DESCRIPTION

Title of Invention

ANALYTICAL DEVICE

Technical Field

The present invention relates to an analytical device utilizing an immunochromatograph device system.

Background Art

In recent years, biochips, which are devices in which a

physiological active substance is fixed over a solid-phase substrate, have been paid attention as a means for achieving a high throughput in drug discovery researches and clinical assays. Representative examples of the physiological active substance are nucleic acids, proteins, antibodies, sugar chains, and aptamers. Among these, nucleic acids are

commercialized and various products are sold on the market as nucleic acid microarrays, which are biochips on which nucleic acids are fixed. The biochips are in the form of being spotted with an arbitrary type of a physiological active substance that is fixed on a substrate, and are mainly used for studies and analyses in research institutions.

Further, studies for miniaturization of systems for chemical reactions, separations, and analyses using micro-fabrication techniques, called micro -analytical chip, μΤΑβ (micro total analytical system), or lab'on-a-chip, have become active, and it has become possible to let various chemical reactions, particularly, physiological reactions occur over a micro-channel (minute flow path). Such analytical systems can analyze trace samples quickly. Therefore, they are paid attention as they are expected to be commercialized as biochips, particularly, diagnostic biochips for medical institutions that take advantage of this feature (see e.g., PTL l).

Back-pressure pumps are often used as a liquid delivering mechanism in such a micro -channel, and a plunger pump, a peristaltic pump, and a syringe pump are used, for example. Further, an

electroosmotic flow is mainly used in capillary electrophoretic systems. Furthermore, pumps obtained by combining a piezoelectric element and a diaphragm, and diffuser-type pumps utilizing asymmetricity in a flow path are being developed with full use of microfabrication. That is, a mechanism for delivering a trace amount of a liquid precisely is

demanded in order to deliver a reagent or the like through a minute flow path. Hence, there is a problem that the prices of these devices are high.

On the other hand, a liquid delivering method employing a simple inexpensive liquid delivery principle utilizing a capillary action is used in point-of-care applications and environment or food analytical applications in which portability is required, and in disposable applications often seen in biological and biochemical fields in which any portions that have been touched by a sample are not used again for avoiding contamination. As the liquid delivering method utilizing the capillary action, an

immunochromatograph method is already used in many fields (see e.g., PTL 2).

In the immunochromatograph method, a simple quick diagnosis for influenza, etc. is performed using a membrane filter (a liquid absorption carrier). In a representative mode of the

immunochromatograph method, the principle of a sandwich method of sandwiching a target substance with two kinds of antibodies is used. Specifically, when an analyte liquid containing a target substance (antigen) flows into a conjugate pad containing a labeled antibody as a labeled biomolecule, an immune complex is formed between the labeled antibody and the antigen. This immune complex moves through the membrane by a capillary action, efficiently comes into contact with an immune complex capture antibody fixed locally (e.g., in a line-shape) on the membrane, and is captured, with the target substance serving as the interface to be captured. As a result, the immune complex is condensed locally on the membrane, which makes it possible to determine whether the target substance is present or absent, by detecting the label contained in the complex.

As shown in Fig. 1A and Fig. IB, an immunochromatograph device 201 generally has a structure obtained by connecting a sample pad 202, a conjugate pad 203, a membrane 204, and an absorption pad 205 such that 202 and 203, 203 and 204, and 204 and 205 partially overlap each other, respectively (see e.g., PTL 3).

In such an immunochromatograph device 201, when an analyte liquid is dropped into the sample pad 202, the analyte liquid moves sequentially to the conjugate pad 203, the membrane 204, and the absorption pad 205 by a capillary action (capillary force). Because the structure includes many members corresponding to the respective functions, the structure is problematic in that it is complicated and expensive proportionally.

Materials used for the immunochromatograph device are fibers in which a capillary action can easily occur, such as organic polymeric fiber such as cellulose acetate fiber, nitrocellulose fiber, polyester fiber, polyethylene fiber, polypropylene fiber, and nylon, and glass fiber (see e.g., PTL 3). Therefore, when an analyte liquid is dropped into such a fiber, the immunochromatograph device entirely becomes wet. Hence, a laboratory technician may touch a pathogen and incur a secondary infection. Hence, the test sheet is sealed and fixed within a plastic housing in order to prevent a secondary infection due to leakage of the analyte liquid. Such a plastic housing is mostly produced by injection molding that is suitable for mass production. Therefore, there is a problem that a molding die having a complicated structure is necessary in view of a sealing property, strength, etc. of the housing, and costs involved are high as a result.

In an analysis of a plurality of kinds of components contained in a sample liquid such as blood in a clinical assay, the sample liquid is divided into the same number of sample groups as the number of the kinds of the components to be analyzed, and the amount of each of the plurality of kinds of components to be analyzed is measured using each of the divided sample liquids.

As a first immunochromatograph method for detecting a plurality of detection targets, there is known a method of detecting two kinds of detection targets with one test strip, by letting one immunochromatograph device carry two test lines. However, although this method can do with small amounts of analytes, it cannot have a membrane treated differently or include different kinds of membranes for both of the different detection targets, because two kinds of lines are applied over the same membrane. Hence, with this method, it is difficult to perform condition optimization for improving the detection sensitivity, which may be a cause of false -positive.

As a second immunochromatograph method, there is known a method of using one test strip, fixing two kinds of antibodies on one test line, and using two kinds of labeling reagents having different color tones to thereby detect two kinds of detection targets on the same line.

However, although this method can do with small amounts of analytes, it cannot have a membrane treated differently or include different kinds of membranes for both of the different detection targets, because two kinds of detection antibodies are applied over the same membrane. Hence, with this method, it is difficult to perform condition optimization for improving the detection sensitivity.

As a third immunochromatograph method, there is proposed a method of connecting a first conjugate pad, a first membrane, a second conjugate pad, and a second membrane in series (see e.g., PTL 4).

However, with this method, an analyte used moves toward the second conjugate pad and the second membrane after it passed through the first conjugate pad and the first membrane. Therefore, it is difficult to perform condition optimization for improving the detection sensitivity, which may be a cause of false -positive. Hence, it has not been successful yet to obtain an analytical device utilizing an immunochromatograph device system that includes a flow path formed as a linear depressed portion inducing no false -positive determination, and needing no liquid delivering mechanism, and that can be constituted with a small number of members. It is requested to provide such an analytical device.

Citation List

Patent Literature

PTL 1 Japanese Patent Application Laid"Open (JP-A) No. 2007-283437

PTL 2 International Publication No. WO 2010/061598

PTL 3 JP-A No. 2012-0189355

PTL 4 JP-A No. 2011-27693

Summary of Invention

Technical Problem

An object of the present invention is to provide an analytical device utilizing an immunochromatograph device system that includes a flow path formed as a linear depressed portion inducing no false -positive determination, and needing no liquid delivering mechanism, and that can be constituted with a small number of members.

Solution to Problem

An analytical device of the present invention as a solution to the problems described above includes:

a base material; and

a linear depressed portion formed in a surface of the base material and having a predetermined length,

wherein when an analyte liquid is dropped into the linear depressed portion, the analyte liquid advances through the linear depressed portion at a liquid flow speed of 0.01 mm/sec or higher.

Advantageous Effects of Invention

The present invention can solve the conventional problems described above, and provide an analytical device utilizing an

immunochromatograph device system that includes a flow path formed as a linear depressed portion inducing no false -positive determination, and needing no liquid delivering mechanism, and that can be constituted with a small number of members.

Brief Description of Drawings

Fig. 1A is a plan view showing an example of a conventional immunochromatograph device.

Fig. IB is a cross-sectional diagram of Fig. 1A.

Fig. 2A is a top plan view showing an example of an analytical device of the present invention.

Fig. 2B is a cross-sectional diagram of Fig. 2A taken along a line

A A.

Fig. 2C is a top plan view showing an example of an analytical device including a flow path formed as a closed linear depressed portion. Fig. 2D is a cross-sectional diagram of Fig. 2C taken along a line

C C.

Fig. 3A is a schematic diagram showing an example of an analytical device used for two kinds of determinations.

Fig. 3B is a schematic diagram showing another example of an analytical device used for two kinds of determinations.

Fig. 3C is a schematic diagram showing another example of an analytical device used for two kinds of determinations.

Fig. 3D is a schematic diagram showing another example of an analytical device used for two kinds of determinations.

Fig. 3E is a schematic diagram showing another example of an analytical device used for two kinds of determinations.

Fig. 4 is a schematic diagram showing an example of an analytical device used for three kinds of determinations.

Fig. 5 is a schematic diagram showing an example of an analytical device used for four kinds of determinations.

Fig. 6A is an image of a flow path of an analytical device of Example 1 formed as a linear depressed portion and captured from above (at a magnification of x200).

Fig. 6B is a cross-sectional image of the flow path of the analytical device of Example 1 formed as a linear depressed portion (at a

magnification of x200).

Fig. 6C is a 3D image of the flow path of the analytical device of Example 1 formed as a linear depressed portion (at a magnification of x200).

Fig. 7A is an image, before an analyte liquid is flowed, of the flow path of the analytical device of Example 1 formed as a linear depressed portion, captured from above (at a magnification of x200).

Fig. 7B is a 3D image, before an analyte liquid is flowed, of the flow path of the analytical device of Example 1 formed as a linear depressed portion (at a magnification of x200).

Fig. 8 A is an image, during an early stage of flowing of an analyte liquid, of the flow path of the analytical device of Example 1 formed as a linear depressed portion, captured from above (at a magnification of x200).

Fig. 8B is a 3D image, during the early stage of the flowing of the analyte liquid, of the flow path of the analytical device of Example 1 formed as a linear depressed portion (at a magnification of x200).

Fig. 9 A is an image, during a final state of the flowing of the analyte liquid, of the flow path of the analytical device of Example 1 formed as a linear depressed portion, captured from above (at a magnification of x200).

Fig. 9B is a 3D image, during the final stage of the flowing of the analyte liquid, of the flow path of the analytical device of Example 1 formed as a linear depressed portion (at a magnification of x200).

Fig. 10A is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing an early state.

Fig. 10B is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing a middle state.

Fig. IOC is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing a final state.

Fig. 11 is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention formed as a linear depressed portion.

Fig. 12A is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a triangular shape.

Fig. 12B is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a bottomless polygonal shape.

Fig. 12C is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a trapezoidal shape.

Fig. 12D is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a polygonal shape.

Fig. 12E is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path does not satisfy a condition that its open end width is a maximum width of linear depressed portion, because its bottom width is greater than its open end width.

Fig. 12F is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein a maximum flow path width of the flow path is present at other than an open end thereof.

Fig. 13A is a cross -sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a semicircular shape.

Fig. 13B is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a semi-elliptical shape.

Fig. 13C is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a U-letter shape with a portion thereof having a semicircular shape.

Fig. 13D is a cross-sectional diagram showing an example of a flow path of an analytical device of the present invention, wherein the flow path is formed as a linear depressed portion having a partially circular shape, of which open end width is not a maximum width of the linear depressed portion. Fig. 14 is a top plan view showing an example of an analytical device of the present invention.

Fig. 15 is a diagram explaining a method of broadening a bottom width of a linear depressed portion by cutting a second linear depressed portion at a 100 μιη interval from a first linear depressed portion, by shifting a blade 100 by 100 μπι.

Fig. 16 is a graph plotting bottom width (μιη) on the horizontal axis and liquid flow speed (mm/sec) on the vertical axis, based on experimental results of Example 14, and Examples 20 to 25.

Fig. 17A is a bottom plan view showing an example of a method of forming a flow path as a closed linear depressed portion by bonding aluminium plates.

Fig. 17B is a cross-sectional diagram taken at a

thickness-direction center, showing an example of a method of forming a flow path as a closed linear depressed portion by bonding aluminium plates.

Fig. 17C is a top plan view showing an example of a method of forming a flow path as a linear depressed portion by bonding aluminium plates.

Description of Embodiments

(Analytical Device)

An analytical device of the present invention includes a base material, and a linear depressed portion formed in a surface of the base material and having a predetermined length, preferably includes at least any of a flow path, a sample addition portion, a labeled substance retaining portion, a determination portion, and an absorption portion, and further includes other members according to necessity.

As a result of earnest studies for solving the problems described above, the present inventors have confirmed that it was when an analyte liquid dropped into the linear depressed portion advanced through the linear depressed portion at a liquid flow speed of 0.01 mm/sec or higher that the analyte liquid passed through the linear depressed portion without a liquid delivering mechanism. The present inventors have also found it possible to detect a plurality of detection targets without making a false-positive determination, by fabricating an analytical device utilizing an immunochromatograph device system including the linear depressed portion described above.

In the analytical device, it is necessary that when an analyte liquid is dropped into the linear depressed portion, the analyte liquid advance through the linear depressed portion at a liquid flow speed of 0.01 mm/sec or higher, and more preferably 0.3 mm/sec or higher.

When such a condition is satisfied that when an analyte liquid is dropped into the linear depressed portion, the analyte liquid advances at a liquid flow speed of 0.01 mm/sec or higher, it is possible to let the analyte liquid move through the linear depressed portion (e.g., a flow path), and satisfy the objective of the analytical device, i.e., being able to detect a plurality of detection targets without a false -positive

determination. When the liquid flow speed is lower than 0.01 mm/sec, the objective of the analytical device is not achieved due to a factor that the analyte liquid may be absorbed into the base material, the analyte liquid may dissipate by vaporization, or the analyte liquid may spread and bleed outside the linear depressed portion (e.g., a flow path).

Here, the liquid flow speed can be calculated based on the formula below, after obtaining a difference between a time taken for an analyte liquid to advance through the linear depressed portion by 10 mm and a time taken for the analyte liquid to advance through the linear depressed portion by 20 mm, when it is dropped into an end point of the linear depressed portion.

10 (mm) ÷ (time (sec) taken to advance through linear depressed portion by 20 mm - time (sec) taken to advance through linear depressed portion by 10 mm) = liquid flow speed (mm/sec)

<Base Material>

The base material is preferably a stack of fiber or textile layers including numerous voids between the fibers.

It is preferable that the stack of fiber or fibrous layers include numerous voids between fibers or textiles. The fibers or textiles may be stacked randomly in three dimensions, or may be stacked to have an orientation in one dimension or two dimensions.

A paper base material is preferable as the base material. A production method, a kind, etc. of the paper base material are not particularly limited, and may be appropriately selected according to the purpose. Examples of the paper base material include mechanical pulps such as KP, SGP, RGP, BCTMP, and CTMP, used paper pulps such as deinking pulp, non-wood pulps such as kenaf, bamboo, straw, and linen, organic synthetic fiber such as polyamide fiber, polyester fiber, and polynosic fiber, and inorganic fiber such as glass fiber, ceramic fiber, and carbon fiber. When the paper base material is a multilayer combination board, respective layers may be made of different pulps.

Use of a paper base material made of a used paper pulp as the pulp is environmentally favorable. For example, a three-layered or more multilayer combination board including at least an intermediate layer made of a used paper pulp having a low whiteness, and a surface layer and a back layer made of a pulp having a high whiteness is one of environmentally favorable configurations, because it can be compounded with a lot of a used paper pulp in an amount of 40% by mass or greater. Each layer may be compounded with a loading material according to necessity.

The loading material is not particularly limited, and an arbitrary loading material may be selected according to the purpose. Examples thereof include various pigments used commonly in high-quality paper, including mineral pigments such as kaolin, fired kaolin, calcium

carbonate, calcium sulfate, barium sulfate, titanium dioxide, talc, zinc oxide, alumina, magnesium carbonate, magnesium oxide, silica, white carbon, bentonite, zeolite, sericite, and smectite, and organic pigments such as a polystyrene resin, a urea resin, a melamine resin, an acrylic resin, and a vinylidene chloride resin, or minute empty particles of these.

In addition to the pulp fiber and the loading material, the paper base material may contain various internally adding auxiliary

papermaking agents appropriately selected according to necessity, such as an anionic, nonionic, cationic or amphoteric yield improver, a water filterability improver, a paper strengthening agent, and an internally adding sizing agent. Furthermore, the paper base material may arbitrarily contain such internally adding auxiliary papermaking agents as a dye, a fluorescent brightener, a pH adjuster, a defoaming agent, a pitch controlling agent, and a slime controlling agent according to the purposes for which the paper is used.

A papermaking method is not particularly limited, and an arbitrary method may be selected according to the purpose. All types of papermaking methods are applicable, including an acidic papermaking method in which a papermaking pH is around 4.5, a weakly acidic papermaking method in which a main component is an alkaline loading material such as calcium carbonate, and a papermaking pH is about 6, and a neutral papermaking method in which a pH is weakly alkaline at about 9.

Examples of paper machines include a Fourdrinier paper machine, a twin wire paper machine, a cylinder paper machine, and a Yankee paper machine.

A surface sizing treatment may be applied to a surface of the produced paper base material, with starch or a surface sizing agent. A surface of the paper base material may be smoothed with a calender or the like.

The size of the base material is not particularly limited, and may be appropriately selected according to the purpose. For example, an average length thereof is preferably from 10 mm to 297 mm, an average width thereof is preferably from 1 mm to 210 mm, and an average thickness thereof is preferably from 0.05 mm to 100 mm. The size of the paper base material is more preferably a regular size such as a credit card size, a postcard size, and an A4 size.

The average thickness of the base material is more preferably from 0.05 mm to 10 mm, and yet more preferably from 0.1 mm to 1 mm. When the average thickness is less than 0.05 mm, the base material may tear or bore when a shape of a linear depressed portion is formed therein. When the average thickness is greater than 100 mm, it may take labor and costs to produce the base material.

A liquid-impermeable film such as a polyethylene terephthalate (PET) film, a polystyrene film, a polyester film, and a polyvinyl chloride film may be pasted over a surface of the base material opposite to a surface thereof in which a flow path is formed, with a double-face tape, an adhesive, a gluing agent, or the like.

A contact angle of a water droplet dropped over the base material indicates the degree of permeation into the base material. That is, the closer to 0° the contact angle is, the easier it is for the water droplet to permeate the base material. The more different from 0° the contact angle is, the harder it is for the water droplet to permeate the base material, and the water droplet is kept in a droplet shape. Typically, an immunochromatograph test strip uses a paper base material made of organic polymeric fiber such as cellulose acetate fiber, nitrocellulose fiber, polyester fiber, polyethylene fiber, polypropylene fiber, and nylon or glass fiber, in which a capillary action can easily occur, that is very easily permeable by water droplets (has a contact angle close to 0°), and that has a high capillary force (a force of sucking up water in a direction perpendicular to a water surface).

However, the base material used in the present invention is a base material made of a stack of fibers or textiles including numerous voids between the fibers, which is very difficult for water droplets to permeate (has a contact angle fairly different from 0°), and has a weak capillary force (a force of sucking up water in a direction perpendicular to a water surface). Therefore, a water droplet propulsive force in the base material is not a capillary force of water droplets in paper fiber as in an immunochromatograph test strip, but instead, a linear depressed portion is formed in the based material by cutting or the like, as a linear depressed portion which is a path through which an analyte liquid passes (e.g., a flow path). Then, the fibers in the cut depressed portion are untwined or pressurized, to thereby increase the number of voids present between the fibers or reduce the size per void, which promotes a capillary action preferentially through the flow path, and advances the analyte liquid along the linear depressed portion (e.g., a flow path).

Therefore, a preferable structure is one in which a propulsive force can be as high as possible, and a spreading force can be as low as possible, where the propulsive force is defined as a force of thrusting a liquid through the flow path, and the spreading force is defined as a force of making a liquid bleed and spread outside the flow path or making a liquid permeate the base material. When the base material does not include numerous voids, the analyte liquid does not advance through the linear depressed portion, because no propulsive force based on a capillary action acts.

In the relationship between the base material and an analyte liquid, the contact angle is preferably 40° or greater, more preferably 45° or greater, and yet more preferably 50° or grater. When the contact angle is less than 40°, it is easy for water droplets to permeate the base material, leading to a problem that a propulsive force based on a surface tension between the walls of the depressed portion and a capillary action may not be obtained.

Here, the testing method in this test is compliant with a JIS testing method, "a method for testing wettability of a surface of a substrate glass" R3257÷ 1999, "6. Sessile drop method", except that a test piece is changed from a glass substrate to a base material. The measurement instrument used in this test may be, for example, a contact angle gauge (DM100 manufactured by Kyowa Interface Science Co., Ltd.). <Flow Path>

The flow path is a linear depressed portion formed in one surface of the base material and depressed from the one surface. The linear depressed portion is opened.

Here, what is meant by "the linear depressed portion being opened" is that at least during use of the analytical device, the linear depressed portion is not hermetically sealed, with no cover or the like present on the surface of the linear depressed portion. At least a portion or preferably the whole of the linear depressed portion is opened.

Terms used for explaining the linear depressed portion of the present invention are defined as follows. The terms explained are illustrated in Fig. 11.

<Open End Width>

An open end width is a width of such a portion of one surface of the base material at which the linear depressed portion is formed in the one surface, measured in a transverse cross-section of the linear depressed portion taken perpendicularly to a direction in which a liquid is delivered along the linear depressed portion.

<Maximum Width of Linear Depressed Portion>

A maximum width of the linear depressed portion is a maximum measure of the linear depressed portion that is found when the linear depressed portion is sliced along a straight line parallel with the surface from which it is depressed, in the transverse cross-section of the linear depressed portion.

<Bottom Width>

A bottom width is the width of the deepest portion in the transverse cross-section of the linear depressed portion in the depth direction.

<Bottom Angle>

A bottom angle is defined for a linear depressed portion of which transverse cross section is outlined with straight lines. As for Fig. 12A and Fig. 12B in which there is no bottom width, a bottom angle is an angle of an acute portion at the bottom. As for Fig. 12C and Fig. 12D in which there is a bottom width, a bottom angle is an angle at which two straight lines each passing either end of the bottom surface and circumscribing the cross-sectional shape of the linear depressed portion cross each other. Note that no bottom angle is defined for a linear depressed portion of which open end width is not the maximum width of the linear depressed portion as in Fig. 12E and Fig. 12F.

The cross- sectional shape of the linear depressed portion cross-section seen perpendicularly to the liquid delivering direction of the linear depressed portion is not particularly limited, and may be

appropriately selected according to the purpose. Examples thereof include a shape formed by straight lines such as a V-letter shape, a triangular shape, a square shape, a rectangular shape, and a polygonal shape, and a partially or wholly curved shape such as a semicircular shape, an elliptical shape, and a U-letter shape. Among these, a triangular shape having no bottom width is preferable.

An average depth of the linear depressed portion is preferably from 1% to 90%, more preferably from 5% to 85%, and yet more

preferably from 10% to 80% of the average thickness of the base material.

When the average depth of the linear depressed portion is greater than 90% of the average thickness of the base material, an analyte liquid may seep out from the back surface of the paper base material, and a laboratory technician may touch a pathogen and incur a secondary infection. When the average depth is less than 1% of the average thickness, an analyte liquid may not be able to flow.

The average depth of the linear depressed portion may be calculated as, for example, an average of depths measured at arbitrary ten positions with a digital microscope (VHX- 1000 manufactured by Keyence Corporation).

An average open end width of the linear depressed portion is preferably from 1 μπι to 1,000 μπι, more preferably from 5 μιη to 850 μιη, and yet more preferably from 10 μπι to 700 μπι. Further, it is preferable that the linear depressed portion taper gradually with its width decreasing from the open end of the linear depressed portion toward the bottom end. It is more preferable that the open end width be the maximum width of the linear depressed portion. Wall surfaces of the linear depressed portion may be damaged or dented, and the damaged or dented portion may be greater in width than the open end of the flow path, as long as such a greater width is confined locally within that portion.

When the average open end width of the linear depressed portion is less than 1 μπι, an analyte liquid may not flow or a labeled substance in the analyte liquid may not advance along the flow path. When the average open end width of the linear depressed portion is greater than 1,000 μπι, a propulsive force based on a surface tension between the walls of the linear depressed portion and a capillary action may not be obtained.

An average bottom width is preferably equal to or less than the open end width, and preferably from 0 μιη to 400 μπι, more preferably 200 μπι or less, and particularly preferably 100 μπι or less. A V-letter shape having no bottom width is the most preferable.

The average open end width and the average bottom width may each be calculated as, for example, an average of widths measured at arbitrary ten positions with a digital microscope (VHX-1000

manufactured by Keyence Corporation).

The bottom angle, which is defined as an angle of an acute portion of the linear depressed portion when the linear depressed portion has no bottom width, or as an angle at which two straight lines each passing either end of the bottom surface and circumscribing the cross-sectional shape of the linear depressed portion cross each other when the linear depressed portion has a bottom width, is preferably from 0° to 120°, more preferably from 15° to 105°, and yet more preferably from 30° to 90°.

When the bottom angle is greater than 120°, an effect attributable to a V-shaped groove is poor, and a propulsive force based on a capillary action may not be expected.

The linear depressed portion is not particularly limited, and an arbitrary linear depressed portion may be selected according to the purpose. For example, it may be formed by cutting, molding, and laser machining. Among these, methods such as cutting and laser machining that remove the region to thereby form the linear depressed portion are preferable.

Preferable examples of the molding include injection molding, hot embossing molding, transfer molding, and compression molding.

Molding conditions such as a molding temperature, a pressurizing pressure, and smoothness and a shape of a molding die are not

particularly limited, and may be appropriately selected according to the purpose.

The cutting is not particularly limited, and an arbitrary cutting method may be selected according to the purpose as long as it performs cutting mechanically. Examples thereof include cutting by various types of end mills, cutting by various types of bites, and polishing by various types of polishing machines.

As for mechanical cutting, a type of machining, specifications of a machine, and a shape, a material, and a surface condition of a cutting jig are not particularly limited. Further, cutting and molding may be used in combination. For example, it is free and unlimited at all if a rough molded product is produced by molding, and then a minute machining may be applied to the product by cutting.

A sample addition portion into which an analyte liquid is added, a labeled substance retaining portion for carrying a labeled substance that causes a reaction (e.g., an antigen-antibody reaction) with a detection target substance in the analyte liquid, and a determination portion at which a fixing substance that causes an antigen-antibody reaction with the detection target substance is fixed may be provided in the base material. Further, an absorption portion for absorbing the analyte liquid having passed through the determination portion may also be provided. The sample addition portion and the labeled substance retaining portion may be the same portion. It is preferable that all of the sample addition portion, the flow path, the labeled substance retaining portion, and the determination portion be linear depressed portions formed in one surface of the base material and depressed from the one surface, and that the linear depressed portions be opened.

The area of each portion is not particularly limited, and may be appropriately selected according to the purpose. Each portion may have a size that can be confined within the width of the flow path formed as a linear depressed portion, or may partially have a width greater than the width of the flow path formed as a linear depressed portion. When each portion partially has a width greater than the width of the flow path formed as a linear depressed portion, the shape of each portion is not particularly limited and may be appropriately selected according to the purpose. Examples of the shape include a circular shape, an elliptical shape, a square shape, a rectangular shape, a rhomboidal shape, and a triangular shape.

The linear depressed portions as the respective portions are not particularly limited, and arbitrary linear depressed portions may be selected according to the purpose. Examples thereof include those formed by cutting, molding, and laser machining. Among these, methods such as cutting and laser machining that remove the region to thereby form the linear depressed portions are preferable.

There may be cases when an analyte liquid flows back in a reverse direction and gives significant influences to the determination result, if the predetermined reaction time is not kept to and the test kit is left as is even after the reaction time has passed. Hence, it is preferable to provide the absorption portion. This makes it possible to prevent a false determination. For example, there have been troubles that an analyte liquid flows back in a large amount and smudges a positive signal that has appeared in the determination portion to make the

determination difficult, and that a labeling reagent having a color flows back and spreads throughout the medium to add to the background signal and reduce the S/N ratio. There have also been false -positive problems that a detection target substance that has formed a complex with a labeled substance passes the determination portion again, an excess amount of the detection target substance is captured additionally, and the test sample that should originally be determined as negative is

determined as positive. A highly water-absorbent polymer may be embedded in the absorption portion in order to prevent the analyte liquid from flowing back.

The highly water-absorbent polymer is not particularly limited, and an arbitrary one may be selected according to the purpose.

Examples thereof include ^: a partially cross-linked product of a polymeric compound having a carboxyl group or a salt thereof, such as a

cross-linked polyacrylic acid salt, a cross-linked vinyl alcohol/acrylic acid salt copolymer, a cross-linked starch/acrylic acid salt graft copolymer, and a cross-linked polyvinyl alcohol/polymaleic anhydride salt graft

copolymer; and a partially cross-linked product of a polysaccharide, such as a cross-linked carboxymethyl cellulose salt. One of these may be used alone, or two or more of these may be used in combination. Among these, a cross-linked polyacrylic acid salt, and a cross-linked starch/acrylic acid salt graft copolymer are preferable, and cross-linked sodium polyacrylate is particularly preferable in terms of a water absorbing performance.

A first biomolecule that is labeled and can bind with a target substance is fixed in the labeled substance retaining portion. A second biomolecule (capture molecule) for capturing a labeled antibody containing the labeled first biomolecule and the target substance is fixed in the determination portion that communicates with the labeled substance retaining portion through the flow path. The target substance is a molecule that is the target of detection by a lateral flow method.

The first biomolecule is a biomolecule that has the ability to bind with the target substance.

It is preferable to form the sample addition portion, the labeled substance retaining portion, the determination portion, and the

absorption portion such that the average depth of the linear depressed portion formed as at least one selected from the sample addition portion, the labeled substance retaining portion, the determination portion, and the absorption portion is greater than the average depth of linear depressed portion formed as the flow path by greater than 0 μηι to equal to or less than 100 μπι. It is more preferable to make the average depth of the linear depressed portion formed as at least one selected from the sample addition portion, the labeled substance retaining portion, the determination portion, and the absorption portion greater than the average depth of the linear depressed portion formed as the flow path by from 5 μπι to 95 μιη. It is yet more preferable to make the average depth of the linear depressed portion formed as at least one selected from the sample addition portion, the labeled substance retaining portion, the determination portion, and the absorption portion greater than the average depth of the linear depressed portion formed as the flow path by from 10 μπι to 90 μιη.

When the average depth of the linear depressed portion formed as the flow path is greater than the average depth of the labeled substance retaining portion by 1 μη or greater, there is a problem that the labeled first biomolecule fixed in the portion and an antigen in the analyte cannot bind with each other to thereby make a false -negative determination.

When the average depth of the linear depressed portion formed as the flow path is greater than the average depth of the determination portion by 1 μπι or greater, there is a problem that the second biomolecule

(capture molecule) fixed in the portion cannot bind with the conjugate of the antigen in the analyte and the labeled first biomolecule to thereby make a false -negative determination. When the average depth of the linear depressed portion formed as the flow path is greater than the average depth of the absorption portion by 1 μπι or greater, there is a problem that the analyte liquid flows back in a large amount and smudges a positive signal that has appeared in the determination portion to make the determination difficult, or that the labeling reagent having a color flows back and spreads throughout the medium to add to the background signal and reduce the S/N ratio. There are also

false-positive problems that the detection target substance that has formed a complex with a labeled substance passes the determination portion again, an excess amount of the detection target substance is captured additionally, and the test sample that should originally be determined as negative is determined as positive.

The analytical device of the present invention will be explained below with reference to the drawings.

Fig. 2A is a top plan view showing an example of an analytical device of the present invention. Fig. 2B is a cross-sectional diagram of Fig. 2A taken along a line A- A. In Fig. 2A and Fig. 2B, the reference sign 101 denotes the sample addition portion, the reference sign 102 denotes the labeled substance retaining portion, the reference sign 103 denotes the determination portion, the reference sign 104 denotes the absorption portion, and the reference sign 105 denotes the flow path. The analyte liquid flows in the direction of the arrow shown in Fig. 2B.

In the present invention, a plurality of flow paths may branch out from the sample addition portion or from between the sample addition portion and the labeled substance retaining portion, and a labeled substance retaining portion and a determination portion may be formed on each flow path, so that a plurality of determinations may be made simultaneously. As specific examples, analytical devices shown in Fig. 3A to Fig. 3E may be used for two kinds of determinations. In Fig. 3A to Fig. 3E, the reference sign 110 denotes a base material, the reference sign 111 denotes a sample addition portion, the reference signs 112 and 116 denote labeled substance retaining portions, the reference signs 113 and 117 denote determination portions, the reference signs 114 and 118 denote absorption portions, and the reference signs 115 and 119 denote flow paths.

An analytical device shown in Fig. 4 may be used for three kinds of determinations. An analytical device shown in Fig. 5 may be used for four kinds of determinations. In Fig. 4 and Fig. 5, the reference sign 110 denotes a base material, the reference sign 111 denotes a sample addition portion, the reference signs 112, 116, 122, and 126 denote labeled substance retaining portions, the reference signs 113, 117, 123 and 127 denote determination portions, the reference signs 114, 118, 124, and 128 denote absorption portions, and the reference signs 115, 119, 125, and 129 denote flow paths.

In Fig. 3A to Fig. 5, the position from which flow paths branch out, and the shape and number of the flow paths are not particularly limited, and may be appropriately selected according to the purpose. By varying shapes from linear depressed portion to linear depressed portion, such as the open end width, the bottom width, the bottom angle, etc. of the liner depressed portions, it is possible to optimize the liquid flow speed necessary for the reaction in each linear depressed portion.

Fig. 11 to Fig. 13 show examples of linear depressed portion cross-sections in the present invention. The reference sign 11 denotes a base material, the reference sign 12 denotes a linear depressed portion cross-section, the reference sign 13 denotes the length of the open end width, the reference sign 14 denotes the length of the bottom width, the reference sign 15 denotes the bottom angle, and the reference sign 16 denotes the maximum width of the linear depressed portion.

In the present invention, it is preferable that the open end width be the maximum width of the linear depressed portion in Fig. 11.

Examples of linear depressed portion shapes that satisfy this condition include the triangular shape shown in Fig. 12A, the pencil shape shown in Fig. 12B, the trapezoidal shape shown in Fig. 12C, and the polygonal shape shown in Fig. 12D, all of which are outlined with straight lines, and the semicircular shape shown in Fig. 13A and the elliptical shape shown in Fig. 13B, which are outlined with a curved line, and the IHetter shape shown in Fig. 13C, which is outlined with a curved line partially.

Examples of linear depressed portion shapes of which maximum width of the linear depressed portion is not present at the open end thereof include Fig. 12E, Fig. 12F, and Fig. 13D.

Among these, shapes of which linear depressed portion width decreases from the open end depth- wise are preferable. To study the reason for this, how a reagent having a color, which was an analyte liquid

(Wetting Tension Test Mixture No. 65.0 (manufactured by Wako Pure

Chemical Industries, Ltd.)), flowed through the linear depressed portion formed in the base material was observed with a digital microscope

(VHX-1000 manufactured by Keyence Corporation). It was confirmed that the analyte liquid first advanced along the edge of the groove, then advanced along the wall surfaces of the groove, and eventually filled the linear depressed portion. In order to reduce a spreading force and increase a propulsive force, a preferable shape of the linear depressed portion is one that has in the center of the linear depressed portion, a groove serving the role of letting an analyte liquid advance through the linear depressed portion, where the propulsive force is defined as a force of thrusting an analyte liquid through the linear depressed portion, and the spreading force is defined as a force of making an analyte liquid bleed and spread outside the linear depressed portion or making an analyte liquid permeate the base material. In a structure of which maximum width of the linear depressed portion is not at the open end and that hence has dents in the wall surfaces of the linear depressed portion (as shown in e.g., Fig. 12F), a spreading force works along vectors deviated from the advancement direction in the linear depressed portion, and the analyte liquid flows out from the linear depressed portion excessively, which consequently reduces the propulsive force to be involved in a capillary action. Hence, a shape that has a V groove edge at which the propulsive force can concentrate, such as the triangular shape shown in Fig. 12A, is preferable.

For these reasons, the bottom width of those among the shapes described above that have their bottom surface outlined with a straight line is preferably from 0 μπι to 400 μπι, more preferably 200 μηι or less, and yet more preferably 100 μιη or less. Furthermore, the triangular shape shown in Fig. 12A, and the pencil shape shown in Fig. 12B, both of which have no bottom width, are the most preferable.

When the bottom width is greater than 400 μπι, there exist grooves at two positions, namely at both ends of the bottom surface, which makes the propulsive force be dispersed and the analyte liquid be branched into two flows to thereby increase the spreading force, which may make it impossible for the analyte liquid to advance through the flow path. A V-letter shape having no bottom width is more preferable because it can concentrate the propulsive force to the groove edge in the center of the linear depressed portion and suppress the spreading force.

Among the shapes described above, those of which linear depressed portion cross-sectional shape is outlined with straight lines and that have no bottom width, such as Fig. 12A and Fig. 12B have a bottom angle of preferably from 0° to 120°, more preferably from 15° to 105°, and yet more preferably from 30° to 90°, where the bottom angle is defined as an angle of the acute portion of the linear depressed portion

cross-sectional shape.

For making a plurality of determinations with a

immunochromatograph test strip, there are proposed a method of detecting two kinds of detection targets with one test strip by making the one test strip carry two test lines, and a method of fixing two kinds of antibodies on one test line and using two kinds of labeling reagents having different color tones to thereby detect two kinds of detection targets from the same line. The problem is, making two kinds of determinations on the same line itself conflicts with condition

optimization for improving the detection sensitivity, and forms a factor of false-positive. Furthermore, any method for detecting three or more kinds of detection targets is considered impossible. However, in the present invention, a labeled substance retaining portion and a

determination portion can be provided on each flow path independently, and condition optimization for improving the detection sensitivity is unnecessary, with no false -positive. Moreover, detection of three or more kinds of detection targets is readily possible.

Fig. 10A is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing an initial state. Fig. 10B is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing a middle state. Fig. IOC is an image showing an advancing state of an analyte liquid through a flow path of an analytical device formed as a linear depressed portion, showing a final state. It was confirmed that the analyte liquid advanced through the flow path formed as a linear depressed portion with the elapse of time. In Fig. 10A to Fig. IOC, Wetting Tension Test Mixture No. 65.0 (manufactured by Wako Pure Chemical Industries, Ltd.) was used as the analyte liquid.

A labeling substance is not particularly limited, and an arbitrary labeling substance may be selected according to the purpose. Examples thereof include an enzyme, a radioactive isotope, a fluorochrome, a luminescent molecule, a nanoparticle containing a fluorochrome, a metal nanoparticle, a semiconductor nanoparticle, and a colored silica nanoparticle. One of these may be used alone, or two or more of these may be used in combination. Among these, a nanoparticle containing a fluorochrome, a metal nanoparticle, a semiconductor nanoparticle, and a colored silica nanoparticle are preferable.

The nanoparticle containing a fluorochrome is not particularly limited, and an arbitrary one may be selected according to the purpose. Examples thereof include a silica nanoparticle containing a fluorochrome (a fluorescent silica nanoparticle).

The fluorochrome is not particularly limited, and an arbitrary fluorochrome may be selected according to the purpose. Examples thereof include an organic fluorescent molecule (e.g., FLUORESCEIN,

RHODAMINE, TEXAS RED, and ALEXA (all being names of products manufactured by Invitrogen Corporation), and CY (a name of a product manufactured by Applied Biosystems Co., Ltd.)), a semiconductor nanoparticle (e.g., CdSe, InGaP, and ZnSSe).

The labeling substance may be prepared according to a common method. For example, a fluorescent silica nanoparticle may be produced with reference to the method described in JP-A No. 2009-221059.

Examples of the metal nanoparticle include a platinum colloid, a gold colloid, a silver colloid, an iron colloid, and an aluminium hydroxide colloid. In the present invention, the nanoparticle is preferably a particle having a particle diameter of from 10 nm to 500 nm.

The particle diameter may be calculated as an average circle diameter (average circle-equivalent diameter), which is equivalent to a value obtained by calculating, with an image processing apparatus, an occupation area of a particle complex based on a total sum of projected areas of fifty labeling particles as the constituents of the particle complex that are selected randomly from an image observed with a transmission electron microscope (TEM), a scanning electron microscope (SEM), or the like, and dividing the occupation area, which is the total value for the particle complex, by the number of selected particles in the particle complex (which is 50).

The labeling substance may be bound directly with the first biomolecule or may be bound indirectly via another substance. It is possible to bind the labeling substance and the first biomolecule with each other by a method of physically adsorbing them to each other through a hydrophobic interaction, a method of chemically binding them via functional groups such as binding between a succinimide group and an amino group, and binding between a maleimide group and a thiol group, and a conventionally publicly-known method (e.g., The Journal of Histochemistry and Cytochemistry, Vo. 30, No. 7, pp. 691-696).

Usable examples of the first biomolecule include compounds having affinity with a specimen, such as an antibody against a specimen (antigen), an antigen against a specimen (antibody), and an aptamer against a specimen (e.g., a protein, and a low-molecular compound).

Usable examples of the second biomolecule include compounds having affinity with a specimen, such as an antibody against a specimen (antigen), an antigen against a specimen (antibody), and an aptamer against a specimen (e.g., a protein, and a low-molecular compound). The second biomolecule may be different from or the same as the first biomolecule. A substance that has an ability to bind with the first biomolecule against a specimen may be the specimen itself, or a

compound having a moiety that can be recognized by the first biomolecule, an example of which is a compound obtained by binding a derivative of the specimen with a protein (e.g., BSA). In the present invention, it is preferable that the first biomolecule, or the second biomolecule, or both be an antibody.

The antibody is not particularly limited, and an arbitrary

antibody may be selected according to the purpose as long as it can bind with a measurement target substance in an analyte to be fixed in the determination portion. The antibody may be any of immunoglobulins

(Ig)G, IgA, IgM, IgE, and IgD. The antibody may be polyclonal or monoclonal. The antibody may be prepared according to a common procedure, using an animal such as a mouse, a rat, and a goat. A detection region is formed in the labeled substance retaining portion and the determination portion, by fixing a fixing reagent.

The fixing reagent may be directly fixed in the portions by physical or chemical binding. The fixing reagent may be physically or chemically bound to particles such as latex particles, and the particles may be trapped and fixed at partial portions of the chromatograph carrier. It is preferable that after fixed, the fixing reagent be treated with a treatment using an inactive protein, or the like, for prevention of non-specific adsorption, before use. For example, it is possible to form the detection region by applying a solution containing the fixing reagent with a device such as BIOJET QUANTI manufactured by BioDot Japan Co., Ltd., drying the solution, and after this, applying a blocking

treatment according to a common method using BSA, skim milk, casein, or the like.

The analytical device is not particularly limited, and an arbitrary analytical device may be selected according to the purpose. Examples thereof include a biosensor (sensing chip) for blood testing and DNA testing, a compact analytical device for the purposes of quality control of foods and beverages, and various types of microfluidic devices.

The analytical device is used for detecting an antigen in an analyte (analyte liquid). Examples of the analyte include- clinical specimens represented by human and animal body fluids such as blood, plasma, serum, lymph, urine, saliva, pancreatic fluid, gastric fluid, expectorated sputum, and swab collected from a mucous membrane of nose, throat, or the like, and human and animal feces; food specimens represented by a liquid beverage, a semisolid food, and a solid food;

analytes sampled from the nature, such as soil, a river, and marine water; wipe samples from a production line of a plant, and a clean room; and atmospheric samples represented by a specimen sampled by an air sampler. Specific examples include^ allergens of food allergies (e.g., gluten, ovomucoid, ovalbumin, soy protein, and chitin); heavy metals (e.g., cadmium, cesium, mercury, and arsenic); viruses (e.g., norovirus, rotavirus, and influenza virus); mycoplasma; spirochaete.' pathogenic protozoa; bacteria (e.g., Escherichia coli, salmonella, pseudomonad aeruginosa, staphylococcus, hymolytic streptococcus, pneumococcus, and tuberculosis bacterium); agonist; antagonist; hormone; cytokine; nucleic acid; DNA; and RNA, or segments of these, or combinations of these. A liquid analyte may be used as is, and a semisolid or solid analyte may be treated by dilution, extraction, or the like, before used.

Examples

The present invention will be explained below by raising

Examples. However, the present invention is not limited to these

Examples.

<Measurement of Contact Angle>

A contact angle was measured according to a JIS testing method,

"a method for testing wettability of a surface of a substrate glass" R3257:

1999, "6. Sessile drop method", except that a test piece was changed from a glass substrate to various base materials. The measurement

instrument used was a contact angle gauge (DM100 manufactured by Kyowa Interface Science Co., Ltd.).

<Measurement of Average Depth, Average Open End Width, and Average Length of Flow Path formed as Linear Depressed Portion>

An average depth, an average open end width, and an average length of the flow path were calculated by averaging depths, open end widths, and lengths measured at arbitrary ten positions with a digital microscope (VHX-1000 manufactured by Keyence Corporation), determination Method and Determination Criteria for Capillary Action of Analyte Liquid through Flow Path formed as Linear Depressed

Portion>

An analyte liquid was prepared by adding an influenza A virus (5x 10 ² FFU/mL) and 0.1% by mass SDBS (manufactured by

Sigma-Aldrich Japan Co.) in a PBS liquid (manufactured by Wako Pure Chemical Industries, Ltd.). The analyte liquid was kept stationary for several minutes, and evaluated in four points, namely "liquid low speed", "flow path advancement degree", "liquid spreading", and "color

development in the determination portion", based on the determination criteria described below.

The following two points can be achieved when the liquid flow speed is 0.01 mm/sec or higher.

(1) Liquid advancement through the flow path will be achieved, and the result of evaluation of "flow path advancement degree" will be C, B, or A.

(2) Because the analyte liquid will advance more preferentially through the flow path than in the other directions, the result of evaluation of "liquid spreading" will be C, B, or A.

As a result, a color development can be observed in the

determination portion.

-Liquid Flow Speed-

The liquid flow speed was calculated based on the formula below, after obtaining a difference between a time taken for an analyte liquid to advance through the linear depressed portion by 10 mm and a time taken for the analyte liquid to advance through the linear depressed portion by 20 mm, when it was dropped into an end point of the linear depressed portion, and the liquid flow speed was evaluated based on the criteria below.

10 (mm) ÷ (time (sec) taken to advance through linear depressed portion by 20 mm - time (sec) taken to advance through linear depressed portion by 10 mm) = liquid flow speed (mm/sec)

A: 5.0 mm/sec or higher

B: 0.3 mm/sec or higher but lower than 5.0 mm/sec

C: 0.01 mm/sec or higher but lower than 0.3 mm/sec

D- Lower than 0.01 mm/sec

■Flow Path Advancement Degree-

A- The analyte liquid dropped into the sample addition portion reached the absorption portion.

B: The analyte liquid dropped into the sample addition portion took 5 minutes or longer to reach the absorption portion.

C- The analyte liquid reached the absorption portion after a long time, by the analyte liquid being dropped into the sample addition portion over a plurality of times dividedly once in every hour.

D- The analyte liquid dropped into the sample addition portion did not advance through the flow path.

■Liquid Spreading-

Α ^' · The analyte liquid advanced preferentially in the flow path advancement direction, and did not spread outside the flow path while it was flowing through the flow path.

B: The analyte liquid did spread outside the flow path, but the spreading did not inhibit the liquid advancement in the flow path advancement direction. As long as the liquid was added in a sufficient amount, the spreading did not give influence to the liquid advancement.

C: Much of the analyte liquid spread outside the flow path, and most of the analyte liquid was lost.

Ό ^' The analyte liquid spread outside the flow path, and did not remain within the flow path.

-Color Development in Determination Portion-

A ^' By being flowed, the analyte liquid was carried to the determination portion, and color development by a gold colloid due to an antigen-antibody reaction was confirmed.

B: Even though the analyte liquid was flowed, it was not carried to the determination portion, and the determination portion did not develop a color.

(Example l)

An analytical device having the configuration shown in Fig. 2A and Fig. 2B was fabricated according the procedures (l) to (4) below. (l) Production of Paper Base Material and Formation of Flow Path

FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd. (with a basis weight of 256 g/m ² , and an average thickness of 250 μηι) was cut into a card size (54 mm x 85 mm), to thereby obtain a paper base material 100.

A contact angle over the paper base material made of FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd., measured using an analyte liquid prepared by adding sodium dodecyl benzene sulfonate (SDBS, manufactured by Sigma-Aldrich Japan Co.) (1% by mass) to a phosphate buffered saline (PBS, manufactured by Wako Pure Chemical Industries, Ltd.) was 54°.

A depressed portion as a sample addition portion, a depressed portion as a labeled substance retaining portion, a depressed portion as a determination portion, a depressed portion as an absorption portion, and a depressed portion as a flow path were formed in the obtained paper base material with FP-21T manufactured by Mits Co., Ltd. (a milling cutter, with a machining speed of 2 mm/s, and a blade rotation speed of

60,000 rpm). That is, the sample addition portion (with an average diameter of 2 mm, and an average depth of 150 μιη) 101, the labeled substance retaining portion (with an average width of 8 mm, an average length of 800 μηι, and an average depth of 160 μιη) 102, the

determination portion (with an average width of 8 mm, an average length of 800 μιη, and an average depth of 160 μιη) 103, the absorption portion

(with an average diameter of 2 mm, and an average depth of 170 μπι) 104, and the flow path (with an average open end width of 300 μιη, and an average depth of 150 μπι) 105 for connecting these portions, which are shown in Fig. 2A and Fig. 2B, were formed.

The distance between the sample addition portion 101 and the labeled substance retaining portion 102 was about 10 mm. The distance between the labeled substance retaining portion 102 and the

determination portion 103 was about 10 mm. The distance between the determination portion 103 and the absorption portion 104 was about 10 mm.

Fig. 6A is an image of the flow path of the analytical device of Example 1, captured from above (at a magnification of x200). Fig. 6B is a cross-sectional image of the flow path of the analytical device of Example 1 (at a magnification of x200). Fig. 6C is a 3D image of the flow path of the analytical device of Example 1 (at a magnification of x200). The magnified images were captured with a digital microscope

(VHX-1000 manufactured by Keyence Corporation).

(2) Preparation of Labeling Substance

5-(and -6)-CARBOXYRHODAMINE 6G SUCCINIMIDYL ESTER

(a name of a product manufactured by HiLyte Biosciences, Inc.) (3.0 mg) was dissolved in dimethylformamide (DMF) (l mL). γ-aminopropyl triethoxysilane (APS) (1.3 μ was added thereto, and they were reacted at room temperature (23°C) for 1 hour. Ethanol (128 mL),

tetraethoxysilane (TEOS) (600 μθ, distilled water (28.8 mL), and 28% by mass ammonia water (400 μL) were added to the obtained reaction liquid

(400 μL), and they were reacted at room temperature for 24 hours, to thereby polymerize and add TEOS. The obtained reaction liquid was subjected to centrifugal separation at a gravitational acceleration of

18,000xg for 30 minutes, to thereby remove a supernatant. Distilled water (4 mL) was added to the obtained precipitated silica particles to disperse the particles, and they were again subjected to centrifugal separation at a gravitational acceleration of 18,000xg for 30 minutes.

This washing operation was repeated for two more times to remove unreacted TEOS, ammonia, etc. contained in the labeling silica

nanoparticle dispersion liquid, to thereby obtain silica nanoparticles having an average particle diameter of 172 nm in an amount of 149.2 mg.

(3) Production of Labeled Substance Retaining Portion

10 mM KH2PO4 at pH of 6.5 (700 μθ, and the above silica nanoparticle dispersion liquid (200 μL) containing 5-(and

-6)-CARBOXYRHODAMINE 6G (10 mg/mL) were added in a centrifuging tube and stirred lightly. A monoclonal anti-influenza A virus

nucleoprotein antibody produced in mouse (product name ^: INFLUENZA

A NP, manufactured by Santa Cruz Biotechnology, Inc.) (100 μΐ) containing the antibody in an amount of 10 μg/mL was added in the centrifuging tube, and they were mixed at room temperature for 1 hour, to thereby adsorb the monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse to the silica nanoparticles. To which, 1% by mass PEG20000 (polyethylene glycol, with a weight average molecular weight of 20,000, manufactured by Wako Pure Chemical Industries, Ltd.)

(100 μL) was added, and they were stirred lightly. To which, 10% by mass BSA (100 μL) was further added, and they were stirred lightly.

The obtained mixture liquid was subjected to centrifugal separation at 12,000xg for 15 minutes to remove a supernatant. A phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaNs) (l mL) was added to the resulting

precipitate, and they were subjected to centrifugal separation to remove a supernatant. Again, the phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaN ₃ ) (l mL) was added to the obtained precipitate, and they were subjected to centrifugal separation to remove a supernatant.

The phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaN ₃ ) (10.67 mL) was added to the obtained precipitate to disperse the precipitate, to thereby obtain a dispersion liquid of silica nanoparticles (187.5 μg mL) to which the monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse was adsorbed.

The dispersion liquid of silica nanoparticles to which the

monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse was adsorbed was applied uniformly in an amount of (0.8 mL) to the labeled substance retaining portion on the flow path formed in the procedure (l), with a dispenser (XYZ3060 manufactured by BioDot Japan

Co., Ltd.). The applied article was dried at reduced pressure in a desiccator at room temperature for one night, to thereby produce the labeled substance retaining portion 102 containing the silica

nanoparticles to which the monoclonal anti-influenza A virus

nucleoprotein antibody produced in mouse was adsorbed.

(4) Production of Determination Portion A solution [(50 mM KH2PO4 at a pH of 7.0) + 5% by mass sucrose] containing a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse in an amount of 0.5 mg/mL was applied over the determination portion 103 in an application amount of 0.75 μ]1Λ:ιη with a dispenser (XYZ3060 manufactured by BioDot Japan Co., Ltd.), to thereby produce the determination portion as an anti-influenza A virus

antibody-applied determination portion 103.

Next, as a blocking treatment, the determination portion 103 was entirely immersed in a blocking buffer at room temperature for 30 minutes. After the determination portion was kept stationary at room temperature for 30 minutes or longer, it was drawn up, and put on a paper towel and dried at room temperature for one night, to thereby complete the influenza A virus detecting antibody-applied determination portion 103.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza A virus detecting

determination portion 103.

Fig. 7A is an image of the flow path of the analytical device of example 1 before the analyte liquid was flowed, captured from above (at a magnification of x200). Fig. 7B is a 3D image of the flow path of the analytical device of Example 1 before the analyte liquid was flowed (at a magnification of x200). Fig. 8A is an image of the flow path of the analytical device of Example 1 during an early stage of flowing of the analyte liquid, captured from above (at a magnification of x200). Fig. 8B is a 3D image of the flow path of the analytical device of Example 1 during the early stage of the flowing of the analyte liquid (at a

magnification of x200). Fig. 9A is an image of the flow path of the analytical device of Example 1 during a final stage of the flowing of the analyte liquid, captured from above (at a magnification of x200). Fig. 9B is a 3D image of the flow path of the analytical device of Example 1 during the final stage of the flowing of the analyte liquid (at a

magnification of x200).

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, and hence satisfied all performance requirements, as compared with micro-channel systems using

micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Example 2)

An analytical device having the configuration shown in Fig. 2A and Fig. 2B was fabricated according the procedures (l) to (4) below. (l) Production of Paper Base Material and Formation of Flow Path

FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd. (with a basis weight of 256 g/m ² , and an average thickness of 250 μπι) was cut into a card size (54 mm x 85 mm), to thereby obtain a paper base material 100.

A depressed portion as a sample addition portion, a depressed portion as a labeled substance retaining portion, a depressed portion as a determination portion, a depressed portion as an absorption portion, and a depressed portion as a flow path were formed in the obtained paper base material with FP-21T manufactured by Mits Co., Ltd. (a milling cutter, with a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm). That is, the sample addition portion (with an average diameter of 4 mm, and an average depth of 200 μιη) 101, the labeled substance retaining portion (with an average width of 8 mm, an average length of 800 μηι, and an average depth of 220 μπι) 102, the

determination portion (with an average width of 8 mm, an average length of 800 μιη, and an average depth of 220 μπι) 103, the absorption portion (with an average diameter of 4 mm, and an average depth of 225 μιη) 104, and the flow path (with an average open end width of 400 μπι, and an average depth of 200 μιη) 105 for connecting these portions, which are shown in Fig. 2A and Fig. 2B, were formed.

The distance between the sample addition portion 101 and the labeled substance retaining portion 102 was about 5 mm. The distance between the labeled substance retaining portion 102 and the

determination portion 103 was about 7 mm. The distance between the determination portion 103 and the absorption portion 104 was about 7 mm.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(3) Production of Labeled Substance Retaining Portion

The labeled substance retaining portion 102 was produced as a labeled substance retaining portion 102 for detecting an influenza B virus, in the same manner as the manner for producing the agent for the labeled substance retaining portion for detecting an influenza A virus, except that a monoclonal anti-influenza B virus nucleoprotein antibody produced in mouse (product name- ^' INFLUENZA B NA, manufactured by Santa Cruz Biotechnology, Inc.) was used instead of a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse.

(4) Production of Determination Portion

The determination portion 103 was produced in the same manner as the manner for producing the agent for the influenza A virus detecting determination portion, except that a monoclonal anti-influenza B virus nucleoprotein antibody produced in mouse, and an anti-IgG antibody were used.

<Evaluation>

An analyte liquid containing an influenza B virus in an amount of

5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza B virus detecting determination portion 103.

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, and hence satisfied all performance requirements, as compared with micro-channel systems using

micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Example 3)

An analytical device having the configuration shown in Fig. 3B was fabricated according the procedures (l) to (4) below,

(l) Production of Paper Base Material and Formation of Flow Path

FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd. (with a basis weight of 256 g/m ² , and an average thickness of 250 μπι) was cut into a card size (54 mm x 85 mm), to thereby obtain a paper base material 110.

A depressed portion as a sample addition portion, a depressed portion as a labeled substance retaining portion, a depressed portion as a determination portion, a depressed portion as an absorption portion, and a depressed portion as a flow path were formed in the obtained paper base material with FP-21T manufactured by Mits Co., Ltd. (a milling cutter, with a machining speed of 2 mm/s, and a blade rotation speed of

60,000 rpm). That is, the sample addition portion (with an average diameter of 6 mm, and an average depth of 140 μπι) 111, the labeled substance retaining portion (with an average width of 8 mm, an average length of 600 μπι, and an average depth of 140 μηι) 112, the

determination portion (with an average width of 8 mm, an average length of 600 μπι, and an average depth of 140 μιη) 113, the absorption portion

(with an average diameter of 6 mm, and an average depth of 140 μιη) 114, and the flow path (with an average open end width of 100 μπι, and an average depth of 25 μπι) 115 for connecting these portions, which are shown in Fig. 3B, were formed. The distance between the sample addition portion 111 and the labeled substance retaining portion 112 was about 8 mm. The distance between the labeled substance retaining portion 112 and the determination portion 113 was about 8 mm. The distance between the determination portion 113 and the absorption portion 114 was about 8 mm.

Furthermore, from the sample addition portion (with an average diameter of 6 mm, and an average depth of 140 μιη) 111, the labeled substance retaining portion (with an average width of 8 mm, an average length of 600 μιη, and an average depth of 140 μηι) 116, the

determination portion (with an average width of 8 mm, an average length of 600 μιη, and an average depth of 140 μιη) 117, the absorption portion

(with an average diameter of 6 mm, and an average depth of 140 μχα) 118, and the flow path (with an average open end width of 200 μπι, and an average depth of 100 μηι) 119 for connecting these portions were formed.

The distance between the sample addition portion 111 and the labeled substance retaining portion 116 was about 8 mm. The distance between the labeled substance retaining portion 116 and the

determination portion 117 was about 8 mm. The distance between the determination portion 117 and the absorption portion 118 was about 8 mm.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(3) Production of Labeled Substance Retaining Portions

The labeled substance retaining portion 112 was produced by applying the agent for the labeled substance retaining portion for detecting an influenza A virus produced in Example 1, over the labeled substance retaining portion 112 in the same manner as in Example 1. Further, the labeled substance retaining portion 116 was produced by applying the agent for the labeled substance retaining portion for detecting an influenza B virus produced in Example 2, over the labeled substance retaining portion 116 in the same manner as in Example 2. (4) Production of Determination Portions

The determination portion 113 was produced by applying the agent for the determination portion containing the monoclonal

anti-influenza A virus nucleoprotein antibody produced in mouse, which was produced in Example 1, over the determination portion 113 in the same manner as in Example 1. Further, the determination portion 117 was produced by applying the agent for the determination portion containing the monoclonal anti-influenza B virus nucleoprotein antibody produced in mouse, which was produced in Example 2, over the

determination portion 117 in the same manner as in Example 2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 111, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza A virus detecting

determination portion 113, and no color development was confirmed in the influenza B virus detecting determination portion 117.

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, could make a plurality of detections, and hence satisfied all performance requirements, as compared with

micro-channel systems using micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Example 4)

An analytical device having the configuration shown in Fig. 3D was fabricated according to the procedures (l) to (4) below.

(1) Production of Paper Base Material and Formation of Flow Path

A paper base material and a flow path were produced and formed in the same manner as in Example 3.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 3.

(3) Production of Labeled Substance Retaining Portions

The labeled substance retaining portions were produced in the same manner as in Example 3.

(4) Production of Determination Portions

The determination portions were produced in the same manner as in Example 3.

<Evaluation>

An analyte liquid containing an influenza B virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 111, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza B virus detecting

determination portion 117, and no color development was confirmed in the influenza A virus detecting determination portion 113.

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, could make a plurality of detections, and hence satisfied all performance requirements, as compared with

micro-channel systems using micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Example 5)

An analytical device was fabricated in the same manner as in Example 1, except that FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd. (with a basis weight of 256 g/m ² , and an average

thickness of 250 μπι) used in example 1 was changed to a copy/print sheet 180K manufactured by NBS Ricoh Company, Ltd. (with an average thickness of 240 μπι).

A contact angle over the copy/print sheet 180K manufactured by NBS Ricoh Company, Ltd. (with an average thickness of 240 μιη) measured in the same manner as in Example 1 was 20°.

In Example 5, depressed portions having the same average depths, the same average lengths and the same average widths as in Example 1 were formed.

<Evaluation>

An analyte liquid containing an influenza A virus i an amount of

5x 10 ² FFU/mL was dropped in an amount of 10 g into the sample addition portion 101, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza A virus detecting determination portion 103, even though the analyte liquid was

necessitated in a large amount because the contact angle between the paper base material and the analyte liquid was smaller than in Example 1, and hence it was easier for the analyte liquid to permeate the paper base material.

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, and hence satisfied all performance requirements, as compared with micro-channel systems using

micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Example 6)

An analytical device was fabricated in the same manner as in Example 1, except that FP-21T manufactured by Mits Co., Ltd. used in Example 1 was changed to a convex press plate made of a metal to form the flow path by molding with the convex press plate at a press pressure of 5 t, instead of by cutting. In the Example 6, depressed portions having the same average depths and the same average widths as in Example 1 were formed. <Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. As a result, color development was confirmed in the influenza A virus detecting

determination portion 103.

It was confirmed possible to obtain an analytical device that needed not have the flow path sealed with a cover or the like, needed no liquid delivering mechanism, could be constituted with a smaller number of members than the number of members used in an

immunochromatograph device system, needed no container such as a housing because the analyte liquid would not leak, would not produce a false -positive determination, and hence satisfied all performance requirements, as compared with micro-channel systems using

micro-fabrication techniques, such as μΤΑβ.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Comparative Example l)

An analytical device having the configuration shown in Fig. 2C and Fig. 2D was fabricated according to the procedures (l) to (5) below, (l) Production of Paper Base Material

Aluminium sulfate (0.5% by mass) was added to a pulp made of bleached broadleaf tree kraft pulp (LBKP, CSF=400 mL) (100% by mass), and they were stirred while cationized corn starch (with a substitution degree of 0.03, and a cationic charge density of +0.1 meq/g) (0.5% by mass) was added thereto. When 30 seconds passed since the stirring, CMC (product name- F1400MC, manufactured by Nippon Paper

Chemicals Co., Ltd., with a substitution degree of 0.73, a 1% by mass viscosity of 14,100 mPa-s, and an anionic charge density of -3.0 meq/g) (0.01% by mass) was added thereto. Then, 30 seconds later, a yield improver (product name: R-300 manufactured by Somar Corp.) (0.01% by mass) was added thereto, to thereby prepare a paper stock. The prepared paper stock was manually made into paper having a basis weight of 2,000 g/m ² , to thereby produce a paper base material. The papermaking method was compliant with JIS P8222.

A contact angle over the produced paper base material measured in the same manner as in Example 1 was 60°.

(2) Formation of Flow Path

A flow path was formed by settling and fixing an aluminium wire

(with a diameter of 0.6 mm, and a length of 30 mm) over the paper stock so as not to float up or attach to the bottom surface, keeping this state for

2 minutes, drying them, and after this, withdrawing the aluminium wire.

After the flow path was formed, using FP-21T manufactured by Mits Co.,

Ltd. (a drill cutter, with a diameter of 3.0 mm, a machining speed of

2mm/s, and a blade rotation speed of 60,000 rpm) at the entrance and exit of the flow path, a sample addition portion 101 and an absorption portion

104 (both having an average diameter of 2 mm, and an average depth of 1 mm), and a labeled substance retaining portion 102 and a determination portion 103 (both having an average length of 1 mm, and an average depth of 1 mm) were formed.

(3) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(4) Production of Labeled Substance Retaining Portion

The labeled substance retaining portion was produced in the same manner as in Example 1.

(5) Production of Determination Portion

The agent for the determination portion made of a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse, which was produced in Example 1, was applied over the determination portion 103 in the same manner as in Example 1, to thereby produce the determination portion 103.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. However, the analyte liquid flowed in directions other than the flow path advancement direction, and color development could not be confirmed in the

determination portion.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Comparative Example 2) ^

An analytical device having the configuration shown in Fig. 2A and Fig. 2B was fabricated according to the procedures (l) to (4) below, (l) Production of Aluminium Plate Base Material and Formation of Flow Path

An aluminium thin plate base material manufactured by

Originalmind Inc. (with a plate thickness of 0.5 mm, made from A5052) was cut into a card size (54 mm x 85 mm), to thereby obtain a base material 100.

A depressed portion as a sample addition portion, a depressed portion as a labeled substance retaining portion, a depressed portion as a determination portion, a depressed portion as an absorption portion, and a depressed portion as a flow path were formed in the obtained

aluminium base material with FP-21T manufactured by Mits Co., Ltd. (a milling cutter, with a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm). That is, the sample addition (with an average diameter of 2 mm, and an average depth of 150 μιη) 101, the labeled substance retaining portion (with an average width of 8 mm, an average length of 800 μπι, and an average depth of 160 μιη) 102, the

determination portion (with an average width of 8 mm, an average length of 800 μιη, and an average depth of 160 μιη) 103, the adsorption portion

(with an average diameter of 2 mm, and an average depth of 170 μπι) 104, and the flow path (with an average open end width of 300 μπι, and an average depth of 150 μιη) 105 for connecting these portions, which are shown in Fig. 2A and Fig. 2B, were formed. The distance between the sample addition portion 101 and the labeled substance retaining portion

102 was about 10 mm, the distance between the labeled substance retaining portion 102 and the determination portion 103 was about 10 mm, and the distance between the determination portion 103 and the absorption portion 104 was about 10 mm.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(3) Production of Labeled Substance Retaining Portion

The labeled substance retaining portion was produced in the same manner as in Example 1.

(4) Production of Determination Portion

The agent for the determination portion made of a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse, which was produced in Example 1, was applied over the determination portion 103 in the same manner as in Example 1, to thereby produce the determination portion 103.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. However, the analyte liquid did not advance through the flow path, and did not reach the determination portion. Hence, no color development could be confirmed in the determination portion.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1. (Comparative Example 3)

An analytical device having the configuration shown in Fig. 2A and Fig. 2B was fabricated according to the procedures (l) to (4) below.

(1) Production of Aluminium Plate Base Material and Formation of Flow Path

An aluminium thin plate base material manufactured by

Originalmind Inc. (with a plate thickness of 0.5 mm, made from A5052) was cut into a card size (54 mm x 85 mm), to thereby obtain a base material 100.

Three aluminium plates bored as shown in Fig. 17A to Fig. 17C were produced. The three aluminium plates were pasted together, and bonded together by diffusion bonding, to thereby form a flow path. The bonding temperature was 680°C, the bonding pressure was 0.2 kg/mm ² , and the bonding time was 15 minutes. When the aluminium plates (with a melting temperature of about 660°C) were heated to the bonding temperature of 680°C, their surfaces became a melted state and started to diffuse to the other aluminium plates, to thereby integrate and bond the aluminium plates. By the three aluminium plates being bonded by diffusion bonding, a flow path was formed in the aluminium plates as a depressed portion that was not opened.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(3) Production of Labeled Substance Retaining Portion

The labeled substance retaining portion was produced in the same manner as in Example 1.

(4) Production of Determination Portion

The agent for the determination portion made of a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse, which was produced in Example 1, was applied over the determination portion 103 in the same manner as in Example 1, to thereby produce the determination portion 103.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. However, the analyte liquid did not advance through the flow path, and did not reach the determination portion. Hence, no color development could be confirmed in the determination portion.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

(Comparative Example 4)

An analytical device having the configuration shown in Fig. 2A and Fig. 2B was fabricated according to the procedures (l) to (4) below, (l) Production of Glass Plate Base Material and Formation of Flow Path

A float plate glass manufactured by Nippon Sheet Glass Company,

Ltd. (with a plate thickness of 2.0 mm) was cut into a card size (54 mm x

85 mm), to thereby obtain a base material 100.

A depressed portion as a sample addition portion, a depressed portion as a labeled substance retaining portion, a depressed portion as a determination portion, a depressed portion as an absorption portion, and a depressed portion as a flow path were formed in the obtained glass base material, with FP-21T manufactured by Mits Co., Ltd. (a milling cutter, with a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm). That is, the sample addition portion (with an average diameter of 2 mm, and an average depth of 300 μπι) 101, the labeled substance retaining portion (with an average width of 8 mm, an average length of 800 μπι, and an average depth of 300 μπι) 102, the determination portion (with an average width of 8 mm, an average length of 800 μιη, and an average depth of 300 μιη) 103, the adsorption portion (with an average diameter of 2 mm, and an average depth of 300 μιη) 104, and the flow path (with an average open end width of 400 μπι, and an average depth of 200 μπι) 105 for connecting these portions, which are shown in Fig. 2A and Fig. 2B, were formed. The distance between the sample addition portion 101 and the labeled substance retaining portion 102 was about 10 mm, the distance between the labeled substance retaining portion 102 and the determination portion 103 was about 10 mm, and the distance between the determination portion 103 and the absorption portion 104 was about 10 mm.

(2) Preparation of Labeling Substance

A labeling substance was prepared in the same manner as in Example 1.

(3) Production of Labeled Substance Retaining Portion

The labeled substance retaining portion was produced in the same manner as in Example 1.

(4) Production of Determination Portion

The agent for the determination portion made of a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse, which was produced in example 1, was applied over the determination portion 103 in the same manner as in Example 1, to thereby produce the determination portion 103.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 101, and kept stationary for 10 minutes. However, the analyte liquid did not advance through the flow path, and did not reach the determination portion. Hence, no color development could be confirmed in the determination portion.

Next, "flow path advancement degree", "liquid flow speed", "liquid spreading", and "color development in the determination portion" were evaluated. The results are shown in Table 1.

Table 1

Next, flow path shape and advancement degree of an analyte liquid will be explained using Examples.

(Example 7)

An analytical device having the configuration shown in Fig. 14 was fabricated according to the procedures (l) to (5) below. Fig. 14 was a top plan view showing an example of an analytical device of the present invention. The reference sign 1 denotes a base material, the reference sign 2 denotes a sample addition portion, the reference sign 3 denotes a labeled substance retaining portion, the reference sign 4 denotes a determination portion, the reference sign 5 denotes an absorption portion, and the reference sign 6 denotes a flow path,

(l) Formation of Flow Path in Base Material

-Papermaking Method- Aluminium sulfate (0.5% by mass) was added to a pulp made of bleached broadleaf tree kraft pulp (LBKP, CSF=400 mL) (100% by mass), and they were stirred while cationized corn starch (with a substitution degree of 0.03, and a cationic charge density of +0.1 meq/g) (0.5% by mass) was added thereto. When 30 seconds passed since the stirring, CMC (product name ^' - F1400MC, manufactured by Nippon Paper

Chemicals Co., Ltd., with a substitution degree of 0.73, a 1% by mass viscosity of 14,100 mPa-s, and an anionic charge density of -3.0 meq/g) (0.01% by mass) was added thereto. Then, 30 seconds later, a yield improver (product name: R-300 manufactured by Somar Corp.) (0.01% by mass) was added thereto, to thereby prepare a paper stock. The prepared paper stock was manually made into paper having a basis weight of 300 g/m ² , to thereby produce paper. The papermaking method was compliant with JIS P8222.

A contact angle over the produced paper base material measured in the same manner as in Example 1 was 60°. -Formation of Flow Path'

To form a flow path, an aluminium mold having a length of 30 mm, and having a right-triangular convex shape having a width 400 μπι and a height of 200 μιη shown in Table 2-1 below was produced. As the pressurizing conditions, an effective pressure was set to 410 kPa ± 10 kPa, and the paper base material was kept in a pressurized state for 2 minutes, and dried. After this, the mold was withdrawn, to thereby form a flow path. After the flow path was formed, the sample addition portion 2 and the absorption portion 5 (both having an average diameter of 2 mm, and an average depth of 300 μιη) were formed at the entrance and exit of the flow path, using FP-21T manufactured by Mits Co., Ltd. (a drill cutter, with a diameter of 3.0 mm, a machining speed of 2mm/s, and a blade rotation speed of 60,000 rpm). A top plan view of the formed flow path is shown in Fig. 14. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-1. (2) Preparation of Labeling Substance

5-(and - 6) - CARBOXYRHOD AMINE 6G SUCCINIMIDYL ESTER

(a name of a product manufactured by HiLyte Biosciences, Inc.) (3.0 mg) was dissolved in dimethylformamide (DMF) (l mL). APS (yaminopropyl triethoxysilane) (1.3 μL) was added thereto, and they were reacted at room temperature (23°C) for 1 hour. Ethanol (128 mL), TEOS

(tetraethoxysilane) (600 μΕ), distilled water (28.8 mL), and 28% by mass ammonia water (400 μL) were added to the obtained reaction liquid (400 L), and they were reacted at room temperature for 24 hours, to thereby polymerize and add TEOS. The obtained reaction liquid was subjected to centrifugal separation at a gravitational acceleration of 18,000xg for 30 minutes, to thereby remove a supernatant. Distilled water (4 mL) was added to the obtained precipitated silica particles to disperse the particles, and they were again subjected to centrifugal separation at a gravitational acceleration of 18,000xg for 30 minutes. This washing operation was repeated for two more times to remove unreacted TEOS, ammonia, etc. contained in the labeling silica nanoparticle dispersion liquid, to thereby obtain silica nanoparticles having an average particle diameter of 172 nm in an amount of 149.2 mg.

(3) Production of Labeled Substance Retaining Portion

10 mM KH2PO4 at pH of 6.5 (700 μΙ_), and the above silica nanoparticle dispersion liquid (200 μϋι) containing 5-(and

- 6) - CARBOXYRHOD AMINE 6G (10 mg/mL) were added in a centrifuging tube and stirred lightly. A monoclonal anti-influenza A virus

nucleoprotein antibody produced in mouse (product name: INFLUENZA

A NP, manufactured by Santa Cruz Biotechnology, Inc.) (100 μΐ)

containing the antibody in an amount of 10 μg/mL was added in the centrifuging tube, and they were mixed at room temperature for 1 hour, to thereby adsorb the monoclonal anti- influenza A virus nucleoprotein antibody produced in mouse to the silica nanoparticles. To which, 1% by mass PEG 20000 (polyethylene glycol, with a weight average molecular weight of 20,000, manufactured by Wako Pure Chemical Industries, Ltd.)

(100 μL) was added, and they were stirred lightly. To which, 10% by mass BSA (100 μL) was further added, and they were stirred lightly.

The obtained mixture liquid was subjected to centrifugal separation at 12,000xg for 15 minutes to remove a supernatant. A phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaN ₃ ) (l mL) was added to the resulting

precipitate, and they were subjected to centrifugal separation to remove a supernatant. Again, the phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaN ₃ ) (l mL) was added to the obtained precipitate, and they were subjected to centrifugal separation to remove a supernatant.

The phosphate buffer (10 mM KH2PO4 (at pH of 7.2), 0.05% by mass PEG 20000, 1% by mass BSA, and 0.1% by mass NaN ₃ ) (10.67 mL) was added to the obtained precipitate to disperse the precipitate, to thereby obtain a dispersion liquid of silica nanoparticles (187.5 μg mL) to which the monoclonal anti- influenza A virus nucleoprotein antibody produced in mouse was adsorbed.

The dispersion liquid of silica nanoparticles to which the

monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse was adsorbed was applied uniformly in an amount of (0.8 mL) to the labeled substance retaining portion on the flow path formed in the procedure (l), with a dispenser XYZ3060 manufactured by BioDot Japan Co., Ltd.. The applied article was dried at reduced pressure in a desiccator at room temperature for one night, to thereby produce the labeled substance retaining portion 3 containing the silica nanoparticles to which the monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse was adsorbed.

(4) Production of Determination Portion A solution [(50 mM KH2PO4 at a pH of 7.0) + 5% by mass sucrose] containing a monoclonal anti- influenza A virus nucleoprotein antibody produced in mouse in an amount of 0.5 mg/mL was applied over the determination portion on the flow path formed in the procedure (l) described above in an application amount of 0.75 μΐνοπι with a dispenser XYZ3060 manufactured by BioDot Japan Co., Ltd., to thereby produce an anti-influenza A virus antibody-applied determination portion 4.

(5) Analyte Liquid Dropping Method and Evaluation Method

An analyte liquid was prepared by adding an influenza A virus (5xl0 ² FFU/mL) and 0.1% by mass SDBS (manufactured by

Sigma-Aldrich Japan Co.) in a PBS liquid (manufactured by Wako Pure Chemical Industries, Ltd.), kept stationary for several minutes, and evaluated in the manner described below.

<Evaluation>

The analyte liquid containing an influenza A virus in the amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 2 minutes. As a result, it was confirmed that the analyte liquid advanced through the flow path and reached the adsorption portion, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 8)

An analytical device was fabricated in the same manner as in

Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having a rectangular shape having a width of 400 μιη and a height of 200 μπι shown in Table 2 1 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-1.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 10 minutes. By being kept stationary for long, the analyte liquid advanced through the flow path and reached the adsorption portion, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 9)

An analytical device was fabricated in the same manner as in Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having an octagonal shape obtained by combining a rectangular shape having a width of 746 μιη and a height of 100 μιη with a rectangular shape having a width of 400 μπι and a height of 100 μκι shown in Table 2 ^_ 1 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-1.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of

5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 30 minutes. By being kept stationary for long, the analyte liquid advanced through the flow path and reached the adsorption portion, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 10)

An analytical device was fabricated in the same manner as in Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having a semicircular shape having a diameter of 400 μπι shown in Table 2-1 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-1.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 5 minutes. As a result, it was confirmed that the analyte liquid advanced through the flow path and reached the adsorption portion, and color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 11)

An analytical device was fabricated in the same manner as in

Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having a trapezoidal shape having an upper base of 400 μπι, a lower base of 800 μηι, and a height of 200 μιη shown in Table 2-2 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2 , and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 12)

An analytical device was fabricated in the same manner as in Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having a hexagonal shape obtained by combining two trapezoidal shapes each having an upper base of 400 μιη, a lower base of 746 μπι, and a height of 100 μπι shown in Table 2-2 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of

5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2, and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 3. (Example 13)

An analytical device was fabricated in the same manner as in Example 7, except that the aluminium mold of Example 7 was changed to an aluminium mold having a partially circular shape having a diameter of 400 μιη (a center angle of 240°) shown in Table 2-2 below. The average open end width, the maximum flow path width, and the bottom width of the flow path are shown in Table 2-2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2, and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and

"liquid spreading" were evaluated. The results are shown in Table 3. Table 2-1

* In Table 2-1, A represents open end width, B represents maximum flow path width, and C represents bottom width.

Table 2-2

* In Table 2-2, A represents open end width, B represents maximum flow path width, and C represents bottom width.

Table 3

Next, bottom angle and liquid advancement degree through flow path will be explained using Examples.

(Example 14)

An analytical device having the configuration shown in Fig. 14 was fabricated according to the procedures described below,

(l) Formation of Flow Path in Base Material

FC WHITE 220 manufactured by Hokuetsu Kishu Paper Co., Ltd. (with a basis weight of 256 g/m ² , and an average thickness of 250 μαι) was cut into a card size (54 mm x 85 mm), to thereby obtain a paper base material 1.

A sample addition portion (with an average diameter of 2 mm, and an average depth of 180 μιη) 2, a labeled substance retaining portion (with an average depth of 8 mm, an average length of 800 μπι, and an average depth of 180 μη ) 3, a determination portion (with an average width of 8 mm, an average length of 800 μπι, and an average depth of 180 μπι) 4, an absorption portion (with an average diameter of 2 mm, and an average depth of 180 μηι) 5, and a flow path 6 for connecting these portions, which are shown in Fig. 14, were formed in the obtained paper base material with FP-21T manufactured by Mits Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm). The average depth, the average open end width, the bottom width, and the bottom angle of the flow path are shown in Table 4-1.

The distance between the sample addition portion 2 and the labeled substance retaining portion 3 was about 10 mm, the distance between the labeled substance retaining portion 3 and the determination portion 4 was about 10 mm, and the distance between the determination portion 4 and the absorption portion 5 was about 10 mm.

(2) Preparation of Labeling Substance, and Production of Labeled

Substance Retaining Portion

The method for preparing a labeling substance was the same as in Example 1, and silica nanoparticles to which monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse was adsorbed were added to the labeled substance retaining portion formed in the procedure (l) above.

(3) Production of Determination Portion A solution [(50 mM KH ₂ P0 ₄ at a pH of 7.0) + 5% by mass sucrose] containing a monoclonal anti-influenza A virus nucleoprotein antibody produced in mouse in an amount of 0.5 mg/mL was applied over the determination portion in an application amount of 0.75 μΐνΰπι with a dispenser XYZ3060 manufactured by BioDot Japan Co., Ltd., to thereby produce an anti-influenza A virus antibody- applied determination portion 4.

(4) Analyte Liquid Dropping Method and Evaluation Method

An analyte liquid was prepared by adding an influenza A virus (5xl0 ² FFU/mL) and SDBS (manufactured by Sigma-Aldrich Japan Co.) (0.1%) in a PBS liquid (manufactured by Wako Pure Chemical Industries, Ltd.), kept stationary for several minutes, and evaluated.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 2 minutes. As a result, the analyte liquid advanced through the flow path and reached the absorption portion, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and

"liquid spreading" were evaluated. The results are shown in Table 5. (Example 15)

An analytical device was fabricated in the same manner as in

Example 14, except that the taper angle of the milling cutter used for forming the flow path in Example 14 was changed to 60°. The average depth, the average open end width, and the bottom width of the flow path are shown in Table 4-1.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 2 minutes. As a result, the analyte liquid advanced through the flow path and reached the absorption portion, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 5. (Example 16)

An analytical device was fabricated in the same manner as in Example 14, except that the taper angle of the milling cutter used for forming the flow path in Example 14 was changed to 30°. The average depth, the average open end width, the bottom width, and the bottom angle of the flow path are shown in Table 4-1.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of

5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 2 minutes. As a result, the analyte liquid advanced through the flow path and reached the absorption portion, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 5. (Example 17)

An analytical device was fabricated in the same manner as in Example 14, except that the taper angle of the milling cutter used for forming the flow path in Example 14 was changed to 120°. The average depth, the average open end width, the bottom width, and the bottom angle of the flow path are shown in Table 4-2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 10 minutes. As a result, it was confirmed that the analyte liquid reached the absorption portion although it took more time to advance through the flow path than in Examples 14 to 16, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 5. (Example 18)

An analytical device was fabricated in the same manner as in Example 14, except that the blade used for forming the flow path was changed from that used in Example 14 to a high frequency milling cutter (with a milling cutter diameter of 0 10 mm, and a milling cutter taper angle of 0°). The average depth, the average open end width, the bottom width, and the bottom angle of the flow path are shown in Table 4" 2. <Evaluation> An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 10 minutes. As a result, it was confirmed that the analyte liquid reached the absorption portion although it took more time to advance through the flow path than in Examples 14 to 16, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 5. (Example 19)

An analytical device was fabricated in the same manner as in Example 14, except that the taper angle of the milling cutter used for forming the flow path in Example 14 was changed to 150°. The average depth, the average open end width, the bottom width, and the bottom angle of the flow path are shown in Table 4-2.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2, and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 5. Table 4-1

Table 4-2

Table 5 Next, a relationship between bottom width and liquid flow speed will be explained in detailed using Examples.

(Example 20)

An analytical device was fabricated in the same manner as in Example 14, except that as shown in Fig. 15, a second flow path 102 was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μπι from the first flow path 101 formed in Example 14.

The formed flow path had an average open end width of 400 μιη, and a bottom width of 100 μπι as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 5 minutes. As a result, the analyte liquid advanced through the flow path and reached the absorption portion, and color development was confirmed in the influenza A virus detecting determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. (Example 21)

An analytical device was fabricated in the same manner as in

Example 14, except that a second flow path was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μπι from the first flow path formed in

Example 14, and a third flow path was formed by cutting at a position reached by shifting the blade by another 100 μιη.

The formed flow path had an average open end width of 480 μπι, and a bottom width of 200 μπι as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5x 10 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 10 minutes. As a result, the analyte liquid reached the absorption portion although it took more time to advance through the flow path than in Examples 14 and 20, and color development was confirmed in the influenza A virus detecting

determination portion 4.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. (Example 22)

An analytical device was fabricated in the same manner as in

Example 14, except that a second flow path was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits

Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μπι from the first flow path formed in

Example 14, a third flow path was formed by cutting at a position reached by shifting the blade by another 100 μηι, and a fourth flow path was formed by cutting at a position reached by shifting the blade by yet another 100 μπι.

The formed flow path had an average open end width of 550 μιη, and a bottom width of 300 μηι as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 30 minutes. As a result, the analyte liquid took more time to advance through the flow path than in Examples 14, 20 and 21, and reached the absorption portion after a long duration of stationary keeping. Color development was confirmed in the influenza A virus detecting determination portion 4, but only slightly.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. (Example 23)

An analytical device was fabricated in the same manner as in

Example 14, except that a second flow path was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits

Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μηι from the first flow path formed in

Example 14, a third flow path was formed by cutting at a position reached by shifting the blade by another 100 μια, a fourth flow path was formed by cutting at a position reached by shifting the blade by yet another 100 μ ^η ι, and a fifth flow path was formed by cutting at a position reached by shifting the blade by still another 100 μηι.

The formed flow path had an average open end width of 650 μιη, and a bottom width of 400 μιη as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped in an amount of 1 g into the sample addition portion 2, and kept stationary for 30 minutes. As a result, the analyte liquid took more time to advance through the flow path than in Examples 14, and 20 to 22, and reached the absorption portion after a long duration of stationary keeping. Color development was confirmed in the influenza A virus detecting determination portion 4, but only slightly.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. (Example 24)

An analytical device was fabricated in the same manner as in

Example 14, except that a second flow path was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits

Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μιη from the first flow path formed in

Example 14, a third flow path was formed by cutting at a position reached by shifting the blade by another 100 μιη, a fourth flow path was formed by cutting at a position reached by shifting the blade by yet another 100 μπι, a fifth flow path was formed by cutting at a position reached by shifting the blade by still another 100 μηι, and a sixth flow path was formed by cutting at a position reached by shifting the blade by yet further 100 μπι.

The formed flow path had an average open end width of 750 μιη, and a bottom width of 500 μιη as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2, and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. (Example 25)

An analytical device was fabricated in the same manner as in

Example 14, except that a second flow path was formed by cutting at a position reached by shifting a blade 100 of FP-21T manufactured by Mits

Co., Ltd. (with a milling cutter diameter of 0.75 mm, a milling cutter taper angle of 90°, a machining speed of 2 mm/s, and a blade rotation speed of 60,000 rpm) by 100 μιη from the first flow path formed in

Example 14, a third flow path was formed by cutting at a position reached by shifting the blade by another 100 μιη, a fourth flow path was formed by cutting at a position reached by shifting the blade by yet another 100 μπι, a fifth flow path was formed by cutting at a position reached by shifting the blade by still another 100 μηι, a sixth flow path was formed by cutting at a position reached by shifting the blade by yet further 100 μπι, a seventh flow path was formed by cutting at a position reached by shifting the blade by another 100 μπι, and an eighth flow path was formed by cutting at a position reached by shifting the blade by yet another 100 μπι.

The formed flow path had an average open end width of 1,000 μπι, and a bottom width of 700 μιη as shown in Table 6 below.

<Evaluation>

An analyte liquid containing an influenza A virus in an amount of 5xl0 ² FFU/mL was dropped over 5 times once in every hour in an amount of 1 g into the sample addition portion 2, and kept stationary for a total of 6 hours. As a result, it was confirmed that the analyte liquid advanced through the flow path, and slight color development was confirmed in the influenza A virus detecting determination portion.

Next, "liquid flow speed", "flow path advancement degree", and "liquid spreading" were evaluated. The results are shown in Table 7. Table 6

Table 7

Next, based on the experimental results obtained in Example 14, and Examples 20 to 25, a graph was plotted as in Fig. 16 by representing bottom width (μιη) on the horizontal axis and liquid flow speed (mm/sec) on the vertical axis. From the results shown in Fig. 16, it was revealed that it was possible to suppress the flow speed by broadening the bottom width, and it was possible to adjust the flow speed by changing the bottom width.

Aspects of the present invention are as follows, for example. <1> An analytical device, including- a base material; and

a linear depressed portion formed in a surface of the base material and having a predetermined length,

wherein when an analyte liquid is dropped into the linear depressed portion, the analyte liquid advances through the linear depressed portion at a liquid flow speed of 0.01 mm/sec or higher.

<2> The analytical device according to <1>,

wherein the liquid flow speed is 0.3 mm/sec or higher.

<3> The analytical device according to <1> or <2>,

wherein the base material is a stack of fiber or textile layers, and includes numerous voids between fibers.

<4> The analytical device according to <3>,

wherein the base material is a paper base material.

<5> The analytical device according to any one of <1> to <4>,

wherein the analytical device includes in the base material a sample addition portion into which a sample is added;

a flow path through which the analyte liquid is delivered) ^' a labeled substance retaining portion configured to carry a labeled substance reactive with a detection target substance contained in the analyte liquid! and

a determination portion in which a fixing substance reactive with the detection target substance is fixed, and

wherein each of the sample addition portion, the flow path, the labeled substance retaining portion, and the determination portion is the linear depressed portion, and the linear depressed portions are opened.

<6> The analytical device according to any one of <1> to <5>,

wherein an open end width, which is a width of an open end of the linear depressed portion, is a maximum width in the linear depressed portion.

<7> The analytical device according to <6>,

wherein in a cross-section of the linear depressed portion taken in a direction perpendicular to a liquid delivering direction in the linear depressed portion, a bottom width of the linear depressed portion is from 0 μιη to 400 μηι.

<8> The analytical device according to <7>,

wherein a cross-sectional shape of the linear depressed portion in the cross-section of the linear depressed portion is a triangle.

<9> The analytical device according to <7> or <8>,

wherein a bottom angle of the linear depressed portion in the cross-section of the linear depressed portion is from 0° to 120°.

<10> The analytical device according to any one of <1> to <9>,

wherein an average depth of the linear depressed portion is from 1% to 90% of an average thickness of the base material.

<11> The analytical device according to any one of <1> to <10>,

wherein the analyte liquid or the base material is prepared such that a contact angle measured using the analyte liquid over a surface of the base material is 40° or greater.

<12> The analytical device according to any one of <5> to <11>,

wherein a plurality of flow paths branch out from the sample addition portion and from between the sample addition portion and the labeled substance retaining portion, and the labeled substance retaining portion and the determination portion are formed on each of the flow paths.

<13> The analytical device according to any one of <5> to <12>, further including:

an absorption portion configured to absorb the analyte liquid that has passed through the determination portion,

wherein the absorption portion is a linear depressed portion. <14> The analytical device according to <13>

wherein an average depth of at least one linear depressed portion selected from the group consisting of the sample addition portion, the labeled substance retaining portion, the determination portion, and the absorption portion is greater than an average depth of the linear depressed portion formed as the flow path.

<15> The analytical device according to any one of <1> to <14>,

wherein the linear depressed portion is formed by any of cutting and imprinting.

<16> The analytical device according to any one of <5> to <15>,

wherein the sample addition portion and the labeled substance retaining portion are same as each other.

Reference Signs List

1, 11, 100, 110 base material

2, 101, 111 sample addition portion

3, 102, 112, 116, 122, 126 labeled substance retaining portion

4, 103, 113, 117, 123, 127 determination portion

5, 104, 114, 118, 124, 128 absorption portion 6, 105, 115, 119, 125, 129 flow path

12 cross-section of linear depressed portion

13 length of open end width

14 bottom angle

15 maximum width of linear depressed portion