Method for adjusting a pressure sensor and liquid chromatography apparatus

Abstract

The inspection and adjustment of the pressure sensor can be easily performed without adding a complicated mechanism. Therefore, in the liquid chromatograph, a first output value P1 of the pressure sensor (107) measured when a flow path is made in an open state to the atmosphere or a first chromatographic column (110) in which a packing is not filled is set in a chromatographic column setting portion (104) is obtained, a second output value P2 of the pressure sensor measured when a second chromatographic column (111) having a known pressure resistance Ps is set in the chromatographic column setting portion is obtained, and the gain of the pressure sensor is updated using the first output value P1 and the second output value P2.

Description

Technical Field

[0001] This invention relates to a method for adjusting a pressure sensor and a liquid chromatography analysis apparatus. Background Technology

[0002] Liquid chromatography (LC) is a chromatograph that uses a liquid as the mobile phase delivered to a chromatographic column for separating samples. The liquid sample, containing the analyte introduced into the analytical flow path from the injection port, is transported to the column via the mobile phase. The liquid sample is separated into multiple components by utilizing the difference in affinity between the stationary phase (packing material) packed in the column and the mobile phase. The separated components are then detected using detectors such as UV / Vis spectrophotometers, fluorometers, and mass spectrometers.

[0003] High-performance liquid chromatography (HPLC) aims to shorten analysis time and improve separation performance by reducing the particle size of the column packing material and using liquid compressed under high pressure via a delivery device for analysis. In particular, HPLC systems employing columns with packing material having a particle size of less than 2 μm are called ultra-high performance liquid chromatographs (UHPLC).

[0004] In liquid chromatography (LC), as a result of performance improvements achieved by miniaturizing the particle size of the column packing material, high pressure resistance is required in the apparatus or flow paths constituting the LC, particularly in the upstream side of the column. This is because, with the increasing pressure of the apparatus, pressure leakage from the delivery device and analytical flow path under high-pressure environments has a greater impact on analytical performance. Therefore, the reliability of the pressure sensors used to detect the pressure in the delivery device and analytical flow path is crucial.

[0005] If the performance of the pressure sensor deteriorates due to changes over time or malfunction, the liquid delivery device may not meet the expected performance, thus requiring regular inspection and adjustment. Previously, users primarily performed offset adjustments as a form of pressure sensor maintenance (Patent Document 1). In contrast, gain adjustment of the pressure sensor is performed by skilled technicians using specialized equipment such as external pressure gauges, which is not easy to execute.

[0006] Existing technical documents

[0007] Patent documents

[0008] Patent Document 1: International Publication No. 2015 / 033664 Summary of the Invention

[0009] The problem that the invention aims to solve

[0010] It can easily perform pressure sensor checks and adjustments without adding complex mechanisms.

[0011] Methods for solving problems

[0012] A method for adjusting a pressure sensor in a liquid chromatography analyzer, the liquid chromatography analyzer comprising: a column mounting section; a delivery device for supplying mobile phase to a column mounted in the column mounting section; and a pressure sensor for detecting pressure in a flow path from the delivery device to the column mounted in the column mounting section, the adjustment method comprising: a first step of obtaining a first output value P1 of the pressure sensor measured with the flow path open to the atmosphere or with a first column unfilled in the column mounting section; a second step of obtaining a second output value P2 of the pressure sensor measured with a second column having a known pressure resistance Ps mounted in the column mounting section; and a gain update step of updating the gain of the pressure sensor using the first output value P1 and the second output value P2.

[0013] Invention Effects

[0014] According to the present invention, a liquid chromatography analysis apparatus and a method for adjusting a pressure sensor are provided, which can easily perform the inspection and adjustment of a pressure sensor without adding a complex mechanism.

[0015] Other issues and new features become clear from the description and accompanying drawings in this specification. Attached Figure Description

[0016] Figure 1 This is a schematic structural diagram of the liquid chromatography analysis apparatus of Example 1.

[0017] Figure 2 This is a flowchart of the pressure sensor inspection and adjustment steps.

[0018] Figure 3 This is used to illustrate the pressure-modified gain update process.

[0019] Figure 4 This is a schematic diagram of the liquid chromatography analysis apparatus of Example 2. Detailed Implementation

[0020] Example 1

[0021] Reference Figure 1The schematic diagram illustrates a structural example of the liquid chromatography analysis apparatus 100. The liquid chromatography analysis apparatus 100 generally consists of a mobile phase chamber 101, a liquid delivery unit 102, a sample introduction unit 103, a column setting unit 104, a detector 105, a control unit 112, an operation unit 113, and a display unit 114.

[0022] As an example, the liquid delivery unit 102 includes a liquid delivery device 106, a pressure sensor 107, a flow path switching valve 108, a liquid delivery flow path C0, an analytical flow path C1, and a liquid discharge flow path C2. The liquid delivery device 106 draws the mobile phase used in sample delivery and separation from the mobile phase tank 101, compresses it under high pressure, and then discharges it. As the liquid delivery unit 102, a structural example is shown where liquid delivery is performed by mixing one or more mobile phases using a single liquid delivery device 106.

[0023] Pressure sensor 107 detects the pressure in the piping of the column, which is located in the column mounting section, from the mobile phase delivery path C0 of the delivery section 102. Flow path switching valve 108 is connected downstream of the delivery device 106 to selectively connect the delivery path C0 to either the analytical path C1 or the discharge path C2 connected to the sample inlet section 103.

[0024] The column setup 104 can be replaced with a separating column 109 during analysis, and can be replaced with an empty column 110 or a column 111 with known pressure resistance during pressure sensor 107 inspection and adjustment. The separating column 109, the empty column 110, and the column 111 with known pressure resistance are all connected to the sample inlet 103 via the analytical flow path C3. The pressure resistance value of column 111 is Ps. During analysis, the separating column 109, located in the column setup 104, separates the sample introduced from the sample inlet 103 through the mobile phase into individual components. The detector 105 is connected downstream of the column setup 104 to detect the individual components of the sample separated in the separating column 109.

[0025] The control unit 112 controls the liquid delivery unit 102, sample introduction unit 103, column setting unit 104, and detector 105, acquiring liquid chromatography data and processing data for pressure sensor inspection and adjustment. The operation unit 113 includes input devices such as a keyboard, numeric keys, and a mouse, allowing the user to input various device-related instructions into the control unit 112. The display unit 114 is a device for displaying analytical conditions and results, and may be, for example, a liquid crystal display or an organic EL display.

[0026] Reference Figure 2 The flowchart describes the sequence of checks and adjustments performed by the control unit 112 on the pressure sensor 107 in Embodiment 1.

[0027] In the first step (steps S201 and S205), the flow path switching valve 108 is switched to the discharge flow path C2 side, and the output value P1 of the pressure sensor 107 is obtained with the flow path where the pressure sensor 107 is installed in an open state to the atmosphere. Alternatively, an empty chromatographic column 110 with pressure resistance infinitely close to zero and no packing material is installed in the column setting section 104, and the output value P1 of the pressure sensor 107 is obtained when the liquid is delivered under specified delivery conditions. The specified delivery conditions refer to the delivery conditions when performing analysis in the liquid chromatography analysis apparatus 100. The same applies to the second step described later. In either case, the true value of the output value P1 is 0.

[0028] In the second process (steps S202 and S206), a chromatographic column 111 with known pressure resistance (Ps) is set in the column setting section 104, and the output value P2 of the pressure sensor 107 is obtained when the liquid is delivered under specified delivery conditions.

[0029] In the pressure sensor output value determination (steps S203 and S207), it is determined whether it is within the allowable range (±Pd) by Equation 1.

[0030] -Pd < (P2 - P1) -Ps < +Pd (Equation 1)

[0031] In Equation 1, it is determined whether the difference (P2﹣P1) between the output value P2 of the pressure sensor 107 obtained in the second process and the output value P1 of the pressure sensor 107 obtained in the first process is within the allowable range (±Pd) relative to the true value (Ps﹣0).

[0032] In step S203, the process ends normally if the output value of the pressure sensor is within the allowable range, and updates the gain of the pressure correction formula if the output value of the pressure sensor is determined to be outside the allowable range.

[0033] use Figure 3 The process of pressure correction gain update (step S204) will be explained below. Pressure sensor 107 corrects the detected pressure value using pressure correction and outputs it. Regarding the pressure correction of pressure sensor 107, the output value (detected value) of pressure sensor 107 before correction is set to P. r Set the output value of the corrected pressure sensor 107 to P. m Set the gain to K G Set the offset to K O It is represented by the following equation 2.

[0034] P m =K G (P r -K O (Equation 2)

[0035] Update gain K G This makes the pressure correction formula expressed by Equation 2 affect the output value P of the pressure sensor 107 before correction. r The corrected output value P m This represents the truth value. Additionally, regarding the offset K... O In the first process, calculate and update to satisfy 0 = P m =P r -K O .

[0036] Let P be the output value before correction in the second process. r =P0. In the second process (step S202), the output value P2 is calculated using the pressure correction formula before the update. When the gain K in the pressure correction formula before the update is... G When =K1, it is (P2﹣P1)=P m =K1(P0﹣K O (Equation 3)

[0037] In the pressure trimming gain update, if the gain K in the updated pressure trimming is... G =K2, then the true value of the pressure resistance of column 111 is Ps, thus determining the gain K. G Make (Ps﹣0)=P m =K2(P0﹣K O (Equation 4) is sufficient.

[0038] Therefore, Equation 5 can be used to update the gain K2.

[0039] K2=K1×Ps / (P2﹣P1) (Equation 5)

[0040] Equation 5 can be derived from Equations 3 and 4.

[0041] After the pressure correction gain update (step S204), the first step (step S205), the second step (step S206), and the pressure sensor output value determination (step S207) are executed again. If the pressure sensor output value determination (step S207) is within the acceptable range, the process ends normally. If it is outside the acceptable range, a pressure sensor malfunction is notified. In this case, the possibility of an malfunction in the pressure sensor 107 and the possibility of an malfunction such as leakage in the liquid delivery device 106 are considered.

[0042] Furthermore, an example is shown where an atmospheric open or empty column 110 is used in the first step. However, the pressure correction is a two-point correction, so correction can be performed as long as the output values ​​of the pressure sensor 107 at low pressure and the pressure sensor 107 at high pressure are available, along with the pressure values ​​that serve as their respective references. Therefore, even if a column with known pressure resistance, which has a smaller pressure resistance than the column 111 used in the second step (steps S202 and S206) is used instead of the empty column 110, pressure correction can still be performed.

[0043] In this way, the gain adjustment of the pressure sensor 107 can be easily performed simply by replacing the separation column installed in the column setting section with an empty column or a column with known pressure resistance, without requiring special knowledge or additional complex mechanisms.

[0044] Example 2

[0045] Next, refer to Figure 4 The liquid chromatography analysis apparatus 100A of Example 2 will be described. Figure 4 In this document, the same reference numerals are used for the same components as in Example 1, and repeated descriptions are omitted below. The liquid chromatography analysis apparatus 100A generally consists of a mobile phase chamber 101, a liquid delivery unit 102, a sample introduction unit 103, a chromatographic column unit 116, a detector 105, a control unit 112, an operation unit 113, and a display unit 114.

[0046] The column unit 116 has column switching valves 115A and 115B on the upstream and downstream sides of the column setting section 104A to 104C for selectively connecting the separating column 109, the empty column 110, and the column 111 with known pressure resistance to the analytical flow path.

[0047] The pressure sensor 107 is inspected and adjusted in the same order as in Example 1. However, during the first step (steps S201 and S205), an empty chromatographic column 110 is connected to the analytical flow path in the column unit 116, and during the second step (steps S202 and S206), a chromatographic column 111 with known pressure resistance is connected to the analytical flow path in the column unit 116.

[0048] Therefore, the chromatographic column can be switched by selecting the flow path through the column switching valves 115A and 115B, so there is no need for manual column switching. The control unit 112 can automatically check and adjust the pressure sensor 107.

[0049] Explanation of reference numerals in the attached figures

[0050] 100, 100A…Liquid chromatography analysis apparatus, 101…Mobile phase chamber, 102…Liquid delivery unit, 103…Sample introduction unit, 104, 104A, 104B, 104C…Column setting unit, 105…Detector, 106…Liquid delivery device, 107…Pressure sensor, 108…Flow path switching valve, 109…Separation column, 110…Empty column, 111…Column with known pressure resistance, 112…Control unit, 113…Operation unit, 114…Display unit, 115A, 115B…Column switching valve, 116…Column unit.

Claims

1. A method for adjusting the pressure sensor of a liquid chromatography analyzer. The liquid chromatography analysis apparatus includes: Column setup section; A liquid delivery device that delivers mobile phase to the chromatographic column disposed in the column mounting section; and A pressure sensor detects the pressure in the flow path from the liquid delivery device to the chromatographic column disposed in the column mounting section. Its features are, The adjustment method has the following characteristics: The first step is to obtain the first output value P1 of the pressure sensor, which is measured by either making the flow path open to the atmosphere or by setting a first chromatographic column without packing material in the chromatographic column setting section. The second step involves obtaining the second output value P2 of the pressure sensor, measured by installing a second chromatographic column with a known pressure resistance Ps in the column setting section; and... In the gain update process, the gain of the pressure sensor is updated using the first output value P1 and the second output value P2.

2. The method for adjusting a pressure sensor according to claim 1, characterized in that, The gain update process is performed when the difference between the second output value P2 and the first output value P1 and the difference between the pressure resistance Ps exceeds the allowable range.

3. The method for adjusting a pressure sensor according to claim 1, characterized in that, The pressure sensor uses a pressure correction method to adjust the detected pressure value P. r Make corrections and use the corrected output value P. m Output pressure sensor, Let the gain K of the pressure sensor be... G Offset K O The pressure correction is formally expressed as P m =K G (P r ﹣K O )。 4. The method for adjusting a pressure sensor according to claim 3, characterized in that, In the first step, the offset K of the pressure sensor is updated. O .

5. The method for adjusting a pressure sensor according to claim 4, characterized in that, In the gain update process, the gain K of the pressure sensor before the update is... G Let K1 be the updated gain K of the pressure sensor. G When K2 is defined as K2, it is K2 = K1 × Ps / (P2 - P1).

6. The method for adjusting a pressure sensor according to claim 5, characterized in that, After performing the gain update process, the first and second processes are performed again. If the difference between the second output value P2 obtained through the repeated first and second processes and the first output value P1 exceeds the allowable range, an anomaly is reported.

7. The method for adjusting a pressure sensor according to claim 1, characterized in that, The liquid chromatography analysis apparatus includes a column unit, which has multiple column mounting sections and a column switching valve. The column switching valve connects any one of the columns mounted in the multiple column mounting sections to the flow path. At least one of the column setup sections of the column unit is provided with a third column filled with packing material, and the other column setup sections are provided with a second column.

8. A liquid chromatography analysis apparatus, characterized in that, The liquid chromatography analysis device has the following features: Column setup section; A liquid delivery device that delivers mobile phase to the chromatographic column provided in the column mounting section; A pressure sensor that detects the pressure in the flow path from the liquid delivery device to the chromatographic column disposed in the column mounting section; and The control unit adjusts the pressure sensor. The control unit acquires the first output value P1 of the pressure sensor, measured when the flow path is open to the atmosphere or when an unfilled first chromatographic column is installed in the column setting section. The control unit obtains the second output value P2 of the pressure sensor, which is measured by installing a second chromatographic column with a known pressure resistance Ps in the chromatographic column setting section. The control unit uses the first output value P1 and the second output value P2 to update the gain of the pressure sensor.

9. The liquid chromatography analysis apparatus according to claim 8, characterized in that, The pressure sensor uses a pressure correction method to adjust the detected pressure value P. r Make corrections and use the corrected output value P. m Output pressure sensor, Let the gain K of the pressure sensor be... G Offset K O The pressure correction is formally expressed as P m =K G (P r ﹣K O )。 10. The liquid chromatography analysis apparatus according to claim 9, characterized in that, The control unit adjusts the gain K of the pressure sensor before the update. G Let K1 be the updated gain K of the pressure sensor. G When K2 is defined as K2, it is K2 = K1 × Ps / (P2 - P1).

11. The liquid chromatography analysis apparatus according to claim 8, characterized in that, The liquid chromatography analysis apparatus includes a column unit, which has multiple column mounting sections and a column switching valve. The column switching valve connects any one of the columns mounted in the multiple column mounting sections to the flow path.

12. The liquid chromatography analysis apparatus according to claim 11, characterized in that, At least one of the column configuration sections of the column unit is provided with a third column filled with packing material, and the other column configuration sections are provided with second columns. In order to obtain the second output value P2, the control unit switches the column switching valve to connect the flow path to the second column.

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