Microfluidic mixer

Abstract

The utility model provides a microfluidic mixer which comprises at least one mixing unit, the mixing unit comprises an inlet end, a mixing area and an outlet end, and the mixing area comprises a first channel and a second channel; the first channel comprises a first inner side wall and an arc-shaped first outer side wall, and the second channel comprises a second inner side wall and an arc-shaped second outer side wall; from the inlet end to the outlet end, the first inner side wall comprises a first inner side wall inlet section and a first inner side wall outlet section which intersect to form a second corner, and the second inner side wall comprises a second inner side wall inlet section and a second inner side wall outlet section which intersect to form a third corner. A channel of the mixing unit adopts a bifurcation-mixing structure, different fluids violently collide to be mixed in the bifurcation-mixing process, Dean vortex and turbulent flow can be generated when the fluids pass through the mixing area, the second corner and the third corner, mixing can be enhanced by combining the bifurcation-mixing structure, the Dean vortex and the turbulent flow, and the mixing efficiency is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of microfluidics, and particularly relates to a microfluidic mixer. Background Art

[0002] The formation mechanism of preparing lipid nanoparticles (LNP) loaded with nucleic acids by using microfluidic technology is to mix and dilute the lipid components in the organic phase and the nucleic acid components in the aqueous phase, reduce the concentration of the organic phase, and promote the self-assembly of the phospholipid components and the nucleic acid components to form.

[0003] Different organic phase concentrations can make the nanoparticles form different morphologies, such as spherical, film-like, tubular, etc.; at the same time, the organic phase concentration will also significantly affect the overall encapsulation rate, size and particle size distribution of the nanoparticles.

[0004] The core component in microfluidic technology is the microfluidic mixing device for realizing the mixing operation. However, in the prior art (for example, the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A), the mixing speed of the microfluidic mixer for different fluids is slow, the mixing efficiency is low, or a large number of mixing units (for example, more than 4 mixing units) are required to achieve complete mixing, which in turn leads to a large volume due to the large number of mixing units in the mixer and is not suitable for product miniaturization.

[0005] Therefore, how to provide a microfluidic mixer that can improve the mixing efficiency and make the mixed solution instantaneously reach a specific organic phase concentration is crucial for the quality of the prepared nanoparticles. Summary of the Utility Model

[0006] The utility model provides a microfluidic mixer, which is characterized by comprising: at least one mixing unit, the mixing unit includes an inlet end, a mixing zone and an outlet end, the mixing zone includes a first channel and a second channel, the inlets of the first channel and the second channel are connected to the inlet end, and the outlets of the first channel and the second channel are connected to the outlet end; the first channel includes a first inner wall and an arc-shaped first outer wall, and the second channel includes a second inner wall and an arc-shaped second outer wall; the first inner wall includes a first inner wall inlet section and a first inner wall outlet section sequentially arranged from the inlet end to the outlet end, and the second inner wall includes a second inner wall inlet section and a second inner wall outlet section sequentially arranged from the inlet end to the outlet end; the intersection of the first inner wall inlet section and the first inner wall outlet section forms a first corner; the intersection of the second inner wall inlet section and the second inner wall outlet section forms a second corner.

[0007] In some alternative embodiments, the first corner and the second corner are arc-shaped corners.

[0008] In some alternative embodiments, the two ends of the first inner wall and the second inner wall are respectively in contact and enclose an island where fluid cannot pass through. The island includes a liquid diversion part near the inlet end and a liquid merging part near the outlet end.

[0009] In some alternative embodiments, in the first view cross-section of the mixing zone, the curve of the first outer wall of the mixing zone and the curve of the second outer wall of the mixing zone corresponding to the first outer wall and the second outer wall form at least a part of a circle.

[0010] In some alternative embodiments, the inlet sections of the first inner wall and the second inner wall intersect near the inlet end to form a third corner. Preferably, the third corner is an arc-shaped corner. More preferably, the third corner is an acute angle.

[0011] In some alternative embodiments, the inlet section of the first inner wall, the outlet section of the first inner wall, the inlet section of the second inner wall, and the outlet section of the second inner wall all smoothly extend in the direction from the inlet end to the outlet end.

[0012] In some alternative embodiments, the outlet sections of the first inner wall and the second inner wall intersect near the outlet end to form an arc-shaped part.

[0013] In some alternative embodiments, the inlet section of the first inner wall and the outlet section of the first inner wall are arc-shaped side wall sections.

[0014] In some alternative embodiments, the centers of curvature of the inlet section of the first inner wall and the outlet section of the first inner wall are different.

[0015] In some alternative embodiments, the inlet section of the second inner wall and the outlet section of the second inner wall are arc-shaped side wall sections.

[0016] In some alternative embodiments, the centers of curvature of the inlet section of the second inner wall and the outlet section of the second inner wall are different.

[0017] In some alternative embodiments, the inlet section of the first inner wall and the inlet section of the second inner wall have the same radius of curvature, and the outlet section of the first inner wall and the outlet section of the second inner wall have the same radius of curvature.

[0018] In some alternative embodiments, the microfluidic mixer further includes at least two liquid inlet channels. The inlet of each liquid inlet channel is configured to communicate with a liquid supply device, and the outlet communicates with the inlet end of each mixing unit.

[0019] In some alternative embodiments, the microfluidic mixer includes at least two of the mixing units.

[0020] In some alternative embodiments, the at least two mixing units are arranged in sequence and connected in series, and the outlet end of the upstream mixing unit in any two adjacent mixing units is connected to the inlet end of the downstream mixing unit.

[0021] In some alternative embodiments, the roundabout center points of the respective mixing units are all located on the same straight line in both the first view section and the second view section.

[0022] In some alternative embodiments, the roundabout center points of the respective mixing units are not all located on the same straight line in the first view section, but are all located on the same straight line in the second view section.

[0023] In some alternative embodiments, the first view is a top view.

[0024] In some alternative embodiments, the second view is a front view.

[0025] In some alternative embodiments, the path lengths of the first channel and the second channel are the same.

[0026] In some alternative embodiments, the first channel and the second channel are symmetrically arranged with respect to the roundabout.

[0027] In some alternative embodiments, the first channel and the second channel are symmetrically arranged with respect to the center plane of the roundabout in the front view, where the center plane of the roundabout in the front view is a plane obtained by intercepting the roundabout in the front view direction along the connection line between the first point and the second point.

[0028] As described above, to solve the problem of the low mixing efficiency of existing microfluidic mixers, the present utility model proposes a microfluidic mixer, comprising: at least one mixing unit, the mixing unit including an inlet end, a mixing zone, and an outlet end, the mixing zone including a first channel and a second channel, the inlets of the first channel and the second channel being in communication with the inlet end, and the outlets of the first channel and the second channel being in communication with the outlet end. Among them, the first channel includes a first inner wall and an arc-shaped first outer wall, the second channel includes a second inner wall and an arc-shaped second outer wall, the portions of the first outer wall and the second outer wall close to the inlet end form the inlet end, and the portions of the first outer wall and the second outer wall close to the outlet end form the outlet end. The first inner wall includes a first inner wall inlet section and a first inner wall outlet section arranged in sequence from the inlet end to the outlet end, the second inner wall includes a second inner wall inlet section and a second inner wall outlet section arranged in sequence from the inlet end to the outlet end; the intersection of the first inner wall inlet section and the first inner wall outlet section forms a first corner; the intersection of the second inner wall inlet section and the second inner wall outlet section forms a second corner. That is, the internal channel structure of the mixing unit adopts a bifurcated-mixing structural design, enabling different fluids to collide violently during the bifurcated-mixing process to achieve mixing, improving the mixing efficiency, and enabling Dean vortices to be generated when the fluid passes through the first channel and the second channel of the mixing zone, and enabling turbulence to be generated when passing through the first corner and the second corner. The combination of the bifurcated-mixing structure, Dean vortices, and turbulence can enhance mixing and improve the mixing efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The drawings described herein are used to provide a further understanding of the present utility model and form a part of the present utility model. The schematic embodiments of the present utility model and their descriptions are used to explain the present utility model and do not constitute an improper limitation to the present utility model. In the drawings:

[0030] Figure 1 is a schematic structural diagram of a microfluidic mixer provided by some embodiments of the present utility model;

[0031] Figure 2 、 Figure 3 、 Figure 4 is a schematic structural diagram of the mixing unit 10 provided by some embodiments of the present utility model;

[0032] Figure 5 is a schematic structural diagram of a microfluidic mixer with a dual-channel inlet provided by some embodiments of the present utility model;

[0033] Figure 6 is a schematic structural diagram of a microfluidic mixer with a triple-channel inlet provided by some embodiments of the present utility model;

[0034] Figure 7 is a schematic structural diagram of a DVBM microfluidic mixer in the prior art;

[0035] Figure 8 Schematic diagram of the mixing effect comparison between the microfluidic mixer provided by some embodiments of the present invention and the DVBM microfluidic mixer in the prior art.

[0036] Explanation of reference numerals / symbols:

[0037] 10 - mixing unit, 1a - inlet end, 1 - mixing zone, 11 - first channel, 11I - first inner wall, 11Ia - first inner wall inlet section, 11Ib - first inner wall outlet section, 11O - first outer wall, 12 - second channel, 12I - second inner wall, 12Ia - second inner wall inlet section, 12Ib - second inner wall outlet section, 12O - second outer wall, 1b - outlet end, 13 - roundabout, 131 - liquid diversion part, 132 - liquid merging part, C - circle formed by the first outer wall curve and the second outer wall curve of the mixing zone, α - second corner formed by the intersection of the first inner wall inlet section and the first inner wall outlet section, β - second corner formed by the intersection of the second inner wall inlet section and the second inner wall outlet section, γ - third corner formed by the intersection of the first inner wall inlet section and the second inner wall inlet section, δ - arc formed by the intersection of the first inner wall outlet section and the second inner wall outlet section, 20 - liquid inlet channel, 21 - first liquid inlet channel, 22 - second liquid inlet channel, 23 - third liquid inlet channel, 24 - first liquid injection port, 25 - second liquid injection port.

[0038] It should be understood that the dimensions of the various parts shown in the drawings are not drawn according to the actual proportional relationship. In addition, the same or similar reference numerals represent the same or similar components. Detailed implementation manners

[0039] The following describes the detailed implementation manners of the present invention in conjunction with the drawings and embodiments. Those skilled in the art can easily understand the technical problems solved by the present invention and the technical effects produced through the content recorded in this specification. It can be understood that the specific embodiments described herein are only used to explain the related technical solutions and do not limit the present invention. In addition, for the convenience of description, only the parts related to the related technical solutions are shown in the drawings.

[0040] The "first", "second" and similar terms used in the present invention do not indicate any order, quantity or importance, but are only used to distinguish different parts. The terms such as "including" or "comprising" mean that the elements before this term cover the elements listed after this term, and do not exclude the possibility of also covering other elements. The terms such as "upper", "lower", "left" and "right" are only used to represent the relative position relationship. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0041] In the present utility model, when it is described that a specific device is located between a first device and a second device, there may or may not be an intermediate device between the specific device and the first device or the second device. When it is described that a specific device is connected to other devices, the specific device may be directly connected to the other devices without an intermediate device, or may not be directly connected to the other devices but have an intermediate device.

[0042] It should be easily understood that the meanings of "on...", "above...", and "over..." in the present utility model should be interpreted in the broadest sense, such that "on..." not only means "directly on something", but also means "on something" including intermediate components or layers between the two.

[0043] In addition, for ease of description, spatial relative terms such as "below...", "beneath...", "lower part", "above...", "upper part", etc. may be used herein to describe the relationship between one element or component and another element or component shown in the drawings. In addition to the orientations described in the figures, the spatial relative terms are also intended to cover different orientations during the use or operation of the device.

[0044] All terms used in the present utility model (including technical terms or scientific terms) have the same meanings as understood by those of ordinary skill in the art to which the present utility model pertains, unless otherwise specifically defined. It should also be understood that terms defined in a general dictionary, for example, should be interpreted as having meanings consistent with their meanings in the context of the relevant art, and should not be interpreted in an idealized or overly formal sense, unless specifically defined as such here.

[0045] Technologies, methods, and devices known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the said technologies, methods, and devices should be regarded as part of the specification.

[0046] It should be noted that the structures, ratios, sizes, etc. shown in the drawings of the specification are only used to cooperate with the content recorded in the specification for the understanding and reading of those skilled in the art, and are not used to limit the conditions for the implementation of the present utility model. Therefore, they do not have technical substantial meanings. Any modification of the structure, change of the ratio relationship, or adjustment of the size, without affecting the effects that the present utility model can produce and the purposes that can be achieved, should still fall within the scope that can be covered by the technical content disclosed by the present utility model.

[0047] In addition, without conflict, the embodiments and the features in the embodiments of the present utility model can be combined with each other. The present utility model will be described in detail below with reference to the drawings and in combination with the embodiments.

[0048] Please refer to Figure 1 、Figure 2 , Figure 3 and Figure 4 , Figure 1 Structural schematic diagram of a microfluidic mixer according to an embodiment of the present utility model, Figure 2 , Figure 3 and Figure 4 are Figure 1 structural schematic diagrams of the mixing unit 10 in the microfluidic mixer shown.

[0049] Here, the microfluidic mixer is used to mix multiple liquids, for example, for mixing two liquids, three liquids, four liquids or more liquids. The multiple liquids enter the microfluidic mixer through the mixing channel inlet.

[0050] As Figure 1 shown, the microfluidic mixer includes at least one mixing unit 10.

[0051] As Figure 2 and Figure 4 shown, the mixing unit 10 includes an inlet end 1a, a mixing zone 1, and an outlet end 1b. The mixing zone 1 includes a first channel 11 and a second channel 12. The inlets of the first channel 11 and the second channel 12 are connected to the inlet end 1a, and the outlets of the first channel 11 and the second channel 12 are connected to the outlet end 1b.

[0052] The first channel 11 includes a first inner wall 11I and an arcuate first outer wall 11O. The second channel includes a second inner wall 12I and an arcuate second outer wall 12O. The first inner wall 11I includes a first inner wall inlet section 11Ia and a first inner wall outlet section 11Ib arranged in sequence from the inlet end 1a to the outlet end 1b. The second inner wall 12I includes a second inner wall inlet section 12Ia and a second inner wall outlet section 12Ib arranged in sequence from the inlet end 1a to the outlet end 1b.

[0053] The intersection of the first inner wall inlet section 11Ia and the first inner wall outlet section 11Ib forms a first corner α, and the intersection of the second inner wall inlet section 12Ia and the second inner wall outlet section 12Ib forms a second corner β.

[0054] Here, the two channels of the mixing unit 10 adopt a bifurcated - mixing structural design, enabling different fluids to collide violently during the bifurcated - mixing process and thus mix, improving the mixing efficiency. And the first channel 11 and / or the second channel 12 of the mixing unit 10 are configured such that the liquid flowing therein forms Dean vortices, which can generate turbulence when passing through the first corner α and the second corner β. The combination of the bifurcated - mixing structure, Dean vortices, and turbulence can strengthen the mixing and improve the mixing efficiency.

[0055] In some alternative embodiments, both ends of the first inner wall 11I and the second inner wall 12I are in contact with each other and enclose to form a roundabout 13 through which fluid cannot pass. The roundabout 13 includes a liquid diversion portion 131 near the inlet end 1a and a liquid merging portion 132 near the outlet end 1b.

[0056] It should be noted that the microfluidic mixer may include one mixing unit 10 or at least two mixing units 10. The specific number of the mixing units 10 and the connection manner between different mixing units 10 can be designed and selected according to the actual mixing requirements, so that the liquid is fully mixed in the microfluidic mixer. When at least two mixing units 10 are included, the inlet ends 1a and the outlet ends 1b of different mixing units 10 may be connected.

[0057] In some alternative embodiments, the width or height of the first channel 11 and the second channel 12 ranges from 20 μm to 5 mm. Preferably, the width or height of the first channel 11 and the second channel 12 ranges from 50 μm to 2 mm.

[0058] The path lengths of the first channel 11 and the second channel 12 may be the same or different.

[0059] Preferably, the path lengths of the first channel 11 and the second channel 12 are the same, which can make the average flow rates of the liquids separated into the first channel 11 and the second channel 12 basically consistent. Furthermore, the liquids separated into the first channel 11 and the second channel 12 are always mixed in the mixing unit 10 at a set flow rate ratio and rate, further improving the mixing speed and mixing efficiency per unit time and ensuring the stable and rapid production of nucleic acid nanoparticles. In addition, through mold flow analysis, it can also be obtained that when the path lengths of the first channel 11 and the second channel 12 are the same, the mixing efficiency is higher than when the path lengths of the first channel 11 and the second channel 12 are different.

[0060] In some alternative embodiments, the portions of the first outer wall 11O and the second outer wall 12O near the inlet end 1a form the inlet end 1a, and the portions of the first outer wall 11O and the second outer wall 12O near the outlet end 1b form the outlet end 1b.

[0061] In some alternative embodiments, in the mixing unit 10, the axial directions of the inlet end 1a and the outlet end 1b are both parallel to the extension direction from the inlet end 1a to the outlet end 1b.

[0062] In some alternative embodiments, such as Figure 3As shown, the first outer wall 11O and the second outer wall 12O form at least a part of a circular C in the cross-section of the first view of the mixing zone 1, corresponding to the first outer wall curve and the second outer wall curve of the mixing zone. In this way, when the liquid flows through the first channel 11 and the second channel 12, it will reach the outlet end 1b along the shortest path, thereby increasing the liquid flow rate and improving the liquid mixing efficiency.

[0063] It can be understood that Figure 1 、 Figure 2 and Figure 3 may be a schematic structural diagram of the cross-section of the first view of the microfluidic mixer and the mixing unit 10. Optionally, the first view may be a top view, and the cross-section of the first view may be a top view cross-section.

[0064] In some alternative embodiments, as Figure 2 and Figure 4 shown, the first inner wall inlet section 11Ia and the second inner wall inlet section 12Ia are both connected to the inlet end 1a, and the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib are both connected to the outlet end 1b. The portions of the first inner wall inlet section 11Ia and the second inner wall inlet section 12Ia close to the inlet end 1a intersect to form a third corner γ, and the first corner α is an arcuate corner and an acute angle.

[0065] In some alternative embodiments, as Figure 2 、 Figure 3 and Figure 4 shown, the transition from the first inner wall inlet section 11Ia to the first inner wall outlet section 11Ib is non-smooth or non-smoothly extended. In this way, when the liquid transitions from the first inner wall inlet section 11Ia to the first inner wall outlet section 11Ib in the first channel 11, post-corner turbulence will be generated, expanding the eddy current effect and further increasing the mixing efficiency of the liquid in the first channel 11. Correspondingly, the transition from the second inner wall inlet section 12Ia to the second inner wall outlet section 12Ib is non-smooth or non-smoothly extended. In this way, when the liquid transitions from the second inner wall inlet section 12Ia to the second inner wall outlet section 12Ib in the second channel 12, post-corner turbulence will be generated, expanding the eddy current effect and further increasing the mixing efficiency of the liquid in the second channel 12.

[0066] In some alternative embodiments, as Figure 2 、 Figure 3 and Figure 4As shown, the first inner wall inlet section 11Ia, the first inner wall outlet section 11Ib, the second inner wall inlet section 12Ia, and the second inner wall outlet section 12Ib all smoothly extend in the direction from the inlet end to the outlet end. In this way, after the liquid is split by the liquid splitting portion 131, since the first inner wall inlet section 11Ia and the second inner wall inlet section 12Ia are smooth, the flow rate of the liquid in the first inner wall inlet section 11Ia of the first channel 11 and the second inner wall inlet section 12Ia of the second channel 12 can be increased, thereby achieving the effect of improving the mixing efficiency. And when the liquid reaches the first inner wall outlet section 11Ib and the second inner wall outlet section, similarly, since the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib are smooth, the flow rate of the liquid in the first inner wall outlet section 11Ib of the first channel 11 and the second inner wall outlet section 12Ib can be increased, thereby achieving the effect of improving the mixing efficiency.

[0067] In some alternative embodiments, as Figure 4 shown, the portions of the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib close to the outlet end 1b intersect to form an arc portion δ. In this way, the two streams of liquid in the first channel 11 and the second channel 12 can be quickly fused at the outlet end 1b, achieving the effect of improving the mixing efficiency.

[0068] In some alternative embodiments, the first corner α and the second corner β are arc-shaped corner portions, and the first corner α and the second corner β can be the same. The first corner α and the second corner β can be acute angles, right angles, or obtuse angles.

[0069] In some alternative embodiments, as Figure 4 shown, the first inner wall inlet section 11Ia and the first inner wall outlet section 11Ib are arc-shaped side wall sections. In this way, the liquid quickly flows from the first inner wall inlet section 11Ia in the first channel 11 to the first inner wall outlet section 11Ib, and forms a corner and then turbulent flow in the first inner wall outlet section 11Ib and quickly flows to the outlet end 1b, that is, generally increasing the flow rate of the liquid in the first channel.

[0070] In some alternative embodiments, the centers of curvature of the first inner wall inlet section 11Ia and the first inner wall outlet section 11Ib are different. The two inner wall sections 11Ia and 11Ib with different centers of curvature of the first inner wall can enable the first inner wall 11I to form a corner at the intersection of the two inner wall sections 11Ia and 11Ib. This corner can collide with the liquid flowing from the inlet end 1a, causing the liquid to generate turbulent flow. And due to the curvature effect of the first inner wall inlet section 11Ia and the first inner wall outlet section 11Ib, the liquid generates Dean vortices. Therefore, the liquid flowing in the first channel 11 can form Dean vortices and turbulent flow, and the combination of Dean vortices and turbulent flow can deepen the mixing and improve the mixing efficiency.

[0071] In some alternative embodiments, the second inner wall inlet section 12Ia and the second inner wall outlet section 12Ib are arc sections. In this way, the liquid quickly flows from the second inner wall inlet section 12Ia to the second inner wall outlet section 12Ib in the second channel 12, and after forming an angle in the second inner wall outlet section 12Ib, the liquid turbulently flows quickly towards the outlet end 1b, that is, generally improving the flow rate of the liquid in the second channel.

[0072] In some alternative embodiments, the centers of curvature of the second inner wall inlet section 12Ia and the second inner wall outlet section 12Ib are different. The two inner wall sections 12Ia and 12Ib with different centers of curvature of the second inner wall can form a corner at the fourth point P4 where the two inner wall sections 12Ia and 12Ib intersect. This corner can collide with the liquid flowing from the inlet end 1a to the fourth point P4, causing the liquid to generate turbulence. And due to the curvature effect of the second inner wall inlet section 12Ia and the second inner wall outlet section 12Ib, Dean vortices are generated in the liquid. Therefore, the liquid flowing in the second channel 12 can form Dean vortices and turbulence, and the combination of Dean vortices and turbulence can deepen the mixing and improve the mixing efficiency.

[0073] In some alternative embodiments, the radius of curvature of the first inner wall inlet section 11Ia and the second inner wall inlet section 12Ia is the same, and the radius of curvature of the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib is the same. In this way, when the liquid is split by the liquid splitting section 131, the volumes and flow rates of the two streams of liquid split into the first channel 11 and the second channel 12 will be substantially the same, and will reach the first corner α and the second corner β substantially simultaneously, and the flow rates will be substantially the same. In addition, the flow rates of the above two streams of liquid in the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib are also substantially the same, and thus the time and flow rate to reach the outlet end 1b are also substantially the same, which can improve the efficiency of microfluidic splitting and mixing.

[0074] In some alternative embodiments, the centers of curvature and the radii of curvature of the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib are both the same. That is, the first inner wall outlet section 11Ib and the second inner wall outlet section 12Ib together form an arc section. In some alternative embodiments, the microfluidic mixer may further include at least two liquid inlet channels, and the inlet of each liquid inlet channel is configured to communicate with a liquid supply device, and the outlet communicates with the inlet end of one or more mixing units.

[0075] For example, as Figure 5As shown, the microfluidic mixer includes two liquid inlet channels 20: a first liquid inlet channel 21 and a second liquid inlet channel 22. The inlet of the first liquid inlet channel 21 is connected to the first liquid injection port 24, and the outlet is communicated with the inlet end 1a of the mixing unit 10. The inlet of the second liquid inlet channel 22 is connected to the second liquid injection port 25, and the outlet is communicated with the inlet end 1a of the mixing unit 10. The first liquid injection port 24 is communicated with the first solution providing device ( Figure 5 not shown in the figure), and the second liquid injection port 25 is communicated with the second solution providing device ( Figure 5 not shown in the figure).

[0076] Figure 5 The shown microfluidic mixer is a double-inlet channel chip. The double-inlet channels form a Y shape and can mix at least two kinds of liquids. One kind of liquid enters from the first liquid inlet channel 21, and other kinds of liquids enter from the second liquid inlet channel 22. They converge at the inlet end 1a of the mixing unit 10. The converged liquid then enters the two channels 11 and 12 of the mixing unit 10 and converges again at the outlets of the two channels 11 and 12, and enters the outlet end 1b of the mixing unit 10.

[0077] Next, please refer to Figure 6 , Figure 6 As shown, the microfluidic mixer includes three liquid inlet channels 20: a first liquid inlet channel 21, a second liquid inlet channel 22, and a third liquid inlet channel 23. The inlet of the first liquid inlet channel 21 and the inlet of the third liquid inlet channel 23 are connected to the first liquid injection port 24, and the outlet is communicated with the inlet end 1a of the mixing unit 10. The inlet of the second liquid inlet channel 22 is connected to the second liquid injection port 25, and the outlet is communicated with the inlet end 1a of the mixing unit 10. The inlet of the second liquid inlet channel 22 is connected to the second liquid injection port 25, and the outlet is communicated with the inlet end 1a of the mixing unit 10. The first liquid injection port 24 is communicated with the first solution providing device ( Figure 6 not shown in the figure), and the second liquid injection port 25 is communicated with the second solution providing device ( Figure 6 not shown in the figure).

[0078] Figure 6 The shown microfluidic mixer is a triple-inlet channel chip and can mix N (N is a positive integer greater than or equal to 2) kinds of liquids. The first liquid inlet channel 21, the second liquid inlet channel 22, the third liquid inlet channel 23 and the inlet end of the mixing unit 10 form a "plus" shape structure. N1 kinds of liquids are injected from the first liquid injection port 24 and enter from the first liquid inlet channel 21 and the third liquid inlet channel 23. N2 kinds of liquids are injected from the second liquid injection port 25 and enter from the second liquid inlet channel 22. N1 and N2 are positive integers respectively, and the sum of N1 and N2 is N. The N kinds of liquids converge at the inlet end 1a of the mixing unit 10. The converged liquid then enters the two channels 11 and 12 of the mixing unit 10 and converges again at the outlets of the two channels 11 and 12, and enters the outlet end 1b of the mixing unit 10.

[0079] In some alternative embodiments, the microfluidic mixer includes at least two mixing units 10. For example, as Figure 5 and Figure 6 shown, the microfluidic mixer includes four mixing units 10.

[0080] Optionally, the microfluidic mixer includes two mixing units 10.

[0081] In some alternative embodiments, at least two mixing units 10 are arranged in sequence and connected in series, and the outlet end of the upstream mixing unit 10 in any two adjacent mixing units 10 is connected to the inlet end of the downstream mixing unit 10. For example, Figure 1 , Figure 5 and Figure 6 exemplarily show 4 mixing units 10. It can be understood that the number of mixing units 10 that can be included in the microfluidic mixer can be selected according to actual mixing needs.

[0082] In some alternative embodiments, the microfluidic mixer may include at least one mixing unit 10 connected in series and a DVBM (Dean vortex bifurcation mixer) mixing unit. Wherein, the outlet end 1b of the upstream mixing unit 10 is connected to the inlet end of the downstream DVBM mixing unit. Or, the outlet end of the upstream DVBM mixing unit 10 is connected to the inlet end 1a of the downstream mixing unit 10.

[0083] Here, the DVBM mixing unit can refer to the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A.

[0084] In some alternative embodiments, as Figure 5 and Figure 6 shown, the central points of the roundabouts 13 of each mixing unit 10 are located on the same straight line in both the first view section and the second view section. Here, the first view section and the second view section can be mutually perpendicular planes. For example, the first view section is the top view section, and the second view section is the front view section, that is, each mixing unit 10 is arranged in a straight line in the top view section, and each mixing unit 10 is also at the same height in terms of height. In this way, it is relatively simple to prepare the mixing units arranged in a row at the same height, that is, it is beneficial to simplify the production manufacturing process and facilitate large-scale production.

[0085] In some alternative embodiments, the central points of the roundabouts 13 of each mixing unit 10 are not all on the same straight line in the first view section, but are all on the same straight line in the second view section. For example, the first view section is a top view section, and the second view section is a front view section, that is, the mixing units 10 are not arranged in a straight line in the top view section, but the mixing units 10 are at the same height in terms of height. In this way, although the mixing units 10 are not arranged in a straight line in the top view section, there is an angle between two adjacent mixing units 10. Although this is not conducive to simplifying the production process, it can cause the flow direction of the liquid to change between two adjacent mixing units 10, and then turbulence can be formed after the direction change, accelerating the liquid fusion, and further accelerating the mixing efficiency.

[0086] In some alternative embodiments, the first view is a top view and the second view is a front view.

[0087] In some alternative embodiments, as Figures 1 to 6 shown, the path lengths of the first channel 11 and the second channel 12 in the mixing unit 10 are the same.

[0088] The first channel 11 and the second channel 12 in the mixing unit 10 can be symmetrically arranged or asymmetrically arranged with respect to the roundabout 13.

[0089] In some alternative embodiments, as Figures 1 to 6 shown, the first channel 11 and the second channel 12 in the mixing unit 10 are symmetrically arranged with respect to the roundabout 13. The symmetrical arrangement can make the average flow velocities of the two streams of liquid separated into the first channel 11 and the second channel 12 basically the same, and perform mixing in the mixing unit 10 according to the set flow rate ratio and rate, further increasing the mixing speed and mixing efficiency per unit time, and ensuring the stable and rapid production of nucleic acid nanoparticles. Here, the set flow rate ratio is the ratio of the flow velocity of the liquid in the first channel 11 divided by the flow velocity of the liquid in the second channel 12.

[0090] In some alternative embodiments, as Figures 1 to 6As shown, in the mixing unit 10, the first channel 11 and the second channel 12 are symmetrically arranged with respect to the central plane of the front view of the roundabout 13, where the central plane of the front view of the roundabout is a plane obtained by intercepting the roundabout 13 along the connection line of the first point P1 and the second point P2 in the front view direction. In addition, the first channel 11 and the second channel 12 may be at the same height or not at the same height. That is to say, the top and bottom surfaces of the first channel 11 and the second channel 12 may be substantially the same or different. If the first channel 11 and the second channel 12 are symmetrically arranged with respect to the central plane of the front view of the roundabout 13 and are at the same height, the manufacturing process of the microfluidic mixer can be simplified and the production efficiency is high; conversely, if the first channel 11 and the second channel 12 are symmetrically arranged with respect to the central plane of the front view of the roundabout 13 but are at different heights, although the manufacturing process is relatively complex, it can make the liquid flow turbulently rather than laminarly in the first channel 11 and the second channel 12, which can further improve the mixing efficiency.

[0091] In some embodiments, the microfluidic mixer can also be combined with known fluid components, such as inlets, outlets, syringes, pumps, detectors, or other mixers. The microfluidic mixer can also be fixed to a base.

[0092] The microfluidic mixer provided by the embodiments of the present invention can achieve the following technical effects including but not limited to:

[0093] First, the structural design is simple, the chip channels are easy to be amplified in multiples, suitable for linear amplification production, easy for industrial manufacturing, capable of mass-producing nano preparations, and can meet the growing demand for nucleic acid preparations.

[0094] Second, by adopting a mixing method combining Dean vortices and turbulence, the mixing efficiency is high, less affected by the flow rate, and the encapsulation rate will not decrease with the increase of the flow rate or scale.

[0095] Third, it can quickly and effectively mix liquid microfluids, and can be used for the rapid mixing of various liquids or the manufacture of nanoparticles, such as lipid nanoparticles or PLGA (poly(lactic-co-glycolic acid)) nanoparticles, etc.

[0096] Next, a microfluidic chip (hereinafter referred to as the METIS chip, referring to the microfluidic mixer as shown in Figure 6 ) provided by some embodiments of the present invention and the exemplary DVBM microfluidic mixer (hereinafter referred to as the DVBM chip, referring to Figure 7 ) with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A will be compared and designed for experimental comparison.

[0097] Experimental Example 1: Comparison of Mixing Effects of Microfluidic Mixers

[0098] The chip was prepared using polydimethylsiloxane (PDMS) material:

[0099] The reverse structure of the target chip (e.g., METIS chip or DVBM chip) was replicated on a silicon mold using soft lithography technology.

[0100] Then, PDMS and a curing agent were stirred at a mass ratio of PDMS:curing agent of 10:1, degassed to remove bubbles, and the resulting PDMS glue was poured into the silicon mold and dried at 85°C for 30 min to 40 min.

[0101] Next, through steps such as peeling, cutting, and punching, a PDMS base surface with the structure of the target chip was obtained. Then, the PDMS base surface and the glass bottom surface were subjected to processes such as plasma cleaning and bonding to obtain a PDMS chip.

[0102] The METIS chip and the DVBM chip were prepared according to the above method.

[0103] The structure of the METIS chip is as Figure 6 shown. Among them, the METIS chip is a three-inlet channel chip, or a "cross"-shaped channel inlet. The width of the narrowest part of the first channel 11 and the second channel 12 of the mixing unit 10 is 140 μm, and the depth (or height) is 75 μm. The METIS chip includes four mixing units 10 arranged in sequence and connected in series.

[0104] The structure of the DVBM chip is as Figure 7 shown. It is a two-channel inlet chip. Among them, the annular mixing devices are connected through connecting channels. The channel width is 140 μm, the depth (or height) is 75 μm, and the neck angle is 120°, which corresponds to the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A.

[0105] Mixing Efficiency Test:

[0106] The two chips were respectively fixed in an inverted fluorescence microscope.

[0107] The aqueous phase was passed with a PBS solution at pH 7.4 to obtain an aqueous phase solution, and the organic phase was passed with a fluorescent ethanol solution at a certain concentration to obtain an organic phase solution.

[0108] Pump the organic phase solution and the aqueous phase solution into the target chip at a flow rate ratio of 1:3 and a total flow rate of 5 mL / min. Among them, for the METIS chip, the organic phase enters from the second liquid injection port 25, and the aqueous phase enters from the first liquid injection port 24. For the DVBM chip, the organic phase and the aqueous phase enter from two different channels respectively.

[0109] When the flow rate is stable, take pictures through a high-speed fluorescence microscope, and read the fluorescence values at the outlet ends 1b of each mixing unit 10 in the METIS chip and the fluorescence values at the outlet ends of each annular mixing device in the DVBM chip, and calculate the mixing index (MI, Mixing Index) based on the fluorescence difference per unit distance in the channel. Among them, MI = 1 means complete non-mixing, and MI = 0.1 means complete mixing.

[0110] Take the mixing index as the ordinate and the number (or position) of the mixing units 10 in the METIS chip or the annular mixing devices in the DVBM chip as the abscissa, and plot to obtain the Figure 8 mixing effect diagram as shown.

[0111] At the same time, Table 1 shows the comparison results of the MI at the outlet ends of the mixing units 10 at different positions in the METIS chip and the MI at the outlet ends of the annular mixing devices at different positions in the DVBM chip for the mixed solution.

[0112] Among them, for the calculation of MI, the reference document can be: RSC Adv., 2017, 7, 10906 formula (2). The mixing index is usually defined based on the ratio of fluorescence differences or the normalized difference. The specific calculation formula may vary according to the specific requirements and applications of the research.

[0113] From Table 1 and Figure 8 it can be seen that the MI of the first mixing unit in the METIS chip can reach 0.2684, and the MI of the second mixing unit can reach 0.0182. That is to say, complete mixing can be achieved after the second mixing unit (0.0182 is much less than 0.1). That is to say, according to the above design, only two mixing units need to be designed to achieve complete mixing, without four units.

[0114] For the DVBM chip, the MI of the fourth annular mixing device is 0.1621, which is still greater than 0.1, and complete mixing is not achieved. This shows that the mixing effect of the METIS chip is significantly higher than that of the DVBM chip.

[0115] In addition, from the perspective of the time required to finally achieve complete mixing, the time required for the METIS chip to achieve complete mixing is also much lower than that of the DVBM chip.

[0116] Table 1

[0117]

[0118] The formation mechanism of lipid nanoparticles (LNPs) loaded with nucleic acids is achieved by mixing and diluting the lipid components in the organic phase and the nucleic acid components in the aqueous phase, reducing the concentration of the organic phase, and promoting the self-assembly of phospholipid components and nucleic acid components. Different organic phase concentrations can result in different morphologies of the nanoparticles, such as spherical, film-like, tubular, etc. Film-like and tubular forms have low or no encapsulation efficiency for mRNA, which significantly affects the overall encapsulation efficiency of the nanoparticles. Additionally, it also affects the size and particle size distribution of the nanoparticles. The mixing efficiency refers to the mixing ratio achieved per unit time. The higher the mixing efficiency, the shorter the mixing time (in the ms level). Instantaneous and sufficient mixing can avoid the generation of concentration gradients during the dilution of the organic phase, thereby preventing the formation of nanoparticles with different morphologies, sizes, and encapsulation efficiencies.

[0119] Therefore, the channel design of the METIS chip has better mixing efficiency, enabling the mixed solution to instantaneously reach a specific organic phase concentration, improving the encapsulation efficiency of the nanoparticles, which is crucial for the quality of the nanoparticles.

[0120] Experimental Example 2: Comparison of chips of different scales

[0121] Experimental Example 2-1: Preparation of laboratory-scale (Lab) chips and lipid nanoparticles

[0122] The chips were prepared using polydimethylsiloxane (PDMS) material: The reverse structure of the target chip (e.g., METIS chip or DVBM chip) was replicated on a silicon mold using soft lithography technology.

[0123] Then, according to the mass ratio of PDMS:curing agent of 10:1, PDMS and the curing agent were stirred and degassed to remove air bubbles to obtain PDMS glue, which was then poured into the silicon mold and dried at 85°C for 30 min to 40 min.

[0124] Next, through steps such as peeling, cutting, and punching, a PDMS base surface with the structure of the target chip was obtained. Then, the PDMS base surface and the glass bottom surface were subjected to processes such as plasma cleaning and bonding to obtain a PDMS chip.

[0125] The METIS chip and DVBM chip were prepared according to the above method.

[0126] The structure of the METIS chip is as Figure 6As shown, the METIS chip is a three-inlet channel chip, or a "cross"-shaped channel inlet. The narrowest width of the first channel 11 and the second channel 12 of the mixing unit 10 is 140 μm, and the depth (or height) is 75 μm. The METIS chip includes four mixing units 10 arranged in sequence and connected in series.

[0127] The DVBM chip structure is as Figure 7 shown, which is a two-channel inlet chip. Among them, the annular mixing devices are connected through connecting channels. The channel width is 140 μm, the depth (or height) is 75 μm, and the neck angle is 120°, that is, it corresponds to the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A.

[0128] Lipid nanoparticle preparation:

[0129] The cationic lipid (DLin-MC3-DMA), ionizable phospholipid (DSPC), PEGylated lipid (PEG2000-DMG) and cholesterol were added to anhydrous ethanol in a mass ratio of (50:10:1.5:38.5) and dissolved to obtain an organic phase.

[0130] The nucleic acid drug (luc mRNA) was dissolved in 0.1 M citric acid-sodium citrate buffer with a pH of 4 to prepare an aqueous phase with a nucleic acid content of 0.1 mg / mL.

[0131] Mixing efficiency test:

[0132] The organic phase and the aqueous phase were pumped into the target chip at a flow rate ratio of 1:3 and a total flow rate of 5 mL / min. Among them, for the METIS chip, the organic phase enters from the second injection port 25, and the aqueous phase enters from the first injection port 24. For the DVBM chip, the organic phase and the aqueous phase enter from two different channels respectively.

[0133] The mixed solution was collected at the outlet of the target chip (that is, the chip outlet set downstream of the outlet end of the last mixing unit 10).

[0134] Finally, the mixed solution was diluted with PBS buffer at a volume ratio of 1:4 to obtain a nucleic acid nanoparticle suspension.

[0135] Among them, the preparation of the small-scale (Lab) chip usually refers to the process of fabricating small chips or micro-devices on a laboratory scale.

[0136] Experimental Example 2-2: Preparation of pilot-scale (Pilot) chips and nucleic acid nanoparticles

[0137] Chip preparation using glass material: Chips made of glass material can be prepared by laser etching and wet etching processes. In this experiment, the chip structure of the target chip (e.g., METIS chip or DVBM chip) is etched on a glass substrate using the laser etching method, and then bonded to another glass substrate to obtain the target chip.

[0138] Prepare METIS chips and DVBM chips according to the above method.

[0139] The structure of the METIS chip is as Figure 6 shown. Among them, the METIS chip is a three-inlet channel chip, or a "cross"-shaped channel inlet. The width of the narrowest part of the first channel 11 and the second channel 12 of the mixing unit 10 of the METIS chip is 700 μm, and the depth (or height) is 700 μm. The METIS chip includes four mixing units 10 arranged in sequence and connected in series.

[0140] The structure of the DVBM chip is as Figure 7 shown, which is a two-channel inlet chip. Among them, the annular mixing devices are connected by connecting channels. The width of the channel is 700 μm, the depth (or height) is 700 μm, and the neck angle is 120°, which corresponds to the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A.

[0141] Preparation of nucleic acid nanoparticles:

[0142] Obtain the organic phase and the aqueous phase with reference to the sample preparation method in Experimental Example 2-1.

[0143] Mixing efficiency test:

[0144] Pump the organic phase and the aqueous phase into the target chip at a flow rate ratio of 1:3 and a total flow rate of 7.5 L / H. Among them, for the METIS chip, the organic phase enters from the second injection port 25, and the aqueous phase enters from the first injection port 24. For the DVBM chip, the organic phase and the aqueous phase enter from two different channels respectively.

[0145] Collect the mixed solution at the outlet of the target chip (i.e., the chip outlet set downstream of the outlet end of the last mixing unit 10).

[0146] Finally, dilute the mixed solution and the PBS buffer solution at a volume ratio of 1:4 to obtain the nucleic acid nanoparticle suspension.

[0147] Among them, pilot chip preparation refers to the chip manufacturing process in an intermediate stage after the successful development and optimization of the chip design and preparation process at the small-scale (laboratory scale), but before large-scale production.

[0148] Experimental Example 2-3: Preparation of Amplification (GMP) Chips and Nucleic Acid Nanoparticles

[0149] The chips were prepared using stainless steel:

[0150] First, the outer shapes of the upper and lower stainless steel covers were machined using a CNC milling machine.

[0151] Then, the chip structure of the target chip was etched on the stainless steel substrate of the upper cover, and the sealing gasket was machined according to the contour of the lower cover stainless steel base surface.

[0152] Next, the upper cover, the sealing gasket, and the lower cover were fixed together by screws to form an integrated stainless steel chip.

[0153] The METIS chip and the DVBM chip were prepared according to the above method.

[0154] The structure of the METIS chip is as Figure 6 shown. Among them, the METIS chip is a three-inlet channel chip, or a "cross"-shaped channel inlet. The width of the narrowest part of the first channel 11 and the second channel 12 of the mixing unit 10 of the METIS chip is 980 μm, and the depth (or height) is 980 μm.

[0155] The structure of the DVBM chip is as Figure 7 shown, which is a two-channel inlet chip. Among them, the annular mixing devices are connected by connecting channels. The width of the channel is 980 μm, the depth (or height) is 980 μm, and the neck angle is 120°, which corresponds to the exemplary DVBM microfluidic mixer with the best mixing effect disclosed in paragraph 0180 of the specification of Chinese Patent CN108778477A.

[0156] Preparation of nucleic acid nanoparticles:

[0157] The organic phase and the aqueous phase were obtained with reference to the sample preparation method of Experimental Example 2-1.

[0158] Mixing efficiency test:

[0159] The organic phase and the aqueous phase were pumped into the target chip at a flow rate ratio of 1:3 and a total flow rate of 20 L / H. Among them, for the METIS chip, the organic phase enters from the second injection port 25, and the aqueous phase enters from the first injection port 24. For the DVBM chip, the organic phase and the aqueous phase enter from two different channels respectively.

[0160] The mixed solution was collected at the outlet of the target chip (i.e., the chip outlet set downstream of the outlet end of the last mixing unit 10).

[0161] Finally, dilute the mixture with PBS buffer in a volume ratio of 1:4 to obtain a nucleic acid nanoparticle suspension.

[0162] Among them, the preparation of the amplified (GMP) chip refers to the large-scale production process of the chip carried out in accordance with Good Manufacturing Practice (GMP).

[0163] The nanoparticles prepared in Experimental Examples 2-1 (small-scale), 2-2 (medium-scale), and 2-3 (amplified) were characterized by DLS and the encapsulation efficiency was tested. The results showed that under different flow rates (scales), there were no significant differences in the particle size (SIZE) and particle size distribution (PDI) of the nucleic acid nanoparticles prepared by the METIS chip and the DVBM chip provided by the embodiments of the present invention. However, the encapsulation efficiency (EE%) of the nucleic acid nanoparticles prepared by the DVBM chip decreased significantly with the increase of the flow rate, while the encapsulation efficiency of the METIS chip provided by the embodiments of the present invention did not change significantly. At the same time, it also showed that the structural design of the METIS chip had good compatibility in different materials, such as PDMS, glass, and stainless steel, and there were no significant differences in its particle size, particle size distribution, and encapsulation efficiency. Therefore, the chips provided by the experimental examples of the present invention had low restrictions on materials and sizes, and different materials and sizes had no significant differences in particle size, particle size distribution, and encapsulation efficiency.

[0164] As used herein, the terms "substantially", "substantial", "about", and "approximate" are used to indicate and interpret minor variations. For example, when used in conjunction with a numerical value, the above terms may refer to a range of variation less than or equal to ±10% of the corresponding numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05% of the variation range.

[0165] Based on the above embodiments of the present invention, without explicit negation or conflict, the technical features of one embodiment can be beneficially combined with one or more other embodiments.

[0166] Although some specific embodiments of the present invention have been described in detail by way of examples, those skilled in the art should understand that the above examples are only for illustration and not for limiting the scope of the present invention. Those skilled in the art should understand that the above embodiments can be modified or some technical features can be equivalently replaced without departing from the scope and spirit of the present invention. The scope of the present invention is defined by the appended claims.

Claims

1. A microfluidic mixer, characterized in that, Comprising: At least one mixing unit, the mixing unit including an inlet end, a mixing zone, and an outlet end, the mixing zone including a first channel and a second channel, the inlets of the first channel and the second channel connecting to the inlet end, and the outlets of the first channel and the second channel connecting to the outlet end; The first channel includes a first inner wall and an arcuate first outer wall, and the second channel includes a second inner wall and an arcuate second outer wall; The first inner wall includes a first inner wall inlet section and a first inner wall outlet section sequentially arranged from the inlet end to the outlet end, and the second inner wall includes a second inner wall inlet section and a second inner wall outlet section sequentially arranged from the inlet end to the outlet end; The intersection of the first inner wall inlet section and the first inner wall outlet section forms a first corner; The intersection of the second inner wall inlet section and the second inner wall outlet section forms a second corner.

2. The microfluidic mixer according to claim 1, wherein The two ends of the first inner wall and the second inner wall are respectively in contact and enclose to form a roundabout through which fluid cannot pass, and the roundabout includes a liquid diversion part near the inlet end and a liquid merging part near the outlet end.

3. The microfluidic mixer according to claim 1, characterized in that, The intersection of the first inner wall inlet section and the second inner wall inlet section near the inlet end forms a third corner; or, the intersection of the first inner wall outlet section and the second inner wall outlet section near the outlet end forms an arcuate part.

4. The microfluidic mixer according to claim 1 or 3, characterized in that, The first corner, the second corner, and the third corner are arcuate corners.

5. The microfluidic mixer according to claim 3, characterized in that, The first inner wall inlet section, the first inner wall outlet section, the second inner wall inlet section, and the second inner wall outlet section all smoothly extend in the direction from the inlet end to the outlet end.

6. The microfluidic mixer according to claim 1, characterized in that, The first inner wall inlet section and the first inner wall outlet section are arcuate sidewall sections.

7. The microfluidic mixer according to claim 6, wherein The centers of curvature of the first inner wall inlet section and the first inner wall outlet section are different, and the second inner wall inlet section and the second inner wall outlet section are arcuate sidewall sections.

8. The microfluidic mixer according to claim 6, wherein The centers of curvature of the second inner wall inlet section and the second inner wall outlet section are different.

9. The microfluidic mixer according to claim 6, characterized in that, The first inner wall inlet section and the second inner wall inlet section have the same radius of curvature, and the centers of curvature and the radii of curvature of the first inner wall outlet section and the second inner wall outlet section are the same.

10. The microfluidic mixer according to claim 1, characterized in that, The microfluidic mixer further includes at least two liquid inlet channels, the inlet of each liquid inlet channel being configured to communicate with a liquid supply device, and the outlet communicating with the inlet end of each of the mixing units.

11. The microfluidic mixer according to claim 1, characterized in that, The microfluidic mixer includes at least two of the mixing units.

12. The microfluidic mixer according to claim 11, wherein The at least two mixing units are arranged in sequence and connected in series, and the outlet end of the upstream mixing unit in any two adjacent mixing units is connected to the inlet end of the downstream mixing unit.

13. The microfluidic mixer according to claim 1, wherein, The path lengths of the first channel and the second channel are the same.

14. The microfluidic mixer according to claim 2, wherein The first channel and the second channel are symmetrically arranged with respect to the roundabout.

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