KR101873318B1 - Celll imaging device and mehtod therefor - Google Patents

Abstract

An embodiment of the present invention is directed to a method of imaging a cell, comprising: selecting a region of a biological sample including a target cell as a focusing region; Moving the objective lens or the biological sample in a first direction to a first pitch such that a distance between the objective lens and the focusing region sequentially decreases; Selecting a cell region in the focusing region, moving the objective lens or the biological sample in a second direction so that the objective lens is located at a second position, and moving the objective lens or the biological sample Moving a target cell in the cell region through a captured optical image; An edge detection step of performing edge detection on the objective lens and the biological sample to determine an optimum focal distance between the objective lens and the biological sample at a point where a contrast difference between the target cell and the background becomes maximum through the edge detection; A focal length selecting step and an imaging step of performing imaging in a temporal or sequential manner over the entire area of the biological sample at the selected optimum focal distance.

Description

[0001] CELL IMAGING DEVICE AND MEHTOD THEREFOR [0002]

The present invention relates to a cell imaging device and a method thereof, and more particularly, to a highly-identifiable automated cell imaging device capable of counting target cells by photographing and analyzing target cells for each wavelength of light, .

Fluorescence microscopy is the most widely used device for observing cell images in biological, chemical, and medical fields. After obtaining an optical image through a fluorescence microscope, the user can obtain statistical data such as the number of the specific cells (target cells) and the presence ratio. For this purpose, it is essential to obtain a high-quality optical image.

Cell imaging is also applied to cell-based screening or screening. Gene analysis, cancer diagnosis, etc., various methods of examining or examining cells using cells have been developed. For this purpose, imaging through a fluorescence microscope and analysis of the imaged images are required for biological samples containing target cells. An example of such a target cell is blood cancer cells. Circulating Tumor Cells (CTCs) are a primary tumor tissue, a small number of tumor cells that move away from a primary carcinoma and circulate in the blood. It is known that blood cancer cells are present at a rate of about 1 per 10 ⁸ to 10 ⁹ blood cells. It is very important to accurately determine the number or the ratio of blood cancer cells in cancer screening and verification of chemotherapy.

In order to determine the number of target cells and determine their type, the size and shape of each cell must be specified, and the cell boundaries must be clearly identified. Therefore, there is a demand for an apparatus and a method having excellent reliability and economical efficiency for cell imaging so as to clearly identify cell boundaries.

In addition, there is a need for automated cell imaging devices and methods that can process large numbers of biological samples at high rates. These devices and methods are of even greater importance, particularly in the field of digital image analysis involving cell counting (cell counting) functions.

U.S. Published Patent Application No. 2012-0148142 (Published on June 14, 2012)

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made in view of the above problems, and an object of the present invention is to provide an automated cell imaging apparatus and method capable of counting target cells by photographing the target cells according to their wavelengths.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not intended to limit the invention to the precise form disclosed. There will be.

According to an aspect of the present invention, there is provided a method of imaging a cell, the method comprising: selecting a region of a biological sample including a target cell as a focusing region; Moving the objective lens or the biological sample in a first direction to a first pitch so that the distance between the objective lens and the focusing area is sequentially decreased; Selecting a cell region in the focusing region through a picked-up optical image; moving the objective lens or the biological sample in a second direction so that the objective lens is located at a second position; Moving the lens or the biological sample to a second pitch in a first direction, The method comprising: an edge detection step of performing edge detection with respect to a target cell in the cell region through an edge detection step of detecting a distance between the objective lens and a biological sample at a point where a contrast difference between a target cell and a background becomes maximum through the edge detection; An optimal focal length selection step of selecting an optimal focal length as a best focal length, and an imaging step of performing imaging in a temporal or sequential manner over the entire area of the biological sample at the selected optimal focal distance do.

In an embodiment of the present invention, the distance between the objective lens and the biological sample in the second position may be less than the distance between the objective lens and the biological sample in the first position.

In an embodiment of the present invention, the second pitch may be smaller than the first pitch.

In an embodiment of the present invention, in the optimum focal length selecting step, a section having the largest intensity difference between two adjacent pixels on a predetermined line profile in the cell region is detected, and a size difference between the two pixels The optimum focal distance between the objective lens and the biological sample can be selected.

In an embodiment of the present invention, in the imaging step, an optical image for each of the biological samples can be obtained in two or more wavelength regions.

According to an aspect of the present invention, there is provided a method of imaging a biological sample including a target cell, the method comprising: moving an objective lens to a first pitch, And moving the objective lens at a second pitch smaller than the first pitch in the selected cell area and moving the objective lens at a second pitch smaller than the first pitch in the selected cell area, Obtaining an optical image and selecting an optimal focal distance between the objective lens and the biological sample through edge detection for a target cell in the second optical image do.

In an embodiment of the present invention, in the step of selecting the optimum focal length, the distance between the objective lens and the biological sample at the point where the contrast difference between the target cell and the background is maximized through the edge detection is set as an optimal focal distance Can be selected.

In an embodiment of the present invention, in the step of selecting the optimal focal length, a section having a largest size difference between two adjacent pixels on a predetermined line profile in the cell region is detected, and a size difference between the two pixels The optimum focal distance between the objective lens and the biological sample can be selected.

In an embodiment of the present invention, the target cell may be a blood cancer cell (CTC).

According to an aspect of the present invention, there is provided a biological sample including a plate on which a biological sample containing a target cell is placed, a light source for irradiating incident light on the plate side, an objective lens for condensing light excited by the biological sample, And a drive unit for moving the objective lens or the plate in the z-axis direction. The apparatus includes an optical system for analyzing the optical image picked up by the image pickup unit, Wherein the control unit selects the cell region while moving the objective lens or the plate at the first pitch in the first direction after positioning the objective lens at the first position, Moving the objective lens or plate in a second direction to position the objective lens at a second position, Or moving the plate to a second pitch in a first direction, and selecting an optimal focal distance.

In an embodiment of the present invention, the controller may select an optimal focal length through edge detection on the target cell.

In the embodiment of the present invention, the controller may select a distance between the objective lens and the biological sample as an optimal focal distance at a point where the contrast difference between the target cell and the background becomes maximum through the edge detection.

In the embodiment of the present invention, the control unit detects an interval in which a size difference between two adjacent pixels is largest on a predetermined line profile in the cell region, and uses the difference in size between the two pixels, The optimum focal length between the samples can be selected.

According to an embodiment of the present invention, it is possible to provide a highly-distinguishable automated cell imaging device and method thereof capable of counting target cells by photographing and analyzing target cells that require analysis by light wavelengths. In addition, according to the cell imaging apparatus and method of the present invention, the boundaries of cells can be clearly distinguished and the number and type of target cells can be accurately determined. In addition, a large number of biological samples can be processed at high speed.

It should be understood that the effects of the present invention are not limited to the above effects and include all effects that can be deduced from the detailed description of the present invention or the configuration of the invention described in the claims.

1 is a photograph of an optical image sample according to the distance between a cell and an objective lens.
2 is a schematic block diagram of a cell imaging device according to an embodiment of the present invention.
3 is a flowchart illustrating a cell imaging method according to an embodiment of the present invention.
Figure 4 is a photograph showing a cell region in a biological sample.
FIGS. 5 and 6 are reference views showing an actual process of edge detection for one target cell.
7 is a photograph showing an optical image of a target cell according to a focal distance.
8 is a flowchart illustrating a cell imaging method according to another embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described with reference to 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. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout the specification, when a part is referred to as being "connected" (connected, connected, coupled) with another part, it is not only the case where it is "directly connected" "Is included. Also, when an element is referred to as "comprising ", it means that it can include other elements, not excluding other elements unless specifically stated otherwise.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, the terms "comprises" or "having" and the like refer to the presence of stated features, integers, steps, operations, elements, components, or combinations thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the drawings attached to the present invention, an optical image for a cell uses a monochrome inverted image in an actual image.

FIG. 1 is a photograph of an optical image sample according to a distance between a cell and an objective lens, and FIG. 2 is a schematic diagram of a cell imaging device according to an embodiment of the present invention.

The cell imaging system is a system for observing and photographing cells at various wavelengths by placing stained cells on a platform such as a slide glass. The cell imaging system includes an automated cell counting module, a fluorescence intensity analysis module, a transfection efficiency analysis module, a 3D deconvolution module, a cytology-based cell sorting / classification / cognition module. Also, as a user-friendly function, a measurement function, an automatic report generation function, and a DB management function can be included as a user interface.

These cell imaging systems include digital image analysis equipment to distinguish cells, culture fluids, debris, and to identify and count cells that the user desires. There is a need for a high quality optical image extraction device, i. E., A cell imaging device, for accurately determining cell boundaries in such cell imaging systems.

Figs. 1 (a) to 1 (f) are optical image sample photographs of the distance between the target cell and the objective lens, and it can be seen that the identification of the cells takes place only when an appropriate focal length is given. For example, the boundaries of the cells can be appropriately determined only through the optical image of FIG. 1 (d) to determine the size and shape of the cells, and the type of the cells can be determined and counted. In the remaining optical images, it is difficult to identify or delimit cells.

2, a cell imaging apparatus 10 according to the present invention includes a plate 1, a light source 2, an objective lens 3, an imaging unit 4, a driving unit 5, and a control unit 6 do.

The plate (1) is placed with a biological sample (S) containing target cells. The target cell may be a fluorescently stained cell by a specific sample, or a specific cell such as a specific hemocyte cell or a blood cancer cell (CTC), and there is no particular limitation on its type. It does not matter whether it is a live cell or a dead cell. The plate 1 may be a slide glass, and a jig for fixing the slide glass may be included. It is also possible that one biological sample S is placed on the plate 1, a plurality of samples are arranged on one plate, or a plurality of independent plates are juxtaposed. The plate 1 may also be located in the chamber.

The light source 2 irradiates incident light to the plate 1 side. The light source 2 may be an LED-like illumination, and the light emission time may be adjusted within a predetermined range according to a control operation of the user's selection or control unit. The light source 2 may also be a transmission light source or a fluorescence light source. Also, the light source 2 may be provided so as to have two or more modes. In this case, for example, a dark field mode and a bright field mode may be provided.

The objective lens 3 condenses the excited light in the biological sample. The light introduced through the objective lens 3 is directed to the imaging section 4 via an optical element. The optical element may include a filter for detecting cells stained with a fluorescent dye or an intracellular material.

The imaging unit 4 detects light that has passed through the objective lens 3 and imaged it. The image pickup section 4 may be, for example, a CCD camera.

The driving unit 5 moves the objective lens 3 or the plate 1 in the z-axis direction. Here, the z-axis direction indicates the direction in which the objective lens 3 and the plate 1 are opposed to each other and generally refers to the gravitational direction, but this is not necessarily the case. The distance in the normal direction between the objective lens 3 and the plate 1 can be increased or decreased by moving the objective lens 3 or the plate 1 in the z-axis direction. In the figure, the distance between the objective lens 3 and the plate 1 is represented by d, and d can be changed according to the operation of the driving unit 5. [

The control section 6 analyzes the optical image picked up by the image pickup section 4 and also generates a control signal for the drive section 5. [ The control unit 6 may include a microprocessor, a memory, and the like.

By the processing and signal generation in the control section 6, the objective lens 3 is first positioned at the first position. Next, the cell area is selected while moving the objective lens 3 or the plate 1 in the first direction to the first pitch. Next, the objective lens 3 or the plate 1 is moved in the second direction in the cell region to position the objective lens at the second position. Next, the objective lens 3 or the plate 1 is moved to the second pitch in the first direction, and the optimum focal length is selected.

Here, the first position corresponds to a position where the distance between the objective lens 3 and the plate 1 is considerably larger than the optimum focal distance. The first direction means a direction in which the objective lens 3 and the plate 1 are brought closer to each other, and the second direction is a direction opposite to the first direction. For example, when the objective lens 3 is positioned on the lower side of the plate 1 and the objective lens 3 is movable and the position of the plate 1 is fixed, as shown in Fig. 2, And the second direction means the lower direction of the z axis.

On the other hand, when the first position corresponds to a position where the distance between the objective lens 3 and the plate 1 is considerably smaller than the optimum focal distance, the first direction is the distance between the objective lens 3 and the plate 1, Direction, and the second direction is the reverse direction of the first direction.

Meanwhile, the controller 6 selects the optimal focusing distance through edge detection on the target cell. Generally, the focal length is given as a constant in a lens or optical system, but it is assumed herein to mean the distance between the objective lens and the plate, specifically the distance between the center plane of the objective lens and the biological sample or target cell on the plate.

The controller 6 selects the distance between the objective lens 3 and the biological sample S as the optimum focal distance at a point where the contrast difference between the target cell and the background becomes maximum through the edge detection. For this purpose, the controller 6 detects an interval in which a size difference between two adjacent pixels is largest on a predetermined line profile in a cell region, and uses the difference in size between the two pixels, The optimum focal distance between the biological sample 3 and the biological sample S can be selected.

The above-described analysis of the optical image in the control unit 6 and the control process of the driving unit 5 will be described in detail below with reference to the cell imaging method.

FIG. 3 is a flow chart showing a cell imaging method according to an embodiment of the present invention, FIG. 4 is a photograph showing a cell region in a biological sample, and FIGS. 5 and 6 are actual processes of edge detection for one target cell FIG. 7 is a photograph showing an optical image of a target cell according to a focal distance. FIG.

In the cell imaging method according to the embodiment of the present invention, first, a partial area of the biological sample including the target cell is selected as the focusing area (step S10). Here, the target cell may be a blood cancer cell (CTC).

Referring to Fig. 2, a part of the biological sample S placed on the plate 1 becomes a focusing area F. Fig. In the embodiment of the present invention, by selecting a part of the region where the target cell is located in the biological sample as the focusing region and selecting the optimum focal distance in this focusing region, finally, a clear optical image of the entire region of the biological sample can be obtained .

Next, the objective lens is positioned at the first position so that lens focusing (i.e., selection of an optimum focal length) is performed in the focusing area (step S20).

Next, the objective lens or the biological sample is moved to the first pitch in the first direction so that the distance between the objective lens and the focusing area sequentially decreases (S30). Moving a biological sample is synonymous with moving the plate or target cell in the z-direction.

Next, a cell area is selected in the focusing area through the picked-up optical image (step S40). Referring to FIG. 4, the cell region refers to a region in which one or more cells to be processed are present for the selection of an optimum focal length in the focusing region.

Next, the objective lens or the biological sample is moved in the second direction so that the objective lens is located at the second position (step S50). Here, the distance between the objective lens and the biological sample in the second position may be smaller than the distance between the objective lens and the biological sample in the first position in the step S20 previously.

Next, the objective lens or the biological sample is moved to the second pitch in the first direction (step S60). Here, the second pitch may be smaller than the first pitch.

In the above description, the meanings of the first position, the first direction, and the second direction are the same as those described in the foregoing embodiment. For example, the first position may correspond to a position where the distance between the objective lens and the plate or biological sample is significantly greater than the optimal focal distance. The first direction means a direction in which the objective lens and the biological sample come close to each other, and the second direction can be a direction opposite to the first direction.

It is assumed that the z-axis position of the plate or biological sample is fixed, only the objective lens moves in the z-axis direction, and the objective lens is located on the lower side of the plate. It should be noted that the figures below are for experiments or illustrations only.

First, in step S20, the objective lens moves to a position of -1000 mu m. That is, the first position is -1000 mu m.

Next, in step S30, the objective lens moves at intervals of +10 占 퐉. That is, the first direction is the upward direction of the z axis, and the first pitch is 10 占 퐉. If it is assumed that the z-axis moving unit is a step and a movement of 0.5 [mu] m is performed per step, a movement of 20 steps occurs at the time of one movement in step S30.

In this manner, the measurement of the cell area is performed while the objective lens is moving. After the objective lens is moved a predetermined number of times, the cell area is selected (step S40). Here, the selection of the cell region means that one or more cells to be processed for the selection of the optimum focal length in the optical image have been selected, and that the objective lens has moved closer to the optimum focal distance do.

When the cell region is selected, the position of the objective lens is shifted by -100 m from the current position. That is, the position moved by 100 占 퐉 in the downward direction of the z axis in the step S50 becomes the second position.

Next, in step S60, the objective lens moves at + 2 占 퐉 intervals. That is, the second pitch becomes 2 탆, and the movement of 4 steps occurs when moving once. The movement in steps S20 to S60 is performed so that the moving distance of the objective lens is firstly increased (first pitch) so that the focal distance serving as the candidate is firstly selected, and then the range is narrowed so that the moving distance of the objective lens is reduced (Second pitch), and searching for the optimum focal length. This can reduce the time consumption to reach the optimum focal length.

In the above description, it is assumed that the objective lens moves. Alternatively, the plate (or the biological sample) may move, or the objective lens and the plate may move. In this case, the actual meaning of the first direction and the second direction may be changed.

Referring again to FIG. 3, edge detection is performed on the target cells in the cell region through the captured optical image (step S70). Edge detection determines the boundaries of specific objects in an image, and edge detection of a cell image detects differences in feature contrast so as to distinguish backgrounds from cells to be detected. In order to increase the contrast difference, the cells are stained with fluorescent dye or labeled with a marker.

Referring to FIG. 5, a pixel value is measured on a line A-A 'around a cell in a cell region (see FIG. 5 (a)). Figure 5 (b) shows the distribution of pixel values along the line profile A-A '. The gradient information of the pixel values distributed along the line profile is shown in FIG. 5 (c). The gradient represents the size difference between adjacent two pixels on the line profile in terms of edge strength. The gradient is a difference in size between two adjacent pixels at the points E1 and E2 corresponding to the edge of the cell on the line A-A ' The absolute value of the intensity becomes the largest. That is, the point where the absolute value of the edge intensity is largest can be defined as the cell boundary.

Referring again to FIG. 3, in step S80, the distance between the objective lens and the biological sample is selected as the optimum focal distance at a point where the contrast difference between the target cell and the background becomes maximum through the edge detection.

Here, an interval in which a size difference between two adjacent pixels is largest on a predetermined line profile in a cell region is detected, and an optimum focal length between the objective lens and the biological sample is selected using the difference in size between the two pixels.

In Fig. 6, the optical images (a, b, c) taken at different focal lengths and accordingly the edge intensities on the line profile are shown. As shown, it can be seen that the A image shows a sharper edge than the B and C images because the edge intensity on the line profile corresponding to the A image is less than the edge on the line profile corresponding to the B and C images It can be confirmed by having a larger value as compared with the strength. That is, when an optical image having the largest difference in magnitude (edge strength) between two adjacent pixels on the line profile is detected and the size difference between these two pixels is the largest, the optical image is picked up The optimum focal length can be selected.

Fig. 7 shows an optical image (total of 63 optical images) of the captured cell region moving the objective lens at the second pitch interval. In the figure, it can be seen that the 48th optical image has the sharpest edge through the edge strength measurement on the line profile, and thus the focal length corresponding to the 48th optical image is selected as the optimum focal length.

Finally, the imaging is performed temporally or sequentially over the entire area of the biological sample at the selected optimum focal distance (S90). Optical images for biological samples can be obtained in two or more wavelength regions, respectively. For example, after obtaining an optical image in the blue wavelength region, it is then possible to obtain an optical image in the green wavelength region and the red wavelength region.

8 is a flowchart illustrating a cell imaging method according to another embodiment of the present invention. The configuration steps of the cell imaging method according to this embodiment are similar to the configuration steps individually described in the previous embodiment.

In the cell imaging method for a biological sample containing a target cell according to the present embodiment, first, the objective lens is moved to the first pitch, a first optical image for the target cell is obtained for each pitch, A cell area is selected through step S100.

Next, in step S100, the objective lens is moved to a second pitch smaller than the first pitch in the selected cell area, and a second optical image is obtained for each target cell in step S200.

Finally, the optimal focal length between the objective lens and the biological sample is selected through edge detection on the target cell in the second optical image obtained in step S200 (step S300). Here, the distance between the objective lens and the biological sample can be selected as the optimum focal distance at a point where the contrast difference between the target cell and the background becomes maximum through the edge detection. In addition, an interval in which a size difference between two adjacent pixels is largest on a predetermined line profile in a cell region is detected, and an optimum focal length between the objective lens and the biological sample can be selected using the size difference between these two pixels . The detailed configuration thereof is the same as in the above-described embodiment.

Through the embodiments of the present invention described above, the target cells that need to be analyzed can be photographed by the respective wavelengths, and the target cells can be counted. In particular, the cell boundaries can be clearly distinguished to accurately determine the number and type of target cells, and a plurality of biological samples can be processed at high speed.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

10 Cell Imaging Device
1 plate
2 light source
3 objective lens
4 image pickup unit
5 drive unit
6 control unit

Claims (13)

As a cell imaging method,
Selecting a partial region of a biological sample including a target cell as a focusing region,
Causing the objective lens to be in a first position such that lens focusing is performed in the focusing region;
Moving the objective lens or the biological sample to a first pitch in a first direction so that the distance between the objective lens and the focusing region sequentially decreases;
Capturing the biological sample after moving the objective lens or the biological sample to a first pitch in a first direction and selecting a cell region in the focusing area through the captured optical image,
Moving the objective lens or the biological sample in a second direction so that the objective lens is located at a second position;
Moving the objective lens or the biological sample to a second pitch in a first direction,
An edge detection system for imaging the biological sample after the step of moving the objective lens or the biological sample to the second pitch in the first direction and edge detection of the target cell in the cell area through the captured optical image, Step,
Selecting an optimal focal length as a distance between the objective lens and the biological sample at a point where a contrast difference between the target cell and the background is maximized through the edge detection;
An imaging step of performing imaging in a temporal or sequential manner over the entire area of the biological sample at the selected optimum focal distance
Gt; of claim < / RTI >
The method according to claim 1,
Wherein the distance between the objective lens and the biological sample in the second position is smaller than the distance between the objective lens and the biological sample in the first position.
The method according to claim 1,
Wherein the second pitch is smaller than the first pitch.
The method according to claim 1,
The method comprising the steps of: detecting, in the optimum focal length selection step, an interval in which an intensity difference between two adjacent pixels on a predetermined line profile in the cell area is greatest and using the difference in size between the two pixels, Wherein an optimal focal distance between the samples is selected.
The method according to claim 1,
Wherein in the imaging step, an optical image for the biological sample is obtained in two or more wavelength regions, respectively.
A method of cell imaging for a biological sample comprising a target cell,
Moving an objective lens to a first pitch, obtaining a first optical image for a target cell for each pitch, and selecting a cell region through the first optical image,
Moving an objective lens in the selected cell area to a second pitch smaller than the first pitch and obtaining a second optical image for a target cell for each pitch,
Selecting an optimal focal distance between the objective lens and the biological sample through edge detection on a target cell in the secondary optical image
Lt; / RTI >
The distance between the objective lens and the biological sample is selected as the optimum focal distance at the point where the contrast difference between the target cell and the background becomes maximum through the edge detection in the step of selecting the optimal focal distance,
Wherein the step of selecting the optimal focal length includes the step of detecting an interval in which a magnitude difference between two adjacent pixels on the predetermined line profile in the cell region is largest and using the magnitude difference between the two pixels, Wherein the optimal focal distance is selected.
delete delete 7. The method according to any one of claims 1 to 6,
Wherein the target cell is blood cancer cell (CTC).
A plate on which the biological sample containing the target cell is placed,
A light source for irradiating incident light onto the plate side,
An objective lens for condensing the excited light in the biological sample,
An imaging unit that detects light having passed through the objective lens,
A driving unit for moving the objective lens or the plate in the z-axis direction,
And a control unit for analyzing the optical image picked up by the image pickup unit and generating a control signal for the drive unit,
The objective lens or plate is moved in a first direction to select a cell region while the objective lens or plate is moved to a first position after positioning the objective lens at a first position, And moving the objective lens or the plate to a second pitch in a first direction to select an optimum focal length,
The control unit captures the biological sample after moving the objective lens or plate in the first direction to the second pitch, performs edge detection on the target cell in the cell region through the captured optical image , An optimal focal length is selected through edge detection on the target cell,
Also, the controller may select the distance between the objective lens and the biological sample as an optimal focal distance at a point where the contrast difference between the target cell and the background is maximized through the edge detection,
Wherein the controller detects an interval in which a size difference between two adjacent pixels on a predetermined line profile in the cell area is largest and selects an optimum focal length between the objective lens and the biological sample using a size difference between the two pixels The cell imaging device comprising:
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