Immunochromatography testing device

Abstract

This immunochromatography testing device is provided with: a loading unit into which a cartridge, provided with a carrier having a drop application region onto which a specimen is dripped, and a test region of which a color development state changes in accordance with whether the specimen is positive or negative, is detachably loaded; an imaging unit for imaging the test region; and a processor for performing a main determination, which is a determination of whether the specimen is positive or negative, on the basis of a test region image of the test region imaged by the imaging unit. If the development direction of the specimen in the carrier is a row direction, and a direction intersecting the row direction is a column direction, the test region is a line-shaped region extending in the column direction, the test region image is an image in which a plurality of pixels are arranged in two dimensions in a matrix, and the processor performs the main determination using residual pixels obtained by excluding one or more high-concentration pixels having a relatively high concentration within each column in the test region image.

Description

[Technical Field]

[0001] The present disclosure relates to an immunochromatographic testing device. [Background technology]

[0002] Among immunoassay methods, immunochromatography is widely used because it is easy to operate and allows for rapid test determination.

[0003] The immunochromatographic method uses an immunochromatographic carrier equipped with a test area where an antibody that specifically binds to the antigen, the test substance, is immobilized. When a labeled antibody that specifically binds to the antigen is spread on the immunochromatographic carrier together with a sample containing the antigen, the antigen binds to the antibody immobilized in the test area, and the labeled substance is captured via the antigen. The test area develops color due to the labeled substance captured in the test area, and if the color density in the test area is equal to or greater than the reference value, the result is determined to be positive.

[0004] Japanese Patent Application Laid-Open Publication No. 2009-115470 discloses a testing device that optically analyzes the color development state of a test area on an immunochromatographic carrier. The testing device includes a sensor that optically detects the reaction state and a measurement unit that determines whether a result is positive or negative based on the detection results. In Japanese Patent Application Laid-Open Publication No. 2009-115470, the presence or absence of degradation of the immunochromatographic carrier is determined before the determination in order to prevent erroneous determinations due to deterioration of the immunochromatographic carrier. In this case, the amount of change in brightness in a predetermined area on the immunochromatographic carrier is measured while the sample is being developed, and if the change is greater than a predetermined standard value, the immunochromatographic carrier is determined to be degraded. This prevents erroneous determinations due to deterioration of the immunochromatographic carrier. Summary of the Invention [Problem to be solved by the invention]

[0005] In testing devices, in addition to erroneous determinations due to deterioration of the immunochromatographic carrier, color development due to nonspecific adsorption of labeled substances in the test area or near the test area can sometimes result in a positive determination even when the result is actually negative. Such erroneous determinations due to nonspecific adsorption of labeled substances undermine the reliability of immunochromatographic testing. It is desirable for testing devices to provide test results that are more reliable than those of conventional devices.

[0006] The present disclosure has been made in consideration of the above circumstances, and has an object to provide an immunochromatographic testing device that can present test results with higher reliability than conventional devices. [Means for solving the problem]

[0007] The immunochromatographic testing device of the present disclosure comprises: a loading section in which a cartridge having a carrier having a spotting area where a sample is spotted and a test area where a color development state changes depending on whether the sample is positive or negative is detachably loaded; an imaging unit that images the inspection area; a processor for making a primary determination of whether the sample is positive or negative based on the inspection area image of the inspection area captured by the imaging unit; When the direction in which the specimen is developed on the carrier is defined as a row direction and the direction intersecting the row direction is defined as a column direction, the test region is a linear region extending along the column direction, The inspection area image is an image in which a plurality of pixels are arranged two-dimensionally in a matrix form, The processor performs the main determination using the remaining pixels after excluding one or more high density pixels having relatively high density in each column of the inspection area image.

[0008] In the immunochromatographic testing apparatus of the present disclosure, the processor may select, as high-density pixels, a plurality of pixels in each column that are ranked in a predetermined order from the pixel with the highest density.

[0009] In the immunochromatographic testing device of the present disclosure, it is preferable that the number of pixels selected as high-density pixels be the same in each column.

[0010] In the immunochromatographic testing device of the present disclosure, the processor may derive a representative value for each column using the remaining pixels, and make a main judgment using the derived representative value for each column.

[0011] In the immunochromatographic testing device of the present disclosure, it is preferable that the processor derives, as a representative value for each column, the pixel value of one pixel selected from the remaining pixels in each column according to a preset criterion, or the average value of the pixel values ​​of two or more pixels selected from the remaining pixels in each column according to a preset criterion.

[0012] In the immunochromatographic testing device disclosed herein, the imaging unit is an image sensor that captures an image of an observation area including the test area and outputs an observation image including the observation area, and the observation image is an image in which a plurality of pixels are arranged two-dimensionally in a matrix, and the processor creates a row-wise profile based on a representative value of each column in the observation image and extracts an examination area profile corresponding to the test area from the created profile, or alternatively, extracts an examination area image corresponding to the test area from the captured image based on the profile.

[0013] In the immunochromatographic testing device of the present disclosure, the processor may divide the test region image into a plurality of areas extending in the row direction, derive an average or median value of each example within the area, which is an average or median value using at least a portion of the plurality of pixels included in each column, create an area profile in the row direction for each area using the derived average or median value, and perform a condition determination process in the main determination using the area profile derived for each area.

[0014] In the immunochromatographic testing device of the present disclosure, the processor executes, as a condition determination process, at least one of first to third condition determination processes for determining whether or not a value derived based on an area profile satisfies a preset condition, and if at least one condition is not satisfied in the executed condition determination process, the sample is determined to be negative, and if all conditions are satisfied in the executed condition determination process, the sample is determined to be positive, and the first condition determination process uses a differentiated area profile obtained by differentiating the area profile for each area, and derives, for each area, the row position showing the maximum local maximum value in the differentiated area profile, and calculates the standard deviation of the derived multiple row positions. The second condition determination process may be a condition determination process that adds up the differential area profiles for each area, derives the difference between the maximum maximum value in the added differential area profile and the average value of the maximum values ​​other than the maximum maximum value, and determines whether or not the second condition, that is, the difference, is greater than a predetermined second threshold value, is satisfied. The third condition determination process may be a condition determination process that adds up the area profiles for each area, and determines whether or not the value at a predetermined position in the row direction in the added area profile is greater than a third threshold value, is satisfied.

[0015] In the immunochromatographic testing device of the present disclosure, it is preferable that the processor executes all of the first condition determination process, the second condition determination process, and the third condition determination process as the condition determination process.

[0016] In the immunochromatographic testing device of the present disclosure, in the main judgment, the processor judges the sample to be negative if the maximum position, which is the position in the row direction that indicates the maximum concentration in the test area profile, is located in either of the end regions of the test area profile, and if the maximum position is not located in either of the end regions, it derives the center position in the row direction of the test area and the width of the test area that are determined based on the maximum concentration and maximum position, and performs a pre-condition judgment process to judge whether or not the pre-judgment conditions that the maximum concentration is equal to or greater than a fourth threshold value that is set in advance and the center position and width are each within a predetermined range are satisfied, and if the pre-judgment conditions are not satisfied, it judges the sample to be negative, and if the pre-judgment conditions are satisfied, it performs a condition judgment process.

[0017] In the immunochromatographic testing device of the present disclosure, if the processor determines in the main determination that the pre-determination conditions are satisfied in the pre-condition determination process, the processor may be configured to determine whether the maximum concentration is equal to or greater than a predetermined fifth threshold value that is greater than a fourth threshold value before executing the condition determination process, and if the maximum concentration is equal to or greater than the fifth threshold value, to determine that the sample is positive, and if the maximum concentration is less than the fifth threshold value, to execute the condition determination process.

[0018] In the immunochromatographic testing device of the present disclosure, the processor performs an abnormality judgment to determine the presence or absence of an abnormality in the test area image, using as a judgment indicator at least one of the difference between a relatively large pixel value and a relatively small pixel value in at least one column in the test area image, the standard deviation and the coefficient of variation of the pixel values ​​of the pixels contained in at least one column, or the difference between a relatively large representative value and a relatively small representative value among representative values ​​of each row derived based on multiple pixels existing in the same row but different columns in the test area image, and the standard deviation and the coefficient of variation of the representative values ​​of each row, and may determine the processing content related to the main judgment based on the presence or absence of an abnormality.

[0019] In the immunochromatographic testing device of the present disclosure, the processing content may include either a decision as to whether or not to perform a main determination, and a method for presenting the main determination result.

[0020] In the immunochromatographic testing device of the present disclosure, the processor may perform a main judgment and present the judgment result of the main judgment when no abnormality is found, and may not perform a main judgment when an abnormality is found.

[0021] In the immunochromatographic testing device of the present disclosure, when the main determination is not to be performed, the processor preferably presents a message to the effect that the main determination will not be performed.

[0022] In the immunochromatographic testing device of the present disclosure, if an abnormality is detected, the processor may indicate that there may be contamination in the testing area.

[0023] In the immunochromatographic testing device disclosed herein, the processor presents the judgment result of the main judgment if no abnormality is found, and if an abnormality is found and the judgment result of the main judgment is positive, the processor may present the judgment result of the main judgment with a reservation that there is an abnormality in the test area image, or may not present the judgment result of the judgment.

[0024] In the immunochromatographic testing device of the present disclosure, the processor may perform a main determination and, if the determination result is positive, perform an abnormality determination.

[0025] In the immunochromatographic testing device of the present disclosure, if no abnormality is found, the processor presents the judgment result of the main judgment, and if an abnormality is found, the processor presents the judgment result of the main judgment with a reservation that there is an abnormality in the test area image, or it may not present the judgment result. [Effects of the Invention]

[0026] The immunochromatographic testing device of the present disclosure can provide test results that are more reliable than conventional ones. [Brief explanation of the drawings]

[0027] [Figure 1] 1 is a perspective view showing the appearance of an immunochromatographic testing device according to a first embodiment. [Figure 2] FIG. [Figure 3] FIG. [Figure 4] 3 is a diagram showing the positional relationship between a test strip, a multifunctional member, a first reagent container, and a second reagent container within a cartridge. FIG. [Figure 5] FIG. 1 is an explanatory diagram of immunochromatography. [Figure 6] FIG. 2 is a partially cutaway side view of the inspection device with a cartridge loaded therein. [Figure 7] FIG. 10 is a partially cutaway side view of the testing device in a state where a cartridge is loaded and a second reagent supply mechanism is in operation. [Figure 8] FIG. 10 is a diagram showing a first inspection flow. [Figure 9] FIG. 1 is a diagram showing a test flow performed by an immunochromatographic testing device. [Figure 10] FIG. 10 is a diagram showing a first processing procedure of main determination. [Figure 11] FIG. 10 is an explanatory diagram of a process in a first processing procedure of a main determination. [Figure 12] FIG. 10 is a diagram showing a second processing procedure of the main determination. [Figure 13] FIG. 10 is an explanatory diagram of a process in a second processing procedure of the main determination. [Figure 14] FIG. 10 is a partially cutaway side view of an immunochromatographic testing device according to a second embodiment. [Figure 15] 15A and 15B are observed images, and FIG. 15C is a diagram showing the displacement of pixel values ​​in one pixel column extracted from each of the first inspection area L1A in FIG. 15A and the second inspection area L1B in FIG. 15B. [Figure 16] FIG. 10 is an explanatory diagram of data processing for deriving a judgment index. [Figure 17] FIG. 10 is a diagram showing a procedure for determining an abnormality. [Figure 18] FIG. 10 is a diagram showing a test flow performed by the immunochromatographic test device of the second embodiment. [Figure 19] FIG. 10 is a diagram showing a first example of a detailed processing procedure of a main determination accompanied by an abnormality determination. [Figure 20] FIG. 10 is a diagram showing a second example of a detailed processing procedure of a main determination accompanied by an abnormality determination. [Figure 21] FIG. 10 is a diagram illustrating a third example of a detailed processing procedure of a main determination accompanied by an abnormality determination. [Figure 22] FIG. 10 is a diagram illustrating a fourth example of a detailed processing procedure of a main determination accompanied by an abnormality determination. [Figure 23] FIG. 10 is a diagram illustrating a fifth example of detailed processing procedures of a main determination accompanied by an abnormality determination. [Figure 24] FIG. 10 is a diagram showing a process of extracting an inspection area profile, searching for a position showing a maximum density difference, and defining a line position and a line width. [Figure 25] FIG. 10 is a diagram showing details of the step of determining whether a result is positive or negative based on the inspection area profile in the third processing procedure of the main determination. [Figure 26] FIG. 10 is an explanatory diagram of an example in which an observation image is divided into a plurality of areas. [Figure 27] FIG. 10 is a diagram showing an area profile created by dividing an inspection area image into four parts. [Figure 28] FIG. 28 is a diagram showing a differential profile of the area profile shown in FIG. 27. [Figure 29] FIG. 29 is a diagram showing an added differential profile obtained by adding the differential profiles of FIG. 28. [Figure 30] FIG. 28 is a diagram showing an added area profile obtained by adding the area profile shown in FIG. 27. DETAILED DESCRIPTION OF THE INVENTION

[0028] An embodiment of the immunochromatographic testing device of the present disclosure will be described with reference to the drawings.

[0029] (First embodiment) Fig. 1 is a perspective view showing the appearance of an immunochromatographic testing device 110 (hereinafter simply referred to as testing device 110) according to a first embodiment. Fig. 2 is an external view of a cartridge 100 to be attached to testing device 110, and Fig. 3 is an exploded perspective view of cartridge 100. Fig. 4 is a diagram showing the positional relationship of the main components housed inside cartridge 100.

[0030] The cartridge 100 is a single-use type that is used one for each sample to be tested. As shown in Figure 3, the cartridge 100 contains a test strip 1 including an immunochromatographic carrier 2 (hereinafter referred to as carrier 2). The carrier 2 is provided with a test region L1, and the color development state changes depending on whether the sample contains a test substance or not, i.e., whether the sample is positive or negative.

[0031] The specimen is not particularly limited as long as it may contain a substance to be tested. Examples of specimens include biological samples, particularly body fluids such as animal (especially human) blood, serum, plasma, cerebrospinal fluid, tears, sweat, urine, pus, nasal discharge, nasal swabs, pharyngeal swabs, nasal aspirates, or sputum, or liquid samples containing excrement, organs, tissues, mucous membranes, and skin, or swabs containing these, or animals or plants themselves or their dried forms. Examples of specimens include antigens, antibodies, proteins, and low-molecular-weight compounds.

[0032] In this example, a cartridge 100 with a sample applied thereto is loaded into the testing device 110. The testing device 110 then detects the color development state of the testing area L1 of the loaded cartridge 100, determines whether the sample is positive or negative, and presents the test result. In the following, the determination of whether the sample is positive or negative is referred to as the main determination. When testing multiple samples, one cartridge 100 for each sample is loaded into the testing device 110.

[0033] In the following description, cartridge 100 will be described on the assumption that it is loaded into testing device 110, but cartridge 100 in this example has a configuration that allows a user to visually confirm whether a sample is positive or negative without using testing device 110. Such a cartridge 100 is also called an immunochromatographic testing tool or an immunochromatographic testing kit.

[0034] 1, the inspection device 110 includes a housing 111, which includes a loading section 112 into which the cartridge 100 is detachably loaded. As an example, the front of the housing 111 is provided with an opening for inserting the cartridge 100 into the housing 111, and an opening / closing lid 112a for opening and closing this opening. When loading the cartridge 100, the opening / closing lid 112a is opened, and the cartridge 100 is inserted into the housing 111. Once the cartridge 100 is loaded into the loading section 112, the opening / closing lid 112a is closed. The inspection is performed with the opening / closing lid 112a closed.

[0035] A power switch 113 is provided on the front surface of the housing 111, and a monitor 119 is provided on the top surface of the housing 111. Test results, error messages, and the like are displayed on the monitor 119. The monitor 119 is, for example, a touch panel monitor, and various operation screens are displayed on the monitor 119. The user can input operation instructions, such as an instruction to start processing and a selection of an inspection procedure, via the operation screen.

[0036] As shown in FIGS. 2 and 3 , the cartridge 100 includes, for example, a housing 9 composed of a case member 20 and a cover member 10. The housing 9 is formed of, for example, a resin material. The case member 20 has an opening formed at the top, and accommodates the test strip 1 as well as a first reagent holding portion 40 and a second reagent holding portion 45 inside. The cover member 10 is attached to the opening of the case member 20, thereby covering the opening of the case member 20. The housing 9 has an elongated shape overall to match the elongated shape of the test strip 1.

[0037] In this example, a drip port 16, an observation window 18, a first pressed portion 11, and a second pressed portion 12 are provided at the top of the housing 9, which is formed by the cover member 10. As an example, these portions are integrally molded with the cover member 10. The drip port 16 is an opening for dripping a sample into the housing 9. A boss is provided on the edge of the drip port 16, facing upward. The observation window 18 is a window for observing the test region L1 from the outside, and is formed of a transparent member, as an example. In this example, the size of the observation window 18 is such that in addition to the test region L1, a control region L2 and a color-developing region L3, which will be described later, can also be observed.

[0038] The first pressed portion 11 is an operating portion that is operated to supply the first reagent 41 (see FIG. 4) in the first reagent holding portion 40 to the carrier 2. The second pressed portion 12 is an operating portion that is operated to supply the second reagent 46 in the second reagent holding portion 45 to the carrier 2. As will be described later, the first reagent 41 and the second reagent 46 are amplification agents that amplify the color development in the test region L1 when the sample 50 is positive.

[0039] When a pressing force is applied to the first pressure-receiving portion 11 from the outside as an external force, the first pressure-receiving portion 11 is deformed. As an example, the first pressure-receiving portion 11 has a quadrangular pyramid shape, and when a pressing force is applied from above to a region including the apex of the quadrangular pyramid, the apex of the quadrangular pyramid is deformed so that it sinks into the housing 9. When the first pressure-receiving portion 11 is deformed in this manner, a pressing force is applied to the first reagent holding portion 40 inside the housing 9. The first reagent holding portion 40 is deformed by the pressing force applied through the first pressure-receiving portion 11. Due to this deformation, the first reagent 41 held in the first reagent holding portion 40 is supplied to the test strip 1.

[0040] Furthermore, it is preferable that the first pressed portion 11 maintains its deformed state after being deformed by pressing. The reason for this is as follows: As will be described later, the testing device 110 of this example can be loaded with a cartridge 100 in which the first pressed portion 11 has been pressed in advance by the user. If the first pressed portion 11 is pressed by the user before loading into the testing device 110, it is easier to continue supplying the first reagent 41 if the deformation of the first pressed portion 11 is maintained even after the user releases their hand.

[0041] Similarly, when a pressing force is applied to the second pressed portion 12 from the outside as an external force, the second pressed portion 12 is deformed. Like the first pressed portion 11, the second pressed portion 12 in this example also has a quadrangular pyramid shape, and when a pressing force is applied from above to a region including the apex of the quadrangular pyramid, the apex of the quadrangular pyramid is deformed so that it sinks into the housing 9. When the second pressed portion 12 is deformed in this manner, a pressing force is applied to the second reagent holding portion 45 inside the housing 9. The second reagent holding portion 45 is deformed by the pressing force applied through the second pressed portion 12. Due to this deformation, the second reagent 46 held in the second reagent holding portion 45 is supplied to the test strip 1. The second pressed portion 12 in this example is provided with an abutting portion 12b that abuts against the second reagent holding portion 45 (see FIGS. 6 and 7).

[0042] The testing device 110 of this example is capable of selecting from a plurality of testing flows, as will be described later. When selecting a testing flow in which the testing device 110 supplies the second reagent 46 from among the testing flows selectable by the testing device 110, the second pressable portion 12 is pressed by an internal mechanism of the testing device 110. Therefore, it is sufficient that the second pressable portion 12 can be pressed by the internal mechanism. When selecting a testing flow in which the cartridge 100 is loaded into the testing device 110 after the first reagent 41 and the second reagent 46 have been supplied, it is preferable that the cartridge 100 is configured so that the second pressable portion 12 can also be pressed by the user.

[0043] As shown in Figures 3 and 4, a test strip 1 including a carrier 2 is housed in the case member 20 along the longitudinal direction. A first reagent holding section 40 is arranged in the case member 20 at one end side in the longitudinal direction (the upstream side as shown in Figure 4). A first container section 24 having a recessed shape that matches the shape of the first reagent holding section 40 is formed in the case member 20 at the portion where the first reagent holding section 40 is arranged. One end of the test strip 1 is located above the first reagent holding section 40 when housed in the first container section 24.

[0044] The first reagent holding unit 40 holds a first reagent 41. The first reagent holding unit 40 is made of, for example, a resin material and is configured with a container 42 having an opening on one side and a rupturable sheet member 43 covering the opening of the container 42. The container 42 is filled with the first reagent 41, and the opening of the container 42 is sealed with the sheet member 43. The first reagent holding unit 40 is disposed in the first storage unit 24 with the sheet member 43 facing upward. The pressing force applied by the first pressed portion 11 is transmitted to the sheet member 43 of the first reagent holding unit 40 via the end of the test strip 1, causing the sheet member 43 to rupture (see FIGS. 6 and 7). The rupture of the sheet member 43 allows the first reagent 41 to be supplied to the test strip 1. In this example, the first pressed portion 11 is provided with a protrusion 11b that abuts against the sheet member 43 (see FIGS. 6 and 7). The protrusions 11b have, for example, an elongated shape extending longitudinally in the width direction of the test strip 1 and a pointed tip toward the sheet member 43 so as to easily break the sheet member 43.

[0045] The cartridge 100 also includes a multifunctional member 30 that has the function of accommodating a second reagent holding portion 45. The multifunctional member 30 is disposed on the other end side (the downstream side in FIG. 4 ) of the case member 20 and above the test strip 1. The multifunctional member 30 is a member in which a second storage portion 32 and a flow path forming portion 35 are integrally formed. The second storage portion 32 is a portion that accommodates the second reagent holding portion 45. The second storage portion 32 has a box-like shape with an open top. As shown in FIG. 4 , the bottom of the second storage portion 32 is formed with a protrusion 34 for breaking a sheet member 48 (described later) of the second reagent holding portion 45, and an opening 33 for allowing the second reagent 46 flowing out of the second reagent holding portion 45 to flow toward the carrier 2.

[0046] The flow path forming section 35 is provided adjacent to the second storage section 32 toward the upstream side. The flow path forming section 35 is flat and disposed in a position facing the test region L1, etc. in the longitudinal direction of the carrier 2, with a gap between it and the carrier 2. The flow path forming section 35 forms a flow path between itself and the carrier 2, which allows the second reagent 46 flowing out of the second storage section 32 toward the test region L1, etc. In this way, the flow path forming section 35 is disposed between the observation window 18 and the test region L1, etc. of the carrier 2. For this reason, the flow path forming section 35 is formed of a transparent member, so that the test region L1, etc. can be observed through the observation window 18.

[0047] The second reagent holding unit 45 holds a second reagent 46. The second reagent holding unit 45 is made of, for example, a resin material and is composed of a container 47 having an opening on one side, and a breakable sheet member 48 that covers the opening of the container 47. The container 47 is filled with the second reagent 46, and the opening of the container 47 is sealed with the sheet member 48. The second reagent holding unit 45 is placed in the second storage unit 32 with the sheet member 48 facing downward. This causes the sheet member 48 to face the protrusion 34 in the second storage unit 32.

[0048] The pressing force applied from the second pressed portion 12 to the second reagent holding portion 45 acts in a direction pressing the second reagent holding portion 45 downward, thereby pressing the sheet member 48 against the protrusion 34. When the sheet member 48 is pressed against the protrusion 34, the sheet member 48 is broken (see FIGS. 6 and 7). When the sheet member 48 is broken, the second reagent 46 is supplied to the carrier 2 through the flow path formed by the opening 33 at the bottom of the second storage portion 32 and the flow path forming portion 35.

[0049] As shown in FIG. 4, a gap (clearance) D corresponding to the flow path of the second reagent 46 is formed between the back surface 36 of the flow path forming portion 35 of the multifunctional member 30 and the carrier 2 of the test strip 1. The gap D is, for example, in the range of 0.01 mm to 1 mm. The second reagent 46 flows out from the opening 33 at the bottom of the second storage section 32 toward the carrier 2, and the flowed-out second reagent 46 flows through the flow path formed by the gap D and reaches at least above the test region L1. The second reagent 46 that has reached the test region L1 permeates from the flow path into the test region L1.

[0050] An absorbent pad 6, which will be described later, is disposed at the downstream end of the test strip 1. A support section 22 that supports the end of the test strip 1 including the absorbent pad 6 is formed in the case member 20 at a position facing the absorbent pad 6. A second housing section 32 of the multifunctional member 30 is disposed above the absorbent pad 6. The support section 22 also supports the multifunctional member 30 via the absorbent pad 6. The case member 20 also has a support section 21 that supports the center of the test strip 1.

[0051] The test strip 1 includes a carrier 2, a liquid delivery pad 4, and an absorbent pad 6. The carrier 2 is fixed and supported on a back adhesive sheet 7.

[0052] The carrier 2 is a porous, insoluble carrier for developing the sample, and includes a test region L1, a control region L2, and a color-developing region L3. The carrier 2 also includes a label-retaining pad 3. The label-retaining pad 3 forms the spotting region where the sample is applied. When the direction from the spotting region toward the test region L1 is considered the downstream side of the carrier 2, the color-developing region L3 is located downstream of the test region L1. In this example, the test region L1, the control region L2, and the color-developing region L3 are each linear regions extending in a direction perpendicular to the direction in which the sample is developed on the carrier 2.

[0053] Although the test region L1, control region L2, and color-developing region L3 are shown as lines, they are not always visible. As will be described in detail later, before the sample 50 (see FIG. 5), first reagent 41 (see FIG. 4), and second reagent 46 (see FIG. 4) are developed, the colors of the test region L1 and control region L2 are nearly the same as the color of the carrier 2 (e.g., white), and therefore the test region L1 and control region L2 cannot be clearly seen at this stage. The test region L1 appears as a line when the sample 50 is developed, and if the developed sample 50 is positive, the color density increases. This makes the test region L1 visible. The color of the test region L1 is amplified by silver amplification, which will be described later, and the test region L1 turns black.

[0054] When the sample 50 is developed, the color density of the control region L2 increases, and the control region L2 appears as a line. This makes the control region L2 visible. The color of the control region L2 is also amplified by silver, so the control region L2 also turns black.

[0055] On the other hand, only color-developing region L3 appears as a blackish dark green (hereinafter referred to as dark green) line and is visible even before the first reagent 41 is developed. However, once the first reagent 41 is developed, color-developing region L3 changes color from dark green to orange, and appears as an orange line.

[0056] For example, a porous material such as a nitrocellulose membrane can be used as the carrier 2. The back adhesive sheet 7 to which the carrier 2 is fixed is a sheet-like substrate whose surface to which the carrier 2 is attached is an adhesive surface.

[0057] As shown in Figure 5, a labeling substance 53 is immobilized on the label-retaining pad 3. The labeling substance 53 is modified with a first binding substance 52 that specifically binds to an analyte 51 contained in a specimen 50. The label-retaining pad 3 is fixed on the carrier 2 at a position facing the drip opening 16 of the cover member 10. Therefore, the specimen 50 is dripped onto the label-retaining pad 3 from the drip opening 16. Therefore, the label-retaining pad 3 corresponds to a deposition area where the specimen 50 is deposited.

[0058] The label holding pad 3 is fixed at approximately the center position in the longitudinal direction of the carrier 2. For example, gold colloid particles (EM.GC50, manufactured by BBI) with a diameter of 50 nm can be used as the labeling substance 53. The labeling substance 53 is not limited to gold colloids; metal sulfides that can be used in ordinary chromatography, colored particles used in immune agglutination reactions, etc. can also be used, with metal colloids being particularly preferred. Examples of metal colloids include gold colloids, silver colloids, platinum colloids, iron colloids, aluminum hydroxide colloids, and composite colloids of these. Gold colloids are particularly preferred because they are red and silver colloids are yellow at appropriate particle sizes, with gold colloids being the most preferred.

[0059] As shown in FIG. 5 , the test region L1 contains a second binding substance 56 that specifically binds to the analyte 51 and captures the analyte 51. When the second binding substance 56 binds to the analyte 51 in the test region L1, the analyte 51 is captured, and the first binding substance 52 and labeled substance 53 bound to the analyte 51 are also captured. If the specimen 50 contains the analyte 51, the analyte 51 and labeled substance 53 are captured in the test region L1, and the color density of the test region L1 increases to a predetermined standard or higher. The test region L1 is a region for confirming the presence or absence of the analyte 51 based on a labeled signal from the labeled substance 53 captured via the analyte 51. Note that the number of analyte 51 detected with one cartridge 100 is not limited to one, and a plurality of test regions L1 may be provided to simultaneously detect multiple different analytes 51. For example, when the multiple test areas L1 include a first test area L1A and a second test area L1B (see Figure 13), the first test area L1A contains a second binding substance 56 that specifically binds to a first test substance 51, and the second test area L1B contains a second binding substance that specifically binds to a second test substance different from the first test substance 51.

[0060] The control region L2 contains a third binding substance 58 that specifically binds to the first binding substance 52 and captures the labeled substance 53 via the first binding substance 52. When a sample 50 is deposited on the label holding pad 3, the labeled substance 53 modified with the first binding substance 52 and not bound to the analyte 51 also develops within the carrier 2 toward the test region L1 along with the sample 50. The labeled substance 53 not bound to the analyte 51 passes through the test region L1 without being captured in the test region L1. The labeled substance 53 that has passed through the test region L1 is captured in the control region L2 via the first binding substance 52 as a result of the first binding substance 52 binding to the third binding substance 58. The capture of the labeled substance 53 in the control region L2 causes the color density of the control region L2 to increase above a predetermined standard. The control region L2 is a region for confirming the completion of the development of the sample 50 based on a label signal from the labeled substance 53 captured via the first binding substance 52. Therefore, the control region L2 is sometimes called a confirmation region.

[0061] The first binding substance 52 that modifies the labeling substance 53 and specifically binds to the test substance 51 is a substance that specifically binds to the test substance 51, such as, for example, an antibody against the antigen if the test substance 51 is an antigen, an antigen against the antibody if the test substance 51 is an antibody, or an aptamer against the protein, low molecular weight compound, etc. if the test substance 51 is a protein, low molecular weight compound, etc.

[0062] The second binding substance 56 that is immobilized in the test region L1 and that specifically binds to the test substance 51 is, for example, an antibody for the antigen if the test substance 51 is an antigen, an antigen for the antibody if the test substance 51 is an antibody, or an aptamer for the protein, low molecular weight compound, etc. if the test substance 51 is a protein, low molecular weight compound, etc. The first binding substance 52 and the second binding substance 56 may be the same or different.

[0063] The third binding substance 58 that specifically binds to the first binding substance 52 may be the test substance 51 itself, or a compound having a site recognized by the first binding substance 52, such as a compound in which a derivative of the test substance 51 is bound to a protein.

[0064] For example, when the test substance 51 is influenza A virus or a biomarker thereof, an anti-influenza A monoclonal antibody (Anti-Influenza A SPTN-5 7307, manufactured by Medix Biochemica) can be used as the first binding substance 52 and the second binding substance 56, and an anti-mouse IgG antibody (anti-mouse IgG(H+L), rabbit F(ab')2, product number 566-70621, manufactured by Wako Pure Chemical Industries, Ltd.) can be used as the third binding substance 58.

[0065] The color-developing region L3 contains a substance that changes color upon reaction with the first reagent 41. The color-developing region L3 reacts with the first reagent 41 to develop color or change color, indicating that the first reagent 41 has spread to that region. For example, when a mixed aqueous solution of iron nitrate and citric acid (manufactured by Wako Pure Chemical Industries, Ltd., 038-06925) is used as the first reagent 41, a preferred embodiment is one in which the color-developing region L3 is formed by a color-reagent immobilization line in which bromocresol green (manufactured by Wako Pure Chemical Industries, Ltd.) is immobilized in a linear fashion. This embodiment is the embodiment of the color-developing region L3 in this example. As described above, the color-developing region L3 in this example is dark green before reacting with the first reagent 41 and changes to orange when the first reagent 41 reaches the color-developing region L3. The color-developing region L3 is sometimes called an amplification indicator region because the change in color state indicates the timing at which the first reagent 41 is developed and the second reagent 46 is supplied.

[0066] The liquid delivery pad 4 is disposed in contact with one end of the carrier 2, and delivers the first reagent 41 to the carrier 2 from the upstream side of the spotting area (formed by the label holding pad 3). When the first pressed portion 11 is pressed, one end of the liquid delivery pad 4 is immersed in the first reagent holding portion 40. The liquid delivery pad 4 is formed from a porous material, absorbs the first reagent 41, and delivers the absorbed first reagent 41 to the carrier 2 by capillary action.

[0067] The absorbent pad 6 is disposed in contact with the other end of the carrier 2, and absorbs the specimen 50, the first reagent 41, and the second reagent 46 developed on the carrier 2. The absorbent pad 6 is also formed of a porous material.

[0068] In this embodiment, the first reagent 41 and the second reagent 46 are amplification agents that react with each other to amplify the color development in the test region L1 and the control region L2. When a metal-based labeled substance such as gold colloid is used as the labeled substance 53, as in this example, silver amplification is used, for example, as a method for amplifying the labeled signal of the labeled substance 53. The first reagent 41 and the second reagent 46 are amplification agents used in silver amplification, for example, and the reaction of the first reagent 41 and the second reagent 46 with the labeled substance 53 as a catalyst is an amplification reaction. The amplification reaction produces silver particles 60 (see FIG. 5) that are relatively larger in particle size than the labeled substance 53.

[0069] More specifically, in this example, the first reagent 41 is a reducing agent that reduces silver ions, and the second reagent 46 is silver ions. When the first reagent 41, which is a reducing agent, and the second reagent 46, which is silver ions, are brought into contact with the labeled substance 53, silver particles 60 (see FIG. 5) are generated, and the generated silver particles 60 deposit on the labeled substance 53, with the labeled substance 53 serving as a nucleus. The deposition of the silver particles on the labeled substance 53 generates silver particles 60 (see FIG. 5) that are larger in particle size than the labeled substance 53. This amplifies the labeled signal emitted by the labeled substance 53, and as a result, the color development of the labeled substance 53 is amplified in the test region L1 and the control region L2.

[0070] (First Reagent) The reducing agent in the first reagent 41 can be any inorganic or organic material or mixture thereof, as long as it can reduce the silver ions used in the second reagent 46 to silver. The inorganic reducing agent can be Fe 2+ , V 2+ Or Ti 3+ Preferred examples of reducing metal salts and reducing metal complex salts are those whose valence can be changed by metal ions such as Fe. When using inorganic reducing agents, it is necessary to form a complex or reduce the oxidized ions, thereby removing or rendering them harmless. For example, Fe 2+ In systems using ethylenediaminetetraacetic acid (EDTA) as a reducing agent, the oxide Fe is reduced using citric acid or EDTA (ethylenediaminetetraacetic acid). 3+In this system, it is preferable to use such an inorganic reducing agent, and more preferably Fe 2+ Metal salts of the formula are preferred.

[0071] Developing agents used in wet silver halide photographic light-sensitive materials (e.g., methyl gallate, hydroquinone, substituted hydroquinone, 3-pyrazolidones, p-aminophenols, p-phenylenediamines, hindered phenols, amidoximes, azines, catechols, pyrogallols, ascorbic acid (or its derivatives), and leuco dyes), as well as other materials obvious to those skilled in the art, such as those described in U.S. Pat. No. 6,020,117, can also be used.

[0072] Ascorbic acid reducing agents are also preferred as reducing agents. Useful ascorbic acid reducing agents include ascorbic acid, analogs, isomers, and derivatives thereof. Examples of preferred ascorbic acid reducing agents include D- or L-ascorbic acid and its sugar derivatives (e.g., γ-lactoascorbic acid, glucoascorbic acid, fucoascorbic acid, glucoheptoascorbic acid, and maltoascorbic acid), sodium ascorbic acid, potassium ascorbic acid, isoascorbic acid (or L-erythroascorbic acid), salts thereof (e.g., alkali metal salts, ammonium salts, or salts known in the art), enediol-type ascorbic acid, enaminol-type ascorbic acid, and thioenol-type ascorbic acid. D, L, or D,L-ascorbic acid (and its alkali metal salts) or isoascorbic acid (or its alkali metal salts) are particularly preferred, with sodium salts being preferred. Mixtures of these reducing agents can be used if necessary.

[0073] (Second reagent) The solution containing silver ions used as the second reagent 46 is preferably one in which a silver ion-containing compound is dissolved in a solvent. The silver ion-containing compound can be an organic silver salt, an inorganic silver salt, or a silver complex. Preferably, it is an inorganic silver salt or a silver complex. As the inorganic silver salt, a silver ion-containing compound that is highly soluble in a solvent such as water can be used, such as silver nitrate, silver acetate, silver lactate, silver butyrate, or silver thiosulfate. Silver nitrate is particularly preferred. As the silver complex, a silver complex coordinated with a ligand having a water-soluble group such as a hydroxyl group or a sulfonic acid group is preferred, such as silver hydroxythioether.

[0074] <Immunochromatography> The immunochromatography method will be described with reference to Fig. 5. Here, the description will be given on the assumption that the specimen 50 contains the test substance 51, that is, the specimen 50 is positive.

[0075] First, a sample 50 is spotted onto the label holding pad 3, which is the spotting area (step S1). The test substance 51 in the sample 50 spotted on the label holding pad 3 specifically binds to a first binding substance 52 that modifies a label substance 53 contained in the label holding pad 3. The sample 50 is developed downstream from the label holding pad 3 within the carrier 2 due to capillary action in the carrier 2. Some of the sample 50 is also developed upstream. Arrow S indicates the state of the sample 50 as it is being developed.

[0076] Next, the first reagent 41 is supplied (step S2). The first reagent 41 is supplied from the liquid supply pad 4 side. The first reagent 41 is supplied to the carrier 2 via the liquid supply pad 4 and developed downstream.

[0077] Thereafter, the process waits until the first reagent 41 is developed downstream (steps S3-S4). "Wait" in Fig. 5 means waiting. The first reagent 41 is gradually developed downstream, and the specimen 50 and the labeled substance 53 modified with the first binding substance 52 that are being developed from the label holding pad 3 are developed downstream as if pushed by the first reagent 41 (step S3).

[0078] The analyte 51 in the specimen 50 that has developed downstream and reached the test region L1 is captured by the second binding substance 56 in the test region L1. That is, the labeled substance 53 is captured in the test region L1 via the analyte 51 and the first binding substance 52. On the other hand, the labeled substance 53 that has not bound to the analyte 51 passes through the test region L1 without being captured, and is captured by the third binding substance 58 in the control region L2.

[0079] As the development of the first reagent 41 progresses and the first reagent 41 reaches the color-developing region L3 (step S4), the color-developing region L3 reacts with the first reagent 41 and changes color. In this example, the color-developing region L3 is dark green before reacting with the first reagent 41, and changes color to orange upon reacting with the first reagent 41.

[0080] After the first reagent 41 has been sufficiently developed, the second reagent 46 is supplied to the carrier 2 (step S5). The second reagent 46 is supplied to the carrier 2 from the downstream side of the color-developing region L3 and is developed upstream. Here, the first reagent 41 is a first amplification liquid containing a reducing agent that reduces silver ions, and the second reagent 46 is a second amplification liquid containing silver ions. The first amplification liquid and the second amplification liquid react with each other to produce silver particles 60 using gold colloid particles, which are the labeling substance 53, as a catalyst. This amplifies the labeling signal (step S6).

[0081] 6 and 7 are partially cutaway side views of the inspection device 110 in a state where the cartridge 100 is loaded. The configuration and function of the inspection device 110 will be described below with reference to FIGS.

[0082] The testing device 110 of this example can select from the following three testing flows: a first testing flow, a second testing flow, and a third testing flow. In any of the first to third testing flows, the specimen 50 must be applied to the carrier 2 of the cartridge 100 before loading.

[0083] The first testing flow is a flow for testing the cartridge 100 in a state where, before loading, application of the sample 50 and supply of the first reagent 41 have started. In the case of the first testing flow, after loading the cartridge into the testing device 110, of the first reagent 41 and the second reagent 46, only supply of the second reagent 46 to the carrier 2 is performed by the testing device 110.

[0084] The second testing flow is a flow for testing the cartridge 100 to which only the sample 50 has been applied before loading. In the case of the second testing flow, after the cartridge is loaded into the testing device 110, both the first reagent 41 and the second reagent 46 are supplied to the carrier 2 by the testing device 110.

[0085] The third testing flow is a flow for testing the cartridge 100 in a state where, before loading, application of the sample 50, supply of the first reagent 41, and supply of the second reagent 46 have already started. In the case of the third testing flow, after loading the cartridge into the testing device 110, the first reagent 41 and the second reagent 46 are not supplied to the testing device 110.

[0086] In the following, the configuration of the inspection device 110 will be described, and then the first inspection flow will be described.

[0087] (Configuration of inspection device 110) As shown in FIGS. 6 and 7 , the testing device 110 has, as its internal mechanisms, a first reagent supply mechanism 116 and a second reagent supply mechanism 118. The first reagent supply mechanism 116 is a mechanism for starting the supply of the first reagent 41 from the first reagent holding unit 40 to the carrier 2. The first reagent supply mechanism 116 uses an actuator such as a solenoid that includes an electromagnet and a plunger that is movable relative to the electromagnet. For example, as the plunger moves, the plunger comes into contact with the first pressed portion 11 and presses the first pressed portion 11. The first reagent supply mechanism 116 is disposed in a position facing the first pressed portion 11 of the loaded cartridge 100.

[0088] The first reagent supply mechanism 116 is a pressing mechanism that applies a pressing force to the first pressed portion 11 of the cartridge 100 from the outside by pressing the first pressed portion 11. When the first reagent supply mechanism 116 applies a pressing force to the first pressed portion 11, the first reagent 41 is supplied from the first reagent holding portion 40 to the carrier 2 by the above-mentioned action. The first reagent supply mechanism 116 is not used in the first and third testing flows, and is used only in the second testing flow.

[0089] The second reagent supply mechanism 118 is a mechanism for starting the supply of the second reagent 46 from the second reagent holding portion 45 to the carrier 2. Like the first reagent supply mechanism 116, the second reagent supply mechanism 118 also uses an actuator such as a solenoid. The second reagent supply mechanism 118 is disposed at a position facing the second pressure-receiving portion 12 of the loaded cartridge 100. The second reagent supply mechanism 118 is a pressing mechanism that applies a pressing force to the second pressure-receiving portion 12 from the outside by pressing the second pressure-receiving portion 12 of the cartridge 100. When the second reagent supply mechanism 118 applies a pressing force to the second pressure-receiving portion 12, the second reagent 46 is supplied from the second reagent holding portion 45 to the carrier 2 by the above-mentioned action. The second reagent supply mechanism 118 is not used in the third testing flow, and is used only in the first and second testing flows.

[0090] The testing device 110 includes, in addition to a loading unit 112, a first reagent supply mechanism 116, and a second reagent supply mechanism 118, an imaging unit 114, a processor 120, and a memory 121 within a housing 111. In FIG. 6, the processor 120 and the memory 121 are shown outside the housing 111 of the testing device 110, but this is a schematic diagram and they are actually arranged within the housing 111.

[0091] The imaging section 114 captures an image of the observation area including at least the test area L1 and the control area L2, and outputs the observation image of the observation area to the processor 120. It is more preferable that the observation area includes a color-developing area L3.

[0092] The imaging unit 114 is an image sensor such as a CMOS (Complementary Metal Oxide Semiconductor) image sensor or a CCD (Charge Coupled Device) image sensor. The imaging unit 114 is disposed, for example, at a position facing the observation window 18. The imaging unit 114 captures an image of a predetermined range centered on the observation window 18 and including its surroundings. The captured image captured by the imaging unit 114 includes the observation region 68 (see FIG. 11 ) exposed through the observation window 18, such as the test region L1, the control region L2, and the color-developing region L3. The captured image is then output from the imaging unit 114 to the processor 120.

[0093] As an example, light sources 115 such as light emitting diodes are provided on both sides of the imaging unit 114 to illuminate the test area L1, the control area L2, and the color-developing area L3 during imaging.

[0094] The processor 120 comprehensively controls each unit of the inspection device 110. An example of the processor 120 is a CPU (Central Processing Unit) that performs various controls by executing a program. By executing the program, the CPU functions as a control unit having an imaging unit control unit 122, a color development state determination unit 123, a first reagent supply mechanism control unit 124, a second reagent supply mechanism control unit 125, a display control unit 126, and a timer 128. The memory 121 is an example of a memory connected to or built into the CPU as the processor 120. For example, a control program is stored in the memory 121. The processor 120 is realized by the CPU executing the control program.

[0095] The image capturing unit control unit 122 controls the image capturing timing of the image capturing unit 114 .

[0096] The first reagent supply mechanism control section 124 controls the first reagent supply mechanism 116 to operate and press the first pressed section 11.

[0097] The second reagent supply mechanism control section 125 controls the second reagent supply mechanism 118 to operate and press the second pressed section 12 based on the change in the coloring state of the coloring region L3.

[0098] The coloring state determination unit 123 executes a coloring region determination process, a control region determination process, and an inspection region determination process based on the captured image acquired via the imaging unit 114. As described above, the imaging unit 114 outputs a captured image of the observation region 68, which includes the inspection region L1, the control region L2, and the coloring region L3. The coloring state determination unit 123 executes each of the above determination processes based on the captured image.

[0099] The color region determination process is a process for determining, based on the captured image, whether or not the color state of the color region L3 has changed, for example, from the dark green color before the reaction with the first reagent 41 to orange. A "yes" change in the color state means that the first reagent 41 has spread to the color region L3.

[0100] In addition, "change in color state" includes any of the following: a change from a first color different from the color of carrier 2 to a different second color (i.e., discoloration); a change in the color of carrier 2 to a different color due to the development of a color different from carrier 2 (i.e., color development); and a change in the color density (i.e., density change).

[0101] The processor 120 operates the second reagent supply mechanism 118 via the second reagent supply mechanism control unit 125 when the coloring state determination unit 123 determines that the coloring state of the coloring region L3 has changed.

[0102] The control area discrimination process is a process for discriminating whether or not there is a change in the color development state of the control area L2 based on the captured image. In this example, a line appears in the control area L2 when the labeling substance 53 is captured in the control area L2 or when the captured labeling substance 53 is amplified by silver after capture, and the presence or absence of the line development in the control area L2 is discriminated. If the color development state discrimination unit 123 determines that the color development state of the control area L2 has changed, i.e., that there is development in the control area L2, the next process, the test area discrimination process, is executed.

[0103] The test area discrimination process is a process for discriminating whether or not there is a change in the color development state of the test area L1 based on the captured image. In this example, a line appears in the test area L1 when the labeling substance 53 is captured in the test area L1 or when silver is amplified after capture, and therefore, whether or not there is a line appearing in this test area L1 is discriminated as whether or not there is a change in the color development state. When a line appears in the test area L1, it means that the sample 50 is positive, and when no line appears, it means that the sample 50 is negative. The discrimination of whether or not there is a change in the color development state of the test area L1 in this test area discrimination process corresponds to the main determination of whether the sample 50 is positive or negative. The specific steps of the main determination will be described later.

[0104] If the color state determination unit 123 determines that there is a change in the color state of the test area L1, that is, if the sample 50 is determined to be positive, the processor 120 displays the test result "positive" on the monitor 119 via the display control unit 126. On the other hand, if the color state determination unit 123 determines that there is no change in the color state of the test area L1, that is, if the sample 50 is determined to be negative, the processor 120 displays the test result "negative" on the monitor 119 via the display control unit 126.

[0105] The memory 121 stores not only a control program but also setting information that is preset so that the processor 120 can perform various controls. The setting information stores information required by the color state determination unit 123 to determine a change in the color state. Examples of the setting information include a first set time t1, a second set time t2, and a preset number of times K, which will be described later. The first set time t1 is the waiting time until the processor 120 determines again whether or not there has been a change in the color state of the color region L3 if it determines that there has been no change in the color state of the color region L3. The second set time t2 is the allowable time for the processor 120 to repeat the determination of whether or not there has been a change in the color state if it determines that there has been no change in the color state of the color region L3. The setting information also stores a threshold value for determining that the sample 50 is positive when the processor 120 performs the main determination.

[0106] The procedure for immunochromatographic testing using testing device 110 of this embodiment will be described with reference to Figures 8 to 10. Here, a first testing flow will be described in which first reagent 41 is supplied by the user and second reagent 46 is supplied by testing device 110.

[0107] (First inspection flow) FIG. 8 is a diagram showing the first inspection flow. First, the user drips the specimen 50 onto the spotting area of ​​the carrier 2 from the drip port 16 of the cartridge 100 (step S11).

[0108] Next, the user presses the first pressed portion 11 of the cartridge 100 to start supplying the first reagent 41 (step S12).

[0109] Thereafter, the user loads the cartridge 100 into the loading section 112 of the inspection device 110, which is in a powered-on state (step S13).

[0110] In the inspection device 110, an inspection is carried out on the loaded cartridge 100 (step S14).

[0111] The time required for the first reagent 41 to fully develop the carrier 2 after the supply of the first reagent 41 begins varies for each cartridge, but generally takes about 5 to 10 minutes. The time required for the first reagent 41 to be loaded into the loading section 112 after the user presses the first pressed section 11 may be determined according to the user's convenience.

[0112] FIG. 9 shows a detailed inspection flow of the inspection performed by the inspection device 110 shown in FIG. 8 (step S14). When the cartridge 100 is loaded into the inspection device 110, inspection in the inspection device 110 (step S14 in FIG. 8) begins.

[0113] 9, in the testing device 110, the processor 120 first determines whether the color state of the color-producing region L3 has changed (specifically, from dark green to orange) (step S21). Specifically, the processor 120 turns on the light source 115 to illuminate the observation region 68 exposed through the observation window 18, and causes the imaging unit 114 to capture an image in this state. The processor 120 then acquires the captured image from the imaging unit 114 and determines whether the color state of the color-producing region L3 has changed from dark green to orange. If it is determined that the color state of the color-producing region L3 has changed, that is, if the color-producing region L3 has changed from dark green to orange, this means that the first reagent 41 has reached the color-producing region L3 and the test region L1 and control region L2 located upstream of it.

[0114] If the coloring state of the coloring region L3 has changed (step S21: Yes), the processor 120 activates the second reagent supply mechanism 118 to start supplying the second reagent 46 (step S22). In this embodiment, the processor 120 causes the second reagent supply mechanism 118 to press the second pressed portion 12 of the cartridge 100. When the second pressed portion 12 is pressed, the second pressed portion 12 is deformed so as to sink toward the second reagent holding portion 45. Due to this deformation, the sheet member 48 of the second reagent holding portion 45 is pressed against the protrusion 34 and breaks, and the second reagent 46 is supplied onto the carrier 2.

[0115] On the other hand, if the coloring state of the coloring region L3 has not changed (step S21: No), it is determined whether the time is within the second set time t2 (step S23).

[0116] Here, if the second set time t2 has been exceeded (step S23: No), the processor 120 notifies the user of an error (step S26) and ends the inspection flow. For example, the error is notified by displaying an error message on the monitor 119. Note that, as a method of notifying the user of an error, in addition to displaying the error message on the monitor 119, the error message may also be notified by voice.

[0117] On the other hand, if the time is within the second set time t2 (step S23: Yes), the process waits until the first set time t1 has elapsed (step S24). In step S24 of FIG. 9, this is indicated as "t1 wait." The first set time t1 is, for example, about 30 seconds, and the second set time t2 is, for example, preset to 20 minutes. Thereafter, the process returns to step S21, where it is determined whether the coloring state of the coloring region L3 has changed.

[0118] In step S22, the second reagent supply mechanism 118 is operated to start supplying the second reagent 46, and then the system waits until a preset third set time t3 has elapsed (step S27). In step S27 of Fig. 9, this is indicated as "t3 wait." The third set time t3 is, for example, about 3 minutes.

[0119] The processor 120 then determines whether a line has appeared in the control region L2 (step S28). Specifically, the processor 120, similar to step S21, causes the imaging unit 114 to capture an image of the observation region 68 while illuminating the observation region 68. The processor 120 then acquires the captured image from the imaging unit 114 and cuts out an observation image 61 of the observation region 68 from the acquired image. The processor 120 then determines a change in the color development state of the control region L2 in the cut-out observation image 61. For example, the processor 120 determines whether the color development density of the control region L2 has reached a density equal to or greater than a predetermined reference density, and if the density is equal to or greater than the reference density, determines that the control region L2 has appeared. If it is determined that the control region L2 has appeared, this means that the specimen 50 has reached the control region L2 and the test region L1 upstream thereof, and that silver has been amplified.

[0120] In determining whether the control region L2 is expressed in step S28, if the control region L2 is not expressed (step S28: No), an error is reported (step S26), and the test flow ends. Note that if the control region L2 is not expressed after the second reagent 46 is developed, there is a possibility that the specimen 50 has not been deposited.

[0121] On the other hand, if the control region L2 is expressed in step S28 (step S28: Yes), the processor 120 makes a primary determination as to whether the specimen 50 is positive or negative (step S29).

[0122] In the main determination (step S29), the processor 120 determines whether or not the test area L1 is expressed as a line. If it is determined that the test area L1 is expressed, it means that the specimen 50 is positive, and if it is determined that the test area L1 is not expressed, it means that the specimen 50 is negative. In this way, in step S29, the processor 120 determines whether the specimen 50 is positive or negative depending on whether or not the test area L1 is expressed. Details of the main determination will be described later.

[0123] After making the main judgment, processor 120 displays the test result on monitor 119 (step S30) and ends the test flow. Specifically, if processor 120 determines that test region L1 is expressed, it displays the test result as "positive" on monitor 119. On the other hand, if processor 120 determines that test region L1 is not expressed, it displays the test result as "negative" on monitor 119. The test flow within testing device 110 is as described above.

[0124] Next, the details of step S29 of the main judgment in the above inspection flow will be explained. There are multiple possible processing procedures for the main judgment in step S29. Fig. 10 shows a first processing procedure (hereinafter referred to as the first processing procedure of the main judgment), which is an example of the processing procedure of the main judgment in step S29. Fig. 11 shows a conceptual diagram of the processing in the first processing procedure of the main judgment.

[0125] In the first processing procedure of the main determination shown in FIG. 10, the processor 120 first acquires the observation image 61 (see FIG. 11) by cutting out the observation area 68 from the captured image output by the imaging unit 114 (step S41).

[0126] Next, the processor 120 extracts an inspection area L1 from the acquired observation image 61 (step S42). The processor 120 reads, for example, position information of the inspection area L1 in the observation image stored in advance in the memory 121 as setting information, specifies the inspection area L1 in the observation image 61, and extracts the inspection area image 62. The position information of the inspection area L1 is, for example, the distance from one end of the observation image 61.

[0127] The observation image 61 is an image in which a plurality of pixels are arranged two-dimensionally in a matrix, and the inspection area image 62 extracted from the observation image 61 is also an image in which a plurality of pixels are arranged two-dimensionally in a matrix. If the length direction of the carrier 2 is the X direction, which intersects with the X direction, and the length direction of the line of the inspection area L1 is the Y direction, the row direction refers to the X direction and the column direction refers to the Y direction. As shown in FIG. 11 as an example, the inspection area image 62 is composed of pixels arranged in a matrix of 8 rows and 6 columns. The processor 120 converts the signal value of each pixel of the captured image output by the imaging unit 114 into a digital pixel value ranging from 0 to 255. In FIG. 11, each pixel of the inspection area image 62 is indicated by its pixel value. The pixel value of the inspection area image 62 corresponds to, for example, the brightness corresponding to the amount of light incident on each pixel. Therefore, in the inspection area image 62, the higher the brightness, the larger the pixel value, and the lower the brightness, the smaller the pixel value. If the pixels of such an inspection area image 62 are expressed in terms of optical density (hereinafter simply referred to as density), the smaller the pixel value, the higher the density, and the larger the pixel value, the lower the density. Here, pixel values ​​and density values ​​can be converted using a preset conversion formula.

[0128] In the example observation image 61 shown in FIG. 11, the lower region of the test region L1 contains a region d with a locally high density (hereinafter referred to as a high-density region d). If the sample 50 is positive, the color density increases on average across almost the entire test region L1, resulting in the appearance of a line similar to that in the control region L2 of the observation image 61. In contrast, the high-density region d occurring partially within the test region L1 is presumed to be a region where the color density has increased due to nonspecific adsorption of the labeling substance. Such a high-density region d is an unnecessary stain that may induce an erroneous determination in the main judgment. The high-density region d may exhibit an abnormally higher density than the color density when the sample 50 is positive. Such a high-density region d has a small pixel value; for example, in the test region image 62 shown as an example in FIG. 11, it exhibits a pixel value of 130 or less. On the other hand, the other parts of the test region L1 exhibit pixel values ​​of 185 to 208.

[0129] The processor 120 sorts the pixels included in each column in order of pixel value for each column in the inspection area image 62 (step S43). As a result, image data 63 arranged in order of pixel value for each column, as schematically shown in FIG. 11, is created.

[0130] The processor 120 obtains the remaining pixels from the image data 63, excluding pixels with relatively small pixel values ​​in each column, i.e., high-density pixels with relatively high densities. For example, as shown in FIG. 11 , the processor 120 selects the five pixels in each column of the image data 63, from the pixel with the highest density (smallest pixel value) to the fifth highest, as high-density pixels, and then excludes the selected five high-density pixels (step S44). That is, the processor 120 excludes the high-density pixels constituting the high-density area d from the targets for use in subsequent processing, thereby suppressing the influence of the high-density area d in subsequent processing. The processor 120 then derives a representative value for each column using the remaining pixels (step S45) and determines whether the result is positive or negative based on the representative value (step S46). The remaining pixels used to determine whether the result is positive or negative do not include the high-density pixels constituting the high-density area d in the examination area L1, thereby suppressing erroneous determinations due to the high-density area d.

[0131] In step S45, the processor 120 derives the average pixel values ​​of the remaining pixels in each column of the image data 63 as a representative value, as shown in FIG. 11, to create representative value data 65, and compares the derived representative value for each column with a preset reference pixel value (reference concentration, if expressed in terms of density). If the representative value is equal to or less than the reference pixel value (i.e., equal to or greater than the reference concentration), it determines that the linear inspection area L1 is expressed and judges the result as "positive." If the representative value is greater than the reference pixel value (i.e., less than the reference concentration), it determines that the inspection area L1 is not expressed and judges the result as "negative." The presence or absence of expression in the inspection area L1 may be determined by comparing the average of multiple representative values ​​with the reference pixel value, or by comparing the smallest pixel value among the multiple representative values ​​with the reference pixel value.

[0132] As described above, the linear inspection region L1 is not visible in the image 61 of FIG. 11 , but it does include a high-density region d. In such a case, if the main judgment is performed while including all of the pixels that make up the high-density region d, the high-density region d may result in a positive judgment despite the actual result being negative. However, in the inspection device 110, the processor 120 eliminates one or more high-density pixels with relatively high densities in each column. That is, the processor 120 eliminates at least one high-density pixel that makes up the high-density region d. This reduces the influence of the high-density region d on the main judgment, i.e., reduces erroneous judgments due to the high-density region d. Therefore, it is possible to present more reliable inspection results than in the past, when the main judgment was performed without excluding the pixels in the high-density region d.

[0133] In the present disclosure, a pixel with a relatively high density means a pixel with a density higher than that of the remaining pixels. As described above, there is a correlation between the density value of a pixel and the pixel value, and the higher the density value, the lower the pixel value. Therefore, a pixel with a relatively high density corresponds to a pixel with a relatively small pixel value when expressed in terms of pixel value.

[0134] In the above example, when deriving a representative value from the image data 63, the five pixels from the highest density pixel to the fifth pixel in the image data 63 are selected as high-density pixels, and the average value of the three remaining pixels excluding these high-density pixels is derived as the representative value. However, the method for deriving the representative value is not limited to this method. First, the number of high-density pixels excluded from each column is not limited to five pixels and can be set as appropriate to one pixel or more. Furthermore, the number of high-density pixels excluded from each column does not necessarily have to be the same. For example, high-density pixels with a density equal to or higher than a predetermined value may be excluded from each column. In this case, the number of high-density pixels excluded from each column does not necessarily have to be the same. However, as described above, it is preferable that the number of pixels selected as high-density pixels be the same within each column. This simplifies processing and reduces the computational load.

[0135] Alternatively, relatively high-density pixels may be excluded from pixels other than the maximum and minimum pixel values ​​that are likely to be noise, and the representative value may be derived using the remaining pixels. The pixels initially excluded as likely noise are not limited to one each of the maximum and minimum pixel values, but may be multiple pixels of each type. For example, a predetermined number (e.g., two or three) of pixels selected in descending order of pixel value from the maximum pixel value may be initially excluded. Alternatively, a predetermined number (e.g., two or three) of pixels selected in descending order of pixel value from the minimum pixel value may be initially excluded. Furthermore, instead of calculating an average value using all the remaining pixels to derive a representative value, the representative value for each column may be derived from the pixel value of one pixel selected according to a predetermined criterion from the remaining pixels in each column, or the average value of two or more pixels selected according to a predetermined criterion from the remaining pixels in each column. A preset criterion for selecting one pixel from the remaining pixels may be, for example, the pixel showing the median value among the remaining pixels, or the mth pixel among the remaining pixels counting from the largest pixel value. Similarly, a preset criterion for selecting two or more pixels from the remaining pixels may be, for example, a criterion for selecting two pixels, a total of two pixels, including a pixel showing the maximum pixel value and a pixel showing the minimum pixel value among the remaining pixels. Alternatively, a criterion may be a criterion for selecting three pixels, including the median pixel among the remaining pixels and one pixel before and one pixel after it.

[0136] (Modification of the First Embodiment: Second Processing Procedure of Main Determination) The processing procedure for the main judgment is not limited to the first processing procedure described above. A modified example of the first embodiment is a modified processing procedure for the main judgment. FIG. 12 shows a second processing procedure (hereinafter referred to as the second processing procedure for the main judgment), which is another example of step S29. FIG. 13 is an explanatory diagram of the processing in the second processing procedure for the main judgment. The modified example will be described as an example in which the content of the processing procedure for the main judgment is different, and the type of cartridge used is different. The following description will focus on the differences.

[0137] 12, in the second processing procedure of the main judgment, the processor 120 first acquires an observation image 70 (see FIG. 13) by cutting out an observation area from the captured image output by the imaging unit 114 (step S51). This is similar to step S41 (see FIG. 10) in the first processing procedure of the main judgment.

[0138] While Fig. 11 shows the observation image 61 in a schematic diagram, Fig. 13, which shows the modified example, shows the observation image 70 as an actual image rather than a schematic diagram for convenience. The observation image 61 shown in Fig. 11 and the observation image 70 shown in Fig. 13 are common in that they are both images of captured observation areas, but the configurations of the inspection area L1 and other areas are different between the observation area shown in the observation image 61 and the observation area shown in the observation image 70. That is, the observation image 61 shown in Fig. 11 includes three areas: the inspection area L1, the control area L2, and the color-developing area L3, whereas the observation image 70 shown in Fig. 13 includes two areas: a first inspection area L1A and a second inspection area L1B, and a control area L2.

[0139] The cartridge exemplified in the first processing procedure of the main determination above is a cartridge for testing for the presence or absence of one type of test substance, while the cartridge exemplified in the second processing procedure of the main determination is a cartridge for testing for the presence or absence of two types of test substances. For ease of explanation, the types of cartridges exemplified are different in the first processing procedure and the second processing procedure of the main determination, but the types of cartridges are not limited to those in the first processing procedure and the second processing procedure, and either cartridge may be used.

[0140] In a cartridge for testing for the presence or absence of two types of test substances, the two types of test substances are, for example, influenza type A and influenza type B. In FIG. 13, the first test region L1A is a test region containing a capture antibody for influenza type A, and the second test region L1B is a test region containing a capture antibody for influenza type B. These three regions are shown in the observation image 70. The width of the first test region L1A, the second test region L1B, and the control region L2 in the X direction is, for example, 1 mm, and the three regions, first test region L1A, second test region L1B, and control region L2, are arranged, for example, at intervals of 3 mm. Note that, hereinafter, when it is necessary to distinguish between multiple test regions L1, a sub-code A or B is added to the reference symbol for test region L1, and when there is no need to distinguish between them, they are simply referred to as test region L1.

[0141] The observed image 70 is an image in which a plurality of pixels are arranged two-dimensionally in a matrix. The processor 120 sorts the observed image 70 in order of pixel value for each column (step S52). In the first processing procedure of the main judgment described above, as shown in Fig. 11, after extracting the inspection area image 62 from the observed image 61, the pixels included in the inspection area L1 are sorted in order of pixel value for each column. However, in the second processing procedure of the main judgment, all pixels of the observed image 70, including those outside the inspection area L1, are sorted in order of pixel value for each column.

[0142] The processor 120 removes high-density pixels from the image data sorted in order of pixel value, and obtains the remaining pixels to be processed later (step S53).The remaining pixels are then used to derive a representative value for each column (step S54).The method for deriving the representative value from the remaining pixels, excluding the high-density pixels, is the same as the method for deriving the representative value in the first processing procedure of the main determination.

[0143] The processor 120 uses the derived representative values ​​to create a profile of pixel values ​​in the row direction (i.e., the X direction) (step S55). Figure 13 shows an example of a profile created from the observed image 70. In the profile using the representative values ​​of each column, the vertical axis represents the pixel value and the horizontal axis represents the pixel position in the X direction.

[0144] In the observation image 70 shown in Figure 13, the control region L2 is clearly expressed as a line. The first inspection region L1A is also expressed as a line, though it is thinner than the control region L2. On the other hand, the second inspection region L1B is not expressed. The PA, PB, and PC regions in the profile shown in Figure 13 correspond to the first inspection region L1A, the second inspection region L1B, and the control region L2, respectively. That is, in the profile, PA refers to the inspection region profile corresponding to the first inspection region L1A, PB refers to the inspection region profile corresponding to the second inspection region L1B, and PC refers to the control region profile corresponding to the control region L2.

[0145] The processor 120 extracts an inspection region profile from the profile created using the representative values ​​(step S56). Specifically, the processor 120 extracts an inspection region profile PA corresponding to the first inspection region L1A and an inspection region profile PB corresponding to the second inspection region L1B from the profile of FIG. 13. Note that the pixel value profile may be converted into a density profile before extracting the first inspection region L1A and the second inspection region L1B. High-density areas that form valleys in the pixel value profile indicate peaks in the density profile. Therefore, the first inspection region L1A and the second inspection region L1B can be extracted by extracting the peaks from the density profile. For example, the processor 120 identifies the position of the first inspection region L1A by comparing the position information of the first inspection region L1A with the valley positions (peak positions in the case of a density profile) of the inspection region profile PA shown in FIG. 13. The processor 120 then extracts the profile of the identified position as the inspection region profile PA of the first inspection region L1A. Position information of the first inspection region L1A and the second inspection region L1B in the observation image 70 is stored in advance as setting information in the memory 121. The setting information is, for example, the distance from one end of the observation image 70.

[0146] Next, the processor 120 determines whether the sample 50 is positive or negative based on the extracted test region profiles PA and PB (step S57). Specifically, the processor 120 determines whether the signal magnitudes S1A and S1B, which are indicated as the depths of the valleys in the first test region L1A and the second test region L1B (the difference between the BG line and the valley profile value), are equal to or greater than a preset threshold β (step S57). If the signal magnitude S1A is equal to or greater than the threshold β, the processor 120 determines the influenza A test result as "positive." If the signal magnitude S1B is less than the threshold β, the processor 120 determines the influenza A test result as "negative." Similarly, if the signal magnitude S1B is equal to or greater than the threshold β, the processor 120 determines the influenza B test result as "positive." If the signal magnitude S1B is less than the threshold β, the processor 120 determines the influenza B test result as "negative." Note that when multiple test regions L1 are provided as in this example, the signal magnitude thresholds set for the first test region L1A and the second test region L1B may be different. When the inspection area profile is a density profile, the height of the peak is taken as the magnitude of the signal and compared with a preset threshold to determine whether it is positive or negative.

[0147] Due to individual differences in cartridges 100, the position of inspection region L1 in the observation image 70 may be slightly misaligned. Therefore, when inspection region L1 is extracted from the observation image 70 based only on position information, a positional deviation from the actual inspection region L1 may occur. However, as described above, processor 120 creates a profile (or density profile) of pixel values ​​and identifies the position of inspection region L1 by comparing the position of the valley (or peak) corresponding to inspection region L1 extracted from the created profile with the position information of inspection region L1. Therefore, the inspection region profile of inspection region L1 can be extracted more accurately than when only one of the valley position of the profile and the position information is used.

[0148] In the above, the processor 120 creates a row-direction profile based on the representative value of each column in the observation image 70 and extracts an inspection area profile corresponding to the inspection area L1 from the created profile, but it may also be possible to extract an inspection area image corresponding to the inspection area L1 from the observation image 70 based on the created profile. Unlike the first processing procedure for the main judgment, in the second processing procedure for the main judgment, the main judgment is performed based on the inspection area profile, so it is not necessary to extract an inspection area image in the main judgment. However, even when the second processing procedure is applied to the main judgment, the inspection area image extracted in this way can be used for anomaly judgment in the second embodiment, which will be described later.

[0149] In the second processing procedure for the main judgment, the processor 120 also judges whether the sample 50 is positive or negative using the remaining pixels, excluding one or more high-density pixels in each column that have a relatively high density. In other words, by excluding at least some of the pixels in the high-density area d due to contamination, the influence of the high-density area d on the main judgment can be suppressed, and erroneous judgments can be suppressed. Therefore, it is possible to present test results that are more reliable than those obtained in the past when the main judgment was performed without excluding the pixels in the high-density area d. As described above, the processing procedure for the main judgment can be the first processing procedure shown in Figures 10 and 11, as well as the second processing procedure shown in Figures 12 and 13.

[0150] (Modified example of inspection flow) In the above embodiment, the first test flow has been described in which the first reagent 41 is supplied by the user and the second reagent 46 is supplied by the testing device 110. As described above, the testing device 110 can also select the second test flow and the third test flow.

[0151] In the second testing flow, after the user deposits the sample 50, the cartridge 100 is loaded into the loading section 112 of the testing device 110 without supplying the first reagent 41. In the testing device 110 with the cartridge 100 loaded, the processor 120 first operates the first reagent supply mechanism 116 to supply the first reagent 41 to the carrier 2, and then steps S21 to S30 (see FIG. 9) of the first testing flow are performed sequentially.

[0152] In the third testing flow, the user applies a drop of sample 50 and supplies first reagent 41, and then, after a predetermined time has elapsed, the user supplies second reagent 46 and then loads cartridge 100 into loading section 112 of testing device 110. In testing device 110 with cartridge 100 loaded, steps S21-27 (see FIG. 9) of the first testing flow are not performed, and processor 120 performs step S28 (see FIG. 9) of determining whether control region L2 is expressed. Subsequent processing is the same as in the first testing flow described above.

[0153] (Second embodiment) Fig. 14 shows a configuration diagram of an inspection device 110A according to the second embodiment. In Fig. 14, the same components as those in the inspection device 110 according to the first embodiment are denoted by the same reference numerals, and detailed descriptions are omitted. The inspection device 110A according to the second embodiment differs from the inspection device 110 according to the first embodiment in that the processor 120A includes an abnormality determination unit 127.

[0154] The abnormality determination unit 127 performs an abnormality determination to determine the presence or absence of an abnormality in the inspection area image (for example, the inspection area image 62 shown in FIG. 11). Specifically, the abnormality determination unit 127 performs the abnormality determination using at least one of the following as a determination index: a difference in pixel values ​​between a relatively large pixel value and a relatively small pixel value in at least one column in the inspection area image; a standard deviation of pixel values ​​of pixels included in at least one column in the inspection area image; or a coefficient of variation based on pixel values ​​of each column. The determination of the presence or absence of an abnormality in the inspection area image by the abnormality determination unit 127 may be performed before or after the main determination.

[0155] The processor 120A determines the processing content related to the main judgment based on the result of the abnormality judgment, i.e., the presence or absence of an abnormality. The processing content related to the main judgment includes, for example, at least one of whether to perform the main judgment and a method for presenting the main judgment result of the main judgment. Specifically, for example, if the processor 120A determines that an abnormality exists, it terminates the processing without performing the main judgment, and determines that the main judgment will be performed only if it determines that no abnormality exists. Also, for example, if the processor 120A determines that an abnormality exists, it presents the main judgment result as the inspection result with a reservation indicating that an abnormality exists, or it presents an inspection result indicating a judgment failure without presenting the main judgment result. Also, for example, if the processor 120A determines that no abnormality exists, it determines that the judgment result of the main judgment will be presented as the inspection result as is.

[0156] The method for determining an abnormality will be described with reference to Fig. 15 and Fig. 16. In Fig. 15, an observed image 74 shown in Fig. 15A and an observed image 75 shown in Fig. 15B are each an example of an observed image, and Fig. 15C shows the displacement of pixel values ​​in one pixel column extracted from a first inspection region L1A of the observed image 74 in Fig. 15A and a second inspection region L1B of the observed image 75 in Fig. 15B.

[0157] 15A and 15B are images obtained when an influenza test cartridge for testing two types of test substances is used, similar to the image 70 shown in Fig. 13. Similar to the image 70, the images 74 and 75 include two test areas L1A and L1B and a control area L2.

[0158] In the observation image 74 shown in FIG. 15A, a line appears in the first inspection region L1A, but no line appears in the second inspection region L1B. On the other hand, in the observation image 75 shown in FIG. 15B, no line appears in either the first inspection region L1A or the second inspection region L1B, but there is a localized high-density area corresponding to a stain at the bottom of the second inspection region L1B in the observation image 75. When a localized high-density area appears in the inspection region, an abnormality is present in the inspection region. The abnormality determination unit 127 determines whether or not there is an abnormality in the inspection region L1, i.e., whether or not there is a localized high-density area.

[0159] As described above, the observed image 74 and the observed image 75 are images in which a plurality of pixels are arranged two-dimensionally in a matrix. The relationship between the pixel values ​​of one pixel row a in the inspection area image showing the first inspection area L1A in Fig. 15A and the pixel positions in the Y direction, and the relationship between the pixel values ​​of one pixel row b in the inspection area image showing the second inspection area L1B in Fig. 15B and the pixel positions in the Y direction are shown in Fig. 15C.

[0160] As shown in FIG. 15C, the pixel values ​​of pixels included in pixel row b of the second inspection region L1B, which contains an abnormality in the observation image 75, fluctuate more than the pixel values ​​of pixels included in pixel row a of the first inspection region L1A, which contains no abnormality in the observation image 74. When the specimen 50 is positive and a normal line appears in the inspection region L1, the density of pixels in the inspection region L1 increases uniformly, as shown in pixel row a without an abnormality, and there is no significant difference in the pixel values ​​of pixels aligned in the Y direction. Similarly, when the specimen 50 is negative and no line appears in the inspection region L1, the density of pixels in the inspection region L1 does not change, and there is no significant difference in the pixel values ​​of pixels aligned in the Y direction. On the other hand, localized high-density areas caused by nonspecific adsorption rarely occur uniformly in the Y direction. Therefore, as shown in pixel row b with an abnormality, the fluctuation in pixel values ​​of pixels aligned in the Y direction (i.e., pixel value variation) is greater than when no high-density areas exist.

[0161] Therefore, it is possible to determine whether or not an abnormality exists in the inspection area image using the magnitude of variation in pixel values ​​of pixels aligned in the Y direction in the inspection area image as a determination index. Examples of measures for measuring the magnitude of variation in pixel values ​​include the amount of pixel change in a pixel row, standard deviation, and coefficient of variation. Here, the amount of pixel change is the difference between a relatively high pixel value and a relatively low pixel value in the pixel row, and an example is the difference between the maximum and minimum values. However, the amount of change used as the determination index may be any difference between a relatively high pixel value and a relatively low pixel value within a range in which a difference sufficient to distinguish between the presence and absence of an abnormality is recognized. For example, the amount of change may be the difference between the second-largest and second-smallest pixel values ​​in the pixel row, or the difference between the third-largest and third-smallest pixel values.

[0162] Table 1 shows the results of calculating the amount of change (maximum value - minimum value), standard deviation, and coefficient of variation based on the pixel values ​​of the pixels that make up pixel row b in the inspection area L1 with an abnormality shown in Figure 15C and the pixels that make up pixel row a in the inspection area without an abnormality.

[0163] [Table 1]

[0164] As shown in Table 1, pixel row b, which has an abnormality, has a larger standard deviation, change amount, and coefficient of variation than pixel row a, which has no abnormality. Therefore, the presence or absence of an abnormality is determined using at least one of the standard deviation, change amount, and coefficient of variation as a determination index. As an example, when the standard deviation is used as the determination index, if the standard deviation is, for example, 8 or more, it is determined that there is an abnormality, and if it is less than 8, it is determined that there is no abnormality. When the change amount is used as the determination index, for example, it is determined that there is an abnormality if it is 20 or more, and if it is less than 20, it is determined that there is no abnormality. When the coefficient of variation is used as the determination index, for example, it is determined that there is an abnormality if it is 5% or more, and if it is less than 5%, it is determined that there is no abnormality. When the standard deviation and change amount are used as the determination index, for example, if the standard deviation is 8 or more and the change amount is 20 or more, it is determined that there is an abnormality, and if the standard deviation is less than 8 or the change amount is less than 20, it is determined that there is no abnormality. The numerical value that serves as the criterion for determining whether or not there is an abnormality (hereinafter referred to as the judgment criterion value TA) is a value that is appropriately determined depending on the test substance in question, the type of cartridge, the testing device, etc., and the preset value is stored in memory 121 as setting information.

[0165] As described above, at least one of the amount of change, standard deviation, and coefficient of variation for pixel values ​​of pixels included in one column (one pixel column) in the inspection area image representing the inspection area L1 is used as the judgment index. An arbitrary column may be extracted from the inspection area image as the pixel column used to calculate the judgment index, and the extracted column may be used for abnormality judgment. The extraction position is preferably a column near the center in the X direction of the inspection area image. This is because the difference between the presence and absence of an abnormality is often more pronounced near the center. Furthermore, the number of columns is not limited to one, and judgment indices may be calculated for multiple columns in the inspection area image, and an abnormality may be judged to exist if the judgment indices for all or a majority of the columns satisfy the judgment reference value TA.

[0166] Furthermore, the processor 120A may use, as the judgment index, at least one of the difference between a relatively large representative value and a relatively small representative value among the representative values ​​of each row derived based on multiple pixels existing in the same row but different columns in the inspection area image, and the standard deviation and the coefficient of variation based on the representative values ​​of each row. For example, as shown in FIG. 16, multiple columns are extracted from the inspection area image showing the second inspection area L1B in the observation image 75, and the average value of the pixel values ​​of multiple pixels existing in the same row but different columns is derived as the representative value. In FIG. 16, as an example, five pixel columns are extracted. Each column includes 15 rows of pixels. In FIG. 16, the numerical values ​​shown in each pixel of the pixels arranged in a matrix are pixel values. For example, the processor 120A derives the average value for each row of the five pixel columns and sets this average value as the representative value for each row. Using the example pixel values ​​in FIG. 16, for example, the representative value for the first row is (142 + 140 + 140 + 144 + 144) / 5 = 142. The representative values ​​for the 15 rows thus derived are regarded as one column, and at least one of the amount of change, standard deviation, and coefficient of variation is derived in the same manner as above and used as a judgment index.

[0167] In this way, by using at least one of the difference between a relatively large representative value and a relatively small representative value among the representative values ​​of each row derived based on multiple pixels existing in different columns in the same row, and the standard deviation and the coefficient of variation based on the representative values ​​of each row as the judgment index, it is possible to suppress noise and perform more accurate abnormality judgment compared to when the judgment index is obtained using a specific column in the inspection area.

[0168] FIG. 17 shows the procedure for determining abnormality by the processor 120A.

[0169] In the procedure for determining an abnormality, the processor 120A first obtains the observed image 74 (or the observed image 75) by cutting out an observation area from the captured image output by the imaging unit 114 (step S61).

[0170] Next, the processor 120A extracts an inspection area image from the acquired observation image 74 (or observation image 75) (step S62). Note that, when a main judgment is made before an abnormality judgment, steps S61 to S62 are realized by a step of acquiring an observation image in the main judgment (step S41 in FIG. 10 and step S51 in FIG. 12, etc.) and a step of extracting an inspection area image (step S42 in FIG. 10, etc.).

[0171] The processor 120A derives a determination index from the extracted inspection area image (step S63). As described above, for example, the processor 120A derives at least one of the amount of change, standard deviation, and coefficient of variation for pixel values ​​of pixels included in at least one column (one pixel column) in the inspection area image as the determination index. Alternatively, the processor 120A derives at least one of the difference between a relatively large representative value and a relatively small representative value among representative values ​​of each row derived based on multiple pixels existing in the same row but different columns in the inspection area image, or the standard deviation and coefficient of variation based on the representative values ​​of each row as the determination index.

[0172] The processor 120A determines whether the derived judgment index is equal to or greater than a preset judgment reference value TA (step S64). If the judgment index is equal to or greater than the judgment reference value TA (step S64: Yes), the processor 120 determines that an abnormality exists (step S65) and ends the abnormality judgment process. On the other hand, if the judgment index is less than the judgment reference value TA (step S64: No), the processor 120A determines that no abnormality exists (step S66) and ends the abnormality judgment process. The processing procedure for abnormality judgment by the processor 120A is as described above.

[0173] An inspection flow in the inspection device 110A when the inspection device 110A of the second embodiment is used is shown in Fig. 18. In Fig. 18, the same steps as those in the inspection flow in the inspection device 110 shown in Fig. 9 are assigned the same step reference numerals, and detailed explanations thereof will be omitted.

[0174] 18, steps S21 to S28 are the same as the test flow shown in Fig. 9 for the testing device 110. In determining whether or not the control region L2 is expressed (step S28), if the control region L2 is expressed (step S28: Yes), the processor 120A performs a main judgment accompanied by an abnormality judgment, and presents the test result based on the result of the main judgment accompanied by an abnormality judgment (step S31).

[0175] In step S31, the processor 120A performs a process according to the first process procedure for main determination or the second process procedure for main determination described above, as the main determination, to determine whether the specimen 50 is positive or negative. Furthermore, the processor 120A performs a process according to the process procedure for abnormality determination shown in FIG. 17, as the abnormality determination, to determine the presence or absence of an abnormality in the inspection area image. In step S31, in the main determination involving abnormality determination, the processor 120A may perform the abnormality determination before the main determination, or may perform the abnormality determination after the main determination. Therefore, multiple process procedures are conceivable for the process procedure of step S31. Details of step S31 will be described below. Furthermore, five process procedures for step S31 will be illustrated below, and the five process procedures will be referred to as first to fifth examples to distinguish between them.

[0176] FIG. 19 shows a first example of the processing procedure of step S31.

[0177] 19, in a first example of step S31, the processor 120A first makes a main determination as to whether the sample 50 is positive or negative (step S71). In step S71 for making this main determination, the processor 120A performs processing in accordance with the first processing procedure for the main determination described using Figures 10 and 11 or the second processing procedure for the main determination described using Figures 12 and 13.

[0178] If the processor 120A determines that the result of the main judgment is negative (step S72: No), it displays "negative" as the test result on the monitor 119 without making an abnormality judgment, and ends the processing of step S31 in Fig. 18. On the other hand, if the processor 120A determines that the result of the main judgment is positive (step S72: Yes), it makes an abnormality judgment (step S73).

[0179] In the abnormality determination step S73, the processor 120A performs abnormality determination according to the abnormality determination processing procedure shown in FIG. 17, using the inspection area image extracted from the observation image acquired in the main determination step.

[0180] When the processor 120A determines that an abnormality is present as a result of the abnormality determination (step S75: Yes), the processor 120A displays "Positive with reservation" as the test result on the monitor 119 (step S76), and ends the processing of step S31 in Fig. 18. Here, "with reservation" means that a reservation has been made to indicate that there is an abnormality in the inspection area image. In other words, the display of "Positive with reservation" is intended to make the user aware that although the main determination is positive, there is a possibility of a false positive due to the presence of an abnormality in the inspection area L1.

[0181] In step S76, instead of displaying a test result of positive with a reservation, an error message of "bad judgment" may be displayed without displaying the test result. Also, in addition to "bad judgment," it may be indicated that there may be dirt in the test area. When a test result of positive with a reservation or bad judgment is displayed, the user can visually determine whether the test area is colored or not to confirm whether it is positive or negative, or can decide to perform a retest.

[0182] On the other hand, if the processor 120A determines that there is no abnormality as a result of the abnormality determination (step S75: No), it displays "positive" as the test result on the monitor 119 (step S77) and ends the processing of step S31 in FIG.

[0183] In the present inspection device 110A, the processor 120A performs the main judgment using the remaining pixels, excluding one or more high-density pixels in each column of the inspection area image, thereby suppressing erroneous judgments due to localized high-density areas in the inspection area. This allows for more reliable inspection results than ever before. However, if the high-density areas in the inspection area image cover a relatively wide area, it may be impossible to completely eliminate the high-density pixels that make up the high-density areas, which may result in erroneous judgments due to the high-density pixels included in the remaining pixels. However, in the present inspection device 110A, the processor 120A performs the main judgment with anomaly judgment according to the above-described anomaly judgment processing procedure. That is, the processor 120A performs anomaly judgment using, as a judgment index, at least one of the difference between relatively large and relatively small pixel values ​​in at least one column of the inspection area image, the standard deviation based on the pixel values ​​of at least one column, and the coefficient of variation. Alternatively, the processor 120A performs an anomaly determination using, as a determination index, at least one of the difference between a relatively large representative value and a relatively small representative value among representative values ​​for each row derived based on multiple pixels existing in the same row but different columns in the inspection area image, and the standard deviation and the coefficient of variation based on the representative values ​​for each row.The processor 120A then determines the processing content for the main determination based on the presence or absence of an anomaly.Therefore, the presence or absence of an anomaly in the inspection area L1 can be determined with high accuracy, and the processing content for the main determination is determined based on the presence or absence of an anomaly, thereby providing more reliable inspection results.

[0184] In particular, in the first example of step S31 described above, the processor 120A first performs a main judgment, and if the judgment result of the main judgment is positive, performs an abnormality judgment, and the method of presenting the main judgment result as processing content related to the main judgment is changed based on the presence or absence of an abnormality. That is, if the main judgment result is positive and there is no abnormality, the judgment result of the main judgment is presented as the test result as is (here, "positive" is displayed on the monitor 119), and if there is an abnormality, the judgment result of the main judgment is presented with a reservation indicating that there is an abnormality in the inspection area image (here, "positive with reservation" is displayed on the monitor 119). This makes it possible to present to the user whether the judgment result is sufficiently reliable or whether there is a possibility of a false positive, thereby increasing the reliability of the test result.

[0185] Fig. 20 shows a second example of the processing procedure of step S31. In Fig. 20, the same steps as those in the first example shown in Fig. 19 are denoted by the same step reference numerals, and detailed explanations thereof will be omitted.

[0186] The second example of step S31 differs from the first example in the processing that follows when the processor 120A makes a main determination (step S71) and determines that the result is negative (step S72: No). In the second example, even when the processor 120A makes a main determination (step S71) and determines that the result is negative (step S72: No), it still performs an abnormality determination (step S81). Then, when the processor 120A determines that there is an abnormality as a result of the abnormality determination in step S81 (step S82: Yes), it displays "Negative with reservation" on the monitor 119 (step S83) and ends the processing of step S31 in FIG. 18.

[0187] On the other hand, if the processor 120A determines that there is no abnormality as a result of the abnormality determination in step S81 (step S82: No), it displays "Negative" on the monitor 119 (step S84) and ends the processing of step S31 in FIG.

[0188] In the second example shown in Fig. 20, as in the first example shown in Fig. 19, the main judgment is performed using the remaining pixels, excluding one or more high-density pixels with relatively high densities in each column of the inspection area image, thereby suppressing erroneous judgments due to high-density areas occurring partially in the inspection area. Therefore, it is possible to present inspection results with higher reliability than before. In addition, an abnormality judgment is performed to determine the presence or absence of an abnormality in the inspection area image, and the processing content related to the main judgment is determined based on the presence or absence of an abnormality, so it is possible to present inspection results with higher reliability.

[0189] 20, when the processor 120A determines that there is no abnormality (step S75: No and step S82: No), it presents the determination result of the main determination as the test result as is (here, it displays "positive" or "negative" on the monitor 119), and when it determines that there is an abnormality (step S75: Yes and step S82: Yes), it presents the determination result of the main determination with a reservation to the effect that there is an abnormality in the test area image (here, it displays "positive or poor judgment with reservation" or "negative with reservation" on the monitor 119). This makes it possible to present to the user whether the test result is sufficiently reliable or whether it includes the possibility of a false positive, thereby increasing the reliability of the test result.

[0190] In the first example shown in Fig. 19 and the second example shown in Fig. 20, the main judgment is performed first, and then the abnormality judgment is performed. However, in step S31, the abnormality judgment may be performed first, and the main judgment may be performed later. Fig. 21 shows an example of the detailed processing procedure of step S31, and shows a third example in which the abnormality judgment is performed first and the main judgment is performed later.

[0191] 21, in the third example, the processor 120A first performs an abnormality determination (step S91). The processor 120A performs processing in accordance with the abnormality determination processing procedure shown in FIG.

[0192] Then, when the processor 120A determines that there is an abnormality in the abnormality determination (step S92: Yes), it displays "bad determination" on the monitor 119 without performing the main determination (step S93), and ends the processing of step S31 in Fig. 18. At this time, instead of or together with the display of "bad determination," it may display an explanation such as "There is dirt in the inspection area, so no main determination was made" on the monitor 119.

[0193] When the processor 120A determines that there is no abnormality in the abnormality determination (step S92: No), it performs a main determination (step S94). In this main determination step S94, the processor 120A performs processing in accordance with the first processing procedure of the main determination described with reference to Figures 10 and 11 or the second processing procedure of the main determination described with reference to Figures 12 and 13. When the main determination is performed after the abnormality determination, the observed image acquired in the abnormality determination step S91 is used.

[0194] When the processor 120A determines that the result of the main judgment is positive (step S95: Yes), it displays "positive" on the monitor 119 (step S96) and ends the processing of step S31 in Fig. 18. On the other hand, when the processor 120A determines that the result of the main judgment is negative (step S95: No), it displays "negative" on the monitor 119 (step S97) and ends the processing of step S31 in Fig. 18.

[0195] As in the third example shown in Figure 21, even when an abnormality determination is performed first and the main determination is performed after determining that there is no abnormality in the inspection area image, the main determination is performed using the remaining pixels excluding one or more high-density pixels that have relatively high densities in each column of the inspection area image, thereby suppressing erroneous determination due to high-density areas that occur partially in the inspection area. Also, since the main determination is performed after confirming that there is no abnormality through the abnormality determination, the reliability of the inspection results can be improved. Furthermore, in the third example, if it is determined that there is an abnormality in the inspection area image, the inspection is terminated without further occupying the inspection device 110A, thereby shortening the occupancy time of the inspection device 110A.

[0196] As in the third example shown in Fig. 21, when the main judgment is made after the abnormality judgment, the main judgment may be made even if the abnormality judgment determines that an abnormality exists. Fig. 22 is an example showing the detailed processing procedure of step S31, and shows a fourth example where the abnormality judgment is made first and then determines that an abnormality exists. In Fig. 22, the same steps as in the third example shown in Fig. 21 are assigned the same step symbols, and detailed explanations will be omitted.

[0197] 22, in the fourth example, the processor 120A performs an abnormality determination (step S91), and even if it determines that an abnormality is present (step S92: Yes), it performs a main determination (step S103). Then, if the processor 120A determines that the result of the main determination in step S103 is positive (step S105: Yes), it displays "Positive with reservations" on the monitor 119. On the other hand, if the processor 120A determines that the result of the main determination in step S103 is negative (step S105: No), it displays "Negative" on the monitor 119. The other steps are the same as in the third example.

[0198] In addition, if the processor 120A determines that the result of the main judgment in step S103 is positive (step S105: Yes), instead of displaying ``Positive with reservations'' on the monitor 119, it may display an error message (here, display ``Poor judgment'' on the monitor 119) (step S106).

[0199] Fig. 23 shows an example of the detailed processing procedure of step S31, and shows a fifth example in which an abnormality determination is first performed and it is determined that an abnormality is present. In Fig. 23, the same steps as in the third or fourth example are given the same step reference numerals, and detailed explanations thereof will be omitted.

[0200] 23, in the fifth example, the processor 120A performs an abnormality determination (step S91), and even if it determines that an abnormality is present (step S92: Yes), it performs a main determination (step S103). Then, if the result of the main determination in step S103 is determined to be negative (step S105: No), the processor 120 displays "Negative with reservation" on the monitor 119 (step S107). The other steps are the same as in the fourth example.

[0201] For the fourth example shown in Fig. 22 and the fifth example shown in Fig. 23, as with the third example shown in Fig. 21, erroneous judgments due to high-density areas occurring partially in the inspection area can be suppressed by performing the main judgment using the remaining pixels excluding one or more high-density pixels that have relatively high densities in each column of the inspection area image. In addition, since the main judgment is performed after confirming that there are no abnormalities through an abnormality judgment, the reliability of the inspection results can be improved.

[0202] In the above-mentioned first to fifth examples, if the test result is a poor judgment or a judgment result with reservations, the user can visually check whether or not a line has appeared in the test area L1, or can take measures such as processing it as a target for re-testing.

[0203] In the above embodiment, the first and second processing procedures for the main determination have been described. In the first processing procedure, an inspection area image is extracted from the observation image, and a representative value for each column of the inspection area image is calculated using the remaining pixels, excluding pixels that may be noise in the inspection area image. Then, using the remaining pixels, excluding pixels that may be noise, the representative value is compared with a reference pixel value to determine whether the result is positive or negative. In the second processing procedure, a representative value for each column is calculated using the remaining pixels, excluding pixels that may be noise in the observation image, to create a row-wise profile. Then, an inspection area profile is extracted from the row-wise profile of the observation image, and a positive or negative result is determined based on whether the peak magnitude is equal to or greater than a threshold. As described above, when the first or second processing procedure is used, the influence of pixels that have become highly concentrated due to noise such as dirt or shadows can be eliminated. However, the method using the remaining pixels loses information about the column-wise continuity of lines (positive lines) that appear when the sample is actually positive. This means that it is not possible to distinguish between dirt or unevenness on the inspection area and actual positive lines, and false positives may be included among the results determined to be "positive." In order to eliminate such false positives, it is preferable to further execute a condition determination process for eliminating false positives in the main judgment to obtain a highly reliable judgment. Below, the third processing procedure of the main judgment for obtaining a highly reliable judgment will be described.

[0204] The third processing procedure is roughly similar to the second processing procedure shown in Fig. 12, but differs in the details of extracting the inspection area profile and the details of step S57, which determines whether the result is positive or negative based on the inspection area profile. In particular, the third processing procedure includes multiple processing steps in step S57. The third processing procedure is a process related to a main determination that is unrelated to whether or not an abnormality detection process is performed, and therefore can be performed by either the processor 120 of the inspection device 110 of the first embodiment or the processor 120A of the inspection device 110A of the second embodiment. The following description will be given as processing in the processor 120.

[0205] Before explaining the details of step S57, we will first explain the specific technique for step S56, which extracts an inspection area profile from a profile created based on representative values. FIG. 24 schematically shows a range of the profile created based on representative values, including the inspection area profile PA corresponding to the first inspection area L1A. Here, we will explain the procedure for determining whether a line appears in the first inspection area L1A or not, but similar processing is also performed for the second inspection area L1B. FIG. 24 shows the steps of extracting an inspection area profile, searching for the position showing the maximum density difference, and specifying the line position and line width of the line appearing in the first inspection area L1A of the observation image 70.

[0206] First, in each search range set from a certain reference position in the profile created based on the representative value, points BGn and BGn+1 are searched for, which are the ends of the first inspection area L1A for drawing a background line (hereinafter referred to as the BG line) (see step STA in Figure 24). The certain reference is a predetermined position that is a known position or a previously detected position, such as one end of the observation image 70 or one end of the control area L2. The positions of both ends of the first inspection area L1A in the X direction from the reference position are known. The areas near the known positions of both ends of the first inspection area L1A are set as search ranges EA1 and EA2, and points having density values ​​(pixel values) of a predetermined ranking in each search range EA1 and EA2 are defined as BGn and BGn+1, respectively. The predetermined ranking is set appropriately, and may be the third highest density value (third lowest pixel value) or the fifth highest density value (fifth lowest pixel value) in the search ranges EA1 and EA2, for example. The area from BGn to BGn+1 thus determined is the inspection area profile PA. Note that, although the inspection area profile PA is shown schematically in Fig. 24 and the BG line is approximately horizontal, the actual BG line is not necessarily a horizontal line, as shown in Fig. 13.

[0207] The above is the details of the step S56 of extracting the examination area profile PA in the third processing procedure. Fig. 25 shows the detailed steps of determining whether it is positive or negative based on the examination area profile PA in the third processing procedure.

[0208] As shown in Fig. 25, after extracting the inspection area profile PA, the processor 120 searches for the maximum position (hereinafter referred to as ΔODmax position Tp), which is the row direction position Tp of the maximum density difference ΔODmax where the density difference ΔOD between the profile density and the BG density in the inspection area profile PA is maximum (step S5701). As shown in step STB in Fig. 24, the inspection area profile PA is the profile in the range from BGn to BGn+1 searched for in step STA in Fig. 24. The maximum density difference ΔODmax means the maximum density of the inspection area profile PA. The maximum density difference ΔODmax corresponds to the signal magnitude S1A described in the second processing procedure.

[0209] Next, processor 120 determines whether ΔODmax position Tp coincides with either of the two end regions of inspection area profile PA (step S5702). Here, the two end regions of inspection area profile PA refer to BGn and BGn+1, and the two end regions refer to the ranges from BGn to BGn+1, and also refer to the search range EA1 of BGn and the search range EA2 of BGn+1.

[0210] If the ΔODmax position Tp is located at either end of the test region profile PA, it means that the test region profile PA does not indicate the line that appears in the test region L1 when the test region profile PA is positive (hereinafter referred to as the positive line). Therefore, if the ΔODmax position Tp is located at either end of the test region profile PA (step S5702; Yes), the processor 120 determines that the sample 50 is "negative" (step S5703), and ends the main determination.

[0211] On the other hand, if the ΔODmax position Tp is not located in either of the end regions of the inspection area profile PA (step S5702; No), the processor 120 derives the line position and line width in the inspection area profile PA (step S5704). At this point, it is not determined whether a positive line has appeared in the inspection area L1, but assuming that a line has appeared, the processor 120 specifies the line position and line width. The line position corresponds to the center position in the row direction of the inspection area, and the line width corresponds to the width of the inspection area.

[0212] As shown in step STC of Fig. 24, the processor 120 searches the profile left and right from the ΔODmax position Tp, determines the distance between two points e1 and e2 that is α% of ΔODmax as the line width Tw, and derives the center position of the line width Tw as the line position Tn in the first inspection area L1A. α% is, for example, 50%, but can be set to any value, such as 40% or 60%, as appropriate.

[0213] Next, processor 120 executes a pre-condition determination process to determine whether or not the following pre-determination conditions A to C are satisfied (step S5705). A: The line position Tn is within a preset range. B: The line width Tw is within a preset range. C: The maximum density difference ΔODmax is equal to or greater than a preset threshold value β.

[0214] The predetermined range of the line position Tn under condition A is, for example, the range in which the inspection area L1 can exist in the row direction defined from the reference position mentioned above, specifically, a range of 10 mm to 11 mm from the reference position, etc.

[0215] The preset range of the line width Tw under condition B is the range of the designed inspection area width (line width) Xw±Δw, for example, a range of 0.8 mm to 1.2 mm when the designed value of the line width is 1 mm.

[0216] The threshold value β of condition C (corresponding to the fourth threshold value in the claims) is the same as the threshold value β described in the second processing procedure. It is a value that is set in advance as a value that can be reliably considered negative if it is less than β. It is a value that is appropriately determined according to the principle of light emission, the sensitivity of the image sensor, etc. as an index for detecting changes in the light emission state.

[0217] The processor 120 determines that the pre-determination conditions are satisfied if all of the conditions A to C are satisfied, and determines that the pre-determination conditions are not satisfied if any one of the conditions A to C is not satisfied. If the processor 120 determines that the pre-determination conditions are not satisfied (step S5705: No), it determines that the sample 50 is "negative" (step S5703) and ends the main determination.

[0218] On the other hand, if the processor 120 determines that the pre-determination conditions are satisfied (step S5705: Yes), it determines whether ΔODmax is equal to or greater than a threshold value γ (step S5706). Here, the threshold value γ (corresponding to the fifth threshold value in the claims) is set to a value greater than the threshold value β and indicating that ΔODmax clearly appears as a line. Therefore, if the processor 120 determines that ΔODmax is equal to or greater than the threshold value γ (step S5706: Yes), it determines the sample 50 as "positive" (step S5707) and ends the main determination. On the other hand, if the processor 120 determines that ΔODmax is less than the threshold value γ (step S5706: No), it creates a four-division area profile for the observed image (step S5708).

[0219] Here, the creation of a four-divided area profile will be described. FIG. 26 shows a schematic view of an observation image 72. As shown in FIG. 26, the processor 120 divides the observation image 72 into four areas a1 to a4 extending in the row direction. The processor 120 then creates a row-direction area profile for each of the areas a1 to a4. Specifically, the processor 120 derives an average value or median value for each column in the areas a1 to a4, using at least a portion of the pixels included in each column, and creates a row-direction area profile for each of the areas a1 to a4 using the derived average value or median value. FIG. 27 shows examples of area profiles area1 to area4 created by dividing the inspection area image into four. The area profiles area1 to area4 shown in FIG. 27 are profiles of a partial region of the observation image 70 shown in FIG. 13, including the first inspection area L1A. In Fig. 27, positions BGn, BGn+1, and Tn in the row direction (X direction) correspond to the positions of the same symbols in Fig. 24 (the same applies to Figs. 28 to 30). To derive the average or median value for each column in each of areas a1 to a4, at least a portion of the pixels contained in each column may be used, but it is preferable to use more than half of the pixels contained in each column, and more preferably to use all of them. In addition, in this example, the observed image is divided into four areas a1 to a4, but the number of divisions may be two or more and is not limited to four.

[0220] Next, the processor 120 executes a condition determination process using the area profiles area1 to area4 derived for each of the areas a1 to a4 (step S5709). As the condition determination process, the processor 120 executes at least one of the first to third condition determination processes, which determine whether or not a value derived based on the area profiles area1 to area4 satisfies a preset condition. If the processor 120 has executed any one of the condition determination processes that does not satisfy the condition (step S5709: No), the processor 120 determines the sample 50 as "negative" (step S5703). On the other hand, if the processor 120 has executed all of the conditions of the condition determination processes that it has executed, the processor 120 determines the sample 50 as "positive" (step S5707). Here, as an example, a case where all of the first to third condition determination processes are executed will be described.

[0221] The first condition determination process is a condition determination process that determines whether or not a first condition F1 is satisfied. In the first condition determination process, the processor 120 first creates differential area profiles delta1-4 (see FIG. 28) by differentiating the area profiles area1-4 (see FIG. 27) for each area. Next, as shown in FIG. 28, the processor 120 derives row-direction positions x1-x4 (hereinafter referred to as differential peak positions) at which the highest local maximum values ​​Pd1-Pd4 are shown in each of the differential area profiles delta1-delta4. The processor 120 then derives the standard deviation (differential peak position standard deviation) of each of the derived differential peak positions x1-x4, and determines whether or not a first condition F1 is satisfied, that is, the standard deviation is less than a predetermined first threshold. The fact that the standard deviation of the differential peak positions of multiple areas is less than the first threshold means that the differential peak positions highly match. If the differential peak positions match in multiple areas, it is highly likely that a line extending in the column direction has appeared in the inspection region. Conversely, if the first condition F1 is not met, it means that the line is not expressed. Therefore, if the first condition F1 is not met, the processor 120 determines that the specimen 50 is "negative."

[0222] The second condition determination process is a condition determination process that determines whether or not the second condition F2 is satisfied. In the second condition determination process, the processor 120 creates differential area profiles delta1-4 (see FIG. 28) by differentiating the area profiles area1-4 (see FIG. 27) for each area, and then adds these differential area profiles delta1-4 to create an additive differential area profile (see FIG. 29). The processor 120 then derives the difference between the maximum maximum value in the added additive differential area profile and the average value of the maximum values ​​other than the maximum maximum value, and determines whether the difference satisfies a second condition F2, that is, whether the difference is greater than a predetermined second threshold value. In FIG. 29, the maximum values ​​in the additive differential area profile are marked with a circle (○). Of these maximum values, the maximum maximum value Mmax appearing at 107 pixels in the X direction and the average value Mave of the other six maximum values ​​are derived. The range from which the maximum values ​​are extracted is the same range on both sides of the line position Tn determined previously in the X direction. For example, the range may be 0.9 mm to the left and right of Tn, for a total of 1.8 mm. The difference between the maximum maximum value Mmax and the average value Mave of the other maximum values ​​is an indication of the degree of prominence of the maximum maximum value, hereinafter referred to as the differential peak prominence. If this differential peak prominence is greater than the second threshold, it means that there is a high possibility that a line has appeared in the test area. Conversely, if the second condition F2 is not met, it means that no line has appeared. Therefore, if the second condition F2 is not met, the processor 120 determines that the sample 50 is "negative."

[0223] The third condition determination process is a condition determination process that determines whether or not a third condition F3 is satisfied. In the third condition determination process, the processor 120 adds the area profiles area1 to area4 (see FIG. 27) for each area to create an addition area profile (see FIG. 30). The processor 120 then determines whether or not a third condition, that is, a value at a predetermined position in the row direction in the addition area profile is greater than a third threshold, is satisfied. In FIG. 30, BGn, BGn+1, and Tp correspond to the positions of the same symbols in FIG. 24. That is, BGn and BGn+1 are both ends of the examination area profile PA previously searched in the profile using the representative value, and Tp is the ΔODmax position. In the addition area profile shown in FIG. 30, the processor 120 determines the BG line as a straight line connecting the profile value (here, the sum of pixel values) at position BGn in the row direction (X direction) with the profile value at position BGn+1. The processor 120 then derives the difference ΔQL between the profile value at the ΔODmax position Tp and the BG line as a value at a predetermined position in the row direction. The difference ΔQL being greater than the third threshold value means that a certain degree of density change has occurred at the ΔODmax position Tp determined in the examination area profile PA created using the representative value, meaning that the line is likely to have appeared. Conversely, if the third condition F3 is not met, this means that the line has not appeared. Therefore, if the third condition F3 is not met, the processor 120 determines the sample 50 to be "negative."

[0224] As described above, in the condition determination processes using area profiles area1 to area4, if any one of the executed first to third condition determination processes does not satisfy the condition (step S5709: No), processor 120 determines the sample 50 as "negative" (step S5703) and ends the main determination. On the other hand, if all of the executed first to third condition determination processes satisfy the conditions, processor 120 determines the sample 50 as "positive" (step S5705) and ends the main determination.

[0225] The third processing procedure of the main determination is as described above.

[0226] As described above, in the third processing procedure for the main judgment, a row-direction profile is created using the representative value, and in addition to judgment based on this profile using the representative value, the inspection area image is divided into multiple areas extending along the row direction, and condition judgment processing is performed using the area profile created for each area. As mentioned above, if judgment is performed only using the profile using the representative value, false positive samples may be included among the samples judged to be positive. However, by performing condition judgment processing using the area profile as in the third processing procedure, false positive samples can be eliminated, and highly reliable results can be obtained.

[0227] In this embodiment, the processor 120 performs a first condition determination process using an area profile, in which a differentiated area profile obtained by differentiating the area profile for each area is used to determine whether a first condition F1 is satisfied, that is, the standard deviation of the differentiated peak positions of multiple areas is less than a first threshold. The fact that the differentiated peak positions in each area are substantially the same means that there is line continuity in the column direction. By determining whether or not such line continuity exists, false positive samples that do not have line continuity can be eliminated.

[0228] In this embodiment, the processor 120 performs a second condition determination process using the area profile, in which the differential area profiles for each area are added together and the processor 120 determines whether a second condition F2 is satisfied, that is, whether the difference between the maximum maximum value in the added differential area profile and the average value of the maximum values ​​other than the maximum maximum value is greater than a second threshold value. The fact that the prominence of the differential peak in the added differential profile is greater than the second threshold value means that the positions of the maximum maximum values ​​in multiple area profiles are approximately the same, which also means that there is line continuity in the column direction. Therefore, by determining the presence or absence of line continuity in the second determination process, false positive samples that do not have line continuity can be eliminated.

[0229] In this embodiment, the processor 120 performs a third condition determination process using the area profile, in which the area profiles for each area are added together and a third condition determination process is performed to determine whether a value at a predetermined row position in the added area profile is greater than a third threshold value, which satisfies a third condition F3. For example, the predetermined row position is set to the peak (bottom) position in the representative profile. In this case, if the profile value in the added area profile is greater than the third threshold value, the appearance of a line is guaranteed. Therefore, false positive samples can be eliminated by eliminating samples that do not satisfy the third condition in the third condition determination process.

[0230] As described above, the processor 120 may be configured to execute a combination of one or two of the first to third condition determination processes. However, as in the present embodiment, if the processor 120 executes all of the first, second, and third condition determination processes as condition determination processes using an area profile, more reliable results can be obtained compared to when only one or two processes are executed.

[0231] In the above embodiment, the following various processors can be used as the hardware structure of the processing units that perform various processes, such as the processor 120 and its internal components, the imaging unit control unit 122, color development state determination unit 123, first reagent supply mechanism control unit 124, second reagent supply mechanism control unit 125, abnormality determination unit 127, and display control unit 126. As described above, the various processors include a CPU, which is a general-purpose processor that executes software to function as various processing units, as well as dedicated electrical circuits, such as a programmable logic device (PLD), a processor whose circuit configuration can be changed after manufacture, such as an FPGA (Field Programmable Gate Array), and an ASIC (Application Specific Integrated Circuit), which are processors with a circuit configuration designed specifically for performing specific processes.

[0232] A single processing unit may be configured with one of these various processors, or may be configured with a combination of two or more processors of the same or different types (for example, a combination of multiple FPGAs and / or a combination of a CPU and an FPGA). Also, multiple processing units may be configured with a single processor.

[0233] An example of configuring multiple processing units with one processor is a form in which one processor is configured by combining one or more CPUs and software, and this processor functions as multiple processing units. Secondly, there is a form in which a processor is used that realizes the functions of the entire system including multiple processing units with a single IC (Integrated Circuit) chip, as typified by a System on Chip (SoC). In this way, various processing units are configured using one or more of the above various processors as a hardware structure.

[0234] Furthermore, more specifically, the hardware structure of these various processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0235] In the above embodiment, the presence or absence of a change in the color development state of the test area L1 of the carrier 2 provided in the cartridge 100 is determined by determining whether or not a line is generated by gold colloid, which is a label captured in the test area L1, or by amplifying the captured gold colloid with silver ions. The change in the color development state of the test area L1 of the carrier 2 is not limited to the generation of a line by gold colloid or by amplifying the gold colloid with silver ions. For example, the label may be an enzyme label that generates chemiluminescence when contacted with a luminescent reagent, and the line may be generated by the chemiluminescence generated when the enzyme label captured in the test area L1 reacts with the luminescent reagent. Alternatively, the label may be a fluorescent label, and the line may be generated by the fluorescence generated by irradiating the fluorescent label captured in the test area L1 with excitation light.

[0236] The disclosures of Japanese Patent Application No. 2021-050779, filed on March 24, 2021, and Japanese Patent Application No. 2022-046013, filed on March 22, 2022, are incorporated herein by reference in their entireties. All publications, patent applications, and technical standards mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent application, or technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. An immunochromatography testing device, a loading section in which a cartridge having a carrier having a spotting area where a sample is spotted and a test area where a color development state changes depending on whether the sample is positive or negative is removably loaded; an imaging unit that images the inspection area; a processor that performs a primary determination of whether the sample is positive or negative based on the inspection area image of the inspection area captured by the imaging unit, When a direction in which the specimen is developed on the carrier is defined as a row direction and a direction intersecting the row direction is defined as a column direction, the test region is a linear region extending along the column direction, the inspection area image is an image in which a plurality of pixels are two-dimensionally arranged in a matrix, The processor performs the main judgment using remaining pixels obtained by excluding one or more high-density pixels having relatively high densities in each column of the inspection area image.

2. The immunochromatographic testing device according to claim 1 , wherein the processor selects, as the high-density pixels, a plurality of pixels in each of the columns that are ranked in a predetermined order from the pixel with the highest density.

3. The immunochromatographic testing device according to claim 2 , wherein the number of pixels selected as the high-density pixels is the same in each of the columns.

4. The immunochromatographic testing device according to claim 1 , wherein the processor derives a representative value for each of the columns using the remaining pixels, and performs the main judgment using the derived representative value for each of the columns.

5. 5. The immunochromatographic testing device according to claim 4, wherein the processor derives, as the representative value for each of the columns, a pixel value of one pixel selected from the remaining pixels in each of the columns according to a preset criterion, or an average value of pixel values ​​of two or more pixels selected from the remaining pixels in each of the columns according to a preset criterion.

6. the imaging unit is an image sensor that captures an image of an observation area including the inspection area, and outputs an observation image including the observation area, the observed image is an image in which a plurality of pixels are two-dimensionally arranged in a matrix, 6. The immunochromatographic testing device according to claim 4, wherein the processor creates a profile in the row direction based on a representative value of each column in the observation image, and extracts an examination area profile corresponding to the examination area from the created profile, or extracts the examination area image corresponding to the examination area from the observation image based on the profile.

7. the processor divides the inspection area image into a plurality of areas extending in the row direction, derives an average value or a median value of each column in the area, the average value or median value being an average value or median value using at least a portion of a plurality of pixels included in each column, and creates an area profile in the row direction for each of the areas using the derived average value or median value; The immunochromatographic testing device according to claim 6, wherein, in the main judgment, a condition judgment process is executed using the area profile derived for each of the areas.

8. The processor: As the condition determination process, at least one of first to third condition determination processes is executed to determine whether or not a value derived based on the area profile satisfies a preset condition, and if at least one condition is not satisfied in the executed condition determination process, the sample is determined to be negative, and if all conditions are satisfied in the executed condition determination process, the sample is determined to be positive; the first condition determination process is a condition determination process that uses a differentiated area profile obtained by differentiating the area profile for each of the areas, derives, for each of the areas, positions in the row direction showing a maximum local maximum value in the differentiated area profile, derives a standard deviation of the derived positions in the row direction, and determines whether or not a first condition is satisfied that the standard deviation is less than a predetermined first threshold value; the second condition determination process is a condition determination process that adds up the differential area profiles for the respective areas, derives a difference between a maximum local maximum value in the added differential area profile and an average value of local maximum values ​​other than the maximum local maximum value, and determines whether or not a second condition is satisfied that the difference is greater than a predetermined second threshold value; 8. The immunochromatographic testing device according to claim 7, wherein the third condition determination process is a condition determination process that adds up the area profiles for each of the areas and determines whether a value at a predetermined position in the row direction in the added area profile satisfies a third condition that the value is greater than a third threshold value.

9. The immunochromatographic testing device according to claim 8 , wherein the processor executes all of the first condition determination process, the second condition determination process, and the third condition determination process as the condition determination process.

10. The processor: In the main judgment, if a maximum position, which is a position in the row direction showing a maximum concentration in the inspection area profile, is located in either of the end ranges of the inspection area profile, the sample is judged to be negative; If the maximum position is not located in either of the end regions, deriving a center position in the row direction of the inspection area and a width of the inspection area that are determined based on the maximum density and the maximum position; executes a pre-condition determination process for determining whether or not a pre-determination condition is satisfied, that is, whether the maximum density is equal to or greater than a fourth threshold value set in advance, and whether the center position and the width are within respective ranges set in advance; 10. The immunochromatographic testing device according to claim 7, wherein the sample is determined to be negative when the pre-determination condition is not satisfied, and the condition determination process is executed when the pre-determination condition is satisfied.

11. The processor:

11. The immunochromatographic testing device according to claim 10, wherein, in the main judgment, when it is judged in the pre-condition judgment process that the pre-judgment condition is satisfied, it is judged whether or not the maximum concentration is equal to or greater than a preset fifth threshold value that is greater than the fourth threshold value before executing the condition judgment process, and when the maximum concentration is equal to or greater than the fifth threshold value, the sample is judged to be positive, and when the maximum concentration is smaller than the fifth threshold value, the condition judgment process is executed.

12. the processor performs an abnormality determination for determining the presence or absence of an abnormality in the inspection area image, using at least one of the following as a determination index: a difference between a relatively large pixel value and a relatively small pixel value in at least one column in the inspection area image; a standard deviation and a coefficient of variation of pixel values ​​of pixels included in the at least one column; or a difference between a relatively large representative value and a relatively small representative value among representative values ​​of each row derived based on a plurality of pixels existing in the same row but different columns in the inspection area image; and a standard deviation and a coefficient of variation of the representative values ​​of the each row; The immunochromatographic testing device according to claim 1 , wherein the content of processing related to the main judgment is determined based on the presence or absence of the abnormality.

13. The immunochromatographic testing device according to claim 12, wherein the processing content includes either a decision as to whether or not to perform the main judgment, and a method for presenting the judgment result of the main judgment.

14. The immunochromatographic testing device according to claim 13 , wherein the processor performs the main judgment and presents the judgment result of the main judgment when the abnormality is not present, and does not perform the main judgment when the abnormality is present.

15. The immunochromatographic testing device according to claim 14 , wherein, when the main determination is not performed, the processor displays a message to the effect that the main determination will not be performed.

16. The immunochromatographic testing device according to claim 13 or 14, wherein the processor indicates, when the abnormality is detected, that there is a possibility that the testing area is soiled.

17. 14. The immunochromatographic testing device according to claim 13, wherein the processor presents a determination result of the main determination when no abnormality is found, and presents the determination result of the main determination with a reservation that there is an abnormality in the test area image when the abnormality is found and the determination result of the main determination is positive, or does not present the determination result of the main determination.

18. The immunochromatographic testing device according to claim 17 , wherein the processor performs the main determination and, if the determination result is positive, performs the abnormality determination.

19. 14. The immunochromatographic testing device according to claim 13, wherein the processor presents a determination result of the main determination when no abnormality is found, and presents a determination result of the main determination with a reservation that an abnormality is found in the inspection area image when the abnormality is found, or does not present a determination result of the main determination.

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