KR101530114B1

KR101530114B1 - Analyzing device

Info

Publication number: KR101530114B1
Application number: KR1020120041649A
Authority: KR
Inventors: 시게키 마츠모토
Original assignee: 우시오덴키 가부시키가이샤
Priority date: 2011-04-22
Filing date: 2012-04-20
Publication date: 2015-06-18
Also published as: JP2012225864A; JP5482721B2; KR20120120077A; CN102749444B; CN102749444A

Abstract

An object of the present invention is to provide an analyzer capable of performing detection or quantitation of a test substance with high reliability using an immunochromatography method without the risk of human intervention.
(Solution) The analyzing apparatus includes an analyzing unit that includes a reaction area in which a coloring reaction is caused by a substance to be tested, and a reaction area in the test piece having a code area showing information related to the coloring reaction on the same surface and the code area And an image of an analysis area photographed in a first photographing condition in accordance with the photographing apparatus is detected as a code by a code Acquires the image of the analysis area photographed under the second photographing condition different from the first photographing condition as the image data for detecting the test substance.

Description

ANALYZING DEVICE

The present invention relates to, for example, an analyzer used for the detection or quantification of a test substance using the immuno-chromatographic method.

Recently, immunoassay (immunological chromatography) has been attracting attention as a method of point-of-care examination (POCT) performed in a "close location of a patient" such as a doctor's office or a ward, The POCT analyzing apparatus using the chromatography method is required to be able to perform highly reliable measurement in a short time without requiring troublesome operation.

On the other hand, the immunochromatography test strip (strip) used in such POCT does not require the adjustment of the reagent, and the test substance in the immunochromatography test strip (strip) can be obtained by simply dropping the test liquid such as blood or urine onto the test piece. And it is very useful for easily and quickly analyzing a test substance in a test liquid, and therefore a large number of test substances are currently in practical use.

In the immunochromatography test piece, calibration curve information according to the test piece is added in order to correct the reactivity due to the deviation of the reagent for each lot, etc. However, when the calibration curve information is provided by, for example, a magnetic card, There is a possibility that the other magnetic card is used incorrectly, resulting in an incorrect measurement result. Therefore, a code area, for example, a two-dimensional code or the like showing the calibration curve inherent to the test piece is installed separately from the reaction area in the test piece Or the like to be held on the test piece itself.

However, when such a test piece is used, the analyzing apparatus is configured to include a sensor for detecting the degree of color development in the reaction area and a plurality of sensors for reading the code shown in the code area Or a mechanism for relatively moving one of the test piece and the sensor relative to the other in order to detect the degree of color development in the reaction area and to read the code shown in the code area by one sensor Therefore, the structure of the analyzing apparatus becomes complicated, and it can not be produced advantageously from the viewpoint of cost.

With respect to such a problem, an image pickup device including a reaction region causing a coloring reaction by a test substance and an analysis region including the reaction region and the code region in a test piece having a code region marked with a code by a bit pattern, In which a reaction region and a code region of a test piece are simultaneously imaged to obtain information represented by a bit pattern in a code region and a degree of color development in a reaction region is detected (See Patent Document 1).

In this analyzer, various types of information (lot information, expiration date information, calibration curve information, and the like) corresponding to the bit pattern of the test piece recorded on the magnetic card or the IC card are read in advance and acquired from the image picked up by the image pick- And the concentration of the test substance depending on the degree of color development of the reaction region in the acquired image is calculated based on the calibration curve information. The validity period of the test piece can be checked by making the bit pattern shown in the code area include the expiration date information of the test piece.

Japanese Patent Application Laid-Open No. 2006-266882

However, since the reaction region and the code region in the test piece differ in brightness from each other, in the above-described analyzing apparatus capturing the reaction region and the code region of the test piece under the same conditions, the degree of color development in the reaction region is detected , The bit pattern indicated in the code area can not be properly read, and on the other hand, in the case of acquiring the bit pattern indicated by the code area in the image obtained by the photographing conditions adjusted to the appropriate brightness, There is a problem that detection of the test substance can not be performed with high reliability because the reaction area becomes too dark.

The present invention has been made based on the above-described circumstances, and it is an object of the present invention to provide an analyzer capable of performing detection or quantitation of a test substance with high reliability, for example, in an analyzer using the immuno-chromatographic method .

The analyzing apparatus of the present invention is characterized in that the reaction region and the code region in a test piece having a reaction region causing a coloring reaction by a substance to be tested and a code region displaying a code including information relating to the coloring reaction on the same surface Wherein the analyzing apparatus includes a photographing apparatus that includes an analyzing region including the analyzing region in the viewing region and detects the analyte in accordance with the degree of coloring in the reaction region,

An image of the analysis area photographed in the first photographing condition by the photographing device is acquired as code reading image data and an image of the analysis area photographed in a second photographing condition different from the first photographing condition is acquired And is obtained as image data for material detection.

In the analyzing apparatus of the present invention, it is preferable that the second photographing condition has a larger exposure amount than the first photographing condition.

Specifically, the second photographing condition is set such that the exposure amount is set to be larger as the exposure time is set longer than the first photographing condition, or the illuminance in the analysis area by the illumination device illuminating the analysis area Is set to be higher than the first photographing condition, the exposure amount can be set to be large.

In the analyzing apparatus of the present invention, the code displayed in the code area in the test piece includes calibration curve information related to a calibration curve showing the relationship between the degree of color development in the reaction area and the concentration of the test substance,

And a concentration calculating mechanism for calculating the concentration of the test substance from the test substance detecting image data based on the calibration curve information acquired from the code reading image data.

Further, in the analyzing apparatus of the present invention, the code displayed in the code area in the test piece includes reaction time information related to the reaction time at which the color development state in the reaction area can be detected,

It is preferable that the imaging apparatus photographs the image of the analysis area in the second photographing condition after the reaction time acquired from the code reading image has elapsed after the detection of the set of the test piece is detected Do.

Further, in the analyzing apparatus of the present invention, it is preferable that the photographing apparatus comprises a CMOS image sensor.

The analyzing apparatus of the present invention is suitably used because it quantitatively analyzes a substance to be tested in a living body component by an immuno-chromatographic method.

According to the analyzing apparatus of the present invention, by using the photographing apparatus having the view region including the analysis region including the reaction region and the code region in the test piece, the optimum region for the analysis region in the test piece, An image photographed under one photographing condition and an image photographed in a second photographing condition optimal for a reaction region in the test piece are acquired as code reading image data and test substance detecting image data, It is possible to avoid bulldog or misreading of the information included in the code displayed in the code area, and to analyze the color development state in the reaction area with high reliability.

In addition, since the necessary information is included in the code displayed in the code area, there is no fear that an artificial mistake will interfere with the information input by the user or the like. Therefore, the necessary analysis can be easily performed with high reliability .

1 is a perspective view showing an appearance of an example of the analyzing apparatus of the present invention.
2 is a plan view schematically showing the configuration of an example of the immunochromatography test piece used in the analyzer of the present invention.
3 is a perspective view schematically showing the configuration of a detection unit in the analyzer of the present invention.
4 is an operational flow chart of the analyzing apparatus of the present invention.
5 is a diagram showing an example of image data (code reading image data) photographed under the first photographing condition.
6 is a graph showing an example of the luminance profile in the developing direction of the specimen in the image data shown in Fig.
Fig. 7 is a diagram showing image data (image data for detecting test substance) photographed under the second photographing condition. Fig.
8 is a graph showing an example of the luminance profile in the developing direction of the specimen in the image data shown in Fig.
9 is a diagram showing an example of a calibration curve showing the relationship between the concentration of the test substance and the coloring portion concentration as the calibration curve information included in the code displayed in the code region.

Hereinafter, embodiments of the present invention will be described in detail.

The analyzer of the present invention is used for quantitatively analyzing a test substance in a biological component by, for example, immuno-chromatography.

1 is a perspective view showing an appearance of an example of the analyzer of the present invention. In Fig. 1, numeral 11 is a power switch, numeral 12 is a touch panel for inputting ID information related to a specimen to be analyzed, and for inputting an operation command signal. 13 is a strip-shaped immunochromatography test piece (hereinafter referred to as " test piece ") having a test piece insertion port, a reaction area for causing a color reaction by a test substance contained in a specimen and a code area, Quot; test piece ") is inserted in a horizontal posture with the surface having the reaction area and the code area facing upward.

2, a porous support 21 (indicated by a slanting line for convenience in FIG. 2) such as a filter paper is accommodated in the case 20A, and the porous support 21 Two openings 22A and 22B for exposing the sample 21 to the outside are formed at a position spaced apart from the sample development direction (indicated by a white arrow in Fig. 2). In addition, the specimen lower portion 23 is formed by one opening portion 22A and the reading portion 24 is formed by the other opening portion 22B. In the surface region of the porous support 21 exposed to the outside through the other opening 22B in the case 20A, for example, the labeled antibody and the antibody or antigen according to the substance to be tested are released (Vertical direction in Fig. 2) orthogonal to the direction of the reaction (R). As a result, the reaction region R is formed.

A two-dimensional code 25 such as a QR code (registered trademark) is provided at a position on the downstream side of the reading section 24 in the developing direction of the specimen, Respectively.

The information included in the two-dimensional code 25 may include basic information of the test piece 20 such as an analysis item, an effective period, a lot number, and the like, and information unique to the test piece 20 such as reaction time, calibration curve, Information related to the color development reaction, and the like.

As shown in Fig. 3, the detection unit in this analyzer includes a test piece detection sensor 30 for detecting the presence or absence of the test piece 20 and a test piece 20 for detecting the presence or absence of the test piece 20 in the state where the test piece 20 is set at an appropriate position And a code region C in a field of view (indicated by two-dot chain lines in Fig. 2) S, An illuminating device 50 for illuminating an area (illuminated area, indicated by a broken line in Fig. 2) L including a viewing area S in the illuminating device 40, a sensor 30 for detecting a test piece 30, a photographing device 40, And a control means (not shown) for controlling the operation of each of the lighting apparatuses 50.

As the test piece detecting sensor 30, for example, a photo interrupter or the like can be used.

The photographing apparatus 40 receives the light reflected by the analysis region of the test piece 20 and photographs the light intensity distribution on the entirety of the analysis region of the test piece 20. For example, a CMOS (Complementary Metal-Oxide Semiconductor) image It is preferable that the image pickup device is constituted by an image pickup element comprising a sensor 41.

As the illumination device 50, for example, when the gold colloid is used as a label for the test piece 20, color development by, for example, a pink color by the substance to be tested allows the light emission peak wavelength to be near 525 nm And the LED 51 emitting green light as a light source. The light source in the illumination device 50 may be any one that irradiates a color light having a larger contrast with the color development density of the color development portion (line) in the reaction region. For example, a semiconductor laser or a lamp and a band- Or may be constituted by combining them.

The size of the illumination area L by the illumination device 50 can be adjusted, for example, by the arrangement position (separation distance) of the illumination device 50 with respect to the surface of the test piece 20.

The control means adjusts the photographing conditions by the photographing apparatus 40 and outputs two pieces of image data for the analysis region in the test piece 20, which were photographed under different first photographing conditions and second photographing conditions, Code reading image data based on the conditions and image data corresponding to the second photographing condition as subject material detecting image data and analyzing the respective image data.

The code read image data and the image data for detecting the substance to be detected are represented by, for example, a gradation image of 256 gradations of 0 to 255. For example, the maximum gradation portion , Respectively, for example, in the range of 200 to 250, reading of the information displayed in the code area C and reading of the color development state of the reaction area R can be appropriately performed.

The control means is provided with a concentration calculating mechanism for calculating the concentration of the test substance from the test substance detecting image data based on the calibration curve information obtained from the code reading image data.

As a method of adjusting the photographing conditions by the photographing apparatus 40, for example, the exposure time is adjusted by controlling the shutter speed (shutter time) of the electronic shutter of the CMOS image sensor 41 in the photographing apparatus 40 , A method of adjusting the exposure amount (the amount of light received by the CMOS image sensor 41) or a method of adjusting the exposure amount by controlling the amount of light emitted from the LED 51 in the illumination device 50 desirable. As a method of adjusting the exposure amount by adjusting the exposure time, there is a method of adjusting the gain (sensitivity) or iris of the CMOS image sensor 41, for example. However, the gain of the CMOS image sensor 41 is increased A method of adjusting the exposure time by controlling the shutter speed (shutter time) of the electronic shutter of the CMOS image sensor 41 is preferable because noise increases when the exposure amount is increased and the method of shooting is changed when the aperture stop is changed.

The first photographing condition by the photographing apparatus 40 is set so as to have the optimum brightness for photographing the code region C in the analysis area of the test piece 20 and concretely, The shutter speed (exposure time) of the electronic shutter of the CMOS image sensor 41 and / or the shutter speed (exposure time) of the LED 50 in the illumination device 50 are set so that the brightest portion of the periphery of the CMOS image sensor 41 does not exceed the maximum gradation of the CMOS image sensor 41 51, that is, the magnitude of the exposure amount for the CMOS image sensor 41 is set.

The second photographing condition by the photographing apparatus 40 is set so as to have an optimum brightness for photographing the reaction region R in the analysis region of the test piece 20 and concretely, for example, (CMOS image sensor 41) within the range in which the brightest portions other than the color-developed portions (detection lines and control lines) in the reaction region R do not exceed the maximum gradation of the CMOS image sensor 41, The shutter speed (exposure time) of the electronic shutter of the illumination device 50 and / or the magnitude of the amount of light emitted by the LED 51 in the illumination device 50 is larger than the first photographing condition.

The exposure amount for the CMOS image sensor 41 in the second photographing condition is, for example, about 1.3 times the exposure amount for the CMOS image sensor 41 in the first photographing condition.

As described above, the adjustment of the shutter speed of the electronic shutter of the CMOS image sensor 41 can be performed, for example, by changing the operating condition of the CMOS camera module.

The adjustment of the amount of light emitted by the LED 51 can be performed by changing the magnitude of the supply current to the LED 51, for example.

Hereinafter, the operation of the analyzer will be described.

When the power switch 11 of the analyzing apparatus is turned on, a menu screen is displayed on the touch panel 12 to be in a measurable state.

As shown in Fig. 4, when the analysis start button is pressed on the touch panel 12 (S1), the input screen of the ID information related to the specimen to be analyzed is input and the ID information is inputted by operating the touch panel 12 (S2). Thereafter, a specimen is dropped into the specimen lower portion 23 of the test piece 20, and the test piece 20 is inserted into the specimen insertion port 13 from the code region C side.

When it is detected that the test piece 20 is set by the sensor 30 for detecting the test piece in the detecting unit (S3), the test piece 20 And the image is acquired as code detection image data for detecting information displayed on the two-dimensional code 25 installed in the code area C (S4). Fig. 5 shows an example of image data (code reading image data) photographed under the first photographing condition, and Fig. 6 shows an example of the luminance profile in the developing direction of the specimen in the image data shown in Fig. Here, the code reading image data has a sufficient output (a density of about the maximum gradation part 225) for properly reading the information indicated by the two-dimensional code in the pixel (pixel) corresponding to the code area (cdeh line surrounded part) And the pixel corresponding to the reaction region (abfg line surrounding portion) can not obtain a sufficient output for performing the detection of the test substance with high reliability, and the entire image is dark (the maximum gradation portion has a density of about 180) 5 and Fig.

In the image analysis of the code reading image data, the two-dimensional code 25 should be positioned in a state in which the test piece 20 is set at an appropriate position in the viewing area S of the CMOS image sensor 41 A determination process is performed as to whether or not a region having a predetermined size including the region is set as the analysis region A1 and the code region C of the test piece 20 is located in the analysis region A1. If it is confirmed that the two-dimensional code 25 of the test piece 20 is not located in the analysis area A1, it is determined that the test piece 20 is not set at the proper position, and the user is notified. Therefore, even though the reaction region R of the test piece 20 is not actually located in the viewing area S of the CMOS image sensor 41 because the test piece 20 is not properly inserted, It is possible to avoid the problem of performing the analysis based on the output from the CMOS image sensor 41 and completing the analysis.

Next, an appropriate image analysis is performed on the code area C in the analysis area A1 of the obtained code detection image data by the control unit (S5), and the test piece 20 For example, reaction time information related to the reaction time at which the color development state in the reaction region (R) can be detected, calibration curve information related to the calibration curve for calculating (quantifying) the concentration of the test substance contained in the sample Etc. are read out and recorded in the memory.

When it is detected by the control means that the elapsed time from the detection of the setting of the test piece 20 exceeds the reaction time associated with the obtained reaction time information (S6), the photographing condition Is changed to the second photographing condition and the image of the analysis area in the test piece 20 is photographed by the photographing device 40 and the image for detecting the substance to be detected in the reaction region R And acquired as data (S7). An example of image data (image data for detecting the material to be detected) photographed under the second photographing condition is shown in Fig. 7, and an example of the luminance profile in the developing direction of the sample in the image data shown in Fig. 7 Is shown in Fig. Here, in the image data for detecting the test substance, an output of a sufficient size (concentration of about 240 of the maximum gradation portion) for performing detection of the test substance with high reliability is used in the pixel corresponding to the reaction region (abfg line surrounded portion) And it is understood that the output of a part of pixels corresponding to the code region (cdeh line surrounded portion) becomes a size exceeding the maximum gradation of the CMOS image sensor 41 (overexposed). In the above-described analyzer, by using the CMOS image sensor 41 as an image sensing element, for example, noise caused by an overflow of charges generated inside the image sensing element called " smear " The output of the pixel corresponding to the reaction region R is not affected.

Appropriate image analysis is performed by the control means on the reaction region R of the test piece 20 in the analysis region A2 of the acquired image of the material detection image data for detection, Is calculated (S8).

9, the concentration X of the substance to be tested in accordance with the optical density (Y) of the coloring portion calculated above is calculated based on the calibration curve associated with the calibration curve information obtained from the code reading image data (S9), and the result is displayed on the touch panel 12 as an analysis result (S10).

According to the above analyzing apparatus, by the photographing apparatus 40 having the view area S including the analysis area including the reaction area R and the code area C in the test piece 20, The image captured in the first photographing condition optimal for the code area C in the test piece 20 and the second photographing optimized in the reaction area R in the test piece 20 Dimensional code 25 in the code area C is obtained as the code reading image data and the image data for detecting the test substance, And the coloring state in the reaction region R can be analyzed with high reliability.

In addition, since necessary information is included in the two-dimensional code 25 in the code area C, there is no fear that an artificial mistake will interfere with the information input by the user or the like. Therefore, And can be performed with reliability.

Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment, and various modifications can be added.

For example, the test piece used in the analyzing apparatus of the present invention does not need to have a structure in which the reaction region and the code region are arranged at positions separated from each other in the developing direction of the specimen, May be arranged in a position close to each other so that the regions are located.

In addition, the specific arrangement such as the arrangement position and attitude of the lighting apparatus in the detection unit, and the arrangement position and attitude of the photographing apparatus can be appropriately changed.

11: Power switch 12: Touch panel
13: specimen inlet
20: Immunochromatography test piece (test piece)
20A: Case 21:
22A, 22B: opening 23: specimen bottom
24: reading unit 25: two-dimensional code
30: Test piece detection sensor 40: Photographing device
41: CMOS image sensor (imaging element)
50: Lighting device 51: LED
C: code region R: reaction region
S: Field of view L: Lighting area
A1, A2: interpretation area

Claims

As an analyzing apparatus used for detecting an analyte in a biological component by immuno-chromatography,
An analysis including the reaction region and the code region in the test piece having the reaction region causing the color reaction by the substance to be tested contained in the specimen and the code region displaying the code including information related to the color reaction on the same surface An analyzing device for detecting the substance to be tested in accordance with the degree of coloring in the reaction region,
The image of the analysis area photographed in the first photographing condition by the photographing device is acquired as the code reading image data and the image of the analysis area photographed in the second photographing condition with a larger exposure amount than the first photographing condition And is obtained as image data for detecting an analyte.

The method according to claim 1,
Wherein the second photographing condition has a longer exposure time than the first photographing condition.

The method according to claim 1 or 2,
Further comprising a lighting device for illuminating the analysis area,
Wherein the second photographing condition has a higher illuminance in the analysis area than the first photographing condition.

The method according to claim 1 or 2,
Wherein the code displayed in the code area of the test piece includes calibration curve information related to a calibration curve showing a relationship between the degree of color development in the reaction area and the concentration of the test substance,
Further comprising a concentration calculating mechanism for calculating the concentration of the test substance from the test substance detecting image data based on the calibration curve information acquired from the code reading image data.

The method according to claim 1 or 2,
Wherein the code displayed in the code region of the test piece includes reaction time information related to a reaction time at which the color development state in the reaction region becomes detectable,
Characterized in that an image of the analysis area is photographed by the photographing device in the second photographing condition after the reaction time acquired from the code reading image has elapsed after the detection of the set of the test piece is detected Device.

The method according to claim 1 or 2,
Wherein the photographing apparatus is provided with a CMOS image sensor.

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