Microfluidic chip for microsphere preparation

Abstract

The microfluidic chip for preparing microspheres provided in the embodiments of the present disclosure comprises: a chip body; at least one water phase inlet and a plurality of water phase outlets are arranged on a first surface layer of the chip body, and at least one oil phase inlet is arranged on a second surface layer; a microfluid channel structure is arranged in a microfluid layer; the microfluid channel structure is formed with at least one microsphere generation module; the microsphere generation module comprises: a first branch flow channel structure, a second branch flow channel structure, and a plurality of microsphere generation units; each microsphere generation unit comprises: a first resistance flow channel unit formed by a microfluid channel, second resistance flow channel units on both sides, and a microsphere cutting flow channel unit; the first branch flow channel structure is connected with one water phase inlet and each first resistance flow channel unit; and the second branch flow channel structure is connected with one oil phase inlet and each first resistance flow channel unit. Through the microfluid channel design of the oil phase and water phase shunting and resistance in the plurality of microsphere generation units in each module, the preparation speed and efficiency are good, and the demand for large-scale preparation is met.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the technical field of chromatographic packing preparation, in particular to a microfluidic chip for microsphere preparation. BACKGROUND

[0002] The preparation of conventional microspheres is usually prepared by emulsification method, which has the disadvantages of low efficiency and low quality. The microspheres are collected by stacking, and there is a lack of an efficient and batch production method for microspheres. SUMMARY

[0003] In view of the above-mentioned disadvantages of the prior art, the purpose of the present disclosure is to provide a microfluidic chip for microsphere preparation to solve the problems in the related art.

[0004] The first aspect of the present disclosure provides a microfluidic chip for microsphere preparation, comprising: a chip body having a first surface layer, a second surface layer and a microflow layer between the first surface layer and the second surface layer; the first surface layer is provided with at least one water phase inlet and a plurality of water phase outlets, and the second surface layer is provided with at least one oil phase inlet; a microflow channel structure is arranged in the microflow layer; the microflow channel structure is formed with at least one microsphere generation module; each microsphere generation module comprises: a first branch flow channel structure, a second branch flow channel structure, and a plurality of microsphere generation units; wherein each microsphere generation unit comprises: a first resistance flow channel unit, a second resistance flow channel unit symmetrically arranged on both sides of the first resistance flow channel unit, and a microsphere cutting flow channel unit; the outlet of the first resistance flow channel unit is connected to one of the water phase outlets through a microsphere output flow channel; the microsphere cutting flow channel unit is formed by the microflow channel connecting the ball forming position on the microsphere output flow channel and the outlet of each second resistance flow channel unit; the first resistance flow channel unit and the second resistance flow channel unit are formed by the microflow channel winding; the first branch flow channel structure comprises a first inlet connected to a water phase inlet, and each first outlet connected to the inlet of each first resistance flow channel unit in the plurality of microsphere generation units through each branch flow channel from the first inlet; the second branch flow channel structure comprises a second inlet connected to an oil phase inlet, and each second outlet connected to the inlet of each second resistance flow channel unit in the plurality of microsphere generation units through each branch flow channel from the second inlet.

[0005] In an embodiment of the first aspect, the first branch flow channel structure and the second branch flow channel structure are multi-stage flow channel structures; the multi-stage flow channel structure forms a plurality of levels of branch flow channels connected in series from the inlet to the outlet, and each level forms 2n branch flow channels, where n is the number of levels; the outlet of each branch flow channel of the last level of the first branch flow channel structure is connected to the inlet of a first resistance flow channel unit; the outlet of each branch flow channel of the last level of the second branch flow channel structure is connected to the inlet of a second resistance flow channel unit.

[0006] In an embodiment of the first aspect, the first branch flow channel structure and / or the second branch flow channel structure is an axisymmetric structure.

[0007] In an embodiment of the first aspect, the structure between the two second resistance flow channel units in each microsphere generating unit is symmetrical; and / or, the radial width and density of the micro-flow channels in the first resistance flow channel unit are greater than those in the second resistance flow channel unit.

[0008] In an embodiment of the first aspect, the first surface layer and the second surface layer are mutually positive and negative planes; the plurality of water phase inlets are uniformly distributed around an axis vertically passing through the first surface layer and the second surface layer, and the plurality of oil phase inlets are uniformly distributed around the axis; and / or, the position of each water phase inlet corresponds to that of one oil phase inlet.

[0009] In an embodiment of the first aspect, the first branch flow channel structure and the second branch flow channel structure are located in mutually isolated different layers in the micro-flow layer.

[0010] In an embodiment of the first aspect, the plurality of water phase outlets are located at the periphery of the water phase inlets and the oil phase inlets in the distribution position of the chip body; each microsphere generating module is located between a water phase inlet and a plurality of water phase outlets.

[0011] In an embodiment of the first aspect, each microsphere generating unit in each microsphere generating module and the corresponding connected each water phase outlet are arranged in a circular arc shape.

[0012] In an embodiment of the first aspect, the number of the water phase inlets, the oil phase inlets and the microsphere generating modules is at least two; each microsphere generating module is arranged circumferentially around each water phase inlet and oil phase inlet, so that each microsphere generating unit therein is arranged in a circular ring shape; and each water phase outlet is arranged in a circular ring shape at the periphery of each microsphere generating unit.

[0013] In an embodiment of the first aspect, the chip body is in a disc shape, and the first surface layer and the second surface layer are circular end faces at both ends of the chip body.

[0014] As described above, the microfluidic chip for preparing microspheres provided in the embodiments of the present disclosure comprises: a chip body; at least one water phase inlet and a plurality of water phase outlets are arranged on a first surface layer of the chip body, and at least one oil phase inlet is arranged on a second surface layer; a microfluidic channel structure is arranged in the microfluidic layer; the microfluidic channel structure is formed with at least one microsphere generation module; each microsphere generation module comprises: a first branch channel structure, a second branch channel structure, and a plurality of microsphere generation units; each microsphere generation unit comprises: a first resistance channel unit, a second resistance channel unit symmetrically arranged on both sides of the first resistance channel unit, and a microsphere cutting channel unit; the first resistance channel unit is communicated with one water phase outlet; the first resistance channel unit and the second resistance channel unit are formed by microfluidic channel detours; the first branch channel structure is communicated with one water phase inlet and each first resistance channel unit in the module; and the second branch channel structure is communicated with one oil phase inlet and each first resistance channel unit in the module. Through the microfluidic channel design of the oil phase and water phase shunting and resistance in each microsphere generation unit in each module, the preparation speed and efficiency are good, and the demand for large-scale preparation is met. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 A structure schematic diagram of the microfluidic chip in the embodiments of the present disclosure is shown from the side of the first surface layer.

[0016] Figure 2 A structure schematic diagram of the microfluidic chip in the embodiments of the present disclosure is shown from the side of the second surface layer.

[0017] Figure 3 A communication structure schematic diagram between the first branch channel structure, the water phase inlet, the microsphere generation unit, and the water phase outlet in the embodiments of the present disclosure is shown.

[0018] Figure 4 A structure schematic diagram of the second branch channel structure in the embodiments of the present disclosure is shown.

[0019] Figure 5 A structure schematic diagram of the microsphere generation module in the embodiments of the present disclosure is shown. Figure 3 And Figure 4 A structure schematic diagram of the channel superposition in the embodiments of the present disclosure is shown. DETAILED DESCRIPTION

[0020] The embodiments of the present disclosure are described below through specific specific examples, and those skilled in the art can easily understand other advantages and effects of the present disclosure from the disclosed messages. The present disclosure can also be implemented or applied by means of other different specific embodiments, and various modifications or changes can be made to the details in the present disclosure without departing from the spirit of the present disclosure. It should be noted that the embodiments in the present disclosure and the features in the embodiments can be combined with each other without conflict.

[0021] The embodiments of the present disclosure will be described in detail with reference to the drawings, so as to be easily carried out by those skilled in the art to which the present disclosure pertains. The present disclosure can be embodied in various ways, and is not limited to the embodiments described herein.

[0022] In the description of the present disclosure, the expressions "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" etc. mean that the specific features, structures, materials or characteristics represented in connection with the embodiment or example are included in at least one embodiment or example of the present disclosure. Also, the specific features, structures, materials or characteristics represented can be combined in an appropriate way in any one or a group of embodiments or examples. In addition, the different embodiments or examples represented in the present disclosure and the features of the different embodiments or examples can be combined and combined by those skilled in the art without contradiction.

[0023] In addition, the terms "first", "second" are used only for the purpose of description, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features defined with "first", "second" can explicitly or implicitly include at least one of the features. In the description of the present disclosure, the meaning of "a group" is two or more, unless otherwise specifically limited.

[0024] Throughout the specification, when it is said that a certain device is "connected" to another device, it includes not only the case of "direct connection", but also the case of "indirect connection" in which other elements are placed therebetween. In addition, when it is said that a certain device "includes" a certain constituent element, unless otherwise specifically stated, other constituent elements are not excluded, but it means that other constituent elements can also be included.

[0025] Although the terms first, second, etc. are used herein to refer to various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first interface and a second interface, etc. are distinguished from each other. Also, as used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises", "comprising", "includes" and / or "including", when used herein, specify the presence of stated features, steps, operations, elements, modules, items, components, and / or groups thereof, but do not preclude the presence or addition of one or more other features, steps, operations, elements, modules, items, components, and / or groups thereof. As used herein, the terms "or" and "and / or" are construed to be inclusive, or mean any one or any combination of the listed items. Thus, "A, B or C" or "A, B and / or C" means "any of the following: A; B; C; A and B; A and C; B and C; A, B and C". Exceptions to this definition are only present when items are grouped in some manner as in certain embodiments of the disclosure contain the use of intermittent conjunction.

[0026] The most commonly used method for preparing traditional microspheres is the emulsion-solvent evaporation method, which is based on the principle of dissolving raw and auxiliary materials in two mutually insoluble solvents respectively, and then preparing an emulsion through mechanical oscillation or ultrasonic emulsification. The liquid dispersed into droplets is the internal dispersed phase, and the liquid dispersed into droplets is the external continuous phase. Then the internal dispersed phase solvent is volatilized under certain conditions, and the spherical material is precipitated and solidified into microspheres. However, the traditional preparation method has low efficiency and low quality, and it is necessary to collect a large amount of microspheres to obtain the required amount of microspheres, and it is impossible to obtain a high-efficiency and batch microsphere production method.

[0027] In view of this, a microfluidic chip for microsphere preparation is provided in the embodiments of the present disclosure, which solves the above problems through high-efficiency and large-scale microfluidic chips.

[0028] As shown in Figure 1 , a structure schematic diagram of the microfluidic chip 1 under the perspective of the first surface layer 11 in the embodiments of the present disclosure is shown. And as shown in Figure 2 , a structure schematic diagram of the microfluidic chip 1 under the perspective of the second surface layer 12 in the embodiments of the present disclosure is shown.

[0029] In Figure 1In some embodiments, a schematic diagram of a structure of a chip body 10 included in the microfluidic chip 1 is shown. The chip body 10 can be a disc or a wafer structure, for example. In other embodiments, the chip body 10 can be other shapes, not limited to a disc or wafer shape. The upper and lower ends of the chip body 10 can be circular end faces, for example, which can be a first surface layer 11 and a second surface layer 12, respectively. The first surface layer 11 and the second surface layer 12 can be mutually opposite planes. In some embodiments, the first surface layer 11 and the second surface layer 12 can be parallel to each other. Figure 1 In some embodiments, the first surface layer 11 is provided with a water phase inlet 111 and a water phase outlet 112. The water phase inlet 111 is used for input of a water phase solution, such as an agarose solution. The water phase outlet 112 is used for output of each microsphere formed by cutting the water phase solution with an oil phase, such as an agarose microsphere. Agarose microspheres are a natural polysaccharide type of biocompatible, porous, hydrophilic, and non-charged group biological filler, which plays an irreplaceable role as a matrix of chromatographic medium. At the same time, due to the presence of multiple hydroxyl groups in agarose, derivatives with different functional groups can be obtained through chemical bonding. Agarose-based chromatographic medium is widely used in the separation and purification of biological macromolecules, and has become an indispensable separation material for biological samples such as proteins, especially with the rapid development of proteomics. Of course, the chip 1 in the embodiments of the present disclosure can also be used for the preparation of other microspheres, not limited thereto.

[0030] Each water phase inlet 111 can correspond to a plurality of water phase outlets 112. In the example shown in the figure, there are four water phase inlets 111 and thirty-two water phase outlets 112, and each water phase inlet 111 corresponds to eight water phase outlets 112. The water phase is input from each water phase inlet 111 and output to the corresponding water phase outlet 112.

[0031] On the first surface layer 11, the plurality of water phase outlets 112 are located at the periphery of the water phase inlets 111. The plurality of water phase inlets 111 are uniformly distributed around an axis that passes vertically through the first surface layer 11 and the second surface layer 12. In the case of a disc or wafer shape or other central symmetrical shape, the axis can be a central axis.

[0032] Referring again to Figure 2 As shown, a plurality of oil phase inlets 121 are provided on the second surface layer 12. Each oil phase inlet 121 is used for input of an oil phase, and the oil phase inlet 121 is connected to the water phase outlet 112 to deliver the oil phase to cut the water phase to form each microsphere. The number of oil phase inlets 121 can be the same as the number of oil phase outlets, for example, four. Further optionally, each water phase inlet 111 can correspond to a same oil phase inlet 121 in position on the opposite surfaces.

[0033] The plurality of oil phase inlets 121 can also be arranged uniformly around the axial direction in correspondence with the positions of the water phase inlets 111. Of course, in other embodiments, the plurality of oil phase inlets 121 can be arranged uniformly around the axial direction even if the oil phase inlets 121 and the water phase inlets 111 do not correspond to each other in position.

[0034] It should be particularly noted that the number of the oil phase inlets 121 and the water phase inlets 111 is not necessarily four, but can be two or more, which can be changed according to requirements, such as two, three or other numbers.

[0035] The water phase inlets 111 and the oil phase inlets 121 are connected to the water phase outlet 112 through a microfluidic channel structure. Exemplarily, the first surface layer 11 and the second surface layer 12 can be closed layers, and the microfluidic channel structure can be formed in a microfluidic layer 17 between the first surface layer 11 and the second surface layer 12.

[0036] As shown in FIG. 2, a microfluidic channel structure is used for illustration. The microfluidic channel structure is formed with at least one microsphere generation module, and each microsphere generation module includes a first branch flow channel structure 13, a second branch flow channel structure 14, and a plurality of microsphere generation units 15. Figures 3 to 5 As shown in FIG. 3, a schematic diagram of a communication structure between the first branch flow channel structure 13, the water phase inlet 111, the microsphere generation unit 15, and the water phase outlet 112 in an embodiment of the present disclosure is shown. The first branch flow channel structure 13 is connected to one water phase inlet 111 and a corresponding plurality of microsphere generation units 15.

[0037] Figure 3 Exemplarily, the first branch flow channel structure 13 is a multi-stage flow channel structure. The multi-stage flow channel structure forms a plurality of stages of branch flow channels in communication from the inlet to the outlet. Two n n numbers of branch flow channels are formed in each stage, and n is the number of stages. For example, in FIG. 4, the first branch flow channel structure 13 is bifurcated at each stage from the water phase inlet 111, i.e., two branch flow channels are formed in the first stage, the two branch flow channels are bifurcated again in the second stage to form four branch flow channels, the four branch flow channels are bifurcated again in the third stage to form eight branch flow channels, and the eight outlets of the eight branch flow channels are connected to the respective microsphere generation units 15. As an example, the first branch flow channel structure 13 is an axisymmetric structure, i.e., with the radial direction of the center passing through the water phase inlet 111 and the first surface layer 11 as the axis, the branch flow channels of each stage of the first branch flow channel structure 13 are symmetrically distributed on both sides of the axis to ensure that the water phase is as uniformly distributed as possible to each branch flow channel in each stage.

[0038] As another example, as shown in FIG. 5, the first branch flow channel structure 13 is a multi-stage flow channel structure. The multi-stage flow channel structure forms a plurality of stages of branch flow channels in communication from the inlet to the outlet. Two n n numbers of branch flow channels are formed in each stage, and n is the number of stages. For example, in FIG. 4, the first branch flow channel structure 13 is bifurcated at each stage from the water phase inlet 111, i.e., two branch flow channels are formed in the first stage, the two branch flow channels are bifurcated again in the second stage to form four branch flow channels, the four branch flow channels are bifurcated again in the third stage to form eight branch flow channels, and the eight outlets of the eight branch flow channels are connected to the respective microsphere generation units 15. As an example, the first branch flow channel structure 13 is an axisymmetric structure, i.e., with the radial direction of the center passing through the water phase inlet 111 and the first surface layer 11 as the axis, the branch flow channels of each stage of the first branch flow channel structure 13 are symmetrically distributed on both sides of the axis to ensure that the water phase is as uniformly distributed as possible to each branch flow channel in each stage. Figure 3 As another example, as shown in FIG. 5, the first branch flow channel structure 13 is a multi-stage flow channel structure. The multi-stage flow channel structure forms a plurality of stages of branch flow channels in communication from the inlet to the outlet. Two n n numbers of branch flow channels are formed in each stage, and n is the number of stages. For example, in FIG. 4, the first branch flow channel structure 13 is bifurcated at each stage from the water phase inlet 111, i.e., two branch flow channels are formed in the first stage, the two branch flow channels are bifurcated again in the second stage to form four branch flow channels, the four branch flow channels are bifurcated again in the third stage to form eight branch flow channels, and the eight outlets of the eight branch flow channels are connected to the respective microsphere generation units 15. As an example, the first branch flow channel structure 13 is an axisymmetric structure, i.e., with the radial direction of the center passing through the water phase inlet 111 and the first surface layer 11 as the axis, the branch flow channels of each stage of the first branch flow channel structure 13 are symmetrically distributed on both sides of the axis to ensure that the water phase is as uniformly distributed as possible to each branch flow channel in each stage.

[0039] Figure 4The diagram shown illustrates the second branch flow channel structure 14 in an embodiment of this disclosure.

[0040] For example, the second branch flow channel structure 14 is also a multi-stage flow channel structure, that is, a multi-stage branch flow channel is formed from the inlet to the outlet. Each stage forms 2 n The number of branch channels, where n is the number of levels (n = 0, 1, 2...). For example, in... Figure 3 In this example, the first branch channel structure 13 splits into two at each stage starting from the aqueous phase inlet 111. Specifically, it forms two branch channels at the first stage, which are then split again at the second stage to form four branch channels. These four branch channels are further split at the third stage to form eight branch channels, and at the fourth stage, they are split into sixteen branch channels, each connecting to a microsphere generating unit 15. As can be seen from the example, the second branch channel structure 14 is an axisymmetric structure. With the radial direction passing through the center of the oil phase inlet 121 and the first surface layer 11 as the axis, the branches of the second branch channel structure 14 are symmetrically distributed on both sides of this axis to ensure that the oil phase is distributed as uniformly as possible to each branch channel in each stage.

[0041] exist Figure 5 In the middle, Figure 3 and Figure 4 The overlay display of the middle channel allows for a clearer view of the positional relationship between the first branch channel structure 13 and the second branch channel structure 14.

[0042] For example, the first branch channel structure 13 and the second branch channel structure 14 are located at different isolated levels (i.e. at different depths) within the microfluidic layer 17, and remain isolated between channel portions except for the spherical location.

[0043] Back Figure 3 Each microsphere generating unit 15 includes: a first resistance flow channel unit 151, a second resistance flow channel unit 152 symmetrically arranged on both sides of the first resistance flow channel unit 151, and a microsphere cutting flow channel unit 153. The first resistance flow channel unit 151 and the second resistance flow channel unit 152 are composed of meandering flow channels. Figure 3 As shown, the first resistance channel unit 151 and the second resistance channel unit 152 are formed by U-shaped or Z-shaped meandering along a radial direction pointing towards the center. The outlet of the first resistance channel unit 151 is connected to a water phase outlet 112 via a microsphere output channel 16 for outputting microspheres. The first branch channel structure 13 includes a first inlet connected to a water phase inlet 111, and each first outlet connected from the first inlet via branch channels to the inlet of each first resistance channel unit 151 in a set of microsphere generating units 15, for delivering water phase to each first resistance channel unit 151.Figure 3 For example, each water phase inlet 111 corresponds to 8 water phase outlets 112 and 8 groups of microsphere generating units 15, including 8 first resistance flow channel units 151, then the outlets of the 8 branch flow channels of the last stage of the first branch flow channel structure 13 (i.e. the first outlets) are respectively connected to the inlets of the 8 first resistance flow channel units 151. The second branch flow channel structure 14 includes a second inlet connected to an oil phase inlet 121, and each second outlet connected from the second inlet to the inlet of each second resistance flow channel unit 152 of each of the plurality of microsphere generating units 15 through each branch flow channel, so as to output the oil phase from each second resistance flow channel unit 152 respectively. Figure 3 For example, 8 microsphere generating units 15 include 16 second resistance flow channel units 152, then each oil phase inlet 121 corresponds to the outlets of the last stage of 16 branch flow channels (i.e. the first outlets) which are respectively connected to the inlets of the 16 second resistance flow channel units 152.

[0044] The microsphere cutting flow channel unit 153 is formed by the micro flow channel connecting the ball forming position on the microsphere output flow channel 16 and the outlet of each second resistance flow channel unit 152, that is, the outlets of the second resistance flow channel units 152 on both sides are connected to the ball forming position on the microsphere output flow channel 16 through the micro flow channel, so that the transported oil phase cuts the water phase at the ball forming position to obtain microspheres.

[0045] The first resistance flow channel unit 151 is used to provide resistance for the water phase, and the second resistance flow channel unit 152 is used to provide resistance for the oil phase. The transmission speed of the water phase and the oil phase is adjusted by the resistance to cooperatively complete the efficient cutting action. It can be understood that the channel width, density, length, number of detours, length of detours, etc. of the first resistance flow channel unit 151 and the second resistance flow channel unit 152 can be adjusted according to the required resistance. As an example, the width and density of the micro flow channel in the first resistance flow channel unit 151 are greater than those in the second resistance flow channel unit 152.

[0046] Exemplarily, the two second resistance flow channel units 152 on both sides of the first resistance flow channel unit 151 are axially symmetrical structures, and the parts of the microsphere cutting flow channel unit 153 whose outlets are connected to the balling position (i.e. the flow channels on both sides of the balling position) are also axially symmetrical structures, so that the two second resistance flow channel units 152 can symmetrically deliver the oil phase to symmetrically cut the water phase from both sides. In the case that the two second resistance flow channel units 152 in the first branch flow channel structure 13, the second branch flow channel structure 14 and the microsphere generating unit 15 are all axially symmetrical structures, the water phase and the oil phase can be evenly introduced into each branch flow channel, respectively, the water phase is evenly passed through each first resistance flow channel unit 151 to be output to the water phase outlet 112, and the oil phase is evenly introduced into each pair of second resistance flow channel units 152 to symmetrically cut the water phase to form each microsphere.

[0047] In view of the above requirements for uniform and symmetrical flow of the water phase and the oil phase, and the requirement for as many microsphere generating units 15 as possible to be arranged, as shown in Figure 3 and Figure 5 Exemplarily, each microsphere generating unit 15 in each microsphere generating module and the corresponding water phase outlet 112 can be arranged in a circular arc shape, and each microsphere generating module (for example, four as shown in the figure) is arranged circumferentially around the water phase inlet 111 and the oil phase inlet 121, so that each microsphere generating unit 15 in the module is arranged in a circular ring shape. Each water phase outlet 112 is arranged in a circular ring shape around each microsphere generating unit 15. In this way, the water phase and the oil phase are evenly introduced into each branch flow channel from the middle to the periphery of the chip body 10, to pass through 1:8 of each microsphere generating unit 15 between the water phase inlet 111 and the oil phase inlet 121; in the same way, 2 n The two water phase outlets can realize batch and efficient preparation of microspheres.

[0048] It can be understood that the water phase inlet 111, the oil phase inlet 121, the water phase outlet 112, the microsphere generating module, the number of microsphere generating units 15 in the microsphere generating module, and the structure of the corresponding branch flow channel can be changed according to the size of the chip 1, the yield of microspheres and other factors, and are not limited to the figures. For example, Figures 3 to 5The example shows 4 microsphere generation modules, including 8 microsphere generation units 15. The first branch flow channel structure 13 includes 3 levels of branch flow channels, and the last level generates 8 branches to communicate to 8 first resistance flow channel units 151; the first branch flow channel structure 13 includes 4 levels of branch flow channels, and the last level generates 16 branches to communicate to 16 second resistance flow channel units 152. However, this is only an exemplary structure, which can be changed in specific scenarios, and is not limited thereto. For example, the water phase inlet 111, the oil phase inlet 121, and the microsphere generation module are at least two of the same number, which can be an odd number or an even number other than 4, such as 2, 3, 5, 6, 7, 8, etc.

[0049] In summary, the microfluidic chip for microsphere preparation in the embodiment of the present disclosure includes: a chip body; the first surface layer of the chip body is provided with at least one water phase inlet and a plurality of water phase outlets, and the second surface layer is provided with at least one oil phase inlet; a microfluid flow channel structure is arranged in the microfluid layer; the microfluid flow channel structure forms at least one microsphere generation module; each microsphere generation module includes: a first branch flow channel structure, a second branch flow channel structure, and a plurality of microsphere generation units; each microsphere generation unit includes: a first resistance flow channel unit, a second resistance flow channel unit symmetrically arranged on both sides of the first resistance flow channel unit, and a microsphere cutting flow channel unit; the first resistance flow channel unit communicates with one water phase outlet; the first resistance flow channel unit and the second resistance flow channel unit are formed by microfluid flow channel detours; the first branch flow channel structure communicates one water phase inlet and each first resistance flow channel unit in the module; the second branch flow channel structure communicates one oil phase inlet and each first resistance flow channel unit in the module. Through the microfluid flow channel design of the oil phase and water phase shunting and resistance in the plurality of microsphere generation units in each module, the preparation speed and efficiency are good, and the demand for large-scale preparation is met.

[0050] Specifically, by using a plurality of mutually separated microsphere generation modules, independent operation is realized, and the branch flow channel design can effectively reduce the risk of structure damage, avoid the situation that the whole chip cannot be used due to the damage of some flow channels, and effectively improve the reliability.

[0051] In addition, the first resistance flow channel unit and the second resistance flow channel unit are provided to eliminate the difference in flow rate between the branches caused by the slight resistance difference between each fluid. By designing the resistance units corresponding to the water phase and the oil phase in the microsphere generation unit, the individual differences between the fluid in each branch flow channel are offset by controllable large resistance, and finally the microsphere is formed. The size of the microfluid channel at the ball forming position of the microsphere cutting flow channel unit is also obtained through a large amount of calculation and testing, so as to ensure that the microsphere is efficiently and smoothly formed and output, and the reliability, ball forming efficiency and quality are effectively improved.

[0052] In addition, in order to ensure the uniformity of the fluid after the branch, the branch flow passage is designed to have a structure formed after fluid calculation, such as a symmetrical two-branch structure of each stage, a curved shape of each branch flow passage in the drawing, and the like.

[0053] The above embodiments are only illustrative of the principles and effects of the present disclosure, and are not intended to limit the present disclosure. Any person skilled in the art can modify or change the above embodiments without departing from the spirit and scope of the present disclosure. Therefore, all equivalent modifications or changes made by those skilled in the art without departing from the spirit and technical ideas disclosed by the present disclosure should be covered by the claims of the present disclosure.

Claims

1. A microfluidic chip for microsphere preparation, characterized in that, The chip body has a first surface layer, a second surface layer, and a microfluid layer between the first surface layer and the second surface layer. The first surface layer is provided with at least one water phase inlet and a plurality of water phase outlets, and the second surface layer is provided with at least one oil phase inlet. A microfluid channel structure is arranged in the microfluid layer. The microfluid channel structure is formed with at least one microsphere generation module. Each microsphere generation module includes a first branch channel structure, a second branch channel structure, and a plurality of microsphere generation units. Each microsphere generation unit includes a first resistance channel unit, a second resistance channel unit symmetrically arranged on both sides of the first resistance channel unit, and a microsphere cutting channel unit; the outlet of the first resistance channel unit is connected to a water phase outlet through a microsphere output channel. The distribution positions of the plurality of water phase outlets on the chip body are located at the periphery of the water phase inlet and the oil phase inlet; each microsphere generation module is located between a water phase inlet and a plurality of water phase outlets. The first branch flow channel structure and the second branch flow channel structure are multi-stage flow channel structures; the multi-stage flow channel structures form multiple stages of branch flow channels in communication from an inlet to an outlet, 2 n n is the number of branch flow channels in each stage; the outlet of each branch flow channel in the last stage of the first branch flow channel structure is in communication with the inlet of a first resistance flow channel unit; the outlet of each branch flow channel in the last stage of the second branch flow channel structure is in communication with the inlet of a second resistance flow channel unit; The microsphere cutting channel unit is formed by a ball forming position connected to the microsphere output channel and the outlet of each second resistance channel unit; the radial width of the microfluid channel in the first resistance channel unit is greater than that in the second resistance channel unit, and the density of the microfluid channel in the first resistance channel unit is greater than that in the second resistance channel unit. The first resistance channel unit and the second resistance channel unit are formed by a microfluid channel. The first branch channel structure and the second branch channel structure are located in different layers of the microfluid layer and are isolated from each other; the first branch channel structure includes a first inlet connected to a water phase inlet and a first outlet connected to the inlet of each first resistance channel unit in the plurality of microsphere generation units through each branch channel; the second branch channel structure includes a second inlet connected to an oil phase inlet and a second outlet connected to the inlet of each second resistance channel unit in the plurality of microsphere generation units through each branch channel. The first branch channel structure and / or the second branch channel structure is an axisymmetric structure.

2. The microfluidic chip of claim 1, wherein, The two second resistance channel units in each microsphere generation unit are symmetrically arranged.

3. The microfluidic chip of claim 1, wherein, The first surface layer and the second surface layer are mutually opposite planes.

4. The microfluidic chip of claim 1, wherein, The plurality of water phase inlets are uniformly distributed around an axis perpendicular to the first surface layer and the second surface layer, and the plurality of oil phase inlets are uniformly distributed around the axis. Each water phase inlet corresponds to an oil phase inlet in position. Each microsphere generation unit in each microsphere generation module and the corresponding water phase outlet are arranged in a circular arc shape.

5. The microfluidic chip of claim 1, wherein, The number of water phase inlets, oil phase inlets, and microsphere generation modules is at least two; each microsphere generation module is arranged circumferentially around each water phase inlet and oil phase inlet, so that each microsphere generation unit in the module is arranged in a circular ring shape; and each water phase outlet is arranged in a circular ring shape around each microsphere generation unit.

6. The microfluidic chip of claim 1, wherein, The chip body is in the shape of a disc, and the first surface layer and the second surface layer are circular end faces at both ends of the chip body.

7. The microfluidic chip of claim 1, wherein, ​

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