Specimen testing device, specimen testing system, method for controlling specimen testing device, and method for selecting a calibration curve

Abstract

To improve the measurement accuracy of the target substance. [Solution] The specimen testing apparatus according to the embodiment comprises a magnetic field generating unit, a signal detection unit, a measurement unit, and a selection unit. The magnetic field generating unit generates a magnetic field that moves magnetic particles, which are placed on an optical waveguide having a detection area on which a first substance that specifically binds to the target substance is fixed, and which have a second substance that specifically binds to the target substance fixed. The signal detection unit detects an optical signal based on light that has entered the optical waveguide and propagated through the optical waveguide. The measurement unit quantitatively measures the target substance by using a plurality of calibration curves. The selection unit selects a calibration curve to be used for measurement by the measurement unit based on the response of the optical signal when the magnetic field generating unit changes the magnetic field, while the target substance and magnetic particles are placed on the detection area.

Description

Technical Field

[0001] The embodiments disclosed in the present specification and drawings relate to a sample testing apparatus, a sample testing system, a control method for a sample testing apparatus, and a method for selecting a calibration curve.

Background Art

[0002] Conventionally, an optical waveguide sensor chip that measures the concentration of a test substance by using an antibody against the test substance, or when the test substance is an antibody, using an antigen or antibody against the antibody, is known. In the optical waveguide sensor chip, fine particles each having an antibody or the like that specifically binds to the test substance immobilized thereon and an optical waveguide are used. Specifically, the absorbance caused by the fine particles bound to the surface of the optical waveguide due to antigen-antibody reaction or the like is detected based on evanescent waves generated near the surface of the optical waveguide. By detecting the absorbance, the test substance can be quantified without requiring a procedure for washing excess sample or secondary antibody.

[0003] However, while the optical waveguide sensor chip is suitable for high-sensitivity detection, it has a small dynamic range with respect to the concentration of the test substance, which sometimes makes it difficult to quantitatively measure the test substance in a high concentration region. Therefore, conventionally, it has been difficult to improve the measurement accuracy of the target substance.

Prior Art Literature

Patent Literature

[0004]

Patent Literature 1

Summary of Invention

Problem to be Solved by the Invention

[0005] One of the problems that the embodiments disclosed herein and in the drawings aim to solve is to improve the measurement accuracy of the target substance. However, the problems that the embodiments disclosed herein and in the drawings aim to solve are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described later can also be positioned as other problems. [Means for solving the problem]

[0006] The specimen testing apparatus according to this embodiment comprises a magnetic field generating unit, a signal detection unit, a measurement unit, and a selection unit. The magnetic field generating unit generates a magnetic field that moves magnetic particles, which are placed on an optical waveguide having a detection area on which a first substance that specifically binds to the target substance is fixed, and which are magnetic particles on which a second substance that specifically binds to the target substance is fixed. The signal detection unit detects an optical signal based on light that has entered the optical waveguide and propagated within the optical waveguide. The measurement unit quantitatively measures the target substance by using multiple calibration curves. The selection unit selects a calibration curve to be used for measurement by the measurement unit based on the response of the optical signal when the magnetic field generating unit changes the magnetic field, while the target substance and magnetic particles are placed on the detection area. [Brief explanation of the drawing]

[0007] [Figure 1] Figure 1 is a block diagram showing an example configuration of a specimen testing system according to the first embodiment. [Figure 2] Figure 2 is a cross-sectional view showing a measurement cartridge in a specimen testing system according to the first embodiment. [Figure 3] Figure 3 is a flowchart showing an example of the operation of the specimen testing system according to the first embodiment. [Figure 4] Figure 4 shows the optical signal detection process in an example of the operation of a sample testing system according to the first embodiment. [Figure 5] Figure 5 shows the process of applying a downward magnetic field in an example of the operation of the sample testing system according to the first embodiment. [Figure 6] Figure 6 shows an example of the operation of the sample testing system according to the first embodiment, illustrating the application state of a downward magnetic field following Figure 5. [Figure 7] Figure 7 shows the process of stopping the downward magnetic field in an example of the operation of the specimen testing system according to the first embodiment. [Figure 8] Figure 8 is a flowchart showing the details of the calibration curve selection process in an example of the operation of the sample testing system according to the first embodiment. [Figure 9] Figure 9 shows the calculation process for the change in the optical signal in an example of the operation of a sample testing system according to the first embodiment. [Figure 10] Figure 10 is a flowchart showing further details of the calibration curve selection process in an example of the operation of the sample testing system according to the first embodiment. [Figure 11] Figure 11 shows the first and second calibration curves in an example of the operation of the sample testing system according to the first embodiment. [Figure 12] Figure 12 shows an example of the operation of the sample testing system according to the first embodiment, illustrating the state in which the downward magnetic field is stopped, following Figure 7. [Figure 13] Figure 13 shows the process of applying an upward magnetic field in an example of the operation of a sample testing system according to the first embodiment. [Figure 14] Figure 14 shows the detection results of the optical signal for each measurement time in an embodiment of the first embodiment. [Figure 15] Figure 15 shows the relationship between the antigen concentration and the change in the light signal in an example of the first embodiment. [Figure 16] Figure 16 shows the first and second calibration curves in an embodiment of the first embodiment. [Figure 17] Figure 17 is a flowchart showing the details of the calibration curve selection process in an example of operation of a sample testing system according to a first modification of the first embodiment. [Figure 18] Figure 18 shows the process of detecting the peak value of an optical signal in an example of operation of a sample testing system according to a first modified example of the first embodiment. [Figure 19] Figure 19 is a flowchart showing further details of the calibration curve selection process in an example of operation of a sample testing system according to a first modification of the first embodiment. [Figure 20] Fig. 20 is a flowchart illustrating details of a calibration curve selection step in an operation example of the sample inspection system according to a second modification of the first embodiment. [Figure 21] Fig. 21 is a diagram illustrating an optical signal slope detection step in an operation example of the sample inspection system according to the second modification of the first embodiment. [Figure 22] Fig. 22 is a flowchart illustrating further details of the calibration curve selection step in an operation example of the sample inspection system according to the second modification of the first embodiment. [Figure 23] Fig. 23 is a flowchart illustrating an operation example of the sample inspection system according to a third modification of the first embodiment. [Figure 24] Fig. 24 is a diagram illustrating an optical signal detection step in an operation example of the sample inspection system according to the third modification of the first embodiment. [Figure 25] Fig. 25 is a cross-sectional view illustrating a measurement cartridge in the sample inspection system according to the second embodiment. [Figure 26] Fig. 26 is a flowchart illustrating an operation example of the sample inspection system according to the second embodiment. [Figure 27] Fig. 27 is a diagram illustrating an optical signal detection step in an operation example of the sample inspection system according to the second embodiment. [Figure 28] Fig. 28 is a flowchart illustrating an operation example of the sample inspection system according to the third embodiment. [Figure 29] Fig. 29 is a diagram illustrating an optical signal detection step in an operation example of the sample inspection system according to the third embodiment. DESCRIPTION OF EMBODIMENTS

[0008] Hereinafter, embodiments of a sample inspection system will be described with reference to the drawings. In the following description, components having substantially the same functions and configurations are denoted by the same reference numerals, and duplicate description will be given only when necessary.

[0009] (First Embodiment) Figure 1 is a block diagram showing an example configuration of a specimen testing system 1 according to the first embodiment. As shown in Figure 1, the specimen testing system 1 according to the first embodiment comprises a measurement cartridge 2 and a specimen testing device 3. In other words, the specimen testing system 1 is configured when the user inserts and sets the measurement cartridge 2 into the specimen testing device 3. The measurement cartridge 2 is detachable from the specimen testing device 3. The measurement cartridge 2 can also be called a reaction vessel.

[0010] First, the measurement cartridge 2 will be described. Figure 2 is a cross-sectional view showing the measurement cartridge 2 in the sample testing system according to the first embodiment. In the example shown in Figure 2, as indicated by the arrows in the figure, one direction along the thickness direction of the measurement cartridge 2 is defined as "upward," and the direction opposite to upward is defined as "downward." Downward may also be the vertical direction. As shown in Figure 2, the measurement cartridge 2 has a housing 21, a transparent substrate 22, an optical waveguide 23, and a protective member 24.

[0011] The housing 21 is formed of, for example, resin. A first recess 202 is provided on the lower surface 201 of the housing 21. A second recess 203 is partially provided on the first recess 202. In the example shown in Figure 2, both ends (i.e., both internal sides) of the second recess 203 in a direction perpendicular to the vertical direction are located inward from both ends (i.e., both internal sides) of the first recess 202 in a direction perpendicular to the vertical direction. A transparent substrate 22, an optical waveguide 23, and a protective member 24 are arranged inside the first recess 202. The optical waveguide 23 is provided on the transparent substrate 22. The protective member 24 is provided on the optical waveguide 23. The optical waveguide 23 and the protective member 24 may be formed on the transparent substrate 22 by, for example, thin-film technology. The transparent substrate 22 on which the optical waveguide 23 and the protective member 24 are provided is sometimes called a chip. An opening 24a is provided in the center of the protective member 24, penetrating the protective member 24. Through the aperture 24a, a sensing area 231, which is part of the upper surface of the optical waveguide 23, is exposed within the second recess 203. The sensing area 231 is an example of a detection area. The sensing area 231 is the region where evanescent light, described later, is generated. The sensing area 231 is used for the detection, i.e., measurement, of the concentration of the target substance 212 based on evanescent light. In other words, the sensing area 231 is used for the quantitative detection, i.e., measurement, of the target substance 212.

[0012] Multiple first substances 211 are fixed on the sensing area 231. The first substances 211 specifically bind to the target substance 212, which is the object to be measured (i.e., the object to be tested). The target substance 212 may be, for example, an antigen. If the target substance 212 is an antigen, the first substance 211 may be, for example, an antibody. If the first substance 211 is an antibody, the first substance 211 specifically binds to the antigen, which is the target substance 212, through an antigen-antibody reaction. The first substance 211 may be fixed on the sensing area 231 by, for example, hydrophobic interactions or chemical bonds that occur between the first substance 211 and the sensing area 231.

[0013] A mixture 205 of a sample solution containing the target substance 212 and a reagent containing reagent component 213 is contained within the reaction space 204, which is surrounded by the inner upper surface of the second recess 203, the inner side surface of the second recess 203, and the sensing area 231 of the optical waveguide 23. Within the reaction space 204, the target substance 212 contained in the sample solution and the reagent component 213 contained in the reagent react. The reagent component 213 contains a second substance 214 that specifically binds to the target substance 212, and magnetic particles 215 on which the second substance 214 is immobilized. If the target substance 212 is an antigen, the second substance 214 may be, for example, an antibody. If the second substance 214 is an antibody, the second substance 214 specifically binds to the antigen (i.e., the target substance 212) by an antigen-antibody reaction. The second substance 214 may be the same substance as the first substance 211, or it may be a different substance. The combination of the target substance 212 with the first substance 211 and the second substance 214 is not limited to a combination of antigen and antibody. For example, the combination of the target substance 212 with the first substance 211 and the second substance 214 may be a combination of sugar and lectin, a combination of nucleotide chain and complementary nucleotide chain, or a combination of ligand and receptor. The magnetic particles 215 are formed, for example, at least in part from a magnetic material such as magnetite. The magnetic particles 215 may be formed by coating the surface of particles made of a magnetic material with a polymer material, for example. Alternatively, the magnetic particles 215 may be formed by coating the surface of particles made of a polymer material with a magnetic material. The specific form of the magnetic particles 215 is not particularly limited as long as it is dispersible in the mixture 205.

[0014] An injection hole 21a is provided near one end of the inner upper surface of the second recess 203, penetrating the housing 21. The mixed liquid 205 can be injected into the reaction space 204 through the injection hole 21a. A discharge hole 21b is provided near the other end of the inner upper surface of the second recess 203, penetrating the housing 21. Air can be released from the reaction space 204 through the discharge hole 21b. In the example shown in Figure 2, there is one injection hole 21a and one discharge hole 21b. The configuration is not limited to this, and there may be multiple injection holes 21a and multiple discharge holes 21b.

[0015] The reaction space 204 is empty, for example, before being used to measure the target substance 212. When measuring the target substance 212, a mixture 205 of the sample solution and reagent is injected into the reaction space 204 from outside the reaction space 204, for example, through the injection port 21a. Upon injection of the mixture 205, the reaction space 204 contains the target substance 212 in the sample solution and the reagent component 213 contained in the reagent, in addition to the first substance 211 fixed on the sensing area 231. When the mixture 205 is injected into the reaction space 204, the air inside the reaction space 204 is discharged to the outside of the reaction space 204 through the discharge port 21b. The injection of the mixture 205 into the reaction space 204 may be performed automatically or manually.

[0016] The reagent component 213 moves in a dispersible manner within the mixed liquid 205 filling the reaction space 204. The magnetic particles 215 are configured such that the gravitational force acting on them is greater than the buoyant force in the mixed liquid 205 acting in the opposite direction to this gravity. Because the gravitational force acting on the magnetic particles 215 is greater than the buoyant force, the magnetic particles 215 can naturally sink below where the sensing area 231 is located and become fixed on the sensing area 231. That is, the second substance 214 fixed to the magnetic particles 215 specifically binds to the target substance 212, and the target substance 212 specifically binds to the first substance 211 fixed on the sensing area 231, thereby fixing the magnetic particles 215 on the sensing area 231.

[0017] The transparent substrate 22 is formed of a light-transmitting material such as resin and glass. The glass may be, for example, alkali-free glass. The transparent substrate 22 transmits light L incident from the light source 31, which will be described later, provided in the specimen testing device 3, to the optical waveguide 23 side. The transparent substrate 22 also transmits light L emitted from the optical waveguide 23 to the signal detection unit 32, which will be described later, provided in the specimen testing device 3. An incident grating 22a is provided near one end of the upper surface of the transparent substrate 22. The incident grating 22a diffracts the light L incident from the light source 31 at a predetermined angle. An outgoing grating 22b is provided near the other end of the upper surface of the transparent substrate 22. The outgoing grating 22b diffracts the light L emitted from the optical waveguide 23 at a predetermined angle.

[0018] The optical waveguide 23 is, for example, a planar optical waveguide. The optical waveguide 23 is formed of a light-transmitting material such as resin and glass. The refractive index of the material forming the optical waveguide 23 (i.e., the refractive index with respect to the wavelength of light L) may be higher than the refractive index of the material forming the transparent substrate 22. When the optical waveguide 23 is formed of resin, the resin may be a thermosetting resin such as phenolic resin, epoxy resin, and acrylic resin, or a photocurable resin. When the optical waveguide 23 is formed of glass, the glass may be, for example, alkali-free glass. The optical waveguide 23 functions as an optical path for propagating light L that is incident on the transparent substrate 22 and emitted back onto the transparent substrate 22. That is, the optical waveguide 23 has a function similar to the core (i.e., core material) in an optical fiber. On the other hand, the transparent substrate 22 and the protective member 24 are formed of materials having a different refractive index than the material of the optical waveguide 23. For example, the transparent substrate 22 and the protective member 24 are made of a material with a lower refractive index than the material of the optical waveguide 23. The transparent substrate 22 and the protective member 24 confine the light L within the optical waveguide 23 by totally reflecting the light L at the interface with the optical waveguide 23. In other words, the transparent substrate 22 and the protective member 24 have a function similar to cladding in an optical fiber. Furthermore, the transparent substrate 22 and the protective member 24 physically protect the optical waveguide 23.

[0019] The optical waveguide 23 propagates the light L incident from the light source 31 through the transparent substrate 22. In the optical waveguide 23, the light L propagates that is influenced by the concentration of the target substance 212 contained in the reaction space 204 (i.e., the reaction state between the target substance 212 and the first and second substances 211 and 214).

[0020] More specifically, for example, the light L diffracted at the incident grating 22a is incident at an angle of incidence greater than the critical angle at the interface between the optical waveguide 23 and the transparent substrate 22, the interface between the optical waveguide 23 and the protective member 24, or the interface between the optical waveguide 23 and the mixed liquid 205. By being incident at an angle of incidence greater than the critical angle at each interface, the light L propagates through the optical waveguide 23 while being repeatedly totally reflected at each interface. As described above, a sensing area 231 on which the first substance 211 is fixed is provided on a part of the upper surface of the optical waveguide 23. Magnetic particles 215 are fixed on the sensing area 231 through the reaction (i.e., specific bonding) between the target substance 212 and the first substance 211, and the reaction (i.e., specific bonding) between the target substance 212 and the second substance 214. The light L propagating through the optical waveguide 23 is scattered and absorbed by the magnetic particles 215 fixed on the sensing area 231. The light L propagating through the optical waveguide 23 is attenuated by scattering and absorption. That is, the light L propagating through the optical waveguide 23 is attenuated in proportion to the amount of the target substance 212 that binds the first substance 211 and the second substance 214. In other words, the light L propagating through the optical waveguide 23 is attenuated in proportion to the amount of the target substance 212 contained in the reaction space 204. The attenuated light L is diffracted at the exit-side grating 22b and emitted from the optical waveguide 23 to the outside.

[0021] The attenuation of light L propagating within the optical waveguide 23 will be described in more detail. When light L propagates within the optical waveguide 23, evanescent light (i.e., near-field light) is generated on the sensing area 231. Evanescent light is light that seeps out to the low refractive index medium side under total internal reflection conditions. When evanescent light is generated, the magnetic particles 215 fixed on the sensing area 231 scatter and absorb the evanescent light. By scattering and absorbing the evanescent light, the magnetic particles 215 attenuate the evanescent light. The attenuation of evanescent light on the sensing area 231 affects the light L propagating within the optical waveguide 23. That is, the attenuation of evanescent light on the sensing area 231 also attenuates the light L propagating within the optical waveguide 23. Therefore, when evanescent light is greatly attenuated on the sensing area 231, the intensity of light L propagating through the optical waveguide 23 decreases significantly. In other words, the greater the amount of magnetic particles 215 fixed on the sensing area 231, the greater the decrease in the intensity of light L output from the optical waveguide 23. To put it another way, the greater the amount of target substance 212 involved in fixing the magnetic particles 215 on the sensing area 231, the greater the decrease in the intensity of light L output from the optical waveguide 23. Therefore, by measuring the intensity of light L, the concentration of the target substance 212 can be measured.

[0022] Furthermore, the magnetic particles 215 that remain on the sensing area 231 are not limited to those fixed on the sensing area 231 via the target substance 212 being measured. That is, magnetic particles 215 that have naturally settled without being fixed on the sensing area 231 may also remain on the sensing area 231. Therefore, in order to accurately measure the concentration of the target substance 212, it is desirable to move magnetic particles 215 that are not involved in the measurement, i.e., magnetic particles 215 that are not fixed on the sensing area 231, away from the sensing area 231. As will be described later, the sample testing device 3 can move magnetic particles 215 that are not involved in the measurement away from the sensing area 231 by applying a magnetic field.

[0023] The protective member 24 is formed of a light-transmitting material, such as resin. As described above, the refractive index of the material forming the protective member 24 may be lower than that of the material forming the optical waveguide 23. The protective member 24 is placed in close contact with the upper surface of the optical waveguide 23, excluding the sensing area 231. By being placed in close contact with the upper surface of the optical waveguide 23, the protective member 24 constitutes a planar protective layer. Also, as described above, the protective member 24 exposes the sensing area 231 into the reaction space 204 through the opening 24a.

[0024] Next, the specimen testing device 3 will be described. As shown in Figure 1, the specimen testing device 3 includes a light source 31, a signal detection unit 32, a magnetic field generation unit 33, an output interface 34, an input interface 35, a memory circuit 36, and a processing circuit 37.

[0025] The light source 31 is, for example, a diode such as an LED (Light Emitting Diode) or a lamp such as a xenon lamp. Alternatively, the light source 31 may be a laser diode such as a red laser diode. The light source 31 is positioned and oriented so that light L can be incident on the incident grating 22a. Light L emitted from the light source 31 is incident on the incident grating 22a via the transparent substrate 22. Light L incident on the incident grating 22a is diffracted at a predetermined angle by the incident grating 22a and enters the optical waveguide 23. Light L that has entered the optical waveguide 23 propagates through the optical waveguide 23 while repeatedly undergoing total internal reflection. Light L that has propagated through the optical waveguide 23 reaches the exit grating 22b. Light L that has reached the exit grating 22b is diffracted at a predetermined angle by the exit grating 22b and exits to the outside of the optical waveguide 23. Alternatively, a generator that produces electromagnetic waves other than light may be used instead of the light source 31.

[0026] The signal detection unit 32 detects an optical signal based on light L that has entered the optical waveguide 23 and propagated within the optical waveguide 23. For example, the signal detection unit 32 receives light L whose intensity is attenuated according to the amount of magnetic particles 215 fixed on the sensing area 231. The signal detection unit 32 may also detect the optical signal by converting the received light L into an electrical signal, i.e., digital data, corresponding to its intensity. The optical signal detected by the signal detection unit 32 is output to the processing circuit 37. The signal detection unit 32 may be, for example, a photodiode.

[0027] The magnetic field generator 33 generates a magnetic field to move the magnetic particles 215. The magnetic particles 215 are placed on an optical waveguide 23 having a sensing area 231 on which a first substance 211 that specifically binds to the target substance 212 is fixed. That is, the magnetic particles 215 are placed on the optical waveguide 23 by being contained as part of the mixed liquid 205 in the reaction space 204 of the measurement cartridge 2. As described above, the magnetic particles 215 also have a second substance 214 that specifically binds to the target substance 212 fixed to them. The magnetic field generator 33 applies a magnetic field to the magnetic particles 215 contained in the reaction space 204 by applying a magnetic field to the measurement cartridge 2.

[0028] In the example shown in Figure 2, the magnetic field generating unit 33 has an upper magnetic field generating unit 33a and a lower magnetic field generating unit 33b. The magnetic field generating unit 33 also has a drive circuit (not shown) that drives the upper magnetic field generating unit 33a and the lower magnetic field generating unit 33b. For example, under the control of the processing circuit 37, the magnetic field generating unit 33 generates a magnetic field by selectively driving the upper magnetic field generating unit 33a and the lower magnetic field generating unit 33b with the drive circuit.

[0029] The lower magnetic field generator 33b is composed of, for example, a permanent magnet and an electromagnet. The lower magnetic field generator 33b is located below the measuring cartridge 2. The lower magnetic field generator 33b generates a downward magnetic field under the control of the processing circuit 37. That is, the lower magnetic field generator 33b applies a downward magnetic field to the magnetic particles 215 in the reaction space 204. For example, the lower magnetic field generator 33b generates a downward magnetic field such that the strength of the downward magnetic field is uniform in the horizontal direction perpendicular to the vertical direction. When a downward magnetic field is applied from the lower magnetic field generator 33b, the magnetic particles 215 in the reaction space 204 move in a direction toward the sensing area 231, i.e., downward. By moving toward the sensing area 231, the magnetic particles 215 become more easily fixed on the sensing area 231 via the second substance 214, the target substance 212, and the first substance 211. Since the magnetic particles 215 are more easily fixed on the sensing area 231, the detection sensitivity of the target substance 212, which utilizes the attenuation of light L by the magnetic particles 215, can be improved. In addition, by applying a downward magnetic field, the magnetic particles 215 can approach the sensing area 231 in a shorter time than when they settle naturally. By approaching the sensing area 231 in a shorter time, the magnetic particles 215 can be fixed on the sensing area 231 more quickly than when they settle naturally. Because the magnetic particles 215 are quickly fixed on the sensing area 231, quantitative measurement of the target substance 212 can be performed rapidly.

[0030] The upper magnetic field generating unit 33a is composed of, for example, a permanent magnet and an electromagnet. The upper magnetic field generating unit 33a is located above the measuring cartridge 2. The upper magnetic field generating unit 33a generates an upward magnetic field under the control of the processing circuit 37. That is, the upper magnetic field generating unit 33a applies an upward magnetic field to the magnetic particles 215 in the reaction space 204. For example, the upper magnetic field generating unit 33a generates an upward magnetic field so that the strength of the upward magnetic field is uniform in the horizontal direction. When an upward magnetic field is applied from the upper magnetic field generating unit 33a, the magnetic particles 215 in the reaction space 204 that are not fixed on the sensing area 231 move away from the sensing area 231, i.e., upward. By causing magnetic particles 215 that are not fixed on the sensing area 231 to move away from the sensing area 231, it is possible to suppress the retention of magnetic particles 215 that do not participate in the quantitative measurement of the target substance 212 on the sensing area 231. This enables accurate quantitative measurement of the target substance 212.

[0031] The output interface 34 shown in Figure 1 outputs various types of information. The output interface 34 includes, for example, a display. The display shows various types of information. For example, the display may show various images generated by the processing circuit 37, or a GUI (Graphical User Interface) for accepting various operations from the user. For example, the display may be a liquid crystal display, an OLED (Organic Light Emitting Diode) display, or a CRT (Cathode Ray Tube) display. Under the control of the processing circuit 37, the display shows various operation screens, information indicating the intensity of the light signal detected by the signal detection unit 32, time-series data of said information, and measurement results of the target substance 212. The measurement results may be, for example, the concentration, weight, or number of the target substance 212. The output interface 34 may further include a speaker. Under the control of the processing circuit 37, the speaker informs the user of the measurement results of the target substance 212, etc. The output interface 34 may further include a printer. The printer, under the control of the processing circuit 37, prints various types of information, such as those displayed on the screen.

[0032] The input interface 35 receives various instructions and information input operations from the user. Specifically, the input interface 35 converts the input operations received from the user into electrical signals and outputs them to the processing circuit 37. For example, the input interface 35 can be implemented by a trackball, switch buttons, mouse, keyboard, touchpad that performs input operations by touching the operating surface, touchscreen that integrates a display screen and a touchpad, non-contact input circuit using an optical sensor, and audio input circuit. Note that the input interface 35 is not limited to those equipped with physical operating components such as a mouse or keyboard. For example, an electrical signal processing circuit that receives electrical signals corresponding to input operations from an external input device provided separately from the device and outputs these electrical signals to the processing circuit 37 is also included as an example of the input interface 35.

[0033] The memory circuit 36 ​​is a non-transient memory device that stores various types of information, such as an HDD (Hard Disk Drive), optical disc, SSD (Solid State Drive), and integrated circuit memory device. The memory circuit 36 ​​stores, for example, a control program that controls the specimen testing device 3 and various types of data used to execute this control program. In addition to HDDs and SSDs, the memory circuit 36 ​​may also be a drive device that reads and writes various types of information to portable storage media such as CDs (Compact Discs), DVDs (Digital Versatile Discs), and flash memory, or semiconductor memory elements such as RAM (Random Access Memory). Some or all of the programs and data in the storage media of the memory circuit 36 ​​may be configured to be downloaded via an electronic network.

[0034] The processing circuit 37 is a circuit that controls the operation of the entire specimen testing device 3 in response to electrical signals of input operations input from the input interface 35. For example, the processing circuit 37 includes a light source control function 371, a magnetic field control function 372, a selection function 373, and a measurement function 374. The selection function 373 is an example of a selection unit. The measurement function 374 is an example of a measurement unit.

[0035] Here, for example, the processing functions performed by the light source control function 371, magnetic field control function 372, selection function 373, and measurement function 374, which are components of the processing circuit 37 shown in Figure 1, are recorded in the memory circuit 36 ​​in the form of a program that can be executed by a computer. The processing circuit 37 is, for example, a processor. The processor constituting the processing circuit 37 reads each program from the memory circuit 36 ​​and executes it to realize the function corresponding to each program that has been read. In other words, the processing circuit 37 in the state in which each program has been read will have each of the functions shown in the processing circuit 37 of Figure 1.

[0036] In Figure 1, the processing functions of the light source control function 371, magnetic field control function 372, selection function 373, and measurement function 374 are shown to be realized by a single processing circuit 37. However, the embodiments are not limited to this. For example, the processing circuit 37 may be composed of a combination of multiple independent processors, with each processor executing its own program to realize each processing function. Furthermore, each processing function of the processing circuit 37 may be appropriately distributed or integrated across one or more processing circuits to realize it.

[0037] The light source control function 371 controls the emission of light L from the light source 31. For example, the light source control function 371 causes the light source 31 to emit light L continuously or intermittently, at least from the start to the end of the measurement.

[0038] The magnetic field control function 372 controls the generation of a magnetic field by the magnetic field generating unit 33. For example, the magnetic field control function 372 controls the application of a downward magnetic field by the lower magnetic field generating unit 33b and the application of an upward magnetic field by the upper magnetic field generating unit 33a according to the magnetic field application timing (i.e., time schedule) stored in the memory circuit 36.

[0039] The selection function 373 selects a calibration curve to be used for the quantitative measurement of the target substance 212 by the measurement function 374, based on the response of the optical signal when the magnetic field generator 33 changes the magnetic field, while the target substance 212 and magnetic particles 215 are placed on the sensing area 231. For example, the selection function 373 selects a calibration curve based on the response of the optical signal when the magnetic field generator 33 changes the intensity of the magnetic field.

[0040] The selection function 373 may select a calibration curve based on the amount of change in the optical signal, which indicates the response of the optical signal. In this case, the amount of change in the optical signal may be the integrated amount obtained by accumulating the instantaneous amount of change in the optical signal over a set time.

[0041] The selection function 373 may further select a calibration curve based on a threshold for the response of the optical signal. In this case, if the optical signal response is greater than the threshold, the selection function 373 may select a first calibration curve used to measure the concentration of the target substance 212 when the concentration of the target substance 212 is low. On the other hand, if the optical signal response is below the threshold, the selection function 373 may select a second calibration curve used to measure the concentration of the target substance 212 when the concentration of the target substance 212 is high. The first calibration curve may be a calibration curve that shows a higher concentration of the target substance 212 as the signal value of the optical signal increases. The second calibration curve may be a calibration curve that shows a lower concentration of the target substance 212 as the signal value of the optical signal increases.

[0042] The magnetic field generator 33 may change the magnetic field by stopping the generation of a downward magnetic field. The selection function 373 may select a calibration curve based on the response of the optical signal when the magnetic field generator 33 stops generating a downward magnetic field.

[0043] The measurement function 374 quantitatively measures the target substance by using multiple calibration curves. Specifically, the measurement function 374 quantitatively measures the target substance using the calibration curve selected by the selection function 373 from among the multiple calibration curves stored in the memory circuit 36.

[0044] The magnetic field generator 33 may generate an upward magnetic field after it has stopped generating a downward magnetic field and a period of time has elapsed for the magnetic particles 215 to settle naturally. The measurement function 374 may measure the concentration of the target substance 212 based on the calibration curve selected by the selection function 373 and the optical signal detected by the signal detection unit 32 when the magnetic field generator 33 is generating an upward magnetic field.

[0045] Next, an example of operation of the specimen testing system 1 according to the first embodiment configured as described above will be explained. Figure 3 is a flowchart of an example of operation of the specimen testing system 1 according to the first embodiment. Below, an example of measuring the concentration of the target substance 212 will be described as a quantitative measurement of the target substance 212.

[0046] First, with the measurement cartridge 2 set in the sample testing device 3, when a measurement start instruction is input to the processing circuit 37 from the input interface 35, the processing circuit 37 starts measuring the concentration of the target substance 212. Alternatively, the processing circuit 37 may start measuring the concentration of the target substance 212 when it detects that the measurement cartridge 2 has been set in the sample testing device 3 by a contact-type or non-contact-type sensor (not shown). When starting the concentration measurement, the mixed solution 205 is injected into the reaction space 204. Once the concentration measurement has started, the light source control function 371 causes the light source 31 to start emitting light L. The light L emitted from the light source 31 enters the optical waveguide 23 via the transparent substrate 22 and the incident grating 22a. The light L that enters the optical waveguide 23 propagates through the waveguide 23 while undergoing total internal reflection. The light L that has propagated through the optical waveguide 23 is emitted from the optical waveguide 23 to the outside at the exit-side grating 22b. The light L emitted from the optical waveguide 23 is received by the signal detection unit 32.

[0047] As shown in Figure 3, when the concentration measurement is started, the signal detection unit 32 starts detecting an optical signal (step S1). For example, the signal detection unit 32 receives light L whose intensity is attenuated according to the amount of magnetic particles 215 fixed on the sensing area 231. The signal detection unit 32 then detects the optical signal by converting the received light L into an electrical signal, i.e., digital data, corresponding to its intensity. The signal detection unit 32 outputs the detected optical signal to the processing circuit 37.

[0048] After the detection of the optical signal begins, the magnetic field control function 372 determines whether or not it is time to apply a downward magnetic field (step S2).

[0049] If it is time to apply a downward magnetic field (Step S2: YES), the magnetic field control function 372 applies a downward magnetic field to the lower magnetic field generation unit 33b (Step S3). On the other hand, if it is not time to apply a downward magnetic field (Step S2: NO), the magnetic field control function 372 repeatedly determines whether or not it is time to apply a downward magnetic field (Step S2).

[0050] Figure 4 shows the optical signal detection process in an example of the operation of the sample testing system 1 according to the first embodiment. In Figure 4, the horizontal axis represents the measurement time, and the vertical axis represents the signal value (i.e., light intensity) of the optical signal detected by the signal detection unit 32. In the example shown in Figure 4, when the measurement time reaches time t1, it is determined that it is time to apply a downward magnetic field, and a downward magnetic field is applied.

[0051] Specifically, the magnetic particles 215 contained in the mixed liquid 205 injected into the reaction space 204 enter the sensing area 231 by naturally settling due to their own weight until time t1. The magnetic particles 215 that have entered the sensing area 231 are then fixed to the sensing area 231 through a specific bond between the second substance 214 fixed to the magnetic particles 215 and the target substance 212, and a specific bond between the target substance 212 and the first substance 211 fixed to the sensing area 231. The magnetic particles 215 fixed to the sensing area 231 attenuate the light L propagating in the optical waveguide 23. Therefore, as shown in Figure 4, until time t1, the signal value of the optical signal decreases due to the magnetic particles 215 fixed to the sensing area 231 by natural settling.

[0052] Figure 5 shows the process of applying a downward magnetic field in an example of the operation of the sample testing system 1 according to the first embodiment. As shown in Figure 5, when a downward magnetic field M1 is applied at time t1, the magnetic particles 215 are subjected to a magnetic force, i.e., an attractive force, by the downward magnetic field M1, and begin to settle more rapidly than in the case of natural settling.

[0053] Figure 6 shows the state of application of a downward magnetic field following Figure 5 in an example of operation of the sample testing system 1 according to the first embodiment. As shown in Figure 6, the magnetic particles 215 that have started to settle due to the downward magnetic field M1 settle while aligning along the magnetic field lines M1 of the downward magnetic field M1. The second substance 214 fixed to the settled magnetic particles 215 combines with the first substance 211 fixed in the sensing area 231 via the target substance 212.

[0054] In the example shown in Figure 4, immediately after the application of a downward magnetic field M1 at time t1, the signal value of the optical signal decreases significantly in a short time. This is because the downward magnetic field M1 causes a large number of magnetic particles 215 to enter the sensing area 231 in a short time, greatly attenuating the light L propagating in the optical waveguide 23. Subsequently, as the number of magnetic particles 215 newly entering the sensing area 231 decreases, the amount of decrease in the signal value of the optical signal becomes smaller.

[0055] After a downward magnetic field is applied to the lower magnetic field generation unit 33b, the magnetic field control function 372 determines whether or not it is time to stop the downward magnetic field, as shown in Figure 3 (step S4).

[0056] If it is time for the downward magnetic field to stop (Step S4: YES), the magnetic field control function 372 causes the downward magnetic field generation unit 33b to stop generating the downward magnetic field (Step S5). On the other hand, if it is not time for the downward magnetic field to stop (Step S4: NO), the magnetic field control function 372 repeats the determination of whether or not it is time for the downward magnetic field to stop (Step S4).

[0057] In the example shown in Figure 4, when the measurement time reaches time t2, it is determined that the timing for stopping the downward magnetic field has arrived, and the generation of the downward magnetic field is stopped.

[0058] Figure 7 shows the process of stopping the downward magnetic field in an example of the operation of the sample testing system 1 according to the first embodiment. When the generation of the downward magnetic field is stopped, the magnetic field that moves the magnetic particles 215 changes. The change in the magnetic field that moves the magnetic particles 215 results in a response to the optical signal. Specifically, when the generation of the downward magnetic field is stopped, the magnetic particles 215 are released from the constraint of the downward magnetic field and begin to settle naturally. As they are released from the constraint of the downward magnetic field, as shown in Figure 7, some of the magnetic particles 215 temporarily move upward from the sensing area 231. As some of the magnetic particles 215 temporarily move upward from the sensing area 231, as shown in Figure 4, at time t2, the optical signal shows a change (i.e., a response) that draws a spike-like waveform that changes from increasing to decreasing in a short time. In other words, at time t2, an overshoot of the optical signal occurs. Note that when the concentration of the target substance 212 is high, the change in the optical signal is smaller than when the concentration of the target substance 212 is low.

[0059] After the generation of the downward magnetic field is stopped, as shown in Figure 3, the selection function 373 selects a calibration curve from among the multiple calibration curves stored in the memory circuit 36 ​​to be used for measuring the concentration of the target substance 212, based on the response of the optical signal (step S6).

[0060] Figure 8 is a flowchart detailing the calibration curve selection process in an example of the operation of the sample testing system 1 according to the first embodiment.

[0061] Specifically, in the example shown in Figure 8, the selection function 373 first calculates the amount of change in the optical signal, which indicates the response of the optical signal (step S61). Figure 9 is a diagram showing the calculation process of the amount of change in the optical signal in an example of operation of the sample testing system 1 according to the first embodiment. In the example shown in Figure 9, the selection function 373 calculates the cumulative change as the amount of change in the optical signal, which is obtained by accumulating the instantaneous change in the optical signal over a set time (t21-t2). That is, the selection function 373 calculates the amount of change in the optical signal by calculating the area of ​​region R shown in Figure 9.

[0062] After calculating the change in the optical signal, the selection function 373 selects a calibration curve based on the calculated change in the optical signal (step S62), as shown in Figure 8.

[0063] Figure 10 is a flowchart showing further details of the calibration curve selection process in an example of operation of the sample testing system 1 according to the first embodiment. Figure 11 is a diagram showing the first calibration curve and the second calibration curve in an example of operation of the sample testing system 1 according to the first embodiment. In Figure 11, the horizontal axis represents the concentration of the target substance 212. The vertical axis represents the signal value of the optical signal. The signal value is a signal value corresponding to the intensity of light L. The signal value may also be a signal value corresponding to the attenuation of light L by the magnetic particles 215.

[0064] Specifically, in the example shown in Figure 10, first, the selection function 373 determines whether the amount of change in the optical signal is greater than a threshold stored in the memory circuit 36 ​​(step S621). That is, the selection function 373 determines whether or not an optical signal response greater than the threshold is shown.

[0065] If the change in the optical signal is greater than the threshold (step S621: YES), the selection function 373 selects a first calibration curve used for the low-concentration region, i.e., for measuring the concentration when the concentration of the target substance 212 is low (step S622). In the example shown in Figure 11, the first calibration curve is a calibration curve in which a larger signal value of the optical signal indicates a higher concentration of the target substance 212.

[0066] On the other hand, if the amount of change in the optical signal is below a threshold (step S621: NO), the selection function 373 selects a second calibration curve used for the high-concentration region, i.e., for measuring the concentration when the concentration of the target substance 212 is high (step S623). In the example shown in Figure 11, the second calibration curve is a calibration curve that shows the lower the concentration of the target substance 212 as the signal value of the optical signal increases.

[0067] Figure 12 shows the state in which the downward magnetic field stops, following Figure 7, in an example of operation of the sample testing system 1 according to the first embodiment. After a sufficient amount of time has elapsed since the generation of the downward magnetic field stopped, as shown in Figure 12, most of the magnetic particles 215 have completed their natural sedimentation, and the rate of decrease in the optical signal slows down.

[0068] After the calibration curve is selected, the magnetic field control function 372 determines whether it is time to apply an upward magnetic field (step S7), as shown in Figure 3. That is, the magnetic field control function 372 determines whether a period has elapsed for the magnetic particles 215 to settle naturally after stopping the generation of the downward magnetic field.

[0069] If it is time to apply an upward magnetic field (Step S7: YES), the magnetic field control function 372 applies an upward magnetic field to the upper magnetic field generation unit 33a (Step S8). From this point onward, the upward magnetic field is continuously applied. On the other hand, if it is not time to apply an upward magnetic field (Step S7: NO), the magnetic field control function 372 repeatedly determines whether or not it is time to apply an upward magnetic field (Step S7).

[0070] In the example shown in Figure 4, when the measurement time reaches time t3 (i.e., when the period t3-t2 for natural sedimentation has elapsed), it is determined that it is time to apply an upward magnetic field, and an upward magnetic field is applied. Figure 13 is a diagram showing the process of applying an upward magnetic field in an example of the operation of the sample testing system 1 according to the first embodiment. As shown in Figure 13, when an upward magnetic field M2 is applied, magnetic particles 215 that are not fixed on the sensing area 231 are moved upward by the attractive force of the upward magnetic field M2. As the magnetic particles 215 that are not fixed on the sensing area 231 move upward, the signal value of the optical signal increases at time t3.

[0071] After the application of an upward magnetic field is initiated, the measurement function 374 determines whether it is time to calculate the concentration of the target substance 212, as shown in Figure 3 (step S9).

[0072] If it is time to calculate the concentration of the target substance 212 (Step S9: YES), the measurement function 374 calculates the concentration of the target substance 212 based on the selected calibration curve and the signal value of the optical signal (Step S10). On the other hand, if it is not time to calculate the concentration of the target substance 212 (Step S9: NO), the measurement function 374 repeats the determination of whether or not it is time to calculate the concentration of the target substance 212 (Step S9).

[0073] In the example shown in Figure 4, when the measurement time reaches time t4, it is determined that it is time to calculate the concentration of the target substance 212, and the concentration of the target substance 212 is calculated.

[0074] After measuring the concentration of the target substance 212, the measurement function 374 displays the calculated concentration result, as shown in Figure 3 (step S11).

[0075] (Example of the first embodiment) The following describes a specific example of the first embodiment. In this example, the change in the signal value of the optical signal and the concentration of the target substance 212 antigen were measured, and a calibration curve to be used for measuring the antigen concentration (i.e., a calibration curve to be stored in the memory circuit 36) was determined based on the measurement results.

[0076] Figure 14 shows the detection results of the optical signal at each measurement time in an embodiment of the first embodiment. Figure 14 shows the antigen concentration at 2.5 × 10⁻⁶ 2 pg / mL, 2.0 × 10 4 pg / mL, and 1.0 × 10 7 The detection results of the optical signal at each measurement time for the case of pg / mL are shown. In Figure 14, time t1 is the timing of application of the downward magnetic field. Time t2 is the timing of termination of the downward magnetic field. Time t3 is the timing of application of the upward magnetic field. Time t4 is the timing of measurement of the antigen concentration.

[0077] Figure 15 shows the relationship between the antigen concentration (horizontal axis) and the change in the optical signal (vertical axis) in an embodiment of the first embodiment. Figure 15 shows the change in the optical signal value (vertical axis in Figure 15) and the measurement results of the antigen concentration (horizontal axis in Figure 15) in the range of antigen concentrations up to 10,240,000 pg / mL. Frame F2 in Figure 15 shows an enlarged view of the region in frame F1 in Figure 15. As shown in Figures 14 and 15, when the antigen concentration was 100,000 pg / mL or higher, the change in the optical signal value became 0 at time t2, i.e., the timing when the downward magnetic field stopped. On the other hand, when the antigen concentration was 20,000 pg / mL or lower, the change in the optical signal value tended to decrease as the antigen concentration increased.

[0078] Figure 16 shows the first and second calibration curves in an example of the first embodiment. Figure 16 shows the signal value of the optical signal at time t4, i.e., the timing of measurement of the antigen concentration. As shown in Figure 16, in the concentration range of 100,000 pg / mL or less, the signal value of the optical signal tends to increase with increasing antigen concentration. On the other hand, in the concentration range of 100,000 pg or higher, the prozone phenomenon occurs, where the reaction becomes negative when the amount of antigen is in large excess relative to the antibody, so the signal value of the optical signal decreased contrary to the antigen concentration.

[0079] In the example shown in Figure 16, the first calibration curve was determined as the calibration curve to be applied to the measurement of the antigen concentration when the change in the signal value of the light signal at time t2 is positive. In the example shown in Figure 16, the first calibration curve is given by y = 13.185ln(x) - 37.853 (coefficient of determination R), where y is the signal value of the light signal and x is the concentration of the antigen. 2 The equation satisfies =0.987). Furthermore, a second calibration curve was determined as a calibration curve to be applied to the measurement of antigen concentration when the change in the signal value of the light signal at time t2 is 0. In the example shown in Figure 16, the second calibration curve is y = -11.74ln(x) + 249.43(R 2The condition (=0.9296) is satisfied. However, the specific configurations of the first and second calibration curves are not limited to those shown in Figure 16. The determined calibration curves were stored in the memory circuit 36 ​​in association with the threshold value of "0" for the change in signal value.

[0080] Under these conditions, when actually measuring the antigen concentration, the selection function 373 selects a first calibration curve for the low-concentration range if the change in the light signal is greater than 0 (see step S621: YES in Figure 10) (see step S622 in Figure 10).

[0081] On the other hand, if the change in the optical signal is 0 (see step S621:NO in Figure 10), the selection function 373 selects a second calibration curve for the high-concentration region (i.e., for the prozone region) (see step S623 in Figure 10).

[0082] As described above, in the first embodiment, the magnetic field generating unit 33 generates a magnetic field that moves the magnetic particles 215, which are placed on an optical waveguide 23 having a sensing area 231 on which a first substance 211 that specifically binds to the target substance 212 is fixed, and which have a second substance 214 that specifically binds to the target substance 212 fixed. The signal detection unit 32 detects an optical signal based on light L that has entered the optical waveguide 23 and propagated within the optical waveguide 23. The measurement function 374 quantitatively measures the target substance 212 by using multiple calibration curves. The selection function 373 selects the calibration curve to be used for measurement by the measurement function 374 based on the response of the optical signal when the magnetic field generating unit 33 changes the magnetic field, while the target substance 212 and the magnetic particles 215 are placed on the sensing area 231.

[0083] This allows for the appropriate selection of a calibration curve from among multiple calibration curves based on the response of the optical signal when the magnetic field is changed, enabling accurate measurement of the target substance 212 even in high-concentration regions. This increases the dynamic range of quantitative measurement of the target substance 212 and improves the measurement accuracy of the target substance 212.

[0084] In the first embodiment, the selection function 373 selects a calibration curve based on the amount of change in the optical signal that indicates the response of the optical signal.

[0085] This allows for a more appropriate selection of a calibration curve from among multiple calibration curves based on the change in the optical signal, thereby further improving the measurement accuracy of the target substance 212.

[0086] Furthermore, in the first embodiment, the amount of change in the optical signal is the accumulated amount obtained by accumulating the instantaneous amount of change in the optical signal over a set time.

[0087] This allows for a more appropriate selection of a calibration curve from among multiple calibration curves based on the integrated change in the optical signal, thereby further improving the measurement accuracy of the target substance 212.

[0088] Furthermore, in the first embodiment, the selection function 373 further selects a calibration curve based on a threshold for the response of the optical signal, i.e., a threshold for the amount of change in the optical signal.

[0089] This allows for easy selection of a calibration curve from among multiple calibration curves based on a threshold value for the change in the optical signal, thereby easily improving the measurement accuracy of the target substance 212.

[0090] Furthermore, in the first embodiment, the selection function 373 selects a first calibration curve used for measuring the concentration of the target substance 212 when the optical signal response is greater than the threshold, and selects a second calibration curve used for measuring the concentration when the optical signal response is less than or equal to the threshold.

[0091] This allows for the appropriate selection of either a first calibration curve for low-concentration regions or a second calibration curve for high-concentration regions based on a threshold for the change in the optical signal, thereby improving the measurement accuracy of the target substance 212 more simply and appropriately.

[0092] In the first embodiment, the magnetic field generator 33 changes the magnetic field by stopping the generation of a downward magnetic field by the lower magnetic field generator 33b. The selection function 373 selects a calibration curve based on the response of the optical signal when the magnetic field generator 33 stops generating a downward magnetic field.

[0093] This allows for the simple and appropriate selection of a calibration curve based on the response of the optical signal when the generation of the downward magnetic field is stopped.

[0094] In the first embodiment, the magnetic field generating unit 33 generates an upward magnetic field after a period has elapsed for the magnetic particles 215 to settle naturally, following the cessation of the generation of a downward magnetic field. The measurement function 374 measures the concentration of the target substance 212 based on the calibration curve selected by the selection function 373 and the optical signal detected by the signal detection unit 32 when the magnetic field generating unit 33 is generating an upward magnetic field.

[0095] This allows magnetic particles 215 that are not fixed in the sensing area 231 to be moved away from the sensing area 231, and then the concentration of the target substance 212 can be measured, thus enabling accurate measurement of the concentration of the target substance 212.

[0096] The specimen testing system 1 according to the first embodiment can be modified in several ways as shown below.

[0097] (First modification of the first embodiment) First, we will explain the first modification of the first embodiment, which selects a calibration curve based on the peak value of the optical signal, focusing on the differences from the embodiment described above. Figure 17 is a flowchart detailing the calibration curve selection process in an example of operation of the sample testing system 1 according to the first modification of the first embodiment. Figure 18 is a diagram showing the process for detecting the peak value of the optical signal in an example of operation of the sample testing system 1 according to the first modification of the first embodiment. Figure 19 is a flowchart showing further details of the calibration curve selection process in an example of operation of the sample testing system 1 according to the first modification of the first embodiment.

[0098] Up to this point, we have described an example in which the selection function 373 selects a calibration curve based on the amount of change in the optical signal that indicates the response of the optical signal. In contrast, in the examples shown in Figures 17 to 19, the selection function 373 selects a calibration curve based on the peak value of the optical signal that indicates the response of the optical signal.

[0099] Specifically, first, as shown in Figure 17, the selection function 373 detects the peak value of the optical signal based on the detection result of the signal detection unit 32 (step S61a). Specifically, as shown in Figure 18, the selection function 373 detects the maximum value of the optical signal within a predetermined period immediately after the generation of the downward magnetic field is stopped at time t2 as the peak value P. In the example shown in Figure 18, the maximum value of the optical signal when the optical signal changes from increasing to decreasing immediately after the generation of the downward magnetic field is stopped is detected as the peak value P.

[0100] After detecting the peak value of the optical signal, the selection function 373 selects a calibration curve based on the detected peak value of the optical signal, as shown in Figure 17 (step S62a).

[0101] Specifically, as shown in Figure 19, first, the selection function 373 determines whether the peak value of the optical signal is greater than the threshold value of the peak value stored in the memory circuit 36 ​​(step S621a).

[0102] If the peak value of the optical signal is greater than the threshold (step S621a: YES), the selection function 373 selects a first calibration curve for the low-concentration region (step S622a).

[0103] On the other hand, if the peak value of the optical signal is below the threshold (step S621a: NO), the selection function 373 selects a second calibration curve for the high-concentration region (step S623a).

[0104] As described above, in the first modification of the first embodiment, the selection function 373 selects a calibration curve based on the peak value of the optical signal that represents the response of the optical signal.

[0105] This allows for the appropriate selection of a calibration curve from among multiple calibration curves based on the peak value of the optical signal, thereby improving the measurement accuracy of the target substance 212.

[0106] (Second modification of the first embodiment) Next, we will describe a second modification of the first embodiment, which selects a calibration curve based on the slope of an optical signal, focusing on the differences from the embodiment described above. Figure 20 is a flowchart detailing the calibration curve selection process in an example of operation of the sample testing system 1 according to the second modification of the first embodiment. Figure 21 is a diagram showing the optical signal slope detection process in an example of operation of the sample testing system 1 according to the second modification of the first embodiment. Figure 22 is a flowchart showing further details of the calibration curve selection process in an example of operation of the sample testing system 1 according to the second modification of the first embodiment.

[0107] In the examples shown in Figures 20 to 22, the selection function 373 selects a calibration curve based on the slope of the optical signal, which indicates the response of the optical signal.

[0108] Specifically, first, as shown in Figure 20, the selection function 373 calculates the slope of the optical signal based on the detection result of the signal detection unit 32 (step S61b). Specifically, as shown in Figure 21, the selection function 373 calculates the slope of the optical signal as the ratio y / x of the measurement period x immediately after the generation of the downward magnetic field was stopped at time t2 and the increase in the signal value of the optical signal during the measurement period x.

[0109] After calculating the slope of the optical signal, the selection function 373 selects a calibration curve based on the calculated slope of the optical signal, as shown in Figure 20 (step S62b).

[0110] Specifically, as shown in Figure 22, first, the selection function 373 determines whether the slope of the optical signal is greater than the slope threshold stored in the memory circuit 36 ​​(step S621b).

[0111] If the slope of the optical signal is greater than the threshold (step S621b: YES), the selection function 373 selects a first calibration curve for the low concentration region (step S622b).

[0112] On the other hand, if the slope of the optical signal is below the threshold (step S621b: NO), the selection function 373 selects a second calibration curve for the high-concentration region (step S623b).

[0113] As described above, in the second modification of the first embodiment, the selection function 373 selects a calibration curve based on the slope of the optical signal, which indicates the response of the optical signal.

[0114] This allows for the appropriate selection of a calibration curve from among multiple calibration curves based on the slope of the optical signal, thereby improving the measurement accuracy of the target substance 212.

[0115] (Third modification of the first embodiment) Next, we will describe a third modification of the first embodiment, in which a downward magnetic field is applied immediately after the start of optical signal detection, focusing on the differences from the embodiments described above. Figure 23 is a flowchart showing an example of operation of the sample testing system 1 according to the third modification of the first embodiment. Figure 24 is a diagram showing the optical signal detection process in the example of operation of the sample testing system 1 according to the third modification of the first embodiment.

[0116] Up to this point, we have described an example in which, after the detection of an optical signal has started, the downward magnetic field is applied only after it has been determined that it is time to apply a downward magnetic field. In contrast, in the example shown in Figures 23 and 24, the magnetic field control function 372 causes the downward magnetic field generation unit 33b to apply a downward magnetic field (step S3) immediately after the start of optical signal detection (step S1).

[0117] This allows the magnetic particles 215 to settle quickly, thereby promoting their fixation onto the sensing area 231. Therefore, according to the third modification of the first embodiment, the measurement of the target substance 212 can be performed more efficiently.

[0118] (Second embodiment) Next, we will describe a second embodiment in which the magnetic field is changed by applying an upward pulsed magnetic field, focusing on the differences from the embodiments described above. Figure 25 is a cross-sectional view showing the measurement cartridge 2 in the specimen testing system 1 according to the second embodiment. Figure 26 is a flowchart showing an example of operation of the specimen testing system 1 according to the second embodiment. Figure 27 is a diagram showing the optical signal detection process in an example of operation of the specimen testing system 1 according to the second embodiment.

[0119] So far, we have described an example in which the selection function 373 selects a calibration curve based on the response of the optical signal when it stops generating a downward magnetic field. In contrast, in the second embodiment, the selection function 373 selects a calibration curve based on the response of the optical signal when it generates an upward pulsed magnetic field (i.e., when an upward magnetic field is pulsed and applied).

[0120] The magnetic field control function 372 generates an upward pulsed magnetic field, and then generates an upward magnetic field again when a period has elapsed for the magnetic particles 215 to settle naturally. The measurement function 374 measures the concentration of the target substance 212 based on the calibration curve selected by the selection function 373 and the optical signal detected by the signal detection unit 32 when the upper magnetic field generation unit 33a is generating an upward magnetic field.

[0121] Since it is not necessary to generate a downward magnetic field, in the second embodiment, as shown in Figure 25, the magnetic field generating unit 33 does not have a downward magnetic field generating unit 33b, but only an upward magnetic field generating unit 33a.

[0122] Specifically, as shown in Figure 26, the magnetic field control function 372 determines whether or not it is time to apply an upward magnetic field pulse after the detection of the optical signal begins (step S1) (step S21).

[0123] If it is time to apply an upward magnetic field pulse (step S21: YES), the magnetic field control function 372 applies an upward magnetic field pulse to the upper magnetic field generator 33a (step S22). On the other hand, if it is not time to apply an upward magnetic field pulse (step S21: NO), the magnetic field control function 372 repeatedly determines whether or not it is time to apply an upward magnetic field pulse (step S21).

[0124] In the example shown in Figure 27, when the measurement time reaches time t1, it is determined that it is time to apply an upward magnetic field pulse, and an upward magnetic field pulse is applied.

[0125] After an upward magnetic field is pulsed, as shown in Figure 26, the selection function 373 selects a calibration curve to be used to measure the concentration of the target substance 212 based on the response of the optical signal to the pulsed application of the upward magnetic field (step S6). The subsequent steps are the same as in Figure 3.

[0126] In the example shown in Figure 27, when the measurement time reaches t2, it is determined that the period for the natural settling of the magnetic particles 215 (t2-t1) has elapsed since the upward magnetic field pulse was applied, and the upward magnetic field is applied.

[0127] As described above, in the second embodiment, the magnetic field generator 33 changes the magnetic field by generating an upward pulsed magnetic field. The selection function 373 selects a calibration curve based on the response of the optical signal when the magnetic field generator 33 generates an upward pulsed magnetic field.

[0128] This allows for the simple and appropriate selection of a calibration curve based on the response of the optical signal when an upward pulsed magnetic field is generated.

[0129] In the second embodiment, the magnetic field generating unit 33 generates an upward pulsed magnetic field, and then generates an upward magnetic field again after a period has elapsed for the magnetic particles 215 to settle naturally. The measurement function 374 measures the concentration of the target substance 212 based on the calibration curve selected by the selection function 373 and the optical signal detected by the signal detection unit 32 when the magnetic field generating unit 33 is generating an upward magnetic field.

[0130] This allows magnetic particles 215 that are not fixed in the sensing area 231 to be moved away from the sensing area 231, and then the concentration of the target substance 212 can be measured, thus enabling accurate measurement of the concentration of the target substance 212.

[0131] Furthermore, in the second embodiment, the magnetic field generating unit 33 does not generate a downward magnetic field.

[0132] This allows the lower magnetic field generating unit 33b to be omitted, thereby reducing the number of parts and costs.

[0133] (Third embodiment) Next, we will describe a third embodiment in which an upward pulsed magnetic field is generated before a downward magnetic field is generated, focusing on the differences from the embodiments described above. Figure 28 is a flowchart showing an example of operation of the specimen testing system 1 according to the third embodiment. Figure 29 is a flowchart showing an example of operation of the specimen testing system 1 according to the third embodiment.

[0134] In the third embodiment, the magnetic field generating unit 33 generates an upward pulsed magnetic field before generating a downward magnetic field. Specifically, as shown in Figure 28, the magnetic field control function 372 determines whether it is time to apply an upward pulsed magnetic field after the detection of the optical signal begins (step S1) (step S31).

[0135] If it is time to apply an upward magnetic field pulse (step S31: YES), the magnetic field control function 372 applies an upward magnetic field pulse to the upper magnetic field generator 33a (step S32). On the other hand, if it is not time to apply an upward magnetic field pulse (step S31: NO), the magnetic field control function 372 repeatedly determines whether or not it is time to apply an upward magnetic field pulse (step S31).

[0136] In the example shown in Figure 29, when the measurement time reaches time t1, it is determined that it is time to apply an upward magnetic field pulse, and an upward magnetic field pulse is applied.

[0137] After applying an upward pulsed magnetic field, the magnetic field control function 372 determines whether or not it is time to apply a downward magnetic field, as shown in Figure 28 (step S2). The subsequent steps are the same as in Figure 3.

[0138] As described above, in the third embodiment, the magnetic field generating unit 33 generates an upward pulsed magnetic field before generating a downward magnetic field. This allows for a longer time before the downward magnetic field is applied, thereby improving the degree of freedom in quantitative measurement of the target substance 212.

[0139] Furthermore, the timing of magnetic field generation (i.e., application) by the magnetic field generating unit 33 is not limited to the timing described in the above-described embodiment.

[0140] In the above explanation, the term "processor" refers to circuits such as a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), an Application Specific Integrated Circuit (ASIC), or a programmable logic device (e.g., a Simple Programmable Logic Device (SPLD), a Complex Programmable Logic Device (CPLD), and a Field Programmable Gate Array (FPGA)). A processor achieves its function by reading and executing a program stored in a memory circuit. Alternatively, instead of storing the program in a memory circuit, the processor may be configured to directly incorporate the program into its circuitry. In this case, the processor achieves its function by reading and executing the program incorporated into the circuitry. Furthermore, a processor is not limited to being a single circuit; it may also be composed of multiple independent circuits combined to form a single processor and achieve its function. Additionally, the multiple components shown in Figure 1 may be integrated into a single processor to achieve its function.

[0141] According to at least one embodiment described above, the measurement accuracy of the target substance 212 can be improved.

[0142] Although several embodiments have been described above, these embodiments are presented only as examples and are not intended to limit the scope of the invention. The novel apparatus and methods described herein can be implemented in a variety of other forms. Furthermore, various omissions, substitutions, and modifications can be made to the embodiments of the apparatus and methods described herein, without departing from the spirit of the invention. The appended claims and equivalents are intended to include such embodiments and modifications that are included in the scope and spirit of the invention. [Explanation of Symbols]

[0143] 1. Specimen testing system 3. Specimen testing equipment 32 Signal detection unit 33 Magnetic field generation section 373 Selection Function 374 Measurement Functions

Claims

1. A magnetic particle is placed on an optical waveguide having a detection area on which a first substance that specifically binds to a target substance is fixed, and a magnetic field generating unit generates a magnetic field that moves the magnetic particle on which a second substance that specifically binds to the target substance is fixed, A signal detection unit that detects an optical signal based on light that has entered the optical waveguide and propagated within the optical waveguide, A measuring unit that quantitatively measures the target substance by using multiple calibration curves, With the target substance and the magnetic particles arranged on the detection area, a selection unit selects the calibration curve to be used for measurement by the measurement unit based on the response of the optical signal when the magnetic field generating unit changes the magnetic field, A specimen testing device equipped with the following features.

2. The specimen testing apparatus according to claim 1, wherein the selection unit selects the calibration curve based on the amount of change in the optical signal that indicates the response of the optical signal.

3. The specimen testing apparatus according to claim 2, wherein the amount of change in the optical signal is the cumulative amount of change obtained by accumulating the instantaneous amount of change in the optical signal over a set time.

4. The sample testing apparatus according to claim 1, wherein the selection unit selects the calibration curve based on the peak value of the optical signal that indicates the response of the optical signal.

5. The sample testing apparatus according to claim 1, wherein the selection unit selects the calibration curve based on the slope of the optical signal that indicates the response of the optical signal.

6. The specimen testing apparatus according to claim 1, wherein the selection unit further selects the calibration curve based on the threshold of the response of the optical signal.

7. The sample testing apparatus according to claim 6, wherein the selection unit selects a first calibration curve used for measuring the concentration of the target substance when the concentration is low if the response of the optical signal is greater than the threshold, and selects a second calibration curve used for measuring the concentration when the concentration is high if the response of the optical signal is less than or equal to the threshold.

8. The magnetic field generating unit changes the magnetic field by stopping the generation of a downward magnetic field. The specimen testing apparatus according to claim 1, wherein the selection unit selects the calibration curve based on the response of the optical signal when the magnetic field generating unit stops generating the downward magnetic field.

9. The magnetic field generating unit, after stopping the generation of the downward magnetic field, generates an upward magnetic field when a period has elapsed for the magnetic particles to settle naturally. The specimen testing apparatus according to claim 8, wherein the measuring unit measures the concentration of the target substance based on the calibration curve selected by the selection unit and the optical signal detected by the signal detection unit when the magnetic field generating unit is generating the upward magnetic field.

10. The magnetic field generating unit changes the magnetic field by generating an upward pulsed magnetic field. The specimen testing apparatus according to claim 1, wherein the selection unit selects the calibration curve based on the response of the optical signal when the magnetic field generating unit generates the upward pulsed magnetic field.

11. The magnetic field generating unit generates an upward pulsed magnetic field, and then, after a period has elapsed for the magnetic particles to settle naturally, it generates an upward magnetic field again. The specimen testing apparatus according to claim 10, wherein the measuring unit measures the concentration of the target substance based on the calibration curve selected by the selection unit and the optical signal detected by the signal detection unit when the magnetic field generating unit is generating the upward magnetic field.

12. The specimen testing apparatus according to claim 11, wherein the magnetic field generating unit does not generate a downward magnetic field.

13. The specimen testing apparatus according to claim 8, wherein the magnetic field generating unit generates an upward pulsed magnetic field before generating the downward magnetic field.

14. An optical waveguide having a detection area on which a first substance that specifically binds to the target substance is fixed, A magnetic particle arranged on the optical waveguide, wherein a second substance that specifically binds to the target substance is fixed to the magnetic particle, Equipped with a specimen testing device, The aforementioned specimen testing device, A magnetic field generating unit that generates a magnetic field for moving the magnetic particles, A signal detection unit that detects an optical signal based on light that has entered the optical waveguide and propagated within the optical waveguide, A measuring unit that quantitatively measures the target substance by using multiple calibration curves, With the target substance and the magnetic particles arranged on the detection area, a selection unit selects the calibration curve to be used for measurement by the measurement unit based on the response of the optical signal when the magnetic field generating unit changes the magnetic field, A specimen testing system equipped with the following features.

15. A magnetic particle is placed on an optical waveguide having a detection area on which a first substance that specifically binds to a target substance is fixed, and a magnetic field generating unit generates a magnetic field that moves the magnetic particle on which a second substance that specifically binds to the target substance is fixed, A signal detection unit that detects an optical signal based on light that has entered the optical waveguide and propagated within the optical waveguide, A control method for a specimen testing device equipped with, With the target substance and the magnetic particles arranged on the detection area, a calibration curve used for quantitative measurement of the target substance is selected based on the response of the optical signal when the magnetic field generating unit changes the magnetic field. To quantitatively measure the target substance using the selected calibration curve, A control method for a specimen testing device equipped with the following features.

16. A magnetic particle is placed on an optical waveguide having a detection area on which a first substance that specifically binds to a target substance is fixed, and a magnetic field is generated to move the magnetic particle on which a second substance that specifically binds to the target substance is fixed, An optical signal based on light that has entered the optical waveguide and propagated within the optical waveguide is detected. With the target substance and the magnetic particles arranged on the detection area, a calibration curve used for quantitative measurement of the target substance is selected based on the response of the optical signal when the magnetic field is changed. A method for selecting a calibration curve that includes [a specific feature / feature].

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