JP2015141141A - Liquid chromatograph apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a fluid control method for changing a liquid feed characteristic to a characteristic desired by an operator without changing a configuration of a liquid chromatograph.SOLUTION: The liquid chromatograph apparatus includes: a liquid chromatograph part 101 having a pump 102 for feeding eluent to a detector; and a control part for controlling liquid feeding by the pump 102 on the basis of a predetermined time table. The control part is stored with a first liquid feeding characteristic obtained from the liquid chromatograph part at the time of inputting a predetermined command value and a second liquid feeding characteristic desired by the operator. In the control part, the time table is changed based on the first liquid feeding characteristic and the second liquid feeding characteristic so that a liquid feeding mode at the time of controlling the pump by the liquid chromatograph approaches a desired liquid feeding mode. The liquid feeding is executed according to this changed time table.

Description

  The present invention relates to a liquid chromatograph apparatus, and more particularly, to a fluid control method for converting liquid feeding characteristics without making a complicated change in the apparatus configuration.

  An analysis technique using a liquid chromatograph is required to have high accuracy. There is a measurement method as a content set in the apparatus when measuring a chromatogram with a liquid chromatograph apparatus. The measurement method can be defined by, for example, the flow rate of the eluent (solvent), the sample injection amount, the pressure upper limit, the temperature setting of the column oven, and the like.

  In Patent Document 1, a measurement method of a certain device (general-purpose liquid chromatograph) is measured using a measurement method of another device (ultra-high-speed liquid chromatograph) whose linear velocity (speed at which a certain component passes through the column) is faster than that of the device. Techniques are disclosed for converting to. Further, this document discloses that a correction value is obtained using column data or the like when the measurement method is converted.

JP 2009-281897 A

  By the way, various components in the configuration of the liquid chromatograph apparatus, differences in specifications (for example, differences in pipe diameter, pump dead volume, mixer liquid mixing performance, sampler dead volume, sample diffusion capacity outside the column, detector, etc. ) Affects the dead volume of the entire liquid flow path and the mixing behavior of the liquid, and may change the retention time and resolution of the chromatogram.

  Under the circumstances as described above, particularly when the liquid is fed by a gradient method in which the mixing ratio of the eluent is changed with time, the characteristics of the dead volume of the liquid chromatogram and the mixing of the liquid have been conventionally improved. In order to evaluate the effect on retention time and resolution, the configuration of liquid chromatograph equipment such as piping, pump dead volume, mixer liquid mixing performance, sampler dead volume, sample diffusion capacity outside the column, detector, etc. It was necessary to change the behavior of the gradient by changing the parts. For this reason, for example, when trying to obtain a chromatogram of a liquid chromatograph with desired liquid delivery characteristics, change the components and specifications as described above, and adjust until the same results as the desired gradient behavior are shown. It was necessary to repeat. Such adjustment in the change of the hardware configuration involves considerable difficulty because the operator needs to predict a change in the liquid feeding characteristics. In addition, there is a limit to the complete reproduction of desired liquid feeding characteristics.

  The present invention has been made to solve the above-described problems, and its object is to provide means for reproducing the liquid feeding characteristics of the shape desired by the operator without changing the components and specifications of the liquid chromatograph apparatus. Is to provide.

  As an aspect for solving the above-described problem, in the present invention, a liquid chromatograph unit having a liquid feeding unit that sends an eluent to the detection unit and a liquid feeding by the liquid feeding unit are controlled based on a predetermined time table. A control unit, wherein the control unit inputs data relating to liquid feeding, and a first liquid feeding characteristic indicated by the liquid chromatograph unit when a predetermined command value is inputted to the liquid feeding unit. And a storage unit for storing a second liquid feeding characteristic indicated by inputting desired data to the input unit.

  According to the said one aspect | mode, the liquid feeding characteristic which an operator desires is realizable, without changing the component and specification of a liquid chromatograph apparatus. Here, the desired liquid feeding characteristics can be arbitrarily set without requiring an actual apparatus or previously acquired experimental data. Furthermore, since it is not necessary to make a special change to the hardware configuration, it contributes to a reduction in development costs and a development period.

The figure which shows the system configuration | structure of the liquid chromatograph apparatus which concerns on embodiment of this invention. The figure which shows the system configuration | structure of the liquid chromatograph part 101 which concerns on embodiment of this invention. The figure which shows a part of system configuration | structure of the data processor and liquid feeding characteristic conversion processing apparatus 107 which concern on embodiment of this invention. The figure which shows an example of the time table of the pump control of the liquid chromatograph apparatus which concerns on embodiment of this invention. The figure which shows the time table of FIG. 4 as a graph. The flow chart which shows the process of liquid feeding characteristic conversion by the liquid chromatograph apparatus which concerns on embodiment of this invention. The figure which shows the display screen of the output device 109 which concerns on embodiment of this invention. The figure which shows the 1st example of a display of the ideal liquid feeding characteristic display part. The figure which shows the 2nd example of a display of the ideal liquid feeding characteristic display part. The figure which shows the 3rd example of a display of the ideal liquid feeding characteristic display part. The figure which shows the liquid feeding characteristic which an operator desires as a graph. The flowchart which shows the operation procedure which concerns on embodiment of this invention, and the process of the control part 110 accompanying it. The figure which shows the example of the command value output to a pump, when acquiring the liquid feeding characteristic of a liquid chromatograph apparatus.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 shows a system configuration of a liquid chromatograph apparatus according to an embodiment of the present invention. The liquid chromatograph apparatus shown in this figure is a liquid chromatograph unit 101 where a mixed sample is separated and analyzed, and a control device for controlling each device related to the liquid chromatograph unit 101 based on a predetermined measurement method. A control unit 110 is provided.

  The liquid chromatograph unit 101 sends a sample based on a command from the control unit 110 to a pump (liquid feeding unit) 102 that sends the eluent based on a command from the control unit 110 and the eluent from the pump 102. An autosampler (sample injection unit) 103 to be injected, a column oven (separation unit) 104 that maintains the temperature of the column 207 (see FIG. 2), and a component eluted from the column 207 are detected based on a command from the control unit 110 Then, a detector (detection unit) 105 that converts the signal into an electric signal and outputs the electric signal to the control unit 110 is provided.

  The control unit 110 includes a data processing device 106 that executes commands and exchanges of data with each device relating to the liquid chromatograph unit 101, and an input device that inputs various data including measurement methods, instructions from an operator, and the like. For example, a pointing device, a keyboard, a tablet, etc.) 108, a liquid feed characteristic conversion processing device 107 that executes processing (system conversion processing) for converting a measurement method input via the input device 108, and detection by the detector 105 An output device 109 for displaying results and a graphical user interface (GUI) related to various operations of the liquid chromatograph unit 101 and the control unit 110 is provided. The measured value of each component detected by the detector 105 is taken into the data processing device 106, and the analysis result of the sample is transmitted and displayed on the output device 109.

  The measurement method is a time series of control command values to the pump 102 (target value of the liquid delivery mode), and is a data string (hereinafter referred to as “time”) that indicates a time change in the liquid delivery mode of the eluent by the pump 102. Table "or" liquid feeding time table "). The liquid feeding mode includes the flow rate of the eluent and the ratio of each eluent at a predetermined flow rate when there are a plurality of eluents. A specific example of the time table of the pump 102 will be described later. In the present embodiment, by converting the time table of the pump 102, the liquid delivery characteristics desired by the operator (sometimes referred to as “ideal liquid delivery characteristics”) and the measurement results (chromatography) obtained from the ideal liquid delivery characteristics. (Gram) will be described as an example to explain the conversion of liquid feeding characteristics.

  The liquid feeding characteristic of the device is an actual liquid feeding mode of each liquid chromatograph device obtained when a predetermined command value (a specific example of the command value will be described later) is input to the pump 102 (hereinafter, referred to as “liquid feeding characteristic”). It may be referred to as “device feeding characteristics”). For example, when the same command value is input to a plurality of liquid chromatograph devices, the difference in various specifications (for example, pipe diameter, pump dead volume, mixer liquid mixing performance, sampler dead volume, Due to the difference in the sample diffusion capacity outside the column, the detector, etc.), the actual liquid delivery mode differs. That is, the liquid feeding characteristic is a value unique to each liquid chromatograph apparatus.

  As a method for measuring the actual liquid supply mode (apparatus liquid supply characteristics), there is a method of measuring the absorbance of the eluent sent out by the pump 102 based on a predetermined command value. As a means for measuring the absorbance of the eluent, the detector 105 provided in the liquid chromatograph unit 101 can be used.

  The command values input to the pumps of the respective liquid chromatograph devices when acquiring the device liquid feeding characteristics are preferably the same in principle, but may be the same within the resolution range of the detector 105, and finally detected. If the detection results by the device 105 are the same, it does not matter until the command values completely match. That is, the command value only needs to be the same within the range of resolution of the detector 105 or the like, and in this paper, the command values are considered to be the same if the command value is within the range.

  FIG. 2 shows a system configuration of the liquid chromatograph unit 101 according to the embodiment of the present invention. In addition, the same code | symbol is attached | subjected to the same part as the previous figure, and description may be abbreviate | omitted (the following figure is also the same). The liquid chromatograph unit 101 shown in this figure includes a pump 102 (a pump 102A for feeding an eluent 201A and a pump 102B for feeding an eluent 201B), a mixer 203, an autosampler 103, and a column oven 104. And a detector 105.

  The pump 102A and the pump 102B pump up the eluent 201A and the eluent 201B, respectively, based on the contents of the time table stored in the data processing device 106. The eluents sent from the pumps 102A and 102B are mixed by the mixer 203 and then sent to the column oven 104 via the autosampler 103. On the other hand, the sample is injected from the autosampler 103 and sent to the analysis column 207. The detector 105 detects the sample component that has passed through the column 207, and the detection result is stored in the storage device of the data processing device 106 of the control unit 110.

  FIG. 3 is a part of a system configuration diagram of the data processing device 106 and the liquid feeding property conversion processing device 107 according to the embodiment of the present invention. Although not specifically shown here, the data processing device 106 and the liquid feeding property conversion processing device 107 are each an arithmetic processing device (for example, a CPU) as arithmetic means for executing various programs and the program. Storage devices (for example, semiconductor memories such as ROM, RAM and flash memory, and magnetic storage devices such as hard disk drives) as storage means for storing various data, and the devices 101, 106, 107, 108, An input / output arithmetic processing unit for performing input / output control of data and instructions to 109 is provided.

  In FIG. 3, the data processing device 106 includes a time table input unit 61, a time table storage unit 62, and a pump control unit 63.

  The time table input unit 61 is a part to which a time table related to control of the pump 102 (pumps 102A and 102B) is input from the outside. As a time table input method, for example, in addition to input by the input device 108, input through a storage medium in which the time table is stored, communication by communication with another computer in which the time table is stored, etc. There is.

  The time table storage unit 62 stores the time table input via the time table input unit 61 and the time table calculated (converted) by the conversion time table calculation unit 74 in the liquid feeding characteristic conversion processing device 107 described later. It is a part to be done. Here, a time table input via the time table input unit 61 will be described with reference to the drawings.

  4 is a diagram showing an example of a time table (liquid feeding time table) relating to pump control of the liquid chromatograph apparatus shown in FIG. 2, and FIG. 5 is a diagram showing the time table of FIG. 4 in a graph. In the time table of FIG. 4, “% A” indicates the composition ratio of the eluent 201A (pump 102A) in the moving bed, and “% B” indicates the composition ratio of the eluent 201B (pump 102B). The total flow rate of the eluents A and B is always maintained at 1 [ml / min]. Further, “B%” in the graph of FIG. 5 indicates the composition ratio of the eluent 201B in the moving bed. As can be seen from the graph in FIG. 5, the ratio of the eluent is switched to a polygonal line here.

  Returning to FIG. 3, the pump control unit 63 is a part that controls the pumps 102 (pumps 102 </ b> A and 102 </ b> B) of the liquid chromatograph unit 101 based on the time table stored in the time table storage unit 62. When the time table used by the pump control unit 63 is selected by the conversion time table calculation unit 74, the pump control unit 63 controls the pump 102 based on the time table.

  In FIG. 3, the liquid feeding characteristic conversion processing device 107 is different from the apparatus liquid feeding characteristic input unit 71, the device liquid feeding characteristic storage unit 72, the ideal liquid feeding characteristic input unit 73, and the ideal liquid feeding characteristic storage unit 74. A calculation unit 75 and a conversion time table calculation unit 76 are provided.

  The apparatus liquid feeding characteristic input unit 71 is a part to which liquid feeding characteristics of the liquid chromatograph apparatus including the liquid chromatograph unit 101 are input. As an input method of the liquid feeding characteristics to the input unit 71, for example, in addition to the input by the input device 108, input via a storage medium in which the liquid feeding characteristics are stored, and another computer in which the liquid feeding characteristics are stored There are those by communication via a network.

  The apparatus liquid feeding characteristic storage unit 72 is a part in which the liquid feeding characteristics of a plurality of liquid chromatograph devices (including the liquid chromatograph unit 101) input via the liquid feeding characteristic input unit 71 are stored.

  The ideal liquid feeding characteristic input unit 73 is a part to which the liquid feeding characteristic of the liquid chromatograph apparatus desired by the operator is input. As an input method of ideal liquid feeding characteristics to the input unit 73, for example, in addition to input by the input device 108, input via a storage medium in which liquid feeding characteristics are stored, other computers in which liquid feeding characteristics are stored And communication via a network.

  The ideal liquid feeding characteristic storage unit 74 is a part in which the liquid feeding characteristics desired by the operator input via the ideal liquid feeding characteristic input unit 73 are stored.

  The difference calculation unit 75 is a part that calculates a difference (Trans (t)) between the device liquid feeding characteristic of the liquid chromatograph unit 101 and the ideal liquid feeding characteristic desired by the operator. The contents of the calculation will be described later.

  The conversion time table calculation unit 76 is a part that converts the time table stored in the time table storage unit 62 and used for sample analysis based on the difference in the liquid feeding characteristics calculated by the difference calculation unit 75. . The conversion time table calculation unit 76 receives a time table to be converted from the time table storage unit 62. A specific time table conversion process by the conversion time table calculation unit 76 will be described later. The time table converted by the conversion time table calculation unit 76 is output and stored in the time table storage unit 62 of the data processing device 106.

  FIG. 6 is a flow chart of the fluid control method for changing the liquid feeding characteristics without changing the components of the liquid chromatograph apparatus in the liquid chromatograph apparatus according to the embodiment of the present invention. A liquid control method using system conversion (time table conversion of pumps 102A and 102B) will be described with reference to FIG. Here, a case will be described in which a chromatograph in a virtual liquid chromatograph apparatus having ideal liquid delivery characteristics desired by an operator is simulated by converting the time table of the pump 102.

  In FIG. 6, the liquid-feeding characteristic conversion processing device 107 first acquires the liquid-feeding characteristic of the liquid chromatograph device via the liquid-feeding characteristic input unit 71 and stores it in the liquid-feeding characteristic storage unit 72 ( S101). The ideal liquid delivery characteristic desired by the operator is acquired via the ideal liquid delivery characteristic input unit 73 and stored in the ideal liquid delivery characteristic storage unit 74 (S101). The apparatus liquid supply characteristics acquired via the apparatus liquid supply characteristic input unit 71 include the respective pipe diameters, the dead volumes of the pumps 102A and 102B, the liquid mixing performance of the mixer 203, the dead volume of the sampler 103, the sample diffusion capacity outside the column, Derived from the detector 105 and the like. Here, the apparatus liquid feeding characteristic is RA, and the ideal liquid feeding characteristic desired by the operator is RB.

  The apparatus liquid feeding characteristic RA is obtained by measuring an actual liquid feeding mode in the apparatus when a command value (a specific example of the command value will be described later) is input to the pumps 101A and 101B in the apparatus. The apparatus liquid feeding characteristic RA (actual liquid feeding characteristic) can be acquired by measuring the absorbance of the eluent sent through the pumps 102A and 102B and the mixer 203 with the detector 105 of the apparatus, for example. The apparatus liquid supply characteristic RA acquired in this way is stored in the apparatus liquid supply characteristic storage unit 72 via the input device 108 or the like.

  By the way, the measurement results when the pumps 102A and 102B are controlled by the apparatus based on the time tables shown in FIGS. 4 and 5 (that is, the change in the mixing ratio of the eluent 201A and the eluent 201B) (the actual eluent state). (Liquid feeding mode) is modeled as shown in the following formulas (1) and (2) using the device feeding characteristic RA (t) and the ideal feeding characteristic RB (t). The actual liquid supply mode of the eluent can be obtained by measuring the absorbance of the eluent with the detector 105, similarly to the liquid supply characteristic RA (t). Further, in the following, the liquid feeding characteristics RA and RB may be appropriately expressed by functions of time t (RA (t), RB (t)), and “*” indicates a convolution operation.

  As is clear from the above equations (1) and (2), when the same time table (Time Table) is input, the difference between the liquid feeding characteristics RA and RB becomes the difference in the measurement result.

  Therefore, when S101 ends, the liquid feeding characteristic conversion processing device 107 obtains a difference (Trans (t)) between the liquid feeding characteristics RA and RB by the difference calculating unit 75 (S102). Since the expression (2) is equal to the expression (1) convolved with Trans (t), the following expression (3) is established.

  Here, the difference (Trans (t)) between the liquid feeding characteristics RA and RB can be calculated by the deconvolution calculation of Expression (3). Therefore, the time table (TimeTableB (t)) for simulating the chromatogram of the liquid chromatograph apparatus having the ideal liquid feeding characteristic RB desired by the operator with the apparatus having the liquid feeding characteristic RA is the original time table. It is calculated by the following equation (4) using (TimeTableA (t)) and Trans (t). Therefore, the conversion time table calculation unit 76 of the liquid feeding characteristic conversion processing device 107 reads the time table (TimeTableA (t)) to be converted from the time table storage unit 62 and considers the difference between the liquid feeding characteristics RA and RB. The calculated time table (TimeTableB (t)) is calculated based on the equation (4) (S103).

The conversion time table calculation unit 76 outputs the time table (time table after conversion: TimeTableB (t)) calculated in S103 to the time table storage unit 62 of the data processing device 106 (S104). The pump control unit 63 of the data processing device 106 controls the pumps 102A and 102B based on the time table (TimeTableB (t)) (S105).

Next, the operation of the liquid chromatograph device according to the present embodiment based on the screen displayed on the output device 109 will be described.

FIG. 7 is a diagram showing a display screen of the output device 109 according to the present embodiment. The display screen shown in this figure includes an ideal liquid feeding characteristic display unit 701, a liquid feeding characteristic curve display unit 702, a gradient table display unit 703, a gradient curve display unit 704, and a device liquid feeding characteristic selection button 705. A calculation execution button 706, a setting button 707, and a message display unit 708 are provided.

  The ideal liquid feeding characteristic display unit 701 is a part that displays the ideal liquid feeding characteristic RB desired by the operator as a time table. The time table of the ideal liquid feeding characteristic RB may be newly set by directly inputting to the table on the display screen of the output device 109 via the input device 108. A specific example of the ideal liquid feeding characteristic display unit 701 will be described later.

  The liquid feeding characteristic curve display unit 702 includes a command value 81 used for measuring the liquid feeding characteristic, an apparatus liquid feeding characteristic RA82 of the liquid chromatograph apparatus according to the present embodiment, and an ideal liquid feeding characteristic RB83 desired by the operator. This is the part that is displayed. In the apparatus liquid supply characteristic RA82, the liquid supply characteristic related to the apparatus selected via the apparatus selection button 705 is displayed. In the ideal liquid feeding characteristic RB83, the ideal liquid feeding characteristic displayed on the ideal liquid feeding characteristic display unit 701 is drawn. In the illustrated example, the command value 81 has a stepped shape, and the apparatus liquid feeding characteristic RA is a liquid feeding mode obtained by feeding the liquid chromatograph according to the present embodiment based on the command value 81. is there. It can be seen that the device liquid feeding characteristic RA82 has a faster response than the liquid feeding characteristic desired by the operator (ideal liquid feeding characteristic RB83). Note that the command value 81 extends over a minute time on the order of several milliseconds to several seconds, and a specific example of the command value 81 will be described later.

  The gradient table display unit 703 is a part where a time table used for sample measurement (that is, a time table before conversion by the conversion time table calculation unit 76) is displayed. In the illustrated example, the same time table as that shown in FIG. 4 is used and displayed. As the time table used for measurement, an existing time table in the data processing device 106 may be newly set via the input device 108, and the table on the display screen of the output device 109 may be updated.

  The gradient curve display unit 704 is calculated by the graph shape 84 of the time table displayed on the gradient table display unit 703 and the liquid feeding mode (equation (1)) when the apparatus is controlled based on the time table. ) 85 and a liquid supply mode (calculated by the equation (2)) 86 when the apparatus is controlled based on the difference between the time table and the liquid supply characteristics. In the illustrated example, the apparatus was controlled based on the graph shape of the time table shown in FIG. 5, the liquid feeding mode when the apparatus was controlled based on the time table, and the difference between the time table and the liquid feeding characteristics. The liquid feeding mode at the time is displayed.

  The apparatus liquid feeding characteristic selection button 705 is a button for selecting the apparatus liquid feeding characteristic RA of the liquid chromatograph apparatus according to the present embodiment. As a specific method for selecting the apparatus liquid supply characteristic RA, for example, when the apparatus selection button 705 is pressed with the input device 108 such as a pointing device, a plurality of liquid supply characteristics are stored in the apparatus liquid supply characteristic storage unit 72. In some cases, the device name is displayed on the screen in another window or the like, and one of the devices is selected by the operator using the input device 108.

  The calculation execution button 706 calculates a difference between the liquid feeding characteristic of the apparatus selected via the apparatus selection button 705 and the liquid feeding characteristic desired by the operator displayed on the ideal liquid feeding characteristic display unit 701 (S102). ) And a process for calculating a time table in consideration of the difference (S103) in the liquid feeding characteristic conversion processing device 107.

  The setting button 707 outputs a time table (time table after conversion) calculated by pressing the calculation execution button 706 to the data processing device 106 (S104), and uses the time table for controlling the pump 102. It is a button for setting.

  The message display unit 708 is a part where messages relating to operation and processing of the liquid chromatograph apparatus are displayed as appropriate.

  A display example of the ideal liquid feeding characteristic display unit 701 will be described with reference to FIG.

  (FIG. 8-A) shows, as a first example, an example in which the apparatus liquid feeding characteristic RA of the liquid chromatograph apparatus embodying the present invention is shifted in time to the ideal liquid feeding characteristic RB desired by the operator. FIG. Since the pipe capacity changes when the pipe length and pipe diameter are changed, the time required for the solvent to reach the column from the pump is different, and the gradient profile has a time-shifted shape. For this reason, this example is effective as a simulation when, for example, the pipe length and pipe diameter of the liquid chromatograph are changed.

  (FIG. 8B) shows, as a second example, an ideal liquid feed characteristic desired by the operator, in which the gradient rising behavior of the apparatus liquid feed characteristic RA of the liquid chromatograph apparatus embodying the present invention is changed. It is a figure which shows the example at the time of setting it as RB. Even when the internal capacity of the mixer 203 is the same before and after the change, the mixing behavior differs if the internal structure of the mixer 203 changes. In this case, as the gradient profile, the start time of the gradient rise is the same, but the subsequent gradient rise behavior may be different. Therefore, this example is effective as a simulation when the mixer 203 of the liquid chromatograph unit 101 is changed, for example.

  (FIG. 8-C) shows, as a third example, an ideal liquid feeding characteristic desired by an operator, which is obtained by changing the gradient tailing behavior of the apparatus liquid feeding characteristic RA of the liquid chromatograph apparatus embodying the present invention. This is an example in the case of RB. When there is a vortex in the solvent flow, the gradient tailing behavior may differ as a gradient profile. The generation of vortices makes it difficult for the solvent to be discharged and the tailing of the gradient becomes longer. For this reason, in this example, for example, the simulation is effective when a vortex is generated in the solvent flow in the liquid chromatograph unit 101.

  Next, an input operation method of the ideal liquid feeding characteristic RB will be described. FIG. 9 is an example of a time table related to the ideal liquid feeding characteristic RB. In the time table of FIG. 9, “% A” indicates the composition ratio of the eluent 201A (pump 102A) in the moving bed, and “% B” indicates the composition ratio of the eluent 201B (pump 102B). The total flow rate of the eluents A and B is always maintained at 1 [ml / min]. The operator sets a flow rate and a composition ratio of “% A” and “% B” for each time and inputs a desired liquid feeding characteristic via the input device 108. For the desired liquid feeding characteristics, data complementation is performed for the composition ratios of “% A” and “% B” in the time not input by the operator. Data interpolation methods include known techniques such as linear interpolation, spline interpolation, cubic spline interpolation, Lagrangian interpolation, Newton interpolation, Neville interpolation, etc. (reference: edited by Haruhiko Okumura, “Latest Algorithm Dictionary in C Language”, Inc. Technical Review Company, March 1991) is available.

  FIG. 10 is a flowchart showing the operation procedure according to the present embodiment and the processing of the control unit 110 associated therewith.

  The liquid feeding characteristic conversion processing device 107 stands by until the operator presses the device liquid feeding characteristic selection button 705. The operator presses down the device liquid feeding characteristic selection button 705 via the input device 108, and the device liquid feeding characteristic of the liquid chromatograph apparatus that performs the liquid feeding property conversion of the present invention by the “device liquid feeding property selection” button. RA is selected (S1001).

  When the target device is selected in S1001, the liquid feeding property conversion processing device 107 requests the operator to input the ideal liquid feeding property RB desired by the operator via the message display unit 708. Then, the operator inputs the ideal liquid feeding characteristic RB via the input device 108 (S1002). The specific method of input is as described above.

  When the ideal liquid delivery characteristic RB is input in S1002, the liquid delivery characteristic conversion processing device 107 requests the operator to select a time table used for sample measurement via the message display unit 708. Then, the operator inputs or selects a time table used for sample measurement via the input device 108 (S1003). The specific method of input or selection is as described above. If the time table to be used is determined in advance, S1003 can be omitted.

  When the selection of the time table is completed, the liquid feeding property conversion processing device 107 stands by until the calculation execution button 706 is pressed. At this time, the message display unit 708 may be prompted to press the calculation execution button 706 by the operator.

  When the operator presses the calculation execution button 706 by the input device 108, the difference calculation unit 75 of the liquid feeding characteristic conversion processing device 107 performs the apparatus liquid feeding characteristic RA selected in S1001 and the ideal liquid feeding input in S1002. A calculation process of the difference between the characteristics RB is executed (S1005). The specific content of the calculation process at this time is the same as S102 described above. Then, the conversion time table calculation unit 76 of the liquid feeding characteristic conversion processing device 107 executes a process of calculating a time table in consideration of the difference calculated in S1005 (S1006). The specific content of the calculation process at this time is the same as S1003 described above.

  When the process of calculating the time table is completed in S1005, the liquid feeding characteristic conversion processing device 107 stands by until the setting button 707 is pressed. At this time, the message display unit 708 may display a message prompting the operator to press the setting button 707.

  When the operator presses the setting button 707 by the input device 108, the liquid feeding characteristic conversion processing device 107 outputs the time table calculated in S1006 to the time table storage unit 62 of the data processing device 106, and the data processing device 106 The pump controller 63 is set to control the pumps 102A and 102B based on the time table. That is, the time table used when the pump control unit 63 performs the pump control is switched from the one used so far to the one calculated in S1005. After that, when sample measurement is started by the operator, the data processing device 106 controls the pumps 102A and 102B according to the time table calculated in S1006 (S1009). This makes it possible to simulate a liquid chromatograph apparatus having an ideal liquid delivery characteristic RB desired by the operator.

  Next, a method for acquiring the apparatus liquid feeding characteristic RA of the liquid chromatograph apparatus will be described. First, as a hardware configuration for acquiring the apparatus liquid feeding characteristic RA, there is one in which the detector 105 is directly connected to the outlet of the autosampler 103 without using the column 207. The apparatus liquid feeding characteristic RA can be acquired by measuring the absorbance of the eluent sent from the pumps 102A and 102B with the detector 105. Further, the detector 105 may be connected to the outlet of the autosampler 103 through the column 207 as usual. In the latter case, instead of the column 207, a resistance pipe may be connected to the outlet of the autosampler 103, and the detector 105 may be connected to the resistance pipe to acquire liquid feeding characteristics. In addition, from the viewpoint of obtaining the apparatus liquid feeding characteristic RA, it is preferable that the resistance pipe and the column have a low capacity. Although the case where the sample injection unit is the autosampler 103 has been described here, a manual injector may be used.

  Further, here, the case where the eluent discharged from the sample injection unit (autosampler 103) is detected has been described from the viewpoint of prioritizing the use of the existing apparatus, but the eluent is discharged outside the liquid chromatograph apparatus. It is also possible to separately provide an openable / closable exit for the purpose, and attach a detection device capable of measuring absorbance similarly to the detector 105 to the exit.

  Next, a specific example of a command value output to the pump 102 (pumps 102A and 102B) when acquiring the liquid feeding characteristics will be described. The command value defines the control of the pump 102 (102A, 102B) in a minute time on the order of several milliseconds to several seconds, and there are various values. FIG. 11 is a diagram illustrating an example of command values output to the pumps (pumps 102A and 102B) when acquiring the liquid feeding characteristics of the liquid chromatograph apparatus. Here, refer to FIG. 11 for a variation in the case where the ratio of the two types of eluent pumped up by the pumps 102A and 102B is changed over time while the total flow rate of the two types of eluents 201A and 201B is kept constant. While explaining. The liquid feeding characteristic can be acquired from an actual liquid feeding mode (for example, a gradient curve) obtained by detecting the absorbance of the eluent sent from the pump 102 to which the command value is input.

  First, as an example of the command value, as shown in FIG. 11A (or the liquid feed characteristic curve display unit 91 in FIG. 8), the total flow rate of two types of eluents (eluents 201A and 201B). In some cases, the ratio of the two kinds of eluent pumped up by the pumps 102A and 102B is changed like a step function with the passage of time. As a method of calculating the liquid transfer characteristics, normalize the observed value when the observed value after switching the eluent on the actual gradient curve is in a steady state as 1, and differentiate the gradient curve after normalization or Some are calculated by making a difference.

Further, as an example of the command value, there is one that switches the ratio of two kinds of eluents (eluents 201A and 201B) based on H ₁ (t) that is a function of time t defined by the following equation (5). Yes (see FIG. 11B). As a method for calculating the liquid feeding characteristic, there is a method in which a gradient curve obtained when a command value is input to the pumps 102A and 102B is measured, and the gradient curve is calculated by differentiating or subtracting the gradient curve. In the formula (5), A ₁₁ and A ₁₂ are constants, and A ₁₂ > A ₁₁ is set. The difference between t ₂ and t ₁ is preferably about milliseconds to seconds. Further, H ₁ (t) is continuous at t = t ₁ and t ₂ as boundary conditions. That t = t ₁ at _{J 1 (t 1) = A} 11 next, t = t ₂ in J ₁ (t ₂₎ = the A _12. J ₁ (t) is a monotonically increasing function of time t, for example, a polynomial function, an exponential function, or a combination of these functions. If A ₁₂ <A ₁₁ , J ₁ (t) is a monotonically decreasing function.

  In addition, as an example of the command value, there is one that switches the ratio of two types of eluents (eluents 201A and 201B) as a rectangular function (see FIG. 11C). As a method for calculating the liquid feeding characteristic, there is a method of calculating an area value of a peak on a gradient curve actually detected by a detector and normalizing the gradient curve so that the area value of the peak becomes 1. . The liquid feeding property may be a standardized gradient curve. The width of the rectangle function is preferably about milliseconds to seconds.

Further, as an example of the command value, there is one that switches the ratio of two types of eluents (eluents 201A and 201B) based on H ₂ (t) defined by the following equation (6) (FIG. 11D). )reference). In Equation (6), the difference between t _b and t _a and the difference between t _c and t _b are each preferably about milliseconds to seconds. H ₂ (t) is set to be continuous at t = t _a , t _b , and t _c as boundary conditions. That is, t = t _a J ₂₁ (t _a ) = A ₂ , t = t _b and J ₂₁ (t _b ) = J ₂₂ (t _b ), and t = t _c and J ₂₂ (t _c ) = A ₂ It becomes. J ₂₁ (t) is a monotonically increasing function, for example, a monotonically increasing polynomial, a monotonically increasing exponential function, or a combination of these functions. J ₂₂ (t) is a monotonically decreasing function, for example, a monotonically decreasing polynomial, a monotonically decreasing exponential function, or a combination of these functions.

Further, as an example of the command value, there is one that switches the ratio of two types of eluents (eluents 201A and 201B) based on H ₃ (t) defined by the following equation (7) (FIG. 11E )reference). The liquid feeding characteristics at this time may be determined by differentiating the gradient curve actually detected by the detector twice (or subtracting twice) and normalizing the peak area to 1. In Expression (7), A ₃₁ , A ₃₂ , and A ₃₃ are positive constants. The difference between t _f and t _e is preferably about milliseconds to seconds. H ₃ (t) is set to be continuous at t = t _e and t _f as boundary conditions. That is, a J ₃ (t _e) = next A _31, J ₃ at _{t = t f (t f)} = A 32 · t f + A 33 at t = t _e. J ₃ (t) is a monotonically increasing function, for example, a polynomial function, an exponential function, or a combination of these functions.

Further, as an example of the command value, there is one that switches the ratio of two types of eluents (eluents 201A and 201B) based on H ₄ (t) defined by the following equation (8) (FIG. 11F). )reference). The liquid feeding characteristics at this time may be determined by differentiating the gradient curve actually detected by the detector twice (or subtracting twice) and normalizing the peak area to 1. In Expression (8), A ₄₁ , A ₄₂ , and A ₄₃ are constants. H ₄ (t) is set to be continuous at t = t _g as a boundary condition. That is, H ₄ (t _g ) = A ₄₂ · t _g + A ₄₃ at t = t _g .

  By the way, in order to improve the S / N ratio of the liquid feeding characteristic (gradient curve) actually obtained by measuring the absorbance with the detector 105, the moving average method, the Savitzky-Golay method, the Kawata-Minami method, the frequency domain method, Or it is preferable to utilize the smoothing process by these combination. Further, the same smoothing process may be applied to the difference in liquid feeding characteristics between the apparatuses (S102, S904) and the converted time table (S103, S905). In addition, each configuration related to the above liquid chromatograph apparatus, functions and execution processing of each configuration, etc. are partly or entirely hardware (for example, logic for executing each function is designed by an integrated circuit). It may be realized. The configuration related to the above apparatus is a program that realizes each function related to the configuration of the control device by being read and executed by the arithmetic processing device (for example, CPU) of the data processing device 106 and / or the emulation processing device 107. (Software). Information related to the program can be stored in, for example, a semiconductor memory (flash memory, SSD, etc.), a magnetic storage device (hard disk drive, etc.), a recording medium (magnetic disk, optical disc, etc.), and the like.

  In the description of the above embodiment, the control line and the information line are shown to be understood as necessary for the description of the embodiment. However, all the control lines and information lines related to the product are not necessarily included. Not necessarily shown. In practice, it can be considered that almost all the components are connected to each other.

DESCRIPTION OF SYMBOLS 101: Liquid chromatograph part 102: Pump 103: Autosampler 104: Column oven 105: Detector 106: Data processing device 107: Liquid sending characteristic conversion processing device 108: Input device 109: Output device 110: Control part 201: Eluent 203: Mixer 205: Cleaning solution 207: Analysis column 61: Time table input unit 62: Time table storage unit 63: Pump control unit 71: Device liquid supply characteristic input unit 72: Device liquid supply characteristic storage unit 73: Ideal liquid transfer characteristic input Unit 74: Ideal liquid feed characteristic storage unit 75: Difference calculation unit 76: Conversion time table calculation unit 701: Ideal liquid feed characteristic display unit 702: Liquid feed characteristic curve display unit 703: Gradient table display unit 704: Gradient curve display unit 705 : Device liquid feed characteristic selection button 706: Calculation execution button 707: Setting button 708: Message display unit

Claims (18)

A liquid chromatograph part having a liquid sending part for sending an eluent to the detection part;
In a liquid chromatograph apparatus comprising: a control unit that controls liquid feeding by the liquid feeding unit based on a predetermined time table;
The controller is
A first liquid feeding characteristic acquired from the liquid chromatograph device by detecting a liquid feeding mode when a predetermined command value is input to the liquid feeding unit;
A liquid chromatograph apparatus comprising a storage unit for storing desired second liquid feeding characteristics. The liquid chromatograph apparatus according to claim 1,
The controller is
In the liquid chromatograph section showing the first liquid feeding characteristic, in the liquid chromatograph section showing the second liquid feeding characteristic, the liquid feeding mode when the liquid feeding section is controlled based on the time table, The time based on the first liquid feeding characteristic and the second liquid feeding characteristic so as to approach the liquid feeding mode when simulating the case of controlling the liquid feeding unit based on the time table. A liquid chromatograph apparatus for converting a table. In the liquid chromatograph apparatus according to claim 2,
The liquid chromatograph apparatus, wherein the control unit controls the liquid feeding unit using the time table after the conversion. The liquid chromatograph apparatus according to claim 1,
A liquid chromatograph apparatus further comprising an openable and closable outlet for discharging an eluent flowing when the command value is input to the liquid feeding section to the outside of the liquid chromatograph apparatus. In the liquid chromatograph apparatus according to claim 4,
The outlet part is an outlet of a sample injection part in the liquid chromatograph part,
A liquid chromatograph apparatus further comprising a detector connected to the outlet for detecting a liquid feeding mode from the liquid feeding unit. In the liquid chromatograph apparatus according to claim 4,
The outlet part is an outlet of a sample injection part in the liquid chromatograph part,
A resistance pipe or column connected to the outlet;
A liquid chromatograph apparatus further comprising: a detector connected to the resistance pipe or the column and detecting a liquid feeding mode from the liquid feeding unit. The liquid chromatograph apparatus according to claim 1,
The command value is to change the ratio of a plurality of types of eluent pumped up by the liquid feeding unit in a step function over time,
The liquid chromatograph apparatus, wherein the first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit. The liquid chromatograph apparatus according to claim 1,
The command value is used to change the ratio of a plurality of types of eluent pumped up by the liquid delivery unit based on the following function F ₁ (t) over time (t) (where C ₁₁ is a constant) , F ₁ (t) is a continuous function, and t _F1a , t _F1b , t _F1c are constants, G ₁₁ (t) is a monotonically increasing function and G ₁₂ (t) is a monotonically decreasing function, or G11 (t) Is a monotonically decreasing function and G12 (t) is a monotonically increasing function)
The liquid chromatograph apparatus, wherein the first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit.
The liquid chromatograph apparatus according to claim 1,
The command value is to change the ratio of a plurality of types of eluent pumped up by the liquid feeding unit in a step function over time,
The first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit, and differentiating or subtracting the gradient curve. Chromatographic device. The liquid chromatograph apparatus according to claim 1,
The command value is a time (t) indicating a ratio of a plurality of types of eluent pumped by the liquid feeding unit.
) Is changed based on the following function F ₂ (t) (however, C ₂₁ and C ₂₂ are constants, F ₂ (t) is a continuous function, and t _F2a and t _F2b are constants) if .C ₂₁ is less than C ₂₂ G ₂₁ (t) is a monotonically increasing function, if C ₂₁ is greater than C ₂₂ G ₂₁ (t) is a monotonically decreasing function),
The first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit, and differentiating or subtracting the gradient curve. Chromatographic device.
The liquid chromatograph apparatus according to claim 1,
The command value is used to change the ratio of a plurality of types of eluent pumped up by the liquid feeding unit based on the following function F ₃ (t) over time (t) (however, C ₃₁ , C ₃₂ C ₃₃ is a constant, F ₃ (t) is a continuous function, and t _F3a and t _F3b are constants)
The first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit, and calculating the derivative or difference twice of the gradient curve. A liquid chromatograph device.
The liquid chromatograph apparatus according to claim 1,
The command value changes the ratio of a plurality of types of eluent pumped up by the liquid feeding unit based on the following function F ₄ (t) over time (t) (C ₄₁ , C ₄₂ C ₄₃ is a constant, F ₄ (t) is a continuous function, t _F4a and t _F4b are constants, and G ₄₁ (t) is a monotonically increasing function)
The first liquid feeding characteristic is calculated by measuring a gradient curve obtained when the command value is input to the liquid feeding unit, and calculating the derivative or difference twice of the gradient curve. A liquid chromatograph device.
The liquid chromatograph apparatus according to claim 1,
The liquid chromatograph characterized in that the first liquid feeding characteristic is standardized based on an area value thereof. The liquid chromatograph apparatus according to claim 1,
The liquid chromatograph apparatus, wherein the first liquid feeding characteristic is smoothed by a moving average method, a Savitzky-Golay method, a Kawata-Minami method, a frequency domain method, or the like. In the liquid chromatograph apparatus according to claim 2,
The liquid chromatograph apparatus characterized in that a difference between the first liquid feeding characteristic and the second liquid feeding characteristic is smoothed by a Savitzky-Golay method, a Kawata-Minami method, a frequency domain method, or the like. In the liquid chromatograph apparatus according to claim 2,
The liquid chromatograph apparatus, wherein the time table after the conversion is smoothed by a Savitzky-Golay method, a Kawata-Minami method, a frequency domain method, or the like. A procedure for obtaining a first liquid feeding characteristic according to the liquid chromatograph device by detecting a liquid feeding mode when a predetermined command value is input to the liquid feeding unit of the liquid chromatograph device;
A procedure for obtaining a desired second liquid feeding characteristic input to the input unit;
A liquid feeding mode when the liquid feeding unit is controlled based on a predetermined time table in the liquid chromatograph apparatus showing the first liquid feeding characteristic is the liquid chromatograph apparatus showing the second liquid feeding characteristic. The time table is converted based on the first liquid feeding characteristic and the second liquid feeding characteristic so as to approach the liquid feeding mode when simulating the case of controlling the liquid feeding part based on the time table. A method for converting liquid-feeding characteristics of a liquid chromatograph device. A liquid chromatograph part having a liquid sending part for sending an eluent to the detection part;
In a device liquid feeding characteristic conversion program for a liquid chromatograph device comprising a control unit that controls liquid feeding by the liquid feeding unit based on a predetermined time table,
A first liquid feeding characteristic acquired from the liquid chromatograph unit by detecting a liquid feeding mode when a predetermined command value is input to the liquid feeding unit, and a desired second liquid feeding characteristic. Processing to memorize,
The liquid feeding mode when the liquid feeding part is controlled based on the time table in the liquid chromatograph part showing the first liquid feeding characteristic is the liquid chromatograph part showing the second liquid feeding characteristic. The process of converting the time table based on the first liquid feeding characteristic and the second liquid feeding characteristic so as to approximate the liquid feeding mode when simulating the case of controlling the unit An apparatus liquid-feeding characteristic conversion program for a liquid chromatograph apparatus, characterized by being executed by a unit.