JP3761054B2 - Image information reader - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an image information reading apparatus, and more particularly to an improvement of an image information reading apparatus in which the arrangement position of a sample that is a target for reading image information is set stepwise in advance.
[0002]
[Prior art]
Conventionally, in the fields of biochemistry and molecular biology, as a method for detecting nucleic acids and proteins in a membrane filter after blotting, there has been a chemiluminescence method for detecting chemiluminescence imaging using photoelectric reading means such as a film or a CCD. Are known.
[0003]
Here, the image information reading device that reads the chemiluminescence as image information by using the photoelectric reading means can easily obtain the image of chemiluminescence as the digital image information, and image processing is easy. Since the use of the image has a wide dynamic range and good linearity, it has an advantage that image information suitable for quantitative analysis can be obtained, and has been widely used in recent years.
[0004]
This image information reading apparatus generally collects a sample stage (tray) on which a sample such as a membrane filter is placed in a light-shielded dark box and weak chemiluminescent light emitted from the sample on the tray. The lens includes a lens and photoelectric reading means (such as a CCD) that photoelectrically detects chemiluminescent light collected by the lens.
[0005]
In addition, in order to read the image information with an appropriate size according to the size of the sample placed on the tray, a sample stage placement unit in which the tray is placed at a plurality of positions at different distances from the lens. Some devices are provided.
[0006]
[Problems to be solved by the invention]
By the way, in a reading apparatus having a plurality of tray arrangement positions, it is necessary to adjust the lens position (focus adjustment) for each tray arrangement position. Is switched to a focus mode where reading is faster than the mode for acquiring image information for analysis (image information reading mode) and repeated reading is performed, and the image obtained by the CCD is monitored in substantially real time. By displaying the pseudo moving image on the monitor, the operator performs focus adjustment by rotating the focus ring by hand while checking the pseudo moving image displayed on the monitor. In the focus mode, it is necessary to store and transfer charges in a shorter time than in the image information reading mode, but the focus adjustment needs to be detected by exposing weak chemiluminescence light in a dark room for a long time. Unlike the case of reading image information, since natural light is detected in a bright room, charges can be accumulated in a short time.
[0007]
However, as described above, the focus adjustment operation is performed by the operator manually rotating the focus ring. For example, the focus adjustment operation is often performed as it is with the hand that handles the sample. There is also a risk of the sample adhering to the lens. If the sample adheres to the lens, weak chemiluminescence cannot be detected with high accuracy, and if left as it is, there will be inconveniences such as mold on the lens and focus ring.
[0008]
The present invention has been made in view of the above circumstances. Even when the sample stage arrangement part to be selected among the multistage sample stage arrangement parts is changed, the lens has a simple structure without touching the lens or the focus ring. It is an object of the present invention to provide an image information reading apparatus that can move a position to an appropriate position.
[0009]
[Means for Solving the Problems]
The image information reading apparatus of the present invention is provided with a plurality of sample stage arrangement units in advance, lens positions corresponding to the arrangement units are set, and the arrangement unit on which the sample stage is arranged is detected by a sensor. Then, the lens is automatically moved to the lens position corresponding to the detected arrangement portion.
[0010]
That is, the image information reading apparatus of the present invention is a sample on which a sample stage on which a sample is placed, which is provided at a plurality of discrete positions at different distances from a lens that is movable in the optical axis direction. In an image information reading apparatus comprising a stand arrangement unit and a photoelectric reading unit that photoelectrically reads an image of the sample imaged by the lens,
Lens moving means for moving the lens in the optical axis direction;
A sample stage detection sensor for detecting a sample stage arrangement part in which the sample stage is selectively arranged among the plurality of sample stage arrangement parts;
A plurality of discrete lens positions set in advance so as to form an image of the sample on the light receiving surface of the photoelectric reading unit corresponding to each of the plurality of sample stage arrangement units, Storage means for storing in association with
The lens position corresponding to the sample stage arrangement unit detected by the sample stage detection sensor is obtained with reference to the correspondence stored in the storage unit, and the lens is moved to the obtained lens position. And a focus control means for controlling the lens moving means.
[0011]
Here, as the photoelectric reading means, an interline CCD having a cooling element that can detect weak chemiluminescence light with a wide dynamic range and with good linearity and can extract a moving image is used. Is preferred.
[0012]
As a sample from which image information is read, a sample for molecular biological analysis (for example, a membrane filter) containing a substance that emits chemiluminescent light or fluorescence, and various other types can be applied. In the detection of fluorescence emitted by the light source, an excitation light source that emits excitation light that can excite the fluorescence and an excitation light cut filter that prevents the excitation light from entering the photoelectric reading means and that can transmit the fluorescence are further provided. What is necessary is just to take a structure.
[0013]
In addition, the photoelectric reading unit selects the image information reading mode for reading the sample image and the focus mode for reading repeatedly with a shorter reading time than the image information reading mode for focusing the sample image. Can be switched to the focus mode, and a plurality of image information of the sample read by the photoelectric reading means switched to the focus mode is displayed as a pseudo moving image, and moved to the lens position by the focus control means. It is more desirable to employ a configuration further comprising fine adjustment means for controlling the focus control means so as to further move the formed lens further in the optical axis direction.
[0014]
By adopting such a configuration, the sample has a certain thickness, such as a gel support, and the thickness cannot be ignored in the imaging relationship on the light receiving surface of the photoelectric reading means. Sometimes, it can be placed on a sample stage and used as a target for reading image information. That is, the operator can recognize the image of the sample sequentially displayed on the monitor means in substantially real time as a pseudo moving image, so that the focus control means can be adjusted by the fine adjustment means by trial and error while viewing the display image. Can be adjusted to adjust the focus shift according to the thickness of the sample.
[0015]
The image information reading mode for reading an image of a sample is a reading mode that takes approximately two seconds or more to read one frame of image information when weak chemiluminescent light is to be read. The mode is a reading mode for focusing on the image of the sample. The image information can be displayed in substantially real time, and one frame of image information is read in about 0.2 seconds or less. Repeat reading mode. In this way, by switching a large number of frames in a short time and displaying them on the monitor means, the operator can recognize that the moving image is displayed on the monitor means, and based on the displayed image Focus adjustment can be performed by trial and error. Even in this case, the operator can make an adjustment without directly touching the lens or the focus ring.
[0016]
In the focus mode described above, it is necessary to store and transfer charges in a shorter time than in the image information reading mode, but focus adjustment needs to be detected by exposing weak chemiluminescence light in a dark room for a long time. Unlike the case of reading image information, since natural light is detected in a bright room, charges can be accumulated in a short time.
[0017]
Thus, when the position of the lens is moved to a position other than the discrete positions set in advance by the fine adjustment means, the focus control means changes the position of the lens moved by the control of the fine adjustment means, It is desirable to update the association stored in the storage unit as the lens position corresponding to the sample stage arrangement unit. By updating the correspondence in this way, it is possible to save the trouble of performing focus adjustment for each sample in the operation of continuously reading samples having the same thickness, and a lens that is set in advance over time. Even when the position is shifted, the calibration can be easily performed.
[0018]
【The invention's effect】
According to the image information reading apparatus of the present invention, it is possible to arrange the sample stage on which the sample is placed, which is provided at a plurality of discrete positions with different distances from the lens that is movable in the optical axis direction. The sample stage detection sensor detects which sample stage placement part of the sample stage placement part is located, and the focus control means corresponds to the sample stage placement part detected by the sample stage detection sensor. The focus control unit controls the lens moving unit so that the lens position stored in the storage unit is obtained and the lens moving unit moves the lens to the obtained lens position in the optical axis direction. Make.
[0019]
As a result, the operator simply performs an operation of placing the sample stage on the desired sample stage placement section on which the sample stage is to be placed, and the photoelectric reading means receives the image of the sample on the placed sample stage. Since the lens is automatically moved to a lens position suitable for imaging on the surface, the operator does not touch the lens, and thus the operator has conventionally touched the lens and the focus ring with the hand that handled the sample. The problem of the sample adhering to the focus ring or the lens, which may be caused by this, can be solved by the image information reading apparatus of the present invention.
[0020]
In addition, the image information reading apparatus of the present invention is a complicated and advanced technical device such as an autofocus mechanism that is widely used in a single-lens reflex camera and the like and that automatically detects an imaging state and drives a lens. Instead of using means, automatic focusing can be realized with a simple configuration.
[0021]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, specific embodiments of the image information reading apparatus of the present invention will be described with reference to the drawings.
[0022]
FIG. 2 is a perspective view showing a schematic configuration of an embodiment of the image information reading apparatus of the present invention, and FIG. 1 is a diagram showing the entire configuration including the inside of the image information reading apparatus shown in FIG. The illustrated image information reading apparatus 100 is mounted on the tray 10 with a membrane filter 11 onto which a sample containing a substance that emits chemiluminescent light is transferred and accommodated therein, and a dark box 20 that is shielded from the inside, The dark box 20 has a configuration including an interline CCD 51 having a cooling element that photoelectrically detects chemiluminescence light emitted in the dark box 20 and outputs a signal obtained by photoelectric conversion to an external image processing apparatus or the like. As shown in detail in FIG. 1, a lens 40 that can be moved in the optical axis direction (arrow X direction) and a motor 32 that moves the lens 40 in the optical axis direction X are disposed inside 20. In addition, on both side surfaces of the inner wall of the dark box body 25, seven stages of rails 21a, 21b,... Further, tray sensors 22a, 22b,..., 22g for detecting whether or not the tray 10 is disposed on the rails 21a to 21g are provided on the rear surfaces of the inner walls corresponding to the rails 21a to 21g. That is, the tray sensor 22a detects whether or not the tray 10 is placed on the rail 21a, and the tray sensor 22b detects whether or not the tray 10 is placed on the rail 21b. 22c corresponds to the rail 21c, the tray sensor 22d corresponds to the rail 21d, the tray sensor 22e corresponds to the rail 21e, the tray sensor 22f corresponds to the rail 21f, and the tray sensor 22g corresponds to the rail 21g.
[0023]
The CCD 51 is provided so as to penetrate the inner wall upper surface of the dark box body 25. The lens 40 for forming the image of the membrane 11 on the CCD 51 has stop positions (lens positions) in the optical axis direction X corresponding to the tray rails 21a,. It is set step by step. That is, the lens position 41a is a position suitable for forming an image of the membrane 11 on the tray 10 on the CCD 51 when the tray 10 is placed on the tray rail 21a, and the lens position 41b is When the tray 10 is placed on the tray rail 21b, this position is suitable for forming an image of the membrane 11 on the tray 10 on the CCD 51. Similarly, the lens position 41c is positioned on the tray rail 21c. The lens position 41d (41d to 41f not shown) corresponds to the tray rail 21d, the lens position 41e corresponds to the tray rail 21e, the lens position 41f corresponds to the tray rail 21f, and the lens position 41g corresponds to the tray rail 21g. .
[0024]
This movable lens 40 is configured to be moved to each of the lens positions 41a to 41f by a stepping motor 32 provided inside the dark box 20, and each lens position 41a, 41b to the stepping motor 32 is configured. ,..., 41g, the number of input pulses D1, D2, D3, D4, D5, D6, and D7 are stored in the dark box 20 as a reference table previously associated with each of the tray rails 21a to 21g. Stored in the unit 33.
[0025]
Further, in the dark box 20, in response to the detection result by the sensors 22a to 22g on which tray rail 22a to 22g is placed, the number of pulses corresponding to the detection result is stored in the storage unit 33. Focus control means 31 is provided for referring to the obtained reference table and inputting the obtained number of pulses to the stepping motor 32.
[0026]
Next, the operation of the image information reading apparatus 100 of this embodiment will be described.
[0027]
First, the lens 40 is stopped at a predetermined initial position, and the operator places the membrane filter 11 onto which the sample exhibiting chemiluminescence has been transferred on the tray 10, and the tray 10 is placed in the dark box 20 on the membrane filter 11. Depending on the size, it is placed on a rail (for example, the fourth-stage rail 21d) suitable for acquiring image information of a desired size (any one of the first to seventh stages from the top). Close the dark box door.
[0028]
Of the sensors 22a to 22g installed in the dark box 20, the sensor 22d corresponding to the fourth rail 21d on which the tray 10 is placed is placed on the tray 10 by placing the tray 10. And a detection signal is sent to the focus control means 31. At this time, the other sensors 22a to 22c and 22e to 22g do not output detection signals because the trays 10 do not exist on the corresponding rails 21a to 21c and 21e to 21g, respectively.
[0029]
The focus control means 31 receives the detection signal, recognizes that the detection signal is output from the sensor 22d, refers to the reference table stored in the storage unit 33, and refers to the pulse associated with the sensor 22d. The number D4 is obtained, and this number of pulses D4 is input to the stepping motor 32. The stepping motor 32 moves the lens 40 from the initial position to the lens position 41d based on the number of pulses input from the focus control means 31.
[0030]
Here, the lens position 41d is set in advance as a position suitable for forming an image of the membrane 11 on the tray 10 on the CCD 51 when the tray 10 is placed on the fourth tray rail 21d. Therefore, the image of the membrane 11 on the tray 10 disposed on the fourth-stage tray rail 21d is appropriately formed on the CCD 51 without being out of focus.
[0031]
The CCD 51 photoelectrically detects the chemiluminescent light emitted from the membrane 11 thus imaged and outputs the obtained signal to an external image processing device, an image display device or the like.
[0032]
As described above, according to the image information reading apparatus of the present embodiment, the lens position for forming an appropriate image on the CCD 51 can be obtained with a simple configuration without touching the lens 40 by the operator handling the sample. The lens 40 can be moved.
[0033]
FIG. 3 is a diagram showing a configuration of another embodiment of the image information reading apparatus of the present invention, and FIG. 4 is a perspective view showing a schematic configuration of the image information reading apparatus 100 ′ shown in FIG. The image information reading apparatus 100 ′ shown in the figure is configured to further have a focus fine adjustment function and a failure manual adjustment function with respect to the image information reading apparatus 100 shown in FIG. The description of the same components as those of the image information reading apparatus 100 of the embodiment shown in FIG. 1 is omitted.
[0034]
The CCD 51 ′ constituting the image information reading apparatus 100 ′ of the present embodiment reads compared to the image information reading mode for reading an image for image quantification and the image information reading mode for focusing a sample image. The image information reading apparatus 100 'is switched to the focus mode and the camera controller 52 for switching the mode. The focus monitor 60 that displays a plurality of image information of the sample read by the CCD 51 'as a pseudo moving image, and the lens that has been moved to the lens position by the focus control means 31' are further moved in the direction of the optical axis. And a personal computer 70 as a fine adjustment means for controlling the focus control means 31 '. It has.
[0035]
Here, the image information reading mode is a reading mode that takes 3 seconds to read one frame of image information, while the focus mode is a reading mode for focusing a sample image, This is a reading mode in which image information of one frame is sequentially updated and read at a time interval of 0.1 seconds. The image information read in the focus mode is displayed on the focus monitor 60. Since the display interval of each frame is as short as 0.1 seconds, the monitor display can be recognized as a pseudo moving image.
[0036]
Here, as shown in FIG. 4, the personal computer 70 comprises a CRT, a keyboard, a mouse, and a main body of the processing device. The operator changes the mode of the CCD 51 'by the operator and sets the thickness d of the sample placed on the tray 10. In response, a command corresponding to correcting the number of pulses output from the focus control means 31 'to the motor 32 is input from the keyboard or mouse, and a mode switching command is input from the processing device body to the camera controller 52, The camera controller 52 switches the reading mode of the CCD 51 ′.
[0037]
The focus control means 31 'changes the number of pulses corresponding to the tray rails 21a to 21g stored in the storage unit 33 in accordance with the pulse number correction command input from the keyboard or mouse. The number of pulses after the change is output to the motor 32, and the number of pulses corresponding to the tray rails 21a to 21g is replaced with the number of pulses after the change and associated with the tray rails 21a to 21g and stored in the storage unit 33. is there.
[0038]
Next, the operation of the image information reading apparatus 100 ′ of this embodiment will be described.
[0039]
First, an operator inputs a command for switching the mode of the CCD 51 'from the keyboard of the personal computer 70 to the focus mode. This command is input from the processing unit body of the computer 70 to the camera controller 52, and the camera controller 52 is connected to the CCD 51'. Switch the reading mode to the focus mode.
[0040]
On the other hand, the lens 40 is stopped at a predetermined initial position, and an operator places a gel support 11 'having a thickness d on which a sample exhibiting chemiluminescence is distributed on the tray 10, and the tray 10 is placed in a dark box. Depending on the size of the gel support 11 ′, 20 rails (for example, the second step from the top) suitable for obtaining image information of a desired size (for example, the second step) Rail 21b).
[0041]
Of the sensors 22a to 22g installed in the dark box 20, the sensor 22b corresponding to the second rail 21b on which the tray 10 is placed is placed on the tray 10 by placing the tray 10. And a detection signal is sent to the focus control means 31 '. At this time, the other sensors 22a and 22c to 22g do not output the detection signal because the tray 10 does not exist on the corresponding rails 21a and 21c to 21g, respectively.
[0042]
The focus control means 31 ′ receives the detection signal, recognizes that the detection signal is output from the sensor 22b, refers to the reference table stored in the storage unit 33, and is associated with the sensor 22b. The number of pulses D2 is obtained, and this number of pulses D2 is input to the stepping motor 32. The stepping motor 32 moves the lens 40 from the initial position to the lens position 41b based on the number of pulses input from the focus control means 31 '.
[0043]
Here, the lens position 41b is a position suitable for forming an image of a 0 mm-thick sample on the tray 10 on the CCD 51 'when the tray 10 is placed on the second-stage tray rail 21b. Therefore, an image of the gel support 11 'on the tray 10 arranged on the second-stage tray rail 21b is formed on the CCD 51'. This gel support 11 ' Unlike the membrane filter, it has a thickness d that cannot be ignored in the imaging relationship, so that the image is formed on the CCD 51 'as being out of focus.
[0044]
Here, since the CCD 51 ′ is switched to the focus mode, the received image of the gel support 11 ′ is output to the focus monitor 60 via the camera controller 52 at intervals of 0.1 second. As a result, the image of the gel support 11 ′ is sequentially displayed on the focus monitor 60 at intervals of 0.1 seconds. However, since the display interval is short, the operator observing the monitor 60 is allowed to Can be recognized as a dynamic video.
[0045]
While watching the display on the monitor 60, the operator gives a correction command for the number of pulses from the keyboard by trial and error so that the image of the gel support 11 'displayed on the monitor 60 becomes an accurately focused image. input. As long as this correction command is a command to move the lens 40 in the vertical direction in the figure, the number of pulses may be directly input, or simply upward movement / stop / downward movement. It may be an instruction. The correction command input in this way is input to the focus control means 31 '. The focus control means 31' performs control to drive the motor 32 based on the input correction command, and the motor 32 responds to this control. The lens 40 is moved up and down.
[0046]
When the operator recognizes that the image of the gel support 11 'displayed on the monitor 60 has become an accurately focused image, the operator stops inputting the correction command, closes the door of the dark box 20, and closes the CCD 51' A command for switching the mode to the image information reading mode is input from the keyboard. The lens position at this time is expressed as 41b '.
[0047]
A mode switching command input from the keyboard is input to the camera controller 52, and the camera controller 52 switches the CCD 51 'to an image information reading mode with a relatively long exposure time. This mode switching command is also input to the focus control means 31 '. The focus control means 31' is the amount of variation (number of pulses) from the number of pulses previously associated with the second-stage tray rail 21b. The number of pulses associated with each other is corrected, the corrected number of pulses is associated with the second-stage tray rail 21b, and this association is stored in the storage unit 33.
[0048]
As a result, the number of pulses associated with the second-stage tray rail 21b newly stored in the storage unit 33 is the same as that of the tray 10 when the tray 10 is placed on the second-stage tray rail 21b. The number of pulses from the initial position corresponds to the lens position 41b 'suitable for forming an image of the upper sample of dmm in thickness on the CCD 51'.
[0049]
On the other hand, the chemiluminescent light emitted from the gel support 11 'is imaged as an accurately focused image on the CCD 51' by the lens 40 at the lens position 41b '. The CCD 51' The image of the emitted light is photoelectrically converted, and the converted signal is input to the personal computer 70 via the camera controller 52. The personal computer 70 displays the input signal as a visible image on the CRT.
[0050]
As described above, according to the image information reading apparatus 100 ′ of the present embodiment, it is possible to form an appropriate image on the CCD 51 ′ with a simple configuration without touching the lens 40 by the operator handling the sample. The lens 40 can be moved to the lens position. In addition, in the imaging relationship on the light receiving surface of the CCD 51 ′, even if the thickness of the sample cannot be ignored, the lens position can be corrected according to the thickness without touching the lens 40. .
[0051]
Note that the image information reading apparatus 100 ′ of this embodiment is forcibly provided via the clutch 82 as a backup when the personal computer 70, the focus control means 31 ′ or the motor 32 does not operate normally due to a failure or the like. Since a manual rotary knob 81 that rotates the shaft of the machine is provided outside the dark box body 25, when such a failure occurs, the clutch 82 is connected and then protrudes outside the dark box body 25. The lens position can also be adjusted by turning the rotary knob 81. Even in this case, since the operator does not need to touch the lens 40 directly, contamination of the lens can be avoided.
[Brief description of the drawings]
FIG. 1 is a diagram showing a configuration of an embodiment of an image information reading apparatus according to the present invention. FIG. 2 is a schematic perspective view of the image information reading apparatus shown in FIG. FIG. 4 is a schematic perspective view of the image information reading apparatus shown in FIG. 3;
10 trays
11 samples
20 Dark box
21a to 21g tray rail
22a-22g Tray sensor
25 body
31 Focus control means
32 motor
33 Memory
40 lenses
41a to 41g Lens position
51 Cooling CCD
52 Camera controller
60 Focus monitor
70 Personal computer
100 Image information reader

Claims (5)

A sample stage placement section on which a specimen stage on which a specimen is placed can be placed at a plurality of discrete positions at different distances from the lens that is movable in the optical axis direction, and an image is formed by the lens. In the image information reading apparatus provided with a photoelectric reading means for photoelectrically reading the image of the sample,
Lens moving means for moving the lens in the optical axis direction;
A sample stage detection sensor for detecting a sample stage arrangement part in which the sample stage is selectively arranged among the plurality of sample stage arrangement parts;
A plurality of discrete lens positions set in advance so as to form an image of the sample on the light receiving surface of the photoelectric reading unit corresponding to each of the plurality of sample stage arrangement units, Storage means for storing in association with
The lens position corresponding to the sample stage arrangement unit detected by the sample stage detection sensor is obtained with reference to the correspondence stored in the storage unit, and the lens is moved to the obtained lens position. An image information reading apparatus comprising: a focus control unit that controls the lens moving unit. An image information reading mode in which the photoelectric reading means reads the image of the sample, and a focus mode in which the reading time is shorter than the image information reading mode and the reading is repeated for focusing the image of the sample. Can be selectively switched,
Monitor means for displaying a plurality of pieces of image information of the sample read by the photoelectric reading means switched to the focus mode as a pseudo moving image;
The apparatus further comprises fine adjustment means for controlling the focus control means so that the lens moved to the lens position by the focus control means is further moved continuously in the optical axis direction. The image information reading apparatus according to claim 1. The focus control unit updates the association stored in the storage unit with the position of the lens moved under the control of the fine adjustment unit as a lens position corresponding to the sample stage arrangement unit. The image information reading apparatus according to claim 2. 4. The image information reading apparatus according to claim 1, wherein the sample is a sample for molecular biological analysis containing a substance that emits chemiluminescent light or fluorescence. 5. 5. The image information reading apparatus according to claim 1, wherein the photoelectric reading unit is an interline CCD having a cooling element. 6.

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