JP3960679B2 - Densitometer - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a densitometer that obtains photometric data by photometric scanning a support on which an electrophoretic image is formed.
[0002]
[Prior art]
For example, in an electrophoresis apparatus for analyzing serum proteins, a support such as a cellulose acetate membrane is used, and a buffer solution is wetted on the support with a wet part, and then serum is applied on the serum application part, followed by electrophoresis. Electrophoresis of serum in the part, and staining / decoloring / drying the support in the staining / decoloring / drying part, and then supplying the support to a densitometer and performing photometric scanning to obtain photometric data of the electrophoretic image Trying to get.
[0003]
Here, the densitometer generally includes a container having a transparent photometric unit for containing a clarification solution and a decolorization solution, and a light source unit and a light receiving unit disposed so as to be integrally movable in the horizontal direction below and above the container. And a photometric scanning means having photometric scanning means for obtaining photometric data by photometric scanning in the direction of fractionation of the electrophoretic image by the photometric scanning means in a state where the support on which the electrophoretic image is formed is immersed in the liquid in the container. I have to.
[0004]
[Problems to be solved by the invention]
By the way, in a densitometer, in order to increase the measurement accuracy, a test is performed. As an example of the densitometer verification method, the present applicant, for example, in Japanese Examined Patent Publication No. 60-13136, transports an assay film having a predetermined pattern so that it is temporarily stopped by a photometric unit using a normal support transport mechanism. Thus, there has already been proposed a method in which the photometric scanning is performed by photometrically scanning the test film.
[0005]
However, according to various experimental studies by the present inventor, it has been found that the above-described assay method has the following points to be improved. That is, since the test film is repeatedly used, it has its own deterioration, and the liquid in the container is also changed in quality and the stain progresses. For this reason, even if the densitometer is calibrated using an assay film, the photometric data of the electrophoretic image migrated on a normal support will contain those errors, which may reduce the measurement accuracy. is there. Similarly, if the container is fixedly soiled with scratches or dust on the inner and outer surfaces of the bottom of the photometry unit, similarly, an accurate test cannot be performed, and these errors are included in the photometry data of the normal support. As a result, the measurement accuracy may be reduced.
[0006]
The present invention has been made in view of the above-described points, and an object of the present invention is to provide a densitometer appropriately configured so that the densitometer can be managed and the measurement accuracy can be improved.
[0007]
[Means for Solving the Problems]
In order to achieve the above object, the present invention provides a densitometer in which a photometric scanning means is used to obtain photometric data in a state in which a support on which an electrophoretic image is formed is immersed in a liquid in a container. A means for driving the photometric scanning means in the absence of the support , a storage means for storing the empty scan data, and a statistical processing means for statistically processing the empty scan data stored in the storage means. The storage means stores a plurality of empty scan data at different times, and the statistical processing means manages the state of the liquid in the container based on the plurality of empty scan data stored in the storage means. It is characterized by having comprised as follows.
[0008]
In one embodiment of the present invention, there is provided setting means for setting an allowable value of the empty scan data, and comparison means for comparing the allowable value set by the setting means with the empty scan data. Based on the output, a warning is issued when the empty scan data exceeds the allowable value. In this way, it is possible to notify the operator in advance of the abnormal state of the densitometer.
[0009]
Furthermore, in one embodiment of the present invention, there is provided arithmetic means for correcting photometric data of the support on which the electrophoretic image is formed based on the empty scan data stored in the storage means. In this way, it is possible to correct errors due to dirt, scratches, etc. of the photometric part of the densitometer from the photometric data, and it is possible to further improve the measurement accuracy.
[0010]
Furthermore, in one embodiment of the present invention, the statistical processing means is configured to identify and manage the state of the liquid in the container and the state of the container itself. In this way, it becomes possible to identify and notify the operator of liquid contamination, container contamination and scratches, and maintenance becomes easy.
[0011]
Furthermore, in one embodiment of the present invention, a liquid exchanging means for automatically exchanging the liquid in the container based on the liquid state management result is provided. In this way, maintenance becomes easier.
[0012]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, an embodiment of the present invention will be described with reference to the drawings.
FIG. 1 shows a first embodiment of the present invention, which is incorporated in an electrophoresis apparatus. This electrophoresis apparatus has a wet part 1, an application part 2, an electrophoretic part 3, a dyeing / decoloring / drying part 4 and a densitometer 5. In the wet part 1, a support made of, for example, a roll-shaped cellulose acetate film, The buffer is moistened by cutting to a predetermined length with a cutter, the wet support is transported to the applicator 2, a plurality of test sera are simultaneously applied by an applicator, and the serum is applied to the support. Is transported to the electrophoresis unit 3 for migration, and then transported to the staining / decoloring / drying unit 4 for dyeing / decoloring / drying processing, and then transported to the densitometer 5 to sequentially scan the electrophoretic images of each specimen. To do.
[0013]
The densitometer 5 includes a transparent container 7 for storing the transparentizing liquid 6, a light source unit 8 and a light receiving unit disposed below and above the container 7 so as to be integrally movable in the horizontal direction perpendicular to the paper surface in FIG. A photometric scanning means 10 having a section 9 and a transport mechanism 13 such as a roller for transporting a support 12 having an electrophoretic image through a photometric section 11 facing the light source section 8 and the light receiving section 9 of the photometric scanning section 10. The transport mechanism 13 immerses the support 12 in the clearing liquid 6 and sequentially positions and transports the electrophoretic image of each specimen to the photometry unit 11 while synchronizing with the positioning of the electrophoretic image of the sequential specimen. Then, the photometric scanning means 10 is reciprocated from the position of the origin sensor 16 by the motor 14 via the rack and pinion mechanism 15 to photometrically scan the electrophoretic image of each specimen, and the photometric scanning of each specimen obtained from the light receiving unit 9 is performed. De By measuring the protein fraction by supplying data to the arithmetic and control unit 21 is configured to output the analysis result to the output unit 22. The above operation is controlled by the arithmetic control unit 21.
[0014]
In this embodiment, calculation is performed in a state where the support 12 is not in the photometric unit 11 by a preset timing before the analysis sequence, during the analysis sequence, or after the end of the analysis, or by an appropriate command from the input / output unit 22 by the operator. The control unit 21 drives the photometric scanning means 10 (empty scan), stores the empty scan data at that time in a memory in the arithmetic control unit 21, and manages the densitometer 5 based on the empty scan data.
[0015]
In addition, the above-described memory stores sequential empty scan data at different times, and statistically processes the plurality of empty scan data to obtain the state of the clearing liquid 6 in the container 7, the container 7 and The state of the photometric scanning means 10 is identified and managed, and the clearing liquid 6 in the container 7 is automatically replaced based on the result of the state management of the clearing liquid 6. For this reason, the densitometer 5 is provided with a liquid exchange means 29 by connecting a liquid supply tank 26 for storing a new clarified liquid in the container 7 via an electromagnetic valve 25 and a waste liquid tank 28 via an electromagnetic valve 27. In addition, a liquid level sensor 30 for detecting the liquid level of the clearing liquid 6 in the container 7 is provided, and the electromagnetic valves 25 and 27 are controlled based on the management result in the arithmetic control unit 21 and the output of the liquid level sensor 30. To.
[0016]
FIG. 2 is a block diagram showing a configuration of an example of a main part of the arithmetic control unit 21 in the first embodiment. The calculation control unit 21 includes a conveyance drive unit 31, a scan drive unit 32, a storage unit 33, a comparison unit 34, an allowable value setting unit 35, a calculation unit 36, a statistical processing unit 37, and a control for controlling the overall operation. A portion 38 is provided. The transport drive unit 31 controls the transport mechanism 13 under the control of the control unit 38 and, as described above, immerses the normal support 12 in the clearing liquid 6 to measure the electrophoretic image of each specimen. Position and sequentially transport the unit 11.
[0017]
In the photometric measurement of the support 12, the scanning drive unit 32 uses the signal from the origin sensor 16 under the control of the control unit 38, as described above, to sequentially migrate the electrophoretic images of the specimen on the support 12. In synchronism with the positioning by the photometric unit 11, the photometric scanning means 10 is reciprocated from the position of the origin sensor 16, and the electrophoretic image of each specimen is photometrically scanned. In the blank scan, the photometric unit 11 does not have the support 12 at the timing set in advance under the control of the control unit 38 as described above or by an appropriate command from the input / output unit 22 by the operator. Then, the photometric scanning means 10 is reciprocated from the position of the origin sensor 16.
[0018]
The storage unit 33 includes a memory 33a for storing empty scan data and a memory 33b for storing photometric data of electrophoretic images. The memory 33a accumulates and stores the data every time the empty scan is performed, and supplies the latest empty scan data to the comparison unit 34. The comparison unit 34 compares the empty scan data from the memory 33a with the allowable value from the allowable value setting unit 35, and outputs an alarm signal to the input / output unit 22 based on the comparison result. Display an abnormality on a display such as a CRT, turn on or blink a lamp to notify the abnormality, drive a buzzer to notify the abnormality, or print out an abnormality from the printer. Notify abnormalities. The allowable value in the allowable value setting unit 35 is set from the input / output unit 22.
[0019]
Here, the data (absorbance) obtained by causing the photometric scanning means 10 to perform a blank scan is constant from the scan start point to the end point as shown by the solid line in FIG. Value. On the other hand, if the clearing liquid 6 in the container 7 is contaminated or altered, the empty scan data at that time is uniformly shifted as indicated by the broken line with respect to the normal empty scan data indicated by the solid line. Become. Also, if the inner surface or outer surface of the container 7 of the photometry unit 11 is fixedly damaged or partially soiled by dust, the empty scan data at that time ends from the scan start point as shown by the solid line in FIG. 4A. It will have an abnormal peak value between points.
[0020]
As described above, if the sky scan data is different from the normal sky scan data, the photometric data of the electrophoretic image is also shifted uniformly when it is uniformly shifted as shown by the broken line in FIG. . In addition, when there is a fixed abnormal peak value as shown in FIG. 4A, the abnormal peak value is also added to the data of the corresponding measurement point of the electrophoretic image as shown in FIG. 4B. . Here, in obtaining the fractionation pattern and fraction% based on the photometric data of the electrophoretic image, generally, the autospan process is performed so that the maximum value of the photometric data becomes a predetermined value. 4B, there is no effect. However, when an abnormal peak value is fixedly added to the photometric data of the electrophoretic image as shown in FIG. Will occur.
[0021]
Therefore, in this embodiment, as shown in FIGS. 3 and 4A, the comparison unit 34 compares the allowable value indicated by the alternate long and short dash line set by the allowable value setting unit 35 with the latest empty scan data. When the scan data exceeds the allowable value, an alarm signal is output and the above-described operation is performed. The latest sky scan data is also supplied to the calculation unit 36, where the sky scan data is subtracted from the photometric data of each electrophoretic image stored in the memory 33b. When the subtraction process is performed in this way, the photometric data of the electrophoretic image shown in FIG. 4B is as shown in FIG. 4C, and the error due to the state change of the container 7 itself is corrected. The photometric data of each electrophoretic image subjected to the subtraction processing by the calculation unit 36 is supplied to the input / output unit 22 and output so that it can be identified as correction data. Further, the empty scan data stored in the memory 33a and the photometric data (raw data) of the electrophoretic image stored in the memory 33b are supplied to the input / output unit 22 and output as necessary.
[0022]
Furthermore, in this embodiment, a plurality of empty scan data accumulated and stored in the memory 33a are statistically processed by the statistical processing unit 37, and the state of the clearing liquid 6 in the container 7, the container 7, and the photometry The state of the unit 11 is identified and managed, and compared with the allowable value from the allowable value setting unit 35. Here, when the level of the sequential empty scan data gradually shifts uniformly, it is determined that the state of the clearing liquid 6 in the container 7 is changed (dirt or altered), and there is an abnormality between the sequential empty scan data. If a peak appears in a fixed manner, it is determined that the state of the container 7 and the photometry unit 11 is changed (scratches or partial contamination), and if the level of the statistically processed empty scan data exceeds an allowable value, The state change identification signal is supplied to the input / output unit 22 and displayed on a display such as a CRT, a lamp or the like is lit or blinked, a buzzer is driven, or a printer is printed. Identify and notify changes.
[0023]
When the statistical processing unit 37 detects that the state of the clearing liquid 6 in the container 7 exceeds the allowable value, the liquid exchange means 29 of the densitometer 5 is driven based on the detection signal. The clearing liquid 6 in the container 7 is automatically replaced. In this liquid exchange, first, the electromagnetic valve 25 is closed, the electromagnetic valve 27 is opened, and the clearing liquid 6 in the container 7 is discharged into the waste liquid tank 28. Next, the electromagnetic valve 25 is opened and the electromagnetic valve 27 is closed. When a new clearing liquid is supplied from the liquid supply tank 26 into the container 7 and then a predetermined amount of the clearing liquid is supplied into the container 7 based on the output of the liquid level sensor 30. The electromagnetic valve 25 is closed. After the liquid exchange, the empty scan data in the memory 33a is once erased, and then the photometric scanning means 10 is empty scanned before the photometric scan of the support having the electrophoretic image, and the exchanged transparent liquid Capture empty scan data.
[0024]
FIG. 5 shows a second embodiment of the present invention. In this embodiment, the densitometer 5 is also incorporated in the electrophoresis apparatus. In this electrophoresis apparatus, a staining / decoloring unit 41 is provided instead of the staining / decoloring / drying unit 4 of FIG. Is used in place of the clearing solution. For this reason, in this embodiment, the decoloring solution tank 45 is supplied with the decoloring stock solution and the diluting solution, and the decoloring solution is accommodated, and the decoloring solution is dyed and decolored via the switching valve 47 by the liquid feed pump 46. The portion 41 and the densitometer 5 are selectively supplied into the container 7. Further, the container 7 is provided with a liquid level sensor 48 for detecting the liquid level of the supplied decoloring liquid 42, and in order to waste the old decoloring liquid 42 prior to the supply of new decoloring liquid, A waste liquid tank 28 is connected and provided through a valve 27.
[0025]
Thus, in this embodiment, as in the first embodiment, the photometry scanning means 10 is sky-scanned by the arithmetic control unit 21 in the state where the photometric unit 11 does not have the support 12 and the empty scan data is obtained. Based on the empty scan data, the densitometer 5 is managed and an alarm is issued, the photometric data of the electrophoretic image is corrected with the empty scan data, or the accumulated empty scan data is stored in the memory in the arithmetic control unit 21 And the state of the decoloring liquid 42 in the container 7 and the state of the container 7 and the photometry unit 11 are identified and managed, or automatically based on the result of the state management of the decoloring liquid 42 The decolorizing liquid in the container 7 is replaced. In order to replace the decolorizing liquid in the container 7, first, the liquid feed pump 46 is turned off, the switching valve 47 is opened on the container 7 side, and the electromagnetic valve 27 is opened to waste the decoloring liquid 42 in the container 7 into the waste liquid tank 28. Next, by supplying (turning on) the liquid feed pump 46 with the electromagnetic valve 27 closed, supply of new decoloring liquid from the decoloring liquid tank 45 into the container 7 is started, and then the liquid level When it is detected that a predetermined amount of decoloring liquid has been supplied based on the output of the sensor 48, the driving of the liquid feeding pump 46 is stopped (turned off). After the liquid replacement, as in the first embodiment, the empty scan data for the decoloring liquid before replacement stored in the memory in the arithmetic control unit 21 is once erased, and then the support having the electrophoretic image is displayed. Prior to the photometric scan, the photometric scanning means 10 is scanned blank to capture blank scan data for the replaced decolorizing liquid.
[0026]
【The invention's effect】
According to the present invention , the photometric scanning means is idle-scanned at different times in the absence of a support to store empty scan data, and the container important for the densitometer based on the plurality of empty scan data at different times stored. than was the state of the liquid inside be managed, it is possible to improve the measurement accuracy.
[Brief description of the drawings]
FIG. 1 is a diagram showing a first embodiment of the present invention.
2 is a block diagram showing a configuration of an example of a main part of an arithmetic control unit shown in FIG.
FIG. 3 is a diagram for explaining the operation of the first embodiment.
FIG. 4 is also a diagram for explaining the operation.
FIG. 5 is a diagram showing a second embodiment of the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Wetting part 2 Application | coating part 3 Electrophoresis part 4 Dyeing / decoloring / drying part 5 Densitometer 6 Clearing liquid 7 Container 8 Light source part 9 Light receiving part 10 Photometric scanning means 11 Photometric part 12 Support body 13 Conveying mechanism 14 Motor 15 Rack / pinion mechanism 16 Origin sensor 21 Operation control unit 22 Input / output unit 25, 27 Solenoid valve 26 Liquid supply tank 28 Waste liquid tank 29 Liquid exchange means 31 Transport drive unit 32 Scanning drive unit 33 Storage units 33a, 33b Memory 34 Comparison unit 35 Allowable value setting unit 36 arithmetic unit 37 statistical processing unit 38 control unit 41 dyeing / decoloring unit 42 decoloring liquid 45 decoloring liquid tank 46 liquid feed pump 47 switching valve 48 liquid level sensor

Claims (5)

In a densitometer in which the support on which the electrophoretic image is formed is immersed in the liquid in the container and scanned by the photometric scanning means to obtain photometric data,
A means for driving the photometric scanning means in the absence of the support , a storage means for storing the empty scan data, and a statistical processing means for statistically processing the empty scan data stored in the storage means. And
The storage means stores a plurality of empty scan data at different times, and the statistical processing means manages the state of the liquid in the container based on the plurality of empty scan data stored in the storage means. Densitometer characterized by that. The densitometer according to claim 1, wherein
Furthermore, it has setting means for setting an allowable value of the empty scan data, and a comparing means for comparing the allowable value set by the setting means with the empty scan data, and based on the output of the comparing means, A densitometer configured to issue a warning when the empty scan data exceeds the allowable value. The densitometer according to claim 1 or 2,
Furthermore, the densitometer further includes a calculation unit that corrects photometric data of the support on which the electrophoretic image is formed based on the empty scan data stored in the storage unit. The densitometer according to claim 1, 2, or 3,
The densitometer characterized in that the statistical processing means is configured to identify and manage the state of the liquid in the container and the state of the container itself. The densitometer according to claim 4,
The densitometer further comprises a liquid exchanging means for automatically exchanging the liquid in the container based on the liquid state management result.

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