JPH0694622A - Analyzer - Google Patents

Abstract

PURPOSE:To obtain an analyzer of a specimen component with errors less relatively of measured values by enabling the irradiating of a photodetector of a photodetecting means with uniform light. CONSTITUTION:This analyzer 1 measures the intensity of coloring optically of a reagent layer 7 of a tester 5 which has the reagent layer 7 adapted to perform a coloring in reaction with a specified component of a specimen and has a projecting means 3 to irradiate the reagent layer 7 of the tester 5 with light and a condensing means 8 to condense the reflected light from the reagent layer 7 of the tester 5. Moreover, a diffusing plate 9 is provided to diffuse the light condensed by the condensing means 8, a photodetecting means 10 to receive the light from the diffusion plate 9 and a measuring device 11 to measure the intensity of the light received by the photodetecting means 10.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an analyzer for analyzing a specific component in a sample by using a test tool for detecting a specific component in the sample (eg glucose and protein in urine).

[0002]

2. Description of the Related Art Conventionally, a test tool having a reagent layer that develops a color in response to a specific component is immersed in a sample, and the color intensity is optically measured to analyze the sample component. Equipment is widespread. This analyzer generally irradiates the colored reagent layer with light from a light source, receives the wavelength and intensity of the reflected light with a light-receiving element, and further converts it into an electric signal with a standard value stored in advance. By comparing, the measurement and analysis of the sample components are performed. Then, in this type of analyzer, due to diffused reflection in the reagent layer, since the light amount of the reflected light received by the light receiving means is insufficient and the detection sensitivity becomes low,
A convex lens is inserted between the reagent layer and the light-receiving means, and the light diffusely reflected by the reagent layer is condensed on the light-receiving means (the reflected light is imaged on the light-receiving element) to secure the amount of light received by the light-receiving means. However, the detection sensitivity is improved.

[0003]

However, since this type of analyzer irradiates the light receiving elements arranged on the substrate with the light condensed by the convex lens, the light receiving elements are evenly irradiated. I can't. In particular, when a color sensor having a well-balanced sensitivity in the visible light region and a light receiving element or a color filter arranged in a plane and in parallel on the substrate is used as the light receiving means, each light receiving element is irradiated. The amount of light emitted varies and the measured value has an error. In addition, the displacement of the placement position of the measurement object may affect the irradiation of the light receiving element, and an error may occur in the measurement value. Therefore, an object of the present invention is to evenly analyze the light receiving elements even if the analyzer has a light collecting means to secure the amount of received light, and even if the placement position of the measurement target is slightly displaced. An object of the present invention is to provide an analyzer which is irradiated with light and has relatively few errors in measured values.

[0004]

An object of the present invention to solve the above-mentioned problems is to analyze the color intensity of the reagent layer of a test device having a reagent layer that reacts with a specific component in a sample to produce a color and to optically measure the color intensity. An apparatus for projecting light onto the reagent layer of the test tool, a light converging means for collecting reflected light from the reagent layer of the test tool, and a light condensing means. An analyzing device comprising: a diffusion plate for diffusing the light, a light receiving means for receiving the light from the diffusion plate, and a measuring device for measuring the intensity of the light received by the light receiving means. is there.

An embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a schematic view of an embodiment of the analyzer of the present invention. FIG. 2 is a perspective view of the vicinity of the photometric section of an embodiment of the analyzer of the present invention. FIG. 3 is an explanatory diagram for explaining the operation of the analyzer of the present invention. FIG. 4 is a schematic view of another embodiment of the analyzer of the present invention.

As shown in FIG. 1, the analyzer 1 of the present invention optically determines the color intensity of the reagent layer 7 of the test device 5 having the reagent layer 7 which is colored by reacting with a specific component in the sample. Which is a measuring device 1 for irradiating light, a light projecting means 3 for irradiating the reagent layer 7 of the test tool 5 with light, and a light collecting means 8 for collecting the reflected light from the reagent layer 7 of the test tool 5. A diffuser plate 9 for diffusing the light condensed by the condensing means 8, a light receiving means 10 for receiving the light from the diffuser plate 9, and a measuring device 11 for measuring the intensity of the light received by the light receiving means 10. And have.

The light projecting means 3 is for irradiating the reagent layer 7 of the test device 5 with light. In this embodiment, as shown in FIG. And
As the light projecting means 3, for example, a white light source such as a halogen lamp, a tungsten lamp or a xenon lamp can be preferably used. An interference filter 12 (optical filter) may be installed on the optical path between the light projecting means 3 and the reagent layer 7, as shown in FIG. This is for irradiating only the light of a certain wavelength band to the measuring object, and different filters are used depending on the measuring object.

The condensing means 8 is for condensing the reflected light from the reagent layer 7 of the test device 5, and the condensing means 8 is used for the light between the reagent layer 7 and a light receiving means 10 described later. By arranging on the road, the light diffusely reflected by the reagent layer 7 can be condensed, the amount of light received by the light receiving means 10 can be secured, and the detection sensitivity can be improved. In this embodiment, as shown in FIG. 2, the light collecting means 8 is attached inside the photometric unit 4 and between the reagent layer 7 and a diffusion plate 9 described later. A convex lens can be preferably used as the light collecting means 8.

The diffusing plate 9 is for diffusing the incident light from the light collecting means 8 and irradiating the light receiving means 10 with light having a uniform light intensity distribution. By disposing this diffusing plate 9, even when a color sensor is used as the light receiving means 10, it is possible to uniformly irradiate all the light receiving elements with light, and the error in the measured value can be made relatively small. You can The diffusing plate 9 is attached on the optical path between the light collecting means 8 and the light receiving means 10. In addition,
In this embodiment, as shown in FIG. 2, the diffusion plate 9 is attached inside the photometric unit 4 and between the light converging means 8 and the light receiving means 10. However, the invention is not limited to this, and it may be provided on the optical path between the light collecting means 8 and the light receiving means 10. The size of the diffusion plate 9 (light diffusion surface) is preferably the same as or slightly larger than the light receiving area of the light receiving means 10 described later. Thereby, the light incident from the light collecting means 8 can be effectively applied to the light receiving means 10, and the amount of light received by the light receiving means 10 can be secured. The diffusing plate 9 is preferably one that completely diffuses light, such as opal glass having a thin opalescent layer on one side of transparent glass, opal glass entirely composed of opalescent material, opalescent plastic plate, or Sulfuric acid paper or the like can be preferably used. More preferably, it is an opal glass having a thin opalescent layer on a half surface of transparent glass with little light attenuation.

The light receiving means 10 is for receiving the light incident from the diffuser plate 9. In this embodiment, as shown in FIG. It is installed at a position where it can receive light. A photo sensor can be preferably used as the light receiving means 10.
Further, as the light receiving means 10, as shown in FIG. 4, three light receiving elements 10X, 10Y, 10Z and each light receiving element 10 are provided.
You may use the color sensor which has the color filters 10R, 10G, and 10B each planarly arrange | positioned on the optical path near X, 10Y, and 10Z. Since the color sensor has a well-balanced sensitivity in the visible light region, the analyte component can be measured and analyzed more accurately. As the light receiving elements 10X, 10Y, 10Z of the color sensor, for example, a photodiode or an amorphous silicon diode can be preferably used, and these light receiving elements generate a current (analog electric signal) having a strength corresponding to the strength of the received light. . Further, color filters 10R, 10G, 10B
Are capable of transmitting light of different wavelength bands, for example, the maximum wavelength of light passing through the color filter 10R is 620 nm, the maximum wavelength of light passing through the color filter 10G is 540 nm, and the maximum wavelength of light passing through the color filter 10B. The maximum wavelength of light is 460 nm. Then, as shown in FIG. 4, the light receiving element and the color filter are arranged on both surfaces of a substrate such as glass.

The light receiving means 10 is electrically connected to the measuring device 11. The measuring device 11 includes the light receiving means 10
In order to measure the intensity of the light received by, the light receiving means 10 has an A / D converter 11B electrically connected to the light receiving means 10 and an arithmetic means 11A, as shown in FIG. In addition,
When a color sensor is used as the light receiving means 10,
As shown in FIG. 4, the measuring device 10 includes a light receiving element 10X,
A / D electrically connected to each of 10Y and 10Z
It is composed of converters 11X, 11Y and 11Z, and an arithmetic means 11A. The A / D converter converts an analog signal input from the light receiving element into a digital signal, and the arithmetic means 11A is supplied to the reagent layer 7 based on the digital signal from the A / D converter. It has a function of calculating the amount of a specific component in a sample. This computing means 11A
For example, a microcomputer can be preferably used.

The analyzer 1 of this embodiment is shown in FIG.
As shown in (1), it has a tray 2 for mounting the test device 5. Then, the test tool 5 immersed in the sample is placed in the recess provided on the tray 2, and the reagent layer 7 reaches a predetermined position where the light from the light projecting means 3 is irradiated from the front side of the drawing. The structure is such that the specific component in the sample is analyzed by moving the sample until it is moved.

The test tool 5 used in the analyzer 1 of this embodiment has a support 6 and a reagent layer 7 as shown in FIG.
And the support 6 is formed in a plate shape. The support 6 has a thickness of, for example, about 20 to 500 μm and is made of a material inert to the sample. Specific constituent materials of the support 6 include polyethylene terephthalate, cellulose ester, polycarbonate,
Various resins such as polymethylmethacrylate, polyvinyl chloride, polypropylene, polystyrene and polyvinyl alcohol, or glass can be preferably used. Further, the support 6 may be a stack of sheets made of two or more kinds of the above materials.

The reagent layer 7 is formed by supporting a reagent described below on a carrier, and a non-fibrous or fibrous porous material can be preferably used as the carrier. A membrane filter is a typical non-fibrous porous material.
A dispersion in which a porous material such as diatomaceous earth or a microcrystalline material is dispersed in a binder, or a porous aggregate in which microspherical beads of glass or resin are point-bonded to each other can be preferably used. Further, as the fibrous porous material, a woven / knitted fabric, a non-woven fabric, a filter paper, an aggregate of short fibers and the like can be preferably used. Here, the woven and knitted fabric includes a woven fabric, a knitted fabric, and the like. And
The carrier preferably has hydrophilicity, which promotes penetration and diffusion of the sample. Examples of such materials include those in which the material itself that constitutes the carrier is hydrophilic (for example, those composed of fibers such as cotton, silk, nylon, etc.), as well as washing or surfactant for the carrier. Examples include those that have been subjected to a hydrophilic treatment.

Although the thickness of the reagent layer 7 varies depending on the material and properties of the carrier, it is usually about 1 to 500 μm, especially 5 to 3 μm.
The thickness is preferably about 00 μm. Then, the reagent shown below is carried on the reagent layer 7. The reagent composition is appropriately determined depending on the specific component to be detected (quantified) in the sample.
For example, when glucose is detected in a sample, glucose oxidase (GOD) and peroxidase (POD), which are enzymes, and a color former (chromogen) are the main components of the reagent. The method of supporting the reagent is carried out, for example, by immersing the carrier in a liquid containing the reagent or spraying the same liquid on the carrier and then drying. If necessary, the reagent layer 12 may be added with additives such as a pH adjusting agent, a light-reflecting substance, a stabilizer, a sensitizer, an oxidizing agent, a wetting agent, and a viscosity adjusting agent.

The test device 5 as described above uses glucose, ketone bodies, uric acid, BUN, creatinine, calcium in a sample (for example, body fluid such as plasma, serum, urine, feces, saliva, lymph, spinal fluid). Oxalic acid, protein, lipoprotein (LDL, HDL), cholesterol, triglyceride (neutral fat), free fatty acid, bilirubin, urobilinogen, nitrite, ascorbic acid, hemoglobin, myoglobin, leukocyte, GOT, GPT, ALP, γ-G
It can be used to detect T, hydrogen ions (pH measurement) and the like.

[0017]

Next, the operation of the analyzer 1 of the present invention will be described.
First, a sample is dropped on the reagent layer 7 of the test device 5, placed on the tray 2, and aligned so that the reagent layer 7 enters the measurement region. Then, the light source of the light projecting means 3 is turned on, and the reagent layer 7 of the test device 5 is irradiated. The reflected light of the light applied to the reagent layer 7 is condensed by the condensing means 8 and then diffused by the diffusion plate 9.
Incident on. Then, the light incident on the diffusion plate 9 becomes a light having a uniform intensity distribution as shown in FIG.
Irradiate evenly. Thus, the analyzer 1 of the present invention,
Since the light receiving surface of the light receiving means 10 is configured to be uniformly irradiated, it is possible to obtain a measured value with a relatively small error. Then, the light receiving means 10 emits an electric signal (analog signal) having a magnitude corresponding to the intensity of the received light, and this electric signal is converted into a digital signal by the A / D converter 11B of the measuring device 11. After that, the light intensity D is input to the calculation means 11A and measured.

Further, as shown in FIG. 4, when a color sensor is used as the light receiving means 10, the light incident on the diffusion plate 9 has a uniform intensity distribution and is formed on the substrate of the light receiving means 10. Each of the three color filters 10R, 10G, and 10B arranged in parallel and in a plane is uniformly irradiated. Further, the light radiated to the color filter passes through the color filter and the substrate, and is received by the light receiving elements 10X, 10X.
The light is received by Y and 10Z. Further, the light receiving elements 10X, 1
The 0Y and 10Z emit electric signals (analog signals) having a magnitude corresponding to the intensity of the received light, and the electric signals are converted into digital signals by the A / D converters 11X, 11Y and 11Z of the measuring device 11. And is input to the calculating means 11A.
Then, the calculating means 11A measures the reflected light intensities Dx, Dy, Dz of three different maximum wavelengths, and further obtains two or three sets of two ratios among the reflected light intensities Dx, Dy, Dz. , The concentration of the specific component in the sample is analyzed based on these data. For example, the reflected light intensities Dx and D
The ratio Dx / Dy of y and the ratio D of the reflected light intensities Dy and Dz
y / Dz is calculated, and one of these values is set on the horizontal axis of the graph,
The other is plotted on the quadratic plane with the vertical axis, and the concentration of the specific component in the sample is determined from the position. That is, since the color change corresponding to the concentration of the specific component is distributed with a certain tendency on the graph (secondary plane), the pattern of this distribution is stored in advance in the calculating means 11A and the plot is made. The determined position is compared with the pattern of this distribution to determine the component concentration.

(Experiment) 1. Manufacture of test device A test device having a reagent layer on the surface of a support was prepared as follows. (1) Support A support of a polyethylene terephthalate film having a thickness of 200 μm was cut into a size of 5 mm × 90 mm. (2) Reagent layer (2-1) Reagent layer for detecting ketone body A first solution to a third solution having the composition shown below are prepared, and a filter paper having a thickness of 260 μm (manufactured by Advantech,
ADVANTEC No2) is first impregnated with the first solution,
After drying (80 ° C, 60 minutes), impregnation with the second solution, drying under reduced pressure (60 ° C, 90 minutes), further impregnation with the third solution, drying (60 ° C, 20 minutes), and ketone A reagent layer for body detection was prepared. And this reagent layer is 5 mm x 5 m
Cut to m size. (First solution) Trisodium phosphate / 12H2O 20 g Disodium phosphate / anhydrous 10 g Glycine 20 g Water 100 ml (Second solution) Sodium nitroprusside 1.0 g Citric acid / H2O 0.85 g Dimethyl sulfoxide 20 ml Ethanol 80 ml (3rd solution) Solution) Lithium bromide 10g Ethanol 100ml

(2-2) Glucose Detecting Reagent Layer A first solution and a second solution having the compositions shown below were prepared, and a filter paper having a thickness of 260 μm (manufactured by Advantech,
ADVANTEC No2) is first impregnated with the first solution,
It was dried in an oven (40 ° C, 50 minutes), then impregnated with the second solution, and dried in an oven (40 ° C, 20 minutes) to prepare a reagent layer for glucose detection. Then, this reagent layer was cut into a size of 5 mm × 5 mm. (First solution) Glucose oxidase 300 g Peroxidase 50 g Citric acid 1 g Sodium citrate 7 g Tartrazine 0.1 g Sodium alginate 0.5 g Water 100 ml (Second solution) O-tolidine 2.5 g Acetone 100 ml Supporting the reagent layer prepared as above 30 test pieces for detecting ketone bodies and 30 test pieces for glucose detection were prepared on the body.

2. Preparation of adjusted urine (1) Ketone body 2 ml of 1N sodium hydroxide in 2.6 ml of ethyl acetoacetate
0 ml was added, 80 ml of distilled water was further added, and the mixture was allowed to stand at 37 ° C. for 3 hours to obtain an ethyl acetoacetate solution (2000 mg /
dl) was prepared and the ethyl acetoacetate solution was diluted with normal urine to obtain an ethyl acetoacetate concentration of 50 mg / dl, 10 m
Adjusted urine of g / dl was obtained. (2) Glucose Glucose 5.0 g and sodium chloride 0.85 g were dissolved in distilled water to obtain a glucose solution (5000 mg / dl),
The glucose solution was diluted with normal urine to give a glucose concentration of 50.
Adjusted urine of mg / dl and 150 mg / dl was obtained.

3. Measurement The urinary ketone body and urinary sugar were measured by the analyzer 1 of the present invention (Example) and the analyzer not equipped with the diffusion plate 7 (Comparative Example), and the reproducibility of the measurement results was compared. The test device in which the reagent layer was dipped in the adjusted urine was placed on a tray, and white light was emitted from the light projecting means 3 to the test layer through the interference filter 12 (wavelength: 540 nm when measuring ketone bodies, 630 nm when measuring glucose). did. Predetermined coloring time (ketone: 2
The coloring intensity of the reagent layer at 0 seconds, glucose 30 seconds)
With the ketone body detection test tool, the ketone body concentration was 0 mg / d.
10, 10 mg / dl, 50 mg / dl adjusted urine
Each time, with the glucose detection test device, 0 mg / dl, 5
It was measured 10 times each with adjusted urine of 0 mg / dl and 150 mg / dl with the analyzer 1 of the present invention (Example) and the analyzer (comparative example) having a structure in which the diffusion plate 7 was removed from the analyzer 1. .

4. Measurement results Table 1 shows the measurement results for ketone bodies, and Table 2 shows the measurement results for glucose. In Tables 1 and 2, the measured value is a count value obtained by converting the output voltage of the light receiving means 10 by the 8-bit A / D conversion converter (based on white, the count value is 1).
Set to 00).

[0024]

[Table 1]

[0025]

[Table 2]

As shown in Tables 1 and 2, in the analyzer 1 of the present invention, the standard deviation is always small and the error of the measured value is relatively small, as compared with the analyzer without the diffusion plate. .

[0027]

The analyzer of the present invention is an analyzer for optically measuring the coloration intensity of the reagent layer of a test device having a reagent layer that is colored by reacting with a specific component in a sample, A light projecting means for irradiating the reagent layer of the test tool with light, and a light condensing means for collecting the reflected light from the reagent layer of the test tool,
It has a diffusing plate for diffusing the light condensed by the condensing means, a light receiving means for receiving the light from the diffusing plate, and a measuring device for measuring the intensity of the light received by the light receiving means. Since it is an analyzer characterized by the above, even if it has a condensing means for securing the amount of received light, and even if there is some deviation in the mounting position of the measurement object, The light receiving element can be illuminated with uniform light, and the error in the measured value can be relatively reduced.

[Brief description of drawings]

FIG. 1 is a schematic view of an embodiment of an analyzer of the present invention.

FIG. 2 is a perspective view of the vicinity of a photometry section of an embodiment of the analyzer of the present invention.

FIG. 3 is an explanatory diagram for explaining the operation of the analyzer of the present invention.

FIG. 4 is a schematic view of another embodiment of the analyzer of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Analyzing apparatus 2 Tray 3 Light projecting means 4 Photometric part 5 Test tool 6 Support 7 Reagent layer 8 Light collecting means 9 Diffusing plate 10 Light receiving means 10R color filter 10G color filter 10B color filter 10X light receiving element 10Y light receiving element 10Z light receiving element 11 Measuring device 11X A / D converter 11Y A / D converter 11Z A / D converter 11A computing means 11B A / D converter 12 interference filter

Claims (1)

[Claims] 1. An analyzer for optically measuring the color development intensity of the reagent layer of a test device having a reagent layer that develops a color when reacted with a specific component in a sample, the reagent layer of the test device. A light projecting means for irradiating light, a light collecting means for collecting the reflected light from the reagent layer of the test tool, a diffusion plate for diffusing the light collected by the light collecting means, An analyzing device comprising: a light receiving means for receiving light from a diffusion plate; and a measuring device for measuring the intensity of light received by the light receiving means.