JP2003015056A - Method and device for picking up image - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide image pickup device capable of efficiently and quickly detecting, picking up image and analyzing an optimum image pickup position on an object analysis without requiring skill, and an image pickup method. SOLUTION: This device is provided with an optical lighting part 2 as a detecting means for detecting an object such as a plurality of cells, objective lenses 6 and a revolver 7, a digital camera 9 as an image pickup means for imaging the object, a mounting stage 3 for mounting the object as a means for moving a microtitre plate 1 to an optional prescribed position and actuators 4 and 5 for moving the mounting stage 3 in X and Y directions, respectively, and a memory 11 for storing picked up image data, and picks up images of the object from around the center of a well 1a toward the periphery of the well 1a in picking up image of the object of a plurality of positions of the well 1a in the microtitre plate 1.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an image capturing method and apparatus for efficiently capturing a subject image most suitable for analysis when capturing a plurality of regions of a subject such as a large number of cells in a microtiter plate.

[0002]

2. Description of the Related Art Recently, when culturing live cells in a microtiter plate and analyzing the effect of reagents,
There is a demand for an evaluation method for performing detailed evaluation by directly confirming the state of cells with a microscope or the like.

Conventionally, in the method of analyzing a subject such as a large number of cells, some parts which are considered to be optimum for analysis are imaged while looking through an eyepiece of a microscope, and then the imaged parts are analyzed. There is. In this way, the operator manually detects the optimum imaging position for analysis.

[0004]

However, in the above-mentioned conventional method, since the determination of the optimum imaging position is performed manually in the analysis of the subject, a great deal of time and labor are required, and the subject such as a cell is It has a problem that it causes deterioration and increases in labor costs. In addition, since the person determines the optimum imaging position, there is a problem in that variations occur depending on the person, which causes an error in the analysis result.

In view of the above, the present invention provides an image pickup method and apparatus capable of efficiently detecting, at high speed, an optimum image pickup position for analyzing a subject without requiring skill, and performing image pickup and analysis. With the goal.

[0006]

In order to solve the above-mentioned problems, the present invention relates to a detection means for detecting a subject such as a plurality of cells in a microtiter plate, an imaging means for capturing an image of the subject and outputting it as image data, and a subject. An image capturing method using an image capturing apparatus including a mounting stage for mounting an object, a moving unit for moving a subject to a plurality of arbitrary imaging positions by moving the mounting stage, and a storage unit for storing image data. Therefore, when imaging an object at a plurality of positions within one well of the microtiter plate, the imaging position is moved from the vicinity of the center of the well toward the peripheral direction of the well to perform imaging.

According to the present invention, without requiring skill,
In analyzing a subject, the optimum imaging position can be detected efficiently, at high speed, and imaging and analysis can be performed.

[0008]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention according to claim 1 is a detection means for detecting a subject such as a plurality of cells in a microtiter plate, an imaging means for picking up the subject and outputting it as image data, and placing the subject on the mount. An image capturing method using an image capturing apparatus, comprising: a mounting stage for moving; a moving unit that moves the subject to a plurality of arbitrary imaging positions by moving the mounting stage; and a storage unit that stores image data. An image capturing method characterized by moving an image capturing position from the vicinity of the center of the well toward the peripheral direction of the well when capturing an image of an object at a plurality of positions in one well of a microtiter plate. It is possible to detect an optimum imaging position efficiently and at high speed in analyzing a subject without requiring.

According to a second aspect of the present invention, a detection means for detecting a subject such as a plurality of cells in a microtiter plate, an image pickup means for picking up an image of the subject and outputting it as image data, and a mounting stage on which the subject is placed. An image pickup apparatus comprising: a moving unit that moves a subject to a plurality of arbitrary image pickup positions by moving a mounting stage; a storage unit that stores image data; and an analysis unit that analyzes the image data. The image pickup feature is characterized in that the moving means moves the image pickup position from the vicinity of the center of the well toward the circumferential direction of the well when the subject is imaged at a plurality of positions in one well of the microtiter plate. The device is capable of efficiently capturing and analyzing an image of a subject suitable for image analysis at high speed without requiring skill.

According to a third aspect of the present invention, a detecting means for detecting a subject such as a plurality of cells in a microtiter plate, an image capturing means for capturing an image of the subject and outputting it as image data, and a mounting stage for mounting the subject. And an image capturing method using an image capturing apparatus including a moving unit that moves a subject to a plurality of arbitrary image capturing positions by moving a mounting stage, and a storage unit that stores image data,
When moving between wells of a microtiter plate,
An image capturing method characterized by moving an image capturing position to an adjacent well to perform image capturing, without requiring skill,
The optimum imaging position can be detected efficiently and at high speed in analyzing the subject.

According to a fourth aspect of the present invention, a detecting means for detecting a subject such as a plurality of cells in a microtiter plate, an image capturing means for capturing an image of the subject and outputting it as image data, and a mounting stage for mounting the subject. An image pickup apparatus comprising: a moving unit that moves a subject to a plurality of arbitrary image pickup positions by moving a mounting stage; a storage unit that stores image data; and an analysis unit that analyzes the image data. The moving means is an image pickup device characterized by moving the image pickup position to an adjacent well when moving between wells of a microtiter plate, and is suitable for image analysis without requiring skill. An image of a subject can be efficiently captured at high speed and analyzed.

According to a fifth aspect of the present invention, a detecting means having a plurality of image pickup magnifications for detecting a subject such as a plurality of cells in a microtiter plate, an image pickup means for picking up an image of the subject and outputting it as image data, and a subject Image pickup including a mounting stage to be mounted, a moving unit that moves the subject to a plurality of arbitrary imaging positions by moving the mounting stage, a unit that switches the imaging magnification, and a storage unit that stores image data An image capturing method using an apparatus, comprising: an image capturing step of capturing an image of a wide range of a subject; a step of determining a target image capturing position based on image capturing information obtained in the image capturing step; An image capturing method characterized by including the step of It can be imaged efficiently fast.

According to a sixth aspect of the present invention, a detecting means having a plurality of image pickup magnifications for detecting a subject such as a plurality of cells in a microtiter plate, an image pickup means for picking up an image of the subject and outputting it as image data, and A mounting stage for mounting, a moving means for moving the subject to a plurality of arbitrary imaging positions by moving the mounting stage, a means for switching the imaging magnification, a storage means for storing image data, and an image data An image capturing apparatus including an analyzing unit for analyzing, wherein the image capturing unit switches an image capturing magnification to capture an image of a wide range of a subject, and the moving unit determines based on image capturing information obtained by the image capturing unit. An image pickup device characterized in that the mounting stage is moved to a desired image pickup position, which picks up an object without requiring any skill, It captures an image of an object that is suitable for image analysis efficiently fast, can be analyzed.

Embodiments of the present invention will be described below with reference to the drawings.

(First Embodiment) FIG. 1 is a system configuration diagram of an image pickup apparatus according to a first embodiment of the present invention.

The image pickup apparatus according to the first embodiment of the present invention includes an optical illumination unit 2 and an objective lens 6 having a plurality of magnifications as a detecting means for detecting a subject such as a plurality of cells in the microtiter plate 1. , And a revolver 7 to which the objective lens 6 is attached. Further, the image pickup device includes a digital camera 9 as a unit that picks up an image of a subject and outputs the image as image data.

In the image pickup apparatus, the mounting stage 3 and the actuators 4 and Y for moving the mounting stage 3 respectively in the X direction are used as means for moving the microtiter plate 1 containing the subject to an arbitrary predetermined position. An actuator 5 for moving in the direction and a stage control unit 10 for designating a movement amount for the actuators 4, 5 are provided.

The image pickup apparatus also includes a host computer 13 for making an operation decision. The host computer 13 is a memory 1 that stores captured image data.
1, an analysis unit 12 for analyzing captured image data, and a display 1 for inputting and confirming a designated operation.
4, a keyboard 15 and a mouse 16. The data analyzed by the analysis unit 12 is stored in the memory 11
Save to.

FIG. 2 is an explanatory diagram showing an example of an image pickup method of wells in a microtiter plate. An enlarged view 21 of the inside of the well 1a shown in FIG. 2 shows an example of an imaging method in which the imaging positions are selected in the order of m from the center of the well 1a toward the periphery of the well 1a in a spiral shape. There is. In addition, the order is not limited to
When capturing an image of a subject, the well 1a is moved from near the center of the well 1a.
If the image pickup position is selected toward the periphery of, the present invention is applicable.

FIG. 3 is an operation flowchart of the image pickup device according to the first embodiment of the present invention.

First, the display 14 and the keyboard 1
5. The mouse 16 is used to input the initial value of the position of the well 1a to be imaged (S101) and the initial value of the image pickup position in the well 1a to be imaged (S102). Based on this data, the stage control unit 10 is instructed to move to the position of the well 1a to be imaged, and the stage control unit 10 gives an instruction of the amount of movement corresponding to the command value to the actuators 4, 5.
And the mounting stage 3 is moved to the position of the well 1a to be imaged (S103). Next, by the same process, the mounting stage 3 is moved to the imaging position in the well 1a (S1).
04) is executed.

After moving the mounting stage 3 to the image pickup position, an image of the subject is picked up by the digital camera 9 (S105),
The host computer 13 determines whether or not the analysis is performed (S10
Perform 6). Here, if No, the image data is stored in the memory 11 (S108), and if Yes,
The analysis unit 12 executes an analysis designated in advance (S107), and then saves the analysis result in the memory 11 (S108).

Then, the well 1 is set in the host computer 13.
After the presence / absence determination of the next imaging in a (S109) is performed, if Yes, the next imaging position in the well 1a is determined (S110), and a new step S10 is performed.
The operations of 4 to step S109 are executed. If No, the host computer 13 determines whether or not there is a movement to the next well 1a (S111). Here, if Yes, the predetermined position of the next well 1a is determined (S
112), and the operations of steps S102 to S111 are executed. If No, the operation ends.

(Embodiment 2) Since the system configuration of the image pickup apparatus according to the second embodiment of the present invention is the same as that of FIG. 1 described in the first embodiment, a detailed description of FIG. 1 will be given. Omit it.

In the image pickup device according to the second embodiment of the present invention, the well 1 in the microtiter plate 1 is
When the imaging position is moved between a and a, the imaging position is moved to the adjacent well 1a and the subject is imaged.

FIG. 4 is a diagram showing an example of a movement pattern of the image pickup positions to the adjacent wells 1a. FIG. 4A shows an image pickup in which the image pickup position is moved mainly by the movement of the wells 1a in the row direction of the microtiter plate 1. Shows how. Also,
FIG. 1B shows an imaging method in which the imaging position is moved mainly by moving the wells 1 a in the column direction of the microtiter plate 1. It should be noted that if the imaging position is moved to the adjacent well 1a and the object is imaged, the object of the present invention is adapted.

Next, an operation flow chart of the image pickup apparatus according to the second embodiment of the present invention will be described with reference to FIG.

First, the display 14 and the keyboard 1
5. Using the mouse 16, the initial value of the position of the well 1a to be imaged is input (S201). Based on this data, the stage control unit 10 is instructed to move to the position of the well 1a to be imaged, and the stage control unit 10 issues to the actuators 4 and 5 an amount of movement corresponding to the command value. ,
The mounting stage 3 moves to the position of the well 1a to be imaged (S
202) is performed.

After moving the mounting stage 3 to the imaging position, the digital camera 9 images the subject (S203),
Judgment of presence / absence of analysis by the host computer 13 (S20
4) is performed. Here, if No, the image data is saved in the memory 11 (S206), and if Yes,
The analysis unit 12 executes an analysis designated in advance (S205), and then saves the analysis result in the memory 11 (S206).

Next, the host computer 13 judges whether or not there is a movement to the next well 1a (S207), and Yes
If s, the predetermined position of the next well 1a is determined (S208), and new steps S202 to S are performed.
The operation of 207 is executed. If No, the operation ends.

(Third Embodiment) FIG. 6 is a system configuration diagram of an image pickup apparatus according to a third embodiment of the present invention.

The image pickup apparatus according to the third embodiment of the present invention has, in addition to the configuration of FIG. 1 described in the first embodiment, an objective lens switch for rotating a revolver 7 as a means for switching the optical magnification of a subject. An actuator 8 and an objective lens controller 18 for designating a rotation amount of the objective lens switching actuator 8 are provided. Further, the image processing unit 17 that processes the image data captured by the digital camera 9 and determines the image capturing position is provided as means for capturing an image of the subject and outputting the image data as image data.

With the above structure, when the subject of the well 1a in the microtiter plate 1 is imaged, the low-magnification objective lens 6 is first used to image a wide range of the subject, and then the information obtained by this image pickup is used. The target imaging position is determined based on the above, and the target objective lens magnification is switched to image the optimum position.

FIG. 7 shows a subject in the well 1a of the microtiter plate 1 with a low-magnification objective lens (example: 4).
The imaged image 31 obtained by imaging using a magnification) and the objective lens 6 having an intended imaging magnification based on the information obtained by the imaging (example:
10 times), an example of a captured image 32 when a subject is captured at a target imaging position is shown.

An operation flowchart of the image pickup apparatus according to the third embodiment of the present invention will be described with reference to FIG.

First, the display 14 and the keyboard 1
5. Using the mouse 16, the initial value of the position of the well 1a to be imaged is input (S301) and the initial value of the magnification of the objective lens 6 to be imaged (low magnification) is input (S302). Based on this data, the well 1 to be imaged is set to the stage control unit 10.
A command to move to the position a is issued, the stage control unit 10 issues an instruction to the actuators 4 and 5 for the amount of movement corresponding to the command value, and the mounting stage 3 is used as the well 1 to be imaged.
It is moved to the a position (S303).

Next, a command to switch the imaging magnification is issued,
When the objective lens control unit 18 outputs a driving amount corresponding to the input data to the objective lens switching actuator 8, the revolver 7 rotates and the switching operation of the objective lens 6 (S304) is executed. Then, the digital camera 9 captures an image of the subject (S305), and the image processing unit 17
Image processing of the image data imaged in (S306), based on the information, the target imaging position is determined (S307),
It moves to the target imaging position (S308).

Then, the magnification of the objective lens 6 is switched to the target magnification (high magnification) (S309), and the target subject is imaged (S310). The host computer 13 determines whether or not the captured image data is analyzed (S31
Perform 1). Here, if No, the image data is stored in the memory 11 (S313), and if Yes,
The analysis unit 12 executes an analysis designated in advance (S312) and then saves the analysis result in the memory 11 (S313).

Next, the host computer 13 judges whether or not there is a movement to the next well 1a (S314), and Yes
If s, the predetermined position of the next well 1a is determined (S315), and new steps S302 to S are performed.
The operation of 314 is performed. If No, the operation ends.

[0040]

According to the present invention, the following effects can be obtained.

(1) In the invention described in claim 1, the liquid surface curved due to the surface tension of the medium in the wells of the microtiter plate plays a role of a lens, which causes a reduction in the contrast of the observed image. , To obtain an optically good captured image of the subject efficiently by adopting an imaging method in which the imaging position is moved from near the center of the well where the observation image has a relatively good contrast toward the periphery of the well. You can In particular, the advantageous effect of the image pickup means is remarkable during the phase difference observation and the differential interference observation.

(2) In the invention described in claim 2, the image capturing method according to claim 1 is used, and necessary image analysis is performed based on the efficiently acquired optically good image data. Therefore, an error factor that causes an analysis result at the time of capturing an image can be reduced, and an analysis result with good analysis accuracy can be obtained.

(3) In the third aspect of the present invention, when imaging an object such as cells in a plurality of wells of a microtiter plate, when moving to the next well, it is necessary to move to an adjacent well. As a result, the time required for movement can be minimized, the time required for imaging per microtiter plate can be shortened, and damage to cells can be reduced.

(4) According to the invention described in claim 4, the image capturing method according to claim 3 is used to acquire an image at high speed and perform analysis, thereby making it possible to reduce the total analysis time per microtiter plate. Can be the shortest.

(5) In the invention described in claim 5, when a subject such as a cell in a well of a microtiter plate is imaged, a low-magnification objective lens is first used to image a wide range of the subject. Since the imaging position where the target subject exists is determined based on the image information and the subject is imaged, the proportion of the subject included in the captured image can be made substantially uniform.

(6) In the invention described in claim 6, since the image can be acquired under the uniform condition for each well by using the image capturing method described in claim 5, an image necessary for analysis is acquired. In order to eliminate the variation in analysis due to the imaging position at the time, 1
It is not necessary to image and average multiple points in the well,
It is possible to shorten the imaging time and reduce the error factors that are brought to the analysis result at the time of capturing the image, and obtain the analysis result with good analysis accuracy.

[Brief description of drawings]

FIG. 1 is a system configuration diagram of an image pickup apparatus according to a first embodiment of the present invention.

FIG. 2 is an explanatory diagram showing an example of an imaging method of wells in a microtiter plate.

FIG. 3 is an operation flowchart of the image pickup device according to the first embodiment of the present invention.

FIG. 4 is a diagram showing an example of a movement pattern of imaging positions to adjacent wells.

FIG. 5 is an operation flowchart of the image pickup device according to the second embodiment of the present invention.

FIG. 6 is a system configuration diagram of an image pickup device according to a third embodiment of the present invention.

FIG. 7 is an explanatory diagram showing an example of an image obtained by capturing an image of a subject in a well in a microtiter plate.

FIG. 8 is an operation flowchart of the image pickup device according to the third embodiment of the present invention.

[Explanation of symbols]

1 Microtiter plate 1a well 2 Optical illumination unit 3 Placement stage 4,5 actuator 6 Objective lens 7 Revolver 8 Objective lens switching actuator 9 Digital camera 10 Stage control unit 11 memory 12 Analysis Department 13 Host computer 14 displays 15 keyboard 16 mice 17 Image processing section 18 Objective lens controller

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Claims (6)

[Claims] 1. A detection means for detecting an object such as a plurality of cells in a microtiter plate, an imaging means for imaging the object and outputting it as image data, a mounting stage for mounting the object, and An image capturing method using an image capturing apparatus, comprising: a moving unit that moves the subject to a plurality of arbitrary image capturing positions by moving a stage; and a storage unit that stores the image data. An image capturing method, comprising: capturing an image of a subject at a plurality of positions in a well by moving the image capturing position from the vicinity of the center of the well toward the peripheral direction of the well. 2. A detection means for detecting an object such as a plurality of cells in a microtiter plate, an imaging means for imaging the object and outputting it as image data, a mounting stage for mounting the object, Moving means for moving the subject to a plurality of arbitrary imaging positions by moving the stage; storage means for storing the image data;
An image capturing apparatus comprising: an analyzing unit that analyzes the image data, wherein the moving unit captures an image of a subject at a plurality of positions in one well of the microtiter plate from near the center of the well An image pickup device, wherein the image pickup position is moved in a peripheral direction. 3. A detection means for detecting an object such as a plurality of cells in a microtiter plate, an imaging means for imaging the object and outputting it as image data, a mounting stage for mounting the object, and An image capturing method using an image capturing apparatus, comprising: a moving unit that moves the subject to a plurality of arbitrary image capturing positions by moving a stage; and a storage unit that stores the image data, the well of the microtiter plate. An image capturing method, characterized in that the image capturing position is moved to an adjacent well to perform image capturing when moving between them. 4. A detection means for detecting an object such as a plurality of cells in a microtiter plate, an imaging means for imaging the object and outputting it as image data, a mounting stage for mounting the object, Moving means for moving the subject to a plurality of arbitrary imaging positions by moving the stage; storage means for storing the image data;
An image capturing apparatus comprising: an analyzing unit that analyzes the image data, wherein the moving unit moves the imaging position to an adjacent well when moving between the wells of the microtiter plate. An image pickup device characterized by. 5. A detection unit having a plurality of imaging magnifications for detecting a subject such as a plurality of cells in a microtiter plate,
An image pickup means for picking up the image of the subject and outputting it as image data; a placement stage for placing the subject; and a moving means for moving the subject to a plurality of arbitrary image pickup positions by moving the placement stage. An image capturing method using an image capturing apparatus, comprising: a unit for switching the image capturing magnification; and a storage unit for storing the image data; an image capturing step of capturing a wide range of the subject; and an image capturing obtained in the image capturing step. An image capturing method comprising: a step of determining a target image capturing position based on information; and a step of switching the image capturing magnification to capture an image of the subject. 6. A detection means having a plurality of imaging magnifications for detecting a subject such as a plurality of cells in a microtiter plate,
An image pickup means for picking up the image of the subject and outputting it as image data; a placement stage for placing the subject; and a moving means for moving the subject to a plurality of arbitrary image pickup positions by moving the placement stage. An image pickup apparatus comprising: a unit that switches the image pickup magnification; a storage unit that stores the image data; and an analysis unit that analyzes the image data, wherein the image pickup unit switches the image pickup magnification and It is for performing imaging in a wide range, and the moving means moves the placement stage to a target imaging position determined based on the imaging information obtained by the imaging means. Image capturing device.