CN114544838A - Mobile phase preparation facilities - Google Patents

Mobile phase preparation facilities Download PDF

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Publication number
CN114544838A
CN114544838A CN202210245625.9A CN202210245625A CN114544838A CN 114544838 A CN114544838 A CN 114544838A CN 202210245625 A CN202210245625 A CN 202210245625A CN 114544838 A CN114544838 A CN 114544838A
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mobile phase
liquid
filter
phase preparation
vacuum
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不公告发明人
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Priority to CN202210245625.9A priority Critical patent/CN114544838A/en
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Priority to CN202211147551.1A priority patent/CN116794205A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D19/00Degasification of liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D36/00Filter circuits or combinations of filters with other separating devices

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
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  • Pathology (AREA)
  • External Artificial Organs (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

The invention relates to a mobile phase preparation device which comprises a flowmeter, a liquid pump, a liquid pressure sensor, a three-way electromagnetic valve, a filter, a degassing lung, a cooling module 1, a receiving container, a liquid discharge valve, a cooling module 2, an air inlet valve, an air filter, a differential pressure sensor, a vacuum filter, a vacuum pump, a silencer, an upper limit liquid level sensor, a lower limit liquid level sensor, a pH sensor, a dissolved oxygen sensor and a controller. The mobile phase preparation device can realize program management of the liquid chromatogram mobile phase, such as pre-rinsing, mobile phase preparation, mobile phase maintaining and cleaning.

Description

Mobile phase preparation facilities
Technical Field
The invention relates to a mobile phase preparation device, belongs to the fields of medicines, foods and chemistry, and particularly relates to a mobile phase preparation device for liquid chromatography.
Background
Liquid chromatography is a separation and analysis technique characterized by the use of a liquid as the mobile phase. High performance liquid chromatography is used in a wide variety of applications, almost throughout the field of quantitative qualitative analysis. The high performance liquid chromatography system mainly comprises a mobile phase liquid storage bottle, an infusion pump, a sample injector, a chromatographic column, a detector and a recorder. The infusion pump of the high performance liquid chromatography requires constant and stable infusion amount, and the sample injection system requires convenient sample injection and strict switching. Liquid chromatography requires that the mobile phase must be filtered (typically with a pore size of 0.45um and below) to avoid particles entering the system damaging the system and must be degassed to avoid gas entering the system and being trapped in the column and detector flowcells, seriously affecting the analytical results and even damaging the column and detector.
The preparation of mobile phase is a necessary preparation work for liquid chromatography, and in the routine work of analysts, the preparation and filtration of mobile phase often takes much time and is cumbersome to operate. The analyst typically first dissolves the mobile phase desired salts with purified water in a large beaker, adjusts to the target pH using a calibrated pH meter using a specified acid or base to obtain an aqueous phase, and if pre-mixing is desired, then mixes the exact volumes of aqueous and organic phases, and then performs membrane filtration using a glass sand core filtration device, using hydrophilic membranes for the non-organic phase and organic membranes for the organic phase. The glass sand core filtering device comprises a collecting bottle, a glass sand core, a filter membrane, a material cup and an iron clamp, wherein the collecting bottle is usually 1-2 liters, the material cup is usually 500 milliliters of 300-one sand, the filter membrane is placed on the glass sand core when the glass sand core filtering device is used, the material cup is added, the glass sand core and the material cup are clamped tightly by the iron clamp, a vacuum pump is opened, a mobile phase to be filtered is added into the material cup, and the mobile phase is filtered into the collecting bottle below. Because the material cup is small, the material cup is usually required to be attended by people, the mobile phase to be filtered is added into the material cup when the liquid in the material cup is filtered, and sometimes, the mobile phase needs to wait for a long time when the mobile phase is filtered slowly. If the mobile phase needing to be filtered is large in volume (particularly for preparative liquid chromatography, several liters to tens liters of mobile phase are usually needed), after the collection bottle is full of collected liquid, the vacuum tube needs to be pulled out, the vacuum pump is closed, the glass sand core is taken out, the mobile phase in the collection bottle is poured out, then the glass sand core is put back, and the filtration is continued according to the method. After the suction filtration, need pull down whole device, wash repeatedly with the running water, reuse purified water washes repeatedly, and the washing operation is very loaded down with trivial details, and the glass psammitolite is very difficult to wash totally, need reassemble glass psammitolite filter equipment usually after wasing, adds purified water in to the material cup again, lets its slow seepage wash the glass psammitolite.
Although the mobile phase is subjected to vacuum pumping in the suction filtration process, the vacuum degree is poor, the degassing is usually incomplete, and the mobile phase after suction filtration is often required to be placed in an ultrasonic bath for additional ultrasonic degassing. Laboratory ultrasound is a relatively severe noise pollution, and once turned on, harsh noise can be heard in many rooms.
And volatile organic acid (such as trifluoroacetic acid) or organic base (such as triethylamine) or volatile organic solvent (such as methanol, dichloromethane and the like) is often pumped away when the mixture is filtered by a glass sand core filtering device, so that the pH value of a mobile phase is inaccurate or the organic phase ratio is inaccurate, and the result reproducibility of liquid chromatographic analysis is influenced.
In pharmaceutical analysis studies (particularly stability studies), it takes several days to detect the movement of a batch of samples, and thus a large volume is required to formulate a mobile phase (about 10 liters of mobile phase is required for 7 days of operation on a 1mL/min conventional flow rate meter). The mobile phase is usually placed in a mobile phase bottle (usually with a volume of 1 liter), when the mobile phase is insufficient, the prepared mobile phase needs to be added into the mobile phase bottle in time, and in actual use, air enters a liquid phase system due to the fact that the mobile phase is pumped to be dry, so that a chromatographic column is damaged, even gas enters a detector flow cell, and maintenance is required.
During the operation of liquid chromatography, the mobile phase is usually placed for a long time, air can reenter the mobile phase, and as the time is prolonged, the degassing effect of the mobile phase is eliminated, so that peak retention time drift and ghost peaks appear in the later period of an analysis sequence, the analysis result is seriously influenced, and even the whole test is retested due to the fact that a plurality of needle samples in the sequence are analyzed abnormally, so that the repeated labor is undoubtedly greatly increased, and the working efficiency is reduced.
Patent application No. 201620270964.2 provides a high efficiency liquid phase mobile phase preparation machine that prepares mobile phases by drawing a proportion of A, B, C, D of four mobile phases through proportional valves for mixing, followed by filtration and degassing. This approach has the following drawbacks: the aqueous phase of the mobile phase often contains high concentration of salt (such as potassium dihydrogen phosphate, etc.), salting-out is usually generated when the salt is mixed with the organic phase, and if the salt is mixed by using a proportional valve, salting-out particles can block the proportional valve, even cause the blockage of a subsequent flow path, seriously affect the system performance, and can cause incomplete closing of the proportional valve, and affect the proportional adjustment precision. This approach does not solve the problem of re-dissolving air during mobile phase placement.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, an object of the present invention is to provide a mobile phase preparation apparatus, which uses a degassing lung to perform online degassing on a mobile phase, thereby avoiding noise pollution caused by ultrasonic degassing, and the mobile phase preparation apparatus is configured with two liquid level sensors (an upper limit liquid level sensor and a lower limit liquid level sensor) in a mobile phase bottle of a liquid chromatography, and starts the mobile phase preparation when the detected liquid level is lower than the lower limit liquid level sensor, and stops the mobile phase preparation when the detected liquid level reaches the upper limit liquid level sensor, so that the mobile phase in the mobile phase bottle is kept as a freshly prepared degassed mobile phase within the user-set window. When the freshly prepared degassed mobile phase is consumed by the liquid chromatogram in a short time, the new preparation is started immediately, so that the real temporary new preparation is realized, the reliability of the test result is ensured, and the problem that the mobile phase is drained is solved.
In order to achieve the purpose, the invention adopts the following technical scheme:
a mobile phase preparation device comprises an infusion pump, a filter, a degassing lung, a pressure sensor and a vacuum pump, wherein the infusion pump draws liquid, the filter filters the liquid, the degassing lung and the vacuum pump carry out online degassing on the liquid flowing through, the pressure sensor monitors the vacuum degree, and the infusion pump speed is adjusted to ensure that the liquid flowing through is sufficiently degassed; further comprising: and the controller is used for performing operations such as pre-rinsing, mobile phase preparation, mobile phase maintenance, cleaning and the like according to a program set by a user.
Preferably, the mobile phase preparation device further comprises an upper limit liquid level sensor and a lower limit liquid level sensor, wherein the upper limit liquid level sensor and the lower limit liquid level sensor are attached to the mobile phase bottle and used for monitoring the liquid level of the mobile phase, when the mobile phase is prepared to the upper limit liquid level sensor, the preparation is stopped, and when the liquid chromatogram consumes the mobile phase until the liquid level is lower than the lower limit liquid level sensor, the preparation is started, so that the mobile phase in the window set by a user is kept to be prepared and used freshly.
Preferably, the mobile phase preparation device further comprises a liquid pressure sensor, the liquid pressure sensor is positioned between the liquid pump and the filter, the pressure of the filter is monitored, and when the service life of the filter is shortened and the pressure is too high, a user is prompted to replace the filter.
Preferably, the mobile phase preparation device further comprises a flow meter, the flow meter is positioned behind the inlet pipe and can detect the flow of the pipeline and prompt a user when the liquid amount in the source container is insufficient.
Preferably, the mobile phase preparation apparatus further comprises a three-way electromagnetic valve, the three-way electromagnetic valve is located between the liquid pressure sensor and the filter, the outlet of the liquid pressure sensor is selected to be connected with the inlet of the filter or connected with the pre-discharge pipe, when air exists in the filter or the resistance of the filter is too large, the liquid cannot be pumped by the liquid pump, when the liquid pump is just started to work, the outlet of the liquid pressure sensor is selected to be connected with the pre-discharge pipe by the three-way electromagnetic valve, so that the working resistance is reduced, the liquid is smoothly pumped, and when the flow meter detects that the liquid is pumped up and keeps a certain time to fill the pipeline with the liquid, the outlet of the liquid pressure sensor is selected by the three-way electromagnetic valve to be connected with the inlet of the filter, so that the liquid pump continuously pumps the liquid and filters the liquid.
Preferably, the mobile phase preparation device further comprises two cooling modules, a receiving container and a drain valve, wherein the cooling modules are positioned behind the vacuumizing interface of the degassing lung and used for condensing steam pumped from the degassing lung, the receiving container receives condensate, and the drain valve discharges the condensate after vacuumizing is finished.
Preferably, the mobile phase preparation device further comprises an air inlet valve and an air filter, wherein the air inlet valve is opened when the vacuum needs to be released, so that air enters the system, the vacuum is released, and the air filter filters the air entering the system.
Preferably, the mobile phase preparation device further comprises a vacuum filter and a silencer, wherein the vacuum filter is used for filtering the vacuum pipeline to protect the vacuum pump, and the silencer is used for reducing the noise of the vacuum pump.
Preferably, the mobile phase preparation device further comprises a pH sensor and a dissolved oxygen sensor, wherein the pH sensor and the dissolved oxygen sensor are positioned in the mobile phase bottle and used for monitoring and recording the pH and the dissolved oxygen of the mobile phase, so that a user can conveniently trace the test result.
Has the advantages that:
(1) the invention can carry out on-line filtration and degassing on the mobile phase, remove impurities and dissolved gas of the mobile phase, can be automatically finished by starting with one key, and avoids manual complicated operation.
(2) The invention can carry out temporary new preparation on the mobile phase, a user sets a holding window, the preparation is stopped when the prepared mobile phase reaches the upper limit of the window, and the preparation is started when the liquid chromatogram consumes the mobile phase and reaches the lower limit of the window, thus always keeping the mobile phase used by the liquid chromatogram fresh.
(3) The invention can automatically replenish the mobile phase bottle, prompts a user when the mobile phase in the source container is insufficient, and avoids the problem that the gas enters the liquid chromatography system because the mobile phase for replenishing liquid is manually forgotten to be pumped out.
(4) The invention can monitor and record the pH and dissolved oxygen of the mobile phase and provide traceability of mobile phase information in test results for users.
Drawings
FIG. 1 is a schematic view of a mobile phase preparation apparatus according to an embodiment 1 of the present invention
In the figure: 1. a source container, 2, a flowmeter, 3, a liquid pump, 4, a liquid pressure sensor, 5, a three-way electromagnetic valve, 6, a filter, 7, a degassing lung, 8, a cooling module 1, 9, a receiving container, 10, a liquid discharge valve, 11, a cooling module 2, 12, an air inlet valve, 13, an air filter, 14, a differential pressure sensor, 15, a vacuum filter, 16, a vacuum pump, 17, a silencer, 18, an upper limit liquid level sensor, 19, a lower limit liquid level sensor, 20, a controller, 21, a pH sensor, 22, a dissolved oxygen sensor, 23, a mobile phase liquid storage bottle, 24, an inlet pipe, 25, a pre-discharge pipe, 26 and a liquid discharge pipe.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
The first embodiment is as follows:
as shown in fig. 1, a mobile phase preparation apparatus includes a flow meter, a liquid pump, a liquid pressure sensor, a three-way solenoid valve, a filter, a degassing lung, a cooling module 1, a receiving container, a drain valve, a cooling module 2, an air intake valve, an air filter, a differential pressure sensor, a vacuum filter, a vacuum pump, a silencer, an upper limit liquid level sensor, a lower limit liquid level sensor, a pH sensor, a dissolved oxygen sensor, and a controller.
The working procedure of the mobile phase preparation device is as follows:
pre-rinsing: the user places the inlet tube in the source container and the drain tube in the waste liquid receiving container, and performs pre-rinsing. And (3) connecting the three-way electromagnetic valve with A (C- > A), starting the liquid pump, pumping liquid, and running for the time set by a user to pre-rinse the pipeline.
Preparation of a mobile phase: the user places the inlet tube and the preliminary discharge tube in the source container, the discharge tube in the mobile phase bottle, and performs mobile phase preparation. B (C- > B) is communicated with the three-way electromagnetic valve, the liquid pump is started, when the flow meter monitors that liquid flows through the three-way electromagnetic valve and keeps for a few seconds, the liquid pump is closed, A (C- > A) is communicated with the three-way electromagnetic valve, the liquid discharge valve and the air inlet valve are closed, the vacuum pump is started, when the vacuum degree reaches a user set value, the liquid pump is started to pump the liquid, the speed of the liquid pump is adjusted through a Proportion Integration Differentiation (PID) algorithm according to the vacuum degree value, the speed of the liquid pump is reduced when the vacuum degree is reduced, the speed of the liquid pump is increased when the vacuum degree is higher, and the liquid pump works at the optimal speed for effective degassing.
Mobile phase maintenance: the user sets the holding window by setting the positions of the upper limit liquid level sensor and the lower limit liquid level sensor. And stopping the preparation of the mobile phase when the prepared mobile phase reaches the upper limit of the window, opening a liquid discharge valve and an air inlet valve, closing a vacuum pump, discharging condensate, and starting the preparation of the mobile phase when the mobile phase consumed by the liquid chromatogram reaches the lower limit of the window, so that the mobile phase used by the liquid chromatogram is kept fresh. During the mobile phase holding period, when the flow meter monitors that the liquid amount in the source container is insufficient, a prompt is given to a user, so that the situation that the mobile phase is pumped out by the liquid chromatogram caused by the insufficient mobile phase is avoided, and air enters the liquid phase system is avoided.
Cleaning: the user places the inlet tube in the cleaning solution, places the pre-drain tube and the drain tube in the waste liquid receiving container, and performs cleaning. And the three-way electromagnetic valve is communicated with B (C- > B), the liquid pump is started to pump liquid, the pre-discharge pipe is cleaned, then the three-way electromagnetic valve is communicated with A (C- > A), the liquid pump is started to pump liquid, and the pipeline is cleaned within the time set by a user.

Claims (10)

1. A mobile phase preparation device comprises an infusion pump, a filter, a degassing lung, a pressure sensor and a vacuum pump, wherein the infusion pump draws liquid, the filter filters the liquid, the degassing lung and the vacuum pump carry out online degassing on the liquid flowing through, the pressure sensor monitors the vacuum degree, and the infusion pump speed is adjusted to ensure that the liquid flowing through is sufficiently degassed; further comprising: and the controller is used for performing operations such as pre-rinsing, mobile phase preparation, mobile phase maintenance, cleaning and the like according to a program set by a user.
2. A mobile phase preparation apparatus according to claim 1, wherein: the mobile phase preparation device further comprises an upper limit liquid level sensor and a lower limit liquid level sensor, wherein the upper limit liquid level sensor and the lower limit liquid level sensor are attached to the mobile phase bottle and used for monitoring the liquid level of the mobile phase, the preparation is stopped when the mobile phase is prepared to the upper limit liquid level sensor, and the preparation is started when the liquid chromatogram consumes the mobile phase until the liquid level is lower than the lower limit liquid level sensor, so that the fresh preparation and use of the mobile phase in a user setting window are kept.
3. A mobile phase preparation apparatus according to claims 1-2, wherein: the mobile phase preparation device also comprises a flowmeter, wherein the flowmeter is positioned behind the inlet pipe, can detect the flow of the pipeline and gives a prompt to a user when the liquid amount in the source container is insufficient.
4. A mobile phase preparation apparatus according to claim 3, wherein: the mobile phase preparation device also comprises a liquid pressure sensor, wherein the liquid pressure sensor is positioned between the liquid pump and the filter, monitors the pressure of the filter, and prompts a user to replace the filter when the service life of the filter is shortened and the pressure is overhigh.
5. A mobile phase preparation apparatus according to claim 4, wherein: the mobile phase preparation device further comprises a three-way electromagnetic valve, the three-way electromagnetic valve is located between the liquid pressure sensor and the filter, the outlet of the liquid pressure sensor is selected to be connected with the inlet of the filter or connected with the pre-drainage pipe, when air exists in the filter or the resistance of the filter is too large, the liquid cannot be pumped by the liquid pump, when the liquid pump is just started to work, the outlet of the liquid pressure sensor is selected to be connected with the pre-drainage pipe by the three-way electromagnetic valve, the working resistance is reduced, the liquid can be pumped smoothly, when the water inflow flowmeter detects that the liquid is pumped up and keeps for a period of time, so that the pipeline is filled with the liquid, the outlet of the pressure sensor is selected to be connected with the inlet of the filter by the three-way electromagnetic valve, and the liquid can be continuously pumped by the liquid pump and can be filtered.
6. A mobile phase preparation apparatus according to claims 1 to 5, wherein: the mobile phase preparation device further comprises two cooling modules, a receiving container and a liquid discharge valve, wherein the cooling modules are positioned behind the vacuumizing interface of the degassing lung and used for condensing steam pumped from the degassing lung, the receiving container receives condensate, and the liquid discharge valve discharges the condensate after vacuumizing is finished.
7. A mobile phase preparation apparatus according to claims 1 to 6, wherein: the mobile phase preparation device also comprises an air inlet valve and an air filter, wherein the air inlet valve is opened when the vacuum needs to be released, so that air enters the system, the vacuum is released, and the air filter filters the air entering the system.
8. A mobile phase preparation apparatus according to claims 1 to 7, wherein: the mobile phase preparation device also comprises an air inlet valve and an air filter, wherein the air inlet valve is opened when the vacuum needs to be released, so that air enters the system, the vacuum is released, and the air filter filters the air entering the system.
9. A mobile phase preparation apparatus according to claims 1 to 8, wherein: the mobile phase preparation device further comprises a vacuum filter and a silencer, the vacuum filter filters a vacuum pipeline to protect the vacuum pump, and the silencer reduces noise of the vacuum pump.
10. A mobile phase preparation apparatus according to claims 1 to 9, wherein: the mobile phase preparation device further comprises a pH sensor and a dissolved oxygen sensor, wherein the pH sensor and the dissolved oxygen sensor are located in the mobile phase bottle, the pH and the dissolved oxygen of the mobile phase are monitored and recorded, and a user can trace the test result conveniently.
CN202210245625.9A 2022-03-14 2022-03-14 Mobile phase preparation facilities Withdrawn CN114544838A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202210245625.9A CN114544838A (en) 2022-03-14 2022-03-14 Mobile phase preparation facilities
CN202211147551.1A CN116794205A (en) 2022-03-14 2022-09-21 Mobile phase preparation device

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Application Number Priority Date Filing Date Title
CN202210245625.9A CN114544838A (en) 2022-03-14 2022-03-14 Mobile phase preparation facilities

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CN202211147551.1A Pending CN116794205A (en) 2022-03-14 2022-09-21 Mobile phase preparation device

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115290771A (en) * 2022-07-06 2022-11-04 上海瑞暨新材料科技有限公司 Filter device

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115290771A (en) * 2022-07-06 2022-11-04 上海瑞暨新材料科技有限公司 Filter device

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CN116794205A (en) 2023-09-22

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