JP3357162B2 - High-performance liquid chromatograph using system controller - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a high performance liquid chromatograph using a system controller, and more particularly to an improvement of a spectral data acquisition and data processing mechanism.

[0002]

2. Description of the Related Art In a sample analysis by high performance liquid chromatography (HPLC), first, a sample injected by a sample injector together with a mobile phase is sent to a column filled with a stationary phase.
The chromatogram is measured by separating and eluting the components to be measured in the sample. In addition, in order to accurately identify the peak of the chromatogram, it is preferable to perform the spectrum measurement at the time of elution of the peak of the component to be measured simultaneously with the chromatogram measurement. And conventional HPLC
In the spectrum measurement by the detector, when the peak elutes so that the peak elution does not change during the scan, the solution sending is temporarily stopped, and the spectrum is measured by scanning in this state.

As shown in FIG. 7, a conventional detector processes a signal from a photodetector 2 by a preamplifier 6 having a time constant analog circuit 4 and then performs an A / D conversion by an A / D converter 8. That is, high-speed scanning could not be performed. That is, since the processing speed of the detector CPU and the like is slow, even if data is acquired at high speed,
Since processing such as conversion and averaging cannot be performed in time, it is necessary to perform noise reduction processing before performing A / D conversion. It is the most effective noise reduction method to provide a time constant in the circuit of the preamplifier 6. is there. Therefore, in order to acquire the spectrum data at high speed, the grating is rotated quickly, and at the same time, the signal from the preamplifier 6 catches up with the high-speed rotation of the grating, even if the data is to be synchronized with the rotation of the grating. Therefore, an accurate spectrum cannot be obtained.

On the other hand, the spectrum measurement operation in the detector has conventionally been performed by key operation of the detector main body. However, the operability is extremely poor with the few keys of the detector and the extremely small LCD display screen, and the obtained spectrum cannot be viewed until output to the recorder after the end of the chromatogram measurement. Furthermore, although the measured data is stored in the memory of the detector, the data disappears when the power is turned off, so that spectral data could not be saved except for outputting to a recorder. Therefore, recently, an HPL that uses a system controller including a computer to perform a spectrum measurement operation using a keyboard of the system controller, transfers spectrum data to the system controller, and performs display display and data storage.
C is under development.

That is, the system controller is connected to each device of a measuring section such as a pump, an autosampler, a column, a column oven, and a detector via a communication circuit between the devices.
In addition to controlling the measurement conditions such as temperature and wavelength,
The spectral data from the detector is to be processed by the system controller. Here, as a connection method between the system controller and each device, a bus type having a shared line structure that allows each device to share one communication line and communicate even if there are many devices is the most desirable connection at a low cost. Is the way. Conventionally, when data from a detector is transferred to a system controller, the data is transmitted as an ASCII code file because the spectral data itself and the communication end data are easily distinguished.

[0006]

However, if the mobile phase and the sample supply are temporarily stopped during peak elution as in the conventional detector, a gradient or the like is performed by a time program, or an autosampler is connected to the sample injector. In continuous analysis using, for example, the retention time in the chromatogram becomes indefinite even when the solution is restarted, or the column and detector are affected by the stoppage of the solution, resulting in poor data reliability. was there. On the other hand, in the HPLC using the system controller, since the spectrum data of the detector is transferred to the system controller, the already obtained spectrum data is displayed on the display while the measurement is being continued, or the data is transmitted from the system controller to the floppy disk. There is an advantage that the data can be stored in a storage medium such as a disk.

However, on the other hand, the size of the spectrum data from the detector is much larger than that of a normal command, and the data is transferred to the system controller in an ASCII code file. Would. For this reason, there has been a problem that the communication line is occupied for a long time by the data transfer in the bus format having the shared line structure, which hinders real-time control of each device from the system controller. Also,
Although the operability is improved by performing the spectrum measurement operation with the keyboard of the system controller, the system controller has various functions such as controlling each device and processing the measurement results in various ways. Therefore, the problem that the number of keys is insufficient in performing complicated processing remains.

In order to solve the shortage of the number of keys, a conventional keyboard is provided with function keys as general-purpose keys, and functions are assigned to the function keys as needed, or a list of functions is displayed on a screen. There are several ways to select the function keys.However, in the former, the function of the function keys changes depending on the case, so it is necessary to learn the function of the function keys in each case. Due to the limited size, there are problems that display items are limited, and when a large number of items are displayed, it becomes difficult to find a desired function.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems of the prior art, and has as its object to collect spectrum data without stopping liquid feeding and to display the collected data during measurement in liquid chromatography. Another object of the present invention is to provide a high-performance liquid chromatograph using a system controller capable of easily and in real time controlling measurement conditions and the like.

[0010]

[MEANS FOR SOLVING THE PROBLEMS] To achieve the above object
A high performance liquid chromatograph of claim 1 wherein according to the present invention, a pump, sample injector, column, and consists detector, a measurement section for measuring a specimen by separating elution, the measurement
A system control unit that comprehensively controls setting of measurement conditions in each unit of the unit , a data processing unit that performs arithmetic processing on data transferred from the detector, and data that manages data contents of the system control unit and the data processing unit. management unit, setting unit for setting a control content and processing contents of the system control unit and the data processing unit, an input unit for inputting the setting items and setting values in the setting unit, the display comprising a display for displaying the contents of the data management System consisting of
Troller, the measuring unit and the system controller
Has a device communication line connecting over, the, said measuring unit
The system controller is configured as a separate body,
The inter-device communication line is connected to a plurality of devices including the measuring unit and the system.
The communication with the stem controller is collectively handled, and the measuring unit includes a photodetector, a preamplifier to which an analog signal from the photodetector is input, an analog signal from the preamplifier input, and a digital signal. Convert to A /
It is characterized by comprising a D converter, and a calculation unit to which a digital signal from the A / D converter is input and for calculating and averaging the digital signal.

[0011] The high performance liquid chromatograph according to claim 2 of the present invention is a high performance liquid chromatograph.
Oite, characterized by transferring the data from the detector to the data processing unit in a binary file. A high-performance liquid chromatograph according to a third aspect of the present invention is the high-performance liquid chromatograph according to any one of the first to second aspects.
In the body chromatograph, the display section
Adding a memory, connecting the system control unit and the display unit,
A display control unit for displaying the control contents of each layer in a window frame as a control structure of the system control unit in a hierarchical structure and simultaneously displaying a plurality of window frames from an upper layer to a lower layer on one screen; It is characterized by. In the high-performance liquid chromatograph according to claim 4 of the present invention, in the high-performance liquid chromatograph, chromatogram data and spectrum data are measured in the measurement unit, and the measured chromatogram data is measured in the data management unit. The spectrum data is added and managed and stored.

[0012]

According to the high-performance liquid chromatograph of the first aspect of the present invention , as described above, after the analog signal from the preamplifier is converted into a digital signal by the A / D converter in the measuring section , the arithmetic section averages the digital filtering. Therefore, the time constant of the preamplifier can be extremely reduced. Therefore,
The signal from the preamplifier can be extracted in a short time,
Even if the grating of the detector is rotated at a high speed, the output signal from the preamplifier can follow, and the data of the peak-eluted component can be obtained at a high speed. In the high-performance liquid chromatograph according to the second aspect of the present invention, the data from the detector is transferred to the data processing unit in a binary file, so that the system control unit can control each device even on the same line. Real-time control is possible without causing any trouble.

Further, in the high-performance liquid chromatograph according to the third aspect of the present invention, since the control contents of the system control section have a hierarchical structure, the menu of the upper hierarchy is displayed and selected, and then the lower hierarchy included in the upper hierarchy is displayed. Hierarchical functions can be displayed and selected, and a large number of functions can be easily and accurately selected with a small number of keys. Further, the display control unit displays the control content of each layer in a window frame, and simultaneously displays a plurality of window frames from the upper layer to the lower layer on one screen, so that the current layer position and the current layer are displayed. The progress can be clearly understood. Further, the high-performance liquid chromatograph according to claim 4 of the present invention makes it possible to clarify the chromatogram to which each spectrum belongs, and to record the conditions at the time of spectrum measurement more accurately. . Further, the chromatogram data also has more information about the sample as a result of the addition of the spectrum data, and thus can be more accurately grasped.

[0014]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below with reference to the drawings. FIG. 1 shows a high performance liquid chromatograph (HP) using a system controller according to one embodiment of the present invention.
LC) is shown. HPL shown in FIG.
C has a measuring unit 10, a system controller 12, and an inter-device communication line 14 connecting the measuring unit 10 and the system controller 12. The measuring unit 10 includes:
It includes a pump 16, an autosampler 18, a column 20, a column oven 22, and a detector 24. Then, in the measurement section 10, the sample from the autosampler 18 is sent to the column 20 together with the mobile phase 26 by the pump 16. The column 20 is a column oven 2
2 and is maintained at a predetermined temperature. further,
The ultraviolet light absorption intensity and the like of the sample separated in the column 20 are measured by a detector 24 such as an ultraviolet spectrophotometer.

Here, as described above, in the continuous analysis using the autosampler 18 as a sample injector, the analysis becomes impossible if the liquid supply to the column 20 is stopped once. Then, in order to perform the continuous analysis without stopping the liquid sending, the spectral data must be collected by the detector 24 at a high speed during the peak elution of the target component in the sample. For this reason, in the present embodiment, the detector 24 is configured as shown in FIG. That is, in the optical system 28, the light detection element 30 receives the measurement light, and outputs a light reception signal from the light detection element 30 to the preamplifier 32. And the preamplifier 3
After digitally converting the signal from the A / D converter 2 by the A / D converter 34 capable of high-speed sampling, the arithmetic unit 36 performs digital filtering for reducing noise by calculation. Therefore, it is not necessary to remove fine noise in the preamplifier 32, and the time constant of the preamplifier 32 can be extremely reduced. The preamplifier 32 can follow the output signal. As described above, the detector 24 according to the present embodiment can perform a high-speed scan, and can collect spectrum data while the liquid supply is continued and the peak elution does not change.

On the other hand, the system controller 12
It includes a CPU 38, a keyboard 40 as an input unit, and a display unit 42. The CPU 38 includes a setting unit 44, a system control unit 46, a data processing unit 48, a data management unit 50, and a display control unit 52.
The display unit 42 includes a frame memory 54 and a display 56. The measuring unit 1 is inputted by the setting unit 44 according to the input from the keyboard 40.
The measurement condition of each device is set to 0, and the system controller 46 controls the measurement condition of each device through the inter-device communication line 14 based on the setting. The set measurement conditions are also output from the system control unit to the data management unit 50 and stored in the data management unit 50. on the other hand,
The spectral data obtained in the detector 24 is
The data is output to the data processing unit 48 through the inter-device communication line 14, and the processed data is output to the data management unit 50 and stored. The contents stored in the data management unit 50 are displayed on a large display 56 and stored in an external storage medium 58 such as a floppy disk.

The processing data stored in the data management unit 50 is input to the setting unit 4 by the keyboard 40.
By instructing desired data analysis or the like via the data processing unit 4, the data processing unit 48 can perform arithmetic processing again. As described above, in this embodiment, since the spectrum data is transferred to the system controller 12 for processing, storage, and display, complicated and quick data processing, abundant information amount, and confirmation of the measurement result during measurement are achieved. It becomes possible. Hereinafter, an example of spectrum measurement by HPLC according to the present embodiment will be described.

First, at the start of spectrum measurement, a measurement screen 60 as shown in FIG. On this screen, the measurement conditions of each device of the measurement unit 10 controlled by the system control unit 46 are already displayed. Then, the mobile phase 26 is sent to the column 20 for conditioning, and “measurement” is selected by the keyboard 40 when each device is stabilized. This allows
A command for baseline measurement is transmitted to the detector 24, the detector 24 performs a scan, and the obtained data is
4 is stored in the memory. Further, the time at which the baseline is measured is transmitted to and stored in the data management unit 50, and is displayed in the “Base Line” shown in FIG. Next, the sample is injected into the column 20 by the autosampler 18, and the screen 60 is displayed.
Select a memory number above. The chromatogram is observed, and when the peak of the target component elutes, the keyboard 40
Transmits a spectrum measurement command to the detector 24 via the system control unit 46, and the detector 24 scans and stores the obtained spectrum data in the specified memory number. The time at which the spectrum was measured is transmitted and stored in the data management unit 50, and is displayed in “UV.Rt” shown in FIG. By transmitting the data transfer command to the detector 24 from the keyboard 40 via the system control unit 46 while performing the spectrum measurement, the detector 2
4 subtracts the previously measured baseline data from the designated memory spectrum data, and transfers the result to the data processing unit 48. The transferred spectrum data is managed by the data management unit 50 together with the measurement time of the spectrum and the baseline, and the spectrum is graphically displayed on the screen 60.

When "analysis screen" is selected in FIG. 3, a screen 62 as shown in FIG. 4 is displayed on the display 56, "analysis" is selected on the screen, and a memory number is further selected. Thus, a desired spectrum can be displayed on the screen. As described above, by transferring and managing the spectrum data to the data management unit 50, the spectrum with the peak eluted can be measured and the spectrum can be immediately displayed on the display 56. Can be determined.

Further, even when the absorption of the solvent changes gradually as in the gradient elution method, the spectra are measured at the peak position and at the position where the sample before and after the peak is not eluted, and each spectrum is subjected to data processing. If the data is transferred to the section 38 and subtracted, a pure spectrum of the peak component can be immediately obtained. Further, the data management unit 5
At 0, if the spectrum data is added to the measured chromatogram data and managed and stored, the chromatogram to which each spectrum belongs becomes clear, and the conditions at the time of spectrum measurement can be recorded more accurately. Further, the chromatogram data also has more information about the sample as a result of the addition of the spectral data, so that it can be grasped more accurately.

Here, as described above, each device of the measuring section 10 and the system controller 12 are connected to the inter-device communication line 14.
The inter-device communication line 14 is also used to transfer spectrum data and the like from the detector 24 to the data processing unit 48 and the data management unit 50. The inter-device communication line 14 is connected to the system controller 12 and the measuring unit 1 so that all communication can be performed on one line.
The connection with each device of No. 0 is of a bus type having a shared line structure. However, the inter-device communication line 14 is used for transferring spectrum data and the like from the detector 24,
Signals such as changes in the measurement conditions of each device are sent to the system controller 4
6 to each device. And
Since the amount of spectrum data from the detector 24 is large, the transfer of the spectrum data using the conventional ASCII code file occupies the inter-device communication line 14 for a long time. The transmission of the control signal.

Therefore, in this embodiment, the detector 24
Is matched with the data file format stored and managed by the data management unit 50, and the spectrum data from the detector 24 is transferred as a binary file. For this reason, by compressing and transferring the spectrum data from the detector 24, the transfer time can be reduced to about 1/3, which is about 1/3 compared to the conventional ASCII code file transfer.
Seconds. As a result, in the case of HPLC measurement, it takes 5 minutes to several hours to measure a chromatogram, and polling of each device from the system control unit 46 is desired at intervals of about 3 seconds, but the transfer time is shortened. By doing so, it became possible to control each device without any trouble. Further, the transferred spectral data is
For example, it is preferable to transfer the packet by dividing it into 256-byte packets, so that other communication can be interrupted even during the transfer.

In this embodiment, a display control unit 52 is provided in the CPU 38 in order to facilitate and clarify the input operation of the control contents in the system control unit 46. As described above, in the system controller 12, since the control performed by the system control unit 46 is multifunctional, the input key operation from the keyboard 40 has to be complicated.

In this embodiment, the control items in the system control section 46 are first filed in a hierarchical structure as shown in FIG. 5, and each layer is arranged in a window frame from the upper layer to the lower layer of the control items. Surround display 56
Is displayed. Further, the display position of each layer on the display 56 is divided by the display control unit 52, and all the layers selected previously are stored in the frame memory 54.
And the display 56 is displayed simultaneously with the newly selected hierarchy without erasing the selected hierarchy.
That is, as shown in FIG. 6, for example, first, a main menu frame 64 of the uppermost hierarchy, which is the most basic, is displayed on the left end of the screen. When menu 1 is selected from the main menu frame 64, the menu of the selected lower hierarchy is displayed. One frame 66 is displayed at the center of the screen. At this time, the main menu frame 64
Continues to be displayed on the left edge of the screen. When the menu A is selected from the menu 1 frame 66, the selected lower-level menu A frame 68 is displayed at the right end of the screen. At this time, the main menu frame 6 selected so far
4 and the menu 1 frame 66 are also displayed at the same time.

As described above, in the present embodiment, the items are selected in order for each layer using the hierarchical structure, instead of selecting all at once from the functions in the lowest layer shown in FIG. The number of keys on the keyboard 40 required for the operation can be reduced, and a desired function can be easily selected without making a mistake in the selection operation. In addition, since the already selected upper hierarchy is also displayed at the same time,
It is possible to clearly grasp the current hierarchy position and the progress of the hierarchy up to the present.

[0026]

As described above, according to the high-performance liquid chromatograph of the first aspect using the system controller according to the present invention, it is possible to obtain spectrum data at high speed in the detector. According to the high-performance liquid chromatograph according to the second aspect using the system controller according to the present invention, real-time control can be performed without hindering control of each device from the system control unit. According to the high-performance liquid chromatograph of the third aspect using the system controller according to the present invention, it is possible to easily and accurately perform key operations such as control instructions on a keyboard. Further, according to the high performance liquid chromatograph of claim 4 using the system controller according to the present invention, the chromatogram to which each spectrum belongs can be clarified, and the conditions at the time of spectrum measurement can be recorded more accurately. it can. Further, the chromatogram data also has more information about the sample as a result of the addition of the spectral data, so that it can be grasped more accurately.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram of a schematic configuration of an HPLC according to one embodiment of the present invention.

FIG. 2 is an explanatory diagram of a schematic configuration of a detector according to one embodiment of the present invention.

FIG. 3 is an explanatory diagram of an example of a spectrum measurement screen displayed on a display using the HPLC shown in FIG. 1;

FIG. 4 is an explanatory diagram of an example of a spectrum analysis screen displayed on a display using the HPLC shown in FIG. 1;

FIG. 5 is an explanatory diagram of a management structure concept of a control function item in a system controller.

FIG. 6 is an explanatory diagram of a control function item selection screen in the system controller.

FIG. 7 is an explanatory diagram of a schematic configuration of a detector used in a conventional HPLC.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 10 ... Measurement part 12 ... System controller 14 ... Device communication line 24 ... Detector 30 ... Photodetector 32 ... Preamplifier 34 ... A / D converter 36 ... Calculation part 38 ... CPU 40 ... Keyboard 42 ... Display part 44 ... Setting part 46: System control unit 48: Data processing unit 50: Data management unit 52: Display control unit

Continuation of the front page (72) Inventor Miki Kuwashima Inside of Nihon Bunko Co., Ltd., 2967, Ishikawa-cho, Hachioji-shi, Tokyo (72) Inventor Koji Yoshida 5th Nippon Bunko Co., Ltd., 2967 Ishikawacho, Hachioji-shi, Tokyo (72) Inventor Hitomi Abe 5th Japan 2953 Ishikawacho, Hachioji-shi, Tokyo Nippon Bunko Co., Ltd. (72) Invention Shao Ping 5 Nihon Bunko Co., Ltd. at 2967 Ishikawa-cho, Hachioji-shi, Tokyo (56) References JP-A-5-240849 (JP, A) JP-A-5-265682 (JP, A) JP-A-60 JP-A-143765 (JP, A) JP-A-4-356892 (JP, A) JP-A-4-313932 (JP, A) JP-B-56-5936 (JP, B1) (58) Fields investigated (Int. . ^7, DB name) G01N 30/86

Claims (4)

(57) [Claims] 1. A pump, a sample injector, a column, and detection.
A measuring unit configured to separate and elute the sample for measurement,Measurement equipmentComprehensive setting of measurement conditions
Control system controlDepartment,  SaidData transferred from the detectorData to be processed
processingDepartment,  The data contents of the system control unit and the data processing unit are managed.
Data managementDepartment,  Control contents in the system control unit and the data processing unit
And settings to set processing detailsDepartment,  Input for inputting setting items and setting values to the setting unitDepartment,  A display for displaying the contents of the data management
displayDepartment, System controller consisting of ,Device for connecting the measurement unit and the system controller
Communication line between HasThe measuring unit and the system controller
Roller is configured as a separate body, The communication line between the devices is connected to a plurality of devices including the measuring unit.
Communication with the system controller is handled collectively.
I  SaidMeasuring unitIs a photodetector and an analog from the photodetector.
A preamplifier to which a log signal is input and a signal from the preamplifier
A which receives the analog signal of
A / D converter and a digital signal from the A / D converter
Signal is input, and the digital signal is arithmetically averaged.
A high-performance liquid chromatograph comprising: a calculation unit
Graph. (2)The high performance liquid chromatograph according to claim 1.
In the graph,  The data from the detector is stored in a binary file
High-performance liquid chromatograph characterized by being transferred to a data processing unit
Tograph. (3)3. The method according to claim 1, wherein
In high performance liquid chromatography, A frame memory is added to the display unit,  Connecting the system control unit and the display unit,
The control contents of the control section are arranged in a hierarchical structure,
Display in the window frame and on one screen from the upper hierarchy
Display control to simultaneously display multiple window frames in the hierarchyDepartment
ToA high-performance liquid chromatograph comprising: 4. The high-performance liquid chromatograph according to claim 1 , wherein said measuring section measures chromatogram data and spectral data, and said data managing section records the measured chromatogram data into a spectrum. A high-performance liquid chromatograph characterized in that data is added and managed and stored.