JP7661746B2 - Automated Analysis Equipment - Google Patents

Description

The present invention relates to an automatic analyzer that analyzes trace substances contained in samples such as blood, serum, plasma, and urine.

A method used in immunoassays and biochemical tests involves adding a substrate reagent solution to a complex of the substance to be measured in a sample and an enzyme-labeled reagent, producing an optically detectable product, and detecting an optical signal that corresponds to the concentration of the substance to be measured.

In order to improve the storage stability of the reagent liquid, a sealing material is attached to the non-light-transmitting reagent container (see, for example, Patent Document 1), and the tip of the dispensing nozzle pierces the airtight seal of the reagent container to open it (see, for example, Patent Document 2). If the reagent liquid remaining in the reagent container is to be reused, the reagent liquid is stored on-board in the device, but if the on-board time is long, air will flow in and out after the reagent container is opened, causing a decrease in the pH of the reagent liquid due to carbon dioxide, and a decrease due to evaporation of the reagent liquid, causing deterioration of the reagent performance, which may lead to erroneous measurement results.

JP 2017-161349 A JP 2018-004270 A

The objective of the present invention is to provide an automatic analyzer equipped with a mechanism for preventing evaporation or deterioration of liquid in a reagent container after it has been opened and placed on the automatic analyzer.

a holder for mounting and holding a reagent container;
a lid portion that abuts against the holder from above and is capable of sealingly sealing the reagent container without contacting the reagent container;
a conveying unit capable of conveying the holding unit to a lower portion of the lid member;
A lifting means for lifting and lowering the lid member;
The present invention provides an automatic analyzer equipped with the above.

By sealing a reagent container with remaining reagent liquid during analysis, during standby, after analysis, or after the analysis is stopped, it is possible to prevent the reagent from absorbing carbon dioxide and causing a decrease in pH, and to prevent the reduction of reagent liquid due to evaporation. Therefore, when measuring again after the on-board time has elapsed, it is possible to suppress erroneous judgments of the analysis, and it is possible to use the reagent container until it is used up within the on-board time without having to replace it for each measurement. In addition, by sealing the reagent container without contacting the lid of the lid device with the opening of the reagent container, it is possible to prevent contamination by other reagents.

1 is a cross-sectional view showing one embodiment of a lid device and a holder on which a reagent container is placed. FIG. FIG. 2 is a perspective view of one embodiment of a substrate reagent container and a lid arrangement. FIG. 1 is a diagram showing an embodiment of an automatic analyzer of the present invention. FIG. 2 is a diagram showing one aspect of a conveying section. 10 is a side view showing one embodiment of the positional relationship between a holder on which a reagent container is placed and a lid device. FIG. 1 is a front view showing one embodiment of the positional relationship between a holder on which a reagent container is placed and a lid device. FIG.

The present invention relates to an automatic analyzer that analyzes trace substances contained in samples such as blood, serum, plasma, and urine, and is equipped with at least a reagent table on which at least specimen containers and reaction reagent containers are placed, a transport unit on which at least substrate reagent containers are placed, a transport unit that transports various containers, a measurement unit that performs enzyme immunoassays, a holding unit that holds the reaction reagent containers or the substrate reagent containers, a drive unit that moves the holding unit horizontally, a lid unit that can seal the opening of the substrate reagent container, and a lifting unit that raises and lowers the lid unit.

The automated analyzer of the present invention moves the holder so that the substrate reagent container placed on the holder is below the lid during measurement, while waiting for measurement, after measurement is stopped, or after measurement is completed, and then lowers the lid to seal the substrate reagent container. When the next measurement is started or when measurement is resumed, the lid rises and the holder moves while still holding the substrate reagent container.

In the present invention, the holding section is preferably provided with a plurality of holding positions for placing reaction reagent containers or substrate reagent containers, and the holding positions are preferably shaped so that they can be positioned by contacting the sides or bottoms of these reagent containers. The holding section may also have a function of pre-warming the substrate reagent before dispensing it into the reaction container. Furthermore, the holding section may have a function of adjusting the temperature of the substrate reagent container placed on the holding section and sealed with the lid device during standby, during measurement, or after measurement has been stopped. The storage period (on-board time) of the substrate reagent container held in the holding section is preferably within 10 hours, taking into consideration deterioration and evaporation of the substrate reagent liquid.

In consideration of deterioration and evaporation of the substrate reagent liquid, it is preferable to seal the substrate reagent container placed on the holder with the lid when the opened substrate reagent container is left for 5 seconds or more. The container to be sealed with the lid is not limited to the substrate reagent container, and any container having a shape that can be placed on the holder can be used. In order to prevent contamination of the substrate reagent liquid that has evaporated due to heating, it is preferable that the lid of the lid device does not come into contact with the substrate reagent container, but rather the edge of the lid comes into contact with the top surface of the holder, thereby sealing the opened substrate reagent container placed on the holder (see Figure 1).

In the present invention, in order to improve the airtightness of the lid, a cushioning material such as porous silicon or rubber may be attached to the top of the holder. Considering airtightness, the cushioning material should preferably be 2 to 5 mm thick. The shape of the cushioning material is not important as long as it fits the edge of the opening, but considering the cost and airtightness of the automatic analyzer, a flat surface is preferable. It is also preferable to install the cushioning material on the top surface of the holder, excluding the area where the substrate reagent container is placed, so that the cushioning material comes into contact with the entire edge of the lid.

The transport unit of the present invention is equipped with a holding unit, a waste outlet, and a pipette tip rack (see Figure 2), but this is not limited to being an integrated unit, and the holding unit, waste outlet, and pipette tip rack may each be independent.

In the present invention, it is preferable that the dispensing unit that opens the airtight seal of the substrate reagent container is provided with a pipette tip for aspirating the reagent attached to the dispensing nozzle, and the size of the hole at the opening of the substrate reagent container is minimized by piercing the airtight seal.

One embodiment of the present invention will be described in detail below with reference to the attached drawings, but the present invention is not limited to these embodiments.

Each unit of the automated chemiluminescent enzyme immunoassay device (automatic analyzer) 300 performs the analysis process according to a program based on the sample information and measurement items input into the control unit (not shown).

On the reagent table 15, a sample rack 17 in which sample containers 16 are placed and a measurement container tray 18 in which a reaction reagent container 19 containing a reaction reagent is placed are placed. The reaction reagent container has two reagent storage sections, one of which contains a solid-phase reagent in which an antibody that binds to the analyte is fixed using magnetic microparticles as carriers, in a freeze-dried state together with the salt components of the buffer solution and additives, and the other contains a labeled reagent in which an antibody that binds to the analyte is enzyme-labeled, in a freeze-dried state together with the salt components of the buffer solution and additives, and both reagent storage sections are sealed with a moisture-proof airtight seal.

In the transport section 20, there are placed a substrate reagent container 21 containing a substrate reagent to be subjected to an enzyme reaction, an inspection sample container 22 containing an inspection sample for inspecting the device, and a pretreatment reagent container 23 containing a pretreatment reagent for the specimen. The substrate reagent container has two reagent containing sections, one containing a liquid chemiluminescent substrate reagent and the other containing a liquid enhancer reagent, and is sealed with an airtight seal that can prevent evaporation of the reagent, including an aluminum foil layer and a resin film layer such as polyethylene. The inspection container is used to inspect the contamination of the common reagent, and is sealed with an airtight seal.

The transport section 20 further includes a pipette tip rack 25 on which pipette tips 26 are placed, a holding section 200 for pre-heating the substrate reagent before dispensing it into the reaction reagent container, and a disposal port 27 for disposing of used pipette tips 26 and used reaction reagent containers.

The reagent table 15, transport unit 20, and dispensing and mixing unit 24 can each be moved to a position where the code reader 31, etc. can perform their functions as appropriate during the measurement process.

When the control unit instructs the automatic analyzer to start operating, the code reader 31 scans the reagents on the reagent table 15 and the transport unit 20, reads the identification information of the reagents installed in each location, and stores it in the control unit.

When an instruction to start measurement is given, the code reader 31 moves above the reaction reagent container 19 for the target measurement item by moving the dispensing unit drive unit 32 and the reagent table 15, reads the code printed on the sealing seal of the reaction reagent container, and confirms that it is a reaction reagent container containing a reaction reagent for the target measurement item. Once confirmed, the transfer unit 30 transfers the reaction reagent container to the dispensing and mixing unit 24, and the seal breaker 14 pierces the sealant of the two reagent storage sections of the reaction reagent container to open it.

The dispensing unit 33 is fitted with a pipette tip 26, and the dispensing water supply unit 28 aspirates the required amount of dispensing water, which is then dispensed by the dispensing and mixing unit 24 into the labeled reagent in the opened reaction reagent container. The dispensing unit 33 then aspirates the required amount of dispensing water again with the same pipette tip, then moves to the specimen container 16 to be measured, aspirates the required amount of specimen, and dispenses it into the solid-phase reagent in the opened reaction reagent container by the dispensing and mixing unit 24. The dispensing and mixing unit 24 stirs the reaction reagent container to dissolve the solid-phase reagent. The dispensing and mixing unit 24 is heated to the reaction condition temperature, and the solid-phase reagent dissolved in the dispensing water containing the specimen initiates an antibody-antigen reaction if the specimen contains a substance to be measured. The dispensing unit 33 moves to the disposal port 27 and discards the attached pipette tip.

If the substrate reagent container to be used is unopened, the lid device 100 does not operate, but if the substrate reagent container has been opened, the drive motor 40 operates from dispensing the sample into the reaction reagent container until the pipette tip is discarded, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. When the belt rotates, the holder on which the substrate reagent container is placed moves in conjunction with the holder, moving horizontally, and moving to below the lid 11 (see Figure 4). After the movement, the lid device motor 12 associated with the lid device 100 operates, and the lifting unit 13 arranged on the shaft of the lid device motor 12 rotates to lower the lid 11, and the edge of the lid comes into contact with the cushioning material 29 on the top surface of the holder, creating a sealed state (see Figures 5 and 6). Before the reaction reagent container is placed on the transport turntable 36, the lifting unit 13 attached to the shaft of the lid device motor 12 rotates to raise the lid unit 11, opening the substrate reagent container. Next, the drive motor 40 is activated, and the belt pulley 41 attached to the shaft of the drive motor rotates, causing the belt 42 to rotate. As the belt rotates, the holder on which the substrate reagent container is placed moves horizontally in tandem with the belt, returning it to its original position.

The transfer section 30 holds the reaction reagent container in which the antibody-antigen reaction has started, and places it through the container entrance 38 at the container holding position 39 on the transport turntable 36 of the reaction section 35, which has been heated to the reaction temperature of the measurement unit 400.

If the substrate reagent container to be used is unopened, the lid device 100 does not operate, but if the substrate reagent container has been opened, the drive motor 40 operates from dispensing the sample into the reaction reagent container to discarding the pipette tip, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. When the belt rotates, the holder on which the substrate reagent container is placed moves horizontally in tandem to below the lid 11. After the movement, the lid device motor 12 associated with the lid device 100 operates, and the lifting unit 13 arranged on the shaft of the lid device motor 12 rotates to lower the lid 11, causing the edge of the lid and the cushioning material on the upper surface of the holder to come into contact and become sealed. Before the reaction reagent container placed on the turntable 36 is transferred to the dispensing and mixing unit 24, the lid device motor 12 operates, and the lifting unit 13 arranged on the shaft of the lid device motor 12 rotates to raise the lid 11, causing the substrate reagent container to be in an open state. Next, the drive motor 40 is operated, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. As the belt rotates, the holder on which the substrate reagent container is placed moves in conjunction with the belt, moving horizontally to its original position.

The reaction reagent container placed on the transport turntable 36 is incubated on the transport turntable for the time required for the reaction, and then the components that do not bind to the solid phase are sucked out together with the reaction liquid by the washing nozzle. After the B/F washing unit 37 repeatedly discharges the washing liquid, collects the solid phase, and sucks it out, the reaction reagent container is transported to the container inlet/outlet 38 by the transport turntable 36 and is temporarily returned to the dispensing and mixing unit 24 by the transfer unit 30.

If the substrate reagent container to be used is unopened, the lid device 100 does not operate, but if the substrate reagent container has been opened, the drive motor 40 operates from dispensing the sample into the reaction reagent container to discarding the pipette tip, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. When the belt rotates, the holder on which the substrate reagent container is placed moves horizontally in tandem to below the lid 11. After the movement, the lid device motor 12 associated with the lid device 100 operates, and the lifting unit 13 arranged on the shaft of the lid device motor 12 rotates to lower the lid 11, causing the edge of the lid and the cushioning material on the top surface of the holder to come into contact and become sealed. Before transporting the substrate reagent container to the holder 200, the lid device motor 12 operates, and the lifting unit 13 arranged on the shaft of the lid device motor 12 rotates to raise the lid 11, causing the substrate reagent container to be in an open state. Next, the drive motor 40 is operated, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. As the belt rotates, the holder on which the substrate reagent container is placed moves in conjunction with the belt, moving horizontally to its original position.

The transfer unit 30 holds the unopened substrate reagent container 21 placed on the transport unit, moves it to the holding unit 200, and heats the substrate reagent container.

The dispensing unit 33 is fitted with a pipette tip 26 and aspirates the required amount of labeled reagent contained in a reaction reagent container installed in the dispensing and mixing unit 24 and dispenses it into the solid-phase reagent. The mixing unit 29 mixes the reaction solution, initiating an antibody-antigen reaction between the measured substance that was bound to the antibody in the solid-phase reagent and the labeled reagent. The dispensing unit 33 then moves to above the waste port 27 and discards the pipette tip attached to the dispensing nozzle 34.

The transport unit 30 holds the reaction reagent container in which the reaction has started, transports it again to the measurement unit 400, and places it through the container entrance 38 at the container holding position 39 on the transport turntable 36 of the reaction unit, which has been heated to the reaction temperature.

The reaction reagent container placed on the transport turntable 36 is incubated on the transport turntable for the time required for the reaction, and then the components that have not formed a bond consisting of the solid-phase reagent, the substance to be measured, and the labeled reagent are sucked out by the cleaning nozzle together with the reaction liquid. After the B/F cleaning unit 37 repeatedly discharges the cleaning liquid, collects the solid phase, and sucks it out, the reaction reagent container is transported to the container inlet/outlet 38 by the transport turntable 36 and is returned to the dispensing and mixing unit 24 again by the transfer unit 300.

If the substrate reagent container to be used is unopened, the dispensing unit 33 attaches the pipette tip 26 and opens the airtight seal of the substrate reagent container by piercing first the chemiluminescent substrate reagent, then the enhancer reagent, with the tip of the pipette tip, and the dispensing unit 33 moves to above the waste port 27 and discards the attached pipette tip.

The dispensing unit 33 is fitted with a pipette tip 26 and aspirates the required amount of enhancer reagent and chemiluminescent substrate reagent, in that order, from an opened substrate reagent container placed in the holder 200, and dispenses the entire amount into the container containing the solid phase of the reaction reagent container. The dispensing and mixing unit 24 mixes the reaction reagent container to initiate the enzyme reaction of the labeling reagent. The dispensing unit 33 then moves to above the waste port 27 and discards the attached pipette tip.

The transport unit 30 holds the reaction reagent container in which the enzyme reaction has been initiated, transports it again to the measurement unit 400, and places the reaction reagent container through the container inlet/outlet 38 at the container holding position 39 on the transport turntable 36 of the reaction unit, which has been heated to the reaction temperature.

The reaction reagent container placed on the transport turntable 36 is incubated on the table for the required time, then moved to the measurement unit, where the luminescence value is measured and stored in the memory unit. From the measured luminescence value, the analysis unit calculates the concentration of the substance to be measured and displays it on the display unit.

After the analysis by the analysis unit is completed, the reaction reagent container is transported to the container entrance/exit 38 by the transport turntable 36, and the reaction reagent container is disposed of at the disposal port 27 by the transfer unit 30.

Before the reaction reagent container is disposed of in the waste port 27, the drive motor 40 is operated, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate as well. When the belt rotates, the holder on which the substrate reagent container is placed moves in tandem in the horizontal direction until it reaches under the lid 11. After the movement, the lid device motor 12 attached to the lid device 100 is operated, and the lid 11 is lowered by a guide arranged on the shaft of the lid device motor 12, causing the edge of the lid to come into contact with the cushioning material 29 on the top surface of the holder, creating a sealed state.

While the reaction reagent container is being discarded, another reaction reagent container placed on the reagent table is transferred to the dispensing and mixing section by the transfer section 30, the reaction reagent container is transferred to the dispensing and mixing section 24, and the substrate reagent container is kept sealed until it is opened by piercing the sealant in the two reagent storage sections of the reaction reagent container with a seal breaker provided in the dispensing section 33.

After the reaction reagent container is opened, the lid device motor 12 is operated, and the lifting section 13 attached to the shaft of the lid device motor 12 rotates, raising the lid section 11 and opening the substrate reagent container. Next, the drive motor 40 is operated, and the belt pulley 41 attached to the shaft of the drive motor rotates, causing the belt 42 to rotate as well. As the belt rotates, the holder on which the substrate reagent container is placed moves horizontally in tandem with the belt, returning it to its original position.

Note that a substrate reagent container that has been opened and is in use before the start of measurement is placed on the holder 200 and sealed with the lid 11 until the start of measurement.

After the measurement starts, the substrate reagent container is opened by the lifting of the lid 11, and then the drive motor 40 is operated, and the belt pulley 41 arranged on the shaft of the drive motor rotates, causing the belt 42 to rotate. As the belt rotates, the holder on which the substrate reagent container is placed moves in tandem in the horizontal direction and back to its original position.

100: Lid device 200: Holding section 300: Automatic analyzer 400: Measurement unit 11: Lid section 12: Motor for lid device 13: Lifting section 14: Seal breaker 15: Reagent table 16: Sample container 17: Sample rack 18: Measurement container tray 19: Reaction reagent container 20: Transport section 21: Substrate reagent container 22: Inspection sample container 23: Pretreatment reagent container 24: Dispensing and mixing section 25: Pipette tip rack 26: Pipette tip 27: Disposal port 28: Dispensing water supply section 29: Cushioning material 30: Transfer section 31: Code reader 32: Driving section for dispensing section 33: Dispensing section 34: Dispensing nozzle 35: Reaction section 36: Transport turntable 37: B/F cleaning unit 38: Container entrance/exit 39: Container holding position 40: Drive motor 41: Belt pulley 42: Belt

Claims (3)

a holder for mounting and holding a reagent container;
a lid portion that abuts against the holder from above and is capable of sealingly sealing the reagent container without contacting the reagent container;
a conveying unit capable of conveying the holding unit to a lower portion of the lid unit ;
A lifting unit that lifts and lowers the lid unit;
An automatic analyzer equipped with The automatic analyzer according to claim 1, which is provided with a holding unit that adjusts the temperature of the reagent container. An automatic analyzer according to claims 1 and 2, which is provided with a buffer material in the holding section.