Automatic analysis device

Abstract

Provided is an automatic analysis device in which explosive boiling of a liquid sample can be reduced.　This automatic analysis device comprises: a reaction vessel; a heating member; an exhaust part; and a reaction vessel-moving member. The automatic analysis device performs: a first evaporation concentration step in which the exhaust part, in a state where the reaction vessel is located apart therefrom, removes vapor in the reaction vessel through suction while the heating member heats, with a first heat quantity, the reaction vessel; and a second evaporation concentration step in which the exhaust part, in a state where the reaction vessel is located in contact therewith, removes vapor in the reaction vessel through suction while the heating member heats the reaction vessel with a second heat quantity greater than the first heat quantity.

Description

[Technical field]

[0001] The present invention relates to an automatic analyzer. [Background technology]

[0002] One method for analyzing a specific component contained in a liquid sample is, for example, to use LC-MS, which is an online connection between a liquid chromatograph (LC) and a mass spectrometer (MS).

[0003] The use of LC-MS is also expanding into the field of clinical testing, where biological samples such as blood and urine are analyzed using automated analyzers.

[0004] When analyzing liquid biological samples such as blood and urine (hereinafter sometimes simply referred to as samples) using LC-MS, it is necessary to perform pretreatment to improve the degree of purification of the sample. Examples of sample pretreatment include solid phase extraction (SPE) and liquid-liquid extraction (LLE).

[0005] In particular, since SPE can be easily connected online to LC-MS, it is possible to automate pretreatment by SPE and analysis by LC-MS in an integrated manner.

[0006] In order to achieve highly sensitive detection by LC-MS, sample pretreatment may involve evaporation, a process in which the extract containing the target components in the sample is evaporated to increase the concentration of the target components.

[0007] As a technique for evaporating and concentrating such samples, for example, Patent Document 1 discloses an apparatus having a heating section that heats a container to evaporate the sample, and an exhaust section that sucks in the generated vapor.

[0008] In the pretreatment device of such an automatic analyzer, high throughput is required, and therefore, it is expected that the evaporation process will be performed within a limited time. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] International Publication No. 2021 / 002431 Brochure Summary of the Invention [Problem to be solved by the invention]

[0010] However, the conventional technology has a problem in that the liquid sample is prone to bumping.

[0011] For example, in evaporation, it may be difficult to appropriately control the amount of heat applied during evacuation. In such cases, the temperature may rise rapidly while the boiling point of the solution is decreasing, which may lead to bumping of the liquid sample. If bumping occurs, the liquid sample may be sucked into the evacuation section, and the concentration of the target components may not be sufficiently high.

[0012] The present invention has been made in view of the above, and an object of the present invention is to provide an automatic analyzer capable of reducing bumping of a liquid sample. [Means for solving the problem]

[0013] One example of the automatic analyzer according to the present invention is characterized in that it includes a reaction vessel, a heating member, an exhaust unit, and a reaction vessel moving member, and executes a first evaporative concentration step and a second evaporative concentration step. This specification includes the disclosures of Japanese Patent Application No. 2021-190047, which is the priority basis of this application. Effect of the Invention

[0014] The automatic analyzer according to the present invention can reduce bumping of liquid samples. Other objects, configurations and effects will become apparent from the following description of the embodiments. [Brief description of the drawings]

[0015] [Figure 1] 1 is a diagram illustrating an outline of the overall configuration of an automatic analyzer according to a first embodiment of the present invention. [Diagram 2] FIG. 1 is a diagram showing an example of a pretreatment process of an analysis process by an automatic analyzer. [Diagram 3] FIG. 2 is a diagram illustrating an example of an evaporation concentration mechanism according to the first embodiment of the present invention. [Figure 4] FIG. 4 is a schematic diagram of the evaporation and concentration mechanism shown in FIG. 3, viewed from right to left. [Diagram 5] FIG. 4 is a schematic diagram of the evaporation and concentration mechanism shown in FIG. 3, seen from the rear to the front. [Figure 6] 4 is a schematic diagram of a cross section passing through the centers of a reaction vessel and an exhaust unit in the evaporation concentration mechanism shown in FIG. 3, as viewed from the front. [Figure 7] 4 is a diagram showing a schematic diagram of a rotational operation of an exhaust part in the evaporation concentration mechanism shown in FIG. 3. [Figure 8] 4 is a graph showing the operating positions of each part of the automatic analyzer relative to the rotation angle of a rotating cam. [Figure 9] 11 is a diagram showing a schematic representation of the positional relationship between a reaction vessel and an exhaust unit when a rotating cam is operated. FIG. [Figure 10] FIG. 4 is a diagram illustrating a configuration example of a rotating cam. [Figure 11] 11 is a diagram illustrating an example of the positional relationship of parts inside the exhaust unit drive mechanism when a rotating cam is operated. FIG. [Figure 12] 13 is another diagram illustrating an example of the positional relationship of parts inside the exhaust unit drive mechanism when the rotating cam is operated. FIG. [Figure 13] 4 is a cross-sectional view of the evaporation concentration mechanism taken along a horizontal plane passing through the central axis of a rotating cam as viewed from above. FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. In the embodiment, an automatic analyzer that combines a sample pretreatment function with an LC-MS (Liquid Chromatograph - Mass Spectrometer) as an analytical mechanism will be described as an example, but the present invention can also be applied to an automatic analyzer that combines a separation means such as capillary electrophoresis and a detector such as an absorptiometer as an analytical mechanism.

[0017] [Example 1] FIG. 1 is a diagram illustrating an outline of the overall configuration of an automatic analyzer according to a first embodiment of the present invention.

[0018] The automatic analyzer according to the present embodiment aims to reduce bumping of a liquid sample.

[0019] In FIG. 1, the automatic analyzer 100 includes a pre-processing unit 101 for pre-processing a sample, a separation unit 102 for separating components in the sample, an analysis unit 103 for analyzing the separated components, a control unit 104 for controlling the operation of the entire apparatus, an input unit 105 for a user to input information to the apparatus, a display unit 106 for displaying information to the user, and a memory unit 107, such as a storage medium, for storing various information related to the control of the automatic analyzer 100.

[0020] The control unit 104 , the input unit 105 , the display unit 106 , and the storage unit 107 constitute a control device that controls the overall operation of the automatic analyzer 100 .

[0021] In the first embodiment, the input unit 105 and the display unit 106 are shown as separate units, but the input unit 105 and the display unit 106 may be integrally configured, for example, as in a touch panel monitor.

[0022] The pre-treatment unit 101 is equipped with a transport mechanism 112 that transports a sample container 111 containing the sample to be analyzed to a sample dispensing position, a reaction container disk 120 that can maintain the solution in the reaction container 116 at a constant temperature by mounting the reaction containers 116 in multiple openings 119, a reagent disk 122 that holds multiple reagent containers 121 containing reagents, and a sample dispensing mechanism 113 that dispenses the sample from the sample container 111 transported to the sample dispensing position to the reaction container 116 accommodated in the opening 119 of the reaction container disk 120.

[0023] The reaction vessel 116 is capable of containing a liquid sample, has an opening on the upper surface, and is formed in a bottomed shape.

[0024] The pre-processing unit 101 also includes a reagent dispensing mechanism 123 that dispenses reagent from a reagent container 121 to a reaction container 116 of the reaction container disk 120, a dispensing tip mounting rack 115 that mounts unused dispensing tips 115a that are to be mounted on the nozzle of the sample dispensing mechanism 113, and a dispensing tip attachment / detachment unit 114 that removes and discards used dispensing tips 115a from the nozzle of the sample dispensing mechanism 113 and attaches unused dispensing tips 115a to the nozzle.

[0025] The pre-processing unit 101 also includes a reaction vessel mounting rack 117 carrying unused reaction vessels 116, and a transport mechanism 118 which transports unused dispensing tips 115a from the dispensing tip mounting rack 115 to the dispensing tip attachment / detachment unit 114, transports used reaction vessels 116 from an opening 119 in the reaction vessel disk 120 to a disposal unit (not shown), and transports unused reaction vessels 116 from the reaction vessel mounting rack 117 to the opening 119 in the reaction vessel disk 120.

[0026] The pre-treatment unit 101 also includes a magnetic separation mechanism 124 that separates the magnetic beads in the solution contained in the reaction vessel 116 by the magnetic force of a magnet, a transport mechanism 125 that transports the reaction vessel 116 between the reaction vessel disk 120 and the magnetic separation mechanism 124, and an evaporation and concentration mechanism 131 that evaporates and concentrates the components to be analyzed in the solution in the reaction vessel 116.

[0027] Furthermore, the pretreatment unit 101 includes a transport mechanism 132 that transports the reaction vessel 116 between the reaction vessel disk 120 and the evaporation concentration mechanism 131, a separation unit dispensing mechanism 133 that dispenses the solution in the reaction vessel 116 after evaporation and concentration to the separation unit 102 that separates the components in the sample, and an analysis unit 103 that detects and analyzes the components in the solution separated in the separation unit 102.

[0028] The magnetic separation mechanism 124 is provided on a rotation track 126 of the reagent dispensing mechanism 123. The reagent dispensing mechanism 123 can dispense a reagent into a reaction vessel 116 supported by the magnetic separation mechanism 124 and can aspirate a solution in the reaction vessel 116.

[0029] The reaction vessel disk 120 functions as an incubator that keeps the temperature of the reaction vessel 116 placed in the opening 119 constant, and incubates the reaction vessel 116 placed in the opening 119 for a certain period of time.

[0030] The separation unit 102 is, for example, a liquid chromatograph (LC) and includes a column or the like as a functional unit for separating components in the reaction solution dispensed by the separation unit dispensing mechanism 133. The separation unit 102 separates the components in the reaction solution dispensed from the reaction vessel 116 by the separation unit dispensing mechanism 133, and sequentially introduces the separated components to the analysis unit 103.

[0031] The analysis unit 103 is, for example, an MS (Mass Spectrometer) and includes an electron multiplier or the like as a function of ionizing and mass analyzing the components introduced from the separation unit 102. The analysis unit 103 ionizes the components introduced from the separation unit 102, detects the amount of ions (i.e., the amount of the components), and outputs the detection result to the control unit 104.

[0032] The control unit 104 controls the operation of the evaporation concentration mechanism 131, the operation of the separation unit 102, and the operation of the analysis unit 103. The control unit 104 also calculates the concentration values ​​of components in the sample using the detection results (ion amount) from the analysis unit 103 and a previously obtained calibration curve, stores the calculated values ​​as analysis results in the memory unit 107, and causes the display unit 106 to display the analysis results.

[0033] A calibration curve can be obtained, for example, by first analyzing a standard substance with a known concentration at multiple concentrations. Then, the time change in ion amount, i.e., ion intensity, for the m / z (mass / charge ratio) of the ion derived from the standard substance is obtained (mass chromatogram), and the peak area of ​​the mass chromatogram is calculated. A calibration curve is created from the relationship between this area and the concentration of the standard substance.

[0034] By using the calibration curve thus obtained, it is possible to detect the component concentrations of a sample having an unknown concentration but containing the same analyte component as the standard substance.

[0035] Specifically, the peak area of ​​a mass chromatogram of a sample to be analyzed is obtained, and the component concentration of the component to be analyzed is determined from the correspondence between the peak area of ​​the mass chromatogram and a calibration curve.

[0036] Furthermore, if the intensity of the detected ions is normalized based on the intensity of the ions derived from the internal standard, data can be compared with high accuracy. In other words, ion intensities that may vary slightly from analysis to analysis due to the effects of sample pretreatment, sample injection into LC-MS, ionization in LC-MS, etc. can be compared and verified between analyses. This method is called the internal standard method.

[0037] First, the basic steps of the analysis process will be described.

[0038] FIG. 2 is a diagram showing an example of a pretreatment process of an analysis process by an automatic analyzer.

[0039] Prior to starting pretreatment, an unused reaction vessel 116 is placed in an opening 119 on a reaction vessel disk 120 from a reaction vessel mounting rack 117 by a transport mechanism 118. Prior to dispensing a sample, the sample dispensing mechanism 113 is made to access the dispensing tip attachment / detachment part 114 and a dispensing tip 115a is attached to the tip of the nozzle.

[0040] In the pretreatment, first, the sample dispensing mechanism 113 aspirates a sample containing a component to be analyzed from the sample container 111 via the dispensing tip 115a, and dispenses the sample into the reaction container 116 of the reaction container disk 120 (step S200).

[0041] When the sample dispensing mechanism 113 finishes dispensing a sample from one sample container 111, the dispensing tip attachment / detachment section 114 discards the used dispensing tip 115a and attaches an unused dispensing tip 115a.

[0042] Next, the internal standard substance is aspirated as a reagent corresponding to the component to be analyzed from the reagent container 121 of the reagent disk 122 by the reagent dispensing mechanism 123, and is dispensed into the reaction container 116 (step S201).

[0043] Next, a reagent such as a protein removing agent is aspirated from the reagent container 121 of the reagent disk 122 by the reagent dispensing mechanism 123, and is dispensed into the reaction container 116 (step S202).

[0044] Next, the reagent dispensing mechanism 123 aspirates a suspension of magnetic beads as a reagent from the reagent container 121 on the reagent disk 122, and dispenses it into the reaction container 116 (step S203).

[0045] Next, the reaction vessel 116 into which the sample, the internal standard, and the magnetic beads have been dispensed is transported by the transport mechanism 125 to the magnetic separation mechanism 124, where the magnetic beads are washed (step S204). In the magnetic separation mechanism 124, the magnetic beads holding the components to be analyzed and the internal standard are collected on the inner wall surface of the reaction vessel 116 by the magnetic force of the magnet 201 arranged at a position along the outer surface of the reaction vessel 116 (shown as a group of magnetic beads 202 in FIG. 2). In this state, the solution in the reaction vessel 116 is aspirated and discarded by the reagent dispensing mechanism 123.

[0046] At this time, the magnetic beads, the analyte component held on the magnetic beads, and the internal standard remain in the reaction vessel 116.

[0047] Next, the reagent dispensing mechanism 123 aspirates a washing liquid for washing away impurities other than the substances (analyte components and internal standard substances) held by the magnetic beads from the reagent containers 121 on the reagent disk 122, and dispenses it into the reaction containers .

[0048] At this time, the magnetic beads may be temporarily released from the magnetic force of the magnet 201 .

[0049] Next, with the magnetic beads again collected on the inner wall surface of reaction vessel 116 by magnet 201, reagent dispensing mechanism 123 aspirates and discards the solution (washing solution) in reaction vessel 116, thereby washing the magnetic beads.

[0050] Next, the reagent dispensing mechanism 123 aspirates an elution liquid that elutes the analyte component and the internal standard from the magnetic bead group 202 as a reagent from the reagent container 121 of the reagent disk 122, and dispenses it into the reaction container 116 (step S205).

[0051] Next, with the group of magnetic beads 203 from which the components to be analyzed and the internal standard have been eluted collected on the inner wall surface of the reaction vessel 116 by the magnetic force of the magnet 201, the solution (purified liquid) in the reaction vessel 116 is aspirated by the reagent dispensing mechanism 123 (step S206) and dispensed into an unused reaction vessel 116 in a reaction vessel disk 120 different from the reaction vessel 116 placed in the magnetic separation mechanism 124 (step S207).

[0052] The purified liquid contained in the reaction vessel 116 of the reaction vessel disk 120 is incubated as necessary.

[0053] Next, the transport mechanism 132 transports the reaction vessel 116 containing the purified liquid to the evaporation and concentration mechanism 131, where the components in the purified liquid are evaporated and concentrated (step S208). The detailed configuration of the evaporation and concentration mechanism 131 will be described later.

[0054] Next, when the composition of the purified liquid is changed so that the components to be analyzed bind to the separation column (not shown) provided in the separation section 102, the reagent dispensing mechanism 123 aspirates the diluent from the reagent container 121 on the reagent disk 122 and dispenses it into the reaction container 116.

[0055] The purified liquid obtained by the above pretreatment steps is sucked from the reaction vessel 116 by the separation section dispensing mechanism 133 and discharged to the separation section 102, and the components separated in the separation section 102 are ionized in the analysis section 103 to detect the amount of ions (i.e., the amount of components). The detection result in the analysis section 103 is output to the control section 104, and the concentration value of the component in the sample is calculated using a calibration curve.

[0056] Next, the evaporation and concentration process in the first embodiment will be described. The automatic analyzer according to the first embodiment has an evaporation and concentration mechanism and a control method that allow selection of whether or not to perform evaporation and concentration for each component to be analyzed, that is, for each sample. For example, an identification number is assigned to each sample, and which sample with which identification number the evaporation and concentration process is to be performed is stored in the memory unit 107 via the input unit 105, and based on the contents stored by the control unit 104, the control unit 104 selects whether or not to perform evaporation and concentration for each sample, and executes sample processing. That is, the control unit 104 determines whether or not to perform evaporation and concentration for the component to be analyzed in the sample, and causes the evaporation and concentration mechanism 131 to concentrate the component to be analyzed in the sample for which it is determined that the evaporation and concentration process is to be performed.

[0057] 3, 4 and 5 are schematic diagrams showing an example of the evaporation concentration mechanism 131 of the present invention.

[0058] 3, the evaporation concentration mechanism 131 includes a heating means 304 (heating member) for heating the reaction vessel 116 and an exhaust section 305 (exhaust section) for sucking in steam from the reaction vessel 116. The heating means 304 includes one or more bottomed container receiving sections 301 (insertion holes), and the reaction vessel 116 can be inserted into the container receiving section 301. Note that the "bottom" refers to the closed end of the hole, which is the lower end of the container receiving section 301 in this embodiment, but does not necessarily have to be formed vertically downward depending on the shape of the container receiving section.

[0059] Particularly, in this embodiment, the heating means 304 includes a plurality of container receiving portions 301, which are arranged in a row.

[0060] The transported reaction vessels 116 are individually assigned to either the vessel receiving section 301 of the evaporation concentration section 302 where evaporation concentration is performed, or the vessel receiving section 301 of the standby section 303 where evaporation concentration is not performed. The vessel receiving sections 301 of the evaporation concentration section 302 are each provided with a corresponding exhaust section 305.

[0061] Here, the evaporation concentration mechanism 131 includes a heating means 304 for heating the reaction vessel 116 and an exhaust unit 305 for sucking the steam inside the reaction vessel 116. Examples of the heating means 304 include a Peltier element or a heater whose temperature can be controlled by the analysis device.

[0062] Moreover, a vacuum pump whose operation can be controlled by the analytical device is an example of the exhaust unit 305. Moreover, a valve 501 may be provided between the opening of the exhaust unit 305 and the drain.

[0063] As a method for allocating the reaction vessel 116 to either the vessel receiving section 301 of the standby section 303 or the vessel receiving section 301 of the evaporation concentration section 302, there is a method in which the evaporation concentration mechanism 131 is made movable.

[0064] First, the control unit 104 moves the evaporation concentration mechanism 131 so that the access point 306 of the transport mechanism 132 and the container receiving unit 301 coincide with each other. At this time, it is preferable to move the evaporation concentration mechanism 131 in the juxtaposition direction of the container receiving units 301 as shown in FIG. 3. This is because each container receiving unit 301 can be arranged at the same access point 306. This eliminates the need to drive the evaporation concentration mechanism 131 in the left-right direction, so that the entire mechanism can be made smaller. In this example, a motor 307 is used as a drive source for the juxtaposition direction movement, and is converted into linear motion via a belt mechanism 308. Linear motion may also be achieved by combining a solenoid, a ball screw, a gear, or the like.

[0065] 3, the access point 306 is provided at a position corresponding to the waiting section 303, but the access point 306 may be provided at a position corresponding to the heating means 304, and the heating means 304 may be configured to be movable parallel to the arrangement direction of the container receiving section 301. In this way, the same effect can be obtained for the reaction container 116 that performs evaporation and concentration.

[0066] For samples for which the control unit 104 has determined that evaporation and concentration is not to be performed, the reaction container 116 is transported by the transport mechanism 132 to the container receiving section 301 on the waiting section 303, and after waiting for a certain period of time, the purified liquid is introduced into the separation section 102 by the separation section dispensing mechanism 133.

[0067] When evaporative concentration is performed, the reaction vessel 116 is transported to the vessel receiving section 301 above the evaporative concentration section 302 by the transport mechanism 132. At this time, the exhaust section 305 is disposed in the vicinity of the heating means 304 of the evaporative concentration section 302 and at a position spaced apart from the heating means 304 by a certain distance or more.

[0068] In this embodiment, the exhaust section 305 is rotated by the exhaust section driving mechanism 401 as shown in Figures 3 and 4, so that the exhaust section 305 can be positioned at a position where the upper and lower projection areas of the container receiving section 301 and the upper and lower projection areas of the exhaust section 305 do not overlap.

[0069] In this embodiment, the automatic analyzer 100 includes a plurality of exhaust units 305. The exhaust units 305 are arranged in correspondence with the respective container receiving units 301. For example, the exhaust units 305 are arranged in parallel with the container receiving units 301. This allows the exhaust units 305 that need to be driven to be arranged at a fixed position at a fixed distance from the access point 306, and eliminates the need to increase the movable range of the exhaust units 305. In this case, the parallel movement of the exhaust unit drive mechanism 401 is not necessary. Also, as shown in Figures 3 and 4, the exhaust unit drive mechanism 401 is arranged below the exhaust unit 305 so that at least a part of the mechanism coincides with the vertical projection area of ​​the moving range of the evaporation and concentration unit 302, thereby making it possible to reduce the vertical projection area of ​​the mechanism. The "moving range of the evaporation and concentration unit 302" refers to, for example, the space occupied by the evaporation and concentration unit 302 when it moves.

[0070] Next, the exhaust unit 305 is moved so as to be located above the reaction vessel 116 placed in the heating means 304 and in close contact with the reaction vessel 116. In this case, the evaporation and concentration mechanism 131 may be moved.

[0071] In this specification, "close contact" means that two structures are in contact with each other over a finite area. In a modified example, the two structures that are in close contact with each other in this embodiment can be configured to be in contact only at one or more points without being in close contact.

[0072] Then, the reaction vessel 116 is heated by the heating means 304 and evacuated with the valve 501 open for a certain period of time, thereby causing evaporation and concentration.

[0073] In order to increase the evaporation efficiency, it is better to bring the opening of the reaction vessel 116 into close contact with the exhaust part 305 by raising the evaporation concentration part 302 relative to the exhaust part 305 or lowering the exhaust part 305 relative to the reaction vessel 116 .

[0074] In this manner, the exhaust unit driving mechanism 401 moves the exhaust unit 305 to a predetermined open position (a raised position in this embodiment) and a predetermined closed position (a lowered position in this embodiment). In this embodiment, both the open position and the closed position are vertically above the reaction vessel 116.

[0075] The open position and the closed position can be expressed as the relative positions of the exhaust unit 305 with respect to the reaction vessel 116. For example, when the exhaust unit 305 moves up and down together with the reaction vessel 116 while closing the reaction vessel 116, it can be said that the exhaust unit 305 is always in the closed position regardless of the absolute positional fluctuation of the exhaust unit 305.

[0076] In the open position, exhaust unit 305 moves away from the opening of reaction vessel 116 to open the opening, and in the closed position, exhaust unit 305 seals the opening of reaction vessel 116 to reduce the pressure inside reaction vessel 116. In particular, exhaust unit 305 is configured to be freely opened and closed relative to the opening of reaction vessel 116, and seals the opening of reaction vessel 116 in the closed state. With this configuration, the opening and reduction in pressure of reaction vessel 116 can be appropriately controlled.

[0077] However, if the exhaust section 305 starts suction (reducing pressure) inside the reaction vessel 116 while the reaction vessel 116 and the evaporation concentration section 302 are in close contact with each other, a sudden increase in temperature of the solution and a drop in the boiling point occur simultaneously, which may cause the sample inside the reaction vessel 116 to bump. As a countermeasure, there is a method of sufficiently reducing the pressure inside the reaction vessel 116 while reducing the amount of heat input from the heating means 304 to the reaction vessel 116, and then increasing the amount of heat input to the reaction vessel 116 after a certain time has passed.

[0078] For example, by changing the heat transfer area between reaction vessel 116 and container receiving part 301 while the inside of reaction vessel 116 is being depressurized, it is possible to control the amount of heat input to reaction vessel 116. That is, reaction vessel 116 is placed in container receiving part 301 and the evaporation concentration process is started, and when the pressure inside reaction vessel 116 starts to be depressurized, reaction vessel 116 is floated in container receiving part 301 to an extent that allows heat transfer, and after the pressure inside reaction vessel 116 is sufficiently reduced, the floating of reaction vessel 116 is released, and the heat transfer area with container receiving part 301 is increased, thereby accelerating heating inside reaction vessel 116.

[0079] An example of a drive mechanism for realizing this operation in the evaporation concentration mechanism 131 will be described.

[0080] FIG. 6 is a schematic diagram of the cross section passing through the centers of the reaction vessel 116 and the exhaust section 305 in the evaporation concentration mechanism 131, as viewed from the rear.

[0081] The evaporation concentration mechanism 131 includes an evaporation concentration section 302, an exhaust section 305, a reaction vessel lifting member 601, a lever 602 (first lever) that operates the reaction vessel lifting member 601, a lever 603 (second lever) that lifts the exhaust section 305, a lever 604 (third lever) that rotates the exhaust section 305, an exhaust section rotation pin 605, an origin detection lever 606 (fourth lever), and a rotating cam 607 that determines the amount of operation and phase of each lever.

[0082] It is desirable that each lever and the rotating cam 607 are always in close contact with each other. For example, a torsion spring may be provided on the rotation shaft of each lever, and torque may be applied to each lever in a direction in which the lever comes into close contact with the other lever. As in the above mechanism, instead of attaching a driving source to each driving unit, the force of one driving source is transmitted to the cam to operate multiple parts, thereby making it possible to save space.

[0083] The reaction vessel floating member 601 is a reaction vessel moving member that moves the reaction vessel 116. In this embodiment, the reaction vessel 116 moves in the vertical direction, but it is also possible to modify the reaction vessel 116 so that it moves in another direction.

[0084] Here, reaction vessel floating member 601 is passed through a vertical through hole provided in heating means 304, and is constantly pressed downward. That is, when lever 602 is lowered, reaction vessel 116 and heating means 304 come into close contact with each other, and a high amount of heat is input to reaction vessel 116. In this example, a compression spring applies a force in the downward direction.

[0085] On the other hand, when lever 602 is raised and reaction vessel lifting member 601 pushes up reaction vessel 116, a gap is created below reaction vessel 116. At this time, a lower amount of heat is input to reaction vessel 116 compared to when the vessel is in close contact. In this way, since the amount of heat transferred to reaction vessel 116 is controlled by the mechanism, control unit 104 only needs to keep the temperature of heating means 304 constant and does not need to have a function for changing the temperature.

[0086] In this manner, the reaction vessel floating member 601 moves the reaction vessel 116 to a predetermined separation position and contact position along the vessel receiving portion 301 of the heating means 304. At the separation position, the reaction vessel 116 and the bottom of the vessel receiving portion 301 are separated from each other, and at the contact position, the reaction vessel 116 and the bottom of the vessel receiving portion 301 are in contact with each other (in this embodiment, in close contact).

[0087] In this embodiment, the reaction vessel 116 moves up and down, so the separation position is vertically above the contact position.

[0088] Also, when exhaust section 305 is not rotating and lever 603 is pushed up to a certain height or less, it is advisable to apply a vertical force to exhaust section 305 so that reaction vessel 116 and exhaust section 305 come into close contact with each other. This is to reduce leakage of fluid from the contact area. At this time, the opening of reaction vessel 116 and the vent pipe opening of exhaust section 305 are in communication, and the inside of reaction vessel 116 is in a reduced pressure state. In this example, the downward force is applied by a compression spring.

[0089] Next, the configuration of the exhaust unit rotation mechanism related to lever 604 will be described.

[0090] FIG. 7 is a diagram showing a schematic diagram of the rotational movement of the exhaust part 305 in the evaporation concentration mechanism 131. As shown in FIG.

[0091] 7(a), a torque is constantly applied so that the opening of the exhaust part 305 overlaps with the upper and lower projected areas of the opening of the reaction vessel 116. The torque may be applied by a torsion spring.

[0092] From this state, as shown in Fig. 7(b), lever 604 pushes exhaust unit rotation pin 605 in, causing exhaust unit 305 to rotate. It is desirable that when exhaust unit 305 rotates, there is no contact between the opening of reaction vessel 116 and exhaust unit 305. This is to reduce the possibility of exhaust unit 305 getting caught on reaction vessel 116 when rotating. Here, as an example, the opening of exhaust unit 305 overlaps with the upper and lower projection areas of the opening of reaction vessel 116 when not rotating. Any part of the rotation range may overlap.

[0093] An origin detection lever 606 (FIG. 6) is always in close contact with a rotating cam 607 and passes through a detector 608 when pressed by the rotating cam 607 .

[0094] Next, the operation sequence of the evaporation concentration mechanism 131 controlled by the rotating cam 607 will be described.

[0095] 8 is a graph showing the operating positions of each part of the automatic analyzer with respect to the rotation angle of the rotary cam 607. In this case, the state where the origin detection lever 606 passes through the detector 608 is taken as the origin.

[0096] At the start of operation, at the origin, the reaction vessel 116 in which the evaporation and concentration process has been completed is placed in the vessel receiving section 301. At this time, the reaction vessel 116 and the exhaust section 305 are lowered, and the inside of the reaction vessel 116 is sealed.

[0097] Next, the exhaust section 305 and the reaction vessel 116 are floated in that order. The reason for floating the reaction vessel 116 is to reduce the possibility that the reaction vessel 116 will become stuck when it is carried out from the vessel receiving section 301. However, it is not necessary to float the reaction vessel 116 so that it is completely exposed when the mechanism is viewed in the front-back or left-right direction. Note that the amount of floating of the exhaust section 305 is made larger than that of the reaction vessel 116, and the two are separated from each other when they are at their maximum floating.

[0098] Next, the exhaust unit 305 is rotated so that the exhaust unit 305 does not overlap with the vertical projection area of ​​the reaction vessel 116. In other words, the exhaust unit driving mechanism 401 moves the exhaust unit 305 to a position that is not vertically above the reaction vessel 116. This makes it possible to remove the reaction vessel 116 upward from the vessel receiving unit 301 and replace it.

[0099] Next, the reaction vessel 116 that has been subjected to the evaporation and concentration process is replaced with a reaction vessel 116 that has not been subjected to the evaporation and concentration process, using the transport mechanism 132. In this manner, the automatic analyzer 100 replaces the reaction vessel 116 in the vessel receiving section 301 with the exhaust section 305 in the above-mentioned replacement position. In this manner, the reaction vessel 116 being replaced does not come into contact with the exhaust section 305.

[0100] In this embodiment, as shown in Figures 3 and 4, a plurality of exhaust units 305 are provided. The automated analyzer 100 can be configured so that while one exhaust unit 305 is in the replacement position, another exhaust unit 305 reduces the pressure inside the corresponding reaction vessel 116. In this way, a plurality of reaction vessels 116 can be efficiently processed in parallel.

[0101] Next, the exhaust part 305 is rotated so that the vent opening of the exhaust part 305 overlaps with the vertical projection area of ​​the opening of the reaction vessel 116 .

[0102] Next, while the reaction vessel 116 is floated, only the exhaust part 305 is lowered, and while the lid of the exhaust part 305 (having an air vent opening) and the reaction vessel 116 are in close contact with each other, the exhaust part 305 reduces the pressure inside the reaction vessel 116.

[0103] After a predetermined time has elapsed, the reaction vessel 116 is lowered while maintaining the close contact between the reaction vessel 116 and the exhaust unit 305. At this time, since the heat transfer surface area to the reaction vessel 116 is larger than when it was raised, the gas in the reaction vessel 116 is sucked in while a high amount of heat is being input to the sample. At this point, the reaction vessel 116 is returned to the origin.

[0104] Here, a method for maximizing the difference in the area for heat transfer to the sample when the heat quantity is low and when the heat quantity is high in order to further reduce bumping in the above-mentioned operation will be described.

[0105] 9 is a diagram showing a schematic diagram of the positional relationship between the reaction vessel 116 and the exhaust part 305 when the rotating cam 607 is operated. The vessel receiving part 301 of the heating means 304 has a stepped part 301a whose diameter decreases from the open end toward the bottom.

[0106] 9(a), the reaction vessel 116 is floated and placed in a spaced position away from the bottom of the vessel receiving part 301. At the spaced position, a gap 701 is generated between the bottom of the reaction vessel 116 and the vessel receiving part 301, reducing the heat transfer area.

[0107] Here, from the top opening of the container receiving part 301 to a predetermined depth, a gap 702 is provided by the step part 301a between the side surface of the reaction container 116 and the container receiving part 301. In this way, it is possible to further reduce the area of ​​heat transfer to the sample.

[0108] In particular, it is desirable to reduce the heat transfer area to the sample by making the lower end of the gap 702 lower than the liquid level when the reaction vessel 116 is floated. In other words, it is desirable that the liquid level of the sample is higher than the step portion 301a when the reaction vessel 116 is in the separated position.

[0109] 9(b), the exhaust part 305 is lowered to reduce the pressure inside the reaction vessel 116. That is, while the reaction vessel 116 is in the separated position, the exhaust part 305 sucks the steam inside the reaction vessel 116, and the heating means 304 heats the reaction vessel with a predetermined amount of heat (first amount of heat) (first evaporation and concentration step).

[0110] In this first evaporation concentration step, since the transfer of heat through the gap 702 is inhibited, the amount of heat transferred to the reaction vessel 116 is small even without adjusting the output of the heating means 304. This reduces the possibility of a sudden increase in temperature during pressure reduction (while the boiling point of the solution is lowered), and reduces bumping of the sample.

[0111] 9(c), reaction vessel 116 and exhaust unit 305 are further lowered to a contact position where they come into contact with the bottom of vessel receiving unit 301. With reaction vessel 116 in the contact position, exhaust unit 305 sucks in steam from reaction vessel 116, and heating means 304 heats reaction vessel 116 with a predetermined amount of heat (second amount of heat) (second evaporation and concentration step).

[0112] Here, in the second evaporation concentration step, the area of ​​direct contact between the reaction vessel 116 and the heating means 304 becomes larger, so that the second amount of heat transferred to the reaction vessel 116 becomes larger than the first amount of heat even without adjusting the output of the heating means 304. Therefore, heating can be performed efficiently.

[0113] In this state, it is better to make the lower end of the gap 702 higher than the liquid level to maximize the heat transfer area to the sample. In other words, it is better to make the liquid level of the sample lower than the step portion 301a when the reaction vessel 116 is in the contact position.

[0114] Here, the automatic analyzer 100 can be configured to perform the second evaporative concentration step after performing the first evaporative concentration step for a predetermined period of time, thereby more reliably reducing bumping of the sample.

[0115] 9(d) and 9(e) show examples in which the amount of sample is smaller than that shown in Fig. 9(a) to 9(c). Fig. 9(d) shows the contact position where the reaction vessel 116 has descended, and Fig. 9(d) shows the separated position where the reaction vessel 116 has floated.

[0116] Next, the position of each part relative to the rotation angle of the rotating cam 607 will be described with reference to a schematic diagram.

[0117] Fig. 10 shows an example of the configuration of the rotating cam 607 shown in Fig. 6. The rotating cam 607 has a triple cam structure, in which cam member 607a (first cam member) determines the position of lever 603, cam member 607b (second cam member) determines the position of lever 602, and cam member 607c (third cam member) determines the position of lever 604. The cam members 607a, 607b, and 607c are fixed integrally with the rotating cam 607 and operate in conjunction with one another.

[0118] The cam member 607a moves the reaction vessel 116 up and down by changing the position of the lever 603. The cam member 607b moves the exhaust unit 305 up and down, for example to the open position and the closed position, by changing the position of the lever 602. The cam member 607c rotates the exhaust unit 305 by changing the position of the lever 604, for example to the open position and the replacement position.

[0119] By using such a pivoting cam 607, multiple parts can be made to work together in a single mechanism.

[0120] 11 and 12 are diagrams that diagrammatically show examples of the positional relationships of parts inside exhaust unit drive mechanism 401 when rotating cam 607 is operated.

[0121] First, at the origin shown in FIG. 11(a), the rotary cam 607 presses only the origin detection lever 606, and the levers 602 to 604 are released from the pressing.

[0122] When the rotary cam 607 is rotated from the origin, the origin detection lever 606 is released from the depressed state as shown in Fig. 11(b). In this example, the rotation is clockwise, but it may be reversed.

[0123] Next, as shown in FIG. 11(c), FIG. 11(d), and FIG. 11(e), the rotating cam 607 pushes the levers 604, 603, and 602 together.

[0124] 11(f), 12(a), 12(b) and 12(c), the pressing of the rotary cam 607 onto the levers 602, 603 and 604 is released.

[0125] Finally, as shown in Fig. 12(d), the rotary cam 607 pushes the origin detection lever 606, and the rotary cam 607 returns to the origin. Note that the state in Fig. 12(d) is the same as the state in Fig. 11(a).

[0126] The above-mentioned operation shown in Figures 11 and 12 is one example of a specific operation of the automatic analyzer 100, and the operation according to the graph shown in Figure 8 is also possible. Even in this case, the rotating cam 607 rotates as shown in Figures 11 and 12. A specific description will be given below.

[0127] First, the automatic analyzer 100 places the exhaust unit 305 in the replacement position. Next, the automatic analyzer 100 inserts the reaction container 116 into the container receiving portion 301 of the heating means 304. Next, the automatic analyzer 100 moves the exhaust unit 305 from the replacement position to the open position by the action of the cam member 607c. Next, the automatic analyzer 100 moves the exhaust unit 305 from the open position to the closed position by the action of the cam member 607b.

[0128] In this state, the automatic analyzer 100 executes the first evaporative concentration step and the second evaporative concentration step described above.

[0129] Next, the automatic analyzer 100 moves the exhaust unit 305 from the closed position to the open position by the action of the cam member 607b. Next, the automatic analyzer 100 moves the exhaust unit 305 from the open position to the replacement position by the action of the cam member 607c. Next, the automatic analyzer 100 removes the reaction vessel 116 from the vessel receiving portion 301 of the heating means 304 (or replaces it with the next reaction vessel 116 if there is one).

[0130] According to this operation, multiple operations of the automated analyzer 100 can be appropriately controlled by a single rotating cam 607.

[0131] Next, a motor mechanism for operating the rotating cam 607 will be described.

[0132] FIG. 13 shows a cross section of the evaporation concentration mechanism 131 when viewed from above, taken along a horizontal plane passing through the central axis of the rotating cam 607.

[0133] The automatic analyzer 100 includes a motor mechanism. The motor mechanism includes a motor 1101 and the above-mentioned rotating cam 607. The rotating cam 607 is driven by the motor 1101.

[0134] The driving force of the motor 1101 is transmitted to the rotating cam 607 via the output shaft 1102. The motor mechanism may include a reduction gear that transmits power between the motor 1101 and the rotating cam 607. For example, a reduction gear 1103 may be sandwiched between the motor 1101 and the output shaft 1102. In this way, when the speed required for the vertical movement of the reaction vessel 116 and the vertical movement and rotation of the exhaust part 305 is small, the output torque required for the motor 1101 can be reduced.

[0135] In addition, exhaust unit drive mechanism 401 may be enclosed in a box to prevent foreign matter from entering from the outside of the box. Furthermore, reduction gear 1103 may be enclosed or nearly enclosed in a box separate from exhaust unit drive mechanism 401.

[0136] As described above in relation to Fig. 3, the heating means 304 can be configured to be movable. In this case, if the vertical projection area of ​​the movement range of the heating means 304 and the vertical projection area of ​​the motor mechanism are arranged so as to at least partially overlap, the installation area of ​​the automatic analyzer 100 can be reduced. Note that the "movement range of the heating means 304" refers to, for example, the space occupied by the heating means 304 when it moves. Furthermore, if the motor mechanism is arranged below the heating means 304, the space above the motor mechanism can be used efficiently.

[0137] 3 is an example, and can be changed in consideration of the number of samples that can be processed per hour set in the automatic analyzer, i.e., the throughput, the time required for evaporation and concentration, etc. If the throughput is set to 100 samples / hour (36 seconds / sample) and the time required for evaporation and concentration is set to 108 seconds (36 seconds x 3), then by providing three container receiving sections 301 in each of the evaporation and concentration section 302 and the standby section 303, the evaporation and concentration mechanism 131 can process the reaction containers 116 sequentially without idle time even when the same process is performed continuously, and a throughput of 100 samples / hour can be obtained. In this case, an exhaust section 305 is required for each of the three container receiving sections 301 in the evaporation and concentration section 302.

[0138] When exhaust is performed by closely contacting reaction vessel 116 and exhaust section 305, valve 501 can be opened while sucking in steam and closed after the sucking is completed, thereby preventing reaction vessel 116 from becoming stuck in exhaust section 305.

[0139] In addition, after the exhaust part 305 finishes suctioning the steam, it is considered that the condensed steam may drip from the exhaust part 305. One countermeasure to this is to heat the exhaust part 305 itself. In addition, one countermeasure is to perform dry suction by the exhaust part 305 after the exhaust is finished and the exhaust part 305 is separated from the reaction vessel 116.

[0140] As described above, according to the first embodiment of the present invention, the heat transfer area between the reaction vessel 116 and the vessel receiving portion 301 is changed while reducing the pressure inside the reaction vessel 116.

[0141] Therefore, bumping of the sample can be reduced by applying high heat after the inside of the container is sufficiently reduced in pressure, and an automatic analyzer with an increased evaporation concentration rate of the sample can be realized.

[0142] 3, the standby section 303 and the evaporation and concentration section 302 are adjacent to each other, but the standby section 303 may be made of a heat insulating material to limit the effect of heat from the evaporation and concentration section 302. The standby section 303 and the evaporation and concentration section 302 may be arranged apart from each other to avoid thermal effect.

[0143] It should be noted that the present invention is not limited to the above-described embodiment and modifications, but includes various other modifications. For example, the above-described embodiment has been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those having all of the described configurations.

[0144] In the above example, the concentration process includes both heating and evacuation, but the concentration process may include either heating or evacuation, as this is because the sample can be concentrated by only heating or only evacuation.

[0145] In addition, the above-mentioned configurations, functions, etc. may be realized in part or in whole by designing, for example, an integrated circuit, etc. In addition, the above-mentioned configurations, functions, etc. may be realized in software by a processor interpreting and executing a program that realizes each function.

[0146] Furthermore, the analysis unit 103 may be, for example, an optical analysis device other than a mass analysis device. [Explanation of symbols]

[0147] 100…Automatic analyzer 116...Reaction vessel 301...Container receiving portion (insertion hole) 301a…Step 304... Heating means (heating member) 305…Exhaust section 307...Motor 401...Exhaust section drive mechanism 601...Reaction vessel floating member (reaction vessel moving member) 602~604…Lever 605...Exhaust section pivot pin 606...Origin detection lever 607...Rotating cam 607a... Cam member (first cam member) 607b... Cam member (second cam member) 607c...Cam member (third cam member) 1101...Motor 1103...Reduction gear All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety.

Claims

1. A reaction vessel capable of containing a liquid sample and having an opening; a heating member for heating the reaction vessel, the heating member having one or more bottomed insertion holes, the reaction vessel being insertable into the insertion holes; an exhaust unit that sucks in steam from within the reaction vessel, the exhaust unit being configured to be freely opened and closed with respect to an opening of the reaction vessel, and sealing the opening of the reaction vessel when the exhaust unit is closed; a reaction vessel moving member that moves the reaction vessel, the reaction vessel moving member moving the reaction vessel along the insertion hole of the heating member to a spaced position and a contact position, the reaction vessel and a bottom of the insertion hole being spaced apart at the spaced position and the reaction vessel and the bottom of the insertion hole being in contact at the contact position; An automatic analyzer comprising: The automated analyzer comprises: a first evaporation and concentration step in which, while the reaction vessel is in the separated position, the exhaust unit sucks in steam within the reaction vessel and the heating member heats the reaction vessel with a first heat quantity; a second evaporation and concentration step in which, while the reaction vessel is in the contact position, the exhaust unit sucks in steam from within the reaction vessel, and the heating member heats the reaction vessel with a second heat amount greater than the first heat amount; An automatic analyzer characterized by performing the above.

2. 2. The automatic analyzer according to claim 1, wherein the automatic analyzer performs the second evaporation and concentration step after performing the first evaporation and concentration step for a predetermined period of time.

3. The automatic analyzer according to claim 1 , wherein the separated position is located vertically above the contact position.

4. The insertion hole of the heating member has a stepped portion whose diameter decreases from an opening end toward the bottom, When the reaction vessel is in the separated position, the liquid level of the liquid sample is higher than the step portion, When the reaction vessel is in the contact position, the liquid level of the liquid sample is lower than the step portion. The automatic analyzer according to claim 3 .

5. The heating member has a plurality of the insertion holes, and the insertion holes are arranged in a line. The heating member is configured to be movable parallel to the arrangement direction of the insertion holes. The automatic analyzer according to claim 1 .

6. The automated analyzer includes an exhaust unit drive mechanism that moves the exhaust unit to an open position and a closed position, the exhaust unit opens the opening of the reaction vessel by moving away from the opening at the open position, and closes the opening of the reaction vessel at the closed position, thereby enabling the pressure inside the reaction vessel to be reduced. The automatic analyzer according to claim 1 .

7. the open position and the closed position are vertically above the reaction vessel, the exhaust unit drive mechanism moves the exhaust unit to an exchange position that is not vertically above the reaction vessel, the automated analyzer replaces the reaction vessel in the insertion hole with the exhaust unit in the replacement position; The automatic analyzer according to claim 6 .

8. 8. The automatic analyzer according to claim 7, wherein the automatic analyzer includes a plurality of exhaust units, each exhaust unit being arranged corresponding to each insertion hole.

9. 9. The automatic analyzer according to claim 8, wherein while one of the exhaust units is in the replacement position, another of the exhaust units reduces the pressure inside the corresponding reaction vessel.

10. The automated analyzer includes a motor mechanism, The motor mechanism includes a motor and a rotating cam driven by the motor. The rotating cam includes a first cam member, a second cam member, and a third cam member that operate in conjunction with one another, The first cam member moves the reaction vessel, the second cam member moves the exhaust portion to the open position and the closed position, The third cam member moves the exhaust unit to the open position and the replacement position. The automatic analyzer according to claim 7 .

11. 11. The automatic analyzer according to claim 10, wherein the motor mechanism includes a reduction gear that transmits power between the motor and the rotary cam.

12. The heating member is configured to be movable, a vertical projection area of ​​a moving range of the heating member and a vertical projection area of ​​the motor mechanism are disposed so as to at least partially overlap each other; The motor mechanism is disposed below the heating member. The automatic analyzer according to claim 10 .

13. The automated analyzer comprises: inserting the reaction vessel into the insertion hole of the heating member; moving the exhaust unit from the replacement position to the open position by the action of the third cam member; moving the exhaust portion from the open position to the closed position by action of the second cam member; The first evaporation and concentration step and the second evaporation and concentration step; moving the exhaust portion from the closed position to the open position by the action of the second cam member; moving the exhaust portion from the open position to the replacement position by the action of the third cam member; removing the reaction vessel from the insertion hole of the heating member; 11. The automatic analyzer according to claim 10, wherein the steps are carried out in the order listed above.

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