JP7191613B2 - blood coagulation analyzer - Google Patents

Description

Embodiments of the present invention relate to blood coagulation analyzers.

A blood coagulation analyzer mixes a blood sample and a coagulation reagent and measures the amount of transmitted light or scattered light obtained by irradiating the mixture with light. In general, blood coagulation analyzers employ either a transmitted light type or a scattered light type. Measure the time it takes.

By the way, the blood coagulation reaction has a different strength depending on the reagent used for each measurement item. For example, in prothrombin time (PT) measurement, tissue thromboplastin (hereinafter referred to as PT reagent) is added as a reagent to test plasma. On the other hand, in the measurement of fibrinogen (Fbg), a thrombin solution (hereinafter referred to as Fbg reagent) is added as a reagent to test plasma. At this time, it is generally known that the coagulation reaction after addition of the PT reagent is stronger and faster than the coagulation reaction after addition of the Fbg reagent. In other words, the coagulation reaction after the addition of the Fbg reagent is weaker and slower than the coagulation reaction after the addition of the PT reagent.

Therefore, for example, when a transmitted light type blood coagulation analyzer is used, there is no problem in measuring the prothrombin time by adding a PT reagent. However, fibrinogen measurements performed with the addition of Fbg reagents can pose problems when the test plasma contains low concentrations of fibrinogen. That is, the dynamic range tends to be narrow.

JP 2014-173904 A

A problem to be solved by the invention is to realize highly accurate measurement.

According to the embodiment, a blood coagulation analyzer mixes a blood sample with a reagent corresponding to a test item and performs blood coagulation measurement. A blood coagulation analyzer includes a light irradiator, a transmitted light receiver, and a scattered light receiver. The light irradiator irradiates a reaction container containing a mixed liquid in which a blood sample and a reagent are mixed with light of a first wavelength and light of a second wavelength different from the light of the first wavelength. The transmitted light receiving unit receives the transmitted light of the first wavelength that is applied to the reaction container and that passes through the mixed liquid in the reaction container. The scattered light receiving unit receives the scattered light of the second wavelength that is irradiated to the reaction container and scattered by the mixed liquid in the reaction container.

FIG. 1 is a block diagram showing the functional configuration of the blood coagulation analyzer according to this embodiment. FIG. 2 is a diagram showing the configuration of the analysis mechanism shown in FIG. 1; FIG. 3 is a top view of the photometry unit shown in FIG. FIG. 4 is a side view of the photometry unit shown in FIG. FIG. 5 is a diagram showing another configuration example of the photometric unit shown in FIG. FIG. 6 is a flow chart showing the processing procedure of the control circuit shown in FIG. FIG. 7 is a flow chart showing the processing procedure of the analysis circuit shown in FIG. FIG. 8 is a graph showing first and second reaction curves obtained for a mixed solution to which a weakly responsive reagent is added. FIG. 9 is a graph obtained by adding a third reaction curve to the graph shown in FIG. FIG. 10 is a graph showing second and third reaction curves obtained for a mixed solution to which a weakly reactive reagent is added, and a center line. FIG. 11 is a graph obtained by adding a fourth reaction curve to the graph shown in FIG. FIG. 12 is a graph showing the first and fourth reaction curves obtained for the mixed solution to which the weakly reactive reagent is added, and the center line. FIG. 13 is a graph showing first and second reaction curves obtained for a mixed liquid to which a reagent having a strong reaction is added. 14 is a graph obtained by adding a third reaction curve to the graph shown in FIG. 13. FIG. FIG. 15 is a graph showing second and third reaction curves obtained for a mixed solution to which a reagent having a strong reaction is added, and a center line. 16 is a graph obtained by adding a fourth reaction curve to the graph shown in FIG. 15. FIG. FIG. 17 is a graph showing first and fourth reaction curves obtained for a mixed solution to which a reagent having a strong reaction is added, and a center line.

Embodiments will be described below with reference to the drawings.

FIG. 1 is a block diagram showing an example of the functional configuration of a blood coagulation analyzer 1 according to this embodiment. A blood coagulation analyzer 1 shown in FIG.

Analysis mechanism 2 mixes a blood sample and reagents used for each test item. Also, depending on the test item, the analysis mechanism 2 mixes the standard solution diluted by a predetermined magnification with the reagent used for this test item. The analysis mechanism 2 continuously measures optical physical property values of a mixture of a blood sample or a standard solution and a reagent. By this measurement, standard data and test data are generated, which are represented by, for example, transmitted light intensity or absorbance, scattered light intensity, and the like.

The analysis circuit 3 is a processor that analyzes standard data and test data generated by the analysis mechanism 2 to generate calibration data and analysis data regarding coagulation of the blood sample. The analysis circuit 3, for example, reads an analysis program from the storage circuit 8, and analyzes the standard data and the test data according to the read analysis program. Note that the analysis circuit 3 may have a storage area for storing at least part of the data stored in the storage circuit 8 .

The drive mechanism 4 drives the analysis mechanism 2 under the control of the control circuit 9 . The drive mechanism 4 is implemented by gears, stepping motors, belt conveyors, lead screws, and the like, for example.

The input interface 5 receives, for example, settings such as analysis parameters for each test item related to a blood sample for which measurement is requested from an operator or via the hospital network NW. The input interface 5 is implemented by, for example, a mouse, a keyboard, and a touch pad through which instructions are input by touching an operation surface. The input interface 5 is connected to the control circuit 9 , converts an operation instruction input by an operator into an electric signal, and outputs the electric signal to the control circuit 9 . It should be noted that the input interface 5 in this specification is not limited to having physical operation parts such as a mouse and a keyboard. For example, an electrical signal processing circuit that receives an electrical signal corresponding to an operation instruction input from an external input device provided separately from the blood coagulation analyzer 1 and outputs the electrical signal to the control circuit 9 is also input. Included in the interface 5 example.

The output interface 6 is connected to the control circuit 9 and outputs signals supplied from the control circuit 9 . The output interface 6 is implemented by, for example, a display circuit, a printed circuit, an audio device, and the like. Display circuits include, for example, CRT displays, liquid crystal displays, organic EL displays, LED displays, and plasma displays. Note that the display circuit also includes a processing circuit that converts data representing an object to be displayed into a video signal and outputs the video signal to the outside. Printed circuits include, for example, printers and the like. The printed circuit also includes an output circuit for outputting data representing a print target to the outside. Audio devices include, for example, speakers and the like. An output circuit for outputting an audio signal to the outside is also included in the audio device.

The communication interface 7 connects with, for example, an intra-hospital network NW. The communication interface 7 performs data communication with HIS (Hospital Information System) via the hospital network NW. The communication interface 7 may perform data communication with the HIS via a laboratory information system (LIS) connected to the hospital network NW.

The memory circuit 8 includes a processor-readable recording medium such as a magnetic or optical recording medium, or a semiconductor memory. Note that the memory circuit 8 does not necessarily have to be realized by a single memory device. For example, the memory circuit 8 may be realized by a plurality of memory devices.

The storage circuit 8 stores an analysis program to be executed by the analysis circuit 3 and a control program for realizing the functions of the control circuit 9 . The storage circuit 8 stores the calibration data generated by the analysis circuit 3 for each inspection item. The storage circuit 8 stores the analysis data generated by the analysis circuit 3 for each blood sample. The storage circuit 8 stores an examination order input by an operator or an examination order received by the communication interface 7 via the intra-hospital network NW.

The control circuit 9 is a processor that functions as the core of the blood coagulation analyzer 1 . The control circuit 9 executes a program stored in the storage circuit 8 to implement a function corresponding to the executed program. Note that the control circuit 9 may have a storage area for storing at least part of the data stored in the storage circuit 8 .

FIG. 2 is a schematic diagram showing an example of the configuration of the analysis mechanism 2 shown in FIG. The analysis mechanism 2 shown in FIG. 2 includes a reaction disk 201 , a constant temperature section 202 , a rack sampler 203 and a reagent storage 204 .

The reaction disk 201 holds a plurality of reaction vessels (cuvettes) 2011 arranged in a ring. The reaction disk 201 conveys the reaction container 2011 along a predetermined route. Specifically, the reaction disk 201 is alternately rotated and stopped at predetermined time intervals by the driving mechanism 4 . The reaction vessel 2011 is made of polypropylene (PP) or acrylic, for example.

The constant temperature unit 202 stores a heat medium set to a predetermined temperature, and immerses the reaction vessel 2011 in the stored heat medium to raise the temperature of the liquid mixture contained in the reaction vessel 2011 .

The rack sampler 203 movably supports a sample rack 2031 capable of holding a plurality of sample containers containing blood samples requested for measurement. The example shown in FIG. 2 shows a sample rack 2031 capable of holding five sample containers in parallel.

The rack sampler 203 is provided with a transport area for transporting the sample rack 2031 from the loading position where the sample rack 2031 is loaded to the collection position where the sample rack 2031 whose measurement has been completed is collected. In the transport area, a plurality of longitudinally aligned sample racks 2031 are moved in the direction D1 by the drive mechanism 4 .

Further, the rack sampler 203 is provided with a pull-in area for pulling the sample rack 2031 from the transport area in order to move the sample container held by the sample rack 2031 to a predetermined sample suction position. The sample aspiration position is provided, for example, at a position where the rotation track of the sample pipetting probe 207 and the movement track of the opening of the sample container supported by the rack sampler 203 and held by the sample rack 2031 intersect. In the pull-in area, the transported sample rack 2031 is moved in the direction D2 by the drive mechanism 4 .

Further, the rack sampler 203 is provided with a return area for returning the sample rack 2031 holding the sample container into which the sample has been sucked to the transport area. In the return area, the sample rack 2031 is moved by the drive mechanism 4 in direction D3.

The reagent storage 204 cools and insulates a plurality of reagent containers 100 containing standard solutions and reagents used in each test item performed on blood samples. A rotary table is rotatably provided in the reagent storage 204 . The rotary table holds and holds a plurality of reagent containers 100 in an annular shape. In this embodiment, although not shown in FIG. 2, the reagent storage 204 is covered with a detachable reagent cover.

The analysis mechanism 2 shown in FIG. 2 also includes a sample pipetting arm 206 , a sample pipetting probe 207 , a reagent pipetting arm 208 , a reagent pipetting probe 209 , and a photometric unit 211 .

A sample dispensing arm 206 is provided between the reaction disk 201 and the rack sampler 203 . The sample dispensing arm 206 is vertically movable and horizontally rotatable by the drive mechanism 4 . A sample dispensing arm 206 holds a sample dispensing probe 207 at one end.

The sample-dispensing probe 207 rotates along an arc-shaped rotation track as the sample-dispensing arm 206 rotates. A sample aspirating position for aspirating the sample from the sample container held by the sample rack 2031 on the rack sampler 203 is provided on this rotational track. A sample discharge position for discharging the sample aspirated by the sample pipetting probe 207 into the reaction container 2011 is provided on the rotation track of the sample pipetting probe 207 . The sample discharge position corresponds to, for example, the intersection of the rotational trajectory of the sample pipetting probe 207 and the movement trajectory of the reaction container 2011 held by the reaction disk 201 .

The sample pipetting probe 207 is driven by the drive mechanism 4 and moves vertically at the sample aspirating position or the sample discharging position. Also, the sample pipetting probe 207 aspirates the sample from the sample container located directly below the sample aspirating position under the control of the control circuit 9 . Also, the sample pipetting probe 207 discharges the sucked sample into the reaction container 2011 located directly below the sample discharging position under the control of the control circuit 9 .

A reagent dispensing arm 208 is provided between the reaction disk 201 and the reagent storage 204 . The reagent dispensing arm 208 is vertically movable and horizontally rotatable by the drive mechanism 4 . A reagent dispensing arm 208 holds a reagent dispensing probe 209 at one end.

The reagent-dispensing probe 209 rotates along an arc-shaped rotation track as the reagent-dispensing arm 208 rotates. A reagent aspirating position is provided on this rotational track. The reagent aspirating position is provided, for example, at a position where the rotation trajectory of the reagent dispensing probe 209 intersects with the movement trajectory of the opening of the reagent container 100 that is annularly placed on the rotary table. Further, a reagent ejection position for ejecting the reagent aspirated by the reagent dispensing probe 209 into the reaction container 2011 is set on the rotation orbit of the reagent dispensing probe 209 . The reagent ejection position corresponds to, for example, the intersection of the rotation trajectory of the reagent dispensing probe 209 and the movement trajectory of the reaction container 2011 held by the reaction disk 201 .

The reagent dispensing probe 209 is driven by the driving mechanism 4 and moves vertically at the reagent aspirating position or the reagent discharging position on the rotation track. Also, the reagent dispensing probe 209 aspirates the reagent from the reagent container stopped at the reagent aspirating position under the control of the control circuit 9 . Also, the reagent dispensing probe 209 discharges the aspirated reagent into the reaction container 2011 located directly below the reagent discharge position under the control of the control circuit 9 .

The photometry unit 211 continuously measures the optical physical property values in the liquid mixture of the sample and the reagent discharged into the reaction vessel 2011 . Although one photometry unit 211 is illustrated in FIG. 2, a plurality of photometry units 211 are actually provided. For example, the photometry units 211 are provided in the same number as the reaction containers that can be held by the reaction disk 201 . Since each photometric unit 211 has the same configuration, one photometric unit will be described below as a representative.

The photometry unit 211 has, for example, a light source 2111 and photodetectors 2112 and 2113 . 3 and 4 are schematic diagrams showing configuration examples of the photometry unit 211 according to this embodiment. FIG. 3 is a schematic diagram showing an example of the positional relationship of each component when the photometry unit 211 is viewed from above the reaction disk 201. As shown in FIG. FIG. 4 is a schematic diagram showing an example of the positional relationship of each component when the photometry unit 211 is viewed from the cross-sectional direction of the reaction disk 201. As shown in FIG.

The photometry unit 211 shown in FIGS. 3 and 4 has, for example, a light source 2111 on the annular center side of the reaction container 2011 held in an annular shape by the reaction disk 201 . The light source 2111 is provided so as to emit light toward the outside of the ring in which the reaction vessels 2011 are arranged.

The light source 2111 is an example of a light irradiation section that generates light of two wavelengths. The light source 2111 generates, for example, first light with a long wavelength and second light with a short wavelength. For example, the wavelength of the first light is in the red wavelength range of 620-750 nm, and the wavelength of the second light is in the violet to blue wavelength range of 380-495 nm. The wavelengths of the first and second lights may each be included in the red wavelength range of 620 to 750 nm. The light source 2111 is, for example, a multi-wavelength LED that can generate light of a plurality of wavelengths, two LEDs that generate light of predetermined wavelengths, and a light source that transmits light of a desired wavelength from light of a wide wavelength range through a filter. It is implemented by a unit or the like.

The light source 2111 generates first and second lights under the control of the control circuit 9 . Specifically, for example, the light source 2111 alternately generates the first and second lights at a predetermined cycle. At this time, the light source 2111, for example, alternately emits the first and second lights with a period of 0.05 seconds, which is half of 0.1 seconds, which is the minimum measurement unit of coagulation. Light emitted from the light source 2111 enters the reaction vessel 2011 .

Note that the light source 2111 may generate light of one wavelength designated by the control circuit 9 . Also, the light source 2111 may generate the first and second lights at the same time. However, at this time, it is necessary to provide the photodetectors 2112 and 2113 with filters for excluding light of unnecessary wavelengths.

The photometry unit 211 shown in FIGS. 3 and 4 has a photodetector 2112 at a position facing the light source 2111 with the reaction container 2011 interposed therebetween. Light emitted from the light source 2111 is incident on the first side wall of the reaction vessel 2011 and emitted from the second side wall facing the first side wall. A photodetector 2112 detects light emitted from the reaction container 2011 . The photodetector 2112 is, for example, an example of a transmitted light receiving section.

Specifically, for example, the photodetector 2112 detects light transmitted through the mixture of the standard solution and the reagent in the reaction container 2011 . The photodetector 2112 samples the detected light at predetermined time intervals, eg, 0.1 second intervals, and generates standard data represented by transmitted light intensity, absorbance, or the like. The predetermined time interval is, for example, synchronized with the frequency of occurrence of the first light. Note that the photodetector 2112 may, for example, detect only light having a wavelength corresponding to the wavelength of the first light. Also, the photodetector 2112 detects light transmitted through the mixed liquid of the blood sample and the reagent in the reaction container 2011 . The photodetector 2112 samples the detected light at predetermined time intervals to generate test data represented by transmitted light intensity, absorbance, or the like. The photodetector 2112 outputs the generated standard data and test data to the analysis circuit 3 .

In the photometry unit 211 shown in FIGS. 3 and 4, the photodetector 2113 is arranged such that the light irradiation axis of the light source 2111 and the light receiving axis of the photodetector 2113 intersect at approximately 90 degrees in the reaction vessel 2011. is provided. The light emitted from the light source 2111 enters from the first side wall of the reaction vessel 2011, is scattered by particles in the mixed liquid, and is emitted from the third side wall that is adjacent to the first side wall at 90 degrees. A photodetector 2113 detects light emitted from the reaction container 2011 . The photodetector 2113 is an example of a scattered light receiver, for example.

Specifically, for example, the photodetector 2113 detects light scattered by the mixed liquid of the standard liquid and the reagent in the reaction container 2011 . The photodetector 2113 samples the detected light at predetermined time intervals, eg, 0.1 second intervals, and generates standard data represented by scattered light intensity or the like. The predetermined time interval is, for example, synchronized with the frequency of occurrence of the second light. Note that the photodetector 2113 may, for example, detect only light having a wavelength corresponding to the wavelength of the second light. Further, the photodetector 2113 detects light scattered by the mixed liquid of the blood specimen and the reagent in the reaction container 2011 . The photodetector 2113 samples the detected light at predetermined time intervals to generate test data represented by scattered light intensity or the like. The photodetector 2113 outputs the generated standard data and test data to the analysis circuit 3 .

The photodetectors 2112 and 2113 may output the intensity of the detected light to the analysis circuit 3 as a detection signal. At this time, the analysis circuit 3 samples the detection signal at predetermined time intervals, for example, 0.1 second intervals, and generates standard data and test data.

FIG. 5 is a schematic diagram showing another configuration example of the photometry unit 211a according to this embodiment. Similar to FIG. 3, FIG. 5 shows an example of the positional relationship of each component when the photometry unit 211a is viewed from above the reaction disk 201. In FIG. A photometry unit 211a shown in FIG. 5 has two LEDs 51 and 52 as a light source 2111a. In the example shown in FIG. 5 , the light irradiation axis of the LED 52 is tilted by a predetermined angle with respect to the light irradiation axis of the LED 51 . Further, the photodetector 2113a is provided so that the light irradiation axis of the LED 52 and the light receiving axis of the photodetector 2113a intersect at approximately 90 degrees inside the reaction container 2011 .

The analysis circuit 3 shown in FIG. 1 executes an analysis program stored in the storage circuit 8 to implement functions corresponding to the program. For example, the analysis circuit 3 has an analysis function 31 and a composite analysis function 32 by executing an analysis program. In this embodiment, a case where the analysis function 31 and the composite analysis function 32 are realized by a single processor will be described, but the present invention is not limited to this. For example, an analysis circuit may be configured by combining a plurality of independent processors, and the analysis function 31 and composite analysis function 32 may be realized by each processor executing an analysis program.

The analysis function 31 is a function of analyzing standard data and test data generated by the analysis mechanism 2, and is an example of an analysis unit. Specifically, for example, in the analysis function 31, the analysis circuit 3 calculates the coagulation time based on the standard data, and generates calibration data from the calculated coagulation time. The analysis circuit 3 outputs the generated calibration data to the control circuit 9 .

Also, in the analysis function 31, the analysis circuit 3 measures the process of coagulation in the liquid mixture, for example, by analyzing test data. Specifically, the analysis circuit 3 analyzes test data obtained by detecting transmitted light, for example, for analysis of a mixed solution to which a reagent having a strong reaction is added. The analysis circuit 3 acquires a change in the received light intensity for the blood coagulation reaction based on the test data. In the following description, the change in received light intensity is used as a reaction curve. The analysis circuit 3 detects the point of inflection, the point of reaching saturation, etc. in the reaction curve as the end point of coagulation. Detection of inflection points, saturation points, and the like at this time is performed using a mathematical algorithm, such as a first derivative, a second derivative, or other arithmetic method of the reaction curve. The analysis circuit 3 calculates the solidification point and the solidification time, which is the time to reach the solidification point, based on the detected solidification end point. Note that the analysis circuit 3 may analyze test data obtained by detecting scattered light for an abnormal specimen in which coagulation does not proceed after adding a reagent with a strong reaction.

In addition, the analysis circuit 3 analyzes test data obtained by detecting scattered light, for example, for the analysis of a mixed solution to which a reagent that reacts weakly and slowly is added. In addition, in this embodiment, a weakly and slowly reacting reagent is sometimes described as a weakly reacting reagent, but these are treated as the same. The analysis circuit 3 obtains a reaction curve based on the test data, and calculates information on the coagulation of the blood sample, such as the coagulation end point, the coagulation point, and the coagulation time, from the obtained reaction curve.

Further, the analysis circuit 3 calculates a concentration value or the like based on the calculated coagulation time and the calibration data of the inspection item corresponding to the inspection data, depending on the inspection item. The analysis circuit 3 outputs analysis data including coagulation end point, coagulation point, coagulation time, concentration value, etc. to the control circuit 9 .

The combined analysis function 32 is a function for combining and analyzing two types of test data generated by the analysis mechanism 2, and is an example of a combined analysis section. Specifically, in the composite analysis function 32, the analysis circuit 3 acquires test data obtained by detecting transmitted light and test data obtained by detecting scattered light. The analysis circuit 3 extracts information on the coagulation of the blood sample, such as the clotting end point, the coagulation point, and the clotting time, from the reaction curve based on the test data for transmitted light and the reaction curve based on the test data for scattered light. etc. The composite analysis processing by the composite analysis function 32 will be detailed later.

The composite analysis function 32 is implemented according to the control from the control circuit 9 and the analysis result of the analysis function 31, for example. For example, the analysis circuit 3 implements the composite analysis function 32 according to instructions from the control circuit 9 . For example, the analysis circuit 3 performs the composite analysis function 32 when the reaction is slower than expected after adding a weakly reactive reagent in the analysis function 31 .

The analysis circuit 3 outputs analysis data including the coagulation end point, the coagulation point, the coagulation time, etc. to the control circuit 9 .

The control circuit 9 shown in FIG. 1 executes a control program stored in the storage circuit 8 to implement functions corresponding to the program. For example, the control circuit 9 has a system control function 91 and a photometry control function 92 by executing a control program. In this embodiment, the case where the system control function 91 and the photometry control function 92 are implemented by a single processor will be described, but the present invention is not limited to this. For example, a control circuit may be configured by combining a plurality of independent processors, and the system control function 91 and the photometry control function 92 may be realized by each processor executing a control program.

The system control function 91 is a function that controls each unit in the blood coagulation analyzer 1 based on input information input from the input interface 5 . For example, in the system control function 91, the control circuit 9 controls the analysis circuit 3 so as to perform analysis according to inspection items.

The photometry control function 92 is a function of controlling the wavelength of light used for measurement, and is an example of a photometry control unit. Specifically, in the photometry control function 92, the control circuit 9, for example, refers to the inspection order stored in the storage circuit 8, and acquires the reagent information to be used for the inspection item to be measured next. The control circuit 9 determines whether or not the reaction of the reagent to be used next is weak based on, for example, the test item name, reagent name, reaction information, and retest information included in the acquired reagent information. In this embodiment, the information about the reaction is information indicating the strength of the reaction, and is represented by, for example, an identifier or text indicating that the reaction is weak (strong). Information about retesting is information indicating that the reagent to be used next is used for the item to be retested. An item that is subject to retesting is treated as having a weak reaction in the previous test, for example. Information about reexamination is represented by, for example, an identifier or text indicating that the subject is a reexamination target. When determining that the reaction of the reagent to be used next is weak, the control circuit 9 controls the photometric unit 211 and the analysis circuit 3, for example, as described below.

1. An example in which the first and second lights are alternately emitted from the light source 2111 regardless of the characteristics of the reagent
In normal measurement, for example, the first light with a long wavelength and the second light with a short wavelength are measured in the minimum measurement unit, for example, 0.05 seconds, which is half of 0.1 seconds. The light source 2111 is controlled so that it is generated alternately in cycles. In this embodiment, normal measurement means measurement in a state where the reaction of the reagent to be used next is not judged to be weak, for example. At this time, the control circuit 9 controls the analysis function 31 of the analysis circuit 3 so as to analyze the test data obtained by detecting the transmitted light of the first light, for example. The control circuit 9 analyzes at least one of the test data obtained by detecting the transmitted light of the first light and the test data obtained by detecting the scattered light of the second light. The analysis function 31 may be controlled.

When determining that the reaction of the reagent to be used next is weak, the control circuit 9 causes the analysis function 31 of the analysis circuit 3 to analyze the test data obtained by detecting the scattered light of the second light, for example. to control. At this time, the control circuit 9 controls the composite analysis function 32 of the analysis circuit 3 so as to perform composite analysis processing. It should be noted that execution of the composite analysis process is not essential.

2. Example of switching the photometric wavelength according to the characteristics of the reagent
For example, in normal measurement, the control circuit 9 controls the light source 2111 to generate the first light having a long wavelength, and controls the analysis circuit 3 to analyze the test data obtained by detecting the transmitted light. Controls the analysis function 31 .

If it is determined that the reaction of the reagent to be used next is weak, the control circuit 9 controls the light source 2111 so that the first and second lights are emitted alternately with a period of half the minimum measurement unit, for example. do. Then, the control circuit 9 controls the analysis function 31 of the analysis circuit 3 so as to analyze the test data obtained by detecting the scattered light of the second light, for example. At this time, the control circuit 9 may control the composite analysis function 32 of the analysis circuit 3 so as to perform composite analysis processing.

When determining that the reaction of the reagent to be used next is weak, the control circuit 9 may, for example, stop generating the first light and control the light source 2111 to generate the second light. good. At this time, the control circuit 9 controls the analysis function 31 so as to analyze the test data obtained by detecting the scattered light.

Next, the scattered light intensity in the mixture of the blood sample and the reagent will be described.
Light scattering includes Rayleigh scattering and Mie scattering. The wavelengths of light emitted from the light source 2111 used in this embodiment are 620 to 750 nm and 380 to 495 nm. The particle size of fibrinogen contained in a blood sample is approximately 9 nm, which is smaller than the wavelength of light. Therefore, it is considered that the scattering of light that occurs in the mixed liquid during the initial reaction is mainly Rayleigh scattering. The scattering cross section σ of Rayleigh scattering is represented by the formula (1). In the formula (1), d is the particle diameter of the fine particles, λ is the wavelength of incident light, n is the refractive index of the fine particles, and N is the number of fine particles.

From equation (1), it can be seen that the scattered light intensity due to Rayleigh scattering is inversely proportional to the fourth power of the wavelength λ. That is, the shorter the wavelength of the light with which the mixture is irradiated, the higher the scattered light intensity. It can also be seen from equation (1) that the intensity of scattered light due to Rayleigh scattering is proportional to the sixth power of the particle diameter d. In other words, when the coagulation reaction progresses in the mixed solution and fibrinogen changes to fibrin, the scattered light intensity increases.

In this embodiment, the wavelength of the second light used to measure the scattered light is set to be shorter than the wavelength of the first light, preferably within the wavelength range of 380 to 495 nm from violet to blue. It is Then, when the reaction of the reagent to be used next is weak, the test data obtained by detecting the scattered light of the second light is analyzed, and the data on the coagulation of the test plasma is calculated. . As a result, even if the reaction of the reagent used is weak and the concentration of fibrinogen contained in the test plasma is low, it is possible to satisfactorily calculate the data on the coagulation of the test plasma.

Next, the operation of the blood coagulation analyzer 1 configured as described above will be described according to the processing procedure of the control circuit 9. FIG.
FIG. 6 is a flow chart showing an example of the processing procedure of the control circuit 9 when the blood coagulation analyzer 1 shown in FIG. 1 measures the coagulation reaction of test plasma. In the description of FIG. 6, an example will be described in which the control circuit 9 switches the setting of the photometric wavelength according to the characteristics of the reagent. In addition, in the description of FIG. 6, fibrinogen is taken as an example of an Fbg reagent as a weakly reactive reagent and an inspection item using the Fbg reagent. The weakly reactive reagent is not limited to the Fbg reagent. Moreover, the test item is not limited to fibrinogen as long as the test item uses a weakly reactive reagent.

The control circuit 9 reads out the control program stored in the storage circuit 8, for example, when a preset start-up time comes or when a start-up instruction is input from the operator, and the system control function 91 and photometry A control function 92 is implemented. In the system control function 91 , the control circuit 9 centrally controls each part in the blood coagulation analyzer 1 .

Specifically, for example, the control circuit 9 controls the drive mechanism 4 to move the sample rack 2031 supported by the rack sampler 203 (step S61). The sample rack 2031 holds sample containers containing blood samples. When the sample container held in the sample rack 2031 reaches the sample aspirating position, the control circuit 9 determines that the blood sample in the sample container that has arrived is the next test target. (step S62).

At this time, the control circuit 9, in the photometry control function 92, refers to the inspection order and acquires the reagent information used in the inspection item to be measured next (step S63). The control circuit 9 determines whether or not the reaction of the reagent to be used next is weak based on, for example, the test item name, reagent name, reaction information, and retest information included in the acquired reagent information ( step S64). If the reagent name included in the acquired reagent information is "Fbg reagent", the control circuit 9 determines that the reaction of the reagent to be used next is weak (Yes in step S64), and the photometry control function 92 controls the light source 2111 to set the wavelength of the light generated. For example, the control circuit 9 sets the wavelength of the light source 2111 so that the first and second lights are generated alternately with a period of 0.05 seconds, for example. Further, the control circuit 9 outputs to the analysis circuit 3 an instruction to analyze the test data obtained by detecting the scattered light of the second light (step S65). At this time, the control circuit 9 may output to the analysis circuit 3 an instruction to perform the composite analysis process.

If it is determined that the reaction of the reagent to be used next is weak (Yes in step S64), the control circuit 9, for example, controls the light source so that the first light is not emitted and the second light is emitted. 2111 may be set to output to the analysis circuit 3 an instruction to analyze the test data obtained by detecting the scattered light. Further, if the reagent information includes, for example, the test item: "fibrinogen" or the information on the reaction: "weak reaction", the control circuit 9 can determine the reagent to be used next based on these. It may be judged that the reaction of is weak.

If the reagent name included in the acquired reagent information is other than "reagent with weak reaction such as Fbg reagent", for example, "PT reagent", the control circuit 9 determines that the reaction of the reagent to be used next is not weak. Determined (No in step S64), the light source 2111 is set so that only the first light is emitted. Further, the control circuit 9 outputs to the analysis circuit 3 an instruction to analyze the test data obtained by detecting the transmitted light (step S66). In addition to the "PT reagent", reagents that do not react weakly include, for example, reagents added when measuring the activated partial trotonbonplastin time (APTT).

In steps S65 and S66, when the wavelength of light from the light source 2111 is set and an instruction is output to the analysis circuit 3, the control circuit 9 causes the sample dispensing probe 207 to move to the sample aspiration position. The sample pipetting arm 206 is rotated. When the sample pipetting probe 207 reaches the sample aspirating position, the control circuit 9 lowers the sample pipetting probe 207 to aspirate the blood specimen from the sample container positioned directly below the sample aspirating position (step S67).

When the blood sample is aspirated from the sample container, the control circuit 9 raises the sample dispensing probe 207 and rotates the sample dispensing arm 206 so that the sample dispensing probe 207 moves above the sample ejection position. When the sample pipetting probe 207 reaches the sample discharging position, the control circuit 9 lowers the sample pipetting probe 207 and discharges the blood sample into the empty reaction container 2011 located directly below the sample discharging position (step S68). ). The control circuit 9 rotates the reaction disk 201 by the drive mechanism 4 and transfers the empty reaction container 2011 to the sample discharge position before the sample pipetting probe 207 is lowered. The temperature of the blood sample discharged into the reaction container 2011 is raised to a predetermined temperature (eg, 37° C.) by the constant temperature unit 202 .

For example, the control circuit 9 operates the reagent dispensing arm 208, the reagent dispensing probe 209, and the rotary table of the reagent storage 204 in the background of the operation to dispense the blood sample into the reaction container 2011, and displays the test order. The reagent corresponding to the inspection item to be stored is aspirated from the reagent container 100 in the reagent storage 204 (step S69).

When the blood sample is discharged into the reaction container 2011, the control circuit 9 causes the drive mechanism 4 to rotate the reaction disk 201 and move the reaction container 2011 into which the blood sample has been discharged to the reagent discharge position (step S610). . When the reaction container 2011 reaches the reagent ejection position, the control circuit 9 operates the reagent dispensing arm 208 and the reagent dispensing probe 209 to eject the reagent into the reaction container 2011 that has reached the reagent ejection position (step S611). .

When the reagent is discharged into the reaction container 2011, the control circuit 9 notifies the analysis circuit 3 that the reagent has been added to the blood sample, and causes the photometry unit 211 to start photometry of the reaction container 2011 (step S612). As a result, light of the set wavelength is emitted from the light source 2111 to the reaction container 2011 . Light emitted from the light source 2111 is detected by the photodetector 2112 and/or the photodetector 2113 through the liquid mixture in the reaction container 2011 . The photodetector 2112 and/or the photodetector 2113 generates test data based on the detected light and transmits the generated test data to the analysis circuit 3 .

The control circuit 9 refers to the stored inspection order and confirms whether or not there is a next measurement (step S613). If there is no next measurement, the control circuit 9 terminates the process. On the other hand, if there is a next measurement, the control circuit 9 shifts the process to step S61.

In the description of FIG. 6, an example was described in which the control circuit 9 switches the setting of the photometric wavelength according to the characteristics of the reagent. However, the processing of the control circuit 9 when measuring the coagulation reaction of the test plasma is not limited to FIG. For example, the control circuit 9 may alternately generate the first and second lights from the light source 2111 regardless of the properties of the reagent.

Specifically, for example, the light source 2111 is set in advance so that the first and second lights are generated alternately, for example, in a period of 0.05 seconds. When it is determined that the reaction of the reagent to be used next is weak (Yes in step S64), the control circuit 9 causes the photometry control function 92 to detect the scattered light of the second light and obtain test data. An instruction to analyze is output to the analysis circuit 3 . At this time, the control circuit 9 may output to the analysis circuit 3 an instruction to perform the composite analysis process.

If the reaction of the reagent to be used next is not weak (No in step S64), the control circuit 9 instructs the analysis circuit 3 to analyze the test data obtained by detecting the transmitted light of the first light. Output to The control circuit 9 analyzes at least one of the test data obtained by detecting the transmitted light of the first light and the test data obtained by detecting the scattered light of the second light. An instruction may be output to the analysis circuit 3 .

Next, the operation of analyzing the test data by the analysis circuit 3 will be described.
FIG. 7 is a flow chart showing an example of the procedure when the analysis circuit 3 shown in FIG. 1 analyzes test data.

For example, upon receiving the addition notification from the control circuit 9 (step S71), the analysis circuit 3 reads out the analysis program stored in the storage circuit 8 and starts the analysis function 31. FIG. In the analysis function 31 , the analysis circuit 3 analyzes test data sent from the analysis mechanism according to instructions sent from the control circuit 9 . Specifically, based on the instruction received from the control circuit 9, the analysis circuit 3 determines whether or not the test data obtained by detecting the scattered light is to be analyzed (step S72). When receiving an instruction from the control circuit 9 to analyze the test data obtained by detecting the scattered light, the analysis circuit 3 analyzes the test data obtained by detecting the scattered light. (Yes in step S72). On the other hand, when receiving an instruction from the control circuit 9 to analyze the test data obtained by detecting the transmitted light, the analysis circuit 3 detects the test data obtained by detecting the transmitted light. (No in step S72).

If the object of analysis is test data obtained by detecting scattered light (Yes in step S72), the analysis circuit 3 analyzes the mixed liquid to which the weakly reactive reagent is added. In the analysis of the mixture to which the weakly reactive reagent is added, the analysis circuit 3, for example, first determines whether or not it has received from the control circuit 9 an instruction to perform the composite analysis process (step S73). . If the instruction to perform the composite analysis process has not been received from the control circuit 9 (No in step S73), the analysis circuit 3 analyzes the test data generated by the photodetector 2113 (step S74).

Specifically, when the blood coagulation reaction starts after the reagent is added to the reaction container 2011, the turbidity of the mixed liquid increases due to blood coagulation, and the scattered light intensity gradually increases. The analysis circuit 3, for example, uses a predetermined stage from when the scattered light intensity rises after addition of the reagent until it reaches a constant value, for example, the inflection point of the reaction curve and/or the saturation point, etc., as the coagulation end point. To detect. A known method may be used to detect the end point of coagulation. For example, the end point of coagulation can be detected by using a value obtained by first-order differentiation or second-order differentiation of the scattered light intensity with respect to time.

Subsequently, the analysis circuit 3 determines, for example, whether the scattered light intensity at the detected coagulation end point is equal to or greater than a preset threshold, and if the scattered light intensity is less than the threshold, the coagulation end point to explore. If the scattered light intensity at the detected coagulation end point is equal to or greater than the threshold, the analysis circuit 3 calculates the time when the intensity reaches 1/N (N is a predetermined value greater than 1) of the scattered light intensity at this coagulation end point. Calculated as freezing point.

After analyzing the test data on the scattered light, the analysis circuit 3 determines whether or not an abnormality has occurred in the analysis (step S75). For example, the analysis circuit 3 determines that there is an abnormality in the analysis when a coagulation end point with a scattered light intensity equal to or greater than a predetermined threshold value is not detected before a predetermined maximum measurement time elapses ( Yes in step S75). The determination as to whether or not an abnormality has occurred is not limited to this, and other determination methods may be employed. When no abnormality occurs in the analysis and the coagulation end point, the coagulation point, the coagulation time, etc. are calculated (No in step S75), the analysis circuit 3 outputs analysis data including these analysis results to the control circuit 9. (Step S76), the process is terminated.

If it is determined in step S75 that there is an abnormality in the analysis, the analysis circuit 3 performs combined analysis processing for analyzing both the test data obtained by detecting the scattered light and the test data obtained by detecting the transmitted light. (step S77). Specifically, when the first and second lights are alternately generated from the light source 2111 at a predetermined cycle, the analysis circuit 3 detects the test data generated by the photodetector 2113 and It also receives test data generated in . Analysis circuit 3 acquires a response curve (hereinafter referred to as a first response curve) for transmitted light intensity based on the test data from photodetector 2112 . Note that the reaction curve for the scattered light intensity obtained in the process of step S74 is hereinafter referred to as a second reaction curve.

FIG. 8 is a graph showing an example of first and second reaction curves obtained for a mixed solution to which a weakly responsive reagent is added. In FIG. 8, the dashed line represents the first response curve for transmitted light intensity and the solid line represents the second response curve for scattered light intensity. In FIG. 8, the vertical axis represents light intensity, and the horizontal axis represents elapsed time. If the dynamic ranges of the first and second response curves are different, the analysis circuit 3 may, for example, compress one curve with a larger dynamic range to match the other curve with a smaller dynamic range. Note that compression is processing for compressing the light intensity of a curve. This aligns the ranges of the first and second response curves. Note that the processing for matching the ranges between response curves is not limited to compression.

After obtaining the first response curve, the analysis circuit 3 vertically inverts the first response curve, for example, about half the maximum value of the transmitted light intensity. A curve obtained by vertically inverting the first reaction curve is hereinafter referred to as a third reaction curve. FIG. 9 is a graph obtained by adding a third reaction curve to the graph shown in FIG. In FIG. 9, the thick dashed line represents the third response curve.

After obtaining the third response curve, the analysis circuit 3 calculates the center line between the second response curve and the third response curve for scattered light intensity. FIG. 10 is a graph showing an example of the second and third reaction curves and the center line obtained for a mixed solution to which a weakly reactive reagent is added. In FIG. 10, the thin solid line represents the second response curve, the thick dashed line represents the third response curve, and the thick solid line represents the central line.

After calculating the center line, the analysis circuit 3 calculates, for example, the end point of solidification, the solidification point, the solidification time, and the like, based on the center line. Specifically, for example, the analysis circuit 3 detects a predetermined stage from when the center line rises after addition of the reagent until it reaches a constant value as the coagulation end point. A known method may be used to detect the end point of coagulation. Subsequently, the analysis circuit 3, for example, determines whether or not the light intensity at the detected end point of coagulation is equal to or greater than a preset threshold, and if the light intensity is less than the threshold, searches for the end point of coagulation again. do. When the light intensity at the detected coagulation end point is equal to or greater than the threshold, the analysis circuit 3 calculates the time when the light intensity reaches 1/N of the light intensity at the coagulation end point as the coagulation point.

Thus, by generating the center line based on the response curve for the scattered light intensity and the response curve obtained by inverting the response curve for the transmitted light intensity, the increase in the light intensity per elapsed time becomes gentle. . This makes it possible to detect the solidification end point and the like with high accuracy. By the way, if the clotting response is weak, you can try to switch the gain to amplify the response curve. However, this approach amplifies noise along with the actual signal. According to the method of generating the center line according to the present embodiment, it is possible to suppress the amplification of noise and extract only the actual signal.

After executing the composite analysis process, the analysis circuit 3 determines whether or not an abnormality has occurred in the analysis (step S78). For example, the analysis circuit 3 determines that there is an abnormality in the analysis when a coagulation end point with a light intensity equal to or higher than a predetermined threshold value is not detected until a predetermined maximum measurement time elapses (step Yes in S78). The determination as to whether or not an abnormality has occurred is not limited to this, and other determination methods may be employed. If it is determined that there is an abnormality in the analysis (Yes in step S78), the analysis circuit 3 notifies the control circuit 9 of the abnormality (step S79), and terminates the process. If no abnormality has occurred in the analysis (No in step S78), the analysis circuit 3 shifts the process to step S76.

When the control circuit 9 receives notification from the analysis circuit 3 that there is an abnormality, it terminates the photometry by the photometry unit 211 as measurement impossible, and outputs to the output interface 6 that there is an abnormality.

Note that the reaction curve that is turned upside down during the composite analysis process is not limited to the first reaction curve. For example, the second response curve may be vertically inverted around the half value of the maximum transmitted light intensity. A curve obtained by vertically inverting the second reaction curve is referred to as a fourth reaction curve. FIG. 11 is a graph obtained by adding a fourth reaction curve to the graph shown in FIG. In FIG. 11, the thick dashed line represents the fourth response curve.

When the fourth response curve is acquired, the analysis circuit 3 calculates the center line from the first response curve and the fourth response curve for transmitted light intensity. FIG. 12 is a graph showing an example of the first and fourth reaction curves and the center line obtained for a mixed solution to which a weakly reactive reagent is added. In FIG. 12, the thin dashed line represents the first response curve, the thick dashed line represents the fourth response curve, and the thick solid line represents the central line. The analysis circuit 3 calculates, for example, the end point of solidification, the solidification point, the solidification time, and the like, based on the calculated center line.

At this time, the analysis circuit 3 calculates the center line based on the first response curve for the transmitted light intensity. Therefore, the processing for calculating the solidification end point, solidification point, solidification time, etc. based on the center line is slightly different from the processing in step S77. Specifically, for example, the analysis circuit 3 detects, as a coagulation end point, a predetermined stage from when the center line drops after addition of the reagent until it reaches a constant value. Subsequently, the analysis circuit 3 determines, for example, whether the light intensity at the detected coagulation end point is equal to or less than a preset threshold, and if the light intensity exceeds the threshold, searches for the coagulation end point again. When the light intensity at the detected coagulation end point is equal to or less than the threshold, the analysis circuit 3 calculates the time when the light intensity reaches 1/N of the light intensity at the coagulation end point as the coagulation point.

In step S73, if an instruction to perform the combined analysis process has been received from the control circuit 9 (Yes in step S73), the analysis circuit 3 analyzes the test data on the scattered light, A combined analysis of the test data for light is performed (step S710). The analysis circuit 3 may perform only combined analysis of the test data for the scattered light and the transmitted light without analyzing the test data for the scattered light. After performing the analysis of step S710, the analysis circuit 3 shifts the process to step S78.

In step S72, if the object of analysis is test data obtained by detecting transmitted light (No in step S72), the analysis circuit 3 analyzes the mixed liquid to which the reagent having a strong reaction is added. In the analysis of the mixture to which the reagent having a strong reaction is added, the analysis circuit 3 analyzes the test data generated by the photodetector 2112 (step S711).

Specifically, when the blood coagulation reaction starts after the reagent is added to the reaction container 2011, the transmitted light intensity gradually decreases. For example, the analysis circuit 3 uses a predetermined stage from when the transmitted light intensity decreases after addition of the reagent until it reaches a constant value, such as the inflection point of the reaction curve and/or the saturation point, as the coagulation end point. To detect.

Subsequently, the analysis circuit 3, for example, determines whether the detected end point of coagulation is appropriate. For example, the analysis circuit 3 determines whether or not the transmitted light intensity at the detected coagulation end point is equal to or less than a preset threshold, and if the transmitted light intensity exceeds the threshold, searches for the coagulation end point again. If the transmitted light intensity at the detected coagulation end point is equal to or less than the threshold, the analysis circuit 3 calculates the time when the transmitted light intensity reaches 1/N of the transmitted light intensity at this coagulation end point as the coagulation point.

After analyzing the test data for the transmitted light, the analysis circuit 3 determines whether or not an abnormality has occurred in the analysis (step S712). For example, the analysis circuit 3 determines that there is an abnormality in the analysis when a coagulation end point with a transmitted light intensity equal to or lower than a predetermined threshold value is not detected before a predetermined maximum measurement time elapses ( Yes in step S712). The determination as to whether or not an abnormality has occurred is not limited to this, and other determination methods may be employed. If no abnormality occurs in the analysis and the solidification end point, solidification point, solidification time, etc. are calculated (No in step S712), the analysis circuit 3 shifts the process to step S76.

If it is determined that there is an abnormality in the analysis in step S712, the analysis circuit 3 analyzes the test data obtained by detecting the scattered light, for example, in the same procedure as in step S74 (step S713). In addition, in the case of analyzing test data by scattered light for a mixed solution to which a reagent having a strong reaction is added, it is necessary that the first light and the second light are alternately generated from the light source 2111 at a predetermined cycle. There is

After analyzing the test data on the scattered light, the analysis circuit 3 determines whether or not an abnormality has occurred in the analysis (step S714). If it is determined that there is an abnormality in the analysis (Yes in step S714), the analysis circuit 3 shifts the process to step S79. If no abnormality has occurred in the analysis (No in step S714), the analysis circuit 3 shifts the process to step S76.

For example, when there is an abnormality in the analysis in step S714, the analysis circuit 3 analyzes both the test data obtained by detecting the scattered light and the test data obtained by detecting the transmitted light. A composite analysis process may be performed. The analysis circuit 3, for example, refers to the first reaction curve for the transmitted light intensity acquired in step S711 and the second reaction curve for the scattered light intensity acquired in step S713, and performs combined analysis processing. to implement.

FIG. 13 is a graph showing an example of first and second reaction curves obtained for a mixed solution to which a reagent having a strong reaction is added. In FIG. 13, the dashed line represents the first response curve for transmitted light intensity and the solid line represents the second response curve for scattered light intensity. In FIG. 13, the vertical axis represents light intensity, and the horizontal axis represents elapsed time.

For example, the analysis circuit 3 vertically inverts the first response curve shown in FIG. 13 with the half value of the maximum transmitted light intensity as an axis. FIG. 14 is a graph in which a third reaction curve obtained by vertically inverting the first reaction curve is added to FIG. In FIG. 14, the thick dashed line represents the third response curve.

After obtaining the third response curve, the analysis circuit 3 calculates the center line between the second response curve and the third response curve for scattered light intensity. FIG. 15 is a graph showing an example of the second and third reaction curves obtained for a mixed solution to which a reagent having a strong reaction is added, and the center line. In FIG. 15, the thin solid line represents the second response curve, the thick dashed line represents the third response curve, and the thick solid line represents the central line.

After calculating the center line, the analysis circuit 3 calculates, for example, the end point of solidification, the solidification point, the solidification time, and the like, based on the center line. After executing the composite analysis process, the analysis circuit 3 determines whether or not an abnormality has occurred in the analysis. If there is an abnormality in the analysis, the analysis circuit 3 notifies the control circuit 9 of the abnormality. On the other hand, when no abnormality has occurred in the analysis, the analysis circuit 3 outputs analysis data including analysis results to the control circuit 9 .

Note that the reaction curve that is turned upside down during the composite analysis process is not limited to the first reaction curve. For example, the second response curve may be vertically inverted around the half value of the maximum transmitted light intensity. FIG. 16 is a graph in which a fourth response curve obtained by vertically inverting the second response curve is added to FIG. 13 . In FIG. 16, the thick dashed line represents the fourth response curve.

When the fourth response curve is acquired, the analysis circuit 3 calculates the center line from the first response curve and the fourth response curve for transmitted light intensity. FIG. 17 is a graph showing an example of the first and fourth reaction curves and the center line obtained for a mixed solution to which a reagent having a strong reaction is added. In FIG. 17, the thin dashed line represents the first response curve, the thick dashed line represents the fourth response curve, and the thick solid line represents the central line. The analysis circuit 3 calculates, for example, the end point of solidification, the solidification point, the solidification time, and the like, based on the calculated center line.

Moreover, the timing at which the analysis circuit 3 performs the composite analysis process is not limited to after the analysis of the test data on the scattered light. A composite analysis process may be performed instead of the analysis of test data for transmitted light.

As described above, in this embodiment, the light source 2111 generates light of a first wavelength and light of a second wavelength different from the light of the first wavelength. The light source 2111 irradiates the mixed liquid contained in the reaction vessel 2011 with the generated light. The photodetector 2112 receives the transmitted light of the light of the first wavelength that is applied to the reaction container and passes through the mixed liquid in the reaction container. The photodetector 2113 receives the scattered light of the second wavelength that is irradiated to the reaction container and scattered by the mixed liquid in the reaction container. As a result, the blood coagulation analyzer 1 can analyze the blood sample using at least one of the transmitted light reception result and the scattered light reception result.

Further, in this embodiment, the control circuit 9 acquires the characteristics of the reagent used for measurement by the photometry control function 92 . The control circuit 9 selects the wavelength of the light emitted by the light source 2111 based on the acquired characteristics. Then, the analysis circuit 3 uses the analysis function 31 to detect the intensity change of the transmitted light received by the photodetector 2112 or the intensity change of the scattered light received by the photodetector 2113 based on the characteristics acquired by the control circuit 9. I am trying to analyze it. This makes it possible to select the light used for analysis from transmitted light and scattered light according to the intensity of the reaction of the reagent added to the blood sample.

Also, in this embodiment, the second wavelength is set to be shorter than the first wavelength. In other words, the wavelength of the light used to analyze the intensity change of the scattered light is shorter than the wavelength of the light used to analyze the intensity change of the transmitted light. It is known that the shorter the wavelength of the light with which the mixture is irradiated, the higher the scattered light intensity. Therefore, by analyzing the intensity change of the scattered light using light with a short wavelength, it is possible to measure the blood sample satisfactorily even if the reaction of the added reagent is weak.

It is necessary to carefully judge whether or not an abnormal reaction has occurred, for example, no coagulation at all. 201. On the other hand, how long a reaction container suspected of an abnormal reaction is held on the reaction disk 201 greatly affects the overall throughput. According to the present embodiment, it is possible to satisfactorily measure a blood sample to which a weakly reactive reagent has been added, making it easier to determine whether an abnormal reaction has occurred in the reaction container, thereby improving throughput. can be expected.

Further, in the present embodiment, the analysis circuit 3 uses the analysis function 31 to analyze the intensity change of the scattered light received by the photodetector 2113 when the reagent to be added is a weakly reactive reagent such as a fibrinogen reagent. I have to. As a result, even when a weakly reacting reagent is added, it is possible to measure a blood sample because changes in the intensity of scattered light are analyzed.

Further, in this embodiment, the analysis circuit 3 analyzes the intensity change of the transmitted light received by the photodetector 2112 by the analysis function 31 when the added reagent reacts more strongly and faster than the fibrinogen reagent or the like. I have to. As a result, it is possible to carry out the same treatment as usual for reagents that do not react weakly.

In this embodiment, the analysis circuit 3 analyzes the intensity change of the transmitted light received by the photodetector 2112 by the analysis function 31, and then analyzes the intensity change of the scattered light received by the photodetector 2113. I have to. As a result, for example, when the blood coagulation reaction progresses slowly in a mixture to which a highly reactive reagent is added, it is possible to switch to analysis using scattered light.

Further, in the present embodiment, the analysis circuit 3 uses the composite analysis function 32 to compositely analyze the intensity change of the scattered light received by the photodetector 2113 and the intensity change of the transmitted light received by the photodetector 2112. I am trying to As a result, the blood sample can be measured with high accuracy.

In this embodiment, the analysis circuit 3 analyzes the intensity change of the scattered light received by the photodetector 2113 by the composite analysis function 32, and then performs composite analysis processing using two kinds of intensity changes. I'm trying As a result, for example, when the blood coagulation reaction progresses slowly in a mixture to which a weakly reactive reagent is added, it is possible to switch to composite analysis.

Further, in this embodiment, the control circuit 9 acquires the characteristics of the reagent used for measurement by the photometry control function 92 . The control circuit 9 selects the wavelength of the light emitted by the light source 2111 based on the acquired characteristics. Then, the analysis circuit 3 uses the composite analysis function 32 to perform composite analysis processing based on the acquired characteristics. Thereby, for example, it is possible to set whether or not to perform the composite analysis process according to the reagent to be added. That is, for example, it is possible to perform composite analysis processing on a mixed solution to which a weakly reactive reagent is added.

Further, in the present embodiment, the analysis circuit 3 vertically inverts either one of the intensity change of the transmitted light and the intensity change of the scattered light by the combined analysis function 32, and the inverted intensity change, The intermediate line with the other intensity change that is not upside down is analyzed. As a result, the increase in light intensity per elapsed time becomes gentle, and blood samples can be measured with high accuracy. In samples with weak and slow reactions, the initial change after adding the reagent is very important data for calculating the coagulation time. By analyzing the median line, it becomes possible to capture with high accuracy the initial change after the reagent is added.

Moreover, in this embodiment, the first wavelength is included in the red wavelength range, and the second wavelength is included in the violet to blue wavelength range. As a result, the scattered light intensity of the light of the second wavelength becomes sufficiently larger than the scattered light intensity of the light of the first wavelength. Good measurement results can be obtained. In addition, since the red wavelength region has high transmittance in an object with high turbidity, measurement using light of the first wavelength is suitable for a reagent system with high turbidity.

In the above-described embodiment, for a mixed solution to which a weakly reactive reagent is added, test data regarding the light intensity of scattered light is analyzed, for example, as described in step S74. However, it is not limited to this. The analysis circuit 3 may use the analysis function 31 to switch between, for example, the analysis of the test data regarding the light intensity of the scattered light and the analysis of the test data regarding the light intensity of the transmitted light according to the elapsed time. . Specifically, for example, the analysis circuit 3 analyzes the test data regarding the light intensity of the scattered light until a predetermined time has passed since the addition of the reagent. After a predetermined time has passed since the addition of the reagent, the analysis circuit 3 analyzes the test data regarding the light intensity of the transmitted light. Note that the predetermined time is, for example, a time during which the coagulation time can be determined in the response curve of the scattered light intensity.

Further, in the above embodiment, the case where the photodetectors 2112 and 2113 are provided in each of the plurality of photometric units 211 has been described as an example. However, it is not limited to this. Among the provided photometry units 211, some photometry units 211 may be provided with the photodetectors 2112 and 2113, and the other photometry units may be provided with only the photodetector 2112 for detecting transmitted light. . As a result, even if the layout of the reaction disk 201 does not have enough room, it can be handled.

According to at least one embodiment described above, the blood coagulation analyzer 1 can realize highly accurate measurement.

The word "processor" used in the description of the embodiments is, for example, a CPU (central processing unit), a GPU (Graphics Processing Unit), or an application specific integrated circuit (ASIC)), a programmable logic device (eg, Simple Programmable Logic Device (SPLD), Complex Programmable Logic Device (CPLD), and Field Programmable Gate Array (FPGA)). The processor realizes its functions by reading and executing the programs stored in the memory circuit. It should be noted that instead of storing the program in the memory circuit, the program may be directly installed in the circuit of the processor. In this case, the processor implements its functions by reading and executing the program embedded in the circuit. Note that each processor in each of the above embodiments is not limited to being configured as a single circuit for each processor, but may be configured as a single processor by combining a plurality of independent circuits to realize its function. good too. Furthermore, a plurality of components in each of the above embodiments may be integrated into one processor to realize its function.

While embodiments of the invention have been described, the embodiments have been presented by way of example and are not intended to limit the scope of the invention. This embodiment can be implemented in various other forms, and various omissions, replacements, changes, and combinations can be made without departing from the scope of the invention. These embodiments and their modifications are included in the scope and spirit of the invention, as well as the scope of the invention described in the claims and equivalents thereof.

1 Blood coagulation analyzer 2 Analysis mechanism 201 Reaction disk 202 Constant temperature unit 203 Rack sampler 204 Reagent storage 206 Sample dispensing arm 207 Sample dispensing probe 208 Reagent dispensing arm 209 Reagent dispensing probe 211, 211a... Photometry unit 2011... Reaction container 2031... Sample rack 2111, 2111a... Light source 2112... Photodetectors 2113, 2113a... Photodetectors 51, 52... LED
3 Analysis circuit 31 Analysis function 32 Combined analysis function 4 Drive mechanism 5 Input interface 6 Output interface 7 Communication interface 8 Storage circuit 9 Control circuit 91 System control function 92 Photometry control function 100 Reagent container

Claims (10)

A blood coagulation analyzer for measuring blood coagulation by mixing a blood sample with a reagent corresponding to a test item,
a light irradiation unit that irradiates a reaction container containing a mixed liquid in which a blood sample and a reagent are mixed with light of a first wavelength and light of a second wavelength different from the light of the first wavelength;
a transmitted light receiving unit that receives the transmitted light of the light of the first wavelength that is irradiated to the reaction container and that passes through the mixed liquid in the reaction container;
a scattered light receiving unit that receives the scattered light of the light of the second wavelength that is irradiated to the reaction vessel and scattered by the mixed liquid in the reaction vessel ;
a photometry control unit that acquires characteristics of a reagent and selects the first and second wavelengths of the light emitted by the light irradiation unit based on the acquired characteristics;
an analysis unit that analyzes the intensity change of the scattered light received by the scattered light receiving unit or the intensity change of the transmitted light received by the transmitted light receiving unit based on the acquired characteristics;
A blood coagulation analyzer comprising: 2. When the reagent is a fibrinogen reagent or a reagent that exhibits a weaker blood coagulation reaction than the fibrinogen reagent, the analysis unit analyzes the intensity change of the scattered light received by the scattered light receiving unit. A blood coagulation analyzer as described. 2. The blood coagulation analyzer according to claim 1 , wherein said analysis unit analyzes the intensity change of the transmitted light received by said transmitted light receiving unit when said reagent is a reagent having a stronger and faster blood coagulation reaction than a fibrinogen reagent. 4. The blood coagulation analysis according to claim 1 or 3 , wherein the analysis unit analyzes the intensity change of the scattered light received by the scattered light receiving unit after analyzing the intensity change of the transmitted light received by the transmitted light receiving unit. Device. After the intensity change of the scattered light received by the scattered light receiving section is analyzed, the intensity change of the scattered light received by the scattered light receiving section and the intensity change of the transmitted light received by the transmitted light receiving section are analyzed. 5. The blood coagulation analyzer according to claim 1 , comprising a composite analysis unit that A blood coagulation analyzer for measuring blood coagulation by mixing a blood sample with a reagent corresponding to a test item,
a light irradiation unit that irradiates a reaction container containing a mixed liquid in which a blood sample and a reagent are mixed with light of a first wavelength and light of a second wavelength different from the light of the first wavelength;
a transmitted light receiving unit that receives the transmitted light of the light of the first wavelength that is irradiated to the reaction container and that passes through the mixed liquid in the reaction container;
a scattered light receiving unit that receives the scattered light of the light of the second wavelength that is irradiated to the reaction vessel and scattered by the mixed liquid in the reaction vessel ;
a composite analysis unit that analyzes changes in the intensity of the scattered light received by the scattered light receiving unit and changes in the intensity of the transmitted light received by the transmitted light receiving unit;
a photometry control unit that acquires characteristics of a reagent and selects the first and second wavelengths of the light emitted by the light irradiation unit based on the acquired characteristics;
with
The blood coagulation analyzer , wherein the composite analysis unit analyzes the intensity change of the scattered light and the intensity change of the transmitted light based on the acquired characteristics . When the reagent is a fibrinogen reagent or a reagent having a weaker blood coagulation reaction than the fibrinogen reagent and a gentler blood coagulation reaction than the fibrinogen reagent, the combined analysis unit analyzes the intensity change of the scattered light and the intensity change of the transmitted light. 7. A blood coagulation analyzer according to item 6 . The composite analysis unit vertically inverts one of the intensity change of the transmitted light and the intensity change of the scattered light about half the maximum value of the intensity of the transmitted light, and converts the intensity change into the inverted intensity change. 8. The blood coagulation analyzer according to any one of claims 5 to 7 , wherein an intermediate line between one intensity change and another intensity change that is not upside down is analyzed. 9. The blood coagulation analyzer according to claim 1 , wherein said second wavelength is shorter than said first wavelength. The first wavelength is included in the red wavelength range,
10. The blood coagulation analyzer according to any one of claims 1 to 9 , wherein said second wavelength is included in a wavelength range from violet to blue.

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