Mixing runner column and liquid chromatography system mixing device

Abstract

The invention discloses a mixing flow channel column and a liquid chromatography system mixing device, and belongs to the technical field of liquid chromatographs, the surface of the mixing flow channel column is provided with a mixing flow channel groove, the mixing flow channel groove comprises a front end face flow channel, a cylindrical surface flow channel and a rear end face flow channel which are communicated, the cylindrical surface flow channel is in a spiral line shape or a one-way square wave shape or a connecting structure which firstly distributes flow and then converges flow, a plurality of connecting channels are arranged at the two ends of the interior of the mixing flow channel column, and the mixing flow channel column is communicated with the front end face flow channel and the rear end face flow channel from the interior of the flow channel column through the connecting channels. The purpose of mixing multiple mobile phases in the mixing flow channel groove can be achieved, the structure is simple, the machining cost and the machining difficulty are greatly reduced, and the dead volume of the mixing flow channel groove can be better controlled in the design stage of the mixing flow channel groove.

Description

Technical Field

[0001] This invention belongs to the field of liquid chromatography instrument technology, specifically relating to a mixed flow channel column and a liquid chromatography system mixing device. Background Technology

[0002] When users perform chromatographic analysis using a liquid chromatograph, the detection of different target compounds involves different chemical detection methods. This may involve two or more different chemical organic phases that need to be mixed online in a gradient ratio. Currently, various online mixers exist on the market. For example, the domestic patent "CN110787714B" discloses "A Miniature High-Pressure Static Mixer for Liquid Chromatography", which includes a main sleeve, a base, a support ring, a single-hole sealing gasket, a multi-hole sealing gasket, a mixing chamber, and an end sealing gasket. The main sleeve is connected to the base, and at least two sets of the mixing chambers are installed in series inside. The mixing chamber is composed of the support ring and the sealing gaskets at both ends. The sealing gaskets include: a single-hole sealing gasket, a multi-hole sealing gasket, and an end sealing gasket.

[0003] These patents all involve the following issues: first, they have many parts, complex structures, and large dead volumes; second, the forced online distribution of multiple organic phases must pass through multiple levels of metal channels. During this process, the strongly corrosive organic phases will precipitate iron ions from the metal. However, in the analysis methods of clinical protein compounds, these precipitated iron ions from the metal will cause great interference to the analysis results. Therefore, this invention urgently needs to design an online mixer with a simple structure and small dead volume of mixing channels to further avoid the precipitation of iron ions. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the purpose of this invention is to propose a mixing device for a mixing channel column and liquid chromatography system that is simple in structure, has low processing cost and difficulty, and allows for easy control of dead volume.

[0005] Technical solution one of the present invention: To address the problem of large dead volume in the mixing channels of existing mixers, this invention provides a mixing channel column for use in a mixer. The surface of the mixing channel column is provided with mixing channel grooves, each including a front-side channel, a cylindrical channel, and a rear-side channel that are interconnected. The front-side channel includes an inlet end and at least one first connecting end; the cylindrical channel includes at least one inlet end and at least one outlet end; and the rear-side channel includes an outlet end and at least one second connecting end. The first connecting end communicates with the inlet end of the cylindrical channel, and the second connecting end communicates with the outlet end of the cylindrical channel. Multiple connecting channels are provided inside both ends of the mixing channel column, respectively connecting to the first connecting end of the front-side channel and the second connecting end of the rear-side channel. The cylindrical channel is spiral-shaped, unidirectionally shaped, or comprises multiple independent channel groups, with each channel group exhibiting a connection structure of first splitting and then merging.

[0006] Preferably, the front end flow channel and the rear end flow channel are both spiral-shaped, and the cylindrical flow channel is spiral-shaped or has a unidirectional waveform.

[0007] A preferred structure in an embodiment of the present invention is as follows: the front end flow channel is provided with an inlet end and a first connecting end, the rear end flow channel is provided with an outlet end and a second connecting end, and the front end flow channel, the rear end flow channel and the cylindrical flow channel are all spiral-shaped.

[0008] A preferred structure in this embodiment of the invention is as follows: the front end flow channel is provided with an inlet end and a first connecting end, the rear end flow channel is provided with an outlet end and a second connecting end, the front end flow channel and the rear end flow channel are spiral-shaped, and the cylindrical flow channel is a unidirectional square waveform. Specifically, the unidirectional square waveform refers to a flow channel shape with a square wavy curve that flows in one direction.

[0009] A preferred structure in this embodiment of the invention is as follows: the front end flow channel is provided with an inlet end and multiple first connection ends; the rear end flow channel is provided with an outlet end and multiple second connection ends; the cylindrical flow channel includes multiple independent flow channel groups, and each flow channel group has a connection structure of first splitting and then merging; the two ends of the mixing flow channel column are provided with multiple connection channels; the two ends of each flow channel group of the cylindrical flow channel are respectively connected to the first connection end of the front end flow channel and the second connection end of the rear end flow channel through the connection channels.

[0010] Preferably, the front end flow channel includes a first flow channel and two second flow channels, which are joined together to form an "I" shape. The center of the first flow channel is the liquid inlet, and the two ends of the second flow channels are first connecting ends. The rear end flow channel includes an eighth flow channel and two ninth flow channels, which are joined together to form an "I" shape. The center of the eighth flow channel is the liquid outlet, and the two ends of the ninth flow channels are second connecting ends.

[0011] Preferably, the connection structure of first splitting and then merging flows specifically includes a splitting channel, an intermediate channel and a merging channel connected in sequence. The splitting channel is one channel separated into multiple channels, the merging channel is multiple channels merged into one channel, and the intermediate channel includes multiple channels for connecting the splitting channel and the merging channel.

[0012] Preferably, the cylindrical flow channel includes four flow channel groups. In a single independent flow channel group, the branching flow channel includes one third flow channel, two fourth flow channels, one tenth flow channel, and two eleventh flow channels. The intermediate flow channel includes four fifth flow channels. The merging flow channel includes two sixth flow channels, one seventh flow channel, two twelfth flow channels, and one thirteenth flow channel. One end of the third flow channel is connected to the first connecting end through a connecting channel. The other end of the third flow channel is connected to two adjacent fourth flow channels through the tenth flow channel. The other end of each fourth flow channel is connected to two adjacent fifth flow channels through the eleventh flow channel. Each pair of adjacent fifth flow channels is connected to a sixth flow channel through the twelfth flow channel. Each pair of adjacent sixth flow channels is connected to a seventh flow channel through the thirteenth flow channel. The seventh flow channel is connected to the second connecting end through a connecting channel.

[0013] Preferably, the front end face, rear end face, and column surface of the mixing channel column are provided with turbulence grooves, which are disposed on the mixing channel.

[0014] Preferably, the diameter of the turbulent channel is greater than the width of the mixing channel, and the depth of the turbulent channel is greater than the depth of the mixing channel.

[0015] Preferably, the turbulence channels are arranged in an alternating vertical pattern along the axis of the mixing channel.

[0016] Preferably, the connecting channel includes a vertical section and a horizontal section, wherein the vertical section and the horizontal section are perpendicular to each other.

[0017] Preferably, the mixing dead volume of the mixing channel is 20-40 μL.

[0018] Technical Solution Two

[0019] The present invention also provides a liquid chromatography system mixing device, including the above-described mixing channel column, and further including an inlet mounting seat, an outlet mounting seat, and a mixing column. The inlet mounting seat and the outlet mounting seat are sealed together to form a column with a receiving cavity. The mixing column is placed in the receiving cavity. The inlet mounting seat is provided with at least one inlet channel, and the outlet mounting seat is provided with an outlet channel. The inlet channel is connected to the inlet end of the front end face of the mixing column, and the outlet channel is connected to the outlet end of the rear end face of the mixing column.

[0020] Preferably, the inlet mounting base and the outlet mounting base are connected by a thread.

[0021] The mixing column includes a mixing channel column, a sealing cap, and an inner liner. The sealing cap and the inner liner are sealed together to form a column with a mixing chamber. The mixing channel column is placed in the mixing chamber. The front end, cylindrical surface, and rear end of the mixing channel column are provided with interconnected mixing channels. The sealing cap has a liquid collection tank on the side away from the mixing channel column. The liquid collection tank is connected to the multiple inlet channels. The sealing cap is also provided with a first channel, which connects the liquid collection tank and the channel on the front end of the mixing channel column. The bottom of the inner liner has a second channel, which connects to the channel on the rear end of the mixing channel column.

[0022] Preferably, the mixing channel column and the mixing chamber are interference fit.

[0023] Furthermore, to address the problem of iron ion precipitation, the technical solution of this invention is as follows: Preferably, the outer surface of the mixing channel column, the inner surface of the inner liner and the inner surface of the sealing cap are coated with stainless steel.

[0024] Preferably, the iron ion content of the mixed flow channel column is less than 0.3%.

[0025] Preferably, the material of the mixing channel column is selected from PEEK plastic materials, PI plastic materials, and titanium alloys.

[0026] Compared with the prior art, the beneficial effects of the present invention are: 1. The present invention significantly reduces the processing difficulty of precision mixers by setting a spiral, unidirectional square waveform and / or forced flow splitting mixing channel structure on the surface of the mixing channel column, and enables the mixer to have a sample storage function similar to a quantitative ring.

[0027] 2. The present invention has a simple structure, lower processing, manufacturing and assembly costs and difficulties, and lower replacement costs.

[0028] 3. The present invention further incorporates multiple turbulent channels arranged in an alternating pattern within the mixing channel, which further enhances the mixing effect.

[0029] 4. By coating the surface of the mixing channel column or directly selecting materials with an iron ion content of less than 0.04%, such as PEEK, PI-type plastic materials, or titanium alloys, this invention can effectively prevent the precipitation of iron ions when different organic phases flow through the mixing channel column, thus avoiding serious interference from the precipitated iron ions on the results of downstream analysis and achieving inertization and residue-free operation.

[0030] The detailed structure of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0031] Figure 1 This is an isometric schematic diagram of the mixing channel column according to Embodiment 1 of the present invention; Figure 2 This is a front view of the mixing channel column according to Embodiment 1 of the present invention; Figure 3 For the present invention Figure 1 Schematic diagram at point A in the middle; Figure 4 This is a cross-sectional view of the mixing channel column according to Embodiment 1 of the present invention; Figure 5 This is a three-dimensional schematic diagram of the mixing channel column according to Embodiment 2 of the present invention; Figure 6 This is a cross-sectional view of the mixing channel column according to Embodiment 2 of the present invention; Figure 7 This is an isometric schematic diagram of the mixing channel column according to Embodiment 3 of the present invention; Figure 8 This is a front view of the mixing channel column of Embodiment 3 of the present invention; Figure 9 For the present invention Figure 7 Schematic diagram at point B in the middle; Figure 10 This is a cross-sectional view of the mixing channel column in Embodiment 3 of the present invention; Figure 11 This is an isometric schematic diagram of the mixing channel column of the mixing device in Embodiment 4 of the present invention; Figure 12 This is a front view of the mixing channel column of Embodiment 4 of the present invention; Figure 13 For the present invention Figure 11 Diagram at point C; Figure 14 This is an isometric schematic diagram of the mixing channel column of the mixing device in Embodiment 4 of the present invention; Figure 15 This is a front view of the mixing channel column of Embodiment 4 of the present invention; Figure 16 For the present invention Figure 14 Schematic diagram at point D.

[0032] Figure 17 This is a schematic diagram of the overall appearance of the mixing device according to Embodiment 5 of the present invention; Figure 18 This is a cross-sectional view of the mixing device according to Embodiment 5 of the present invention; Figure 19 This is an exploded schematic diagram of the mixing device according to Embodiment 5 of the present invention; Figure 20 The data for Embodiment Six of the present invention are based on the curve graph; Figure 21 This is a gradient curve diagram of Embodiment Six of the present invention.

[0033] Component names and corresponding serial numbers: 1. Inlet mounting base; 11. Inlet channel; 2. Sealing cap; 21. Liquid collection tank; 22. First channel; 3. Inner liner; 31. Second channel; 4. Outlet mounting base; 41. Outlet channel; 5. Mixing flow channel column; 51. Front face flow channel; 511. First flow channel; 512. Second flow channel; 513. Liquid inlet end; 514. First connection end; 52. Rear face flow channel; 521. Eighth flow channel; 522, Ninth flow channel; 523, Liquid outlet end; 524, Second connection end; 525, Tenth flow channel; 526, Eleventh flow channel; 527, Twelfth flow channel; 528, Thirteenth flow channel; 53, Cylindrical flow channel; 531, Third flow channel; 532, Fourth flow channel; 533, Fifth flow channel; 534, Sixth flow channel; 535, Seventh flow channel; 54, Turbulent channel; 55, Connecting channel; 551, Horizontal section; 552, Vertical section. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. 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 claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0035] Unless otherwise defined, the technical or scientific terms used in this disclosure shall have the ordinary meaning understood by a person skilled in the art to which this disclosure pertains. The words “comprising” or “including” and similar terms used in this disclosure mean that the element or object preceding the word covers the element or object listed after the word and its equivalents, without excluding other elements or objects. The words “connected” or “linked” and similar terms are not limited to physical or mechanical connections, but may also include electrical connections, whether direct or indirect. “Up,” “down,” “left,” “right,” etc., are used only to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly. Example 1

[0036] like Figures 1-4 As shown, this invention provides a mixing channel column 5. The surface of the mixing channel column 5 is provided with mixing channel grooves. The mixing channel grooves include a front face channel 51, a cylindrical face channel 53, and a rear face channel 52. The front face channel 51 includes an inlet end 513 and a first connecting end 514. The cylindrical face channel 53 includes an inlet end and an outlet end. The rear face channel 52 includes a second connecting end 524 and an outlet end 523. The first connecting end 514 is connected to the inlet end of the cylindrical face channel 53, and the second connecting end 524 is connected to the outlet end of the cylindrical face channel 53. By providing mixing channel grooves on the surface of the mixing channel column 5, the purpose of mixing multiple mobile phases in the mixing channel grooves can be achieved. Moreover, during the design stage of the mixing channel grooves, the dead volume of the design mixing channel grooves can be better controlled. Multiple connecting channels 55 are provided inside both ends of the mixing channel column 5. The two ends of each group of cylindrical face channels 53 are connected to the first connecting end 514 and the second connecting end 524 respectively through the connecting channels 55.

[0037] The interior of both ends of the mixing channel column 5 refers to the interior of the end of the mixing channel column 5 near the front end face or the interior of the end near the rear end face.

[0038] Specifically, the front flow channel 51 is provided with an inlet end 513 and a first connecting end 514, and the rear flow channel 52 is provided with an outlet end 513 and a second connecting end 524. The front flow channel 51, the rear flow channel 52, and the cylindrical flow channel 53 are all spiral-shaped. In the spiral-shaped flow channel, multiple mobile phases collide with the flow channel wall due to centrifugal force. Because there is a velocity difference between the fluid at the center of the flow channel and the flow channel wall, different mobile phases in the fluid will continuously move back and forth between the center of the flow channel and the inner wall, colliding and converging, and then separating again, repeating this cycle multiple times, thereby achieving the purpose of mixing multiple mobile phases in the fluid.

[0039] Specifically, the connecting channel 55 includes a vertical section 552 and a horizontal section 551. The vertical section 552 and the horizontal section 551 are perpendicular to each other. The right-angled connecting channel 55 is easy to process. When the end face section of the mobile phase in the mixing channel is transferred to the cylindrical channel 53, the various mobile phase components will also collide violently on the inner wall of the connecting channel 55, which enhances the mixing effect.

[0040] Specifically, the outer surface of the mixing column 5, the inner surface of the liner 3, and the inner surface of the sealing cap 2 are coated with stainless steel. This effectively prevents iron ions from precipitating from the mixing column and entering the mobile phase under high pressure, and then following the mobile phase into the chromatographic column and detector, thus affecting the analytical results.

[0041] Alternatively, the mixing column can also be manufactured using materials with an iron ion content of less than 0.04%, such as PEEK plastics, PI plastics, or titanium alloys. Example 2

[0042] like Figure 5 and Figure 6 As shown, this invention provides another mixing device for a mixing channel column and a liquid chromatography system. Based on Embodiment 1, the shape of the column surface channel 53 is changed, making the column surface channel 53 a unidirectional square waveform surrounding the column surface. In this embodiment, the column surface channel 53 is modified from a spiral shape to a unidirectional square waveform, so that multiple solutions achieve a mixing effect at the channel corners through the velocity difference between the inner and outer fluids (the outer fluid flows slowly, and the inner fluid flows rapidly) and multiple collisions and fusions. This can further increase the collision mixing intensity of the mobile phase in the column surface channel 53 and enhance the mixing effect. The mixing channel column 5 has multiple connecting channels 55 inside both ends. The two ends of each group of channels of the column surface channel 53 are connected to the first connecting end 514 and the second connecting end 524 respectively through the connecting channels 55.

[0043] Specifically, the unidirectional square waveform refers to a flow channel shape with a square wave-like curve that flows in one direction. Example 3

[0044] like Figures 7-10 As shown, based on Embodiment 1, the shape of the mixing channel groove on the mixing channel column 5 is changed to form Embodiment 3. The front end channel 51 of Embodiment 3 is provided with an inlet end 513 and multiple first connection ends 514; the rear end channel 52 is provided with an outlet end 513 and multiple second connection ends 524; the cylindrical channel 53 includes multiple sets of independent channel groups, and each channel group has a connection structure of first splitting and then merging. The two ends of the mixing channel column 5 are provided with multiple connection channels 55. The two ends of each channel group of the cylindrical channel 53 are connected to the first connection end 514 and the second connection end 524 respectively through the connection channels 55.

[0045] The connection structure of the flow channel group is as follows: the flow channel is divided into upper and lower parts. The upper part is divided downward by a vertical direct current channel and connected to two vertical direct current channels. The two vertical direct current channels are then divided downward by themselves and connected to a total of four vertical direct current channels, forming a forced flow splitting structure where one channel becomes two channels and two channels become four channels. The lower part is symmetrical to the upper part, that is, a merging structure where four channels become two channels and two channels become one channel.

[0046] Specifically, in this embodiment, the front end flow channel 51 includes a first flow channel 511 and two second flow channels 512. The first flow channel 511 and the second flow channels 512 are joined to form an "I" shape. The center of the first flow channel 511 is the liquid inlet end 513, and the two ends of the second flow channels 512 are the first connecting ends 514. The rear end flow channel 52 includes an eighth flow channel 521 and two ninth flow channels 522. The eighth flow channel 521 and the ninth flow channels 522 are joined to form an "I" shape. The center of the eighth flow channel 521 is the liquid outlet end 513, and the two ends of the ninth flow channels 522 are the second connecting ends 524. The cylindrical flow channel 53 includes four sets of independent flow channels. Each set of independent flow channels includes a third flow channel 531, two fourth flow channels 532, four fifth flow channels 533, two sixth flow channels 534, a seventh flow channel 535, and a tenth flow channel 52. 5. Two eleventh flow channels 526, two twelfth flow channels 527, and one thirteenth flow channel 528. One end of the third flow channel 531 is connected to the connection end of the second flow channel 512 through a connecting channel 55. The other end of the third flow channel 531 is simultaneously connected to two fourth flow channels 532 through a tenth flow channel 525. The end of each fourth flow channel 532 away from the third flow channel 531 is simultaneously connected to two fifth flow channels 533 through the eleventh flow channel 526. The ends of each pair of fifth flow channels 533 away from the fourth flow channel 532 are connected to the same sixth flow channel 534 through the twelfth flow channel 527. The ends of the two sixth flow channels 534 away from the fifth flow channel 533 are merged and connected to the seventh flow channel 535 through the thirteenth flow channel 528. The end of the seventh flow channel 535 away from the sixth flow channel 534 is connected to the second connection end 524 of the rear end flow channel 52 through a connecting channel 55. The fluid enters the first flow channel 511 from the inlet end 513 and passes through the forced diversion channels of one-to-two, two-to-four, four-to-eight, and eight-to-sixteen in succession. Then, it passes through the forced merging channels of sixteen-to-eight, eight-to-four, four-to-two, and two-to-one. The different mobile phases in the fluid are continuously dispersed and reorganized in the flow channel, causing the different mobile phases to collide and merge, resulting in excellent mixing effect.

[0047] It is worth noting that, based on Embodiment 2 of the present invention, different shapes can be formed by increasing or decreasing the number of the first connecting end 514 in the front face flow channel 51 and / or the number of the second connecting segment in the rear face flow channel 52 as needed; the changes in the flow channel structure formed by increasing or decreasing the number of groups of cylindrical flow channels 53, and increasing or decreasing the number of times of flow splitting and merging in each group of cylindrical flow channels 53 are all variations of this technical solution and are all within the protection scope of the present invention.

[0048] In addition, to enhance the mixing effect of the mixing channel, the corners of the mixing channel can be set to right angles to enhance the collision and mixing effect of the fluid in the channel. Example 4

[0049] like Figures 11-16 As shown, based on Embodiment 1, Embodiment 2 and Embodiment 3, the end face and cylindrical surface of the mixing channel column 5 can also be provided with turbulence grooves 54, which are provided on the mixing channel.

[0050] Furthermore, the diameter of the turbulent channel 54 is greater than the width of the mixing channel, and the depth of the turbulent channel 54 is greater than the depth of the mixing channel; the turbulent channels 54 are arranged alternately up and down along the axis of the mixing channel; this can effectively achieve the turbulent effect of deceleration and re-acceleration of the liquid in the mixing channel, which is more conducive to the online mixing of different organic phases and greatly enhances the mixing effect. Example 5

[0051] like Figures 17-19 As shown: The present invention also provides a liquid chromatography system mixing device, including an inlet mounting seat 1, an outlet mounting seat 4, and a mixing channel column 5 of any one of the embodiments 1, 2, 3, and 4. The inlet mounting seat 1 and the outlet mounting seat 4 are sealed together to form a column with a accommodating cavity. The mixing channel column 5 is placed in the accommodating cavity. The inlet mounting seat is provided with at least one inlet channel 11, and the outlet mounting seat is provided with an outlet channel 41. In this embodiment, there are three inlet channels 11, which can be compatible with 1 inlet / 2 inlet / 3 inlet, three channel modes. Unused channels can be blocked with pressure plug screws.

[0052] Specifically, the outer surface of the mixing channel column 5 is also provided with an inner liner 3 and a sealing cover 2. The sealing cover 2 and the inner liner 3 cover each other to form a sealed chamber that can accommodate the mixing channel column 5. The side of the sealing cover 2 away from the mixing channel column 5 is provided with a liquid collection tank 21. The liquid collection tank 21 is connected to the plurality of inlet channels 11. The sealing cover 2 is also provided with a first channel 22. The first channel 22 connects the liquid collection tank 21 and the liquid inlet end 513 of the front end channel 51 of the mixing channel column 5. The bottom of the inner liner 3 is provided with a second channel 31. The second channel 31 connects to the liquid outlet end 523 in the rear end channel 52 of the mixing channel column 5. It is worth noting that the mixing channel column 5 and the inner liner 3 are press-fitted, the sealing cover 2 and the inner liner 3 are press-fitted, the mixing column and the outlet mounting seat 4 are also press-fitted, and the side of the sealing cover 2 away from the inner liner 3 is tightly fitted to the inlet mounting seat 1.

[0053] Working process and principle: During operation, multiple mobile phases enter the mixer through the inlet channel 11 on the inlet mounting base 1. The multiple mobile phases are initially mixed in the collection tank 21, and then enter the mixing chamber through the first channel 22. The mobile phase is first guided by the first channel 22 into the mixing channel on the end face of the mixing channel column 5. The mobile phase entering the mixing chamber moves in the mixing channel under the impetus of the subsequent mobile phase. During the movement, the mobile phase is continuously accelerated, decelerated, split, impacted and oscillated, and merged in the mixing channel to form a turbulent effect, thereby achieving the purpose of mixing multiple mobile phases. The mixed mobile phase is discharged through the second channel 31 and the outlet channel to enter the next process. Example 6

[0054] I. Experimental Objective The test was conducted to determine whether the mixing device using the mixed flow channel column of Example 1 met the requirement of gradient proportioning mixing accuracy ≤ ±0.5% (liquid chromatography industry standard). II. Instrument and Method Parameters Power unit: 1.5mm plunger infusion pump Mobile phase A: 0.2% pentoketone aqueous solution (as a marker) Mobile phase B: Pure water Detector: Ultraviolet detector, wavelength 273nm III. Experimental Data Table 1. Raw data from online mixed test in Example 1

[0055] Table 2. Accuracy test data of gradient ratio mixing in Example 1

[0056] IV. Experimental Conclusions Combining Table 1 and Table 2, Figure 20 and Figure 21 It can be clearly seen that the gradient proportioning accuracy (gradient error) of the mixer using the mixing channel column of Example 1 is ≤ ±0.5%, which meets the standard of the liquid chromatography industry for mixers.

[0057] The mixing channel columns of Examples 2 and 3 are further improved products, with a gradient ratio mixing accuracy (gradient error) of ≤ ±0.5%, which will not be repeated here. They also meet the standards of the liquid chromatography industry for mixers.

[0058] Example 7 I. Experimental Objective Test Example 1, Example 2, and Example 3: the impact of these three mixers on large-volume sample introduction.

[0059] II. Instrument and Method Parameters Coupler: FLC2701 two-dimensional liquid chromatography coupler Chromatography pump: Shimadzu LC-20AT Injector: Shimadzu SIL-20AC Controller: Shimadzu CBM-20A Detector: SPD-20A Analysis mode: LC1; Detection wavelength: 313nm / 240nm Chromatographic column: One-dimensional SC2 column (3.5*25mm, 5μm) Mobile phase: VITD-1E; Flow rate: 0.4 ml / min Assist time: 0.5 min Assisted flow rate: 0.6 ml / min Diluent: Methanol III. Experimental Data Table 3 Experimental results using the mixer from Example 1

[0060] Note: TS is a control experiment conducted using 4μL of conditioning solution.

[0061] Table 4. Experimental results using the mixer with the mixing column from Example 2.

[0062] Note: TS is a control experiment conducted using 4μL of conditioning solution.

[0063] Table 5. Experimental results using the mixer with the mixing column from Example 3.

[0064] Note: TS is a control experiment conducted using 4μL of conditioning solution.

[0065] IV. Experimental Conclusions Based on the experimental data in Tables 3-5, it can be seen from the peak width (50%) that the difference between the mixer in Example 2 and the 200ul injection volume is small. However, the peak width (50%) of other mixers increases to varying degrees with the increase of volume, and the peak width has a significant impact. Therefore, the mixing effect of the three mixing channel columns proposed in Example 1, Example 2 and Example 3 is compared as follows: Example 2 > Example 3 > Example 1.

[0066] The above description is a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and concept of the present invention, should be covered within the scope of protection of the claims of the present invention.

Claims

1. A hybrid flow channel column for use in a mixer, characterized by: The surface of the mixing channel column (5) is provided with a mixing channel groove, which includes a front face channel (51), a cylindrical face channel (53), and a rear face channel (52) that are connected to each other. The front face channel (51) includes an inlet end (513) and at least one first connecting end (514). The cylindrical face channel (53) includes at least one inlet end and at least one outlet end. The rear face channel (52) includes an outlet end (523) and at least one second connecting end (524). The first connecting end (514) is connected to the cylindrical face channel (53). The inlet end is connected, and the second connection end (524) is connected to the outlet end of the cylindrical flow channel (53); the two ends of the mixing flow channel column (5) are provided with multiple connection channels (55), and the connection channels (55) are respectively connected to the first connection end (514) of the front end flow channel (51) and the second connection end (524) of the rear end flow channel (52); the cylindrical flow channel (53) is spiral, unidirectional, or the cylindrical flow channel (53) includes multiple independent flow channel groups, and each flow channel group has a connection structure of first splitting and then merging.

2. A hybrid flow channel column according to claim 1, wherein: The front end flow channel (51) and the rear end flow channel (52) are both spiral-shaped, and the cylindrical flow channel (53) is either spiral-shaped or has a unidirectional waveform.

3. The hybrid flow channel column of claim 1, wherein: The front end flow channel (51) includes a first flow channel (511) and two second flow channels (512). The first flow channel (511) and the second flow channel (512) are joined together to form an "I" shape. The center of the first flow channel (511) is the liquid inlet end (513), and the two ends of the second flow channel (512) are the first connecting ends (514). The rear end flow channel (52) includes an eighth flow channel (521) and two ninth flow channels (522). The eighth flow channel (521) and the ninth flow channel (522) are joined together to form an "I" shape. The center of the eighth flow channel (521) is the liquid outlet end (513), and the two ends of the ninth flow channel (522) are the second connecting ends (524).

4. The hybrid flow channel column of any one of claims 1-3, wherein: The connection structure of first splitting and then merging flows specifically includes a splitting channel, an intermediate channel, and a merging channel that are connected in sequence. The splitting channel is a channel that is separated into multiple channels, and the merging channel is a channel that is merged into a single channel. The intermediate channel includes multiple channels for connecting the splitting channel and the merging channel.

5. A hybrid flow channel column according to claim 4, wherein: The cylindrical flow channel (53) includes four groups of flow channel groups, in a single group of independent flow channel groups, the branch flow channel includes a third flow channel (531), two fourth flow channel (532), a tenth flow channel (525) and two eleventh flow channel (526), the intermediate flow channel includes four fifth flow channel (533), the confluence flow channel includes two sixth flow channel (534), a seventh flow channel (535), two twelfth flow channel (527) and a thirteenth flow channel (528), one end of the third flow channel (531) is communicated with the first connecting end (514) through the connecting channel (55), the other end of the third flow channel (531) is communicated with two adjacent fourth flow channels (532) through the tenth flow channel, respectively, the other end of each fourth flow channel (532) is communicated with two adjacent fifth flow channels (533) through the eleventh flow channel, respectively, each adjacent two fifth flow channels (532) are communicated with a sixth flow channel (534) through the twelfth flow channel, each adjacent two sixth flow channels are communicated with a seventh flow channel (535) through the thirteenth flow channel, and the seventh flow channel (535) is communicated with the second connecting end (524) through the connecting channel (55).

6. A hybrid flow channel column according to any one of claims 1 to 3, wherein: The front end surface, the rear end surface and the cylindrical surface of the mixed flow channel column (5) are provided with a turbulent groove (54), and the turbulent groove (54) is arranged on the mixed flow channel.

7. A hybrid flow channel column according to claim 6 wherein: The diameter of the turbulent groove (54) is greater than the width of the mixed flow channel, and the groove depth of the turbulent groove (54) is greater than the depth of the mixed flow channel.

8. The mixed mode column and liquid chromatography system mixing device of any one of claims 1-3, wherein: The material of the mixed column is selected from one of PEEK plastic material, PI plastic material and titanium alloy.

9. A liquid chromatography system mixing device, characterized by: The mixed flow channel column of any one of claims 1-8 further comprises an inlet mounting seat (1), an outlet mounting seat (4) and a mixed column, characterized in that: the inlet mounting seat (1) and the outlet mounting seat (4) are overlapped and sealedly connected to form a column body with a containing cavity, the mixed column is arranged in the containing cavity, at least one inlet channel (11) is arranged on the inlet mounting seat (1), an outlet channel (41) is arranged on the outlet mounting seat (4), the inlet channel (11) is communicated with the inlet end of the front end surface of the mixed column, and the outlet channel (41) is communicated with the outlet end of the rear end surface of the mixed column.

10. The liquid chromatography system mixing device of claim 9, wherein; The mixing column comprises a mixing flow channel column (5), a sealing cover (2) and an inner lining spacer sleeve (3), the sealing cover (2) and the inner lining spacer sleeve (3) are covered and sealed to form a column body with a mixing chamber, the mixing flow channel column (5) is arranged in the mixing chamber, the front end surface, the column surface and the rear end surface of the mixing flow channel column (5) are provided with mixing flow channels in communication, the side of the sealing cover (2) away from the mixing flow channel column (5) is provided with a liquid collecting groove (21), the liquid collecting groove (21) is communicated with the plurality of inlet channels (11), the sealing cover (2) is further provided with a first channel (22), the first channel (22) is communicated with the liquid collecting groove (21) and the flow channel of the front end surface of the mixing flow channel column (5), the shell bottom of the inner lining spacer sleeve (3) is provided with a second channel (31), and the second channel (31) is communicated with the flow channel of the rear end surface of the mixing flow channel column (5).

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