JP2011099764A - Liquid chromatograph device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To realize a liquid chromatograph device capable of early detecting the liquid leak of the separation column for the liquid chromatograph device without adding a new part and being accompanied by the lowering of performance. <P>SOLUTION: A pressure-time relation calculation part 91 receives the supply of the pressure signal from a pressure sensor 4 to calculate pressure-time relation. The calculated pressure-time relation is supplied to a linearity calculation part 92 and linearity is calculated. The calculated linearity is supplied to a liquid leak judging part 93 and a liquid leak is judged on the basis of the coefficient of correlation stored in a coefficient-of-correlation threshold value memory part 94 to supply an command signal to a pump stopping operation part 95 and an error display indication part 96. The pump stopping operation part 95 stops the operation of a pump 3 according to the command signal from the liquid leak judging part 93. The error display indication part 96 displays the generation of an error on a display part 10 according to the command signal from the liquid leak judging part 93. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a liquid chromatograph apparatus.

  In recent years, a separation column has been developed that can reduce the measurement time by making the particle size of the filler smaller than that of the conventional product. However, this separation column requires a larger pressure than that of the conventional product during liquid feeding.

  Separation columns are performed each time a high-performance liquid chromatograph user installs and removes them, but if they are not adequately attached, the particle size of the packing material is small. Therefore, liquid leakage is likely to occur from the connection site.

  When a liquid leak occurs, there is a method of detecting the liquid leak with a gas sensor installed in a column oven that houses the separation column. This is determined by detecting the vapor of the organic solvent in the eluent.

  Some sensors installed in the column oven are judged from the refraction of light that has changed due to the contact of liquid droplets.

  Furthermore, there is also a method in which a liquid feed pump is operated after closing a flow path opening / closing mechanism incorporated downstream of the flow path, and liquid leakage is detected based on whether or not a value detected by a pressure sensor reaches a set upper limit (Patent Document 1). reference).

Japanese Patent Laying-Open No. 2005-257609

  However, since the method using the gas sensor in the prior art is a method of detecting the vapor of the organic solvent, there are cases where the liquid leakage cannot be detected when the organic solvent is not contained in the eluent.

  Further, in the method of detecting a liquid leak by detecting a change in the refraction of light, it takes time for the liquid droplets to reach the sensor installation portion, and a rapid detection is not possible.

  Furthermore, in the method of detecting a liquid leak with a pressure sensor using a flow path opening / closing mechanism, pressure more than necessary is applied to the separation column, and the performance deterioration is accelerated. In addition, one or more flow path opening / closing mechanisms must be additionally installed, leading to an increase in apparatus cost.

  An object of the present invention is to provide a liquid chromatograph apparatus and a liquid chromatograph apparatus liquid that can detect liquid leakage of a separation column for a liquid chromatograph apparatus at an early stage without adding new parts and without deteriorating performance. It is to realize a leak detection method.

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

  In the liquid chromatograph device and the liquid leakage detection method of the liquid chromatograph device, based on the liquid feed pressure value measured by the pressure sensor, the liquid feed pressure to the separation column, the elapsed time or the liquid feed flow rate from the liquid feed pump, The correlation coefficient representing the linearity of the relationship is calculated, and when the calculated correlation coefficient is equal to or less than a certain value, it is determined that liquid leakage has occurred and the liquid feeding operation of the liquid feeding pump is stopped.

  According to the present invention, a liquid chromatograph apparatus and a liquid chromatograph apparatus liquid that can detect liquid leakage of a separation column for a liquid chromatograph apparatus at an early stage without adding new parts and without deteriorating performance. A leak detection method can be realized.

1 is a schematic configuration diagram of a high performance liquid chromatograph apparatus to which an embodiment of the present invention is applied. It is a functional block diagram in the control part in the high performance liquid chromatograph apparatus with which one Example of this invention is applied. It is a figure which shows the example of a screen which selects the item implemented by the preparatory driving | operation of the high performance liquid chromatograph apparatus which is one Example of this invention. It is a figure which shows the example of a screen of the data processor which performs the setting of the leak check test by the change of the pressure of the high performance liquid chromatograph apparatus which is one Example of this invention. It is a figure which shows the operation | movement flow in one Example of this invention. It is a figure which shows a pressure trace when there is no liquid leak in one Example of this invention. It is a figure which shows a pressure trace when there exists a liquid leak in one Example of this invention. It is a schematic diagram showing the method by which a data processor determines that there is no liquid leak in one Example of this invention. It is a schematic diagram showing the method by which a data processor determines that there exists a liquid leak in one Example of this invention.

  Embodiments of the present invention will be described below with reference to the accompanying drawings.

  FIG. 1 is a schematic configuration diagram of a high performance liquid chromatograph apparatus to which one embodiment of the present invention is applied.

  In FIG. 1, the eluent 2 disposed in the reagent rack 1 is continuously fed to the sample injection device 5 by the liquid feed pump 3.

  Normally, the pressure sensor 4 is arranged in the liquid feed pump 3 in order to judge liquid feed failure or clogging in the flow path. The target component of the sample injected by the sample injection device 5 is separated by a separation column 7 installed in a column oven 6 for maintaining a constant temperature. The target component separated by the separation column 7 is sent to the detector 8 and detected by the detector 8.

  The reagent rack 1, the liquid feed pump 3, the pressure sensor 4, the sample injection device 5, the column oven 6, and the detector 8 constitute a main body 11 of the liquid chromatograph device. The operation of the liquid feed pump 3, the pressure sensor 4, the sample injection device 5, the column oven 6, and the detector 8 is controlled by the operation control unit 9. In addition, the operation control unit 9 performs display control of the display unit 10. The temperature sensor 12 detects the temperature of the column oven 6, and the detected temperature signal is transmitted to the operation control unit 9.

  FIG. 2 is a main internal functional block diagram of the operation control unit 9. However, the function shown in FIG. 2 is a main function in the embodiment of the present invention, and other operation control units of the main body 11 are omitted.

  In FIG. 2, the operation control unit 9 includes a pressure-time relationship calculation unit 91, a linearity calculation unit 92, a liquid leakage determination unit 93, a correlation coefficient threshold value storage unit 94, a pump stop operation unit 95, And an error display instruction unit 96.

  The pressure-time relationship calculation unit 91 is supplied with a pressure signal from the pressure sensor 4 and calculates the pressure-time relationship. The calculated relationship is supplied to the linearity calculation unit 92 to calculate linearity.

  Then, the calculated linearity is supplied to the liquid leakage determination unit 93, and the liquid leakage determination is performed based on the correlation coefficient stored in the correlation coefficient threshold value storage unit 94. A command signal is supplied to the display instruction unit 96.

  The pump stop operation unit 95 stops the operation of the pump 3 in accordance with a command signal from the liquid leakage determination unit 93. Further, the error display instruction unit 96 displays on the display portion 10 that an error has occurred in accordance with a command signal from the liquid leakage determination unit 93.

  FIG. 3 is an example of a display screen displayed on the display unit 10 by the control unit 9 that sets the preparatory operation of the apparatus.

  In FIG. 3, the user of the apparatus designates an operation to be executed by checking any item from item 1 to item 9. Thereafter, detailed parameters are input on a separate screen for each designated operation, and the operation control unit 9 issues a preparatory operation command.

  FIG. 4 shows an example of a screen in which items 5 and 6 in FIG. 3 are checked and detailed parameters relating to “variable liquid feeding” in item 5 are input. In one embodiment of the present invention, this is executed by inputting parameters on the screen shown in FIG.

  In FIG. 4, the flow rate range of the liquid feed pump is input in item 11 and the transition time is input in item 10. When the preparatory operation is started, the liquid feeding pump 3 gradually increases the flow velocity according to the previous setting, and the pressure / time relationship calculating unit 91 of the operation control unit 9 is a pressure sensor 4 mounted on the liquid feeding pump 3. The pressure output value from is traced.

  6 and 7 are traces of pressure values when the flow rate of the liquid fed from the liquid feeding pump 3 is increased over 8 minutes from 0.1 mL / min to 0.9 mL / min. And the vertical axis represent time and pressure values, respectively.

  FIG. 6 shows a case where there is no liquid leak, and FIG. 7 shows a case where there is a liquid leak.

  If there is no problem in attaching the separation column 7 to the flow path or the like, the time and the pressure value are proportional as shown in FIG. 6, but if the separation column 7 is not sufficiently attached to the flow path or the like, it is shown in FIG. However, the increase of the pressure value becomes smaller as after 6 minutes.

  FIGS. 8 and 9 are diagrams schematically illustrating a method in which the linearity calculating unit 92 and the liquid leakage determining unit 93 of the operation control unit 9 determine the proportional relationship between the pressure traces illustrated in FIGS. 6 and 7, respectively. .

  8 and 9, the pressure values at 1/4 (2 minutes), 1/2 (4 minutes), 3/4 (6 minutes), and 1/1 (8 minutes) of the transition time are connected by a straight line. Determination is made by calculating a contribution rate (correlation coefficient) representing linearity.

  The contribution rate (correlation coefficient) at this time was 0.9999 in FIG. 8 showing the case where there was no liquid leak, and 0.9679 in FIG. 9 showing the case where there was a liquid leak.

  FIG. 5 is a diagram showing an operation flow in one embodiment of the present invention. In FIG. 5, the operation control unit 9 proceeds to step 9 and proceeds to the main measurement when the leak test by pressure is not performed in step 1.

  In step 1, when a leak test using pressure is performed, the process proceeds to step 2, and the liquid leakage determination unit 93 determines whether to measure the time after the temperature of the column oven 6 reaches the set value. If the time after the temperature of the column oven 6 reaches the set value is not measured, the process proceeds to step 4. When measuring the time after the temperature of the column oven 6 reaches the set value, the process proceeds to step 3 and the liquid leakage determination unit 93 measures the time after the temperature reaches the set value.

  The liquid feed pressure value of the separation column 7 varies not only with the flow rate but also with temperature. Even if the temperature value of the column oven 6 detected by the temperature sensor 12 reaches the temperature set in the item 15 of FIG. 4, it takes more time for the separation column 7 to reach that temperature completely.

  By inputting the item 16 in FIG. 4, the separation column 7 can also be provided with a time for reaching the set temperature, and after the time is over, the process proceeds to step 4 in FIG.

  In step 4, the liquid leakage determination unit 9 determines whether or not to send an eluent in an amount n times the volume of the separation column 7.

  If the eluent having an amount n times the volume of the separation column 7 is not sent, the process proceeds to Step 6. When the eluent having an amount n times the volume of the separation column 7 is not sent, the process proceeds to Step 5.

  The pressure value also changes depending on the composition of the separation column 7 and the eluent in the flow path. It is known that when 10 times the internal volume of the separation column 7 is fed, the eluent in the separation column 7 is completely replaced. When the user inputs an arbitrary multiple in the item 17 in FIG. 4 and the inner diameter or length of the separation column 7 in the item 18, the liquid leakage determination unit 93 calculates the volume of the separation column 7. In step 5, the eluent of n times the volume of the separation column 7 (for example, 10 times the volume) is sent at the flow rate on the left side of item 11, and then the process proceeds to step 6 in FIG. 5.

  In step 6, the liquid leakage determination unit 93 determines whether or not to check the pressure fluctuation, and proceeds to step 8 if the pressure fluctuation is not confirmed. When confirming the pressure fluctuation, the process proceeds to step 7, and the liquid leakage determining unit 93 confirms the pressure fluctuation.

  In order to eliminate complex factors such as the composition and temperature of the eluent in the separation column 7, by inputting an arbitrary value in the item 19 shown in FIG. You may check. Confirmation is repeated until it becomes less than the pressure change value set as in step 7 of FIG. 5, and after the pressure fluctuation is within a certain range, the process proceeds to the next step 8.

  In step 8, the liquid leakage is determined based on the liquid feeding pressure. The liquid leakage determination unit 93 determines whether or not the contribution rate (correlation coefficient) exceeds the value stored in the correlation coefficient threshold value storage unit 94. Move to this measurement.

  If the contribution rate (correlation coefficient) is smaller than the value stored in the correlation coefficient threshold value storage unit 94 in step 8, it is determined that the liquid is leaking, and the pump stop operation unit is performed as in steps 10 and 11. After the operation of the liquid feed pump is stopped by 95, the error display instruction unit 96 displays that a liquid leak has occurred via the display unit (monitor) 10, and prompts the user to confirm.

  In other words, for example, an error message such as “The liquid feeding pump has been stopped” or “Please check for occurrence of liquid leakage” is displayed on the display unit 10.

  In the example described above, the pressure was measured at intervals of 2 minutes, but the time score for confirming the proportional relationship can be increased or decreased.

  In order to reduce damage caused by liquid leakage, proportional calculation of elapsed time and liquid supply pressure is performed during the liquid supply pressure increase transition time, and if there is no proportional relationship, liquid supply is stopped halfway. The confirmation of liquid leakage may be prompted by the display unit 10.

  In addition, the flow rate is not only increased in proportion to time, but may be increased in stages to check the proportional relationship between the flow rate and the pressure value and perform a liquid leakage test.

  In the example described above, the pressure sensor 4 is disposed in the flow path in the liquid feed pump 3, but is disposed in any position of the flow path between the liquid feed pump 3 and the separation column 7. You can also.

  As described above, according to one embodiment of the present invention, there is a liquid leak in the separation column and the liquid supply piping to the separation column due to the relationship between the pressure and time of the liquid supply to the separation column for the high performance liquid chromatograph apparatus. It is determined using a pressure sensor arranged in the apparatus.

  Therefore, the liquid chromatograph apparatus and the liquid chromatograph apparatus separation column liquid that can detect liquid leakage of the liquid chromatograph apparatus separation column at an early stage without adding new parts and without deteriorating performance. A leak detection method can be realized.

  Further, according to the present invention, since the main measurement can be surely performed in a state where there is no liquid leakage, the measurement accuracy can be improved.

  Further, according to the present invention, not only the liquid leakage of the separation column but also the liquid leakage of the flow path (pipe) from the liquid feed pump to the separation column can be detected.

  In the above-described example, the liquid leakage judgment is performed based on the correlation between the liquid feeding pressure and the elapsed time. However, the liquid leakage judgment may be performed based on the correlation between the liquid feeding pressure and the liquid feeding flow velocity. . In this case, the liquid feed flow rate can be a value that can be calculated based on a command signal to the liquid feed pump.

  DESCRIPTION OF SYMBOLS 1 ... Reagent rack, 2 ... Eluent, 3 ... Liquid feed pump, 4 ... Pressure sensor, 5 ... Sample injection apparatus, 6 ... Column oven, 7 ... Separation column , 8 ... Detector, 9 ... Operation control unit, 10 ... Display unit, 11 ... Main body unit, 12 ... Temperature sensor, 91 ... Pressure-time relation calculation unit, 92 ... Linearity calculation unit, 93 ... Liquid leak judgment unit, 94 ... Correlation coefficient threshold value storage unit, 95 ... Pump stop operation unit, 96 ... Error display instruction unit

Claims (8)

A separation column for separating a specific component in a measurement sample;
A liquid feed pump for feeding the solution to the separation column and increasing the flow rate of the liquid fed over time;
Sample injection means for injecting a measurement sample into the solution sent from the liquid feed pump;
A detector for detecting a specific component separated by the separation column;
A pressure sensor for measuring a liquid feeding pressure of the solution supplied to the separation column;
Based on the liquid feed pressure value measured by the pressure sensor, a correlation coefficient representing the linearity of the relationship between the liquid feed pressure to the separation column and the elapsed time or the liquid feed flow rate from the liquid feed pump is calculated. When the calculated correlation coefficient is a certain value or less, an operation control unit for stopping the liquid feeding operation of the liquid feeding pump,
A liquid chromatograph apparatus comprising: The liquid chromatograph apparatus according to claim 1,
When the calculated correlation coefficient is equal to or less than a predetermined value, the operation control unit stops the liquid feeding operation of the liquid feeding pump and stops the liquid feeding operation of the liquid feeding pump. This is displayed on the display means. In the liquid chromatograph apparatus according to claim 2,
A column oven for maintaining the temperature of the separation column at a constant temperature, and a temperature sensor for measuring the temperature of the column oven; and the operation control unit is configured so that the temperature measured by the temperature sensor reaches a set temperature. The liquid chromatograph is characterized in that the correlation coefficient is calculated on the basis of the liquid feeding pressure value measured by the pressure sensor after the fluctuation of the liquid feeding pressure measured by the pressure sensor falls within a certain range. apparatus. In the liquid chromatograph apparatus according to claim 3,
The operation control unit calculates the linearity of the pressure-time relationship calculated by the pressure-time relationship calculation unit that calculates the relationship between the measured pressure of the pressure sensor and the elapsed time, and the pressure-time relationship calculation unit. A linearity calculation unit that calculates a correlation coefficient to be shown, a correlation coefficient threshold value storage unit that stores a threshold value of a correlation coefficient that indicates linearity of the relationship between pressure and time, and a correlation coefficient calculated by the linearity calculation unit And the correlation coefficient threshold value stored in the correlation coefficient threshold value storage unit to determine whether or not liquid leakage has occurred in the flow path from the separation column or the liquid feed pump to the separation column. When the leakage determination unit and the liquid leakage determination unit determine that the liquid leakage has occurred, the pump stop operation unit that stops the liquid supply operation of the liquid supply pump, and the liquid leakage determination unit determines that the liquid leakage has occurred. Display on the display means that liquid leakage has occurred Liquid chromatograph apparatus characterized by having a color display instruction unit. A separation column for separating a specific component in a measurement sample, a liquid feeding pump for feeding the solution to the separation column, and increasing a flow rate for feeding the liquid over time; a solution fed from the liquid feeding pump; A liquid chromatograph apparatus comprising a sample injection means for injecting a measurement sample, a detector for detecting a specific component separated by the separation column, and a pressure sensor for measuring a liquid feeding pressure of a solution supplied to the separation column In the liquid leak detection method of
Based on the liquid feed pressure value measured by the pressure sensor, a correlation coefficient representing the linearity of the relationship between the liquid feed pressure to the separation column and the elapsed time or the liquid feed flow rate from the liquid feed pump is calculated. The liquid leakage detection method for a liquid chromatograph, wherein the liquid feeding operation of the liquid feeding pump is stopped when the calculated correlation coefficient is equal to or less than a predetermined value. In the liquid leak detection method of the liquid chromatograph device according to claim 5,
The liquid chromatograph includes display means, and when the calculated correlation coefficient is equal to or less than a predetermined value, the liquid feeding operation of the liquid feeding pump is stopped and the liquid feeding operation of the liquid feeding pump is stopped. A liquid leak detection method for a liquid chromatograph apparatus, characterized in that a display means displays the result. In the liquid leak detection method of the liquid chromatograph apparatus according to claim 6,
The liquid chromatograph apparatus includes a column oven for maintaining the temperature of the separation column at a constant temperature, and a temperature sensor for measuring the temperature of the column oven, and the temperature measured by the temperature sensor has reached a set temperature. Thereafter, the correlation coefficient is calculated based on the liquid feeding pressure value measured by the pressure sensor after the fluctuation of the liquid feeding pressure measured by the pressure sensor falls within a certain range. Liquid leak detection method of a graph device. In the liquid leak detection method of the liquid chromatograph apparatus according to claim 7,
Calculate the relationship between the measured pressure of the pressure sensor and the elapsed time, calculate a correlation coefficient indicating the linearity of the relationship between the calculated pressure and time, compare the calculated correlation coefficient with the correlation coefficient threshold value, It is determined whether or not liquid leakage has occurred in the flow path from the separation column or the liquid feed pump to the separation column. If it is determined that liquid leakage has occurred, the liquid feed operation of the liquid feed pump is stopped, A liquid leak detection method for a liquid chromatograph, characterized in that the display means displays that a leak has occurred.

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