Immunochromatographic test strip testing device and testing method, and test system

Abstract

The present invention provides a small device capable of detecting, in a short period of time with a simple operation, fine metal particles that are a labeling substance in an immunochromatographic test strip. The immunochromatographic test strip test device 100 according to the present invention comprises at least: 1) an electron gun 110 that emits electron beams B to an immunochromatographic test strip TS; 2) a detector 120 that detects reflected electrons or secondary electrons from the fine metal particles, generated through irradiation of the immunochromatographic test strip TS with the electron beams B emitted from the electron gun 110; 3) a sample test space 130 that can accommodate the detector 120 and a portion to be tested of the immunochromatographic test strip TS, and that is configured to be adjustable to a degree of vacuum of at most 100 pascals during testing of the immunochromatographic test strip TS; and 4) a specimen holder 140 for introducing the immunochromatographic test strip into the sample test space 130 from the outside of the device that is under the atmospheric pressure condition.

Description

Immunochromatographic test strip testing device, testing method, and testing system

[0001] The present invention relates to an inspection device, an inspection method, and an inspection system for immunochromatographic test strips, and more particularly to an apparatus, a detection method, and a detection system used for detecting a target substance by immunochromatography.

[0002] In order to prevent the spread of infectious diseases caused by pathogens such as bacteria and viruses, early detection and treatment of infection are important, and highly sensitive detection of pathogens is required. Conventionally, culture methods, PCR methods, LAMP methods, ELISA methods, immunochromatography methods, etc. have been used to confirm the diagnosis of infectious diseases.

[0003] Culture methods require a very long time to determine results and can only detect pathogens that are expected in advance. PCR methods can also only detect pathogens that are expected in advance, and a negative result does not necessarily deny the presence of the pathogen. While PCR enables highly sensitive detection by repeatedly amplifying DNA, the need for repeated amplification reactions carries the risk of false positive results due to contamination from positive controls. Furthermore, PCR is more cumbersome to operate than immunochromatography and requires a long time (approximately 5 to 6 hours) to determine the results. Loop-mediated isothermal amplification (LAMP) uses a different primer design from PCR, allowing for a single-step process from DNA amplification to detection. However, like PCR, it is more cumbersome to operate than immunochromatography. ELISA can detect pathogens (antigens) in samples using antibodies against the pathogens, and is faster than PCR and LAMP, but it may result in false positive results due to nonspecific antigen-antibody reactions. Both of these techniques still carry the risk of false positive or false negative results.

[0004] Immunochromatography is currently being implemented in society as a diagnostic aid for various diseases, primarily influenza viruses. Its principle utilizes antigen-antibody reactions, and its simplicity and effectiveness have led to its widespread use in medical settings. Another advantage of immunochromatography is that it can detect a wide range of targets, including not only antigens produced by viruses and bacteria, but also antibodies produced in the human body, tumor-associated proteins, chemical substances such as narcotics, and allergens and chemicals that can cause food and chemical allergies. However, a common drawback of immunochromatography is that its sensitivity is not as high as PCR, meaning that it cannot diagnose infection unless a certain level of virus (pathogen) proliferation has occurred within the patient's body. Furthermore, while immunochromatography can determine whether a test is positive or negative with the naked eye, it has the drawback of making it difficult to quantify the results (e.g., to measure the number of viruses).

[0005] Various methods have been proposed to address the problems and drawbacks of immunochromatography. For example, in a system that combines immunochromatography with a compact densitometry analyzer, densitometry allows for quantitative determination. However, the measurement sensitivity of the detection section (test line) is often poor, making it difficult to achieve high sensitivity. Furthermore, it has been reported that densitometry may be inappropriate for some types of specimens (see Patent Document 1).

[0006] Patent Document 2 proposes amplifying the signal of a gold label by using gold microparticles containing a predetermined amount of silver as a detection label. Although the high sensitivity achieved by silver sensitization as described in Patent Document 2 is more sensitive than conventional methods, the silver sensitization step is involved, which makes the result determination unstable and dependent on the sensitization reaction. Furthermore, signal amplification involving a sensitization step, not limited to silver, merely makes it easier to visually confirm the antigen-antibody reaction on an immunochromatographic test strip, and does not achieve the level of sensitivity expected in practice.

[0007] In response to this potential problem of improving the sensitivity of immunochromatography, the present inventors considered detecting metal microparticles, which are labeling substances in immunochromatographic test strips, using a scanning electron microscope, and discovered that applying an auxiliary liquid (NanoSuit (registered trademark) liquid) that assists observation with a scanning electron microscope to an immunochromatographic test strip makes it possible to successfully detect metal microparticles with a scanning electron microscope, as reported in Non-Patent Document 1. Non-Patent Document 1 states that by detecting metal microparticles, which are labeling substances in an immunochromatographic test strip, using a scanning electron microscope, influenza viruses can be detected with detection sensitivity substantially equivalent to that of the PCR method.

[0008] However, the method using an existing scanning electron microscope as shown in Non-Patent Document 1 raises concerns about its practical use for determining the presence or absence of a viral infection, due to the complicated operation and the long time required for the examination. Furthermore, scanning electron microscopes are generally large, making it difficult to install them in medical institutions, particularly clinics, where viral infections and the like are diagnosed.

[0009] In other words, in order to use immunochromatography for highly sensitive diagnosis using the method proposed in Non-Patent Document 1, it was desirable to develop a small, versatile device that could detect metal microparticles (target substances) with simpler operation and in a shorter time.

[0010] JP 2000-338106 A JP 2009-192224 A JP 2020-031051 A JP 2010-257995 A

[0011] H. Kawasaki et al., Combination of the NanoSuit method and gold / platinum particle-based lateral flow assay for quantitative and highly sensitive diagnosis using a desktop scanning electron microscope, Journal of Pharmaceutical and Biomedical Analysis, 196 (2021) 113924.

[0012] The present invention aims to detect metal microparticles, which are labeled substances in immunochromatographic test strips, with simple operation and in a short time using a small device.Technically, it is intended to provide a device used for detecting targets by immunochromatography that applies the principles of a scanning electron microscope, to provide a method for detecting targets by immunochromatography using said device, and to provide a system for detecting targets by immunochromatography that includes said device as a component.

[0013] As a result of extensive research by the present inventors, it has become possible to solve the above-mentioned problems by an inspection device, an inspection method, and an inspection system having the following aspects.

[0014] (1) An inspection device for immunochromatographic test strips using metal fine particles as a labeling substance by immunochromatography, comprising at least the following 1) to 4): 1) an electron gun unit that irradiates the immunochromatographic test strip with an electron beam, 2) a detector unit that detects backscattered electrons or secondary electrons from the metal fine particles generated when the immunochromatographic test strip is irradiated with an electron beam emitted from the electron gun unit of 1), 3) a sample inspection space that can accommodate the detector unit of 2) and the test portion of the immunochromatographic test strip and is configured so that it can be adjusted to a vacuum of 100 Pa or less when inspecting the immunochromatographic test strip, and 4) a specimen holder for introducing the immunochromatographic test strip from atmospheric pressure conditions outside the device into the sample inspection space of 3). (2) An inspection device for immunochromatographic test strips according to (1), characterized in that the volume of the sample inspection space of 3) after the immunochromatographic test strip is introduced by the specimen holder of 4) is 300 cubic centimeters or less. (3) The sample testing space of 3) is 10 －２An inspection device for immunochromatographic test strips according to (1) or (2), characterized in that it is configured to be adjustable to a degree of vacuum of not less than 10 Pascals. (4) An inspection device for immunochromatographic test strips according to any of (1) to (3), characterized in that the specimen holder of (4) is movable, and the bottom of the sample inspection space of (3) can be opened by movement of the specimen holder of (4). (5) An inspection device for immunochromatographic test strips according to any of (1) to (4), characterized in that it further comprises a vacuum interruption mechanism configured to be able to maintain the degree of vacuum within the electron gun unit of (1) by spatially interrupting the space between the electron gun unit of (1) and the sample inspection space of (3). (6) In the vacuum interruption mechanism, the detector section of 2) is movable, and when the detector section of 2) is positioned on the optical path of the electron beam emitted from the electron gun section of 1), the electron gun section of 1) and the sample inspection space of 3) are spatially isolated from each other, and when the space formed in the detector section of 2) is positioned on the optical path of the electron beam emitted from the electron gun section of 1), the electron gun section of 1) and the sample inspection space of 3) are spatially isolated from each other. (7) In the vacuum interruption mechanism, the detector section of 2) is movable and includes a vacuum interruption member attached to the detector section of 2), and the vacuum interruption member is positioned on the optical path of the electron beam emitted from the electron gun section of 1), thereby spatially interrupting the electron gun section of 1) and the specimen inspection space of 3), and the space formed in the detector section of 2) is positioned on the optical path of the electron beam emitted from the electron gun section of 1), thereby spatially opening the electron gun section of 1) and the specimen inspection space of 3). (8) In the electron gun section of 1), the electron beam generation section is set to 10 －２An inspection device for immunochromatographic test strips according to any one of (1) to (4), characterized in that it is placed in a vacuum tube adjusted to a vacuum of 1 Pa or less. (9) An inspection device for immunochromatographic test strips according to any one of (1) to (8), characterized in that the electron beam generating part of the electron gun part of 1) is of thermionic emission type. (10) An inspection device for immunochromatographic test strips according to 3), characterized in that the sample inspection space of 3) is in a state before the introduction of the immunochromatographic test strip. ４(11) An immunochromatographic test strip inspection device according to any one of (1) to (9), characterized in that it is adjusted to a pressure of 1 Pa or less. (11) An immunochromatographic test strip inspection method using the inspection device according to any one of (1) to (10), characterized in that an aqueous solution of at least one type of surfactant compound is applied to the inspection area of ​​the immunochromatographic test strip before electron beam irradiation. Here, the surfactant compound has the property of polymerizing upon electron beam irradiation to form a coating on the upper surface of the inspection area of ​​the immunochromatographic test strip. (12) An immunochromatographic test strip inspection device according to any one of (1) to (10), for use in the inspection method according to (11). (13) An immunochromatographic test strip inspection device according to (12), characterized in that it has a mechanism and parts for applying the aqueous solution of the surfactant compound to the inspection area of ​​the immunochromatographic test strip. (14) An inspection device for immunochromatographic test strips according to (12) or (13), characterized in that the sample inspection space of the above 3) is provided with an inner wall member, and scattered electrons generated by irradiating the immunochromatographic test strip with an electron beam emitted from the electron gun unit of the above 1) are configured to be collected in a predetermined space within the sample inspection space of the above 3). (15) An inspection system for immunochromatographic test strips comprising the inspection device for immunochromatographic test strips according to any of (1) to (10) and (12) to (14), and an analyzer, wherein the analyzer comprises a control unit that controls the operation of at least the electron gun unit of the above 1), the detector unit of the above 2), the sample inspection space of the above 3), and the specimen holder of the above 4) of the inspection device, an image acquisition unit that acquires image information obtained by the detector unit of the above 2) of the inspection device, a data processing unit that processes data from the control unit and the image acquisition unit, and an output unit that outputs the processing results of the data processing unit, and analyzes the state of the inspection area of ​​the immunochromatographic test strip.

[0015] According to the present invention, an immunochromatographic test strip can be introduced into the sample testing space of a small testing device with simple operations, and the detection of the target metal microparticles by immunochromatography, i.e., the presence or absence of the target virus, etc. can be quickly performed.

[0016] Specifically, the immunochromatographic test strip testing device according to the above aspect (1) includes components 1), 2), and 3) that constitute a conventional scanning electron microscope. The combined use of the specimen holder of component 4) allows for the miniaturization of the testing device and simplification of the target object detection operation. Such specimen holders are often referred to as "sample holders" in the field of electron microscope design. For example, Patent Document 3 describes a specimen holder in which a minute specimen to be observed is placed at the tip of a rod and can be operated from outside the device. Patent Document 4 also proposes the structure of a compact electron microscope with a specimen holder of a different shape. However, no component (specimen holder) for introducing an immunochromatographic test strip into the specimen chamber of an electron microscope has been known to date. Generally, samples to be introduced into the sample chamber of an electron microscope using the above-described sample holder are extremely small. Introducing relatively large samples (typically about 3 to 8 centimeters in length, 3 to 2 centimeters in width, and 1 to 5 millimeters in thickness) such as the immunochromatographic test strips targeted by the present invention into the sample chamber of an electron microscope using a dedicated sample holder is completely unknown and has not been proposed to date. For special applications, there is a critical dimension scanning electron microscope (CD-SEM) for measuring the dimensions of fine patterns formed on semiconductor wafers. While CD-SEMs are equipped with a dedicated transport device for semiconductor wafers, CD-SEMs are typically designed to transport semiconductor wafers stored in advance under vacuum to the measurement area, and their design concept is fundamentally different from that of the inspection device of the present invention, in which the test object is introduced into the sample inspection space from atmospheric pressure outside the inspection device. No device with a mechanism for introducing industrially useful test strips or the like into the sample chamber of an electron microscope from atmospheric pressure outside the device using a holder dedicated to the test strip is known, and the configuration of an inspection device for immunochromatographic test strips equipped with such a mechanism is unique.

[0017] Schematic diagrams showing the configuration of an immunochromatographic test strip testing device according to one embodiment of the present invention. Schematic diagrams showing an example of a configuration in which the electron beam generating unit of the electron gun unit is arranged inside a vacuum tube in the testing device shown in Figure 1. (a) to (c) Schematic diagrams showing one embodiment of a mechanism for opening and closing the sample testing space using a sample holder in the testing device shown in Figure 1. (a) to (c) Schematic diagrams showing another embodiment of a mechanism for opening and closing the sample testing space using a sample holder. Schematic diagrams showing the shape of the sample holder in the testing device shown in Figure 1. (a) Side view, (b) top view, (c) schematic side view showing one embodiment of a sample holder combining a substantially rectangular structure and a ring-shaped structure, and (d) schematic top view of the embodiment shown in (c). Schematic diagrams showing the shape of the sample holder in an embodiment in which the external shape of the sample holder is rod-shaped. (a) Side view, (b) top view, (c) schematic side view showing one embodiment of a sample holder combining a rod-shaped structure and a ring-shaped structure, and (d) schematic top view of the embodiment shown in (c). Schematic diagrams showing the shape of a sample holder in an embodiment where the external shape of the sample holder is plate-shaped. (a) Side view, (b) Top view. Schematic diagrams showing the shape of a sample holder in an embodiment where the external shape of the sample holder is disk-shaped. (a) Side view, (b) Top view. (a) to (f) Schematic diagrams showing exemplary modes of fixing immunochromatographic test strips in the sample holder. (a) to (c) Schematic diagrams showing examples where attachment parts are provided on the sample holder, and the attachment parts are compatible with multiple types of immunochromatographic test strips. (a) and (b) Schematic diagrams showing one embodiment of a vacuum interruption mechanism in the testing device shown in Figure 1. (a) and (b) Schematic diagrams showing another embodiment of a vacuum interruption mechanism in the testing device shown in Figure 1. (a) Schematic diagram showing an embodiment where an inner wall member is provided in the sample testing space in the testing device shown in Figure 1. (b) Enlarged view of a main part of (a). 1. (a) and (b) are schematic diagrams showing an embodiment in which an auxiliary liquid supply unit is provided in the sample testing space in the testing device shown in FIG. 1. A block diagram showing the configuration of an testing system for immunochromatographic test strips according to one embodiment of the present invention. A photographic image showing the appearance of a testing device for immunochromatographic test strips prototyped in an observation example.(a) A state in which the target immunochromatographic test strip has been introduced into the sample testing space, (b) A state in which the target immunochromatographic test strip has been moved from the sample testing space to the outside of the testing device by moving the specimen holder. Observation images of immunochromatographic test strips observed using the testing device shown in Figure 16.

[0018] Hereinafter, embodiments of the present invention will be described. The following description of the components may be based on a representative embodiment of the present invention, but the present invention is not limited to such an embodiment.

[0019] An immunochromatographic test strip testing device according to one embodiment of the present invention (hereinafter also simply referred to as the "test device of the present invention") comprises configurations 1) to 4) of the above aspect (1). That is, the test device of the present invention is a device that uses metal microparticles as a labeling substance by immunochromatography, comprising at least the following 1) to 4): 1) an electron gun unit that irradiates an electron beam onto the immunochromatographic test strip; 2) a detector unit that detects backscattered electrons or secondary electrons from the metal microparticles generated when the immunochromatographic test strip is irradiated with an electron beam emitted from the electron gun unit of 1); 3) a sample testing space that can accommodate the detector unit of 2) and the test portion of the immunochromatographic test strip and is configured so that it can be adjusted to a vacuum of 100 Pa or less during testing of the immunochromatographic test strip; and 4) a specimen holder for introducing the immunochromatographic test strip from atmospheric pressure conditions outside the device into the sample testing space of 3).

[0020] The testing device of the present invention has the sample testing space described in 3) above, but it is desirable that the volume (space volume) of the sample testing space be small in order to shorten the time required to adjust the sample testing space to a vacuum and / or to reduce the burden on the vacuum pump (vacuum exhaust means) and simplify the structure of the vacuum pump. Here, the space volume means the volume obtained by subtracting the occupied volume when the sample holder described in 4) above is introduced into the testing space from the volume of the testing device's testing space (the space into which the immunochromatographic test strip to be tested is introduced during testing of the immunochromatographic test strip; sample testing space), and this volume is preferably 1000 cubic centimeters or less, more preferably 500 cubic centimeters or less, and most preferably 300 cubic centimeters or less.

[0021] A preferred embodiment of the testing device of the present invention includes a mechanism (vacuum interruption mechanism) having a movable member between the electron gun unit (1) and the sample testing space (3), which maintains the vacuum level of the electron gun unit (1) regardless of changes in the vacuum level of the sample testing space (3) during operation of the specimen holder (4). By providing a vacuum interruption mechanism, even if the sample testing space (3) temporarily reaches atmospheric pressure during immunochromatographic test strip replacement, the electron gun unit (1) maintains a predetermined vacuum level, thereby shortening the time required to achieve a predetermined vacuum level in the sample testing space (3) at the start of testing. This movable vacuum interruption mechanism is opened when an immunochromatographic test strip is introduced into the sample testing space (3) and testing begins, so that the electron beam emitted from the electron gun unit is irradiated onto the test area of ​​the immunochromatographic test strip. Therefore, the components constituting the vacuum interruption mechanism may be made of a material that is not electron beam transparent. However, the vacuum interruption mechanism may also be made of a material that is electron beam transparent.

[0022] The sample testing space is evacuated by a vacuum pump (vacuum exhaust means) during testing of the immunochromatographic test strip, and the degree of vacuum is preferably 1000 Pa or less, more preferably 100 Pa or less. On the other hand, if the degree of vacuum is too high, it may cause problems in testing the immunochromatographic test strip, so the preferred degree of vacuum is 10 －４Pascal or more, more preferably 10 －２ The range of the vacuum degree of the sample inspection space in the present invention is 10 －４ Preferably, the pressure is 10 Pa or more and 1000 Pa or less, more preferably 10 －２ Pascal or more and 100 Pascal or less, more preferably 10 －２ Above pascal and below 10 pascal.

[0023] In the testing device of the present invention, it is preferable that the electron gun unit of the above 1) is adjusted to a vacuum before testing the immunochromatographic test strip, separately from the sample testing space of the above 3). This allows for more rapid testing of the immunochromatographic test strip. In this case, the vacuum degree of the electron gun unit is 10 －２ Pascal or less is preferred, and 10 －４ It is below Pascal.

[0024] In order to achieve such a vacuum level in the electron gun section, a vacuum pump may be used to adjust the electron gun section to a vacuum before testing the immunochromatographic test strip, and the above-mentioned vacuum interruption mechanism may be further provided to make it possible to maintain the desired vacuum level, or the electron beam generating section of the electron gun section may be placed in a vacuum tube that has been adjusted to the above-mentioned vacuum level in advance.

[0025] In the inspection device of the present invention, the user may prepare and use a vacuum pump, or the vacuum pump may be provided in advance as an accessory part of the inspection device.

[0026] In the inspection device of the present invention, any type of electron beam generator can be used for the electron gun. Typically, electron beam generators for electron guns are broadly classified into field emission type, Schottky type, and thermionic emission type. Of these, the use of thermionic emission type is preferred for the inspection device of the present invention in terms of miniaturization of the entire device.

[0027] In the test device of the present invention, any method may be used to detect metal particles in the immunochromatographic test strip, and may generally be a backscattered electron mode, a secondary electron mode, or a fluorescent X-ray detection method, which are detection methods used in electron microscopes. Of these, a backscattered electron mode or a secondary electron mode is preferred for the test device of the present invention. That is, in the test device of the present invention, the detector unit in 2) above is preferably a backscattered electron detector or a secondary electron detector.

[0028] Any method for introducing the immunochromatographic test strip into the sample testing space may be used, including, for example, i) a mechanism for using a rod-shaped specimen holder to insert the specimen holder from the side of the testing device to introduce the immunochromatographic test strip into the sample testing space, ii) a mechanism for using a plate-shaped or disk-shaped specimen holder to allow multiple immunochromatographic test strips to be placed on the specimen holder and for introducing the immunochromatographic strips into the sample testing space by sliding or rotating the specimen holder, and iii) a mechanism for introducing the immunochromatographic test strip into the sample testing space by opening and closing the specimen holder (back cover) from below (the bottom) of the sample testing space, in which the specimen holder forms the bottom of the sample testing space. Of these, mechanisms i) and ii) can be cited as preferred embodiments that make it easy to maintain the vacuum in the sample testing space. Moreover, by adopting a structure that utilizes the principle of differential evacuation for adjusting the degree of vacuum in the sample inspection space and the electron gun section, it is also possible to apply the method iii).

[0029] Furthermore, in order to provide compatibility with the various shapes and sizes of immunochromatographic test strips currently in use, it is also preferable that the sample holder has a structure having a basic component and attachment components corresponding to the shape of each immunochromatographic test strip. In this case, the sample holder is configured to be able to hold various immunochromatographic test strips of various widths and lengths, and the attachment components are preferably adjustable to adjust the gap that may occur between the sample holder and each individual immunochromatographic test strip so that the test area of ​​the immunochromatographic test strip is always positioned at the irradiation site of the electron beam emitted from the electron gun (hereinafter simply referred to as the electron beam irradiation site).

[0030] In addition, in the testing device of the present invention, an operating mechanism (a position adjustment mechanism such as an XY table) for adjusting the position of the test area of ​​the immunochromatographic test strip so that it is located at the electron beam irradiation site may be provided in the sample testing space 3), or the specimen holder 4) may be equipped with the operating mechanism.Of these, it is preferable that an operating mechanism that can adjust the position of the immunochromatographic test strip including the specimen holder 4) be provided in the sample testing space 3).

[0031] To make this position adjustment mechanism more effective, the testing device of the present invention is also preferably equipped with a mechanism for recognizing the position of the test area of ​​the immunochromatographic test strip by any means. Specific examples of position recognition methods using this mechanism are described below. However, the position recognition methods that can be used with the testing device of the present invention are not limited to the following specific examples. (Example of Position Recognition (1)) Immunochromatographic test strips currently in practical use usually have printed or textured marks on their exterior parts so that the position of the test area can be identified. The position of the immunochromatographic test strip (including the sample holder) is recognized by reading these marks as images of backscattered electrons or secondary electrons. (Example of Position Recognition Method (2)) The test area of ​​the immunochromatographic test strip to be tested is previously marked with textured or painted marks that can be identified as images of backscattered electrons or secondary electrons, and the test area is accurately identified by reading these marks. (Example of Position Recognition Method (3)) An optical camera mechanism is installed within the testing device, and the marks on the exterior parts of the immunochromatographic test strip are read, and the position of the test area is recognized using these marks. (Example of position recognition method (4)) An optical camera mechanism is placed inside the testing device, the position of the control line on the immunochromatographic test strip is read, and the position of the test area is recognized using this as a mark. (Example of position recognition method (5)) A mark that can be identified as an optical image is attached in advance to the test area of ​​the immunochromatographic test strip to be tested, and by reading this, the test area is identified and read as an image of reflected electrons or secondary electrons. Of these, examples (2), (4), and (5) are cited as preferred methods of position recognition to be adopted in the testing device of the present invention.

[0032] Furthermore, the testing device of the present invention is used to detect metal particles in an immunochromatographic test strip, and may be configured to increase the contrast ratio with the background fibers (nitrocellulose, etc.) in the backscattered electron image or secondary electron image obtained by the detector unit. For example, the angle at which the electron beam is irradiated onto the immunochromatographic test strip is preferably perpendicular to the top surface of the immunochromatographic test strip, but depending on the structure and material of the immunochromatographic test strip, it may be easier to detect metal particles if the incident angle of the electron beam is tilted within a range of 10° to 45° from the perpendicular.

[0033] In the inspection device of the present invention, from the viewpoint of simplifying the mechanism and miniaturizing the device, it is also preferable to fix the distance (working distance) between the objective lens located at the end of the electron gun unit and the test area of ​​the immunochromatographic test strip, and the distance from the test area of ​​the immunochromatographic test strip to the detector unit (backscattered electron detector or secondary electron detector). In conventional electron microscopes, the distance between the test area and the objective lens or electron detector is variable to enable observation of the sample at various magnifications. However, in the inspection device of the present invention, a fixed distance is preferable in terms of simplifying the device design. However, this does not eliminate the need for a mechanism that allows fine adjustment of the distance to adjust the focus when detecting metal microparticles, even if the observation magnification is not actively changed during inspection of the immunochromatographic test strip.

[0034] Any immunochromatographic test strip can be used in the test device of the present invention. A typical immunochromatographic test strip has a membrane component that serves as a flow path for the lateral flow method inside a plastic housing. Since the internal volume of the plastic housing including this membrane component is included in the volume when adjusting the sample testing space of the test device of the present invention to a vacuum in step 3) above, it is preferable that the internal volume of the plastic housing including the membrane component be small, specifically 3 cubic centimeters or less, more preferably 2 cubic centimeters or less, and more preferably 1 cubic centimeter or less.

[0035] When testing an immunochromatographic test strip using the testing device of the present invention, it is preferable to use an auxiliary liquid such as that shown in Non-Patent Document 1.

[0036] The auxiliary liquid applicable to the immunochromatographic test strip testing method using the testing device of the present invention improves the clarity of the results (analysis image) output by data processing of image information obtained by the detector unit, and by applying this auxiliary liquid, an analysis image with high contrast can be obtained in the testing of the immunochromatographic test strip. In one aspect of the auxiliary liquid, the auxiliary liquid has the property of becoming conductive under the testing conditions and / or the property of polymerizing to form a coating by electron beam irradiation under the testing conditions, thereby making it possible to efficiently obtain the above-mentioned effects.

[0037] That is, the auxiliary liquid improves the clarity of the analytical image when testing an immunochromatographic test strip using the testing device of the present invention. The auxiliary liquid preferably has the property of being conductive under the test conditions and / or of polymerizing to form a coating upon electron beam irradiation under the test conditions. More specifically, the auxiliary liquid contains, as essential components, at least one surface-active compound selected from glycerin and glycerin substitutes; polysorbates such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, and polysorbate 85; and polysorbate substitutes, and optionally contains at least one compound selected from monosaccharides, disaccharides, salts, and buffer solutions.

[0038] Glycerin is a trihydric alcohol (so-called polyhydric alcohol), has a hydroxyl group in the molecule, and is a low vapor pressure substance. Glycerin also has viscosity. Substances with these characteristics can be included in the auxiliary liquid as alternatives to glycerin. Specific examples of glycerin alternatives include polyethylene glycol, polyvinyl alcohol, triglyceride, polyresorcinol, polyphenols, tannic acid, urushiol, and saponin. Glycerin and glycerin alternatives may be used alone or in combination of two or more.

[0039] As used herein, the term "polysorbates" refers to those prepared by reacting sorbitan fatty acid esters (nonionic surfactants) with ethylene oxide. Currently available polysorbates include polysorbate 20 (Tween 20), polysorbate 40 (Tween 40), polysorbate 60 (Tween 60), polysorbate 65 (Tween 65), polysorbate 80 (Tween 80), and polysorbate 85 (Tween 85), but the polysorbates that can be included in the auxiliary liquid are not limited to these. Furthermore, substances classified as nonionic surfactants, like polysorbates, can be included in the auxiliary liquid as alternative components to polysorbates. Specific examples of polysorbate substitutes include polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, polyoxyethylene monofatty acid esters, sucrose fatty acid esters, polyglycerin fatty acid esters, alkyl polyglycosides, N-methyl alkyl glucamides, etc. Polysorbates and polysorbate substitutes may be used alone or in combination of two or more.

[0040] Examples of monosaccharides include glucose and fructose. Examples of disaccharides include sucrose and trehalose. Examples of salts include imidazolium salts, pyridinium salts, piperidinium salts, pyrrolidinium salts, and quaternary ammonium salts. Examples of buffer solutions include acetate buffer (acetic acid / sodium acetate buffer), phosphate buffer (phosphoric acid / sodium phosphate buffer), citrate buffer (citric acid / sodium citrate buffer), citrate phosphate buffer (citric acid / sodium phosphate buffer), borate buffer, tartaric acid buffer, and Tris buffer. These monosaccharides, disaccharides, salts, and buffer solutions may be used alone or in combination of two or more.

[0041] The essential component consisting of at least one compound selected from glycerin, a glycerin substitute, polysorbates, and polysorbate substitutes is preferably contained in the auxiliary liquid in an amount of 0.01 to 10% by weight, more preferably 0.1 to 2% by weight.

[0042] A preferred embodiment of the testing device of the present invention is that it is equipped with an auxiliary liquid supply unit that supplies the above-mentioned auxiliary liquid to the immunochromatographic test strip. For example, a preferred embodiment is one that is equipped with a nozzle and a solution storage unit like the ink cartridges used in inkjet printers, and ejects an appropriate amount of auxiliary liquid into the test area of ​​the immunochromatographic test strip before the test. The auxiliary liquid may be supplied so that it permeates the entire membrane of the immunochromatographic test strip, or it may be supplied only to the test area, i.e., only to the area that captures reflected electrons or secondary electrons from metal fine particles generated by irradiating the electron beam and acquires image information.

[0043] The amount of auxiliary liquid supplied per test is preferably 100 microliters or less, more preferably 30 microliters, and when the auxiliary liquid is supplied only to the area to be tested, the amount is preferably 10 microliters or less, more preferably 1 microliter or less. As a mechanism that enables the ejection of such small amounts of auxiliary liquid, for example, a method that provides a piezo element in the auxiliary liquid supply section and utilizes the deformation of the piezo element due to the application of voltage can be used.

[0044] By applying the above-mentioned auxiliary liquid, good testing of immunochromatographic test strips using the test device of the present invention is possible, but in order to further improve the clarity of the test results (analysis images), it is also preferable that the test device of the present invention be provided with an electrical grounding part for the membrane part, which enables electrical conduction between the membrane part of the immunochromatographic test strip and any of the metal parts that make up the test device.

[0045] Particularly preferred embodiments of the testing device of the present invention include the following: A testing device for immunochromatographic test strips using metal fine particles as a labeling substance by immunochromatography, comprising at least the following 1) to 4), wherein the sample holder in 4) below has either i) a rod-shaped (rod-like) external shape and a mechanism for introducing the immunochromatographic test strip into the sample testing space in 3) below from the side of the testing device, ii) a plate-shaped (flat) or disk-shaped (disc-like) external shape and a mechanism for introducing the immunochromatographic strip into the sample testing space in 3) below by sliding or rotating the sample holder, or iii) a structure in which the sample holder forms the bottom of the sample testing space, and a mechanism for introducing the immunochromatographic test strip into the sample testing space by opening and closing the sample holder (back cover) from below (the bottom) of the sample testing space, and these have a structure including attachment parts configured to allow the use of various immunochromatographic test strips, The volume of the sample testing space in 3) below is 300 cubic centimeters or less, and the sample testing space is 10 －２The electron beam generating section of the electron gun section described below in 1) is a space that is adjusted to a vacuum of 10 Pa to 10 Pa. －２ A thermionic emission type device arranged in a vacuum tube adjusted to 100 Pascal or less, having an auxiliary liquid supply unit that automatically supplies auxiliary liquid to the test portion of the immunochromatographic test strip, and analyzing image information acquired by the detector unit in 2) below with artificial intelligence (AI) to provide the number of metal microparticles or any physical quantity correlated to the number of metal microparticles as an output: 1) an electron gun unit that irradiates the immunochromatographic test strip with an electron beam; 2) a detector unit that detects backscattered electrons or secondary electrons from the metal microparticles generated when the immunochromatographic test strip is irradiated with the electron beam emitted from the electron gun in 1); 3) a sample testing space that can accommodate the detector unit in 2) and the test portion of the immunochromatographic test strip and is configured to be adjustable to a vacuum of 100 Pascal or less when testing the immunochromatographic test strip; and 4) a specimen holder for introducing the immunochromatographic test strip from atmospheric pressure conditions outside the device into the sample testing space in 3).

[0046] In the present invention, the principle of immunochromatography and the method for detecting a target substance are not particularly limited. A typical embodiment is immunochromatography using a labeled antibody carrying metal fine particles as a labeling substance and a capture antibody that has the property of binding to a complex between the labeled antibody and the target substance. However, it should be noted that the specific embodiment of immunochromatography in the present invention is not limited to this.

[0047] The number of metal microparticles can be measured visually using the testing device of the present invention. Alternatively, the number of metal microparticles can be measured automatically using image processing technology. For example, a method (commonly referred to as pattern recognition) can be used to determine whether a microparticle is a metal microparticle based on image features such as the shape and size of the metal microparticles contained in the immunochromatographic test strip or the size, contour shape, brightness ratio to the surrounding area, and frequency characteristics of the brightness information of the metal microparticle image that appears in the analysis image. Alternatively, the number of metal microparticles can be measured using an image recognition system using machine learning or deep learning. An automated analysis system can also be used to identify metal microparticles by using artificial intelligence to identify them in the analysis image. Among these, pattern recognition methods using image features such as the frequency characteristics, size, and contour shape of the brightness information of the metal microparticle image, or methods using artificial intelligence, are preferred.

[0048] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings, but the present invention is not limited to the scope of the following embodiments.

[0049] [Immunochromatographic Test Strip Inspection Device] FIG. 1 is a schematic diagram showing the configuration of an immunochromatographic test strip inspection device according to one embodiment of the present invention.

[0050] As shown in FIG. 1, the immunochromatographic test strip testing device 100 of this embodiment (hereinafter also simply referred to as testing device 100) comprises an electron gun unit 110, a detector unit 120, a sample testing space 130, and a specimen holder 140.

[0051] 1) Electron Gun Unit The electron gun unit 110 irradiates an electron beam B onto the immunochromatographic test strip TS to be inspected.

[0052] Specifically, the electron gun unit 110 has a housing 111, inside which an electron beam generator (electron gun) 112 is disposed. An objective lens 113 is disposed at the lower end of the housing 111. An electron beam B emitted from the electron beam generator 112 passes through electron optical components, such as condenser lenses 114a and 114b, a condenser aperture 115, and a deflection coil 116, provided within the housing 111, and is irradiated via the objective lens 113 onto the immunochromatographic test strip TS (more specifically, onto the test area of ​​the immunochromatographic test strip TS (a portion where metal fine particles serving as a labeling substance are present, such as a test line and a control line)). The configuration and arrangement of the electron optical system (group of electron optical components) within the housing 111 shown in FIG. 1 are merely exemplary, and the configuration and arrangement of the electron optical system in a general electron microscope can be appropriately adopted.

[0053] Furthermore, a vacuum exhaust means 150a is attached to the housing 111, and is capable of adjusting the interior of the housing 111 to a predetermined vacuum level by exhausting air in the direction of the arrow. The vacuum exhaust means 150a is composed of a vacuum pump.

[0054] A small hole (orifice) is provided between the electron gun section 110 and the specimen inspection space 130 to provide a narrow path for the flow of gas molecules, utilizing the principle of differential evacuation. The diameter of the orifice is preferably 1 μm to several hundred μm.

[0055] 1, an orifice 117 for differential evacuation is formed in (at the bottom of) the objective lens 113. When the specimen inspection space 130 is opened to atmospheric pressure, a vacuum interruption mechanism (described later) is provided between the objective lens 113 and the electron gun unit 110.

[0056] Generally, the effect of differential pumping increases if the number of orifices is increased, but in the inspection device 100 shown in Fig. 1, the orifice 117 also functions as a diaphragm through which the electron beam B passes, so multiple orifices may be provided as long as they can accurately pass the electron beam B. However, as shown in Fig. 1, even if there is only one orifice, the effect of differential pumping can be sufficiently obtained.

[0057] As described above, in the inspection device 100, the electron beam generating unit 112 may be placed in a vacuum tube that has been adjusted to a predetermined vacuum level in advance. Fig. 2 is a schematic diagram showing the configuration of the inspection device 100 in this mode.

[0058] In the embodiment shown in FIG. 2, the electron beam generating unit 112 is －２ The inspection device 100 is provided inside a vacuum tube 118 adjusted to a vacuum level of 0.1 Pa or less. This allows the vacuum exhaust means 150a to be omitted in the inspection device 100 shown in FIG. 2, thereby further simplifying the configuration required for operation of the inspection device. Note that other configurations may be similar to those shown in FIG. 1, and the same applies to various modified examples described below. Therefore, the following description of each component will be made solely with reference to the inspection device 100 shown in FIG. 1.

[0059] 2) Detector Section The detector section 120 detects reflected electrons or secondary electrons from metal particles generated when the immunochromatographic test strip TS is irradiated with the electron beam B emitted from the electron gun section 110 .

[0060] In the inspection device 100 shown in Fig. 1, the detector unit 120 is a backscattered electron detector 120A, which is provided below the objective lens 113. In Fig. 1, the black circle shown below the objective lens 113 is a sealing material (O-ring).

[0061] Here, in the inspection device 100, the detector unit 120 may be composed of one type of detector, or may be composed of a combination of multiple types of detectors. Specifically, the detector unit 120 may be either or both of a backscattered electron detector and a secondary electron detector, and may further be combined with an X-ray fluorescence detector. Note that when the detector unit 120 is composed of a combination of multiple types of detectors, their arrangement (specifically, their positional relationship with the objective lens 113, their positional relationship with each other, etc.) can be appropriately designed by a person skilled in the art.

[0062] 3) Sample Inspection Space The sample inspection space 130 is capable of accommodating the detector section 120 and the inspected portion of the immunochromatographic test strip TS, and is configured so that it can be adjusted to a vacuum level of 100 Pa or less when inspecting the immunochromatographic test strip TS.

[0063] 1, the sample testing space 130 is formed by being roughly surrounded by the opposing sidewall members 160, the lower bottom surface of the electron gun unit 110, and the upper surface of the sample holder 140, and accommodates the objective lens 113, the detector unit 120, and the immunochromatographic test strip TS fixed to the sample holder 140. In the testing device 100 shown in FIG. 1, the upper surface of the immunochromatographic test strip TS fixed to the sample holder 140 and the upper surface of the sample holder 140 form approximately the same plane, but in this specification, as long as the test portion of the immunochromatographic test strip TS faces the inside of the sample testing space 130, such an embodiment will also be treated as the sample testing space 130 accommodating the immunochromatographic test strip TS (the test portion of the immunochromatographic test strip TS).

[0064] Furthermore, a vacuum exhaust means 150b is attached to the side wall member 160, and by exhausting air in the direction of the arrow, the sample testing space 130 can be adjusted to a vacuum level of 100 Pa or less when testing the immunochromatographic test strip TS. The vacuum exhaust means 150b is composed of a vacuum pump.

[0065] 4) Sample Holder The sample holder 140 is used to introduce the immunochromatographic test strip TS from the atmospheric pressure conditions outside the testing device 100 into the sample testing space 130 .

[0066] Specifically, in the testing device 100 shown in Fig. 1, the sample holder 140 has a substantially rectangular shape in side view and a recess formed at any position on the top surface, in which an immunochromatographic test strip TS can be fixed. In the testing device 100 shown in Fig. 1, the width (left-right length) of the sample holder 140 in side view is shown to be approximately the same as the length to both side ends of the opposing sidewall members 160, but it should be noted that the shape and size of the sample holder 140 and the manner in which the immunochromatographic test strip TS is fixed to the sample holder 140 are not limited to this. Details will be described later.

[0067] During testing of the immunochromatographic test strip TS, the specimen holder 140 seals the sample testing space 130 by contacting the lower bottom surface of the sidewall member 160. Here, by providing a seal portion 160a on the lower bottom surface of the sidewall member 160, the above-mentioned sealed state is more reliably maintained, and therefore, adjustment of the degree of vacuum in the sample testing space 130 by the vacuum exhaust means 150b is more easily ensured.

[0068] On the other hand, when testing of the immunochromatographic test strip TS is completed and when the immunochromatographic test strip TS is replaced, the specimen holder 140 is released from contact with the lower bottom surface of the side wall member 160. That is, in the testing device 100, the specimen holder 140 is movable, and the bottom of the sample testing space 130 can be opened by the movement of the specimen holder 140. In other words, one of the features of the testing device 100 is that the bottom of the specimen testing space 130 is openable and closable, and when testing of the immunochromatographic test strip TS is completed and when the immunochromatographic test strip TS is replaced, the specimen testing space 130 becomes an atmospheric atmosphere.

[0069] <Mechanism for Opening and Closing the Sample Testing Space by the Sample Holder> Here, the mechanism for opening and closing the sample testing space 130 by the sample holder 140 will be described with reference to FIGS. 3 and 4. FIG.

[0070] FIG. 3( a ) is a schematic diagram showing the state in which the sample inspection space 130 is closed, and the specimen holder 140 makes the sample inspection space 130 airtight by contacting the lower bottom surface of the opposing side wall member 160 .

[0071] 3(b) is a schematic diagram showing a state in which the sample testing space 130 is opened, and the sample holder 140 is moved in the direction of the arrow (X direction) from the state shown in FIG. 3(a) to open the bottom of the sample testing space 130. Naturally, the sample holder 140 may be moved in the opposite direction (leftward) or in the Y direction (through the paper surface of FIG. 3).

[0072] Here, the movement of the specimen holder 140 may be solely in the X direction (left-right direction) or the Y direction, or may be a combination of the Z direction (up-down direction) and the X direction, as shown in FIG. 3( c). A variation of the latter may be a combination of the Z direction and the Y direction, or a combination of the Z direction and the X direction with movement in the Y direction. Note that although a mechanism for enabling movement of the specimen holder 140 is omitted in FIGS. 3( a) to 3( c), the configuration and arrangement of such a mechanism can be appropriately designed by a person skilled in the art. For example, a convex portion (or concave portion) having a predetermined shape may be provided at any position on the side of the specimen holder 140, so that the user can grip the convex portion (or concave portion) to move the specimen holder 140 in the desired direction.

[0073] 4(a) to 4(c) are schematic diagrams showing another embodiment of the opening and closing mechanism of the sample testing space 130 using the sample holder 140. In this embodiment, a support member 161 is provided on the side end surface (the end surface opposite the sample testing space 130) of the sidewall member 160, and the support member 161 has a rotation shaft 161a. Naturally, the support member 161 may be disposed on the left side of the sample testing space 130. In addition, the sample holder 140 is a structure having a connection portion 140a into which the rotation shaft 161a can be fitted, and is configured to be rotatable about the rotation shaft 161a when the rotation shaft 161a is fitted into the connection portion 140a.

[0074] FIG. 4( a ) is a schematic diagram showing the state in which the sample inspection space 130 is closed, and the specimen holder 140 makes the sample inspection space 130 airtight by contacting the lower bottom surface of the opposing side wall member 160 .

[0075] Figure 4(b) is a schematic diagram showing the state in which the sample inspection space 130 is open, and the specimen holder 140 rotates downward from the state shown in Figure 4(a) around the pivot shaft portion 161a of the support member 161 as a fulcrum, thereby opening the bottom of the sample inspection space 130.

[0076] In this embodiment, in the sample holder 140, the portion including the fixing portion of the immunochromatographic test strip TS and the portion including the connecting portion 140a connected to the pivot shaft portion 161a of the support member 161 may be integrally configured as shown in Figures 4(a) and (b), or may be configured as separate structures 141, 142 connected by any connecting means as shown in Figure 4(c).

[0077] <Modifications of the Structure of the Specimen Holder> Next, the structure of the specimen holder 140 and modifications thereof will be described with reference to FIGS.

[0078] 5(a) and 5(b) are schematic diagrams showing the side and top views, respectively, of the shape of the specimen holder 140 in the inspection device 100 shown in Fig. 1. In Fig. 5(b), a rectangular frame F indicated by a dashed line schematically shows the portion where the end face of the sidewall member 160 is located when the specimen inspection space 130 is closed. The same applies to Figs. 6(b), 7(b), and 8(b), which will be described later.

[0079] 5(a) and (b), the specimen holder 140 has a substantially rectangular external shape, and in that sense, it can be said to be similar in shape to the specimen table (specimen stage) used in conventional electron microscopes. Meanwhile, in conventional electron microscopes, the specimen table is usually configured to be able to move in a plane (X, Y), move in the vertical direction (Z), and also tilt (T) and rotate (R) the specimen placed thereon. However, since the testing device 100 of this embodiment is solely intended to test immunochromatographic test strips TS, complex operations of the specimen holder 140 are not required, and it is sufficient if a relatively simple combination of movements in the X, Y, and Z directions is possible.

[0080] Therefore, one of the features of the testing device 100 is the high degree of freedom in the structure of the sample holder 140. Specifically, the outer shape of the sample holder 140 may be the generally rectangular shape described above, or may be rod-shaped, plate-shaped, disk-shaped, or the like. Alternatively, a structure having the above shape may be used as a portion including the fixing portion of the immunochromatographic test strip TS, and this may be combined with another structure to form a sample holder 140 consisting of multiple structures. Figures 5(c) and (d) are schematic diagrams showing an example of the latter embodiment.

[0081] The sample holder 140 shown in Figures 5(c) and (d) is composed of a structure 141, which is a portion including a fixing portion for the immunochromatographic test strip TS, and a ring-shaped structure 143 configured so that the structure 141 can be inserted therein. For ease of understanding, the bottom of the structure 143 is not depicted in Figure 5(d), but as shown in Figure 5(c), the bottom of the structure 143 is closed and the top is open. Here, the structure 141 has the same configuration as the sample holder 140 described with reference to Figures 5(a) and (b). In this modification, the structure 143 constitutes the main body of the sample holder 140, and during testing of the immunochromatographic test strip TS, the top surface of the structure 143 comes into contact with the lower bottom surface of the sidewall member 160, sealing the sample testing space 130. Therefore, in this modification, the sidewall member 160 is disposed so as to surround the housing 111 of the electron gun unit 110 or to conform to the shape of the structure 143 at the bottom of the housing 111. As a result, when the sample testing space 130 is closed, the portion where the end face of the sidewall member 160 is located is schematically shown as a circular frame F' indicated by a dashed line in FIG. 5( d ). Comparing the frame F' shown in FIG. 5( d ) with the frame F shown in FIG. 5( b ), the frame F' is wider, but it is possible to set the volume (space volume) of the sample testing space 130 within the preferred range described above. In an observation example described later, a prototype specimen holder 140 employing the configuration of this modification was fabricated, and immunochromatographic test strips were observed. As a result, it was confirmed that the sample testing space could be evacuated in a short time using a vacuum pump (vacuum exhaust means) with a simple structure.

[0082] 5(c) and 5(d), the sample holder 140 has a structure 141, which is a portion including a fixing portion for the immunochromatographic test strip TS, separate from the structure 143 that constitutes the main body of the sample holder 140, and therefore has the advantage that it is relatively easy to further provide a position adjustment mechanism such as the X-Y table described above. Specifically, for example, a base (stage portion) of the X-Y table is provided inside the structure 143 and below the structure 141, and two drive members that enable movement of this base in the X direction (the longitudinal direction of the structure 141) and the Y direction (the lateral direction of the structure 141) are provided so as to penetrate the side of the structure 143 and extend to the outside of the structure 143. By making these two drive members drivable by a drive means such as a motor, the position of the structure 143 that forms the bottom of the sample inspection space 130 can be maintained while adjusting the position of the structure 141 in the X and Y directions by operating the XY table, and the position of the inspection portion of the immunochromatographic test strip TS can be adjusted to be located at the electron beam irradiation site.

[0083] 6A and 6B are schematic diagrams showing the side and top views of the specimen holder 140 in an embodiment in which the specimen holder 140 has a rod-like external shape.

[0084] In the embodiment shown in Figures 6(a) and (b), the specimen holder 140 is longer in the X direction than the embodiment shown in Figures 5(a) and (b), and a recess for fixing the immunochromatographic test strip TS is formed on one end side (right side) of the specimen holder 140 rather than the center.

[0085] In the specimen holder 140 of this embodiment, as shown by the double-headed arrow in Figure 6 (b), the specimen holder 140 operates mainly in the X direction, which is suitable for opening and closing the sample testing space 130 and replacing the immunochromatographic test strip TS, etc. Of course, the movement of the specimen holder 140 is not limited to the X direction, and movement in the Y direction and Z direction may be combined.

[0086] Alternatively, a modified example of this embodiment may have the configuration shown in Figures 6(c) and (d). The sample holder 140 shown in Figures 6(c) and (d) is composed of a structure 141, which is a portion including a fixing portion for the immunochromatographic test strip TS, and a ring-shaped structure 143 configured so that the structure 141 can be inserted therein. For ease of understanding, the bottom of the structure 143 is not depicted in Figure 6(d). However, as shown in Figure 6(c), the bottom of the structure 143 is closed and the top is open. Here, the configuration of the structure 141 is the same as that of the sample holder 140 described with reference to Figures 6(a) and (b). In this modified example, the structure 143 constitutes the main body of the sample holder 140, and during testing of the immunochromatographic test strip TS, the top surface of the structure 143 comes into contact with the lower bottom surface of the sidewall member 160, sealing the sample testing space 130. Therefore, in this modification, the sidewall member 160 is disposed so as to surround the housing 111 of the electron gun unit 110, or so as to fit the shape of the structure 143 below the housing 111. As a result, when the specimen inspection space 130 is closed, the portion where the end face of the sidewall member 160 is located is schematically shown as a circular frame F' indicated by a dashed line in Fig. 6(d) . Note that, when the frame F' shown in Fig. 6(d) is compared with the frame F shown in Fig. 6(b) , the frame F' is wider, but it is possible to set the volume (space volume) of the specimen inspection space 130 within the above-mentioned preferred range.

[0087] 7A and 7B are schematic diagrams showing the side and top views of the specimen holder 140 in an embodiment in which the specimen holder 140 has a plate-like external shape.

[0088] In the embodiment shown in Figures 7(a) and (b), the specimen holder 140 is longer in the Y direction than the embodiment shown in Figures 6(a) and (b), and has multiple recesses (five in the example) formed on one end side (right side) of the specimen holder 140 for fixing the immunochromatographic test strip TS.

[0089] In the specimen holder 140 of this embodiment, as shown by the double-headed arrow in Figure 7(b), by moving the specimen holder 140 in the Y direction (or by fixing the position of the specimen holder 140 and making members such as the electron gun unit 110 and the side wall member 160 movable), it is possible to inspect multiple immunochromatographic test strips TS fixed to one specimen holder 140. Furthermore, when opening and closing the sample inspection space 130, and when replacing the immunochromatographic test strips TS, the specimen holder 140 can be operated by appropriately combining movements in the X direction, Y direction, and Z direction.

[0090] In this way, the inspection device 100 can use a specimen holder 140 that is larger in length in the X direction and / or Y direction than the specimen stage used in conventional electron microscopes.

[0091] 8A and 8B are schematic diagrams showing the side and top views of the specimen holder 140 in an embodiment in which the outer shape of the specimen holder 140 is disk-shaped.

[0092] In the embodiment shown in Figures 8(a) and (b), the sample holder 140 has multiple recesses (eight in this example) formed radially from its center for fixing the immunochromatographic test strips TS.

[0093] In the specimen holder 140 of this embodiment, as shown by the double-headed arrow in Figure 8 (b), by rotating the specimen holder 140 in the XY plane (or by fixing the position of the specimen holder 140 and making members such as the electron gun unit 110 and side wall member 160 movable (rotating)), it is possible to inspect multiple immunochromatographic test strips TS fixed to one specimen holder 140. Furthermore, when opening and closing the sample inspection space 130 and when replacing the immunochromatographic test strips TS, the specimen holder 140 can be operated by appropriately combining movements in the X direction, Y direction, and Z direction.

[0094] Note that the manner in which the immunochromatographic test strip TS is fixed in the specimen holder 140 is not limited to the above-described manner and can be modified in various ways. For example, when describing a specimen holder 140 having a rod-shaped external shape (see FIGS. 6(a) and 6(b)), examples of modifications shown in FIGS. 9(a) to 9(f) can be given.

[0095] In the embodiment shown in Figure 9(a), similar to that shown in Figure 6(a), the immunochromatographic test strip TS is fixed in a recess formed in the sample holder 140, and the upper surface of the sample holder 140 and the upper surface of the immunochromatographic test strip TS form approximately the same plane.

[0096] 9(b), the depth of the recess formed in the sample holder 140 is smaller than the height of the immunochromatographic test strip TS, and when the immunochromatographic test strip TS is fixed, a portion of the immunochromatographic test strip TS protrudes above the upper surface of the sample holder 140. In this embodiment, when the sample holder 140 is housed inside the sample testing space 130, the volume of the sample testing space 130 is reduced by the volume corresponding to the portion of the immunochromatographic test strip TS protruding above the upper surface of the sample holder 140.

[0097] In the embodiment shown in Figure 9(c), the immunochromatographic test strip TS is placed on the upper surface of the sample holder 140. As described above, the testing device 100 of this embodiment does not require complex operations for the sample holder 140, so a format like this can also be adopted. However, in order to prevent the immunochromatographic test strip TS from unintentionally shifting from its predetermined position on the sample holder 140 or falling off the sample holder 140 when testing the immunochromatographic test strip TS or when replacing the immunochromatographic test strip TS, it is more preferable to provide any fixing means such as an attachment part 144, as shown in Figure 9(d), and fix the immunochromatographic test strip TS to the attachment part 144.

[0098] Furthermore, when an attachment part 144 such as that shown in Figure 9(d) is provided on the sample holder 140, the upper surfaces of the attachment part 144 and the immunochromatographic test strip TS fixed thereto may be made to be approximately flush, as shown in Figure 9(e), or as shown in Figure 9(f), the attachment part 144 may be fitted into a recess formed in the sample holder 140, and when the immunochromatographic test strip TS is fixed to the attachment part 144, a portion of the immunochromatographic test strip TS may protrude beyond the upper surface of the attachment part 144 (the upper surface of the sample holder 140).

[0099] Furthermore, in an embodiment in which the specimen holder 140 is provided with an attachment part 144, the attachment part 144 may be compatible with one type of immunochromatographic test strip, or may be compatible with multiple types of immunochromatographic test strips. Figures 10(a) to 10(c) are schematic diagrams showing the configuration of the latter embodiment.

[0100] In the embodiment shown in Figures 10(a) to 10(c), the attachment part 144 provided on the sample holder 140 is compatible with three immunochromatographic test strips TS1, TS2, and TS3 having different external dimensions. Here, the attachment part 144 is adjustable so that the positions of the test areas M1, M2, and M3 (typically test lines) are approximately the same when each immunochromatographic test strip TS1 to TS3 is fixed. This is conceptually shown by a dashed rectangular frame P in Figures 10(a) to 10(c). This reduces the effort required to change the design of the sample holder 140 or change the settings of the testing device 100 during testing depending on the external dimensions of the immunochromatographic test strips to be tested, thereby further improving the efficiency of testing immunochromatographic test strips.

[0101] <Vacuum Breakdown Mechanism> Here, the differential pumping system and the vacuum breakdown mechanism in the inspection apparatus 100 of this embodiment will be described with reference to FIG. 1, FIG. 11 and FIG.

[0102] 1, the orifice 117 for differential evacuation is formed inside (at the bottom of) the objective lens 113. In conventional differential evacuation systems, an electron beam transparent film (e.g., a collodion film) that can withstand a vacuum and is transparent to electron beams is attached to this orifice, but in the inspection device 100 of this embodiment, such an electron beam transparent film is not an essential component.

[0103] 11A and 11B are schematic diagrams showing one embodiment of a vacuum interruption mechanism in the inspection device 100. FIG.

[0104] 11( a) and 11(b), the backscattered electron detector 120A is attached to a position control means 121, and the position control means 121 is configured to be able to move the backscattered electron detector 120A in the left-right direction by moving it in the X direction. Furthermore, the backscattered electron detector 120A has, at a predetermined position corresponding to the orifice 117, a space 122 through which the electron beam B can pass.

[0105] In this embodiment, as shown in Figure 11 (a), when the sample testing space 130 is in a closed state, the space 122 is on the optical path (downward arrow) of the electron beam B, making it possible to irradiate the electron beam B onto the immunochromatographic test strip TS.

[0106] 11(b), when the specimen inspection space 130 is in an open state, the position control means 121 moves in the direction of the arrow to change the position of the backscattered electron detector 120A, and the backscattered electron detector 120A is positioned on the optical path of the electron beam B (in other words, the orifice 117 is closed by the upper surface of the backscattered electron detector 120A), thereby spatially isolating the electron gun unit 110 from the specimen inspection space 130. This makes it possible to maintain the degree of vacuum within the housing 111 of the electron gun unit 110.

[0107] Then, when the specimen testing space 130 is returned from the open state to the closed state, the specimen testing space 130 can be evacuated (pre-evacuated) while the position of the backscattered electron detector 120A remains as shown in FIG. 11B. This allows the specimen testing space 130 to be brought to a desired vacuum level (or a vacuum level substantially equivalent thereto) in a short time while maintaining the vacuum level inside the housing 111 of the electron gun unit 110. Thereafter, when testing the immunochromatographic test strip TS, the position of the backscattered electron detector 120A is set to the state shown in FIG. 11A, thereby ensuring an optical path for the electron beam B emitted from the electron beam generator 112 of the electron gun unit 110, and the electron beam B is irradiated onto the immunochromatographic test strip TS.

[0108] The configuration of the position control means 121 and the mechanism for changing the position of the backscattered electron detector 120A in this embodiment are not limited to the embodiments shown in FIGS. 11( a) and 11(b), and a person skilled in the art can make appropriate design changes.

[0109] 12(a) and 12(b) are schematic diagrams showing another embodiment of the vacuum interruption mechanism in the inspection device 100. FIG.

[0110] 12(a) and 12(b), the backscattered electron detector 120A is attached to a position control means 121 via a vacuum interrupter 170, and the position control means 121 is configured to be able to move the backscattered electron detector 120A in the left-right direction by moving it in the X direction. In addition, the objective lens 113 is provided with a housing member 171 configured to be able to house the backscattered electron detector 120A on the side opposite to the side on which the vacuum interrupter 170 is located.

[0111] In this embodiment, as shown in Figure 12(a), when the sample inspection space 130 is in a closed state, the space 122 of the backscattered electron detector 120A is on the optical path (downward arrow) of the electron beam B, making it possible to irradiate the electron beam B onto the immunochromatographic test strip TS.

[0112] 12(b), when the specimen inspection space 130 is in an open state, the position control means 121 moves in the direction of the arrow to change the position of the backscattered electron detector 120A, and the backscattered electron detector 120A is housed in the housing member 171, and the vacuum interrupter member 170 is positioned on the optical path of the electron beam B (in other words, the orifice 117 is closed by the upper surface of the vacuum interrupter member 170), thereby spatially isolating the electron gun unit 110 from the specimen inspection space 130. This makes it possible to maintain the degree of vacuum within the housing 111 of the electron gun unit 110.

[0113] Then, when the specimen testing space 130 is returned from the open state to the closed state again, evacuation (preliminary evacuation) of the specimen testing space 130 can be performed with the backscattered electron detector 120A still housed in the housing member 171 (the state shown in FIG. 12(b)). As a result, in this embodiment, the specimen testing space 130 can be brought to a desired vacuum level (or a vacuum level substantially equivalent thereto) in a short time while maintaining the vacuum level inside the housing 111 of the electron gun unit 110. In addition, contamination of the backscattered electron detector 120A and / or the orifice 117 by debris (e.g., debris resulting from moisture or the like contained in the test portion of the immunochromatographic test strip TS) that may be generated from the immunochromatographic test strip TS during preliminarily evacuation can be suppressed.

[0114] In this regard, in the embodiment shown in Fig. 11, if the above-mentioned scattered matter is generated during pre-evacuation, although it can suppress contamination of the orifice 117, there is a possibility that the scattered matter will adhere to the surface (underside) of the backscattered electron detector 120A. In this way, when the immunochromatographic test strip TS (especially the test portion thereof) to be tested is not (or may be) in a sufficiently dry state to the extent that some scattered matter will not be generated in the process of being exposed from atmospheric pressure conditions to vacuum conditions, it is more preferable to adopt the embodiment shown in Fig. 12 as the vacuum interruption mechanism.

[0115] The configurations of the position control means 121, the vacuum interrupter 170, and the housing member 171 in this embodiment, and the mechanism for changing the position of the backscattered electron detector 120A and accommodating the backscattered electron detector 120A in the housing member 171 are not limited to the embodiments shown in FIGS. 12( a) and 12(b), and a person skilled in the art can make appropriate design changes.

[0116] <Inner Wall Member> In addition, in the testing device 100, an inner wall member may be provided in the sample testing space 130 so that scattering of electrons (scattered electrons) generated when the immunochromatographic test strip TS is irradiated with the electron beam B is collected in a predetermined space within the sample testing space 130. Figures 13(a) and 13(b) are schematic diagrams showing a configuration example of this aspect.

[0117] 13(a) and 13(b), the inner wall member 180 is disposed so as to surround both ends of the backscattered electron detector 120A provided below the objective lens 113. Furthermore, the inner wall member 180 is disposed so as to be inclined from its upper end to its lower end, so that scattered electrons SE are collected in a space including the upper surface of the test portion of the immunochromatographic test strip TS, as indicated by multiple arrows in the enlarged view of the main part in FIG. 13(b). This allows the brightness (luminosity) of the obtained image information (analysis image) to be improved compared to conventional electron microscopes (e.g., tabletop scanning electron microscopes).

[0118] More specifically, when the backscattered electron detector 120A is a semiconductor type (a detector made of semiconductor crystal), the backscattered electron detector 120A detects electrons having an energy equal to or higher than a certain level (for example, 2 to 3 kV or higher) and does not react to electrons having an energy lower than that level. Therefore, by providing the inner wall member 180, the backscattered electron detector 120A can capture more electrons having an energy equal to or higher than that certain level, thereby increasing the brightness of the obtained image information.

[0119] In contrast to this, conventional electron microscopes employ a method of discriminating based on the energy and scattering angle of electrons in order to increase resolution, contrary to the idea of ​​providing the above-mentioned inner wall member 180. However, with this discrimination method, there is a concern that the brightness of the image information obtained is relatively low.

[0120] In order to take advantage of its compact size, the inspection device 100 of the present invention uses an arrangement of the inner wall member 180 that is completely different from the concept of the electronic discrimination method, thereby increasing the brightness of the image information and thus the contrast between the background and the metal particles to be detected. As a result, it is possible to achieve improved detection sensitivity and improved accuracy of the judgment results.

[0121] There are no particular restrictions on the material of the inner wall member 180, but from the viewpoint of making it easier to generate more scattered electrons, it is preferable that it be made of an element with a relatively large atomic weight, such as Au (gold), or that the surface (the surface facing the immunochromatographic test strip) be coated with such an element.

[0122] In addition, the inner wall member 180 may be configured to be movable within the sample inspection space 130 by any moving means (not shown), and when the electron beam B is not being irradiated, such as before or after the inspection, it can be retracted to a position that does not interfere with various operations (manipulations) of the inspection device 100.

[0123] <Auxiliary Liquid Supply Unit> Here, the configuration of arranging the above-described inner wall member 180 can be more effective in an aspect in which the above-described auxiliary liquid is applied. That is, in a space in which the condition in which scattered electrons SE are more likely to be generated by providing the inner wall member 180 in the sample testing space 130, the formation of a coating on the test portion of the immunochromatographic test strip TS to which the auxiliary liquid is applied can proceed more efficiently.

[0124] 14(a) and (b) are schematic diagrams showing an embodiment in which an auxiliary liquid supply unit is provided in the sample testing space 130 in the testing device 100.

[0125] The auxiliary liquid supply unit 190 shown in Figures 14(a) and (b) has a mechanism and components for applying auxiliary liquid (the aqueous solution of the surfactant compound described above) to the test portion of the immunochromatographic test strip TS. Specifically, as shown in the enlarged view of the main part on the right side of Figure 14(a), the auxiliary liquid supply unit 190 includes a nozzle portion 191 and a solution storage portion 192, and is configured to eject a predetermined amount of auxiliary liquid NS stored in the solution storage portion 192 from the nozzle portion 191 by utilizing deformation of the piezoelectric element 193 due to application of a voltage to the piezoelectric element 193, thereby applying the auxiliary liquid NS to the test portion of the immunochromatographic test strip TS. As described above, the configuration of such an auxiliary liquid supply unit can be a configuration used in inkjet printers, and those skilled in the art can make appropriate design modifications, etc.

[0126] Furthermore, the auxiliary liquid supply unit 190 is configured to be movable within the sample testing space 130 by any moving means, as shown by the double-headed arrow in Figure 14 (b), and when applying the auxiliary liquid NS (before the test), the nozzle portion 191 is aligned with the test portion of the immunochromatographic test strip TS, and after applying the auxiliary liquid NS (during the test), it can be retracted to a position that does not obstruct the optical path of the electron beam B irradiated onto the immunochromatographic test strip TS.

[0127] It should be noted that in an embodiment in which the testing device 100 is provided with an auxiliary liquid supply unit, it is not essential that the auxiliary liquid supply unit be provided within the sample testing space 130. For example, the auxiliary liquid supply unit may be provided outside the sample testing space 130. In this case, the auxiliary liquid supply unit has a mechanism and components for applying the auxiliary liquid NS to the test portion of the immunochromatographic test strip TS on the sample holder 140 before the immunochromatographic test strip TS is introduced into the sample testing space 130.

[0128] <Other Modifications> In the testing device 100 according to the above-described embodiment, the bottom of the sample testing space 130 can be opened by the operation of the sample holder 140. However, a pre-evacuation space may be provided separately from the sample testing space 130. In this embodiment, the sample holder 140 is not in contact with the lower bottom surface of the sidewall member 160, and a pre-evacuation space for inserting and removing the sample holder 140 is provided at any position on the sidewall member 160. The sample holder 140, with the immunochromatographic test strip TS to be tested fixed therein, is inserted into the sample testing space 130 through a portion (also referred to as a gate valve) that communicates with the sample testing space 130 from the pre-evacuation space, thereby introducing the immunochromatographic test strip TS into the sample testing space 130. Note that the method for adjusting the vacuum level of the sample testing space 130 and the pre-evacuation space in this embodiment, as well as the device configuration for doing so, can be those used in conventional electron microscopes and can be designed appropriately by a person skilled in the art.

[0129] Furthermore, in the inspection device 100 according to the above-described embodiment, it is desirable to fix the distance (working distance) between the objective lens 113 located at the end of the electron gun unit 110 and the test area of ​​the immunochromatographic test strip TS at a constant value in terms of simplifying the mechanism and miniaturizing the device. However, a mechanism that enables fine adjustment of the distance to adjust the focus when detecting metal microparticles (labeled substances) (e.g., a mechanism that enables movement (fine movement) of the immunochromatographic test strip TS in the X and Y directions during inspection) may be provided. Alternatively, a mechanism that assists in opening and closing the bottom of the sample inspection space 130 by the operation of the specimen holder 140 (e.g., a mechanism that assists in contact and release between the specimen holder 140 and the lower bottom surface of the sidewall member 160) may be provided.

[0130] [Immunochromatographic Test Strip Inspection System] FIG. 15 is a block diagram showing the configuration of an immunochromatographic test strip inspection system according to one embodiment of the present invention.

[0131] As shown in FIG. 15, the immunochromatographic test strip testing system 300 of this embodiment includes a testing device 100 and an analysis device 200.

[0132] As the inspection device 100, the inspection device 100 of this embodiment described with reference to FIGS. 1 to 14 can be used.

[0133] The analysis device 200 includes a control unit 210 , an image acquisition unit 220 , a data processing unit 230 , and an output unit 240 .

[0134] The control unit 210 controls the operations of at least the electron gun unit 110, the detector unit 120, the specimen inspection space 130, and the specimen holder 140 of the inspection device 100. Information (data) related to the control of the inspection device 100 by the control unit 210 can be transmitted to the data processing unit 230.

[0135] The image acquisition unit 220 acquires image information obtained by the detector unit 120 of the inspection device 100. The image information (image data) acquired by the image acquisition unit 220 can be transmitted to the data processing unit 230.

[0136] The data processing unit 230 processes the data from the control unit 210 and the image acquisition unit 220 and is capable of transmitting the processing results to the output unit 240 .

[0137] The output unit 240 outputs the processing results of the data processing unit 230. For example, a liquid crystal display device, a printer, etc. may be used as the output unit 240. Note that the output unit 240 may also be a recording device that records the processing results of the data processing unit 230 on a recording medium such as a USB memory.

[0138] The condition of the test portion of the immunochromatographic test strip TS is analyzed by the test system 300 having such a configuration. Here, detection of metal microparticles, which are the labeled substance in the immunochromatographic test strip TS, may be performed by displaying an image of the test portion of the immunochromatographic test strip TS on the output unit 240 and visually counting the number of metal microparticles in the image, or by displaying an image of the test portion of the immunochromatographic test strip TS on the output unit 240 and using artificial intelligence to identify the metal microparticles in the image, thereby outputting the number of metal microparticles or any physical quantity correlated to the number of metal microparticles.

[0139] In particular, in the latter case, the user attaches and detaches the immunochromatographic test strip TS to and from the sample holder 140 of the testing device 100, replaces the immunochromatographic test strip TS, and starts the analysis device 200, whereby the testing system 300 becomes an automatic analysis system that automatically measures the metal particles in the immunochromatographic test strip TS using artificial intelligence. Furthermore, by combining such a testing system 300 with an industrial robot or the like that is currently in practical use, it may be possible to create an immunochromatographic test strip testing system in which the user only needs to place the immunochromatographic test strip TS in a predetermined location, with the other operations being automated.

[0140] [Example of Observation of Immunochromatographic Test Strip] A prototype testing device for immunochromatographic test strips having the configuration described with reference to FIG. 1 was produced, and the test area was observed using a commercially available immunochromatographic test strip.

[0141] Figure 16(a) is a photographic image showing the appearance of the immunochromatographic test strip testing device prototyped in this observation example, showing the state in which the target immunochromatographic test strip has been introduced into the sample testing space. Here, the mechanism for opening and closing the sample testing space using the sample holder 140 is configured so that the sample holder 140 moves in the Y direction (the short side direction of the immunochromatographic test strip) or in a combination of the Z and Y directions to open the bottom of the sample testing space, as described with reference to Figures 3(b) and (c). The sample holder 140 also has the configuration described with reference to Figures 5(c) and (d). That is, the sample holder 140 has a ring-shaped structure 143 as its main body, and a structure containing the fixing portion of the immunochromatographic test strip is inserted into the structure 143. Furthermore, an XY table for adjusting the position of the immunochromatographic test strip (the structure to which the immunochromatographic test strip is fixed) is arranged inside the structure 143, and two drive members that enable movement of the base of the XY table are provided so as to extend outside the structure 143 by penetrating the side of the structure 143.

[0142] Figure 16(b) is a photographic image showing the state in which the target immunochromatographic test strip TS has actually been moved from the sample testing space to the outside of the testing device by moving the sample holder 140. The word "User" on the left side of the image is the hand of the user operating the drive motor attached to the end of the drive member that extends outside the sample holder 140 (structure 143) and moves the X-Y table in the Y direction. The black, roughly rectangular parallelepiped member at the bottom left of Figure 16(b) is the drive motor attached to the end of the drive member that moves the X-Y table in the X direction.

[0143] As shown in Figures 16(a) and (b), the immunochromatographic test strip testing device of the present invention can be made smaller as a whole, and is excellent in terms of space saving even when including a vacuum pump as a vacuum exhaust means.

[0144] Figure 17 is an image of an immunochromatographic test strip observed using this testing device. In Figure 17, the gray areas with varying shades are the fibers (nitrocellulose) that make up the membrane part of the immunochromatographic test strip, observed as the background, and the bright spots are the metal particles to be detected.

[0145] The image shown in Figure 17 was analyzed using commercially available image recognition software (Mitani Corporation, WinROOF2021) to automatically count the number of metal particles, resulting in a result of 2,050. This result was in good agreement with the visual measurement results. This confirmed that the number of metal particles can be measured using the inspection device of the present invention both visually and automatically using image processing technology.

[0146] According to the present invention, metal microparticles, which are the labeling substances in the immunochromatographic test strip, can be detected using a small device with simple operations and in a short time, making it suitable for use in determining the presence or absence of viral infection.

[0147] REFERENCE SIGNS LIST 100 Immunochromatographic test strip inspection device 110 Electron gun section 111 Housing 112 Electron beam generating section (electron gun) 113 Objective lens 114a, 114b Condenser lens 115 Condenser aperture 116 Deflection coil 117 Orifice 118 Vacuum tube 120 Detector section 120A Backscattered electron detector 121 Position control means 122 Space 130 Sample inspection space 140 Specimen holder 140a Connection section 141 Section (structure) including immunochromatographic test strip fixing section 142 Section (structure) including connection section 143 Main body section (structure) 144 Attachment parts 150a, 150b Vacuum exhaust means 160 Side wall member 160a Sealing section 161 Support member 170 Vacuum interrupter member 171 LIST OF REFERENCE SIGNS 180 Inner wall member 190 Auxiliary liquid supply unit 191 Nozzle unit 192 Solution storage unit 193 Piezo element 200 Analytical device 210 Control unit 220 Image acquisition unit 230 Data processing unit 240 Output unit 300 Inspection system for immunochromatographic test strips TS Immunochromatographic test strips TS1, TS2, TS3 Immunochromatographic test strips M1, M2, M3 Inspected area of ​​immunochromatographic test strip B Electron beam SE Scattered electrons NS Auxiliary liquid

Claims

1. An immunochromatographic test strip inspection device using metal microparticles as a labeling substance by immunochromatography, comprising at least the following 1) to 4). 1) Electron gun section that irradiates the immunochromatographic test strip with an electron beam 2) A detector section that detects reflected electrons or secondary electrons from metal particles generated by irradiating the immunochromatographic test strip with the electron beam emitted from the electron gun section of 1). 3) A sample testing space capable of accommodating the detector portion of 2) and the test portion of the immunochromatographic test strip, and capable of adjusting the degree of vacuum to 100 Pa or less when testing the immunochromatographic test strip. 4) A specimen holder for introducing an immunochromatographic test strip from atmospheric pressure conditions outside the device into the sample testing space in 3).

2. 2. The immunochromatographic test strip testing device according to claim 1, wherein the volume of the sample testing space (3) after the immunochromatographic test strip is introduced by the sample holder (4) is 300 cubic centimeters or less.

3. The sample testing space of the above 3) is 10 －２ 2. The immunochromatographic test strip inspection device according to claim 1, characterized in that it is configured so as to be adjustable to a degree of vacuum of from 1 Pa to 10 Pa.

4. The immunochromatographic test strip inspection device according to claim 1, characterized in that the sample holder (4) is movable, and the bottom of the sample inspection space (3) can be opened by the movement of the sample holder (4).

5. The immunochromatographic test strip inspection device described in claim 1, further comprising a vacuum interruption mechanism configured to maintain the degree of vacuum within the electron gun section of 1) by spatially insulating the space between the electron gun section of 1) and the sample inspection space of 3).

6. In the vacuum interruption mechanism, the detector unit of 2) is movable, the detector unit of the above 2) is located on the optical path of the electron beam emitted from the electron gun unit of the above 1), thereby spatially isolating the electron gun unit of the above 1) and the specimen inspection space of the above 3); The immunochromatographic test strip inspection device according to claim 5, characterized in that the space formed in the detector section (2) is positioned on the optical path of the electron beam emitted from the electron gun section (1), thereby providing a spatial gap between the electron gun section (1) and the sample inspection space (3).

7. In the vacuum interruption mechanism, the detector unit of 2) is movable and includes a vacuum interruption member attached to the detector unit of 2); the vacuum interrupter is located on an optical path of an electron beam emitted from the electron gun unit of the above 1), thereby spatially isolating the electron gun unit of the above 1) from the specimen inspection space of the above 3); The immunochromatographic test strip inspection device according to claim 5, characterized in that the space formed in the detector section (2) is positioned on the optical path of the electron beam emitted from the electron gun section (1), thereby providing a spatial gap between the electron gun section (1) and the sample inspection space (3).

8. In the electron gun unit of the above 1), the electron beam generating unit is previously －２ 2. The immunochromatographic test strip inspection device according to claim 1, characterized in that it is placed in a vacuum tube adjusted to a vacuum level of less than Pascal.

9. 2. The immunochromatographic test strip inspection device according to claim 1, wherein the electron beam generating section of the electron gun section in 1) is of thermionic emission type.

10. The sample testing space of the above 3) is in a state before the introduction of the immunochromatographic test strip, and is previously set to 10 ４ 2. The immunochromatographic test strip inspection device according to claim 1, characterized in that the pressure is adjusted to a value equal to or less than Pascal.

11. A method for testing an immunochromatographic test strip using the testing device according to claim 1, characterized in that an aqueous solution of at least one type of surface-active compound is applied to the test area of ​​the immunochromatographic test strip before the electron beam irradiation, whereby the surface-active compound has the property of being polymerized by the electron beam irradiation to form a coating on the upper surface of the test area of ​​the immunochromatographic test strip.

12. An inspection device for the immunochromatographic test strip according to claim 1, for use in the inspection method according to claim 11.

13. 13. The immunochromatographic test strip testing device according to claim 12, further comprising a mechanism and components for applying the aqueous solution of the surface active compound to the test area of ​​the immunochromatographic test strip.

14. The immunochromatographic test strip inspection device according to claim 12, characterized in that it is provided with an inner wall member within the sample inspection space of 3), and is configured so that scattered electrons generated when the electron beam emitted from the electron gun section of 1) is irradiated onto the immunochromatographic test strip are collected within a predetermined space within the sample inspection space of 3).

15. An inspection device for an immunochromatographic test strip according to any one of claims 1 to 10 and claims 12 to 14; Equipped with an analytical device, The analysis device comprises: a control unit that controls the operation of at least the electron gun unit (1), the detector unit (2), the sample inspection space (3), and the specimen holder (4) of the inspection device; an image acquisition unit that acquires image information obtained by the detector unit of the inspection device; a data processing unit that processes data from the control unit and the image acquisition unit; an output unit that outputs a processing result in the data processing unit; An immunochromatographic test strip inspection system that analyzes the condition of the inspected area of ​​an immunochromatographic test strip.