阅读说明：本技术 一种酶促反应的层析系统及其控制方法 (Chromatographic system for enzymatic reaction and control method thereof ) 是由 孙梁 陆平 吴警 朱文渊 于 2021-06-29 设计创作，主要内容包括：本发明公开了一种酶促反应的层析系统及其控制方法,所述酶促反应的层析系统包括：层析柱与层析柱管道连接的待上柱液釜、自动控制装置,在所述层析柱的进料口的管路上设置有流量计和自动控制阀,所述层析柱的出料口设置有流量计和自动控制阀,其中的自动控制阀、流量计分别与自动控制装置电连接。通过在层析柱系统中设置流量计和自动控制阀,由流量计检测进出层析柱的原料流量大小,根据流量大小控制自动控制阀的开启度,从而对进出所述层析柱流量和流速,保证层析柱进出口流量处于平衡状态,使得各种原料的加入量更加的准确,降低了产品的损失。(The invention discloses a chromatography system for enzymatic reaction and a control method thereof, wherein the chromatography system for enzymatic reaction comprises: the device comprises a chromatographic column, a liquid kettle to be subjected to column feeding and an automatic control device, wherein the chromatographic column is connected with a pipeline of the chromatographic column, a flow meter and an automatic control valve are arranged on a pipeline of a feeding hole of the chromatographic column, a discharge hole of the chromatographic column is provided with the flow meter and the automatic control valve, and the automatic control valve and the flow meter are respectively and electrically connected with the automatic control device. The flow meter and the automatic control valve are arranged in the chromatographic column system, the flow meter detects the flow of raw materials entering and exiting the chromatographic column, and the opening degree of the automatic control valve is controlled according to the flow, so that the flow and the flow rate of the entering and exiting chromatographic column are ensured to be in a balanced state, the addition of various raw materials is more accurate, and the product loss is reduced.)

1. An enzymatic reaction chromatography system comprising:

the chromatographic column comprises a feeding end and a discharging end; the feeding end is provided with a first feeding hole, the discharging end is provided with a first discharging hole, and the first discharging hole is fixedly connected with a first automatic control valve;

the column liquid feeding kettle comprises a second discharge hole, the second discharge hole is connected with the first feed hole through a first pipeline, and a second automatic control valve is arranged on the first pipeline;

the first flowmeter is fixed on the first pipeline between the second automatic control valve and the first feeding hole and is used for detecting the flow of the liquid to be loaded into the chromatographic column;

the second flow meter is fixedly connected with the first automatic control valve and is used for detecting the flow of the upper column liquid flowing out of the first automatic control valve; and

and the first automatic control valve, the second automatic control valve, the first flowmeter and the second flowmeter are respectively and electrically connected with the automatic control device.

2. The chromatography system for enzymatic reactions of claim 1, further comprising: a second conduit in communication with the first conduit; one end of the second pipe is fixed on the first pipe between the first flowmeter and the second control valve; the second pipeline is respectively connected with a first branch pipe for conveying alkali and a second branch pipe for conveying acid; a third automatic control valve is arranged on the first branch pipe, and a fourth automatic control valve is arranged on the second branch pipe; the third automatic control valve and the fourth automatic control valve are respectively and electrically connected with the automatic control device.

3. The chromatography system for enzymatic reactions according to claim 1, wherein said feeding end is further provided with a feed back port; one end, away from the chromatographic column, of the second flowmeter is connected with a first tee joint, a middle port of the first tee joint is connected with the feed back port through a third pipeline, the other port of the first tee joint is fixedly connected with a first regulating valve, one end of the first regulating valve is connected with a second tee joint, and a middle port of the second tee joint is fixedly connected with a first manual valve; and a fifth automatic control valve is arranged on the third pipeline and is electrically connected with the automatic control device.

4. The chromatography system according to claim 3, wherein a second manual valve is provided on said third conduit between said fifth automatic control valve and the middle port of said first tee.

5. The enzymatically reacted chromatographic system according to claim 3, further comprising: the feed port of the pump body is connected with the second discharge port of the column liquid to be fed kettle through a pipeline, and the discharge port of the pump body is connected with the first feed port through a pipeline; the first automatic control valves are arranged in two numbers, wherein one first automatic control valve is fixedly connected with the second discharge hole, and the other first automatic control valve is arranged on a pipeline between the pump body discharge hole and the first feed hole.

6. The chromatography system for enzymatic reactions according to claim 2, wherein a second regulating valve is provided on the first pipe between the first flow meter and the first feed port.

7. The chromatography system for enzymatic reaction according to claim 2, wherein a third branch pipe for conveying a raw material liquid is further connected to the second pipeline, and a sixth automatic control valve is provided on the third branch pipe; and the sixth automatic control valve is electrically connected with the automatic control device.

8. The chromatography system for enzymatic reaction of claim 1, wherein the discharge end is further provided with a gas back-flushing pipeline communicated with the chromatography column, and a seventh automatic control valve is arranged on the gas back-flushing pipeline and is electrically connected with the automatic control device.

9. The chromatography system for enzymatic reactions according to claim 3, characterized in that a waste line is connected to the port of said second tee facing away from said first regulating valve; and the second tee joint is connected with a discharge pipeline for discharging the filtered upper column liquid from the chromatographic column, and the discharge pipeline is provided with an eighth automatic control valve which is electrically connected with the automatic control device.

10. A control method of a chromatography system for enzymatic reactions according to claim 1, characterized in that the control method comprises:

acquiring a first flow of a liquid to be loaded in the first pipeline;

adjusting an opening degree of the second automatic control valve according to the first flow rate;

obtaining a second flow rate of upper column liquid flowing through the first automatic control valve;

adjusting an opening degree of the first automatic control valve according to the second flow rate.

Technical Field

The invention relates to the technical field of enzyme catalytic synthesis, in particular to a chromatographic system for enzymatic reaction and a control method thereof.

Background

When the enzymatic synthesis reaction generates adenosylmethionine disulphonate, the synthesized crude product needs to be purified, and the chromatography process is an important step in the purification process.

In the prior chromatographic procedures, such operations as sample loading, elution of chromatographic columns, activation of resin and the like are performed, wherein the consumption of raw materials is realized by manually operating a manual valve to adjust the opening degree of the manual valve when the manual valve is opened or closed so as to control the flow and the flow rate of an inlet and an outlet, and ensure that the flow and the flow of the inlet and the outlet are basically in a balanced state.

Disclosure of Invention

In view of the above-mentioned shortcomings of the prior art, the present invention provides a chromatography system for enzymatic reaction and a control method thereof, which is used to solve the problem of low accuracy of raw material dosage caused by the manual valve used in the prior chromatography process.

In a first aspect, the present invention provides an enzymatic reaction chromatography system comprising: the chromatographic column comprises a feeding end and a discharging end; the feeding end is provided with a first feeding hole, the discharging end is provided with a first discharging hole, and the first discharging hole is fixedly connected with a first automatic control valve;

the column liquid feeding kettle comprises a second discharge hole, the second discharge hole is connected with the first feed hole through a first pipeline, and a second automatic control valve is arranged on the first pipeline;

the first flowmeter is fixed on the first pipeline between the second automatic control valve and the first feeding hole and is used for detecting the flow of the liquid to be loaded into the chromatographic column;

the second flow meter is fixedly connected with the first automatic control valve and is used for detecting the flow of the upper column liquid flowing out of the first automatic control valve; and

and the first automatic control valve, the second automatic control valve, the first flowmeter and the second flowmeter are respectively and electrically connected with the automatic control device.

Optionally, the chromatography system for enzymatic reaction further comprises: a second conduit in communication with the first conduit; one end of the second pipeline is fixed on the first pipeline between the flow meter and the second control valve; the second pipeline is respectively connected with a first branch pipe for conveying alkali and a second branch pipe for conveying acid; a third automatic control valve is arranged on the first branch pipe, and a fourth automatic control valve is arranged on the second branch pipe; the third automatic control valve and the fourth automatic control valve are respectively and electrically connected with the automatic control device.

Optionally, the chromatography system for enzymatic reaction, wherein the feeding end is further provided with a feed back port; one end, away from the chromatographic column, of the second flowmeter is connected with a first tee joint, a middle port of the first tee joint is connected with the feed back port through a third pipeline, the other port of the first tee joint is fixedly connected with a first regulating valve, one end of the first regulating valve is connected with a second tee joint, and a middle port of the second tee joint is fixedly connected with a first manual valve; and a fifth automatic control valve is arranged on the third pipeline and is electrically connected with the automatic control device.

Optionally, the chromatography system for enzymatic reaction further comprises a third automatic control valve, wherein a third manual valve is arranged on the third pipeline between the third automatic control valve and the middle port of the third tee.

Optionally, the chromatography system of an enzymatic reaction, wherein the chromatography system of an enzymatic reaction further comprises: the feed port of the pump body is connected with the second discharge port of the column liquid to be fed kettle through a pipeline, and the discharge port of the pump body is connected with the first feed port through a pipeline; the first automatic control valves are arranged in two numbers, wherein one first automatic control valve is fixedly connected with the second discharge hole, and the other first automatic control valve is arranged on a pipeline between the pump body discharge hole and the first feed hole.

Optionally, the chromatography system for enzymatic reaction, wherein a second regulating valve is disposed on the first pipe between the first flowmeter and the first feed inlet.

Optionally, the chromatography system for enzymatic reaction, wherein a third branch pipe for conveying a raw material liquid is further connected to the second pipeline, and a sixth automatic control valve is arranged on the third branch pipe; and the sixth automatic control valve is electrically connected with the automatic control device.

Optionally, the discharge end of the chromatography system for enzymatic reaction is further provided with a gas back-flushing pipeline communicated with the chromatography column, the gas back-flushing pipeline is provided with a seventh automatic control valve, and the seventh automatic control valve is electrically connected with the automatic control device.

Optionally, the chromatography system for enzymatic reaction, wherein a waste pipe is connected to a port of the second tee away from the first regulating valve; and the second tee joint is connected with a discharge pipeline for discharging the filtered upper column liquid from the chromatographic column, and the discharge pipeline is provided with an eighth automatic control valve which is electrically connected with the automatic control device.

In a second aspect, the present invention provides a method for controlling a chromatography system for an enzymatic reaction, wherein the method comprises:

acquiring a first flow of a liquid to be loaded in the first pipeline;

adjusting an opening degree of the second automatic control valve according to the first flow rate;

obtaining a second flow rate of upper column liquid flowing through the first automatic control valve;

adjusting an opening degree of the first automatic control valve according to the second flow rate.

Has the advantages that: the embodiment of the invention provides a chromatography system for enzymatic reaction, which is characterized in that a flow meter and an automatic control valve are arranged in a chromatography column system, the flow meter is used for detecting the flow of raw materials entering and exiting a chromatography column, and the opening degree of the automatic control valve is controlled according to the flow, so that the flow and the flow speed of the raw materials entering and exiting the chromatography column are ensured to be in a balanced state, the addition of various raw materials is more accurate, and the loss of products is reduced.

Drawings

FIG. 1 is a schematic diagram of a chromatography system for enzymatic reactions.

Detailed Description

The present invention provides a chromatography system for enzymatic reaction and a control method thereof, and the present invention will be described in further detail below in order to make the objects, technical solutions and effects of the present invention clearer and clearer. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

Referring to fig. 1, an embodiment of the present invention provides a chromatography system for enzymatic reaction, including a chromatography column 10, a to-be-applied column liquid kettle 30 connected to the chromatography column 10 (a first pipeline 11), and an automatic control device 50, wherein a feeding end of the chromatography column 10 is provided with a first feeding port 12, a feeding back port 23, and a discharging end of the chromatography column 10 is provided with a first discharging port 13; the bottom of the column liquid to be fed 30 is provided with a second discharge port 31, a pipeline between the second discharge port 31 and the first feed port 12 is provided with two second automatic control valves 14 (two), a first flow meter 15 and a first regulating valve 42, and the outlet of the first discharge port 13 is fixed with a first automatic control valve 16 and a second flow meter 17 for detecting the outlet flow of the first automatic control valve 16. The first automatic control valve 16, the second automatic control valve 14, the first flow meter 15 and the second flow meter 17 are electrically connected to the self-control device 50, respectively. It should be noted that a pump body 110 is further disposed on the first pipeline 11, and the to-be-applied column liquid in the to-be-applied column liquid kettle is pumped into the chromatography column 10 through the pump body 110. A manual valve 111 is provided at the inlet of the pump body 110, and a manual valve 112 is provided at the outlet of the pump body 110. It will be readily appreciated that the flow of the liquid to be pillared into the pump body can be controlled by controlling the manual valve.

In this embodiment, the chromatography column 10 is a chromatography column commonly used in the art, and the specific structure thereof is not limited herein. The column liquid to be fed refers to a raw material liquid to be filtered and purified, the column liquid to be fed kettle is a container for containing the column liquid to be fed, it should be noted that a stirring device (not shown) is arranged in the column liquid to be fed kettle, and the upper end of the column liquid to be fed kettle is connected with raw material inlet pipelines 32 and 33.

By arranging the automatic control device, the flow of the raw materials entering and exiting the chromatographic column is monitored by the automatic control device, and the automatic control valve in the pipeline is adjusted according to the monitored flow, so that the raw material amount entering and exiting the chromatographic column can be accurately controlled, and the raw material loss is reduced.

In one implementation form of this embodiment, the chromatography system for enzymatic reaction further comprises: a second pipe 18, wherein the second pipe 18 is communicated with the first pipe 11, and the junction point of the second pipe 18 and the first pipe 11 is located between the inlet end of the first flowmeter 15 and the second automatic control valve. In this embodiment, a first branch pipe 19 and a second branch pipe 20 are connected to the second pipeline 18, respectively, the first branch pipe 19 may be used for conveying alkali, and the second branch pipe 20 may be used for conveying acid. A third automatic control valve 21 is arranged on the first branch pipe 19, and a fourth automatic control valve 22 is arranged on the second branch pipe 20; the third automatic control valve 21 and the fourth automatic control valve 22 are electrically connected to the automatic control device 50, respectively. Wherein, through setting up and being used for acid, alkali conveying branch pipe, can handle the chromatographic column according to actual need.

Further, a third branch pipe 40 is further provided on the second pipeline 18, and a sixth automatic control valve 41 is provided on the third branch pipe 40, it is easily understood that the sixth automatic control valve 41 is electrically connected to the automatic control device 50. Wherein the third leg may be used to deliver, for example, butanedisulfonic acid, 0.1M acid, and the like.

A conduit for delivering WPU (concentrated water) is further connected to the end of the second conduit 18, and an automatic control valve 42 is provided in the conduit to allow the column 10 to be cleaned with concentrated water.

It will be readily understood that the monitoring of the flow rate of the feed liquid flowing into the chromatography column through the second conduit 18 can be achieved by providing the access point of the second conduit 18 between the first flow meter 15 and the second self-controlled valve 14, the flow rate of the feed liquid flowing into the chromatography column through the second conduit 18 being measured by the first flow meter 15 when the second self-controlled valve 14 is closed, and the flow rate of the feed liquid flowing into the chromatography column through the first conduit 11 and the second conduit 12 being measured by the first flow meter 15 when the second self-controlled valve 14 is opened. By monitoring the flow, the opening of the automatic control valve can be accurately controlled.

In one implementation manner of this embodiment, a first tee 24 is connected to a discharge end of the second flowmeter 17, a port in the middle of the first tee 24 is connected to the feed back port 23 through a pipeline, a second manual valve 29 is disposed on the pipeline, a first regulating valve 25 is connected to another port of the first tee 24, a second tee 26 is connected to one end of the first regulating valve 25, and a first manual valve 27 is fixedly connected to a port in the middle of the second tee; a fifth automatic control valve 28 is arranged on the third pipeline, and the fifth automatic control valve 28 is electrically connected with the automatic control device 50. It should be noted that the second tee is used for manual sampling analysis.

In this embodiment, cooperate with first manual valve through setting up artifical sampling point, when detecting out that the product purity after filtering can not reach the technological requirement, open first manual valve and carry out the column chromatography once more, it is qualified until the sample analysis result.

In one implementation manner of this embodiment, the discharge end of the chromatography column 10 is further provided with an air backflushing pipeline 60, and a seventh automatic control valve 61 is arranged on the air backflushing pipeline 60, and it is easy to understand that the seventh automatic control valve 61 is electrically connected with the automatic control device. The chromatographic column can be cleaned conveniently by providing a gas back flushing line 60.

In one implementation manner of the present embodiment, a waste discharge pipe 70 is connected to a port of the second three-way valve 26 away from the first regulating valve 25; and a discharge pipeline 80 for discharging the filtered upper column liquid from the chromatographic column is connected to the second tee joint, an eighth automatic control valve 81 is arranged on the discharge pipeline, and the eighth automatic control valve is electrically connected with the automatic control device. That is to say, the exit end of second tee bend is connected with waste discharge pipeline, ejection of compact pipeline respectively, can discharge the washing sewage in the chromatographic column through setting up waste discharge pipeline.

Based on the same inventive concept, the present invention also provides a control method of the enzymatic system described above, comprising the steps of:

acquiring a first flow of a liquid to be loaded in the first pipeline; and adjusting the opening degree of the second automatic control valve according to the first flow rate.

Specifically, the crude ademetionine disulfonate raw material liquid synthesized in the previous step is pumped into a to-be-added column liquid kettle, the pH value of the raw material liquid is adjusted according to the process requirement, then a valve at the bottom of the to-be-added column liquid kettle is opened, a pump body 110 is opened, the crude ademetionine disulfonate raw material liquid is pumped into a chromatographic column 10 (the flow direction of the crude ademetionine disulfonate raw material liquid is shown by an arrow in fig. 1), the flow of the crude ademetionine disulfonate raw material liquid in a pipeline is monitored through a flow meter 15 on the pipeline, the detected flow data is compared with the process control flow set in an automatic controller, and if the monitored flow is smaller than the process control flow, an action instruction can be sent to the automatic control valve at this time to increase the opening degree of the automatic control valve. If the monitored flow is larger than the process control flow, the opening degree of the automatic control valve can be reduced by sending an action command to the automatic control valve. Of course, if the monitored flow is within the process control range, no adjustments may be made, wherein the monitoring of the flow in the pipeline is performed in real time.

In this embodiment, the operation of the automatic control valve and the flow meter by the automatic control device is a technical operation commonly used in process control in the art, and a specific operation process is not limited herein.

Obtaining a second flow rate of upper column liquid flowing through the first automatic control valve; adjusting an opening degree of the first automatic control valve according to the second flow rate.

Specifically, the flow rate of the raw material liquid (filtered) flowing out of the discharge port of the chromatography column 10 is monitored by the flow meter 17, and if the monitored flow rate is larger than the process control flow rate, the opening degree of the automatic control valve at the discharge port is controlled (the opening degree is decreased) by the automatic control device, and if not, the opening degree is increased. It should be noted that, in this embodiment, the flow rate of the raw material liquid entering and exiting the chromatography column is adjusted only by controlling the opening of the feed end and the discharge end self-understood control valve, and in actual production, there are many pipelines involved, and the flow rate can also be adjusted by matching with other control valves, for example, the power of the pump body can be adjusted.

In this embodiment, when the chromatography column needs to be eluted or the resin in the chromatography column needs to be activated, a certain amount of butanedisulfonic acid or 0.5M acid, or alkali liquor, acid, or the like needs to be added into the chromatography column, and the opening of the automatic control valve can be controlled by the automatic control device by calculating the required addition, so that the amount of the added raw material is relatively accurate, and the waste of the raw material is avoided.

In an implementation of this embodiment, can come the sampling analysis through artifical sampling point, learn the filter effect according to the analysis result, when the analysis result shows that the filter effect is less than the technology management and control requirement, then the governing valve that can the control pipeline makes the liquid after the filtration flow back to the chromatographic column and carries out secondary chromatography (filtration), and it is qualified until manual sampling analysis detects.

In this embodiment, because the valve on the pipeline is automatic control valve, controls its opening and closing through autonomous control device, compares in artifical manual control valve, has promoted control accuracy, has avoided artifical improper operation, has reduced the raw materials loss.

It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.