JP2010175342A - Automatic analyzer and reaction vessel - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an automatic analyzer adapted to wide-ranging analytical work by using the same reaction vessel, and to provide the reaction vessel. <P>SOLUTION: The automatic analyzer which includes the reaction vessel 4 for putting an object to be measured therein, a light source 26 for irradiating the reaction vessel 4 with measurement light from the side, and a spectrophotometer 10 for detecting transmitted light from the reaction vessel 4 and measuring an absorbance change in the object to be measured is characterized in that the reaction vessel 4 is formed so that its optical path length d is continuously varied in accordance with a height S at which the measurement light is transmitted. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an automatic analyzer and a reaction container that perform qualitative and quantitative analysis of biological samples such as serum and urine.

  In the automatic analyzer, the absorbance of the sample in the reaction vessel is measured by irradiating the reaction vessel with the measurement light from the side and detecting the transmitted light of the reaction vessel. Generally, the reaction vessel is made of a light-transmitting material such as glass or plastic. Therefore, the optical path length is set to one value for each reaction vessel. When the optical path length is constant, the number of measurement items exceeding the measurement limit increases depending on the specimen, and the specimen must be re-examined after diluting to a constant concentration.

  On the other hand, as a method of obtaining highly reliable data in one measurement, a reaction vessel is formed in a step shape to secure a plurality of optical paths having different lengths in one reaction vessel, and measurement light is sent to each reaction vessel. A technique has been proposed in which a plurality of different absorbances are obtained by transmitting through a stepped portion (see Patent Document 1, etc.).

JP 2004-101381 A

  However, in the technique described in Patent Document 1, each optical path length is determined at the production stage of the reaction container, and therefore, when there is no step portion having an appropriate optical path length, another reaction having a step portion having an appropriate optical path length. It was necessary to select a container.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an automatic analyzer and a reaction vessel that can cope with a wider range of analysis work in the same reaction vessel.

  In order to achieve the above object, the first invention provides a reaction container for storing an object to be measured, a light source for irradiating the reaction container with measurement light from the side, and a light to be measured by detecting transmitted light from the reaction container. And a photometer for measuring a change in absorbance of the reaction vessel, wherein the reaction vessel is formed such that the optical path length changes continuously according to the height of transmission of the measurement light. To do.

  According to a second invention, in the first invention, at least one of the incident surface and the transmission surface of the measurement light of the reaction vessel is inclined upward or downward in the traveling direction of the measurement light. .

  A third invention is characterized in that, in the second invention, a surface parallel to the measurement light of the reaction vessel is trapezoidal.

  A fourth invention is characterized in that, in the second invention, a plane parallel to the measurement light of the reaction vessel is triangular.

  A fifth invention is characterized in that, in any one of the first to fourth inventions, a display device for displaying a screen capable of selecting an optical path length for each measurement item is provided.

  According to a sixth invention, in any one of the first to fifth inventions, the measurement results obtained by using a standard solution with a known concentration as a measurement object with a plurality of optical path lengths of the reaction vessel are used as a plurality of standards having different concentrations. The liquid is converted into a measurement result obtained with the same optical path length as an object to be measured, and a means for creating a multi-inspection quantity curve from the conversion result is provided.

  According to a seventh invention, in any one of the first to sixth inventions, a plurality of calibration curves are created from measurement results respectively obtained with a plurality of optical path lengths of the reaction vessel using a standard solution having a known concentration as a measurement object. Means are provided.

  According to an eighth invention, in any one of the first to seventh inventions, from a measurement result obtained by using a plurality of standard solutions with known concentrations as a measurement object at a plurality of optical path lengths of the reaction vessel, The measurement result acquired with a long optical path length and the measurement result acquired with a short optical path length in a high concentration region are deleted, and a calibration curve is created from the remaining measurement results.

  A ninth aspect of the invention is a reaction vessel for transmitting measurement light to an object to be received, which is used in an automatic analyzer equipped with a photometer for measuring a change in absorbance of the object to be measured, and transmits the measurement light. The optical path length is formed so as to continuously change depending on the height of the light.

  According to the present invention, a wider range of analysis work can be handled in the same reaction vessel.

It is the vertical sectional view which looked at the example of 1 composition of the reaction container concerning one embodiment of the present invention from the direction orthogonal to the optical axis of measurement light. It is a perspective view showing the appearance composition of the example of 1 composition of the reaction container block which has two or more reaction containers concerning one embodiment of the present invention. It is the schematic showing the whole structure of the automatic analyzer which concerns on one embodiment of this invention. It is an example of the multi-inspection quantity curve created from one type of standard solution with the automatic analyzer which concerns on one embodiment of this invention. It is an example of the several calibration curve created from one type of standard solution with the automatic analyzer which concerns on one embodiment of this invention. It is a related figure for the calibration curve preparation by the automatic analyzer which concerns on one embodiment of this invention.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 3 is a schematic diagram showing the overall configuration of the automatic analyzer according to the present embodiment.

  The automatic analyzer shown in FIG. 3 includes a sample disk mechanism 1, a reagent disk mechanism 5, and a reaction disk 3.

  A number of sample containers 25 are installed in the sample disk mechanism 1. A serum sampling mechanism 2 is arranged beside the sample disk mechanism 1, and a sample in the sample container 25 is sucked by the sample nozzle 27 of the serum sampling mechanism 2, and a predetermined reaction container installed in the reaction disk 3. 4 is injected.

  A large number of reagent containers 6 are installed in the reagent disk mechanism 5. A reagent pipetting mechanism 7 is disposed beside the reagent disk mechanism 5, and the reagent in the reagent container 6 is sucked by the reagent nozzle 28 of the reagent pipetting mechanism 7 and is installed on the reaction disk 3. It is injected into the reaction vessel 4.

  The reaction disk 3 is entirely maintained at a predetermined temperature by a thermostatic chamber 9, and a large number (for example, about 120) of reaction vessels 4 (details will be described later) are placed in an annular shape on the outer periphery thereof. ing. A light source 26 for irradiating measurement light from the side to the reaction container 4 that has come to the opposite position is provided on the inner peripheral side of the reaction disk 3, and the light transmitted through the reaction container 4 is detected on the outer peripheral side to change the absorbance of the object to be measured. The reaction vessel 4 is located between the light source 26 and the spectrophotometer 10. The reaction container 4 also serves as a photometric container. Aside from the reaction disk 3, a stirring mechanism 8 that stirs a mixed solution (measurement object) of the sample and reagent injected into the reaction container 4 with a stirring rod 29, and a reaction container in which the absorbance of the measurement object has been measured. 4 and a cleaning mechanism 11 for cleaning the stirring rod 29 are arranged.

  Reference numeral 19 is a microcomputer, 23 is an interface, 18 is a converter (A / D converter and Log converter), 17 is a reagent pipettor, 16 is a washing water pump, and 15 is a serum pipettor. Reference numeral 20 denotes a printer, 21 denotes a display device (for example, a CRT), 22 denotes a hard disk as a storage device, and 24 denotes an operation panel.

  When operating the automatic analyzer configured as described above, the operator first inputs analysis request information on the operation panel 24. The analysis request information input by the operator is stored in a memory (not shown) in the microcomputer 19. In accordance with the analysis request information stored in the memory of the microcomputer 19, the sample to be measured in the sample container 25 set at a predetermined position of the sample disk mechanism 1 is fed by the serum pipettor 15 and the sample nozzle 27 of the serum sampling mechanism 2. A predetermined amount is dispensed into the reaction vessel 4. The sample nozzle 27 is washed with water by the washing mechanism 11. In addition, a predetermined amount of reagent in the reagent container 6 set at a predetermined position of the reagent disk 5 is dispensed into the reaction container 4 by the reagent pipettor 17 and the reagent nozzle 28 of the reagent pipetting mechanism 7. After the reagent nozzle 28 is washed with water, it dispenses a reagent for the next reaction vessel 4. The mixed solution (measurement object) of the sample and the reagent in the reaction container 4 is stirred by the stirring rod 29 of the stirring mechanism 8. After the stirring rod 29 is washed with water, the next mixed solution in the reaction vessel 4 is stirred.

  The reaction vessel 4 is maintained at a constant temperature by a thermostatic chamber 9. Measurement light is incident on the reaction vessel 4 from the light source 26, and transmitted light that has passed through the reaction vessel 4 and the object to be measured therein is measured by the spectrophotometer 10. The reaction process is measured by the spectrophotometer 10 at regular time intervals, and the absorbance of the mixed solution is measured using two set wavelengths. The absorbance measured by the spectrophotometer 10 is converted into a digital value by a converter (A / D converter and Log converter) 18, converted into a concentration value, and taken into the microcomputer 19 via the interface 23. The density value captured by the microcomputer 19 is appropriately stored in the hard disk 22 or output to the printer 20 or CRT 21. After completion of the measurement, the reaction vessel 4 is washed with water by the washing mechanism 11. The washed reaction vessel 4 is sequentially used for the next analysis.

  Next, the structure of the reaction container 4 in this Embodiment is demonstrated.

  FIG. 2 is a perspective view showing an external configuration of a configuration example of a reaction vessel block having a plurality of reaction vessels 4. FIG. 1 is a vertical view of a configuration example of the reaction vessel 4 viewed from a direction orthogonal to the optical axis of measurement light. It is sectional drawing.

  As shown in FIG. 2, a plurality of reaction vessels 4 are provided side by side on the outer periphery of the arc-shaped plate 32, and the reaction vessel 4 is attached to the outer periphery of the reaction disc 32 by attaching the plate 32 to the reaction disc 3. An annular row of is formed. The plate 32 is positioned with respect to the reaction disk 3 by inserting a pin (not shown) into the fixed pin hole 35, and fixed to the reaction disk 3 by screwing a screw (not shown) into the fixed screw hole 34. The plate 32 is provided with a handle 33 that is gripped when the plate 32 is attached to or detached from the reaction disk 3.

  As shown in FIG. 1, the reaction vessel 4 has a trapezoidal shape in which two surfaces parallel to the optical axis at the time of photometry are shorter at the lower base than at the upper base at the stage of molding. The surface of the reaction vessel 4 that intersects the optical axis of the measurement light, that is, the incident light surface (the surface on which the measurement light is incident) 4a and the transmitted light surface (the surface on which the transmitted light is emitted) 4b are inclined with respect to the optical axis of the measurement light. ing. In the case of the present embodiment, the incident light surface 4a is inclined downward and the transmitted light surface 4b is inclined upward in the traveling direction of the measurement light, but the inclination directions of both surfaces 4a and 4b are the same. However, it is sufficient if the two surfaces parallel to the optical axis of the measurement light are constricted upward or downward. Further, either the incident light surface 4a or the transmitted light surface 4b may have a configuration (vertical surface) orthogonal to the optical axis of the measurement light. The reaction container 4 may have a shape formed in a triangular shape in which two surfaces parallel to the optical axis of the measurement light are constricted downward. In this case, either the incident light surface 4a or the transmitted light surface 4b may have a configuration (vertical surface) orthogonal to the optical axis of the measurement light.

  With this configuration, the optical path length d continuously changes depending on the height S from the bottom surface 4c of the reaction vessel 4 through which the measurement light passes. By transmitting the measurement light from the bottom surface 4c of the reaction vessel 4 to the optical path of any height (receiving the measurement light transmitted through the optical path of any height), the optical path length d is set between the minimum value and the maximum value. It can be set arbitrarily. In this example, since the incident light surface 4a and the transmitted light surface 4b are flat, the optical path length d is directly proportional to the height S. For example, the heights S1, S2, and S3 (S1 <S2 <S3) from the bottom surface 4c. The relationship of S1: S2: S3 = d1: d2: d3 is established in the optical path lengths d1, d2, and d3 of the measurement light that passes through. However, the incident light surface 4a and the transmitted light surface 4b are not limited to the configuration in which the light path length d is directly proportional to the height S, but the incident light surface 4a and the transmitted light surface 4b are curved surfaces, and the height S is increased or decreased. The optical path length d can be increased or decreased.

  In addition, when acquiring the measurement results of different optical path lengths, for example, the light source 26 and the spectrophotometer 10 or the reaction disk 3 can be configured to move up and down, or a pair of light receiving units of the light source 26 and the spectrophotometer 10 can be used. It is also possible to adopt a configuration in which a large number are arranged in parallel vertically and the detection results of the pair of light receiving units corresponding to the set optical path length are adopted.

  Next, a calibration curve creation method using the reaction vessel 4 will be described.

  If the reaction vessel 4 of the present embodiment is used, the optical path length d can be arbitrarily set without replacing the reaction vessel 4 as long as the value is between the maximum value and the minimum value. Can handle a wider range of analytical work. In addition, by obtaining absorbance measurement results for multiple different optical path lengths on the same object, it is possible to expand the measurement area, greatly reduce the dilution and retesting of high-concentration samples, and realize high-accuracy measurement of low-concentration samples In addition, it is possible to improve the reliability of the measured value by detecting foreign matter in the object to be measured. Furthermore, as will be described below, (1) two or more multi-inspection calibration curves with one type of standard solution and (2) a plurality of calibration curves with one type of standard solution can be created.

(1) Creation of multi-inspection quantity curve A method for creating a multi-inspection quantity curve with one type of standard solution using the reaction vessel 4 of the present embodiment will be described. Here, two linear calibration curves are illustrated.

  First, the operator prepares one standard solution with a known concentration other than 0. Then, the operation panel 24 is operated, and two distances S1 and S2 from the bottom surface 4c of the reaction vessel 4 are set on a calibration setting screen (not shown) displayed on the display device 21, and thereby the optical path lengths of different distances are set. d1 and d2 are determined, and the execution of calibration is instructed on the operation panel 24. The distances S1 and S2 can be set for each measurement item.

  When receiving an instruction to execute calibration, the microcomputer 19 measures the measurement light transmitted through the optical path lengths d1 and d2 at the distances S1 and S2 from the bottom surface 4c of the reaction container 4, and measures the absorbances A1 and A2. At this time, as known from the Lambert-Beer law, the relationship of “E = ecl” (E: absorbance, e: molar extinction coefficient, c: molar concentration, I: optical path length) is established, and the spectrophotometer 10 The absorbance is proportional to the concentration of the light absorbing substance in the reaction vessel 4 and the optical path length d of the reaction vessel 4. On the basis of this principle, a predetermined program is stored in advance in the storage unit of the microcomputer 19, and the microcomputer 19 uses a standard solution with a known concentration as the object to be measured, and a plurality of optical path lengths (in this case d 1). , D2) are converted into measurement results obtained with the same optical path length (for example, d1), using a plurality of standard solutions with different concentrations, and a multi-inspection quantity curve is created from the conversion results. can do. For example, when d1: d2 = 1: 2, that is, d2 = 2 × d1, the absorbance A2 obtained with the optical path length d2 is replaced with the absorbance of the optical path length d1 when a standard solution having a double concentration is measured. Can do. That is, from the measurement results of the optical path lengths d1 and d2 of one type of standard solution having a concentration Cx, the result of the same optical path length d1 of the standard solutions having different known concentrations Cx and 2Cx is assumed, and the two inspection quantities shown in FIG. You can get a line. By increasing the set number of optical path lengths d, it is possible to create three or more straight lines or curve calibration curves.

  When obtaining a multi-inspection standard curve with one type of standard solution, a standard curve that normally requires measurement of multiple standard solutions with different concentrations can be created with one type of standard solution, and the frequency of use of expensive standard solutions and reagents is reduced. This also reduces running costs. Moreover, since the optical path length can be changed continuously, the reliability of the calibration curve can be improved by adjusting the interval and the number of points to be plotted according to the application. Moreover, since the obtained absorbance is proportional to the optical path length, and the optical path length corresponds to the shape of the reaction vessel 4, an effect of facilitating the creation of a calibration curve can be expected.

(2) Creation of a plurality of calibration curves Next, a method of simultaneously creating a plurality of calibration curves with one type of standard solution using the reaction vessel 4 of the present embodiment will be described. Here, a case where two linear calibration curves of one linear point are created is illustrated.

  First, the operator prepares one standard solution with a known concentration other than 0. Then, the operation panel 24 is operated, and two distances S1 and S2 from the bottom surface 4c of the reaction vessel 4 are set on a calibration setting screen (not shown) displayed on the display device 21, and thereby the optical path lengths of different distances are set. d1 and d2 are determined, and the execution of calibration is instructed on the operation panel 24. The distances S1 and S2 can be set for each measurement item.

  When receiving an instruction to execute calibration, the microcomputer 19 measures the measurement light transmitted through the optical path lengths d1 and d2 at the distances S1 and S2 from the bottom surface 4c of the reaction container 4, and measures the absorbances A1 and A2. A predetermined program is stored in the storage unit of the microcomputer 19 in advance, and the microcomputer 19 uses a standard solution with a known concentration as an object to be measured for a plurality of optical path lengths (in this case, d1 and d2) of the reaction vessel 4, respectively. A plurality of calibration curves (calibration curves 1, 2) can be created from the acquired measurement results. By increasing the set number of optical path lengths d, three or more calibration curves can be created.

  Since multiple calibration curves can be created with one type of standard solution, if the measurement results deviate significantly at a certain optical path length due to the presence of bubbles or foreign substances in the reaction vessel 4, report the measurement results at other optical path lengths. This makes it possible to eliminate the need for re-inspection.

  Here, with respect to the calibration curve obtained as described above, the following possibilities are estimated due to the measurement sensitivity. When the optical path lengths d1, d2, and d3 (d1 <d2 <d3) are set, d2 is a standard optical path length, d1 is a short optical path length with respect to the standard optical path length d2, and d3 is a long optical path length with respect to the standard optical path length d2. (D1 <d2 <d3), the linear calibration curve obtained with the optical path length d1 is linear in the low concentration region of the standard solution and easily deviates from linear in the high concentration region. On the other hand, the linear calibration curve obtained with the optical path length d3 is linear in the high concentration region of the standard solution and easily deviates from linear in the low concentration region.

  Therefore, the microcomputer 19 obtains a low concentration region (a low concentration standard) from the measurement results obtained by using a plurality of standard solutions with known concentrations as a measurement object at a plurality of optical path lengths d as shown in FIG. The measurement result 36 obtained with the long optical path length of liquid) and the measurement result 37 obtained with the short optical path length of the high concentration region (high concentration standard solution) are deleted, and a calibration curve 38 is created from the remaining measurement results To do. As a result, a calibration curve can be created using only the results measured within the appropriate range, and the reliability can be further improved.

  When measuring a patient sample, there is no problem as long as the absorbance is within the measurement range of the spectrophotometer 10. However, when measuring a high-concentration sample whose absorbance exceeds the measurement range of the spectrophotometer 10, measurement can be performed without dilution by measuring the distance from the bottom surface 4c of the reaction vessel 4 with the shortest optical path length.

DESCRIPTION OF SYMBOLS 1 Sample disk 2 Serum sampling mechanism 3 Reaction disk 4 Reaction container 5 Reagent disk 6 Reagent container 7 Reagent pipetting mechanism 8 Stirring mechanism 9 Thermostatic chamber 10 Spectrophotometer 11 Cleaning mechanism 12 Suction nozzle 13 Detergent 14 Detergent injection nozzle 15 For serum Pipetter 16 Washing water pump 17 Reagent pipetter 18 Converter 19 Microcomputer 20 Printer 21 Display device 22 Hard disk 23 Interface 24 Operation panel 25 Sample container 26 Light source 27 Sample nozzle 28 Reagent nozzle 29 Stirring rod 33 Handle 34 Fixing screw hole 35 Fixing pin Hole 36 Measurement result acquired with long optical path length in high concentration region 37 Measurement result acquired with short optical path length in low concentration region 38 Calibration curve

Claims (9)

Automatic analysis provided with a reaction container for storing an object to be measured, a light source for irradiating measurement light to the reaction container from the side, and a photometer for detecting a transmitted light of the reaction container and measuring a change in absorbance of the object to be measured A device,
An automatic analyzer characterized in that the reaction container is formed such that the optical path length continuously changes depending on the height at which the measurement light is transmitted.   2. The automatic analyzer according to claim 1, wherein at least one of the measurement light incident surface and the transmission surface of the reaction vessel is inclined upward or downward in the traveling direction of the measurement light. .   3. The automatic analyzer according to claim 2, wherein a surface parallel to the measurement light of the reaction vessel has a trapezoidal shape.   3. The automatic analyzer according to claim 2, wherein a plane parallel to the measurement light of the reaction vessel is triangular.   5. The automatic analyzer according to claim 1, further comprising a display device that displays a screen on which an optical path length can be selected for each measurement item.   The automatic analyzer according to any one of claims 1 to 5, wherein a plurality of standard solutions having different concentrations are measured based on measurement results obtained with a plurality of optical path lengths of the reaction vessel using a standard solution with a known concentration as a measurement object. An automatic analyzer comprising means for converting a measurement result obtained with the same optical path length as an object and creating a multi-inspection quantity curve from the conversion result.   The automatic analyzer according to any one of claims 1 to 6, further comprising means for creating a plurality of calibration curves from measurement results respectively obtained with a plurality of optical path lengths of the reaction vessel using a standard solution with a known concentration as a measurement object. An automatic analyzer characterized by that.   The automatic analyzer according to any one of claims 1 to 7, wherein a plurality of standard solutions with known concentrations are used as measurement objects, and the measurement results obtained respectively with the plurality of optical path lengths of the reaction container are used to obtain a long optical path length in a low concentration region. An automatic analyzer characterized by deleting an acquired measurement result and a measurement result acquired with a short optical path length in a high concentration region, and creating a calibration curve from the remaining measurement results. A reaction vessel used for an automatic analyzer equipped with a photometer for measuring a change in absorbance of an object to be measured, and for allowing measurement light to pass through the received object to be measured,
A reaction vessel characterized in that the optical path length is continuously changed according to the height at which measurement light is transmitted.

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