JP2014215123A - Filling device, method, and analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a filling device for improving an accuracy of a filling amount of several milligrams of fine particles without breaking a shape of the fine particles.SOLUTION: The filling device includes: a slurry container 14a; an optical detection part composed of a light source for measuring an absorbance in the slurry container and a light receiving part; and a calculation system 45 for deciding a suction amount of slurry based on the absorbance in the slurry container. Alternately, the filling device includes: actuators 56, 57 for adjusting measurement positions of the light source and the light receiving part; a control unit 50 for controlling the actuators; and the calculation system 45 for deciding a suction position of the slurry from the absorbance in the slurry container. Alternately, the filling device controls a rotation speed of the slurry from the absorbance in the slurry container by a stirrer 55 for controlling a rotation speed of the slurry in the slurry container and a control unit for controlling the stirrer 55.

Description

    The present invention relates to an analyzer for analyzing fine particles, and particularly to a filling technique for filling fine particles to be analyzed.

  There are various methods and apparatuses for filling fine particles. However, there are few devices for filling a small amount of fine particles of several mg. As such a filling device, for example, a powder described in Patent Document 1, a pipe attached to an ultrasonic vibration body on a plate of metal or plastic resin, or a powder filled in a hole formed in a block body is used. There are a powder filling device that discharges by ultrasonic vibration and instantaneously fills the inside of the die, or a device described in Patent Document 2 that collects and supplies a fixed amount after compression molding of fine particles.

JP 2001-49302 A JP-T-2006-505803

  In Patent Document 1 described above, when powder is uniformly filled in a plurality of pipes having a cylindrical diameter, variation in the filling amount of each pipe should be within ± 3% of the average. Is described as being possible. Here, assuming that the cylindrical volume is 100 mg, the accuracy of the filling amount in the pipe is 6 mg. Further, when the powder is supplied from the pipe into the die, the accuracy of the amount of powder supplied in the die becomes 6 mg + α. Since fine particles such as a solid phase extraction material used for analysis are expensive, a difference of 6 mg leads to an increase in cost. Furthermore, in the 6 mg fluctuation range, the extraction efficiency may be significantly reduced depending on the measurement target.

  In addition, Patent Document 2 discloses a method and apparatus for handling an individual in powder form by pressurizing a controlled amount of powder to a plug, handling an individual by collecting a powder program core from a powder bed, and powder. Individual handling by pushing out the plug is described. However, some solid-phase extraction materials used in analyzers and the like may be disintegrated with a force of about 10 Newton (N). If the extractant collapses, it will lead to clogging in the flow path of the analyzer and decrease the accuracy of the analysis result. Moreover, although the handling of the solid by manufacturing a slurry suspension is described, the excipient | filler is used in the slurry. Generally, lactose and starch are generally used as excipients. Therefore, when an extract material containing excipients is used in an analyzer, the amount of contaminants increases, and the sensitivity of the detector increases. This may lead to a decrease in the accuracy of measurement results.

  An object of the present invention is to provide a fine particle filling apparatus, method, and analysis apparatus that can solve the above-described problems and that can detect a small amount of fine particles with high accuracy.

  In order to achieve the above object, in the present invention, a slurry container, an optical detection unit for measuring the physical quantity of the slurry in the slurry container, and the suction from the slurry container based on the output of the optical detection unit, Provided is a filling device having a control unit that controls a filling amount of slurry to be filled in an extraction container.

  In order to achieve the above object, in the present invention, the physical quantity of the slurry in the slurry container is measured by the optical detection unit, and the suction is drawn from the slurry container based on the measured physical quantity of the slurry and filled in the extraction container. Provided is a filling method configured to control a filling amount of a slurry.

  Furthermore, in order to achieve the above object, the present invention includes a pretreatment unit that injects a measurement sample into an extraction container to generate an extraction sample solution, and a sample analysis unit that analyzes the extraction sample solution. The optical detector for measuring the physical quantity of the slurry in the slurry container, and a controller for controlling the filling amount of the slurry sucked from the slurry container and filled in the extraction container based on the output of the optical detector An analyzer having a configuration including:

  According to the present invention, it is possible to provide a filling device, a filling method, and an analysis device that improve the accuracy of the filling amount of a small amount of fine particles without disrupting the shape of the fine particles such as the solid phase extraction material.

1 is a diagram illustrating a configuration example of an analyzer according to Embodiment 1. FIG. It is a figure which shows an example of the filling process of the solid-phase extraction material based on Example 1. FIG. FIG. 3 is a flowchart illustrating an example of an operation of supplying a solid phase extraction material according to the first embodiment. It is a figure which shows an example of the method of measuring the light absorbency of a slurry using the optical detection part based on Example 1. FIG. It is a figure which shows an example of the graph of the relationship between the light absorbency and slurry suction amount based on Example 1. FIG. FIG. 6 is a flowchart showing an example of a supply operation of a solid phase extraction material related to Example 2. It is a figure which shows an example of the graph which shows the relationship between the light absorbency based on Example 2, and a light absorbency measurement position. FIG. 10 is a flowchart showing a supply operation of a solid phase extraction material according to a third embodiment. It is a figure which shows an example of the graph of the relationship between the light absorbency and the rotational speed of a slurry based on Example 3. FIG. It is a figure which shows one structural example of the filling apparatus based on each Example.

  Hereinafter, various embodiments of the present invention will be described in detail with reference to the drawings. In addition, description of the component which is common in various Example was performed in description of Example 1, and description was abbreviate | omitted in the other Example. Moreover, in the filling apparatus of each example, the absorbance is illustrated as a physical quantity of the slurry detected by the optical detector described in detail later, but is not limited to the absorbance, and the concentration, turbidity, etc. It may be used. In various embodiments of the present invention, the slurry filling amount is controlled based on the detected physical amount of the slurry. For controlling the slurry filling amount, the slurry suction amount, the slurry suction position, and the slurry are controlled. The rotational speed and the like are determined. These embodiments will be described in order below.

  FIG. 1 is a diagram illustrating a configuration example of an analyzer according to a first embodiment that determines a slurry suction amount in order to control a slurry filling amount. As shown in the figure, the analysis apparatus 1 according to the first embodiment includes a solid phase extraction processing unit 10, a sample setting unit 20, a reagent supply unit 30, and a sample analysis unit 40, and is a control unit that is a control unit. 50. The solid-phase extraction processing unit 10 of the analyzer 1 constitutes a part of the pre-processing unit of the analyzer 1 and performs so-called solid phase extraction (SPE) as a pre-processing stage. In this solid phase extraction (SPE), a chemical substance to be analyzed / measured is captured on the surface of fine particles having a particle diameter of several μm to several tens μm, which is called a solid phase extraction material, in a sample container. It is a method of separating and purifying from other substances present.

  The sample setting unit 20 includes a sample transport table 22 that transports a sample container 21 into which a sample solution Liq2 that is a solution in which a measurement component to be analyzed is dispensed is dispensed, and a sample transported to a predetermined position by the sample transport table 22 A sample dispensing mechanism 23 for transferring the sample liquid Liq2 from the container 21 to the solid phase extraction processing unit 10 is configured. An injection mechanism (not shown) for injecting the sample liquid Liq2 into the sample container 21, for example, is provided at a predetermined position around the sample transport table 22, and the sample liquid Liq2 is dispensed into the sample container 21 by this injection mechanism. The

  A sample dispensing mechanism 23 is installed at a predetermined position around the sample transport table 22. The sample dispensing mechanism 23 includes a sample dispensing arm 23 a configured to be movable between the sample setting unit 20 and the solid phase extraction processing unit 10. The sample dispensing arm 23a is provided above the sample transport table 22 (in the vertical direction in FIG. 1), and a sample nozzle 23a1 for sucking up the sample liquid Liq2 is provided at the end thereof. The sample dispensing mechanism 23 sucks up the sample liquid Liq2 dispensed in the sample container 21 that has been transported to the predetermined position by the sample transport table 22 by the sample nozzle 23a1, and the sample liquid Liq2 that has been sucked up by the sample dispensing arm. 23a is configured to be movable to the solid phase extraction processing unit 10.

  The solid-phase extraction processing unit 10 constituting a part of the pre-processing unit has a plurality of solid-phase extraction containers 11 attached thereto, an extraction container table 12 that conveys the solid-phase extraction containers 11 around, an extraction processing unit 13, The solid phase extraction material filling mechanism 14 for filling the solid phase extraction container 11 with the solid phase extraction material, the discharge mechanism 15 for discharging the solid phase extraction material from the solid phase extraction container 11, the reagent injection mechanism 16, and the container washing mechanism 17. The extraction container table 12 is formed in, for example, a circular disk shape, and a central part is rotatably attached to the analyzer 1 and is configured to convey a plurality of solid phase extraction containers 11 in a circle. The solid phase extraction container 11 of this embodiment functions as a container filled with a solid phase extraction material that adsorbs the measurement component contained in the sample liquid Liq2.

  The solid-phase extraction material filling mechanism 14 determines the position of the filter in the solid-phase extraction container 11 and the filter supply mechanism 14a that supplies the solid-phase extraction container 11 with a filter that removes dust and the like from the sample solution containing the measurement component. The filter positioning mechanism 14b includes a solid-phase extraction material supply mechanism 14c that supplies a solid-phase extraction material that adsorbs a measurement component to the solid-phase extraction container 11, a slurry supply unit 14d, and a slurry container 14e.

  The solid-phase extraction material supply mechanism 14c includes a slurry dispensing arm 14c1 configured to be movable between the extraction container table 12 and the slurry supply unit 14d. The slurry dispensing arm 14c1 is provided above the slurry container 14e of the slurry supply unit 14d, and a slurry nozzle 14c2 for sucking up the slurry is provided at the end thereof. The solid phase extraction material supply mechanism 14c sucks up the slurry Liq1 in the slurry container 14e of the slurry supply unit 14d by the slurry nozzle 14c2, and can move the sucked slurry Liq1 to the extraction container table 12 by the slurry dispensing arm 14c1. Composed.

  Further, the filter supply mechanism 14 a is disposed above the extraction container table 12 attached to the analyzer 1, and is configured to drop, for example, a spherical filter onto the solid phase extraction container 11. The solid-phase extraction material supply mechanism 14 c is disposed above the extraction container table 12 attached to the analyzer 1. The filter positioning mechanism 14b is disposed above the extraction container table 12 attached to the analyzer 1, and positions the filter after supplying the filter 14a.

  The extraction container table 12 attached to the analyzer 1 is disposed below the sample dispensing arm 23a of the sample dispensing mechanism 23 (in the vertical direction in FIG. 1), and the solid phase extraction container 11 is directly below the sample dispensing arm 23a. It is equipped to convey. The sample liquid Liq2 sucked from the sample container 21 by the sample nozzle 23a1 of the sample dispensing arm 23a from the sample container 21 is discharged into the solid phase extraction container 11.

  Further, the extraction container table 12 is disposed below the slurry dispensing arm 14c1 of the solid phase extraction material supply mechanism 14c, and is provided to transport the solid phase extraction container 11 directly below the slurry dispensing arm 14c1. The slurry nozzle 14c2 of the slurry dispensing arm 14c1 is configured such that the slurry Liq1 sucked up from the slurry container 14e by the slurry supply unit 14d is discharged to the solid phase extraction container 11.

  Further, the extraction processing unit 13, the discharge mechanism 15, the reagent injection mechanism 16, the container cleaning mechanism 17, and the extraction mechanism cleaning unit 18 are appropriately arranged at predetermined positions around the extraction container table 12. The extraction processing unit 13 includes a pressurizing nozzle 13 a that outputs high-pressure air, and has a function of pressurizing the solid-phase extraction container 11 by discharging high-pressure air into the solid-phase extraction container 11.

  The discharge mechanism 15 has a function of discharging the used solid phase extraction material from the solid phase extraction container 11. The extraction mechanism cleaning unit 18 cleans the discharge mechanism 15 after discharging the used solid-phase extraction material from the solid-phase extraction container 11. Reference numeral 15 a denotes a work arm of the discharge mechanism 15. The reagent injection mechanism 16 injects into the solid phase extraction container 11 a cleaning reagent Liq3 for cleaning the solid phase extraction container 11 that is a reagent supplied from the reagent supply unit 30 and an elution reagent Liq4 for extracting the measurement component by solid phase. It has the function to do. Moreover, the container washing | cleaning mechanism 17 wash | cleans the solid-phase extraction container 11 used for the solid-phase extraction.

  Next, the sample analysis unit 40 includes an eluate transport table 42 that transports the eluate storage container 41 that is extracted from the solid phase extraction container 11 and that contains the eluate containing the measurement component, and the eluate storage. The liquid feeding part 44 for feeding the eluate contained in the container 41 to the analysis execution part 43 and the analysis execution part 43 using mass spectrometry (Mass Spectrometry: MS) measure the measurement components in the eluate. A calculation system unit 45 that executes and calculates a predetermined analysis processing program on the measurement data that is the acquired measurement value, and an analysis result obtained by calculation by the calculation system unit 45 is displayed on a monitor, a printer, etc. An external communication interface 45a that outputs to the output device and a container storage unit 46 that stores the eluate container 41 are configured.

  The eluate storage container 41 is preferably configured to store the eluate containing the measurement component dropped from the solid phase extraction container 11 of the extraction container table 12 attached to the analyzer 1. A configuration provided below the extraction container table 12 is preferable. The analysis execution unit 43 is a device that acquires data by measuring the measurement components in the eluate extracted by the solid phase extraction processing unit 10, and includes the above-described MS that is suitable for the purpose of the analysis device 1. Consists of the equipment used. The measurement method of the measurement component in the analysis execution unit 43 is liquid chromatography, mass spectrometry, or the like, but this is not limited.

  Then, the measurement value acquired by the analysis execution unit 43 is input to the arithmetic system unit 45. The calculation system unit 45 calculates the analysis result of the measurement component based on the input measurement value. In addition, the calculation system unit 45 outputs an analysis result calculated as necessary via the external communication interface 45a. Here, a normal computer can be used as the arithmetic system unit 45.

  That is, the arithmetic system unit 45 receives a variety of measurement data from the analysis execution unit 43 and receives a central processing unit (CPU) that performs arithmetic processing on the measurement data, measurement data, processing result data, and various types of data. It can be configured by a computer having a memory for storing control and processing programs, an input / output unit, an input / output interface unit, and the like. In that case, an input / output interface unit or an input / output unit of a computer can be used as the external communication interface 45a and the output device. Further, this computer can also be used as the computer constituting the control unit 50 described above. In this case, the arithmetic system unit 45 and the control unit 50 are collectively referred to as a control unit. If necessary, the control program of the control unit 50, the calculation program of the calculation system unit 45, and the analysis result data can be stored in a storage medium (Hard Disk Drive: HDD) (not shown).

  The eluate container 41 that is not used may be stored in the container storage unit 46 and set on the eluate transport table 42 by a transport device such as a transport arm (not shown) as necessary.

  The reagent supply unit 30 circulates around the reagent container 31 filled with the cleaning reagent Liq3 for cleaning the solid phase extraction container 11 and the elution reagent Liq4 for solid phase extraction of the measurement component contained in the sample solution. 32. The reagent transport table 32 is disposed below the reagent injection arm 16a of the reagent injection mechanism 16, and transports the reagent container 31 directly below the reagent injection arm 16a. The reagent injection arm 16a is provided with a reagent nozzle 16a1 for sucking the cleaning reagent Liq3 and the elution reagent Liq4 from the reagent container 31, and the cleaning reagent Liq3 and the elution reagent Liq4 sucked from the reagent container 31 are attached to the analyzer 1. Then, it is discharged into the solid phase extraction container 11 of the extraction container table 12. For this reason, the reagent injection arm 16 a is provided above the extraction container table 12.

  The reagent supply unit 30 also includes a replenishment mechanism (not shown) that replenishes the reagent container 31 that has been emptied by the suction of the cleaning reagent Liq3 and the elution reagent Liq4 with the cleaning reagent Liq3 and the elution reagent Liq4. ). In addition, there are a method of replenishing the cleaning reagent Liq3 and the elution reagent Liq4, such as a method of replacing the reagent container 31 or a method of supplying only the cleaning reagent Liq3 and the elution reagent Liq4 to the reagent container 31. However, it is not limited to these methods. The reagent supply unit 30 can continuously supply the cleaning reagent Liq3 and the elution reagent Liq4 by the configuration of the analyzer of the present embodiment as described above.

  Further, for example, information such as the cleaning reagent Liq3 and the elution reagent Liq4, which are reagents in the reagent container 31 set on the reagent transport table 32, from an input / output unit of a computer such as a personal computer connected to the external communication interface 45a. However, a configuration in which the information is input together with the position information of the reagent container 31 in the reagent transport table 32 and written in the arithmetic system unit 45 is preferable.

  Further, the control unit 50 obtains the position information of the reagent container 31 and the information of the reagent to be supplemented from the arithmetic system unit 45, thereby replenishing the reagent container 31 and the reagent in which the reagent container 31 is set. The position of the transfer table 32 can be identified. Alternatively, a barcode indicating information on the filled reagent may be attached to the reagent container 31, and the barcode reader 33 may transmit information read from the barcode of the reagent container 31 to the control unit 50. The control unit 50 can identify the reagent in the reagent container 31 based on information read from the barcode by the reagent injection arm 16a.

  Alternatively, the reagent container 31 may be provided with a chip such as RFID (Radio Frequency Identification) in which information can be freely written, and the barcode reader 33 may be provided with a reader for reading information written on the chip. The bar code reader 33 may transmit information read from the chip to the control unit 50. Further, if the information for identifying the cleaning reagent Liq3 and the elution reagent Liq4, which are the reagents replenished to the reagent container 31 by a replenishment mechanism (not shown), is written on this chip, the information that the barcode reader 33 is written on the chip. Is read and transmitted to the control unit 50, the control unit 50 can identify the reagent in the reagent container 31.

  As described above, as shown in FIG. 1, the analyzer 1 according to the present embodiment includes a pretreatment unit such as the solid phase extraction processing unit 10, the sample setting unit 20, the reagent supply unit 30, and the sample analysis unit 40. And is controlled by the control unit 50 constituting the control unit. The control unit 50 includes a step of filling the solid phase extraction container 11 described in detail below with a solid phase extraction material (solid phase extraction material filling step) and a solid phase extraction container 11 filled with the solid phase extraction material. A step of solid-phase extraction of the measurement component contained in the sample liquid (solid-phase extraction step) and a step of washing the solid-phase extraction container 11 after the solid-phase extraction (container washing step) are appropriately executed, and the solid-phase extraction material The filling amount is controlled, the measurement component contained in the sample solution is subjected to solid phase extraction, and the measurement component is analyzed.

<Filling operation of solid phase extraction material>
FIG. 2 shows a solid phase extraction material filling process in which the control unit 50 of the analyzer 1 of this embodiment controls the solid phase extraction material filling mechanism 14 to fill the solid phase extraction container 11 with the solid phase extraction material M1. Yes. That is, the control unit 50 which is a control part controls the filling amount of the solid-phase extraction material M1 with which the solid-phase extraction container 11 is filled by executing this process.

  As shown in FIG. 2, in the solid phase extraction material filling step, the solid phase extraction material M1 is filled into the solid phase extraction container 11 in seven steps (first step SA1 to seventh step SA7). FIG. 2 shows a solid phase extraction material filling step of filling the solid phase extraction container 11 with the powdery solid phase extraction material M1. Hereinafter, the solid phase extraction material filling step in the present embodiment will be described with reference to FIG.

  In the first step SA1, the control unit 50 controls the extraction container table 12 to transport the solid phase extraction container 11 directly below the filter supply mechanism 14a. The control unit 50 controls the filter supply mechanism 14a to supply the lower filter F1 as a filter to the solid phase extraction container 11. In this embodiment, the lower filter F1 is spherical and has elasticity, and the filter supply mechanism 14a has a function of dropping the spherical lower filter F1 into the solid-phase extraction container 11 conveyed immediately below.

  Then, the spherical lower filter F <b> 1 is introduced from the filter supply mechanism 14 a into the body portion 11 a of the solid phase extraction container 11. The diameter of the filter is formed larger than the diameter of the inner surface of the discharge path 11b, and the lower filter F1 stops at the boundary between the reduced diameter portion 11c and the discharge path 11b.

  The shape of the lower filter F1 is not limited to a spherical shape. It may be a cylindrical shape, a tapered cylindrical shape, a stepped cylindrical shape, or the like. The cross-sectional shape may be a prismatic filter having a trapezoidal shape, a rhombus shape, a square shape, a rectangular shape, or the like.

  In the second step SA2, the control unit 50 controls the extraction container table 12 to convey the solid phase extraction container 11 into which the lower filter F1 has been introduced, directly below the filter positioning mechanism 14b. Further, the control unit 50 moves the positioning rod 14b1 of the filter positioning mechanism 14b downward. The positioning rod 14b1 enters the solid-phase extraction container 11 into which the lower filter F1 has been charged. Further, the positioning rod 14b1 itself enters the discharge path 11b while pushing the lower filter F1 into the discharge path 11b and proceeding. When the lower filter F1 contacts the convex portion 11d, the positioning mechanism 14b stops moving and completes the positioning of the lower filter F1.

  In the third step SA3, the control unit 50 controls the extraction container table 12 and conveys the solid phase extraction container 11 filled with the lower filter F1 directly below the solid phase extraction material supply mechanism 14c. Then, the control unit 50 controls the solid phase extraction material supply mechanism 14c to fill the solid phase extraction container 11 with the solid phase extraction material M1.

  Specifically, the solid-phase extraction material supply mechanism 14 c is configured to inject the slurry Liq 1 in which the powdery solid-phase extraction material M 1 is dispersed in the solution into the body portion 11 a of the solid-phase extraction container 11. The slurry is a mixture of fine particles of an organic solvent such as ethanol or methanol and solid phase extraction material, or a mixture of water and fine particles, or a mixture of water, organic solvent and fine particles, but is not limited thereto. . Slurry Liq1 injected into the body portion 11a of the solid phase extraction container 11 flows into the discharge path 11b, is blocked by the lower filter F1, and accumulates above the lower filter F1.

  In the fourth step SA4, the control unit 50 controls the extraction container table 12 and conveys the solid phase extraction container 11 into which the slurry Liq1 has been injected, directly below the extraction processing unit 13. Then, the control unit 50 controls the extraction processing unit 13 to fit the pressurizing nozzle 13 a provided in the extraction processing unit 13 into the body unit 11 a of the solid phase extraction container 11. Then, the control unit 50 controls the extraction processing unit 13 to send high-pressure air into the solid phase extraction container 11 from the tip of the pressurizing nozzle 13a. The solid phase extraction container 11 is pressurized, the liquid component Liq1a of the slurry liq1 is discharged through the lower filter F1 by pressurization, and the powdery solid phase extraction material M1 dispersed in the slurry liq1 is above the lower filter F1. Remain. That is, the solid phase extraction material M1 is locked by the lower filter F1.

  In the fifth step SA5, the control unit 50 controls the extraction container table 12 and conveys the solid phase extraction container 11 filled with the solid phase extraction material M1 directly below the filter supply mechanism 14a. The control unit 50 controls the filter supply mechanism 14a to supply the upper filter F2 that is a filter to the body portion 11a of the solid phase extraction container 11. The upper filter F2 stops at the boundary between the reduced diameter portion 11c and the discharge path 11b.

  In the sixth step SA6, the control unit 50 controls the extraction container table 12 to convey the solid phase extraction container 11 into which the upper filter F2 has been introduced, directly below the filter positioning mechanism 14b. Then, the control unit 50 controls the filter positioning mechanism 14b to position the upper filter F2 similarly to the positioning of the lower filter F1.

  The upper filter F2 pushed into the discharge path 11b by the positioning rod 14b1 stops at a position where the solid-phase extraction material M1 is appropriately compressed. In this way, the position of the upper filter F2 is determined by the filter positioning mechanism 14b, whereby the position of the solid phase extraction material M1 is determined, and the solid phase extraction material M1 is filled in the solid phase extraction container 11.

  By the solid phase extraction material filling step including the first step SA1 to the seventh step SA7, the solid phase extraction material M1 is sandwiched between the lower filter F1 and the upper filter F2 in the discharge path 11b of the solid phase extraction container 11. Is filled.

<Filling with extraction material (third step SA3)>
FIG. 3 is a diagram illustrating details of an example of the supply / filling operation of the solid phase extraction material in the third step SA3 of FIG. 2 described above, which is controlled by the control unit 50 of the analyzer 1 of the present embodiment. When the supply operation of the solid phase extraction material is started (S01), the filling amount of the solid phase extraction material is read from the control unit 50 according to each measurement component (S02), and the absorbance measurement in the slurry container 14e is started (S03). . A slurry suction amount X μl (0.01 ≦ X ≦ 2000) is calculated by the calculation system unit 45 from the measured absorbance and the filling amount of the solid-phase extraction material (S04), and the slurry (liq1) in the slurry container 14e from the slurry nozzle 14c2 is calculated. ) Is sucked in the slurry suction amount X μl corresponding to the above filling amount (S05). A method for measuring absorbance using the optical detection unit in this embodiment will be described in detail later with reference to FIG. After the slurry suction amount X μl corresponding to the filling amount is sucked, the slurry supply arm 14C1 rotates and supplies the slurry (liq1) into the solid phase extraction container 11 of the extraction container table 12 (S06). The supply operation is completed (S07).

<Method for measuring absorbance of slurry>
FIG. 4 is a diagram for explaining a method of measuring the absorbance of the slurry that is constantly stirred by a stirrer or the like using the optical detection unit, corresponding to the absorbance measurement S03 of FIG. In the present embodiment, the absorbance measurement of the slurry is performed in the triaxial direction of the orthogonal coordinate system xyz with respect to the slurry container 14e. In the configuration of FIG. 4, the light source X and the light receiving unit X, the light source Y and the light receiving unit Y, and the light source Z and the light receiving unit Z constitute an optical detection unit.

4A shows an example of measurement of absorbance of the transmitted light method and the transmitted light scattering method, and FIG. 4B of FIG. 4B shows an example of measurement of the absorbance of the scattered light method. The absorbances in the x, y, and z directions are the incident light intensities I _ox , I _0y , I _0z from the respective light sources, and the transmitted light intensities I _x , I _y , I _z detected by the light receiving unit, and A _λx = −log ₁₀ (I _x / I _0x ), A _λy = _{−log 10} (I _y / I _0y ), and A _λz = −log ₁₀ (I _z / I _0z ). The absorbance of each axis is calculated by the calculation system unit 45 performing calculations such as an integrated value, a differential value, and an average value for y seconds (10 ⁻⁶ ≦ y ≦ 10 ² ) from the start of measurement.

  When the absorbance measurement location and the measurement direction are one direction, there are a plurality of slurry suction positions on the line. Therefore, there is a high possibility that the slurry suction amount varies depending on the suction position. Therefore, as shown in FIG. 4, it is desirable that the absorbance is measured so as to have an intersection point from two or more different axis directions and the slurry is sucked at the intersection point, but the present invention is not limited to this. In the figure, the measurement is performed in the three-axis directions of the x-axis, y-axis, and z-axis, but it is sufficient to measure at least one axis direction. The absorbance measurement method by the optical detector is not limited to the transmitted light method, scattered light method, and transmitted light scattering method, but other methods such as the surface scattered light method and the integral rapid measurement method are used. May be.

<Determination method of suction volume>
FIG. 5 is a graph shown for explaining the method of determining the slurry suction amount in S04 of FIG. The vertical axis represents absorbance, and the horizontal axis represents the amount of slurry sucked. As the absorbance, a value obtained by calculating the absorbance or absorbance in at least one axis direction among the absorbances A _λx , A _λy , and A _{λz in} the triaxial direction in FIG. 4 is used. When the absorbance is low, the slurry suction amount is decreased (A ₁ ), and when the absorbance is high, the amount is increased (A ₂ ). The vertical axis in the figure, have been described product of absorbance in three axial directions, the sum of the three axial directions, the difference quotient, 2 axial absorbance of the product _{(A λx · A λy, A} λx · A λz _, A _λy · A _λz ), sum (A _λx + A _λy, A _λx + A _λz, A _λy + A _λz ), difference, quotient, uniaxial absorbance (A _λx, A _λy, A _λz ), and the like. Further, in this embodiment, the absorbance is used as the physical quantity of the slurry, which is a condition for determining the slurry suction amount in order to control the filling amount of the slurry. However, instead of the absorbance, the slurry concentration or turbidity is used as the physical quantity of the slurry. As described above, it may be used.

  Next, as Example 2, an example showing a modification of extraction material filling (third step SA3) in FIG. 2 of Example 1 described above will be described. In the present embodiment, in order to control the filling amount of the slurry, an actuator that adjusts the measurement position for measuring the physical quantity of the slurry by the optical detection unit is provided, and the control unit sucks the slurry based on the absorbance of the slurry. A calculation system unit that determines a position and determines a suction position for sucking the slurry at this position is included. In addition, about the structure operation | movement similar to the apparatus of Example 1 of the analyzer 1 other than 3rd process SA3, description is abbreviate | omitted here.

FIG. 6 shows the details of the supply operation of the solid phase extraction material in the third step SA3 of FIG. 2 in the present embodiment. When the supply operation of the solid phase extraction material is started (S21), the filling amount of the solid phase extraction material is read from the control unit 50 according to each measurement component (S22), and the absorbance which is the physical quantity of the slurry in the slurry container 14e is measured. Is started (S23). In this embodiment, the slurry suction amount is constant. Next, in order to reduce the accuracy of the filling amount of the solid phase extraction material M1 to ± 0.05 mg or less (the range of the weight that does not affect the analysis performance when filling with 1 mg of the solid phase extraction material), An allowable range of absorbance corresponding to ± 0.05 mg (A ₁₁ ≦ Absorbance ≦ A _h1 ) is provided, and it is determined whether or not it is within the range. (S24). Note that A ₁₁ and A _h1 are calculated by the calculation system unit 45 for each filling amount. Alternatively, a preset allowable range can be read from a table in the memory.

In the permissible range (A ₁₁ ≦ Absorbance ≦ A _h1 ), the slurry liq1 in the slurry container 14e is sucked from the slurry nozzle 14c2 (S26). After the slurry suction, the slurry supply arm 14C1 rotates and moves to supply the slurry liq1 into the solid phase extraction container 11 of the extraction container table 12 (S27), and the supply operation of the solid phase extraction material M1 is completed (S28).

If it is out of the allowable range (absorbance < _{A11, Ah1} <absorbance), the absorbance measurement position is changed (S25), and the absorbance of the slurry is measured again (S23).

  Position control of the light source and light receiving unit, which is an optical detection unit, which is an absorbance measurement position, is performed by a biaxial actuator via the control unit 50. Details of the biaxial actuator will be described later with reference to FIG. The adjustment of the measurement position is not limited to the driving of the light source and the light receiving unit, which are optical detection units, but by a three-axis actuator using an xyz orthogonal coordinate axis system (not shown) installed in the slurry supply unit 14d. The position of the slurry container may be adjusted. Although not shown in the flow of FIG. 6, in the present embodiment, when the outside of the allowable range is continuously detected 30 times, the apparatus abnormally stops.

<Change in absorbance measurement position>
FIG. 7 is a graph showing the allowable range of absorbance in S24 of FIG. The vertical axis represents the absorbance, and the horizontal axis represents the measurement position. The definition of absorbance is the same as in FIG. A _O1 within the permissible range moves to the slurry suction operation (S26), and A _N1 and A _N2 outside the permissible range change the measurement position (S25), and the absorbance is measured again (S23). As a result of the re-measurement, when the absorbance falls within the allowable range, slurry suction is performed with the position as the suction position (S26). In this embodiment, the absorbance is used as the condition for determining the slurry measurement position. However, the slurry concentration and turbidity may be used instead of the absorbance as in the first embodiment.

  As a third embodiment, a modified embodiment of the first and second embodiments will be described. In this embodiment, in order to control the filling amount of the slurry, a stirrer for controlling the rotation speed of the slurry in the slurry container is provided, and the control unit follows the rotation speed determined by the calculation system unit based on the absorbance of the slurry. To control. Also in the present embodiment, the description of the same configuration and processing as in the first embodiment other than the third step SA3 in FIG. 2 is omitted here.

FIG. 8 is a diagram showing details of an example of the operation of supplying the solid phase extraction material in the third step SA3 of FIG. In the figure, the supply operation of the solid phase extraction material is started (S31), the filling amount of the solid phase extraction material is read from the control unit 50 according to each measurement component (S32), and the absorbance measurement in the slurry container 14e is started. (S33). In this embodiment, unlike the above-described embodiment, the slurry suction amount is constant and the absorbance measurement position is fixed. Next, the accuracy of the filling amount of the solid phase extraction material M1 is ± 0.05 mg or less, that is, the filling amount is set to a range of weight that does not affect the analysis performance in the filling of 1 mg of the solid phase extraction material. tolerance in absorbance corresponding to ± 0.05 mg from the _{(a l2} ≦ absorbance ≦ _{a h2)} is provided, determines whether the range (S34). A _l2 and _Ah2 are calculated by the calculation system unit 45 for each filling amount. Alternatively, it may be configured to read out the contents of a table prepared in advance and stored in a memory (not shown).

If within the allowable range of _{(A l2} ≦ absorbance ≦ _{A h2),} to suck the slurry liq1 in the slurry container 14e from a slurry nozzle 14c2 (S38). After the slurry suction, the slurry supply arm 14C1 rotates and moves to supply the slurry liq1 into the solid phase extraction container 11 of the extraction container table 12 (S39), and the supply operation of the solid phase extraction material M1 is completed (S40).

As shown in FIG. 8, if the allowable range (absorbance <A _l2), the control unit 50, sends electrical signals to the stirrer, 10 rpm up (S36) the rotational speed of the slurry, measuring the absorbance of the slurry solution again (S33). When the value is outside the allowable range (A _h2 <absorbance), an electric signal is sent from the control unit to the stirrer, the rotational speed of the slurry is reduced by 10 rpm (S37), and the absorbance of the slurry solution is measured again (S33). When it falls within the allowable range, slurry suction (S38) is performed as in the previous embodiment. Although omitted in the flow of FIG. 8, the apparatus abnormally stops when 20 times outside the allowable range is detected continuously.

<Method of determining the rotational speed of the slurry>
FIG. 9 is a graph showing the allowable range of absorbance in S34 of FIG. The vertical axis represents the absorbance, and the horizontal axis represents the rotational speed of the slurry. The definition of absorbance is the same as in FIG. _{A O2} within the allowable range, the sequence proceeds to the operation of the slurry suction (S38), _{A N3} acceptable range (absorbance _{<A l2)} is 10 rpm up (S36) the rotational speed of the slurry, measuring the absorbance of the slurry solution again (S33). A _N3 outside the allowable range (A _h2 <absorbance) lowers the rotational speed of the slurry by 10 rpm (S37) and measures the absorbance of the slurry solution again (S33). The rotation speed of the slurry is controlled by a stirrer installed in the slurry supply unit 14d via the control unit 50. The configuration of this stirrer is shown in the filling device in FIG. 10 described later. The use of a stirrer as an example of the stirring method of the slurry liq1 is not limited to this, and other stirring means may be used. In this embodiment, the absorbance is used as a condition for determining the number of revolutions of the slurry for controlling the filling amount of the slurry. However, the slurry concentration and turbidity may be used instead of the absorbance. This is the same as the embodiment.

<Configuration of filling device>
FIG. 10 is a diagram illustrating an example of a configuration of a filling apparatus that is the solid-phase extraction material filling mechanism 14 in the analysis apparatus 1 of FIG. 1 in each of the embodiments described above. The filling mechanism includes a slurry nozzle 14c2, a syringe pump 51 for sucking the slurry, a cleaning electromagnetic valve 52 for cleaning in the distribution, a pump 53 for feeding solvent, a solvent circulation electromagnetic valve 54, a control unit 50, and an arithmetic system. The unit 45, the stirrer 55, the y direction, and the z direction actuators 56 and 57 are included. Positioning of the light source X and the light receiving unit X constituting the optical detection unit is performed in the vertical direction (z direction) and the depth direction (y direction) via the control unit 50 based on the measurement position information calculated by the arithmetic system unit 45. The actuator is used.

  The control unit 50 calculates the suction amount of the syringe pump, the absorbance measurement position, and the rotation speed of the stirrer based on the suction amount of the syringe pump, the measurement position of the absorbance, or the rotation speed of the stirrer calculated from the absorbance of the slurry liq1. Take control.

  In addition, this figure has shown only the light source X and the light-receiving part X which are the optical detection parts of the YZ plane of FIG. . It is also possible to control the measurement position of absorbance in the same manner with respect to the light source Y and the light receiving unit Y constituting the optical detection unit on the XZ plane and the light source Z and the light receiving unit Z constituting the optical detection unit on the XY plane. Needless to say.

  While various embodiments of the present invention have been described with reference to the drawings, the present invention is not limited to these embodiments, and can be appropriately changed in design without departing from the spirit of the invention. The above-described embodiments have been described in detail for better understanding of the present invention, and are not necessarily limited to those having all the configurations described above. Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. Further, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment. For example, the filling amount may be controlled by combining the above-described slurry suction amount, change in the measurement value of the absorbance measurement position, and change in the rotation speed of the slurry.

  Further, the above-described configuration, function, processing unit, and the like have been described as an example of creating a program that realizes part or all of them. Needless to say, it can be realized with this.

DESCRIPTION OF SYMBOLS 1 Analyzer 11 Solid phase extraction container 11a Body part 11b Discharge path 11c Diameter reduction part 11d Convex part 12 Extraction container table 13 Extraction processing part 13a Pressure nozzle 14 Solid phase extraction material filling mechanism 14a Filter supply mechanism 14b Filter positioning mechanism 14b1 Positioning Rod 14c Solid phase extraction material supply mechanism 14c1 Slurry dispensing arm 14c2 Slurry nozzle 14d Slurry supply unit 14e Slurry container 15 Discharge mechanism 15a Work arm 16 of discharge mechanism 15 Reagent injection mechanism 16a Reagent injection arm 16a1 Reagent nozzle 17 Container cleaning mechanism 18 Extraction mechanism cleaning unit 20 Sample setting unit 21 Sample container 22 Sample transport table 23 Sample dispensing mechanism 23a Sample dispensing arm 23a1 Sample nozzle 30 Reagent supply unit 31 Reagent container 32 Reagent transport table 40 Sample analysis unit 41 Eluate storage container 4 Eluent conveying table 43 analysis execution unit 44 feeding unit 45 computing system unit 45a external communication interface 46 container storage unit 50 control unit 51 syringe pumps 52, 54 solenoid valve 53 pump 55 stirrer 56 and 57 actuator

Claims (20)

A slurry container;
An optical detector for measuring the physical quantity of the slurry in the slurry container;
A controller for controlling the filling amount of the slurry sucked from the slurry container and filled in the extraction container based on the output of the optical detection unit,
A filling device characterized by that. The filling device according to claim 1,
The optical detection unit detects the absorbance, concentration, or turbidity of the slurry as a physical quantity of the slurry.
A filling device characterized by that. The filling device according to claim 1,
The control unit includes an arithmetic system unit that determines a slurry suction amount to be sucked from the slurry container based on a physical amount of the slurry.
A filling device characterized by that. The filling device according to claim 1,
The optical detection unit further comprises an actuator for adjusting a measurement position for measuring the physical quantity of the slurry,
The control unit includes an arithmetic system unit that determines a suction position for sucking the slurry from the slurry container based on a physical quantity of the slurry.
A filling device characterized by that. The filling device according to claim 1,
A stirrer for controlling the rotational speed of the slurry in the slurry container; and the control unit controls the stirrer based on a physical quantity of the slurry.
A filling device characterized by that. The filling device according to claim 1,
The optical detection unit is installed in two or more different directions, respectively.
A filling device characterized by that. The filling device according to claim 4,
The controller is
If the physical quantity of the slurry is outside the allowable range, the measurement position is adjusted and controlled to measure the physical quantity of the slurry again.
A filling device characterized by that. The filling device according to claim 5,
The controller is
When the physical quantity of the slurry is outside the allowable range, the rotational speed is controlled, and the physical quantity of the slur is measured again.
A filling device characterized by that. The physical quantity of the slurry in the slurry container is measured by an optical detection unit, and based on the measured physical quantity of the slurry, the amount of the slurry sucked from the slurry container and filled in the extraction container is controlled.
The filling method characterized by the above-mentioned. The filling method according to claim 9,
Measuring the absorbance, concentration, or turbidity of the slurry as a physical quantity of the slurry;
The filling method characterized by the above-mentioned. The filling method according to claim 9,
Based on the physical amount of the slurry, determine the amount of slurry sucked from the slurry container,
The filling method characterized by the above-mentioned. The filling method according to claim 9,
Adjust the measurement position to measure the physical quantity of the slurry in the optical detection unit,
Based on the physical quantity of the slurry, determine a suction position for sucking the slurry from the slurry container,
The filling method characterized by the above-mentioned. The filling method according to claim 9,
Based on the physical quantity of the slurry, the rotational speed of the slurry in the slurry container is controlled.
The filling method characterized by the above-mentioned. The filling method according to claim 9,
A plurality of the optical detection units are installed in two or more different directions, and a physical quantity of the slurry is detected.
The filling method characterized by the above-mentioned. A pretreatment unit for injecting a measurement sample into the extraction container and generating an extraction sample solution;
A sample analyzer for analyzing the extracted sample liquid,
The pre-processing unit is
An optical detector for measuring the physical quantity of the slurry in the slurry container;
A controller for controlling the filling amount of the slurry that is sucked from the slurry container and filled in the extraction container based on the output of the optical detection unit;
An analyzer characterized by that. The analyzer according to claim 15, wherein
The optical detection unit detects the absorbance, concentration, or turbidity of the slurry as a physical quantity of the slurry.
An analyzer characterized by that. The analyzer according to claim 15, wherein
The control unit includes an arithmetic system unit that determines a slurry suction amount to be sucked from the slurry container based on a physical amount of the slurry.
An analyzer characterized by that. The analyzer according to claim 15, wherein
The optical detection unit further comprises an actuator for adjusting a measurement position for measuring the physical quantity of the slurry,
The control unit includes an arithmetic system unit that determines a suction position for sucking the slurry from the slurry container based on a physical quantity of the slurry.
An analyzer characterized by that. The analyzer according to claim 15, wherein
A stirrer for controlling the rotational speed of the slurry in the slurry container; and the control unit controls the stirrer based on a physical quantity of the slurry.
An analyzer characterized by that. The analyzer according to claim 15, wherein
The optical detection unit is installed in two or more different directions, respectively.
An analyzer characterized by that.

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