JP6657016B2 - Automatic analyzer - Google Patents

Description

  The present disclosure relates to an automatic analyzer, for example, to an automatic analyzer that quantifies the concentration of a substance to be measured contained in a sample (sample) such as blood or urine.

  Measure the amount of attenuation of the transmitted light that is applied to the reaction mixture obtained by mixing the reagent and the sample, such as blood and urine, as the absorbance, and determine the concentration of the analyte in the sample from the change in the absorbance according to Lambert-Beer's law. Automatic analyzers for quantification are widely used. Automated analyzers include a colorimetric method that determines the concentration of the analyte from the absorbance change due to the color reaction between the enzyme and the substrate, and an immunoassay that determines the concentration of the analyte from the change in the absorbance caused by the agglutination reaction between the antigen and antibody. Turbidimetry exists. Among the immunoturbidimetric methods, there is a latex immunoturbidimetric method in which a change in absorbance is increased by aggregating latex particles sensitized with an antibody that immunologically reacts with a substance to be measured in a sample. Of these three analytical methods, the latex immunoturbidimetric method is suitable for detecting a lower concentration of the substance to be measured, and further improvement in the sensitivity of this analytical method is desired.

  Efforts to achieve high sensitivity in latex immunoturbidimetry include improving reagents to be mixed with a sample and improving equipment. As an improvement of the apparatus, in recent years, a technical development has been made on high sensitivity by measuring scattered light from latex particles.

  For example, Patent Document 1 discloses an apparatus configuration for performing scattered light measurement on an automatic analyzer. In Patent Document 1, an absorption photometer and a scatter photometer are used in combination, and an attempt is made to increase the sensitivity to various types of latex reagents by providing scattered light receivers at a plurality of angles. There is an advantage that a reagent prepared for measuring absorbance can be measured with high sensitivity to scattered light. Patent Literature 2 discloses a device configuration and a reagent composition proposal for increasing sensitivity by scattered light measurement. Patent Literature 2 also proposes a reagent composition that uses both an absorption photometer and a light scattering photometer on an automatic analyzer and can measure scattered light with high sensitivity.

Japanese Patent No. 5318206 JP 2013-64705 A

  In an automatic analyzer, absorbance measurement is mainly performed using an absorptiometer, and a reagent to be mixed with a specimen (sample) is prepared for absorbance measurement. When a latex agglutination reaction using this reagent is measured by scattered light using a light scattering photometer, the dynamic range (quantitable range) becomes narrower, although the sensitivity is higher than that of the absorbance measurement. For this reason, it is desirable to adopt a device configuration that uses both an absorption photometer and a scatter photometer as in Patent Documents 1 and 2. At this time, in the absorbance measurement, it is necessary to increase the optical path length in order to measure the amount of light attenuation as the absorbance, while in the scattered light measurement, it is desirable to measure with a short optical path length in order to suppress the absorption of the scattered light. .

  However, in the automatic analyzer configurations disclosed in Patent Documents 1 and 2, the optical path length for measuring the absorbance and the optical path length for measuring the scattered light are the same, and the optical path length is optimized for the scattered light measurement. Not. Therefore, the sensitivity of the scattered light measurement is not sufficient, and it is necessary to further increase the sensitivity.

  The present disclosure has been made in view of such a situation, and proposes a configuration of an automatic analyzer that can measure scattered light with higher sensitivity.

  In order to solve the above problems, an automatic analyzer according to the present disclosure has a first optical path and a second optical path, and contains at least one reaction solution generated by mixing a sample and a reagent. A cell, an absorbance measurement unit that irradiates light for measuring absorbance along the first optical path of the cell, and measures light transmitted through a reaction solution contained in the cell, and transmits light for measuring scattered light to the cell. A scattered light measurement unit that irradiates along the second optical path and measures scattered light after the sample and the reagent interact with each other in the reaction solution contained in the cell. Here, the optical path length of the first optical path is set longer than the optical path length of the second optical path.

  Further features related to the present disclosure will be apparent from the description of the present specification and the accompanying drawings. Further, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements, the following detailed description, and the appended claims.

  According to the automatic analyzer of the present disclosure, scattered light can be measured with higher sensitivity.

It is a figure showing the example of composition of the light scattering photometer for explaining the principle of measuring the amount of scattered light. FIG. 4 is a diagram illustrating a relationship between an initial transmittance of a reaction solution 7 and a scattered light change amount. 1 is a diagram illustrating an overall schematic configuration example of an automatic analyzer 100 according to a first embodiment of the present disclosure. FIG. 2 is a top view of the reaction disk 9 of the automatic analyzer 100 according to the first embodiment. FIG. 5 is a top view of a quadrangular prism-shaped cell 8 whose bottom is a parallelogram. 1 is a diagram illustrating a schematic configuration example of an absorbance measurement unit 13 used in an embodiment of the present disclosure. 1 is a diagram illustrating a schematic configuration example of a scattered light measurement unit 16 according to an embodiment of the present disclosure. It is a top view of reaction disk 9 of the automatic analyzer by a 2nd embodiment of this indication.

  The present disclosure proposes a technique for improving the detection sensitivity of scattered light measurement of a mixed solution (reaction liquid) of a sample and a reagent. More specifically, in the automatic analyzer according to the present disclosure, the absorbance measurement increases the optical path length and the measurement is performed with the same sensitivity as before, while changing the composition of the reagent prepared for the absorbance measurement. The scattered light is measured with high sensitivity under the optical conditions suitable for the scattered light measurement (the scattered light is measured using an optical path having a shorter optical path length than the optical path length of the absorbance measurement). In the present disclosure, the absorbance measurement and the scattered light measurement are performed by the same automatic analyzer.

  Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. In the accompanying drawings, functionally the same elements may be represented by the same numbers. The attached drawings show specific embodiments and implementation examples in accordance with the principles of the present disclosure, but these are for understanding of the present disclosure, and are not intended to limit the present invention in any way. Not used.

  Although the present embodiment has been described in sufficient detail for those skilled in the art to implement the present disclosure, other implementations and forms are also possible without departing from the scope and spirit of the technical idea of the present disclosure. It is necessary to understand that the configuration / structure can be changed and various elements can be replaced. Therefore, the following description should not be construed as being limited thereto.

(1) First Embodiment <Principle of Scattered Light Measurement in the Present Disclosure>
FIG. 1 is a diagram showing a configuration example of a light scatter photometer for explaining the principle of measuring the amount of scattered light.

  The light scattering photometer includes a light source 17 for measuring scattered light that emits light 18, a transmitted light receiver 20 that receives light (transmitted light) 19 transmitted through the cell 8, and a scattered light that receives scattered light 21 from the cell 8. And a light receiver 22.

  Light 18 from the scattered light measurement light source 17 is applied to the reaction solution 7 in the cell 8 whose temperature is controlled by the constant temperature fluid 15 held in the fluid container. Then, the transmitted light 19 is received by the transmitted light receiver 20 and the scattered light 21 is received by the scattered light receiver 22.

  FIG. 2 is a diagram showing the relationship between the initial transmittance of the reaction solution 7 and the amount of change in scattered light. For example, here, sample 1 and reagent 4 containing C-reactive protein (CRP: C reactive protein) at a concentration of 0.01 mg / dL (the first reagent and the latex reagent (second 2 shows the relationship between the amount of change in scattered light in the 20 ° direction generated in the latex agglutination reaction of the reaction solution 7 produced by mixing the two reagents) and the initial transmittance of the reaction solution 7. The scattered light is measured based on the principle of measuring the amount of scattered light shown in FIG.

  When acquiring the “relationship between the initial transmittance of the reaction solution and the amount of scattered light change” shown in FIG. 2, the change in scattered light due to the latex agglutination reaction was measured for 5 minutes, and 300 seconds and 18 seconds after the start of measurement. Is calculated as a scattered light change amount. The higher the analyte concentration, the larger the size of the aggregate, and the greater the amount of light scattered at a certain angle. Therefore, the concentration of the specimen can be quantified from the amount of light measured as the reaction process data.

A cell having an optical path length of 5 mm is used as the cell 8 in which the reaction solution 7 is to be placed. However, in this specification, the transmittance and the absorbance of the solution are all converted into the transmittance and the absorbance when measured at an optical path length of 10 mm. For example, if the transmittance of a certain solution is 10% (absorbance 1 abs) in a cell having an optical path length of 5 mm, the transmittance of this solution is converted to that measured at an optical path length of 10 mm, and is therefore 20% (absorbance 2 abs). Notation. The transmittance T is represented by the following equation, where A is the absorbance, and Ls is the optical path length in the reaction solution up to the scattered light receiver 22.

  As the latex particles to be contained in the latex reagent, particles having diameters of 200 nm, 350 nm, and 500 nm are used. From FIG. 2, it can be seen that, for any latex reagent of any particle size, the amount of change in scattered light is maximized when the initial transmittance of the reaction mixture obtained by mixing the sample and the latex reagent immediately before the reaction starts is around 35%, and the initial transmittance is 15%. It can be seen that the scattered light change amount does not change significantly (the change in the scattered light change amount is small) in the range of ~ 53%. In addition, the results of FIG. 2 show that when the latex agglutination reaction was measured by scattered light under the condition that the initial transmittance of the reaction mixture obtained by mixing the sample and the latex reagent immediately before the start of the reaction was 15 to 53%, the amount of change in scattered light was larger. It is possible to obtain a large value, which indicates that high sensitivity measurement can be obtained.

  The present disclosure is based on the results of the experiment, and performs scattered light measurement in a situation where the initial transmittance of the reaction solution is 15 to 53%, in addition to the absorbance measurement, which is a conventional method, and more sensitive scattered light measurement. Can also be realized. Since the turbidity of the latex reagent varies depending on the purpose (test item), the optical path length for scattered light measurement is adjusted so that the initial transmittance falls within the range of 15 to 53%. (That is, the length of the short side of the cell 8 is shortened). As described above, when the scattered light measurement is performed, it is more sensitive to set the initial transmittance of the reaction solution (sample + first reagent + second reagent (latex reagent)) in the range of 15 to 53%. It is necessary to make measurements. However, if the optical path length for measuring the scattered light is set shorter than the optical path length for measuring the absorbance, the scattered light can be measured with higher sensitivity as compared with the related art (Patent Documents 1 and 2). is there. Hereinafter, a specific configuration and operation of the automatic analyzer will be described.

<Configuration of automatic analyzer>
FIG. 3 is a diagram illustrating an example of the overall schematic configuration of the automatic analyzer 100 according to the present disclosure. The automatic analyzer 100 irradiates different surfaces of one cell with light from a light source for measuring absorbance and light from a light source for measuring scattered light, respectively, and uses different optical paths for latex agglutination reaction in a reaction solution in the cell. It measures absorbance and scattered light along a long optical path.

  The automatic analyzer 100 includes, for example, three types of disks, a sample disk 3, a reagent disk 6, and a reaction disk 9, a sample dispensing mechanism 10 for moving the sample 1 between these disks, and a reagent between these disks. Reagent dispensing mechanism 11 for moving sample 4, stirrer 12 for stirring and mixing sample 1 and reagent 4 in cell 8, which is a storage container for reaction solution 7, washing unit 14 for washing cell 8, and each disk And a control circuit 23 for controlling the operation of each dispensing mechanism, an absorbance measuring unit 13 for receiving the transmitted light of the reaction solution 7, and information on the amount of transmitted light received by the absorbance measuring unit 13 to perform the absorbance measurement. An absorbance measurement circuit 24 that outputs the reaction process data, a scattered light measurement unit 16 that receives the scattered light from the reaction solution 7, and a light amount of the scattered light received by the scattered light measurement unit 16. And a data processing unit 26 such as a PC (computer) for processing data measured by each measurement circuit, and a data processing unit 26. It has an input unit 27 as an interface and an output unit 28. Note that the data processing unit 26 includes a data storage unit 2601 and an analysis unit 2602. The data storage unit 2601 stores control data, measurement data, data used for analysis, analysis result data, and the like. The analysis unit 2602 calculates, for example, a change in the amount of light within a predetermined time specified by the operator as a calculation value. The input unit 27 and the output unit 28 input and output data to and from the data storage unit 2601. In the example of FIG. 3, the input unit 27 is a keyboard, but may be a touch panel, a numeric keypad, or another input device.

  On the circumference of the sample disk 3, a plurality of sample cups 2, which are storage containers for the sample 1, are arranged. A plurality of reagent bottles 5 containing the reagents 4 are arranged on the circumference of the reagent disk 6. On the circumference of the reaction disk 9, a plurality of cells 8, which are containers for accommodating the reaction liquid 7 in which the sample 1 and the reagent 4 are mixed, are arranged.

  The sample dispensing mechanism 10 is a mechanism used when dispensing a fixed amount of the sample 1 from the sample cup 2 to the cell 8. The sample dispensing mechanism 10 can be configured by, for example, a nozzle that discharges or sucks a solution, a robot that positions and transports the nozzle at a predetermined position, and a pump that discharges or sucks the solution from the nozzle. The reagent dispensing mechanism 11 is a mechanism used when dispensing a certain amount of the reagent 4 from the reagent bottle 5 to the cell 8. The reagent dispensing mechanism 11 can also be configured by, for example, a nozzle that discharges or sucks the solution, a robot that positions and transports the nozzle at a predetermined position, and a pump that discharges or sucks the solution from the nozzle.

  The stirring section 12 stirs and mixes the sample 1 and the reagent 4 in the cell 8. The washing unit 14 is a mechanism for washing the cell 8 by discharging the reaction solution 7 from the cell 8 on which the analysis has been completed. The next sample 1 is dispensed again from the sample dispensing mechanism 10 into the washed cell 8, and a new reagent 4 is dispensed from the reagent dispensing mechanism 11 and used for another reaction. The cell 8 is immersed in a thermostatic fluid 15 in a thermostat in which the temperature and the flow rate are controlled, and the temperature of the cell 8 and the reaction liquid 7 therein is kept constant even during the movement by the reaction disk 9. In the case of this embodiment, water is used as the constant temperature fluid 15, and the temperature of the constant temperature fluid is controlled to 37 ± 0.1 ° C. by the control circuit. Although water is used as the constant temperature fluid 15 here, another medium may be used as the constant temperature fluid 15. Further, the temperature control temperature is merely an example, and can be changed as appropriate.

<Arrangement relationship between cell, absorbance measurement unit, and scattered light measurement unit>
FIG. 4 is a top view of the reaction disk 9 of the automatic analyzer 100 according to the first embodiment. The cell 8 has, for example, a rectangular parallelepiped shape, and has a long side surface and a short side surface. Assuming that an optical path through which light enters from the short side surface of the cell 8 passes is a first optical path, and an optical path through which light enters from the long side surface of the cell 8 passes is a second optical path. The optical path length of the first optical path is longer than the optical path length of the second optical path. When the cell 8 has a rectangular parallelepiped shape, the first optical path and the second optical path are orthogonal to each other. Then, the absorbance is measured along the first optical path, and the scattered light is measured along the second optical path. For example, when the shape of the cell 8 is a rectangular parallelepiped, by setting the short side wall surface to the transmitted light irradiation surface 34 and the long side wall surface to the scattered light irradiation surface 35, the absorbance and the scattered light measurement can be performed at different optical path lengths. Can be implemented. That is, the optical path length when measuring the scattered light is shorter than the optical path length when measuring the absorbance, and this relationship does not change.

  As an example, the cell 8 passes through the center point of the cell 8 parallel to the transmitted light irradiation surface 34 with respect to a straight line 33 connecting the center point of the cell 8 and the center point of the reaction disk 9 when the cell 8 is viewed from the upper surface side. The line 36 can be arranged in a state where the line 36 is inclined by about 45 ° counterclockwise, and the line 37 passing through the center point of the cell 8 parallel to the scattered light irradiation surface 35 is inclined by about 45 ° clockwise. An absorbance measuring unit 13 and a scattered light measuring unit 16 are arranged on a part of the circumference of the reaction disk 9. As the reaction disk 9 rotates, the cell 8 containing the reaction solution 7 passes through the measurement position where the absorbance measurement unit 13 is arranged and the measurement position where the scattered light measurement unit 16 is arranged. Each time the cell 8 passes through each measurement position while the reaction disk 9 is rotating, the transmitted light and the scattered light from the reaction solution 7 are measured via the corresponding absorbance measurement unit 13 and scattered light measurement unit 16, respectively. The optical axes of the transmitted light and the scattered light are an optical axis 38 and an optical axis 39, respectively. When the cell 8 is arranged, a line 36 passing through the center point of the cell 8 parallel to the transmitted light irradiation surface 34 is approximately 45 ° with respect to a straight line 33 connecting the center point of the cell 8 and the center point of the reaction disk 9. Alternatively, the arrangement may be such that the line 37 passing through the center point of the cell 8 parallel to the scattered light irradiation surface 35 is inclined at an angle of about 45 ° counterclockwise. At this time, the absorbance arranged on the circumference of the reaction disk 9 The positions of the measurement unit 13 and the scattered light measurement unit 16 are also replaced. With such an arrangement relationship between the cells 8, the absorbance measurement unit 13, and the scattered light measurement unit 16, as many cells 8 as possible can be arranged on the circumference of the reaction disk 9, and at the same time, absorbance measurement and scattering are performed. Both of the optical measurement can be performed by one automatic analyzer 100. If the number of cells 8 arranged on the reaction disk 9 is reduced, it is not necessary to arrange the cells 8 at an angle of 45 ° as described above. If light can be irradiated to different surfaces of the cell 8 in the absorbance measurement unit 13 and the scattered light measurement unit 16, the angle of the line 36 with respect to the straight line 33 and the angle of the line 37 with respect to the straight line 33 can be set arbitrarily.

  For example, when a rectangular parallelepiped is adopted as the shape of the cell 8, the length of the wall surface (optical path length) on the long side and the short side can be, for example, 5 mm on the long side and 3 mm on the short side. For example, when scattered light is measured with an optical path length of 3 mm, the reaction solution in which the sample, the first reagent, and the second reagent (latex reagent) are mixed has an initial absorbance of 0.92 to 2.75 abs immediately before the start of the reaction. Has an initial transmittance of 15 to 53%, which falls within the range of 15 to 53% at which the above-described high sensitivity measurement is possible.

  The size of the latex particles contained in the latex reagent (second reagent) is preferably 100 to 700 nm in diameter, and the initial permeation of the reaction solution 7 in which the sample 1, the first reagent, and the second reagent (latex reagent) are mixed. What is necessary is just to measure the scattered light with an optical path length in which the ratio is in the range of 15 to 53%.

  The shape of the cell 8 is not limited to a rectangular parallelepiped. For example, it is also possible to adopt a quadrangular prism shape having a parallelogram bottom. In this case, since the light from the light source needs to be perpendicularly incident on each of the long side wall surface and the short side wall surface (in order to prevent refraction of light), the first optical path and the second optical path The two optical paths are not orthogonal (see FIG. 5: FIG. 5 is a top view of a quadrangular prism-shaped cell 8 whose bottom surface is a parallelogram). Also in this case, the optical path length of the first optical path may be 4 mm or more and 10 mm or less, and the optical path length of the second optical path may be 1 mm or more and less than 4 mm. Sample 1, the first reagent, and the second reagent (latex reagent) The scattered light measurement may be performed at an optical path length such that the initial transmittance of the reaction solution 7 in which is mixed with the above immediately before the start of the reaction is in the range of 15 to 53%.

<Configuration of absorbance measurement section>
FIG. 6 is a diagram illustrating a schematic configuration example of the absorbance measurement unit 13 used in the embodiment of the present disclosure. The absorbance measurement unit 13 includes, for example, a halogen lamp light source 29, a diffraction grating 31, and a light receiver (photodiode array) 32.

  While the reaction disk 9 is rotating, the cell 8 is irradiated with light emitted from the halogen lamp light source 29. The light 30 transmitted through the reaction solution in the cell 8 is split by the diffraction grating 31. Since the halogen lamp light source 29 is, for example, white light, it is split by the diffraction grating 31 into light of each wavelength. The photodiode array 32 receives the transmitted light split by the diffraction grating 31.

  The wavelengths received by the photodiode array 32 are, for example, 340 nm, 405 nm, 450 nm, 480 nm, 505 nm, 546 nm, 570 nm, 600 nm, 660 nm, 700 nm, 750 nm, and 800 nm. The transmitted light amount data incident on these light receivers is sent to the absorbance measurement circuit 24. The absorbance measurement circuit 24 acquires a light receiving signal of each wavelength range at regular time intervals, and stores the acquired light amount value in the data storage unit 2601 in the data processing unit 26. In this case, measurement data corresponding to all wavelengths is obtained and stored in the data storage 2601. Since necessary data differs depending on the reagents and test items used (different measurement data at which wavelengths), only necessary data is acquired from the data storage unit 2601 at the time of analysis or output.

<Configuration of scattered light measurement unit>
FIG. 7 is a diagram illustrating a schematic configuration example of the scattered light measurement unit 16 according to the embodiment of the present disclosure. The scattered light measuring unit 16 includes, for example, a light source 17, a transmitted light receiver 20, a scattered light receiver 22a, and a scattered light receiver 22b.

  As the light source 17, for example, an LED light source unit can be used. The irradiation light 18 emitted from the light source 17 is applied to the cell 8 located on the optical path, and the transmitted light 19 transmitted through the reaction solution in the cell 8 is received by the transmitted light receiver 20. For example, 700 nm is used as the wavelength of the irradiation light. In the scattered light measurement, it is preferable to use irradiation light having a wavelength of 600 to 800 nm in consideration of being less susceptible to scatterers (milk, hemolysis, jaundice) contained in the sample and being visible light. In this embodiment, an LED is used as the light source 17, but a laser light source, a xenon lamp, a halogen lamp, or the like may be used.

  The scattered light receiver 22a receives the scattered light 21a in a direction away from the optical axis of the irradiation light 18 or the transmitted light 19 by 20 degrees in the air. Further, the scattered light receiver 22b receives the scattered light 21b in a direction away from the optical axis of the irradiation light 18 or the transmitted light 19 by an angle of 30 ° in the air. The light receiving angles of the scattered light receivers 22a and 22b are respectively 20 ° and 30 °, and specifically have a certain width such as 17.5 to 22.5 ° and 27.5 to 32.5 °, respectively. ing. In the present embodiment, since latex particles are aggregated, aggregates of latex particles grow randomly in the reaction solution 7. When the latex particles have a particle diameter of 200 nm to 500 nm and are subjected to scattered light measurement of the latex agglutination reaction when reacted with the sample containing CRP, the relationship between the size of the agglomerates and the scattering angle is determined. It is important to employ scattered light of 20 ° to 30 ° (more precisely, 17.5 ° to 32.5 °).

  The scattered light receivers 22a and 22b are arranged in a plane substantially perpendicular to the direction of movement of the cell 8 due to the rotation of the reaction disk 9. Here, the reference position of the light receiving angle (the starting point of scattering) is set at the center of the optical path of the light passing through the cell 8. The scattered light receivers 22a and 22b can be composed of, for example, photodiodes. The light reception signals of the scattered light receivers 22a and 22b are transmitted to the data storage 2601 of the data processor 26 through the scattered light measurement circuit 25.

  The scattered light measurement circuit 25 obtains two light reception signals having different light reception angles at regular intervals, and outputs the obtained light amount value to the data processing unit 26. In FIG. 7, the case where the scattered light receivers 22a and 22b are arranged so as to correspond to the light receiving angles of 20 ° and 30 °, respectively, is described. A configuration in which scattered light of an angle is received at a time may be employed. By using a linear array, it is possible to widen the options of the light receiving angle. Also, an optical system such as an optical fiber or a lens may be arranged near the cell 8 instead of the light receiver, and the light may be guided to a scattered light receiver arranged at another position.

<Measurement / analysis procedure>
The concentration of the substance to be measured contained in the sample 1 is determined by the following procedure (sequence).
(I) Sequence 1
The control circuit 23 cleans the cell 8 in the cleaning unit 14.

(Ii) Sequence 2
The control circuit 23 dispenses a fixed amount of the sample 1 in the sample cup 2 to the cell 8 by the sample dispensing mechanism 10.

(Iii) Sequence 3
The control circuit 23 dispenses a certain amount of the reagent 4 (first reagent) in the reagent bottle 5 to the cell 8 by the reagent dispensing mechanism 11. At the time of dispensing each solution, the control circuit 23 controls the corresponding drive unit to rotate the sample disk 3, the reagent disk 6, and the reaction disk 9 in rotation. At this time, the sample cup 2, the reagent bottle 5, and the cell 8 are positioned at predetermined dispensing positions according to the drive timing of the corresponding dispensing mechanism. That is, the sample disk 3, the reagent disk 6, and the reaction disk 9 repeatedly rotate and stop under the control of the control circuit 23, respectively.

(Iv) Sequence 4
The control circuit 23 controls the stirring unit 12 to stir the sample 1 and the reagent 4 dispensed into the cell 8 to generate the reaction solution 7.

(V) Sequence 5
Due to the rotation of the reaction disk 9, the cell 8 containing the reaction solution 7 passes through the absorbance measurement position where the absorbance measurement unit 13 is arranged and the scattered light measurement position where the scattered light measurement unit 16 is arranged. Each time the cell 8 passes the measurement position during the rotation of the reaction disk, the transmitted light and the scattered light from the reaction solution 7 are measured via the corresponding absorbance measurement unit 13 and scattered light measurement unit 16, respectively.

(Vi) Sequence 6
The measurement data representing the change over time in the amount of light received by the absorbance measurement unit 13 and the scattered light measurement unit 16 is sequentially output to the data storage unit 2601 and accumulated as reaction process data. In the case of the present embodiment, for example, each measurement time is set to about 10 minutes.

  While the reaction process data is being accumulated (typically, after a certain period of time (for example, 5 minutes) after the dispensing of reagent 4 (first reagent)), another type of reagent (Second reagent: a reagent containing latex particles sensitized to an antibody that reacts immunologically with the substance to be measured) is additionally dispensed into the cell 8 by the reagent dispensing mechanism 11, and immediately after dispensing, the latex agglutinates. Reaction starts (dispensing the second reagent after a certain period of time after dispensing the first reagent means that the first reagent removes substances that may be present in the sample and that are not desirable for the agglutination reaction) And so on). After dispensing the second reagent, the stirring unit 12 performs stirring again. The reaction process data is measured for a certain period of time (about 5 minutes) after dispensing the second reagent. As a result, the reaction process data of the latex agglutination reaction obtained at certain time intervals is stored in the data storage unit 2601. After measuring for a certain period of time, for example, about 10 minutes, the inside of the cell 8 is washed by the washing unit 14, and the next inspection item is analyzed.

  The scattered light measurement circuit 25 separately outputs the reaction process data corresponding to the light receiving angle of 20 ° and the reaction process data corresponding to the light receiving angle of 30 °. Further, the absorbance measurement circuit 24 outputs the reaction process data acquired by the absorptiometer. The analysis unit 2602 calculates, as a calculation value, a change in the amount of light within a predetermined time specified through an analysis setting screen (not shown). Here, the certain time used for calculating the calculation value is defined by the operator designating the calculation start point and the calculation end point from the photometry points. The calculation value is calculated as a difference between the light amount at the calculation end point and the light amount at the calculation start point.

  The data storage unit 2601 holds, in addition to the calculated value, calibration curve data indicating the relationship between the calculated value and the measured substance concentration when a known concentration of the measured substance is measured in advance. The analysis unit 2602 quantifies the concentration of the substance to be measured in the sample by comparing the calculated value with the calibration curve data. The determined concentration value is displayed by the output unit 28. Data necessary for control / analysis of each unit is input from the input unit to the data storage unit 2601, and data, results, and alarms of various storage units are output and displayed by the output unit.

(2) Second Embodiment In a second embodiment of the present disclosure, the optical system is configured such that light from the light source 29 for measuring absorbance and light from the light source 17 for measuring scattered light are orthogonal to each other. . In the optical system, when the cell 8 on the reaction disk 9 comes to the photometric position, different surfaces of one cell 8 are irradiated with light for measuring absorbance and light for measuring scattered light, respectively. The absorbance and scattered light are measured at the same timing for the latex agglutination reaction in the liquid. Hereinafter, a second embodiment will be described.

<Configuration of automatic analyzer>
The basic device configuration is the same as in the first embodiment. However, in the second embodiment, the arrangement of the absorbance measurement unit 13 and the scattered light measurement unit 16 on the circumference of the reaction disk 9 is different from that of the first embodiment. FIG. 8 is a top view of the reaction disk 9 of the automatic analyzer according to the second embodiment of the present disclosure.

(I) Configuration of Cell Also in the second embodiment, the cell 8 has a first optical path and a second optical path having different lengths. The optical path length of the first optical path is longer than the optical path length of the second optical path. Then, when the cell 8 is at a certain position (photometric position), the absorbance measuring unit is configured to measure the scattered light along the second optical path at the same timing as measuring the absorbance along the first optical path. 13 and a scattered light measuring unit 16 are arranged. For example, the shape of the cell 8 is a rectangular parallelepiped, and the wall surface on the short side is a transmitted light irradiation surface 34 and the wall surface on the long side is a scattered light irradiation surface 35. That is, the optical path length when measuring the scattered light is shorter than the optical path length when measuring the absorbance, and this relationship does not change. When the cell 8 is a rectangular parallelepiped, the first optical path is orthogonal to the second optical path. Note that, as described in the first embodiment, the cell 8 may be configured to have a shape other than a rectangular parallelepiped. For example, similarly to the above, the cell 8 may be a quadrangular prism whose bottom surface is a parallelogram. Even in this case, the length of the optical path at the time of measuring the scattered light needs to be shorter than the length of the optical path at the time of measuring the absorbance, but these optical paths are not orthogonal (see FIG. 5).

(Ii) Cell Arrangement Example In the cell 8, a line 36 passing through the center point of the cell 8 parallel to the transmitted light irradiation surface 34 is counterclockwise with respect to a straight line 33 connecting the center point of the cell 8 and the center point of the reaction disk 9. A line 37 passing around the central point of the cell 8 parallel to the scattered light irradiation surface 35 by about 45 ° is inclined clockwise by about 45 °. Each time the cell 8 passes the measurement position while the reaction disk 9 is rotating, the transmitted light and the scattered light from the reaction solution 7 are simultaneously measured via the corresponding absorbance measurement unit 13 and scattered light measurement unit 16, respectively. The optical axes of the transmitted light and the scattered light are an optical axis 38 and an optical axis 39, respectively. With this configuration, it is possible to acquire absorbance data and scattered light data measured at the same timing. If data can be acquired at the same timing, if an abnormal value is found in the reaction process data of the absorbance measurement or scattered light measurement, it is possible to collate each data of the measurement timing that resulted in the abnormal value, This is effective for identifying the cause of the value. When the cell 8 is arranged, a line 36 passing through the center point of the cell 8 parallel to the transmitted light irradiation surface 34 is approximately 45 ° with respect to a straight line 33 connecting the center point of the cell 8 and the center point of the reaction disk 9. Alternatively, the arrangement may be such that the line 37 passing through the center point of the cell 8 parallel to the scattered light irradiation surface 35 is inclined at an angle of about 45 ° counterclockwise. At this time, the absorbance arranged on the circumference of the reaction disk 9 The positions of the measurement unit 13 and the scattered light measurement unit 16 are also replaced.

  If the number of cells 8 arranged on the reaction disk 9 is reduced, it is not necessary to arrange the cells 8 at an angle of 45 ° as described above. If light can be irradiated to different surfaces of the cell 8 in the absorbance measurement unit 13 and the scattered light measurement unit 16, the angle of the line 36 with respect to the straight line 33 and the angle of the line 37 with respect to the straight line 33 can be set arbitrarily.

(Iii) Specific Example Consider a case where the cell 8 is a rectangular parallelepiped, and the length of the wall surface (optical path length) on the long side and the short side is, for example, 5 mm on the long side and 3 mm on the short side. For example, when scattered light is measured with an optical path length of 3 mm, a reaction in which the initial absorbance immediately before the start of the reaction of the reaction mixture in which the sample, the first reagent, and the second reagent (latex reagent) are mixed is 0.92 to 2.75 abs. The initial transmittance of the liquid is 15 to 53%, which is within the range of 15 to 53% at which high sensitivity measurement is possible. The size of the latex particles contained in the latex reagent is not particularly specified, and the initial transmittance of the reaction mixture obtained by mixing the sample, the first reagent, and the second reagent (latex reagent) is in the range of 15 to 53%. What is necessary is just to measure the scattered light with the optical path length as follows. The shape of the cell 8 is not limited to a rectangular parallelepiped, and it is sufficient that the cell 8 has a first optical path and a second optical path having different lengths. At this time, the optical path length of the first optical path may be 4 mm or more and 10 mm or less, and the optical path length of the second optical path may be 1 mm or more and less than 4 mm. Then, the scattered light is measured at an optical path length where the initial transmittance of the reaction liquid 7 in which the sample 1, the first reagent, and the second reagent (latex reagent) are mixed immediately before the start of the reaction is in the range of 15 to 53%. Just do it. When the shape of the cell 8 is a rectangular parallelepiped, it is desirable that the first optical path and the second optical path are orthogonal to each other.

(3) Modifications The features of the present disclosure are not limited to the above embodiments, and include various modifications. For example, the above-described embodiments have been described in detail for easy understanding of the present disclosure, and are not necessarily limited to those having all the configurations described above. In addition, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of one embodiment can be added to the configuration of another embodiment. Further, for a part of the configuration of each embodiment, it is possible to add, delete, or replace another configuration.

(I) In the above-described embodiment, the light source for measuring the absorbance and the light source for measuring the scattered light are prepared. However, only one light source (for example, a white halogen lamp) is installed, and the light emitted from the light source is provided. The light for measuring the absorbance and the light for measuring the scattered light may be generated by spectral separation and used for each measurement.

(Ii) In the above-described embodiment, a configuration is adopted in which the first reagent and the second reagent are dispensed with one reagent disk, but the reagent disk for the first reagent and the reagent disk for the second reagent are used. You may prepare each.

(4) Conclusion In the embodiment of the present disclosure, transmitted light and scattered light are measured by irradiating light for measuring absorbance and light for measuring scattered light from different sides of the cell containing the reaction solution. By irradiating light from different sides, the optical path (first optical path) for transmitted light measurement and the optical path (second optical path) for scattered light measurement can be made different. At this time, the optical path length of the first optical path is longer than the optical path length of the second optical path. In this way, the absorbance measurement can achieve the same sensitivity as the conventional measurement, and the reagent prepared for the absorbance measurement can be applied to the scattered light measurement without changing the composition, and the higher sensitivity can be obtained. It becomes possible to measure scattered light with high sensitivity.

  A rectangular parallelepiped can be adopted as the cell shape. In this case, the first optical path and the second optical path are orthogonal. However, the cell shape is not limited to a rectangular parallelepiped, and may be, for example, a quadrangular prism whose bottom surface is a parallelogram. In this case, the first light path and the second light path are not orthogonal to each other because the light from the light source needs to be irradiated perpendicularly to the surface of the cell.

  In the first embodiment, the absorbance and the scattered light of the reaction solution in one cell are measured at different timings. That is, the absorbance measurement unit and the scattered light measurement unit are arranged at different positions. This makes it easy to secure a space for installing the absorbance measurement unit and the scattered light measurement unit (there is little restriction on installation). On the other hand, in the second embodiment, the absorbance and the scattered light of the reaction solution in one cell are measured simultaneously. That is, the absorbance measurement unit and the scattered light measurement unit are arranged at positions where the light for the absorbance measurement and the light for the scattered light measurement intersect the cell at the same position. In this way, absorbance and scattered light are measured at the same time, so if an abnormal value is found in the reaction process data of absorbance measurement or scattered light measurement, it is possible to collate each data of the measurement timing that became the abnormal value Thus, the cause of the abnormal value can be specified effectively.

  Further, the transmitted light irradiation surface of the cell is inclined about 45 ° clockwise with respect to a straight line connecting the center point of the cell and the center point of the reaction disk, and the scattered light irradiation surface of the cell is about 45 ° counterclockwise. The cells may be arranged in an inclined state. In addition, the scattered light irradiation surface of the cell is inclined approximately 45 ° clockwise with respect to a straight line connecting the center point of the cell and the center point of the reaction disk, and the transmitted light irradiation surface of the cell is approximately 45 ° counterclockwise. The cells may be arranged in an inclined state. By doing so, more cells can be placed on the reaction disk, and the sample can be efficiently analyzed.

  In addition, specifically, it is preferable that the optical path length of the first optical path is 4 mm or more and 10 mm or less, the optical path length of the second optical path is 1 mm or more and less than 4 mm, and the initial transmittance of the reaction solution is 15 to 53%. . This makes it possible to measure scattered light with higher sensitivity. Further, the optical path length in the scattered light measurement is more preferably such that the transmittance of the reaction solution immediately before the reaction is in the range of 20 to 48%, and the transmittance of the reaction solution immediately before the reaction is in the range of 25 to 43%. Is more preferable.

1 sample, 2 sample cups, 3 sample discs, 4 reagents, 5 reagent bottles, 6 reagent discs, 7 reaction liquids, 8 cells, 9 reaction discs, 10 sample dispensing mechanism, 11 reagent dispensing mechanism, 12 stirring section, 13 Absorbance measuring unit, 14 washing unit, 15 constant temperature fluid, 16 scattered light measuring unit, 17 light source, 18 irradiation light, 19 transmitted light, 20 transmitted light receiver, 21, 21a, 21b scattered light, 22, 22a, 22b scattered light Light receiver, 27 input part, 28 output part, 29 light source, 30 transmitted light, 31 diffraction grating, 32 light receiver, 33 straight line connecting the center point of the cell and the center point of the reaction disk, 34 transmitted light irradiation surface, 35 scattered light Irradiation surface, 36 Line parallel to transmitted light irradiation surface, 37 Line parallel to scattered light irradiation surface, 38 Optical axis of transmitted light, 39 Optical axis of scattered light, 100 Automatic analyzer

Claims (8)

At least one cell having a first optical path and a second optical path and containing a reaction solution generated by mixing a sample and a reagent,
Light for absorbance measurement is irradiated along the first optical path of the cell, and an absorbance measurement unit that measures light transmitted through the reaction solution contained in the cell,
Scattered light for irradiating light for scattered light measurement along the second optical path of the cell, and measuring scattered light after the sample and the reagent interact in the reaction solution contained in the cell A measuring unit,
A reaction disk for mounting the at least one cell on a circumference;
A control unit for driving the reaction disk to rotate ,
It said first optical path length of the optical path is rather long than the optical path length of said second optical path,
The absorbance measurement unit and the scattered light measurement unit are arranged so that the light for the absorbance measurement and the light for the scattered light measurement intersect on the cell at the same position, and during rotation of the reaction disk. An automatic analyzer that simultaneously measures absorbance and scattered light . In claim 1,
An automatic analyzer, wherein the first optical path is orthogonal to the second optical path. In claim 2,
The cell has a rectangular parallelepiped shape,
The absorbance measurement unit measures the absorbance of the reaction solution using a short-side wall surface at the bottom surface of the cell as a transmitted light irradiation surface,
An automatic analyzer, wherein the scattered light measurement unit measures scattered light from the reaction solution using a wall surface on a long side of a bottom surface of the cell as a scattered light irradiation surface. In claim 1 ,
With respect to a straight line connecting the center point of the cell and the center point of the reaction disk, the transmitted light irradiation surface of the cell is inclined clockwise by about 45 °, and the scattered light irradiation surface of the cell is rotated counterclockwise by 45 °. An automatic analyzer in which the cells are arranged at an angle of about °. In claim 1 ,
The scattered light irradiation surface of the cell is inclined clockwise by about 45 ° with respect to a straight line connecting the center point of the cell and the center point of the reaction disk, and the transmitted light irradiation surface of the cell is rotated counterclockwise by 45 °. An automatic analyzer in which the cells are arranged at an angle of about °. In claim 1,
Under the conditions that the optical path length of the first optical path is 4 mm or more and 10 mm or less, the optical path length of the second optical path is 1 mm or more and less than 4 mm, and the initial transmittance of the reaction solution is 15 to 53%, An automatic analyzer in which the scattered light is measured by irradiating the scattered light measurement light along an optical path. In claim 1,
The cell has a rectangular parallelepiped shape,
The optical path length of the first optical path corresponds to the length of the long side at the bottom of the rectangular parallelepiped,
An automatic analyzer wherein an optical path length of the second optical path corresponds to a length of a short side on a bottom surface of the rectangular parallelepiped. In claim 7 ,
The long side on the bottom surface of the cell is 4 mm or more and 10 mm or less,
An automatic analyzer, wherein a short side of the bottom surface of the cell is 1 mm or more and less than 4 mm.

Images