JP2003098078A - Sample concentration measuring device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sample concentration measuring device capable of performing the quantitative analysis of immunity chromatography with high accuracy, and reducing the cost. SOLUTION: A semiconductor laser 14 is used as a light source, and the irradiation beam 13 emitted from the semiconductor laser 14 is deformed into the elliptical beam by a cylindrical lens 18, and is applied to an immunity chromatographic test piece in a state of being inclined to the direction vertical to a surface of the immunity chromatographic test piece 8 by five degree.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample concentration measuring device, and more particularly to a sample concentration measuring device for measuring immunochromatographic test strips and the like. The present invention also relates to a device capable of improving the quantitativeness of the sample concentration.

[0002]

2. Description of the Related Art A conventional sample concentration measuring device will be described below with reference to FIG. FIG. 5A is a schematic diagram showing the outline of a conventional sample concentration measuring apparatus. In FIG. 5 (a),
1 is a lamp as a light source, 2 is a reflector, 3 is a diffraction grating, 4
Is an opening, 5 is a glass plate, 6 is a reference light reflected by the glass plate 5, 7 is a photomultiplier tube for receiving the reference light 6, 8 is an immunochromatographic test piece, and 9 is from an immunochromatographic test piece 8. Is a photomultiplier tube that receives scattered light 9.

Next, the operation of the sample concentration measuring device having such a configuration will be described. In FIG. 5A, the beam emitted from the lamp 1 is incident on the diffraction grating 3 via the reflection plate 2. Then, the wavelength is determined by the diffraction grating 3, the beam is focused by the opening 4, and the beam is incident on the glass plate 5. The beam reflected by the glass plate 5 is received by the photomultiplier tube 7 as the reference light 6. On the other hand, the beam transmitted through the glass plate 5 is incident on the immunochromatographic test piece 8. The scattered light 9 from the immunochromatographic test piece 8 is received by the photomultiplier tube 10. The outputs from the photomultiplier tubes 7 and 10 are respectively Log-converted, and the subtraction result of these is output as an absorbance signal.

Next, FIG. 5 (b) shows the structure of the immunochromatographic test piece. The immunochromatographic test strip 8 utilizing the antigen-antibody reaction is a substance that moves specifically by permeation of the liquid sample and a portion to which the liquid sample is added, and that specifically binds to the analyte contained in the flowing liquid. And a detection unit 11 for binding and immobilizing the labeling reagent and the analyte, a unit for absorbing the flowing sample, and another base unit 12. Has been done. A calibration curve between the difference between the absorbance signals of the base 12 and the detector 11 and the concentration of the sample to be measured has been obtained in advance. By detecting the difference between the absorbance signals of the base 12 and the detector 11, the sample The concentration can be determined.

In general, immunochromatographic analysis is qualitative, but quantitative analytical methods have been developed. For example, in Japanese Unexamined Patent Publication No. 8-240591, a sample is added to an immunochromatographic test strip, and after a reaction is performed, a spectrophotometer is used to measure signals such as absorption and reflection of a colored portion on the test strip. By doing so, a method for quantifying the degree of coloration is disclosed. In addition, JP-A-1
Japanese Laid-Open Patent Publication No. 1-142338 discloses a method of measuring the absorbance of a colored portion without the influence of external light by using a light emitting diode as a light source.

[0006]

The conventional sample concentration measuring apparatus is constructed as described above, and there is no problem in performing qualitative analysis using immunochromatography. However, when performing quantitative analysis, for example, when analyzing a liquid sample containing cellular components such as blood, the viscosity of the liquid sample and the presence of cellular components cause partial clogging, so Coloring unevenness occurs on the base part. Since the sample concentration is obtained from the difference between the absorbance signals of the base section and the detection section, there is a problem that an error occurs due to uneven coloring of the base section depending on the position of the irradiation beam, which hinders quantitative measurement.

Further, in the conventional sample concentration measuring device using a lamp as a light source, there is a problem that it is difficult to reduce the size and cost of the device. The present invention has been made in order to solve the above problems, and enables a highly accurate quantitative analysis of immunochromatography, and a sample concentration that can reduce the size and cost of the device. An object is to provide a measuring device.

[0008]

A sample concentration measuring apparatus according to claim 1 of the present application uses a semiconductor laser as a light source to irradiate the sample with a beam emitted from the light source, and transmits or reflects light from the sample. In a sample concentration measuring device for detecting a sample concentration by detecting by optical means, the beam is irradiated onto the sample at an angle with respect to a direction perpendicular to the sample surface. is there.

The sample concentration measuring apparatus according to claim 2 of the present application is the sample concentration measuring apparatus according to claim 1, wherein the beam is deformed into an elliptical or rectangular beam by an optical means and is perpendicular to the sample surface. It is characterized in that the sample is irradiated with an angle in the minor axis direction of the elliptical or rectangular beam with respect to this direction.

Further, the sample concentration measuring apparatus according to claim 3 of the present application is the sample concentration measuring apparatus according to claim 1 or 2, wherein the light source and the optical means are all arranged in the same housing, By tilting the housing, the beam is irradiated onto the sample at an angle with respect to a direction perpendicular to the sample surface.

A sample concentration measuring device according to claim 4 of the present application is the sample concentration measuring device according to claim 1 or 2, further comprising an optical element for reflecting the beam emitted from the housing. By inclining the optical element, the beam is irradiated onto the sample at an angle with respect to a direction perpendicular to the sample surface.

A sample concentration measuring device according to claim 5 of the present application is the sample concentration measuring device according to any one of claims 1 to 4, wherein the beam is parallel to the sample surface. It is characterized in that the sample concentration is quantitatively measured by scanning in the length direction of.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION (Embodiment 1) A sample concentration measuring device and an immunochromatographic test strip according to Embodiment 1 of the present invention will be described below with reference to FIGS. 1 and 2.

FIG. 1A is a block diagram showing the outline of the sample concentration measuring apparatus according to the first embodiment. In the figure, 4
Is an aperture, 6 is a reference light reflected by the polarization beam splitter 16, 8 is an immunochromatographic test piece, 9 is scattered light from the immunochromatographic test piece 8, 14 is a semiconductor laser as a light source, and 15 is a semiconductor laser 14. Collimating lens that converts the beam emitted from
Reference numeral 16 is a polarization beam splitter that polarizes the beam that has passed through the aperture 4, 17 is a photodiode that monitors the reference light 6, 18 is a cylindrical lens that guides the beam that has passed through the polarization beam splitter 16 to the immunochromatographic test piece 8, and 19 is The photodiode receives scattered light 9 from the immunochromatographic test strip 8.

FIG. 1 (b) is a view showing the structure of the immunochromatographic test piece used in the first embodiment. In the figure, 11 is a detection unit, 12 is a base unit, and 1
Reference numeral 3 is an elliptical beam emitted by a semiconductor laser. The immunochromatographic test piece 8 used in the first embodiment has a length of about 50 mm and a width of about 5 mm, and the length of the detection unit 11 is about 1 mm. The surface has a thickness of about 100 μm to protect it from scratches. A transparent tape is attached.

Next, the operation of the sample concentration measuring device having the above structure will be described. In FIG. 1A, the beam emitted from the semiconductor laser 14 is made into a parallel beam via a collimator lens 15. The wavelength of the semiconductor laser 14 is 635 nm. The reason for selecting this wavelength is that (1) a sufficient difference in absorbance between the gold colloid of the labeling reagent and the blood (red blood cells) of the sample can be obtained, (2) sufficient absorbance sensitivity of the gold colloid can be obtained, and (3) an optical disc. It is used in etc. The parallel beam obtained by the collimator lens 15 has an aperture 4 (φ3 m
It is incident on the polarization beam splitter 16 via m).
Here, the reason why the polarization beam splitter is used is that light is effectively used by utilizing the polarization characteristics of the laser. The beam reflected (split) by the polarization beam splitter 16 is
The photodiode 17 receives the reference light 6. On the other hand, the beam transmitted through the polarization beam splitter 16 is incident on the cylindrical lens 18. The immunochromatographic test piece 8 is irradiated at a position of about 30 mm from the cylindrical lens 18. Cylindrical lens 1
The image of the immunochromatographic test strip 8 is imaged only in the longitudinal direction by the image pickup 8.

Since the immunochromatographic test piece 8 used in the first embodiment has a structure as shown in FIG. 1B, the irradiation beam is subject to mounting error, scanning accuracy, etc. of the immunochromatographic test piece 8. Considering the long axis 3m
An elliptical beam 13 having a length m and a minor axis of 0.4 mm was used. Here, in order to transform the beam into an elliptical beam, the use of the cylindrical lens 18 is more than 5 times more efficient in light utilization than the aperture 4. Therefore, in the first embodiment, the cylindrical lens 18 is used to transform the beam into an elliptical beam. It has been transformed into.

Further, when a laser is used as the light source, the laser oscillation of the semiconductor laser 14 is disturbed (noise) due to the return light due to the reflection from the transparent protective tape attached to the surface of the immunochromatographic test piece 8. Fluctuations in the amount of light and wavelengths cause errors in measurement. The return light reaches several% of the irradiation light, although it depends on the material of the protective tape and the surface condition. Further, when the monitor photodiode built in the semiconductor laser 14 is used to control the light quantity of the laser light, the monitor photodiode detects the return light and an error occurs in the light quantity control of the laser light, causing an error factor of the measurement value. Becomes Therefore, in order to avoid the returning light to the semiconductor laser 14 due to the reflection from the protective tape attached to the surface of the immunochromatographic test piece 8, in the sample concentration measuring device according to the first embodiment, the immunochromatographic test is performed. The beam irradiating the strip 8 was inclined about 5 degrees in the minor axis direction of the elliptical beam 13 with respect to the direction perpendicular to the surface of the immunochromatographic test strip 8.

Next, the scattered light 9 from the immunochromatographic test piece 8 is received by the photodiode 19. The photodiode 19 is an immunochromatographic test strip 8
Is placed at a distance of 30 mm from the sample with an inclination of about 45 ° with respect to the direction perpendicular to the surface of the sample. The light receiving area of the photodiode 19 is 10 × 10 mm, and the scattered light 9 of about 1/1000 of the emission power of the semiconductor laser 14 is received. Next, the outputs of the photodiodes 17 and 19 receiving the reference light 6 and the scattered light 9 are respectively Log
After conversion, these subtractions are output as an absorbance signal.

Next, immunochromatographic test strip 8
The immunochromatographic test piece 8 is horizontally scanned in the lengthwise direction while irradiating a beam to the base portion 12 and the detection portion 1.
The difference in absorbance at 1 is measured. Here, the base portion 12 and the detection portion 11 of the immunochromatographic test strip 8 are previously prepared.
The calibration curve with the sample concentration to be measured is obtained in consideration of the difference in the absorbance signal of.

After that, the sample concentration measuring apparatus according to the first embodiment detects the difference in the absorbance signal between the base section 12 and the detecting section 11 on which the sample is actually mounted, and the concentration of the sample is obtained from the calibration curve.

Next, the adjustment of the size of the elliptical beam will be described with reference to FIG. FIG. 2 is a cross-sectional view (a) in which the beam irradiated to the sample is tilted in the minor axis direction and a cross-sectional view (b) in which the beam is irradiated in the minor axis direction in the sample concentration measuring device according to the first embodiment. As shown in FIG. 2A, since the beam is condensed in the minor axis direction of the elliptical beam 13, the distortion of the beam diameter due to the inclination of the irradiation beam causes the position of the surface 8a of the immunochromatographic test piece in the focal direction. The adjustment can be performed without moving the light amount only by moving. On the other hand, in the major axis direction, the beam is parallel light as shown in FIG. Therefore, in order to adjust the beam diameter in the major axis direction, the beam needs to be narrowed by the opening 4, so that the irradiation light amount decreases.

Further, in order to further reduce the size of the sample concentration measuring apparatus according to the first embodiment, the distance from the cylindrical lens 18 to the immunochromatographic test piece 8 may be shortened. However, the cylindrical lens 18
Therefore, for example, when the beam is irradiated to the immunochromatographic test piece 8 at a position of about 10 mm, the beam needs to be tilted by about 30 degrees, and the beam diameter is distorted by about 15%. When tilted in the direction, the amount of irradiation light decreases greatly.

As described above, in the sample concentration measuring apparatus according to the first embodiment, the laser light to be irradiated is elliptical beam 1
Since it is set to 3, there is an effect that the uneven coloring in the width direction of the immunochromatographic test piece 8 can be alleviated and the quantitative measurement with a small measurement error can be performed.

The beam irradiating the immunochromatographic test piece 8 is inclined about 5 degrees in the minor axis direction of the elliptical beam 13 with respect to the direction perpendicular to the surface of the immunochromatographic test piece 8. The return light to the semiconductor laser 14 due to the reflection from the protective tape attached to the surface of the immunochromatographic test piece 8 can be avoided, and the measurement can be performed with high accuracy.

Further, since the beam is made to scan in the longitudinal direction of the immunochromatographic test piece 8, the base portion 1 of the immunochromatographic test piece 8 is made by one beam.
It is possible to obtain the difference between the absorbance signals of the detector 2 and the detector 11, and it is possible to perform efficient measurement.

In the sample concentration measuring apparatus according to the first embodiment, by scanning the immunochromatographic test piece 8 in the longitudinal direction, the difference between the absorbance signals of the base section 12 and the detecting section 11 can be obtained by one beam. However, even if the entire optical system is moved to scan the beam, one beam can similarly be used to measure the base 12 and the detector 11.
It is possible to determine the difference in the absorbance signals of the.

(Second Embodiment) Next, a sample concentration measuring device according to a second embodiment of the present invention will be described with reference to FIG. FIG. 3 is a sectional view of an optical portion of the sample concentration measuring device according to the second embodiment. In the figure, 4 is an aperture, 6 is a reference beam reflected by a polarization beam splitter 16, 8 is an immunochromatographic test piece, 14 is a semiconductor laser that serves as a light source, and 15 is a beam emitted from the semiconductor laser 14, which is a parallel beam. A collimating lens for conversion, 16 is a polarization beam splitter for polarizing the beam passing through the aperture 4, 17 is a photodiode for monitoring the reference light 6, 1
Reference numeral 8 is a cylindrical lens that guides the beam that has passed through the polarization beam splitter 16 to the immunochromatographic test piece 8, and 20 is an optical stand.

Next, the operation of the sample concentration measuring device having such a configuration will be described. The beam emitted from the semiconductor laser 14 is made into a parallel beam via the collimator lens 15. This parallel beam is incident on the polarization beam splitter 16 through the aperture 4. Then, the beam reflected by the polarization beam splitter 16 is received by the photodiode 17 as the reference light 6. On the other hand, the beam transmitted through the polarization beam splitter 16 is incident on the cylindrical lens 18. Cylindrical lens 18
Thereby, only the longitudinal direction of the immunochromatographic test strip 8 is imaged and the immunochromatographic test strip 8 is irradiated. At this time, the semiconductor laser 14 and the collimator lens 1
5, polarization beam splitter 16, photodiode 1
7. The cylindrical lenses 18 are all arranged in an optical base 20 made of aluminum die cast. The optical table 20 is attached at an angle of about 5 degrees with respect to the direction perpendicular to the surface of the immunochromatography 8.

As described above, according to the sample concentration measuring apparatus according to the second embodiment, the semiconductor laser 14, the collimator lens 15, the polarization beam splitter 16, the photodiode 17, and the cylindrical lens 18 are all made of an aluminum die cast optical material. Since the optical table is arranged in the table 20 and the optical table is tilted by about 5 degrees with respect to the direction perpendicular to the surface of the immunochromatographic test piece 8, it is not necessary to tilt the individual parts, and The effect of returning light from the transparent protective tape attached to the surface of the immunochromatographic test strip 8 can be avoided with a simple device configuration.

(Third Embodiment) Next, a sample concentration measuring apparatus according to a third embodiment of the present invention will be described with reference to FIG. FIG. 4 is a sectional view of an optical part of the sample concentration measuring device according to the third embodiment. In the figure, 4 is an aperture, 6 is a reference beam reflected by a polarization beam splitter 16, 8 is an immunochromatographic test piece, 14 is a semiconductor laser that serves as a light source, and 15 is a beam emitted from the semiconductor laser 14, which is a parallel beam. A collimating lens for conversion, 16 is a polarization beam splitter that polarizes the beam that has passed through the aperture 4, 17 is a photodiode that monitors the reference light, and 18
Is a cylindrical lens for guiding the beam that has passed through the polarization beam splitter 16 to the immunochromatographic test piece 8, 20 is an optical stand, and 21 is a reflection mirror.

Next, the operation of the sample concentration measuring device having such a structure will be described. The beam emitted from the semiconductor laser 14 is made into a parallel beam via the collimator lens 15. This parallel beam is incident on the polarization beam splitter 16 through the aperture 4. Then, the beam reflected by the polarization beam splitter 16 is received by the photodiode 17 as the reference light 6. On the other hand, the beam transmitted through the polarization beam splitter 16 is incident on the cylindrical lens 18. Cylindrical lens 18
The beam emitted from is reflected by the reflection mirror 21, an image is formed only in the longitudinal direction of the immunochromatographic test strip 8, and the immunochromatographic test strip 8 is irradiated with the image. At this time, the semiconductor laser 14, the collimator lens 15, the polarization beam splitter 16, the photodiode 17, and the cylindrical lens 18 are all arranged in an optical table 20 made of aluminum die cast. The optical table 20 is arranged in parallel with the scanning direction of the immunochromatographic test piece 8. Further, by changing the angle of the reflection mirror 21, it is possible to irradiate the beam with an inclination of about 5 degrees with respect to the direction perpendicular to the surface of the immunochromatographic test piece 8.

As described above, according to the sample concentration measuring apparatus according to the third embodiment, the semiconductor laser 14, the collimating lens 15, the polarization beam splitter 16, the photodiode 17, and the cylindrical lens 18 are all made of an aluminum die cast optical material. The optical table 20 is arranged in the table 20.
Are installed in parallel with the scanning direction of the immunochromatographic test strip 8 and the angle of the reflection mirror 21 is changed to irradiate the beam at an angle of about 5 degrees with respect to the direction perpendicular to the surface of the immunochromatographic test strip 8. Because of the constitution, there is an effect that it is possible to avoid the influence of the return light from the transparent protective tape attached to the surface of the immunochromatographic test piece 8.

Further, in the sample concentration measuring apparatus according to the second embodiment, it was necessary to arrange the optical components in the height direction of the immunochromatographic sample piece 8 as shown in FIG.
According to the sample concentration measuring apparatus of the third embodiment, there is no need to dispose optical components in the height direction of the immunochromatographic sample piece 8, so that there is an effect that the apparatus can be further downsized.

[0035]

As described above, according to the sample concentration measuring apparatus of the first aspect of the present invention, the semiconductor laser is used as the light source, the beam emitted from the light source is irradiated onto the sample, and the transmitted light from the sample is transmitted. Alternatively, in a sample concentration measuring device for measuring the sample concentration by detecting reflected light by an optical means, the beam is applied to the sample at an angle with respect to a direction perpendicular to the sample surface. Therefore, it is possible to avoid the influence of the return light from the transparent protective tape attached to the surface of the immunochromatographic test piece, and even if a semiconductor laser is used as the light source, quantitative measurement with less measurement error can be performed. There is an effect that can be done.

Further, according to a sample concentration measuring apparatus according to claim 2 of the present invention, in the sample concentration measuring apparatus according to claim 1, the beam is transformed into an elliptical or rectangular beam by optical means, and the sample is measured. Since the sample is irradiated with an angle in the minor axis direction of the elliptical or rectangular beam with respect to the direction perpendicular to the surface, there is no light quantity loss even if a semiconductor laser is used as the light source, and Since the coloration unevenness in the width direction of the immunochromatographic test piece can be reduced, there is an effect that quantitative measurement with less measurement error can be performed.

According to a third aspect of the sample concentration measuring apparatus of the present invention, in the sample concentration measuring apparatus according to the first aspect or the second aspect, the light source and the optical means are all provided in the same housing. Since the beam is radiated to the sample at a certain angle with respect to the direction perpendicular to the sample surface by arranging and tilting the housing,
Since it is not necessary to tilt and attach individual parts, it is possible to avoid the effect of returning light from the transparent protective tape attached to the surface of the immunochromatography test piece with a simple device configuration, so the semiconductor laser is used as the light source. Even if is used, there is an effect that quantitative measurement with a small measurement error can be performed.

According to a fourth aspect of the sample concentration measuring apparatus of the present invention, in the sample concentration measuring apparatus according to the first aspect or the second aspect, an optical element for reflecting the beam emitted from the casing. And by tilting the optical element, the beam is irradiated onto the sample at an angle with respect to the direction perpendicular to the sample surface, so that the surface of the immunochromatographic test strip is The effect of returning light from the attached transparent protective tape can be avoided, and even if a semiconductor laser is used as a light source, there is an effect that quantitative measurement can be performed with less measurement error. Moreover, since it is not necessary to dispose optical components in the height direction of the immunochromatographic sample piece, there is an effect that the apparatus can be further downsized.

According to a fifth aspect of the sample concentration measuring apparatus of the present invention, in the sample concentration measuring apparatus according to any one of the first to fourth aspects, the beam is parallel to the sample surface. Since the sample concentration is quantitatively measured by scanning the sample in the lengthwise direction, the operation of measuring the difference between the absorbance signals of the detection unit and the base unit is simplified, and an efficient measurement can be performed. There is.

[Brief description of drawings]

FIG. 1 is a configuration diagram (a) showing an outline of a sample concentration measuring device according to a first embodiment of the present invention, and a diagram (b) showing a configuration of an immunochromatographic test strip.

2A and 2B are a sectional view in which the beam of the sample concentration measuring device according to the first embodiment of the present invention is tilted in the minor axis direction and a sectional view in which the beam is tilted in the major axis direction.

FIG. 3 is a sectional view of an optical system constituting a sample concentration measuring device according to a second embodiment of the present invention.

FIG. 4 is a sectional view of an optical system constituting a sample concentration measuring device according to a third embodiment of the present invention.

FIG. 5 is a configuration diagram (a) showing an outline of a conventional sample concentration measuring device, and a diagram (b) showing a configuration of an immunochromatographic test strip.

[Explanation of symbols]

1 lamp 2 reflector 3 diffraction grating 4 openings 5 glass plates 6 Reference light 7 Photomultiplier tube 8,8a Immunochromatographic test strip 9 scattered light 10 Photomultiplier tube 11 Detector 12 Base 13 Irradiation beam 14 Semiconductor laser 15 Collimating lens 16 Polarizing beam splitter 17 Photodiode 18 Cylindrical lens 19 photodiode 20 Optical stand 21 reflective mirror

Continued front page    F term (reference) 2G045 FA12 FA29 FB03 FB06 FB15                       GC10 GC11                 2G059 AA01 BB04 BB12 CC16 EE01                       EE02 EE05 FF01 FF08 GG01                       GG04 GG05 HH02 HH06 JJ11                       JJ13 JJ19 JJ22 KK01 LL04                       MM01 MM12

Claims (5)

[Claims] 1. A sample concentration measuring device for measuring a sample concentration by irradiating a sample with a beam emitted from the light source using a semiconductor laser as a light source, and detecting transmitted light or reflected light from the sample by an optical means. The sample concentration measuring device, wherein the beam is applied to the sample at an angle with respect to a direction perpendicular to the sample surface. 2. The sample concentration measuring device according to claim 1, wherein the beam is deformed into an elliptical or rectangular beam by an optical means, and the ellipse or rectangular beam has a minor axis direction with respect to a direction perpendicular to the sample surface. A sample concentration measuring device, characterized in that the sample is irradiated at an angle of. 3. The sample concentration measuring device according to claim 1, wherein the light source and the optical means are all arranged in the same housing, and the housing is tilted to cause the beam to move to the sample. A sample concentration measuring device, characterized in that the sample is irradiated at an angle to a direction perpendicular to the surface. 4. The sample concentration measuring device according to claim 1 or 2, further comprising an optical element that reflects the beam emitted from the housing, and the beam is moved by tilting the optical element. A sample concentration measuring device, characterized in that the sample is irradiated at an angle to a direction perpendicular to the sample surface. 5. The sample concentration measuring device according to claim 1, wherein the beam is scanned in the length direction of the sample parallel to the surface of the sample to quantitatively measure the sample concentration. A sample concentration measuring device, which is characterized by: