JP2013076614A - Dry analysis element - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make a reflection distribution of diffused reflected light in a dry analysis element more isotropic.SOLUTION: In a dry analysis element 1 where a reaction layer 1b is laminated by application, bonding or the like on an optically transparent support layer 1c consisting of a plastic sheet such as an organic polymer sheet of polyethylene terephthalate (PET), polystyrene or the like, and a development layer 1a is further laminated thereon by a lamination method or the like, a fluorescent material 1d is contained in the reaction layer 1b to make the reaction layer 1b function also as a scattering layer for scattering of measuring light.

Description

  The present invention relates to a dry analytical element used for biochemical tests and the like.

  In recent years, various inspections have been performed by irradiating measurement objects with measurement light and detecting diffusely reflected light scattered by the measurement objects. For example, a small droplet of a sample is applied to a dry analytical element. A colorimetric measurement method for quantitatively analyzing a specific chemical component or a formed component contained in a specimen after receiving and supplying it is performed.

  As shown in Patent Document 1, in this colorimetric measurement method, after a sample is spotted on a dry analytical element, the sample is held at a constant temperature in an incubator for a color reaction (dye generation reaction), and then in the sample. The dry analytical element is irradiated with measurement light having a wavelength selected in advance by a combination of a predetermined biochemical substance and a reagent contained in the dry analytical element, and the light scattered and reflected by the dry analytical element (hereinafter simply diffused). The optical density of the reflected light is measured, and from this optical density, the concentration of the biochemical substance is determined using a calibration curve representing the correspondence between the optical density obtained in advance and the substance concentration of the predetermined biochemical substance. It is what you want.

  In an apparatus for performing such a colorimetric measurement method, a liquid sample is accommodated in a sample container (such as a blood collection tube) and set in the apparatus, and a dry analytical element necessary for the measurement is set in the apparatus, and dry analysis is performed. While the element is transported from the mounting position to the spotting unit and the incubator, the specimen is supplied from the mounting position to the spotting part by the spotting nozzle of the spotting mechanism and spotted on the dry analytical element.

Japanese Patent Laid-Open No. 10-019784

  The apparatus as described above has a problem that, when measuring the optical density of diffuse reflected light, the measurement light is mixed as a noise component, so that only diffuse reflected light cannot be accurately detected.

  Here, such a phenomenon will be described in detail. FIG. 5 is a diagram showing a detection state of diffuse reflected light when the measurement light is irradiated from the direction of 180 ° in the drawing to the dry analytical element (center position in the drawing). In addition, the dotted line in a figure has shown the detection state of the diffuse reflection light before a color reaction, and the continuous line has shown the detection state of the diffuse reflection light after a color reaction. As shown in FIG. 5, the detection intensity of the diffuse reflected light is high in the 180 ° direction because the specular reflection component of the measurement light is detected together with the diffuse reflected light. Therefore, in order not to be affected by the measurement light, the diffuse reflection light is usually detected by arranging a detector at a position (for example, a position of 135 ° or 225 °) different from the irradiation position of the measurement light.

  In this case, when distortion (for example, directions of 195 °, 165 °, etc. in FIG. 7) occurs in the reflection distribution of the diffuse reflected light in the dry analytical element, the amount of light detected to the detector may decrease and the S / N may decrease. In addition, if the change in the amount of light due to the angle increases, the detected light amount greatly changes with respect to the installation error of the dry analysis element (the position shift or the angle shift of the dry analysis element), so that the measurement accuracy may be deteriorated.

  Such distortion of the reflection distribution is caused by the non-isotropic reflection distribution of the woven fabric or porous film used for the spreading layer of the dry analytical element. Specifically, in the case of a woven fabric, the scattering and reflection intensity depends on the angle due to the checkered pattern of warp and weft due to the alternately knitted structure. In the case of a porous film, the scattering and reflection intensity depends on the angle depending on the size and interval of the porous pores and the shape of the pores (spherical and elliptical spherical). The anisotropy of these reflection distributions is further enhanced by the formation of speckle noise and interference patterns when a high coherency laser or the like is used as a light source for measurement light.

  In view of this point, the present invention has an object to provide a dry analytical element in which the reflection distribution of diffusely reflected light is more isotropic.

  The dry analytical element of the present invention is a dry analytical element used for biochemical examinations, etc., and a development layer for spreading the supplied sample liquid around, a layer below the development layer, and reaction with the sample liquid. And a reaction layer containing a reagent that generates a dye, and a scattering layer that is laminated below the spreading layer and includes a scattering material that scatters measurement light irradiated from the lower surface side of the reaction layer. .

  Here, the “scattering layer” may be an independent layer, or the reaction layer and the scattering layer may be integrally formed by containing a scattering material in the reaction layer.

  In the dry analytical element of the present invention, the scattering layer is preferably laminated above the reaction layer.

  The scattering material may be spherical fine particles.

  The scattering material may be metal nanoparticles.

  According to the dry analytical element according to the present invention, in the dry analytical element used for biochemical examinations, etc., a spread layer for spreading the supplied sample liquid around, and a layer below the spread layer are reacted with the sample liquid. And a reaction layer containing a reagent that generates a dye, and a scattering layer that is laminated below the spreading layer and includes a scattering material that scatters measurement light irradiated from the lower surface side of the reaction layer. Since the reflection distribution can be made isotropic as compared with an embodiment in which no scattering layer is provided, the distortion of the reflection distribution can be reduced. Therefore, measurement accuracy can be improved by performing measurement using the dry analytical element of the present invention.

1 is a schematic configuration diagram of a biochemical analyzer using a dry analytical element according to an embodiment of the present invention. Schematic configuration diagram of the dry analytical element The figure which shows the detection state of a diffuse reflected light at the time of irradiating measurement light with respect to the said dry analytical element Schematic configuration diagram of dry analysis element of other embodiment The figure which shows the detection state of diffuse reflected light at the time of irradiating measurement light with respect to the conventional dry analytical element

  Hereinafter, a biochemical analyzer using a dry analytical element according to an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a schematic configuration diagram of a biochemical analyzer using a dry analytical element according to an embodiment of the present invention, FIG. 2 is a schematic structural diagram of the dry analytical element, and FIG. 3 is a measuring beam for the dry analytical element. It is a figure which shows the detection state of the diffuse reflected light at the time of irradiation.

  The biochemical analyzer 10 includes a dry analytical element supply device 11 (supplier) that stores a plurality of cartridges 20 in which unused dry analytical elements 1 having a substantially square shape or rectangular shape are stacked, and the dry analytical element supply described above. An incubator 12 that is disposed on the side of the apparatus 11 and that is held at a constant temperature for a predetermined time and the dry analytical element 1 on which a sample solution is spotted is adsorbed by the suction cup 70 from the dry analytical element supply apparatus 11 to the incubator 12. Film transporting means 13 for transporting while transporting, sample liquid storage means 14 (sampler) for storing a plurality of sample liquids such as serum and urine, and sample liquid storage means until the film transporting means 13 transports them to the incubator 12. The sample solution 14 is taken out, and then spotting means 15 for spotting the sample solution on the dry analytical element 1 is disposed below the incubator 12. Measuring means 16 and an (optical measurement means).

  Details of the biochemical analyzer 10 are described in Japanese Patent Application Laid-Open No. 7-35746 (EP 0 634 657A) already disclosed by the applicant of the present application.

  The dry analytical element 1 is formed by laminating a reaction layer 1b on a light-transmitting support layer 1c made of a plastic sheet such as an organic polymer sheet such as polyethylene terephthalate (PET) or polystyrene by coating or bonding, and further. Further, a dry analytical element (chip) in which the development layer 1a is laminated by a laminating method or the like.

  The reaction layer 1b is composed of a hydrophilic polymer binder such as gelatin or a porous layer such as filter paper, cloth, and a microporous polymer sheet, a detection reagent that selectively reacts with an analyte, and a reagent that is necessary for a color reaction (chemical analysis). (Reagent or immunoassay reagent) component is comprised of at least one layer.

In addition, the reaction layer 1b includes a scattering material 1d for scattering measurement light. The scattering material 1d is not particularly limited as long as it is isotropically scattered, and for example, spherical particles made of SiO ₂ or resin (polystyrene) can be used. The particle size is not particularly limited, but since the reaction layer 1b has a thickness of several to several tens of micrometers, particles having a particle size of 10 nm to 1000 nm are particularly preferable.

  Further, when metal nanoparticles are used, the scattering intensity of the measurement light can be enhanced by utilizing the effect of electric field enhancement by plasmon resonance, so that the S / N in the biochemical analyzer 10 can be improved. it can.

  As described above, since the reaction layer 1b contains the scattering material 1d, the reaction layer 1b also functions as a scattering layer for scattering the measurement light.

  The spreading layer 1a is made of a material that is strong against the outside, such as a woven fabric or a knitted fabric made of synthetic fibers such as polyester, a woven fabric made by blending natural fibers and synthetic fibers, a knitted fabric, a non-woven fabric, or paper. In addition to functioning as a protective layer, the sample liquid spotted on the spreading layer 1a is spread so that it can be uniformly supplied onto the reaction layer 1b.

  As described above, the spotted dry analytical element 1 is incubated by the incubator 12 and measured by the measuring means 16 disposed below the incubator 12. This measuring means 16 has a photometric head for measuring the optical density due to the color reaction between the dry analytical element 1 and the sample liquid. This photometric head irradiates the reaction layer 1b with measurement light L containing light of a predetermined wavelength and irradiates the reaction layer 1b, and is scattered and reflected by the dry analytical element 1 (hereinafter simply referred to as diffuse reflection light). ) L ′ is detected by a photodetecting element. Light from the light source is incident on the photometric head, and the reaction layer 1b is irradiated with the light in the photometric head.

  The diffuse reflected light carries optical information (specifically, light quantity) corresponding to the amount of dye generated in the reaction layer 1b, and the diffuse reflected light L ′ carrying this optical information is transmitted from the photometric head. The light is incident on the photodetection element, photoelectrically converted, and sent to a substance concentration determination unit (not shown) via an amplifier. The light detection element is disposed at a position (for example, a position of 135 ° or 225 °) different from the irradiation position of the measurement light L (position of 180 ° in FIG. 3) so as not to be affected by the measurement light L. Has been.

  In the substance concentration determination unit, the optical density of the dye generated in the reaction layer 1b is determined based on the level of the input electric signal, and then a calibration curve which is a conversion function of optical density-substance density (or activity). Is used to perform a calculation process for specifying the concentration of a predetermined biochemical substance in the sample solution.

  As shown in FIG. 3, the dry analytical element 1 of the present embodiment includes a layer that functions as a scattering layer for scattering measurement light. Therefore, measurement using the conventional dry analytical element shown in FIG. In comparison, it can be seen that the reflection distribution of the diffuse reflected light L ′ in the dry analytical element is improved more isotropically.

  Therefore, measurement accuracy can be improved by performing measurement using the dry analytical element 1.

  As mentioned above, although preferable embodiment of this invention was described, this invention is not limited to the said embodiment.

  For example, the scattering layer of the dry analytical element 1 is not limited to being integrally formed with the reaction layer 1b as described above, and as shown in FIG. 4, a layer independent of the reaction layer 1b (scattering layer 1e). ). The scattering layer 1e may be arranged on either the upper side or the lower side of the reaction layer 1b. However, by arranging the scattering layer 1e on the upper side of the reaction layer 1b as shown in FIG. First, since it is absorbed by the dye generated in the reaction layer 1b, the change in optical density due to the color reaction can be strengthened, and thereby the detection sensitivity can be improved.

  In addition to the above, it goes without saying that various improvements and modifications may be made without departing from the scope of the present invention.

1,1 'dry analytical element 1a spreading layer 1b reaction layer 1c support layer 1d scattering material 1e scattering layer 10 biochemical analyzer 11 dry analytical element supply device 12 incubator 13 dry analytical element transport means 14 sample liquid storage means 15 spotting means 16 Measuring means 20 Cartridge containing stacked dry analytical elements

Claims (4)

A dry analytical element used for biochemical testing,
A spreading layer for spreading the supplied sample liquid around,
A reaction layer that is laminated below the spreading layer and contains a reagent that reacts with the sample solution to produce a dye;
A dry analysis element comprising: a scattering layer that is laminated below the spreading layer and includes a scattering material that scatters measurement light irradiated from the lower surface side of the reaction layer.   The dry analytical element according to claim 1, wherein the scattering layer is laminated above the reaction layer.   The dry analytical element according to claim 1, wherein the scattering material is a spherical fine particle.   The dry analytical element according to claim 1, wherein the scattering material is metal nanoparticles.

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