Chromatography device

Abstract

The invention discloses a chromatography device. The chromatography device comprises a sample online adjustment mechanism, a sample storage mechanism, a bubble trap mechanism and a chromatography mechanism. The sample online adjustment mechanism comprises a sample adjustment tank, a stirring assembly, an acid inlet pipe, an alkali inlet pipe, a conductivity adjustment liquid inlet pipe, a pH sensor and a conductivity sensor. The sample adjustment tank is provided with a sample inlet port. The acid inlet pipe, the alkali inlet pipe and the conductivity adjustment liquid inlet pipe are all connected to the sample adjustment tank. The pH sensor and the conductivity sensor are both connected to the sample adjustment tank. The stirring assembly is connected to the sample adjustment tank to achieve stirring of the liquid in the sample adjustment tank. The sample storage mechanism, the bubble trap mechanism and the chromatography mechanism are connected to the sample adjustment tank in sequence. A chromatography buffer interface is provided between the sample storage mechanism and the bubble trap mechanism. The chromatography device can save time and labor, improve chromatography efficiency and has high stability.

Description

Technical Field

[0001] The invention relates to the field of biotechnology, in particular to a chromatography device. Background Art

[0002] Many samples need to be conditioned for pH and conductivity before chromatography purification before loading. In the prior art, this adjustment process is generally performed manually. For example, a certain amount of acidic or alkaline solution is added to the sample to lower or increase the pH, the sample is diluted with a low-salt solution to reduce the sample conductivity, or a high-salt solution is added to the sample to increase the sample conductivity. After each addition of a certain amount of adjustment solution, the pH and conductivity must be sampled to prevent exceeding the target range. After the sample adjustment is completed, the chromatography loading can be started. The manual adjustment process is time-consuming and laborious, and since the pH and conductivity of the sample cannot be detected in real time, this not only increases the operation but also increases the risk of sample contamination. Such manual adjustment generally adjusts more than ten liters or dozens of hundreds of liters of samples at a time, and the loading process generally takes several hours. If the sample is not stable under the pH and conductivity conditions required for loading, this will increase the risk of sample damage. If a batch of samples is divided into multiple batches for adjustment, although the exposure time of the sample is reduced and the risk of sample damage is reduced, this will increase the number of manual operations and labor. Summary of the invention

[0003] Based on this, it is necessary to provide a chromatography device that can save time and energy, improve chromatography efficiency, and has high stability.

[0004] A chromatography device comprises a sample online adjustment mechanism, a sample storage mechanism, a bubble trap mechanism and a chromatography mechanism, wherein the sample online adjustment mechanism comprises a sample adjustment tank, a stirring assembly, an acid inlet pipe, an alkali inlet pipe, a conductivity adjustment liquid inlet pipe, a pH sensor and a conductivity sensor, wherein a sample inlet port is arranged on the sample adjustment tank, the acid inlet pipe, the alkali inlet pipe and the conductivity adjustment liquid inlet pipe are all connected to the sample adjustment tank, the pH sensor and the conductivity sensor are both connected to the sample adjustment tank, the stirring assembly is connected to the sample adjustment tank to achieve stirring of the liquid in the sample adjustment tank, the sample storage mechanism, the bubble trap mechanism and the chromatography mechanism are connected to the sample adjustment tank in sequence, and a chromatography buffer interface is also arranged between the sample storage mechanism and the bubble trap mechanism.

[0005] In one embodiment, the sample online adjustment mechanism further includes a sample inlet tube, and the sample inlet tube is connected to the sample inlet port.

[0006] In one embodiment, the sample online adjustment mechanism further includes a pneumatic valve, and the acid solution inlet pipe, and / or the alkali solution inlet pipe, and / or the conductivity adjustment liquid inlet pipe, and / or the sample inlet pipe are provided with the pneumatic valve.

[0007] In one embodiment, the sample online adjustment mechanism further includes a metering pump, and the metering pump is provided on the acid solution inlet pipe and / or the alkali solution inlet pipe.

[0008] In one embodiment, the sample online adjustment mechanism further includes a diaphragm pump, and the conductivity adjustment liquid inlet pipe and / or the sample inlet pipe are provided with the diaphragm pump.

[0009] In one embodiment, an acid liquid discharge port is provided at one end of the acid liquid inlet pipe close to the sample conditioning tank;

[0010] And / or, an alkali solution discharge port is provided at one end of the alkali solution inlet pipe close to the sample adjustment tank;

[0011] And / or, a conductivity regulating liquid discharge port is provided at one end of the conductivity regulating liquid inlet pipe close to the sample regulating tank;

[0012] And / or, a sample discharge port is provided at one end of the sample inlet tube close to the sample conditioning tank.

[0013] In one embodiment, the sample regulating tank is provided with a regulating tank exhaust port, and a pneumatic valve for opening or closing the regulating tank exhaust port is provided at the regulating tank exhaust port.

[0014] In one embodiment, one or more of a bubble sensor, a pH sensor, a conductivity sensor, a pressure sensor and a diaphragm pump are arranged on the pipeline between the sample storage mechanism and the bubble trap mechanism.

[0015] In one embodiment, the bubble trap mechanism is connected to the sample storage mechanism and the chromatography mechanism through a pneumatic valve group with a bypass function, and a plurality of liquid level sensors are arranged on the bubble trap mechanism.

[0016] In one embodiment, the chromatography mechanism is connected to the bubble trap mechanism via a pneumatic valve group with a bypass function.

[0017] In one embodiment, a flow meter and / or a pressure sensor is provided on the pipeline between the bubble trap mechanism and the chromatography mechanism.

[0018] In one embodiment, the liquid outlet of the chromatography mechanism is further provided with one or more of a UV detector, a pH sensor, a conductivity sensor, and a multi-channel pneumatic valve group.

[0019] The chromatography device of the present invention saves time and effort, improves chromatography efficiency, and has high stability when used for chromatography work. The present invention solves the problem that the manual adjustment process in the traditional technology is time-consuming and labor-intensive, and because the pH and conductivity of the sample cannot be detected in real time, the risk of sample contamination is reduced, and such manual adjustment is avoided to adjust more than ten liters or tens or hundreds of liters of samples at a time, saving a lot of time. The sample has high stability in the pH and conductivity conditions required for loading, reducing the risk of sample damage. The present invention can realize continuous operation of a batch of samples, and can achieve the purpose of reducing sample exposure time and reducing the risk of sample damage without increasing the number of manual operations and labor.

[0020] When the chromatography device of the present invention is used, the sample, the conductivity regulating liquid, the acid and / or the alkali solution first fill the corresponding pipeline, and then the sample, the conductivity regulating liquid, the acid and / or the alkali solution enter the sample regulating tank according to the pre-tested ratio, and are stirred and mixed at a low speed. At the same time, the pH sensor and the conductivity sensor in the sample regulating tank are detected in real time, and the system program controls the amount of sample added, the amount of conductivity regulating liquid added, the amount of acid added and / or the amount of alkali added according to the feedback data for fine adjustment. When the pH and conductivity reach the preset control range, the sample adjustment stops. The sample regulating tank is connected to the sample storage mechanism, and all the adjusted samples enter the sample storage mechanism. The sample regulating tank is disconnected from the sample storage mechanism, the chromatography starts, and the loading begins. During the loading process, the sample regulating tank starts to repeat the aforementioned sample adjustment work, and the adjusted sample enters the sample storage mechanism. The sample storage mechanism always keeps the adjusted sample for loading, and the sample regulating tank adjusts the sample in batches, thereby realizing the online adjustment and loading of the sample, until all the sample adjustments are completed, so as to realize the cycle of adjustment and loading, and realize the online continuous chromatography work. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of a chromatography device according to an embodiment of the present invention.

[0022] Description of Reference Numerals

[0023] 10. Chromatographic device; 100. Sample online adjustment mechanism; 101. Sample adjustment tank; 1011. Adjustment tank exhaust port; 102. Stirring assembly; 103. Sample inlet pipe; 1031. Sample discharge port; 104. Conductivity adjustment liquid inlet pipe; 1041. Conductivity adjustment liquid discharge port; 105. Acid inlet pipe; 1051. Acid discharge port; 106a, 106b, 106c, pH sensor; 107a, 107b, 107c, conductivity sensor; 108. Alkaline solution inlet pipe; 1081. Alkaline solution discharge port; 109a, 109b, 109c, 109d, 109e, 109f, pneumatic valve; 110a, 110b, 110c 0c, diaphragm pump; 111a, 111b, 111c, 111d, 111e, flow meter; 112a, 112b, metering pump; 200, sample storage mechanism; 201, storage exhaust port; 300, bubble trap mechanism; 301, trap mechanism exhaust port; 302, trap mechanism drain port; 400, chromatography mechanism; 500a, 500b, multi-channel pneumatic valve group; 600a, 600b, pressure sensor; 700, UV detector; 800a, 800b, pneumatic valve group with bypass function; 900a, 900b, liquid level sensor; 1001, chromatography buffer interface; 1002, liquid outlet; 1100, bubble sensor. DETAILED DESCRIPTION

[0024] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0025] In the description of the present invention, it should be understood that the terms "center", "upper", "lower", "bottom", "inside" and "outside" used in the present invention to indicate the orientation or position relationship are based on the orientation or position relationship shown in the drawings, which is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0026] It should be understood that the present invention uses the terms "first", "second", etc. to describe various information, but these information should not be limited to these terms, and these terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of the present invention, "first" information may also be referred to as "second" information, and similarly, "second" information may also be referred to as "first" information.

[0027] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "connected" and "connection" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, and it can be the internal connection of two elements. That is, when an element is referred to as "fixed to" another element, it can be directly on the other element or there can also be an intermediate element. When an element is considered to be "connected" to another element, it can be directly connected to the other element or there can be an intermediate element at the same time. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0029] See also Figure 1 As shown, an embodiment of the present invention provides a chromatography device 10.

[0030] The chromatography device 10 includes a sample online adjustment mechanism 100, a sample storage mechanism 200, a bubble trap mechanism 300, a chromatography mechanism 400 and a control mechanism. The control mechanism is electrically connected to the sample online adjustment mechanism 100, the bubble trap mechanism 300 and the chromatography mechanism 400. The control mechanism can be a PLC, PID, etc. Figure 1 Not shown.

[0031] The sample online adjustment mechanism 100 comprises a sample adjustment tank 101, a stirring assembly 102, an acid inlet pipe 105, an alkali inlet pipe 108, a conductivity adjustment liquid inlet pipe 104, a pH sensor 106a and a conductivity sensor 107a. A sample inlet port is provided on the sample adjustment tank 101. The acid inlet pipe 105, the alkali inlet pipe 108 and the conductivity adjustment liquid inlet pipe 104 are all connected to the sample adjustment tank 101. The pH sensor 106a and the conductivity sensor 107a are both connected to the sample adjustment tank 101. The stirring assembly 102, the pH sensor 106a and the conductivity sensor 107a are electrically connected to the control mechanism, and the control mechanism controls the amount of sample added, the amount of conductivity adjustment liquid added, the amount of acid added and / or the amount of alkali liquid added according to the data fed back by the pH sensor 106a and the conductivity sensor 107a, and performs fine adjustment.

[0032] Furthermore, a sample inlet tube 103 is connected to the sample inlet.

[0033] The acid inlet pipe 105 is provided with a pneumatic valve 109c, the alkali inlet pipe 108 is provided with a pneumatic valve 109f, and / or the conductivity regulating liquid inlet pipe 104 is provided with a pneumatic valve 109b, and / or the sample inlet pipe 103 is provided with a pneumatic valve 109a. The pneumatic valves 109a, 109b, 109c, and 109f can all be electrically connected to the control mechanism.

[0034] In one embodiment, the chromatography device 10 further includes a flowmeter, wherein a flowmeter 111a is provided on the sample inlet pipe 103, and the flow rate of the sample inlet pipe 103 is monitored and controlled by the flowmeter 111a. And / or a flowmeter 111b is provided on the conductivity regulating liquid inlet pipe 104, and the flow rate of the conductivity regulating liquid inlet pipe 104 is monitored and controlled by the flowmeter 111b. And / or a flowmeter 111c is also provided on the acid inlet pipe 105, and the flow rate of the acid inlet pipe 105 is monitored and controlled by the flowmeter 111c. And / or a flowmeter 111e is provided on the alkali solution inlet pipe 108, and the flow rate of the alkali solution inlet pipe 108 is monitored and controlled by the flowmeter 111e. The flowmeters 111a, 111b, 111c, and 111e can all be electrically connected to the control mechanism.

[0035] The stirring assembly 102 is connected to the sample conditioning tank 101 to achieve stirring of the liquid in the sample conditioning tank 101. Furthermore, the stirring assembly 102 includes a stirring paddle and a stirring motor electrically connected to the control mechanism. The stirring paddle is arranged in the sample conditioning tank 101, and the stirring motor is installed on the top of the sample conditioning tank 101 and connected to the stirring paddle. The stirring motor is used to drive the stirring paddle to rotate, and the speed of the stirring motor is adjustable and controllable, so that the speed of the stirring paddle can be adjusted and controlled. The stirring paddle and the stirring motor are attached to the Figure 1 Not shown.

[0036] The sample storage mechanism 200, the bubble trap mechanism 300 and the chromatography mechanism 400 are sequentially connected to the sample conditioning tank 101. Specifically, the sample storage mechanism 200 is connected to the sample conditioning tank 101, and the sample storage mechanism 200 is sequentially connected to the bubble trap mechanism 300 and the chromatography mechanism 400 through a pipeline.

[0037] The sample storage mechanism 200 may be a sample storage tank. When set, the sample storage mechanism 200 is located below the sample conditioning tank 101. This arrangement allows the conditioned sample to enter the sample storage mechanism 200 under the action of gravity, without the need for a mechanical pump, thus saving electrical energy resources. A pneumatic valve 109d is provided on the pipeline between the sample conditioning tank 101 and the sample storage mechanism 200.

[0038] A chromatography buffer interface 1001 is provided between the sample storage mechanism 200 and the bubble trap mechanism 300, and the chromatography buffer interface 1001 is used to supply the chromatography buffer. In one embodiment, there are multiple chromatography buffer interfaces 1001, and the multiple chromatography buffer interfaces 1001 are connected to the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300 through the multi-channel pneumatic valve group 500a.

[0039] Furthermore, an external liquid inlet mechanism may be provided at the chromatography buffer interface. Specifically, the liquid inlet mechanism is connected to the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300 through the multi-channel pneumatic valve group 500a. The multi-channel pneumatic valve group 500a is connected to the liquid inlet mechanism through multiple chromatography buffer interfaces 1001. The liquid inlet mechanism is used to pump chromatography buffer into the chromatography buffer interface 1001 and the chromatography mechanism 400. The liquid inlet mechanism may be a syringe, a sample injection bottle, a sample injection pump connected to the chromatography buffer, etc. Figure 1 It should be noted that the liquid inlet mechanism may be a third-party environmental component or a part of the chromatography device 10 of the present invention.

[0040] The bubble trap mechanism 300 has a trap mechanism exhaust port 301 and a trap mechanism drain port 302 .

[0041] The chromatography device 10 of the present invention saves time and effort, improves chromatography efficiency, and has high stability when used for chromatography work. The present invention solves the problem that the manual adjustment process in the traditional technology is time-consuming and labor-intensive, and because the pH and conductivity of the sample cannot be detected in real time, the risk of sample contamination is reduced, and such manual adjustment is avoided. It is necessary to adjust more than ten liters or tens or hundreds of liters of samples at a time, saving a lot of time. The sample has high stability in the pH and conductivity conditions required for loading, reducing the risk of sample damage. The present invention can also achieve a batch of samples that can be operated continuously, without increasing the number of manual operations and the amount of labor, and can achieve the purpose of reducing the exposure time of the sample and reducing the risk of sample damage.

[0042] In a specific example, the sample online adjustment mechanism 100 further includes a diaphragm pump. A diaphragm pump 110a is provided on the sample inlet pipe 103, and / or a diaphragm pump 110b is provided on the conductivity adjustment liquid inlet pipe 104. Both the diaphragm pumps 110a and 110b can be electrically connected to the control mechanism.

[0043] In a specific example, an acid liquid discharge port 1051 is provided at one end of the acid liquid inlet pipe 105 close to the sample conditioning tank 101. The purpose of the acid liquid discharge port 1051 is as follows: before the chromatography starts, the acid liquid inlet pipe 105 needs to be filled with acid liquid, and a small portion is discharged through the acid liquid discharge port 1051, so that it can be quickly confirmed that the acid liquid inlet pipe 105 is filled with acid liquid. After the acid liquid inlet pipe 105 is filled with acid liquid, the accuracy of the regulation can be improved, and the regulation efficiency can be improved.

[0044] And / or, an alkali liquid discharge port 1081 is provided at one end of the alkali liquid inlet pipe 108 close to the sample adjustment tank 101. The purpose of setting the alkali liquid discharge port 1081 is as follows: before the chromatography starts, the alkali liquid inlet pipe 108 needs to be filled with alkali liquid, and a small portion is discharged through the alkali liquid discharge port 1081, so that it can be quickly confirmed that the alkali liquid inlet pipe 108 is filled with alkali liquid. After the alkali liquid inlet pipe 108 is filled with alkali liquid, the accuracy of adjustment can be improved, and the adjustment efficiency can be improved.

[0045] And / or, a conductivity regulating liquid inlet pipe 104 is provided with a conductivity regulating liquid discharge port 1041 at one end close to the sample regulating tank 101. The purpose of setting the conductivity regulating liquid discharge port 1041 is as follows: before the start of chromatography, the conductivity regulating liquid inlet pipe 104 needs to be filled with the conductivity regulating liquid, and a small portion is discharged through the conductivity regulating liquid discharge port 1041, so that it can be quickly confirmed that the conductivity regulating liquid inlet pipe 104 is filled with the conductivity regulating liquid. After the conductivity regulating liquid inlet pipe 104 is filled with the conductivity regulating liquid, the accuracy of regulation can be improved and the regulation efficiency can be improved.

[0046] And / or, a sample discharge port 1031 is provided at one end of the sample inlet tube 103 close to the sample adjustment tank 101. The purpose of setting the sample discharge port 1031 is as follows: before the chromatography starts, the sample inlet tube 103 needs to be filled with the conductivity adjustment liquid, and a small portion is discharged through the sample discharge port 1031, so that it can be quickly confirmed that the sample inlet tube 103 is filled with the sample. After the sample inlet tube 103 is filled with the sample, the accuracy of the adjustment can be improved, and the adjustment efficiency can be improved.

[0047] In a specific example, the sample regulating tank 101 is provided with a regulating tank exhaust port 1011. The regulating tank exhaust port 1011 is provided with a pneumatic valve 109e for opening or closing the regulating tank exhaust port 1011. The sample storage mechanism 200 is provided with a storage exhaust port 201.

[0048] In a specific example, the sample online adjustment mechanism 100 further includes a metering pump, which can be a high-precision metering pump. A metering pump 112a is provided on the acid inlet pipe 105. And / or a metering pump 112b is provided on the alkali solution inlet pipe 108. Both the metering pumps 112a and 112b can be electrically connected to the control mechanism. The metering pumps 112a and 112b can accurately control the amount of acid or alkali solution added, which can improve the accuracy and efficiency of the adjustment.

[0049] In a specific example, one or more of a bubble sensor 1100, a pressure sensor 600a, and a diaphragm pump 110c are arranged on the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300. The bubble sensor 1100, the pressure sensor 600a, and the diaphragm pump 110c can all be electrically connected to the control mechanism. Preferably, the bubble sensor 1100, the pressure sensor 600a, and the diaphragm pump 110c are arranged on the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300. The positions of the bubble sensor 1100, the pressure sensor 600a, and the diaphragm pump 110c can be adjusted as needed. Furthermore, one or more of a pH sensor 106b and a conductivity sensor 107b are also arranged on the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300, and the pH sensor 106b and the conductivity sensor 107b can all be electrically connected to the control mechanism. Preferably, a pH sensor 106 b and a conductivity sensor 107 b are provided on the pipe between the sample storage mechanism 200 and the bubble trap mechanism 300 .

[0050] A flow meter 111 c is also provided on the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300, and the flow on the pipeline is monitored and controlled by the flow meter 111 c. The flow meter 111 c can be electrically connected to the control mechanism.

[0051] In a specific example, the bubble trap mechanism 300 is connected to the sample storage mechanism 200 and the chromatography mechanism 400 through a pneumatic valve group 800a with a bypass function. A plurality of liquid level sensors are arranged on the bubble trap mechanism 300, at least one liquid level sensor is arranged on the top of the bubble trap mechanism 300, and at least one liquid level sensor is arranged on the bottom of the bubble trap mechanism 300. Preferably, see Figure 1 As shown, one embodiment of the present invention shows two liquid level sensors 900a and 900b, wherein one liquid level sensor 900a is disposed at the top of the bubble trap mechanism 300, and one liquid level sensor 900b is disposed at the bottom of the bubble trap mechanism 300. The pneumatic valve group 800a with bypass function and the liquid level sensors 900a and 900b can be electrically connected to the control mechanism.

[0052] A pressure sensor 600b may be provided on the pipeline between the bubble trap mechanism 300 and the chromatography mechanism 400. A flow meter 111d may also be provided on the pipeline between the bubble trap mechanism 300 and the chromatography mechanism 400, and the flow on the pipeline is monitored and controlled by the flow meter 111d. The pressure sensor 600b and the flow meter 111d may be electrically connected to the control mechanism.

[0053] In a specific example, the chromatography mechanism 400 is connected to the bubble trap mechanism 300 via a pneumatic valve group 800b with a bypass function. The pneumatic valve group 800b with a bypass function can be electrically connected to the control mechanism.

[0054] In a specific example, the liquid outlet of the chromatography mechanism 400 is also connected to a UV detector 700, and the UV detector 700 is used to detect the protein concentration in the liquid outlet. The UV detector 700 can be electrically connected to the control mechanism.

[0055] In a specific example, the liquid outlet end of the chromatography mechanism 400 is further provided with a liquid outlet 1002. The number of the liquid outlets 1002 can be multiple. When the number of the liquid outlets 1002 is multiple, the liquid outlet end is connected to the multiple liquid outlets 1002 through the multi-channel pneumatic valve group 500b. The chromatographic liquid after chromatography can flow out through any liquid outlet 1002 through the multi-channel pneumatic valve group 500b.

[0056] A conductivity sensor 107c and / or a pH sensor 106c may also be provided on the pipeline at the liquid outlet of the chromatography mechanism 400. The conductivity sensor 107c and the pH sensor 106c may be electrically connected to the control mechanism.

[0057] The chromatography device 10 of the present invention comprises the following steps when used for chromatography:

[0058] Open the pneumatic valves 109a, 109b, 109c, and 109f on the sample inlet pipe 103, the conductivity regulating liquid inlet pipe 104, the acid inlet pipe 105, and the alkali liquid inlet pipe 108, fill the acid inlet pipe 105 with acid, discharge a small portion through the acid liquid discharge port 1051, and quickly confirm that the acid inlet pipe 105 is filled with acid. Fill the alkali liquid inlet pipe 108 with alkali liquid, discharge a small portion through the alkali liquid discharge port 1081, and quickly confirm that the alkali liquid inlet pipe 108 is filled with alkali liquid. Fill the conductivity regulating liquid inlet pipe 104 with conductivity regulating liquid, discharge a small portion through the conductivity regulating liquid discharge port 1041, and quickly confirm that the conductivity regulating liquid inlet pipe 104 is filled with conductivity regulating liquid. Fill the sample inlet pipe 103 with sample, discharge a small portion through the sample discharge port 1031, and quickly confirm that the sample inlet pipe 103 is filled with sample.

[0059] Conductivity regulating liquid, acid and / or alkali solution enter the sample regulating tank 101 according to the pre-tested ratio, and the stirring motor drives the stirring paddle to rotate at a predetermined speed and low speed. The pH value and conductivity of the sample in the sample regulating tank 101 are detected by the pH sensor 106a and the conductivity sensor 107a, and the pH value and conductivity data are fed back to the control mechanism in real time. The control mechanism compares the preset values ​​of the data. When the pH and conductivity data exceed the preset control range, the amount of sample added, the amount of conductivity regulating liquid added, the amount of acid added and / or the amount of alkali solution added are fine-tuned, and the stirring motor keeps driving the stirring paddle to rotate at a predetermined speed and low speed. The pH sensor 106a and the conductivity sensor 107a in the sample regulating tank 101 are detected in real time, and when the pH and conductivity reach the preset control range, the sample regulation stops.

[0060] The pneumatic valve 109d between the sample adjustment tank 101 and the sample storage mechanism 200 is opened, and the sample in the sample adjustment tank 101 enters the sample storage mechanism 200 under the action of gravity. All the adjusted samples enter the sample storage mechanism 200, and the pneumatic valve 109d between the sample adjustment tank 101 and the sample storage mechanism 200 is disconnected.

[0061] When the chromatography starts, the liquid inlet mechanism starts to input the chromatography buffer into the pipeline between the sample storage mechanism 200 and the bubble trap mechanism 300 through the chromatography buffer interface 1001 and the multi-channel pneumatic valve group 500a, so as to achieve the mixing of the chromatography buffer and the sample. The chromatography buffer and the sample are mixed to form a mixed solution, which is detected by the bubble sensor 1100, the pH sensor 106b, the conductivity sensor 107b and the pressure sensor 600a. After each detection, the mixed solution reaches the bubble trap mechanism 300, and the bubble trap mechanism 300 removes bubbles from the mixed solution. After the bubbles are removed, the mixed solution is again subjected to the pressure detection of the pressure sensor 600b. During the loading process, the sample conditioning tank 101 starts to repeat the sample conditioning work again, and the conditioned sample enters the sample storage mechanism 200 for storage, so that the sample storage mechanism 200 always has the conditioned sample for loading, and at the same time, the sample conditioning tank 101 is conditioning the sample in batches.

[0062] After being processed by the bubble trap mechanism 300 and pressure-detected by the pressure sensor 600b, the mixed liquid enters the chromatography mechanism 400 for chromatography. The flow rate of the mixed liquid entering the chromatography mechanism 400 can be monitored and controlled by the flow meter 111d. After being detected by the UV detector 700, the chromatographic liquid is discharged through the multi-channel pneumatic valve group 500b. The chromatographic liquid can flow out through any one or more liquid outlets 1002 through the multi-channel pneumatic valve group 500b.

[0063] In summary, when the chromatography device 10 of the present invention is used, the sample, the conductivity regulating liquid, the acid and / or the alkali solution first fill the corresponding pipes, and then the sample, the conductivity regulating liquid, the acid and / or the alkali solution enter the sample regulating tank 101 according to the pre-tested ratio, and are stirred and mixed at a low speed. At the same time, the pH sensor 106a and the conductivity sensor 107a in the sample regulating tank 101 are detected in real time, and the control mechanism controls the amount of sample added, the amount of conductivity regulating liquid added, the amount of acid added and / or the amount of alkali added according to the feedback data to make fine adjustments. When the pH and conductivity data fed back by the pH sensor 106a and the conductivity sensor 107a reach the preset range of the control mechanism, the sample adjustment stops. The sample regulating tank 101 is connected to the sample storage mechanism 200, and all the adjusted samples enter the sample storage mechanism 200, and the sample regulating tank 101 is disconnected from the sample storage mechanism 200. The chromatography starts, and the liquid inlet mechanism and the chromatography mechanism 400 work. The liquid inlet mechanism starts to pump in the chromatography buffer solution and mixes it with the sample and then enters the chromatography mechanism 400. During the operation of the chromatography mechanism, the sample conditioning tank 101 starts to repeat the aforementioned sample conditioning work, and the conditioned sample enters the sample storage mechanism 200. The sample storage mechanism 200 always keeps the conditioned sample for loading. At the same time, the sample conditioning tank 101 adjusts the sample in batches and intervals to achieve online sample conditioning and loading until all samples are conditioned. In this way, the cycle of conditioning and loading is realized, and online continuous chromatography is achieved.

[0064] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0065] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A chromatography device, characterized in that: The invention comprises a sample online adjustment mechanism, a sample storage mechanism, a bubble trap mechanism and a chromatography mechanism, wherein the sample online adjustment mechanism comprises a sample inlet pipe, a sample adjustment tank, a stirring component, an acid inlet pipe, an alkali inlet pipe, a conductivity adjustment liquid inlet pipe, a pH sensor and a conductivity sensor, the sample adjustment tank is provided with a sample inlet port, the sample inlet pipe is connected to the sample inlet port, the acid inlet pipe, the alkali inlet pipe and the conductivity adjustment liquid inlet pipe are all connected to the sample adjustment tank, the pH sensor and the conductivity sensor are all connected to the sample adjustment tank, the stirring component is connected to the sample adjustment tank In order to achieve stirring of the liquid in the sample regulating tank, the sample regulating tank, the sample storage mechanism, the bubble trap mechanism and the chromatography mechanism are connected in sequence, the bubble trap mechanism is connected with the sample storage mechanism and the chromatography mechanism through a pneumatic valve group with a bypass function, a plurality of liquid level sensors are arranged on the bubble trap mechanism, a chromatography buffer interface is also arranged between the sample storage mechanism and the bubble trap mechanism, and a bubble sensor, a pH sensor, a conductivity sensor, a pressure sensor and a diaphragm pump are arranged on the pipeline between the sample storage mechanism and the bubble trap mechanism.

2. The chromatography device according to claim 1, characterized in that The sample online adjustment mechanism also includes a pneumatic valve, and the acid solution inlet pipe, and / or the alkali solution inlet pipe, and / or the conductivity adjustment liquid inlet pipe, and / or the sample inlet pipe are provided with the pneumatic valve.

3. The chromatography device according to claim 1, characterized in that The sample online adjustment mechanism further comprises a metering pump, and the metering pump is arranged on the acid solution inlet pipe and / or the alkali solution inlet pipe.

4. The chromatography device according to claim 1, characterized in that The sample online adjustment mechanism further comprises a diaphragm pump, and the conductivity adjustment liquid inlet pipe and / or the sample inlet pipe are both provided with the diaphragm pump.

5. The chromatography device according to claim 1, characterized in that An acid liquid discharge port is provided at one end of the acid liquid inlet pipe close to the sample regulating tank; And / or, an alkali solution discharge port is provided at one end of the alkali solution inlet pipe close to the sample adjustment tank; And / or, a conductivity regulating liquid discharge port is provided at one end of the conductivity regulating liquid inlet pipe close to the sample regulating tank; And / or, a sample discharge port is provided at one end of the sample inlet tube close to the sample conditioning tank.

6. The chromatography device according to claim 1, characterized in that The sample regulating tank is provided with a regulating tank exhaust port, and a pneumatic valve for opening or closing the regulating tank exhaust port is provided at the regulating tank exhaust port.

7. The chromatography device according to any one of claims 1 to 6, characterized in that: The chromatography mechanism is communicated with the bubble trap mechanism via a pneumatic valve group with a bypass function.

8. The chromatography device according to any one of claims 1 to 6, characterized in that: A flow meter and / or a pressure sensor is arranged on the pipeline between the bubble trap mechanism and the chromatography mechanism.

9. The chromatography device according to any one of claims 1 to 6, characterized in that: The liquid outlet of the chromatography mechanism is also provided with one or more of a UV detector, a pH sensor, a conductivity sensor, and a multi-channel pneumatic valve group.

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