WO2011001647A1

WO2011001647A1 - Automatic analysis device and measurement method

Info

Publication number: WO2011001647A1
Application number: PCT/JP2010/004219
Authority: WO
Inventors: 水谷貴行; 渡部恭子
Original assignee: ベックマンコールター，インコーポレイテッド
Priority date: 2009-06-30
Filing date: 2010-06-24
Publication date: 2011-01-06
Also published as: JP2011013042A

Abstract

An automatic analysis device and a measurement method which are capable of performing multiple items of analysis processing using a simple configuration. An automatic analysis device (1) for performing analysis processing of a specimen by optically measuring the reaction between the specimen and a reagent. The automatic analysis device (1) comprises: a magnetic particle extraction unit (2) which is provided with a magnetic flux concentration member (24) having disposed therein a magnetic body for concentrating the magnetic flux of magnetic particles (B) from the inside of a reaction container (12) and retaining the magnetic particles (B), the magnetic particles (B) being contained in fluid which is held in the reaction container (12) and having bonded thereto a marker substance to be measured, the magnetic particle extraction unit (2) being adapted to extract the magnetic particles (B) to the outside of the reaction container (12); and a magnetic particle measuring unit (10) which optically measures the marker substance bonded to the magnetic particles (B) extracted to the outside of the reaction container (12) by the magnetic particle extraction unit (2).

Description

Automatic analyzer and measuring method

The present invention relates to an automatic analyzer and a measuring method for performing analysis processing of a specimen by measuring optical characteristics of a reaction product of a specimen and a reagent containing magnetic particles.

In recent years, with the trend of labor saving in laboratories, biochemical analysis and immunological analysis integrated devices equipped with modules corresponding to various immunological analysis items in biochemical analysis devices and automatic analysis devices Complex devices incorporating chemical analysis modules and immunological analysis modules have been developed.

Furthermore, an automatic analyzer that includes a detector such as a turbidity meter and a turbidimetric meter in one analysis unit and can perform a plurality of items of analysis processing in one system is disclosed (for example, Patent Documents). 1).

Special table 2007-536500 gazette

However, the automatic analyzer shown in Patent Document 1 needs to use a reaction container corresponding to each item for each measurement item. Therefore, a plurality of types of reaction vessels have to be arranged, and the apparatus configuration is complicated.

The present invention has been made in view of the above, and an object of the present invention is to provide an automatic analyzer and a measurement method capable of performing analysis processing of a plurality of items with a simple configuration.

In order to solve the above-described problems and achieve the object, the automatic analyzer of the present invention (1) collects and holds the magnetic particles from inside a reaction vessel containing a fluid containing magnetic particles to be measured. A magnetic particle take-out part that has a magnetic collecting member on which a magnetic material is arranged and takes out the magnetic particles out of the reaction container; and (2) is coupled to the magnetic particles taken out of the reaction container by the magnetic particle take-out part. And a magnetic particle measuring unit for optically measuring the labeled substance.

In the above-described automatic analyzer of the present invention, the magnetic body is a permanent magnet.

In the above-described automatic analyzer of the present invention, the magnetic body is an electromagnet.

In the automatic analyzer of the present invention, the magnetic flux collecting member is a covering member that covers the magnetic body.

Moreover, in the above-described automatic analyzer of the present invention, the magnetic body is movable in the covering member.

In the above-described automatic analyzer of the present invention, the covering member can be attached to and detached from the magnetic body.

Further, the automatic analyzer according to the present invention for optically measuring the reaction between the sample and the reagent and performing the analysis process of the sample, the sample and the reagent for the first analysis process, or the first A reaction table holding a plurality of the same reaction vessels capable of accommodating the sample for analysis of 2 and the reagent containing magnetic particles, and the sample and reagent for the first analysis, or A dispensing part that dispenses the specimen and the reagent containing the magnetic particles for the second analysis process; and a magnetic collecting member in which a magnetic material that collects and holds the magnetic particles in the reaction container is disposed. A magnetic particle extraction unit that extracts the magnetic particles out of the reaction vessel, and a magnetic particle measurement unit that performs optical measurement for the second analysis process using the magnetic particles extracted by the magnetic particle extraction unit; Said And a measurement unit for performing optical measurement on the analysis process.

In addition, the automatic analyzer according to the present invention further includes a magnetic flux collecting member cleaning unit for cleaning the magnetic flux collecting member.

In the above-described automatic analyzer of the present invention, the magnetic flux collecting member is a covering member that covers the magnetic body and is detachable from the magnetic body, and a covering member discarding unit that discards the covering member; A covering member supply unit that supplies a covering member.

Further, in the above-described automatic analyzer of the present invention, the reaction table includes a plurality of the same reaction containers arranged at predetermined intervals, and is driven according to processing to sequentially move each reaction container to each processing position. . The interval at which the dispensing unit dispenses the reaction container for the second analysis process on the reaction table is equal to the time required for the measurement unit to perform the optical measurement with respect to the time required for the magnetic particle measurement unit to perform the optical measurement. It is an integer value greater than or equal to the ratio.
In various embodiments, the automated analyzer of the present invention includes any one or more of the features described above.

Further, the measuring method of the present invention includes a magnetic flux collecting step for collecting and holding magnetic particles in a fluid accommodated in a reaction vessel, and the collected magnetic particles at a predetermined measurement position outside the reaction vessel. And a measuring step for optically measuring the labeling substance bound to the magnetic particles transferred to the measurement position.
The present invention is also a computer-readable recording medium recording a program for executing a measurement method for performing an optical measurement of a labeling substance bound to magnetic particles, the measurement method comprising:
A magnetic flux collecting step for collecting and holding magnetic particles in the fluid contained in the reaction vessel;
A transfer step of transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel;
A measurement step for performing an optical measurement of the labeling substance bound to the magnetic particles transferred to the measurement position;
A recording medium is provided.
The present invention is also a program for executing a measurement method for optically measuring a labeling substance bound to magnetic particles, the measurement method comprising:
A magnetic flux collecting step for collecting and holding magnetic particles in the fluid contained in the reaction vessel;
A transfer step of transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel;
A measurement step for performing an optical measurement of the labeling substance bound to the magnetic particles transferred to the measurement position;
A program including

The automatic analyzer and measurement method according to the present invention collects and holds the magnetic particles accommodated in the reaction vessel, takes out of the reaction vessel, and optically measures them. There is an effect that the analysis process can be performed efficiently.

FIG. 1 is a schematic diagram showing a configuration of an automatic analyzer according to an embodiment of the present invention. FIG. 2 is a cross-sectional view showing a cross section of the magnetic flux collecting member shown in FIG. FIG. 3 is a schematic diagram showing a conventional immunoassay process. FIG. 4 is a schematic diagram showing an immunoassay process according to the embodiment of the present invention. FIG. 5 is a cross-sectional view showing a first modification of the magnetic flux collecting member shown in FIG. FIG. 6 is a cross-sectional view showing a second modification of the magnetic flux collecting member shown in FIG. FIG. 7 is a schematic diagram showing the configuration of the automatic analyzer according to the embodiment of the present invention. FIG. 8 is a schematic diagram showing the configuration of the magnetic particle cleaning unit shown in FIG. FIG. 9 is a schematic view showing a modification of the magnetic particle cleaning unit shown in FIG. FIG. 10 is a schematic diagram showing an analysis cycle example 1 for the reaction vessel of the reaction table shown in FIG. FIG. 11 is a schematic diagram showing an analysis cycle example 2 for the reaction vessel of the reaction table shown in FIG. FIG. 12 is a flowchart showing analysis processing performed by the automatic analyzer shown in FIG. FIG. 13 is a schematic diagram showing a modification of the automatic analyzer shown in FIG.

Hereinafter, an embodiment for carrying out the automatic analyzer and the magnetic particle measuring method of the present invention will be described with reference to the drawings. The present invention is not limited to the embodiments and modifications illustrated below, and various modifications can be made without departing from the spirit of the present invention. In the description of the drawings, the same parts are denoted by the same reference numerals.

FIG. 1 is a schematic diagram showing a configuration of an automatic analyzer according to an embodiment of the present invention. The automatic analyzer 1 shown in FIG. 1 performs photometry of a magnetic particle extraction unit 2 that extracts magnetic particles accommodated in a reaction vessel 12 and a labeling substance that is bonded to the magnetic particles extracted by the magnetic particle extraction unit 2. And a magnetic particle measuring unit 10 to be performed.

The magnetic particle extraction unit 2 includes a support column 21 that can be moved up and down and rotated by a drive unit 22, and an arm 23 that is supported by the support column 21 and has a magnetic collecting member 24 that collects and holds magnetic particles on the other side. In addition, under the control of the control unit 11, the drive unit 22 moves the magnetic flux collecting member 24 by moving the column 21 up and down or rotationally. The magnetic particles B accommodated in the reaction vessel 12 are collected at the tip of the magnetic collecting member 24 and transferred to the magnetic particle measuring unit 10. In the magnetic flux collecting member 24, the magnetic material is covered with a chemically resistant resin such as Teflon (registered trademark).

The magnetic particle measuring unit 10 has a measurement mechanism capable of measuring the intensity of each wavelength light by a light receiving element such as a PDA, and the magnetic collecting member 24 collecting the magnetic particles B is inserted into the measurement hole 10a. Then, the measurement process is directly performed on the magnetic particles B. Here, the magnetic flux collecting member 24 is provided with a flange portion 24a. The flange portion 24a is a circle having a slightly smaller diameter than the measurement hole 10a, and the magnetic flux collection member 24 is inserted into the measurement hole 10a. In this case, the measurement hole 10a is closed. As a result, it is possible to prevent light from entering the measurement hole 10a from the outside. The measured light amount information is output to the control unit 11, and the control unit 11 calculates an analysis value based on the obtained light amount information.

In the automatic analyzer 1 described above, under the control of the control unit 11, the magnetic collecting member 24 of the magnetic particle extraction unit 2 collects and holds the magnetic particles B accommodated in the reaction vessel 12, and the driving unit 22. The magnetic particles B collected by driving the columns 21 are transferred to the magnetic particle measuring unit 10 and the magnetic particle measuring unit 10 performs a measurement process. Thereby, it becomes possible to take out only the magnetic particle which is a measuring object, and a highly accurate analysis process can be performed. By incorporating the configuration of the automatic analyzer 1 into another analyzer, the analysis process using magnetic particles can be performed individually on the reaction vessels that are sequentially transported. Analysis is possible even if the reaction vessels are the same, without the need to carry out in the reaction vessel.

Here, the magnetic flux collecting member 24 will be described with reference to FIG. FIG. 2 is a cross-sectional view showing a cross section of the magnetic flux collecting member 24 shown in FIG. The magnetism collecting member 24 is formed using a chemical resistant resin such as Teflon (registered trademark), and a magnetic body 241 is inserted therein. As the magnetic body 241, a permanent magnet is used, and as shown in FIG. 2, the bottom end is formed in a conical shape, and magnetic particles to be magnetized gather together. Note that a magnetic material such as a metal processed into a cone shape may be used at the tip of the columnar permanent magnet, or an electromagnet may be used as the magnetic body. Moreover, the collar part 24a may be formed using Teflon (trademark), may use other chemical-resistant resin, and may be formed separately. When formed as a separate body, the flange portion 24a can be moved up and down, so that the height of the flange portion 24a can be adjusted according to the height of the measurement hole 10a.

Next, a conventional immune analysis process and an immune analysis process according to an embodiment of the present invention will be described. First, a conventional immune analysis process will be described with reference to FIG. In the conventional immunoassay process, as shown in FIG. 3 (1), a first reagent dispensing process is performed in which a first reagent containing antibody solid phase magnetic particles 41 is dispensed in a reaction container 30. Thereafter, as shown in FIG. 3 (2), a sample dispensing process is performed in which a sample containing the antigen 42 to be analyzed is dispensed in the reaction container 30. In the antibody solid phase magnetic particles 41, an antibody against the antigen 42 in the specimen is solid phased on a magnetic particle carrier. Then, as shown in FIG. 3 (3), after the reaction vessel 30 is agitated, a reaction product 44 in which the antigen 42 in the specimen and the antibody solid phase magnetic particles 41 are combined is generated after a predetermined reaction time. Is done.

Next, in the conventional analysis, the first BF cleaning process for the first time in the BF cleaning mechanism is performed. In the first BF cleaning process, as shown in FIG. 3 (3), the reactant 44 and the antibody solid phase magnetic particles 41 are collected in the vicinity of the magnetic collecting mechanism 31 for collecting the magnetic material by the BF cleaning nozzle 32. By injecting and suctioning the cleaning liquid, the unreacted substance 43 in the reaction vessel 30 is removed. As a result, as shown in FIG. 3 (4), the unreacted substance 43 is separated and removed in the reaction vessel 30, and the antibody solid phase magnetic particles 41 and the reactant 44 remain.

In the conventional analysis, as shown in FIG. 3 (4), a second reagent dispensing process for dispensing a reagent containing the labeling substance 45 as the second reagent in the reaction container 30 after the first BF cleaning process is performed. Done. As a predetermined reaction time elapses, an immune complex 46 in which the reaction product 44 and the labeling substance 45 are combined is generated as shown in FIG.

In the conventional analysis, as shown in FIG. 3 (5), the second BF cleaning process for the second time in the BF cleaning mechanism is performed. In the second BF cleaning process, as in the first BF cleaning process, the cleaning liquid is injected and sucked by the BF cleaning nozzle 32 in a state where the magnetic material is collected in the vicinity of the magnetic flux collecting mechanism 31. In other words, in the second BF cleaning process, the reaction is performed by injecting and sucking the cleaning liquid by the BF cleaning nozzle 32 in a state where the immune complex 46 and the antibody solid phase magnetic particles 41 are collected in the vicinity of the magnetic collecting mechanism 31. Unbound labeling substance 45 in container 30 is removed. As a result, the antibody solid phase magnetic particles 41 and the immune complex 46 remain in the reaction vessel 30.

Then, the irradiation treatment of the excitation light Le corresponding to the labeling substance 45 to be excited is performed on the reaction vessel 30. In the reaction container 30, light L1 is emitted in proportion to the amount of the labeling substance 45 bound as the immune complex 46. Next, a measurement process for measuring the light amount of the light L1 emitted from the immune complex 46 is performed, and an arithmetic process for obtaining the concentration of the antigen 42 based on the light emission amount of the labeling substance 45 measured in the measurement process is performed. (FIG. 3 (6)).

Thus, in the conventional analysis, the unreacted substance 43 in the sample and the labeling substance 45 unbound with the reactant 44 are removed by performing the BF washing treatment twice, and the immune complex to be measured Only 46 is obtained and measurement processing is performed.

Subsequently, an immune analysis process using the automatic analyzer according to the embodiment of the present invention will be described with reference to FIG. FIG. 4 is a schematic diagram showing an immunoassay process according to the embodiment of the present invention. First, the first reagent containing the antibody solid phase magnetic particles 41, the specimen containing the antigen 42 to be analyzed, and the second reagent containing the labeling substance 45 are respectively dispensed into the reaction container 30 (FIG. 4A). After dispensing the specimen, the first reagent, and the second reagent, stirring and reaction processing are performed to bind the antibody solid phase magnetic particles 41, the antigen 42 to be analyzed, and the labeling substance 45 (FIG. 4B). By this reaction process, the reacted immune complex 46, the unreacted antibody solid phase magnetic particles 41, the unreacted substance 43 contained in the specimen, and the unreacted labeling substance 45 are present in the reaction container 30.

After completion of the reaction process in FIG. 4B, the magnetism collecting member 24 is inserted into the reaction vessel 30 (FIG. 4C). After descending the magnetic collecting member 24 to a predetermined position, the magnetic collecting member 24 is stopped in the reaction vessel 30 for a predetermined time, and the immune complex 46 and the antibody solid phase magnetic particles 41 are collected (FIG. 4D). . After collecting the magnetism for a predetermined time, the magnetism collecting member 24 is extracted from the reaction container 30 (FIG. 4E). When the magnetism collecting member 24 is extracted, the immune complex 46 and the antibody solid phase magnetic particles 41 are taken out of the reaction container 30, and unreacted substances 43 and labeling substances 45 that are not measurement targets remain in the reaction container 30. .

The immune complex 46 and the antibody solid phase magnetic particles 41 taken out of the reaction container 30 in FIG. 4 (e) are transferred to the measurement unit (FIG. 4 (f)), and are transferred to the immune complex 46 in the measurement unit. The labeling substance 45 to be bound is irradiated with the excitation light Le, and the amount of light L2 emitted from the excited labeling substance 45 is measured (FIG. 4G).

By performing the series of immunological analysis processes described above, it is possible to collect the immune complex 46 to be measured without performing the BF washing process, and to remove the unreacted labeling substance 45 and perform the measurement process. It is possible to perform high-analysis processing. Further, since the magnetic flux can be collected in the fluid as compared with the magnetic flux collection from the side surface of the reaction vessel 30, the magnetic flux collection efficiency is improved and the time required for the analysis process can be shortened.

Here, a modified example of the magnetic flux collecting member 24 shown in FIG. 2 will be described with reference to FIGS. FIG. 5 is a cross-sectional view showing Modification 1 of the magnetic flux collecting member 24 shown in FIG. In Modification 1 shown in FIG. 5, the bottom of the magnetic flux collecting member 25 is formed in a substantially conical shape. By forming the bottom in a substantially conical shape, it is possible to suppress turbulence of the fluid when entering the fluid in the reaction vessel, and to perform analysis processing without dissociating even for reactions with weak binding force it can.

When the measurement process is completed, the magnetic collecting member 24 is washed with a cleaning agent to remove the magnetic particles collected. In order to further facilitate cleaning of the magnetic particles, the magnetic body inside the magnetic flux collecting member may be moved inside, and a distance may be provided between the magnetic body and the magnetic particles. 6 is a cross-sectional view showing a second modification of the magnetic flux collecting member 24 shown in FIG. The magnetic flux collecting member 26 shown in FIG. 6 is configured such that the magnetic body 241 can move inside the magnetic flux collecting member 26. When the magnetic body 241 moves upward in the magnetic flux collecting member 26, the adhesion force of the magnetic particles collected at the bottom to the magnetic flux collecting member 26 is reduced, and the magnetic particles can be easily cleaned. The magnetic body 241 is moved, for example, by providing a plurality of rollers for gripping the magnetic body 241 inside the magnetic flux collecting member 26 or at the tip of the arm 23, and electrically rotating the rollers to move the magnetic flux collecting member 26 inside. Can be moved up and down. In addition, you may make it replace a coating | coated member for every use as a magnetic collecting member as a coating | coated member which can be attached or detached with a magnetic body. Furthermore, the covering member may be attached only to the liquid intrusion portion of the magnetic body or the magnetic flux collecting member. Here, the magnetic body insertion hole 26a is preferably formed to have a slight space with the magnetic body 241 in order to smoothly insert and remove the magnetic body 241.

Furthermore, when the above-described magnetic particle extraction unit and measurement unit are incorporated in an automatic analyzer that performs biochemical analysis and analysis processing is performed, the configuration shown in FIG. 7 can be applied. FIG. 7 is a schematic diagram showing a configuration of the automatic analyzer 5 according to the embodiment of the present invention. The automatic analyzer 5 shown in FIG. 7 includes a measurement mechanism 6 that dispenses a specimen and a reagent to be analyzed into the reaction container 51 and optically measures a reaction that occurs in the reaction container 51, and a measurement mechanism 6. A control mechanism 7 that controls the entire automatic analyzer 5 and analyzes the measurement result in the measurement mechanism 6 is provided. The automatic analyzer 5 automatically and sequentially performs biochemical analysis for detecting the concentration of the detection target in the sample by cooperation of these two mechanisms.

First, the measurement mechanism 6 will be described. The measurement mechanism 6 is roughly divided into a reaction table 60, a first reagent storage 61, a first reagent dispensing mechanism 62, a sample transfer unit 63, a sample dispensing mechanism 64, a second reagent storage 65, a second reagent dispensing mechanism 66, A stirring unit 67, a measuring unit 68, and a cleaning unit 69 are provided.

The reaction table 60 transfers the reaction container 51 to a predetermined position in order to dispense a sample or reagent into the reaction container 51, to stir, wash or measure the reaction container 51. This reaction table 60 is rotatable about a vertical line passing through the center of the reaction table 60 as a rotation axis by driving a drive mechanism (not shown) under the control of the control unit 71. An openable / closable lid and a thermostat (not shown) are provided above and below the reaction table 60, respectively.

The first reagent container 61 can store a plurality of first reagent containers 61a in which the first reagent to be dispensed first among the two types of reagents dispensed in the reaction container 51 is accommodated. In the first reagent storage 61, a plurality of storage chambers are arranged at equal intervals, and a first reagent container 61a is detachably stored in each storage chamber. The first reagent storage 61 rotates clockwise or counterclockwise about a vertical line passing through the center of the first reagent storage 61 as a driving mechanism (not shown) is driven under the control of the control unit 71. The desired first reagent container 61a is transferred to the reagent aspirating position by the first reagent dispensing mechanism 62. An openable / closable lid (not shown) is provided above the first reagent storage 61. Further, the first reagent storage 61 is kept cold. For this reason, when the first reagent container 61a is stored in the first reagent container 61 and the lid is closed, the reagent stored in the first reagent container 61a is kept in a cold state and the first reagent container 61a Evaporation and denaturation of the reagent contained in the container can be suppressed.

A recording medium on which reagent information related to the reagent stored in the first reagent container 61a is recorded is attached to the side surface of the first reagent container 61a. For example, the recording medium records analysis items in which the reagent stored in the first reagent container 61a is used, reagent names, lot information, bottle information, and the like. The recording medium displays various encoded information and is optically read.

A first reagent reading unit 61b that optically reads the recording medium is provided on the outer periphery of the first reagent storage 61. The first reagent reading unit 61b reads the information on the recording medium by emitting infrared light or visible light to the recording medium and processing the reflected light from the recording medium. In addition, the first reagent reading unit 61b may capture the recording medium, decode the image information obtained by the imaging process, and acquire the recording medium information. The first reagent reading unit 61b outputs the read information of the recording medium to the control unit 71 in association with the position in the first reagent storage 61 of the first reagent container 61a to which the recording medium is attached.

The first reagent dispensing mechanism 62 includes an arm 62a to which a probe for aspirating and discharging the first reagent is attached to the tip. The arm 62a freely moves up and down in the vertical direction and rotates around a vertical line passing through its base end as a central axis. The first reagent dispensing mechanism 62 includes a suction / discharge mechanism using a suction / discharge syringe or a piezoelectric element (not shown). The first reagent dispensing mechanism 62 sucks into the probe the reagent in the first reagent container 61a corresponding to the analysis item designated by the sample to be analyzed that has been moved to a predetermined position on the first reagent container 61. Then, the arm 62a is rotated clockwise in the figure and dispensed into the reaction container 51 conveyed to a predetermined position on the reaction table 60. In addition, the first reagent dispensing mechanism 62 is provided with a sensor that can detect the liquid surface height by utilizing a change in capacitance at the tip of the probe, and the reagent contained in each detected first reagent container 61a. Is output to the control unit 71.

The sample transfer unit 63 includes a plurality of sample racks 63b that hold a plurality of sample containers 63a that store liquid samples such as blood and urine, and sequentially transfer them in the direction of the arrows in the figure. The sample in the sample container 63a transferred to a predetermined position on the sample transfer unit 63 is dispensed by the sample dispensing mechanism 64 into the reaction container 51 that is arranged and transported on the reaction table 60. A recording medium on which sample information related to the sample stored in the sample container 63a is recorded is attached to the side surface portion of the sample container 63a. The sample information includes information on the provider who provided the sample, an analysis item instructed to analyze the sample stored in the sample container 63a, and the collection date of the sample.

A sample reading unit 63c that optically reads the recording medium attached to the sample container 63a is provided outside the sample transfer unit 63. Similar to the first reagent reading unit 61b, the sample reading unit 63c emits infrared light or visible light to the recording medium, and reads the information on the recording medium by processing the reflected light from the recording medium. Further, the sample reading unit 63c may acquire the information on the recording medium by performing an imaging process on the recording medium and decoding the image information obtained by the imaging process. The sample reading unit 63c outputs the read sample information to the control unit 71.

Similar to the first reagent dispensing mechanism 62, the sample dispensing mechanism 64 includes an arm 64a in which a probe for aspirating and discharging the sample is attached to the tip, and an intake / exhaust mechanism using an unillustrated intake / exhaust syringe or piezoelectric element. Prepare. The sample dispensing mechanism 64 sucks the sample into the probe from the sample container 63a transferred to the predetermined position on the sample transfer unit 63 described above, and rotates the arm 64a counterclockwise in the drawing to dispense the sample. To do.

The second reagent container 65 can store a plurality of second reagent containers 65a in which the second reagent to be dispensed after the sample is dispensed among the two types of reagents dispensed in the reaction container 51 is accommodated. Similar to the first reagent storage 61, the second reagent storage 65 is provided with a plurality of storage chambers in which the second reagent containers 65a are detachably stored. Similar to the first reagent storage 61, the second reagent storage 65 can be rotated clockwise or counterclockwise, and the desired second reagent container 65a is transferred to the reagent suction position by the second reagent dispensing mechanism 66. To do. Similar to the first reagent storage 61, an openable / closable lid (not shown) is provided above the second reagent storage 65, and the second reagent storage 65 is kept cold. Similar to the first reagent container 61a, a recording medium on which reagent information related to the second reagent stored in the second reagent container 65a is recorded is attached to the side surface of the second reagent container 65a. In addition, a second reagent reading unit 65b that has the same function as the first reagent reading unit 61b and optically reads a recording medium attached to the second reagent container 65a is provided on the outer periphery of the second reagent storage 65. It has been.

Similar to the first reagent dispensing mechanism 62, the second reagent dispensing mechanism 66 uses an arm 66a to which a probe for aspirating and discharging the second reagent is attached to the tip, and an unillustrated suction / discharge syringe or piezoelectric element. A reaction table after aspirating the reagent in the second reagent container 65a corresponding to the analysis item designated by the sample to be analyzed that has been moved to a predetermined position on the second reagent storage 65 into the probe. Dispense into the reaction container 51 conveyed to the predetermined position on 60. In addition, the second reagent dispensing mechanism 66 is provided with a sensor that can detect the liquid surface height by utilizing a change in capacitance at the tip of the probe, and the reagent contained in each detected second reagent container 65a. Is output to the control unit 71. The stirring unit 67 stirs the first reagent, the sample, and the second reagent dispensed in the reaction container 51 to promote the reaction.

The measuring unit 68 emits light of a predetermined wavelength to the reaction vessel 51, receives the light that has passed through the reaction solution of the reagent in the reaction vessel 51 and the sample, performs spectral intensity measurement, and measures absorbance and the like. The measurement result by the measurement unit 68 is output to the control unit 71 and analyzed by the analysis unit 73. The measurement unit 68 may be configured to irradiate the reaction vessel 51 with white light and to detect the output of a predetermined wavelength by transmitting the reaction solution and then performing spectroscopy.

The cleaning unit 69 sucks and discharges the mixed liquid in the reaction vessel 51 that has been measured by the photometric unit 68 by a nozzle (not shown), and performs cleaning by injecting and sucking cleaning liquid such as detergent and cleaning water. . The washed reaction vessel 51 is reused. Depending on the contents of the inspection, the reaction vessel 51 may be discarded after completion of one measurement, and a new reaction vessel 51 may be automatically supplied although not shown.

Next, the control mechanism 7 will be described. The control mechanism 7 includes a control unit 71, an input unit 72, an analysis unit 73, a storage unit 74, a transmission / reception unit 75, and an output unit 76. These units included in the measurement mechanism 6 and the control mechanism 7 are electrically connected to the control unit 71.

The control unit 71 is configured using a CPU or the like, and controls processing and operation of each unit of the automatic analyzer 5. The control unit 71 performs predetermined input / output control on information input / output to / from each of these components, and performs predetermined information processing on this information. The control unit 71 also sets the liquid level height of the reagent stored in each first reagent container 61a and each second reagent container 65a detected by the first reagent dispensing mechanism 62 and the second reagent dispensing mechanism 66. Originally, the amount of reagent in each first reagent container 61a and each second reagent container 65a installed in the automatic analyzer 5 is detected.

The input unit 72 is configured by using a keyboard, a mouse, and the like, and acquires various information necessary for analyzing the specimen, instruction information for analysis operation, and the like from the outside. The analysis unit 73 obtains the concentration of the detection target in the sample based on the absorbance measured by the measurement unit 68 and performs component analysis of the sample. The storage unit 74 is configured by using a hard disk that magnetically stores information and a memory that loads various programs related to the processing from the hard disk and electrically stores them when the automatic analyzer 5 executes the processing. Various information including the analysis result of the specimen is stored. The storage unit 74 may include an auxiliary storage device that can read information stored in a storage medium such as a CD-ROM, a DVD-ROM, or a PC card.

The transmission / reception unit 75 has a function as an interface for performing transmission / reception of information according to a predetermined format via a communication network (not shown). The output unit 76 is configured using a printer, a speaker, and the like, and outputs various information including the analysis result of the sample. The output unit 76 is configured using a display, and includes a display unit that displays and outputs the analysis result of the sample and various selection menus.

As described above, the automatic analyzer 5 operates under the control of the control unit 71, and the sample dispensing mechanism 64 supplies the plurality of reaction containers 51 conveyed along the circumferential direction by the rotating reaction table 60. Samples are sequentially dispensed from a plurality of sample containers 63a held in the sample rack 63b.

Reagent dispensing mechanisms

62 and 66 sequentially dispense reagents from the

reagent containers

61a and 65a into the reaction container 51 into which the specimens are sequentially dispensed. The reaction container 51 into which the reagent and the sample are dispensed is sequentially stirred by the stirring unit 67 every time the reaction table 60 stops, and the reagent and the sample react with each other. When the reaction table 60 rotates again, the measurement unit 68 is rotated. Pass through. At this time, the reaction liquid in which the reagent in the reaction container 51 has reacted with the sample is photometrically measured by the measuring unit 68 and the component concentration and the like are analyzed by the analyzing unit 73. Then, after the photometry of the reaction liquid is completed, the reaction container 51 is transferred to the cleaning unit 69 and cleaned, and then used again for analyzing the specimen.

The biochemical analysis process proceeds with the above configuration. Further, here, the measurement mechanism 6 is provided with a magnetic particle extraction unit 52 and a magnetic particle measurement unit 53, which are driven when performing analysis processing using magnetic particles such as immunological analysis processing.

As in the case of the magnetic particle extraction unit 2 shown in FIG. 1, the magnetic particle extraction unit 52 reacts when the arm 52a having a magnetic collecting member at the tip is driven up and down or rotated under the control of the control unit 71. The magnetic particles in the container 51 are taken out of the reaction container 51.

The magnetic particle measurement unit 53 measures the labeling substance bound to the magnetic particles transferred by the magnetic particle extraction unit 52, similarly to the magnetic particle measurement unit 10 shown in FIG. The magnetic flux collecting member is inserted into the magnetic particle measuring unit 53 through the measurement hole 53a, and measurement is performed. The measurement result is output to the control unit 71 and analyzed by the analysis unit 73.

With the above-described configuration, the biochemical analysis process and the immune analysis process can be performed using the same reaction table and the same reaction container. Since analysis processing is possible using the same reaction vessel, analysis processing of a plurality of analysis items can be performed with a simple apparatus configuration. The first reagent store 61 and the second reagent store 65 contain biochemical and immunization reagents. In addition, a disposable tip is attached to each probe of the first reagent dispensing mechanism 62 and the second reagent dispensing mechanism 66 when dispensing each reagent, thereby preventing contamination.

Here, the magnetic particles that have been subjected to the measurement process in the magnetic particle measuring unit 53 are cleaned by the magnetic particle cleaning unit 54. FIG. 8 is a schematic diagram showing the configuration of the magnetic particle cleaning unit 54 shown in FIG. The magnetic particle cleaning unit 54 shown in FIG. 8 accommodates the magnetism collecting member 52b, and can receive a cleaning liquid or the like therein, a liquid inlet 541 provided on the side of the liquid receiving container 540, and a liquid A liquid discharge port 542 provided at the bottom of the receiving container 540. The liquid inlet 541 is connected to the liquid supply pipe 541a, and the other end of the liquid supply pipe 541a is connected to the three-way valve 543. The three-way valve 543 connects the cleaning liquid feeding pipe 541d and the water feeding pipe 541e, respectively, and the control unit 71 switches the opening and closing of each pipe to drive the

pumps

544 and 545 to drive the cleaning liquid tank 541b and the water tank 541c. These liquids are fed into the liquid receiving container 540.

Also, the liquid discharge port 542 connects the discharge pipe 542a, and sends the liquid in the liquid receiving container 540 to the waste liquid tank 542b. Here, the discharge pipe 542a is provided with an electromagnetic valve 542c, and the valve is opened / closed under the control of the control unit 71 to adjust the liquid stored in the liquid receiving container 540. In addition, the collar part 52c is formed corresponding to the measurement hole 53a of the magnetic particle measurement part 53 in FIG. 7, and shields the light from the outside in the measurement.

Furthermore, in order to improve the cleaning efficiency, the magnetic body 52d inside the magnetic flux collecting member 52b may be moved for cleaning. FIG. 9 is a schematic view showing a modification of the magnetic particle cleaning unit 54 shown in FIG. In the modification shown in FIG. 9, the magnetic body 52d fixed to the arm 52a moves upward as the arm 52a moves upward, thereby moving away from the bottom of the magnetism collecting member 52b. At this time, a gripping mechanism for gripping the magnetism collecting member 52b is provided at the tip of the arm 52a, and when the cleaning is performed, the magnetism collecting member 52b is released so that only the magnetic body 52d is extracted from the liquid receiving container 540, and the magnetism The adhesion of the particles to the magnetism collecting member 52b is reduced to facilitate cleaning. Here, the bottom part of the magnetic flux collecting member 52b is not in contact with the inner wall of the bottom part of the liquid receiving container 540 by the flange part 52c being supported by the end part of the liquid receiving container 540.

Next, the analysis cycle of each analysis item for the reaction vessel 51 arranged in the reaction table 60 will be described with reference to FIGS. 10 is a schematic diagram showing an analysis cycle example 1 for the reaction container of the reaction table shown in FIG. 7, and FIG. 11 is a schematic diagram showing an analysis cycle example 2 for the reaction container of the reaction table shown in FIG. Both analysis cycle examples 1 and 2 are based on the assumption that the biochemical analysis process A1 and the immune analysis process A2 are performed by the automatic analyzer 5.

An analysis cycle example 1 shown in FIG. 10 is a cycle example showing a case where the optical measurement time in the immunological analysis process A2 is three times as long as the optical measurement time in the biochemical analysis process A1, and the samples and reagents corresponding to the analysis items are It is the example of arrangement | positioning of the reaction container dispensed. As the reaction table 60 rotates, the measurement unit 68 sequentially performs measurements on the biochemical analysis process A1. Here, when the reaction container for performing the immunological analysis process A2 is set between the reaction containers for performing the biochemical analysis process A1, the reaction container for performing the next immunochemical analysis process A2 is performed twice with the biochemical analysis process A1. Set to do. By performing the two biochemical analysis processes A1 during the immunological analysis process A2, the reaction table 60 shown in FIG. ) And the analysis process can be continuously performed without stopping the rotation of the reaction table 60. Note that the time required for the magnetic flux collection process is preferably the same as the time required for the dispensing process.

Further, the analysis cycle example 2 shown in FIG. 11 is a cycle example showing a case where the optical measurement time in the immunological analysis process A2 is four times as long as the optical measurement time in the biochemical analysis process A1, depending on the analysis item. This is an example of a reaction container arrangement in which samples and reagents are dispensed. Similarly, in FIG. 11, the biochemical analysis process A1 is set to be performed three times while the immune analysis process A2 is performed. As described above, when the measurement time ratio between the immunological analysis process A2 and the biochemical analysis process A1 is n times, the biochemical analysis process A1 is performed n-1 times during the immunological analysis process A2. Even for a plurality of analysis items, continuous analysis processing can be performed. It is also possible to set an analysis period in consideration of the cleaning time and the like.

Next, analysis processing performed by the automatic analyzer 5 will be described with reference to FIG. FIG. 12 is a flowchart showing an analysis process performed by the automatic analyzer 5 shown in FIG. First, the control unit 71 confirms whether or not the item to be analyzed is an analysis including an immune analysis (step S102). When there is information indicating that immunoassay is to be performed from the input unit 72 (step S102: Yes), the control unit 71 dispenses the sample and reagent corresponding to the analysis item to the reaction container 51 in association with the analysis cycle described above. Each dispensing mechanism is instructed to do so (step S106). When dispensing of the specimen and the reagent is completed, the reaction containers 51 are stirred and reacted (step S108). When there is information indicating that the analysis does not include immunological analysis from the input unit 72 (step S102: No), the control unit 71 proceeds to step S104 and performs biochemical analysis processing.

When the reaction process in step S108 is completed, it is determined whether or not the measurement target for each reaction container 51 that is sequentially conveyed is an immunoassay (step S110). Here, when the reaction container 51 to be measured is an immunoassay (step S110: Yes), the control unit 71 instructs the magnetic particle extraction unit 52 and the magnetic particle measurement unit 53 to collect light and perform photometric processing. (Step S112). In step S110, when the measurement target reaction vessel 51 is biochemical analysis (step S110: No), the control unit 71 instructs the measurement unit 68 to perform photometric processing of the target reaction vessel 51 (step S110). S114).

When the photometric processing in steps S112 and S114 is completed, the control unit 71 confirms whether or not there is a reaction vessel 51 to be measured next (step S116). Here, when there exists the reaction container 51 which measures next (step S116: Yes), the control part 71 transfers to step S110, and judges the analysis item of the target reaction container 51. FIG. If there is no reaction vessel 51 to be measured next (step S116: No), the controller 71 checks whether or not there is a next analysis processing instruction (step S118), and if there is an analysis instruction (step S118). (S118: Yes), the process proceeds to step S102 and the above-described processing is repeated. If there is no analysis instruction (step S118: No), the analysis processing is terminated.

複数 By performing the above-described series of analysis processes, a plurality of items of analysis processes can be continuously performed. In addition, the reaction vessel 51 can use the same type of reaction vessel, and can be dealt with by simply assigning the sample and reagent according to the item to each reaction vessel 51 as appropriate, so that the analysis process can be efficiently performed with a simple apparatus configuration. It can be performed.

Further, when the magnetic flux collecting member is disposable and replaced every time it is used, it can be dealt with by providing a magnetic flux collecting member discarding portion 55 and a magnetic flux collecting member supply portion 56 as shown in FIG. Furthermore, the magnetic flux collecting member cleaning unit 54 shown in FIG. 7 may be provided, the number of uses may be set, cleaning may be performed within the number of uses, and the magnetic flux collecting member may be replaced when the number of uses has passed.

By using the automatic analyzer and the measurement method described above, the labeling substance bound to the magnetic particles and the specimen can be reliably captured, the unreacted labeling substance can be excluded, and the measurement process can be performed. Since it is not necessary to use this, it can be easily incorporated into another automatic analyzer and each analysis process can be performed efficiently. In addition, various analysis processes can be supported, and the analysis items include chemiluminescence, fluorescence, Raman spectroscopy, infrared spectroscopy, ultraviolet spectroscopy, etc. It can respond by adding.

The above-described method of the present invention described in FIG. 12 and the like can be executed entirely or partly by a computer having a CPU. In this case, the CPU collects and holds the magnetic particles in the fluid stored in the reaction vessel and transfers the collected magnetic particles to a predetermined measurement position outside the reaction vessel. A program for causing a computer to execute a measurement method including a transfer step and a measurement step of optically measuring the labeling substance bound to the magnetic particles transferred to the measurement position is executed. The program is stored in the memory. The program may be installed in the memory before the computer is shipped, or may be installed in the memory after the computer is shipped. The program may be installed in the memory by reading the program recorded on the recording medium, or the program downloaded via a network such as the Internet may be installed in the memory. In this way, a magnetic flux collecting step for collecting and holding the magnetic particles in the fluid accommodated in the reaction vessel, and a transfer step for transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel. And a computer installed with a program for executing a measurement method including an optical measurement of a labeling substance bound to the magnetic particles transferred to the measurement position is a fluid stored in a reaction vessel. A magnetic flux collecting step for collecting and holding the magnetic particles therein, a transferring step for transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel, and the magnetic particles transferred to the measurement position It functions as a measuring means or a measuring device including a measuring step for optically measuring the labeling substance bound to.

As a computer that can be used in the present invention, any computer including a CPU that executes various programs and a memory that stores various data can be used.

All or some of the functions in FIG. 12 described in detail above are not limited to being implemented by software (for example, a program. The functions of each step shown in FIG. 12 are implemented by hardware (for example, a circuit, a board, a semiconductor, etc.). Chip), or a combination of software and hardware.

As described above, the present invention has been exemplified using the preferred embodiment of the present invention, but the present invention should not be construed as being limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and references cited herein should be incorporated by reference in their entirety as if the contents themselves were specifically described herein. Understood.

This application claims priority to Japanese Patent Application No. 2009-156233, the entire contents of which are the same as those described in this specification. It should be understood that it should be incorporated as a component.

As described above, the automatic analyzer and the measurement method according to the present invention are useful for performing analysis processing using magnetic particles, and in particular, integrated analysis for performing analysis processing on the same table as biochemical analysis or the like. Suitable for equipment.

DESCRIPTION OF

SYMBOLS

1,5

Automatic analyzer

2,52 Magnetic particle extraction part 6 Measurement mechanism 7

Control mechanism

10,53 Magnetic

particle measurement part

10a,

53a Measurement hole

11,71

Control part

12,30,51 Reaction vessel 21 Support column 22

Drive part

24, 25, 26, 52b Magnetic

flux collecting members

24a,

52c Gutter part

241, 52d

Magnetic body

23, 52a, 62a, 64a, 66a Arm 31 Magnetic flux collecting mechanism 32 BF cleaning nozzle 54 Magnetic particle cleaning part 55 Magnetic flux collecting member discarding part 56 Magnetic flux collecting part Member supply section 60 Reaction table 61 First reagent storage 62 First reagent dispensing mechanism 63 Sample transfer section 64 Sample dispensing mechanism 65 Second reagent storage 66 Second reagent dispensing mechanism 67 Stirring section 68 Photometric section 69 Washing section 72 Input Unit 73 Analysis unit 74 Storage unit 75 Transmission / reception unit 76 Output unit B Magnetic particles

Claims

A magnetic particle take-out having a magnetic collecting member in which a magnetic material for collecting and holding the magnetic particles from a reaction vessel containing a fluid containing magnetic particles to be measured is disposed, and taking out the magnetic particles out of the reaction vessel And
A magnetic particle measuring unit for optically measuring the labeling substance bound to the magnetic particles taken out from the reaction container by the magnetic particle taking-out unit;
An automatic analyzer comprising:
The automatic analyzer according to claim 1, wherein the magnetic body is a permanent magnet.
The automatic analyzer according to claim 1, wherein the magnetic body is an electromagnet.
The automatic analyzer according to claim 1, wherein the magnetic flux collecting member is a covering member that covers the magnetic body.
The automatic analyzer according to claim 4, wherein the magnetic body is movable in the covering member.
The automatic analyzer according to claim 4, wherein the covering member is detachable from the magnetic body.
An automatic analyzer that optically measures a reaction between a sample and a reagent and performs analysis of the sample, and includes the following:
A reaction table holding a plurality of identical reaction vessels capable of accommodating the sample and the reagent for the first analysis process, or the reagent including the sample and the magnetic particles for the second analysis process;
A dispensing unit for dispensing the sample and the reagent for the first analysis process, or the reagent containing the sample and the magnetic particles for the second analysis process;
A magnetic particle take-out part that has a magnetic collecting member in which a magnetic body that collects and holds the magnetic particles in the reaction vessel is disposed, and takes out the magnetic particles out of the reaction vessel;
A magnetic particle measurement unit that performs optical measurement on the second analysis process using the magnetic particles extracted by the magnetic particle extraction unit; and
A measurement unit for performing optical measurement on the first analysis process;
An automatic analyzer comprising:
The automatic analyzer according to claim 7, further comprising a magnetic flux collecting member cleaning unit for cleaning the magnetic flux collecting member.
The automatic analyzer according to claim 7,
Here, the magnetic flux collecting member is a covering member that covers the magnetic body and is detachable from the magnetic body.
And here, the automatic analyzer is
A covering member discarding unit for discarding the covering member;
A covering member supply section for supplying a new covering member;
An automatic analyzer.
The automatic analyzer according to claim 7, wherein:
The reaction table arranges the plurality of the same reaction containers at a predetermined interval, and sequentially moves each reaction container to each processing position by driving according to the process,
The dispensing unit is an integer value equal to or greater than a ratio of a dispensing interval with respect to the second analytical processing reaction vessel, a ratio of the time required for the optical measurement by the measuring unit to the time required for the optical measurement by the magnetic particle measuring unit. To
Automatic analyzer.
A magnetic flux collecting step for collecting and holding magnetic particles in the fluid contained in the reaction vessel;
A transfer step of transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel;
A measurement step for performing an optical measurement of the labeling substance bound to the magnetic particles transferred to the measurement position;
Including a measuring method.
A computer-readable recording medium recording a program for executing a measurement method for optically measuring a labeling substance bound to magnetic particles, the measurement method comprising:
A magnetic flux collecting step for collecting and holding magnetic particles in the fluid contained in the reaction vessel;
A transfer step of transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel;
A measurement step for performing an optical measurement of the labeling substance bound to the magnetic particles transferred to the measurement position;
Including a recording medium.
A program for executing a measurement method for optically measuring a labeling substance bound to magnetic particles, the measurement method comprising:
A magnetic flux collecting step for collecting and holding magnetic particles in the fluid contained in the reaction vessel;
A transfer step of transferring the magnetically collected magnetic particles to a predetermined measurement position outside the reaction vessel;
A measurement step for performing an optical measurement of the labeling substance bound to the magnetic particles transferred to the measurement position;
Including the program.