Light quantity measuring device and program

Abstract

According to one aspect of the present application, there is provided a light amount measuring device including: a light emitting section that irradiates an object with excitation light; a light path for passing light emitted from the object; a light receiving section that receives the light that has passed through the light path; and a shutter that is disposed on the light path and that is capable of switching between an open state in which the light is allowed to pass and a shut-off state in which the light is not allowed to pass; the light amount measuring device measuring the light amount of the light that has passed through the light path while repeating switching between the open state and the shut-off state.

Description

Technical Field

[0001] This invention relates to a light intensity measurement device and program. Background Technology

[0002] Patent document 1 discloses a shutter assembly for protecting a high-sensitivity photodetector from harmful light exposure.

[0003] In this shutter assembly, the first shutter blade has a first toothed arm and a first opening, and the second shutter blade is arranged parallel to the first shutter blade. The second shutter blade has a second toothed arm and a second opening. The first and second shutter blades are supported so that they can move in parallel linear motion. The motor has a gear meshing between the first and second toothed arms. By rotating the gear, the first and second shutter blades move in opposite directions in a linear motion between an open position and a closed position. In the open position, the first and second openings are in an overlapping relationship, and in the closed position, the first and second openings are in a non-overlapping relationship.

[0004] In addition, Patent Document 2 discloses a fluorescence detection method capable of detecting fluorescence emitted from various encryption fluorescent substances contained in the inspected object.

[0005] This fluorescence detection method is a fluorescence detection method that detects fluorescence by irradiating the object under inspection with excitation light emitted from an excitation source and having a spectrometer receive the fluorescence emitted from the object under inspection due to the excitation light irradiation. A chopper is configured in the optical path connecting the object under inspection and the spectrometer to allow fluorescence to pass through after a predetermined delay time from the excitation light emitted from the excitation source, and to block the fluorescence after a predetermined exposure time from the passage of the fluorescence.

[0006] Existing technical documents Patent documents Patent Document 1: Japanese Patent Publication No. 2017-161929 Patent Document 2: Japanese Patent Publication No. 2005-091346 Summary of the Invention The technical problem that the invention aims to solve In the prior art described in Patent Documents 1 and 2, there is a problem that the measurement of light intensity cannot be adequately addressed based on the state of light emitted from the object.

[0007] In view of the above, the present invention aims to provide a light quantity measurement device and program capable of adjusting the light emitted from an object to the amount of light corresponding to the measurement range of the light receiving part.

[0008] Solution to the above technical problems According to one aspect of the present invention, a light intensity measuring device is provided, comprising: a light-emitting part that irradiates an object with excitation light; an optical path for light emitted from the object to pass through; a light-receiving part that receives light passing through the optical path; and a shutter disposed on the optical path, capable of switching between an open state that allows light to pass through and a blocked state that does not allow light to pass through, wherein the light intensity measuring device measures the light intensity of light passing through the optical path while repeatedly switching between the open state and the blocked state.

[0009] In this way, the light emitted from the object can be adjusted to the amount of light corresponding to the measurement range of the light-receiving part. Attached Figure Description

[0010] Figure 1 This is a diagram showing an example of the overall configuration of an inspection device 1 according to one embodiment.

[0011] Figure 2 This is an exploded perspective view of an inspection device 1 according to one embodiment.

[0012] Figure 3 This is an exploded perspective view of the inspection device 1, which is used to illustrate the positional relationship between the mounting part 2, the temperature control part 5, the magnetic force application part 6, and the inspection instrument 900.

[0013] Figure 4 This is a top view of a light quantity measuring device 200 according to one embodiment.

[0014] Figure 5 It is along Figure 4 The AA arrow indicates the direction of the light measurement device 200 in a cross-sectional view.

[0015] Figure 6 This is a top view showing the internal structure of the light quantity measuring device 200, omitting some components.

[0016] Figure 7 This is an exploded perspective view of an inspection apparatus 900 according to one embodiment.

[0017] Figure 8 This is a schematic cross-sectional view of the inspection instrument 900.

[0018] Figures 9A to 9C This is a graph showing the relationship between the excitation light irradiation of the simulated LED 310, the switching state of the rotary shutter 510, the fluorescence amount from the fluorescent material, and the amount of light received by the PMT 410.

[0019] Figure 10A and Figure 10BThis is a graph showing the relationship between the excitation light irradiation of the simulated LED 310, the switching state of the rotary shutter 510, the fluorescence amount from the fluorescent material, and the amount of light received by the PMT 410.

[0020] Figure 11 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200.

[0021] Figure 12 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200.

[0022] Figure 13 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200.

[0023] Figure 14 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200.

[0024] Figure 15 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200.

[0025] Figure 16 This is a schematic cross-sectional view of the inspection device 1 equipped with a light intensity measurement device 200. Detailed Implementation

[0026] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. The various features shown in the embodiments described below can be combined with each other.

[0027] Furthermore, the program used to implement the software in one embodiment may be provided as a non-transitory computer-readable medium, may be configured to be downloadable from an external server, or may be configured to implement its function on a client terminal by launching the program on an external computer (so-called cloud computing).

[0028] Furthermore, in various information processing methods involved in one embodiment, both input and corresponding output can be realized. Here, as long as the output is obtained as a result of the input, the manner in which the information referenced in the information processing (hereinafter referred to as reference information) is not limited. Reference information may be, for example, rule-based information such as databases, lookup tables, or predetermined functions (including regression formulas and other decision formulas constructed through statistical methods), or a learned model that has pre-learned the correlation between input and output, or generative AI such as a large-scale language model or visual language model that can output the expected result upon input prompts.

[0029] Furthermore, in one embodiment, the "component" may include, for example, hardware resources implemented by a generalized circuit, and a combination of software information processing that can be specifically implemented through these hardware resources. Additionally, in one embodiment, various types of information are processed, such as physical values ​​representing voltage / current signal values, high or low signal values ​​as sets of binary bits consisting of 0s or 1s, or quantum superpositions (so-called qubits), and communication / computation can be performed on a generalized circuit.

[0030] Furthermore, in a broader sense, a circuit is a circuit implemented by at least appropriately combining circuits, circuitry, processors, and memory. In addition, a processor can be a general-purpose processor or a special-purpose circuit. That is, it includes Application Specific Integrated Circuits (ASICs), programmable logic devices (e.g., Simple Programmable Logic Devices (SPLDs), Complex Programmable Logic Devices (CPLDs), and Field Programmable Gate Arrays (FPGAs)).

[0031] Inspection device 1 First, the inspection device 1 of one embodiment will be described. Figure 1 This is a diagram showing an example of the overall configuration of an inspection device 1 according to one embodiment. Figure 2 This is an exploded perspective view of an inspection device 1 according to one embodiment. Figure 3 This is an exploded perspective view of the inspection device 1, which is used to illustrate the positional relationship between the mounting part 2, the temperature control part 5, the magnetic force application part 6, and the inspection instrument 900. Figure 4 This is a top view of a light quantity measuring device 200 according to one embodiment. Figure 5 It is along Figure 4 The AA arrow indicates the direction of the light measurement device 200 in a cross-sectional view. Figure 6 This is a top view showing a portion of the light quantity measuring device 200, omitting some components, used to illustrate the internal structure of the light quantity measuring device 200. Figure 7 This is an exploded perspective view of an inspection apparatus 900 according to one embodiment. Figure 8 This is a schematic cross-sectional view of the inspection instrument 900.

[0032] It is important to note here that... Figures 2 to 7In this diagram, the orientations of the inspection device 1, the light intensity measuring device 200, the inspection instrument 900, and the components constituting these devices are defined based on the terms "up," "down," "left," "right," "front," and "back" as shown. In this context, "up" is also referred to as "upper side" or "above," and "down" is also referred to as "lower side" or "below." The direction formed by "up" and "down" is called "up-down" or "up-down direction," and the same applies to "down," "left," "right," "front," and "back." Furthermore, in... Figure 8 ( Figures 11 to 16 Similarly, the upper side is referred to as "upper" or "above", and the lower side is referred to as "lower" or "below".

[0033] Figure 1 The examination device 1 shown is used, for example, to quantitatively examine the antigen concentration in a sample by placing the examination instrument 900 on the mounting section 2. The examination device 1 includes: a housing 1a, a mounting section 2, a temperature control section 5, a magnetic force application section 6, a liquid supply section 7, a liquid removal section 8, a control device 9, a display section 94, an input section 95, and a light intensity measurement device 200.

[0034] <Shell 1a> The housing 1a is a box that houses the mechanical and electrical equipment used for inspecting samples in the inspection device 1. Inside the housing 1a, all or part of the following are housed: the mounting section 2, the temperature control section 5, the magnetic force application section 6, the liquid supply section 7, the liquid removal section 8, the control device 9, the display section 94, the input section 95, and the light intensity measuring device 200. Furthermore, the housing 1a has an opening and closing section (not shown), which is configured to allow the inspection instrument 900 to be placed inside or removed from the housing 1a, and to block light from outside the housing 1a during inspection by the inspection device 1.

[0035] <Loading section 2> like Figure 2 As shown, the mounting section 2 has a plate-shaped component, which is configured to mount an inspection instrument 900 on the plate-shaped component. A temperature control unit 5, a magnetic force application unit 6, a liquid supply unit 7, a liquid removal unit 8, and a light intensity measuring device 200 are mechanically connected to the mounting section 2.

[0036] <Temperature Control Unit 5> like Figure 3 As shown, the temperature control unit 5, which is mechanically connected to the mounting section 2, is located below the mounting section 2. The temperature control unit 5 is configured to control the temperature of the inspection instrument 900, and is preferably configured by combining a heater 51, a thermistor (not shown), and a controller (not shown). Hereinafter, the following description will be based on the case where the temperature control unit 5 uses a heater 51, a thermistor, and a controller.

[0037] <Magnetic Force Application Section 6> like Figure 3 As shown, the magnetic force application part 6, which is mechanically connected to the mounting part 2, is disposed below the mounting part 2. Furthermore, the magnetic force application part 6 is configured to apply magnetic force to a magnetic material, and is preferably, for example, a permanent magnet 61 or an electromagnet. Hereinafter, the case where a permanent magnet 61 is used in the magnetic force application part 6 will be described as an example.

[0038] like Figure 1 As shown, the magnetic force application part 6 is mechanically connected to the drive mechanism 6a. The drive mechanism 6a is configured to move the magnetic force application part 6. Specifically, the magnetic force application part 6 moves within the through hole 5a of the temperature control part 5 via the drive mechanism 6a, thereby approaching and moving away from the inspection instrument 900 mounted on the mounting part 2. That is, the temperature control part 5 has a through hole 5a that allows the magnetic force application part 6 to approach and move away from the inspection instrument 900 mounted on the mounting part 2. It should be noted that the drive mechanism 6a is preferably configured to move the magnetic force application part 6 in the vertical direction relative to the inspection instrument 900 mounted on the mounting part 2, and in the forward and backward direction orthogonal to the vertical direction.

[0039] <Liquid Supply Department 7> like Figure 2 As shown, the liquid supply unit 7, which is mechanically connected to the mounting unit 2, is disposed below the mounting unit 2. The liquid supply unit 7 includes a cleaning fluid supply nozzle 71, which is configured to supply cleaning fluid CS to the inspection instrument 900.

[0040] like Figure 1 As shown, the liquid supply unit 7 is mechanically connected to the drive mechanism 7a. The drive mechanism 7a is configured to move the cleaning fluid supply nozzle 71 of the liquid supply unit 7. Specifically, the cleaning fluid supply nozzle 71 is moved by the drive mechanism 7a between a position that allows the supply of cleaning fluid CS to the inspection instrument 900 placed on the mounting unit 2 and a position that stops the supply of cleaning fluid CS.

[0041] <Liquid Removal Section 8> like Figure 2As shown, a liquid removal unit 8, mechanically connected to the mounting unit 2, is disposed below the mounting unit 2. The liquid removal unit 8 includes a removal nozzle 81 configured to remove waste liquid from the reaction detection unit 912 of the inspection apparatus 900. Furthermore, the liquid removal unit 8 removes waste liquid from the reaction detection unit 912 by creating a negative pressure state within the inspection apparatus 900 via the removal nozzle 81. In this case, the liquid removal unit 8 can remove only the air within the inspection apparatus 900, moving the waste liquid from the reaction detection unit 912 to any area within the inspection apparatus 900, thereby removing the waste liquid from the reaction detection unit 912. Alternatively, the liquid removal unit 8 can remove both air and waste liquid from the inspection apparatus 900, removing the waste liquid from the reaction detection unit 912. It should be noted that details regarding the reaction detection unit 912 will be described later.

[0042] like Figure 1 As shown, the liquid removal unit 8 is mechanically connected to the drive mechanism 8a. The drive mechanism 8a is configured to move the removal nozzle 81 of the liquid removal unit 8. Specifically, the removal nozzle 81 is moved between a position that allows the removal of waste liquid from the inspection instrument 900 placed on the mounting unit 2 and a position that stops the removal of waste liquid via the drive mechanism 8a.

[0043] <Control Device 9> like Figure 1 As shown, the control device 9 includes a communication unit 91, a storage unit 92, and a control unit 93, which are electrically connected via a communication bus 90. Each component will be further described below.

[0044] The communication unit 91 is capable of communicating with various hardware components of the inspection device 1, and includes input / output interfaces capable of transmitting and receiving various signals with these hardware components. While wired communication is preferred, the communication unit 91 may also include wireless communication as needed. Data communication for performing various inspection procedures in the inspection device 1 is conducted within the network comprised of the communication units 91.

[0045] Storage unit 92 stores various types of information. This can be implemented, for example, as a storage device such as a solid-state drive (SSD) storing programs used to perform various inspection procedures in inspection device 1, or as a memory such as random access memory (RAM) storing information temporarily needed for program operations (parameters, arrays, etc.). Storage unit 92 stores programs or variables used to perform various inspection procedures in inspection device 1.

[0046] The control unit 93 performs processing and control of the inspection device 1. The control unit 93 includes, for example, a central processing unit (CPU) not shown. The control unit 93 implements various functions relating to the inspection device 1 by reading a predetermined program stored in the storage unit 92. That is, the information processing performed by the software stored in the storage unit 92 is specifically implemented by a processor, which is a type of hardware, and can be executed as various functional units included in the processor. It should be noted that the control unit 93 is not limited to a single unit; it can also be implemented with multiple control units 93 for each function. It can also be a combination of them. That is, the inspection device 1 has a control unit 93 that is at least one processor. The control unit 93, as a processor, is configured to execute the inspection process described later by reading the program. It should be noted that the control unit 93, as a processor, preferably uses a programmable logic device. For example, a device classified as a Field Programmable Gate Array (FPGA) or other logic device can also be used as the control unit 93 of this invention. In this case, control of the inspection device 1 can be implemented by control of rewritable logic circuits such as an FPGA.

[0047] Specifically, the control unit 9 acquires information from various sensors on the inspection device 1, as well as information input from outside the inspection device 1, via the communication unit 91. The control unit 93 reads the program from the storage unit 92 and performs various calculations using the information. Based on the calculations performed by the control unit 93, a control signal is generated to control the inspection device 1, and various devices (sensors, actuators, etc.) operate according to the control signal. Then, the control unit 9 outputs the acquired information (inspection results, etc.) to the display unit 94, etc.

[0048] <Display Unit 94> The display unit 94 is electrically connected to the control device 9 via the communication unit 91. For example, it can be included in the inspection device 1 or it can be external. The display unit 94 is a display device such as a liquid crystal display or an organic EL display, which displays a user-operable graphical user interface (GUI) screen.

[0049] <Input Section 95> The input unit 95 is electrically connected to the control device 9 via the communication unit 91, and can be included in the inspection device 1 or externally connected. For example, the input unit 95 can be integrated with the display unit 94 as a touch panel. If it is a touch panel, the user can input click operations, swipe operations, etc. Of course, a switch button, mouse, QWERTY keyboard, etc., can be used instead of a touch panel. That is, the input unit 95 accepts operation input from the user. This input is transmitted as a command signal to the control unit 93 via the communication unit 91, and the control unit 93 can perform specified control or calculation as needed.

[0050] <Light Measurement Device 200> The light intensity measuring device 200 is configured to measure the amount of light emitted from an object by irradiating it with excitation light. The light emitted from the object may be, for example, fluorescence, phosphorescence, or phosphorescence. Hereinafter, an example will be provided where a time-resolved fluorescence measuring device 201 is used in the light intensity measuring device 200. In this case, the object contains a fluorescent material, and the time-resolved fluorescence measuring device 201 measures the amount of fluorescence emitted from that fluorescent material. Figure 2 The time-resolved fluorescence measurement device 201 shown is positioned above the mounting section 2 and is mechanically connected to the mounting section 2. Furthermore, as... Figures 4 to 6 As shown, the time-resolved fluorescence measurement device 201 includes a light-emitting unit 300, a light-receiving unit 400, a shutter 500, and a position detection sensor 600.

[0051] <Light-emitting part 300> like Figure 5As shown, the light-emitting unit 300 is disposed above the base 210 and configured to irradiate excitation light through the light path 230a (an example of light path 230) formed by the base 210. This configuration enables the irradiation of excitation light onto the inspection instrument 900 mounted on the mounting unit 2. In other words, the time-resolved fluorescence measuring device 201, as an example of a light intensity measuring device 200, includes a light-emitting unit 300 that irradiates excitation light onto an object containing a fluorescent material. In the time-resolved fluorescence measuring device 201, light is emitted from the object through irradiation with excitation light, and then the amount of light emitted from the object is measured during the extinguishing period. Furthermore, the light-emitting unit 300 included in the time-resolved fluorescence measuring device 201 is configured to repeatedly irradiate and extinguish the excitation light at any given time. Furthermore, the light-emitting unit 300 is not particularly limited as long as it can irradiate excitation light; for example, an LED 310 (LightEmitting Diode) is preferred. When an LED 310 is used in the light-emitting unit 300, the light-emitting unit 300 can provide illumination with a constant irradiation amount through long-term on / off control. It should be noted that although the irradiation amount of the LED 310 can be increased or decreased by changing the current value, it is preferable to provide illumination with a constant current value when a stable irradiation amount is desired. That is, by using a constant current value for on / off control, the LED 310 can provide more stable illumination. As a result, the measurements of the time-resolved fluorescence measurement device 201 can be performed more stably. The following explanation uses the case where an LED 310 is used in the light-emitting unit 300 as an example.

[0052] <Light-receiving section 400> like Figure 5 As shown, the light-receiving unit 400 is disposed above the base 210 and the spacer 220, configured to receive fluorescence from the fluorescent material passing through the light path 230. Specifically, it is configured to allow fluorescence from the fluorescent material to pass through the light path 230b (an example of the light path 230) formed by the base 210 and the spacer 220, and the light-receiving unit 400 receives the passing fluorescence. In other words, the time-resolved fluorescence measuring device 201, as an example of the light intensity measuring device 200, includes: a light path 230 through which light emitted from an object (an example of a fluorescent material) passes; and a light-receiving unit 400 that receives the light passing through the light path 230. The light-receiving unit 400 is not particularly limited as long as it can receive fluorescence from the fluorescent material and convert it into an electrical signal according to the light intensity; for example, a PMT 410 (Photomultiplier Tube) or a PD (Photo Diode) (not shown) is preferred. Hereinafter, the case of using a PMT 410 in the light-receiving unit 400 will be described as an example.

[0053] <Shutter speed 500> like Figure 5As shown, the shutter 500 is positioned between the base 210 and the spacer 220, thereby being disposed on the optical path 230b (an example of the optical path 230). Furthermore, by being disposed on the optical path 230, the shutter 500 is configured to switch between an open state M1 that allows fluorescence to pass through and a blocked state M2 that does not allow fluorescence to pass through. In other words, the time-resolved fluorescence measurement device 201, as an example of a light quantity measurement device 200, includes a shutter 500 disposed on the optical path 230, which is capable of switching between an open state M1 that allows light to pass through and a blocked state M2 that does not allow light to pass through.

[0054] With this configuration, the time-resolved fluorescence measurement device 201 adjusts the fluorescence from the fluorescent material to a light intensity corresponding to the measurement range of the light-receiving unit 400 based on the excitation light illumination from the LED 310 and the switching between the open state M1 and the closed state M2 of the shutter 500. Then, the time-resolved fluorescence measurement device 201 measures the amount of fluorescence passing through the optical path 230 via the PMT 410. In other words, as an example of a light intensity measurement device 200, the time-resolved fluorescence measurement device 201 measures the amount of light passing through the optical path 230 while repeatedly switching between the open state M1 and the closed state M2. In this way, the light emitted from the object can be adjusted to a light intensity corresponding to the measurement range of the light-receiving unit 400. As a result, the PMT 410 can avoid receiving light intensity exceeding its measurement range. That is, the PMT 410 can be used in a long-term stable measurement environment.

[0055] also, Figure 6 The shutter 500 shown is a rotary shutter 510 capable of switching between an open state M1 and a blocked state M2 by rotation. The rotary shutter 510 has a rotation shaft 511, a through hole 512, and a blocking section 513. Figure 6 In the rotary shutter 510 shown, a rotation axis 511 is arranged along the vertical direction. By rotating around the rotation axis 511, the through hole 512 and the blocking part 513 alternately pass through the optical path 230b. Thus, the rotary shutter 510 (an example of shutter 500) can switch between an open state M1 and a blocked state M2 by rotation. The shutter 500 is not particularly limited as long as it can switch between the open state M1 and the blocked state M2. For example, it can be a mechanical shutter such as a sliding shutter, or a shutter such as an electronic sunshade or a dimming glass that switches between the open state M1 and the blocked state M2 by electrically changing the light transmittance. The following explanation uses the case where a rotary shutter 510 is used in shutter 500 as an example.

[0056] exist Figure 6In the rotary shutter 510 shown, two through holes 512 are provided across the rotation axis 511. That is, during one rotation of the rotary shutter 510, the through holes 512 pass through the optical path 230 twice. That is, during one rotation of the rotary shutter 510, the switching between the open state M1 and the closed state M2 is performed four times. The number of through holes 512 in the rotary shutter 510 is not particularly limited, preferably one to sixteen, more preferably two to eight, and even more preferably two to four. Hereinafter, the case where two through holes 512 of the same shape are provided at equal intervals on a circular rotary shutter 510 will be described as an example. With this configuration, the rotary shutter 510 does not vibrate during high-speed rotation and can rotate stably.

[0057] <Position Detection Sensor 600> The position detection sensor 600 is configured to detect both an open state M1 and an closed state M2. Specifically, Figure 6The position detection sensor 600 shown is configured to detect the through-hole 512 and the blocking portion 513 of the rotary shutter 510. That is, the position detection sensor 600 detects the rotational position of the rotary shutter 510 by detecting the through-hole 512 and the blocking portion 513, thereby detecting whether it is in an open state M1 or a blocked state M2. Specifically, the position detection sensor 600 is disposed on a surface defined by front-back and left-right, at a position opposite to the optical path 230b, across the rotation axis 511 of the rotary shutter 510. Since two through-holes 512 of the same shape are equally spaced on the rotary shutter 510, the position detection sensor 600 detects the through-hole 512 of the rotary shutter 510 in the open state M1 and detects the blocking portion 513 in the blocked state M2. It should be noted that the position detection sensor 600 is not particularly limited as long as it can detect both the open state M1 and the closed state M2. For example, an inductive, magnetostrictive, or optical position detection sensor 600 is preferred. When using an optical position detection sensor 600, the open / closed state of the shutter 500 is determined by the light emitted by the position detection sensor 600. This light becomes interference light (optical noise) when measuring fluorescence intensity using the PMT 410. Therefore, when using an optical position detection sensor 600, it is preferable to control the emission of light from the position detection sensor 600 during fluorescence intensity measurement using the PMT 410. Furthermore, when using a stepper motor in the drive mechanism of the rotary shutter 510, it is preferable to correlate information about the boundary between the through-hole 512 and the closed portion 513 of the rotary shutter 510 (i.e., the shape of the rotary shutter 510) with information about the rotational position of the stepper motor. Specifically, before the time-resolved fluorescence measurement device 201 measures the fluorescence intensity, the rotary shutter 510 is rotated at least one revolution, and the switching between the open state M1 and the closed state M2 accompanying the rotation of the rotary shutter 510 is detected by the position detection sensor 600. The detected switching information between the open state M1 and the closed state M2 is correlated with the rotational position information of the stepper motor. Then, while the time-resolved fluorescence measurement device 201 is measuring the fluorescence intensity, the open state M1 and the closed state M2 are detected based on the rotational position information of the stepper motor. It should be noted that the position detection sensor 600 that detects the boundary between the through hole 512 and the closed portion 513 of the rotary shutter 510 is preferably an inductive, magnetostrictive, or optical position detection sensor.

[0058] ·Inspection equipment 900 Next, an inspection apparatus 900 according to one embodiment will be described. The inspection apparatus 900 according to one embodiment is used to quantitatively check the antigen concentration in a sample by placing it on the mounting part 2 of the inspection device 1.

[0059] Figure 3The inspection device 900 shown includes an inspection device body 910 that defines a chamber 911, and a liquid supply port 941 and a liquid suction port 942 provided on the inspection device body 910 and communicating with the chamber 911.

[0060] The inspection instrument body 910 is formed by attaching a transparent cover plate 940 to a dark (black) or transparent base 920 via a transparent spacer 930. In one embodiment, the base 920, spacer 930, and cover plate 940 are all flat, and the inspection instrument body 910 is also generally flat (card-shaped).

[0061] The base 920 is made of a large plate. The thickness of the base 920 is not particularly limited, but is preferably about 0.1 mm to 2.0 mm, more preferably about 0.2 mm to 1.0 mm, and even more preferably about 0.225 mm to 0.275 mm.

[0062] The constituent materials of the base 920 (spacer 930, cover plate 940) are not particularly limited, and can include various resin materials such as polyethylene terephthalate (PET), polyethylene (PE), polycarbonate (PC), cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polymethyl methacrylate (PMMA), and various ceramic materials.

[0063] like Figure 7 As shown, the spacer 930 is made of a small plate with a through hole 931 of a predetermined shape formed in its center. When the base 920, the spacer 930 and the cover plate 940 are overlapped, the through hole 931 is closed by the base 920 and the cover plate 940, thereby defining the chamber 911.

[0064] The thickness of the spacer 930 is not particularly limited, but is preferably about 0.025 mm to 0.5 mm, more preferably about 0.05 mm to 0.25 mm, and even more preferably about 0.0675 mm to 0.0875 mm. Thus, a chamber 911 with a sufficiently small capacity can be defined.

[0065] The capacity of chamber 911 is not particularly limited, but is preferably 5.0 mm. 3 Above 50.0mm 3 The lower left and right sides, preferably 10.0mm. 3 Above 40.0mm 3 The following dimensions are preferred, specifically 20.0 mm. 3 Above 30.0mm 3 Below, left and right.

[0066] like Figure 8As shown, chamber 911 has a reaction detection unit 912 in a portion thereof, which houses the aforementioned reagent kit. Within this reaction detection unit 912, the reagent kit reacts with the antigen in the sample. It should be noted that details regarding the reagent kit will be described later.

[0067] like Figure 7 As shown, the cover plate 940 is made of a small plate with the same thickness and material as the spacer 930, and forms two spaced-apart circular through holes, forming a liquid supply port 941 and a liquid suction port 942. Furthermore, with the base 920, spacer 930 and cover plate 940 overlapping each other, the liquid supply port 941 and liquid suction port 942 are respectively connected to the chamber 911.

[0068] For example, liquids such as samples, samples diluted with diluent, and cleaning solutions are supplied to chamber 911 (reaction detection unit 912) via liquid supply port 941. On the other hand, liquids such as waste liquid are removed from chamber 911 (reaction detection unit 912) via liquid suction port 942.

[0069] like Figure 7 As shown, the base 920 and the spacer 930 are bonded together by an adhesive sheet 950, and the spacer 930 and the cover plate 940 are bonded together by an adhesive sheet 960. Each adhesive sheet 950 and 960 has the same or similar shape as the spacer 930.

[0070] For example, double-sided tapes of adhesive sheets 950 and 960 (double-sided tapes) with a thickness of 0.05 mm to 0.2 mm can be listed as double-sided tapes of anaerobic adhesives such as acrylic adhesives, or double-sided tapes of thermosetting adhesives such as epoxy adhesives, melamine adhesives, and phenolic adhesives.

[0071] ·Reagent kit The reagent kit of one embodiment is in a dry state and includes a first reagent and a second reagent.

[0072] The reagent kit contains fluorescent particles (an example of fluorescent materials). For instance, the first reagent contains fluorescent particles immobilized with a first antibody that recognizes an antigen, and the second reagent contains magnetic particles immobilized with a second antibody that recognizes an antigenic epitope different from the first antibody.

[0073] The following sections will explain each of the constituent elements in turn.

[0074] "antigen" Antigens can be selected from various substances that can be used as detection targets, such as fibrin degradation products (e.g., D-dimer), soluble fibrin, fibronectin, TAT, PIC and other coagulation and fibrinolysis markers; tumor markers such as CA19-9, CA125, PSA and other tumor markers; circulation-related markers such as oxidized LDL, BNP and other circulation-related markers; metabolism-related markers such as adiponectin and other metabolism-related markers; inflammation-related markers such as CRP, IgA, IgG, IgM and other inflammation-related markers; infectious disease-related markers such as influenza, HBV, HCV, HIV, toxoplasmosis, chlamydia, syphilis and other infectious disease-related markers; allergen-specific IgE, hormones, drugs, nucleic acids and their fragments involving SNPs, lipids, sugars, etc.

[0075] Fluorescent Particles Fluorescent particles, as an example of fluorescent materials, are particles labeled with fluorescent substances. These particles can contain fluorescent substances internally or have fluorescent substances loaded on their surface. Specific examples of fluorescent particles include fluorescent resin particles containing fluorescent substances internally and fluorescent silica particles with fluorescent substances loaded on their surface. Examples of usable resins include polystyrene, polyamide, polyacrylonitrile, polyxylene, and phenolic resins.

[0076] The average particle size of the fluorescent particles is not particularly limited, but is preferably between 70 nm and 500 nm, more preferably between 70 nm and 300 nm, even more preferably between 80 nm and 250 nm, and particularly preferably between 90 nm and 200 nm.

[0077] In this specification, the average particle size refers to the particle size (D50) at which the cumulative particle quantity from the smallest particle size side reaches 50% in the particle distribution measured by dynamic light scattering.

[0078] Examples of fluorescent substances include europium (III), terbium (III), samarium (III), and dysprosium (III). These fluorescent substances can be used individually or in combination of two or more. Among them, europium (III) is preferred due to its long fluorescence half-life. When europium (III) is irradiated with excitation light of approximately 340 nm, it emits long-wavelength fluorescence (around 610 nm). This fluorescence peak is well separated from the excitation peak.

[0079] It should be noted that fluorescent particles can also be composed solely of the fluorescent substances described above.

[0080] First Antibody The primary antibody can be any type of immunoglobulin molecule, or a fragment of an immunoglobulin molecule with an antigen-binding site, such as the Fab fragment. Furthermore, the primary antibody can be a monoclonal antibody or a polyclonal antibody.

[0081] The primary antibody can directly bind to fluorescent particles using physical adsorption or chemical binding methods. Alternatively, it can indirectly bind to fluorescent particles via ligand-antiligand binding, such as avidin-biotin binding, glutathione-glutathione S-transferase binding, or ligand-antiligand binding, such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC)-N-hydroxysuccinimide (NHS).

[0082] Magnetic Particles Magnetic particles are particles containing magnetic materials. These can be particles with magnetic materials internally or particles with magnetic materials on their surface. Specific examples of magnetic particles include magnetic resin particles containing magnetic materials internally and magnetic silica particles with magnetic materials on their surface. Examples of usable resins include polystyrene, polyamide, polyacrylonitrile, polyxylene, and phenolic resins.

[0083] Examples of magnetic materials include magnetite, hematite, ferrite, nickel oxide, cobalt iron oxide, carbon steel, and tungsten steel. It should be noted that magnetic particles can also be composed solely of these magnetic materials.

[0084] The average particle size of the magnetic particles is not particularly limited, but is preferably around 70 nm to 500 nm, more preferably around 70 nm to 400 nm, even more preferably around 80 nm to 300 nm, and particularly preferably around 90 nm to 250 nm. Magnetic particles with this average particle size are more likely to prevent aggregation.

[0085] Second Antibody A secondary antibody is an antibody that recognizes an antigenic epitope different from that of the primary antibody. This secondary antibody can be any type of immunoglobulin molecule, or a fragment of an immunoglobulin molecule with an antigen-binding site, such as a Fab fragment. Furthermore, the secondary antibody can be a monoclonal antibody or a polyclonal antibody.

[0086] The second antibody can directly bind to magnetic particles using physical adsorption or chemical binding methods. Alternatively, it can indirectly bind to magnetic particles via ligand-antiligand binding, such as avidin-biotin binding, glutathione-glutathione S-transferase binding, or EDC-NHS binding.

[0087] • Method of manufacturing inspection equipment One embodiment of the manufacturing method for the inspection instrument is a method for manufacturing the inspection instrument 900 as described above. The manufacturing method includes: a preparation step (first step) of preparing the inspection instrument body 910 and the reagent kit; a dispersion preparation step (second step) of preparing a dispersion containing the reagent kit; a hydrophilic treatment step of hydrophilicating the chamber 911; a filling step (third step) of filling the chamber 911 with the dispersion to at least the reaction detection section 912; a freeze-drying step (fourth step) of freeze-drying the dispersion and storing the reagent kit in the reaction detection section 912; and a packaging step of packaging the resulting inspection instrument 900 in aluminum foil.

[0088] As a buffer solution for preparing dispersions, there are no particular limitations as long as the buffer solution has a buffering effect in the pH range of 6.0 to 8.0. Examples include 10mM HEPES-NaOH (pH=7.35) and 10mM Tris-HCl (pH=7.5).

[0089] Furthermore, the dispersion preferably contains sucrose and sucrose fatty acid esters. The concentration of sucrose in the dispersion is not particularly limited, but is preferably about 0.1% (W / V) to 20.0% (W / V), and particularly preferably about 0.2% (W / V) to 15.0% (W / V).

[0090] Examples of sucrose fatty acid esters include sucrose stearate, sucrose palmitate, sucrose oleate, and sucrose laurate. The concentration of the sucrose fatty acid ester in the dispersion is not particularly limited, but is preferably between 10 μg / μL and 500 μg / μL, and particularly preferably between 20 μg / μL and 350 μg / μL.

[0091] It should be noted that the dispersion can also be obtained by preparing a first dispersion containing a first reagent and a second dispersion containing a second reagent, and then mixing them.

[0092] Furthermore, a hydrophilization process is included, in which an aqueous solution containing a surfactant is added from the liquid supply port 941 and removed from the liquid suction port 942 before the dispersion is filled into the chamber 911 (i.e., between the dispersion preparation process (second process) and the filling process (third process)). This hydrophilization process is preferably performed on the chamber 911.

[0093] Examples of nonionic surfactants include polyoxyethylene alkylphenyl ethers, polyoxyethylene alkylene alkyl ethers, polyoxyethylene alkyl ethers, polyoxyethylene polycyclic phenyl ethers, sorbitan fatty acid esters, and fatty acid alkanolamides.

[0094] The concentration of the nonionic surfactant in the aqueous solution is preferably between 0.1% (W / V) and 1.0% (W / V), and particularly preferably between 0.3% (W / V) and 0.7% (W / V).

[0095] There are no particular limitations on the freezing method. For example, a general method can be used, such as: after dispensing the dispersion into the chamber 911 from the liquid supply port 941, freezing the main body of the inspection instrument 910 overnight in a freezer with the temperature set below -30°C, or freezing the main body of the inspection instrument 910 overnight in a freeze dryer with the rack temperature set below -30°C.

[0096] Furthermore, there are no particular limitations on the freeze-drying method for the frozen inspection instrument body 910. For example, the freeze-drying method can be described as follows: the frozen inspection instrument body 910 is linearly heated from -30°C to -20°C under vacuum for 24 hours, then linearly heated from -20°C to 30°C for 20 hours, and finally held at 30°C for 3 hours. The vacuum is then released using nitrogen gas, thereby obtaining the inspection instrument 900.

[0097] After freeze-drying, the inspection instrument 900 is preferably immediately sealed with an aluminum foil in a dehumidified environment. This dehumidified environment is not particularly limited, but is preferably an environment with a temperature range of approximately 22°C to 27°C and a relative humidity of approximately 35% or less. Furthermore, the specifications of the aluminum foil are not particularly limited, but a five-layer aluminum foil (86 μm thick) consisting of a polyester film (12 μm thick), a polyethylene film (15 μm thick), an aluminum foil (9 μm thick), a polyethylene film (20 μm thick), and a polyethylene film (30 μm thick) bonded together with an AC coating agent is preferred. The entire inspection instrument 900 is enclosed in this aluminum foil and sealed by heat fusion. The inspection instrument 900 is preferably refrigerated in a sealed state before use for inspection.

[0098] Measurement method of time-resolved fluorescence measurement device 201 Next, the measurement method of the time-resolved fluorescence measuring device 201 will be described using another attached figure. Figures 9A to 9C as well as Figure 10A and Figure 10B This is a graph showing the relationship between the simulated excitation light intensity of LED 310, the switching state of rotary shutter 510, the fluorescence intensity from the fluorescent material, and the amount of light received by PMT 410. The following explains the measurement method of the time-resolved fluorescence measurement device 201 using the simulation results. It should be noted that although the fluorescence intensity from the fluorescent material and the amount of light received by PMT 410 are much smaller than the excitation light intensity of LED 310, in… Figures 9A to 9C as well as Figure 10A and Figure 10B The simulation results shown have been scaled for comparison purposes.

[0099] First, let me explain Figures 9A to 9C The simulation shown. Figures 9A to 9C The simulation shown illustrates half a rotation (=10ms) of the rotary shutter 510 at a rotation speed of 20ms per full rotation. Furthermore, the horizontal axis represents time [ms], and the vertical axis represents the excitation light intensity [-], shutter opening [%], fluorescence intensity from the fluorescent material [-], and light intensity received by the PMT 410 [-].

[0100] In addition, the rotary shutter 510 is in the open state M1 for 0ms to 4ms, in the blocked state M2 for 4ms to 8ms, and in the open state M1 for 8ms to 10ms.

[0101] In this case, the moment of switching from the open state M1 to the blocked state M2 (hereinafter also referred to as the "blocking moment Tc") is the moment when the passage of fluorescence is gradually blocked as the rotary shutter 510 rotates, and then the passage of fluorescence is completely blocked. Figures 9A to 9C In the simulation, the time is 4ms. In other words, the blocking time Tc is the moment when the rotary shutter 510 (an example of shutter 500) is switched from the open state M1 to the blocked state M2.

[0102] Furthermore, the moment of switching from the blocked state M2 to the open state M1 (hereinafter also referred to as "open moment To") is the moment when fluorescence is allowed to pass through as the rotary shutter 510 rotates. Figures 9A to 9C In the simulation, this is 8ms. In other words, the opening time To is the moment when the rotary shutter 510 (an example of shutter 500) switches from the blocked state M2 to the open state M1. It should be noted that the blocked time Tc and the opening time To can be arbitrarily defined. The blocked time Tc can be the moment when fluorescence begins to be blocked or when fluorescence is blocked to any extent. The opening time To can be the moment when all fluorescence is allowed to pass or when fluorescence is allowed to pass to any extent.

[0103] The excitation light irradiated by LED 310 is in Figures 9A to 9C The simulations shown depict illumination at different times. Specifically, in Figure 9A In the simulation shown, the excitation light is set to be irradiated for a period of 4ms to 6ms (hereinafter referred to as "Setting A"). Furthermore, in Figure 9B In the simulation shown, the excitation light is set to be irradiated for a period of 5ms to 7ms (hereinafter referred to as "Setting B"). Furthermore, in Figure 9C In the simulation shown, the excitation light is set to be irradiated for a period of 6ms to 8ms (hereinafter referred to as "Setting C").

[0104] That is, the excitation light emitted by LED 310 is emitted for an irradiation time of 2ms at any time during the time when it is in the blocked state M2. This "any time" is defined by the irradiation start time Tis, which is the time when LED 310 begins irradiating the excitation light, and the irradiation end time Tit, which is the time when LED 310 ends irradiation. In other words, as an example of the light-emitting unit 300, LED 310 begins irradiating the excitation light at the irradiation start time Tis and ends irradiating the excitation light at the irradiation end time Tit.

[0105] Furthermore, although the excitation light irradiation amount of LED 310 differs at different times in settings A to C, it is a constant irradiation amount because the irradiation of the same intensity lasts for the same duration. In other words, LED 310, as an example of the light-emitting unit 300, preferably irradiates the excitation light with a constant irradiation amount. In this way, the excitation light irradiation of LED 310 can be stabilized. It should be noted that... Figures 9A to 9C In the simulation shown, by keeping the excitation light irradiating the fluorescent material at a constant irradiation level, the fluorescence intensity from the fluorescent material is also constant.

[0106] and, Figures 9A to 9C The light received by PMT 410 in the simulation are as follows. Figure 9B The amount of light received in setting B shown is... Figure 9A The light intake shown in setting A is a baseline, approximately five times the normal light intake. Furthermore, Figure 9C The amount of light received in setting C shown is... Figure 9A The light intake shown in setting A is a baseline, approximately 20 times the light intake. That is, Figure 9A The light received is minimal in setting A shown. Figure 9C The setting shown, C, receives the most light. Figure 9B The amount of light received in setting B shown is the amount of light received between setting A and setting C. That is, the amount of light received by PMT 410 can be adjusted by changing the irradiation end time Tit while irradiating the excitation light with a constant irradiation amount. Furthermore, the irradiation end time Tit is preferably defined based on the opening time To. In this way, by adjusting the irradiation end time Tit, the fluorescence from the fluorescent material can be adjusted to the amount of light corresponding to the measurement range of the light-receiving section 400. It should be noted here that... Figures 9A to 9C The simulation results shown are an example of results under arbitrary conditions. The value of the light received and the ratio of each light received may vary depending on the type of fluorescent material, the configuration of the time-resolved fluorescence measurement device 201, and the control settings. Furthermore, since the appropriate control period, the value of the light received, and the ratio of each light received may vary depending on the type of fluorescent material, it is preferable to perform control in accordance with the type of fluorescent material.

[0107] In addition, Figure 9C In setting C shown, both the irradiation end time Tit and the opening time To are 8ms. As mentioned above, Figure 9C The amount of light received in setting C is greater than that in settings A and B. That is, when the fluorescence from the fluorescent material is low, the end time Tit of the irradiation is preferably approximately simultaneous with the opening time To. In this way, by irradiating the excitation light until approximately simultaneous with the opening time To, the amount of light passing through the optical path 230 can be increased. As a result, when the fluorescence from the fluorescent material is low, the fluorescence from the fluorescent material can be adjusted to an amount of light corresponding to the measurement range of the light-receiving section 400. It should be noted here that... Figure 9C In the simulation shown, the illumination end time Tit and the opening time To are simultaneous at 8ms, but a slight time difference is also possible. In this case, the time difference is preferably 0.01ms to 0.5ms, more preferably 0.03ms to 0.3ms, and even more preferably 0.05ms to 0.1ms. Specifically, the time difference can be, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, or 0.5ms, or it can be within the range of any two values ​​exemplified here. Furthermore, the relationship between the illumination end time Tit and the opening time To is preferably appropriately determined based on the illumination characteristics such as the response speed of the LED 310, the shape of the shutter 500 and the optical path 230, the switching speed of the shutter 500, and the method for determining the opening time To.

[0108] In addition, Figure 9A In the setting A shown, the irradiation end time Tit is the time 2ms back from the opening time To. Figure 9BIn setting B shown, the irradiation end time Tit is the moment 1 ms back from the opening time To. In other words, when there is a lot of fluorescence from the fluorescent material, the irradiation end time Tit is preferably the moment tracing back any time from the opening time To. Furthermore, the irradiation end time Tit is preferably the moment tracing back a longer time from the opening time To, depending on the amount of fluorescence from the fluorescent material. In this way, when there is a lot of fluorescence from the fluorescent material, the amount of fluorescence from the fluorescent material can be adjusted to correspond to the measurement range of the light-receiving part 400. In this case, the arbitrary time is preferably set arbitrarily according to the duration of the blocking state M2, the switching speed characteristics of the shutter 500, etc. Specifically, for example, the arbitrary time is 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5 ms, or it can be within the range of any two values ​​exemplified here.

[0109] Next, an explanation Figure 10A and Figure 10B The simulation shown. Figure 10A and Figure 10B The simulation shown illustrates half a revolution (=10ms) when the rotation speed of the rotary shutter 510 is 20ms per revolution. Figure 10A And, indicating that the rotation speed of the rotary shutter 510 is half a rotation (=5ms) when one rotation is 10ms. Figure 10B In addition, the horizontal axis represents time [ms], and the vertical axis represents the amount of excitation light [-], shutter opening [%], fluorescence intensity from the fluorescent material [-], and light intensity received by PMT 410 [-].

[0110] exist Figure 10A In, it is shown Figure 9C The simulation shown. That is, Figure 10A The simulation is set as C.

[0111] exist Figure 10B In the simulation shown, the rotary shutter 510 is in the open state M1 for 0ms to 1ms, in the blocked state M2 for 1ms to 3ms, and in the open state M1 for 3ms to 5ms.

[0112] exist Figure 10B In the simulation shown, the excitation light is set to be irradiated for a period of 1 ms to 3 ms (hereinafter referred to as "Setting D"). Furthermore, the amount of excitation light irradiated by the LED 310 is also a constant amount in Setting D because the irradiation duration is the same as in Settings A to C. That is, in Figures 9A to 9C The simulation shown is Figure 10A and Figure 10B In the simulation shown, by keeping the excitation light irradiating the fluorescent material at a constant irradiation level, the fluorescence intensity from the fluorescent material is also constant.

[0113] exist Figure 10A The simulation shown is Figure 10B In the simulation shown, due to the different rotation speeds of the rotary shutter 510, the switching time TS required for switching between the open state M1 and the closed state M2 is different. Specifically, Figure 10A The simulation shown requires 1 ms for the switching time TS. Furthermore, Figure 10B The simulation shown requires 0.5ms for the switching time TS.

[0114] and, Figure 10A and Figure 10B The light received by PMT 410 in the simulation are as follows. Figure 10B The amount of light received in setting D shown is... Figure 10A The light received in setting C shown is based on a baseline of approximately 2.8 times the light received. That is, Figure 10B The amount of light received in setting D shown is greater than Figure 10A The amount of light received in setting C is shown. By changing the settings, the amount of light received changes. Based on setting A, setting B is approximately 5 times the amount of light received, setting C is approximately 20 times the amount of light received, and setting D is approximately 56 times the amount of light received. That is, the amount of light received by PMT 410 can be further adjusted by changing the switching time TS while irradiating the excitation light with a constant irradiation amount. In other words, the rotary shutter 510 (an example of shutter 500) preferably repeats the switching between open state M1 and closed state M2 with an arbitrarily set switching time TS. In this case, the switching time TS is the time required to switch from closed state M2 to open state M1. In this way, the fluorescence from the fluorescent material can be further adjusted to the amount of light corresponding to the measurement range of PMT 410 by changing the switching time TS. It should be noted that... Figure 10A and Figure 10B The simulation results shown are an example of results under arbitrary conditions. The value of the light received and the ratio of each light received may vary depending on the type of fluorescent material, the configuration of the time-resolved fluorescence measurement device 201, and the control settings. Furthermore, since the appropriate control period, the value of the light received, and the ratio of each light received may vary depending on the type of fluorescent material, it is preferable to perform control in accordance with the type of fluorescent material.

[0115] Furthermore, in the case of the rotary shutter 510, the switching time TS is determined based on the rotation speed of the shutter 500. That is, it is preferable to change the switching time TS according to the rotation speed of the rotary shutter 510. In this way, by changing the rotation speed of the rotary shutter 510, the switching time TS is changed, and as a result, the fluorescence from the fluorescent material can be adjusted to the amount of light corresponding to the measurement range of the light-receiving section 400.

[0116] Therefore, the switching time TS preferably includes a first switching time TS1 and a second switching time TS2. Specifically, Figure 10A In the simulation shown, the switching time TS is set to 1ms as the first switching time TS1. Figure 10B In the simulated scenario, the switching time TS is set to 0.5 ms as the second switching time TS2. That is, the first switching time TS1 is longer than the second switching time TS2. Furthermore, the rotary shutter 510 (an example of shutter 500) preferably repeats the switching between the open state M1 and the closed state M2 with either the first switching time TS1 or the second switching time TS2. In this way, the fluorescence from the fluorescent material can be adjusted to the amount of light corresponding to the measurement range of the light-receiving section 400 based on the first switching time TS1 and the second switching time TS2. It should be noted that the switching time TS is not limited to 1 ms or 0.5 ms, and is preferably set arbitrarily according to the shape of the shutter 500 and the optical path 230, the switching speed characteristics of the shutter 500, etc. Specifically, the switching time TS can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2 ms, or it can be within the range of any two values ​​listed here.

[0117] Furthermore, the time set as the switching time TS is not limited to the first switching time TS1 and the second switching time TS2, but can also be three or more times. Specifically, for example, the time set as the switching time TS can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or it can be within the range of any two values ​​exemplified here.

[0118] • How to use the inspection device 1 Next, the method of using the inspection device 1 will be explained using another attached drawing. Figures 11 to 16This is a schematic cross-sectional view of the examination apparatus 1 equipped with the light intensity measurement device 200. Hereinafter, taking the examination apparatus 1 equipped with the time-resolved fluorescence measurement device 201 as an example, which uses the examination instrument 900 to quantitatively examine the antigen concentration in the sample, an example of the use of the time-resolved fluorescence measurement device 201 will be described.

[0119] [1] First, as Figure 11 As shown, the inspection instrument 900 is placed on the mounting section 2 of the inspection device 1. Here, as... Figure 11 As shown, the intersection of the optical axis OA3 of LED 310 and the optical axis OA4 of PMT 410 is preferably located inside the reaction detection section 912 of the inspection device 900 mounted on the mounting section 2. In this manner, the amount of fluorescence from the fluorescent particles (an example of a fluorescent material) contained in the inspection device 900 can be measured (hereinafter also referred to as "photon counting") more accurately using PMT 410. It should be noted that the inspection device 1 can also be configured such that, after the inspection device 900 is placed in a predetermined position on the inspection device 1, any drive mechanism is controlled by the control section 93 to move the inspection device 900 and place it on the mounting section 2.

[0120] In this case, when excitation light is irradiated from LED 310 to reaction detection unit 912, since the fluorescent particles present in reaction detection unit 912 are at their maximum, it is preferable to use PMT 410 to receive fluorescence from fluorescent particles and perform photon counting based on setting A with the minimum amount of light received, under the control of control unit 93.

[0121] [2] Next, as Figure 12 As shown, using a micropipette 10 or a dropper, the sample S, diluted with diluent, is supplied into chamber 911. At this time, the sample S permeates into chamber 911 due to capillary action, and the dry reagent kit containing the first and second reagents is dissolved by the sample S.

[0122] The buffer used as a diluent can be, for example, the same buffer listed above as the buffer used to prepare the dispersion.

[0123] In addition, in order to effectively generate an antigen-antibody reaction, it is preferable to contain about 150 mM of NaCl in the diluent.

[0124] In addition, it is preferable to add a protein denaturant to the diluent used to dilute the sample.

[0125] The protein denaturant concentration (final concentration) of sample S (in the sample) after dilution with diluent is preferably less than 1M, more preferably more than 0.01M and less than 1M, and even more preferably more than 0.1M and less than 0.5M.

[0126] Examples of protein denaturing agents include guanidine hydrochloride, guanidine thiocyanate, potassium thiocyanate, sodium thiocyanate, and urea.

[0127] Examples of samples that can be listed here include urine, lymph, blood, plasma, serum, saliva, cervical secretions, vaginal secretions, breast secretions, breast milk, synovial fluid, semen, seminal plasma, feces, sputum, cerebrospinal fluid, tears, mucus, interstitial fluid, follicular fluid, amniotic fluid, aqueous humor, vitreous fluid, peritoneal fluid, ascites, and sweat.

[0128] [3] Next, as Figure 13 As shown, based on the control of the control unit 93, the liquid inside the reaction detection unit 912 is heated by the heater 51. Therefore, when antigen Ag is present in the sample, an antigen-antibody reaction occurs, forming an immune complex IC.

[0129] The preferred heating temperature (reaction temperature) is between 25°C and 45°C, and the preferred heating time (reaction time) is between 30 seconds and 100 seconds.

[0130] [4] Next, as Figure 14 As shown, a permanent magnet 61 is brought close to the inspection instrument 900 through a through-hole provided in the heater 51. This attracts magnetic particles to the permanent magnet 61, capturing the immune complex IC and the second reagent.

[0131] At this time, the permanent magnet 61 can also be positioned within the chamber 911, along the longitudinal direction of the inspection instrument 900. Figure 3 (Move in the forward and backward directions).

[0132] [5] Next, as Figure 15 As shown, after the permanent magnet 61 is brought to rest, the removal nozzle 81 is brought close to the inspection device 900 and brought into close contact with the liquid inlet 942. In addition, the cleaning fluid supply nozzle 71 is brought close to the inspection device 900, with its tip (lower end) positioned above the liquid supply inlet 941.

[0133] In this state, a few drops of cleaning solution CS are supplied to the chamber 911 through the cleaning solution supply nozzle 71, and waste liquid is aspirated and removed from the chamber 911 through the removal nozzle 81. Thus, the first reagent and sample S, which did not contribute to the antigen-antibody reaction, can be discarded.

[0134] At this time, the supply of cleaning fluid CS is set to be greater than or equal to the amount of waste liquid removed, and cleaning is performed while the chamber 911 is always filled with cleaning fluid CS. In addition, the flow rate during waste liquid recovery (liquid aspiration) is preferably set to a level that will not cause the immune complex IC to detach from the chamber 911.

[0135] The buffer solution for the washing solution CS can be the same as the buffer solutions listed above used as the preparation of the dispersion. Furthermore, it is desirable for the washing solution CS to contain approximately 150 mM of NaCl.

[0136] Furthermore, it is preferable to also add a protein denaturant to the washing solution CS. The concentration of the protein denaturant in the washing solution CS is preferably 1M or less, more preferably 0.01M or more but less than 1M, and even more preferably 0.1M or more but less than 0.5M. In particular, it is most preferably the same as the protein denaturant concentration (final concentration) of the sample S after dilution with the diluent.

[0137] Examples of protein denaturing agents include guanidine hydrochloride, guanidine thiocyanate, potassium thiocyanate, sodium thiocyanate, and urea.

[0138] In this case, when excitation light is irradiated from LED 310 onto the reaction detection unit 912, the fluorescent particles present in the reaction detection unit 912 gradually decrease as waste liquid is drawn from and removed from the chamber 911. Therefore, it is preferable to change the setting from setting A to setting B based on the control of the control unit 93, and use PMT 410 to receive the fluorescence from the fluorescent particles and perform photon counting. This allows the fluorescence from the fluorescent particles to be adjusted to an amount of light corresponding to the measurement range of the light receiving unit 400.

[0139] In this cleaning process, it is preferable to combine the operation of supplying cleaning fluid CS from the cleaning fluid supply nozzle 71 to the reaction detection unit 912 with the operation of removing waste liquid from the reaction detection unit 912 through the removal nozzle 81 as one cycle, and repeat this cycle multiple times.

[0140] When multiple cycles are repeated, the number of repetitions is preferably between 2 and 10 times, more preferably between 3 and 8 times, and even more preferably between 4 and 6 times. This allows for accurate measurement of antigen concentration while preventing an overall increase in measurement time.

[0141] [6] Next, the cleaning fluid supply nozzle 71 and the removal nozzle 81 are removed from the inspection instrument 900.

[0142] like Figure 16 As shown, with the chamber 911 filled with cleaning solution CS, excitation light is irradiated from LED 310 to the reaction detection unit 912, and the fluorescence from the fluorescent particles is received by PMT 410 and photon counting is performed.

[0143] In this case, since the fluorescent particles present in the reaction detection unit 912 are at their minimum, it is preferable to change the setting from setting B to setting C or setting D based on the control of the control unit 93, and use the PMT 410 to receive the fluorescence from the fluorescent particles and perform photon counting. This allows the fluorescence from the fluorescent particles to be further adjusted to the amount of light corresponding to the measurement range of the light receiving unit 400.

[0144] Thus, the time-resolved fluorescence measuring device 201 mounted on the inspection device 1 adjusts the fluorescence from the fluorescent material to the amount of light corresponding to the measurement range of the PMT 410 by appropriately changing the settings according to the fluorescence state of the fluorescent particles.

[0145] ·other In the above embodiment, the configuration of the inspection device 1 has been described, but a program that allows a computer to execute as processing by the control unit 93 in the inspection device 1 can also be provided. That is, the program is configured to cause the computer to perform irradiation processing, light reception processing, switching processing, and measurement processing. In the irradiation processing, excitation light is irradiated onto the object. In the light reception processing, light passing through the optical path 230 is received. The optical path 230 is the path through which light emitted from the object passes. In the switching processing, an open state M1 that allows light to pass and a blocked state M2 that does not allow light to pass are switched. In the measurement processing, the amount of light passing through the optical path 230 is measured while repeatedly switching between the open state M1 and the blocked state M2. In this manner, information processing performed by a distributable program can adjust the amount of light emitted from the object to correspond to the measurement range of the light receiving unit 400.

[0146] In the above embodiment, the case where the light intensity measuring device 200 is mounted on the inspection device 1 is described, but it is not limited to this. The light intensity measuring device 200 may also be mounted on a device other than the inspection device 1. Furthermore, although the case where the control device 9 is mounted on the inspection device 1 has been described as an example, the light intensity measuring device 200 may also include the control device 9.

[0147] In the above embodiment, it is described that the light intensity measuring device 200 detects the switching between the open state M1 and the closed state M2 by the position detection sensor 600, but it is not limited to this. The light receiving unit 400 may also detect the switching between the open state M1 and the closed state M2. That is, the light intensity measuring device 200 may not have the position detection sensor 600. Specifically, before measuring the amount of fluorescence light, the light intensity measuring device 200 rotates the rotary shutter 510 at least once, and detects the slight change in the amount of light passing through the light path 230 by the light receiving unit 400, thereby detecting the switching between the open state M1 and the closed state M2 that accompanies the rotation of the rotary shutter 510. The detected switching information of the open state M1 and the closed state M2 is associated with the rotational position information of the stepper motor, which is the drive mechanism of the rotary shutter 510. Then, while the light intensity measuring device 200 is measuring the amount of fluorescence light, the open state M1 and the closed state M2 are detected based on the rotational position information of the stepper motor. In this manner, the boundary between the through-hole 512 and the blocking part 513 can be determined by the light-receiving part 400, thereby eliminating the need for the position detection sensor 600. As a result, the mechanism of the light quantity measurement device 200 is expected to be simplified.

[0148] In addition, it can also be provided through the various methods described below.

[0149] (1) A light intensity measuring device, comprising: a light emitting unit that irradiates an object with excitation light; an optical path for allowing light emitted from the object to pass through; a light receiving unit that receives the light passing through the optical path; and a shutter disposed on the optical path, capable of switching between an open state that allows the light to pass through and a blocked state that does not allow the light to pass through; the light intensity measuring device measures the light intensity of the light passing through the optical path while repeatedly switching between the open state and the blocked state.

[0150] In this way, the light emitted from the object can be adjusted to the amount of light corresponding to the measurement range of the light-receiving part.

[0151] (2) According to the light quantity measurement device described in (1) above, the light-emitting part ends the irradiation of the excitation light at the end of the irradiation time, wherein the end of the irradiation time is defined based on the opening time, and the opening time is the time when the shutter is switched from the blocked state to the open state.

[0152] In this way, by adjusting the end time of irradiation, the light emitted from the object can be adjusted to the amount of light corresponding to the measurement range of the receiving part.

[0153] (3) According to the light quantity measurement device described in (2) above, the irradiation end time and the opening time are approximately simultaneous.

[0154] In this way, by irradiating the object with excitation light until approximately the same time as the opening moment, the amount of light passing through the optical path can be increased. In this way, when the amount of light emitted from the object is low, the amount of light emitted from the object can be adjusted to correspond to the measurement range of the light-receiving part.

[0155] (4) According to the light quantity measurement device described in (2) above, wherein the irradiation end time is a time that traces back any time from the opening time.

[0156] In this way, when there is a lot of light emitted from the object, the amount of light emitted from the object can be adjusted to correspond to the measurement range of the light-receiving part.

[0157] (5) The light quantity measuring device according to any one of (1) to (4) above, wherein the light-emitting part irradiates the excitation light with a constant irradiation amount.

[0158] In this way, the excitation light irradiation of the light-emitting part can be stabilized.

[0159] (6) The light measurement device according to any one of (1) to (5) above, wherein the shutter repeats the switching between the open state and the blocked state at an arbitrarily set switching time, wherein the switching time is the time required to switch from the blocked state to the open state.

[0160] In this way, by switching the time, the light emitted from the object can be adjusted to the amount of light corresponding to the measurement range of the light-receiving part.

[0161] (7) According to the light measurement device described in (6) above, the shutter can switch between the open state and the blocked state by rotation, and the switching time is a time determined according to the rotation speed of the shutter.

[0162] In this way, by changing the rotation speed of the rotary shutter, the switching time is changed, and as a result, the amount of light emitted from the object can be adjusted to correspond to the measurement range of the light-receiving part.

[0163] (8) The light measurement device according to (6) or (7) above, wherein the switching time includes a first switching time and a second switching time, wherein the first switching time is a longer time than the second switching time, and the shutter repeats the switching between the open state and the blocked state at the first switching time or the second switching time.

[0164] In this way, the light emitted from the object can be adjusted to the amount of light corresponding to the measurement range of the light-receiving part based on the first switching time and the second switching time.

[0165] (9) The light measurement device according to any one of (1) to (8) above, wherein the object comprises a fluorescent material and the light-receiving part receives fluorescence emitted from the fluorescent material.

[0166] In this way, the fluorescence emitted by the fluorescent material can be adjusted to the amount of light corresponding to the measurement range of the light-receiving part.

[0167] (10) A program configured to cause a computer to perform an illumination process, a light receiving process, a switching process, and a measurement process, wherein, in the illumination process, an excitation light is irradiated onto an object; in the light receiving process, light passing through an optical path is received, wherein the optical path is the path through which the light emitted from the object passes; in the switching process, an open state that allows the light to pass through and a blocked state that does not allow the light to pass through are switched; and in the measurement process, the amount of light passing through the optical path is measured while the switching between the open state and the blocked state is repeated.

[0168] In this way, information processing through a program can adjust the light emitted from the object to the amount of light corresponding to the measurement range of the light-receiving part.

[0169] Of course, it's not limited to this.

[0170] As described above, while various embodiments of the present invention have been illustrated, these are merely examples and are not intended to limit the scope of the invention in any way. This novel embodiment can be implemented in various other ways, with various omissions, substitutions, and modifications possible without departing from the spirit of the invention. This embodiment and its variations are included within the scope and spirit of the invention, as well as within the scope of the invention described in the claims and its equivalents.

Claims

1. A light intensity measurement device, comprising: The light-emitting part irradiates excitation light onto the object; An optical path, used to allow light emitted from the object to pass through; A light-receiving part that receives the light passing through the optical path; as well as A shutter, configured in the optical path, is capable of switching between an open state that allows light to pass through and a blocked state that does not allow light to pass through; The light quantity measuring device measures the light quantity passing through the optical path while repeatedly switching between the open state and the blocked state.

2. The light intensity measuring device according to claim 1, wherein, The light-emitting part stops irradiating with the excitation light at the end of the irradiation time, wherein, The irradiation end time is defined based on the opening time. The opening moment is the moment when the shutter is switched from the blocked state to the open state.

3. The light quantity measuring device according to claim 2, wherein, The irradiation end time and the opening time are approximately simultaneous.

4. The light quantity measuring device according to claim 2, wherein, The irradiation end time is any time traversed from the opening time.

5. The light quantity measuring device according to any one of claims 1 to 4, wherein, The light-emitting part irradiates the excitation light with a constant irradiation amount.

6. The light quantity measuring device according to any one of claims 1 to 5, wherein, The shutter repeats the switching between the open state and the blocked state at an arbitrarily set switching time, wherein the switching time is the time required to switch from the blocked state to the open state.

7. The light quantity measuring device according to claim 6, wherein, The shutter can be rotated to switch between the open state and the closed state. The switching time is determined based on the rotation speed of the shutter.

8. The light quantity measuring device according to claim 6 or 7, wherein, The switching time includes a first switching time and a second switching time, wherein the first switching time is a longer time than the second switching time. The shutter repeats the switching between the open state and the blocked state at either the first switching time or the second switching time.

9. The light quantity measuring device according to any one of claims 1 to 8, wherein, The object contains fluorescent materials. The light-receiving part receives fluorescence emitted from the fluorescent material.

10. A program configured to cause a computer to perform illumination processing, light receiving processing, switching processing, and measurement processing, wherein, In the irradiation process, excitation light is irradiated onto the object; In the light-receiving process, light passing through an optical path is received, wherein the optical path is the path through which the light emitted from the object passes; In the switching process, the open state that allows the light to pass through and the blocked state that does not allow the light to pass through are switched; In the measurement process, the amount of light passing through the optical path is measured while repeatedly switching between the open state and the blocked state.

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