JP7226522B2 - Liquid chromatography analysis system - Google Patents

Description

The present invention relates to a modular liquid chromatography analysis system configured by combining a plurality of modules.

Modular analysis systems exist as analysis systems for performing liquid chromatography analysis. A modular analysis system is a system composed of a combination of multiple modules. The modules that make up the system include a liquid transfer device that transfers the mobile phase, an autosampler that injects the sample, and the temperature of the separation column. a column oven for adjusting , a detector for detecting sample components, a system controller, and the like (see Patent Document 1).

JP 2016-080466 A

In the modular liquid chromatography analysis system as described above, the internal capacity of the analysis system differs depending on the modules and piping incorporated in the system. When performing a gradient analysis in which the composition of the mobile phase changes over time, even if the conditions such as the mobile phase flow rate and the separation column temperature are the same, the analysis will not be possible if the analysis systems have different internal volumes. The problem was that the results were different. Therefore, the analysis results for the same sample differed depending on the analysis system.

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and it is an object of the present invention to reduce the influence of differences in the configuration of analysis systems on analysis results.

The liquid chromatography analysis system according to the present invention is a modular liquid chromatography analysis system configured by a combination of a plurality of modules, and the modules are for gradient liquid feeding of a plurality of types of solvents as a mobile phase. A liquid delivery device having a liquid delivery pump, and at least an autosampler for injecting a sample into the mobile phase delivered by the liquid delivery device, a mixer for mixing the plurality of types of solvents, and delivery from the mixer. a system capacity holding unit that holds, as a system capacity, the internal capacity of the system that affects the time it takes for the collected mobile phase to reach the sample temporarily held in the autosampler, and held in the system capacity holding unit and an injection timing determining unit configured to determine the timing of sample injection by the autosampler using the system capacity set, and the autosampler at the injection timing determined by the injection timing determining unit. A sample injection is configured to be performed.

In a liquid chromatography system, when performing gradient analysis in which the composition of the mobile phase changes over time, if the system capacity differs for each analysis system, the mobile phase sent from the mixer reaches the sample in the autosampler. Therefore, even if the sample is injected at the same timing, there is a difference in the time required for the initial concentration mobile phase to wash away the sample in the separation column. In an analysis system with a large system capacity, the initial concentration mobile phase sweeps away the sample in the separation column for a long time, so the elution time of sample components from the separation column differs. Therefore, different chromatograms are obtained between analysis systems with different system capacities.

Therefore, in the liquid chromatography analysis system according to the present invention, a system capacity holding unit that holds the system capacity and the system capacity held in the system capacity holding unit are used to determine the injection timing of the sample by the autosampler. and an injection timing determination unit configured to determine the sample injection timing by the autosampler at the injection timing determined by the injection timing determination unit. This makes it possible to adjust the sample injection timing according to the time required for the mobile phase delivered from the mixer to reach the sample in the autosampler. As a result, the influence on the analysis result due to the difference in the configuration of the analysis system is reduced.

1 is a schematic configuration diagram showing an example of a liquid chromatography analysis system; FIG. FIG. 4 is a schematic configuration diagram showing another embodiment of the liquid chromatography analysis system; FIG. 10 is a schematic configuration diagram showing still another embodiment of the liquid chromatography analysis system; 7 is a flow chart showing an example of a system capacity registration operation; 4 is a flowchart showing an example of analysis operation;

Hereinafter, embodiments of a liquid chromatography analysis system according to the present invention will be described with reference to the drawings.

FIG. 1 shows a schematic configuration of an embodiment of a liquid chromatography analysis system.

The liquid chromatography analysis system of this embodiment is a modular analysis system configured by combining a plurality of modules. 10.

The liquid-sending device 2 includes two liquid-sending pumps 12a and 12b for sending different solvents as mobile phases, and a pump capacity holding unit 14 for holding information about the internal capacities of the liquid-sending pumps 12a and 12b. ing. The pump capacity holding unit 14 is implemented by a partial storage area of a storage device mounted on an electronic circuit board provided in the liquid transfer device 2 . In this embodiment, the column oven 6 is equipped with a mixer 18 for mixing two kinds of solvents sent by the two liquid sending pumps 12a and 12b.

The autosampler 4 is for injecting a sample into the mobile phase consisting of the solvent mixed in the mixer 18 . The autosampler 4 includes a needle for collecting a sample, a sample loop for temporarily holding the sample collected by the needle, and whether or not the sample loop is inserted between the liquid transfer device 2 and the separation column 20. By inserting the sample loop holding the sample between the liquid transfer device 2 and the separation column 20, the mobile phase transferred by the liquid transfer device 2 Inject the sample. In the autosampler 4, the internal volume of the inlet pipe in the autosampler 4 connecting between the liquid delivery device and the switching valve, the internal volume of the system including the switching valve, the sample loop, the needle and the injection port, the switching valve and A sampler capacity holding unit 16 is provided for holding information about the internal capacity of the outlet pipe in the autosampler 4 that connects to the switching valve 20 . The sampler capacity holding unit 16 is implemented by a partial storage area of a storage device mounted on an electronic circuit board provided in the autosampler 4 .

The column oven 6 accommodates therein a separation column 20 for separating the sample into components and adjusts the temperature of the separation column 20 . The column oven 6 is provided with a mixer 18 and a mixer capacity holding unit 22 that holds information about the internal capacity of the mixer 18 . The mixer capacity holding section 22 is implemented by a partial storage area of a storage device mounted on an electronic circuit board provided in the column oven 6 .

Note that the mixer 18 does not necessarily have to be mounted on the column oven 6 , and may be mounted on either module of the liquid transfer device 2 or the autosampler 4 . In that case, the mixer capacity holding unit 22 may be provided in the module on which the mixer 18 is mounted.

Each liquid-sending pump 12a, 12b of the liquid-sending device 2 is fluidly connected to the inlet of the mixer 18 in the column oven 6 through a predetermined pipe, and the outlet of the mixer 18 is connected to the input port of the autosampler 4 by a predetermined pipe. fluidly connected via The output port of the autosampler 4 is fluidly connected to the inlet of the separation column 20 inside the column oven 6 through a predetermined pipe. The outlet of the separation column 20 inside the column oven 6 is connected to the input port of the detector 8 through a predetermined pipe.

The detector 8 is for detecting sample components separated in the separation column 20 .

The system controller 10 is connected to each module of the liquid transfer device 2, the autosampler 4, the column oven 6 and the detector 8 by, for example, a communication cable so as to enable electrical communication. It has a function of controlling the operations of 6 and 8.

The system controller 10 includes a system capacity holding section 24 , a system configuration holding section 26 , a system capacity calculation section 28 and an injection timing determination section 30 . The system capacity holding section 24 and the system configuration holding section 26 are implemented by a partial storage area of the storage device provided in the system controller 10 . The system capacity calculation unit 28 and the injection timing determination unit 30 are functions obtained by executing a predetermined program by a central processing unit (CPU) provided in the system controller 10 .

The system capacity holding unit 24 holds the internal capacity of the system, which affects the time it takes for the mobile phase sent from the mixer 18 to reach the sample temporarily held in the sample loop in the autosampler 4, as the system capacity. do. The system capacity is calculated by the system capacity calculator 28 .

The system configuration holding unit 26 holds information about the system configuration of this analysis system, that is, information about what kind of modules are used and what kind of pipes each module is connected to each other to configure the system. . The system controller 10 controls the information obtained from each module 2, 4, 6 and 8 by communication between each module 2, 4, 6 and 8 and/or input by the user (worker who built the analysis system) The system configuration can be recognized based on the received information. The system configuration holding unit 26 holds information about the system configuration thus recognized.

The system capacity calculator 28 determines that the mobile phase sent from the mixer 18 based on the system configuration information held in the system configuration holder 26 reaches the sample temporarily held by the sample loop in the autosampler 4. The system capacity is calculated by identifying the elements present in the system that affect the time to complete and adding up the internal capacities of those elements.

The system configuration in FIG. 1 is configured for high-pressure gradient liquid feeding in which two types of solvents are fed by two liquid feeding pumps 12a and 12b, and a mixer 18 is connected downstream of the liquid feeding pumps 12a and 12b. It is Therefore, the elements in the system that affect the time it takes for the mobile phase sent from the mixer 18 to reach the sample temporarily held in the sample loop in the autosampler 4 include the mixer 18, the mixer 18 and the autosampler 4. It includes piping connecting to the sampler 4, inlet piping in the autosampler 4, a switching valve, and a sample loop. The system capacity calculation unit 28 uses the information held in the mixer capacity holding unit 22 and the sampler capacity holding unit 16 to calculate the sum of the internal capacities of these elements as the system capacity. The system capacity calculated by the system capacity calculator 28 is held in the system capacity holder 24 .

The injection timing determining unit 30 determines the sample injection timing by the autosampler 4 before the sample analysis is started, based on the system capacity held in the system capacity holding unit 24 and the liquid feed flow rate at the start of analysis. configured to determine The sample injection timing is the timing for switching the switching valve so that the sample loop holding the sample in the autosampler 4 is inserted between the mixer 18 and the separation column 20 .

The time T required for the mobile phase sent from the mixer 18 to reach the sample in the autosampler 4 can be obtained by dividing the system capacity by the liquid sending flow rate. When there are an analysis system with T = t and an analysis system with T = t + α, if gradient liquid transfer is started in both analysis systems and sample is injected at the same timing to start analysis, T = t + α In the analysis system of T=t, the mobile phase arrives at the sample later than the analysis system of T=t by the time α from the start of analysis. Therefore, by delaying the injection timing of the analysis system for T = t + α by the time α from that for the analysis system for T = t, it is possible to match the timing at which the mobile phase sent from the mixer 18 reaches the sample in the autosampler 4. can. As a result, it is possible to match the time for the sample to be swept away by the mobile phase having the initial concentration in the separation column 18 between the analysis systems having different system capacities. The injection timing determination section 30 is configured to determine the injection timing by considering the time required for the mobile phase sent from the mixer 18 to reach the sample in the autosampler 4 .

Since the embodiment of FIG. 1 is a system configuration for high-pressure gradient liquid feeding, the liquid feeding pumps 12a and 12b are not included as elements in the system between the mixer 18 and the sample in the autosampler 4. FIG. Therefore, the internal capacities of the liquid-sending pumps 12a and 12b are not required for calculating the system capacity, and the liquid-sending device 2 does not necessarily need to include the pump capacity holding unit .

Further, as shown in FIG. 2, a low-pressure gradient liquid feeding apparatus 2' for feeding a plurality of types of solvents using a single liquid feeding pump 12 may be used. In this case, the mixer 18 may be mounted on the liquid transfer device 2', and the mixer capacity holding unit 22 may also be provided on the liquid transfer device 2' instead of the column oven 6'. Further, when the liquid-sending pump 12 is connected downstream of the mixer 18 , the liquid-sending pump 12 is included as an element in the system from the mixer 18 to the separation column 20 . Therefore, the system capacity calculator 28 calculates the total value of the internal capacities of the elements in the system from the mixer 18 including the liquid feed pump 12 to the separation column 20 as the system capacity.

It should be noted that in the embodiment of FIGS. 1 and 2, modules having elements that can be incorporated into the system from mixer 18 to separation column 20 have the function of retaining information about the internal volumes of those elements. Part or all of the information regarding the internal capacity of each element may be held in the system controller. In the embodiment of FIG. 3, the column oven 6 ″ is equipped with a mixer 18 , but the column oven 6 ″ does not have the ability to retain information about the internal volume of the mixer 18 . In this embodiment, the system controller 10' is provided with a mixer capacity holding section 22', and the system controller 10' manages information on the internal capacity of the mixer 18 mounted in the column oven 6''. In addition, the system controller may be provided with a function of managing information on the internal capacity of the liquid transfer pump and information on the internal capacity of the autosampler.

1 to 3 described above, the system controller 10 or 10' has functions such as the system capacity holding unit 24, the system configuration holding unit 26, the system capacity calculation unit 28, and the injection timing determination unit 30. However, the present invention is not limited to this, and these functions may be provided in a computer capable of communicating with the system controller 10 or 10'.

The operation of registering the system capacity in the above embodiment will be described with reference to FIGS. 1 to 3 and the flow chart of FIG.

A system configuration is set when constructing an analysis system, and the set system configuration is held in the system configuration holding unit 26 (step 101). The system capacity calculator 28 determines the system configuration that affects the time required for the mobile phase sent from the mixer 18 to reach the sample in the autosampler 4 based on the system configuration held in the system configuration holder 26. Elements are identified (step 102), and the sum of the internal capacities of those elements is calculated as the system capacity (step 103). The system capacity calculated by the system capacity calculating section 28 is registered by being stored in the system capacity holding section 24 (step 104).

Next, the analysis operation in the above embodiment will be described with reference to FIGS. 1 to 3 and the flow chart of FIG.

First, analysis conditions such as the flow rate of the mobile phase and the column temperature are set (step 201). The injection timing determining section 30 determines the sample injection timing in the autosampler 6 using the system capacity held in the system capacity holding section 24 and the set liquid transfer flow rate (step 202). After that, when the system controller 10 (or 10') sends an instruction to start analysis (step 203), the liquid transfer device 2 starts gradient liquid transfer (step 204). After the gradient liquid transfer is started, the autosampler 6 injects the sample at the injection timing determined by the injection timing determination unit 30 (steps 205 and 206). After that, the analysis is terminated when a preset analysis time has elapsed (step 207). When analyzing a plurality of samples continuously, steps 203 to 207 are performed for all samples (step 208).

It should be noted that the examples described above merely exemplify aspects of embodiments of the liquid chromatography analysis system according to the present invention. Embodiments of the liquid chromatography analysis system according to the present invention are as follows.

An embodiment of the liquid chromatography analysis system according to the present invention is a modular liquid chromatography analysis system configured by a combination of a plurality of modules, and as the modules, a plurality of types of solvents are used as mobile phases for gradient liquid feeding. and an autosampler for injecting a sample into the mobile phase delivered by the liquid delivery device, and the sample injected into the mobile phase by the autosampler for each component. A sample comprising at least a column oven containing a separation column for separation, a mixer for mixing the plurality of types of solvents, and a mobile phase sent from the mixer temporarily held in the autosampler Injection of a sample by the autosampler using a system capacity holding unit that holds the internal capacity of the system that affects the time required to reach as a system capacity, and the system capacity held in the system capacity holding unit and an injection timing determination unit configured to determine timing, wherein sample injection is performed by the autosampler at the injection timing determined by the injection timing determination unit.

In the first aspect of the above embodiment, the autosampler includes a sample loop for temporarily holding a sample, and whether or not the sample loop is interposed between the liquid transfer device and the separation column. A switching valve for switching is provided, and the sample is injected into the mobile phase by inserting the sample loop holding the sample between the liquid delivery device and the separation column, and the system capacity is the mixer. to the switching valve.

In the second aspect of the above-described embodiment, the injection timing determination unit, when the liquid transfer device performs gradient liquid transfer that changes the mixing ratio of a plurality of types of solvents with time, causes the system capacity holding unit to The injection timing is determined in consideration of the time obtained by dividing the retained system capacity by the flow rate of liquid sent by the liquid sending device. With this aspect, the injection timing can be determined so as to eliminate the influence of the difference in system capacity on the elution time of sample components from the separation column.

In the third aspect of the above embodiment, a pump capacity holding unit that holds information about the internal capacity of the liquid transfer pump, a sampler capacity holding unit that holds information about the internal capacity in the autosampler, and an internal capacity of the mixer a mixer capacity holding unit that holds information about the system configuration of the liquid chromatography analysis system; a system configuration holding unit that holds information about the system configuration of the liquid chromatography analysis system; the pump capacity holding unit; and a system capacity calculation unit for calculating the system capacity using information held in each system configuration holding unit, wherein the system capacity holding unit holds the system capacity calculated by the system capacity calculation unit. is configured to According to this aspect, the system capacity is automatically calculated based on the system configuration registered in the device, so the user does not need to calculate the system capacity. This second aspect can be combined with the first aspect.

In the third aspect, the pump capacity holding section may be provided in the liquid transfer device, and the sampler capacity holding section may be provided in the autosampler.

In the above case, the mixer is mounted in any module of the liquid transfer device, the autosampler, or the column oven, and the mixer capacity holding unit is provided in the module in which the mixer is mounted. may be

In the third aspect, the module includes a system controller for controlling the operation of the liquid transfer device, the autosampler, and the column oven, and the pump capacity holding section, the mixer capacity holding section, and the sampler. At least one of the capacity holding units may be provided in the system controller.

2, 2' Liquid sending device 4 Auto sampler 6, 6', 6'' Column oven 8 Detector 10 System controller 12, 12a, 12b Liquid sending pump 14 Pump capacity holder 16 Sampler capacity holder 18 Mixer 20 Separation column 22 , 22′ mixer capacity holding unit 24 system capacity holding unit 26 system configuration holding unit 28 system capacity calculation unit 30 injection timing determination unit

Claims (5)

A modular liquid chromatography analysis system configured by combining a plurality of modules,
As the module, a liquid delivery device having a liquid delivery pump for gradient delivery of a plurality of types of solvents as a mobile phase, an autosampler for injecting a sample into the mobile phase delivered by the liquid delivery device, and At least a column oven containing a separation column for separating each component of the sample injected into the mobile phase by the autosampler,
a mixer for mixing the plurality of types of solvents;
a system capacity holding unit that holds, as a system capacity, the internal capacity of the system that affects the time it takes for the mobile phase delivered from the mixer to reach the sample temporarily held in the autosampler;
an injection timing determination unit configured to determine the injection timing of the sample by the autosampler using the system capacity held in the system capacity holding unit;
The autosampler is configured to perform sample injection at the injection timing determined by the injection timing determination unit,
The injection timing determination unit determines the system capacity held in the system capacity holding unit when the liquid transfer device performs gradient liquid transfer in which the mixing ratio of a plurality of types of solvents is changed with time. A liquid chromatography analysis system configured to determine the injection timing in consideration of a time obtained by dividing the flow rate of the liquid sent by the liquid device. A modular liquid chromatography analysis system configured by combining a plurality of modules,
As the module, a liquid delivery device having a liquid delivery pump for gradient delivery of a plurality of types of solvents as a mobile phase, an autosampler for injecting a sample into the mobile phase delivered by the liquid delivery device, and At least a column oven containing a separation column for separating each component of the sample injected into the mobile phase by the autosampler,
a mixer for mixing the plurality of types of solvents;
a system capacity holding unit that holds, as a system capacity, the internal capacity of the system that affects the time it takes for the mobile phase delivered from the mixer to reach the sample temporarily held in the autosampler;
an injection timing determination unit configured to determine the injection timing of the sample by the autosampler using the system capacity held in the system capacity holding unit;
The autosampler is configured to perform sample injection at the injection timing determined by the injection timing determination unit,
a pump capacity holding unit that holds information about the internal capacity of the liquid transfer pump;
a sampler capacity holding unit that holds information about the internal capacity in the autosampler;
a mixer capacity holding unit that holds information about the internal capacity of the mixer;
a system configuration holding unit that holds information about the system configuration of the liquid chromatography analysis system;
a system capacity calculation unit that calculates the system capacity using information respectively held in the pump capacity holding unit, the mixer capacity holding unit, the sampler capacity holding unit, and the system configuration holding unit;
The liquid chromatography analysis system, wherein the system capacity holding section is configured to hold the system capacity calculated by the system capacity calculating section. 3. The liquid chromatography analysis system according to claim 2 , wherein said pump capacity holding section is provided in said liquid transfer device, and said sampler capacity holding section is provided in said autosampler. The mixer is mounted in any one of the liquid transfer device, the autosampler, and the column oven module, and the mixer capacity holding section is provided in the module in which the mixer is mounted. 3. The liquid chromatography analysis system according to 3 . The module comprises a system controller for controlling the operation of the liquid transfer device, the autosampler and the column oven,
3. The liquid chromatography analysis system according to claim 2 , wherein at least one of said pump capacity holding section, said mixer capacity holding section, and said sampler capacity holding section is provided in said system controller.

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