Flow component collecting device

Abstract

A fraction collecting device can perform online cleaning and purging on a collecting end, and has the advantages that no residue exists, samples do not interfere with one another, and the like.

Description

Technical Field

[0001] The invention relates to a fraction collecting device, belonging to the fields of medicine, biology and chemistry, and in particular to a fraction collecting device for liquid chromatography. Background Art

[0002] Liquid chromatography is a separation and analysis technique characterized by the use of a liquid as the mobile phase. A high-performance liquid chromatography (HPLC) system primarily consists of a mobile phase reservoir, an infusion pump, an injector, a chromatographic column, a detector, and a recorder. HPLC is widely used in virtually every area of ​​quantitative and qualitative analysis. Liquid chromatography effectively separates the target principal component from various impurities, and quantifies each component by integrating the detector signal.

[0003] In the fields of medicine and biosynthesis, crude macromolecular products need to be purified. This is usually done by injecting the synthesized compound into a high-performance liquid chromatography instrument, separating it through a chromatographic column, and collecting the fractions corresponding to the main peak. The fraction collectors available on the market install a three-way valve (liquid inlet, liquid outlet, and collection end) on the motion module, making the tubing at the collection end thinner and shorter, thereby reducing residue at the collection end. Despite this, there will still be approximately ten to several dozen microliters of residual sample at the collection end that cannot be discharged and will remain in the next collected sample. This means that the fraction collector cannot be used when high-purity target compounds are required, and manual liquid collection is often used to complete the task. Summary of the Invention

[0004] To address the aforementioned shortcomings of existing treatment methods, the present invention aims to provide a fraction collection device that purges residual sample from the collection end and automatically cleans and dries the pipeline after each sample is collected. This keeps the pipeline clean and dry before each sample is collected, preparing for the next sample purification and significantly reducing sample carryover. Furthermore, the purge and cleaning process of the present invention does not affect the normal flow of the HPLC mobile phase. Furthermore, the present invention provides semiconductor refrigeration temperature control at the sample position, which helps improve the stability of relatively unstable biological samples during preparation.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions: A flow fraction collection device comprises a first three-way solenoid valve (1), a second three-way solenoid valve (2), a third three-way solenoid valve (3), an XYZ motion mechanism (4), a fourth three-way solenoid valve (5), a peristaltic pump (6), a one-way valve (7), a collection end (8), a waste liquid outlet (9), a physical three-way valve (10) and a controller (11), wherein the first three-way solenoid valve (1) is connected to a liquid chromatography detector (18), the second three-way solenoid valve (2) and the one-way valve (7), the second three-way solenoid valve (2) is connected to the first three-way solenoid valve (1), the peristaltic pump (6) and the third three-way solenoid valve (3), the third three-way solenoid valve (3) is installed on the XYZ motion mechanism (4), connected to the second three-way solenoid valve (2), the collection end (8) and the physical three-way valve (10), the XYZ motion mechanism (4) The third three-way solenoid valve (3) is positioned above the fraction collection bottle (15) or the waste liquid outlet (9), and the fourth three-way solenoid valve (5) is connected to the peristaltic pump (6), the cleaning liquid interface and the air interface for switching to cleaning liquid or air. The peristaltic pump (6) is connected to the fourth three-way solenoid valve (5) and the second three-way solenoid valve (2) for extracting cleaning liquid or air to purge, clean or empty the pipeline. The one-way valve (7) is connected to the first three-way solenoid valve (1) and the physical three-way valve (10) to prevent the liquid flow or air flow generated by the peristaltic pump from affecting the liquid chromatography. The physical three-way valve (10) is connected to the one-way valve (7), the third three-way solenoid valve (3) and the waste liquid. The controller (11) performs motion positioning, fraction collection, post-collection purge, post-collection cleaning and post-collection drying operations according to the user-set program.

[0006] Preferably, the first three-way solenoid valve (1) and the second three-way solenoid valve (2) are connected to the same solenoid valve drive interface, and a high and low level signal of the controller (11) is used to realize simultaneous switching of situation one (the first three-way solenoid valve (1) is connected to the one-way valve (7), and the second three-way solenoid valve (2) is connected to the peristaltic pump (6)) and situation two (the first three-way solenoid valve (1) is connected to the second three-way solenoid valve (2), and the second three-way solenoid valve (2) is connected to the first three-way solenoid valve (1)), thereby improving the simultaneity of valve switching and further reducing the influence of the peristaltic pump starting to work on the liquid chromatography.

[0007] Preferably, the fraction collecting device further comprises a semiconductor refrigeration plate (16), and the controller (11) controls the semiconductor refrigeration plate (16) to maintain the target set temperature through a proportional integral differential (PID) algorithm according to the user set temperature.

[0008] Preferably, the fraction collecting device further comprises an air filter (13), wherein the air filter (13) is located before the air interface of the fourth three-way solenoid valve (5) and filters the inhaled air to prevent dust particles from entering the system.

[0009] Preferably, the fraction collecting device further comprises a detector, which is connected to the waste liquid port of the third three-way solenoid valve (3). The dead volume from the liquid chromatography detector (18) to the collecting end (8) can be accurately calculated by the retention time difference of the chromatographic peak between the detector and the liquid chromatography detector (18), thereby enabling accurate execution of delayed switching. Beneficial effects

[0010] (1) There is no residue at the collection end of the present invention, which improves the purity of the collected sample.

[0011] (2) The present invention can purge the tail liquid at the collection end to improve the sample yield.

[0012] (3) The present invention can perform automatic cleaning and drying after collecting a sample, ensuring that the collected samples do not interfere with each other.

[0013] (4) The present invention can cool the sample, which is beneficial to improving the stability of the sample during collection.

[0014] (5) After the equipment is used, it can be cleaned and emptied online without the help of high-performance liquid chromatography. There is no need to disconnect the connection with the high-performance liquid chromatography. It can be normally connected to the liquid chromatography and started when collection is required. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Schematic diagram of the flow fraction collection device embodiment 1 of the present invention In the figure: 1. First three-way solenoid valve, 2. Second three-way solenoid valve, 3. Third three-way solenoid valve, 4. XYZ-axis motion mechanism, 5. Fourth three-way solenoid valve, 6. Peristaltic pump, 7. One-way valve, 8. Collection end, 9. Waste liquid outlet, 10. Physical three-way valve, 11. Controller, 12. Air, 13. Air filter, 14. Cleaning liquid bottle, 15. Fraction collection bottle, 16. Semiconductor refrigeration plate, 17. Waste liquid receiving bottle, 18. Liquid chromatography detector.

[0016] Figure 2 This is a structural diagram of the flow fraction collection device of the present invention DETAILED DESCRIPTION

[0017] The preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings. Example

[0018] like Figure 1As shown, a flow fraction collection device includes a first three-way solenoid valve, a second three-way solenoid valve, a third three-way solenoid valve, an XYZ motion mechanism, a fourth three-way solenoid valve, a peristaltic pump, a one-way valve, a collection end, a waste liquid discharge port, a physical three-way valve, an air filter, a controller, and a semiconductor refrigeration plate.

[0019] The working procedure of the fraction collection device is as follows: Temperature control: The user sets the temperature to be controlled in the UI. After clicking Set, the controller uses a separate thread to perform temperature control according to the set temperature.

[0020] Sequence collection and run: The user selects the sample rack type, start sample number and end sample number, sets the trigger collection threshold, and automatically executes the run after clicking Run. For each needle sample run, the current needle run will start when the liquid chromatography injection trigger signal is received. After the movement ends, the next needle will automatically run until the sequence run ends.

[0021] Each needle operates: under normal conditions, the first three-way solenoid valve (1) is connected to the second three-way solenoid valve (2), the second three-way solenoid valve (2) is connected to the third three-way solenoid valve (3), and the third three-way solenoid valve (3) is connected to the physical three-way valve (10). After the liquid chromatography injector injects the sample, the external interrupt of the controller (11) is triggered, and the controller (11) controls the XYZ motion mechanism to move to the top of the corresponding sample position. At the same time, the controller (11) starts to monitor the liquid chromatography detector signal. When the signal intensity exceeds the set threshold, the collection timing is started and the cumulative delay volume is calculated. When the cumulative delay volume reaches the system dead volume, the third three-way solenoid valve (3) is connected to the collection end (4) to perform flow collection. When the liquid chromatography detector signal is detected to be lower than the set threshold, the collection timing is started and the cumulative delay volume is calculated. When the cumulative delay volume reaches the system dead volume, the third three-way solenoid valve (3) is connected to the physical three-way valve (10) to end the collection.

[0022] Purging after collection: After the collection of this needle is completed, the first three-way solenoid valve (1) is connected to the one-way valve (7), the fourth three-way solenoid valve (5) is connected to the air filter (13), the second three-way solenoid valve (2) is connected to the peristaltic pump (6), the third three-way solenoid valve (3) is connected to the physical three-way valve (10), the peristaltic pump (6) is turned on, air is pumped in, the pipeline is emptied, and the peristaltic pump (6) is stopped. The third three-way solenoid valve (3) is connected to the collection end (8), the peristaltic pump (6) is turned on, air is pumped in, the residual sample at the collection end is purged, and the peristaltic pump (6) is stopped.

[0023] Cleaning after collection: The controller (11) controls the XYZ motion mechanism to move to the top of the waste liquid outlet (9), the first three-way solenoid valve (1) is connected to the one-way valve (7), the fourth three-way solenoid valve (5) is connected to the cleaning liquid (14), the second three-way solenoid valve (2) is connected to the peristaltic pump (6), and the third three-way solenoid valve (3) is connected to the collection end (8). The peristaltic pump (6) is turned on, the cleaning liquid is pumped in, the pipeline is cleaned, and the peristaltic pump (6) is stopped.

[0024] Blow dry after collection: The XYZ motion mechanism moves and remains above the waste liquid outlet (9), the first three-way solenoid valve (1) is connected to the one-way valve (7), the fourth three-way solenoid valve (5) is connected to the air filter (13), the second three-way solenoid valve (2) is connected to the peristaltic pump (6), the third three-way solenoid valve (3) is connected to the collection end (8), the peristaltic pump (6) is turned on, air is pumped in, the pipeline is blown dry, and the peristaltic pump (6) is stopped.

Claims

1. A flow fraction collection device, comprising a first three-way solenoid valve (1), a second three-way solenoid valve (2), a third three-way solenoid valve (3), an XYZ motion mechanism (4), a fourth three-way solenoid valve (5), a peristaltic pump (6), a one-way valve (7), a collection end (8), a waste liquid outlet (9), a physical three-way valve (10) and a controller (11), wherein the first three-way solenoid valve (1) is connected to a liquid chromatography detector (18), the second three-way solenoid valve (2) and the one-way valve (7), the second three-way solenoid valve (2) is connected to the first three-way solenoid valve (1), the peristaltic pump (6) and the third three-way solenoid valve (3), the third three-way solenoid valve (3) is installed on the XYZ motion mechanism (4), connected to the second three-way solenoid valve (2), the collection end (8) and the physical three-way valve (10), the XYZ motion mechanism (4 ) carries a third three-way solenoid valve (3) positioned above the fraction collection bottle (15) or the waste liquid outlet (9), the fourth three-way solenoid valve (5) is connected to the peristaltic pump (6), the cleaning liquid interface and the air interface, and is used to switch to cleaning liquid or air, the peristaltic pump (6) is connected to the fourth three-way solenoid valve (5) and the second three-way solenoid valve (2), and is used to extract cleaning liquid or air to purge, clean or empty the pipeline, the one-way valve (7) is connected to the first three-way solenoid valve (1) and the physical three-way (10) to prevent the liquid flow or air flow generated by the peristaltic pump from affecting the liquid chromatography, the physical three-way (10) is connected to the one-way valve (7), the third three-way solenoid valve (3) and the waste liquid, and the controller (11) performs motion positioning, fraction collection, post-collection purge, post-collection cleaning and post-collection drying operations according to the user-set program.

2. A fraction collection device according to claim 1, characterized in that: The first three-way solenoid valve (1) and the second three-way solenoid valve (2) are connected to the same solenoid valve drive interface, and a high and low level signal of the controller (9) is used to realize simultaneous switching between situation one (the first three-way solenoid valve (1) is connected to the one-way valve (7), and the second three-way solenoid valve (2) is connected to the peristaltic pump (6)) and situation two (the first three-way solenoid valve (1) is connected to the second three-way solenoid valve (2), and the second three-way solenoid valve (2) is connected to the first three-way solenoid valve (1)).

3. A fraction collecting device according to claim 1-2, characterized in that: The fraction collection device further comprises a semiconductor refrigeration plate (16), and the controller (11) controls the semiconductor refrigeration plate (16) to maintain the target set temperature through a proportional integral differential (PID) algorithm according to a user set temperature.

4. A fraction collecting device according to claims 1-3, characterized in that: The flow fraction collecting device further comprises an air filter (13), which is located before the air interface of the fourth three-way solenoid valve (5) and filters the inhaled air to prevent dust particles from entering the system.

5. A fraction collecting device according to claims 1-4, characterized in that: The fraction collection device further comprises a detector, which is connected to the waste liquid port of the third three-way solenoid valve (3). The dead volume from the liquid chromatography detector (18) to the collection end (8) can be accurately calculated by the difference in retention time of the chromatographic peak between the detector and the liquid chromatography detector (18), thereby enabling accurate execution of delayed switching.

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