimodal imaging analysis of samples (such as tissue sections, cell smears, and protein chips) has become commonplace. Traditional manual operation methods are no longer sufficient to meet the demands for efficient and standardized processing of large-scale samples. Therefore, high-throughput fully automated scanning systems have emerged and are widely used in fields such as digital pathology, biobank construction, and drug screening. For example, Chinese patent CN117554291A discloses a high-throughput fully automated focusing scanning analysis system for medical sample testing. This system uses a robotic arm and a material receiving device to automatically transfer samples, and combines a piezoelectric crystal to drive the stage for rapid Z-axis focusing. Focusing scanning is completed through automatic high-magnification digital zoom technology, achieving full automation from sample loading to image acquisition, significantly improving testing efficiency and reducing manual workload. However, current high-throughput scanning systems still suffer from limited functionality and imaging modes, making it difficult to perform multi-dimensional analysis of complex samples. This necessitates frequent sample transfers between different devices, which is not only cumbersome and inefficient but also prone to sample contamination or temporal and spatial inconsistencies in the data. Utility Model Content

[0005] This invention aims to solve at least one of the technical problems existing in the prior art. To this end, this invention proposes a high-throughput automatic sample detection device to solve the technical problems of traditional single-function devices requiring multiple sample changes and difficulty in data correlation.

[0006] This utility model provides a high-throughput automatic sample detection device, which adopts the following technical solution: A high-throughput automated sample detection device, comprising: A temperature-controlled storage chamber is used to store multiple sample slides in a controlled temperature environment; An automatic stage is used to carry the sample slide and move it in three dimensions to achieve automatic imaging and focusing; The microscope body is positioned above the automated stage and is used to collect optical signals from the sample slide (i.e., probe excitation signals from the sample slide). A multimodal imaging device, integrated with the microscope body in the same imaging optical path, is used to image samples. The multimodal imaging device includes a dual-port output module, a hyperspectral imaging module, and an ultra-high magnification imaging module. The dual-port output module is located behind the microscope body. The hyperspectral imaging module and the ultra-high magnification imaging module are respectively mounted on the two output ports of the dual-port output module. The dual-port output module is used to simultaneously guide light from the same sample area to the hyperspectral imaging module and the ultra-high magnification imaging module, so as to realize the synchronous acquisition of spectral information and high-definition morphological information of local cell internal structures of the same sample area. A sample transfer device is disposed between the constant temperature storage chamber and the automatic loading stage, for automatically transferring the sample slides between the two. The control system is communicatively connected to the constant temperature storage chamber, the automatic stage, the multimodal imaging device, and the sample transfer device, and controls a single sample slide to complete the entire process of being taken out of the constant temperature storage chamber, transferred to the automatic stage for multimodal imaging, and then sent back to the constant temperature storage chamber after imaging.

[0007] Sample slides are stored long-term in a temperature-controlled storage chamber and automatically transferred to an automated stage for detection using a sample transport device. After imaging, the slides are automatically returned to the temperature-controlled environment. The entire process requires no manual intervention, minimizing the time samples are exposed to room temperature or contaminated environments. This is particularly suitable for temperature-sensitive fluorescently labeled samples, live-cell imaging, or experiments requiring long-term dynamic monitoring, ensuring the biological authenticity and reproducibility of the test results.

[0008] The temperature-controlled storage chamber is not only for preserving samples, but also to ensure that the state of temperature-sensitive biochemical samples (such as live cells and specific proteins) remains consistent throughout the entire process from storage to simultaneous imaging. This results in higher spatiotemporal consistency and biological value of the synchronously acquired spectral and morphological data. This is something that cannot be achieved with distributed equipment or time-sharing detection.

[0009] It is precisely because of the implementation of "synchronous acquisition" that it becomes possible to acquire multidimensional data in a high-speed, high-throughput fully automated process. If time-sharing acquisition were used, it would severely slow down the throughput of the entire system, which contradicts the design goal of high-throughput automation.

[0010] As a preferred embodiment of this utility model, the hyperspectral imaging module and the ultra-high magnification imaging module are positioned side by side at intervals above the automatic stage in the horizontal direction; the hyperspectral imaging module includes a hyperspectral camera and a magnification conversion interface disposed between the hyperspectral camera and the dual-port output module to adapt to the imaging magnification.

[0011] The hyperspectral imaging module and the ultra-high magnification imaging module are arranged side by side in a horizontal direction, sharing the same microscope body and automatic stage, thus avoiding mechanical docking errors and optical path calibration problems between multiple devices. This integrated design not only reduces the system size and improves space utilization, but also enhances the overall rigidity and thermal stability of the imaging system, which is beneficial for imaging consistency under long-term continuous operation.

[0012] A magnification conversion interface is installed in front of the hyperspectral camera, allowing for flexible adjustment of the imaging magnification according to different sample types or detection requirements. This ensures that the hyperspectral imaging module achieves optimal spatial resolution and field-of-view matching under different objectives. This design enhances the system's versatility, making it compatible with various application scenarios ranging from low-magnification panoramic scanning to medium- and high-magnification fine analysis.

[0013] As a preferred embodiment of this utility model, the ultra-high magnification imaging module is arranged from top to bottom as follows: an area array camera, an adjustable focus lens mount, a lens barrel mount, a base plate, and an imaging focal length interface mount. An interface is provided on the base plate. The imaging focal length interface mount is fixed to the lower end of the interface. The lens barrel mount is fixed to the upper end of the interface. A zoom lens group is arranged inside the lens barrel mount. The adjustable focus lens mount is located between the camera and the lens barrel mount and is connected to a gear transmission mechanism. The adjustable focus lens mount is used to drive the lens of the zoom lens group to move to change the focal length.

[0014] As a preferred technical solution of this utility model, the multimodal imaging device further includes a strobe light source device, which is set below the automatic stage as a transmission illumination source for bright-field imaging of the sample; the emission timing of the strobe light source device is synchronized with the exposure timing of the area array camera, so that the strobe light source device is only turned on and off instantaneously during the uninterrupted bright-field continuous high-speed capture imaging process of the camera.

[0015] The strobe light source operates in a pulsed manner, with average power consumption far lower than that of continuous light sources. It is completely powered off during non-exposure periods, generating extremely low heat and avoiding the heat radiation produced by traditional halogen lamps or high-brightness LEDs during continuous operation. This not only reduces the equipment's heat dissipation requirements but also effectively prevents heat from the light source from being conducted to the sample area, causing localized temperature rises, cover glass fogging, or sample deformation, thus ensuring the stability of the constant-temperature storage environment and imaging consistency. By improving the illumination method, the inherent trade-off between high speed and high quality in the core optical imaging process of high-throughput scanning systems has been resolved.

[0016] As a preferred technical solution of this utility model, the multimodal imaging device further includes a piezoelectric focusing component based on the piezoelectric effect, which is used to carry the sample slide and perform micron-level focal length adjustment based on the piezoelectric effect.

[0017] As a preferred embodiment of this utility model, the piezoelectric focusing assembly includes a piezoelectric focusing controller and a piezoelectric crystal adjustment block. The piezoelectric focusing controller is disposed between the output end of the optical path of the microscope body and the input end of the optical path of the dual-port output module. The piezoelectric crystal adjustment block is disposed below the sample slide, and the piezoelectric focusing controller is electrically connected to the piezoelectric crystal adjustment block.

[0018] As a preferred embodiment of this utility model, the constant temperature storage chamber includes an insulated cavity, heating units, and a temperature sensor. Multiple heating units are disposed on multiple inner surfaces of the insulated cavity, and the temperature sensor is disposed within the insulated cavity. The heating units and the temperature sensor are electrically connected to the control system to achieve constant temperature control within the insulated cavity.

[0019] As a preferred technical solution of this utility model, the heat insulation cavity is provided with a multi-layer support structure for carrying the sample slide, and the support structure is provided with a guide buffer mechanism for guiding the insertion of the sample slide and providing buffer.

[0020] As a preferred embodiment of this utility model, the guide buffer mechanism includes a roller, a slider, and a fixed base. One end of the slider is connected to the roller via a pin, and the other end is connected to the fixed base via a spring. The fixed base is fixedly connected to the heat insulation cavity via fasteners.

[0021] When the sample slide is inserted, the roller contacts the edge of the slide and moves with it. The slider provides flexible support under the action of the spring, which can guide the slide to slide smoothly along the predetermined trajectory and absorb the impact energy during the insertion process. It can effectively prevent the slide from being scratched, warped or broken due to operation error or positioning deviation of the sample transport device. It is especially suitable for the automated operation of fragile samples such as glass slides.

[0022] As a preferred embodiment of this invention, the sample slide is provided with a groove that matches the roller to position the sample slide.

[0023] When the slide is inserted into position, the roller engages with the groove, creating a slight change in resistance. This mechanical feedback is used by the control system to determine the "insertion complete" status. Simultaneously, the groove structure restricts the slide's degrees of freedom in the X / Y directions, ensuring precise alignment in the storage location and facilitating accurate grasping by the subsequent sample transport device. This design achieves dual functions of physical positioning and status awareness, enhancing the reliability and fault tolerance of the automated system.

[0024] The beneficial effects are: 1. This invention integrates a dual-port output module at the rear end of the microscope substrate, simultaneously splitting light signals from the same sample area to both a hyperspectral imaging module and an ultra-high magnification imaging module. This achieves truly synchronous acquisition of spectral information and high-definition morphological information of local cell internal structures. Compared to traditional single-function devices that require time-sharing switching and multiple scans to acquire multimodal data, this invention fundamentally avoids spatial misalignment problems caused by sample drift, mechanical repetitive positioning errors, or environmental changes. It ensures complete registration of the two modal images at the pixel level, providing a high-fidelity data foundation for subsequent co-localization analysis, image fusion, and quantitative modeling.

[0025] 2. By setting up a constant-temperature storage chamber, the state of temperature-sensitive biochemical samples (such as live cells and specific proteins) remains consistent throughout the entire process from sample slide storage to simultaneous imaging. This results in higher spatiotemporal consistency and biological value of the synchronously acquired spectral and morphological data. This is something that cannot be achieved with distributed equipment or time-sharing detection. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the structure of a high-throughput automatic sample detection device according to the present invention; Figure 2 This is a schematic diagram of the structure of a constant temperature storage chamber; Figure 3 for Figure 2 A schematic diagram of the cross-sectional structure; Figure 4 for Figure 3 A magnified view of part A in the image; Figure 5 This is a schematic diagram of the structure of the automatic stage, the microscope body, the multimodal imaging device, and the second preview camera; Figure 6 This is a schematic diagram of the structure of an ultra-high magnification imaging module (without the outer casing); the outer casing opens downwards, and the base plate is located at the opening end of the outer casing, forming a sealed cavity with the outer casing; Figure 7 This is a schematic diagram of the structure of a stroboscopic flash source; Figure 8 for Figure 7 A schematic diagram of the cross-sectional structure; Figure 9 This is a schematic diagram of the structure after the sample carrier (back side) and the piezoelectric crystal adjustment block are assembled.

[0027] Explanation of reference numerals in the attached figures: 1. Constant temperature storage chamber; 11. Insulated cavity; 12. Support bar; 13. Guide buffer mechanism; 131. Roller; 132. Slider; 133. Fixing base; 14. Chamber door; 2. Sample transfer device; 3. First preview camera; 4. Automatic stage; 421. Piezoelectric crystal adjustment block; 422. Piezoelectric focusing controller; 43. Infrared detection device; 5. Multimodal imaging device; 51. Dual-port output module; 521. Hyperspectral camera; 522. Magnification conversion adapter 53. High-magnification imaging module; 531. Area array camera; 532. Adjustable focus lens mount; 533. Lens barrel mount; 534. Base plate; 535. Imaging focal length interface mount; 54. Explosion flash source device; 541. Heat sink; 542. Integrated LED light source; 543. Aspherical lens; 545. Multispectral chip combination; 546. Condenser lens; 61. Electric objective lens turntable; 621. Electric fluorescence switching mechanism; 622. Control box; 623. Fluorescence light source; 7. Control system; 8. Sample slide; 81. Groove; 9. Second preview camera. Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below in conjunction with specific embodiments and corresponding drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0029] In the description of this application, it should be noted that, unless otherwise stated, "multiple" means two or more; the terms "upper," "lower," "inner," "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and 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 above-mentioned orientation or positional relationship terms should not be understood or interpreted as a limitation of this application. The terms "first," "second," etc., used in the specification and claims of this application are used to distinguish similar objects and are not used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that embodiments of this application can be implemented in orders other than those illustrated or described herein, and the objects distinguished by "first," "second," etc., are generally of the same class and are not limited in number; for example, a first object can be one or more.

[0030] In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "installation," "setup," "equipped with," and "connection" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in this application depending on the specific circumstances.

[0031] Existing high-throughput scanning systems still have significant shortcomings in core imaging performance. In particular, while pursuing high-speed scanning, it is difficult to guarantee image clarity, resolution, and information richness. Specifically, this manifests in the following ways: Firstly, regarding rapid imaging: In pursuit of high-throughput scanning, shortening the exposure time of a single image has become crucial for improving overall speed. However, traditional continuous illumination sources require high light intensity to compensate for the signal-to-noise ratio under short exposures, which exacerbates photobleaching of fluorescent samples and easily intensifies minor vibrations of the mechanical platform, resulting in motion blur and severely affecting image sharpness and detail resolution. Although CN117554291A employs a piezoelectric crystal carrier for rapid focusing, the limitations of the illumination method remain a bottleneck in achieving high-speed, high-definition imaging.

[0032] Secondly, regarding imaging modalities: existing systems are limited in function, with most systems equipped with only a single camera, failing to simultaneously meet the diverse needs of rapid panoramic scanning and fine spectral analysis or ultra-high magnification detail observation. Switching between different imaging modes (such as bright field and fluorescence, low magnification and high magnification) requires physical switching of mechanical components (such as changing objectives and filter wheels), a process that is time-consuming, introduces positioning errors, and interrupts the continuity of scanning, making true "one-click" multimodal correlation analysis impossible.

[0033] In summary, current high-throughput detection systems still have significant shortcomings in terms of high speed, high definition, and multimodal collaborative imaging, making it difficult to meet the comprehensive demands of modern pathological diagnosis for high-throughput, high-fidelity, and full-information-dimensional detection. Therefore, a new type of integrated detection device is urgently needed to overcome these technical bottlenecks.

[0034] To address the aforementioned technical problems, this utility model provides a high-throughput automatic sample detection device.

[0035] like Figure 1-9 The high-throughput automated sample detection device shown includes a frame, and a temperature-controlled storage chamber 1, a sample transfer device 2, a first preview camera 3, an automatic stage 4, a microscope body, a multimodal imaging device 5, a second preview camera 9, and a control system 7, all mounted on the frame. The control system 7 is communicatively connected to the temperature-controlled storage chamber 1, the sample transfer device 2, the first preview camera 3, the automatic stage 4, the microscope body, the multimodal imaging device 5, and the second preview camera 9. The temperature-controlled storage chamber 1 is located at one end of the frame, the automatic stage 4 is located at the scanning station, and the microscope body is positioned above the automatic stage 4 to collect light signals from sample slides 8 at the scanning station. The multimodal imaging device 5 is positioned above the microscope body and is used for imaging based on the light signals collected by the microscope objectives. The sample transfer device 2 travels between the constant temperature storage chamber 1 and the automatic loading stage 4. The first preview camera 3 is located at the opening of the constant temperature storage chamber 1; the second preview camera 9 is located above the automatic loading stage 4; thus forming an automated system that integrates constant temperature storage, transfer, preview and multimodal imaging of samples.

[0036] like Figure 2-3 As shown, the constant temperature storage chamber 1 is used to store multiple sample slides 8 in a controlled temperature environment. The constant temperature storage chamber 1 includes a heat-insulating cavity 11, a heating unit, and a temperature sensor. The heating unit and the temperature sensor are used to maintain a constant temperature inside the chamber.

[0037] In this embodiment, the constant temperature storage chamber 1 is disposed above the belt drive mechanism and can rotate around the central axis. The constant temperature storage chamber 1 is fixed to the top of the central axis of the driven wheel and can rotate synchronously with the driven wheel around the central axis; and the constant temperature storage chamber 1 has a left-right symmetrical structure, with the components on its left and right sides (such as the internal sample storage space, heating unit and temperature sensor, etc.) symmetrically distributed about the central axis.

[0038] The heat-insulating cavity 11 has doors 14 on both sides, and these doors 14 can be opened and closed. The opening and closing of the doors 14 are linked to the storage and retrieval of the sample slides 8 to minimize heat exchange between the inside and outside of the cavity. Double linear guide rails are arranged along both sides of the doors 14, with guide rail sliders 132 fixed to the doors 14, providing high-precision vertical guidance for the doors 14. The doors 14 are driven to open and close by ball screws, which are electrically connected to the control system 7. In this embodiment, the combination of ball screws and linear guide rails achieves micron-level positioning accuracy for the opening and closing of the doors 14, and ensures smooth movement, preventing vibration from affecting the samples inside the cavity.

[0039] The interior of the heat-insulating cavity 11 is divided into multiple independent sample storage spaces by multiple horizontally arranged support strips 12, which are used to accommodate sample slides 8. Each sample storage space is provided with a guide buffer mechanism 13. Of course, in other embodiments, the support structure can also be protrusions. The protrusions are arranged in pairs along the horizontal direction on the inner walls of the left and right sides of the heat-insulating cavity 11 (one or more protrusions at corresponding positions on each side of the compartment plate, forming a layer of support surface to replace the support strips 12 and achieve layered support. Of course, the support structure can also be an adjustable support pin, etc.

[0040] like Figure 4 As shown, the guide buffer mechanism 13 includes a roller 131, a slider 132, and a fixed base 133. One end of the slider 132 is connected to the roller 131 via a pin, and the other end is connected to the fixed base via a spring. The fixed base 133 is securely connected to the heat insulation cavity 11 via fasteners.

[0041] Roller 131 is made of wear-resistant and low-friction materials (such as nylon, polyurethane, etc.). Roller 131 can roll around the pivot pin and contacts the side of the inserted sample tray 8, providing smooth guidance for the sample tray 8 and significantly reducing insertion resistance. The sample tray 8 is provided with a groove 81 that matches roller 131, which ensures accurate insertion of the sample tray 8. During the insertion or removal of the sample tray 8 from the storage space, roller 131 is squeezed by the sample tray 8, which pushes slider 132 backward to compress the spring. With the help of the spring's rebound force, roller 131 can form a continuous and gentle clamping force on the sample tray 8, which not only ensures that the sample holder does not shift due to vibration during equipment operation, but also avoids damage to the sample tray 8 that may be caused by rigid collisions, achieving the dual effect of "elastic fastening" and buffering. Fixed seat 133 provides support for the entire guiding and buffering mechanism 13, ensuring that its position remains stable under the repeated insertion or removal of sample tray 8, achieving the function of "guiding + elastic clamping".

[0042] Multiple heating units are disposed on multiple inner surfaces of the heat insulation cavity 11, and temperature sensors are disposed inside the heat insulation cavity 11. The heating units and temperature sensors are electrically connected to the control system 7 to achieve constant temperature control inside the heat insulation cavity 11.

[0043] like Figure 1 As shown, the sample transfer device 2 is located between the constant temperature storage chamber 1 and the automatic stage 4, used to automatically transfer samples between the storage position and the scanning position. The sample transfer device 2 includes an XY horizontal displacement module, a Z-axis vertical lifting module, and a clamping mechanism. The clamping mechanism is installed at the end of the Z-axis and is used to grip and place the sample slide 8. The Z-axis lifting module uses a precision ball screw drive with a self-locking function to prevent the sample slide 8 from falling in the event of a power failure. The clamping surface of the clamping mechanism is covered with an elastic anti-slip material (such as rubber or silicone), and its clamping force is precisely controlled by the control system 7. The clamping force is adjustable, sufficient to firmly grip the slide without causing it to break due to excessive clamping force.

[0044] The first preview camera 3 is located on the opening side of the constant temperature storage chamber 1, and is used to continuously and preferentially collect information from multiple sample slides 8 within the constant temperature storage chamber 1 to accelerate the initial processing of sample slide 8 information, directly corresponding to the sample slide 8 information scanned by the automatic stage 4. In some other optional embodiments, the first preview camera 3 may be omitted.

[0045] The automatic stage 4 includes a worktable and a three-dimensional motion device; the three-dimensional motion device is connected to the worktable and is used to drive it to perform macroscopic movements along the X, Y, and Z axes. An infrared detection device 43 is installed above the three-dimensional motion device for precise positioning of the sample and setting of the scanning boundary.

[0046] like Figure 5 As shown, the microscope body is positioned above the automatic stage 4. The microscope body includes an electro-acoustic microscope turret 61, an objective lens switching drive mechanism, and a multi-channel fluorescence light source switching device. Multiple microscope objectives of different magnifications are mounted on the electro-acoustic microscope turret 61, which are used to collect light signals from the sample slide 8. The objective lens switching drive mechanism (such as a servo motor and gear set) drives the electro-acoustic microscope turret 61 to rotate, thereby inserting the selected magnification microscope objective into the imaging optical path. The multi-channel fluorescence light source switching device is used to select different fluorescence excitation bands, and thus select different imaging modes. The multi-channel fluorescence light source switching device includes an electric fluorescence switching mechanism 621, a control box 622, and a fluorescence light source 623. The control box 622 is electrically connected to the electric fluorescence switching mechanism 621, the fluorescence light source 623, and the control system 7. The control box 622 is the control center of the device, used to receive commands from the control system 7 and coordinate the actions of each component.

[0047] The electric fluorescence switching mechanism 621 includes a filter assembly unit and a precision transmission unit, the precision transmission unit being used to drive the filter assembly unit to rotate.

[0048] The filter unit consists of a rotating wheel and multiple individual lens groups mounted on it.

[0049] Lens sets include at least two types: Bright field lens group without filtering function: used for bright field imaging, can be a light-transmitting lens or a blank aperture.

[0050] Fluorescent lens assemblies with filtering functions: used for fluorescence imaging, each assembly contains at least one dichroic mirror, one excitation filter, and one emission filter to meet the excitation and emission spectrum requirements of specific fluorescent dyes. Different fluorescent lens assemblies have different filter parameters to accommodate fluorescent probes of different wavelengths.

[0051] The precision transmission unit includes a motor and a synchronous belt. The motor is either a stepper motor or a servo motor and is connected to the control box 622. The synchronous belt is fitted between the motor output shaft and the pulley to accurately transmit the rotational motion of the motor to the pulley.

[0052] When the device is in operation, the control system 7 issues commands according to imaging requirements; the control box 622 drives the motor to rotate the rotating wheel via a synchronous belt; the rotating wheel drives the lens group to rotate and stop at the working position of the target lens group, thereby cutting the required filter combination (i.e., lens group) into the microscopic optical path to achieve automatic switching between multi-band fluorescence or bright field imaging modes. This device solves the problems of low efficiency, poor positioning accuracy, and susceptibility to human error in traditional manual switching.

[0053] The multimodal imaging device 5 is integrated with the microscope body in the same imaging optical path for imaging the sample. The multimodal imaging device 5 includes a piezoelectric focusing component, a dual-port output module 51, a hyperspectral imaging module, an ultra-high magnification imaging module 53, and a strobe source device 54. The dual-port output module 51 is located behind the microscope objective; in this embodiment, it is located at the output port of the piezoelectric focusing controller 422. The hyperspectral imaging module and the ultra-high magnification imaging module 53 are respectively mounted on the two output ports of the dual-port output module 51. The dual-port output module 51 is used to simultaneously guide light from the same sample area to both the hyperspectral imaging module and the ultra-high magnification imaging module 53, thereby achieving synchronous acquisition of spectral and spatial morphological information of the same sample area.

[0054] The piezoelectric focusing assembly includes a piezoelectric crystal adjustment block 421 and a piezoelectric focusing controller 422. The piezoelectric crystal adjustment block 421 is disposed on the bearing surface of the stage and is used to directly support the sample slide 8 and perform micron-level precision displacement along the Z-axis. Figure 9As shown, the piezoelectric crystal adjustment block 421 is positioned below the sample slide 8, and the piezoelectric focusing controller 422 is located between the imaging optical path of the microscope body (i.e., the multi-channel fluorescence light source switching device) and the optical path input of the dual-port output module 51. The control system 7, based on the feedback signal from the piezoelectric focusing controller 422, controls the piezoelectric crystal adjustment block 421 to drive the stage to perform precise Z-axis displacement to achieve focusing. The piezoelectric focusing controller 422 and the piezoelectric crystal adjustment block 421 constitute a piezoelectric focusing assembly to achieve precise Z-axis displacement.

[0055] The optical input of the dual-port output module 51 is aligned with the output of the piezoelectric focusing controller 422, and can distribute light to the first and second imaging optical outputs in a time-division or simultaneously manner. A hyperspectral imaging device is installed at the first imaging optical output to acquire spatial images and continuous spectral information of the sample, achieving integrated image and spectrum data acquisition. An ultra-high magnification imaging device is installed at the second imaging optical output to acquire high-resolution images of the local cellular morphology and structure of the sample. The dual-port output module 51 integrates an optical beam splitter, whose optical input is connected to the imaging optical output of the microscope body, guiding light simultaneously to both output ports. The optical beam splitter is a beam-splitting prism or a dichroic mirror.

[0056] The hyperspectral imaging module includes a hyperspectral camera 521 and an optical interface, namely a magnification conversion interface 522, disposed between the hyperspectral camera 521 and the dual-port output module 51 to adapt to the imaging magnification. In this embodiment, the hyperspectral imaging device uses a linear CCD sensor and operates in a pushbroom scanning mode to generate a continuous spectral curve for each pixel in the image.

[0057] like Figure 6 As shown, the ultra-high magnification imaging module 53 is arranged from top to bottom as follows: area array camera 531, adjustable lens mount 532, lens barrel mount 533, base plate 534, and imaging focal length interface mount 535. The base plate 534 has an interface. The imaging focal length interface mount 535 is fixed to the lower end of the interface. The lens barrel mount 533 is fixed to the upper end of the interface. The lens barrel mount 533 contains a zoom lens group, which includes a front lens group, a middle coaxial lens group, and a rear lens group. The adjustable lens mount 532 is located between the camera and the lens barrel mount 533 and is connected to a gear transmission mechanism. The adjustable lens mount 532 is used to drive the lens of the zoom lens group to move to change the focal length.

[0058] like Figure 7 and 8As shown, the strobe light source device 54 is positioned below the automatic stage 4 as a transmitted illumination source for bright-field imaging of the sample. The strobe light source device 54 is communicatively connected to the control system 7. The strobe light source device 54 provides high-intensity pulse illumination at the millisecond or microsecond level during exposure by the area array camera 531. This strobe light source device 54 is a high-power strobe light source device, a type of instantaneous pulse illumination source employing a coaxial stacked sectional structure. The device, from top to bottom along the optical axis, includes a focusing output module, an optical control module, a light source emission module, and a base support and thermal management module. These modules are coaxially connected via precise mechanical interfaces, forming a compact, optically precise integrated device. Its core function is to provide high-brightness, multispectral, and thermally stable instantaneous pulse illumination for high-throughput imaging systems.

[0059] The basic support and thermal management module is located at the bottom of the device and serves as the mechanical foundation and core of the entire system's thermal management. This module includes a heat sink 541 and a wiring mounting bracket 133. The heat sink 541, as the core load-bearing and heat-conducting component, is made of a metal material with high thermal conductivity (such as aluminum alloy or copper). Its function is to quickly absorb and dissipate the heat generated by the upper light source, ensuring the thermal reliability of the device under repeated high-power "strobe" operation. The wiring mounting bracket 133 is fixedly connected to the heat sink 541. This component integrates the wiring and interface of the LED driver circuit, providing power and signal transmission channels for the upper light source and also serving as a structural connector between the upper and lower components.

[0060] The light source emitting module directly supports and drives the light-emitting unit, serving as the light source origin layer. The light source emitting module includes an LED light source mounting bracket and an integrated LED light source 542. The LED light source mounting bracket is installed above the wiring bracket 133, ensuring insulation and structural rigidity. The integrated LED light source 542 consists of multiple high-power LED chips, precisely fixed in an array on the LED light source mounting bracket. In this example, the integrated LED light source 542 comprises four 10W LED chips, precisely fixed in an array on the LED light source mounting bracket, which work together to instantly generate the high-intensity luminous flux required for imaging.

[0061] Of course, in some other alternative embodiments, the LED chips of the LED integrated light source 542 can also be set to three, five, six or more groups, and the power of the LED chips can be 15W, 20W, 30W, 40W or even higher.

[0062] The optical control module is responsible for "processing" and "modulating" the raw light, which is crucial for improving lighting quality. The optical control module includes an aspherical lens 543, a lens mount 133, and a multispectral chip assembly 545. The aspherical lens 543 is mounted in the light-emitting direction of the LED integrated light source 542 via the lens mount 133. Its function is to collimate the Lambertian divergent light emitted by the LED, effectively correct spherical aberration, and form an initial beam with excellent parallelism. The lens mount 133 is a key optical connection structure; its lower part fixes the aspherical lens 543, while its upper part is used to mount the multispectral chip assembly 545. Precision slots or threads ensure the coaxiality of the upper and lower optical components. The multispectral chip assembly 545 can be a filter, beam splitter, or other spectral modulation element used to select or synthesize specific excitation light bands to meet the needs of multi-channel fluorescence imaging.

[0063] The focusing output module, located at the top of the device, is responsible for the final output of the light. The focusing output module includes a focusing lens mount and a focusing lens 546. The focusing lens mount is connected to the top of the optical control module.

[0064] The condenser lens 546 is integrated inside the condenser lens mount and is a set of lenses. Its function is to finally converge and shape the modulated light beam, so that the light energy is projected onto the sample plane with high density and high uniformity.

[0065] In summary, the working process of the high-power strobe light source device 54 described in this embodiment is as follows: When the system triggers an imaging command, the LED integrated light source 542 is instantly illuminated under the control of the driving circuit. The emitted light is collimated sequentially by the aspherical lens 543, then spectrally selected by the multispectral chip combination 545, and finally focused into a high-quality light spot by the condenser lens 546 to illuminate the sample. During this process, the heat sink 541 continuously and efficiently dissipates the generated heat.

[0066] When the camera acquires each frame of image, it outputs an exposure pulse. The start and end times and width of the exposure pulse are synchronized with the start and end times and width of the frame image exposure. The LED integrated light source 542 turns on when it receives the rising edge of the exposure pulse and turns off on the falling edge, maintaining synchronization with the frame image exposure. This can significantly shorten the lighting time of the LED integrated light source 542, reduce energy consumption, and reduce the heat dissipation requirements of the LED integrated light source 542, thereby simplifying the design of the strobe light source device 54 and reducing the size of the device.

[0067] This device achieves high integration and precise control of the optical path through its coaxial stacked structure. Its beneficial effects are as follows: First, the modular design ensures the coaxiality and stability of each functional component, providing a high-quality illumination field for imaging; second, the powerful thermal management capability ensures the lifespan and stability of the light source in high-power strobe mode; finally, the integration of spectral modulation function allows a single light source to meet the needs of multiple imaging modes, greatly improving the efficiency and reliability of high-throughput automated imaging systems.

[0068] In some other alternative embodiments, the control system 7 controls the strobe light source device 54 to be triggered synchronously with the rapid focusing action of the piezoelectric focusing component on the automatic stage 4, so that the strobe light source device 54 is turned on only for a very short time after the platform stabilizes, thereby eliminating motion blur and significantly reducing photobleaching of the fluorescent sample.

[0069] The control system 7 controls a single sample slide 8 to complete the entire process of being taken out of the constant temperature storage chamber 1, transferred to the multimodal imaging device 5 for multimodal imaging, and then sent back to the constant temperature storage chamber 1 after imaging.

[0070] The control system 7 synchronously controls the automatic stage 4, the microscope body, the piezoelectric focusing assembly, and the multimodal imaging device 5 to execute a preset multimodal scanning process.

[0071] The control system 7 performs AI algorithm recognition, multi-layer image fusion, and full-image stitching processing on the images and spectral data acquired by the multimodal imaging device 5. Specifically, the control system 7 performs depth-of-field fusion processing on the acquired multiple or multi-layer focal plane images and seamlessly stitches multiple images of a large scanning area to generate a high-definition panoramic browsing image.

[0072] The control system 7 prioritizes controlling the hyperspectral imaging device to perform rapid panoramic scanning at a lower magnification, and automatically identifies suspicious areas and their coordinates in the sample based on the acquired spectral data; subsequently, it controls the automatic stage 4 to automatically move to the target coordinate point, and the ultra-high magnification imaging device performs high-resolution imaging of the suspicious areas at a higher magnification, realizing automated correlation analysis from spectral screening to morphological confirmation.

[0073] The specific workflow is as follows: Sample information pre-acquisition and isothermal storage: After the equipment is started, the isothermal storage chamber 1 maintains a constant temperature inside the chamber under the closed-loop control of the heating unit and temperature sensor. The first preview camera 3 located at the chamber opening prioritizes rapid imaging of multiple sample slides 8 stored inside the chamber to obtain their identification information (such as barcodes or QR codes) in advance, providing data support for intelligent scheduling of subsequent processes.

[0074] Automated sample transfer and precise positioning: The control system 7, based on the detection command, directs the sample transfer device 2 to move to the designated position in the constant-temperature storage chamber 1. The chamber door 14 opens precisely under the drive of the ball screw and linear guide rail. The clamping mechanism of the transfer device removes the target sample slide 8 with a controllable clamping force and transfers it to the automated stage 4 at the scanning station via XYZ three-axis motion. The second preview camera 9, located above the stage, images the sample again, correlates the data with that of the first preview camera 3, and assists in achieving the final precise positioning of the sample at the scanning position.

[0075] Multimodal Imaging and Intelligent Focusing: Imaging preparation: The three-dimensional motion device of the automatic stage 4 drives the sample for macroscopic positioning, while the infrared detection device 43 on it assists in rapid positioning. The objective lens switching drive mechanism of the microscope body drives the electro-optical objective lens turntable 61 to cut the microscope objective lens of the required magnification into the optical path according to the preset scanning process.

[0076] Rapid focusing: When the piezoelectric focusing component is activated, its piezoelectric focusing controller 422 detects the defocus amount in real time and feeds it back to the control system 7. The control system 7 then instructs the piezoelectric crystal adjustment block 421 to perform micron-level precision displacement along the Z-axis, thereby achieving rapid automatic focusing of the sample.

[0077] Synchronous data acquisition: After focusing is complete, the multimodal imaging device 5 is activated. The dual-port output module 51 simultaneously guides light from the same sample area to the hyperspectral imaging module and the ultra-high magnification imaging module 53, achieving synchronous acquisition of high-resolution images of the sample's spectral information and internal morphological structure. When the sample is subjected to bright-field imaging, the strobe light source device 54 is strictly synchronized with the camera's exposure signal, providing instantaneous illumination to ensure image clarity and reduce light damage.

[0078] Intelligent data analysis and decision guidance: The control system 7 processes the collected multidimensional data in real time. First, using the spectral data obtained by the hyperspectral imaging module, the system quickly screens and locates "suspicious areas" in the sample through AI algorithms. Then, the system automatically guides the automatic stage 4 to move the area to the field of view of the ultra-high magnification imaging module 53 for higher-magnification morphological observation and imaging, realizing automated and correlated analysis from "chemical composition screening" to "microstructure confirmation".

[0079] Sample return and closed-loop process: After scanning and analysis, the sample transport device 2 operates again, removing the tested sample slide 8 from the automated stage 4 and returning it to its original position in the constant-temperature storage chamber 1, at which point the chamber door 14 closes. At this point, the fully automated process of "storage-retrieval-imaging-analysis-return" for a single sample is completed in a closed loop. The system then prepares to execute the next sample testing task.

Claims

1. A high-throughput automatic sample detection device, characterized in that, include: A temperature-controlled storage chamber is used to store multiple sample slides in a controlled temperature environment; An automatic stage is used to carry the sample slide and move it in three dimensions to achieve automatic imaging and focusing; The microscope body is positioned above the automated stage and is used to collect light signals from the sample slides; A multimodal imaging device, integrated with the microscope body in the same imaging optical path, is used to image samples. The multimodal imaging device includes a dual-port output module, a hyperspectral imaging module, and an ultra-high magnification imaging module. The dual-port output module is located behind the microscope body. The hyperspectral imaging module and the ultra-high magnification imaging module are respectively mounted on two output ports of the dual-port output module. The dual-port output module is used to simultaneously guide light from the same sample area to the hyperspectral imaging module and the ultra-high magnification imaging module, so as to realize the synchronous acquisition of spectral information and high-definition morphological information of the internal structure of cells in the same sample area. A sample transfer device is disposed between the constant temperature storage chamber and the automatic loading stage, for automatically transferring the sample slides between the two. The control system is communicatively connected to the constant temperature storage chamber, the automatic stage, the multimodal imaging device, and the sample transfer device, and controls a single sample slide to complete the entire process of being taken out of the constant temperature storage chamber, transferred to the automatic stage for multimodal imaging, and then sent back to the constant temperature storage chamber after imaging.

2. The high-throughput automatic sample detection device as described in claim 1, characterized in that, The hyperspectral imaging module and the ultra-high magnification imaging module are positioned side-by-side at intervals above the automatic stage in a horizontal direction; the hyperspectral imaging module includes a hyperspectral camera and a magnification conversion interface disposed between the hyperspectral camera and the dual-port output module to adapt to the imaging magnification.

3. The high-throughput automatic sample detection device as described in claim 2, characterized in that, The ultra-high magnification imaging module is arranged from top to bottom as follows: an area array camera, a focusable lens mount, a lens barrel mount, a base plate, and an imaging focal length interface mount. An interface is provided on the base plate. The imaging focal length interface mount is fixed to the lower end of the interface. The lens barrel mount is fixed to the upper end of the interface. A zoom lens group is arranged inside the lens barrel mount. The focusable lens mount is located between the camera and the lens barrel mount and is connected to a gear transmission mechanism. The focusable lens mount is used to drive the lens of the zoom lens group to move to change the focal length.

4. The high-throughput automatic sample detection device as described in claim 3, characterized in that, The multimodal imaging device also includes a strobe light source device, which is set below the automatic stage as a transmitted illumination source for bright-field imaging of the sample; the emission timing of the strobe light source device is synchronized with the exposure timing of the area array camera.

5. The high-throughput automatic sample detection device as described in claim 4, characterized in that, The multimodal imaging device also includes a piezoelectric focusing component based on the piezoelectric effect, used to carry sample slides and perform micrometer-level focal length adjustment based on the piezoelectric effect.

6. The high-throughput automatic sample detection device as described in claim 1, characterized in that, The constant temperature storage chamber includes an insulated cavity, heating units, and temperature sensors. Multiple heating units are disposed on multiple inner surfaces of the insulated cavity, and the temperature sensors are disposed within the insulated cavity. The heating units and temperature sensors are electrically connected to the control system.

7. The high-throughput automatic sample detection device as described in claim 6, characterized in that, The heat-insulating cavity is provided with a multi-layer support structure for carrying the sample slide. The multi-layer support structure is provided with a guide and buffer mechanism to guide the insertion of the sample slide and provide buffering.

8. The high-throughput automatic sample detection device as described in claim 7, characterized in that, The guide buffer mechanism includes a roller, a slider, and a fixed base. One end of the slider is connected to the roller via a pin, and the other end is connected to the fixed base via a spring. The fixed base is fixedly connected to the heat insulation cavity via fasteners.

9. The high-throughput automatic sample detection device as described in claim 8, characterized in that, The sample slide has a groove adapted to the roller to position the sample slide.

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