JP2007093275A - Inspection chip and inspection method using it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an integrated type inspection chip, capable of inspecting a specimen by simple operation and having high usability. <P>SOLUTION: The inspection chip 10 is equipped with a chip body 11, the pretreatment part 12 provided to the chip body 11 to store a liquid L to be inspected, the reaction part 13 provided to the chip body 11 to house and hold a reagent 15 and the specimen transport part 21 attached to the chip body 11, in a freely slidable manner. A liquid absorbing part 23 is provided to the specimen transport part 21 and brought into contact with the liquid L to be inspected stored in the pretreatment part 12 at a first position where the specimen transport part 21 is slid to absorb the liquid L to be inspected, while the liquid absorbing part 23, having absorbed the liquid L to be inspected, is brought into contact with the reagent 15 held to the reaction part 13 at a second position where the specimen transport part 21 is slid. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention provides an integrated analysis for analyzing one or more components contained in a sample such as blood, urine, body fluid, tissue, cell, food, waste liquid, pond water, river water, sea water, or rainwater. The present invention relates to a chip and a measuring method.

  A method for diagnosing a human disease using blood, urine or the like as a specimen has long been performed as a method that can be easily diagnosed without damaging the human body. One of the methods is a wet chemistry analysis method. Wet chemistry analysis is a method that uses so-called solution reagents, and has a long history, detection reagents have been developed for many test items, and there are various measuring instruments ranging from simple small machines to large fully automatic machines. . Specimens used for wet chemistry are plasma, serum, urine, etc., and whole blood is usually not used as it is.

  Wet chemistry analysis method is divided into several groups in consideration of the stability of the reagent during the storage period, and can be mixed at the time of dissolution and preparation, and the reagent addition procedure is divided into several steps. Is also possible. Furthermore, since an appropriate amount of reagent can be dissolved and prepared according to the number of samples to be measured, the reagent cost per measurement can be reduced. In wet chemistry analysis, it is complicated and cumbersome to automate the handling of a large number of solutions. However, the development of clinical laboratory equipment has a long history and high social demands. Efficient automatic equipment has also been developed and put to practical use in fields that require a high processing capacity. However, many of them have the problem that the process is complicated and the apparatus is large, and it often fails to meet the needs of practitioners and emergency hospitals that require immediate diagnosis.

  For example, Patent Documents 1 and 2 below describe biological analysis methods for liquid samples using compartmented plastic containers that require many centrifugation steps. In these biological analysis methods, the container is composed of a large number of storage chambers, reaction chambers, and calibration chambers, and the chambers are connected by capillaries. In such a configuration, the structure is complicated, and the centrifuge device requires a complicated operation process.

  Further, the following Patent Document 3 does not require a centrifugal operation and a complicated flow path structure, but performs a sequential analysis in a liquid analysis mixture and requires only a minimum number of work steps. Provided an analyzer that is easy. Easily used by practitioners and small clinical laboratories.

US Pat. No. 4,673,653 U.S. Pat. No. 4,743,558 Japanese Patent Laid-Open No. 3-46566

  However, in recent years, home care has been advocated as a core of the future health care system in response to the rapid transition to an aging society and the rise in medical expenses due to the development of advanced treatment. A specific method is being studied.

  Home care basically means that the patient is always under proper monitoring, guidance, and management by a doctor while at home, and can be treated appropriately as needed. For example, in the case of chronic patients and the elderly, it is most important that the patient is in a stable physiological state if there is no sudden pathological change, and that the treatment is continuously monitored and the treatment effect is continuously monitored. It will be.

For home care systems, it is desirable to have a blood analysis method that can (1) be small, (2) simply (3) use a small amount of blood, (4) measure multiple items, (5) quickly (6) accurately. Needless to say. In particular, in the case of targeting elderly people (sometimes children), it is desired to develop an analytical method that requires collection of a small amount of blood.
On the other hand, an integrated home analysis apparatus using a wet chemistry analysis method has been proposed (Japanese Patent Laid-Open No. 2001-258868), but it is not satisfactory in terms of simplicity, size, and low cost. .

  In the prior arts disclosed in Patent Documents 1 to 3, various operations for inspecting one item are concentrated in one apparatus, and a large amount of test solution is used to perform the operation. A large-scale operation is required, for example, rotating the device before the inspection is performed with a large scale.

  The object of the present invention is to have an all-in-one type structure that does not require maintenance, in which all reagents other than the sample are enclosed in an analysis chip, and the amount of sample and reagent required for analysis can be reduced. A small amount that can be analyzed in a short amount of time, can be analyzed easily in a short time and at a low cost, can perform one inspection with a single mechanism, and does not require complicated operations. An object of the present invention is to provide a small inspection chip that facilitates inspection of multiple items by one operation with a liquid and an inspection method using the inspection chip.

The above object of the present invention is achieved by the following configurations.
(1) A test chip for reacting a liquid to be inspected with a reagent and inspecting the liquid to be inspected, the chip main body, a pretreatment unit provided in the chip main body for storing the liquid to be inspected, and the chip A reaction part that is provided in the main body and accommodates and holds the reagent; and a sample transporting part that is slidably attached to the chip main body, wherein the sample transporting part is provided with a liquid absorber, In the first position where the specimen transport section is slid, the liquid absorber absorbs liquid by contacting with the test liquid stored in the pretreatment section, and the specimen transport section is slid. The test chip, wherein the liquid absorber that has absorbed the test liquid contacts the reagent held in the reaction part at a position.
(2) The sample transporting portion is provided with a residual liquid absorbing material that can be sucked in contact with the liquid to be inspected remaining in the pretreatment portion while being slid with respect to the chip body. The inspection chip according to (1) above, wherein
(3) The above (2), wherein the residual liquid absorbent is in contact with the liquid to be inspected remaining in the pretreatment part in a state where the liquid absorber is in contact with the reaction part. ) Inspection chip.
(4) The chip body is provided with an introduction part for introducing the liquid to be inspected into the pretreatment part, according to any one of (1) to (3), Inspection chip.
(5) The test chip according to any one of (1) to (4), wherein a dry reagent is held in the reaction unit.
(6) The inspection chip according to any one of (1) to (5), wherein a plurality of the reaction units are provided.
(7) The inspection chip according to any one of (1) to (6), wherein a plurality of the liquid absorption portions are provided.
(8) The test chip according to any one of (1) to (7), wherein the reagent is a material that detects HbA1c.
(9) The inspection chip according to any one of (1) to (7), wherein the reagent is a material that detects CRP.
(10) A test chip for reacting a liquid to be inspected with a reagent and inspecting the liquid to be inspected, the chip main body, a pre-processing unit provided in the chip main body for storing the liquid to be inspected, and the chip A sample transporting part slidably attached to the main body, the sample transporting part is provided with a liquid absorber, and the liquid absorber is provided with a reaction part capable of holding the reagent, The liquid absorber absorbs the liquid to be inspected by contacting the liquid to be inspected stored in the pretreatment part at the first position where the transport part is slid, and the liquid to be inspected is An inspection chip which contacts the reagent in the reaction part.
(11) A test method comprising performing a test for reacting the liquid to be tested with the reagent using the test chip according to any one of (1) to (10).

  In the inspection chip according to the present invention, the chip substrate material may be an inorganic material or an organic material. Examples of inorganic materials used for the substrate include metals, silicon, Teflon (registered trademark), glass, ceramics, and the like. Organic materials include plastic and rubber.

  Examples of the plastic include PCO, PS, PC, PMMA, PE, PET, PP, and the like. Examples of rubber include natural rubber, synthetic rubber, silicon rubber, PDMS and the like. Examples of the silicon-containing substance include amorphous silicon such as glass, quartz, and silicon wafer, and silicone such as polymethylsiloxane.

  Plastic is preferable in terms of cost and ease of processing. Particularly preferred examples include PMMA, PCO, PS, PC, PET, PEN and the like.

  As a means for collecting a sample and supplying it to the pretreatment unit, it is preferable to use a capillary capable of constant weighing. The material of the capillary is preferably plastic or glass.

  It is necessary to have hydrophilicity on the inner surface of the capillary. When the material of the capillary is not hydrophilic, a hydrophilic treatment is necessary. A conventional surface treatment method can be applied as the hydrophilic treatment method. Broadly divided, there are chemical surface treatment methods and physical surface treatment methods. Chemical surface treatment methods include chemical treatment, treatment with a coupling agent, steam treatment, grafting, electrochemical methods, and surface modification with additives. Examples of physical surface treatment methods include UV irradiation, electron beam treatment, ion beam irradiation, low-frequency plasma treatment, CASING treatment, glow, corona discharge treatment, and oxygen plasma.

  As described above, a predetermined volume of the processing reagent solution is enclosed in a container for pre-processing the specimen by mixing the liquid specimen and the processing reagent. The volume of the treatment reagent solution is preferably 20 to 20000 μL, more preferably 50 to 2000 μL, and still more preferably 100 to 1000 μL.

  Further, it is preferable that the treatment reagent solution in the sample pretreatment container is sealed with a seal member so as not to leak. The reagent site is preferably a non-fluid reaction reagent. Further preferred are multilayer dry analytical elements (dry reagents).

  The multilayer dry analysis element referred to in the present invention refers to a dry analysis element in which all or a part of reagents necessary for qualitative / quantitative analysis of a component to be measured in a sample are incorporated in one or more layers. It is an analytical element using so-called dry chemistry. Specifically, an example of such a multilayer dry analytical element is described in Fuji Film Research Report, No. 40 (Fuji Photo Film Co., Ltd., 1995) p. 83, clinical pathology, extra edition, special feature No. 106, new development of dry chemistry / simplified test (Clinical Pathology Publication, published in 1997), and the like.

  The multilayer dry analytical element described above usually includes at least one functional layer. The number of functional layers is not particularly limited as long as it is one or more, and may be one layer or a plurality of layers of two or more layers.

  Specific examples of the functional layer include a spreading layer, an adhesive layer that bonds the spreading layer and a functional layer other than the spreading layer, a water absorbing layer that absorbs liquid reagent, a mordant layer that prevents diffusion of a dye generated by a chemical reaction, a gas A gas permeable layer that selectively transmits light, an intermediate layer that suppresses and promotes mass transfer between layers, a light shielding layer for stably performing reflection photometry, a color shielding layer that suppresses the influence of endogenous dyes, and an analyte A reagent layer containing a reagent that reacts with the coloring agent, a coloring layer containing a coloring agent, and the like, and these can be appropriately selected as necessary.

  As an example of the multilayer dry analytical element, for example, a hydrophilic polymer layer can be provided on the support as a functional layer via another layer such as an undercoat layer in some cases. The hydrophilic polymer layer is, for example, a non-porous, water-absorbing and water-permeable layer, basically a water-absorbing layer consisting only of a hydrophilic polymer, or a coloring reagent that directly participates in a coloring reaction using a hydrophilic polymer as a binder. A reagent layer including a part or all of it, and a detection layer containing a component (for example, mordant) that fixes and immobilizes the coloring dye in the hydrophilic polymer can be provided.

(Reagent layer)
The reagent layer is a water-absorbing material in which at least a portion of the reagent composition that reacts with a test component in an aqueous liquid to produce an optically detectable change is substantially uniformly dispersed in the hydrophilic polymer binder. It is a water-permeable layer. This reagent layer also includes an indicator layer, a coloring layer and the like.

  Hydrophilic polymers that can be used as a binder in the reagent layer generally have natural or synthetic hydrophilic properties with a water swell ratio of from about 150% to about 2000%, preferably from about 250% to about 1500% at 30 ° C. Polymer. Examples of such hydrophilic polymers include gelatin (eg, acid-treated gelatin, deionized gelatin, etc.) and gelatin derivatives (eg, phthalated gelatin, hydroxyacrylate) disclosed in JP-A-60-108753 and the like. Graft gelatin, etc.), agarose, pullulan, pullulan derivatives, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone and the like.

  The reagent layer can be a layer that is appropriately crosslinked and cured using a crosslinking agent. Examples of cross-linking agents include, for example, known vinyl sulfone cross-linking agents such as 1,2-bis (vinylsulfonylacetamido) ethane and bis (vinylsulfonylmethyl) ether for gelatin, aldehydes for methallyl alcohol copolymers, There are glycidyl group-containing epoxy compounds and the like.

  The dry thickness of the reagent layer is preferably in the range of about 1 μm to about 100 μm, more preferably in the range of about 3 μm to about 30 μm. The reagent layer is preferably substantially transparent.

  As a reagent to be included in the reagent layer and other layers of the multilayer dry analytical element, a reagent suitable for the detection can be selected according to the test substance.

(Light shielding layer)
A light shielding layer can be provided on the reagent layer as necessary. The light shielding layer has water permeability or water penetration in which fine particles having a light absorbing property or light reflecting property (collectively referred to as light shielding property) are dispersed and held in a hydrophilic polymer binder having a small amount of film forming ability. Is a sex layer. The light shielding layer is a color of an aqueous liquid spotted and supplied to a developing layer, which will be described later, when a detectable change (color change, color development, etc.) generated in the reagent layer is reflected and measured from the support side having light permeability. Especially, when the sample is whole blood, the red color of hemoglobin is shielded and also functions as a light reflection layer or a background layer.
Examples of the light-reflecting fine particles include titanium dioxide fine particles (rutile type, anatase type or brookite type fine crystal particles having a particle diameter of about 0.1 μm to about 1.2 μm, etc.), barium sulfate fine particles, aluminum fine particles or Examples of the light-absorbing fine particles include carbon black, gas black, and carbon micro beads. Among these, titanium dioxide fine particles and barium sulfate fine particles are preferable. Particularly preferred are anatase-type titanium dioxide fine particles.

  Examples of the hydrophilic polymer binder having a film-forming ability include weakly hydrophilic regenerated cellulose, cellulose acetate, etc. in addition to the hydrophilic polymer similar to the hydrophilic polymer used in the production of the reagent layer described above. Of these, gelatin, gelatin derivatives, polyacrylamide and the like are preferable. In addition, gelatin and a gelatin derivative can be used by mixing a known hardening agent (crosslinking agent).

  The light shielding layer can be provided by applying an aqueous dispersion of light shielding fine particles and a hydrophilic polymer on the reagent layer by a known method and drying. Further, instead of providing the light shielding layer, light spreading fine particles may be contained in the above-described spreading layer.

(Adhesive layer)
An adhesive layer may be provided on the reagent layer in order to adhere and laminate the spreading layer, optionally via a layer such as a light shielding layer.

  The adhesive layer is preferably made of a hydrophilic polymer that can adhere the spreading layer when wetted with water or when swollen with water, thereby allowing the layers to be integrated. Examples of the hydrophilic polymer that can be used for the production of the adhesive layer include hydrophilic polymers similar to the hydrophilic polymer used for the production of the reagent layer. Of these, gelatin, gelatin derivatives, polyacrylamide and the like are preferable. The dry film thickness of the adhesive layer is generally in the range of about 0.5 μm to about 20 μm, preferably about 1 μm to about 10 μm.

  In addition to the reagent layer, the adhesive layer may be provided on a desired layer in order to improve the adhesive strength between other layers. The adhesive layer can be provided by a known method, such as a method of applying an aqueous solution containing a hydrophilic polymer and a surfactant added as necessary onto a support or a reagent layer.

(Water absorption layer)
The multilayer dry analytical element can be provided with a water absorbing layer between the support and the reagent layer. The water-absorbing layer is a layer mainly composed of a hydrophilic polymer that swells by absorbing water, and is a layer that can absorb water of an aqueous liquid sample that reaches or penetrates the interface of the water-absorbing layer. In particular, a whole blood sample is used as a specimen. In some cases, it has the effect of promoting the penetration of plasma, which is an aqueous liquid component, into the reagent layer. The hydrophilic polymer used for the water absorbing layer can be selected from those used for the reagent layer. In general, gelatin or a gelatin derivative, polyacrylamide, polyvinyl alcohol, particularly the aforementioned gelatin or deionized gelatin is preferred for the water-absorbing layer, and the aforementioned gelatin as the reagent layer is most preferred. The dry thickness of the water-absorbing layer is about 3 μm to about 100 μm, preferably about 5 μm to about 30 μm, and the coating amount is about 3 g / m ² to about 100 g / m ² , preferably about 5 g / m ² to about 30 g. / M ² range. The water-absorbing layer can contain a pH buffer, which will be described later, a known basic polymer, or the like to adjust the pH during use (when the analysis operation is performed). Further, the water-absorbing layer can contain a known mordant, polymer mordant and the like.

(Detection layer)
The detection layer is generally a layer in which a dye or the like produced in the presence of a test component diffuses and can be optically detected through a light-transmitting support, and can be composed of a hydrophilic polymer. A mordant may be included, for example, a cationic polymer relative to the anionic dye. The above-mentioned water-absorbing layer generally refers to a layer in which the dye produced in the presence of the test component does not substantially diffuse, and is distinguished from the detection layer in this respect.

  The multilayer dry analytical element can be prepared and produced by a known method, and can be used by cutting into small pieces such as a square having a side of about 1 mm to about 30 mm or a circle having substantially the same size. It is also possible to make it smaller. Many such dry analytical elements have already been developed and commercialized, such as Fuji Dry Chem (manufactured by Fuji Photo Film Co., Ltd.). In the present invention, such a multilayer dry analytical element itself is used. Alternatively, a part thereof can be used.

  A plurality of the multilayer dry analytical elements are arranged in the reagent part. The arrangement direction of the multilayer dry analysis element is preferably parallel to the liquid absorption part (development layer). As a means for moving the sample, a liquid absorber is used, the liquid absorber is fixed to the slider, and the slider passes through the upper part of the sample pretreatment container, thereby bringing the liquid absorber into contact with the sample processing liquid. Further, the absorber is moved to the reaction part and combined with the multilayer dry analysis element in the reaction part, thereby completing the transfer of the specimen.

  The liquid absorber may be a fibrous material or a non-fibrous material as long as it has the property of containing a certain amount of the specimen liquid when it comes into contact with the specimen liquid. Examples of the fibrous material include filter paper, non-woven fabric, and woven fabric (for example, woven fabric described in JP-A-55-164356, JP-A-57-66359, etc.), and knitted fabric (for example, JP-A-60 Knitted fabrics described in JP-A-22222769, etc.), glass fiber filter paper, and the like can be used.

  As the non-fibrous material, the membrane filter (brush polymer layer), polymer microbeads, glass microbeads, and diatomaceous earth described in JP-B-53-21777, US Pat. No. 3,992,158 etc. are retained in the hydrophilic polymer binder. Non-fiber isotropic porous material layer such as a porous layer containing continuous microvoids, and polymer microbeads described in JP-A-55-90859 are bonded in a point contact manner with a polymer adhesive that does not swell with water It is possible to use a non-fiber isotropic porous material layer made of a continuous fine void-containing porous material layer (three-dimensional lattice-like granular structure layer).

  As the porous material film, a porous film made of an organic polymer can also be used. Specifically, 6,6-nylon, 6-nylon, acrylate copolymer, polyacrylate, polyacrylonitrile, polyacrylonitrile copolymer, polyamide, polyimide, polyamideimide, polyurethane, polyethersulfone, polysulfone, polyethersulfone And polysulfone mixtures, polyester, polyester carbonate, polyethylene, polyethylene chlorotrifluoroethylene copolymer, polyethylene tetrafluoroethylene copolymer, polyvinyl chloride, polyolefin, polycarbonate, polytetrafluoroethylene, polyvinylidene difluoride, polyphenylenesulfur Ferene sulfide, polyfluorocarbonate, polypropylene, polybenzimidazole, poly (methyl acrylate), styrene-acrylic Nitrile copolymer, styrene-butadiene copolymer, saponified product of ethylene-vinyl acetate copolymer, polyvinyl alcohol, saponified product of cellulose acetate butyrate, cellulose acetate butyrate butyrate, saponified product of cellulose acetate butyrate or these Mixtures and the like can be used.

  JP 61-4959 (corresponding US Patent 5,019,347; Corresponding European publication EP 0166365A), JP 62-116258, JP 62-138756 (corresponding European publication EP 0226465A), JP 62-138757 (corresponding European publication) EP 0226465A), JP-A 62-138758 (corresponding European publication EP 0226465A) and the like, and a laminate of a plurality of partially bonded porous layers is also suitable.

  In addition, polymer gel (natural polymer gel: gelatin, agar, agaropectin, starch, amylose, amylopectin, carrageenan, dielan gum, chitansan gum, curdlan, collagen, arginic acid, pectin, konjac mannan, methylcellulose, hydroxypropyl cellulose, Dextran; synthetic polymer gel: polyethylene, polystyrene, polyacrylate, polyacrylic acid, polymethacrylic acid, polyglutamic acid, polyvinylpyridine, polyvinylimidazole, acrylamide, vinylpyrrolidone, hydroxyethyl methacrylate, 0-benzyl-L-glutamate, polyethylene glycol , Hyaluronic acid), latex particles, inorganic materials (porous carbon porous silicon carbide, porous glass beads, silica gel, oxidized aluminum Na, zeolites, mesoporous) are also suitable.

  As a detection means, the color development or discoloration in the multilayer dry analytical element is reflected and photometrically measured from the light-transmitting support side, and the amount of the test substance in the sample is obtained by the principle of the colorimetric measurement method using the calibration curve prepared in advance. Can do. In addition, transmission photometry can be performed as necessary. Furthermore, the analysis chip of the present invention can also be measured by an area sensor.

  An area sensor is a solid-state imaging device such as a CCD, and receives light reflected by light emitted from a light source when a reagent of a reagent carrying part in a multi-measurement dry analysis element reacts with a sample such as blood. The received light is converted into an electrical signal and output to a computer. The area sensor can receive the light reflected from the reagent carrying unit on a surface basis. Therefore, it is possible to measure each reagent area simultaneously, that is, for a plurality of items. In addition, although the reflected light from the specimen is received using an area sensor such as a CCD, the line sensor is not limited to the area sensor.

  According to the present invention, an all-in-one type structure in which all the reagents other than the sample are enclosed in the analysis chip and does not require maintenance, and the amount of the sample and the reagent required for the analysis can be reduced. It can be made in a very small amount, and can be easily analyzed in a short time and at a low cost. One inspection can be carried out with one mechanism, and there is no need for complicated operations, and a small amount of inspection. It is possible to provide an inspection method using a small inspection chip and an inspection chip that facilitates inspection of many items by one operation with a liquid.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
First, the configuration of the inspection chip according to the present invention will be described.
FIG. 1 is an exploded perspective view of the inspection chip. FIG. 2 is a top view of the inspection chip. FIG. 3 is a cross-sectional view of the inspection chip. 4 and 5 are diagrams showing the state of operation of the inspection chip.

  The test chip 10 is schematically configured from a chip body 11, a sample transport section 21, and an attachment member 31 that slidably attaches the sample transport section 21 to the chip body 11.

  The chip body 11 has a substantially rectangular shape and is made of a transparent or translucent material that can be seen through. The chip body 11 has a rectangular shape when viewed from above (as viewed from above in FIG. 1), and includes a support plate portion 11a that supports the specimen transporting portion 21 that slides, and three of the peripheral edges of the support plate portion 11a. And a side plate portion 11b erected vertically from the side.

  The support plate portion 11a of the chip body 11 is formed with a recessed surface 11e that is recessed on the upper surface, which is a surface that is in sliding contact with the lower surface side of the sample transport portion 21 during sliding. Further, on the upper surface side of the concave surface 11e, a pretreatment portion 12 that is a concave portion and a reaction portion 13 that is recessed in the upper surface of the support plate portion 11a in the vicinity of the pretreatment portion 12 are provided.

  In the present embodiment, the pretreatment unit 12 stores in advance a diluent that is a specimen, and a small amount of blood is introduced into the pretreatment unit 12 at the time of the examination. The liquid L to be inspected is generated by mixing the above. The reaction unit 13 accommodates and holds a reagent for examining the reaction of the test liquid L.

  In the inspection chip 10 of this embodiment, in order to seal the pretreatment unit 12 and the reaction unit 13, it is preferable that a tape-shaped sealing member 16 is bonded to the concave surface 11 e. By doing so, it is possible to prevent the diluent stored in the pretreatment unit 12 and the reagent stored and held in the reaction unit 13 from leaking out.

  Further, the chip body 11 is provided with a notch portion 11c in a part of the side plate portion 11c in the vicinity of the concave surface 11e. A part of the seal member 16 to which the concave surface 11e is bonded is disposed in the notch 11c and protrudes to the outside of the chip body 11. At the time of inspection, the user grasps and pulls out the seal member 16 protruding from the cutout portion 11c of the chip body 11, whereby the seal member 16 is peeled off from the recess surface 11e, and the pretreatment unit 12 and the reaction unit 13 are opened. The

  The chip body 11 is provided with a pair of introduction portions 14 a and 14 b that have one end communicating with the pretreatment unit 12 and the other end communicating with the outer surface of the chip body 11. Blood is introduced into the pretreatment section 12 through one of the pair of introduction sections 14a and 14b. At this time, one of the introduction portions 14a and 14b (introduction portion 14b in the present embodiment) is previously loaded with a plug member (not shown), and the plug member 18 is inserted into the introduction portion 14b at the time of inspection. Is extruded into the pretreatment unit 12 to open the introduction unit 14b, and then blood is introduced into the pretreatment unit 12 through the introduction unit 14b. At this time, the other introduction part 14a functions as an air vent for preventing blood introduced from the introduction part 14b from flowing back by the air in the pretreatment part 12. Moreover, it is preferable that the other introduction part 14a functions as a pin holding part for accommodating and holding the opening pin 18 except at the time of inspection.

  The sample transport part 21 is a plate-like member having a substantially rectangular parallelepiped shape. On the lower surface of the sample transporting part 21, there is a liquid absorption which is recessed so as to accommodate and hold the residual liquid absorbing material 24 and recessed so as to accommodate and hold the liquid absorbing body 25. A portion 23 is formed.

  When the sample transporting part 21 is attached to the chip body 11, the position of the three sides is supported by the side plate part 11 c of the chip body 11, so that the position with respect to the chip body 11 is regulated.

  The attachment member 31 is a rectangular plate-like member having substantially the same dimension as the longitudinal dimension of the side plate portion 11b of the chip body 11, and a plurality of (three in this embodiment) screw insertion holes 31a are formed in each. ing. A plurality of screw holes 11d are formed in the upper end surface of the side plate portion 11b of the chip body. When attaching the attachment member 31 to the chip body 11, the screw 32 is inserted into the screw insertion hole 31a, and the tip of the screw 32 is screwed into the screw fixing hole 11d of the side plate portion 11b of the chip body. The member 31 can be fixed to the chip body 11.

  As shown in FIG. 2, in a state where the attachment member 31 is fixed to the chip body 11, a part of the upper surface of the sample transport unit 21 supported on the chip body 11 is between the chip body 11 and the attachment member 31. It is sandwiched and supported. For this reason, it is avoided that the sample transport part 21 is horizontally separated from the upper surface of the chip body 11.

  The test chip 10 of this embodiment is slid by the user pushing and moving the sample transporting part 21 with the fingers toward the edge side on the support plate part 11a of the chip body 11 where the side plate part 11b is not provided. Can move.

  In the test chip 10 of the present embodiment, the number of the reaction parts 13 of the chip body 11 and the number of the liquid absorption parts 23 of the sample transport part 21 are two, but depending on the quantity to be inspected, the test items, etc. The number may be changed.

Next, an example of the operation of the inspection chip according to the present invention will be described.
First, the diluent is stored in advance in the pretreatment unit 12 of the test chip 10, and the reagent 15 is stored and held in the reaction unit 13. Then, a small amount of blood is introduced into the pretreatment unit 12 from one of the introduction units 14a and 14b. In the pretreatment unit 12, the liquid to be inspected L is generated by mixing the diluent and blood. Thereafter, the seal member 16 is peeled off to open the recess of the pretreatment unit 12.

  Next, a part of the sample transport unit 21 is gripped with fingers, and the sample transport unit 21 is slid as shown in FIGS. 2 and 3 to change the position relative to the chip body 11.

  As shown in FIG. 4, when the liquid absorption unit 23 of the sample transport unit 21 is slid and moved to a position (first position) above the preprocessing unit 12 of the chip body 11, the liquid absorption unit 23 is accommodated and held. A part of the liquid absorber 25 comes into contact with the liquid to be inspected L stored in the pretreatment unit 12 to absorb the liquid to be inspected L.

  Here, in a state where the sample transport unit 21 is at the first position, the liquid absorber 25 is preferably a shape, a configuration, or such a material that part of the liquid absorber 25 is elastically deformed toward the pretreatment unit 12 side. . If it carries out like this, the liquid absorber 25 can be reliably made to contact with the to-be-tested liquid L stored by the pre-processing part 12. FIG.

  Subsequently, as shown in FIG. 5, when the sample transport unit 21 is further slid and the liquid absorption unit 23 of the sample transport unit 21 moves to a position (second position) that is above the reaction unit 13 of the chip body 11. The liquid L to be inspected, which is absorbed in the liquid absorber 25 of the liquid absorption unit 23, comes into contact with the reagent 15 of the reaction unit 13. At this time, the liquid to be inspected L and the reagent 15 cause a predetermined reaction, and the user can visually recognize from the outside of the test chip 10 through the transparent chip body 11 and the sample transport unit 21. Based on the reaction between the liquid L and the reagent 15, the state of the inspection can be observed.

  At this time, the residual liquid absorbing material 24 of the specimen transport unit 21 comes into contact with the liquid L to be inspected remaining in the pretreatment unit 12, so that the residual liquid L to be inspected is absorbed by the residual liquid absorbing material 24. It is preferable that By doing so, it is possible to prevent the liquid L to be inspected remaining from the pretreatment unit 12 from leaking out, which is convenient.

Since the test chip 10 can store all other reagents, etc., excluding the sample (blood in this embodiment) introduced at the time of the test, in the chip body 11 in advance and stored before the test, no maintenance is required. is there. In addition, a sufficient amount of specimen necessary for the test is introduced into the pretreatment room,
In addition, since a minimum amount of reagent only needs to be accommodated and held in the reaction unit, the amount of specimen and reagent necessary for the inspection can be made very small.
Furthermore, since the sample transport unit 21 has a simple configuration in which the finger is slid with respect to the chip body 11, the work for the inspection can be simplified and the time required for the inspection can be shortened. And inspection can be performed at low cost.

  Since the mechanism is provided with the specimen transporting portion 21 that is slidable with respect to the chip body 11, one inspection can be performed by one mechanism, and there is no need to perform a complicated operation unlike the conventional inspection method. By increasing the number of the parts 13 and the liquid absorption parts 23, multiple items of inspection can be easily performed by one operation.

Hereinafter, the present invention will be described in detail by way of examples according to the present invention and comparative examples thereof. In addition, this invention is not limited to a following example. In this example, the inspection chip of the above embodiment shown in FIGS. 1 to 5 was used.
Example 1
The operation of the first embodiment will be described.
First, a blood collection capillary is inserted into the introduction part 14 b of the test chip 10 to introduce blood into the pretreatment part 12. Here, the blood collection capillary is a member that sucks blood extracted on the skin by a separate puncture device (not shown) by capillary action and weighs it simultaneously with suction.
A blood collection capillary 1 containing 1 μL of the weighed blood is pushed by capillary push (not shown) and inserted into the pretreatment unit 12 (enclosed with 200 μL of a diluent). Thereafter, the blood in the blood collection capillary weighed by shaking the entire test chip 10 is dissolved in the diluent stored in the pretreatment unit 12 and mixed with the diluent. At this time, the blood collection capillary in the pre-processing unit 12 serves as a stirring bar to assist mixing.

  Thereafter, the test reagent part seal 16 is pulled in the direction of the arrow to peel off the seal, and preparation for transporting the liquid to be inspected by the liquid absorbing part 23 is completed.

  Next, by holding the upper surface of the sample transporting portion 21 with the abdominal surface of the finger and pushing it in the direction of the arrow shown in FIGS. 2 and 3, the positions of the liquid absorbing portion 23 and the absorbent holding portion 22 are changed. The liquid absorber 25 absorbs the liquid L to be inspected 25 by passing over the pretreatment unit 12. Then, when the liquid absorber 25 comes into contact with the reagent 15 accommodated and held in the reaction unit 13, a reaction is performed between the liquid L to be tested and the reagent 15 absorbed in the liquid absorber 25, The user can visually recognize the colorimetric test after the reaction. The residual liquid absorbent 24 held in the absorbent holder 22 of the sample transport section 21 reaches the pretreatment section 12, and the liquid to be examined L that has remained in the pretreatment section 12 is retained in the pretreatment section 12. Absorb to prevent leakage from inside the inspection chip.

(Example 2)
Next, the CRP detection operation will be described.
In this example, a multilayer dry slide for CRP was produced in the same manner as in the example described in JP-A-2003-75445.
1 μL of CRP standard serum with a known CRP concentration is weighed with a capillary 1 and inserted into the pretreatment unit 12 (with 200 μL of diluent pre-filled). Thereafter, the entire test chip 10 is vibrated to mix the diluent and blood. Thereafter, the seal member 16 was peeled off to open the recess of the pretreatment unit 12. By sliding the specimen transport section 21, both the liquid absorber 25 and the residual liquid absorber 24 start moving, and the liquid absorber 25 passes over the pretreatment chamber 12 to absorb the liquid L to be inspected. , Reaches and contacts the reagent 15 of the reaction unit 13.

Here, while maintaining the ambient atmosphere in the vicinity of the inspection chip 10 at 37 ° C., the reflection optical density was measured with a spectrophotometer (MCPD-2000 (Otsuka Electronics)) from the PET support side with visible light having a center wavelength of 650 nm. The difference in reflection optical density (ΔOD _5-3 ) 3 minutes and 5 minutes after the spotting is determined, and the amount of CRP is determined from the calibration curve (number of measurements, N = 5). The measured value (g / dL) of CRP was 3.3 ± 0.15, and CV was 4.5%.

(Example 3)
Next, as in the following examples, hemoglobin (Hb) and glycated hemoglobin (HbA1c) were detected.
In this example, a multilayer dry slide for hemoglobin A1c was produced in the same manner as in Example 2 described in JP-A-8-122335. Then, 1 μL of whole blood is weighed with a capillary and inserted into the pretreatment unit 12 (preliminarily charged with 200 μL of hemolyzed blood). Thereafter, the entire test chip 10 is vibrated to mix the blood and the diluent. Thereafter, the seal member 16 was peeled off to open the recess of the pretreatment unit 12. By sliding the specimen transport unit 21, the liquid absorber 25 and the residual liquid absorber 22 move, and when the liquid absorber 25 passes over the pretreatment unit 12, the liquid L to be inspected is absorbed, and the reagent 15 To touch.

The ambient atmosphere in the vicinity of the inspection chip 10 was maintained at 37 ° C., and the reflection optical density was measured with a spectrophotometer (MCPD-2000 (Otsuka Electronics)) from the PET support side with visible light having a center wavelength of 650 nm. The difference in reflection optical density (ΔOD _5-3 ) 3 minutes and 5 minutes after the spotting was determined, and the amount of hemoglobin A1C was determined from the calibration curve (the number of measurements was N = 3). The measured value (g / dL) of hemoglobin A1C was 1.07 ± 0.04, and the CV was 3.7%. At the same time, the reflection optical density was measured with visible light having a central wavelength of 420 nm from the support side of another hemoglobin (Hb) slide. The amount of hemoglobin (Hb) is obtained from the calibration curve from the reflected optical density OD 0.5 minutes after the spotting (number of measurements, N = 3). The measured value (g / dL) of hemoglobin (Hb) was 13.2 ± 0.4, and the CV was 3.0%.

  6 and 7 show modifications of the inspection chip according to the present invention. In the embodiments described below, members having the same configuration / action as those already described are denoted by the same or corresponding reference numerals in the drawings, and description thereof is simplified or omitted. FIG. 6 is a top view showing a modification of the inspection chip according to the present invention. FIG. 7 is a diagram showing the configuration of the liquid absorber of the inspection chip shown in FIG. The inspection chip 20 shown in FIG. 6 is basically the same as the configuration and operation of the inspection chip 10 of the above embodiment. Only different points will be described below.

  The test chip 20 has a configuration in which the liquid absorber 55 accommodated and held in the liquid absorption unit 23 of the sample transport unit 21 has a function of absorbing the test liquid and a function of reacting with the reagent. For this reason, although the test chip 20 has the pre-processing unit 12 formed in the chip body 11, the reaction unit 13 in the test chip 10 of the above embodiment is not formed.

  The liquid absorber 55 is deformed with respect to the base end portion 55a fixed to the liquid absorption portion 23 of the sample transport portion 21 and the base end portion 55a, and when the sample transport portion 21 is slid, It is comprised from the contact part 55b which is a site | part which contacts the to-be-inspected liquid stored by the pre-processing part 12. FIG. The contact portion 55b is formed with a reaction portion 45 that holds a reagent containing a reagent that causes a predetermined change when it comes into contact with the liquid to be inspected. As the material for the reagent contained in the reaction unit 45, the same material as the reagent 15 accommodated and held in the reaction unit 13 of the above embodiment can be used.

  In the vicinity of the pretreatment unit 12 of the chip body 11, an opening 43 is provided at a position facing the second position of the liquid absorber 55 of the slidable specimen transport unit 21. The user brings the liquid absorber 55 into contact with the liquid L to be inspected in the pretreatment unit 12 at the first position, and then moves the sample transport unit 21 to the second position, thereby allowing the liquid to pass through the opening 43. The color change of the reaction part 45 of the absorber 55 can be observed.

  As described above, the test chip of the present invention can be accurately tested by weighing and mixing with a diluent, producing a test liquid with high mixing accuracy, and bringing the liquid absorber into contact with the test liquid. it can. For this reason, in the prior art, a large amount of test solution is used to perform one item of inspection, and a large-scale operation is required such as rotating the device until the inspection reaches a large scale. According to the inspection chip and the inspection method using the inspection chip of the present invention, the conventional problems can be avoided and the inspection efficiency can be increased.

  The present invention can be used as a test chip that can be used as an allergy reaction test reagent and can test several items of allergic reaction at a time.

It is a disassembled perspective view of a test | inspection chip. It is a top view of an inspection chip. It is sectional drawing of a test | inspection chip. It is a figure which shows the state which has a sample conveyance part in a 1st position. It is a figure which shows the state which has a sample conveyance part in a 2nd position. It is a top view which shows the modification of the test | inspection chip based on this invention. It is a figure which shows the structure of the liquid absorber of the test | inspection chip shown in FIG.

Explanation of symbols

10, 20 Test chip 11 Chip body 12 Pretreatment unit 13 Reaction unit 15 Reagent 21 Specimen transport unit 22 Absorbent holding unit 23 Liquid absorption unit 24 Residual liquid absorption material 25 Liquid absorber L Test liquid

Claims (11)

A test chip for reacting a liquid to be inspected with a reagent and inspecting the liquid to be inspected,
A chip body;
A pre-processing unit that is provided in the chip body and stores the liquid to be inspected;
A reaction part provided in the chip body and containing and holding the reagent;
A specimen transporting part slidably attached to the chip body,
The sample transport section is provided with a liquid absorber, and the liquid absorber contacts the liquid to be tested stored in the pretreatment section at a first position where the sample transport section is slid. The liquid absorber that has absorbed the liquid and sucked the liquid to be inspected contacts the reagent held in the reaction part at a second position where the specimen transport part is slid. Chip.   The specimen transporting section is provided with a residual liquid absorbing material that can be sucked in contact with the liquid to be inspected remaining in the pretreatment section while being slid with respect to the chip body. The inspection chip according to claim 1.   3. The structure according to claim 2, wherein the residual liquid absorbent is in contact with the liquid to be inspected remaining in a pretreatment section in a state where the liquid absorber is in a position in contact with the reaction section. Inspection chip.   The inspection chip according to claim 1, wherein the chip body is provided with an introduction portion for introducing the liquid to be inspected into the pretreatment portion.   The test chip according to any one of claims 1 to 4, wherein a dry reagent is held in the reaction section.   The test chip according to claim 1, wherein a plurality of the reaction units are provided.   The inspection chip according to claim 1, wherein a plurality of the liquid absorption parts are provided.   The test chip according to claim 1, wherein the reagent is a material that detects HbA1c.   The test chip according to claim 1, wherein the reagent is a material that detects CRP. A test chip for reacting a liquid to be inspected with a reagent and inspecting the liquid to be inspected,
A chip body;
A pre-processing unit that is provided in the chip body and stores the liquid to be inspected;
A specimen transporting part slidably attached to the chip body,
The sample transport part is provided with a liquid absorber, the liquid absorber is provided with a reaction part capable of holding the reagent, and at the first position where the sample transport part is slid, the liquid absorber is An inspection chip that absorbs the liquid to be inspected by coming into contact with the liquid to be inspected stored in the pretreatment unit, and the liquid to be inspected contacts the reagent in the reaction unit.   11. An inspection method, wherein the inspection chip according to any one of claims 1 to 10 is used to perform an inspection for reacting the liquid to be inspected with the reagent.

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