Automatic analysis device with HPLC and control method for the automatic analysis device

Abstract

The present application provides an automatic analysis device with HPLC, which can automatically determine the completion of column equilibration for preparation action of measurement, and determine the error position when an error occurs during equilibration. The automatic analysis device (100) comprises: a liquid feeding part (102) with a liquid feeding device (106) and a liquid feeding flow path (C0) and feeding mobile phase; a sample introduction part (103) for introducing sample into mobile phase; a separation column (113) for separating sample into multiple components; a detector (105) for detecting components; and a control part (114). The pressure sensor (107) detects the pressure of the liquid feeding flow path (C0), and the control part (114) calculates the pressure rise rate after the start of mobile phase feeding, the compression pressure change amount and the pressure average after the mobile phase feeding lasts for a certain time based on the pressure detected by the pressure sensor (107), and determines the completion of equilibration of the separation column (113).

Description

Technical Field

[0001] This invention relates to an automated analytical apparatus with HPLC and a control method for the automated analytical apparatus. Background Technology

[0002] HPLC (High-Speed ​​Liquid Chromatography) is an analytical instrument that uses liquid as the mobile phase delivered to the separation column to separate the sample. In liquid chromatography, the goal is to shorten the analysis time and improve the separation performance by reducing the particle size of the packing material in the separation column and using the liquid compressed under high pressure through a liquid delivery device for analysis.

[0003] The liquid sample containing the analyte, introduced from the injection section into the analytical flow path, is fed by the mobile phase to the separation column. The component detection method performed by an automated HPLC system is as follows: the liquid sample is separated into multiple components using the difference in affinity between the stationary phase packed into the separation column and the mobile phase, and each separated component is detected using a detector.

[0004] HPLC data are expressed as peak values ​​representing the relationship between sample retention time and detector signal intensity. Retention time is the time to the peak, and under identical analytical conditions, each sample component represents substantially the same value. Therefore, retention time is used as information for identifying separated components.

[0005] At the start of an HPLC analysis, as preparation for the assay, the initial solvent for analysis is introduced for column equilibration. Column equilibration typically involves introducing solvent at least 10 times the column volume. The completion of equilibration is judged by the user based on criteria such as pressure fluctuations and detector baseline stability.

[0006] After the measurement begins, sometimes the liquid delivery pressure and the detection time of the analyte components change in one direction, or sometimes the user judges that the equilibration is not sufficient and performs a re-measurement.

[0007] In addition, the liquid delivery in HPLC analysis is carried out under high pressure.

[0008] Patent document 1 describes a technique that monitors the upper and lower limits of the pump's normal pressure, and for example, issues a pressure abnormality alarm when the pressure exceeds the upper limit, prompting the user to check. In the event of a pressure abnormality, the pumping operation needs to be stopped immediately to prevent damage to the pump, and it should be confirmed whether the flow path is blocked.

[0009] In addition, if the level is below the lower limit, check whether the delivery pump is malfunctioning or whether there is a leak from the piping connection.

[0010] Existing technical documents

[0011] Patent documents

[0012] Patent Document 1: US2016 / 0236114A1 Summary of the Invention

[0013] The technical problem that the invention aims to solve

[0014] However, in the technology described in Patent Document 1, as mentioned above, in the event of abnormal pressure, it is necessary to immediately stop the liquid delivery to prevent damage to the liquid delivery pump and to check whether the flow path is blocked.

[0015] In addition, if the level is below the lower limit, it is necessary to check whether the delivery pump is malfunctioning or whether there is a leak from the piping connection.

[0016] These confirmations involve complex tasks such as disassembling piping and locating leaks, increasing solvent consumption. Furthermore, users must verify the completion of column equilibration, further increasing their workload.

[0017] The purpose of this invention is to provide an automated analytical apparatus with HPLC and a control method for the automated analytical apparatus, which can automatically determine the completion of column equilibration as a preparatory action for determination, and can identify the location of the error if an error occurs during the equilibration process.

[0018] Technical means for solving technical problems

[0019] To achieve the above objectives, the present invention is configured as follows.

[0020] An automated analytical apparatus with HPLC includes: a delivery unit having a delivery device and a delivery flow path connected to the delivery device for delivering a mobile phase; a sample introduction unit for introducing a sample into the mobile phase delivered from the delivery unit; a separation column for introducing the sample from the sample introduction unit and separating the sample into multiple components; a detector for detecting the components separated from the separation column; and a control unit for controlling the delivery unit, the sample introduction unit, and the detector. The delivery unit has a pressure sensor that detects the pressure in the delivery flow path. Based on the pressure detected by the pressure sensor, the control unit calculates the pressure rise rate after the initial delivery of the mobile phase, the pressure change and pressure average after the delivery of the mobile phase continues for a certain period of time, and determines the completion of column equilibration.

[0021] Furthermore, in the control method of an automated analytical apparatus with HPLC, the automated analytical apparatus includes: a liquid delivery unit having a liquid delivery device and a liquid delivery flow path connected to the liquid delivery device for delivering a mobile phase; a sample introduction unit for introducing a sample into the mobile phase; a separation column for separating the sample into multiple components; a detector for detecting the separated components; and a control unit for controlling the liquid delivery unit, the sample introduction unit, and the detector. The control method detects the pressure of the liquid delivery flow path, and based on the detected pressure, calculates the pressure rise rate after the initial delivery of the mobile phase by the liquid delivery unit, the change in compression pressure and the average pressure after the delivery of the mobile phase by the liquid delivery unit continues for a certain period of time, and determines the completion of the equilibration of the separation column.

[0022] Invention Effects

[0023] According to the present invention, an automated analytical apparatus having HPLC and a control method for the automated analytical apparatus can be provided, which can automatically determine the completion of column equilibration as a preparatory action for determination, and can also determine the location of the error if an error occurs during the equilibration process. Attached Figure Description

[0024] Figure 1 This is a simplified structural diagram of the automated analytical apparatus with HPLC involved in Example 1.

[0025] Figure 2 This is a flowchart for determining the completion of column balancing in Example 1.

[0026] Figure 3A Is Figure 2 A graph showing the rate of increase in pressure within a specified range.

[0027] Figure 3B Is Figure 2 A graph showing the rate of increase in pressure when it exceeds the specified value.

[0028] Figure 4 This is a flowchart of the process for determining the leakage location in Implementation Example 1.

[0029] Figure 5 This is a simplified structural diagram of the automated analytical apparatus with HPLC involved in Example 2.

[0030] Figure 6 This is a flowchart of the process for determining the leakage location in Example 2.

[0031] Figure 7 This is a schematic diagram of the display unit in Embodiment 2. Detailed Implementation

[0032] The embodiments of the present invention will be described with reference to the accompanying drawings.

[0033] The workflow of the automated analysis device according to the present invention will be described. It consists of the following steps: a "start-up step" in which the automated analysis device is started after the power is turned on, and communication between the analysis unit and the control unit is confirmed, and the status of each sensor and each consumable is confirmed; a "pre-measurement preparation step" in which the user or service personnel select and perform maintenance items; a "formal measurement step" in which calibration measurement, QC (Quality Control) measurement used to maintain analytical quality, and sample measurement are performed; a "standby step" in which the device is in standby mode after the formal measurement step; a "post-measurement preparation step" in which preparations are made to shut down the automated analysis device; and a "shutdown step" in which the automated analysis device is shut down.

[0034] The present invention is implemented in the "preparation process before measurement" of the workflow described above.

[0035] [Example]

[0036] (Example 1)

[0037] Figure 1 This is a simplified structural diagram of the automated analytical apparatus 100 with HPLC involved in Embodiment 1 of the present invention.

[0038] Figure 1 The automated HPLC analyzer 100 generally consists of a mobile phase tank 101, a liquid delivery unit 102 (liquid delivery section), a sample introduction unit 103 (sample introduction section), a column temperature adjustment unit (column temperature adjustment section) 104, a detector 105, an integrated control unit 114, an operation unit 118, and a display unit 119.

[0039] The liquid delivery unit 102 (liquid delivery section) and the sample introduction unit 103 (sample introduction section) are connected via the analytical flow path C1 (first analytical flow path), and the mobile phase is introduced into the sample introduction unit 103.

[0040] As an example, the liquid delivery unit 102 includes a liquid delivery device 106, a pressure detector 107, a purge valve 108, a liquid delivery flow path C0, an analytical flow path C1 (first analytical flow path), and a waste liquid flow path C2. The liquid delivery device 106 has the function of drawing mobile phase from the mobile phase tank 101 for conveying and separating the sample, compressing it under high pressure, and discharging it.

[0041] As an example, the liquid delivery unit 102 can be configured as an HPLC system capable of delivering one or more mobile phases from a single liquid delivery device 106.

[0042] Pressure detector 107 is a sensor device (pressure sensor) that detects (monitors) the pressure in the delivery flow path C0 of the mobile phase in delivery unit 102 and in the piping up to detector 105. Purge valve 108 is connected downstream of delivery device 106 and has the function of selectively connecting delivery flow path C0 to analytical flow path C1 or waste flow path C2 connected to sample introduction unit 103.

[0043] Furthermore, the purge valve 108 is configured to form a sealed state that is not connected to either the analytical flow path C1 or the waste liquid flow path C2 when a pressure test is performed.

[0044] The sample introduction unit 103 generally consists of a sample introduction valve 109, a sample metering pump 110, and a needle 111. The sample introduction valve 109 is connected to the aforementioned analytical flow path C1 and has a switching function for introducing the mobile phase into the downstream analytical flow path C3 (the second analytical flow path). The sample introduction valve 109 has a sample inlet 112 for introducing the sample. The sample metering pump 110 has the function of discharging the analyte sample through the needle 111 into the sample inlet 112. The sample introduced from the sample metering pump 110 into the sample introduction valve 109 mixes with the mobile phase and is discharged into the analytical flow path C3. The sample introduction valve 109 is also connected to the waste liquid flow path C4.

[0045] The column temperature adjustment unit 104 can accommodate the separation column 113, which is connected to the sample introduction unit 103 via the analytical flow path C3, so that the sample introduced from the sample introduction unit 103 through the mobile phase is separated into multiple components. The detector 105 is connected downstream of the column temperature adjustment unit 104 via the analytical flow path C5 (the third analytical flow path), and has the function of detecting the components of the sample separated in the separation column 113.

[0046] The integrated control unit 114 is a control unit used to control the liquid delivery unit 102, the sample introduction unit 103, the column temperature adjustment unit 104, and the detector 105 and to acquire HPLC data.

[0047] As an example, the integrated control unit 114 includes: an analysis condition setting unit 115, which sets the analysis conditions for controlling the liquid delivery unit 102, the sample introduction unit 103, and the column temperature adjustment unit 104; a data processing unit 116, which analyzes the analysis results output from the detector 105; and an analysis control unit 117, which causes each unit 102-104 to output the start time of each analysis, etc.

[0048] The integrated control unit 114 calculates the pressure rise rate after the liquid delivery unit (liquid delivery section) 102 starts delivering the mobile phase, the amount of pressure change after the liquid delivery continues for a certain period of time, and the average pressure based on the pressure detected by the pressure sensor 107, and automatically determines the completion of the balancing of the separation column 113.

[0049] The operation unit 118 includes input devices such as a keyboard, keypad, and mouse, and is a device for users to input various instructions related to control in the integrated control unit 114.

[0050] The display unit 119 is a device for displaying analysis conditions and analysis results, and may be composed of, for example, a liquid crystal display or an organic EL display.

[0051] Next, refer to Figure 2 The flowchart shown illustrates an example of the steps for determining the completion of column equilibration in the automated HPLC analyzer 100 of Example 1. The determination of column equilibration completion is performed by the integrated control unit 114.

[0052] Once the liquid delivery begins as a preparatory step for the measurement, for example in the case of blockage in the separation column 113 or piping, the rate of pressure rise increases. If the liquid delivery continues as before, even if the liquid delivery is stopped under pressure limits, there will be a significant overpressure, which may adversely affect the components within the automatic analyzer 100.

[0053] Therefore, after the liquid delivery begins in step S201, the integrated control unit (hereinafter referred to as the control unit) 114 calculates the rate of increase of pressure detected by the pressure detector 107, and determines in step S202 whether the rate of increase of pressure is within the specified rate of increase value.

[0054] If the pressure rise rate is greater than the specified rise rate value, proceed to step S206, display alarm 1 (replacement alarm for separation column or piping) on ​​display unit 119, and immediately stop liquid delivery, thereby minimizing damage to the automatic analysis device 100.

[0055] Figure 3A It is a graph showing the pressure changes during normal liquid delivery. Figure 3B This is a graph showing the pressure changes during abnormal conditions. By monitoring pressure and time (P / T), abnormal pressure rises can be detected instantly, and fluid delivery can be stopped. The specified values ​​vary depending on the separator column 113, piping system, and flow path system used, and are determined experimentally. If the pressure rise rate is greater than the specified value, alarm 1 is generated as described above, prompting the user to replace the separator column or piping.

[0056] In step S202, if the pressure rise rate is within the specified value, the liquid delivery continues, proceeding to step S203, where the liquid delivery continues until the pressure change is within the specified pressure change value.

[0057] That is, in step S203, it is determined whether the pressure change is within the specified pressure change value. If it is within the specified value, the process proceeds to step S207 to determine whether the number of retries is less than N (the specified number of determinations). If it is less than N, the process returns to step S203.

[0058] In step S207, if the number of retries is N, it is determined that the pressure change is not within the specified pressure change value. In this case, proceed to step S210 and display alarm 2 (alarm for purging and cleaning of the flow path) on the display unit 119.

[0059] The duration of continued liquid delivery varies depending on the column capacity and solvent used, and users can set the duration. Furthermore, if the pressure change does not reach the specified value within the set time, liquid delivery can continue (retry) until the set time has elapsed again; users can set the number of retries.

[0060] In step S203, if the pressure change reaches a specified value within a set time, the process proceeds to step S204 to determine whether the average pressure is within a specified pressure range. For example, if the user uses a separation column 113 typically operating at 60 MPa and sets 55 MPa-65 MPa as a specified value, then if the pressure is within the specified range, balancing is considered complete.

[0061] Then, proceed to step S205 to complete the balancing process.

[0062] In step S204, if the average pressure is not within the specified pressure range, proceed to step S208 to determine if it is higher than the specified pressure range. In step S208, if the average pressure is higher than the specified upper pressure limit (e.g., 65 MPa), proceed to step S209, and display alarm 3 (replacement warning for the separation column or piping) on ​​the display unit 119, urging the user to replace the column and piping.

[0063] In step S208, if the average pressure is lower than the specified lower pressure limit (e.g., 55 MPa), a leak from the piping connection or other parts is suspected, and the process proceeds to step S211, following the leak confirmation procedure. Figure 4 The workflow shown is used to determine which part of the pipeline caused the leak.

[0064] Reference Figure 4 ,Should Figure 4 Show Figure 2The leakage confirmation process is shown in step S211.

[0065] Figure 4 In step S401, it is determined whether the amount of compression pressure change k in the compression zone of the liquid delivery device 106 is below a constant value (a specified amount of compression pressure change). If the amount of compression pressure change k is below a constant value, the process proceeds to step S405, where it is determined that there is a leak from the cylinder in the liquid delivery device 106, and an alarm 4 (alarm indicating a liquid delivery leak from the cylinder in the liquid delivery device 106) is displayed on the display unit 119.

[0066] In this case, the user needs to replace consumable parts such as the plunger seal in the cylinder of the liquid delivery device 106.

[0067] In step S401, if the compression pressure change k is not below a constant value (specified compression pressure change) and there is no abnormality, proceed to step S402, set the purge valve 108 to a sealed state, and perform a pressure resistance test to determine if it is normal. As described above, the purge valve 108 can be set to a sealed state by moving it to a position not connected to any flow path.

[0068] In addition, the purge valve 108 can be sealed by disassembling the piping and installing a sealing plug at one time, or by preparing the port of the purge valve 108 to install a sealing plug.

[0069] In step S402, if the pressure test result of the purge valve 108 is abnormal, proceed to step S406, and display alarm 5 (alarm that there is a liquid leakage on the upstream side of the purge valve 108) on the display unit 119, determine that there is a leak in the flow path piping on the upstream side of the purge valve 108, and urge the user to replace the part, etc.

[0070] In step S402, if the pressure test result of the purge valve 108 is normal, proceed to step S403 to continue performing the pressure test of the sample inlet valve (injection valve) 109. In step S403, if the pressure test result of the sample inlet valve 109 is abnormal, proceed to step S407, and display alarm 6 (alarm indicating liquid leakage between the sample inlet valve 109 and the purge valve 108) on the display unit 119, determining that there is a leak in the flow path piping between the sample inlet valve 109 and the purge valve 108, and urging the user to replace it.

[0071] In step S403, if the pressure test result of the sample inlet valve 109 is normal, it is determined that there is a liquid delivery leak downstream of the sample inlet valve 109, and the process proceeds to step S404. An alarm 7 (alarm that there is a leak downstream of the sample inlet valve 109) is displayed on the display unit 119, urging the user to replace it.

[0072] Figure 2 In step S208, leaks are visually identifiable when the pressure is significantly low, but sometimes slight, slow leaks that are not visible to the naked eye occur when the pressure is slightly low. Figure 4 The workflow shown helps in identifying leak locations.

[0073] As described above, according to Embodiment 1 of the present invention, the completion of column balancing, which is performed as a preparatory action for measurement, is automatically determined. At the same time, if an error occurs during the balancing process, the location of the error is identified and alarms 1 to 7 are displayed on the display unit 119.

[0074] Therefore, an automated analytical apparatus with HPLC and a control method for the automated analytical apparatus can be provided, which can automatically determine the completion of column equilibration and identify the location of the error if an error occurs during the equilibration process.

[0075] (Example 2)

[0076] Next, Embodiment 2 of the present invention will be described.

[0077] Figure 5 This is a simplified structural diagram of the automated analytical apparatus 100A with HPLC involved in Example 2. Figure 5 In this document, the same reference numerals are used to mark the same components as in Example 1, and repeated descriptions are omitted below.

[0078] The difference between the automated HPLC analysis device 100A in Example 2 and Example 1 is that the liquid delivery unit 102 includes two liquid delivery devices 106A (first liquid delivery device) and 106B (second liquid delivery device), and the two liquid delivery devices 106A and 106B are respectively connected to different mobile phase tanks 101A (first mobile phase tank) and 101B (second mobile phase tank).

[0079] Pressure detectors 107A and 107B are connected to liquid delivery paths C01 and C02, respectively, which are connected to the outlets of liquid delivery devices 106A and 106B. Furthermore, a purge valve 108A is provided downstream of the two liquid delivery devices 106A and 106B for selectively switching between the analytical flow path and the waste liquid flow path. The mobile phase discharged from the purge valve 108A is introduced into the sample introduction unit 103 via the confluence section Q1.

[0080] The structure of the sample introduction unit 103 is the same as in Example 1. Additionally, Figure 5In the example, the confluence section Q1 is located downstream of the purge valve 108A, but it can also be located upstream of the purge valve 108A. In this case, the pressure detector shared by the liquid delivery devices 106A and 106B can be located downstream of the confluence section Q1 and upstream of the purge valve 108A.

[0081] On the other hand, the column temperature adjustment unit 104 is configured to accommodate multiple separation columns 113A, 113B, 113C, 113D, and 113E arranged side by side. The multiple separation columns 113A-113E contain packing materials with different properties. Furthermore, the column temperature adjustment unit 104 includes a bypass flow path 120 for introducing the mobile phase into the detector 105 without passing through the separation columns 113A-113E.

[0082] The bypass flow path 120 is arranged side by side with the multiple separation columns 113A-113E in the column temperature adjustment unit 104.

[0083] The column temperature adjustment unit 104 has a column switching valve (first column switching valve) 121 and a column switching valve 122 (second column switching valve) on the upstream and downstream sides of the separation columns 113A-113E for selectively connecting any separation column 113A-113E or bypass flow path 120 to the analysis flow path.

[0084] The column switching valves 121 and 122 include multiple first piping connections connected to the separation columns 113A-113E and the bypass flow path 120, a second piping connection connected to the analytical flow path (analytical flow path C3, analytical flow path connecting column switching valve 122 and detector 105), and a movable flow path for selectively connecting the first and second piping connections.

[0085] By rotating the movable flow path around one end of the second piping connection, one end of the movable flow path can be connected to any one of the first piping connections, thereby connecting any one of the multiple separation columns 113A-113E and the bypass flow path 120 to the analysis flow path.

[0086] Here, the column switching valves (column selection valves) 121 and 122 can not only be set to connect any one of the multiple separation columns 113A-113E and the bypass flow path 120 to the analysis flow path C3 or C5, but can also be set to selectively not connect to any one of the separation columns 113A-113E or the bypass flow path 120 (sealed state).

[0087] The structure, which has column selector valves 121 and 122, can be in a sealed state, thus... Figure 6 As shown in the flowchart, in Figure 4If the pressure test result of the sample inlet valve 109 in step S403 is normal, the pressure test process steps S601 to S605 of the column switching valves 121 and 122 can be executed to determine where the leak occurred. Figure 6 Step S403 and the steps before Figure 4 They are the same, so they are omitted.

[0088] Figure 6 In step S601, the column selector valve 121 is set to a sealed state to perform a pressure test. If the pressure test result is abnormal, the process proceeds to step S604, where an alarm 6-1 (an alarm indicating a leak between the sample inlet valve (injection valve) 109 and the column selector valve 121) is displayed on the display unit 119, and the user is urged to replace the valve.

[0089] In step S601, if the pressure test result of column switching valve 121 is normal, proceed to step S602 to perform a pressure test on column switching valve (column selector valve) 122.

[0090] Here, the flow path between the column switching valves 121 and 122 is connected to 120 as a bypass flow path.

[0091] When performing a pressure test on a flow path connected to a column, the column can be removed and connected using a coupling or similar means, or an empty column without filler can be used for the pressure test.

[0092] In step S602, if the pressure test result of the column switching valve 122 is abnormal, an alarm 6-2 (an alarm indicating a leak in the flow path piping between the column switching valve (column selector valve) 121 and the column switching valve (column selector valve) 122) is displayed on the display unit 119, and the user is urged to replace it.

[0093] In step S602, if the pressure test of the column switching valve 122 is normal, an alarm 6-3 (an alarm indicating a leak has occurred in the flow path piping downstream of the column switching valve 122) is displayed on the display unit 119, and the user is urged to replace it.

[0094] Here, in Figure 7 Detailed description Figure 5 The display unit 119 shown.

[0095] like Figure 7 As shown, the display unit 119 can display measurement results, error messages, the number of times each replacement part has been used, the replacement history of each replacement part, the determination result of this preparation action, and the historical change information (trend) of the pressure value. Figure 5 A schematic diagram of such a device structure Figure 1 It can display the predicted level of danger based on trends on a schematic diagram.

[0096] By implementing the above process, it is possible to determine which part of the flow path has leaked, prevent water leakage accidents from happening in advance, and prepare for accurate analysis.

[0097] In other words, in Example 2, similar to Example 1, an automated analytical apparatus with HPLC and a control method for the automated analytical apparatus can be provided. The column equilibration performed as a preparatory action for the determination can be automatically determined, and the location of the error can be identified if an error occurs during the equilibration process.

[0098] Furthermore, in Example 2, an automated analytical apparatus with HPLC and a control method for the automated analytical apparatus are provided. When configured to house multiple separation columns 113A, 113B, 113C, 113D, and 113E in a column temperature adjustment unit 104, it is possible to determine at which part of the column temperature adjustment unit 104 a leak occurs.

[0099] (Regarding variations of the present invention)

[0100] This invention is not limited to the embodiments described above, but also includes various modifications. For example, the above embodiments are detailed descriptions provided to facilitate understanding of the invention, and the invention is not limited to including all the structures described. That is, various changes, additions, and omissions can be made to some of the structures in the embodiments.

[0101] For example, the fault detection of the automatic analysis device of the present invention may not be limited to checking the pressure sensor value during the preparation operation, but may also be performed by detecting the fault location. In addition, besides the preparation operation, fault location detection may also be performed based on information such as "changes in holding time", "changes in pressure curve", "peak intensity of sample", and "peak amplitude" during the QC measurement described above.

[0102] Label Explanation

[0103] 101, 101A, 101B Flow Phase Tanks

[0104] 102 Liquid Delivery Unit

[0105] 103 Sample Introduction Unit

[0106] 104-column temperature control unit

[0107] 105 detector

[0108] 106, 106A, 106B liquid delivery device

[0109] 107, 107A, 107B pressure detectors (pressure sensors)

[0110] 108, 108A purge valve

[0111] 109 Injection Valve

[0112] 110 Sample metering pump

[0113] 111 needles

[0114] 112 Sample Inlet

[0115] Separation columns 113, 113A, 113B, 113C, 113D, and 113E

[0116] 114 Integrated Control Department

[0117] 115 Analysis Condition Setting Section

[0118] 116 Data Processing Department

[0119] 117 Analysis and Control Department

[0120] 118 Operations Department

[0121] 119 Display Department

[0122] 120 Bypass Flow Path

[0123] 121 and 122 column switching valves.

Claims

1. An automated analytical apparatus with HPLC, comprising: The liquid delivery unit has a liquid delivery device and a liquid delivery flow path connected to the liquid delivery device for delivering liquid to the mobile phase; A sample introduction section that introduces the sample into the mobile phase delivered from the liquid delivery section; A separation column that introduces the sample from the sample inlet and separates the sample into multiple components; A detector that detects the components separated from the separation column; and The control unit controls the liquid delivery unit, the sample introduction unit, and the detector. The automated analytical device with HPLC is characterized in that, It also has a display section. The liquid delivery unit includes: a pressure sensor that detects the pressure in the liquid delivery path; and a purge valve connected to the liquid delivery path. And a waste liquid flow path, wherein the liquid delivery section and the sample inlet section are connected to each other via a first analytical flow path. The purge valve is controlled by the control unit, selectively connecting the liquid delivery path to the first analytical path or the waste liquid path. The sample inlet section has a sample inlet valve that introduces the sample into the mobile phase introduced from the first analytical flow path. The control unit calculates the pressure rise rate after the liquid delivery unit starts delivering the mobile phase, the pressure change, and the average pressure after the liquid delivery unit continues delivering the mobile phase for a certain period of time, based on the pressure detected by the pressure sensor. It determines whether the balancing of the separation column is complete by judging whether the pressure rise rate is within a specified rise rate value, whether the pressure change is within a specified pressure change value, and whether the average pressure is within a specified pressure range. If the pressure rise rate is greater than the specified rise rate value, the display unit displays an alarm indicating that the separation column or piping needs replacement. If the pressure rise rate is within the specified rise rate value and the pressure change is not within the specified pressure change value, the pressure change is determined to be within the specified pressure change value after a specified number of determinations. If the pressure change is not within the specified pressure change value, the display unit displays an alarm for purging and cleaning of the flow path. When the pressure rise rate is within the specified rise rate value, the pressure change is within the specified pressure change value, and the average pressure is within the specified pressure range, it is determined that the balancing of the separator column is completed. When the average pressure is higher than the specified upper pressure value, the display unit displays an alarm for the replacement of the separator column or piping. When the average pressure is lower than the specified lower pressure value, it is determined in which part a leak has occurred.

2. The automated analytical apparatus with HPLC as described in claim 1, characterized in that, When the average pressure is lower than the specified lower pressure limit, the control unit determines whether the change in compression pressure is below a specified change in compression pressure. If the change in compression pressure is below the specified change in compression pressure, the display unit displays an alarm indicating a leakage of fluid from the cylinder in the fluid delivery unit. If the change in compression pressure is not below the specified change in compression pressure, a pressure test is performed on the purge valve. If the result of the pressure test is abnormal, the display unit will show an alarm indicating that a fluid leakage has occurred on the upstream side of the purge valve. If the pressure test result is not abnormal, a pressure test is performed on the sample inlet valve. If the pressure test result of the sample inlet valve is abnormal, the display unit displays an alarm indicating a leakage in the liquid supply between the sample inlet valve and the purge valve. If the pressure test result of the sample inlet valve is not abnormal, the display unit displays an alarm indicating a leakage in the liquid supply downstream of the sample inlet valve.

3. The automated analytical apparatus with HPLC as described in claim 1, characterized in that, The separation columns are multiple separation columns arranged side by side. The automated analytical apparatus with HPLC includes: A bypass flow path, which is arranged in parallel with the plurality of said separation columns; A first-column switching valve, which can selectively connect any one of the plurality of separation columns and the bypass flow path to the sample inlet valve, and can be set to selectively not connect to any one of the plurality of separation columns and the bypass flow path; and The second-column switching valve can selectively connect any one of the plurality of separation columns and the bypass flow path to the detector, and can be set to selectively not connect to any one of the plurality of separation columns and the detector. When the average pressure is lower than the specified lower pressure limit, the control unit determines whether the change in compression pressure is below a specified change in compression pressure. If the change in compression pressure is below the specified change in compression pressure, the display unit displays an alarm indicating a leakage of fluid from the cylinder in the fluid delivery unit. If the change in compression pressure is not below the specified change in compression pressure, a pressure test is performed on the purge valve. If the result of the pressure test is abnormal, the display unit will show an alarm indicating that a fluid leakage has occurred on the upstream side of the purge valve. If the pressure test result is normal, a pressure test is performed on the sample inlet valve. If the pressure test result of the sample inlet valve is abnormal, the display unit shows an alarm indicating a leakage in the liquid supply between the sample inlet valve and the purge valve. If the pressure test result of the sample inlet valve is normal, a pressure test is performed on the first column switching valve. If the pressure test result of the first column switching valve is abnormal, the display unit shows an alarm indicating a leakage in the liquid supply between the sample inlet valve and the first column switching valve. If the pressure test result of the first column switching valve is not abnormal, a pressure test of the second column switching valve is performed. If the pressure test result of the second column switching valve is abnormal, the display unit displays an alarm indicating that a fluid leakage has occurred between the first column switching valve and the second column switching valve. If the pressure test result of the second column switching valve is not abnormal, the display unit displays an alarm indicating that a leakage has occurred downstream of the second column switching valve.

4. A control method for an automated analytical apparatus with HPLC, the automated analytical apparatus comprising: The liquid delivery unit has a liquid delivery device and a liquid delivery flow path connected to the liquid delivery device for delivering liquid to the mobile phase; A sample introduction section that introduces the sample into the mobile phase delivered from the liquid delivery section; A separation column that introduces the sample from the sample inlet and separates the sample into multiple components; A detector that detects the components separated from the separation column; and The control unit controls the liquid delivery unit, the sample introduction unit, and the detector. The control method of the automated analytical apparatus with HPLC is characterized in that, The liquid delivery unit has a purge valve and a waste liquid flow path connected to the liquid delivery flow path. The liquid delivery unit and the sample inlet unit are connected to each other via a first analytical flow path. The purge valve selectively connects the liquid delivery path to either the first analytical path or the waste liquid path. The sample inlet section has a sample inlet valve that introduces the sample into the mobile phase introduced from the first analytical flow path. Detect the pressure in the liquid delivery path. Based on the detected pressure, the pressure rise rate after the liquid delivery unit starts delivering the mobile phase, the pressure change after the liquid delivery unit continues delivering the mobile phase for a certain period of time, and the average pressure are calculated. It is then determined whether the pressure rise rate is within a specified rise rate value, whether the pressure change is within a specified pressure change value, and whether the average pressure is within a specified pressure range. If the pressure rise rate is greater than the specified rise rate value, the display unit will show an alarm indicating the replacement of the separator column or piping. If the pressure rise rate is within a specified rise rate value and the pressure change is not within a specified pressure change value, the pressure change is determined to be within the specified pressure change value after a specified number of determinations. If the pressure change is not within the specified pressure change value, the display unit displays an alarm for purging and cleaning the flow path. If the pressure rise rate is within a specified rise rate value, the pressure change is within a specified pressure change value, and the average pressure is within a specified pressure range, it is determined that the balancing of the separator column is complete. If the average pressure is higher than the specified upper pressure limit, the display unit displays an alarm indicating the replacement of the separator column or piping. If the average pressure is lower than the specified lower pressure limit, it is determined in which part a leak has occurred.

5. The control method for an automated analytical apparatus with HPLC as described in claim 4, characterized in that, If the average pressure is lower than the specified lower pressure limit, it is determined whether the change in compression pressure is below the specified change in compression pressure. If the change in compression pressure is below the specified change in compression pressure, the display unit displays an alarm indicating that a leakage has occurred from the cylinder in the liquid delivery section. If the change in compression pressure is not below the specified change in compression pressure, a pressure test is performed on the purge valve. If the result of the pressure test is abnormal, the display unit will show an alarm indicating that a fluid leakage has occurred on the upstream side of the purge valve. If the pressure test result is not abnormal, a pressure test is performed on the sample inlet valve. If the pressure test result of the sample inlet valve is abnormal, the display unit displays an alarm indicating a leakage in the liquid supply between the sample inlet valve and the purge valve. If the pressure test result of the sample inlet valve is not abnormal, the display unit displays an alarm indicating a leakage in the liquid supply downstream of the sample inlet valve.

6. The control method for an automated analytical apparatus with HPLC as described in claim 4, characterized in that, The separation columns are multiple separation columns arranged side by side. The automatic analysis device includes: A bypass flow path, which is arranged in parallel with the plurality of said separation columns; A first-column switching valve, which can selectively connect any one of the plurality of separation columns and the bypass flow path to the sample inlet valve, and can be set to selectively not connect to any one of the plurality of separation columns and the bypass flow path; and The second-column switching valve can selectively connect any one of the plurality of separation columns and the bypass flow path to the detector, and can be set to selectively not connect to any one of the plurality of separation columns and the detector. If the average pressure is lower than the specified lower pressure limit, it is determined whether the change in compression pressure is below the specified change in compression pressure. If the change in compression pressure is below the specified change in compression pressure, the display unit displays an alarm indicating that a leakage has occurred from the cylinder in the liquid delivery section. If the change in compression pressure is not below the specified change in compression pressure, a pressure test is performed on the purge valve. If the result of the pressure test is abnormal, the display unit will show an alarm indicating that a fluid leakage has occurred on the upstream side of the purge valve. If the pressure test result is normal, a pressure test is performed on the sample inlet valve. If the pressure test result of the sample inlet valve is abnormal, the display unit shows an alarm indicating a leakage in the liquid supply between the sample inlet valve and the purge valve. If the pressure test result of the sample inlet valve is normal, a pressure test is performed on the first column switching valve. If the pressure test result of the first column switching valve is abnormal, the display unit shows an alarm indicating a leakage in the liquid supply between the sample inlet valve and the first column switching valve. If the pressure test result of the first column switching valve is not abnormal, a pressure test of the second column switching valve is performed. If the pressure test result of the second column switching valve is abnormal, the display unit displays an alarm indicating that a fluid leakage has occurred between the first column switching valve and the second column switching valve. If the pressure test result of the second column switching valve is not abnormal, the display unit displays an alarm indicating that a leakage has occurred downstream of the second column switching valve.

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