WO2021250919A1 - 液体クロマトグラフィ分析システム - Google Patents

液体クロマトグラフィ分析システム Download PDF

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Publication number
WO2021250919A1
WO2021250919A1 PCT/JP2021/000477 JP2021000477W WO2021250919A1 WO 2021250919 A1 WO2021250919 A1 WO 2021250919A1 JP 2021000477 W JP2021000477 W JP 2021000477W WO 2021250919 A1 WO2021250919 A1 WO 2021250919A1
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WO
WIPO (PCT)
Prior art keywords
liquid feed
liquid
flow rate
mobile phase
feed pump
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.)
Ceased
Application number
PCT/JP2021/000477
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English (en)
French (fr)
Japanese (ja)
Inventor
信也 今村
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.)
Shimadzu Corp
Original Assignee
Shimadzu 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 Shimadzu Corp filed Critical Shimadzu Corp
Priority to JP2022530014A priority Critical patent/JP7260063B2/ja
Priority to CN202180027991.0A priority patent/CN115398225B/zh
Priority to US17/924,996 priority patent/US12416606B2/en
Publication of WO2021250919A1 publication Critical patent/WO2021250919A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
    • G01N2030/324—Control of physical parameters of the fluid carrier of pressure or speed speed, flow rate
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
    • G01N2030/326—Control of physical parameters of the fluid carrier of pressure or speed pumps
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8804—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 automated systems

Definitions

  • the present invention relates to a liquid chromatography analysis system.
  • Validation in the LC system includes various items such as confirmation of the accuracy of the detector (see Patent Document 1).
  • the accuracy check of the detector has been automated, but some items have not been automated.
  • One of the non-automated validation items is the confirmation of the flow rate of the liquid feed pump.
  • the liquid feed pump performs a calculation using the correlation (design value) between the feed amount of the plunger of the plunger pump and the liquid feed flow rate, and adjusts the operating speed of the plunger so that the calculated liquid feed flow rate becomes the set flow rate. It is basically adjusted, and control based on the measured value of the flow rate of the mobile phase is not generally performed.
  • the user For validation to confirm the flow rate of liquid to be sent, the user sets the flow rate in the liquid feed pump as the set flow rate, sends a predetermined mobile phase such as water, and the user determines the amount of mobile phase sent in a certain period of time. It is generally performed by measuring, obtaining the actual liquid feed flow rate from the amount by calculation, and comparing the measured value with the set flow rate.
  • the present invention has been made in view of the above problems, and an object of the present invention is to provide an LC system capable of automatically checking the liquid feed flow rate of a liquid feed pump.
  • the LC system according to the present invention is a liquid feed pump that feeds a mobile phase, and the liquid feed flow rate of the mobile phase is set to a set flow rate based on a pre-designed correlation between the operating speed and the liquid feed flow rate.
  • a liquid feed pump that operates in such a manner, an auto sampler that injects a sample into the mobile phase downstream of the liquid feed pump, a separation column for separating components in the sample downstream of the auto sampler, and the separation.
  • a predetermined flow rate is applied to the liquid feed pump at a timing different from the sample analysis.
  • the amount (including weight and flow rate) of the liquid feed confirmation unit configured to execute the liquid feed confirmation mode to be set and operated, and the mobile phase to be fed by the liquid feed pump during the liquid feed confirmation mode.
  • the liquid feed confirmation unit is provided with a measuring instrument for measuring the above, and the liquid feed confirmation unit is operated by setting the predetermined flow rate in the liquid feed pump using the measured value by the measuring instrument in the liquid feed confirmation mode. It is configured to obtain the measured value of the flow rate of the mobile phase at that time.
  • the present invention includes a liquid feed confirmation unit that executes the liquid feed confirmation mode and a measuring instrument that measures the amount of the mobile phase to be fed during the liquid feed confirmation mode, the liquid feed of the liquid feed pump is provided. The flow rate can be confirmed automatically.
  • FIG. 1 shows an embodiment of the LC system.
  • the LC system of this embodiment includes a liquid feed pump 2, a degassing device 4, an autosampler 6, a separation column 8, a column oven 9, a detector 10, a switching valve 12, a weighing scale 14, and a control device 16. ..
  • the liquid feed pump 2 is provided so as to pump the mobile phase from the mobile phase container 18 and feed the liquid.
  • the liquid feed pump 2 is composed of a plunger pump, and the operation of the plunger required to make the liquid feed flow rate a set flow rate by using a pre-designed correlation between the operating speed of the plunger and the liquid feed flow rate. It is configured to pump a mobile phase with a set flow rate by calculating the speed and operating the plunger based on the calculated value.
  • the degassing device 4 is provided on the flow path for pumping the mobile phase from the mobile phase container 18 by the liquid feed pump 2.
  • the degassing device 4 is for degassing the mobile phase pumped from the mobile phase container 18 by the liquid feed pump 2.
  • the autosampler 6 is fluid-connected downstream of the liquid feed pump 2 and is configured to automatically inject a sample into the mobile phase fed by the liquid feed pump 2.
  • the separation column 8 is fluid-connected downstream of the autosampler 6 and is for separating the components in the sample injected by the autosampler 6.
  • the separation column 8 is housed in a column oven 9 capable of controlling the internal temperature to a set temperature.
  • the detector 10 is fluid-connected downstream of the separation column 8 and is for detecting the components in the sample separated in the separation column 8.
  • the switching valve 12 is for switching the connection destination of the outlet flow path 20 of the detector 10 between the waste liquid flow path 24 leading to the waste liquid collection container 22 and the collection flow path 28 leading to the collection container 26.
  • the switching valve 12 can be realized by a three-way solenoid valve, a rotary valve, or the like.
  • the switching valve 12 is normally in a state of connecting the outlet flow path 20 to the waste liquid flow path 24 (normal state), and connects the outlet flow path 20 to the collection flow path 28 only in the liquid feed confirmation mode described later. (The state for confirming the delivery of liquid).
  • the weight scale 14 is for measuring the weight of the collection container 26.
  • the weighing scale 14 constitutes a measuring instrument for measuring the amount of the mobile phase to be fed by the liquid feeding pump 2 during the liquid feeding confirmation mode described later.
  • the weighing scale 14 has a measurement accuracy of about 1 mg and a measurement range of about 200 g.
  • the control device 16 is for managing the operation of the liquid feed pump 2, the degassing device 4, the auto sampler 6, the column oven 9, and the switching valve 12, and includes a CPU (central processing unit) and an information storage device. It is realized by a dedicated computer or a general-purpose personal computer.
  • the control device 16 is provided with a liquid feed confirmation unit 30.
  • the liquid feed confirmation unit 30 is a function obtained by the CPU executing a program.
  • the liquid feed confirmation unit 30 is a function that automatically executes validation for confirming the liquid feed flow rate of the liquid feed pump 2. An example of the operation of the LC system realized by the liquid feed confirmation unit 30 will be described with reference to the flowchart of FIG.
  • the liquid feed confirmation unit 30 executes the liquid feed confirmation mode and confirms the liquid feed from the switching valve 24 from the normal state. Switch to the state for use (step 101). Further, the liquid feed confirmation unit 30 sets the set flow rate of the liquid feed pump 2 to a predetermined flow rate for liquid feed confirmation (step 102), and sets a predetermined mobile phase (for example, water) to the liquid feed pump 2 at the set flow rate. The liquid is sent (step 103).
  • the liquid feed confirmation unit 30 feeds the liquid at a predetermined time (for example, 1 minute) based on the weight change of the collection container 26 measured by the weigh scale 14 while the liquid feed pump 2 is feeding the liquid at a set flow rate.
  • the weight of the mobile phase fed by the liquid pump 2 is measured (step 104), and the actual liquid feed flow rate (actual measurement value) by the liquid feed pump 2 is calculated using the measured weight and the specific gravity of the mobile phase (step 104). 105).
  • the liquid feed confirmation unit 30 takes a difference between the measured value obtained by calculation and a predetermined flow rate (set flow rate of the liquid feed pump 2), and sets the difference value (absolute value) as a preset reference value (for example, a predetermined flow rate).
  • the liquid feeding accuracy of the liquid feeding pump 2 is evaluated (step 106). If the difference value between the measured value and the predetermined flow rate is less than or equal to the reference value, it is determined to be "normal” (step 107), and if the difference value between the measured value and the predetermined flow rate exceeds the reference value, it is determined to be "abnormal”. (Step 108). The determination result is displayed on, for example, a display electrically connected to the control device 16.
  • a dedicated weighing scale 14 is provided as a measuring instrument for measuring the weight of the mobile phase to be fed during the liquid feed confirmation mode, but as shown in FIG. 3, the mobile phase is provided.
  • the weight measuring device 32 for monitoring the remaining amount of the mobile phase of the container 18 is provided, the weight of the collecting container 26 is measured by one weight measuring cell 32B of the weight measuring device 32. May be good.
  • the weight measuring cell 32A for measuring the weight of the mobile phase container 18 needs to measure the weight of the mobile phase container 18 having a larger capacity than that of the collecting container 26, and therefore the measurement range is designed to be wide. ing.
  • the weight measurement cell 32B is designed to have higher measurement accuracy and a narrower measurement range than the weight measurement cell 32A.
  • the switching valve that fulfills such a function may be provided at any position as long as it is downstream from the liquid feed pump 2.
  • the high-pressure valve 6A provided in the autosampler 6 guides the mobile phase to be fed by the liquid feed pump 2 to the collection container 26 only during the liquid feed confirmation mode. Has been realized.
  • a flow meter 34 may be provided as a measuring instrument for measuring the amount of the mobile phase to be fed by the liquid feed pump 2 during the liquid feed confirmation mode.
  • the flow meter 34 has a measurement accuracy on the order of ⁇ L / min.
  • Such a flow meter 34 cannot be used for operation control of the liquid feed pump 2 because the measurement range is narrower than the flow rate range used in the analysis.
  • the flow meter 34 is provided on the outlet flow path 20 of the detector 10, but it may be anywhere downstream from the liquid feed pump 2. However, from the viewpoint of minimizing the dead volume upstream of the detector 10, it is preferable to provide the flow meter 34 downstream of the detector 10.
  • a liquid feed pump that feeds the mobile phase
  • the liquid feed flow rate of the mobile phase is set based on a pre-designed correlation between the operating speed and the liquid feed flow rate.
  • a liquid feed pump that operates to achieve the specified flow rate, an auto sampler that injects a sample into the mobile phase downstream of the liquid feed pump, and a separation column for separating components in the sample downstream of the auto sampler.
  • the liquid feed pump is performed at a timing different from the sample analysis.
  • the liquid feed confirmation unit configured to execute the liquid feed confirmation mode that is operated by setting a predetermined flow rate.
  • the liquid feed confirmation unit is operated in the liquid feed confirmation mode by setting the predetermined flow rate to the liquid feed pump using the measured value by the measuring instrument. It is configured to obtain the measured value of the flow rate of the mobile phase.
  • a collection container for collecting the mobile phase fed by the liquid feed pump during the liquid feed confirmation mode is further provided, and the measuring instrument is trapped in the collection container. It is a weighing scale for confirming liquid feeding that measures the weight of the collected mobile phase.
  • the collection container is connected to the downstream of the liquid feed pump via a switching valve, and the switching valve is switched when the liquid feed confirmation mode is executed to switch the liquid feed.
  • the collection container may be configured to be connected to the downstream of the pump.
  • the switching valve may be a high pressure valve provided in the autosampler. By doing so, it is not necessary to add a new switching valve, and it is possible to suppress an increase in the installation area and cost of the LC system.
  • the remaining amount for measuring the weight of the mobile phase container which has a wider measurement range than the weighing scale for confirming liquid feeding and stores the mobile phase before being fed by the liquid feeding pump.
  • An additional weighing scale for measurement may be provided.
  • the weight scale for confirming the liquid feed and the weight scale for measuring the remaining amount can be realized by different weight measuring cells provided in a common weight measuring device.
  • the measuring instrument is provided downstream of the liquid feed pump and has a flow meter having a measurement range narrower than the flow rate range of the mobile phase used in the analysis of the LC system. Is.
  • the liquid feed confirmation unit has the measured value obtained in the liquid feed confirmation mode and the predetermined value set for the liquid feed pump in the liquid feed confirmation mode. By comparing the difference with the flow rate with the reference value, it is configured to determine whether or not the liquid feeding of the liquid feeding pump is normal. According to such an aspect, the user can easily recognize whether or not the liquid feed pump is operating normally.
  • This third aspect can be combined with either one of the first aspect and the second aspect.
  • Liquid feed pump 4
  • Degassing device 6
  • Auto sampler 6A
  • High pressure valve 8
  • Separation column 9
  • Column oven 10
  • Detector 12
  • Switching valve 14
  • Weighing scale 16
  • Control device 18
  • Mobile phase container 20
  • Outlet flow path 22
  • Waste liquid container 24
  • Waste liquid flow path 26
  • Collection Container 28
  • Liquid feed confirmation unit 32
  • Weight measuring device 32A, 32B Weight measuring cell 34 Flow meter

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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)
  • Sampling And Sample Adjustment (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
PCT/JP2021/000477 2020-06-09 2021-01-08 液体クロマトグラフィ分析システム Ceased WO2021250919A1 (ja)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2022530014A JP7260063B2 (ja) 2020-06-09 2021-01-08 液体クロマトグラフィ分析システム
CN202180027991.0A CN115398225B (zh) 2020-06-09 2021-01-08 液相层析分析系统
US17/924,996 US12416606B2 (en) 2020-06-09 2021-01-08 Liquid chromatography analysis system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2020-100123 2020-06-09
JP2020100123 2020-06-09

Publications (1)

Publication Number Publication Date
WO2021250919A1 true WO2021250919A1 (ja) 2021-12-16

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PCT/JP2021/000477 Ceased WO2021250919A1 (ja) 2020-06-09 2021-01-08 液体クロマトグラフィ分析システム

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US (1) US12416606B2 (https=)
JP (1) JP7260063B2 (https=)
CN (1) CN115398225B (https=)
WO (1) WO2021250919A1 (https=)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62132442U (https=) * 1986-02-13 1987-08-21
JPH09145701A (ja) * 1995-11-29 1997-06-06 Shimadzu Corp 液体クロマトグラフ装置
JPH1123557A (ja) * 1997-07-04 1999-01-29 Tosoh Corp 液体クロマトグラフ
JPH1123549A (ja) * 1997-07-03 1999-01-29 Tosoh Corp 液漏れ検知機構付き液体クロマトグラフ
JP2006313093A (ja) * 2005-05-06 2006-11-16 Hitachi High-Technologies Corp 液体クロマトグラフ装置

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4288825B2 (ja) * 2000-03-30 2009-07-01 株式会社島津製作所 液体クロマトグラフ
DE112004000853D2 (de) * 2003-03-10 2006-02-02 Flux Instr Ag Basel Überwachung des Teilungsverhältnisses eines Volumenstroms
JP3763841B1 (ja) 2005-09-07 2006-04-05 豊瑛電研株式会社 発電装置
CN101400418B (zh) * 2006-03-17 2012-11-14 沃特世科技公司 保持流体完整性和预先形成梯度的适于液相色谱的溶剂输送系统
WO2009098125A1 (en) * 2008-02-06 2009-08-13 Proxeon Biosystems A/S Flow control in high performance liquid chromatography
JP2011137676A (ja) * 2009-12-28 2011-07-14 Hitachi High-Technologies Corp 分注装置，自動分析装置、および液量測定方法
JP2013217816A (ja) * 2012-04-11 2013-10-24 Hitachi High-Technologies Corp 液体クロマトグラフ

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62132442U (https=) * 1986-02-13 1987-08-21
JPH09145701A (ja) * 1995-11-29 1997-06-06 Shimadzu Corp 液体クロマトグラフ装置
JPH1123549A (ja) * 1997-07-03 1999-01-29 Tosoh Corp 液漏れ検知機構付き液体クロマトグラフ
JPH1123557A (ja) * 1997-07-04 1999-01-29 Tosoh Corp 液体クロマトグラフ
JP2006313093A (ja) * 2005-05-06 2006-11-16 Hitachi High-Technologies Corp 液体クロマトグラフ装置

Also Published As

Publication number Publication date
JP7260063B2 (ja) 2023-04-18
CN115398225A (zh) 2022-11-25
US12416606B2 (en) 2025-09-16
JPWO2021250919A1 (https=) 2021-12-16
US20230184723A1 (en) 2023-06-15
CN115398225B (zh) 2023-09-19

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