WO2023127182A1

WO2023127182A1 - Automatic analysis device and automatic analysis method

Info

Publication number: WO2023127182A1
Application number: PCT/JP2022/026174
Authority: WO
Inventors: 純一近藤; 恭一岩橋; 智英浅井; 弘至高橋
Original assignee: 積水メディカル株式会社
Priority date: 2021-12-28
Filing date: 2022-06-30
Publication date: 2023-07-06
Also published as: JP7114794B1; JP2023097818A

Abstract

Provided is an automatic analysis device and an automatic analysis method with which it is possible to select whether mounting of a chip is necessary, and to measure β-D glucan and another target of testing at once while preventing contamination.　This automatic analysis device has control modes for controlling measurement sequences in which a plurality of reagents are dispensed into a reaction container in several additions by means of a reagent suction nozzle and agitated, and B/F separation is carried out to clean and dispose of a marker antibody which has not formed an immune complex. The measurement sequences include a first measurement sequence in which the B/F separation is carried out a specified number of times after the dispensing of the reagents, and a second measurement sequence in which the number of steps is reduced by omitting a prescribed number of times carrying out the B/F separation. The control modes include a first control mode which is executed during testing of a normal item and controls the first measurement sequence or the second measurement sequence without attaching a reagent chip to the end of the nozzle, and a second control mode which is executed during testing of a special item, attaches a reagent chip to the end of the nozzle, and controls the second measurement sequence.

Description

Automatic analysis device and automatic analysis method

The present invention relates to an automatic analyzer and an automatic analysis method that can obtain measurement information on various analysis items (test items) by treating and measuring samples (specimens) such as blood and urine with various reagents. .

Blood coagulation analyzers, electrochemiluminescence immunoassay (ECLIA) analysis and measurement devices, etc., treat biological samples such as blood and urine with various reagents and measure various test items (measurement items). Various forms of automated analyzers capable of obtaining measurement information regarding are known. For example, a specimen as a biological sample is dispensed from a specimen container into a reaction container, and the dispensed specimen is mixed with reagents corresponding to test items to perform various measurements and analyses.

By the way, various mechanisms and reaction containers, such as a mechanism for dispensing specimens and reagents, a reaction container (cuvette) for reacting specimens and reagents, and a mechanism for stirring specimens and reagents, are shared in the measurement of a plurality of test items. In the case of multi-item analyzers, measurement results may be erroneous due to contamination occurring between the respective reaction solutions and reagents. For example, if the reagent component of analysis item A contains a substance that participates in the reaction of analysis item B (reaction inhibition, promotion, etc.), when analysis item A and analysis item B are continuously measured, If the reagent for analysis item A contaminates the reagent for analysis item B, the reaction for analysis item A proceeds simultaneously with the reaction for analysis item B, which may cause an error in the measurement result. Therefore, in such multi-item analyzers, in order to avoid such contamination, instruments such as nozzle tips for aspirating specimens and reagents and reaction vessels (cuvettes) into which specimens are dispensed are usually , are exchanged each time a measurement (or reaction) is performed (see, for example, Patent Document 1).

JP 2020-60587 A

Conventional analyzers that use disposable reagent tips to prevent contamination between reagents consistently use disposable tips when dispensing reagents for all measurements. It was not possible to select whether or not to wear the Therefore, even when the chip mounting is unnecessary, it takes time to attach and detach the chip, which lengthens the overall measurement time and costs.

In addition, there are currently only dedicated analyzers for measuring specific test objects, especially β-D glucan, which is a major fungal cell wall component and a cardiomyopathy marker. When it was necessary to measure -D glucan and other test objects, it was necessary to use a dedicated analyzer for measuring β-D glucan and another analyzer separately ( equipment had to be used). That is, since one apparatus cannot complete the measurement of all test items including β-D glucan measurement, a dedicated machine had to be intervened in the middle of the measurement to measure β-D glucan. Therefore, continuous inspection cannot be performed, and the entire inspection time required to complete the measurement of all inspection items is lengthened. , and the measurement accuracy may decrease. In addition, if the examination time becomes long in this way, there is concern about deterioration (change in property) of the sample over time and a decrease in measurement accuracy associated therewith.

Therefore, it is desirable to be able to measure β-D glucan and other test objects with a single analyzer. However, since β-D glucan is a component that exists as normal bacteria, in order to accurately measure its abundance in the blood, consumables such as nozzle tips and reaction vessels must contain β-D glucan. It is required to be uncontaminated, ie β-D glucan free. At present, many problems still remain and it is not easy to perform multiple analyzes including β-D glucan in the same apparatus while preventing such contamination.

The present invention has been made with a focus on the above-mentioned problems, and it is possible to select whether or not to attach a chip as needed, and to separate β-D glucan from other test objects while preventing contamination. An object of the present invention is to provide an automatic analyzer and an automatic analysis method that enable batch measurement.

In order to achieve the above object, the present invention comprises a reaction section that holds a reaction container into which a specimen is dispensed, and a reagent supply section that supplies a reagent. By reacting with and measuring the reaction process or reaction result, measurement information is obtained regarding a specific test item for measuring β-D glucan in a sample and a normal test item for measuring other test objects Automatic In an analyzer, a test item selection unit for alternatively selecting the specific test item and the normal test item; a nozzle moving mechanism for moving a suction nozzle for suctioning a specimen and a reagent within the device; A sample chip supply unit for supplying a disposable sample chip attached to the tip of a sample aspiration nozzle, the sample chip supply unit supplying a first sample chip used when a normal test item is selected by the test item selection unit. a first sample chip supply unit; and a second sample chip supply unit that supplies a β-D glucan-free second sample chip used when a specific test item is selected by the test item selection unit. and a reagent chip supply unit for supplying a β-D glucan-free disposable reagent chip attached to the tip of a reagent suction nozzle when a specific test item is selected by the test item selection unit. , and a controller for controlling the operation of each part of the device and the nozzle moving mechanism, the controller using the reagent suction nozzle to dispense and agitate the plurality of types of reagents into the reaction vessel in several batches. and a control mode for controlling a measurement sequence for performing B/F separation for washing and discarding the labeled antibody that has not formed an immune complex, and the measurement sequence performs B/F separation for a specified number of times after reagent dispensing. A first measurement sequence, and a second measurement sequence in which the number of steps is reduced compared to the first sequence by omitting B/F separation a predetermined number of times after reagent dispensing, and the control mode includes: Executed when the normal test item is selected by the test item selection unit, and controls the first measurement sequence or the second measurement sequence without attaching the reagent chip to the tip of the reagent suction nozzle. and a first control mode that is executed when the specific test item is selected by the test item selection unit, and controls the second measurement sequence with attachment of the reagent chip to the tip of the reagent suction nozzle. and a second control mode for

According to the automatic analyzer having the above configuration, measurement information regarding specific test items for measuring β-D glucan and normal test items for measuring other test objects can be obtained with a single device. -Because all inspection items, including D-glucan measurement, can be completed with a single device, there is no need to use a dedicated machine to measure β-D-glucan as in the past (need to use different devices) do not have). Therefore, continuous inspection becomes possible, and the overall inspection time until the measurement of all inspection items is completed can be shortened. Measurement accuracy can also be improved by minimizing the impact of time loss on measurement accuracy. In addition, since the test time is shortened by the continuous test, it is not affected by deterioration (change in property) of the specimen over time, so that more accurate measurement values can be obtained. Furthermore, since the control mode can be selected according to the inspection item (it is possible to select whether or not the reagent chip is attached and the measurement sequence can be selected), a measurement sequence suitable for the inspection object can be realized. That is, by adopting a second measurement sequence with a small number of steps in a specific test item for measuring β-D glucan and using a β-D glucan-free disposable reagent chip, the opportunity to be exposed to the risk of contamination is reduced as much as possible. can be less. Therefore, it is possible to reduce the contamination risk and improve the measurement accuracy.

In the above configuration, the first measurement sequence includes: a first step of inducing a first reaction by dispensing and stirring a sample diluent and a sample as a first reagent into a reaction container; Antibody-bound magnetic beads are added as a second reagent to the reaction solution obtained in step 1 to cause a second reaction, and the magnetic beads after the reaction are captured with a magnet to draw out the liquid in the reaction vessel, followed by a washing solution. a second step of performing a first B/F separation in which the magnetic beads are washed with to remove non-specific binding substances other than the antigen-antibody reaction, and a ruthenium complex as a third reagent in the liquid after the second step A third reaction is caused by adding a labeled antibody, the magnetic beads after the reaction are captured with a magnet, the liquid in the reaction vessel is extracted, and the magnetic beads are washed with a washing solution to remove non-specific binding substances other than the antigen-antibody reaction. and a third step of removing a second B/F separation, wherein said second measurement sequence preferably consists of said first measurement sequence omitting said first B/F separation. .

In general, in the first B/F separation after the second reaction, if a magnetic bead washing solution (BF solution) contaminated with β-D glucan is used, the subsequent Sandwich formation of the Therefore, when using a light-emitting electrolyte (EB solution), a magnetic bead cleaning solution (BF solution), a nozzle cleaning solution (CC solution), etc. in an inspection, it is necessary to use a dedicated β-D glucan-free BF solution. . However, as in the above configuration, in the specific test item for measuring β-D glucan, by eliminating the first B / F separation after the second reaction, the above-mentioned BF solution accompanying β-D glucan contamination inconvenience can be avoided. As a result, while reducing the risk of contamination and improving measurement accuracy, common EB, BF, and CC solutions can be used in all control modes (there is no need to use a dedicated β-D glucan-free BF solution). ).

Further, in the above configuration, the second sample chip supply unit and the reagent chip supply unit perform a first measurement sequence or a second measurement sequence executed when the inspection item selection unit selects a normal inspection item. It is preferably positioned so as not to interfere with the movement path of the nozzle movement mechanism in the measurement sequence. β-D glucan is measured by providing the second sample chip supply unit and the reagent chip supply unit that supply β-D glucan-free chips at positions that do not interfere with the nozzle movement path during normal test item measurement. This avoids the risk of contamination between a measurement sequence for measuring an object to be inspected and a measurement sequence for measuring another object to be inspected. For example, specifically, it is possible to avoid the risk of contamination such as dripping or contamination of foreign matter that may occur during normal test item measurement without providing a complicated device mechanism. This leads to improved measurement accuracy.

In addition, in the above configuration, it is preferable that a contamination check section for checking the β-D glucan-free state in the device is further provided. In this case, the contamination check unit may be individually provided in each part of the apparatus. etc. are contaminated with β-D glucan. By providing such a contamination checker, the reliability of β-D glucan measurement can be improved.

Further, in the above configuration, a reaction container supply unit for supplying reaction containers is further provided. A first reaction container supplying unit that supplies reaction containers, and a second reaction that supplies a β-D glucan-free second reaction container used when a specific test item is selected by the test item selection unit. It is preferred to have a container feeder. Thus, by preparing a β-D glucan-free reaction vessel as well as a chip, the reliability of β-D glucan measurement can be dramatically improved.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to select whether or not to attach a chip as necessary, and to simultaneously measure β-D glucan and other test objects while preventing contamination. and automated analysis methods are provided.

1 is a schematic overall external view of an automatic analyzer according to an embodiment of the present invention; FIG. FIG. 2 is a schematic plan view showing the internal configuration of the automatic analyzer of FIG. 1; FIG. 2 is a block diagram showing the main components of the autoanalyzer of FIG. 1; FIG. 2 is a flowchart showing an example of processing steps of the automatic analyzer of FIG. 1; FIG. A first measurement sequence that performs B/F separation in which multiple types of reagents are divided into several batches by a reagent aspirating nozzle and stirred into reaction containers, and labeled antibodies that do not form immune complexes are washed and discarded. It is a figure which shows an example typically.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a schematic overall external view of the automatic analyzer of this embodiment, FIG. 2 is a schematic plan view showing the internal configuration of the automatic analyzer of FIG. 1, and FIG. 2 is a block diagram showing the components of the system; FIG. 2 and 3, the automatic analyzer 1 of the present embodiment includes a reaction section 40 (see FIGS. 2 and 3) that holds reaction containers (cuvettes) C into which samples are dispensed. and a reagent supply unit 30 (see FIG. 2) that supplies a reagent. It is possible to obtain measurement information regarding specific test items for measuring β-D glucan and normal test items for measuring other test objects. Therefore, the automatic analyzer 1 has an inspection item selection unit 120 for alternatively selecting the specific inspection item and the normal inspection item (see FIG. 3).

In addition, the automatic analyzer 1 of the present embodiment includes a nozzle moving mechanism 130 (see FIG. 3) that moves a suction nozzle (not shown) for sucking a sample and a reagent within the device 1, and each part of the device (reaction part 40 (to be described later) and a control unit 110 for controlling the operation of the nozzle moving mechanism 130 . Furthermore, the automatic analyzer 1 of this embodiment has a contamination check section 114 that checks the β-D glucan-free state in the device 1 . The contamination check unit 114 may be provided in at least one of the

processing units

10, 20, 30, 40, and 50 of the apparatus 1 or individually, and for example, the detection value detected by the component detection sensor and the like By comparing with a predetermined reference value, it is checked whether or not each processing section, instrument, etc. in the device 1 is contaminated with β-D glucan. For example, the control unit 110 constantly monitors the state of contamination by β-D glucan by constantly receiving the detection signal from the contamination check unit 114, and when the state of contamination is detected, notifies the operator to that effect. generate a signal or take some other action (for example, stop the device 1).

As shown in FIGS. 2 and 3, the automatic analyzer 1 of the present embodiment has a rack R loaded with a predetermined number of disposable instruments used in the automatic analyzer 1, and a predetermined instrument take-out device described later. A transport unit 10 for transporting to position II, a sample supply unit 20 for supplying a predetermined sample such as a biological sample, and a reagent supply unit for supplying a reagent corresponding to a predetermined inspection item (analysis item). a reaction unit 40 for reacting a sample and a reagent; and a B/F separation/measurement unit 50 for processing and measuring the reacted sample. , 30, 40 and 50 are arranged in a housing 100 (see FIG. 1).

The rack R transported by the transport unit 10 includes a sample chip supply unit for supplying disposable sample chips T attached to the tip of a sample aspirating nozzle (not shown) moved by the nozzle moving mechanism 130, and a reaction container C. and a reaction vessel supply for supplying the In particular, in this embodiment, the rack R is a first sample chip supply section 300A that supplies the first sample chips T1 used when a normal test item is selected by the test item selection section 120 (FIG. 3). and a first reaction container supply unit 200A for supplying the first reaction container C1 used when the test item selection unit 120 selects a normal test item. In this case, for example, the first sample chips T1 are two-dimensionally arranged and held in the first sample chip supply unit 300A, and the first reaction containers C1 are two-dimensionally arranged in the first reaction container supply unit 200A. are arranged and held.

In addition, the automatic analyzer 1 includes the above-described control unit 110 (FIG. 3) for controlling the operations of these

processing units

10, 20, 30, 40, and 50, and a transfer mechanism (not shown) that moves in the XY directions. The transfer mechanism includes a nozzle movement mechanism 130, and uses a holding part such as a grip arm to transfer various instruments (specimen chips, reaction containers, etc.), and moves in the XY direction to perform aspiration of specimens and reagents by the nozzles. can move. The transfer mechanism can not only move in the XY directions within the housing 100 along, for example, extended rails, but can also move (lift) in the vertical direction (Z direction) at a predetermined position. By providing a display input unit 60 composed of a touch panel as illustrated in FIG. 1 and a user interface for controlling the display input unit 60, the inspection item selection unit 120 described above can be configured.

In the apparatus 1, the transport unit 10 vertically stacks the plurality of racks R loaded with the first sample chips T1 and the first reaction containers C1, and lifts the racks R by an elevating mechanism. The sample is transported toward the rack standby position (supply side position) I facing the upper sample processing space (hereinafter simply referred to as processing space) S in the housing 100 . After that, the rack R is moved to the take-out position (recovery side position) II where the sample chips T1 and the reaction containers C1 are taken out for analysis and measurement processing, and the sample chips T1 and the reaction containers C1 are all taken out and the rack R is empty. are sequentially lowered by an elevating mechanism to be collected.

Specifically, as shown in the lower right of FIG. 2, the operator pulls out the conveying unit 10 to the outside of the apparatus 1 along the Y direction (the pulled out conveying unit is denoted by reference numeral 10' in FIG. 2). ), an empty rack R can be recovered from the transport section 10, and the transport section 10 can be replenished with unused racks R loaded with sample chips T and reaction containers C, respectively.

In addition, in the present embodiment, the automatic analyzer 1 has a β-D glucan-free β-D glucan-free sample used when a specific test item is selected by the test item selection unit 120, adjacent to the take-out position (recovery side position) II. A second sample chip supply unit 300B (left half) that supplies a second sample chip T2, and a β-D glucan-free second sample chip used when a specific test item is selected by the test item selection unit 120. and a second reaction container supply section 200B (right half) for supplying the reaction container C2. These

second supply units

200B and 300B are configured so that the operator can manually put in and take out a rack holding a second sample chip T2 and a second reaction container C2 for measuring β-D glucan, for example. It's becoming

There is also a temporary storage place adjacent to these

second supply units

200B and 300B (at a position below the second supply unit in FIG. 2). This temporary storage site becomes a tip/reaction container standby position III where the first sample chip T1 and the first reaction container C1 in the rack R located at the take-out position II are transferred by the transfer mechanism and temporarily placed. However, in another modification, the reaction container C1 may be transferred and set directly from the rack R to the reaction section 40 by the holding section of the instrument transfer section without going through the tip/reaction container standby position III.

The sample supply unit 20 is placed on a sample table 23 that is movable along the X direction in FIG. The sample rack supply unit 20 has a configuration in which a plurality of box-shaped sample racks 22 are arranged along the moving direction of the sample table 23, for example. Each sample rack 22 is loaded with a plurality of sample containers 21, and each of these sample containers 21 contains a sample to be analyzed or measured. In particular, in this embodiment, at a predetermined timing in the measurement sequence of the automatic analyzer 1, for example, the sample supply unit 20 arranged on the right side in FIG. 2 moves to the left side in FIG. 22 is transferred to the specimen aspirating position IV between the reaction section 40 and the tip/reaction container standby position III and waits at this position.

In the area of the processing space S where the chip/reaction container standby position III, the sample aspirating position IV, and at least a part of the reaction unit 40 are aligned along a straight line, a sample transporting unit for transporting the sample constituting the transport mechanism A first uniaxial transfer line (first sample transfer line) L1 is formed along this straight line along which the sample moves only in one axial direction (X-axis direction). Specifically, when a normal test item is selected by the test item selection unit 120, a holding unit that holds a sample suction nozzle (not shown) is moved along the first uniaxial transfer line L1 by the sample transfer unit. It is moved only in the X-axis direction. This sample aspirating nozzle is moved in the + direction of the X axis (rightward in FIG. 2) by the sample transfer section, and the tip thereof reaches the first sample chip T1 temporarily placed at the tip/reaction container standby position III. After being connected (when connecting, the specimen aspirating nozzle is moved up and down in the Z-axis direction by the specimen transfer section), while holding the first specimen chip T1 at the tip, it is further moved in the - direction of the X-axis (to the left in FIG. 2). ) to aspirate the sample through the first sample chip T1 from the sample container 21 waiting at the sample aspirating position IV, and then move toward the reaction section 40 in the - direction of the X axis. At this time, the first reaction container C1 temporarily placed at the chip/reaction container standby position III has already been set in the reaction unit 40 using the holding unit transferred by the device transfer unit constituting the transfer mechanism. being waited for. Therefore, the specimen aspirating nozzle dispenses (discharges) the specimen aspirated through the first specimen chip T1 into the first reaction container C1 on the reaction section 40 . After that, the specimen aspirating nozzle is moved by the specimen transfer section toward the tip disposal section 121 (provided between the reaction section 40 and the specimen aspiration position IV) on the first uniaxial transfer line L1. , and the used first sample chip T1 is detached from the sample aspirating nozzle and discarded by the tip disposal unit 121 thereof.

Similarly, in the region of the processing space S where the second reaction container supply section 200B, the second sample chip supply section 300B, the sample aspirating position IV, and at least part of the reaction section 40 are aligned along a straight line, A second uniaxial transfer line (second sample transfer line) L2 along which a sample transfer section for transferring a sample, which constitutes the transfer mechanism, moves only in one axial direction (X-axis direction) along this straight line is the first uniaxial transfer line. It is formed without interfering with the transfer line L1. Specifically, when a specific test item is selected by the test item selection unit 120, a holding unit that holds a sample suction nozzle (not shown) is moved along the second uniaxial transfer line L2 by the sample transfer unit. It is moved only in the X-axis direction. This specimen aspirating nozzle is moved in the + direction of the X axis (rightward in FIG. 2) by the specimen transporting section, and the tip thereof is held by the second specimen chip supplying section 300B. After being connected to the second sample chip T2 (during connection, the sample aspirating nozzle is moved up and down in the Z-axis direction by the sample transfer unit), while holding the second sample chip T2 at the tip, it is further moved in the - direction of the X-axis. The sample is aspirated from the sample container 21 that is moved (to the left in FIG. 2) and stands by at the sample aspirating position IV through the second sample chip T2. be. At this time, the β-D glucan-free second reaction vessel C2 held in the second reaction vessel supply section 200B is transferred to the reaction section 40 by the instrument transfer section constituting the transfer mechanism. It has already been set and awaited using the unit. Therefore, the specimen aspirating nozzle dispenses (discharges) the specimen aspirated through the second specimen chip T2 into the second reaction container C2 on the reaction section 40 . After that, the specimen aspirating nozzle is moved by the specimen transfer section toward the tip disposal section 122 (provided between the reaction section 40 and the specimen aspiration position IV) on the second uniaxial transfer line L2. , and the used second sample chip T2 is detached from the sample aspirating nozzle and discarded by the tip disposal unit 122 thereof.

The reaction section 40 includes a rotary table 42 that is driven to rotate, and a plurality of reaction vessel support sections 43 are provided on the outer periphery of the rotary table 42 at predetermined intervals over the entire circumference. The reaction vessels C (C1, C2) are transferred and set on these reaction vessel support parts 43 by using the holding parts transferred by the instrument transfer part constituting the transfer mechanism as described above. Then, the sample is discharged from the sample suction nozzle into the reaction container C (C1, C2) rotated to the sample receiving position (dispensing position) by the rotary table 42, as described above.

The reagent supply unit 30 holds a plurality of reagent storage units 32 that store reagents corresponding to various types of analysis items in a unit form, for example, by a rotary table 34. 32 are rotated by the rotary table 34 to the corresponding reagent suction positions V (FIG. 2) positioned on a third uniaxial transfer line L3 (described later) that does not interfere with the first and second uniaxial transfer lines L1 and L2. (inside only one reagent aspiration position is labeled V). In particular, the reagent supply unit 30 of the present embodiment is integrated so that a plurality of (three in the figure) reagent storage units 32 each form an elongated reagent container and are arranged along the radial direction of the turntable 34 . A plurality of reagent storage units U configured by storing and holding formed container units in container holders are provided. A predetermined number of reagent storage units U are radially arranged along the circumferential direction of the rotary table 34 . The reagent supply unit 30 also includes a cooling device 36 for cooling the inside of the reagent storage, and a reagent container lid opening/closing unit for opening and closing container lids that close the openings of the reagent storage units 32 that constitute the reagent storage unit U. and a mechanism 160 .

A reagent chip supply unit 70 is provided on the outside of the reagent supply unit 30, that is, on the side opposite to the reaction unit 40 with respect to the reagent supply unit 30. The reagent chip supply unit 70 is a β-D glucan-free sample attached to the tip of a reagent suction nozzle (not shown) that is moved by the nozzle moving mechanism 130 when a specific test item is selected by the test item selection unit 120. It has a rack 74 loaded with disposable reagent tips 72 . Specifically, the reagent chip supply unit 70 moves the reagent chip 72 on the rack 74 along the Y direction under position control using a position sensor, thereby moving the reagent chip 72 on the rack 74 to a third uniaxial transfer line described later. Position it on L3. Inside the reagent supply unit 30, more specifically, between the reagent supply unit 30 and the reaction unit 40, a third uniaxial transfer line L3, which will be described later, is positioned so that the reagent suction nozzle is a nozzle cleaning liquid ( A plurality (three in this embodiment) of nozzle washing units 29 for washing with CC liquid) and a plurality (three in this embodiment) of tip discarding units 25 for discarding reagent chips 72 are provided. .

In the region of the processing space S where the reagent chip supply unit 70, the reagent supply unit 30, the nozzle cleaning unit 29, the tip disposal unit 25, and the reaction unit 40 are aligned along a straight line, the reagent transfer that constitutes the transfer mechanism is performed. A third uniaxial transfer line (reagent transfer line) L3 is formed in which the reagent transfer section for the reagent moves only in one axial direction (X-axis direction) along this straight line. In particular, in this embodiment, since three nozzle cleaning units 29 and three chip discarding units 25 are provided, three third uniaxial transfer lines L3 are also provided (of course, the number of third uniaxial transfer lines L3 is It is not limited to 3. It may be 4 or more, or 2 or less). Specifically, when a normal test item is selected by the test item selection unit 120, a holding unit that holds a reagent suction nozzle (not shown) is attached to the reagent transfer unit in each of the third uniaxial transfer lines L3. is moved only in the X-axis direction along the third uniaxial transfer line L3. The reagent aspirating nozzle directly aspirates the reagent corresponding to the inspection item from the reagent storage portion 32 positioned at the reagent aspirating position V on the rotary table 34 in the reagent supplying portion 30 through the nozzle aspirating portion at the tip thereof, After that, it is moved in the + direction of the X-axis toward the reaction section 40 . At this time, in the reaction section 40, the first reaction container C1, which has already received the sample at the aforementioned sample receiving position, is rotated to the reagent receiving position by the rotary table 42. is dispensed (discharged) into this first reaction vessel C1. After that, the reagent aspirating nozzle is moved in the - direction of the X axis and washed in the nozzle washing section 29 .

On the other hand, when performing β-D glucan measurement, which is an inspection item with a high contamination risk (when nozzle cleaning alone is insufficient), that is, when a specific inspection item is selected by the inspection item selection unit 120, the reagent Before the reagent is aspirated by the reagent supply unit 30, the aspiration nozzle is operated after the reagent chip 72 is connected to the tip of the reagent chip supply unit 70 (at the time of connection, the reagent aspiration nozzle is moved in the Z-axis direction by the reagent transfer unit). ), is further moved in the + direction of the X-axis while holding the reagent tip 72 at the tip, and sucks the reagent through the reagent tip 72 in the reagent supply section 30 . After that, the reagent suction nozzle is further moved in the + direction of the X-axis toward the reaction section 40, and the reagent is applied to the β-D glucan-free second reaction container C2 positioned at the reagent receiving position as described above. is dispensed (dispensed). After that, the reagent aspirating nozzle is moved in the - direction of the X-axis toward the corresponding tip disposal section 25 of the tip disposal section 25 by the reagent transfer section, and the used reagent tip 72 is removed in the tip disposal section 25. It is detached from the reagent suction nozzle and discarded.

In the reaction unit 40, the mixed liquid of the sample and the reagent dispensed into the reaction containers C (C1, C2) as described above is reacted on the turntable 42 at a predetermined temperature for a predetermined time, and then the reaction product is is formed, the reaction container C (C1, C2) is rotated to the reaction container take-out position VI by the rotation of the turntable 42 . The reaction container C (C1, C2) positioned at the reaction container take-out position VI is gripped by a holding part (grasping arm, etc.) transferred by the corresponding transfer part constituting the transfer mechanism, and B/F separation/measurement is performed. Introduced into unit 50 .

The B/F separation/measurement unit 50 performs predetermined processing on the introduced reaction product and performs electrical and optical measurements. Specifically, in analytical measurements using electrochemiluminescence immunoassay (ECLIA), B/F separation is performed to wash and discard labeled antibodies that do not form immune complexes. , B/F separation is provided. In addition, a photometric part (chemiluminescence introduction/photometric part) 120 is also provided for sucking the processed material treated by them and measuring it based on electrochemiluminescence. The used reaction vessel C for which the measurement has been completed is moved to a predetermined position by the rotation of the rotary table 52, and is gripped by the holding section transferred by the corresponding transfer section constituting the transfer mechanism and disposed of as a predetermined disposal. discarded by the department.

All of the above-described operations of the automatic analyzer 1 of the present embodiment with the configuration described above are controlled by the control unit 110 (see FIG. 3). A control that controls a measurement sequence that performs B/F separation in which reagents are divided into several times and dispensed into reaction containers C (C1, C2) and stirred, and labeled antibodies that do not form immune complexes are washed and discarded. have a mode. The measurement sequence includes a first measurement sequence in which B/F separation after reagent dispensing is performed a specified number of times, and a B/F separation after reagent dispensing that is omitted a predetermined number of times, resulting in a larger number of steps than the first sequence. and a second measurement sequence in which is reduced.

Specifically, in the first measurement sequence, as shown in FIG. 5, a sample diluent (R1) as a first reagent and a sample are dispensed into a first reaction container C1 and stirred. A first step S1 for causing the first reaction, and antibody-bound magnetic beads (R2) are added as a second reagent to the reaction solution obtained in the first step S1 to cause a second reaction, and after the reaction The magnetic beads are captured by the magnet 90, the liquid in the first reaction vessel C1 is extracted, and the magnetic beads are washed with a magnetic bead washing liquid (BF liquid) to remove non-specific binding substances other than the antigen-antibody reaction. A second step S2 of performing B/F separation, and adding a ruthenium complex-labeled antibody (R3) as a third reagent to the liquid after the second step S2 causes a third reaction, and magnetic beads after the reaction is captured by a magnet 90, the liquid in the first reaction vessel C1 is extracted, and the magnetic beads are washed with a washing liquid to remove non-specific binding substances other than the antigen-antibody reaction. and the steps of These first to third steps are performed in the B/F separation section (reaction system) of the reaction section 40 and the B/F separation/measurement section 50 . After a third step S3, a voltage is applied to the electrodes 95 in the presence of a buffer solution containing tripropylamine (TPA), which is a light-emitting electrolyte (EB solution), and the resulting electrochemiluminescence signal is read by a photodetector (photoelectron A step S4 of processing the resulting signal by recording it with a multiplier 96 is performed. This step S4 is executed by the photometry section 120 (photometry system) of the B/F separation/measurement section 50 . Note that in the first measurement sequence including these steps S1 to S4, the first sample chip T1 is used during sample dispensing, but the β-D glucan-free reagent chip 72 is used during reagent dispensing. is not used.

Also, the second measurement sequence is obtained by omitting the first B/F separation (B/F separation after the second reaction in the second step S2) from the above-described first measurement sequence. Further, in this second measurement sequence, when the normal test item is selected by the test item selection unit 120, the first sample chip T1 is used when the sample is dispensed, and the reagent Although the β-D glucan-free reagent chip 72 is not used at the time of dispensing, when a specific test item is selected by the test item selection unit 120, a β-D glucan-free chip is used instead of the first reaction container C1. A second reaction container C2 is used, a β-D glucan-free second sample chip T2 is used during sample dispensing, and a β-D glucan-free reagent is used during reagent dispensing Chip 72 is used.

The above-described control mode of the control unit 110 for controlling such a measurement sequence is executed when a normal test item is selected by the test item selection unit 120. A first control mode that controls the first measurement sequence or the second measurement sequence without involving and a second control mode for controlling the second measurement sequence with attachment of the reagent tip 72 to the tip. Specifically, as shown in the flowchart of FIG. 4, the inspection item selection unit 120 alternatively selects the specific inspection item and the normal inspection item (inspection item selection step S10), and the selection is the specific inspection item. (YES in step S11), the control unit 110 executes the control steps of the second control mode. That is, the sample aspirating nozzle for aspirating the sample is moved along the second uniaxial transfer line L2 by the nozzle moving mechanism 130 (nozzle moving step), and held by the second sample chip supply section 300B as described above. A β-D glucan-free second sample chip T2 is attached to the tip of the sample aspiration nozzle (sample chip attachment step S12). After that, as described above, the sample is aspirated by the sample aspiration nozzle from the sample container 21 waiting at the sample aspiration position IV through the second sample chip T2, and the sample is transferred to the β-D glucan-free second sample on the reaction section 40. is dispensed (discharged) into the reaction container C2 (step S13). After that, the reagent aspirating nozzle for aspirating the reagent is moved along the third uniaxial transfer line L3 by the nozzle moving mechanism 130 (nozzle moving step). β-D glucan-free reagent chip 72 is attached to (reagent chip attaching step S14). Thereafter, as described above, the reagent is aspirated by the reagent aspirating nozzle through the reagent chip 72 in the reagent supply unit 30, and the reagent is dispensed into the second reaction container C2 at the reagent receiving position to which the sample has already been dispensed. (ejection) (step S15). Then, in this way, the B/F separation is performed by dividing the plurality of types of reagents into several batches and distributing them into the second reaction container C2, stirring them, and washing and discarding the labeled antibodies that do not form immunocomplexes. The second control mode ends by completing the second measurement sequence (step S16).

On the other hand, the specific inspection item and the normal inspection item are alternatively selected by the inspection item selection unit 120 (inspection item selection step S10), and when the selection is the normal inspection item (NO in step S11), control Unit 110 executes the control steps of the first control mode. That is, the sample aspirating nozzle for aspirating the sample is moved along the first uniaxial transfer line L1 by the nozzle moving mechanism 130 (nozzle moving step), and is temporarily placed at the chip/reaction container standby position III as described above. The first sample chip T1 that has been held is attached to the tip of the sample aspiration nozzle (sample chip attaching step S17). Thereafter, as described above, the sample is aspirated from the sample container 21 waiting at the sample aspirating position IV by the sample aspirating nozzle through the first sample chip T1, and the sample is transferred into the first reaction container C1 on the reaction section 40. It is dispensed (discharged) (step S18). After that, the reagent aspirating nozzle for aspirating the reagent is moved along the third uniaxial transfer line L3 by the nozzle moving mechanism 130 (nozzle moving step), and the β-D glucan-free reagent chip 72 is removed as described above. The reagent is aspirated by the reagent aspirating nozzle in the reagent supply unit 30 without attachment, and the reagent is dispensed (discharged) into the first reaction container C1 at the reagent receiving position where the sample has already been dispensed ( step S19). Then, in this way, a plurality of types of reagents are divided into several times, and the B/F separation is performed by dispensing and stirring into the first reaction container C1, and washing and discarding the labeled antibody that does not form an immune complex. The first control mode ends by completing the first measurement sequence or the second measurement sequence (step S20).

As can be seen from the above, each of the uniaxial transfer lines L1, L2, and L3 is separated from each other in the first control mode and the second control mode in order to eliminate the movement paths in which the β-D glucan may be mutually contaminated. In other words, the second sample chip supply unit 300B and the reagent chip supply unit 70 are executed when the normal test item is selected by the test item selection unit 120. Since it is located at a position that does not interfere with the movement path of the nozzle moving mechanism 130 in the first measurement sequence or the second measurement sequence, the measurement sequence for measuring β-D glucan and the measurement sequence for measuring other test objects avoid the risk of contamination between

In the automatic analyzer 1 of the present embodiment, in addition to the above control modes, the order of measurement of β-D glucan (measurement of specific test items) and other measurements (measurement of normal test items) is changed. may be specified. In this case, for example, it is possible to perform contamination risk control according to inspection items, and obtain the effect of obtaining highly accurate measurement results.

As described above, according to the automatic analyzer 1 of the present embodiment, measurement information on specific test items for measuring β-D glucan and normal test items for measuring other test objects can be collected by one device. In other words, all inspection items, including β-D glucan measurement, can be completed with one device. (There is no need to use different devices), so continuous inspection is possible and the overall inspection time until measurement of all inspection items is completed can be shortened. can be reduced. Furthermore, the influence of time loss on measurement accuracy can be minimized to improve measurement accuracy. In addition, since the test time is shortened by the continuous test, it is not affected by deterioration (change in property) of the specimen over time, so that more accurate measurement values can be obtained. Furthermore, since the control mode can be selected according to the inspection item (it is possible to select whether or not the reagent chip is attached and the measurement sequence can be selected), a measurement sequence suitable for the inspection object can be realized. That is, by adopting a second measurement sequence with a small number of steps in a specific test item for measuring β-D glucan and using a β-D glucan-free disposable reagent chip, the opportunity to be exposed to the risk of contamination is reduced as much as possible. can be less. Therefore, it is possible to reduce the contamination risk and improve the measurement accuracy.

1 Automatic analyzer 30 Reagent supply unit 40 Reaction unit 70 Reagent chip supply unit 110 Control unit 114 Contamination check unit 120 Inspection item selection unit 130 Nozzle movement mechanism 200A First reaction container supply unit 200B Second reaction container supply unit 300A 1 sample chip supply unit 300B 2nd sample chip supply unit C1 1st reaction container C2 2nd reaction container T1 1st sample chip T2 2nd sample chip

Claims

comprising a reaction unit holding a reaction container into which a specimen is dispensed, and a reagent supply unit for supplying a reagent,
A specific test item for measuring β-D glucan in a sample and other test objects are measured by reacting the reagent supplied from the reagent supply unit with the sample and measuring the reaction process or reaction result. In an automatic analyzer that obtains measurement information on ordinary inspection items and
an inspection item selection unit for alternatively selecting the specific inspection item and the normal inspection item;
a nozzle moving mechanism for moving an aspiration nozzle for aspirating a sample and a reagent within the apparatus;
A sample chip supply unit for supplying a disposable sample chip attached to the tip of a sample aspiration nozzle, the sample chip supply unit supplying a first sample chip used when a normal test item is selected by the test item selection unit. a first sample chip supply unit; and a second sample chip supply unit that supplies a β-D glucan-free second sample chip used when a specific test item is selected by the test item selection unit. a sample chip supply unit,
a reagent chip supply unit for supplying a β-D glucan-free disposable reagent chip attached to the tip of a reagent suction nozzle when a specific test item is selected by the test item selection unit;
a control unit that controls the operation of each part of the device and the nozzle moving mechanism;
with
The control unit dispenses a plurality of types of reagents several times into the reaction container by the reagent suction nozzle and agitates the reagents, and B/F separation for washing and discarding labeled antibodies that do not form immune complexes. has a control mode for controlling the measurement sequence for
The measurement sequence includes a first measurement sequence in which B/F separation after reagent dispensing is performed a specified number of times, and a B/F separation after reagent dispensing that is omitted a predetermined number of times, resulting in a larger number of steps than the first sequence. a second measurement sequence in which is reduced;
The control mode is executed when the normal test item is selected by the test item selection unit, and the first measurement sequence or the second measurement sequence is performed without attaching the reagent chip to the tip of the reagent suction nozzle. and the second control mode which is executed when the specific test item is selected by the test item selection unit and is accompanied by attachment of the reagent chip to the tip of the reagent suction nozzle. a second control mode for controlling the measurement sequence of
An automatic analyzer characterized by:
The first measurement sequence includes a first step of dispensing a sample diluent and a sample as a first reagent into a reaction container and stirring them to cause a first reaction; Antibody-bound magnetic beads are added as a second reagent to the resulting reaction solution to cause a second reaction, the magnetic beads after the reaction are captured with a magnet, the liquid in the reaction vessel is removed, and the magnetic beads are washed with a washing solution. a second step of performing a first B/F separation to remove non-specific binding substances other than the antigen-antibody reaction, and adding a ruthenium complex-labeled antibody as a third reagent to the liquid after the second step to cause the third reaction, capture the magnetic beads after the reaction with a magnet, extract the liquid in the reaction vessel, wash the magnetic beads with a washing solution, and remove non-specific binding substances other than the antigen-antibody reaction. a third step of performing /F separation;
the second measurement sequence consists of the first measurement sequence omitting the first B/F separation;
The automatic analyzer according to claim 1, characterized in that:
The nozzle movement in the first measurement sequence or the second measurement sequence executed by the second sample chip supply unit and the reagent chip supply unit when the normal inspection item is selected by the inspection item selection unit. 3. The automatic analyzer according to claim 1, wherein the automatic analyzer is positioned so as not to interfere with the moving path of the mechanism.
The automatic analyzer according to any one of claims 1 to 3, further comprising a contamination check unit that checks the β-D glucan-free state in the device.
A reaction container supply unit for supplying the reaction container is further provided, and the reaction container supply unit supplies the first reaction container used when a normal inspection item is selected by the inspection item selection unit. and a second reaction container supply unit for supplying a β-D glucan-free second reaction container used when a specific test item is selected by the test item selection unit. The automatic analyzer according to any one of claims 1 to 4.
β-D glucan in the specimen is measured by reacting the reagent supplied from the reagent supply part with the specimen dispensed into the reaction vessel held in the reaction part and measuring the reaction process or reaction result. In an automatic analysis method for obtaining measurement information regarding specific inspection items and normal inspection items for measuring other inspection objects,
an inspection item selection step of alternatively selecting the specific inspection item and the normal inspection item;
a nozzle moving step of moving an aspiration nozzle for aspirating a sample and a reagent by a nozzle moving mechanism;
a sample chip attachment step of attaching a disposable sample chip supplied by a sample chip supply unit to a tip of a sample suction nozzle moved by the nozzle moving mechanism, wherein the disposable sample chip is supplied by a first sample chip supply unit; A first sample chip supplied and used when a normal test item is selected by the test item selection unit, and a second sample chip supplied by the sample chip supply unit and selected by the test item selection unit for a specific test item. a sample chip attachment step, including a second sample chip that is β-D glucan free to be used when selected;
When a specific test item is selected by the test item selection unit, a β-D glucan-free disposable reagent chip supplied by the reagent chip supply unit is attached to the tip of the reagent suction nozzle moved by the nozzle moving mechanism. a reagent tip attachment step;
a control step of controlling the operation of each part and the nozzle moving mechanism;
including
In the control step, a plurality of types of reagents are divided into several batches by the reagent aspirating nozzle, and the reagents are dispensed into the reaction container and stirred, and labeled antibodies that do not form immune complexes are washed and discarded in B/F separation. has a control mode for controlling the measurement sequence for
The measurement sequence includes a first measurement sequence in which B/F separation after reagent dispensing is performed a specified number of times, and a B/F separation after reagent dispensing that is omitted a predetermined number of times, resulting in a larger number of steps than the first sequence. a second measurement sequence in which is reduced;
The control mode is executed when the normal test item is selected by the test item selection unit, and the first measurement sequence or the second measurement sequence is performed without attaching the reagent chip to the tip of the reagent suction nozzle. and the second control mode which is executed when the specific test item is selected by the test item selection unit and is accompanied by attachment of the reagent chip to the tip of the reagent suction nozzle. a second control mode for controlling the measurement sequence of
An automatic analysis method characterized by:
The first measurement sequence includes a first step of dispensing a sample diluent and a sample as a first reagent into a reaction container and stirring them to cause a first reaction; Antibody-bound magnetic beads are added as a second reagent to the resulting reaction solution to cause a second reaction, the magnetic beads after the reaction are captured with a magnet, the liquid in the reaction vessel is removed, and the magnetic beads are washed with a washing solution. a second step of performing a first B/F separation to remove non-specific binding substances other than the antigen-antibody reaction, and adding a ruthenium complex-labeled antibody as a third reagent to the liquid after the second step to cause the third reaction, capture the magnetic beads after the reaction with a magnet, extract the liquid in the reaction vessel, wash the magnetic beads with a washing solution, and remove non-specific binding substances other than the antigen-antibody reaction. a third step of performing /F separation;
the second measurement sequence consists of the first measurement sequence omitting the first B/F separation;
The automatic analysis method according to claim 6, characterized by:
The nozzle movement in the first measurement sequence or the second measurement sequence executed by the second sample chip supply unit and the reagent chip supply unit when the normal inspection item is selected by the inspection item selection unit. 8. The automatic analysis method according to claim 6 or 7, wherein the position is such that it does not interfere with the moving path of the mechanism.