JP2018040795A5 - - Google Patents

Description

Specimen measuring device

Embodiments of the present invention relate to a sample measuring device.

The sample measuring device determines the presence or absence of the target substance in the sample by measuring the measurement sample prepared from the sample and the reagent by using an optical or electrical method. The sample measuring device detects an electric signal based on the reaction state in the container containing the mixed solution of the sample and the reagent, and determines the presence or absence of the target substance in the sample based on the detected electric signal.

In the above method, it takes a predetermined time for the reaction state in the container containing the mixed solution of the sample and the reagent to become steady, so the presence or absence of the target substance in the sample is determined until the predetermined time elapses. Can not do it.

Japanese Patent No. 2510551 Japanese Patent No. 2603843 Japanese Patent No. 4381752 JP-A-2009-133842 Japanese Unexamined Patent Publication No. 2012-215553

An object is to provide a sample measuring device capable of improving a work workflow.

According to the embodiment, the sample measuring device includes a reaction state signal output unit, a reaction promotion unit, an application state switching control unit, a determination unit, and a qualitative state output unit. The reaction state signal output unit outputs an electric signal based on the reaction state in the reaction vessel containing the mixed solution of the test substance and the reagent. The reaction accelerating unit applies energy for accelerating the reaction in the reaction vessel to the reaction vessel. The application state switching control unit switches the energy application state according to a predetermined time schedule. The determination unit determines the qualitative state of the test substance based on the electric signal output after the energy application state is switched. The qualitative state output unit outputs the qualitative state obtained by the above determination.

FIG. 1 is a block diagram showing a configuration of a sample measuring device according to the first embodiment. FIG. 2 is a diagram showing a detailed configuration of the reaction mechanism according to the first embodiment. FIG. 3 is a diagram showing an example of a flowchart of an operation controlled by the system control circuit according to the first embodiment. FIG. 4 is a diagram showing an example of a flowchart of an operation controlled by the system control circuit according to the first embodiment. FIG. 5 is a graph showing an example of time-series changes in the light intensity of the emitted light. FIG. 6 is a cross-sectional view showing a state in the reaction mechanism at time t = t ₀ shown in FIG. FIG. 7 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₀ to t = t ₁ shown in FIG. FIG. 8 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₁ to t = t ₂ shown in FIG. FIG. 9 is an enlarged view of a part of the curve C in FIG. FIG. 10 is a cross-sectional view showing a state in the reaction unit 2 at time t = t ₂ shown in FIG. FIG. 11 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₃ to t = t ₄ shown in FIG. FIG. 12 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₄ to t = t ₅ shown in FIG. FIG. 13 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₆ to t = t ₇ shown in FIG. FIG. 14 is a diagram showing an example of a flowchart of an operation controlled by the system control circuit according to the modified example. FIG. 15 is a diagram showing an example of a flowchart of an operation controlled by the system control circuit according to the modified example.

[First Embodiment]
Hereinafter, the sample measuring device according to the first embodiment will be described with reference to the drawings.

FIG. 1 is a block diagram showing a configuration of a sample measuring device 1 according to the first embodiment. FIG. 2 is a diagram showing a detailed configuration of the reaction unit 2. As shown in FIG. 1, the sample measuring device 1 includes a reaction unit 2 and a measuring system 3. The reaction unit 2 is removable from the sample measuring device 1.

As shown in FIG. 2, the reaction unit 2 has a housing 21, a transparent substrate 22, an optical waveguide 23, and a protective member 24. A part of the lower surface of the housing 21 is open, and a chip in which the optical waveguide 23 and the protective member 24 are formed by thin film technology is fitted on the transparent substrate 22 in the opening. A part of the protective member 24 is open (open end 24a). Further, the reaction vessel 201 is formed by the housing 21, the optical waveguide 23, the protective member 24, and the like. The reaction unit 2 is configured to accommodate a sample solution containing a test object (test substance) inside the reaction unit 2, that is, in the reaction vessel 201.

The housing 21 is made of, for example, resin or the like. A first recess is formed on the lower surface of the housing 21. A second recess forming the upper surface and the side surface of the reaction vessel 201 is formed on a part of the upper surface of the first recess. A protective member 24, an optical waveguide 23, and a transparent substrate 22 are arranged in the first recess in this order from the top. Further, a hole 21a for introducing a sample solution, a reagent, etc. is formed in the reaction vessel 201 inside the housing 21 so as to penetrate upward near one end of the upper surface of the second recess, and near the other end. A hole 21b is formed so as to penetrate the housing 21 upward and allow air to escape from the reaction vessel 201. A plurality of holes 21a and 21b may be formed.

The transparent substrate 22 is made of, for example, resin or optical glass. The transparent substrate 22 allows the light incident from the light source 311 provided in the measurement system 3 to pass through the optical waveguide 23. Further, the transparent substrate 22 allows the light incident from the optical waveguide 23 to pass through the photodetector 312 provided in the measurement system 3.

The optical waveguide 23 is formed of a material that allows light to pass through, such as resin or optical glass. As the resin, for example, phenol resin, epoxy resin, acrylic resin and the like can be used. The optical waveguide 23 serves as an optical path for light incident from the transparent substrate 22 and emitted to the transparent substrate 22. That is, the optical waveguide 23 fulfills the same role and function as the core (core material) in the optical fiber. The protective member 24 and the transparent substrate 22 are formed of a material having a refractive index different from that of the optical waveguide 23, totally reflect light at the interface with the optical waveguide 23, and confine the light in the optical waveguide 23. It functions as a clad. Further, the protective member 24 and the transparent substrate 22 physically protect the optical waveguide 23.

The optical waveguide 23 propagates the light incident from the measurement system 3 through the transparent substrate 22. In the optical waveguide 23, light affected by the concentration of the test substance contained in the reaction vessel 201, that is, the reaction state is propagated.

Further, a grating 23a is arranged on the protective member 24 side in the vicinity where light is incident on the optical waveguide 23. The grating 23a diffracts the incident light L1 incident on the optical waveguide 23 at a predetermined angle. The light diffracted by the grating 23a is incident on the interface between the optical waveguide 23 and the surface composed of the transparent substrate 22, the protective member 24, or the mixed solution 202 at an angle equal to or less than the complementary angle of the critical angle. As a result, the incident light L1 propagates (waveguides) while being repeatedly reflected in the optical waveguide 23 at the interface of the optical waveguide 23.

A grating 23b is arranged on the protective member 24 side in the vicinity where light is emitted from the optical waveguide 23. The grating 23b diffracts the light optically waveguide by the optical waveguide 23 at a predetermined angle. The light diffracted by the grating 23b is emitted from the optical waveguide 23 to the outside at a predetermined angle.

The protective member 24 has an opening at the position of the second recess of the housing 21. The protective member 24 is arranged in close contact with the upper surface of the optical waveguide 23. The protective member 24 is arranged in close contact with the upper surface of the optical waveguide 23 to form a plane protective layer. Further, as shown in FIG. 2, the protective member 24 has an opening end 24a for exposing the main surface (for example, the upper surface) of the optical waveguide 23. The opening end 24a is a vertical surface that forms an opening inside the protective member 24. The upper surface of the optical waveguide 23 is exposed by the open end 24a.

The upper surface of the reaction vessel 201 is composed of the upper surface of the second recess of the housing 21, the side surface is composed of the side surface of the second recess of the housing 21 and the opening end 24a of the protective member 24, and the lower surface is the optical waveguide 23. It is composed of the upper surface of.

The reaction vessel 201 contains the sample solution and the reagent, and reacts the test substance contained in the sample solution with the reagent. A plurality of first antibodies 211 are immobilized on the lower surface of the surface forming the reaction vessel 201, that is, the upper surface of the optical waveguide 23. The first antibody 211 is a substance that specifically reacts with the antigen 212 contained in the test substance by an antigen-antibody reaction. The first antibody 211 is fixed to the upper surface of the optical waveguide 23 by, for example, a hydrophobic interaction or a chemical bond that occurs with the upper surface of the optical waveguide 23.

The reaction vessel 201 is, for example, emptied in advance. At the time of measuring the test substance, for example, the mixed solution 202 of the sample solution and the reagent is injected from the outside into the reaction vessel 201 through the hole 21a. The sample solution contains a test substance containing the antigen 212. The reagent includes reagent component 213. The reagent component 213 includes, for example, a second antibody 214 that specifically reacts with the antigen 212 by an antigen-antibody reaction, and magnetic particles 215 on which the second antibody 214 is immobilized. At least a part of the magnetic particles 215 is formed of a magnetic material such as magnetite. In the magnetic particles 215, for example, the surface of particles formed from a magnetic material is coated with a polymer material. The magnetic particles 215 may be configured to cover the surface of the particles made of a polymer material with a magnetic material. Further, the magnetic particles 215 may be replaced with any magnetic particles 215 as long as they are dispersible in the mixed solution 202.

By injecting the mixed solution 202, in addition to the first antibody 211 fixed on the upper surface of the optical waveguide 23, the antigen 212 contained in the test substance in the sample solution and the reagent contained in the reagent are injected into the reaction vessel 201. Ingredients 213 are contained. When the mixed solution 202 is injected into the reaction vessel 201, the air in the reaction vessel 201 is discharged to the outside through the holes 21b.

The reagent component 213 moves in a dispersible manner in the mixed solution 202 filled in the reaction vessel 201. At this time, the magnetic particles 215 are selected so that the gravity applied to the magnetic particles 215 is larger than the buoyancy in the mixed liquid 202 applied in the direction opposite to the gravity. The magnetic particles 215 on which the second antibody 214 is immobilized are immobilized near the upper surface of the optical waveguide 23 by binding the second antibody 214 to the first antibody 211 via the antigen 212. The second antibody 214 may be the same as or different from the first antibody 211.

In the reaction unit 2, the first antibody 211 fixed on the upper surface of the optical waveguide 23 reacts with the antigen 212 contained in the test substance, so that the magnetic particles 215 on which the second antibody 214 is immobilized are formed on the optical waveguide 23. It is fixed near the top surface. The light guided through the optical waveguide 23 is scattered and absorbed by the magnetic particles 215 fixed in the vicinity of the upper surface of the optical waveguide 23. As a result, the light guided through the optical waveguide 23 is attenuated and emitted from the optical waveguide 23. That is, the incident light L1 depends on the amount of the antigen 212 that binds the first antibody 211 and the second antibody 214 immobilized on the magnetic particles 215, in other words, the amount of the antigen 212 contained in the reaction vessel 201. Is attenuated.

Hereinafter, in the reaction vessel 201, the region from the surface of the optical waveguide 23 to the broken line in FIG. 2, that is, the region near the surface of the optical waveguide 23 is defined as the sensing area 205.

When light propagates in the optical waveguide 23, near-field light (evanescent light) is generated on the upper surface of the optical waveguide 23. The sensing area 205 is an area where near-field light can be generated. In the sensing area 205, the first antibody 211 immobilized on the upper surface of the optical waveguide 23 is immobilized on the magnetic particles 215 contained in the reagent component 213 via the antigen 212 contained in the test substance in the sample solution. 2 Binds to antibody 214. As a result, the magnetic particles 215 on which the second antibody 214 is immobilized are held in the vicinity of the upper surface of the optical waveguide 23.

Next, the influence of the light propagating on the optical waveguide 23 due to the antigen-antibody reaction or the like occurring in the reaction vessel 201 will be described. The first antibody 211, the second antibody 214, and the antigen 212 are very small as compared with the magnetic particles 215. In FIGS. 2, 7 to 13, in order to schematically show the binding reaction, the first antibody 211, the antigen 212, the second antibody 214, and the magnetic particles 215 are shown as having the same size.

When the magnetic particles 215 enter the sensing area 205, the second antibody 214 immobilized on the magnetic particles 215 binds to the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212. As a result, the magnetic particles 215 on which the second antibody 214 is immobilized remain in the sensing area 205. When near-field light is generated on the upper surface of the optical waveguide 23 while the magnetic particles 215 remain in the sensing area 205, the magnetic particles 215 remaining in the sensing area 205 scatter and absorb the near-field light, and the near-field light. To attenuate. Scattering and absorption of near-field light in the sensing area 205 affect the light propagating in the optical waveguide 23. That is, by attenuating the near-field light in the sensing area 205, the light optically waveguide in the optical waveguide 23 is also attenuated. Therefore, when near-field light is strongly scattered and absorbed in the sensing area 205, the intensity of the light propagating in the optical waveguide 23 decreases. In other words, the greater the amount of magnetic particles 215 staying in the sensing area 205, the lower the intensity of the light output from the optical waveguide 23.

However, the magnetic particles 215 that remain in the sensing area 205 include the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212 to be measured and the second antibody 214 immobilized on the magnetic particles 215. Is not limited to the combination of. Therefore, in order to measure the accurate concentration of the antigen 212 contained in the test substance, the magnetic particles 215 on which the second antibody 214 that is not involved in the measurement, that is, that is not bound to the antigen 212, is immobilized is measured in the sensing area. You need to stay away from 205. As a specific method, for example, there is a method of moving the magnetic particles 215 in which the second antibody 214 is not bound to the antigen 212 by the proximity action by a magnetic field.

As a result, the magnetic particles 215 that finally stay in the sensing area 205 are bound to the first antibody 211 fixed on the upper surface of the optical waveguide 23 via the antigen 212 and the second antibody 214. Therefore, the value of the intensity of the light emitted from the reaction unit 2 and the time-series change in the intensity correspond to the amount and concentration of the magnetic particles 215 remaining in the sensing area 205.

The reaction unit 2 may have a configuration capable of simultaneously measuring the same test substance on a plurality of channels in parallel for the same measurement item. At this time, the reaction unit 2 has, for example, an independent optical waveguide for each channel.

As shown in FIG. 1, the measurement system 3 includes a detection unit 31, a magnetic field generator 32, an output unit 33, an input interface circuit 34, a storage circuit 35, and a system control circuit 36.

The detection unit 31 has a light source 311 and a photodetector 312.

The light source 311 is, for example, a diode such as an LED or a lamp such as a xenon lamp. The light source 311 is arranged at a position where light can be incident on the optical waveguide 23 toward the grating 23a. The light source 311 incidents the incident light L1 into the optical waveguide 23 via the transparent substrate 22 of the reaction unit 2. The incident light L1 enters the optical waveguide 23 and is diffracted by the grating 23a. The incident light L1 diffracted by the grating 23a propagates while being totally reflected in the optical waveguide 23 and reaches the grating 23b. The light that has reached the grating 23b is diffracted by the grating 23b and is emitted from the optical waveguide 23 to the outside as emitted light L2 at a predetermined angle. Instead of the light source 311, a light source that generates electromagnetic waves other than light may be used.

The photodetector 312 is a reaction state signal output unit that outputs an electric signal based on the reaction state in the reaction vessel 201 in which the mixed solution 202 is housed. Specifically, the photodetector 312 detects the emitted light L2 emitted to the outside of the optical waveguide 23 and generates an electric signal indicating the intensity of the detected emitted light L2, that is, digital data regarding the light detection intensity. .. Digital data on the photodetection intensity generated by the photodetector 312 is supplied to the system control circuit 36.

The detection unit 31 may have a configuration capable of simultaneously measuring the same test substance on a plurality of channels in parallel for the same measurement item. At this time, the detection unit 31 may have a light source and a photodetector for each channel, for example, or may share the light source and the photodetector.

The magnetic field generator 32 promotes the reaction in the reaction vessel 201, that is, the binding of the second antibody 214 immobilized on the magnetic particles 215 and the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212. It is a reaction promoting part that generates energy. Specifically, the magnetic field generator 32 has an upper magnetic field generator 32a and a lower magnetic field generator 32b, as shown in FIG. Further, the magnetic field generator 32 has a drive circuit (not shown). The magnetic field generator 32 applies a magnetic field to the reaction vessel 201 under the control of the system control circuit 36.

The upper magnetic field generator 32a is composed of, for example, a permanent magnet and an electromagnet. The upper magnetic field generator 32a is provided above the reaction unit 2 as shown in FIG. The upper magnetic field generator 32a uniformly generates a vertically upward magnetic field in the reaction vessel 201 in the horizontal direction. Due to the generated vertical upward magnetic field, the magnetic particles 215 on which the second antibody 214 is immobilized rise by receiving a force in the vertically upward direction. At this time, the upper magnetic field generator 32a selectively moves the magnetic particles 215 on which the second antibody 214 is immobilized away from the sensing area 205 by generating a magnetic field having a predetermined strength. That is, in the upper magnetic field generator 32a, by adjusting the strength of the generated magnetic field, the first antibody 211 and the second antibody 214 that bind to each other via the antigen 212 are immobilized on the upper surface of the optical waveguide 23. It is possible to retain only the magnetic particles 215 that have been formed in the sensing area 205.

The lower magnetic field generator 32b is composed of, for example, a permanent magnet, an electromagnet, or the like. The lower magnetic field generator 32b is provided below the reaction unit 2. The lower magnetic field generator 32b uniformly generates a vertically downward magnetic field, which is energy for promoting the reaction in the reaction vessel 201, in the horizontal direction. Due to the generated vertical downward magnetic field, the magnetic particles 215 on which the second antibody 214 is immobilized are lowered by receiving a vertical downward force.

The output unit 33 includes a display circuit 331, an alarm 332, and a printer 333.

The display circuit 331 has a general display output device such as a liquid crystal display or an OLED (Organic Light Emitting Diode) display under the control of the system control circuit 36. The display circuit 331 is controlled by the system control circuit 36, and has various operation screens, information indicating the light intensity of the emitted light L2 supplied from the photodetector 312, time-series data of information indicating the light intensity, and the test substance. Display measurement results, etc. The measurement result is, for example, the concentration, weight or number of antigen 212.

The alarm 332 is, for example, a speaker. Under the control of the system control circuit 36, the alarm 332 notifies the operator of the determination result of the test substance and the like.

When the printer 333 is under the control of the system control circuit 36, for example, various operation screens displayed on the display circuit 331, information indicating the light intensity of the emitted light L2 supplied from the photodetector 312, and information indicating the light intensity. Print the series data and the measurement results of the test substance.

The input interface circuit 34 is realized by, for example, a trackball, a switch button, a mouse, a keyboard, a touch pad that performs an input operation by touching an operation surface, a touch panel display in which a display screen and a touch pad are integrated, and the like. The input interface circuit 34 outputs an operation input signal corresponding to the operation of the operator to the system control circuit 36. In this embodiment, the input interface circuit is not limited to the one provided with physical operating parts such as a mouse and a keyboard. For example, an example of an input interface circuit includes an electric signal processing circuit that receives an electric signal corresponding to an input operation from an external input device provided separately from the device and outputs the electric signal to the system control circuit 36. Is done.

The storage circuit 35 has a recording medium that can be read by a processor, such as a magnetic or optical recording medium or a semiconductor memory. The storage circuit 35 stores a program executed by the circuit of the sample measuring device 1 according to the present embodiment. A part or all of the program and data in the storage medium of the storage circuit 35 may be configured to be downloaded via an electronic network.

The storage circuit 35 stores information indicating the light intensity of the emitted light L2 supplied from the photodetector 312, time-series data of the information indicating the light intensity, measurement results of the test substance to be measured, and the like.

The storage circuit 35 stores the setting information for measuring the target test substance. The setting information includes, for example, information that defines the timing for executing a predetermined process required for measurement. The timing of executing the predetermined processing required for the measurement is, for example, the timing at which the application of the lower magnetic field generated by the lower magnetic field generator 32b is started, the timing at which the detection section is started, and the calculation timing (the application of the lower magnetic field is The timing to stop), the timing to end the detection section, the timing to start applying the upper magnetic field, and the timing to execute the second determination (final determination) . The information that defines these timings includes the relative elapsed time from a predetermined time or the absolute time when a predetermined process is executed. The relative elapsed time from the predetermined time or the absolute time for executing the predetermined process is obtained empirically and experimentally in advance.

Storage circuit 35 stores the specified value T _S, which is set in advance. Specified value T _S is a predetermined value for the integrated value of the variation of light intensity corresponding to the concentration of the analyte. Specified value T _S is used to determined whether the measurement results of a test substance is likely positive.

Storage circuit 35 stores a preset threshold T _A. Threshold T _A is the threshold for the light intensity corresponding to the concentration of the analyte. Threshold T _A is used to determine the qualitative state of the test substance. The qualitative state is, for example, the degree of positive or negative indicated by the measurement result. Threshold T _A is used to measure the results of a test substance to a second determination possibility of whether high positive. The threshold T _A may be a plurality of stepwise threshold. That is, by comparing the light intensity contained in the digital data with a plurality of stepwise threshold values, it is possible to make a determination representing a more detailed measurement result.

The system control circuit 36 is, for example, a processor that controls each component circuit of the sample measuring device 1. The system control circuit 36 functions as the center of the sample measuring device 1. The system control circuit 36 calls each operation program from the storage circuit 35 and executes the called program to execute the light source control function 361, the magnetic field control function 362, the calculation function 363, the first determination function 364, and the second determination function. The 365 and the output control function 366 are realized.

The light source control function 361 is a function that controls the light source 311 and generates light under predetermined conditions. In the light source control function 361, the system control circuit 36 continuously or intermittently generates incident light L1 from the light source 311 from the start of measurement to the end of measurement.

The magnetic field control function 362 is an application state switching control function that controls the magnetic field generator 32 according to a time schedule stored in advance in the storage circuit 35 and switches the application state of energy that promotes the reaction in the reaction vessel 201. Specifically, in the magnetic field control function 362, the system control circuit 36 reads setting information from the storage circuit 35, controls the magnetic field generator 32 based on the read setting information, and generates a magnetic field in the magnetic field generator 32. ..

The calculation function 363 is a function that performs various calculations based on time-series digital data of light intensity supplied from the photodetector 312. In the calculation function 363, the system control circuit 36 uses the supplied time-series digital data of the light intensity to calculate the average value of the light intensity, the fluctuation rate of the light intensity, the integrated value of the fluctuation rate, and the like.

The first determination function 364 performs a first determination (prediction determination) for determining whether or not the sample solution is likely to be positive based on the integrated value of the fluctuation rate of the light intensity calculated by the calculation function 363. It is a function to do. The first determination may be paraphrased as a pre-determination. In the first determination function 364, the system control circuit 36 reads for example a preset prescribed value T _S from the memory circuit 35. The system control circuit 36, when the integrated value of the variation of light intensity calculated by the calculation function 363 is equal to or smaller than the prescribed value T _S, determines the measurement results of a test substance to be likely positive. The system control circuit 36, the integrated value of the variation of light intensity calculated by the calculating function 363 is larger than the prescribed value T _S, the measurement results of the test substance is not likely positive, i.e. weakly positive Or, it is judged that there is a high possibility of being negative.

The second determination function 365 is a function for performing a second determination for determining the qualitative state of the test substance based on the digital data of the light intensity supplied from the photodetector 312 during the application of the upper magnetic field described later. is there. That is, the second determination function 365 is a function of executing the second determination after the first determination is performed by the first determination function 364. The second determination in the second determination function 365 may be paraphrased as a post-determination. In the second determination function 365, the system control circuit 36 reads the setting information and the threshold value _{T A} from the memory circuit 35. The system control circuit 36 determines the qualitative state of the test substance in accordance with the execution timing included in the read setting information. The system control circuit 36 determines if the light intensity contained in the digital data of the light intensity of the supplied time series is equal to or less than the threshold value T _A, for example, the measurement results of a test substance to be likely positive. The system control circuit 36, when the light intensity contained in the digital data is larger than the threshold value T _A, for example, measurement results of a test substance is determined that there is a high possibility of weakly positive or negative.

Here, in the pre-determination and the post-determination, the determination timing is represented in chronological order before and after, the determination by the first determination function 364 is the pre-determination, and the determination by the second determination function 365 is the post-determination. Thus, without performing the second determination by the second determination function 365 as will be described later, when the first determination result by the first determination function 364 is the result of the second determination, the first Even if the judgment of is substantially the second judgment , it is referred to as a pre-judgment.

The output control function 366 is a function that controls the output unit 33 and outputs a determination result such as a qualitative state of the test substance to the operator. The output control device 366, the system control circuit 36 controls the display circuit 331 or the printer 333, presents the results of the results and / or a second determination of the first determination to the operator. The presentation includes a display via a display and a method of printing using a printer. The system control circuit 36 controls the annunciator 332 notifies the result of the result and / or the second determination of the first determination to the operator. The notification includes a method of notifying by sound or the like.

Next, the operation of the first embodiment will be described.

3 and 4 are diagrams showing an example of a flowchart of the operation controlled by the system control circuit 36 according to the first embodiment. Further, FIG. 5 is a graph showing an example of time-series changes in the light intensity of the emitted light L2. In the graph shown in FIG. 5, the horizontal axis represents the time t, and the vertical axis represents the light intensity of the emitted light L2. Further, the curve drawn in the graph is obtained by plotting the temporal change of the light intensity A represented by the digital data output from the photodetector 312 based on the reaction state in the reaction unit 2.

First, at time t = 0, injection of the mixed solution 202 composed of the sample solution and the reagent into the reaction vessel 201 is started. The injection of the mixed solution 202 into the reaction vessel 201 may be performed automatically or manually.

For example, when the injection of the mixed solution 202 into the reaction vessel 201 is started, the light source 311 continuously injects light of a constant intensity into the optical waveguide 23. The light emitted from the light source 311 is incident on the optical waveguide 23 via the transparent substrate 22. The light incident on the optical waveguide 23 propagates while being totally reflected in the optical waveguide 23, and is emitted to the photodetector 312 via the transparent substrate 22. The photodetector 312 receives the light emitted from the optical waveguide 23 and supplies the light intensity data to the system control circuit 36 at predetermined time intervals.

The system control circuit 36 uses, for example, the elapsed time included in the information defining the timing at which the application of the lower magnetic field is started, and determines whether or not a predetermined elapsed time has elapsed from the time t = 0, that is, applies the lower magnetic field. It is determined whether or not the time t = t ₀ is reached (step SA1). The elapsed time in step SA1 is the time until the light intensity A increases from A = 0 to A = A ₀₀ . In the period from time t = 0 to t = t ₀ , the measured light intensity increases. This is because when the reaction vessel 201 is filled with the sample solution and the reagent, the sugar-containing water-soluble film previously attached to the upper surface of the optical waveguide 23 is dissolved in order to enhance the storage stability. The sugar is, for example, a disaccharide. The system control circuit 36 determines in advance whether or not the time t = t ₀ when the lower magnetic field is applied is determined by, for example, monitoring the time-series change of the light intensity sequentially supplied from the photodetector 312. It may be performed based on the determined judgment rule. The determination rule is a rule for determining that the time t = t ₀ when the lower magnetic field is applied is reached when, for example, the light intensity is detected to be the peak value.

When the time t = t _{0 at} which the lower magnetic field is applied is reached (Yes in step SA1), the system control circuit 36 controls the magnetic field generator 32 to start applying the lower magnetic field (step SA2). FIG. 6 is a cross-sectional view showing a state in the reaction unit 2 at time t = t ₀ shown in FIG. As shown in FIG. 6, the application of the lower magnetic field is started at time t = t ₀ . Downward arrow in FIG. 6 shows the direction of the magnetic flux B ₁ generated by the application of lower magnetic field. The magnetic flux B ₁ is composed of a plurality of magnetic field lines b and substantially penetrates the reaction vessel 201 downward.

After the application of the lower magnetic field is started, the light intensity converges to a predetermined value A ₀₁ when the time t = t ₁ . FIG. 7 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₀ to t = t ₁ shown in FIG. As shown in FIG. 7, a plurality of magnetic particles 215 on which the second antibody 214 is immobilized in the reaction vessel 201 filled with the sample solution receives a vertically downward magnetic force due to a lower magnetic field, and some of them are subjected to vertical downward magnetic force. By being attracted to the magnetic field lines b, they begin to be aligned along the magnetic field lines b. Magnetic particles 215 on which the second antibody 214 aligned along the lines of magnetic force b is immobilized gradually settles according to gravity and magnetic force and enters the sensing area 205. The second antibody 214 immobilized on the magnetic particles 215 that has entered the sensing area 205 binds to the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212.

On the other hand, the magnetic particles 215 on which the second antibody 214 not aligned along the magnetic field line b is immobilized gradually settles according to gravity and enters the sensing area 205. The second antibody 214 immobilized on the magnetic particles 215 that has entered the sensing area 205 binds to the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212.

From time t = t ₀ to t = t ₁ , the magnetic particles 215 on which the second antibody 214 is immobilized enter the sensing area 205 one after another, so that the light intensity decreases. The light intensity begins to decrease at a large reduction rate (tilt) immediately after time t = t ₀ . The rate of decrease in light intensity decreases with the passage of time. After that, the reduction rate of the light intensity becomes almost 0 at the time t = t ₁ . That is, the light intensity converges to the intensity A ₀₁ at time t = t ₁ .

FIG. 8 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₁ to t = t ₂ shown in FIG. As shown in FIG. 8, the entry of the magnetic particles 215 on which the second antibody 214 is immobilized into the sensing area 205 is stopped. Therefore, the light intensity converges to the intensity A ₀₁ at time t = t ₁ . Even from time t = t ₁ to t = t ₂ , a part of the antigen 212 contained in the reaction vessel 201 is sequentially bound to the second antibody 214.

FIG. 9 is an enlarged view of the partial curve C1 which is a part of the curve C in FIG. As shown in FIG. 9, in the present embodiment, the starting point is D _s (t = t _s ) and the ending point is _De (t = t ₃ ) at a predetermined time between the times t = t ₁ and t = t _2. The section is called the detection section.

After starting the application of the lower magnetic field, the system control circuit 36 uses the elapsed time included in the information defining the timing at which the detection section is started, for example, to determine a predetermined time from time t ₀ when the application of the lower magnetic field is started. It is determined whether or not the elapsed time has elapsed, that is, whether or not the time t = t _s has been reached (step SA3). The elapsed time included in the information defining the timing at which the detection section is started may be a predetermined elapsed time from time 0.

When the time t = t _s , which is the time indicating the start of the detection section, is reached (Yes in step SA3), the system control circuit 36 obtains one value of the light intensity data continuously supplied from the photodetector 312. Obtained as a reference value R (= A ₀₁ ) (step SA4).

After acquiring the reference value R, the system control circuit 36 uses one of the light intensities _An (n = 1, 2, 3 ...) Included in the light intensity data sequentially supplied from the photodetector 312 as a measured value. Acquire (step SA5). The system control circuit 36 may use the reference value R acquired in step SA4 as a measured value.

The system control circuit 36, after obtaining a measured value A _n, whether the number of data of the acquired measured value is 3 or more is judged (step SA6). When the number of acquired measured value data is less than N (No in step SA6), the system control circuit 36 returns to step SA5 and acquires the measured value to be supplied next.

When the number of acquired measured value data is N or more (Yes in step SA6), the system control circuit 36 starts applying a lower magnetic field using, for example, the elapsed time included in the information defining the calculation timing. It is determined whether or not a predetermined elapsed time has elapsed from the time t = t ₀ at which the processing is performed, that is, whether or not the time t = t ₂ has been reached (step SA7). The elapsed time in step SA7 is the relative elapsed time from the time t = t ₀ when the application of the lower magnetic field is started, and is the time acquired in advance empirically and experimentally, as in the elapsed time in step SA3. Is. The system control circuit 36 may set the calculation timing to, for example, the case where (N-1) light intensity data exceeds the reference value R among the N light intensity data acquired most recently. The elapsed time included in the information defining the calculation timing may be a predetermined elapsed time from the time t = 0.

When the time t = t ₂ has not been reached (No in step SA7), the system control circuit 36 returns to step SA5 and acquires the measured value to be supplied next.

When the time t = t ₂ is reached (Yes in step SA7), the system control circuit 36 controls the magnetic field generator 32 to stop the application of the lower magnetic field (step SA8).

When the application of the lower magnetic field is stopped, the magnetic particles 215 on which the second antibody 214 is immobilized are released from the binding by the lower magnetic field and start spontaneous precipitation. FIG. 10 is a cross-sectional view showing a state in the reaction unit 2 at time t = t ₂ shown in FIG. As shown in FIG. 10, the internal state of the reaction vessel 201 immediately after the application of the lower magnetic field is stopped is almost the same as the state shown in FIG.

As shown in FIGS. 5 and 9, the light intensity A draws a spike-like waveform that changes from an increase to a decrease because the overshoot OS1 occurs from time t = t ₂ to t = t ₃ . A portion of the reagent component 213 is momentarily detached from the sensing area 205, resulting in overshoot OS1 at time t = t ₂ to t = t ₃ , as shown in FIGS. 5 and 9. The time t = t ₃ is the time when the occurrence of the overshoot OS1 has subsided. The time required from when the application of the lower magnetic field is stopped until the generation of the overshoot OS1 is stopped is known because the time when the operation of generating the lower magnetic field is stopped is set in advance, and is known in advance in the storage circuit 35. Be remembered. This time is used, for example, when determining the elapsed time from the time when the application of the lower magnetic field is stopped. The elapsed time required for the occurrence of the overshoot OS1 to subside may be experimentally determined in advance.

In addition, as a criterion for determining whether or not the sample solution containing the test substance to be measured is likely to be positive, focus on the degree of overshoot that occurs between the time t = t ₂ and t = t _3. To do. For example, as shown in FIG. 9, the system control circuit 36 according to the present embodiment represents the end of the detection section from the point D _c (t = t ₂ ) indicating, for example, the calculation timing by performing a predetermined calculation. When a sudden spike-like overshoot as plotted up to point D _e1 (t = t ₃ ) occurs, it is determined that there is a high possibility of weak positive or negative. Further, the system control circuit 36 has a gentle spike as plotted between, for example, a point D _c (t = t ₂ ) indicating the calculation timing and a point D e ₂ (t = t ₃ ) indicating the end of the detection section. When the overshoot occurs, it is judged that the possibility of positive is high. Specifically, the system control circuit 36 calculates the cumulative integration of the light intensity fluctuation rates between the times t = t ₂ and t = t ₃ , and the calculated integrated value of the light intensity fluctuation rates is preset. If was below has been prescribed value T _S, it determines that there is a high possibility of positive. The system control circuit 36 determines that the integrated value of the variation rate of the computed light intensity is greater than the specified value T _S, is likely weakly positive or negative.

The light intensity A decreases from time t = t ₃ to t = t _{4 when} the generation of noise current in the overshoot OS 1 subsides. FIG. 11 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₃ to t = t ₄ shown in FIG. As shown in FIG. 11, the magnetic particles 215 on which the second antibody 214 aligned along the magnetic field line b is immobilized are released from the binding by the lower magnetic field, so that the aligned state is broken and the optical light is emitted. It settles disorderly toward the upper surface of the waveguide 23. As shown in FIG. 5, the light intensity A has a large reduction rate because the magnetic particles 215 on which the second antibody 214 is immobilized enter the sensing area 205 one after another from time t = t ₃ to t = t ₄ . Decreases with. The rate of decrease in light intensity A decreases with the passage of time. Then, reduction of the light intensity A at time t = _{t 4,} is substantially zero. That is, the light intensity converges to the intensity A ₀₃ at time t = t ₄ .

FIG. 12 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₄ to t = t ₅ shown in FIG. As shown in FIG. 12, the invasion of the magnetic particles 215 on which the second antibody 214 is immobilized into the sensing area 205 is stopped. Therefore, the light intensity converges to the intensity A ₀₃ at time t = t ₄ . At this time, a part of the plurality of magnetic particles 215 on which the second antibody 214 in contact with the upper surface of the optical waveguide 23 is immobilized is specific to the first antibody 211 immobilized on the upper surface of the optical waveguide 23 via the antigen 212. Combine with. The magnetic particles 215 on which the second antibody 214 is immobilized are aligned and deposited on the upper surface of the optical waveguide 23. That is, the inside of the sensing area 205 is occupied by the magnetic particles 215 on which the second antibody 214 is immobilized almost without gaps. A part of the plurality of magnetic particles 215 in which the second antibody 214 is immobilized that were not bound to the first antibody 211 which is fixed on the top surface of the optical waveguide 23 at the stage of t = t _4, the time At t = t ₄ to t = t ₅ , it binds to the first antibody 211 immobilized on the upper surface of the optical waveguide 23.

After finishing the application of the lower magnetic field, the system control circuit 36 calculates the average value Ave (n) of the most recently acquired N data among the light intensity data sequentially supplied from the photodetector 312 (step SA9). ). The calculation formula is represented by, for example, as follows.

After calculating the average value Ave (n) of the light intensity, the system control circuit 36 uses the reference value R acquired in step SA4 and the average value Ave (n) of the light intensity calculated in step SA9 to change the light intensity. The rate H _n is calculated (step SA10). The calculation formula is represented by, for example, as follows.

The system control circuit 36, after calculating the variation rate _{H n} of the light intensity, and calculates the integrated value _{S n} of the variation ratio _{H n} of the light intensity (step SA11). The calculation formula is represented by, for example, as follows.

The system control circuit 36, after calculating the integrated value S _n of the variation ratio H _n of the light intensity, using the elapsed time included in the information defining the timing of for example the detection interval is terminated, from the time t = t ₂ It is determined whether or not a predetermined elapsed time has elapsed, that is, whether or not the time t = t ₃ has been reached (step SA12). The elapsed time included in the information defining the timing at which the detection section ends may be a predetermined elapsed time from time 0.

When the time t = t ₃ indicating the end of the detection section has not been reached (No in step SA12), the system control circuit 36 acquires the next measured value (step SA13). After that, the system control circuit 36 executes steps SA9 to SA12.

The system control circuit 36, (Yes in step SA12) detecting section ends to reach the time t = _{t 3} shown in, stored as the integrated value _{S n} of the variation ratio _{H n} of the calculated light intensity in the storage circuit 35 comparing the specified value _{T S,} determines whether the integrated value _{S n} is equal to or less than the specified value _{T S} (step SA14).

The system control circuit 36, when the integrated value _{S n} is equal to or less than the specified value _{T S} (Yes in step SA14), and executes the output control function 366, the first determination of the analyte to be measured The fact that the result is likely to be positive is presented or notified to the operator via the output unit 33 (step SA15).

The system control circuit 36, after the presentation or notification to the operator to continue the measurement of the time t = t ₃ or later (step SA16).

The system control circuit 36, when the integrated value _{S n} is determined to be larger than the specified value _{T S} (No at step SA14), without the presentation or notification of the first determination results, the time t = _{t 3} or later The measurement is continued (step SA16).

The system control circuit 36 uses, for example, the elapsed time included in the information that defines the timing at which the upper magnetic field is applied to determine whether or not a predetermined elapsed time has elapsed from the time t = t ₂ , that is, the time t = t _5. Is determined (step SA17). The elapsed time included in the information defining the timing at which the upper magnetic field is applied may be a predetermined elapsed time from time t = 0.

When the time t = t _{5 at} which the upper magnetic field is applied is reached (Yes in step SA17), the system control circuit 36 controls the magnetic field generator 32 to start applying the upper magnetic field (step SA18).

Immediately before time t = t ₅ , the magnetic particles 215 on which the second antibody 214 is immobilized are aligned and deposited on the upper surface of the optical waveguide 23. At this time, most of the magnetic particles 215 on which the second antibody 214 in contact with the upper surface of the optical waveguide 23 is immobilized is specifically bound to the first antibody 211 immobilized on the upper surface of the optical waveguide 23.

FIG. 13 is a cross-sectional view showing a state in the reaction mechanism from time t = t ₆ to t = t ₇ shown in FIG. The upward arrow in FIG. 13 indicates the direction of the magnetic flux B ₂ generated by the application of the upper magnetic field. The magnetic flux B ₂ is composed of a plurality of magnetic field lines b and substantially penetrates the reaction vessel 201 upward. As shown in FIG. 13, the light intensity A converges to A = A ₀₂ because the magnetic particles 215 on which the second antibody 214 is immobilized stops entering the sensing area 205.

When the light intensity A converges to A = A ₀₂ , as shown in FIG. 13, the sensing area 205 has a second antibody specifically bound to the first antibody 211 immobilized on the upper surface of the optical waveguide 23. Only the magnetic particles 215 on which 214 is immobilized are present.

The system control circuit 36, after starting the application of the above magnetic field, for example, a second determination using the elapsed time included in the information defining the timing to be performed, from time t = t ₅ predetermined elapsed time has elapsed It is determined whether or not the time has been reached, that is, whether or not the time t = t ₇ has been reached (step SA19). The elapsed time included in the information defining the timing at which the second determination is performed may be a predetermined elapsed time from the time t = 0.

After the application of the lower magnetic field is stopped, the system control circuit 36 executes the timing at which the reaction in the reaction vessel 201 converges and finally determines the qualitative state of the test substance, that is, the second determination function 365. When the time t = t ₇ is reached (Yes in step SA19), the second determination function 365 is executed, and the value A ₀₂ of the data of the light intensity after convergence, which is continuously supplied from the photodetector 312, is acquired. (Step SA20).

The system control circuit 36 performs a second determination function 365, by comparing the threshold value T _A stored value A ₀₂ of the data of the acquired light intensity in the storage circuit 35, a second determination. The system control circuit 36 executes the output control function 366, and presents or notifies the operator of the result of the second determination via the output unit 33 (step SA21). Note that the system control circuit 36, when outputting the second determination result may be displayed first determination result on the result at the same time the same display, the second determination. Further, an identifier in which the result of the first determination and the result of the second determination can be clearly distinguished, for example, "*" may be added to the result of the first determination and displayed or printed.

According to the first embodiment, the photodetector 312 outputs an electrical signal based on the reaction state in the reaction vessel 201 containing the mixture 202. The system control circuit 36 controls the magnetic field generator 32 according to a predetermined schedule, applies a lower magnetic field to the reaction unit 2, and stops applying the lower magnetic field to the reaction unit 2. The system control circuit 36 determines the qualitative state of the test substance based on the electric signal output from the photodetector 312 after the application of the lower magnetic field is stopped. The system control circuit 36 outputs the qualitative state obtained by the determination. As a result, the sample measuring device can notify the operator of the determination result of the test substance without waiting for the execution of the second determination . Therefore, the operator can recognize the qualitative state of the test substance before the second determination is performed, and can quickly start preparing for the next treatment based on the recognized qualitative state.

Therefore, according to the sample measuring device 1 according to the first embodiment, it is possible to provide a sample measuring device capable of improving the work workflow.

Further, according to the first embodiment, the system control circuit 36, in a predetermined detection interval overshoot OS1 occurs, it calculates an integrated value S _n of the variation ratio H _n of the light intensity. The system control circuit 36, when the integrated value S _n is equal to or less than the specified value T _S, determines that the first determination result of a test substance is likely positive. This makes it possible to reduce the influence of current noise and the like that are randomly generated during measurement.

Further, according to the first embodiment, the system control circuit 36 controls the output unit 33 displays or prints the first determination result before carrying out the second judgment. As a result, the operator can recognize the result of the first determination of the test substance in advance before the second determination is made.

Further, according to the first embodiment, the system control circuit 36 controls the output unit 33, and determines an identifier in which the result of the first determination and the result of the second determination can be clearly distinguished in the first determination . Display or print in addition to the results. As a result, the operator can easily recognize whether the displayed or printed measurement result is the measurement result by the first determination or the measurement result by the second determination .

[Modification example]
In the first embodiment, when the first determination is performed and the determination result indicates that the possibility of being positive is high, the measurement is continued after the result of the first determination is displayed or notified, and then the second determination is made. The case of carrying out the above was explained. In a variant, to indicate that the first determination was carried out the judgment result is likely positive, after outputting or notifying the first determination result, time t = t ₃ subsequent measurement operator display prompting a manipulation input to decide to suspend, when receiving an input of the measurement stop interrupts the measurement time t = t ₃ or later, the first without the second determination description will be given of a case where outputs or reports the result of the determination as a result of the second determination.

The sample measuring device 1A according to the modified example includes a reaction unit 2 and a measuring system 3A.

The measurement system 3A includes a detection unit 31, a magnetic field generator 32, an output unit 33, an input interface circuit 34, a storage circuit 35, and a system control circuit 36A.

The system control circuit 36A is, for example, a processor that controls each component circuit of the sample measuring device 1A. The system control circuit 36A functions as the center of the sample measuring device 1A. The system control circuit 36A calls each operation program from the storage circuit 35 and executes the called program to execute the light source control function 361, the magnetic field control function 362A, the calculation function 363, the first determination function 364, and the second determination function. The 365A and the output control function 366A are realized.

The magnetic field control function 362A is a function of controlling the magnetic field generator 32 to generate a magnetic field under predetermined conditions. In the magnetic field control function 362, the system control circuit 36A reads the setting information from the storage circuit 35 and generates a magnetic field from the magnetic field generator 32 based on the read setting information. The system control circuit 36A via the input interface circuit 34, and stops when receiving a command input that means to interrupt the measurement from the operator, interrupt the processing performed at the time t ₃ after, i.e. the start of the application of the above magnetic field ..

The second determination function 365A is a function of performing a second determination of determining the qualitative state of the test substance based on the digital data of the light intensity supplied from the photodetector 312 while the upper magnetic field is applied. In the second determination function 365A, the system control circuit 36A reads the setting information and the threshold value _{T A} from the memory circuit 35. The system control circuit 36 determines the qualitative state of the test substance in accordance with the execution timing included in the read setting information. The system control circuit 36A determines if the light intensity contained in the digital data of the light intensity of the supplied time series is equal to or less than the threshold value T _A, for example, the measurement results of a test substance to be likely positive. The system control circuit 36A, when the light intensity contained in the digital data is larger than the threshold value T _A, for example, measurement results of a test substance is determined that there is a high possibility of weakly positive or negative. Further, when the system control circuit 36A receives an operation input to the effect that the measurement is interrupted from the operator via the input interface circuit 34, the system control circuit 36A interrupts the process performed after the time t = t ₃ , that is, the second determination . Stop the implementation.

The output control function 366A is a function that controls the output unit 33 and outputs a determination result or the like to the operator. In the output control function 366A, the system control circuit 36A controls the display circuit 331 and displays the result of the first determination or the result of the second determination to the operator. The system control circuit 36 controls the alarm 332 and notifies the operator of the result of the first determination or the result of the second determination . The notification includes a method of notifying by sound or the like. The system control circuit 36A controls the printer 333 and prints the result of the first determination or the result of the second determination . The system control circuit 36A is operated first determination result of determining that the interruption when indicating likely positive, the measurement of the time t = t ₃ after the operator controls the display circuit 331 Display a button that accepts input. When the system control circuit 36A receives an operation input to interrupt the measurement from the operator via the input interface circuit 34, the system control circuit 36A outputs the result of the first determination as the result of the second determination .

Next, the operation of the embodiment of the modified example will be described.

14 and 15 are diagrams showing an example of a flowchart of the operation controlled by the system control circuit 36A according to the modified example. Hereinafter, steps SB1 to SB14 are the same as steps SA1 to SA14 shown in FIGS. 3 and 4, so steps SB15 to SB27 will be described here.

The system control circuit 36A, when the integrated value _{S n} is equal to or less than the specified value _{T S} (Yes in step SB 14), executes the output control function 366A, the first determination of the analyte to be measured The fact that the result is likely to be positive is presented or notified to the operator via the output unit 33 (step SB15).

The system control circuit 36A, when the integrated value _{S n} is determined to be larger than the specified value _{T S} (No in step SB 14), without the presentation or notification of the result of the first determination, t = time _{t 3} after The measurement is continued (step SB20).

The system control circuit 36A executes the output control function 366 after presenting or notifying the operator, and determines to interrupt the measurement after the time t = t ₃ to the operator via the display circuit 331. A button for accepting operation input is displayed (step SB16).

The system control circuit 36A determines whether or not an operation input for determining to interrupt the measurement is performed by the operator via the input interface circuit 34 (step SB17).

The system control circuit 36A interrupts the subsequent measurement when there is an operation input from the operator to decide to interrupt the measurement (Yes in step SB17). That is, the second determination by the execution of the second judgment function 365 is not performed.

After interrupting the measurement in step SB18, the system control circuit 36A executes the output control function 366 and outputs the result of the first determination as the result of the second determination via the output unit 33 (step SB19). At this time, the measurement result is not output as the determination is unconfirmed for the channel other than the channel that outputs the result of the first determination that the possibility of being positive is high. An identifier in which the result of the first determination and the result of the second determination can be clearly distinguished, for example, "*" may be added to the result of the first determination and displayed or printed.

The system control circuit 36A, when there is no operation input to the effect that interrupt the measurement from the operator (No at step SB17), the time t = _{t 3} to continue the subsequent measurements (step SB20).

The system control circuit 36A determines whether or not an operation input for determining to interrupt the measurement is performed by the operator via the input interface circuit 34 (step SB21).

The system control circuit 36A interrupts the subsequent measurement (step SB18) when there is an operation input from the operator that determines that the measurement is interrupted (Yes in step SB21). If the result of the first determination is not output in step SB15 (No in step SB14), the measurement is not interrupted even if the operator receives an operation input for deciding to interrupt the measurement. Then, the process proceeds to step SB22. However, the measurement may be interrupted when the result of the first determination is output on another channel, such as when performing simultaneous parallel measurement on a plurality of channels (step SB18).

The system control circuit 36A uses the elapsed time included in the information defining when the upper magnetic field is applied, for example, when there is no operation input from the operator to determine to interrupt the measurement (No in step SB21). It is determined whether or not a predetermined elapsed time has elapsed from the time t = t ₂ , that is, whether or not the time t = t ₅ has been reached (step SB22).

When the time t = t _{5 at} which the upper magnetic field is applied is reached (Yes in step SB22), the system control circuit 36A controls the magnetic field generator 32 to start applying the upper magnetic field (step SB23).

When the time t = t _{5 at} which the upper magnetic field is applied has not been reached (No in step SB22), the system control circuit 36A receives an operation input for determining to interrupt the measurement from the operator via the input interface circuit 34 again. It is determined whether or not it has been performed (step SB21).

After starting the application of the upper magnetic field, the system control circuit 36A determines whether or not an operation input for determining to interrupt the measurement is performed from the operator via the input interface circuit 34 (step SB24).

When the operator receives an operation input for determining to suspend the measurement (Yes in step SB24), the system control circuit 36A interrupts the subsequent measurement (step SB18). If the result of the first determination is not output in step SB15 (No in step SB14), the measurement is not interrupted even if the operator receives an operation input for deciding to interrupt the measurement. Then, the process proceeds to step SB25. However, the measurement may be interrupted when the result of the first determination is output on another channel, such as when performing simultaneous parallel measurement on a plurality of channels (step SB18).

When there is no operation input from the operator to interrupt the measurement (No in step SB24), the system control circuit 36A uses the elapsed time included in the information defining the timing when the second determination is performed, for example . It is determined whether or not a predetermined elapsed time has elapsed from time t = t ₅ , that is, whether or not time t ₇ has been reached (step SB25).

If the time t = t ₇ has not been reached in the system control circuit 36A (No in step SB25), whether or not an operation input for determining to interrupt the measurement from the operator is performed again via the input interface circuit 34. Is determined (step SB24).

When the time t = t ₇ is reached (Yes in step SB25), the system control circuit 36A executes the second determination function 365A, and the data of the light intensity after convergence continuously supplied from the photodetector 312. The value A _{02 of} is acquired (step SB26).

The system control circuit 36A performs a second determination function 365A, by comparing the threshold value T _A stored value A ₀₂ of the data of the acquired light intensity in the storage circuit 35, a second determination. The system control circuit 36 executes the output control function 366A, and presents or notifies the operator of the result of the second determination via the display circuit 331 or the alarm 332 (step SB27). Note that the system control circuit 36A, at the time of outputting the second determination result may be displayed first determination result on the result at the same time the same display, the second determination. Further, an identifier in which the result of the first determination and the result of the second determination can be clearly distinguished, for example, "*" may be added to the result of the first determination and displayed or printed.

According to the modification, the system control circuit 36A stops the execution of the second determination when there is an operation input from the operator that determines to interrupt the measurement via the input interface circuit 34. As a result, the operator can select to use the measurement result of the first determination as the measurement result of the second determination according to the measurement situation, and the measurement time can be shortened.

In addition, according to this modification, it is possible to further simplify the flow described with reference to FIGS. 14 and 15. For example, in the processing after step SB14 shown in FIG. 15, processing such as operation input (steps SB15 to SB17, SB21, and SB24) can be omitted, and the result of the second determination can be automatically output (. Step SB19, step SB27).

Specifically, the system control circuit 36A, in step SB14 shown in FIG. 15, when the integrated value _{S n} is equal to or less than the specified value _{T S} (Yes in Step SB14), omit Step SB15~SB17 , Immediately interrupt the measurement (step SB18). The system control circuit 36A outputs the result of the first determination as the result of the second determination (step SB19).

The system control circuit 36A, when the integrated value _{S n} is determined to be larger than the specified value _{T S} (No in step SB 14), skip step SB21, and reaches the time t = _{t 5} for applying the above magnetic field ( Yes) in step SB22, the magnetic field generator 32 is controlled to apply an upper magnetic field (step SB23). The system control circuit 36A omits step SB24, and when time t = t ₇ is reached (Yes in step SB25), it executes the second determination function 365A, and after convergence, which is continuously supplied from the photodetector 312. The value A ₀₂ of the light intensity data of is acquired (step SB26). The system control circuit 36A outputs the result of the second determination based on the value A ₀₂ of the light intensity data after convergence (step SB27).

With the above simplification, it is possible to automatically output the result of the first determination by the first determination function 364 as the result of the second determination , that is, the result of the previous determination as it is. This eliminates the need to perform the post-judgment, which requires more time to obtain the result of the judgment than the pre-judgment.

By simplifying the above, if there were possible first determination is automatically output as a result of the immediate second determination a first determination result. In other words, the determination result obtained by the first determination is not output as the result of the first determination . This makes it possible to perform a quick inspection without waiting for a post-determination.

[Other Embodiments]
The present invention is not limited to the above embodiment. For example, in the first embodiment and the modified example, was an index for measuring the results integrated value S _n of the variation ratio H _n of the light intensity obtained at the detection zone to determine whether there is a high possibility of positive However, the slope or integral value of the light intensity acquired in the detection section may be used as an index for determining whether or not the measurement result is likely to be positive. This makes it possible to make the first determination with a lower calculation load.

The word "processor" used in the above description means, for example, a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), an application specific integrated circuit (ASIC), or a programmable logic device (for example, a programmable logic device). It means a circuit such as a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), and a field programmable gate array (FPGA). The processor realizes the function by reading and executing the program stored in the storage circuit. Instead of storing the program in the storage circuit, the program may be directly embedded in the circuit of the processor. In this case, the processor realizes the function by reading and executing the program embedded in the circuit. It should be noted that each processor of the first embodiment and the first modification is not limited to the case where each processor is configured as a single circuit, and a plurality of independent circuits are combined to form one processor, and its functions are combined. It may be realized. Further, the plurality of components in FIG. 1 may be integrated into one processor to realize the function.

Although some embodiments of the present invention have been described, these embodiments are shown as examples and are not intended to limit the scope of the invention. These novel embodiments can be implemented in various other embodiments, and various omissions, replacements, and changes can be made without departing from the gist of the invention. These embodiments and modifications thereof are included in the scope and gist of the invention, and are included in the scope of the invention described in the claims and the equivalent scope thereof.

1, 1A ... Specimen measuring device, 2 ... Reaction unit, 3 ... Measuring system, 21 ... Housing, 22 ... Transparent substrate, 23 ... Optical waveguide, 24 ... Protective member, 31 ... Detection unit, 32 ... Magnetic field generator, 33 ... output unit, 34 ... input interface circuit, 35 ... storage circuit, 36, 36A ... system control circuit, 201 ... reaction vessel, 311 ... light source, 312 ... light detector, 32a ... upper magnetic field generator, 32b ... lower magnetic field generation Instrument, 331 ... Display circuit, 332 ... Alarm, 333 ... Printer, 361 ... Light source control function, 362, 362A ... Magnetic field control function, 363 ... Calculation function, 364 ... First judgment function, 365, 365A ... Second Judgment function, 366, 366A ... Output control function.

Claims (18)

A reaction status signal output unit that outputs an electrical signal based on the reaction status in the reaction vessel containing the mixed solution of the test substance and the reagent.
A reaction promoting unit that applies energy for promoting the reaction in the reaction vessel to the reaction vessel,
An application state switching control unit that switches the energy application state according to a predetermined time schedule,
A determination unit that determines the qualitative state of the test substance based on the electric signal output after the energy application state is switched, and
It is provided with a qualitative state output unit that outputs the qualitative state obtained by the above determination .
The determination unit is a sample measuring device configured to be able to perform a first determination based on the electric signal and a second determination based on an electric signal output after the first determination . The sample measuring device according to claim 1, wherein the reaction state signal output unit detects light related to the reaction state in the reaction vessel and generates the electric signal based on the detected light. The reaction state signal output unit detects light propagating through an optical waveguide provided as one surface of the reaction vessel, and the electricity is based on the intensity of the detected light that changes according to the reaction state in the reaction vessel. The sample measuring device according to claim 2, which generates a signal. The determination unit receives the electric signal output after the energy application state is switched, and is based on a spike-like change in light intensity obtained from the electric signal and a predetermined value set in advance. The sample measuring device according to claim 3, wherein the qualitative state of the test substance is determined. The determination unit receives the electric signal output after the energy application state is switched, and the integrated value of the value in the time zone in which the spike-like change of the light intensity obtained from the electric signal occurs, and the integrated value in advance. The sample measuring device according to claim 3, wherein the qualitative state of the test substance is determined based on a set specified value. The determination unit receives the electric signal output after the energy application state is switched, and the cumulative integrated amount of values in a time zone in which a spike-like change occurs in the light intensity obtained from the electric signal. The sample measuring device according to claim 3, wherein the qualitative state of the test substance is determined based on a predetermined value set in advance. When a predetermined time for the reaction in the reaction vessel to converge after the energy application state is switched, the determination unit determines the qualitative state of the test substance as the second determination.
The sample measuring device according to any one of claims 1 to 6, wherein the qualitative state output unit outputs the result of the determination before the second determination . The sample measuring device according to claim 7, wherein the determination unit does not perform the second determination when a predetermined instruction is input to the output of the determination result. The sample measuring device according to claim 8, wherein the qualitative state output unit outputs the result of the determination as the result of the second determination . The sample measuring device according to claim 9, wherein the qualitative state output unit identifiablely outputs that the output result of the second determination is the result of the determination. The sample measuring device according to claim 7, wherein the qualitative state output unit outputs the result of the determination and the result of the second determination in an identifiable manner. The sample measuring device according to any one of claims 1 to 11, wherein the reaction promoting unit applies a magnetic field to the reaction vessel. The sample measuring device according to any one of claims 1 to 12, wherein the determination unit determines the qualitative state of the test substance based on the electric signal output after stopping the application of the energy. The sample measuring device according to any one of claims 1 to 13, wherein the qualitative state of the test substance is the degree of positive or negative indicated by the measurement result of the test substance. The sample measuring device according to any one of claims 8 to 10, wherein the predetermined instruction is an instruction to suspend the measurement of the test substance. The sample measuring device according to claim 1, wherein the qualitative state output unit outputs a qualitative state obtained by the determination when the electric signal satisfies a predetermined condition. The sample measuring device according to claim 6, wherein the qualitative state output unit outputs the qualitative state obtained by the determination when the cumulative integrated amount is equal to or less than the specified value. The determination unit makes the first determination based on the electric signal output after the application of the energy is stopped, and the second determination is based on the electric signal output after the application of the energy is started. I do,
The sample measuring device according to any one of claims 1 to 17.