Micro-channel derivative chip for liquid chromatography and preparation method of micro-channel derivative chip

Abstract

When the microchannel derivatization chip for the liquid chromatography is used, liquid sample components and chemical derivatization reagents are added into the first liquid inlet hole and the second liquid inlet hole respectively and enter the transition cavity through the first liquid inlet channel and the second liquid inlet channel respectively to be premixed, premixed liquid is fully mixed through the mixer and reacts with each other, and then the liquid sample components and the chemical derivatization reagents are separated. The liquid after reaction flows to the liquid outlet hole through the liquid outlet channel, the liquid after reaction can be taken out from the liquid outlet hole, and the upper middle flow channel of the upper C-shaped structure of the mixing unit of the mixer can be located at the same height as the upper inlet and outlet flow channel and can also be different from the upper inlet and outlet flow channel. The lower middle flow channel of the lower C-shaped structure can be located at the same height as the lower inlet and outlet flow channel or can be different from the lower inlet and outlet flow channel. Related preparation methods are also provided. The micro-channel derivative chip for the liquid chromatography is good in mixing effect, small in reflux zone, controllable in reaction time, simple in structure and simple and convenient to prepare, and the preparation method and the preparation process are simple and easy to operate.

Description

Technical Field

[0001] This invention relates to the field of liquid chromatography technology, and particularly to the field of liquid chromatography derivatization chip technology, specifically to a microchannel derivatization chip for liquid chromatography and its preparation method. Background Technology

[0002] Liquid chromatography derivatization technology utilizes chemical derivatization reagents (or labeling reagents) to react with components of a liquid sample, and the reaction products facilitate chromatographic detection.

[0003] In derivatization reactions, strict requirements are placed on the mixing of liquids. First, rapid mixing is required. Second, for certain analytes, there should be no large-scale reflux zone in the reaction process to prevent the increase of side reactions. Third, the reaction time must be controllable, which requires the reaction volume to be controllable according to actual needs.

[0004] Mixing, based on its mechanism, can be divided into diffusion and convection. At larger sizes (above 100 micrometers), diffusion-dominated mixing has very low efficiency. Convection-diffusion, by controlling the macroscopic flow of fluids, increases the contact area between different fluids, thereby improving mixing efficiency.

[0005] Studies have shown that chaotic convection can achieve rapid mixing. Chaotic convection causes rapid distortion and elongation of the contact surfaces between liquids, greatly increasing the contact area and achieving rapid mixing.

[0006] Herringbone-like structures, Tesla valves, and curved flow channels can all achieve chaotic mixing. However, these structures may create significant backflow zones, causing some fluid to remain trapped for extended periods, or the flow field may be complex, making it difficult to accurately control the reaction time.

[0007] For example, Chinese invention patent application CN116466089A discloses a detection kit and identification method for CTCs based on SCLC molecular typing using microfluidic chips and multiple immunofluorescence probe technology. It designs and develops a microfluidic matrix CTC enrichment chip based on a grooved herringbone double-row herringbone structure, which effectively enhances the probability of contact between CTC surface antigens and capture agents. However, the herringbone structure size is selective for leukocyte (WBC) retention, thus greatly limiting the size of the reactants.

[0008] Chinese invention patent CN117504769B discloses a method for the continuous preparation of formate using a microreactor. This method achieves continuous, large-scale, high-crystallinity, and high-quality formate products. The microchannels include one or more of the following structures: U-shaped, heart-shaped, Tesla-shaped, herringbone-shaped, and spiral structures. It is noted that the Tesla structure has the longest residence time and the highest degree of mixing for the same equivalent length.

[0009] Chinese invention patent application CN116637537A discloses a two-dimensional microchannel master-side mixing structure, pointing out that although the Tesla structure has good mixing properties, it has a large inlet-outlet pressure difference, poor flowability, and a clogging zone, making it unsuitable for microchannel chemical reactions. Symmetrical structures such as the heart-shaped structure have small inlet-outlet pressure differences, good flowability, and no clogging zone; however, they have poor mixing properties, requiring a longer reaction time when used in microchannel chemical reactions.

[0010] Chinese invention patent application CN120754781A discloses a microchannel reactor with a cylindrical spiral structure, which has a good mixing effect, but its shape is complex and cannot be fabricated on a microfluidic chip.

[0011] Therefore, it is desirable to provide a microchannel derivatization chip for liquid chromatography that has good mixing effect, small reflux zone, controllable reaction time, simple structure, and easy preparation. Summary of the Invention

[0012] In order to overcome the shortcomings of the prior art, one object of the present invention is to provide a microchannel derivatization chip for liquid chromatography, which has good mixing effect, small reflux zone, controllable reaction time, simple structure, easy preparation, and is suitable for large-scale application.

[0013] Another objective of this invention is to provide a method for preparing a microchannel derivatization chip for liquid chromatography. The preparation process is simple and easy to operate. The prepared microchannel derivatization chip for liquid chromatography has a simple structure, good mixing effect, small reflux zone, and controllable reaction time, making it suitable for large-scale application.

[0014] To achieve the above objectives, in a first aspect of the present invention, a microchannel derivatization chip for liquid chromatography is provided, comprising a chip body horizontally arranged and positioned along a left-right direction. The microchannel derivatization chip for liquid chromatography further includes a first inlet port, a first inlet channel, a second inlet port, a second inlet channel, a transition chamber, a mixer, an outlet channel, and an outlet port, wherein: The first liquid inlet, the second liquid inlet, and the liquid outlet are all vertically arranged and horizontally spaced apart from each other on the top surface of the chip body. The transition cavity is arranged in the chip body. The first liquid inlet channel is horizontally arranged in the chip body and located between the bottom of the first liquid inlet and the transition cavity, and respectively connects the bottom of the first liquid inlet and the transition cavity. The second liquid inlet channel is horizontally arranged in the chip body and located between the bottom of the second liquid inlet and the transition cavity, and respectively connects the bottom of the second liquid inlet and the transition cavity. The mixer includes a mixing unit disposed in the chip body and includes an upper C-shaped structure and a lower C-shaped structure; The upper C-shaped structure includes an upper inlet channel, an upper outlet channel, an upper intermediate channel, an upper first connecting channel, and an upper second connecting channel. The upper inlet channel and the upper outlet channel are both horizontally arranged along the left-right direction and are spaced apart from each other. The upper intermediate channel is horizontally arranged along the left-right direction and is located behind, above, or behind the interval between the upper inlet channel and the upper outlet channel. The upper first connecting channel and the upper second connecting channel are spaced apart from each other. The upper first connecting channel is located at... The upper inlet channel is located between the right end of the upper inlet channel and the left end of the upper middle channel, and is connected to the right end of the upper inlet channel and the left end of the upper middle channel, respectively. The upper second connecting channel is located between the left end of the upper outlet channel and the right end of the upper middle channel, and is connected to the left end of the upper outlet channel and the right end of the upper middle channel, respectively. The upper first connecting channel and the upper second connecting channel are arranged parallel to each other, or the angle between the extension line of the upper first connecting channel and the extension line of the upper second connecting channel is >0° and ≤135°. The lower C-shaped structure includes a lower inlet channel, a lower outlet channel, a lower intermediate channel, a lower first connecting channel, and a lower second connecting channel. The lower inlet channel and the lower outlet channel are both horizontally arranged along the left-right direction and are spaced apart from each other. The lower intermediate channel is also horizontally arranged along the left-right direction and is located in front of, below, or below the interval between the lower inlet channel and the lower outlet channel. The lower first connecting channel and the lower second connecting channel are spaced apart from each other. The lower first connecting channel is located at... The lower inlet channel is located between the right end of the lower inlet channel and the left end of the lower middle channel, and is connected to the right end of the lower inlet channel and the left end of the lower middle channel, respectively. The lower second connecting channel is located between the left end of the lower outlet channel and the right end of the lower middle channel, and is connected to the left end of the lower outlet channel and the right end of the lower middle channel, respectively. The lower first connecting channel and the lower second connecting channel are arranged parallel to each other, or the angle between the extension line of the lower first connecting channel and the extension line of the lower second connecting channel is >0° and ≤135°. The right end of the upper outlet channel is located on the left end of the lower inlet channel and connects to the left end of the lower inlet channel. The left end of the upper inlet channel is located beside the transition cavity and connects to the transition cavity. The liquid outlet channel is horizontally arranged in the chip body. One end of the liquid outlet channel is located on the right end of the lower outlet channel and connects to the right end of the lower outlet channel. The other end of the liquid outlet channel is located beside the bottom of the liquid outlet hole and connects to the bottom of the liquid outlet hole.

[0015] Preferably, the first liquid inlet and the second liquid inlet are spaced apart from each other, and the transition cavity is located to the right of the middle position between the bottom of the first liquid inlet and the bottom of the second liquid inlet. The first liquid inlet channel is inclined to the right front in a left-to-right direction, and the second liquid inlet channel is inclined to the right rear in a left-to-right direction.

[0016] Preferably, the left end of the upper inlet channel is located on the right side of the transition cavity.

[0017] Preferably, the liquid outlet channel is arranged along the left-right direction, the left end of the liquid outlet channel is located on the right end of the lower outlet channel and connects to the right end of the lower outlet channel, and the right end of the liquid outlet channel is located to the left of the bottom of the liquid outlet hole and connects to the bottom of the liquid outlet hole.

[0018] Preferably, there are multiple mixing units arranged sequentially from left to right. In two adjacent mixing units, the left end of the upper inlet channel of the right mixing unit is located on the right end of the lower outlet channel of the left mixing unit and connects to the right end of the lower outlet channel of the left mixing unit. The left end of the upper inlet channel of the leftmost mixing unit is located beside the transition cavity and connects to the transition cavity. One end of the liquid outlet channel is located on the right end of the lower outlet channel of the rightmost mixing unit and connects to the right end of the lower outlet channel of the rightmost mixing unit.

[0019] More preferably, the number of the hybrid units is seven.

[0020] Preferably, the chip body includes an upper chip layer and a lower chip layer, both of which are horizontally arranged and aligned along the left-right direction. The upper chip layer is disposed on the lower chip layer. The first liquid inlet hole, the first liquid inlet channel, the second liquid inlet hole, the second liquid inlet channel, the transition cavity, the upper C-shaped structure of the mixing unit, the liquid outlet channel, and the liquid outlet hole are all disposed in the upper chip layer, and the lower C-shaped structure of the mixing unit is disposed in the lower chip layer.

[0021] More preferably, the upper layer of the chip is heat-pressed or glued onto the lower layer of the chip.

[0022] Preferably, the chip body is a polymer chip body or a metal chip body.

[0023] In a second aspect of the invention, a method for preparing the above-described microchannel derivatization chip for liquid chromatography is provided, characterized in that the method comprises the following steps: forming the microchannel derivatization chip for liquid chromatography by 3D printing; or, The chip body includes an upper chip layer and a lower chip layer, both of which are horizontally arranged and aligned along the left-right direction. The upper chip layer is disposed on the lower chip layer. The first liquid inlet, the first liquid inlet channel, the second liquid inlet, the second liquid inlet channel, the transition cavity, the upper C-shaped structure of the mixing unit, the liquid outlet channel, and the liquid outlet are all disposed in the upper chip layer. The lower C-shaped structure of the mixing unit is disposed in the lower chip layer. The preparation method of the microchannel derivatization chip for liquid chromatography includes the following steps: (1) The upper layer and the lower layer of the chip are obtained by 3D printing or machining. (2) The upper layer of the chip is hot-pressed or glued onto the lower layer of the chip.

[0024] The main beneficial effects of this invention are: 1. The microchannel derivatization chip for liquid chromatography of the present invention, in use, involves adding liquid sample components and chemical derivatization reagents to the first and second inlet holes, respectively, and then entering the transition chamber for premixing through the first and second inlet channels. The premixed liquids are thoroughly mixed and react with each other through a mixer. After the reaction, the liquid flows through the outlet channel to the outlet hole, where it can be removed. The upper C-shaped structure of the mixing unit of the mixer has an upper inlet channel and an upper outlet channel at the same height, while the upper middle channel can be at the same height as the upper inlet channel and the upper outlet channel, or they can be at different heights. Similarly, the lower C-shaped structure has a lower inlet channel and a lower outlet channel at the same height, while the lower middle channel can be at the same height as the lower inlet channel and the lower outlet channel, or they can be at different heights. The increased height difference accelerates the mixing efficiency and reduces the reaction time. Therefore, it has good mixing effect, a small reflux zone, controllable reaction time, and a simple structure, making it easy to prepare and suitable for large-scale application.

[0025] 2. The preparation method of the microchannel derivatization chip for liquid chromatography of the present invention includes the following steps: forming the microchannel derivatization chip for liquid chromatography by 3D printing; or, the chip body includes an upper chip layer and a lower chip layer, and the preparation method of the microchannel derivatization chip for liquid chromatography includes the following steps: (1) obtaining the upper chip layer and the lower chip layer by 3D printing or mechanical processing; (2) hot pressing or gluing the upper chip layer onto the lower chip layer. Therefore, its preparation process is simple and easy to operate. The prepared microchannel derivatization chip for liquid chromatography has a simple structure, good mixing effect, small reflux zone, and controllable reaction time, and is suitable for large-scale promotion and application.

[0026] These and other objects, features and advantages of the present invention will be fully apparent from the following detailed description and drawings, and can be achieved by the means, devices and combinations thereof specifically pointed out in the summary of the invention. Attached Figure Description

[0027] Figure 1 This is a three-dimensional perspective view of a specific embodiment of the microchannel derivatization chip for liquid chromatography of the present invention.

[0028] Figure 2 yes Figure 1 The diagram shows a top perspective view of a specific embodiment.

[0029] Figure 3 yes Figure 1 A three-dimensional perspective schematic diagram of the components of the three hybrid units in the specific embodiment shown.

[0030] Figure 4 yes Figure 1 A three-dimensional perspective view of the hybrid unit of the specific embodiment shown.

[0031] Figure 5 yes Figure 1 A three-dimensional perspective view of the upper C-shaped structure of the hybrid unit in the specific embodiment shown.

[0032] Figure 6 yes Figure 1 A three-dimensional perspective view of the lower C-shaped structure of the hybrid unit in the specific embodiment shown.

[0033] Figure 7 yes Figure 1 A schematic left view of the hybrid unit of the specific embodiment shown.

[0034] (Explanation of reference numerals in the attached image) 1. Chip body; 11. Upper chip layer; 12. Lower chip layer; 2 First liquid inlet; 3 First liquid inlet channel; 4 Second liquid inlet; 5 Second liquid inlet channel; 6 Transition cavity; 7 mixers; 71 mixing units; 711 Upper C-shaped structure; 7111 Upper inlet channel; 7112 Upper outlet channel; 7113 Upper intermediate channel; 7114 Upper first connecting channel; 7115 Upper second connecting channel; 712 Lower C-shaped structure; 7121 Lower inlet flow channel; 7122 Lower outlet flow channel; 7123 Lower intermediate flow channel; 7124 Lower first connecting flow channel; 7125 Lower second connecting flow channel; 8. Liquid outlet channel; 9. Liquid outlet hole. Detailed Implementation

[0035] To better understand the technical content of this invention, the following embodiments are provided for detailed explanation.

[0036] In the description of this invention, it should be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0037] Please see Figures 1-6 As shown, in a specific embodiment of the present invention, the template fastening, moving, rotating, and flipping device of the present invention includes a chip body 1, a first liquid inlet 2, a first liquid inlet channel 3, a second liquid inlet 4, a second liquid inlet channel 5, a transition cavity 6, a mixer 7, a liquid outlet channel 8, and a liquid outlet 9, wherein: The chip body 1 is horizontally positioned and arranged along the left-right direction; The first liquid inlet 2, the second liquid inlet 4, and the liquid outlet 9 are all vertically arranged and horizontally spaced apart from each other in the top surface of the chip body 1. The transition cavity 6 is arranged in the chip body 1. The first liquid inlet channel 3 is horizontally arranged in the chip body 1 and located between the bottom of the first liquid inlet 2 and the transition cavity 6, and respectively connects the bottom of the first liquid inlet 2 and the transition cavity 6. The second liquid inlet channel 5 is horizontally arranged in the chip body 1 and located between the bottom of the second liquid inlet 4 and the transition cavity 6, and respectively connects the bottom of the second liquid inlet 4 and the transition cavity 6. The mixer 7 includes a mixing unit 71, which is disposed in the chip body 1 and includes an upper C-shaped structure 711 and a lower C-shaped structure 712. The upper C-shaped structure 711 includes an upper inlet channel 7111, an upper outlet channel 7112, an upper intermediate channel 7113, an upper first connecting channel 7114, and an upper second connecting channel 7115. The upper inlet channel 7111 and the upper outlet channel 7112 are both horizontally arranged along the left-right direction and spaced apart from each other. The upper intermediate channel 7113 is horizontally arranged along the left-right direction and located above and behind the space between the upper inlet channel 7111 and the upper outlet channel 7112 (obviously, the upper intermediate channel 7113 can also be located behind or above the space between the upper inlet channel 7111 and the upper outlet channel 7112). The upper first connecting channel 7114 and the upper second connecting channel 7115 are located to the left and right of each other. The upper first connecting channel 7114 is located between the right end of the upper inlet channel 7111 and the left end of the upper middle channel 7113, and connects the right end of the upper inlet channel 7111 and the left end of the upper middle channel 7113, respectively. The upper second connecting channel 7115 is located between the left end of the upper outlet channel 7112 and the right end of the upper middle channel 7113, and connects the left end of the upper outlet channel 7112 and the right end of the upper middle channel 7113, respectively. The angle between the extension lines of the upper first connecting channel 7114 and the upper second connecting channel 7115 is >0° and ≤135° (obviously, the upper first connecting channel 7114 and the upper second connecting channel 7115 can also be arranged parallel to each other). The lower C-shaped structure 712 includes a lower inlet channel 7121, a lower outlet channel 7122, a lower intermediate channel 7123, a lower first connecting channel 7124, and a lower second connecting channel 7125. The lower inlet channel 7121 and the lower outlet channel 7122 are both horizontally arranged along the left-right direction and spaced apart from each other. The lower intermediate channel 7123 is horizontally arranged along the left-right direction and is located slightly below and in front of the gap between the lower inlet channel 7121 and the lower outlet channel 7122 (obviously, the lower intermediate channel 7123 can also be located in front of or below the gap between the lower inlet channel 7121 and the lower outlet channel 7122). The lower first connecting channel 7124 and the lower second connecting channel 7125... The lower first connecting channel 7124 is located between the right end of the lower inlet channel 7121 and the left end of the lower middle channel 7123, and connects the right end of the lower inlet channel 7121 and the left end of the lower middle channel 7123, respectively. The lower second connecting channel 7125 is located between the left end of the lower outlet channel 7122 and the right end of the lower middle channel 7123, and connects the left end of the lower outlet channel 7122 and the right end of the lower middle channel 7123, respectively. The angle between the extension lines of the lower first connecting channel 7124 and the lower second connecting channel 7125 is >0° and ≤135° (obviously, the lower first connecting channel 7124 and the lower second connecting channel 7125 can also be arranged parallel to each other). The right end of the upper outlet channel 7112 is located on the left end of the lower inlet channel 7121 and connects to the left end of the lower inlet channel 7121. The left end of the upper inlet channel 7111 is located beside the transition cavity 6 and connects to the transition cavity 6. The liquid outlet channel 8 is horizontally arranged in the chip body 1. One end of the liquid outlet channel 8 is located on the right end of the lower outlet channel 7122 and connects to the right end of the lower outlet channel 7122. The other end of the liquid outlet channel 8 is located beside the bottom of the liquid outlet hole 9 and connects to the bottom of the liquid outlet hole 9.

[0038] The first liquid inlet 2, the second liquid inlet 4, and the liquid outlet 9 can have any suitable relative position. Please refer to [link / reference]. Figures 1-2 As shown, in a specific embodiment of the present invention, the first liquid inlet hole 2 and the second liquid inlet hole 4 are arranged at intervals from each other, the transition cavity 6 is located to the right of the middle position between the bottom of the first liquid inlet hole 2 and the bottom of the second liquid inlet hole 4, the first liquid inlet channel 3 is inclined to the right front in the direction from left to right, and the second liquid inlet channel 5 is inclined to the right rear in the direction from left to right.

[0039] The left end of the upper inlet channel 7111 and the transition cavity 6 can have any suitable relative positional relationship; please refer to [link / reference]. Figures 1-2 As shown, in a specific embodiment of the present invention, the left end of the upper inlet channel 7111 is located to the right of the transition cavity 6.

[0040] The transition cavity 6 can have any suitable shape; please refer to [link / reference]. Figure 1 As shown, in a specific embodiment of the present invention, the transition cavity 6 is a cylindrical transition cavity.

[0041] The right end of the lower outlet channel 7122, the bottom of the liquid outlet channel 8, and the liquid outlet hole 9 can have any suitable relative positional relationship. Please refer to [link to relevant documentation]. Figures 1-2 As shown, in a specific embodiment of the present invention, the liquid outlet channel 8 is arranged along the left-right direction, the left end of the liquid outlet channel 8 is arranged on the right end of the lower outlet channel 7122 and connected to the right end of the lower outlet channel 7122, and the right end of the liquid outlet channel 8 is located to the left of the bottom of the liquid outlet hole 9 and connected to the bottom of the liquid outlet hole 9.

[0042] The angle between the extension line of the upper first connecting channel 7114 and the extension line of the upper second connecting channel 7115 can be determined as needed. In a specific embodiment of the present invention, the angle between the extension line of the upper first connecting channel 7114 and the extension line of the upper second connecting channel 7115 is 30°.

[0043] The angle between the extension line of the lower first connecting channel 7124 and the extension line of the lower second connecting channel 7125 can be determined as needed. In a specific embodiment of the present invention, the angle between the extension line of the lower first connecting channel 7124 and the extension line of the lower second connecting channel 7125 is 30°.

[0044] The number of mixing units 71 can be determined as needed. Preferably, there are multiple mixing units 71 arranged sequentially from left to right. In two adjacent mixing units 71, the left end of the upper inlet channel 7111 of the right mixing unit 71 is located on the right end of the lower outlet channel 7122 of the left mixing unit 71 and connects to the right end of the lower outlet channel 7122 of the left mixing unit 71. The left end of the upper inlet channel 7111 of the leftmost mixing unit 71 is located beside the transition cavity 6 and connects to the transition cavity 6. One end of the liquid outlet channel 8 is located on the right end of the lower outlet channel 7122 of the rightmost mixing unit 71 and connects to the right end of the lower outlet channel 7122 of the rightmost mixing unit 71. "Multiple" refers to two or more. Please refer to [link to relevant documentation]. Figures 1-2 As shown, in a specific embodiment of the present invention, the number of mixing units 71 is 7.

[0045] The chip body 1 can have any suitable configuration; please refer to [link / reference]. Figure 1 As shown, in a specific embodiment of the present invention, the chip body 1 includes an upper chip layer 11 and a lower chip layer 12. Both the upper chip layer 11 and the lower chip layer 12 are horizontally arranged and arranged along the left-right direction. The upper chip layer 11 is disposed on the lower chip layer 12. The first liquid inlet hole 2, the first liquid inlet channel 3, the second liquid inlet hole 4, the second liquid inlet channel 5, the transition cavity 6, the upper C-shaped structure 711 of the mixing unit 71, the liquid outlet channel 8, and the liquid outlet hole 9 are all disposed in the upper chip layer 11. The lower C-shaped structure 712 of the mixing unit 71 is disposed in the lower chip layer 12.

[0046] The upper chip layer 11 is disposed on the lower chip layer 12 and can adopt any suitable structure. More preferably, the upper chip layer 11 is hot-pressed or glued to the lower chip layer 12. In a specific embodiment of the present invention, the upper chip layer 11 is hot-pressed onto the lower chip layer 12.

[0047] The chip body 1 can be made of any suitable material; preferably, it is a polymer chip body or a metal chip body. In one specific embodiment of the present invention, the chip body 1 is a polymer chip body.

[0048] The method for preparing the microchannel derivatization chip for liquid chromatography of the present invention may involve 3D printing the entire microchannel derivatization chip for liquid chromatography.

[0049] When the chip body 1 includes an upper chip layer 11 and a lower chip layer 12, the method for preparing the microchannel derivatization chip for liquid chromatography of the present invention can also be carried out by the following method: (1) The upper layer 11 and the lower layer 12 of the chip are obtained by 3D printing or machining. (2) The upper layer 11 of the chip is hot-pressed or glued onto the lower layer 12 of the chip.

[0050] In use, the liquid sample components and chemical derivatizing reagents are added to the first inlet hole 2 and the second inlet hole 4, respectively, and then enter the transition chamber 6 for premixing through the first inlet channel 3 and the second inlet channel 5. The premixed liquids are fully mixed and react with each other through the mixer 7. After the reaction, the liquids flow through the outlet channel 8 to the outlet hole 9, and the reacted liquids can be taken out from the outlet hole 9.

[0051] In this invention, the first inlet hole 2 and the second inlet hole 4 are used to introduce the liquid to be mixed, the mixer 7 is used to promote liquid mixing, and the outlet hole 9 is used to lead out the mixed liquid. The mixer 7 is formed by connecting at least one mixing unit 71 end to end to form a serpentine structure, which can effectively control the length of the mixed liquid passing through the mixer 7, thereby controlling the reaction time. At the same time, it can maximize the flow path in a limited microscale space, save space, and improve the economics of manufacturing.

[0052] The upper inlet channel 7111 and the upper outlet channel 7112 of the upper C-shaped structure 711 of each mixing unit 71 are at the same height. The upper intermediate channel 7113 can be at the same height as the upper inlet channel 7111 and the upper outlet channel 7112 (i.e., the upper intermediate channel 7113 is located behind the gap between the upper inlet channel 7111 and the upper outlet channel 7112), or it can be different (i.e., the upper intermediate channel 7113 is located above and behind the gap between the upper inlet channel 7111 and the upper outlet channel 7112). The increased height difference will accelerate the mixing efficiency and reduce the reaction time.

[0053] The lower inlet channel 7121 and the lower outlet channel 7122 of the lower C-shaped structure 712 of each mixing unit 71 are at the same height. The lower intermediate channel 7123 can be at the same height as the lower inlet channel 7121 and the lower outlet channel 7122 (i.e., the lower intermediate channel 7123 is located in front of the gap between the lower inlet channel 7121 and the lower outlet channel 7122), or it can be different (i.e., the lower intermediate channel 7123 is located in front of and below the gap between the lower inlet channel 7121 and the lower outlet channel 7122). The increased height difference will accelerate the mixing efficiency and reduce the reaction time.

[0054] Compared with the prior art, the present invention has the following beneficial effects: 1. The flow field of this invention is simple, avoiding the generation of large-scale chaotic convection, so that the distribution of derivatization reaction within the chip is relatively uniform.

[0055] 2. This invention controls the tilt angles θ and φ of the curved flow channel (where θ is the angle between the upper first connecting flow channel and the upper second connecting flow channel (see...)). Figure 3 The angle between the lower first connecting channel and the lower second connecting channel is 0°≤θ≤135°; φ is the angle between the upper first connecting channel and the upper inlet channel (see...). Figure 7 The angles between the upper second connecting channel and the upper outlet channel, the lower first connecting channel and the lower inlet channel, and the lower second connecting channel and the lower outlet channel (0°≤φ≤90°) reduce the reflux zone of the derivatization reaction and reduce the influence of side reactions.

[0056] 3. The present invention allows for controllable reaction time by reasonably setting the number of mixing units.

[0057] Therefore, this invention provides a novel 3D curved flow channel, which reduces the reflux zone of the derivatization reaction by controlling the tilt angle of the curved flow channel. The smaller the reflux zone, the less the impact of side reactions. By controlling the number of mixing units, the reaction time of the mixed liquid in the chip can be controlled.

[0058] In summary, the microchannel derivatization chip for liquid chromatography of the present invention has good mixing effect, small reflux zone, controllable reaction time, simple structure, and easy preparation. Its preparation method is simple, easy to operate, and suitable for large-scale promotion and application.

[0059] Therefore, it is evident that the objective of this invention has been fully and effectively achieved. The function and structural principles of this invention have been demonstrated and explained in the embodiments. Any modifications can be made to the implementation methods without departing from these principles. Therefore, this invention includes all modified embodiments based on the spirit and scope of the claims.

Claims

1. A microchannel derivatization chip for liquid chromatography, comprising a chip body, the chip body being horizontally disposed and arranged along a left-right direction, characterized in that, The microchannel derivatization chip for liquid chromatography further includes a first inlet port, a first inlet channel, a second inlet port, a transition chamber, a mixer, an outlet channel, and an outlet port, wherein: The first liquid inlet, the second liquid inlet, and the liquid outlet are all vertically arranged and horizontally spaced apart from each other on the top surface of the chip body. The transition cavity is arranged in the chip body. The first liquid inlet channel is horizontally arranged in the chip body and located between the bottom of the first liquid inlet and the transition cavity, and respectively connects the bottom of the first liquid inlet and the transition cavity. The second liquid inlet channel is horizontally arranged in the chip body and located between the bottom of the second liquid inlet and the transition cavity, and respectively connects the bottom of the second liquid inlet and the transition cavity. The mixer includes a mixing unit disposed in the chip body and includes an upper C-shaped structure and a lower C-shaped structure; The upper C-shaped structure includes an upper inlet channel, an upper outlet channel, an upper intermediate channel, an upper first connecting channel, and an upper second connecting channel. The upper inlet channel and the upper outlet channel are both horizontally arranged along the left-right direction and are spaced apart from each other. The upper intermediate channel is horizontally arranged along the left-right direction and is located behind, above, or behind the interval between the upper inlet channel and the upper outlet channel. The upper first connecting channel and the upper second connecting channel are spaced apart from each other. The upper first connecting channel is located at... The upper inlet channel is located between the right end of the upper inlet channel and the left end of the upper middle channel, and is connected to the right end of the upper inlet channel and the left end of the upper middle channel, respectively. The upper second connecting channel is located between the left end of the upper outlet channel and the right end of the upper middle channel, and is connected to the left end of the upper outlet channel and the right end of the upper middle channel, respectively. The upper first connecting channel and the upper second connecting channel are arranged parallel to each other, or the angle between the extension line of the upper first connecting channel and the extension line of the upper second connecting channel is >0° and ≤135°. The lower C-shaped structure includes a lower inlet channel, a lower outlet channel, a lower intermediate channel, a lower first connecting channel, and a lower second connecting channel. The lower inlet channel and the lower outlet channel are both horizontally arranged along the left-right direction and are spaced apart from each other. The lower intermediate channel is also horizontally arranged along the left-right direction and is located in front of, below, or below the interval between the lower inlet channel and the lower outlet channel. The lower first connecting channel and the lower second connecting channel are spaced apart from each other. The lower first connecting channel is located at... The lower inlet channel is located between the right end of the lower inlet channel and the left end of the lower middle channel, and is connected to the right end of the lower inlet channel and the left end of the lower middle channel, respectively. The lower second connecting channel is located between the left end of the lower outlet channel and the right end of the lower middle channel, and is connected to the left end of the lower outlet channel and the right end of the lower middle channel, respectively. The lower first connecting channel and the lower second connecting channel are arranged parallel to each other, or the angle between the extension line of the lower first connecting channel and the extension line of the lower second connecting channel is >0° and ≤135°. The right end of the upper outlet channel is located on the left end of the lower inlet channel and connects to the left end of the lower inlet channel. The left end of the upper inlet channel is located beside the transition cavity and connects to the transition cavity. The liquid outlet channel is horizontally arranged in the chip body. One end of the liquid outlet channel is located on the right end of the lower outlet channel and connects to the right end of the lower outlet channel. The other end of the liquid outlet channel is located beside the bottom of the liquid outlet hole and connects to the bottom of the liquid outlet hole.

2. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The first liquid inlet and the second liquid inlet are spaced apart from each other. The transition cavity is located to the right of the middle position between the bottom of the first liquid inlet and the bottom of the second liquid inlet. The first liquid inlet channel is inclined to the right front in the direction from left to right, and the second liquid inlet channel is inclined to the right rear in the direction from left to right.

3. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The left end of the upper inlet channel is located on the right side of the transition cavity.

4. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The liquid outlet channel is arranged along the left-right direction. The left end of the liquid outlet channel is located on the right end of the lower outlet channel and connects to the right end of the lower outlet channel. The right end of the liquid outlet channel is located to the left of the bottom of the liquid outlet hole and connects to the bottom of the liquid outlet hole.

5. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The number of mixing units is multiple, and the multiple mixing units are arranged sequentially from left to right. In two adjacent mixing units, the left end of the upper inlet channel of the right mixing unit is located on the right end of the lower outlet channel of the left mixing unit and connects to the right end of the lower outlet channel of the left mixing unit. The left end of the upper inlet channel of the leftmost mixing unit is located beside the transition cavity and connects to the transition cavity. One end of the liquid outlet channel is located on the right end of the lower outlet channel of the rightmost mixing unit and connects to the right end of the lower outlet channel of the rightmost mixing unit.

6. The microchannel derivatization chip for liquid chromatography as described in claim 5, characterized in that, The number of the hybrid units is 7.

7. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The chip body includes an upper chip layer and a lower chip layer. Both the upper chip layer and the lower chip layer are horizontally arranged and are arranged along the left-right direction. The upper chip layer is disposed on the lower chip layer. The first liquid inlet hole, the first liquid inlet channel, the second liquid inlet hole, the second liquid inlet channel, the transition cavity, the upper C-shaped structure of the mixing unit, the liquid outlet channel, and the liquid outlet hole are all disposed in the upper chip layer. The lower C-shaped structure of the mixing unit is disposed in the lower chip layer.

8. The microchannel derivatization chip for liquid chromatography as described in claim 7, characterized in that, The upper layer of the chip is heat-pressed or glued onto the lower layer of the chip.

9. The microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The chip body is a polymer chip body or a metal chip body.

10. A method for preparing a microchannel derivatization chip for liquid chromatography as described in claim 1, characterized in that, The method for fabricating the microchannel derivatization chip for liquid chromatography includes the following steps: molding the microchannel derivatization chip for liquid chromatography using 3D printing; or, The chip body includes an upper chip layer and a lower chip layer, both of which are horizontally arranged and aligned along the left-right direction. The upper chip layer is disposed on the lower chip layer. The first liquid inlet, the first liquid inlet channel, the second liquid inlet, the second liquid inlet channel, the transition cavity, the upper C-shaped structure of the mixing unit, the liquid outlet channel, and the liquid outlet are all disposed in the upper chip layer. The lower C-shaped structure of the mixing unit is disposed in the lower chip layer. The preparation method of the microchannel derivatization chip for liquid chromatography includes the following steps: (1) The upper layer and the lower layer of the chip are obtained by 3D printing or machining. (2) The upper layer of the chip is hot-pressed or glued onto the lower layer of the chip.

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