A multi-stage membrane separation coupled chromatography online sampling device

Abstract

The invention relates to a multi-stage membrane separation coupled chromatographic online sampling device, which comprises a multi-stage membrane separation module, a chromatographic module and a multi-channel sampling switching valve. The multi-stage membrane separation module comprises at least two separation membrane units, and the separation membrane unit comprises a liquid inlet, a permeate outlet and a concentrated liquid outlet. The multi-channel sampling switching valve has a permeate inlet, a concentrated liquid inlet and a common outlet. The permeate inlet is connected to the permeate outlet in a one-to-one correspondence, the concentrated liquid inlet is connected to the concentrated liquid outlet in a one-to-one correspondence, the common outlet can be connected to any permeate inlet or concentrated liquid inlet, and the common outlet is connected to the chromatographic module. According to material properties and separation targets, the units inside the membrane separation module and the chromatographic module can be freely modularly combined, which is suitable for a variety of differentiated separation systems and targets.

Description

Technical Field

[0001] The invention relates to the technical field of preparation and separation, and in particular to a multi-stage membrane separation coupled chromatographic online sampling device. Background Art

[0002] Membrane separation technology is a commonly used technical means in the field of separation. According to the selectivity of the separation membrane, it can be divided into various forms such as microfiltration, ultrafiltration, nanofiltration, reverse osmosis, etc. It can cut materials into segments within the range of 0.0001 to 100 microns, effectively achieving the purpose of separation, purification, and concentration of different components. Since the membrane separation process is a purely physical separation, it does not involve thermal, chemical or biological changes, and has basically no effect on the material. In addition, the membrane separation process is composed of components, which can meet the needs of different production capacities and is more suitable for scale.

[0003] Chromatography is a separation method with a wide range of applications in the field of chemistry. The separation principle of chromatographic separation technology is to separate substances based on their adsorption capacity on the stationary phase or the different distribution coefficients between the stationary phase and the mobile phase. A variety of separation modes are produced according to the different stationary phases. It has the characteristics of wide applicability of separation objects, mild separation conditions, and high separation degree. It is an important supplement to preparative separation technology. There are one-dimensional column chromatography technology and two-dimensional column chromatography technology in chromatographic separation technology. Two-dimensional column chromatography is a technology developed on the basis of one-dimensional column chromatography. It provides a larger peak capacity by collecting the first-dimensional chromatographic fractions directly or through a special interface and then introducing them into the second-dimensional chromatography for two-dimensional separation, so that it can more effectively deal with the separation problems of complex systems. It is an important tool for the preparative separation of natural products.

[0004] In recent years, with the continuous improvement of quality standards in the fields of biology, medicine and chemistry, the high purity requirements of products have promoted the development of separation methods, among which membrane separation coupled with chromatographic separation is a separation method that can simultaneously meet high separation efficiency and economy. For example, a method for separating and purifying dehydratedaptomycin disclosed in the Chinese invention patent application with application publication number CN103724400A uses nanofiltration membrane and chromatography to obtain dehydratedaptomycin with a purity greater than 98%. For example, a total alkaloid component extracted from Coptis chinensis and a purification method thereof disclosed in the Chinese invention patent application with application publication number CN111329905A combines membrane filtration and high-performance reverse phase chromatography to achieve the enrichment and purification preparation of total alkaloids from Coptis chinensis. For example, a preparation method and application of a high-content mogroside monomer product disclosed in the Chinese invention patent with authorization announcement number CN110343141B uses nanofiltration membrane and chromatography to obtain a high-content mogroside monomer product. For example, a method for preparing high-purity tea polyphenol compounds in summer and autumn tea leaves is disclosed in a Chinese invention patent application with application publication number CN111602730A, which combines membrane filtration with chromatographic purification to obtain high-purity tea polyphenols.

[0005] The above existing technologies all achieve good separation effects through membrane separation coupled with chromatography. However, in the existing separation systems, the membrane components (membrane separation modules) and the chromatography systems (chromatography modules) are all specifically set up to meet the separation of specific material components, and the coupling method of the separation components is only effective for specific separation systems. Due to the different properties of materials in different systems to be separated, the separation target under the same separation system may also change due to changes in preparation purposes or experimental purposes. Therefore, the existing membrane separation coupled with chromatography method is difficult to cope with the changing systems and targets. Summary of the invention

[0006] The object of the present invention is to provide a multi-stage membrane separation coupled chromatography online sample injection device to solve the problem that the existing membrane separation coupled chromatography method is difficult to cope with the variable separation system and separation target.

[0007] The technical solution of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention is:

[0008] The multi-stage membrane separation coupled chromatography online sampling device comprises a membrane separation module and a chromatography module. The membrane separation module is a multi-stage membrane separation module. The multi-stage membrane separation module comprises at least two separation membrane units. The membrane pore sizes of different types of separation membrane units are different and the membrane pore sizes of the separation membrane units from the upstream to the downstream of the multi-stage membrane separation module gradually decrease. The separation membrane unit comprises a liquid inlet, a permeate outlet, and a concentrated liquid outlet. Among the two adjacent separation membrane units, the permeate outlet of the separation membrane unit located upstream is connected to the liquid inlet of the separation membrane unit located downstream so as to The upstream permeate is separated into the downstream permeate and the downstream concentrate flowing out from the downstream separation membrane unit; and the multi-channel sampling switching valve is also included. The multi-channel sampling switching valve has a permeate inlet, a concentrate inlet and a common outlet. The number of the permeate inlets is equal to the number of the permeate outlets and they are connected one-to-one. The number of the concentrate inlets is equal to the number of the concentrate outlets and they are connected one-to-one. The multi-channel sampling switching valve has an injection switching position. Each injection switching position is used to connect the common outlet with any one of the permeate inlets or the concentrate inlet. The common outlet is connected to the chromatography module.

[0009] Beneficial effect: A multi-stage membrane separation module is formed by arranging different types of separation membrane units, and the permeate outlet and the concentrate outlet of each separation membrane unit are connected to the corresponding channel inlets of the multi-channel injection switching valve. When used in conjunction with a chromatography module, according to the required number of separations, the concentrate or permeate flowing out of a separation membrane unit whose number of separations meets the requirements is selected to be connected to the common outlet, and the permeate and concentrate of the separation membrane units at different stages can be selectively transported to the chromatography module by switching the multi-channel injection switching valve. Each separation membrane unit forms a different separation unit, and the output liquid of different separation units can enter the chromatography module. Therefore, the units inside the membrane separation module and the chromatography module can be freely modularized according to the material properties and separation targets, and online connection and continuous injection of membrane separation and chromatography can be realized in one device. It is suitable for a variety of differentiated separation systems and targets, and efficient coupling of membrane separation and chromatography can be achieved.

[0010] Furthermore, the chromatography module is a two-dimensional chromatography module, comprising a first-dimensional chromatography unit and a second-dimensional chromatography unit, the common outlet is connected to the first-dimensional chromatography unit or the second-dimensional chromatography unit, and the first-dimensional chromatography unit is connected to the second-dimensional chromatography unit.

[0011] Beneficial effect: By setting up a two-dimensional chromatography, the fractions of the first-dimensional chromatography can enter the second-dimensional chromatography for re-separation, which is beneficial to improving the separation effect.

[0012] Furthermore, it also includes a multi-channel diversion switching valve, which has a first sample outlet, a second sample outlet, and a common inlet. When the common inlet is connected to the first sample outlet or the second sample outlet, the multi-channel diversion switching valve is in an open state, and the common inlet is connected to the common outlet. The first-dimensional chromatography unit includes a first chromatography inlet and a first chromatography connecting port, and the second-dimensional chromatography unit includes a second chromatography inlet and a second chromatography connecting port. The first sample outlet is connected to the first chromatography inlet, the second sample outlet is connected to the second chromatography inlet, and the first chromatography connecting port is connected to the second chromatography connecting port.

[0013] Beneficial effect: By setting a multi-channel diversion switching valve and connecting the first-dimensional chromatography unit and the second-dimensional chromatography unit to the corresponding sample outlets, the first-dimensional chromatography unit and the second-dimensional chromatography unit inside the chromatography module can be used in combination with the membrane separation module, respectively, thereby improving the applicability to a variety of differentiated separation systems and targets.

[0014] Furthermore, the multi-stage membrane separation module includes an ultrafiltration membrane unit and a nanofiltration membrane unit, and the ultrafiltration membrane unit and the nanofiltration membrane unit each constitute a separation membrane unit.

[0015] Beneficial effects: The ultrafiltration membrane unit and the nanofiltration membrane unit are used in combination to ensure separation effect and be economical and applicable.

[0016] Furthermore, the ultrafiltration membrane unit is a ceramic ultrafiltration membrane unit or an organic ultrafiltration membrane unit; or the ultrafiltration membrane unit includes a ceramic ultrafiltration membrane unit and an organic ultrafiltration membrane unit connected in series.

[0017] Beneficial effect: By selecting or combining ceramic ultrafiltration membrane units and organic ultrafiltration membrane units, different separation systems and separation targets can be applied.

[0018] Furthermore, the multi-stage membrane separation module further comprises a reverse osmosis membrane unit, which constitutes a separation membrane unit, and the reverse osmosis membrane unit is arranged at the most downstream of the multi-stage membrane separation module.

[0019] Beneficial effects: By setting up a reverse osmosis membrane unit and placing the reverse osmosis membrane unit downstream of an ultrafiltration membrane unit and a nanofiltration membrane unit, the reverse osmosis membrane unit can be directly connected to the nanofiltration membrane unit, so that the permeate of the ultrafiltration membrane unit enters the nanofiltration membrane unit and then the permeate of the nanofiltration membrane unit enters the reverse osmosis membrane unit; it can also be directly connected to the ultrafiltration membrane unit, so that the permeate of the ultrafiltration membrane unit directly enters the reverse osmosis membrane unit, and the permeate of the ultrafiltration membrane unit or the nanofiltration membrane unit can be concentrated as needed to increase the sample concentration so that it is more suitable for sampling and separation of the chromatographic module; and the combination forms are increased to improve the applicability to different separation systems and separation targets.

[0020] Furthermore, it also includes a cleaning liquid storage tank, and the multi-channel injection switching valve also has a cleaning liquid inlet, which is connected to the cleaning liquid storage tank. The cleaning liquid inlet is used to supply cleaning liquid into the multi-channel injection switching valve when it is connected to the public outlet. A waste liquid outlet is provided between the multi-channel injection switching valve and the chromatography module.

[0021] Beneficial effect: By arranging a cleaning liquid inlet on the multi-channel injection switching valve, the multi-stage membrane separation coupled chromatography online injection device has a self-cleaning function to avoid cross contamination.

[0022] Furthermore, a waste liquid outlet is arranged on the multi-channel diversion switching valve, the waste liquid outlet is connected to a waste liquid tank, and the waste liquid outlet is used to discharge the waste liquid when connected to the public inlet of the multi-channel diversion switching valve.

[0023] Beneficial effect: The waste liquid outlet is set on the multi-channel diversion switching valve, which is convenient for controlling the on-off of the pipeline through the valve and convenient for operation.

[0024] Furthermore, between two adjacent separation membrane units, the permeate outlet of the upstream separation membrane unit is connected to the liquid inlet of the downstream separation membrane unit through an inter-membrane pipeline, and the inter-membrane pipeline is connected to the permeate inlet.

[0025] Beneficial effect: the permeate inlet is connected to the membrane pipeline, so that the permeate inlet and the permeate outlet are connected, which is convenient for pipeline setting.

[0026] Furthermore, the chromatography module is a column chromatography module.

[0027] Beneficial effects: Column chromatography is simple to operate, has high separation, good reproducibility and is reliable to use. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a schematic diagram of the multi-stage membrane separation coupled chromatography online sample injection device in Example 1 of the present invention when it is in a self-cleaning state;

[0029] Figure 2 It is a schematic diagram of the multi-stage membrane separation coupled chromatography online sampling device of Example 1 of the present invention when it is used for separation of characteristic flavor groups of Henan tobacco extract and is in a permeate sampling state of the reverse osmosis membrane unit;

[0030] Figure 3 This is a schematic diagram of the multi-stage membrane separation coupled chromatography online sampling device of Example 1 of the present invention when it is used for extracting solanesol and chlorogenic acid from tobacco and is in a concentrated liquid sampling state of the nanofiltration membrane unit;

[0031] Figure 4 This is a schematic diagram of the concentrated liquid injection state of the reverse osmosis membrane unit when the multi-stage membrane separation coupled chromatography online injection device of Example 1 of the present invention is used for extracting solanesol and chlorogenic acid from tobacco.

[0032] In the figure: 1. Multi-channel injection switching valve; 2. Multi-channel diversion switching valve; 3. Cleaning liquid storage tank; 4. Waste liquid tank; 5. Ultrafiltration membrane unit; 7. Nanofiltration membrane unit; 8. Reverse osmosis membrane unit; 9. First dimension chromatography unit; 10. Second dimension chromatography unit; 11. First membrane inter-pipeline; 12. Second membrane inter-pipeline. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention, that is, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The components of the embodiments of the present invention described and shown in the drawings herein can be arranged and designed in various different configurations.

[0034] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work are within the scope of protection of the present invention.

[0035] It should be noted that the terms that may appear in the specific embodiments of the present invention, such as relational terms such as "first" and "second", are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms that may appear, such as "include", "comprise" or any other variants thereof, are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements that are not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the possible statements "including one...", etc., do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0036] In the description of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected" and "connected" that may appear 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 it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood by specific circumstances.

[0037] In the description of the present invention, unless otherwise clearly specified and limited, the term "provided with" that may appear should be understood in a broad sense. For example, the object "provided with" may be a part of the body, or may be arranged separately from the body and connected to the body, and the connection may be a detachable connection or an inseparable connection. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0038] The present invention is described in further detail below in conjunction with embodiments.

[0039] Embodiment 1 of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention:

[0040] like Figure 1As shown, the multi-stage membrane separation coupled chromatography online injection device includes a membrane separation module, a multi-channel injection switching valve 1, a multi-channel diversion switching valve 2, and a chromatography module. The membrane separation module is a multi-stage membrane separation module, which includes a plurality of separation membrane units, each of which is connected to the multi-channel diversion switching valve 2. The chromatography module is a two-dimensional column chromatography module, which includes a first-dimensional chromatography unit 9 and a second-dimensional chromatography unit 10, which are both connected to the multi-channel diversion switching valve 2. Different separation membrane units can be switched through the multi-channel injection switching valve 1 and the multi-channel diversion switching valve 2 to be used in combination with the first-dimensional chromatography unit 9 or the second-dimensional chromatography unit 10 to cope with different separation systems and separation targets.

[0041] Each separation membrane unit is an ultrafiltration membrane unit 5, a nanofiltration membrane unit 7, and a reverse osmosis membrane unit 8. The separation membrane unit includes a liquid inlet, a permeate outlet, and a concentrated liquid outlet. The ultrafiltration membrane unit 5 is located upstream of the nanofiltration membrane unit 7, and the nanofiltration membrane unit 7 is located upstream of the reverse osmosis membrane unit 8. The permeate outlet of the upstream separation membrane unit is connected to the liquid inlet of the downstream separation membrane unit to separate the upstream permeate flowing out of the upstream separation membrane unit into the downstream permeate and the downstream concentrated liquid flowing out of the downstream separation membrane unit. By setting up three separation membrane units, the combination mode can be increased, and the applicability to different separation systems and separation targets can be improved.

[0042] In this embodiment, the ultrafiltration membrane unit 5 is a ceramic ultrafiltration membrane unit, which includes a ceramic ultrafiltration membrane assembly. The permeate outlet of the ultrafiltration membrane unit 5 is connected to the liquid inlet of the nanofiltration membrane unit 7 via a first inter-membrane pipeline 11, and the permeate outlet of the nanofiltration membrane unit 7 is connected to the liquid inlet of the reverse osmosis membrane unit 8 via a second inter-membrane pipeline 12. The nanofiltration membrane unit 7 includes a nanofiltration membrane assembly, and the reverse osmosis membrane unit 8 includes a reverse osmosis membrane assembly.

[0043] The multi-channel injection switching valve 1 is a multi-position multi-way selection valve with one outlet and multiple inlets. The multi-channel injection switching valve 1 has a permeate inlet, a concentrate inlet and a common outlet. The number of the permeate inlets is equal to the number of the permeate outlets and is connected one-to-one, that is, the multi-channel injection switching valve 1 has three permeate inlets respectively connected to the permeate outlet of the ultrafiltration membrane unit 5, the permeate outlet of the nanofiltration membrane unit 7, and the permeate outlet of the reverse osmosis membrane unit 8. The number of the concentrate inlets of the multi-channel injection switching valve 1 is equal to the number of the concentrate outlets and is connected one-to-one, that is, the multi-channel injection switching valve 1 has three concentrate inlets respectively connected to the concentrate outlet of the ultrafiltration membrane unit 5, the concentrate outlet of the nanofiltration membrane unit 7, and the concentrate outlet of the reverse osmosis membrane unit 8. The multi-channel injection switching valve 1 has different injection switching positions. When the multi-channel injection switching valve 1 is in one of the injection switching positions, the common outlet can be connected to a corresponding permeate inlet or a concentrate inlet. When the common outlet is connected to any permeate inlet or concentrate inlet, the common outlet is connected to the chromatography module. The multi-channel injection switching valve 1 also has a cleaning liquid inlet, which is connected to the cleaning liquid storage tank 3. The multi-channel injection switching valve 1 also has a cleaning switching position. When the multi-channel injection switching valve 1 is in the cleaning switching position, the cleaning liquid inlet is connected to the common outlet to allow the cleaning liquid to enter the multi-channel injection switching valve 1.

[0044] The three permeate inlets, three concentrate inlets and cleaning liquid inlet of the multichannel injection switching valve 1 are arranged in the circumferential direction, and the common outlet of the multichannel injection switching valve 1 is set at the center. The three concentrate inlets are respectively port 1, port 3, and port 5 of the multichannel injection switching valve 1 shown in the figure, the three permeate inlets are respectively port 2, port 4, and port 6 of the multichannel injection switching valve 1 shown in the figure, and the cleaning liquid inlet is port C of the multichannel injection switching valve 1 shown in the figure. The concentrated liquid outlet of the ultrafiltration membrane unit 5 is connected to port 1, the first membrane inter-pipe 11 is connected to port 2 to realize that the permeate outlet of the ultrafiltration membrane unit 5 is connected to port 2 through the first membrane inter-pipe 11, the concentrated liquid outlet of the nanofiltration membrane unit 7 is connected to port 3, the second membrane inter-pipe 12 is connected to port 4 to realize that the permeate outlet of the nanofiltration membrane unit 7 is connected to port 4 through the second membrane inter-pipe 12, the concentrated liquid outlet of the reverse osmosis membrane unit 8 is connected to port 5, and the permeate outlet of the reverse osmosis membrane unit 8 is connected to port 6.

[0045] The multi-channel flow splitter switching valve 2 is a multi-position multi-way selection valve with one inlet and multiple outlets. The multi-channel flow splitter switching valve 2 has a common inlet, a first sample outlet, a second sample outlet, and a waste liquid outlet. The common inlet is used to open the multi-channel flow splitter switching valve 2 when it is connected to the first sample outlet, the second sample outlet, or the waste liquid outlet. The multi-channel flow splitter switching valve 2 has different flow splitter switching positions, and there are two flow splitter switching positions, so that when the multi-channel flow splitter switching valve 2 is in the corresponding flow splitter switching position, the common inlet is connected to the first sample outlet or the second sample outlet. The multi-channel flow splitter switching valve 2 also has a liquid discharge switching position, and when the multi-channel flow splitter switching valve 2 is in the liquid discharge switching position, the common inlet is connected to the waste liquid outlet. The common inlet of the multi-channel flow splitter switching valve 2 is connected to the common outlet of the multi-channel injection switching valve 1. The waste liquid outlet is connected to a waste liquid tank 4. The cleaning liquid can enter the multi-channel injection switching valve 1, then enter the multi-channel diversion switching valve 2, and then be discharged through the waste liquid outlet, so that the multi-stage membrane separation coupled chromatography online injection device has a self-cleaning function to avoid cross contamination.

[0046] The first sample outlet, the second sample outlet, and the waste liquid outlet of the multi-channel flow diversion switching valve 2 are arranged in the circumferential direction, and the common inlet of the multi-channel flow diversion switching valve 2 is set at the center. The waste liquid outlet is port 1 of the multi-channel flow diversion switching valve 2 shown in the figure, the first sample outlet is port 2 of the multi-channel flow diversion switching valve 2 shown in the figure, and the second sample outlet is port 3 of the multi-channel flow diversion switching valve 2 shown in the figure.

[0047] The multi-stage membrane separation coupled chromatography online injection device also includes a controller, which is connected to the multi-channel injection switching valve 1 and the multi-channel diversion switching valve 2. The controller is used to control the multi-channel injection switching valve 1 and the multi-channel diversion switching valve 2 to switch to the corresponding switching position to realize automatic switching for cleaning operation, concentrate injection operation, and permeate injection operation.

[0048] The chromatographic module is a column chromatographic module, the chromatographic module adopts column chromatographic, the chromatographic module is a two-dimensional chromatographic module, the chromatographic module includes a first-dimensional chromatographic unit 9 and a second-dimensional chromatographic unit 10, the first-dimensional chromatographic unit 9 includes a first chromatographic inlet and a first chromatographic connecting port, the second-dimensional chromatographic unit 10 includes a second chromatographic inlet and a second chromatographic connecting port, and the first sample outlet is connected to the first chromatographic inlet, so that the common outlet of the multi-channel injection switching valve 1 is connected to the first-dimensional chromatographic unit 9 through the common inlet of the multi-channel diversion switching valve 2 and the first sample outlet. The second sample outlet is connected to the second chromatographic inlet, so that the common outlet of the multi-channel injection switching valve 1 is connected to the second-dimensional chromatographic unit 10 through the common inlet of the multi-channel diversion switching valve 2 and the second sample outlet. The first chromatographic connecting port is connected to the second chromatographic connecting port to realize the connection between the first-dimensional chromatographic unit 9 and the second-dimensional chromatographic unit 10. By setting a two-dimensional chromatogram, the flow fraction of the first-dimensional chromatogram can enter the second-dimensional chromatogram for re-separation, which is conducive to improving the separation effect.

[0049] When used for separation of characteristic flavor groups of Henan tobacco extract, the operation mode of the multi-stage membrane separation coupled chromatography online injection device is as follows:

[0050] (1) Dissolve the Yuyan extract in 50% ethanol to a solution with a dry matter content of 20%, and remove the insoluble matter by centrifugation. Take 9000 g of the Yuyan extract centrifuge, filter it with a 50 μm filter membrane, and use the ultrafiltration membrane unit 5, nanofiltration membrane unit 7, and reverse osmosis membrane unit 8 of the multi-stage membrane separation module for membrane separation in turn. The permeate of each membrane separation stage is used for the next membrane separation stage while retaining the concentrate of each membrane separation stage and the permeate of the last stage;

[0051] (2) Figure 1 As shown, the C port of the multi-channel injection switching valve 1 is connected to the common outlet, and the 1 port of the multi-channel diversion switching valve 2 is connected to the common inlet, and a cleaning operation is performed to clean the multi-stage membrane separation coupled chromatography online injection device;

[0052] (3) Port 1 of the multichannel injection switching valve 1 is connected to the common outlet, and port 2 of the multichannel diversion switching valve 2 is connected to the common inlet, and the concentrated liquid of the ultrafiltration membrane unit 5 is injected into the first dimension chromatography unit 9 of the two-dimensional column chromatography module for operation, and at the same time, the permeate of the ultrafiltration membrane unit is separated in the nanofiltration membrane unit;

[0053] (4) After the concentrated liquid of the ultrafiltration membrane unit has completed chromatographic separation, the port C of the multi-channel injection switching valve 1 is connected to the common outlet, and the port 1 of the multi-channel diversion switching valve 2 is connected to the common inlet, and a cleaning operation is performed;

[0054] (5) Port 3 of the multichannel injection switching valve 1 is connected to the common outlet, and port 2 of the multichannel diversion switching valve 2 is connected to the common inlet, and the concentrated liquid of the nanofiltration membrane unit 7 is injected into the first dimension chromatography unit 9 of the two-dimensional column chromatography module for operation, and at the same time, the permeate of the nanofiltration membrane unit is separated in the reverse osmosis membrane unit;

[0055] (6) After the concentrated liquid of the nanofiltration membrane unit completes chromatographic separation, the C port of the multi-channel injection switching valve 1 is connected to the common outlet, and the 1 port of the multi-channel diversion switching valve 2 is connected to the common inlet, and a cleaning operation is performed;

[0056] (7) Port 5 of the multichannel injection switching valve 1 is connected to the common outlet, and port 3 of the multichannel diversion switching valve 2 is connected to the common inlet, and the concentrated liquid of the reverse osmosis membrane unit 8 is injected into the second dimension chromatography unit 10 of the two-dimensional column chromatography module for operation;

[0057] (8) After the concentrated liquid of the reverse osmosis membrane unit has completed chromatographic separation, the port C of the multi-channel injection switching valve 1 is connected to the common outlet, and the port 1 of the multi-channel diversion switching valve 2 is connected to the common inlet for cleaning operation;

[0058] (9) Figure 2 As shown, port 6 of the multi-channel injection switching valve 1 is connected to the common outlet, and port 3 of the multi-channel diversion switching valve 2 is connected to the common inlet, and the permeate of the reverse osmosis membrane unit 8 is injected into the second dimension chromatography unit 10 of the two-dimensional column chromatography module for operation;

[0059] (10) After the permeate of the reverse osmosis membrane unit completes chromatographic separation, port C of the multichannel injection switching valve 1 is connected to the common outlet, and port 1 of the multichannel diversion switching valve 2 is connected to the common inlet for cleaning operation.

[0060] When used to extract solanesol and chlorogenic acid from tobacco, the operation mode of the multi-stage membrane separation coupled chromatography online injection device is as follows:

[0061] (1) After 1000g of tobacco is crushed into powder, the powder that passes through is sieved with a sieve, and 10000mL of 80% ethanol-water solution is added, heated at 60°C, and extracted three times, each time for 2 hours, and the clear liquid is filtered to be the extract. 9000g of the extract is taken and filtered with a 50μm filter membrane. The filtrate is sequentially subjected to membrane separation using an ultrafiltration membrane unit 5, a nanofiltration membrane unit 7, and a reverse osmosis membrane unit 8 of a multi-stage membrane separation unit, and the permeate of each stage of membrane separation is subjected to membrane separation of the next stage while retaining the concentrated liquid of each stage of membrane separation;

[0062] (2) The port C of the multi-channel injection switching valve 1 is connected to the common outlet, and the port 1 of the multi-channel diversion switching valve 2 is connected to the common inlet, and a cleaning operation is performed to clean the multi-stage membrane separation coupled chromatography online injection device;

[0063] (3) Figure 3 As shown, port 3 of the multi-channel injection switching valve 1 is connected to the common outlet, and port 2 of the multi-channel diversion switching valve 2 is connected to the common inlet, and the concentrated liquid of the nanofiltration membrane unit 7 is injected into the first-dimension chromatography unit 9 of the two-dimensional column chromatography module for operation, and then the separated flow fraction of the first-dimension chromatography unit is injected into the second-dimension chromatography unit through the first chromatography connecting port and the second chromatography connecting port for separation; at the same time, the permeate of the nanofiltration membrane unit 7 is concentrated in the reverse osmosis membrane unit 8;

[0064] (4) After the concentrated liquid of the nanofiltration membrane unit completes the two-dimensional chromatographic separation, the C port of the multi-channel injection switching valve 1 is connected to the common outlet, and the 1 port of the multi-channel diversion switching valve 2 is connected to the common inlet, and a cleaning operation is performed;

[0065] (5) Figure 4 As shown, position 5 of the multichannel injection switching valve is connected to the common outlet, and position 3 of the multichannel diversion switching valve 2 is connected to the common inlet, and the concentrated liquid of the reverse osmosis membrane unit 8 is injected into the second dimension chromatography unit 10 of the two-dimensional column chromatography module for column chromatography separation;

[0066] (6) After the concentrated liquid of the reverse osmosis membrane unit has completed chromatographic separation, port C of the multi-channel injection switching valve 1 is connected to the common outlet, and port 1 of the multi-channel diversion switching valve 2 is connected to the common inlet, and the multi-stage membrane separation coupled chromatographic online injection device is cleaned.

[0067] In this way, for different material systems and separation targets, a multi-stage membrane separation module is formed by setting different types of separation membrane units, and the permeate outlet and the concentrated liquid outlet of each separation membrane unit are connected to the corresponding channel inlets of the multi-channel injection switching valve 1, and a multi-channel diversion switching valve 2 is set and the first-dimensional chromatography unit 9 and the second-dimensional chromatography unit 10 are respectively connected to the corresponding sample outlets. In this way, when the membrane separation module is used in conjunction with the chromatography module, the multi-stage membrane can perform multiple separations. According to the required number of separations, the concentrated liquid or permeate flowing out of a separation membrane unit whose number of separations meets the requirements is selected to be connected to the common outlet. By switching the multi-channel injection switching valve, the permeate and concentrated liquid of the separation membrane units at different stages can be selectively transported to the chromatography module, and can be selectively transported to different chromatographic columns through the multi-channel diversion switching valve 2. The separation membrane unit forms different separation units, and the output liquids of different separation units can all enter the chromatography module. The first-dimensional chromatography unit 9 and the second-dimensional chromatography unit 10 inside the chromatography module can be used in combination with different separation membrane units of the membrane separation module respectively. At the same time, the first-dimensional chromatography unit 9 and the second-dimensional chromatography unit 10 can also be used in series, so that the units inside the membrane separation module and the units inside the chromatography module can be freely modularly combined according to the material properties and separation targets, and the online connection and continuous sampling of membrane separation and chromatography can be realized in a set of equipment. It is suitable for a variety of differentiated separation systems and targets, can cope with changing systems and targets, and realize efficient coupling of membrane separation and chromatography. There is no need to set a relay intermediate storage tank between the membrane separation module and the chromatography module, thereby reducing the dead volume of the connection unit, and can reduce the amount of solvent required for cleaning to reduce the amount of waste liquid generated.

[0068] Embodiment 2 of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention:

[0069] The difference between this embodiment and embodiment 1 is that in embodiment 1, the membrane separation module has three separation membrane units, namely, an ultrafiltration membrane unit, a nanofiltration membrane unit, and a reverse osmosis membrane unit. In this embodiment, the membrane separation module has two separation membrane units, namely, an ultrafiltration membrane unit and a nanofiltration membrane unit.

[0070] Embodiment 3 of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention:

[0071] The difference between this embodiment and embodiment 1 is that in embodiment 1, the chromatography module is a two-dimensional chromatography module, while in this embodiment, the chromatography module is a one-dimensional chromatography module.

[0072] Embodiment 4 of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention:

[0073] The difference between this embodiment and embodiment 1 is that in embodiment 1, the ultrafiltration membrane unit is a ceramic ultrafiltration membrane unit, while in this embodiment, the ultrafiltration membrane unit is an organic ultrafiltration membrane unit.

[0074] Embodiment 5 of the multi-stage membrane separation coupled chromatography online sample injection device of the present invention:

[0075] The difference between this embodiment and embodiment 1 is that in embodiment 1, the waste liquid outlet is arranged on the multi-channel diversion switching valve, while in this embodiment, the waste liquid outlet is arranged on the pipeline between the multi-channel diversion switching valve and the first dimension chromatography unit.

[0076] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention is described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions recorded in the aforementioned embodiments without creative work, or replace some of the technical features therein with equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.

Claims

1. A multi-stage membrane separation coupled chromatographic online sampling device, comprising a membrane separation module and a chromatographic module, characterized in that: The membrane separation module is a multi-stage membrane separation module, which includes at least two separation membrane units. The membrane pore sizes of different types of separation membrane units are different and the membrane pore sizes of the separation membrane units gradually decrease from the upstream to the downstream of the multi-stage membrane separation module. The separation membrane unit includes a liquid inlet, a permeate outlet, and a concentrated liquid outlet. Among the two adjacent separation membrane units, the permeate outlet of the upstream separation membrane unit is connected to the liquid inlet of the downstream separation membrane unit to separate the upstream permeate flowing out of the upstream separation membrane unit into the downstream permeate flowing out of the downstream separation membrane unit and the downstream concentrated liquid; and also includes a multi-channel injection switching valve, which has a permeate inlet, a concentrated liquid inlet and a common outlet, and the permeate inlet The number of the multi-channel injection switching valve is equal to the number of the permeate outlets and they are connected one-to-one, the number of the concentrate inlets is equal to the number of the concentrate outlets and they are connected one-to-one, the multi-channel injection switching valve has an injection switching position, each injection switching position is used to allow the common outlet to be connected to any one of the permeate inlet or the concentrate inlet, the common outlet is connected to the chromatography module, the chromatography module is a two-dimensional chromatography module, including a first-dimensional chromatography unit and a second-dimensional chromatography unit, the common outlet is connected to the first-dimensional chromatography unit or the second-dimensional chromatography unit, the first-dimensional chromatography unit is connected to the second-dimensional chromatography unit, the first-dimensional chromatography unit includes a first chromatography connecting port, the second-dimensional chromatography unit includes a second chromatography connecting port, and the first chromatography connecting port is connected to the second chromatography connecting port.

2. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 1 is characterized in that: It also includes a multi-channel diversion switching valve, which has a first sample outlet, a second sample outlet, and a common inlet. When the common inlet is connected to the first sample outlet or the second sample outlet, the multi-channel diversion switching valve is in an open state, and the common inlet is connected to the common outlet. The first-dimensional chromatography unit includes a first chromatography inlet, and the second-dimensional chromatography unit includes a second chromatography inlet. The first sample outlet is connected to the first chromatography inlet, and the second sample outlet is connected to the second chromatography inlet.

3. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 1 or 2, characterized in that: The multi-stage membrane separation module comprises an ultrafiltration membrane unit and a nanofiltration membrane unit, and the ultrafiltration membrane unit and the nanofiltration membrane unit each constitute a separation membrane unit.

4. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 3 is characterized in that: The ultrafiltration membrane unit is a ceramic ultrafiltration membrane unit or an organic ultrafiltration membrane unit; or the ultrafiltration membrane unit includes a ceramic ultrafiltration membrane unit and an organic ultrafiltration membrane unit connected in series.

5. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 3 is characterized in that: The multi-stage membrane separation module further comprises a reverse osmosis membrane unit, which constitutes a separation membrane unit. The reverse osmosis membrane unit is arranged at the most downstream of the multi-stage membrane separation module.

6. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 1 or 2, characterized in that: It also includes a cleaning liquid storage tank, and the multi-channel injection switching valve also has a cleaning liquid inlet, which is connected to the cleaning liquid storage tank. The cleaning liquid inlet is used to supply cleaning liquid into the multi-channel injection switching valve when it is connected to the public outlet. A waste liquid outlet is provided between the multi-channel injection switching valve and the chromatography module.

7. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 6 is characterized in that: The waste liquid outlet is arranged on the multi-channel diversion switching valve, the waste liquid outlet is connected to a waste liquid tank, and the waste liquid outlet is used for discharging waste liquid when connected with the public inlet of the multi-channel diversion switching valve.

8. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 1 or 2, characterized in that: Between two adjacent separation membrane units, the permeate outlet of the upstream separation membrane unit is connected to the liquid inlet of the downstream separation membrane unit through an inter-membrane pipeline, and the inter-membrane pipeline is connected to the permeate inlet.

9. The multi-stage membrane separation coupled chromatography online sample injection device according to claim 1 or 2, characterized in that: The chromatography module is a column chromatography module.

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