WO2020059290A1 - 液体クロマトグラフを有する分析装置および液体クロマトグラフの分析方法 - Google Patents

液体クロマトグラフを有する分析装置および液体クロマトグラフの分析方法 Download PDF

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WO2020059290A1
WO2020059290A1 PCT/JP2019/029082 JP2019029082W WO2020059290A1 WO 2020059290 A1 WO2020059290 A1 WO 2020059290A1 JP 2019029082 W JP2019029082 W JP 2019029082W WO 2020059290 A1 WO2020059290 A1 WO 2020059290A1
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Prior art keywords
liquid
liquid chromatograph
stream
sample
separation column
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Ceased
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PCT/JP2019/029082
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English (en)
French (fr)
Japanese (ja)
Inventor
晋弥 松岡
和之 杉目
大介 海老原
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Hitachi High Tech Corp
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Hitachi High Technologies Corp
Hitachi High Tech Corp
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Priority to US17/277,749 priority Critical patent/US11567044B2/en
Priority to CN201980057815.4A priority patent/CN112740030B/zh
Priority to JP2020548052A priority patent/JP7262472B2/ja
Priority to EP19862833.1A priority patent/EP3855179B1/en
Publication of WO2020059290A1 publication Critical patent/WO2020059290A1/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
    • G01N30/88—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
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • 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
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/38—Flow patterns
    • G01N30/46—Flow patterns using more than one column
    • 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
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • 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
    • G01N2030/889—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 monitoring the quality of the stationary phase; column performance

Definitions

  • the present invention relates to an analyzer having a liquid chromatograph and a method for analyzing a liquid chromatograph.
  • a liquid chromatograph mass spectrometer is a device that combines a mass spectrometer as a liquid chromatograph detector. By combining separation by chemical structure of a substance by liquid chromatography and separation by mass of a substance by a mass spectrometer, each component of a similar substance can be qualitatively and quantitatively determined. This feature enables the qualitative and quantitative determination of the target substance even in systems where many similar substances are metabolized in the body, such as pharmaceuticals in biological samples, and is expected to be applied to the clinical testing field. Have been.
  • the number of samples that can be processed per hour is called throughput, and the throughput of the above-described automatic biochemical analyzer is 1000 samples / hour.
  • the separation time of the liquid chromatograph is, for example, 240 seconds in a commercially available testosterone (male hormone) measurement kit.
  • the throughput when using this measurement kit is 15 samples / hour. This is only 1.5% of the throughput of 1000 samples / hour, which is an example of the throughput of a biochemical automatic analyzer, and is a problem in processing samples in a clinical laboratory.
  • the above issues limit the number of samples measured by a liquid chromatograph mass spectrometer that can be measured within a fixed time in a clinical laboratory, require a long time to report results, and process many samples. For this purpose, it is necessary to introduce a large number of devices, which causes a financial burden and an increase in space for installing the devices.
  • One of the methods to improve throughput is to install multiple liquid chromatographs on a single test device and measure with a mass spectrometer while sequentially switching the eluate eluted from multiple liquid chromatographs. .
  • a liquid chromatograph mass spectrometer having such a configuration is referred to as a multi-stream liquid chromatograph mass spectrometer.
  • the mass spectrometer (mass spectrometer) only needs to measure the time zone of the eluate eluted from the liquid chromatograph containing the substance to be measured. Therefore, the time for using the mass spectrometer for one measurement is about several tens of seconds. If the time required for measurement with a mass spectrometer is 36 seconds per measurement and the time required for liquid chromatographic separation is 144 seconds (36 ⁇ 4), if there are four liquid chromatographs, each The eluate from the liquid chromatograph can be sequentially processed by the mass spectrometer without any idle time, and a throughput of 100 samples / hour can be obtained.
  • each liquid chromatograph is called a stream.
  • the stream comprises at least a liquid feed pump and a separation column.
  • a flow switching valve is required to select one of the eluates from the plurality of streams and introduce it into the mass spectrometer.
  • the sample introduction device to the liquid chromatograph may be provided for each stream, or may be shared by a plurality of streams.
  • Patent Literature 1 As a multi-stream liquid chromatograph mass spectrometer, for example, in Patent Literature 1, a plurality of separation columns are arranged in parallel, a flow path from a mobile phase liquid sending section is switched by a switching valve, and a separation column to be used is selected. A configuration in which a single detector is connected by a switching valve provided at a subsequent stage is described.
  • Patent Document 1 aims to enable a highly efficient and accurate search for a separation column and a mobile phase suitable for separation of a target component by such a configuration.
  • Patent Document 2 discloses that a plurality of separation columns are installed via a switching valve so that when one separation column reaches the end of its life, it is automatically switched to another separation column. A method for continuously analyzing a sample is described.
  • the multi-stream liquid chromatograph mass spectrometer is configured to be able to exchange the separation column of a stream that requires replacement of the separation column while continuing measurement in another stream, After performing the separation column exchange, it can be returned as a stream used for analysis.
  • Patent Document 2 The technology described in Patent Document 2 is a technology that automatically switches to another healthy separation column when one separation column reaches the end of its life.
  • An object of the present invention is to prevent a plurality of separation columns from reaching the end of life at the same or close timing and to prevent a plurality of streams from being unusable at the same time, and to suppress a significant decrease in throughput or an apparatus stoppage.
  • An object of the present invention is to realize an analyzer having a liquid chromatograph and a method for analyzing a liquid chromatograph.
  • the present invention is configured as follows to achieve the above object.
  • a plurality of liquid chromatographs each having a separation column for separating a substance to be measured from a sample, a liquid chromatograph selecting unit for selecting one of the plurality of liquid chromatographs, and a liquid chromatograph selected by the liquid chromatograph selecting unit
  • a detector for detecting and analyzing the substance to be measured from the eluate eluted from the liquid chromatograph
  • a control unit for controlling the plurality of liquid chromatographs, the liquid chromatograph selection unit and the detector, wherein the control unit is provided in each of the plurality of liquid chromatographs.
  • the liquid chromatograph selection unit is controlled so as to compare the remaining usable times of the separation column with each other and select a liquid chromatograph having the separation column with the small usable times.
  • a plurality of liquid chromatographs having a separation column for separating a substance to be measured from a sample, one of the plurality of liquid chromatographs is selected, and an eluate eluted from the selected liquid chromatograph is selected.
  • the liquid chromatograph analysis method of detecting and analyzing a substance to be measured by a detector the remaining usable times of the separation columns of each of the plurality of liquid chromatographs are compared with each other, and the usable times are small. Select a liquid chromatograph with a separation column.
  • a liquid chromatograph capable of preventing a plurality of separation columns from reaching the end of their life and preventing a plurality of streams from being unusable at the same time, significantly reducing the throughput, and suppressing the shutdown of the apparatus. And an analysis method for a liquid chromatograph can be realized.
  • FIG. 1 is a diagram illustrating a minimum configuration of a multi-stream liquid chromatograph mass spectrometer to which an embodiment of the present invention is applied. It is explanatory drawing of a sample introduction mechanism.
  • 9 is a flowchart for determining a stream to be used. It is a figure showing the table explaining the method of judging the stream to be used from the use state of the stream and the remaining use count. It is a figure showing the table explaining the method of judging the stream to be used from the use state of the stream and the remaining use count. It is a figure showing the table explaining the method of judging the stream to be used from the use state of the stream and the remaining use count. It is a figure showing the table explaining the method of judging the stream to be used from the use state of the stream and the remaining use count. It is a figure showing the table explaining the method of judging the stream to be used from the use state of the stream and the remaining use count.
  • FIG. 1 An overall configuration of a multi-stream liquid chromatograph mass spectrometer to which an embodiment of the present invention is applied will be described with reference to FIG.
  • One embodiment is an example in which a mass spectrometer is used as an analyzer.
  • FIG. 1 is a diagram showing a minimum configuration of a multi-stream liquid chromatograph mass spectrometer to which one embodiment of the present invention is applied. It should be noted that the present invention can be configured to include additional elements such as the number of streams, additional pumps, additional valves, and the like.
  • a multi-stream liquid chromatograph mass spectrometer to which an embodiment of the present invention is applied is an example having three streams, a stream 1, a stream 2, and a stream 3, as described later. Each stream constitutes a liquid chromatograph.
  • the multi-stream liquid chromatograph / mass spectrometer includes a mobile phase liquid sending unit 101 for sending mobile phase liquids (100a, 100b) in stream 1.
  • the mobile phase liquid sending section 101 is provided with two pumps (102a, 102b), sends two kinds of different liquids at a specified ratio, mixes them by a mixer section 103, and sends them. This function is called a gradient, and is commonly used in liquid chromatography.
  • the mobile phase liquid sending section is connected to one port (circled 1) of the sample introduction switching valve 105 by the flow path A104.
  • a pressure gauge 123 is disposed in the flow path A104.
  • a sample suction nozzle 107 is connected to another port (circle 5) of the sample introduction switching valve 105 via a flow path B106.
  • the sample suction nozzle 107 is inserted into the sample container 108 by a drive mechanism (not shown), and sucks the sample 109 in the sample container.
  • the suction of the sample 109 is performed by a sample suction unit 110 such as a syringe pump.
  • the sample suction unit 110 is connected to a port (circled 4) of the sample introduction switching valve 105 via a flow path C111.
  • a sample loop 112 is connected between the port (circle 3) and the port (circle 6) of the sample introduction switching valve 105.
  • the sample loop 112 is used to keep the amount of sample introduced into the liquid chromatograph constant.
  • a sample introduction unit is constituted by the sample suction nozzle 107, the sample introduction switching valve 105, and the sample suction unit 110.
  • a separation column 114 for separating a substance to be measured from a sample is connected to a port (circle 2) of the sample introduction switching valve 105 via a channel D113.
  • the flow path D113 is connected to the upstream side of the separation column 114, and the flow path E115 is connected to the downstream side.
  • the port (circle 1) of the detector introduction stream switching valve A116, which is another switching valve, is connected via the flow path E115. Connected to.
  • the sample introduction switching valve 105 has six ports, and adjacent ports are connected inside the sample introduction switching valve 105.
  • the port indicated by the circle 1 and the port indicated by the circle 2 the port indicated by the circle 3 and the port indicated by the circle 4, the port indicated by the circle 5 and the port indicated by the circle 6 are connected to each other. ing.
  • the ports to be connected are the ports indicated by the circles 2 and 3, the ports indicated by the circles 4 and 5, and the ports indicated by the circles.
  • the ports 6 and 1 are switched to the connected state.
  • the sample suction nozzle 107 is introduced into the sample 109 of the sample container 108, and the sample suction unit 110 performs a suction operation. Through the sample loop 112.
  • the port of the circle 1, the port of the circle 6, the sample loop 112, the port of the circle 3, and the port of the circle 2 are connected.
  • the mobile phase is sent from the mobile phase liquid sending unit 101 toward the port indicated by the circle 1.
  • the sample 109 cut (introduced) into the sample loop 112 is introduced into the separation column 114.
  • the sample container 108 can be moved to a predetermined sample nozzle suction position by a sample introduction mechanism described later.
  • a multi-stream liquid chromatograph / mass spectrometer a plurality of streams are provided as described above.
  • three streams are provided, that is, a stream 2 shown in a dashed line in FIG. 1 and a stream 3 shown in a two-dot chain line. Therefore, a description will be given using three stream configurations as an example.
  • the configuration of the stream 2 and the stream 3 is the same as the configuration of the stream 1 described above, and the description of each component will be omitted.
  • the downstream side of the separation column 117 of the stream 2 (on the detector introduction stream switching valve 116 side) is connected to the port indicated by the circle 3 of the detector introduction stream switching valve A 116 via the flow path F118.
  • the port of circle 2 of the detector introduction stream switching valve A116 is connected to the port of circle 1 of another detector introduction stream switching valve B122.
  • the separation column 119 of the stream 3 is connected to the port of the circle 3 of the detector introduction stream switching valve B122 via the flow path G120.
  • Each of the detector introduction stream switching valves A116 and B122 has four ports and is connected to an adjacent port.
  • a liquid chromatograph selection unit is constituted by the detector introduction stream switching valves A116 and B122.
  • Detector introduction stream switching valve A116 switches between stream 1 and stream 2 between the side to be sent to detector introduction stream switching valve B122 on the detector 121 (mass spectrometer) side and the side to be sent to the drain.
  • the detector 121 detects and analyzes a substance to be measured from the eluate eluted from the liquid chromatograph.
  • the detector introduction stream switching valve B122 on the detector 121 switches between the eluate (the eluate from the stream 1 or the stream 2) coming out of the detector introduction stream switching valve A116 and the eluate from the stream 3, and performs detection.
  • the eluate to be sent to the vessel 121 is selected.
  • the detector introduction stream switching valves A116 and B122 By switching the detector introduction stream switching valves A116 and B122, the streams measured by the detector 121 can be switched, and the single detector 121 can be shared among the plurality of streams 1, 2, and 3. .
  • the port 1 of the detector introduction stream switching valve A116 is connected to the port 2 of the circle, and the port 3 is connected to the port 3 of the circle.
  • the port marked 4 is connected.
  • the port of the circle 1 of the detector introduction stream switching valve B122 and the port of the circle 2 are connected, and the port of the circle 3 is connected. And the port indicated by the circle 4 are connected.
  • the port 1 of the detector introduction stream switching valve A116 and the port 4 are connected, and the port 3 is connected to the port 3 of the circle.
  • the port marked 2 is connected.
  • the port of the circle 1 of the detector introduction stream switching valve B122 and the port of the circle 2 are connected, and the port of the circle 3 is connected. And the port indicated by the circle 4 are connected.
  • the port 1 of the detector introduction stream switching valve A116 is connected to the port 4 of the circle, and the port 3 is connected to the port 3 of the circle.
  • the port marked 2 is connected.
  • the display unit 124 is connected to the detector 121.
  • the display unit 124 displays the necessity of replacement of the separation column that reaches the end of its life.
  • FIG. 2 is an explanatory diagram of the sample introduction mechanism.
  • the stream 1, 2 or 3 in which a sample is introduced and measurement is performed is selected by the sample introduction mechanism 200 according to a measurement item and a use situation.
  • the sample introduction mechanism 200 has a sample disk 202 having a plurality of sample container holding units 201 for holding the sample containers 108.
  • a sample nozzle 107 for stream 1 for introducing a sample to stream 1, a sample nozzle 204 for stream 2 for introducing a sample to stream 2, and a sample nozzle 205 for stream 3 for introducing a sample to stream 3 are arranged near the sample disk 202. Is done.
  • the stream 1 sample nozzle 106, the second stream 2 sample nozzle 204, and the stream 3 sample nozzle 205 can be moved up and down and rotated by a drive mechanism not shown.
  • the sample nozzles 107, 204, and 205 are all installed at positions on the circumference of the sample disk 202 where the sample container holding unit 201 is installed so as to be accessible by the above-described vertical and rotational operations.
  • the sample introduction mechanism 200 is controlled by the control unit 206 so that the sample container 108 moves to a predetermined sample nozzle suction position.
  • the control unit 206 controls the liquid chromatograph (stream 1, stream 2, stream 3), the liquid chromatograph selecting units (116, 122), the detector 121, and the display unit 124.
  • the control unit 206 includes: measurement request information, which is a measurement item measurement order of a plurality of samples 109 that are continuously measured; information on streams 1, 2, or 3 to be used that is determined by the measurement items; The stream 1, 2, or 3 to which the sample 109 is to be sent is determined using the information of 2, 3 as a determination criterion.
  • FIG. 3 is a flowchart for determining a stream to be used.
  • FIGS. 4A to 4D are tables showing a table for explaining a method of judging a stream to be used from the use state of the stream and the remaining number of times of use.
  • the control unit 206 determines the stream to be used based on the flow shown in FIG. 3, and the sample introduction mechanism 200, the streams 1 to 3, the detector introduction stream switching valve A116, the detector introduction stream switching valve B122, the detector 121 and the operation of the display unit 124 are controlled.
  • the control unit 206 stores the remaining use count of each stream.
  • the present invention is applicable to a multi-stream liquid chromatograph mass spectrometer having two or more streams.
  • FIG. 3 is a flowchart of a method for determining a stream to be used.
  • the multi-stream liquid chromatograph mass spectrometer has a specific time (for example, 60 seconds) as a cycle, and has one sample introduction timing within one cycle.
  • the measurement is performed in units of cycles, and the number of cycles used differs depending on the measurement item. This is because the time required for separation in liquid chromatography differs depending on the substance.
  • the control unit 206 determines whether there is one or more streams that can be used in the cycle (step S1). If there is no usable stream, the sample introduction in the cycle is skipped (step S3).
  • FIG. 4A shows an example of this case.
  • a circle indicates that the stream is in use and the next measurement cannot be started.
  • the timing at which the next measurement is to be started is defined as the 0th cycle, and the cycles before and after it are defined as ⁇ 1 cycle and +1 cycle.
  • the 0th cycle At the time of the 0th cycle, all of stream 1, stream 2, and stream 3 are being used in the previous measurement, and the next measurement cannot be started. Therefore, the measurement cannot be started in the 0th cycle, and the next measurement start timing is shifted after the next cycle.
  • the stream 1 is usable (triangle), so the next measurement is started using the stream 1.
  • step S2 If it is determined in step S1 that there is one or more available streams in the current cycle, in step S2, it is determined whether there is only one available stream in the cycle. If only one stream is available in the cycle, the available stream is used (step S5).
  • FIG. 4B shows an example of this case.
  • step S2 when there are a plurality of streams that can be used in the cycle, a determination is made by a method unique to one embodiment of the present invention. That is, in step S2, if there are a plurality of streams that can be used in the cycle, the process proceeds to step S4, and it is determined whether there are a plurality of streams that have the least number of remaining uses of the separation column.
  • step S4 If, in step S4, there are a plurality of streams for which the number of remaining uses of the separation column is the least, the process proceeds to step S7, and the stream having the smallest stream number is used.
  • FIG. 4C shows an example of this case.
  • step S4 if the number of streams in which the number of remaining uses of the separation column is the least is not a plurality but only one, the process proceeds to step S6, and the stream to which the number of remaining columns is used is used.
  • FIG. 4D shows an example of this case.
  • two streams, stream 1 and stream 2 can be used in the 0th cycle.
  • Stream 1 is usable, but the next measurement has not been started (black triangle).
  • Stream 2 is available and indicates the case where the next measurement is started (triangle mark).
  • the stream 2 is selected according to the criterion according to the embodiment of the present invention, and the next measurement is started using the stream 2 (step S6).
  • the criterion is to use the stream with the smaller stream number, so the stream with the smaller stream number will reach the end of its life earlier, and multiple streams will end Can be avoided.
  • how many times the separation column can be used is defined as the number of remaining uses.
  • the remaining number of times the separation column can be used can be defined by the number of times it can be used, the upper limit of the pressure in the flow channel, the limit of the fluctuation of the retention time of the liquid chromatogram, and the like.
  • the method has been described in which the remaining number of uses is defined based on the number of usable times.
  • a method of determining the increased upper limit of the pressure of the flow path and making the separation column usable until the pressure reaches the upper limit is a method of defining the remaining use number of the separation column by the upper limit of the flow path pressure.
  • the remaining number of uses is calculated from the difference between the pressure at that time and a predetermined allowable pressure upper limit (reference pressure), and the difference from the allowable pressure upper limit is the smallest (the remaining The stream with the least number of uses) is used preferentially.
  • a reference value of the retention time of the specific component of the measurement target substance is set in advance, and the retention time of the specific component of the actually detected measurement target substance is set.
  • a limit value is set for the difference (deviation time) between the threshold value and the retention time reference value, and when the difference value is exceeded, the separation column life is determined.
  • the stream having the largest divergence time from the reference value of the holding time is preferentially used. This can be performed by calculating the number of remaining uses from the value of the difference between the retention time of the specific component of the measurement target substance and the retention time reference value, and selecting and using a stream with a small number of remaining uses. it can.
  • the retention time of the liquid chromatogram can be determined by the data output from the detector 121, and the output of the detector 121 is supplied to the control unit 206, and the control unit 206 transmits the liquid chromatogram in each of the streams 1, 2, and 3. Judge the holding time and decide which stream to use.
  • a stream having a separation column with a small number of remaining uses and a short period of time can be preferentially used.
  • a stream having a separation column that has a small number of remaining uses at a certain point in time is likely to be used later according to the criterion according to one embodiment of the present invention, and thus may reach a life earlier than other streams. The nature becomes high.
  • An analyzer having a liquid chromatograph and a method for analyzing a liquid chromatograph can be realized which can suppress the occurrence.
  • the detector 121 is a mass spectrometer
  • the present invention is not limited to an example in which a mass spectrometer is used as a detector, and an ultraviolet-visible absorptiometer, an electrochemical measurement detector Can also be used as a detector.
  • a detector refers to a device having an element that converts the concentration of a substance to be measured into an electric quantity such as a voltage or an electric current, and includes, for example, a mass spectrometer (mass spectrometer), an ultraviolet-visible absorption spectrophotometer, There are chemical measurement detectors and the like.
  • 100a, 100b mobile phase liquid
  • 101 mobile phase liquid sending section
  • 102a, 102b pump
  • 103 mixer section
  • 104 flow path A
  • 105 sample introduction switching Valve
  • 106 flow channel B sample suction nozzle
  • 108 sample container sample container
  • 109 sample 110 sample suction unit
  • 111 flow channel C 112, etc.
  • -Sample loop 113 ... Flow path D, 114 ... Separation column, 115 ... Flow path E, 116 ... Detector introduction stream switching valve A, 117 ... Separation column, 118 ...
  • Channels F, 119 Separation column, 120: Channel G, 121: Detector, 122: Detector introduction stream switching valve B, 123: Pressure gauge, 124: Display Part, 200 ... Sample introduction mechanism, 201 ... sample container holder, 202 ... sample disk, 204 ... Stream 2 sample nozzle, the sample nozzle 205 ... stream 3, 206 ... control unit

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PCT/JP2019/029082 2018-09-21 2019-07-24 液体クロマトグラフを有する分析装置および液体クロマトグラフの分析方法 Ceased WO2020059290A1 (ja)

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US17/277,749 US11567044B2 (en) 2018-09-21 2019-07-24 Analysis device having a liquid chromatograph and method for analyzing a liquid chromatograph
CN201980057815.4A CN112740030B (zh) 2018-09-21 2019-07-24 具有液相色谱仪的分析装置以及液相色谱仪的分析方法
JP2020548052A JP7262472B2 (ja) 2018-09-21 2019-07-24 液体クロマトグラフを有する分析装置および液体クロマトグラフの分析方法
EP19862833.1A EP3855179B1 (en) 2018-09-21 2019-07-24 Analysis device having liquid chromatograph, and liquid chromatograph analysis method

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JP2018-178002 2018-09-21
JP2018178002 2018-09-21

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US12320787B2 (en) * 2020-06-22 2025-06-03 Waters Technologies Corporation Insulated serial column chromatography arrangements and systems
US20230417781A1 (en) * 2020-12-11 2023-12-28 Hitachi High-Tech Corporation Method of controlling automatic analyzer
CN117571897B (zh) * 2023-11-15 2024-04-30 青岛惠安康生物工程有限公司 一种液相色谱-质谱联用仪及切换装置

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6454350A (en) * 1987-08-26 1989-03-01 Japan Spectroscopic Co Separation column for chromatograph and administration device thereof
JPH06324027A (ja) 1993-05-12 1994-11-25 Hitachi Ltd 自動液体クロマトグラフ
JP2004085357A (ja) * 2002-08-27 2004-03-18 Shimadzu Corp クロマトグラフ装置用データ管理装置
JP2004163339A (ja) * 2002-11-15 2004-06-10 Shimadzu Corp クロマトグラフ用データ管理装置
JP2015052533A (ja) * 2013-09-06 2015-03-19 株式会社日立製作所 クロマトグラフィー装置およびクロマトグラフィー方法
JP2015166724A (ja) * 2014-03-04 2015-09-24 株式会社島津製作所 液体クロマトグラフ制御装置及び液体クロマトグラフ制御方法
JP2017161335A (ja) 2016-03-09 2017-09-14 株式会社島津製作所 流体クロマトグラフ

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2800509B2 (ja) * 1990-11-30 1998-09-21 株式会社日立製作所 液体クロマトグラフ装置
JP3053131B2 (ja) * 1991-09-17 2000-06-19 株式会社日立製作所 ガードカラムを備えた高速液体クロマトグラフ
JP3346965B2 (ja) * 1995-09-14 2002-11-18 株式会社日立製作所 アミノ酸分析装置
DE19540527A1 (de) * 1995-10-31 1997-05-07 Hewlett Packard Gmbh Vorrichtung zur Erkennung austauschbarer Teile in analytischen Meßgeräten
EP1709440A2 (en) * 2004-01-28 2006-10-11 Council Of Scientific And Industrial Research A method for standardization of chemical and therapeutic values of foods medicines using animated chromatographic fingerprinting
US20080244437A1 (en) 2007-03-29 2008-10-02 Fischer Gregory T Quick Glance Maintenance Interface for an Analytical Device
CN102008837B (zh) * 2010-09-30 2012-09-05 中国科学院昆明植物研究所 含串联制备色谱柱的分离制备色谱仪器
US9835597B2 (en) * 2012-03-07 2017-12-05 Waters Technologies Corporation Device capable of pressurization and associated systems and methods
JP6203557B2 (ja) * 2013-07-05 2017-09-27 株式会社日立製作所 分離装置及び分離方法
US10890566B2 (en) * 2013-08-28 2021-01-12 Shimadzu Corporation Automatic analysis control device and program
WO2016105514A1 (en) * 2014-12-23 2016-06-30 Biotech Institute, Llc A reliable and robust method for the analysis of cannabinoids and terpenes in cannabis
US11835501B2 (en) * 2015-07-13 2023-12-05 Sartorius Stedim Chromatography Systems Ltd. Optimizing operating binding capacity for a multiple column chromatography process
WO2018083706A1 (en) * 2016-11-04 2018-05-11 Rosemount Analytical Inc. A method of monitoring the components of gas analyser
DE102016121516B4 (de) * 2016-11-10 2019-03-28 Dionex Softron Gmbh Verfahren und Vorrichtung zur Probenbeschickung
CN106680353B (zh) * 2017-03-21 2019-04-16 上海通微分析技术有限公司 一种电色谱装置
JP6790963B2 (ja) * 2017-03-30 2020-11-25 株式会社島津製作所 液体クロマトグラフ
CN108037233B (zh) * 2017-12-28 2024-05-03 大连博迈科技发展有限公司 基于同一检测器的全在线检测的多维液相色谱分离系统
CN108310902A (zh) * 2018-04-02 2018-07-24 苏州阿洛斯环境发生器有限公司 VOCs处理设备
LT3781941T (lt) * 2018-04-20 2026-04-10 Janssen Biotech, Inc. Chromatografijos kolonėlės kvalifikavimas gamybos būduose, skirtuose anti-tnf antikūnų kompozicijoms gaminti

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6454350A (en) * 1987-08-26 1989-03-01 Japan Spectroscopic Co Separation column for chromatograph and administration device thereof
JPH06324027A (ja) 1993-05-12 1994-11-25 Hitachi Ltd 自動液体クロマトグラフ
JP2004085357A (ja) * 2002-08-27 2004-03-18 Shimadzu Corp クロマトグラフ装置用データ管理装置
JP2004163339A (ja) * 2002-11-15 2004-06-10 Shimadzu Corp クロマトグラフ用データ管理装置
JP2015052533A (ja) * 2013-09-06 2015-03-19 株式会社日立製作所 クロマトグラフィー装置およびクロマトグラフィー方法
JP2015166724A (ja) * 2014-03-04 2015-09-24 株式会社島津製作所 液体クロマトグラフ制御装置及び液体クロマトグラフ制御方法
JP2017161335A (ja) 2016-03-09 2017-09-14 株式会社島津製作所 流体クロマトグラフ

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"LABOSPECT006, AUTOMATIC ANALYSIS DEVICE AND ATTACHMENT THEREOF", June 2017, HITACHI HIGH-TECHNOLOGIES CORPORATION, article "Overall Mechanism of Independent Administration Medical Device"
See also references of EP3855179A4

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2026070108A1 (ja) * 2024-09-27 2026-04-02 株式会社日立ハイテク 自動分析装置

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