CN115529410A - Cell image capturing system and cell image capturing method - Google Patents

Cell image capturing system and cell image capturing method Download PDF

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Publication number
CN115529410A
CN115529410A CN202110712338.XA CN202110712338A CN115529410A CN 115529410 A CN115529410 A CN 115529410A CN 202110712338 A CN202110712338 A CN 202110712338A CN 115529410 A CN115529410 A CN 115529410A
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China
Prior art keywords
cell
imaging device
cell image
shooting
mode
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CN202110712338.XA
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Chinese (zh)
Inventor
邢圆
罗玮
王齐耀
余珊
祁欢
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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Priority to CN202110712338.XA priority Critical patent/CN115529410A/en
Publication of CN115529410A publication Critical patent/CN115529410A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84Systems specially adapted for particular applications

Abstract

The embodiment of the invention relates to a cell image shooting system and a cell image shooting method. The cell image photographing system includes a supporting device and an imaging device. The supporting device receives a current biological sample to be tested; the imaging device shoots a working area of a current biological sample to be detected in a first shooting mode to obtain a first cell image containing target cells; when a target cell meeting a preset condition exists in the first cell image, shooting the specified cell in a second shooting mode different from the first shooting mode by the imaging device to acquire a second cell image containing the specified cell; and unloading the current biological sample to be tested from the supporting device. According to the embodiment of the invention, the image shooting efficiency can be improved, and the image shooting quality of the cells related to the abnormality can be considered.

Description

Cell image capturing system and cell image capturing method
Technical Field
The invention relates to the field of cell image analysis, in particular to a cell image shooting system and a cell image shooting method.
Background
A sample image analyzer is an apparatus for analyzing cells, formed components, or the like in a sample such as blood, body fluid, bone marrow, urine, tissue, or the like, and is, for example, a cell morphology analyzer or a urine analyzer. The cytomorphological analyzer, which may also be referred to as a blood cell digital image analyzer or a digital microscope, is used to analyze cells in a sample of blood (e.g., peripheral blood), body fluid, bone marrow, etc. smeared on a slide.
The blood cell digital image analyzer can automatically assemble and disassemble blood smears, complete cell positioning and shooting, cell identification and pre-classification and show shot blood cell images to users, and can replace the manual microscopic examination work to a certain extent. Compared with manual microscopic examination, the detection speed of the blood cell digital image analyzer is greatly improved.
The current method for capturing blood cell digital image analyzer is as follows: the motor drives the blood smear and the imaging device to move relatively so that a first target position on the blood smear is under the visual field of the imaging device, then the motor stops, the imaging device focuses and shoots a sample at the first target position, and a clear image of the first target position is obtained; then the motor drives the blood smear and the imaging device to move relatively, so that the next target position on the blood smear is under the visual field of the imaging device, then the motor stops again and the imaging device focuses and shoots the sample at the next target position, and a clear image of the next target position is obtained, and the steps are repeated. In this manner, the motor is continuously and repeatedly started and stopped, and the imaging apparatus needs to perform focus shooting for each field of view, which is slow. If the area that needs to shoot is great or the field of vision that needs to shoot is when great, the shooting time will prolong greatly, has greatly influenced cell morphology analyzer's whole detection efficiency.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a cell image capturing system and a cell image capturing method, which can improve the capturing speed and simultaneously achieve the image capturing quality of abnormal cells.
To solve the task of the present invention, a first aspect of the present invention provides a cell image capturing system comprising:
the supporting device is used for bearing a biological sample to be tested;
the imaging device is used for shooting the biological sample to be tested on the supporting device;
horizontal driving means for driving the supporting means and the image forming means to move relatively in a horizontal direction; and
a controller communicatively coupled with the imaging device and configured to:
enabling the imaging device to shoot a working area of a biological sample to be detected in a first shooting mode so as to obtain at least one first cell image containing target cells, and enabling the horizontal driving device to drive the supporting device to horizontally move relative to the imaging device when the imaging device shoots the image in the first shooting mode;
when a target cell satisfying a preset condition is present in the first cell image, causing the imaging device to capture a specified cell in a second capture mode in which the imaging device and the support device are relatively stationary in a horizontal direction while the imaging device captures the specified cell to acquire a second cell image containing the specified cell.
A second aspect of the present invention provides a cell image capturing system comprising:
the supporting device is used for bearing a biological sample to be tested;
the imaging device is arranged in a relative motion way with the supporting device and is used for shooting the biological sample to be detected on the supporting device;
a controller communicatively coupled with the imaging device and configured to:
enabling an imaging device to shoot a working area of a biological sample to be detected in a first shooting mode to obtain a first cell image containing target cells, and in the first shooting mode, carrying out prediction focusing and shooting on the working area in the visual field range of the imaging device;
when target cells meeting preset conditions exist in the first cell image, the imaging device is made to shoot the specified cells in a second shooting mode to obtain a second cell image containing the specified cells, and in the second shooting mode, the imaging device carries out accurate focusing and shooting on the specified cells in the visual field range of the imaging device.
A third aspect of the present invention provides a cell image capturing method including:
the supporting device receives a current biological sample to be tested;
the imaging device shoots a working area of a current biological sample to be detected in a first shooting mode to obtain a first cell image containing target cells;
when a target cell meeting a preset condition exists in the first cell image, shooting the specified cell in a second shooting mode different from the first shooting mode by the imaging device to acquire a second cell image containing the specified cell;
and unloading the current biological sample to be tested from the supporting device.
Based on the aspects of the present invention, when the imaging device scans and photographs the working area of the biological sample to be measured in the first photographing mode, the photographed first image is analyzed to determine whether there is a possible abnormality, such as a possible abnormal cell, in the biological sample to be measured, and when there is a possible abnormality, the imaging device is switched to the second photographing mode, and in the second photographing mode, the imaging device precisely focuses and photographs the specified cell related to the abnormality, such as an abnormal cell, so that the photographing efficiency is improved while the image photographing quality of the cell related to the abnormality is taken into consideration.
Further features and advantages of various aspects of the present invention may be had with reference to the following description of embodiments of the invention, taken in conjunction with the accompanying drawings.
Drawings
FIG. 1 is a schematic flow chart of a focusing photographing mode of a conventional cell image analyzer;
FIG. 2 is a schematic block diagram of a cell image capture system according to an embodiment of the present invention;
FIG. 3 is a schematic diagram of a cell image capturing system according to an embodiment of the present invention;
FIG. 4 is a schematic flow chart of a cell image capturing method according to an embodiment of the present invention;
FIG. 5 is a schematic diagram of obtaining a reference point according to an embodiment of the invention;
FIG. 6 is a schematic view of a focusing surface according to an embodiment of the present invention;
fig. 7 and 8 are schematic views of scanning a work area according to an embodiment of the present invention.
Detailed Description
The embodiments of the invention will be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the invention are shown. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the terms "first \ second \ third" related to the embodiments of the present invention only distinguish similar objects, and do not represent a specific ordering for the objects, and it should be understood that "first \ second \ third" may exchange a specific order or sequence when allowed.
As already mentioned at the outset, the sample image analyzer is used for analyzing cells, formed components, etc. in samples of blood, body fluids, bone marrow, urine, tissue, etc.
In some embodiments, a specimen image analyzer is used to capture a biological specimen applied to a slide. Here, the biological sample may be, for example, peripheral blood, which forms a blood film on a slide glass, and red blood cells, white blood cells, platelets, and the like in the peripheral blood are taken as an imaging target. The biological sample may be, for example, bone marrow, which forms a bone marrow smear on a slide, and the bone marrow examination generally includes various cells of different maturation stages, such as erythroid cell lines, granulocyte lines, lymphocyte lines, monocyte lines, and plasma cell lines, and also includes megakaryocytes, reticulocytes, phagocytes, endothelial cells, and adipocytes. For another example, the biological sample may be other excreta and secretions, which are formed into a sample smear on a slide glass, and the object to be imaged is, for example, cellular components in a sample such as feces, vaginal secretions, semen, prostatic fluid, sputum, and the like, and is usually red blood cells, white blood cells, crystals, pathogenic microorganisms, epithelial cells, parasites, sperm, trichomonas, prostacholine corpuscles, prostatic granular cells, alveolar macrophages, tumor cells, and the like. Or the biological sample can be body cavity liquid, a body cavity liquid smear is formed on the slide, and the shooting object is cerebrospinal fluid, serosal cavity effusion, joint cavity effusion and cell components in amniotic fluid, which are commonly red blood cells, white blood cell clusters, bacteria, yeast-like bacteria, epithelial cells, parasites and the like. Alternatively, the biological sample may be exfoliated cells, which form a sample smear on a slide, and the subject to be imaged may be epithelial cells, mesothelial cells, cancer cells, red blood cells, white blood cells, macrophages or tissue cells, necrotic material, parasites, or the like.
In other embodiments, the sample image analyzer is used for capturing urine in the counting chamber, the urine forms a urine sediment in the counting chamber, and the captured object is a visible component of the urine, mainly including red blood cells, white blood cell clusters, bacteria, yeast-like bacteria, epithelial cells, small round epithelial cells, crystals, hyaline casts, non-hyaline casts, mucus filaments, and the like, which are common in urine.
Currently, the image of a cell image analyzer is usually captured as shown in fig. 1. The horizontal driving device drives the blood smear 10 and the imaging device to move horizontally relative to each other, namely to move along the X and/or Y directions, so that the first target position S1 on the blood smear 10 is under the shooting visual field of the imaging device, then the horizontal driving device stops driving, and the vertical driving device drives the blood smear to move vertically relative to the imaging device, so as to focus and shoot a sample at the first target position S1, and obtain a clear image of the first target position S1; then the vertical driving device stops moving, the horizontal driving device drives the blood smear and the imaging device to move horizontally relatively, so that the next target position S2 on the blood smear 10 is under the shooting visual field of the imaging device, then the horizontal driving device stops again, the vertical driving device drives the blood smear to move vertically relative to the imaging device, so that the imaging device can focus and shoot a sample at the next target position S2, and a clear image of the next target position S2 is obtained; and then repeating the steps, shooting a clear image of the next target position S3, and repeating the steps until all images of the preset target positions are shot. In this case, the horizontal driving device and the vertical driving device are repeatedly started and stopped continuously, and the imaging device needs to perform focus shooting for each shooting field, resulting in a slow shooting speed while also adversely affecting the life of the driving device. Once the shooting area is large and the visual field needing to be shot is large, the shooting time is greatly prolonged. The capture mode shown in fig. 1 may be referred to as a fine focus capture mode in embodiments of the present invention, in which the imaging device is in fine focus for a sample region within its capture field of view.
In view of the above problems, embodiments of the present invention provide a cell image capturing system, which analyzes a captured image during flying scan capturing to identify an abnormality in a sample, and switches to a precise focus capturing mode when there is an abnormality to capture a cell related to the abnormality, so as to improve the capturing efficiency and improve the image capturing quality of the cell related to the abnormality.
As shown in fig. 2 and 3, in some embodiments, the cell image photographing system 100 includes a support device 110, an imaging device 120, a horizontal driving device 130, a vertical driving device 140, and a controller 150.
The support device 110 is used for carrying a biological sample to be tested. In some embodiments, the support device 110 is used to carry a slide to be tested, which is coated with a biological sample to be tested, such as a blood sample to be tested. In other embodiments, the support device 110 is used to carry a counting chamber that is filled with a biological sample to be tested, such as urine. The support device 110 is configured, for example, as a detection stage capable of horizontally supporting a slide to be tested, and the detection stage may have a recess for horizontally receiving the slide to be tested.
The imaging device 120 is used to photograph a biological sample to be tested, such as a slide 10 to be tested, on the support device 110. As shown in fig. 3, in some embodiments, the imaging device 120 may also be referred to as a micro-optical mechanism. The micro-optical mechanism 120 includes a lens group 121 and a camera 122, and the lens group 121 may include a first objective lens 1211 and a second objective lens 1212. The first objective lens 1211 may be a 10-fold objective lens or a 40-fold objective lens, for example, and the second objective lens 1212 may be a 40-fold objective lens or a 100-fold objective lens, for example. The lens group 121 may further include a switching mechanism 1213 for switching the first objective lens 1211 and the second objective lens 1212 so that the camera 122 captures images of different magnifications. In other embodiments, lens group 121 may include only one objective lens, e.g., a 40-fold objective lens or a 100-fold objective lens, and switching mechanism 1213 is eliminated. In still other embodiments, lens group 121 may be eliminated.
The carrier device 110 is arranged opposite the micro-optical means 120 and is designed to be movable in three dimensions, so that the micro-optical means 120 can take images of specific areas of the specimen coating of the slide 10 to be examined, which is supported on the carrier device 110. To this end, the cell image taking system 100 includes a horizontal driving device 130 and a vertical driving device 140, and the horizontal driving device 130 is used to drive the supporting device 110 and the imaging device 120 to move relatively in the horizontal direction, so that the imaging device 120 can take pictures of different positions of the sample area of the slide 10 to be measured. The vertical driving device 140 is used to drive the supporting device 110 and the imaging device 120 to move relatively in the vertical direction, so that the imaging device 120 can focus on the sample in the shooting field of view.
The controller 150 is communicatively connected to the imaging apparatus 120 for switching the photographing mode of the imaging apparatus 120 so that the imaging apparatus 120 can perform a photographing job in different photographing modes.
In some embodiments, the controller 150 may be a master module (not shown) or part of a master module of the cell image capture system configured to store and analyze the cell images, and store the image analysis results. In other embodiments, the controller 150 may also be a controller communicatively connected to a main control module of the cell image capturing system, the main control module sends a capturing command to the controller 150, and the controller 150 receives the capturing command and controls the capturing operation of the imaging device 120 according to the capturing command.
In some embodiments, the controller 150 may be configured to transmit the cell image captured by the imaging device 120 to the main control module for analysis, and the main control module may generate a corresponding capturing command according to the analysis result and transmit the capturing command to the controller 150. Of course, in other embodiments, the controller 150 may be configured to analyze the cell images captured by the imaging device 120 and generate corresponding capture commands based on the analysis results.
In some embodiments, the controller 150 may be further configured to be connected to the horizontal driving device 130 and the vertical driving device 140 and control driving actions thereof. In an alternative embodiment, the cell image photographing system may further include another controller (not shown) for controlling the horizontal driving device 130 and the vertical driving device 140, and the other controller may be communicatively connected with the controller 150 and/or the main control module of the cell image photographing system 100.
As shown in fig. 2, the cell image capturing system 100 may further be communicatively connected to the sample management system 200 through a main control module for managing the sample analysis results. The sample management system 200 may be implemented as software or hardware. In some embodiments, a plurality of blood cell morphology analyzers may be connected to the sample management system 200.
Alternatively or additionally, the sample management system 200 may also be communicatively coupled to the hospital information system 300. Of course, in other embodiments, the hospital information system 300 may also be directly connected to the main control module of the cell image capturing system 100.
In an embodiment of the present invention, the controller 150 is configured to:
causing the imaging device 120 to capture a working area of the biological sample to be tested, such as a leukocyte working area, in a first capture mode to obtain at least one first cell image containing target cells, such as leukocytes;
when the imaging device 120 performs the photographing operation in the first photographing mode, when a target cell satisfying a preset condition exists in the first cell image or when a specified photographing command indicating that the target cell satisfying the preset condition exists in the first cell image is acquired, the imaging device 120 is caused to photograph the specified cell in a second photographing mode different from the first photographing mode to acquire a second cell image including the specified cell.
The main working process and the working principle of the cell image shooting system are as follows: the method comprises the steps of automatically identifying a monolayer cell area by adopting an imaging device (such as a micro-optical mechanism) and applying an intelligent image processing algorithm, searching and shooting blood cells (white blood cells, red blood cells, platelets and the like) in the monolayer cell area, carrying out necessary image processing on the shot image, identifying the type, the quantity and the characteristics of the shot cells through the intelligent identification algorithm, and displaying the cells on a display in a classified mode according to the characteristics of the cells. The operation user can adjust the instrument classification result according to clinical experience and patient related information and give corresponding clinical conclusion.
It will therefore be appreciated that the working area of the biological sample to be tested can be a single layer of cells as described above, for example a single layer of cells of a sample film (e.g. blood film) on a smear to be tested, which is suitable for obtaining an image of a single cell.
For example, when counting leukocytes in a blood sample, a cell image capturing system usually determines a fixed leukocyte working area on a blood membrane, and then captures and counts the leukocytes in the fixed leukocyte working area, so as to obtain a clinically required number of leukocytes.
Taking a blood sample as an example, the cell image photographing system photographs a blood smear coated with a blood film. The blood membrane comprises a head part, a body part and a tail part along the coating direction, wherein the head part is coated thickly to cause dense cell distribution, and the tail part is coated thinly to cause sparse cell distribution, so that the blood membrane is generally not suitable for white blood cell shooting in the two parts. The cells of the body are distributed relatively uniformly and therefore the working area of the white blood cells is usually searched at the junction of the body or the body and the tail. When a cell image recording system records white blood cells in a blood smear, a recording area or a working area is first searched by a camera under a low-power objective lens (e.g., a 10-power objective lens). In the search of the imaging area, the supporting device 110 and the micro-optical mechanism 120 are moved relatively to each other so that the head of the blood smear can be searched under the macro objective lens to determine the working area, which can be, but is not limited to, the monolayer cell area at the junction of the tail and the body of the blood smear (also called the junction of the tail and the body).
Here, the specific cell is particularly a cell associated with the predetermined condition, and for example, includes at least one of the target cells satisfying the predetermined condition.
In the embodiment of the present invention, in the first photographing mode, the horizontal driving device 130 continuously drives the supporting device 110 to continuously move horizontally relative to the imaging device 120 during image photographing by the imaging device 120, and/or the imaging device performs predictive focusing and photographing on the working area within the visual field of the imaging device. For example, during the continuous horizontal movement, the vertical driving device 140 drives the supporting device 110 to move vertically relative to the imaging device 120, so that the imaging device 120 performs predictive focusing and photographing on a work area within a visual field range thereof. In the embodiment of the present invention, the first photographing mode may also be referred to as a flying scan photographing mode, in which a working area on a biological sample to be measured can be quickly scanned and photographed without stopping the driving of the horizontal driving device 130 and/or the vertical driving device 140, the photographing speed is increased, and the lifetime of the driving device is prolonged.
In the second photographing mode, when the imaging device 120 photographs a specific cell, for example, a specific target cell, in the embodiment of the present invention, the imaging device 120 and the supporting device 110 are relatively stationary in the horizontal direction, and/or the imaging device performs precise focusing and photographing on the specific cell within the visual field thereof. For example, the horizontal driving device 130 drives the supporting device 110 to move horizontally relative to the imaging device 120, and stops driving until the designated cell is within the field of view of the imaging device 120, so that the imaging device 120 can precisely focus and photograph the designated cell within the field of view of the imaging device 120 during the period when the horizontal driving device stops driving. In the embodiment of the present invention, the second photographing mode may also be referred to as a fine focus photographing mode, as mentioned above with reference to fig. 1.
Therefore, when the imaging device 120 performs the photographing operation in the first photographing mode, the cell image photographing system according to the present invention determines whether or not there is a target cell satisfying a preset condition in the first cell image, and when there is a target cell satisfying the preset condition, switches the first photographing mode to the second photographing mode so as to acquire the cell image of the specified cell. This enables, on the one hand, a fast scanning of the working area by the first recording mode and, on the other hand, a precise and clear recording of the specific cells, in particular of abnormal cells, by the second recording mode.
In some embodiments, the biological sample to be tested remains on the support device 110 from the beginning of the capture in the first capture mode until the end of the capture in the second capture mode. That is to say, the scheme provided by the invention can realize the real-time switching between the first shooting mode and the second shooting mode when shooting the current biological sample to be detected, so that the clear image of the specified cell can be obtained in time, and the user does not need to reload the biological sample to be detected into the cell image shooting system again.
Fig. 4 is a flowchart illustrating a cell image photographing method according to an embodiment of the present invention. The cell imaging method is implemented by the cell imaging system according to the embodiment of the present invention.
As shown in fig. 4, in step S410, the supporting device 110 receives the current biological sample to be tested, i.e., the current biological sample to be tested is loaded on the supporting device 110. In step S420, the imaging device 120 is caused to capture a working area of the current biological sample to be tested in a first capture mode to obtain a first cell image including the target cell. In step S430, it is determined whether a target cell satisfying a preset condition exists in the first cell image. In step S440, when it is determined that the target cell satisfying the preset condition exists in the first cell image, the imaging device 120 is caused to capture the specified cell in a second capture mode different from the first capture mode to acquire a second cell image containing the specified cell. In step S450, after the photographing in the first photographing mode and the second photographing mode is completed, the current biological sample to be tested is unloaded from the supporting device 110.
In some preferred embodiments, the controller 150 determines whether a target cell satisfying a preset condition exists in the first cell image by analyzing the first cell image that has been photographed, and generates a specific photographing command for photographing a specific cell in the second photographing mode when it is determined that the target cell satisfying the preset condition exists in the first cell image. In other embodiments, the main control module may also determine whether a target cell satisfying a preset condition exists in the first cell image by analyzing the first cell image that has been captured, generate a designated capture command for capturing the designated cell in the second capture mode when it is determined that the target cell satisfying the preset condition exists in the first cell image, and send the designated capture command to the controller 150.
Alternatively or additionally, the controller 150 may also be configured to receive, as the specified photographing command, an instruction input by a user indicating that there is a target cell satisfying a preset condition in the first cell image. For example, when the user finds an abnormality while analyzing or viewing the first cell image that has been captured and wants to further precisely view the abnormality, a capture instruction may be directly input to cause the imaging apparatus to enter the second capture mode.
In other embodiments, the controller 150 may also be configured to: analyzing the first cell image to judge whether target cells meeting preset conditions exist in the first cell image; when the target cell meeting the preset condition exists in the first cell image, outputting the cell image of the target cell meeting the preset condition to a display device for highlighting display so as to prompt a user whether to shoot in the second shooting mode, and determining whether to shoot in the second shooting mode by the user. If the user confirms that photographing in the second photographing mode is to be performed, the user may input a corresponding instruction through the display device.
In some embodiments, the designated cells may include at least one target cell that satisfies the preset condition and is photographed by the imaging device in the first photographing mode. That is, when it is found that the cell image captured in the first capturing mode contains the target cell satisfying the preset condition, the target cell satisfying the preset condition needs to be accurately captured again to obtain a clear image of the target cell satisfying the preset condition.
In some embodiments, the target cells satisfying the preset condition may include abnormal cells (that is, cells with abnormal conditions), and the specified cells include at least one of the abnormal cells. For example, when the target cells are leukocytes, the target cells satisfying the preset condition may include abnormal leukocytes (that is, abnormal leukocytes exist under the preset condition) photographed in the first photographing mode, such as abnormal lymphocytes and immature leukocytes, and the specific cells may include at least one abnormal leukocyte. Of course, in other embodiments, the target cells may also be platelets, and the target cells satisfying the preset condition may include platelet aggregation cells captured in the first capture mode (that is, the preset condition is that the platelet aggregation cells are present).
To enable re-photographing of target cells that have already been photographed, in some embodiments, the controller 150 may be further configured to: in a first shooting mode, recording position information of a target cell shot by an imaging device; in the second photographing mode, the imaging device is controlled to photograph the specified cell according to the recorded position information. Therefore, the target cell which is shot in the first shooting mode can be quickly positioned in the second shooting mode, and the target cell can be accurately focused and shot. In this case, the biological sample to be tested is applied to the sample carrier, which is supported by the support device, and the positional information of the target cells can be understood as positional information of the imaging positions of the imaged target cells in the coordinate system of the support device when the sample carrier to which the biological sample to be tested is applied is supported by the support device. For example, in the first or flight scan recording mode, the position of each cell image in the coordinate system, here the horizontal position, is acquired by means of image registration. Specifically, in the first shooting mode or the flight scanning shooting mode, at least a partial overlap of two images continuously shot before and after shooting is ensured, and then the relative positional relationship between the respective shot images can be acquired by means of image registration (relative registration or absolute registration), for example, the relative positional relationship between the respective shot images and a reference image (for example, the first shot image) is determined in the case of relative registration, so that the position of each shot cell image in the coordinate system can be acquired.
In other embodiments, the imaging position of the target cell to be imaged again may be determined based on the imaging position of the first image (reference image) imaged in the first imaging mode, the XY movement speed of the support device, and the frame rate of the camera. The imaging position of the first image, the XY movement speed of the support device, and the frame rate of the camera are known in advance, and for example, when it is recognized that an abnormal cell is included in the tenth image, it is necessary to image the abnormal cell again at this time, and the relative positional relationship between the imaging position of the tenth image and the imaging position of the first image can be determined by the XY movement speed of the support device and the frame rate of the camera, and the imaging position of the tenth image can be determined based on the relative positional relationship.
In some preferred embodiments, the controller 150 may be configured to cause the imaging apparatus 120 to perform photographing in the second photographing mode after the imaging apparatus 120 completes photographing of a preset number of target cells in the first photographing mode. That is to say, after the required scanning and shooting of the biological sample to be detected are completed in the first shooting mode, that is, after a preset number of target cells (for example, 100 white blood cells) are shot, the second shooting mode is switched to perform accurate shooting, so that frequent switching of the shooting mode after the target cells meeting a preset condition are found is avoided, and the shooting efficiency is improved.
Of course, in other embodiments, the controller 150 may also be configured to: after the specified photographing command is acquired, that is, after it is determined that there is a target cell satisfying the preset condition in the first cell image, the imaging apparatus is caused to interrupt photographing in the first photographing mode and start photographing in the second photographing mode. Further, the controller may be further configured to: after the photographing in the second photographing mode is ended, the imaging apparatus is caused to continue the photographing in the first photographing mode.
In some embodiments, the target cells satisfying the preset condition include abnormal cells photographed in the first photographing mode. At this time, the controller 150 may be further configured to set the designated cells to all target cells photographed in the first photographing mode or to all target cells of a preset number to be photographed in the first photographing mode when the number of abnormal cells photographed in the first photographing mode exceeds a preset threshold and/or when the number of types of abnormal cells photographed in the first photographing mode exceeds a preset threshold. That is, when there are too many abnormal cells and/or a plurality of abnormal cells, in order to avoid risks, all the target cells photographed in the first photographing mode may be accurately photographed again, or the second photographing mode may be directly switched to, and a preset number of target cells may be photographed in the second photographing mode, and photographing in the first photographing mode is not performed any more.
In some embodiments, the controller 150 may be further configured to, in the first photographing mode, cause the imaging device to perform a predictive focusing of the sample in the photographing field of view according to a focusing surface characterization function that characterizes a relationship between horizontal position coordinates and focusing parameters of respective points to be photographed in the working area.
For example, for each newly loaded sample carrier to be tested, before formal shooting, a new focusing function f (S, P) is established according to the characteristics of the sample carrier to be tested, where S is the horizontal position coordinate of the point to be shot and P is the focusing parameter of the point to be shot. Here, the horizontal position coordinate represents a relative position relationship between the sample carrier to be measured and the imaging device in a horizontal plane, and the focusing parameter may be a focusing distance or a parameter of a camera of the imaging device.
In some embodiments, the controller 150 may be further configured to acquire horizontal position coordinates of at least three reference points in the biological sample to be tested, control the horizontal driving device to horizontally move the supporting device with the biological sample to be tested supported by the supporting device relative to the imaging device such that the at least three reference points are respectively located within a field of view of the imaging device, control the imaging device to respectively focus on the at least three reference points to acquire focusing parameters of the at least three reference points, and determine the focusing surface characterization function according to the horizontal position coordinates and the focusing parameters of the at least three reference points.
Specifically, a plane equation a X + b Y + c Z + d =0 may be solved according to the horizontal position coordinates and the focusing height of the at least three reference points to obtain a predicted focusing surface, where X and Y are horizontal position coordinates, Z is the focusing height, and a, b, c, and d are coefficients to be solved of the plane equation.
Taking a blood smear as a sample carrier to be measured as an example, as shown in fig. 5, first, a plurality of reference points, for example, fifteen reference points S1 to S15, are selected on a blood sample area of the blood smear, wherein the positions (horizontal position coordinates) of the reference points are settable. The blood smear is then moved horizontally relative to the imaging device such that the fifteen reference points each stop within the field of view of the imaging device, so that the imaging device is focused on the fifteen reference points and records the focus position or focus height (focus distance) of each reference. The in-focus plane of the entire blood smear is then fitted based on the horizontal position coordinates and in-focus position of these fifteen points, as shown in fig. 6, so that the in-focus position anywhere in the entire blood smear can be predicted. It will be appreciated that the predicted focus plane may also be a fitted surface.
Thus, in the first photographing mode, the horizontal driving means continuously moves the supporting means horizontally with respect to the imaging means while the vertical driving means vertically moves the supporting means with respect to the imaging means, so that the sample carrier to be measured is always in the predicted focus plane during the continuous horizontal movement. That is, during the continuous horizontal movement of the supporting device relative to the imaging device by the horizontal driving device, the supporting device is moved vertically relative to the imaging device by the vertical driving device at the same time so that the sample carrier to be measured is always in a focusing state, so that the imaging device can dynamically scan and shoot images of each point to be shot of the sample carrier to be measured. The drive device therefore does not need to be stopped for focusing during the continuous horizontal movement, and the imaging device is able to rapidly scan images of the individual points to be imaged in the sample area on the sample carrier to be measured, since the sample carrier to be measured always satisfies its focusing surface characterization function, i.e. is in the in-focus state, during the continuous horizontal movement.
A photographing process in the first photographing mode is described with reference to fig. 7 and 8. For example, the driving device includes a first motor as an X-direction motor, a second motor as a Y-direction motor, and a third motor as a Z-direction motor. The imaging device is fixed, the first motor drives the blood smear to move along the X direction, the second motor drives the blood smear to move along the Y direction, the third motor drives the blood smear to move along the Z direction, namely, the first motor and the second motor drive the blood smear to move horizontally relative to the imaging device, and the third motor drives the blood smear to move vertically relative to the imaging device, namely, in the direction perpendicular to the horizontal plane, so that the focusing height can be adjusted. In this example, the motion scan of the working area is shown in fig. 7 and 8. For example, the C1-C4 scan shooting may be performed column by column in the working area 20, or may be performed line by line scan shooting or tilt scan shooting. The column-by-column scanning and shooting mode is as shown in fig. 7, a motor in the Y direction drives a blood smear to be detected to move along a column C1 relative to an imaging device, and the imaging device shoots a sample image on the column C1 of the blood smear; then the X-direction motor drives the blood smear to be detected to move to a C2 row relative to the imaging device, the Y-direction motor drives the blood smear to be detected to move along the C2 row relative to the imaging device, and the imaging device shoots a sample image on the C2 row of the blood smear; this was repeated to column C4. As shown in fig. 8, the Y-direction motor drives the blood smear to be measured to move from one end of C1 to the other end of C1 at a constant speed without stopping relative to the imaging device, and the Z-direction motor (vertical driving component) drives the blood smear to be measured to move vertically relative to the imaging device along the Z-direction (perpendicular to the XY plane or the plane where the blood smear is horizontally placed) to ensure that the blood smear to be measured is always in a focused state, during which the camera of the imaging device continuously shoots to obtain an image M of an entire column of area (each small square in the figure represents one image). And in the process that the X/Y motor moves the blood smear to be detected to the target position, the Z-direction motor also simultaneously moves the blood smear to be detected to the predicted focusing surface of the target position, namely the X/Y motor and the Z motor simultaneously move and stop so as to ensure that the blood smear to be detected is always positioned on the focusing surface in the moving process.
In some embodiments, to ensure that the imaging device can take sharp images during continuous relative movement of the sample carrier to be measured and the imaging device, the exposure time of the camera of the imaging device should match the movement speed of the horizontal drive, i.e. the horizontal movement distance of the sample carrier to be measured relative to the imaging device/the horizontal drive movement speed during the exposure time < = exposure time. To avoid the occurrence of image blur, the horizontal movement distance should be set small. That is, the drive speed of the horizontal drive is designed such that the horizontal movement distance of the sample carrier to be measured relative to the imaging device within the exposure time of the imaging device is not more than 2 micrometers, in particular not more than 1 micrometer, in particular in the case of a 40-fold or 100-fold objective lens.
In some embodiments, the method of using the focusing surface characterization function of the present invention can realize that a sample image with a larger area is taken in a shorter time. For example, during said continuous horizontal movement the area taken by the imaging device per second is not less than 1 square millimeter, in particular not less than 1.3 square millimeters, in particular in the case of a 40-fold or 100-fold objective lens. For example, the imaging device continuously takes sample images of an area of at least 20 square millimeters of the sample carrier to be measured during a continuous horizontal movement of at most 15 seconds.
In some embodiments, the imaging device may be configured to take a photograph with the same objective lens, e.g. a 40-fold or 100-fold objective lens, both in the first and in the second photographing mode, i.e. to take a scan photograph of the working area with the objective lens in the first photographing mode and to take a photograph of the specified cell with the same objective lens in the second photographing mode.
In some embodiments, the controller may be further configured to output the first cell image and the second cell image to a display device for display, replacing an image of the specified cell in the first cell image with the second cell image. Then, for a given cell that has undergone two shots, the user can directly view the clear cell image that has been accurately shot when viewing through the display device.
The features or combinations of features mentioned above in the description, in the drawings and in the claims can be used in any combination with one another or alone, provided that they are meaningful and not mutually contradictory within the scope of the invention. The advantages and features explained for the cell image recording system according to the invention apply in a corresponding manner to the cell image recording method according to the invention and vice versa.
The above description is only a preferred embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent modifications made by the present specification and drawings, or directly/indirectly applied to other related technical fields, within the spirit of the present invention, are included in the scope of the present invention.

Claims (22)

1. A cell image capturing system, comprising:
the supporting device is used for bearing a biological sample to be tested;
the imaging device is used for shooting the biological sample to be tested on the supporting device;
horizontal driving means for driving the supporting means and the image forming means to move relatively in a horizontal direction; and
a controller communicatively coupled with the imaging device and configured to:
enabling the imaging device to shoot a working area of the biological sample to be tested in a first shooting mode to obtain at least one first cell image containing target cells, wherein in the first shooting mode, the horizontal driving device drives the supporting device to horizontally move relative to the imaging device when the imaging device shoots the image;
when a target cell satisfying a preset condition exists in the first cell image, the imaging device is caused to shoot a specified cell in a second shooting mode to acquire a second cell image containing the specified cell, and in the second shooting mode, the imaging device and the supporting device are relatively stationary in a horizontal direction when the imaging device shoots the specified cell.
2. The cell image capturing system according to claim 1,
in the first photographing mode, the imaging device performs predictive focusing and photographing on the working area within the visual field range thereof.
3. The cell image capturing system according to claim 2, wherein in the second capturing mode, the horizontal driving means drives the supporting means to move horizontally with respect to the imaging means until the designated cell is within the field of view of the imaging means, and then stops driving, and during the stopping of driving of the horizontal driving means, the imaging means performs precise focusing and capturing of the designated cell within the field of view thereof.
4. The cell image capturing system according to any one of claims 1 to 3, wherein the controller is further configured to:
after the imaging device completes photographing of a preset number of the target cells in the first photographing mode, causing the imaging device to perform photographing in the second photographing mode.
5. The cell image capturing system according to any one of claims 1 to 3, wherein the controller is further configured to:
after it is determined that there is an abnormal cell that satisfies a preset condition, causing the imaging device to interrupt the photographing in the first photographing mode and start the photographing in the second photographing mode.
6. The cell image capturing system according to claim 5, wherein the controller is further configured to:
after the end of the shooting in the second shooting mode, causing the imaging apparatus to continue the shooting in the first shooting mode.
7. The cell image capturing system according to any one of claims 1 to 6, wherein the controller is further configured to:
analyzing the first cell image to judge whether target cells meeting preset conditions exist in the first cell image.
8. The cell image capturing system according to any one of claims 1 to 6, wherein the controller is further configured to:
receiving an instruction input by a user, wherein the instruction indicates that target cells meeting preset conditions exist in the first cell image.
9. The cell image capture system of claim 8, wherein the controller is further configured to, prior to receiving the user-input instruction:
analyzing the first cell image to judge whether target cells meeting preset conditions exist in the first cell image;
when the target cell meeting the preset condition exists in the first cell image, outputting the cell image of the target cell meeting the preset condition to a display device for highlighting display so as to prompt a user whether to shoot in the second shooting mode.
10. The cell image capturing system according to any one of claims 1 to 9, wherein the target cells satisfying a preset condition include abnormal cells, and the specified cells include at least one of the abnormal cells.
11. The cell image capturing system according to claim 10, wherein the target cell is a white blood cell, and the abnormal cell includes an abnormal white blood cell.
12. The cell image capturing system according to claim 7, wherein the target cell satisfying the preset condition includes an abnormal cell captured in the first capturing mode, and the controller is further configured to:
setting the designated cell as all of the target cells photographed in the first photographing mode or a preset number of all of the target cells to be photographed in the first photographing mode when the number of the abnormal cells photographed in the first photographing mode exceeds a preset threshold.
13. The cell image capturing system according to any one of claims 1 to 12, wherein the controller is further configured to:
under the first shooting mode, recording the position information of the target cell shot by the imaging device;
in the second photographing mode, the imaging device is controlled to photograph the specified cell according to the recorded position information.
14. The cell image capturing system according to claim 2 or 3, wherein the controller is further configured to:
and in the first shooting mode, the imaging device carries out prediction focusing on the samples in the shooting field of view according to a focusing surface characterization function, wherein the focusing surface characterization function characterizes the relationship between the horizontal position coordinates and focusing parameters of each point to be shot in the working area.
15. The cell image capturing system according to claim 14,
the controller is further configured to:
acquiring horizontal position coordinates of at least three reference points in the biological sample to be detected,
controlling the horizontal driving device to enable the supporting device and the biological sample to be tested supported by the supporting device to horizontally move relative to the imaging device, so that the at least three reference points are respectively positioned in the visual field range of the imaging device, and controlling the imaging device to respectively focus on the at least three reference points to acquire the focusing parameters of the at least three reference points,
and determining the focusing surface characteristic function according to the horizontal position coordinates of the at least three reference points and the focusing parameters.
16. A cell image capturing system according to any of claims 1 through 15, characterized in that the imaging device includes a 40-fold or 100-fold objective lens, and the imaging device is configured to capture with the objective lens in both the first capturing mode and the second capturing mode.
17. The cell image capturing system according to any one of claims 1 to 16, wherein the controller is further configured to:
and outputting the first cell image and the second cell image to a display device for displaying, wherein the second cell image replaces the image of the specified cell in the first cell image.
18. The cell image shooting system according to any one of claims 1 to 17, wherein the supporting device is used for bearing a slide to be tested, and the slide to be tested is coated with the biological sample to be tested;
or, the supporting device is used for bearing a counting cell, and the biological sample to be detected is filled in the counting cell.
19. A cell image capturing system, characterized by comprising:
the supporting device is used for bearing a biological sample to be tested;
the imaging device is arranged in a relative motion way with the supporting device and is used for shooting the biological sample to be tested on the supporting device;
a controller communicatively coupled with the imaging device and configured to:
enabling the imaging device to shoot a working area of the biological sample to be detected in a first shooting mode to acquire a first cell image containing target cells, and in the first scanning mode, the imaging device carries out prediction focusing and shooting on the working area in the visual field range of the imaging device;
when target cells meeting preset conditions exist in the first cell image, the imaging device is made to shoot the specified cells in a second shooting mode to obtain a second cell image containing the specified cells, and in the second shooting mode, the imaging device carries out accurate focusing and shooting on the specified cells in the visual field range of the imaging device.
20. The cell image photographing system according to claim 19, further comprising a horizontal driving means for driving the supporting means to move horizontally with respect to the imaging means;
in the first photographing mode, the horizontal driving device constantly drives the supporting device to move continuously horizontally relative to the imaging device, and during the continuous horizontal movement, the imaging device performs predictive focusing and photographing on the working area within the visual field range of the imaging device.
21. The cell image capturing system according to claim 20, wherein in the second capturing mode, the horizontal driving means drives the supporting means to move horizontally with respect to the imaging means until the designated cell is within the field of view of the imaging means, and then stops driving, and during the stopping of driving of the horizontal driving means, the imaging means performs precise focusing and capturing of the designated cell within the field of view thereof.
22. A cell image capturing method, comprising:
the supporting device receives a current biological sample to be tested;
the imaging device shoots a working area of the current biological sample to be tested in a first shooting mode to obtain a first cell image containing target cells;
when a target cell satisfying a preset condition exists in the first cell image, the imaging device shoots a specified cell in a second shooting mode different from the first shooting mode to acquire a second cell image containing the specified cell;
and unloading the current biological sample to be tested from the supporting device.
CN202110712338.XA 2021-06-25 2021-06-25 Cell image capturing system and cell image capturing method Pending CN115529410A (en)

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