JP4857223B2 - Automatic analyzer - Google Patents

Description

  The present invention relates to a reagent dispensing mechanism of an automatic analyzer, and particularly to an automatic analyzer having a function that can be used up from a container with a small remaining amount when the same reagent is mounted in a plurality of containers.

  In automatic analyzers, particularly immunoassays, competitive methods or sandwich methods are known as methods for detecting and measuring antigens or antibodies. This is a method in which an antigen-antibody reaction is carried out in a reaction vessel, and a fluorescent dye or enzyme previously labeled on a conjugate that forms a complex with the antigen-antibody is detected. In this method, only the conjugate that has formed a complex with the antigen-antibody is left in the reaction vessel, and the conjugate that has not formed the complex is removed from the reaction chamber, and this removal operation is generally performed using B / F (bound / free). ) Called separation. Peroxidase, alkaline phosphatase, glucose oxidase and the like are known as enzymes that realize highly sensitive analysis.

  In order to carry out the measurement efficiently, reagents such as a luminescent solution, a pH adjusting solution, or a suspension of magnetic particles that are commonly used regardless of the items are usually dispensed from one bottle and used for the reaction. Is done. Since it is used in common across multiple items, the amount of consumption is also large, each reagent is loaded with multiple bottles, and when one bottle is empty or the amount of solution is sufficiently reduced, automatic bottle change is performed, Many devices allow analysis to be performed without interruption. The ability to change bottles automatically means that users do not need to change reagents during the analysis, and the analysis is not interrupted. It is an important performance. Luminol derivatives, 4-methylumbelliferyl phosphate, adamantyl dioxetane phenyl phosphate, and the like are known as luminescent color formers (substrates) for realizing highly sensitive analysis.

  In such an immunoassay device, bottle change has been performed by switching the flow path with a valve such as an electromagnetic valve in accordance with the remaining usable amount index. For this automatic bottle change, an on-off valve, an electromagnetic valve, or a switch valve is used, and a switch that switches a large number of three or more flow paths with one valve is also produced. Usually, the bottle change in the automatic analyzer is performed with 2 to 3 bottles, and it is common to start using an unused bottle solution after empty or after using a predetermined number of analysis. Therefore, it is rare to collect and mix with a prescribed ratio of solution at the same time. Such an immunoassay device is described in Patent Document 1, for example.

JP 2006-292541 A

  An object of this invention is to provide the automatic analyzer provided with the function to perform a bottle change simply and at low cost.

  Since the present invention performs reagent dispensing with a simple mechanism, when a plurality of bottles of the same reagent solution are mounted, a mechanism and solution liquid in which the position of the bottle is adjusted by a balance, spring pressure, or air pressure according to the bottle weight. It is equipped with a mechanism in which solutions are used in order from the bottle with the highest surface, the lightest bottle is selected, the liquid level is set higher, and the potential energy of the solution is increased, so that the solution flows preferentially to the lower position and used. Also, when sufficiently reduced or lost, the use of the solution from another bottle filled with the solution is started, and the position advantage is enhanced by the weight reduction of the bottle, Similarly, the solution is used until it is sufficiently reduced or not.

  According to the automatic analyzer of the present invention, a plurality of bottles are connected without connecting a tube from a plurality of bottles to a solenoid valve, selecting one of the plurality of bottles, and feeding a solution by a motor pump or a syringe pump. In addition to simplifying the mechanism and measuring the liquid transfer efficiency, it can reduce the influence on the analysis of soluble components used in the pump material, and the tube connection point Liquid leakage or precipitation of dried salt, elution of metal components or resin components with a solenoid valve, and generation of mold and bacteria can be avoided, and high analytical performance can be realized.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

  FIG. 1 is a main configuration diagram of an immunoassay device. The sample on the sample lane 101 is dispensed into the reaction container on the reaction disk 105 by the first dispensing pipette 112. At the same time, the first dispensing pipette also dispenses the magnetic beads on the outer periphery 102 of the first reagent disk, and dispenses them to the reaction vessel 30 at position (1). The reaction disk is temperature-controlled and rotates every predetermined time. When the reaction container reaches position (2) after a certain time, the gripper 107 carries the reaction container to the B / F separation unit, and the first B / F separation is performed.

  When the reaction vessel that has completed the first B / F separation is moved back to the position (3) by the gripper again to the position (3), the conjugate of the second reagent disk 104 is moved to the second dispensing pipette 114. To dispense into the reaction vessel. After the reaction on the reaction disk, when this reaction vessel reaches the position (4), it is carried again to the B / F separation unit by the gripper and returns to the position (4) after the B / F separation. Thereafter, the substrate placed on the inner periphery 103 of the first reagent disk is dispensed by the third dispensing pipette 110 into the reaction container, and the fluorescence is measured by the optical detection device. Reference numerals 113, 115, and 111 denote movable ranges of the first dispensing pipette, the second dispensing pipette, and the third dispensing pipette, respectively.

  FIG. 2 shows a general method of immunoassay. The antibody or antigen solid phase magnetic particles and the sample collected by the first dispensing pipette are mixed in a predetermined amount in the reaction container 30 and reacted for a certain time while being heated to about 37 ° C. by the reaction disk 105. Thereafter, the reaction vessel 16 moves to the B / F separation unit and the magnetic particles are collected by the magnet 19. The supernatant is aspirated with the syringe 15, then the cleaning liquid is supplied with the syringe, and the magnetic flux is collected. The above-described supernatant aspiration, cleaning liquid supply, and magnetic flux collection are repeated several times. At this time, only the magnetic particles and the antigen or antibody derived from the specimen bound to the surface thereof remain in the reaction container.

  Next, an enzyme-labeled antibody or antigen (conjugate) is dispensed with the second dispensing pipette 114. Thereafter, the reaction vessel 16 moves and the magnetic particles are collected by the magnet 19. The supernatant is aspirated with the syringe 15, and then the cleaning liquid is supplied with the syringe, and the magnetic flux is further collected. The above-described supernatant aspiration, supply of the cleaning liquid, and magnetic collection are repeated several times. At this time, the magnetic particles and the antigen or antibody bound to the surface thereof, and further, the enzyme-labeled antibody or antigen bound to the antigen or antibody remain in the reaction container.

  Next, the reaction vessel is moved to the optical detection unit, and a predetermined amount of substrate (luminescence color developing solution) is dispensed with the third dispensing pipette 110, and light emission or color development due to the reaction between the enzyme remaining in the reaction vessel and the substrate is photomultiplied. The amount of enzyme and further the amount of antigen or antibody contained in the specimen is calculated from a calibration curve, captured by a tube (PMT).

  The dispensing method of the substrate reagent etc. common to the analysis item of FIG. 3 is shown. There are a plurality of reagent bottles 11 having the same reagent composition. The tube 12 is immersed in the solution in the bottle, and the tubes from a plurality of bottles merge at one place or a plurality of places to finally become one. The reagent solution in the bottle is sucked by the syringe 15 and sent to the reagent storage tank 13. At this time, the electromagnetic valve 14 is in a direction to open the storage tank and the syringe. Further, the solution is sucked into the syringe.

  Next, the solenoid valve is switched in a direction to open the syringe 15 and the reaction container 16, and a syringe plunger is pushed to dispense a fixed amount of solution into the reaction container.

  In the left figure of FIG. 4, when the solution in the reagent bottle is used and one of the bottles becomes light, the two bottles are mounted on the balance, and the lightweight bottle A is positioned higher due to the weight of the bottle B. Move to. When the liquid level moves to a higher position, potential energy is obtained, and the solution in the bottle A is sent to the reagent storage tank 13.

  When the solution in the bottle A runs out, or when the specified number of analyzes are completed and the amount is sufficiently small, supply of the solution from the bottle B is started. It is desirable to remove the bottle A before the solution of the bottle B runs out or finish the specified number of analyzes and install another new bottle (for example, the bottle C) at that position. The weight exceeds the bottle B, and the bottle B moves to a higher position and the reagent is continuously supplied from the bottle B.

  In the right diagram of FIG. 4, the bottle is mounted on a spring and a pedestal, and the difference in level of the solution liquid level in the bottle is obtained from the relative weight of the bottle weight. Move to a position higher than B. When the liquid level moves to a higher position, potential energy is obtained, and the solution in the bottle A is sent to the reagent storage tank 13.

  The mechanism that gives the liquid level in the bottle is reversible in position or shape depending on the weight of the mounted bottle, such as one using a balance, spring, rubber, seesaw, etc., or one using air pressure, hydraulic pressure, etc. Anything can be used as long as it changes.

  Thus, if the bottle is in use, it is at a higher position than other unused bottles. If the other bottle is a used container, the reagent is supplied from the bottle with the solution.

  In addition, the bottle may shorten the tube in a bottle and the location of a cap may be in the downward direction, and may be placed horizontally. Moreover, you may provide another tube used as a gas movement path for the movement of the air etc. inside a bottle.

It is a block diagram of an automatic analyzer. Example 1 It is a block diagram of an automatic bottle change unit. Example 1 It is a flowchart of an immunoassay. Example 1 It is a block diagram of the unit in which the bottle is changed by increasing the position of one bottle by a balance (left figure) or a spring (right figure). Example 1

Explanation of symbols

11 Reagent bottle 12 Tube 13 Reagent storage tank 14 Solenoid valve 15 Syringe 16 Reaction vessel 17 Photomultiplier tube (PMT)
30 reaction container 101 specimen lane 102 first reagent disk outer periphery 103 first reagent disk inner periphery 104 second reagent disk 105 reaction disk 106 optical detection unit 107 gripper 110 third dispensing pipette 111 third dispensing pipette movable range 112 first Dispensing pipette 113 First dispensing pipette movable range 114 Second dispensing pipette 115 Second dispensing pipette movable range A Reagent bottle B Reagent bottle (A and B are reagents of the same composition)

Claims (2)

A liquid container installation position capable of installing a plurality of liquid containers containing the same liquid;
A mechanism for positioning a liquid container having a small weight higher than a liquid container having a large weight by any one of a balance, a spring pressure, and an air pressure;
A plurality of tubes housed in the liquid container and for sucking liquid from the liquid container;
A flow path formed by joining the plurality of tubes at one place or a plurality of places;
A syringe for sucking liquid through the flow path,
An automatic analyzer that sequentially draws liquid from a liquid container positioned at a high position . The automatic analyzer according to claim 1, wherein
When the inside of the liquid container positioned at the highest position among the plurality of liquid containers becomes empty or becomes smaller than a predetermined amount,
An automatic analyzer for aspirating the liquid in the liquid container positioned at the next higher position .

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