LIQUID CHROMATOGRAPH AND METHOD FOR CONTROLLING SAME

A liquid chromatography (LC) that can supply a mobile phase to a storage bottle and can prevent mixing of air bubbles into a flow path without stopping analysis and liquid feeding. The LC includes a liquid feeding device that feeds out a mobile phase, a sample injection portion that injects a sample into the mobile phase, a column that separates the sample carried by the mobile, and a detection device that detects the sample. The LC further comprises a storage bottle that stores the mobile phase fed by the liquid feeding device, a mobile phase supply bottle that supplies the mobile phase to the storage bottle, a mobile phase supply pump that supplies the mobile phase to the storage bottle, and a control unit that controls an operation of the mobile phase supply pump and determines an amount of the mobile phase to be supplied to the storage bottle.

TECHNICAL FIELD

The present invention relates to a liquid chromatograph and a method for controlling the liquid chromatograph.

BACKGROUND ART

The liquid chromatograph (LC) is an analysis method in which a liquid sample that is a measurement target is introduced into a column that separates the liquid sample into components contained in the liquid sample with a liquid mobile phase and the separated components are detected by a detector connected to the downstream side of the column. In order to detect the components of the liquid sample separated in the column, a detection device such as an ultraviolet-visible absorption spectrophotometer, a fluorophotometer, and a mass spectrometer is connected on the downstream side of the column.

The main part of the separation performance of the LC is determined according to the type of a packing that is packed in the column. For example, nowadays, with the use of an ultra-high performance liquid chromatograph (UHP) that achieves high separation and highly sensitive analysis by packing a packing having a small diameter of 2 μm or less in a column, continuous analysis of multiple samples is performed, resulting in improving throughput.

In the LC, the mobile phase fed from a liquid feeding device not only serves the function of carrying the measurement target sample but also serves the function of separating the measurement target sample into components according to the difference of an affinity for the stationary phase of the packing packed in the column. In the LC, various types of mobile phases such as ultrapure water, an organic solvent, and a buffer solvent are used, and an operator selects a mobile phase used in an LC system corresponding to purposes for measurement and to types of liquid samples.

As described above, the mobile phase used in the LC serves the function of carrying a measurement sample, on one hand, and at the same time, the mobile phase affects measured results, on the other hand. For example, when air bubbles in the mobile phase are mixed in the liquid feeding device or the downstream passage of the liquid feeding device, this sometimes results in a great change in the measured results. Therefore, the operator using the LC monitors the remaining amount of the mobile phase so as not to enter air bubbles into the inside of the analysis passage of the LC, and the operator replaces and supplies the mobile phase when the amount of the mobile phase is a certain amount or less, and analysis is continued.

In the LC, during the progress of the analysis process, the liquid feeding device continuously feeds the mobile phase to the column and the detection device all the time. Therefore, in the case in which the remaining amount of the mobile phase decreases, since the operator has to temporarily stop the LC to conduct the replacement work of the mobile phase, the operator has to conduct experiments while confirming the volume of the mobile phase to be consumed in analysis and the remaining amount of a solvent that is provided. Therefore, in order to avoid an event that air is absorbed due to a shortage of the solvent in the bottle, the LC is sometimes assembled with a liquid level detection sensor that detects the remaining amount of the solvent on a solvent supply bottle or with a function of obviating the mixing of air bubbles into the analyzer by detecting the remaining amount by a weight detection sensor, for example.

As a monitoring method or a management method for the mobile phase used in the LC, Patent Literature 1 shows a method in which the liquid feeding device of an LC calculates the consumed volume and the remaining amount of a mobile phase from a discharge flow rate, time, mixing conditions for the mobile phase, and the like.

Moreover, Patent Literature 2 shows a system in which a sensor that monitors the remaining amount of a mobile phase is provided at a site where the mobile phase used by an LC is provided to conduct the monitoring of the remaining amount and an operator is notified in the case in which the remaining amount reaches a certain value or less.

Moreover, Patent Literature 3 shows a system that monitors the amount of consumption and the remaining amount for individual types of solvents from output values from a sensor monitoring the conditions for the mobile phase and the remaining amount of the mobile phase; the sensor is provided on a plurality of LCs connected on a network.

Mounting such a monitoring system on the LC enables the operator to recognize a reduction in the remaining amount of the mobile phase before the remaining amount of the mobile phase is reduced and this affects analysis, and the operator can conduct the replacement work or supply work of the mobile phase.

Here, a solvent replacement process for the mobile phase provided on the LC will be briefly described. Typically, the mobile phase is provided on the LC system in the state in which the mobile phase is packed in a glass or resin bottle. In the case in which the mobile phase in the bottle decreases, the analysis by the LC is stopped, the liquid feeding device is stopped, and the bottle is replaced with a new bottle filled with the mobile phase.

As described above, the mixing of air bubbles into the liquid feeding device causes no stable feeding of the mobile phase, sometimes resulting in the influence on analyzed results. Therefore, the operator using the LC progresses the work paying close attention so as not to mix air bubbles in a supply tube at the time of replacement work of mobile phase bottles and the time of additional supply of the mobile phase to the bottle. However, it is difficult to make the possibility of mixing air bubbles zero. This is because not only simple oversights of air bubbles or operational mistakes by the operator and so on but also the work experience of the operator, the installation environment of analyzers, and types of solvents for use cause influence.

Therefore, in most cases, as typical procedures, an air bubble discharge process for removing air bubbles in a pipe is conducted as a preparation operation after the replacement of mobile phase bottles or the work to additionally supply the mobile phase into bottles, regardless of the presence or absence of mixing of air bubbles.

CITATION LIST

Patent Literature

SUMMARY OF INVENTION

Technical Problem

Nowadays, in the LC, automation proceeds in multiple functional aspects. Like the techniques described in Patent Literature 1 to 3, an automatic monitoring system and a system for notifying operators are also provided in regard to the remaining amount of the mobile phase.

However, in the case in which the bottle of the mobile phase is actually replaced or the mobile phase is added to the bottle, the analysis of the LC and the liquid feeding device have to be temporarily stopped, and the operator has to conduct the replacement work and the preparation operation after the replacement.

Since this work depends on the operator, the operator is inevitably constrained for a certain period of time in order to conduct the preparation operation including bottle replacement and mobile phase supply work after recognizing the notification of a reduction in the remaining amount of the mobile phase.

Moreover, the work by the operator may cause risks to other problems such as the mixing of air bubbles in the passage. Also from the viewpoint of analysis time, time for which the LC is not allowed for use occurs, and this might cause a situation in which throughput is reduced as well as analysis is stopped for a longer time when the operator is not able to recognize the notification of a reduction in the remaining amount of the mobile phase.

An object of the present invention is to realize a liquid chromatograph and a method for controlling a liquid chromatograph that are capable of supplying a mobile phase to a storage bottle and capable of suppressing the mixing of air bubbles into a passage.

Solution to Problem

In order to achieve the object, the present invention is configured as below.

A liquid chromatograph includes: a liquid feeding device configured to feed out a mobile phase; a sample injection portion configured to inject a sample into the mobile phase fed out from the liquid feeding device; a separation column configured to separate the sample carried by the mobile phase fed out from the sample injection portion; and a detection device configured to detect the sample separated by the separation column. The liquid chromatograph further includes: a storage bottle storing the mobile phase fed by the liquid feeding device; a mobile phase supply bottle configured to supply the mobile phase to the storage bottle; a mobile phase supply pump configured to supply the mobile phase stored in the mobile phase supply bottle to the storage bottle; and a control unit configured to control an operation of the mobile phase supply pump and determine an amount of the mobile phase to be supplied from the mobile phase supply bottle to the storage bottle.

A method for controlling a liquid chromatograph, the liquid chromatograph including: a liquid feeding device configured to feed out a mobile phase; a sample injection portion configured to inject a sample into the mobile phase fed out from the liquid feeding device; a column configured to separate the sample carried by the mobile phase fed out from the sample injection portion; and a detection device configured to detect the sample separated by the separation column, the method for controlling the liquid chromatograph includes: storing, in a storage bottle, the mobile phase fed by the liquid feeding device; storing the mobile phase in a mobile phase supply bottle that supplies the mobile phase to the storage bottle; determining an amount of the mobile phase to be supplied from the mobile phase supply bottle to the storage bottle; and supplying the mobile phase stored in the mobile phase supply bottle to the storage bottle by controlling an operation of a mobile phase supply pump.

Advantageous Effects of Invention

According to the present invention, a liquid chromatograph and a method for controlling a liquid chromatograph that are capable of supplying a mobile phase to a storage bottle and that are capable of suppressing the mixing of air bubbles into a passage without stopping analysis and feeding.

DESCRIPTION OF EMBODIMENTS

In the following, embodiments of the present invention will be described with reference to the accompanying drawings. Although the accompanying drawings show the embodiments based on the principle of the present invention, the embodiments are typical exemplifications for understanding the principle of the present invention, and the embodiments do not limit the present invention.

EMBODIMENT

First Embodiment

FIG.1is a schematic block diagram of a liquid chromatograph100according to the first embodiment of the present invention.

InFIG.1, the liquid chromatograph100includes a liquid feeding device104that feeds a mobile phase, a sample injection portion105that introduces a measurement target sample (also simply referred to as a sample) into an analysis passage, a separation column106that separates the measurement target sample, which is introduced into the analysis passage and carried by the mobile phase fed by the liquid feeding device104, into components, and a detection device108that detects the components contained in the measurement target sample and separated at the separation column106.

Moreover, the liquid chromatograph100includes a storage bottle102that is provided on the upstream part of the liquid feeding device104and stores the mobile phase, a monitoring sensor109that detects the remaining amount of the mobile phase in the storage bottle102, a mobile phase supply bottle101that stores the mobile phase in order to supply the mobile phase to the storage bottle102, a mobile phase supply pump103that supplies the mobile phase from the mobile phase supply bottle101to the storage bottle102, and a control unit111that monitors the remaining amount of the mobile phase and supplies the mobile phase.

On the mobile phase supply bottle101and the storage bottle102, a vent110is provided to equal the bottle internal pressure to the atmospheric pressure. Therefore, one end of the vent110is disposed in the storage bottle102, and the other end of the vent110opens to the atmosphere.

The separation column106of the liquid chromatograph100is housed in the thermostatic device107for use in order to maintain the column ambient temperature constantly. However, the separation column106may be used without being housed in the thermostatic device107.

When the liquid chromatograph100is in operation, the liquid feeding device104carries the measurement target sample introduced from the sample injection portion105to the separation column106, dissolves the measurement target sample from the separation column106, and feeds a mobile phase suitable for analysis for the purpose of carrying the measurement target sample to the detection device108.

FIG.2is a flowchart of a process for supplying the mobile phase from the mobile phase supply bottle101to the storage bottle102corresponding to the mobile phase that is decreasing when the liquid chromatograph100is in operation.

When the liquid feeding device104aspirates the mobile phase from the storage bottle102and supplies the mobile phase into the LC analysis system, this decreases the remaining amount of the mobile phase in the storage bottle102, and the remaining amount of the mobile phase detected by the monitoring sensor109is a specified value or less, the control unit111determines that the remaining amount of the mobile phase in the storage bottle102is less (Step S201).

As the monitoring sensor109that monitors the remaining amount of the mobile phase, a weight sensor, a floating sensor, an electrostatic sensor, an optical sensor, and any other sensors are considered.

Upon detecting that the remaining amount of the mobile phase is a specified value or less by the monitoring sensor109, the control unit111starts the mobile phase supply process (Step S202). Then, the mobile phase supply pump103is driven to start the supply of the mobile phase from the mobile phase supply bottle101to the storage bottle102(Step S203).

At the time of the supply of the mobile phase to the storage bottle102by the mobile phase supply pump103, the control unit111determines whether the mobile phase in the storage bottle102reaches a certain amount or more based on the remaining amount of the mobile phase detected by the monitoring sensor109(Step S204). When the control unit111determines that the mobile phase in the storage bottle102is a certain amount or more, the control unit111stops the mobile phase supply pump103to stop the supply of the mobile phase to the storage bottle102from the mobile phase supply bottle101(Step S205). Then, the mobile phase supply process is stopped (ended) (Step S206).

As described above, according to the first embodiment of the present invention, the configuration is provided in which the amount of the mobile phase detected by the monitoring sensor109in the remaining amount of the mobile phase in the mobile phase storage bottle102is monitored, when the remaining amount of the mobile phase in the storage bottle102reaches specified value or less, the control unit111drives the mobile phase supply pump103to supply the mobile phase from the mobile phase supply bottle101to the storage bottle102. Thus, the recognition of a reduction in the remaining amount of the mobile phase and the supply of the mobile phase by the operator are eliminated, and it is possible to avoid the mixing of air bubbles in the passage due to the operator's work as well.

In other words, according to the first embodiment, it is possible to realize the liquid chromatograph and the method for controlling a liquid chromatograph that are capable of supplying a mobile phase into the storage bottle102and capable of suppressing the mixing of air bubbles into the passage without stopping analysis and feeding.

Note that in the first embodiment, the timing of stopping the mobile phase supply pump103is decoded based on information on the remaining amount of the mobile phase in the storage bottle102determined by the monitoring sensor109. For example, by a method in which the drive time of the mobile phase supply pump103is calculated from the discharge flow rate of the mobile phase supply pump103and the volume of the mobile phase that is desired to be supplied to the storage bottle102and the mobile phase supply pump103is operated and stopped based on the calculated drive time, it is also possible to realize a similar mobile phase supply process.

Moreover, the control unit111may calculate the remaining amount of the mobile phase in the storage bottle102from the feeding amount and operating time of the liquid feeding device104per time unit, determine that the remaining amount reaches a specified value or less, and drive the mobile phase supply pump103to start the supply of the mobile phase from the mobile phase supply bottle101to the storage bottle109. In this case, as described above, a configuration is provided in which the drive time of the mobile phase supply pump103is calculated from the discharge flow rate of the mobile phase supply pump103and the volume of the mobile phase that is desired to be supplied to the storage bottle102and the mobile phase supply pump103is stopped based in the calculated drive time. This enables the omission of the monitoring sensor109.

Second Embodiment

Next, a second embodiment of the present invention will be described with reference toFIG.3.

InFIG.3, a sample injection portion105, a thermostatic device107, and a detection device108on the downstream side of the liquid feeding device104are omitted from the drawings. A liquid chromatograph100A includes a storage bottle102that is provided on the upstream part of a liquid feeding device104and stores a mobile phase, a monitoring sensor109that detects the remaining amount of the mobile phase in the storage bottle102, a mobile phase supply bottle101that supplies the mobile phase into the storage bottle102, an information storage unit301that is provided on the mobile phase supply bottle101, an information reading unit302that reads information recorded in the information storage unit301, a mobile phase supply pump103that supplies the mobile phase from the mobile phase supply bottle101to the storage bottle102, an air bubble detection sensor303that detects air bubbles in a pipe provided between the mobile phase supply pump103and the mobile phase supply bottle101, a display unit306, and a control unit111that monitors the remaining amount of the mobile phase and supplies the mobile phase.

The inside of the mobile phase supply bottle101and the inside of the storage bottle102are connected to each other using a gas conduit304that is provided to equal a bottle internal pressure. In other words, the gas conduit304connects the storage bottle102to the mobile phase supply bottle101, and maintains the pressure in the storage bottle102and the pressure in the mobile phase supply bottle101. Moreover, in the mobile phase supply bottle101, one end of a vent110that equals the pressure in the mobile phase supply bottle101to the atmospheric pressure is disposed. The other end of the vent110located on the outer side of the mobile phase supply bottle101is connected to a filter305that obviates the external spread of the mobile phase in the supply bottle101and that obviates the penetration of dirt and dust around the mobile phase supply bottle101into the inside of the mobile phase supply bottle101.

The information storage unit301of the mobile phase supply bottle101stores information on the mobile phase such as the type, date of manufacture, and the like of the mobile phase housed in the mobile phase supply bottle101. The control unit111determines that the mobile phase supply bottle101is appropriately provided from the presence or absence of the provision of the mobile phase supply bottle101, faulty provision, and the expiration date, based on the information read by the information reading unit302and stored in the information storage unit301.

As the information storage unit301, an RFID tag and the like are considered.

FIG.4is a flowchart of a mobile phase supply process according to the second embodiment of the present invention.

When the remaining amount of the mobile phase reaches a specified value or less, which is determined from the detected value of the monitoring sensor109, the control unit111determines that the remaining amount of the mobile phase in the storage bottle102is less (Step S401), and starts the mobile phase supply process (Step S402).

After starting the mobile phase supply process in Step S402, the control unit111reads information stored in the information the storage unit301provided on the mobile phase supply bottle101through the information reading unit302, and confirms that the mobile phase supply bottle101is appropriately provided (Step S403). At this time, in the case in which the mobile phase supply bottle101to which the mobile phase has already been supplied, or in the case in which it is determined that the remaining amount of the mobile phase in the mobile phase supply bottle101is less, the control unit111displays, on the display unit306, an instruction to provide or replace the mobile phase supply bottle101(Step S404).

In the case in which the control unit111determines that the mobile phase supply bottle101is in an appropriate state, the control unit111drives the mobile phase supply pump103to start the supply of the mobile phase from the mobile phase supply bottle101to the storage bottle102(Step S405)

In the case in which the air bubble sensor303detects air bubbles in the pipe connecting the mobile phase supply pump103to the mobile phase supply bottle101in the middle of discharging the mobile phase by the mobile phase supply pump103(Step S406), the control unit111supplies all the mobile phase in the mobile phase supply bottle101into the storage bottle102, determines that the inside of the mobile phase supply bottle101becomes empty, and stops the mobile phase supply pump103(Step S408).

Subsequently to Step S408, the control unit111displays, on the display unit306, an instruction for the replacement of the mobile phase supply bottle101(Step S410), and ends the mobile phase supply process (Step S412).

In Step S406, when the air bubbles the sensor303does not detect air bubbles in the pipe, the process goes to Step S407. In Step S407, the monitoring sensor109monitors overflows such that the mobile phase in the storage bottle102does not exceed the storage threshold capacity of the storage bottle102during which the mobile phase supply pump103supplies the mobile phase into the storage bottle102. When the monitoring sensor109detects no overflow, the process returns to Step S406.

In Step S407, in the case in which the mobile phase is a specified value or more from the output value of the monitoring sensor109, the control unit111determines that overflows are highly likely to occur, and detects overflows, stops the mobile phase supply pump103, and ends the supply of the mobile phase (Step S409). In the case in which the mobile phase supply pump103is stopped due to the detection of overflows, the control unit111calculates the remaining amount of the mobile phase in the mobile phase supply bottle101from the drive time and flow rate of the mobile phase supply pump103and updates and records the remaining amount (Step S411). Then, the mobile phase supply process is ended (S412).

According to the second embodiment of the present invention, it is possible to obtain the effect similar to the first embodiment, and it is possible to obtain the following effect.

In the second embodiment, since the inside of the mobile phase supply bottle101is connected to the inside of the storage bottle102using the gas conduit304, the internal pressure of the mobile phase supply bottle101and the internal pressure of the storage bottle102pressure are made equal. This enables avoidance of the occurrence of errors in the detection of the remaining amount of the mobile phase in the storage bottle102due to pressure differences, and it is possible to conduct a more accurate detection of the remaining amount.

Moreover, in the second embodiment, the configuration is provided in which the mobile phase supply bottle101is provided with the information storage unit301that records information such as the type, date of manufacture, and the like of the mobile phase in the mobile phase supply bottle101, the information reading unit302reads the information recorded in the information storage unit301, the control unit111determines the presence or absence of the provision of the mobile phase supply bottle101, faulty provision, and expiration date, and confirms that the mobile phase supply bottle101is appropriately provided. Thus, it is possible to recognize whether the mobile phase supply bottle101is appropriately provided before the operation of the mobile phase to the liquid chromatograph100.

Furthermore, in the second embodiment, since the filter305is connected to the vent110of the mobile phase supply bottle101, it is possible to obviate the external spread of the mobile phase in the mobile phase supply bottle101, and it is possible to obviate the penetration of dirt and dust around the mobile phase supply bottle101into the mobile phase supply bottle101.

Note that a configuration may be possible in which a monitoring sensor (a sensor similar to the monitoring sensor109) that detects the remaining amount of the mobile phase in the mobile phase supply bottle101is provided, the control unit111recognizes the remaining amount of the mobile phase in the mobile phase supply bottle101, and displays the remaining amount on the display unit306.

Third Embodiment

In the examples shown in the first embodiment and the second embodiment, functions of preparing the operation of a mobile phase supply bottle101and urging the provision will be described with reference toFIG.5, as a stage prior to the detection of a reduction in the remaining amount of a mobile phase in a storage bottle102by a monitoring sensor109to drive a mobile phase supply pump103.

The configuration of a liquid chromatograph in the third embodiment is similar to the configuration of the first embodiment or the second embodiment, and the drawings and the detailed description are omitted. However, it is supposed that to the first embodiment, a display unit306similar to that of the second embodiment is additionally provided.

FIG.5is an illustration of the operation of the third embodiment, showing a transition example of the remaining amount of the mobile phase in the storage bottle102calculated from the output value of the monitoring sensor109, in which the vertical axis expresses the remaining amount of the mobile phase, and the horizontal axis expresses a lapse of days.

InFIG.5, immediately after the supply of the mobile phase from the mobile phase supply bottle101to the storage bottle102, the storage bottle102is in a state501in which the inside is filled with the mobile phase. When the mobile phase is consumed due to the analysis operation of the liquid chromatograph100or100A, the remaining amount of the mobile phase in the storage bottle102is reduced. At this time, an operation preparation mobile phase remaining amount VAthat urges the preparation of operation of the mobile phase supply bottle101is set before reaching the mobile phase remaining amount state503in which the control unit111operates the mobile phase supply pump103.

After the remaining amount of the mobile phase in the storage bottle102calculated from the detected value of the monitoring sensor109reaches the operation preparation mobile phase remaining amount VA, the control unit111displays the preparation of operation of the mobile phase supply bottle101on the display unit306at that point in time (state502).

In the case in which the liquid chromatograph of the third embodiment is formed in a configuration similar to the second embodiment, a configuration may be provided in which the control unit111recognizes the presence or absence of the mobile phase supply bottle101or the remaining amount of the mobile phase in the mobile phase supply bottle101at the point in time (state502) at which the operation preparation mobile phase remaining amount VAis reached before reaching the state503in which the mobile phase supply pump103is operated, by reading the information in an information storage unit301provided on the mobile phase supply bottle101by the information reading unit302, and in the case in which no mobile phase necessary to be supplied into the storage bottle102is present, the display unit306is caused to output instructions to provide or replace the mobile phase supply bottle101.

According to the third embodiment, it is possible to obtain the effect similar to the first embodiment and the second embodiment, and it is possible to display the preparation of operation of the mobile phase supply bottle101and the like before reaching the operation preparation mobile phase remaining amount state503in which the control unit111operates the mobile phase supply pump103. Accordingly, it is possible to conduct the preparation and replacement of the mobile phase supply bottle101and the like before the remaining amount of the mobile phase in the mobile phase supply bottle101becomes the amount necessary to supply the mobile phase to the storage bottle102.

Fourth Embodiment

Next, a fourth embodiment of the present invention will be described with reference toFIG.6.

In the example described in the second embodiment, in a liquid chromatograph100B according to the fourth embodiment, a storage bottle102is housed in a case601having high light shielding properties, and in the case601, a deuterium lamp602is provided.

A control unit111lights the deuterium lamp602in order to sterilize the inside of the storage bottle102. At this time, the deuterium lamp602is desirably normally lit. However, since ultraviolet rays emitted from the deuterium lamp602have sterilization effects as well as the ultraviolet rays might become a cause of the degradation in materials, the deuterium lamp602may be lit by a control algorithm that provides lighting for a certain time every constant time period, every 24 hours, for example.

Moreover, in the fourth embodiment, a form is described in which ultraviolet rays are applied from the deuterium lamp602outside the storage bottle102. For example, a small deuterium lamp is connected to the cap of the storage bottle102to directly apply ultraviolet rays to the inside of the storage bottle102, which also expects similar effects.

Furthermore, the fourth embodiment proposes the sterilization function by the deuterium lamp602for the storage bottle102that is highly likely to store the mobile phase for a long time. The similar function may be mounted by disposing a deuterium lamp that applies ultraviolet rays on the mobile phase supply bottle101.

According to the fourth embodiment, it is possible to obtain the effect similar to the second embodiment, and it is possible to sterilize the mobile phase in the storage bottle102for a long time.

LIST OF REFERENCE SIGNS