KR101882696B1 - Examination method of sputum smear sample for automatic inspection system consisting of focus-tunable microscope - Google Patents

Abstract

The present invention relates to a method for inspecting a sputum smear sample of an automatic inspection system having a varifocal speculum, which comprises the following steps of: deducing statistics information on a depth direction inspected range of a real inspected sample based on inspection for individual distribution in at least one inspected sample; and detecting an individual while moving a focus of a varifocal lens by the thickness of the depth direction in accordance with the statistics information with respect to the real inspected sample by reflecting the statistics information.

Description

[0001] The present invention relates to a sputum smear sample inspection method, and more particularly, to a sputum smear sample inspection method,

The present invention relates to a sputum smear sample inspection method of an automatic inspection system constituted by a focus variable microscope, and more particularly, to a method of inspecting a sputum smear sample using a fouling automatic lens inspection system And a focal variable optical microscope capable of automatically inspecting an object to be inspected.

 In general, the microscopy is the most common observation tool for examining living cells and bacteria, and its composition and application are very diverse.

2. Description of the Related Art In recent years, research and development of an automatic inspection system capable of effectively detecting and analyzing an object from images acquired by the development of artificial intelligence technology as well as development of a high-performance optical system have been actively conducted. It also belongs to this field.

The sputum smear test first smears the sputum with a certain area on the slide, then stains the individual to look prominent, and then detects the individual by observing the specimen.

In this case, as shown in FIG. 1, when the observation object is accurately located at the focus of the objective lens, the light from the objective lens is collimated and is imaged on the image sensor through the tube lens, The light transmitted through the objective lens is transmitted to the tube lens in the form of convergence or figuration and the convergent or divergent light forms an image out of the focal position of the tube lens, .

In particular, since the general magnification used in automation of sputum inspection is a high magnification, the depth of focus that can be observed, that is, the depth range is very narrow within a few microns, so when observing a sample having a depth volume such as sputum, Mature tuberculosis at different depths may be blurry or unobserved. In order to identify mycobacteria existing outside the depth of the scope of the sperm, And confirms the presence of M. tuberculosis.

However, in the conventional method, since the height adjustment of the platform or the optical system is used for the focus movement, the conveying speed is slow and it is not suitable for the implementation of the automatic inspection system. There is a method of changing the focal position of the probe by applying a zoom optical system configuration, but a normal mechanical zoom optical system can cause mechanical vibration and its operation characteristic is not fast enough.

In addition, in the case of test samples such as sputum, the smear is relatively thick and the thickness deviation is comparatively large. However, in the conventional automatic inspection system, only a single layer, that is, , And a judgment was made. There is a problem in that the individual observation method for the single layer does not reflect individuals existing at a depth, and thus the inspection system is highly likely to make a judgment error.

Korean Patent Registration No. 10-0164281

In order to solve the above problems, the present invention proposes an automatic inspection system comprising a focus variable microscope capable of easily detecting a position of an object existing in a sample volume having a depth volume, The object of the present invention is to provide a sputum smear sample inspection method.

According to another aspect of the present invention, there is provided a sputum smear sample inspection method of an automatic inspection system comprising a focus variable microscope according to an embodiment of the present invention, And detecting the object by moving the focal point of the focus variable lens with respect to the actual inspection sample by the thickness in the depth direction according to the statistical information with reference to the statistical information.

As described above, in the sputum smear sample inspection method of the automatic inspection system configured by the focus variable microscope according to the embodiment of the present invention, the sputum smear sample is automatically inspected using the liquid phase focus variable lens capable of focusing, The time can be shortened, the judgment performance can be improved, and it can be utilized for tracking an object existing in a sample having a depth volume.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view of a general configuration of a probe. Fig.
2 is a schematic view of a focus variable mirror according to an embodiment of the present invention.
3 is a flowchart illustrating a sputum smear sample inspection process in an automatic inspection system configured with a focus variable microscope according to an embodiment of the present invention.
FIG. 4 is a flowchart showing a process of setting control data for controlling the focus variable lens of FIG. 3; FIG.
FIG. 5 is a flowchart showing a process of deriving the statistical information of FIG. 3;

The advantages and features of the present invention and the techniques for achieving them will be apparent from the following detailed description taken in conjunction with the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. The present embodiments are provided so that the disclosure of the present invention is not only limited thereto, but also may enable others skilled in the art to fully understand the scope of the invention.

The terms used herein are intended to illustrate the embodiments and are not intended to limit the invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. It is to be understood that the terms 'comprise', and / or 'comprising' as used herein may be used to refer to the presence or absence of one or more other components, steps, operations, and / Or additions.

In addition, like reference numerals denote like elements throughout the drawings, and a detailed description of known features and techniques may be omitted so as to avoid unnecessarily obscuring the discussion of the described embodiments of the present invention .

2 is a view schematically showing a focus variable mirror according to an embodiment of the present invention.

As shown in FIG. 2, the focus variable optical probe according to the embodiment of the present invention includes an objective lens for converting light emitted from an object to be measured (smear sample) into a parallel light beam, and an objective lens for focusing the parallel light rays, A focus variable lens, and an image sensor in which condensed light is imaged. In this case, the focus variable lens may be a liquid lens, in which a liquid having an optical performance is filled between polymer membranes, and the shape of the polymer membrane changes to a concave or a convex shape by driving an actuator located at the edge of the membrane.

The sputum smear sample inspection method of the automatic inspection system configured with the focus variable micro-mirror according to the embodiment of the present invention will be described as follows.

FIG. 3 is a flowchart showing a sputum smear sample inspection process of an automatic inspection system configured with a focus variable microscope according to an embodiment of the present invention. FIG. 4 is a flowchart showing a process of setting control data for controlling the focus variable lens of FIG. And FIG. 5 is a flowchart showing the process of deriving the statistical information of FIG.

As shown in FIGS. 3 to 5, the sputum smear sample inspection method of the automatic inspection system configured by the focus variable microscope according to the embodiment of the present invention includes: controlling the focus shift amount of the focus variable lens and the focus shift of the focus variable lens Control data for controlling the focus variable lens is set based on the control current amount (S100).

Here, in order to apply a microscope composed of a focus variable lens using a liquid lens to automation, it is necessary to control the focus variable lens in a fixed amount. In particular, it is necessary to be able to accurately control the amount of focus movement, and to derive control data for precisely controlling the focus variable lens from the relationship between the amount of focus movement and the amount of control current for controlling the focus variable lens.

Referring to FIG. 4, the process of setting the control data will be described in detail. In step S110, a resolution target is moved in a vertical direction and a current is applied to the focus variable lens so that the resolution target is clearly observed.

Specifically, the resolution target may be a stage capable of vertically moving directly below the objective lens, and a resolving target for measuring the sharpness of the mirror image is disposed on the upper surface of the stage. Thereafter, the stage is moved vertically to move the resolution target in the vertical direction, and the focus of the focus variable lens is adjusted to apply a current to the focus variable lens so that the resolution target photographed through the image sensor is clearly observed. At this time, the moving distance of the resolving target may be set according to the object size of the sample to be inspected or the depth of the microscope composed of the objective lens and the focus variable lens.

In step S120, a focus position and a current applied to the focus variable lens are sequentially measured in accordance with the vertical movement of the resolution target and the focus movement amount and the control current amount are set as control data.

Here, the control current value, which is the current applied to the focus variable lens, is measured at the focus position where the resolution target is clearly observed and at the focus position where the resolution target is clearly observed.

At this time, the resolution target is moved vertically by a predetermined interval, and the focus shift amount and the control current value are sequentially measured and accumulated at each movement interval, and the accumulated measurement values are converted into data. Thus, quantitative control for automatically controlling the focus variable lens Create and set data.

Accordingly, the present invention can control the focus variable lens using quantitative control data to enable precise focus movement for object detection.

On the other hand, by using the control data, it is possible to correct the mechanical mounting error between the probe and the ground on which the sample is placed. In the automatic inspection system, the specimen should be mounted at a right angle to the ground, but it may be inclined at a right angle due to a mechanical error during fabrication and assembly. In this case, A problem occurs. It is possible to measure the amount of focus movement in the outer area where the sharpness is degraded through the resolution target, to derive the tilt between the ground and the sight using the size of the observation area and the amount of focus movement, and to correct the tilt using this.

Next, based on the individual distribution test in the sample test sample, it is possible to obtain statistical information on the depth range of the actual test sample spooled (S200).

Specifically, referring to FIG. 3, a reference position is set for the sample inspection sample and the inspection area is divided (S210).

Here, the reference position setting is for measuring the individual distribution in the test sample in the form of a coordinate system through the microscope comprising the focus variable lens, and the reference position of the measurement can set the reference position for the plane and the reference position for the depth direction.

First, a reference position for a plane is set. At this time, the reference position for the plane can be set according to the direction in which the smeared sample inspection sample is scanned. For example, when the scan direction of the sample inspection sample is a scan of the scan line direction, one side edge of the plane to be observed can be set as the reference position. Alternatively, when the direction of scanning the sample to be inspected is a spiral scan, the center of the plane to be observed can be set as the reference position.

Further, when the reference position for the plane is set, the reference position for the direction perpendicular to the set plane, i.e., the depth direction is set. In this case, the reference position for the depth direction is set as a reference position for the depth direction by driving a focus variable lens, and a relative position with respect to the position is measured as a depth position of the individuals.

In addition, an inspection area for the sample inspection sample is set. At this time, the inspection area is determined according to the area of the test sample to be examined. The inspection area is divided into a plurality of local areas in consideration of the area that can be inspected at one time according to the magnification of the inspection area and the sensing area of the image sensor, And the local distribution of the entire smear region is measured by integrating the local regions that have been divided by the coordinate management and the inspection is completed.

Next, three-dimensional grid coordinates are assigned according to the reference position and the inspection area (S220).

Here, the inspection region may be represented by three-dimensional grid coordinates based on the reference position, and the positions of the objects detected in the inspection sample may be represented by three-dimensional grid coordinates.

Specifically, the plane is divided into N (horizontal) X M (vertical) lattice planes about the reference position in the inspection region, and the depth direction is divided into K layers based on the reference position.

At this time, the lattice spacing of the divided three-dimensional grid coordinates can be set in consideration of the maximum size of the object existing in the test sample and the depth range of the specimen.

The lattice spacing is used as a basic interval of layer division when inspecting specimens smeared in the automatic inspection system by dividing them into layers, or between the range of the depth of the specimen and the maximum size of the object Lt; / RTI > For example, an individual (Mycobacterium tuberculosis) has a size range of 2 to 5 microns and a depth range of 2 to 10 microns depending on the magnification of the optical system used. At this time, it is possible to set the lattice spacing of the three-dimensional lattice co-ordinates so that the smallest numerical value in the object size and the depth range of the optical system is minimized and the largest numerical value is maximized.

Thereafter, an object distributed in the sample inspection sample is detected through focus movement of the focus variable lens (S230).

At this time, the object detection in the sample inspection sample can be performed by applying a separate pattern matching optimized for the object detection or a deep learnign detection algorithm based on the artificial intelligence.

In operation S240, the 3D grid coordinates of the detected object are stored.

Here, the position of the detected object may be stored in the internal memory or a separate recording device as coordinates according to the set three-dimensional grid coordinates.

Thereafter, when the focal point of the focal variable lens shifts and the sample is removed, the focal point shift of the focal variable lens is completed, and the detection of the object for one sample inspection sample is completed.

At this time, the object detection process can be repeated as many times as the number of sample inspection samples prepared. That is, the step of setting the reference position for the sample inspection sample and storing the position of the detected object in the step of detecting the object from the step S210 of dividing the inspection region into the assigned three-dimensional grid coordinates (S240 ) To perform object detection on a plurality of sample inspection samples (S250). This is because significant statistical information can not be obtained only by the object detection information for one sample inspection sample.

Next, statistical information on the detected three-dimensional grid coordinates of the object is derived (S260).

Here, statistical information on the individual distribution can be derived by collectively processing the individual information detected from the plurality of sample inspection samples.

At this time, the statistical information may be a minimum and a maximum depth value, an average value and a deviation of the positions of the objects.

Next, an automatic inspection system composed of a focus variable microscope in which the above-described statistical information is reflected is used to determine the focus of the focusable lens only within a predetermined depth range (the minimum depth position and the maximum depth position where the object is distributed) Movement is performed to detect objects existing at respective depths.

Therefore, the sputum smear sample inspection method of the automatic inspection system constituted by the above-mentioned focus variable microscope can limit the inspection range to the depth direction of the thick smear sample, thereby eliminating the inspection for the unnecessary area, It is possible to shorten the inspection time of the sample that is automatically performed using the variable lens, improve the determination performance, and can be utilized for rapid tracking management of the object existing in the sample having the depth volume.

The singular forms herein include plural forms unless the context clearly dictates otherwise. Also, components, steps, operations, and elements referred to in the specification as " comprises " or " comprising " refer to the presence or addition of one or more other components, steps, operations, elements, and / or devices.

The present invention has been described with reference to the preferred embodiments. It is to be understood that all embodiments and conditional statements disclosed herein are intended to assist the reader in understanding the principles and concepts of the present invention to those skilled in the art, It will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (6)

Deriving statistical information on a depth direction inspection range of an actual inspection sample on the basis of an individual distribution inspection in at least one sample inspection sample; And
Detecting the object by moving the focal point of the focus variable lens by the thickness in the depth direction according to the statistical information with respect to the actual test sample by reflecting the statistical information;
, ≪ / RTI &
The step of deriving the statistical information may include:
Setting a reference position for the sample inspection sample and dividing the inspection area;
Assigning three-dimensional grid coordinates according to the reference position and the inspection area;
Detecting an object distributed in the sample inspection sample through a focus shift of the focus variable lens;
Storing three-dimensional grid coordinates of the detected entity in the detecting the entity; And
Deriving statistical information on the detected three-dimensional grid coordinates of the object;
The method comprising the steps of: detecting a sputum smear sample in an automatic inspection system,
The method according to claim 1,
Prior to deriving the statistical information,
Further comprising the step of setting control data for controlling said focus variable lens on the basis of a focus shift amount of said focus variable lens and a control current amount for controlling focus shift of said focus variable lens, Sample Inspection Method.
3. The method of claim 2,
Wherein the step of setting control data for controlling the focus variable lens comprises:
Moving a resolution target in a vertical direction and applying a current to the focus variable lens such that the resolution target is clearly observed; And
Sequentially measuring a position that is observed clearly according to a vertical movement of the resolving target and a current applied to the focus variable lens to set the focus shift amount and the control current amount as data for control data;
The method comprising the steps of: detecting a sputum smear sample in an automatic inspection system,
delete The method according to claim 1,
The reference position
And a focus variable microscope for setting a reference position for the plane of the sample inspection sample and a reference position for the depth direction.
The method according to claim 1,
Prior to deriving statistical information on the three-dimensional grid coordinates of the detected entity,
Setting a reference position for the sample inspection sample, storing the position of the detected object in the three-dimensional grid coordinates assigned in the step of dividing the inspection area to the step of detecting the object, The method of testing the sputum smear sample in an automatic inspection system composed of variable focus microscope.

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