CN209803001U - A Chromosome Scanning Imaging System - Google Patents

Abstract

A chromosome scanning imaging system, at least composed of a slide feeding device, a microscope system and an overall control system, wherein the overall control system is used to control the camera unit to sequentially observe the object from the objective lens with the smallest magnification to the objective lens with the highest magnification At the same time, the detection object is scanned in three consecutive rounds, the first round of scanning is to obtain the area where the detection object is distributed; the second round of scanning is to obtain the focal plane at the second magnification, and the whole slice is scanned to obtain the second magnification The overall control system sorts and positions the detected objects in the images obtained under the second magnification; and in the third round of scanning, the camera unit uses the objective lens with the highest magnification to locate the detected objects in the front according to the positioning A series of high-definition images are obtained by focusing shooting, so that the diagnosis or treatment of diseases can be provided by the high-definition images.

Description

A Chromosome Scanning Imaging System

technical field

The invention relates to the field of chromosome technology, in particular to a chromosome scanning imaging system and an imaging scanning method.

Background technique

Many medical diagnostic tests require the physician to collect cells by brushing and/or scraping the integument or mucous membrane with an instrument in the target area. The collected cells are usually smeared (or fixed) on a glass slide and stained to facilitate examination by cytotechnologists and/or pathologists under a microscope. For example, pathologists can use multicolor techniques characterized by staining portions of the nucleus to determine the presence of dysplasia or neoplasia. Pathologists can also use contrast stains to visualize the cytoplasm of cells.

The mechanical structure of the current scanning imaging system is composed of a device for storing glass slides, a mechanical arm, a microscope and a microscope object platform. The manipulator takes slices from the slide storage device through process control, and places them on the microscope platform, scans, takes slices, and analyzes chromosomes or cells on the slides through the microscope. However, to capture high-definition patterns of chromosomes or cells on slides, it is generally found that the pattern is unclear or the resolution is insufficient after shooting, and then the objective lens with different magnifications is replaced to scan and shoot, but it is very time-consuming and labor-intensive. manpower. In addition, when the number of detection objects is huge, the current microscopic scanning system can only scan and capture patterns on one glass slide at a time, and the use of an objective lens with the same magnification may not be able to capture all the detection objects. For images with clear resolution, it is necessary to rely on human judgment to replace the objective lens with different magnifications and re-scan and shoot, which is very uneconomical.

Utility model content

The main purpose of this creation is to provide a chromosome scanning imaging system, which uses the overall control system to control multiple slides with test objects to observe the test objects on the two-way moving stage of the microscope in a three-round continuous manner. Use the scanning unit to scan the detection objects on each slide sequentially from low magnification to high magnification under three objective lenses of different magnifications, and take multiple photos at each magnification.

Another purpose of this creation is to provide a chromosome scanning imaging system, which uses the overall control system to sort the detection objects of multiple images captured by the camera unit for each detection object, and sort the top ones after sorting A series of high-definition images are captured according to the positioning and focusing of the detected object to provide subsequent analysis or diagnosis.

According to the above purpose, this creation discloses a chromosome scanning imaging system, which is at least composed of a slide feeding device, a microscope system and an overall control system, wherein the slide feeding device includes a plurality of slide boxes, and each slide box contains There are a plurality of glass slides and each of the slides has a detection object; the microscope system includes: a microscope bidirectional moving stage, an imaging unit, an optical path unit and an objective lens unit, wherein the objective lens unit is composed of three objective lenses of different multiples according to The order is from the smallest multiple to the highest multiple to observe the detection object; and the overall control system has a continuous supply system, which is composed of X-Y-Z three-axis linkage robotic arm, and the Y axis in the X-Y-Z three-axis linkage robotic arm is the basic axis, so that the continuous supply system The front and rear directions move, the Z axis moves up and down on the Y axis, and the X axis moves left and right on the Z axis. The slides are placed on the two-way moving stage of the microscope.

The main technical features of this creation are: the overall control system also includes; controlling the movement of the two-way mobile stage of the microscope, so that the microscope system controls the movement of the two-way mobile stage of the microscope in the first direction and the second direction, and controls the objective lens in the first direction and the second direction through the microscope system. The movement in the third direction is used to control the two-way moving stage of the microscope to move with the objective lens in the third direction; the objective lens unit is controlled from the objective lens with the smallest magnification to the objective lens with the highest magnification in order to match the glass on the two-way moving stage of the microscope The overall control system controls the camera unit in the microscope system to scan the detection object on the glass slide on the two-way moving stage of the microscope, and judges whether the detection object adopts three rounds according to the objective lens with the smallest magnification. scanning, if so, the overall control system controls the camera unit in the microscope system to scan the object in three consecutive rounds while observing the object from the objective lens with the smallest magnification to the objective lens with the highest magnification, wherein the overall control system controls the camera The unit performs the first round of scanning, and the camera unit scans the detection object on the slide with the objective lens with the smallest multiple to obtain the area where the detection object is distributed; the overall control system controls the camera unit to perform the second round of scanning, and the camera unit uses the second round of scanning. multiple objective lens to observe and select the points in the area where the detected object is distributed and focus to obtain the focal plane under the second multiple, and scan the whole film to obtain multiple images under the second multiple, and are controlled by the overall The system sorts and positions the images obtained at the second magnification; and the overall control system controls the camera unit to perform the third round of scanning, and the camera unit uses the highest magnification objective lens to position and focus to obtain a series of high-definition images, which are provided by the high-definition images Diagnosis or treatment of disease.

Description of drawings

FIG. 1 and FIG. 2 are front views showing a chromosome scanning imaging machine according to the technology disclosed in this creation.

FIG. 3 is a schematic block diagram of the chromosome scanning imaging machine shown in FIG. 1 and FIG. 2 further represented by a chromosome scanning imaging system according to the technology disclosed in this creation.

FIG. 4 is a schematic block diagram showing each unit in the chromosome scanning imaging system according to the technology disclosed in this work.

Fig. 5 is a schematic diagram showing the image of the main distribution area of the detection object obtained after splicing and taken by scanning with a 1.25x objective lens according to the technology disclosed in this creation.

Fig. 6 is a schematic diagram showing the focal plane of the entire glass slide obtained by selecting the focal point range to focus in the recognition area during 10x scanning according to the technology disclosed in this creation.

Detailed ways

In order to make the purpose, technical features and advantages of this creation more understandable to those in the relevant technical field, and to be able to implement this creation, the technical features and implementation methods of this creation are specifically clarified with the attached drawings, and listed The preferred embodiment is further described. The diagrams compared in the following text are for the purpose of expressing the representation related to the characteristics of this creation, and they are not and need not be completely drawn according to the actual situation. The description of the implementation of this case involves technical content well known to those skilled in the art, and will not be stated again.

First, please refer to Figure 1 and Figure 2 at the same time. 1 and 2 are schematic diagrams showing a chromosome scanning imaging machine. In FIGS. 1 and 2, the chromosome scanning imaging machine 1 includes a front cabinet assembly 10, a rear cabinet assembly 12, a storage assembly unit 14, a basic component unit 16, a microscope system 18, a microscope two-way mobile stage 20, a The oil system 22, the overall control system 24 and the oil bottle assembly 26. In addition, the chromosome scanning system 1 in FIG. Other components are the same as in FIG. 1 , and are not repeatedly marked in FIG. 2 to avoid complexity of the drawing. Wherein, all components of rear box assembly 10, storage assembly unit 14, microscope system 18 and continuous supply system 28 are installed on the large plane of basic assembly unit 16; storage assembly unit 14, microscope system 18, oil supply system 22 and the overall control system 24 are arranged on the left side of the basic component unit 16, and the scanning unit 32 is arranged on the microscope frame (not shown in the figure) above the microscope two-way movable stage 20. The circuit board 30 is used for circuit control devices and is arranged in the rear box assembly 12 .

Please refer to Figure 3 and Figure 4 at the same time. FIG. 3 is a schematic block diagram of the chromosome scanning imaging system shown in FIG. 1 and FIG. 2 and FIG. 4 is a block diagram showing each unit in the chromosome scanning imaging system. It should be noted here that some components in FIG. 1 and FIG. 2 are the same as those in the prior art. In order to focus on the chromosome scanning imaging system, only the components related to the chromosome scanning imaging system will be described.

In FIG. 3 , the chromosome scanning imaging system 4 includes a slide feeding device 40 , a microscope system 42 , and an overall control system 44 . Wherein, the microscope system 42 in FIG. 3 is the microscope system 18 disclosed in FIG. 1, but for the convenience of understanding, the following description is represented by the microscope system 42, and the scanning unit 32 is equivalent to the one shown in FIG. The camera unit 424. The following is a detailed description of each unit and operation of the entire chromosome scanning imaging system 4 , while the description is accompanied by FIG. 1 and FIG. 2 , so as to facilitate understanding of the operation of the entire chromosome scanning imaging system 4 .

As shown in Figure 3, in this invention, the slide feeding device 40 has a plurality of slide boxes 402, taking one of the slide boxes 402 as an example, a slide box 402 has a plurality of slides 4022, and each A slide 4022 is loaded with detection substances 40222 . For the preferred embodiment of the present invention, the slide feeding device 40 has at least four slide boxes 402, and 40 slides 4022 are arranged in each slide box 402. There are at least 160 slides 4022 scanned and photographed.

The microscope system 42 includes a microscope bidirectional movable stage 422, an imaging unit 424, an optical path unit 426, and an objective lens unit 428, wherein the microscope bidirectional movable stage 422 is the same assembly as the microscope bidirectional movable stage 20 in FIG. It is used to carry the glass slide 4022 with the detection object 40222 . The camera unit 424 scans the detection object 40222 on each slide 4022 in the slide feeding device 40 and takes an image of the detection object 40222 . The optical path unit 426 is a total collection of optical components of the entire microscope system 42, which is used to provide a light source to illuminate the detection object 40222 placed on the microscope system 40 and the microscope bidirectional movable stage 422, and the objective lens unit 428 is composed of three objective lenses with different multiples. Composition, wherein the objective lens unit 428 is used to observe the detection object 40222 placed on the two-way movable stage 422 of the microscope. In a more preferred embodiment of the present creation, the objective lenses of three different multiples of the objective lens unit 428 are respectively a 1.25 multiple objective lens with the smallest multiple, a 10 multiple objective lens with the second multiple and a 100 multiple objective lens with the highest multiple. For the objective lens unit 428 The actual operation steps are detailed below. In addition, it should be noted that the objective lenses with the minimum magnification, the second magnification, and the highest magnification mentioned above are based on the objective lenses used in this creation, which means that among the three objective lenses used in this creation, the 1.25 magnification It is the smallest magnification, 10 is the second magnification, and 100 is the highest magnification. It does not refer to the smallest or highest magnification of all microscope objectives.

The overall control system 44 has a continuous supply system 442, wherein the continuous supply system 442 is composed of an X-Y-Z three-axis linkage mechanical arm (not shown in the figure), and the Y axis in the X-Y-Z three-axis linkage mechanical arm is the basic axis, so that the continuous supply The system 442 moves forward and backward, the Z axis moves upward and downward on the Y axis, and the X axis moves left and right on the Z axis. The continuous supply system 442 is controlled by the overall control system 44 from the slide supply device 40 Take the glass slide 4022 placed on the two-way moving stage 422 of the microscope. In the embodiment of this invention, the front, back, left and right directions refer to the user standing on the platform as shown in Fig. 1 or Fig. 2 The relative direction in front of the chromosome scanning imaging machine 1 .

Therefore, according to the above, the overall control system 44 uses the X-Y-Z three-axis linkage robot arm of the continuous supply system 442 to take out the slides 4022 from the numbered slide cassettes 402 in the slide supply device 40 in a single-sheet continuous supply mode and place them On the two-way moving stage 422 of the microscope, after the detection object 40222 on the glass slide 4022 is scanned and photographed, the X-Y-Z three-axis linkage mechanical arm of the continuous supply system 442 is used to move the slide 4022 from the microscope to the two-way moving stage 422, and place the next slide 4022 to be scanned and photographed. The advantage of using the slide feeding device 40 to continuously pick and place the slide 4022 on the bidirectional moving stage 422 of the microscope is that it does not need to be done manually. In addition to saving manpower, it can also avoid contamination of the slide 4022 during manual operations. In addition, using the slide feeding device 40, a large number of detection objects 40222 can be scanned and photographed, and the results of a large number of detection objects 40222 can be obtained in a short time.

In addition, the overall control system 44 is used to control the operation of each hardware component in the entire chromosome scanning system 4, wherein the overall control system 44 controls the movement of the microscope's two-way moving stage 422, so that the microscope's two-way moving stage 422 is in the first direction and the second direction, and the microscope system 42 controls the movement of the objective lens unit 428 in the third direction to control the microscope bidirectional mobile stage 422 to move in the third direction along with the objective lens unit 428, wherein the first direction, the second direction and the third direction respectively refer to the X direction, the Y direction and the Z direction indicated on the drawing of FIG. 1 or FIG. 2 .

In addition, the overall control system 44 controls the objective lens unit 428 to observe the detection object 40222 of the glass slide 4022 on the two-way moving stage 422 of the microscope from the objective lens with the smallest magnification to the objective lens with the highest magnification. 40222 at the same time, the overall control system 44 controls the camera unit 424 in the microscope system 42 to scan the detection object 40222 on the glass slide 4022 on the two-way mobile stage 422 of the microscope, and the objective lens with the minimum multiple (1.25 multiple objective lens) To scan the detection object 40222 and judge whether it is necessary to adopt three rounds of scanning by the overall control system 44, the mode of scanning is as follows:

The first round of scanning uses a 1.25x objective lens, that is, after the three-axis linkage mechanical arm 28 of the slide supply device 40 takes out the slide 4022 with the detection object 40222 from the slide box 402, it is placed in the microscope to move the load in two directions On the stage 422, the optical path unit 426 of the microscope system 42 provides a light source and illuminates the glass slide (the glass slide with the detection object 40222) 4022 on the two-way movable stage 422 of the microscope, and allows the camera unit 424 to transmit through the minimum magnification ( 1.25 times) objective lens scans the detection object 40222 of the glass slide 4022 on the two-way moving stage 422 of the microscope as a whole, and obtains the area where the detection object 40222 is distributed.

Then, the second round of scanning is performed. At this time, the overall control system 44 controls the objective lens unit 428 to align the objective lens of the next multiple, the 10 times objective lens, with the detection object 40222 of the glass slide 4022 on the two-way movable stage 422 of the microscope, At this time, the 10x objective lens will first focus on the points in the area where the detection objects 40222 are distributed by scanning the camera unit 424 while the 1.25x objective lens 442 is observing in the aforementioned first round of scanning steps, so as to obtain the detection The 10X focal plane of the object 40222 is scanned, and then the whole slide (that is, the detection object 40222 on the entire glass slide 4022) is scanned, and the detection objects 40222 of each 10X image acquired are sorted and positioned. Then a third round of scanning is performed, and the third round of scanning is to use the camera unit 424 to obtain the high-definition pattern of the detection object 40222 when observing with a 100 times objective lens.

In addition, in this creation, when the third round of scanning is performed every time, that is, when the object 40222 is observed with a 100 times objective lens and scanned by the camera unit 424, the overall control system 44 will control the oil supply system 22 and the oil bottle Component 26 (as shown in Figure 1) will provide cedar oil to drop on the glass slide 4022. The purpose of using cedar oil is because the magnification of the 100 times objective lens is high, but the lens is very small, and the light passes through medium substances of different densities (such as glass, air, objective lens), part of the light will be refracted and lost, the light entering the lens barrel is less, the field of view is darker, and the detection object 40222 cannot be observed clearly, so glass and glass will be added between the objective lens and the glass slide 4022 Cedar oil (refractive index 1.515) with a similar refractive index (1.52) increases the light entering the oil lens and enhances the brightness of the field of view so that the detection object 40222 can be clearly observed.

It should be noted that, in the embodiment of this creation, the scanning of the high-definition image of the detection object 40222 on each glass slide 4022 by the imaging unit 424 is performed by a low-magnification objective lens to a high-magnification objective lens, from 1.25 times The objective lens first obtains the area where the detection object 40222 is distributed, and then the 10-fold objective lens obtains the 10-fold focal plane and comprehensive scanning, and the overall control system 44 sorts and positions, and finally observes and obtains the detection object by the 100-fold objective lens 40222 HD images. It should be noted that the general control system 44 sorts the obtained images based on the feature set of the detection object 40222. Taking the detection object 40222 as a chromosome as an example, the basis for sorting is according to the length of the chromosome, the size of the chromosome, and the length of the chromosome. The number and area of chromosomes and other characteristics are used to rank comprehensively.

In addition, when the scanning area does not need to be determined, the objective lens unit 428 will not be activated for three rounds of scanning, that is, it is not necessary to use the 1.25x objective lens for the first round of scanning. In this creation, the discussion is mainly focused on the three-round scanning mode, so the steps that do not need to perform the three-round scanning mode are not stated here.

In addition, in this creation, when the three-round scanning mode is not required, the objective lens with a general multiple can be used for scanning, and the image of the detection object 40222 can be taken by focusing at 100 times, but if the three-round scanning mode is required, then The overall control system 44 conducts the three rounds of scan mode in the manner described above. Judging whether to perform three-round scanning mode depends on whether to use whole-slice staining, three-round scanning is required for spot-spot staining, and three-round scanning is not required for whole-staining staining.

According to the above, the process of the three-round scanning mode is illustrated by way of example. First, the first round of scanning is performed with a 1.25 times objective lens, and the image of the detection object 40222 on the glass slide 4022 is scanned as a whole and the image is captured by the camera unit 424. Therefore The captured images are stitched into a large image according to their scanning order, as shown in Figure 5. The main distribution area of the detection object 0222 is obtained through image processing and recognition on the large image, and the detection object 40222 is a chromosome in this embodiment.

Then, use the 10x objective lens to perform the second round of scanning, calculate the height in the Z direction (vertical direction of the objective lens) of the microscope according to the 10x focal plane of the glass slide 4022 and the X, Y position of the current microscope system 42 and move to this position to acquire an image , as shown in Figure 6, the overall control system 44 controls X, Y, Z synchronous movement to collect images, obtains and sorts chromosome 40222 from each 10 times image, and provides 100 times objective lens (or claims oil lens observation) .

Next, the overall control system controls the oil supply system 22 and the oil bottle assembly 26 to provide dripping oil on the glass slide 4022. After the dripping of oil is completed, the oiling operation is completed by the 100 times objective lens. According to the chromosome 40222 at the top position of 10 times, the overall control system 44 obtains a clear image by focusing on the position and uses the camera unit 424 to take pictures. This focusing algorithm can perform a large-scale focus and a small-scale focus, and finally output The 100x objective lens 446 images are used for diagnosis and/or analysis.

The above description is only a preferred embodiment of this creation, and is not intended to limit the scope of rights of this creation; at the same time, the above description should be understandable and implementable for professionals in the relevant technical fields, so others do not deviate from the disclosure of this creation Equivalent changes or modifications completed under the spirit should be included in the scope of the patent application.

Claims (10)

1. A chromosome scanning imaging system, comprising:

The slide feeding device comprises a plurality of slide boxes, wherein each slide box is internally provided with a plurality of slides and each slide is provided with a detection object;

A microscope system, comprising:

A microscope bi-directional movement stage to carry the slide with the test object;

An image pickup unit that scans a detection object on each slide in the slide supply device and picks up an image of the detection object;

An optical path unit that provides a light source to irradiate the inspection object placed on the microscope bi-directional movement stage of the microscope system; and

An objective lens unit composed of three objective lenses of different multiples, each objective lens being used for observing the object to be detected on the slide placed on the microscope bidirectional moving stage; and

The overall control system is provided with a continuous supply system, the continuous supply system is composed of an X-Y-Z three-axis linkage mechanical arm, a Y axis in the X-Y-Z three-axis linkage mechanical arm is a basic axis, so that the continuous supply system moves in the front and back directions, the Z axis moves in the up and down direction on the Y axis and the X axis moves in the left and right direction on the Z axis, the continuous supply system controls the slide supply device to take and place the slide on the microscope bidirectional moving stage by the overall control system, and the overall control system further comprises:

Controlling the movement of the microscope bidirectional moving object stage to enable the microscope bidirectional moving object stage to move in a first direction and a second direction, and controlling the movement of the objective lens unit in a third direction through the microscope system to control the movement of the microscope bidirectional moving object stage along with the objective lens unit in the third direction;

Controlling the objective lens unit to sequentially observe the object to be detected on the slide on the microscope bi-directional movement stage from the objective lens with the smallest multiple to the objective lens with the highest multiple;

The overall control system controls the camera unit in the microscope system to scan the detected object on the slide on a microscope bidirectional moving stage, and judges whether the detected object adopts three rounds of scanning by the objective lens with the minimum multiple, if so, the overall control system controls the camera unit in the microscope unit to scan the detected object in three rounds of continuous modes while observing the detected object sequentially from the objective lens with the minimum multiple to the objective lens with the highest multiple, wherein the overall control system controls the camera unit in the microscope system to scan the detected object on the slide on the microscope bidirectional moving stage, and if so, the overall control system controls the camera unit in the microscope unit to sequentially observe the detected object from the objective lens

The overall control system controls the image pickup unit to perform a first round of scanning, the image pickup unit performs overall scanning on the detection objects on the slide for the objective lens with the minimum multiple to acquire a region where the detection objects are distributed;

The overall control system controls the image pickup unit to perform a second round of scanning, the image pickup unit observing and selecting points within the area of the distribution of the detection objects with a second multiple of the objective lens and focusing to obtain a focal plane at the second multiple, and performing a full-scan to obtain a plurality of images at the second multiple, while the detection objects of the images obtained at the second multiple are sorted and positioned by the overall control system; and

And the overall control system controls the camera unit to execute a third round of scanning, and the camera unit utilizes the objective lens with the highest multiple to shoot the detection object with the front sequencing to obtain a series of high-definition images according to positioning focusing.

2. the chromosome scanning imaging system of claim 1, wherein the slide feeder has four slide cassettes and each of the slide cassettes has 40 slides therein.

3. The chromosome scanning imaging system of claim 1, wherein the detection object is a chromosome or a cell.

4. The chromosome scanning imaging system of claim 1, wherein the microscope system further comprises a determination unit for determining whether the object is scanned in three rounds.

5. the chromosome scanning imaging system of claim 1, wherein the overall control system further comprises an oil supply system and an oil bottle assembly.

6. The chromosome scanning imaging system of claim 5, wherein the overall control system takes out oil from the oil supply system and the oil bottle assembly to drip on the objective lens with the highest magnification before the scanning unit takes a picture of the test object with the objective lens with the highest magnification to obtain the high-definition image.

7. The chromosome scanning imaging system of claim 6, wherein the objective lens with the highest magnification is a 100-fold objective lens.

8. the chromosome scanning imaging system of claim 1, wherein the objective lens with the smallest multiple is a 1.25-fold objective lens, the objective lens with the second multiple is a 10-fold objective lens, and the objective lens with the highest multiple is a 100-fold objective lens.

9. The chromosome scanning imaging system of claim 1, wherein the overall control system further comprises a sequencing unit to sequence and locate the detectors of the images taken at the second multiple.

10. The chromosome scanning imaging system of claim 9, wherein the sorting unit sorts according to the length of each of the detection objects, the number of each of the detection objects, or the area of each of the detection objects.