Processing device and automatic analysis device

Abstract

The purpose of the present invention is to provide a processing device capable of filtering a liquid without increasing the size of the device. To achieve this, a processing device according to the present invention comprises: a placement part on which a first container having a first opening on an upper surface and accommodating a liquid is placed; a pressing part that presses a second container having a filter on a bottom surface and a second opening on an upper surface downward against the first container through the first opening; and a nozzle that suctions filtrate transferred from the first container to the second container through the filter. The nozzle is constructed to move vertically in conjunction with vertical movement of the pressing part.

Description

Processing device and automatic analyzer

[0001] The present invention relates to a processing device and an automatic analyzer.

[0002] One method for analyzing specific components contained in biological samples such as blood and urine (hereinafter simply referred to as "samples") uses, for example, liquid chromatography-mass spectrometry (LC-MS), which connects liquid chromatography (LC) and mass spectrometry (MS) online. Patent Document 1 discloses a technique in which, in an analytical system equipped with a pretreatment device and an LC-MS, the pretreatment device removes proteins from the sample by filtration.

[0003] Japanese Patent Application Laid-Open No. 2018-4327

[0004] According to Patent Document 1, a dedicated filtration port needs to be installed in the pretreatment device, which may increase the size of the entire analysis system.

[0005] An object of the present invention is to provide a treatment device that can filter a liquid without increasing the size of the device.

[0006] In order to achieve the above-mentioned object, the processing device of the present invention comprises a mounting section for mounting a first container having a first opening on its top surface and containing a liquid, a pressing section for pressing a second container having a filter on its bottom surface and a second opening on its top surface against the first container from above downward via the first opening, and a nozzle for sucking up filtrate that has moved from the first container to the second container via the filter, and the nozzle is configured to move up and down together with the up and down movement of the pressing section.

[0007] Fig. 1 is a diagram showing an overall configuration of an automatic analyzer. Fig. 2 is a diagram showing an example of a pretreatment step of an analytical process. Fig. 3 is a diagram showing an outline of the configuration of a filtration treatment device. Fig. 4 is a flowchart showing the filtration operation of a purified liquid. Fig. 5 is a diagram showing a state in which a pressing part contacts a second container. Fig. 6 is a diagram showing a state in which a pressing part has reached a pressing end position. Fig. 7 is a diagram showing a state in which a nozzle has reached a suction position.

[0008] Below, we will explain an example of an automatic analyzer that combines LC-MS as an analytical mechanism with a sample pretreatment function. However, the present invention can also be applied to an automatic analyzer that combines, for example, a separation means such as capillary electrophoresis with a detector such as an absorptiometer as an analytical mechanism.

[0009] 1 is a diagram showing a schematic diagram of the overall configuration of an automatic analyzer 100. The automatic analyzer 100 includes a preprocessing unit 101 that purifies a sample using magnetic beads, a separation unit 102 that performs LC separation of components in the purified sample, an analysis unit 103 that analyzes the LC-separated components, a control unit 104 that controls the operation of the entire apparatus, an input unit 105 that allows a user to input information to the apparatus, a display unit 106 that displays information to the user, and a storage unit 107 such as a storage medium that stores various information related to the control of the automatic analyzer 100.

[0010] 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 .

[0011] Although the input unit 105 and the display unit 106 are shown as separate units in FIG. 1, the input unit 105 and the display unit 106 may be integrated into one unit, for example, like a touch panel monitor.

[0012] The pretreatment unit 101 comprises a transport mechanism 112 that transports a sample container 111 containing the sample to be analyzed to a sample dispensing position, a reaction disk 120 that can maintain the solution in the reaction container 116 at a constant temperature by mounting the reaction container 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 into the reaction container 116 accommodated in the opening 119 of the reaction disk 120.

[0013] The pre-processing unit 101 also includes a reagent dispensing mechanism 123 that dispenses reagent from a reagent container 121 into a reaction container 116 on the reaction disk 120, a dispensing tip mounting rack 115 that mounts unused disposable dispensing tips 115a that are attached to 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, or attaches unused dispensing tips 115a to the nozzle.

[0014] The pre-processing unit 101 also includes a container mounting rack 117 carrying unused reaction containers 116, and a transport mechanism 118 that transports unused dispensing tips 115a from the dispensing tip mounting rack 115 to the dispensing tip attachment / detachment unit 114, transports used reaction containers 116 from the opening 119 of the reaction disk 120 to a disposal unit (not shown), and transports unused reaction containers 116 from the container mounting rack 117 to the opening 119 of the reaction disk 120.

[0015] The pretreatment unit 101 also includes a magnetic separation mechanism 124 that separates magnetic beads in the solution contained in the reaction vessel 116 using the magnetic force of a magnet, a transport mechanism 125 that transports the reaction vessel 116 between the reaction 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.

[0016] Furthermore, the pretreatment unit 101 includes a transport mechanism 132 that transports the reaction vessel 116 between the reaction disk 120 and the evaporation and concentration mechanism 131, and a purified liquid 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.

[0017] 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.

[0018] The reaction 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.

[0019] The separation unit 102 is, for example, a liquid chromatograph, and includes a column or the like for separating components in the reaction solution dispensed by the purified liquid dispensing mechanism 133. The separation unit 102 separates the components in the reaction solution dispensed from the reaction vessel 116 by the purified liquid dispensing mechanism 133, and sequentially introduces the separated components into the analysis unit 103.

[0020] The analysis unit 103 is, for example, a mass spectrometer, and includes an electron multiplier or the like for the 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 components), and outputs the detection result to the control unit 104.

[0021] The control unit 104 controls the operation of the transport mechanism 132, the operation of the purified liquid dispensing mechanism 133, the operation of the evaporation and concentration mechanism 131 (evaporation and concentration unit), 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 amounts) from the analysis unit 103 and a calibration curve obtained in advance, stores the results as analysis results in the memory unit 107, and displays the analysis results on the display unit 106.

[0022] The basic steps of the analytical processing will now be described. Fig. 2 is a diagram showing an example of the pre-processing steps of the analytical processing.

[0023] Prior to starting the analysis process, the transport mechanism 118 places an unused reaction vessel 116 from the vessel mounting rack 117 into the opening 119 on the reaction disk 120. Prior to dispensing the sample, the sample dispensing mechanism 113 accesses the dispensing tip attachment / detachment unit 114, and a dispensing tip 115a is attached to the tip of the nozzle.

[0024] In the analysis process, 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 it into the reaction container 116 on the reaction disk 120 (step S200).

[0025] When the sample dispensing mechanism 113 has finished dispensing the sample from one sample container 111, the dispensing tip attaching / detaching unit 114 discards the used dispensing tip 115a and attaches an unused dispensing tip 115a.

[0026] Next, the reagent dispensing mechanism 123 aspirates an internal standard substance as a reagent corresponding to the component to be analyzed from the reagent container 121 on the reagent disk 122, and dispenses it into the reaction container 116 (step S201).

[0027] Next, the reagent dispensing mechanism 123 aspirates a reagent, such as a protein removal agent, from the reagent container 121 on the reagent disk 122 and dispenses it into the reaction container 116 (step S202).

[0028] 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).

[0029] Next, the reaction vessel 116 into which the sample, internal standard, and 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 carrying the analyte component and internal standard are collected on the inner wall surface of the reaction vessel 116 by the magnetic force of the magnet 201 positioned along the outer surface of the reaction vessel 116 (shown as a group of magnetic beads 202 in FIG. 2). In this state, the reagent dispensing mechanism 123 aspirates and discards the solution in the reaction vessel 116.

[0030] At this time, the magnetic beads, the analyte component held by the magnetic beads, and the internal standard remain in the reaction vessel 116 .

[0031] Next, the reagent dispensing mechanism 123 aspirates a cleaning solution for washing away impurities other than the substances (analyte components and internal standard substances) held by the magnetic beads from the reagent container 121 on the reagent disk 122, and dispenses it into the reaction container 116. At this time, the magnetic beads may be temporarily released from the magnetic force of the magnet 201.

[0032] Next, the magnetic beads are collected again on the inner wall surface of the reaction vessel 116 by the magnet 201, and the reagent dispensing mechanism 123 aspirates and discards the solution (cleaning solution) from the reaction vessel 116, thereby washing the magnetic beads.

[0033] Next, the reagent dispensing mechanism 123 aspirates an eluate as a reagent from the reagent container 121 on the reagent disk 122, which elutes the analyte component and internal standard from the magnetic bead group 202, and dispenses it into the reaction container 116 (step S205).

[0034] Next, with the magnetic bead group 203 from which the analyte components and internal standard substances have been eluted collected on the inner wall surface of the reaction vessel 116 by the magnetic force of the magnet 201, the reagent dispensing mechanism 123 aspirates the solution (purified solution) from the reaction vessel 116 (step S206) and dispenses it into an unused reaction vessel 116 on the reaction disk 120 different from the reaction vessel 116 placed on the magnetic separation mechanism 124 (step S207).

[0035] The purified solution contained in the reaction vessel 116 of the reaction disk 120 is incubated as needed.

[0036] Next, the transport mechanism 132 transports the reaction vessel 116 containing the purified liquid to the evaporation and concentration mechanism 131, and the evaporation and concentration mechanism 131 evaporates and concentrates the components in the purified liquid (step S208).

[0037] 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 diluted liquid from the reagent container 121 on the reagent disk 122 and dispenses it into the reaction container 116.

[0038] The purified liquid obtained by the above processing steps may contain magnetic beads or precipitates, and if it is supplied to the separation unit 102 as is, it is possible that the analytical sensitivity will decrease due to clogging of the flow path of the separation unit 102, contamination of the column, etc. Therefore, the purified liquid in the reaction vessel 116 in the evaporation concentration mechanism 131 is automatically filtered to remove the magnetic beads and the like. The specific method of filtration will be described later.

[0039] The purified liquid dispensing mechanism 133 aspirates the filtrate, which is the purified liquid after filtration, and dispenses it into the separation unit 102. The analysis unit 103 then ionizes the components separated by the separation unit 102 and detects the amount of ions (i.e., the amount of components). The detection results from the analysis unit 103 are output to the control unit 104, which then calculates the concentration values ​​of the components in the sample using a calibration curve.

[0040] 3 is a diagram showing a schematic configuration of a filtration device for filtering a purified liquid. As shown in FIG. 3, the filtration device includes a mounting unit 301, a pressing unit 302, a nozzle 303, an arm 304, and a vertical rotation mechanism 305.

[0041] The mounting portion 301 has a recess or hole for mounting the first container 401. The first container 401 is a container having a first opening on its top surface for containing a liquid, and is intended to be the aforementioned reaction container 116 for containing the purified liquid. The aforementioned evaporation and concentration mechanism 131 also serves as the mounting portion 301, and the recess or the like of the mounting portion 301 corresponds to a receiving portion for receiving the reaction container 116 when evaporation and concentration is performed.

[0042] The pressing portion 302 presses the second container 402 downward against the first container 401 through the first opening of the first container 401. The lower surface of the pressing portion 302 has a larger area than the second opening formed in the upper surface of the second container 402, so that when the pressing portion 302 descends, the lower surface of the pressing portion 302 comes into contact with the edge of the second container 402, and when the pressing portion 302 descends further, the lower surface of the pressing portion 302 presses down the edge of the second container 402.

[0043] The second container 402 is a filtering container having a filter 402A on its bottom surface. The mesh opening of the filter 402A is, for example, 0.2 μm or more and 0.45 μm or less, making it possible to separate magnetic beads and precipitates. With mesh openings of this size, the weight of the second container 402 alone is not enough to filter the purified liquid in the first container 401, so the pressing unit 302 must press down on the second container 402. The second container 402 is mounted on the container mounting rack 117, similar to an unused reaction container 116, for example, and is attached to the first opening of the first container 401 (reaction container 116) containing the purified liquid by the transport mechanism 118 or the transport mechanism 132.

[0044] The nozzle 303 aspirates the filtrate that has moved from the first container 401 to the second container 402 through the filter 402A. The filtrate aspirated by the nozzle 303 is discharged into the separation unit 102. The tip of the nozzle 303 protrudes downward from the lower surface of the pressing unit 302, and can move up and down relative to the pressing unit 302.

[0045] The arm 304 extends horizontally, and has a flow path formed therein that communicates with the nozzle 303. The pressing unit 302 and the nozzle 303 are attached to one end of the arm 304, and the other end of the arm 304 is fixed to a vertical rotation mechanism 305, which will be described later.

[0046] The vertical rotation mechanism 305 moves the arm 304 horizontally (rotates) and vertically. The pressing unit 302, the nozzle 303, the arm 304, and the vertical rotation mechanism 305 correspond to a part of the purified liquid dispensing mechanism 133 described above.

[0047] Next, the filtering operation of the purified liquid by the filtering device will be described with reference to a flow chart of FIG.

[0048] First, the transport mechanism 132 sets the first container 401 (reaction container 116) containing the purified liquid on the mounting section 301 (evaporation concentration mechanism 131), and sets the second container 402 on the first opening of the first container 401 (step S401), resulting in the state shown in Figure 3.

[0049] Thereafter, the vertical rotation mechanism 305 moves the arm 304 from above to below, thereby lowering the pressing unit 302 and the nozzle 303 (step S402). During the downward movement of the arm 304, the lower surface of the pressing unit 302 first comes into contact with the edge of the second opening of the second container 402, resulting in the state shown in FIG. 5, and then presses down the second container 402.

[0050] The control unit 104 determines whether the pressing end position has been reached (step S403), and if it determines that the pressing end position has not been reached, returns to step S402 and continues to lower the pressing unit 302 etc. using the up / down rotation mechanism 305.

[0051] 6 , when it is determined that the pressing end position has been reached, the control unit 104 stops the downward movement of the arm 304 by the vertical rotation mechanism 305 and also stops the descent of the pressing unit 302 (step S404). The pressing end position is the position where the filter 402A of the second container 402 contacts the bottom surface of the first container 401, and is determined in advance based on the height dimensions of the first container 401 and the second container 402, etc.

[0052] Even after the pressing unit 302 has finished descending together with the arm 304, the nozzle 303 continues to descend (moves downward relative to the pressing unit 302) (step S405). Thereafter, the control unit 104 determines whether the nozzle 303 has reached the suction position (step S406), and if it determines that the nozzle 303 has not reached the suction position, the process returns to step S405 and the nozzle 303 continues to descend.

[0053] 7, when it is determined that the nozzle 303 has reached the suction position, the control unit 104 stops the descent of the nozzle 303 (step S407). Note that the suction position is preferably set to a position immediately before the tip of the nozzle 303 comes into contact with the filter 402A.

[0054] Thereafter, the control unit 104 causes the nozzle 303 to perform a suction operation, thereby suctioning the filtrate that has moved from the first container 401 to the second container 402 via the filter 402A (step S408).

[0055] By this operation, the purified liquid in the first container 401 (reaction container 116) is filtered to remove magnetic beads and the like, thereby preventing a decrease in analytical sensitivity. Furthermore, because filtration is performed automatically using the purified liquid dispensing mechanism 133 and the like that is originally provided in the automated analyzer, there is no need to install a dedicated filtration device or centrifuge in the automated analyzer or to perform filtration or centrifugation manually.

[0056] Furthermore, by lowering the tip of nozzle 303 relatively to pressing portion 302, even when the amount of filtrate is small, it is possible to efficiently aspirate the filtrate with the tip of nozzle 303 in close proximity to the bottom surface of second container 402. Nozzle 303 has an extendable structure, and when nozzle 303 retracts, that is, when the tip of nozzle 303 rises relative to pressing portion 302, part of nozzle 303 is folded. Therefore, the upper end of nozzle 303 does not protrude above pressing portion 302 or arm 304, and space can be used effectively.

[0057] The height dimension of the second container 402 is equal to or greater than the height dimension of the first container 401, but is desirably not too large because if it is too large, it will be necessary to increase the length (height dimension) of the nozzle 303. On the other hand, the outer diameter dimension of the second container 402 is smaller than the inner diameter dimension of the first container 401, but if it is too small, the position of the second container 402 will become unstable, so it is desirably not too small.

[0058] Furthermore, although the filtration device according to the above embodiment is used to filter a purified sample in the pretreatment section of an automatic analyzer, it may also be used to filter other liquids. For example, the filtration device may be used in a beverage production process to remove particles of a predetermined size or larger from juice obtained by mashing fruit.

[0059] 100...automatic analyzer, 101...preprocessing unit, 102...separation unit, 103...analysis unit, 104...control unit, 105...input unit, 106...display unit, 107...memory unit, 111...sample container, 112...transport mechanism, 113...sample dispensing mechanism, 114...dispensing tip attachment / detachment unit, 115...dispensing tip mounting rack, 115a...dispensing tip, 116...reaction container, 117...container mounting rack, 118...transport mechanism, 119...opening, 120...reaction disk, 12 1... reagent container, 122... reagent disk, 123... reagent dispensing mechanism, 124... magnetic separation mechanism, 125... transport mechanism, 126... rotational orbit, 131... evaporation concentration mechanism, 132... transport mechanism, 133... purified liquid dispensing mechanism, 201... magnet, 202... magnetic bead group, 203... magnetic bead group, 301... placement portion, 302... pressing portion, 303... nozzle, 304... arm, 305... up and down rotation mechanism, 401... first container, 402... second container, 402A... filter

Claims

1. A processing device comprising: a mounting section for mounting a first container having a first opening on its top surface and containing a liquid; a pressing section for pressing a second container having a filter on its bottom surface and a second opening on its top surface from above downward onto the first container via the first opening; and a nozzle for sucking filtrate that has moved from the first container to the second container via the filter, wherein the nozzle is configured to move up and down in conjunction with the up and down movement of the pressing section.

2. The processing device according to claim 1, wherein when the pressing portion descends, the lower surface of the pressing portion comes into contact with the edge of the second container, and when the pressing portion descends further, the lower surface of the pressing portion presses down the edge of the second container.

3. The processing device according to claim 2, wherein the lowering of the pressing part is completed when the filter contacts the bottom surface of the first container.

4. The processing device according to claim 2, wherein after the pressing part has completed its descent, the nozzle further descends and then sucks the filtrate.

5. The processing device according to claim 4, wherein the nozzle completes its descent before the tip of the nozzle contacts the filter.

6. The processing device according to claim 4, further comprising: an arm to which the pressing part and the nozzle are attached; and an up-and-down rotation mechanism for moving the arm horizontally and up-and-down, wherein the up-and-down movement of the pressing part is accompanied by the up-and-down movement of the arm.

7. The processing device according to claim 6, wherein the nozzle is extendable and retractable, and when the tip of the nozzle rises against the pressing portion, a part of the nozzle is folded.

8. An automatic analyzer comprising: a pretreatment section that purifies samples using magnetic beads; a separation section that performs LC separation of the samples purified in the pretreatment section; and an analysis section that analyzes the samples separated by LC in the separation section, wherein the pretreatment section has a purified liquid dispensing mechanism that aspirates the purified sample from a reaction vessel and discharges it into the separation section, and the purified liquid dispensing mechanism comprises: a pressing section that presses a filtration vessel having a filter on its bottom surface and an opening on its top surface from top to bottom into the reaction vessel containing the purified liquid, and a nozzle that aspirates filtrate that has moved from the reaction vessel to the filtration vessel through the filter, and the nozzle is configured to move up and down together with the up and down movement of the pressing section.

9. The automated analyzer according to claim 8, further comprising a transport mechanism for transporting the filtration vessel to the position of the reaction vessel.

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