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WO2025204616A1 - Dispositif de traitement - Google Patents

Dispositif de traitement

Info

Publication number
WO2025204616A1
WO2025204616A1 PCT/JP2025/007886 JP2025007886W WO2025204616A1 WO 2025204616 A1 WO2025204616 A1 WO 2025204616A1 JP 2025007886 W JP2025007886 W JP 2025007886W WO 2025204616 A1 WO2025204616 A1 WO 2025204616A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
unit
reaction vessel
concentration
vacuum suction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/JP2025/007886
Other languages
English (en)
Japanese (ja)
Inventor
匠 伊藤
和広 野田
洋晃 酒井
晋弥 松岡
真結子 伊藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hitachi High Tech Corp
Original Assignee
Hitachi High Tech Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hitachi High Tech Corp filed Critical Hitachi High Tech Corp
Publication of WO2025204616A1 publication Critical patent/WO2025204616A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples

Definitions

  • Patent Document 1 discloses an automatic analyzer that includes an evaporative concentration unit that performs a concentration process to concentrate the analyte components by evaporating an extract that has extracted the analyte components in the sample, an analytical unit that analyzes the analyte components in the sample, and a control unit that controls the operation of the evaporative concentration unit and analytical unit.
  • the present invention was made in consideration of the above, and its purpose is to provide a treatment device that can evaporate and concentrate in a short period of time while preventing bumping.
  • a processing device comprising an evaporation concentration unit that performs a concentration process to concentrate the target components by evaporating an extract liquid that has extracted the target components from a sample, and a control unit that controls the operation of the evaporation concentration unit.
  • the evaporation concentration unit comprises a container receiving unit that has an opening on its upper surface and receives a container that contains a liquid, and a vacuum suction unit that can evacuate gas from the container by contacting the container.
  • the lower surface of the vacuum suction unit is configured to be flush with the upper surface of the container, and the lower surface is provided with an outside air inlet port that introduces outside air into the container and a reduced pressure suction port that evacuates gas from the container.
  • the present invention provides a processing device that can evaporate and concentrate in a short period of time while preventing bumping.
  • FIG. 1 is a diagram schematically illustrating the overall configuration of an automatic analyzer.
  • FIG. 10 is a diagram showing an example of processing steps of an analysis process.
  • FIG. 2 is a diagram schematically illustrating an example of an evaporation and concentration mechanism. A transparent cross-sectional view of the evaporation and concentration mechanism.
  • FIG. 10A and 10B are diagrams showing the up/down and rotation mechanism of the vacuum suction unit.
  • SPE solid phase extraction
  • LLE liquid-liquid extraction
  • SPE solid phase extraction
  • LLE liquid-liquid extraction
  • evaporation concentration is sometimes performed to increase the concentration of the target components by evaporating the extract that has been extracted from the sample, in order to achieve highly sensitive detection using LC-MS.
  • FIG. 1 is a diagram showing a schematic overall configuration of an automatic analyzer.
  • the automatic analyzer 100 includes a processing unit (processing device) 101 for processing samples, 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 device, an input unit 105 for a user to input information to the device, 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.
  • processing unit processing device
  • 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 device
  • an input unit 105 for a user to input information to the device
  • a display unit 106 for displaying information to the user
  • a memory unit 107 such as a storage medium for storing various information related to the control of the automatic analyzer 100.
  • 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 configured as an integrated unit, for example, like a touch panel monitor.
  • the processing unit 101 also includes a reaction vessel mounting rack 117 that mounts unused reaction vessels 116, and a transport mechanism 118 that transports unused dispensing tips 115a from the dispensing tip mounting rack 115 to the dispensing tip mounting unit 114, transports used reaction vessels 116 from the opening 119 of 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 of the reaction vessel disk 120.
  • a reaction vessel mounting rack 117 that mounts unused reaction vessels 116
  • a transport mechanism 118 that transports unused dispensing tips 115a from the dispensing tip mounting rack 115 to the dispensing tip mounting unit 114, transports used reaction vessels 116 from the opening 119 of 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 of the reaction vessel disk 120.
  • the processing 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 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.
  • 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 vessel disk 120 and the magnetic separation mechanism 124
  • an evaporation and concentration mechanism 131 that evaporates and concentrates the components to be analyzed in the solution in the reaction vessel 116.
  • 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.
  • a calibration curve for example, first analyze a standard substance of known concentration at multiple concentrations. Then, obtain the time-dependent change in ion quantity, i.e., ion intensity (mass chromatogram) for the m/z (mass-to-charge ratio) of the ions derived from the standard substance, and calculate the peak area of the mass chromatogram. A calibration curve is created from the relationship between this area and the concentration of the standard substance.
  • the calibration curve obtained in this way it is possible to detect the component concentrations of samples whose concentrations are unknown but which contain the same analyte components as the standard substance. Specifically, the peak area of the mass chromatogram for the sample to be analyzed is determined, and the component concentration of the analyte is determined from the correspondence between this mass chromatogram peak area and the calibration curve.
  • ion intensities which may show some variation between analyses due to the effects of sample processing, sample injection into LC-MS, and ionization in LC-MS, can be compared and verified between analyses. This method is known as the internal standard method.
  • Fig. 2 is a diagram showing an example of the processing steps of the analysis process.
  • 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.
  • the sample dispensing mechanism 113 is made to access the dispensing tip attachment/detachment unit 114, and a dispensing tip 115a is attached to the tip of the nozzle.
  • the sample dispensing mechanism 113 aspirates a sample containing the components to be analyzed from the sample container 111 via the dispensing tip 115a and dispenses it into the reaction container 116 on the reaction container disk 120 (step S200).
  • the sample dispensing mechanism 113 when the sample dispensing mechanism 113 has finished dispensing the sample from one sample container 111, it discards the used dispensing tip 115a in the dispensing tip attachment/detachment unit 114 and attaches an unused dispensing tip 115a.
  • 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).
  • 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).
  • the magnetic beads, the analyte component held by the magnetic beads, and the internal standard remain in the reaction vessel 116.
  • the reagent dispensing mechanism 123 aspirates an eluate, which elutes the analyte components and internal standard substances from the magnetic bead group 202, from the reagent container 121 on the reagent disk 122 and dispenses it into the reaction container 116 (step S205).
  • 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.
  • 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.
  • the purified liquid obtained by the above processing steps is sucked from the reaction vessel 116 by the separation section dispensing mechanism 133 and discharged into 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 results in the analysis section 103 are output to the control section 104, and the concentration values of the components in the sample are calculated using a calibration curve.
  • Figure 3A is a schematic diagram showing an example of an evaporation concentration mechanism 131.
  • the evaporation concentration mechanism 131 has multiple container receiving sections 301 that receive reaction vessels 116 containing the purified liquid obtained by the processing steps described above, and each reaction vessel 116 transported to the container receiving section 301 is distributed to the container receiving section 301 of the evaporation concentration section 302 that performs the evaporation concentration.
  • the evaporation and concentration mechanism 131 includes a heating unit 303 for heating the reaction vessel 116 and a vacuum suction unit 304 for sucking vapor from inside the reaction vessel 116.
  • the heating unit 303 include a Peltier element or heater whose temperature can be controlled by the analytical device.
  • the vacuum suction unit 304 is a vacuum pump whose operation can be controlled by the analytical device.
  • the vacuum suction unit 304 is provided with an outside air introduction hole 305.
  • the outside air introduction hole 305 will be explained later using Figure 3B.
  • the reaction vessel 116 is transported by the transport mechanism 132 to the vessel receiving section 301 above the evaporative concentration section 302.
  • the vacuum suction section 304 is positioned near the heating section 303 of the evaporative concentration section 302, at a position (first position) that is at least a certain distance away from the heating section 303.
  • the vacuum suction section (exhaust section) 304 is moved so that it is positioned above the reaction vessel 116 placed in the heating section 303, in close contact with the reaction vessel 116 (position in close contact with the heating section 303: second position).
  • the evaporative concentration mechanism 131 may also be moved.
  • evaporation is performed by performing vacuum suction (reduced pressure exhaust) on the reaction vessel 116 for a certain period of time while it is heated by the heating section (heating section) 303.
  • the evaporation concentration section 302 is raised relative to the vacuum suction section 304, or the vacuum suction section 304 is lowered relative to the reaction vessel 116, thereby bringing the opening of the reaction vessel 116 into tight contact with the vacuum suction section 304.
  • the reaction vessel 116 may be pressed toward the vessel receiving section 301 by the vacuum suction section 304, causing it to come into close contact with the vessel receiving section 301, which could prevent the reaction vessel 116 from being removed from the vessel receiving section 301.
  • a rod-shaped member ejector pin
  • the ejector pin may be designed to move up and down simultaneously with the vacuum suction section 304, thereby reducing the need for driving means such as a motor.
  • the second example is a method in which the installation position of the evaporation concentration mechanism 131 is fixed.
  • the control unit 104 causes the transport mechanism 132 to transport the reaction vessel 116 to the vessel receiving section 301 of the evaporation concentration section 302, and then moves the vacuum suction section 304 relative to the reaction vessel 116 on the evaporation concentration section 302 so that the vacuum suction section 304 is positioned above the reaction vessel 116.
  • the simplest method of movement is to rotate the vacuum suction section 304 around the rotation axis as shown in Figure 3A.
  • the rotation axis When rotating the position of the vacuum suction section 304, the rotation axis is moved upward to move away from the reaction vessel 116, and when bringing it into close contact with the reaction vessel 116, the rotation axis is lowered to allow for close contact.
  • a mechanism for linear movement in the X and Y directions can also be used as a movement method.
  • the reaction vessel 116 is then heated and evacuated (vacuum suctioned) for a certain period of time to cause evaporation and concentration.
  • the purified liquid in the reaction vessel 116 is then introduced into the separation section 102 by a separation section dispensing mechanism 133, which has access to the vessel receiving section 301 of the evaporation and concentration mechanism 131.
  • the number of container receiving sections 301 in Figure 3A is just one example, and can be changed taking into account the number of samples that can be processed per hour set in the automated analyzer, i.e., the throughput, and the time required for evaporation and concentration. 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), providing three container receiving sections 301 in each evaporation and concentration section 302 allows the evaporation and concentration mechanism 131 to process the reaction containers 116 sequentially without any idle time, even when the same process is performed continuously, and a throughput of 100 samples/hour can be achieved. In this case, a vacuum suction section 304 is required for each of the three container receiving sections 301 in the evaporation and concentration section 302.
  • One way to address this is to heat the vacuum suction unit 304 itself. Additionally, another way to address this is to perform dry suction using the vacuum suction unit 304 after exhaust has finished and the vacuum suction unit 304 has been moved away from the reaction vessel 116.
  • samples that require evaporation and concentration processing are moved to the evaporation and concentration section 302, where the sample undergoes evaporation and concentration processing before being moved to the separation section 102.
  • the components separated in the separation section 102 are then moved to the analysis section 103 for analysis.
  • Figure 3B is a perspective view of the evaporation and concentration mechanism 131 seen from the side.
  • Figure 3B shows the state in which the opening of the reaction vessel 116 is in tight contact with the vacuum suction part 304.
  • the vacuum suction unit 304 When the vacuum suction unit 304 is in close contact with the reaction vessel 116, it acts as a lid for the reaction vessel, with the underside 306 of the lid being in close contact with the top surface of the reaction vessel 116. In this state, vacuum suction is performed through an exhaust pipe (shown by a dashed line in Figure 3B) installed inside the vacuum suction unit 304. However, if the vacuum suction unit 304 begins suction (reducing pressure) inside the reaction vessel 116 while the reaction vessel 116 and vacuum suction unit 304 are in close contact, a sudden rise in temperature and a drop in boiling point of the solution may occur simultaneously, potentially causing the sample inside the reaction vessel 116 to bump.
  • an exhaust pipe shown by a dashed line in Figure 3B
  • the outside air introduction hole 305 is a cylindrical through-hole with tapers at the top and bottom.
  • the taper is not essential, but is provided in this embodiment to improve the efficiency of introducing outside air.
  • the vertical length of the cylinder is on the order of a few millimeters.
  • a decompression intake hole (vacuum suction hole) 307 for reducing the pressure inside the reaction vessel 116 is provided so as to surround the outside air introduction hole 305.
  • the decompression intake hole 307 evacuates the reaction vessel 116 via a decompression piping inside the vacuum suction part 304.
  • the top surface of the reaction vessel 116 is configured to be flush with the bottom surface of the vacuum suction part 304 (lid bottom surface 306) when the vacuum suction part 304 is in close contact with the reaction vessel 116.
  • the lid also serves as the underside of the vacuum suction section 304, which simplifies the structure of the evaporation and concentration mechanism and shortens the time required for the evaporation and concentration process. Furthermore, since there is no need for a complex lid mechanism, the cost of the device can also be reduced.
  • the airflow is less affected by wall resistance, making it easier for the airflow to reach the bottom of the container. As a result, evaporation and concentration are promoted, improving the concentration rate. Furthermore, by providing a vacuum suction hole 307 near (on the same surface as) the outside air inlet 305, pressure loss near the lid can be minimized, maximizing the flow rate of the airflow from the outside air inlet 305. This makes it possible to achieve the short time and target evaporation and concentration rate required for this processing device.
  • the lid opening and closing mechanism (a combination of a cam mechanism and an elevating mechanism) uses a rotational action to enable access from the top of the reaction vessel by the reaction vessel transport mechanism. Furthermore, by providing a rotational function on the lid side, this operation can be achieved with a single elevating mechanism. This allows for simple, space-saving evaporation processing by connecting the lid mechanism according to the evaporation concentration processing requirements.
  • the vacuum suction unit (lid) 304 is connected to a rotating cam 401, and by rotating the rotating cam 401, it rotates around the rotation axis 308.
  • the rotating cam 401 is connected to a lifting/pushing unit 402, and by lifting/pushing unit 402 being pushed up by a lifting mechanism 403, the vacuum suction unit (lid) 304 moves up and down.
  • the evaporation/concentration unit 302, in which the container receiving unit 301 is provided, is connected to/supported by the lifting mechanism 403 via a first connecting unit 404 and a second connecting unit 405 via a slide unit 406.
  • the slide unit 406 allows the reaction container transport mechanism to access the container receiving unit 301.
  • the "processing device” that is the subject of this invention does not only refer to a “preprocessing device” that performs so-called preprocessing such as separation, concentration, dilution, etc. of a sample to be fed to an "analytical device,” but also includes a device that integrates a "preprocessing device” and an “analytical device.”

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

La présente invention présente la configuration suivante afin de fournir un dispositif de traitement permettant d'obtenir une concentration par évaporation en un court laps de temps tout en empêchant le choc. Le dispositif de traitement comprend : une unité de concentration par évaporation qui effectue un traitement de concentration pour évaporer un liquide d'extraction obtenu par extraction d'un composant en cours d'analyse à partir d'un échantillon, et condenser le composant en cours d'analyse; et une unité de commande qui commande le fonctionnement de l'unité de concentration par évaporation. L'unité de concentration par évaporation est pourvue d'une partie de réception de récipient pour recevoir un récipient qui a une ouverture dans sa surface supérieure et stocke un liquide, et une partie d'aspiration sous vide permettant d'évacuer le gaz depuis l'intérieur du récipient en étant mise en contact avec le récipient. La surface inférieure de la partie d'aspiration sous vide est conçue pour affleurer la surface supérieure du récipient. La surface inférieure est pourvue d'un trou d'introduction d'air extérieur à travers lequel de l'air extérieur est introduit dans le récipient, et d'un trou d'aspiration de décompression à travers lequel le gaz est évacué depuis l'intérieur du récipient.
PCT/JP2025/007886 2024-03-27 2025-03-05 Dispositif de traitement Pending WO2025204616A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2024050610 2024-03-27
JP2024-050610 2024-03-27

Publications (1)

Publication Number Publication Date
WO2025204616A1 true WO2025204616A1 (fr) 2025-10-02

Family

ID=97216443

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2025/007886 Pending WO2025204616A1 (fr) 2024-03-27 2025-03-05 Dispositif de traitement

Country Status (1)

Country Link
WO (1) WO2025204616A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014222148A (ja) * 2011-09-06 2014-11-27 株式会社バイオクロマト 試料溶液の同時濃縮装置
WO2022185707A1 (fr) * 2021-03-03 2022-09-09 株式会社日立ハイテク Mécanisme de concentration par évaporation et procédé de commande de mécanisme de concentration par évaporation
WO2023286493A1 (fr) * 2021-07-15 2023-01-19 株式会社日立ハイテク Dispositif de concentration par évaporation et dispositif d'analyse automatique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014222148A (ja) * 2011-09-06 2014-11-27 株式会社バイオクロマト 試料溶液の同時濃縮装置
WO2022185707A1 (fr) * 2021-03-03 2022-09-09 株式会社日立ハイテク Mécanisme de concentration par évaporation et procédé de commande de mécanisme de concentration par évaporation
WO2023286493A1 (fr) * 2021-07-15 2023-01-19 株式会社日立ハイテク Dispositif de concentration par évaporation et dispositif d'analyse automatique

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