Immunoassay system

Abstract

To expand a dynamic range concerning concentration and to improve measuring accuracy.SOLUTION: An immunoassay system according to an embodiment includes a measurement unit, a calculation unit, and a selection unit. The measurement unit measures a measurement target substance contained in a sample according to a measurement sequence, and acquires a measurement signal reflecting the concentration of the measurement target substance. The calculation unit calculates an index value related to a fluctuation in the intensity of the measurement signal in the first period. The selection unit selects one measurement sequence to be used after the first period according to a concentration range corresponding to the index value of the measurement target substance.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The embodiments disclosed in this specification and drawings relate to immunoassay systems. [Background technology]

[0002] Various techniques are known for measuring target substances in biological samples, including various detection methods that utilize antigen-antibody reactions. These detection methods include immunoturbidimetry, such as ELISA (enzyme-linked immune-sorbent assay) and latex agglutination, immunochromatography, surface plasmon resonance, and immuno-optical waveguide detection. For example, immuno-optical waveguide detection uses an optical waveguide and microparticles immobilized with antibodies or other substances that specifically bind to the target substance. The target substance is measured by detecting the complex formed on the surface of the optical waveguide through the attenuation of light.

[0003] When this detection method is used to aim for high sensitivity, quantitative measurement in the high concentration range may be lacking and the dynamic range may be narrowed. Furthermore, if an excessive amount of antigen is contained in the sample, the prozone phenomenon, which causes the apparent measured value to be low, may result in erroneous measurement results. Thus, for test items that require a wide dynamic range in terms of concentration, it is difficult to achieve both high sensitivity and wide-range quantitative measurement. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-133842 [Patent Document 2] Japanese Patent Application Laid-Open No. 2009-133836 Summary of the Invention [Problem to be solved by the invention]

[0005] One of the problems to be solved by the embodiments disclosed in this specification and the drawings is to expand the dynamic range of concentrations and improve measurement accuracy. However, the problems to be solved by the embodiments disclosed in this specification and the drawings are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described below can also be positioned as other problems. [Means for solving the problem]

[0006] The immunoassay system according to the embodiment includes a measurement unit, a calculation unit, and a selection unit. The measurement unit measures a substance to be measured contained in a sample according to a measurement sequence and acquires a measurement signal reflecting the concentration of the substance to be measured. The calculation unit calculates an index value relating to fluctuations in intensity of the measurement signal during a first period. The selection unit selects one measurement sequence to be used after the first period, depending on a concentration range corresponding to the index value of the substance to be measured. [Brief explanation of the drawings]

[0007] [Figure 1] FIG. 1 is a diagram showing an example of the configuration of an immunoassay system according to the first embodiment. [Figure 2] FIG. 2 is a diagram showing the optical measurement principle of the optical measurement device. [Figure 3] FIG. 3 is a diagram comparing the time change in the measurement signal intensity when measuring a high concentration antigen and when measuring a low concentration antigen. [Figure 4] FIG. 4 is a diagram showing the procedure of optical measurement by the immunoassay system according to the first embodiment. [Figure 5] FIG. 5 is a diagram showing an example of a display screen of the quantitative value according to the first embodiment. [Figure 6] FIG. 6 is a diagram showing an example of the configuration of an immunoassay system according to the second embodiment. [Figure 7] FIG. 7 is a diagram showing the procedure of optical measurement by the immunoassay system according to the second embodiment. [Figure 8] FIG. 8 is a diagram showing an example of a display screen of the quantitative value according to the second embodiment. [Figure 9] FIG. 9 is a diagram showing the procedure of optical measurement by the immunoassay system according to the third embodiment. [Figure 10] FIG. 10 is a diagram showing the procedure of optical measurement by the immunoassay system according to the third embodiment. [Figure 11] FIG. 11 is a diagram showing an example of a display screen of quantitative values ​​according to the third embodiment. [Figure 12] FIG. 12 is a diagram showing measurable concentration ranges for each measurement condition according to the first embodiment. [Figure 13] FIG. 13 is a diagram showing measurable concentration ranges for each measurement condition according to the second embodiment. [Figure 14] FIG. 14 is a diagram showing measurable concentration ranges for each measurement condition according to the third embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0008] The immunoassay system according to this embodiment will be described in detail below with reference to the drawings. The immunoassay system according to this embodiment can be applied to any system capable of optically measuring a target substance using an antigen-antibody reaction, such as turbidimetric immunoassays typified by ELISA (enzyme-linked immune-sorbent assay) and latex agglutination, immunochromatography, surface plasmon resonance, or immuno-optical waveguide detection. The principle of optical measurement is not particularly limited. Furthermore, in embodiments using magnetic particles, the target substance can be measured not only by optical measurement but also by magnetism or electromagnetic waves. Some of the embodiments described below employ, as an example, an immuno-optical waveguide detection method, which uses magnetic particles bound to antibodies that specifically bind to the target substance and performs optical measurement, as the measurement principle for quantifying the target substance.

[0009] (First embodiment) FIG. 1 is a diagram showing an example of the configuration of an immunoassay system 100 according to the first embodiment. The immunoassay system 100 is a system that optically measures a target substance by utilizing an immuno-optical waveguide detection method using magnetic particles. The target substance is not particularly limited as long as it can be detected by the immunoassay system 100, but examples include antigens of influenza virus, adenovirus, respiratory syncytial virus (RS) virus, coronavirus (COVID-19, etc.), etc. As shown in FIG. 1, the immunoassay system 100 includes a test cartridge 200A and an optical measurement device 300.

[0010] The test cartridge 200A has a substrate (hereinafter referred to as a light-transmitting substrate) on which a first substance that specifically binds to the substance to be measured is immobilized. The test cartridge 200A has a drip hole that connects to a reaction chamber provided inside. A mixture of magnetic particles and a specimen treatment liquid in which a specimen (biological sample) containing the substance to be measured is suspended is dripped into the reaction chamber through the drip hole. As an example of the specimen treatment liquid, a buffer solution containing a surfactant is used. A second substance that specifically binds to the substance to be measured is bound to the magnetic particles. The mixture of the specimen treatment liquid, the substance to be measured, and the magnetic particles will be referred to as the test solution.

[0011] 1, the optical measurement device 300 includes a support base 310, a magnet 320, an optical device 330, a processing circuit 340, an input device 350, a display 360, and a storage device 370. The support base 310, the magnet 320, the optical device 330, the processing circuit 340, the input device 350, the display 360, and the storage device 370 are connected via a signal line such as a bus so as to be able to send and receive signals to and from each other.

[0012] The support base 310 is a support mechanism that detachably supports the test cartridge 200A. The attachment and detachment of the test cartridge 200A to the support base 310 is detected electrically, magnetically, or mechanically.

[0013] The magnet 320 applies a magnetic field that moves the magnetic particles introduced into the test cartridge 200A. The magnetic field applied by the magnet 320 is controlled by a measurement control function 341A of the processing circuit 340. The magnet 320 is an example of a measurement unit.

[0014] The optical device 330 detects light incident on the light-transmitting substrate of the test cartridge 200A, propagates through the light-transmitting substrate, and is emitted from the light-transmitting substrate. An electrical signal representing the intensity of the detected light represents a measurement signal that reflects the concentration of the measurement target substance contained in the sample. The measurement signal is supplied to the processing circuit 340. The optical device 330 is an example of a measurement unit.

[0015] The processing circuit 340 is a processor that functions as the control center of the optical measurement device 300. By executing a program stored in the storage device 370 or the like, the processing circuit 340 realizes the functions corresponding to the program, namely, the measurement control function 341A, the calculation function 342, the selection function 343A, the quantification function 344, and the output control function 345. Note that in this embodiment, a case where the measurement control function 341A, the calculation function 342, the selection function 343A, the quantification function 344, and the output control function 345 are realized by a single physical processor is described, but this is not limiting. For example, the processing circuit may be configured by combining multiple independent processors, and the measurement control function 341A, the calculation function 342, the selection function 343A, the quantification function 344, and the output control function 345 may be realized by each processor executing a program.

[0016] By implementing the measurement control function 341A, the processing circuit 340 optically measures the target substance contained in the sample according to a measurement sequence and acquires a measurement signal reflecting the concentration of the target substance. Specifically, the processing circuit 340 controls the magnet 320 and the optical device 330 according to the measurement sequence. The applied magnetic fields include a magnetic field for bringing the magnetic particles closer to the light-transmitting substrate (hereinafter referred to as the lower magnetic field) and a magnetic field for moving the magnetic particles away from the light-transmitting substrate (hereinafter referred to as the upper magnetic field). The processing circuit 340 repeatedly acquires the measurement signal output from the optical device 330 during optical measurement. The measurement control function 341A is an example of a measurement unit.

[0017] The measurement sequence refers to the time series of various processes executed for optical measurement. The control parameters of the measurement sequence related to control of the magnet 320 are not particularly limited, and various parameters are used as appropriate. For example, the parameters used include the application time of the upper or lower magnetic field to the complex containing the substance to be measured, the strength of the upper or lower magnetic field, and / or the natural settling time of the complex. The natural settling time refers to the time when the upper or lower magnetic field is not applied. The control parameters of the measurement sequence related to control of the optical device 330 include the on and off timing of light irradiation by the optical device 330.

[0018] By implementing the calculation function 342, the processing circuit 340 calculates an index value (hereinafter, "fluctuation index value") related to the fluctuation of the measurement signal during the first period. The fluctuation index value can be any parameter that reflects the concentration of the target substance. For example, the fluctuation index value can be the rate of fluctuation of the measurement signal intensity during the first period, the integrated value of the fluctuation rate, or the maximum or minimum value of the measurement signal intensity. The fluctuation index value can be a single parameter or a combination of multiple parameters, or it can be a value calculated from various calculation results using a combination of multiple parameters. The first period is a period during which the measurement signal used to calculate the fluctuation index value is acquired. It is a local period during which the behavior of the measurement signal intensity changes typically depending on the concentration range of the target substance. The first period may be included in the second period during which the measurement signal used to quantify the target substance is acquired. However, specifically, it is preferably set to a portion of the period from the start of optical measurement of the target substance to the application of the upper magnetic field. The first period is a period during which control parameters of the measurement sequence are determined. Hereinafter, the first period will be referred to as the fluctuation measurement period. The second period may be any period during which a measurement signal used to quantify the substance to be measured is obtained, and may be arbitrarily set to include, for example, some or all of the lower magnetic field application time, natural sedimentation time, and upper magnetic field application time.

[0019] By implementing the selection function 343A, the processing circuit 340 selects a measurement sequence to be used after the fluctuation measurement period, depending on the concentration range corresponding to the fluctuation index value of the target substance. The measurement control function 341A acquires a measurement signal using the selected measurement sequence after the fluctuation measurement period. The concentration range refers to a range of concentrations of the target substance. If the processing circuit 340 determines that the concentration range is a first concentration range based on a comparison between the fluctuation index value and a threshold value corresponding to the fluctuation measurement period, it selects a measurement sequence configured with measurement parameters suitable for quantifying the first concentration range. On the other hand, if the processing circuit 340 determines that the concentration range is a second concentration range lower than the first concentration range, it selects a measurement sequence configured with measurement parameters suitable for quantifying the second concentration range. Note that the threshold can be set to any value based on experiments, predictive calculations, etc., as long as it is a value corresponding to the fluctuation index value and the fluctuation measurement period. Specifically, the threshold is calculated by performing statistical processing taking into account parameters that affect the reaction, such as sample influence, reaction temperature, and the subtype of the target substance.

[0020] By implementing the quantification function 344, the processing circuit 340 quantifies the target substance based on the measurement signal acquired during the second period. Specifically, the processing circuit 340 calculates the concentration value of the target substance based on the intensity of the measurement signal, and a determination result regarding whether the target substance is negative or positive based on the concentration value, as the quantitative value of the test item. More specifically, the processing circuit 340 quantifies the test item of the target substance based on the measurement signal acquired during the second period and a calibration curve corresponding to the target substance. The calibration curve may be stored in advance in the storage device 370 for each type of substance, or may be imported from outside using various media or means, such as portable storage media such as flash memory, CD-ROM, DVD, or magnetic media, one-dimensional and two-dimensional codes, or communication.

[0021] By implementing the output control function 345, the processing circuitry 340 outputs various information via an output interface such as a display 360. As an example, the processing circuitry 340 displays on the display 360 the measurement sequence selected by the selection function 343A, the quantitative values ​​of various test items obtained by the quantification function 344, etc.

[0022] The input device 350 receives various input operations from an operator and converts the received input operations into operation signals. The operation signals are supplied to the processing circuit 340. Examples of the input device 350 that can be used include physical switches, touch panels, touch pads, joysticks, and keyboards. A voice input device that recognizes the operator's speech detected by a microphone and converts it into operation signals may also be used as the input device 350.

[0023] The display 360 displays various information using the output control function 345. As the display 360, for example, a liquid crystal display (LCD), a cathode ray tube (CRT) display, an organic electroluminescence display (OLED), a plasma display, or any other display can be appropriately used. The display 360 may also be a projector.

[0024] The storage device 370 may be a storage device such as a read-only memory (ROM), a random access memory (RAM), a hard disk drive (HDD), a solid state drive (SSD), or an integrated circuit storage device that stores various information. The storage device 370 may also be a drive device or a recognition device that reads and writes various information from / to portable storage media such as flash memory, CD-ROM, DVD, or magnetic media, or one-dimensional and two-dimensional barcodes. The storage device 370 may also include a communication function or a communication device that retrieves information via a network or wireless communication. The storage device 370 does not necessarily have to be realized by a single storage device. For example, the storage device 370 may be realized by multiple storage devices, or by any combination of one or more storage devices and one or more of the above-mentioned drive devices, recognition devices, and / or communication devices. The storage device 370 stores one or more programs according to this embodiment. For example, the programs may be pre-stored in the storage device 370. Alternatively, the control program may be stored in a non-transitory storage medium, distributed, read from the non-transitory storage medium, and installed in the storage device 370. Alternatively, the control program may be downloaded from a network, for example, and installed in the storage device 370.

[0025] Fig. 2 is a diagram showing the optical measurement principle of the optical measurement device 300. Fig. 2 shows a cross section of the optical measurement device 300 in which the inspection cartridge 200A is mounted on a support base 310 (not shown in Fig. 2).

[0026] The test cartridge 200A has a housing 211. The housing 211 is formed in a substantially rectangular parallelepiped shape from a resin such as ABS (acrylonitrile butadiene styrene). The housing 211 may be colored black for the purpose of blocking light. A drip hole 212 is formed on the surface of the housing 211. The drip hole 212 is connected to a reaction chamber 213 inside the housing 211 via a flow path.

[0027] A light-transmitting substrate 214 is provided on the back surface of the housing 211. The light-transmitting substrate 214 is an example of a measurement unit. The light-transmitting substrate 214 is a light-transmitting substrate on which a first substance 215 that specifically binds to the measurement target substance 231 is fixed. Specifically, the light-transmitting substrate 214 has a light-transmitting base 216. The base 216 is formed of, for example, non-alkali glass. An optical waveguide 217 is formed on the surface of the base 216 facing the reaction chamber 213.

[0028] As an example, a planar optical waveguide is used as the optical waveguide 217. The optical waveguide 217 can be formed from, for example, a thermosetting resin such as a phenolic resin, an epoxy resin, or an acrylic resin, or can be formed from a photocurable resin or alkali-free glass. The optical waveguide 217 is preferably transparent to a predetermined light and is made of, for example, a resin having a higher refractive index than the base 216.

[0029] A part of the surface of optical waveguide 217 forms detection surface (sensing area) 218, which forms the bottom surface of reaction vessel 213. A first substance 215 that reacts specifically with measurement target substance 231 is immobilized on detection surface 218. First substance 215 is immobilized, for example, by hydrophobic interaction or chemical bonding with the surface of optical waveguide 217. Detection surface 218 refers to an area where near-field light (evanescent light) generated on the surface of optical waveguide 217 can be generated.

[0030] A test solution is introduced into reaction chamber 213 via drip hole 212. As described above, second substance 253 that specifically binds to the substance to be measured is bound to magnetic particles 251. Also, first substance 215 that specifically reacts with substance to be measured 231 is immobilized on detection surface 218. It is assumed that substance to be measured 231 is an antigen, second substance 253 is an antibody (secondary antibody), and first substance 215 is an antibody (primary antibody).

[0031] An incident grating 219 and a reflecting grating 220 are provided on both ends of the surface of base 216. Grating 219 has a structure that reflects (diffracts) light, and is placed at a position where light is incident on optical waveguide 217. Grating 220 has a structure that reflects (diffracts) light, and is placed at a position where light propagating through optical waveguide 217 is reflected to the outside.

[0032] The optical measuring device 300 is equipped with an optical device 330 including a light source 331 and a photodetector 332. The light source 331 irradiates a light beam L1 toward the light-transmitting substrate 214 under the control of the processing circuit 340. A laser diode, a light-emitting diode, or the like may be used as the light source 331. The light beam L1 may be shaped to be approximately parallel by a lens or the like that is added separately. The photodetector 332 detects a light beam L2 emitted from the light-transmitting substrate 214. A photodiode may be used as the photodetector 332. The photodetector 332 generates a measurement signal that indicates the intensity of the detected light beam L2. The optical device 330 is an example of a measurement unit.

[0033] As shown in Fig. 2, a magnet 320 is provided inside the optical measurement device 300. As shown in Fig. 2, the magnet 320 has a lower magnetic field magnet 321 and an upper magnetic field magnet 322 that sandwich the test cartridge 200A. The lower magnetic field magnet 321 and the upper magnetic field magnet 322 are realized by permanent magnets or electromagnets. The lower magnetic field magnet 321 applies a lower magnetic field to bring the magnetic particles 251 closer to the detection surface 218 under the control of the processing circuit 340. The upper magnetic field magnet 322 applies an upper magnetic field to move the magnetic particles 251 away from the detection surface 218 under the control of the processing circuit 340. The magnet 320 is an example of a measurement unit.

[0034] FIG. 3 is a diagram comparing the change in measurement signal strength over time when measuring a high concentration antigen and when measuring a low concentration antigen. FIG. 3(A) is a graph showing the change in measurement signal strength over time when measuring a high concentration antigen, and FIG. 3(B) is a graph showing the change in measurement signal strength over time when measuring a low concentration antigen. The vertical axis of both graphs represents the measurement signal strength [%], and the horizontal axis represents time [seconds]. 0 seconds represents the start of the optical measurement. At the start of the optical measurement, the test solution is assumed to have been introduced into the reaction chamber 213. A high concentration in FIG. 3 means a concentration higher than the reference concentration, and a low concentration means a concentration lower than the reference concentration. The reference concentration means the upper limit concentration at which quantitative accuracy is good. In other words, a low concentration means a non-high concentration.

[0035] First, a standard measurement sequence according to this embodiment will be described with reference to Figures 3(A) and (B). In optical measurement, the light source 331 emits a light beam into the light-transmitting substrate 214 in response to a command from the processing circuit 340. The light beam incident on the light-transmitting substrate 214 passes through the base 216, is reflected or diffracted by the grating 219, and enters the optical waveguide 217, where it propagates. The light beam is then reflected or diffracted by the grating 220 and exits the light-transmitting substrate 214. The photodetector 332 detects the emitted light beam and outputs a measurement signal representing the intensity of the detected light beam. The output measurement signal is supplied to the processing circuit 340. The measurement signal is repeatedly acquired during optical measurement.

[0036] When the reaction chamber 213 is empty, the light propagating through the optical waveguide 217 is not totally reflected, and evanescent light is generated at the detection surface 218. In this case, the signal intensity of the measurement signal is lower than in the case of total reflection. As time passes from the start of the optical measurement (0 seconds), the test solution dropped into the test cartridge 200A flows into the reaction chamber 213. When the detection surface 218 is immersed in the test solution, the light propagating through the optical waveguide 217 is totally reflected. In other words, as time passes from the start of the optical measurement (0 seconds), the signal intensity of the measurement signal increases.

[0037] 3(A) and 3(B), at time t1 after the start of optical measurement, magnet 320 starts applying the lower magnetic field in accordance with a command from processing circuit 340. At time t2, after a predetermined period of time (hereinafter referred to as the lower magnetic field application period) has elapsed since time t1, magnet 320 stops applying the lower magnetic field in accordance with a command from processing circuit 340. The application of the lower magnetic field attracts magnetic particles to detection surface 218. As the magnetic particles are attracted to detection surface 218 one after another, angular bundles of magnetic particles are arranged on detection surface 218 along the magnetic field lines of the lower magnetic field, and many bundles are arranged on detection surface 218.

[0038] The magnetic field-free state is maintained from time t2 until time t3, after a predetermined period of time (hereinafter referred to as the natural settling period) has elapsed. During the natural settling period, the bundles of magnetic particles arranged in an angular pattern on the detection surface 218 loosen and settle to the bottom of the detection surface 218. At this point, the intensity of the leaked light from the detection surface 218 increases, and the signal intensity of the measurement signal decreases accordingly.

[0039] At time t3, magnet 320 starts applying the upper magnetic field in response to a command from processing circuit 340. At time t4, a predetermined period of time (hereinafter referred to as the upper magnetic field application period) has elapsed since time t3, magnet 320 stops applying the upper magnetic field in response to a command from processing circuit 340. Application of the upper magnetic field causes magnetic particles that have settled on detection surface 218 to be pulled away from detection surface 218. This increases the signal strength of the measurement signal. On the other hand, magnetic particles that are bound to antigens are bound to antibodies immobilized on detection surface 218, and therefore remain on detection surface 218 even when the upper magnetic field is applied. Therefore, if no antigen is present in the sample, the signal strength of the light detection signal returns to its initial state. However, if an antigen is present in the sample, the signal strength of the measurement signal does not return to its initial state and remains at a value lower than the initial state.

[0040] The signal intensity of the measurement signal acquired during the upper magnetic field application period reflects the concentration of the substance to be measured. Therefore, the quantification function 344 quantifies the test item of the substance to be measured using all or part of the measurement signal during the upper magnetic field application period. As an example, the upper magnetic field application period in a standard measurement sequence is set to a period of 400 to 500 seconds from the start of measurement. Note that the measurement signals required for quantification are not limited to all or part of the measurement signals during the upper magnetic field application period; other measurement signals can also be used, and quantification can also be performed using calculation results that combine multiple measurement signals.

[0041] As shown in Figures 3(A) and 3(B), the signal intensity of the measurement signal behaves differently for high-concentration antigens and low-concentration antigens. In the first example, the measurement signal intensity peaks during a period P1 immediately after the start time t1 of the lower magnetic field application. The decline from this peak is steep for high concentrations but gentler for low concentrations. Therefore, the concentration range of the measurement target substance is determined based on the fluctuation index value of the measurement signal intensity during a fluctuation measurement period TM1 corresponding to period P1. The fluctuation index value may be the rate of fluctuation or the integrated value of the rate of fluctuation of the measurement signal intensity during the fluctuation measurement period TM1. The concentration range is typically classified into a high-concentration range (hereinafter referred to as the high-concentration range) and a low-concentration range (hereinafter referred to as the low-concentration range). If the fluctuation index value is greater than threshold A, the range is determined to be a high-concentration range, and if it is smaller than a first threshold, the range is determined to be a low-concentration range. The threshold A can be determined arbitrarily through experiments, predictive calculations, etc.

[0042] The fluctuation measurement period TM1 is set to a local period including the time when the measurement target substance is not highly concentrated and the measurement signal intensity peaks with the start of application of the lower magnetic field. As an example, the period TM1 is set to a local period including the time when the peak empirically arrives within the period from the start of the optical measurement through time t1 to time t2. The time width of the period TM1 can be set arbitrarily.

[0043] In the second example, during the period P2 immediately after the stop time t2 of the application of the lower magnetic field, there is a jump in the measurement signal intensity at low concentrations, but no jump at high concentrations. Therefore, the concentration range of the substance to be measured is determined based on the fluctuation index value of the measurement signal intensity during the fluctuation measurement period TM2 corresponding to period P2. The fluctuation index value may be the rate of fluctuation of the measurement signal intensity during the fluctuation measurement period TM2 or an integrated value of the fluctuation rate. If the fluctuation index value is larger than threshold B, it is determined to be in the low concentration range, and if it is smaller than threshold B, it is determined to be in the high concentration range. Threshold B can be determined arbitrarily through experiments, predictive calculations, etc.

[0044] When the concentration of the substance to be measured is not high, the fluctuation measurement period TM2 is set to a local period including the time when the measurement signal intensity jumps up as the application of the lower magnetic field ends. As an example, the fluctuation measurement period TM2 is set to the period from time t2 to the time when the jump can be detected. The detectable time may be set to a time from time t2 to the time when the peak of the jump arrives, or may be set to a time longer than or shorter than the time when the jump can be detected based on the fluctuation index value.

[0045] In the third example, during the period P3 in which the measurement signal intensity falls from time t2 when the application of the lower magnetic field is stopped, the degree of fall in the measurement signal intensity is steep at high concentrations but gentler at low concentrations. Therefore, the concentration range of the substance to be measured is determined based on the fluctuation index value of the measurement signal intensity during the fluctuation measurement period TM3 corresponding to the fall period P3. The fluctuation index value may be the rate of fluctuation of the measurement signal intensity during the fluctuation measurement period TM3 or an integrated value of the fluctuation rate. If the fluctuation index value is greater than the threshold C, the concentration range is determined to be high; if it is smaller than the threshold C, the concentration range is determined to be low. The threshold C can be determined arbitrarily through experiments, predictive calculations, or the like.

[0046] The fluctuation measurement period TM3 is set to a local period during which the measurement signal strength decreases as the application of the lower magnetic field ends. As an example, the fluctuation measurement period TM3 is set to the period from the detectable time to the estimated convergence time. The estimated convergence time is set to a time when it is empirically estimated that the decrease in the measurement signal strength will converge. The estimated convergence time is set before the start time t3 of the upper magnetic field.

[0047] The fluctuation measurement period is not limited to the fluctuation measurement periods TM1, TM2, and TM3 in the above example, and can be set to any measurement period. Furthermore, the fluctuation measurement period may be single or multiple. It is preferable to select the fluctuation measurement period from among TM1, TM2, and TM3. However, calculating the concentration range during the fluctuation measurement period TM1, which is the initial section of the measurement, allows for diversification of the subsequent measurement sequence conditions, so it is most preferable to calculate the concentration range during the fluctuation measurement period as early as possible in the measurement stage.

[0048] Next, the procedure of optical measurement by the immunoassay system 100 according to the first embodiment will be described.

[0049] 4 is a diagram showing the processing procedure of optical measurement by the immunoassay system 100 according to the first embodiment. It is assumed that, at the start of step SA1, the sample treatment liquid has been introduced into the reaction chamber 213 of the test cartridge 200A. It is also assumed that the first period used to calculate the fluctuation index value is the fluctuation measurement period TM2 shown in FIG. 3, and the fluctuation index value is the integrated value of the fluctuation rate of the intensity of the measurement signal over the fluctuation measurement period TM2.

[0050] First, the processing circuit 340 starts optical measurement using the measurement control function 341A (step SA1). In the optical measurement in step SA1, the processing circuit 340 repeatedly acquires a measurement signal reflecting the concentration of the measurement target substance contained in the sample treatment liquid from the optical device 330 using the measurement control function 341A. At the start of the optical measurement, the optical measurement may be performed according to a standard measurement sequence.

[0051] After step SA1 is performed, the processing circuit 340 uses the calculation function 342 to calculate an integrated value of the fluctuation rate of the measured value during the fluctuation measurement period TM2 (step SA2). Specifically, in step SA2, the processing circuit 340 calculates the difference in the intensity of the measurement signal between two adjacent measurement points during period TM2. This difference represents the slope of the intensity of the measurement signal, in other words, the fluctuation rate. In this way, the processing circuit 340 calculates the fluctuation rate for each measurement point during period TM2. The processing circuit 340 then calculates the sum of the multiple fluctuation rates corresponding to the multiple measurement points obtained during period TM2 as an integrated value.

[0052] When step SA2 is performed, the processing circuit 340 uses the selection function 343A to determine whether the integrated value calculated in step SA2 is smaller than a threshold value (step SA3).

[0053] If it is determined in step SA3 that the integrated value is not smaller than the threshold value (step SA3: NO), the processing circuit 340 selects a low-concentration measurement sequence using the selection function 343A (step SA4). A low-concentration measurement sequence is a measurement sequence suitable for quantifying a substance to be measured in a low concentration range, and has a measurement time longer than that of a standard measurement sequence. As an example, the measurement time of a standard measurement sequence is set to approximately 450 seconds, while the measurement sequence for a low concentration is preferably set to approximately 600 seconds. The measurement time can be extended, for example, by extending the natural settling time compared to that of the standard measurement sequence. It is assumed that the duration of the application period of the upper magnetic field is equivalent to that of the standard measurement sequence.

[0054] If it is determined in step SA3 that the integrated value is smaller than the threshold value (step SA3: YES), the processing circuit 340 selects a high-concentration measurement sequence using the selection function 343A (step SA5). A high-concentration measurement sequence is a measurement sequence that is suitable for quantifying a substance to be measured in a high-concentration range and has a measurement time that is shorter than that of a standard measurement sequence. A low-concentration measurement sequence should be set to approximately 180 seconds. The measurement time can be reduced by, for example, shortening the natural settling time. The duration of the application period of the upper magnetic field is assumed to be equivalent to that of the standard measurement sequence.

[0055] When step SA4 or SA5 is performed, the processing circuit 340, using the measurement control function 341A, performs optical measurements from period TM2 onward in accordance with the measurement sequence selected in step SA4 or SA5 (step SA6). That is, when a measurement sequence for a high concentration is selected, the natural settling time is shortened, and accordingly the start point of application of the upper magnetic field is advanced, whereas when a measurement sequence for a low concentration is selected, the natural settling time is extended, and accordingly the start point of application of the upper magnetic field is delayed.

[0056] After step SA6, the processing circuit 340 quantifies the target substance using the quantification function 344 (step SA7). In step SA7, the processing circuit 340 calculates a quantitative value based on the signal intensity of the measurement signal acquired during the quantitative measurement period set after the variable measurement period TM2. The processing circuit 340 then calculates the target substance concentration and a determination result, such as a negative or positive result, based on the concentration value. Specifically, the processing circuit 340 first selects a calibration curve corresponding to the target substance from among multiple calibration curves corresponding to multiple substances stored in the storage device 370. A calibration curve is a straight line or curve representing the relationship between the concentration of the target substance, whose concentration value is known, and the calculated measurement value of the measurement signal intensity. The processing circuit 340 then calculates the target substance concentration based on a comparison between the selected calibration curve and the signal intensity of the measurement signal acquired during the upper magnetic field application period. For example, if the calculated concentration value exceeds a threshold, the processing circuit 340 determines the target substance to be positive, and if it is below a threshold, the processing circuit 340 determines the target substance to be negative.

[0057] After step SA7 is performed, the processing circuitry 340 outputs the quantitative values ​​obtained in step SA7 using the output control function 345 (step SA8). As an example, the processing circuitry 340 displays the quantitative values ​​on the display 360 in a predetermined layout.

[0058] FIG. 5 is a diagram showing an example of a display screen I1 for quantitative values ​​according to the first embodiment. As shown in FIG. 5, the display screen I1 includes a display field I11 for the substance to be measured, a display field I12 for the concentration range, a display field I13 for the measurement sequence, a display field I14 for the determination result, and a display field I15 for the concentration value. The display field I11 displays the name of the substance to be measured, such as "XXX virus." The display field I12 displays a character string indicating the type of concentration range of the substance to be measured determined in step SA3, such as "low concentration." The display field I13 displays a character string indicating the type of measurement sequence selected in step SA4 or SA5, such as "long time (10 minutes)." The display field I14 displays a character string indicating the positive / negative determination result obtained in step SA7, such as "positive." The display field I15 displays a numerical value indicating the concentration value of the substance to be measured obtained in step SA7, such as "YYYY." By displaying the concentration range and type of measurement sequence together with the positive / negative determination result and quantitative values ​​such as concentration values, the user can understand the measurement sequence that was performed and the reasons for selecting that measurement sequence. Note that some of the display columns I11 to I15 may be omitted, or other information may be displayed.

[0059] When step SA7 is performed, the optical measurement procedure shown in FIG. 4 ends.

[0060] As described above, according to the first embodiment, the immunoassay system 100 simply determines the concentration range of the substance to be measured based on the measurement signal acquired during the variable measurement period before the quantitative measurement period, selects a measurement sequence corresponding to that concentration range, and performs optical measurements after the variable measurement period using the selected measurement sequence. This allows the measurement sequence to be executed according to the concentration range of the substance to be measured, thereby expanding the dynamic range of concentration and improving measurement accuracy.

[0061] (Second embodiment) The immunoassay system 100 according to the second embodiment selects a measurement channel depending on the concentration range of the substance to be measured. The immunoassay system 100 according to the second embodiment will be described below. In the following description, components having substantially the same functions as those in the first embodiment will be given the same reference numerals and will be described only when necessary.

[0062] FIG. 6 is a diagram showing an example of the configuration of an immunoassay system 100 according to the second embodiment. As shown in FIG. 6, the immunoassay system 100 according to the second embodiment has a test cartridge 200B instead of the test cartridge 200A. The test cartridge 200B has multiple combinations of a detection surface 218 and an optical device 330 prepared for one reaction vessel. The combination of the detection surface 218 and the optical device 330 constitutes a measurement channel. The test cartridge 200B has multiple measurement channels with different reagent characteristics of the primary antibody immobilized on the detection surface 218. The reagent characteristics include the reaction rate and / or reaction efficiency between the primary antibody and the substance to be measured. The measurement signals obtained in each measurement channel are supplied to a processing circuit 340.

[0063] As shown in FIG. 6, the processing circuitry 340 implements a calculation function 342, a quantification function 344, and an output control function 345, as well as a measurement control function 341B and a selection function 343B.

[0064] By implementing the measurement control function 341B, the processing circuit 340 optically measures the analyte contained in the sample using some or all of multiple measurement channels with different reagent characteristics of the immobilized primary antibody, and acquires a measurement signal reflecting the concentration of the analyte. Specifically, the processing circuit 340 controls the magnet 320 and the optical device 330 according to a measurement sequence. The measurement control function 341B uses a standard measurement sequence. During optical measurement, the processing circuit 340 repeatedly acquires the measurement signal output from the optical device 330 using some or all of the implemented multiple measurement channels. After the selection of a measurement channel by the selection function 343B, the selected measurement channel is used. Before the selection of a measurement channel by the selection function 343B, any measurement channel is used. The measurement control function 341B is an example of a measurement unit.

[0065] By implementing the selection function 343B, the processing circuit 340 selects one measurement channel from multiple measurement channels to be used after the fluctuation measurement period, depending on the concentration range corresponding to the fluctuation index value of the measurement target substance. The measurement control function 341B acquires a measurement signal using the selected measurement channel after the fluctuation measurement period. When the processing circuit 340 determines that the concentration range is a first concentration range based on a comparison between the fluctuation index value and a threshold value corresponding to the fluctuation measurement period, it selects one measurement channel having reagent characteristics suitable for quantification of the first concentration range. On the other hand, when the processing circuit 340 determines that the concentration range is a second concentration range lower than the first concentration range, it selects one measurement channel having reagent characteristics suitable for quantification of the second concentration range.

[0066] "Selecting a measurement channel" means that the measurement signal output from that measurement channel is used in subsequent processing. That is, this includes not only the case where the selected measurement channel is driven and the unselected measurement channel is stopped, but also the case where both the selected and unselected measurement channels are driven. In the latter case, the measurement signals output from both measurement channels are supplied to processing circuit 340, and only the measurement signal from the selected measurement channel is used in subsequent processing.

[0067] Next, the procedure of optical measurement by the immunoassay system 100 according to the second embodiment will be described.

[0068] FIG. 7 is a diagram showing the procedure for optical measurement by the immunoassay system 100 according to the second embodiment. It is assumed that, at the start of step SB1, the reaction chamber of the test cartridge 200B is filled with a sample treatment liquid. The first period used to calculate the fluctuation index value is the period TM2 shown in FIG. 3, and the fluctuation index value is the integrated value of the fluctuation rate of the intensity of the measurement signal over the period TM2. It is also assumed that the immunoassay system 100 is equipped with two types of measurement channels: a low-concentration measurement channel and a high-concentration measurement channel. The low-concentration measurement channel is a measurement channel on which an antibody having highly reactive reagent characteristics is immobilized, making it suitable for quantifying a substance to be measured in a low concentration range compared to the high-concentration measurement channel. The high-concentration measurement channel is a measurement channel on which an antibody having less reactive reagent characteristics is immobilized, making it suitable for quantifying a substance to be measured in a high concentration range compared to the low-concentration measurement channel.

[0069] First, the processing circuit 340 starts optical measurement using the measurement control function 341B (step SB1). In the optical measurement in step SB1, the processing circuit 340 repeatedly acquires a measurement signal reflecting the concentration of the measurement target substance contained in the sample treatment liquid from the optical device 330 using the measurement control function 341B. From the start of the optical measurement to the end of the fluctuating measurement period, either the measurement channel for low concentration or the measurement channel for high concentration may be used, or both may be used.

[0070] After step SB1 is performed, the processing circuit 340 calculates the integrated value of the fluctuation rate of the measured value during the fluctuation measurement period TM2 using the calculation function 342 (step SB2). The method for calculating the integrated value of the fluctuation rate is the same as in step SA2.

[0071] When step SB2 is performed, the processing circuit 340 uses the selection function 343B to determine whether the integrated value calculated in step SB2 is smaller than a threshold value (step SB3).

[0072] If it is determined in step SB3 that the integrated value is not smaller than the threshold value (step SB3: NO), the processing circuit 340 selects the measurement channel for low concentration using the selection function 343B (step SB4).If it is determined in step SB3 that the integrated value is smaller than the threshold value (step SB3: YES), the processing circuit 340 selects the measurement channel for high concentration using the selection function 343B (step SB5).

[0073] When step SB4 or SB5 is performed, the processing circuit 340 causes the measurement control function 341B to use the measurement channel selected in step SB4 or SB5 to perform optical measurements after the fluctuation measurement period TM2 (step SB6).

[0074] After step SB6 is performed, processing circuit 340 quantifies the measurement target substance using quantification function 344 (step SB7). In step SB7, processing circuit 340 calculates a quantitative value based on the signal intensity of the measurement signal acquired from the measurement channel selected in step SB6 during the quantitative measurement period set after variable measurement period TM2, and the concentration value of the measurement target substance and a determination result regarding whether the measurement target substance is negative or positive based on the concentration value. The method for calculating the quantitative value is the same as in step SA7.

[0075] After step SB7 is performed, the processing circuitry 340 outputs the quantitative values ​​obtained in step SB7 using the output control function 345 (step SB8). As an example, the processing circuitry 340 displays the quantitative values ​​on the display 360 in a predetermined layout.

[0076] FIG. 8 is a diagram showing an example of a display screen I2 for quantitative values ​​according to the second embodiment. As shown in FIG. 8, the display screen I2 includes a display field I21 for the substance to be measured, a display field I22 for the concentration range, a display field I23 for the measurement channel, a display field I24 for the determination result, and a display field I25 for the concentration value. The display field I21 displays the name of the substance to be measured, such as "XXX virus." The display field I22 displays a character string, such as "low concentration," indicating the type of concentration range of the substance to be measured determined in step SB3. The display field I23 displays a character string, such as "high reactivity," indicating the type of measurement channel selected in step SB4 or SB5. The display field I24 displays a character string, such as "positive," indicating the positive / negative determination result obtained in step SB7. The display field I25 displays a numerical value, such as "YYYY," indicating the concentration value of the substance to be measured obtained in step SB7. By displaying the concentration range and the type of measurement channel together with the positive / negative determination result and quantitative values ​​such as concentration values, the user can understand the measurement channel used and the reasons for selecting that measurement channel. Note that some of the display columns I21 to I25 may be omitted, or other information may be displayed.

[0077] When step SB7 is performed, the optical measurement procedure shown in FIG. 7 ends.

[0078] As described above, according to the second embodiment, the immunoassay system 100 simply determines the concentration range of the substance to be measured based on the measurement signal acquired during the variable measurement period before the quantitative measurement period, selects a measurement channel corresponding to that concentration range, and performs optical measurements after the variable measurement period using the selected measurement channel. This allows the measurement channel corresponding to the concentration range of the substance to be measured to be performed, thereby expanding the dynamic range of concentration and improving measurement accuracy.

[0079] (Third embodiment) The immunoassay system 100 according to the third embodiment selects a measurement sequence and a measurement channel depending on the concentration range of the substance to be measured. The immunoassay system 100 according to the third embodiment will be described below. In the following description, components having substantially the same functions as those in the first and second embodiments will be given the same reference numerals and will be described only when necessary.

[0080] Fig. 9 is a diagram showing an example of the configuration of an immunoassay system 100 according to the third embodiment. As shown in Fig. 9, a test cartridge 200C is provided. The immunoassay system 100 according to the second embodiment has a test cartridge 200C instead of the test cartridge 200A. Like the test cartridge 200B, the test cartridge 200C has multiple measurement channels with different reagent characteristics of the primary antibodies immobilized on the detection surface 218.

[0081] As shown in FIG. 9, the processing circuitry 340 implements a calculation function 342, a quantification function 344, and an output control function 345, as well as a measurement control function 341C and a selection function 343C.

[0082] By implementing the measurement control function 341C, the processing circuit 340 optically measures the analyte contained in the sample in some or all of the multiple measurement channels with different reagent characteristics of the immobilized primary antibody according to the measurement sequence, and acquires a measurement signal reflecting the concentration of the analyte. Specifically, the processing circuit 340 controls the magnet 320 and the optical device 330 according to the measurement sequence. As in the first embodiment, multiple measurement sequences corresponding to different concentration ranges are prepared as measurement sequences according to the first embodiment. As in the second embodiment, the processing circuit 340 repeatedly acquires the measurement signal output from the optical device 330 during optical measurement using all or some of the multiple implemented measurement channels. After the selection function 343C selects a measurement channel and measurement sequence, the selected measurement channel and measurement sequence are used. Before the selection of a measurement channel by the selection function 343C, an arbitrary measurement channel is used, as in the second embodiment. Before the selection of a measurement sequence by the selection function 343C, a standard measurement sequence is used, as in the first embodiment. The measurement control function 341C is an example of a measurement unit.

[0083] By implementing the selection function 343C, the processing circuit 340 selects one measurement channel and one measurement sequence to be used in a second period following the first period, depending on the concentration range corresponding to the fluctuation index value of the measurement target substance. The measurement control function 341C performs optical measurement of the measurement target substance using the selected measurement channel and measurement sequence during the second period. The processing circuit 340 selects one measurement channel and one measurement sequence based on a comparison between the fluctuation index value and a threshold value corresponding to the fluctuation measurement period. The threshold value according to the third embodiment includes a threshold value for selecting a measurement sequence and a threshold value for selecting a measurement channel. As an example, if the measurement sequences and measurement channels are each divided into high concentration and low concentration, there are four selectable combinations of measurement sequences and measurement channels: a high concentration measurement sequence and a high concentration measurement channel, a high concentration measurement sequence and a low concentration measurement channel, a low concentration measurement sequence and a high concentration measurement channel, and a low concentration measurement sequence and a low concentration measurement channel.

[0084] Next, the procedure of optical measurement by the immunoassay system 100 according to the third embodiment will be described.

[0085] Figure 10 is a diagram showing the processing procedure of optical measurement by the immunoassay system 100 according to the third embodiment. It is assumed that, at the start of step SB1, the sample treatment liquid has been introduced into the reaction chamber of the test cartridge 200B. It is also assumed that the first period used to calculate the fluctuation index value is the period TM2 shown in Figure 3, and the fluctuation index value is the integrated value of the fluctuation rate of the intensity of the measurement signal over the period TM2. It is also assumed that the immunoassay system 100 is equipped with two types of measurement channels: a measurement channel for low concentrations and a measurement channel for high concentrations.

[0086] First, the processing circuit 340 starts optical measurement using the measurement control function 341C (step SC1). In the optical measurement in step SC1, the processing circuit 340 repeatedly acquires a measurement signal reflecting the concentration of the measurement target substance contained in the sample treatment liquid from the optical device 330 using the measurement control function 341C. The measurement channel used may be either the measurement channel for low concentration or the measurement channel for high concentration, or both. In this embodiment, for simplicity, it is assumed that one measurement channel (initial channel) is used. At the start of the optical measurement, the optical measurement may be performed according to a standard measurement sequence.

[0087] After step SC1 is performed, the processing circuit 340 calculates the integrated value of the fluctuation rate of the measured value during the fluctuation measurement period TM2 using the calculation function 342 (step SC2). The method for calculating the integrated value of the fluctuation rate is the same as in step SA2.

[0088] After step SC2 is performed, the processing circuit 340 uses the selection function 343C to determine whether the integrated value calculated in step SC2 is smaller than the first threshold value (step SC3).

[0089] If it is determined in step SC3 that the integrated value is not smaller than the first threshold value (step SC3: NO), the processing circuitry 340 selects the measurement sequence for low concentrations using the selection function 343C (step SC4).

[0090] After step SC4, the processing circuit 340 determines whether the integrated value calculated in step SC2 is smaller than the second threshold (step SC5). If it is determined in step SC5 that the integrated value is not smaller than the second threshold (step SC5: NO), the processing circuit 340 selects the measurement channel for low concentration using the selection function 343C (step SC6). If it is determined in step SC5 that the integrated value is smaller than the threshold (step SC5: YES), the processing circuit 340 selects the measurement channel for high concentration using the selection function 343C (step SC7).

[0091] On the other hand, if it is determined in step SC3 that the integrated value is smaller than the first threshold (step SC3: YES), the processing circuit 340 selects the measurement sequence for high and low concentrations using the selection function 343C (step SC8). After step SC8 is performed, the processing circuit 340 determines whether the integrated value calculated in step SC2 is smaller than the third threshold (step SC9). If it is determined in step SC9 that the integrated value is not smaller than the third threshold (step SC9: NO), the processing circuit 340 selects the measurement channel for low concentration using the selection function 343C (step SC10). If it is determined in step SC9 that the integrated value is smaller than the threshold (step SC9: YES), the processing circuit 340 selects the measurement channel for high concentration using the selection function 343C (step SC11).

[0092] When steps SC6, SC7, SC10 or SC11 are performed, the processing circuit 340 uses the measurement control function 341C to perform optical measurements after the fluctuation measurement period TM2 according to the measurement sequence selected in step SC4 or SC9, using the measurement channel selected in step SC6, SC7, SC10 or SC11 (step SC12).

[0093] After step SC12, the processing circuit 340 quantifies the measurement target substance using the quantification function 344 (step SC13). The processing circuit 340 calculates a quantitative value based on the signal intensity of the measurement signal acquired from the measurement channel selected in step SC13 during the quantitative measurement period set after the variable measurement period TM2, and the concentration value of the measurement target substance and the determination result regarding whether the measurement target substance is negative or positive based on the concentration value. The method for calculating the quantitative value is the same as in step SA7.

[0094] After step SC13 is performed, the processing circuitry 340 outputs the quantitative values ​​obtained in step SC13 using the output control function 345 (step SC14). As an example, the processing circuitry 340 displays the quantitative values ​​on the display 360 in a predetermined layout.

[0095] FIG. 11 is a diagram showing an example of a display screen I3 for quantitative values ​​according to the third embodiment. As shown in FIG. 11, the display screen I3 includes a display field I31 for the substance to be measured, a display field I32 for the concentration range, a display field I33 for the measurement sequence, a display field I34 for the measurement channel, a display field I35 for the determination result, and a display field I36 for the concentration value. The display field I31 displays the name of the substance to be measured, such as "XXX virus." The display field I32 displays a character string, such as "low concentration," indicating the type of concentration range of the substance to be measured determined in step SC3. The display field I33 displays a character string, such as "long time (10 minutes)," indicating the type of measurement sequence selected in step SC4 or SC8. The display field I34 displays a character string, such as "high reactivity," indicating the type of measurement channel selected in SC6, SC7, SC10, or SC11. The display field I35 displays a character string, such as "positive," indicating the positive / negative determination result obtained in step SC13. Display field I36 displays a numerical value, such as "YYYY," that represents the concentration value of the substance to be measured obtained in step SC13. By displaying the concentration range, measurement sequence type, and measurement channel type together with the positive / negative determination result and quantitative values ​​such as concentration values, the user can understand the measurement sequence and measurement channel used, as well as the reasons for selecting the measurement sequence and measurement channel. Note that some of display fields I31 to I36 may be omitted, or other information may be displayed.

[0096] When step SC13 is performed, the optical measurement procedure shown in FIG. 10 ends.

[0097] In the above embodiment, the selection of the measurement channel is performed after the selection of the measurement sequence, but the measurement of the measurement sequence may be performed after the selection of the measurement channel.

[0098] As described above, according to the third embodiment, the immunoassay system 100 simply determines the concentration range of the substance to be measured based on the measurement signal acquired during the variable measurement period before the quantitative measurement period, selects a measurement sequence corresponding to that concentration range, and performs optical measurements after the variable measurement period using the selected measurement sequence. This allows the measurement sequence to be executed according to the concentration range of the substance to be measured, thereby expanding the dynamic range of concentration and improving measurement accuracy.

[0099] Example 1 The antigen concentration value was measured according to the first, second, and third embodiments using a sample containing a predetermined concentration of antigen. The period TM1 shown in Figure 3 was used as the first period. The fluctuation index value was the integrated value Sx1 of the fluctuation rate of the measured signal intensity. The measurement was performed three times.

[0100] Figure 12 shows the measurable concentration range for each measurement condition. The vertical axis of the graph in Figure 12 represents the signal strength [%] of the measurement signal, and the horizontal axis represents the antigen concentration [pg / ml]. The measurement conditions shown in Figure 12 refer to combinations of measurement sequences and measurement channels.

[0101] In the first embodiment, when Sx1<threshold, the antigen concentration range is a low concentration range. In this case, a measurement sequence with a long measurement time (measurement time 10 minutes) suitable for quantifying the antigen concentration range in the low concentration range indicated by the black circle marks in FIG. 12 was used, which has a longer measurement time than the 4-minute sequence indicated by the black triangle marks in FIG. 12. As a result, it can be seen that even when measuring a sample containing an antigen at a concentration higher than 1000 pg / ml, the signal strength of the measurement signal asymptotically approaches its maximum value. On the other hand, when Sx1>threshold, the antigen concentration range is a high concentration range, so a measurement sequence with a short measurement time (measurement time 3 minutes) suitable for quantifying the high concentration range indicated by the black square marks in FIG. 12 was used. In this case, it can be seen that the signal strength of the measurement signal asymptotically approaches its maximum value at concentrations of 10,000 pg / ml or higher. These measurement results show that the quantifiable range is expanded by at least 10 times compared to when the measurement time is not changed depending on the concentration range.

[0102] Example 2 This example is an example in which only the reference point of Example 1 is changed. In Example 1, a sequence with a measurement time of 4 minutes was used as the measurement reference, but in this example, the reference measurement time is set to 3 minutes. When Sx1<threshold, it is shown that the range in which quantifiable concentration can be expanded can be expanded by performing measurement using a sequence (measurement time 10 minutes) with a long measurement time indicated by the black circle mark in Figure 12 that is suitable for quantitative detection of antigen concentrations in the low concentration range.

[0103] Example 3 This example is an example in which only the reference point of Example 1 is changed. In Example 1, a sequence with a measurement time of 4 minutes was used as the measurement reference, but in this example, the reference measurement time is set to 10 minutes. When Sx1 is greater than the threshold, the range in which quantifiable concentrations can be expanded is shown by performing measurement using sequence B (measurement time 3 minutes), which has a short measurement time indicated by the black square mark in Figure 12 and is suitable for quantitative detection of antigen concentrations in the high concentration range.

[0104] Example 4 In the second embodiment, when Sx1<threshold, the antigen concentration range is a low concentration range, so a highly reactive measurement channel (high reactivity channel) suitable for quantification in a low concentration range, indicated by a black circle in FIG. 13, was used. As described above, it can be seen that even when measuring a sample containing an antigen at a concentration higher than 1000 pg / ml, the signal strength of the measurement signal asymptotically approaches its maximum value. On the other hand, when Sx1>threshold, the antigen concentration range is a high concentration range, so a less reactive measurement channel (low reactivity channel) suitable for quantification in a high concentration range, indicated by a white circle in FIG. 13, was used. In this case, it can be seen that the signal strength of the measurement signal asymptotically approaches its maximum value at concentrations of 5000 pg / ml or higher. These measurement results show that the quantifiable range is expanded by at least five times compared to when the measurement channel is not changed depending on the concentration range.

[0105] Regarding the third embodiment, when Sx1 < the second threshold < the first threshold, a measurement sequence with a long measurement time (measurement time: 10 minutes) suitable for quantification in the low concentration range, indicated by the black circle marks in FIG. 14, and a highly reactive measurement channel (high-reactivity channel) suitable for quantification in the low concentration range were used. When the second threshold < Sx1 < the first threshold, a measurement sequence with a long measurement time (measurement time: 10 minutes) suitable for quantification in the low concentration range, indicated by the white circle marks in FIG. 14, and a low-reactivity measurement channel (high-reactivity channel) suitable for quantification in the high concentration range were used. Also, when the first threshold < the third threshold < Sx1, a measurement sequence with a short measurement time (measurement time: 3 minutes) suitable for quantification in the high concentration range, indicated by the white square marks in FIG. 14, and a low-reactivity measurement channel (low-reactivity channel) suitable for quantification in the high concentration range were used. When the first threshold < Sx1 < the third threshold, a measurement sequence with a short measurement time (measurement time: 3 minutes) suitable for quantification in the high concentration range, indicated by the black square marks in FIG. 14, and a highly reactive measurement channel (high-reactivity channel) suitable for quantification in the low concentration range were used. From these measurement results, it can be seen that compared with the case where the measurement time is not changed and the measurement channel is not selected according to the concentration range in the sample, the quantifiable region is expanded by at least 10 times, and the measurement accuracy is expected to be improved due to an increase in the judgment index.

[0106] (Modification example) The above embodiment was applied to an immunophotonic waveguide detection method using magnetic particles. However, this embodiment is not limited thereto, and it is applicable to various immunological measurement methods regardless of the use of magnetic particles. Examples of such optical measurement methods according to this modification example include immunoturbidimetry without using magnetic particles, immunochromatography, and other methods. In the case of these optical measurement methods, the parameters of the measurement sequence include the concentration of the reagent added to the sample, the type of reagent, the stirring time, the stirring intensity, the wavelength of the irradiation light, and / or the measurement time.

[0107] According to at least one of the embodiments described above, it is possible to expand the dynamic range regarding concentration and improve the measurement accuracy.

[0108] The term "processor" used in the above description refers to a circuit such as a CPU, a GPU, an application specific integrated circuit (ASIC), 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 realizes its function by reading and executing a program stored in a memory circuit. Note that instead of storing a program in a memory circuit, the program may be directly embedded in the processor circuit. In this case, the processor realizes its function by reading and executing the program embedded in the circuit. On the other hand, if the processor is, for example, an ASIC, instead of storing a program in a memory circuit, the function is directly embedded in the processor circuit as a logic circuit. Note that each processor in this embodiment is not limited to being configured as a single circuit for each processor, but may be configured as a single processor by combining multiple independent circuits to realize its function. Furthermore, the functions of the components in FIGS. 1, 6 and 9 may be implemented by integrating them into a single processor.

[0109] Although several embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, modifications, and combinations of embodiments can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims. [Explanation of symbols]

[0110] 100 Immunoassay System 200A, 200B, 200C Inspection Cartridge 211 Cabinet 212 Drip hole 213 Reactor 214 Transparent substrate 215 First substance 216 Base 217 Optical waveguide 218 Sensing surface (sensing area) 219,220 Grading 231 Measurement target substances 251 Magnetic particles 253 Second substance 300 Optical measurement equipment 310 Support stand 320 Magnet 321 Lower Field Magnet 322 Upper Field Magnet 330 Optical equipment 331 Light source 332 Photodetector 340 Processing Circuit 341A, 341B, 341C measurement control function 342 Calculation Function 343A, 343B, 343C selection function 344 Quantitative Function 345 Output Control Function 350 Input Devices 360 display 370 Storage device

Claims

1. a measurement unit that measures a measurement target substance contained in a sample according to a measurement sequence and acquires a measurement signal that reflects the concentration of the measurement target substance; a calculation unit that calculates an index value related to fluctuations in the intensity of the measurement signal during a first period; a selection unit that selects one measurement sequence to be used after the first period in accordance with a concentration range corresponding to the index value of the measurement target substance; An immunoassay system comprising:

2. a measurement unit that measures a substance to be measured contained in a sample using some or all of a plurality of measurement channels having different reagent properties of immobilized antibodies, and acquires a measurement signal that reflects the concentration of the substance to be measured; a calculation unit that calculates an index value related to fluctuations in the intensity of the measurement signal during a first period; a selection unit that selects one measurement channel to be used after the first period from among the plurality of measurement channels according to a concentration range corresponding to the index value of the measurement target substance; An immunoassay system comprising:

3. a measurement unit that measures a substance to be measured contained in a sample in some or all of a plurality of measurement channels having different immobilized antibody reagent properties according to a measurement sequence and acquires a measurement signal that reflects the concentration of the substance to be measured; a calculation unit that calculates an index value related to fluctuations in the intensity of the measurement signal during a first period; a selection unit that selects one measurement sequence and one measurement channel to be used after the first period in accordance with a concentration range corresponding to the index value of the measurement target substance; An immunoassay system comprising:

4. The immunoassay system according to claim 1 , further comprising a quantification unit that quantifies the substance to be measured based on a measurement signal acquired during a second period that follows the first period.

5. a storage unit for storing calibration curve information for each type of substance and / or information on the calibration curve; the quantification unit quantifies the substance to be measured based on the measurement signal acquired during the second period and a calibration curve corresponding to the substance to be measured. The immunoassay system according to claim 4.

6. The measurement unit a light-transmitting substrate on which a first substance that specifically binds to the substance to be measured is immobilized; a magnet that applies a magnetic field to move magnetic particles to which a second substance that specifically binds to the substance to be measured is bound; and an optical device that causes light to be incident on the substrate, that detects light that propagates through the substrate and is emitted from the substrate, and that outputs an output signal of the detected light as the measurement signal; The immunoassay system according to any one of claims 1 to 3.

7. The immunoassay system of claim 6, wherein the first period is set to a local period including the time when the signal strength of the measurement signal peaks with the start of application of the lower magnetic field, a local period including the time when the signal strength of the measurement signal jumps with the end of application of the lower magnetic field, and / or a local period during which the signal strength of the measurement signal decreases with the end of application of the lower magnetic field.

8. The immunoassay system of claim 6, wherein the first period is set to a local period including the time when an empirical peak occurs within the period from the start of the measurement signal by the measurement unit, through the start of application of the lower magnetic field, to the end of application of the lower magnetic field, the period from the end of application of the lower magnetic field to the time when a jump can be detected, and / or the period from the detectable time to the estimated time when the decrease in intensity of the measurement signal converges.

9. The selection unit when the concentration range is determined to be a first concentration range based on a comparison between the index value and a threshold value corresponding to the first period, selecting the one measurement sequence configured with measurement parameters suitable for quantifying the first concentration range; selecting the one measurement sequence configured with measurement parameters suitable for quantifying the second concentration range when the concentration range is determined to be a second concentration range lower than the first concentration range; The immunoassay system according to claim 1 or 3.

10. The immunoassay system according to claim 1 or 3, wherein the parameters of the measurement sequence, in the case of an immunological optical waveguide detection method using magnetic particles, are the application time of a magnetic field to a complex containing the substance to be measured, the strength of the magnetic field, and / or the natural sedimentation time of the complex.

11. The immunoassay system according to claim 1 or 3, wherein the measurement sequence, in the case of an optical measurement method that does not use magnetic particles, includes the concentration of a reagent added to the sample, the type of reagent, the stirring time, the stirring intensity, the wavelength of the irradiated light, and / or the measurement time.

12. The selection unit When the concentration range is determined to be a first concentration range based on a comparison between the index value and a threshold value corresponding to the first period, the one measurement channel having reagent characteristics suitable for quantification of the first concentration range is selected; determining that the concentration range is a second concentration range that is lower than the first concentration range, and selecting the one measurement channel having reagent characteristics suitable for quantifying the second concentration range; The immunoassay system according to claim 2 or 3.

13. 4. The immunoassay system according to claim 2, wherein the reagent characteristic is a reaction rate and / or reaction efficiency between the antibody and the substance to be measured.

14. The immunoassay system according to claim 1 , wherein the measurement section measures the target substance using the one measurement sequence after the first period.

15. The immunoassay system according to claim 2 , wherein the measurement section measures the target substance using the one measurement channel after the first period.

16. The immunoassay system according to claim 3 , wherein the measurement section measures the target substance using the one measurement sequence and the one measurement channel after the first period.

17. The immunoassay system according to claim 1 , wherein the measurement section optically measures the measurement target substance.

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