CN117903906A - Microfluidic structure and microfluidic chip - Google Patents

Abstract

A microfluidic structure and a microfluidic chip. The microfluidic structure includes at least one microfluidic unit, and each microfluidic unit includes a plurality of curved channels and a plurality of turning channels. The plurality of curved channels are arranged at intervals along the arrangement direction, and each turning channel is located between two adjacent curved channels and connects the two adjacent curved channels; the two turning channels connected to a curved channel are respectively located at the two ends of the curved channel. Each curved channel has a first side and a second side relative to each other in the arrangement direction, and each curved channel bends toward a first position located on the second side. The microfluidic structure can achieve the focusing of particles of two or more sizes at different positions, and thus can achieve separation; at the same time, the microfluidic structure also has the characteristics of large redundancy in the effective flow rate range, large flow rate, high separation efficiency, simple manufacture, easy operation, not easily interfered by impurities, insensitive to structural dependence and high robustness, and has a broad application space.

Description

Microfluidic structure and microfluidic chip

Technical Field

Embodiments of the present disclosure relate to a microfluidic structure and a microfluidic chip.

Background Art

Among all the passive sorting methods of unlabeled particles or granules (such as circulating tumor cells, CTCs) based on physical characteristics, inertial focusing technology uses fluid mechanics methods to focus and separate particles of different physical properties (such as size) by using the inertial lift and other forces generated by the shape of the inertial microfluidic channel. This method, which only relies on the shape of the device and not on external forces, makes the manufacturing process simple and easy to operate. Inertial focusing can achieve relatively high processing capacity, avoiding the rupture of cells caused by excessive shear force. It can also separate particles only by inertial effect without using buffer, and it is easy to combine with other separation methods. Inertial focusing has always been at the forefront of scientific research and applied research due to its advantages such as high throughput far higher than other methods and extremely high robustness.

Summary of the invention

The disclosed embodiments provide a microfluidic structure and a microfluidic chip. The microfluidic structure can achieve the focusing of particles of two or more sizes at different positions, thereby achieving separation; at the same time, the microfluidic structure also has the characteristics of large redundancy in the effective flow rate range, large flow rate, high separation efficiency, simple manufacture, easy operation, not easily interfered by impurities, insensitive to structural dependence and high robustness, and has a broad application space.

At least one embodiment of the present disclosure provides a microfluidic structure, including at least one microfluidic unit, each of the microfluidic units including a plurality of curved channels arranged at intervals along an arrangement direction; and a plurality of turning channels, each of the turning channels being located between two adjacent curved channels and connecting the two adjacent curved channels, the two turning channels connected to one curved channel being respectively located at two ends of the curved channel, each of the curved channels having a first side and a second side opposite to each other in the arrangement direction, and each of the curved channels being bent toward a first position located on the second side.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the plurality of first positions of the plurality of curved channels are located on the same side of the plurality of curved channels in the arrangement direction.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the lengths of the plurality of curved channels gradually change along the arrangement direction.

For example, in the microchannel structure provided in an embodiment of the present disclosure, each of the curved channels is an arc-shaped channel, and the first position of each of the curved channels is the center of curvature of the curved channel.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the plurality of first positions of the plurality of curved channels are located on the same straight line.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the plurality of first positions of the plurality of curved channels overlap with each other.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the lengths of the multiple curved channels gradually decrease along the arrangement direction; among the multiple curved channels, the arc radius of the longest curved channel is r _max , and the value range of r _max is 10 mm to 50 mm; the arc radius of the shortest curved channel is r _min , and the value range of r _min is 1 mm to 20 mm.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the number of the plurality of curved channels is N, and the value range of N is 2-50.

For example, in the microfluidic channel structure provided in an embodiment of the present disclosure, the value range of N is 4-8.

For example, in the microfluidic structure provided in an embodiment of the present disclosure, along the arrangement direction, the lengths of the multiple curved channels gradually decrease, the multiple curved channels are equidistantly arranged, and the parameters of the microfluidic unit satisfy the following formula: (N-1)·d+N·D=r _max -r _min ; wherein N is the number of the multiple curved channels, d is the distance between two adjacent curved channels, D is the width of each of the multiple curved channels, and among the multiple curved channels, r _max is the arc radius of the curved channel with the longest length, and r _min is the arc radius of the curved channel with the shortest length.

For example, in the microchannel structure provided in one embodiment of the present disclosure, each of the turning channels includes an inner wall and an outer wall, the inner wall is arranged opposite to the outer wall and is located on the side of the outer wall close to the interval between two adjacent curved channels.

For example, in the microfluidic channel structure provided in one embodiment of the present disclosure, the shape of the orthographic projection of the inner wall on the reference plane is a first arc, the shape of the orthographic projection of the outer wall on the reference plane is a second arc, and the reference plane is parallel to the arrangement direction and the extension direction of each of the curved channels.

For example, in the microfluidic channel structure provided in one embodiment of the present disclosure, among the multiple turning channels located on the same side of a reference straight line extending along the arrangement direction and passing through the multiple curved channels, the outer wall of the first turning channel and the outer wall of the last turning channel in the arrangement direction have their orthographic projections on the reference plane tangent to the first straight line.

For example, the microchannel structure provided in one embodiment of the present disclosure also includes: an inlet channel, which is connected to the first curved channel in the arrangement direction; and an outlet channel, which is connected to the last curved channel in the arrangement direction, the outlet channel and the first straight line are respectively located on both sides of a reference straight line extending along the arrangement direction and passing through the multiple curved channels, the side wall of the last curved channel in the arrangement direction close to the first position and the orthographic projection of the side wall of the outlet channel close to the first straight line on the reference plane have an intersection, the first position of the last curved channel in the arrangement direction and the intersection are located on a second straight line, the first straight line and the second straight line have an angle θ, and the value range of θ is 10 degrees to 90 degrees.

For example, in the microfluidic channel structure provided in an embodiment of the present disclosure, the value range of θ is 15 degrees to 30 degrees.

For example, in the microfluidic channel structure provided in one embodiment of the present disclosure, the shape of the orthographic projection of the inner wall on the reference plane is a first straight line segment, the shape of the orthographic projection of the outer wall on the reference plane is a second straight line segment, and the reference plane is parallel to the arrangement direction and the extension direction of each of the curved channels.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the second straight line segments of the plurality of turning channels located on the same side of a reference straight line extending along the arrangement direction and passing through the plurality of curved channels are parallel to each other.

For example, in the microchannel structure provided in an embodiment of the present disclosure, the ratio of the width to the height of the plurality of curved channels ranges from 1 to 20, and the height of the plurality of curved channels ranges from 10 μm to 150 μm.

For example, the microfluidic structure provided in an embodiment of the present disclosure further includes a connecting channel, the microfluidic structure includes a plurality of microfluidic units, the connecting channel is located between two adjacent microfluidic units, and connects the two adjacent microfluidic units.

For example, in the microfluidic structure provided in one embodiment of the present disclosure, the multiple microfluidic units are arranged in sequence along an arc, and the arc bends toward a second position; the second position and the multiple first positions of the multiple curved channels of any one of the microfluidic units are located on the same side of the arc.

For example, in the microfluidic structure provided in one embodiment of the present disclosure, the multiple microfluidic units include a first microfluidic unit, a second microfluidic unit and a third microfluidic unit which are sequentially arranged in the extension direction of the arc line, the last curved channel of the first microfluidic unit in the arrangement direction is connected to the last curved channel of the second microfluidic unit in the arrangement direction through the connecting channel, and the first curved channel of the second microfluidic unit in the arrangement direction is connected to the first curved channel of the third microfluidic unit in the arrangement direction through the connecting channel.

For example, in the microfluidic channel structure provided in an embodiment of the present disclosure, the second position overlaps with a plurality of the first positions of the plurality of curved channels of any of the microfluidic channel units.

For example, in the microfluidic channel structure provided in an embodiment of the present disclosure, the plurality of microfluidic channel units are arranged in sequence along a circumferential line.

At least one embodiment of the present disclosure provides a microfluidic chip, comprising a microfluidic structure according to any of the above descriptions; and a first separation structure, comprising a first sub-inlet and a plurality of first sub-outlets, wherein the microfluidic structure comprises an inlet and an outlet, and the first sub-inlet is connected to the outlet of the microfluidic structure.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings of the embodiments will be briefly introduced below. Obviously, the drawings in the following description only relate to some embodiments of the present disclosure, rather than limiting the present disclosure.

FIG1A is a schematic top view of a spiral inertial focusing channel;

FIG1B is a schematic top view of a serpentine inertial focusing channel;

FIG1C is a schematic top view of a contraction-expansion inertial focusing channel;

FIG2A is a schematic structural diagram of a microfluidic unit of a microfluidic structure provided by an embodiment of the present disclosure;

FIG2B is a schematic top view of the microfluidic unit shown in FIG2A ;

FIG2C is a schematic top view of another microfluidic unit provided by an embodiment of the present disclosure;

FIG3A is a schematic top view of another microfluidic unit provided in one embodiment of the present disclosure;

FIG3B is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3C is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3D is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3E is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3F is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3G is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3H is a schematic top view of another microfluidic unit provided in one embodiment of the present disclosure;

FIG3I is a schematic top view of another microfluidic unit provided in one embodiment of the present disclosure;

FIG3J is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3K is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG3L is a schematic top view of another microfluidic unit provided in an embodiment of the present disclosure;

FIG4 is a distribution simulation diagram of secondary flows caused by different turning flow channels provided in an embodiment of the present disclosure;

FIG5 is a schematic top view of a microfluidic channel structure provided by an embodiment of the present disclosure;

FIG6A is a schematic top view of another microfluidic channel structure provided by an embodiment of the present disclosure;

FIG6B is an experimental diagram of the focusing position of particles in the microfluidic channel structure shown in FIG6A as the Reynolds number changes;

FIG6C is a schematic diagram of the focusing position of particles of three sizes as the flow rate changes in the microchannel structure shown in FIG6A when r _min =2 mm and β=22.5 degrees;

FIG6D is a schematic diagram of the focusing position of particles of three sizes as the flow rate changes in the microchannel structure shown in FIG6A when r _min =6.05 mm and β=22.5 degrees;

FIG6E is a schematic diagram of the focusing position of particles of three sizes as the flow rate changes in the microchannel structure shown in FIG6A when r _min =12.8 mm and β=22.5 degrees;

FIG6F is a schematic diagram of the focusing position of particles of three sizes as the flow rate changes in the microchannel structure shown in FIG6A when r _min =6.05 mm and β=30 degrees;

FIG6G is a schematic diagram of the focusing position of particles of three sizes as the flow rate changes in the microchannel structure shown in FIG6A when r _min =6.05 mm and β=45 degrees;

FIG7A is a schematic top view of another microfluidic channel structure provided by an embodiment of the present disclosure;

FIG7B is a schematic top view of the microchannel structure shown in FIG7A after it is repeated four times;

FIG7C is an experimental diagram of particle focusing positions of the microfluidic structure shown in FIG7A at different numbers of repetitions;

FIG8A is a schematic diagram of another microfluidic channel structure provided by an embodiment of the present disclosure;

FIG8B is a schematic diagram of another microfluidic channel structure provided by an embodiment of the present disclosure;

FIG9A is a schematic diagram of a microfluidic chip provided by an embodiment of the present disclosure;

FIG9B is a partial enlarged schematic diagram of the first separation structure shown in FIG9A ;

FIG9C is a schematic diagram of separation of particles of different sizes in the first separation structure shown in FIG9A ;

FIG9D is an enrichment diagram of particles of different sizes collected at the four first sub-outlets shown in FIG9A ;

FIG10A is a schematic diagram of another microfluidic chip provided by an embodiment of the present disclosure;

FIG10B is a graph showing the capture efficiency of target particles in whole blood using the microfluidic chip shown in FIG10A ;

FIG10C is a diagram showing the enrichment of human breast cancer cells spiked into whole blood at three outlets of the microfluidic chip shown in FIG10A ;

FIG11A is a schematic diagram of the structure of another microfluidic chip provided by an embodiment of the present disclosure;

FIG11B is a schematic diagram of separation of particles of different sizes at the first separation structure shown in FIG11A ;

FIG11C is a schematic diagram of separation of particles of different sizes at the second separation structure shown in FIG11A ;

FIG11D is a schematic diagram of separation of particles at the third separation structure shown in FIG11A ;

FIG11E is a schematic diagram showing the capture efficiency of target particles using the microfluidic chip shown in FIG11A under different conditions;

FIG11F is an enrichment diagram of human breast cancer cells collected in phosphate buffered saline using the microfluidic chip shown in FIG11A ; and

FIG. 11G is a diagram showing the collection of human breast cancer cells and waste fluid from ten-fold diluted blood using the microfluidic chip shown in FIG. 11A .

DETAILED DESCRIPTION

In order to make the purpose, technical solution and advantages of the embodiments of the present disclosure clearer, the technical solution of the embodiments of the present disclosure will be clearly and completely described below in conjunction with the drawings of the embodiments of the present disclosure. Obviously, the described embodiments are part of the embodiments of the present disclosure, not all of the embodiments. Based on the described embodiments of the present disclosure, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present disclosure.

Unless otherwise defined, the technical terms or scientific terms used in the present disclosure should be understood by people with ordinary skills in the field to which the present disclosure belongs. "First", "second" and similar words used in the present disclosure do not indicate any order, quantity or importance, but are only used to distinguish different components. "Include" or "comprise" and similar words mean that the elements or objects appearing before the word cover the elements or objects listed after the word and their equivalents, without excluding other elements or objects. "Connect" or "connected" and similar words are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly.

Unless otherwise defined, the features such as "parallel", "perpendicular" and "same" used in the embodiments of the present disclosure include the situations of "parallel", "perpendicular", "same" in a strict sense, as well as the situations of "approximately parallel", "approximately perpendicular", "approximately the same" and the like which contain certain errors. For example, the above-mentioned "approximately" may mean that the difference of the compared objects is within 10% or 5% of the average value of the compared objects. When the number of a component or element is not particularly specified in the following of the embodiments of the present disclosure, it means that the component or element may be one or more, or may be understood as at least one. "At least one" means one or more, and "plurality" means at least two.

Among all the passive separation and classification methods of unlabeled particles or particulates (such as circulating tumor cells) based on physical characteristics, the membrane filtration and pillar filtration methods cannot meet the processing volume and capture rate at the same time due to the problems caused by their orthogonal flow. At the same time, the inability to improve purity is also an important problem. The lateral flow, deterministic lateral displacement (DLD) and pinched flow fractionation (PFF) methods inevitably require a large amount of buffer for processing, which has a great impact on the subsequent cell analysis. In contrast, inertial focusing can achieve a relatively high processing capacity, avoiding the rupture of particles such as cells due to excessive shear force. It can also separate cells only by inertial effect without using buffer, and it is easy to combine with other separation methods. One of the important application scenarios of this separation method is the separation of CTC. CTC can be used as a target for "liquid biopsy", providing a non-invasive method for the study, diagnosis and treatment of metastatic cancer. The main technical challenge of enriching CTCs from peripheral blood is that CTCs are very rare in the blood, and the concentration is usually estimated to be a few CTCs in billions of red blood cells and millions of white blood cells per milliliter of whole blood. Therefore, how to efficiently and selectively capture CTCs is the first key step in analysis.

Compared to conventional microfluidics, inertial microfluidics operates in a moderate Reynolds number (Re) range between the Stokes flow region and the turbulent flow region (1 < Re < 100). In this intermediate range, both the inertial viscosity and the fluid viscosity are limited and produce some interesting effects that form the basis of inertial microfluidics, including inertial migration and secondary flow. Cells in the channel are affected by these two effects, causing particles of different sizes to begin to separate.

Inertial migration refers to the phenomenon that randomly dispersed particles at the entrance of a straight channel shift to multiple equilibrium positions after traveling a sufficiently long distance. The phenomenon of inertial migration was first observed in a circular tube in 1961, where particles or granules aggregate into a ring with a radius of approximately 0.6 times the radius of the tube. The inertial lift force varies with the fourth power of the cell size and is responsible for focusing the cells at different equilibrium positions within the cross section of the microchannel.

where ρ is the fluid density (kg/m ³ ), U is the average flow velocity (m/s), _DH is the hydraulic diameter of the channel (m), f is the lift coefficient which varies with the position of the particle in the channel, and a is the particle diameter (m).

Secondary flows are generated when a curved channel is introduced. The fluid flowing through the curved channel experiences radial outward centrifugal acceleration, resulting in the formation of two counter-rotating vortices in the upper and lower halves of the channel. The magnitude of these secondary flows is quantified by a dimensionless parameter, the Dean number (De), given by the following formula:

Wherein, ρ is the fluid density, U is the average flow velocity, μ is the viscosity of the fluid, R is the radius of curvature of the channel path (m), _DH is the channel hydraulic diameter (m), and Re is the flow Reynolds number (ratio of inertial to viscous forces).

Where ρ is the fluid density, υ is the flow velocity, μ is the viscosity of the fluid, d is the characteristic length of the channel (m), and the hydraulic diameter of the _DH channel (m) is often used instead. The Reynolds number (Re) is a dimensionless number that can be used to characterize the flow conditions of the fluid.

The relationship between the secondary flow velocity and the Dean number is:

Where ρ is the fluid density, μ is the fluid viscosity, _DH is the channel hydraulic diameter, and k is an empirically determined proportionality factor for these curvilinear channels of approximately 0.01. The value of k can be verified using a COMSOL model of the set channel.

The drag force on the particle in the secondary flow can be given by Stokes' law:

F _D ＝3πμaU _De

where μ is the viscosity of the fluid, a is the particle diameter, and U _De is the flow rate of the secondary flow.

Then for particles or granules flowing in curved channels, as a first-order approximation, we can make an assumption that the effects of inertial migration and secondary flow are superimposed, that is, "Dean drag" competes with inertial lift in the secondary flow, acting on the particles to change the equilibrium position. The ratio of these two forces (inertial lift/Dean drag) will be the key parameter to describe the behavior of these systems.

in,

Among them, when R _f →0, the inertial force is small compared to the resistance, so the particles will ignore the inertial equilibrium position and be entrained by the secondary flow, and then remain in the secondary flow; while R _f →∞, the particles are mainly dominated by the inertial force, and the particles will migrate to the inertial focusing equilibrium position without being affected by the secondary flow. Our main concern is that for the intermediate R _f , the inertial equilibrium position produced by inertial focusing can be modified by the secondary flow, resulting in interesting new focusing results. This intermediate range starts from R _f >~0.04. The effect of R _f related to the particle size makes two particles of different sizes behave differently in the channel. The smaller particles are completely entrained by the secondary flow, while the larger particles are concentrated in the inertial equilibrium position. When we choose the channel shape and Reynolds number appropriately, we can achieve the separation of particles of different sizes.

In some systems with high-density particle collisions (such as blood), the purity may be reduced when separating unlabeled particles (such as circulating tumor cells) from undiluted blood due to cell-cell collisions.

Existing inertial focusing devices mainly separate particle sizes through three shapes, namely spiral, serpentine and contraction-expansion shapes. Figure 1A is a top-down schematic diagram of a spiral inertial focusing channel; Figure 1B is a top-down schematic diagram of a serpentine inertial focusing channel; and Figure 1C is a top-down schematic diagram of a contraction-expansion inertial focusing channel.

As shown in Figure 1A, the spiral inertial focusing channel focuses particles of different sizes near the inner wall and separates them by using the difference in focusing positions. However, the focusing positions of particles of different sizes are very close, and their relative positions will change with the flow rate. In order to stably collect particles of a fixed size, it is necessary to add a second inlet at the inlet to introduce a buffer solution to enhance the intensity of the secondary flow, or to add an extended outlet at the outlet to expand the slightly different focusing positions and thereby collect particles of the target size.

As shown in FIG1B , a symmetrical or asymmetrical serpentine inertial focusing channel focuses large particles in the center of the channel (“single focusing” effect) and small particles on both sides of the channel (“double focusing” effect), thereby separating particles of different sizes. This is very effective for separating particles with a large size difference. However, for particles with a small size difference, if we want to select a certain cutoff diameter and collect particles larger or smaller than this size separately, it will be very difficult, because in the process from “double focusing” to “single focusing”, the particles are basically in a defocused state, and particles of different sizes cannot be distinguished.

As shown in Figure 1C, for a symmetrical contraction-expansion channel, the focusing effect is similar to that of a symmetrical serpentine structure, where large particles are focused in the center and small particles are focused on both sides. For an asymmetric structure, depending on whether a buffer solution is added at the inlet and the shape of the channel, large particles are focused at different locations from small particles. If we want to select a certain cutoff diameter, it will also be very difficult to collect particles larger or smaller than that size separately.

Among the existing inertial focusing technologies, one part is based on the improvement of the serpentine pattern. As mentioned above, the focusing effect of this part is mostly to focus larger particles or granules in the center of the channel, and smaller particles on both sides of the channel. Particles of different sizes can be separated within a small specific flow rate range. This method has a relatively stable separation effect for particles with a certain size difference, and the structure is easy to connect in series. However, this method is difficult to separate particles of multiple sizes at the same time, and the separation effect for particles of similar sizes is not good. The other part is based on the improvement of the spiral pattern. The focusing effect of this part is mostly focused near the channel wall. Although the focusing effect is better, the separation of different sizes can only be magnified by using a buffer or a structure similar to PFF to amplify the tiny difference in focusing position, and it is very sensitive to changes in flow rate.

In addition, there are some designs (for example, maze-shaped inertial focusing channels) that use a combination of irregular corners and arcs to achieve a certain focusing effect, but this design does not have a reasonable theoretical support and an effective improvement plan, and is too sensitive to the structure, making the robustness low, and the focusing efficiency is extremely sensitive to the flow rate. In summary, the main problems with these designs are that it is difficult to control the impact of changes in factors such as flow, and there are few parameters that can be adjusted and controlled, and the expected results cannot be obtained by improving the parameters.

Existing inertial focusing separation devices (such as serpentine focusing or spiral focusing) still have problems with flow rate and structure sensitivity. This problem seriously limits practical applications. In many existing inertial focusing separation device chips, a change of 0.1mL/min in flow rate will bring about a huge change in separation efficiency and results, and the capture efficiency will also be greatly reduced; some existing inertial focusing separation device chips are also highly sensitive to structure. Chips from different batches of the same mold have significant differences in their optimal flow rates due to factors such as errors.

In this regard, the embodiments of the present disclosure provide a microfluidic structure and a microfluidic chip. The microfluidic structure includes at least one microfluidic unit, and each microfluidic unit includes a plurality of curved channels and a plurality of turning channels. The plurality of curved channels are arranged at intervals along the arrangement direction, and each turning channel is located between two adjacent curved channels and connects the two adjacent curved channels; the two turning channels connected to a curved channel are respectively located at both ends of the curved channel. Each curved channel has a first side and a second side opposite to each other in the arrangement direction, and each curved channel is bent toward a first position located on the second side.

The multiple curved channels in each microchannel unit of the microchannel structure provided by the embodiment of the present disclosure are arranged at intervals along the arrangement direction, each curved channel has a relative first side and a second side in the arrangement direction, and each curved channel is bent toward the first position located on the second side; according to the previous theoretical basis, when particles of different sizes are introduced into the curved channel, secondary flow will be generated, and the fluid flowing through the curved channel will experience radial outward centrifugal acceleration, resulting in the formation of two counter-rotating vortices in the upper and lower halves of the curved channel; particles with smaller sizes are more easily entrained by the secondary flow, while particles with larger sizes are concentrated in the inertial equilibrium position. When particles pass through multiple curved channels, the radial outward centrifugal acceleration to which the particles are subjected in each curved channel deviates from the first position located on the second side. Therefore, after passing through multiple curved channels that are all bent toward the second side, the particles will gradually focus on a position deviating from the center of the curved channel; at the same time, under the action of the secondary flow of the curved channel and the turning channel, particles of different sizes deviate from the center of the curved channel to different degrees. In this way, particles of different sizes can be focused at different positions deviating from the center of the flow channel, thereby achieving separation of particles of different sizes. Different from the serpentine channel in the prior art, the multiple curved channels in the microfluidic structure are all bent toward the first position located on the second side, so that particles of different sizes can be focused at positions deviating from the center of the curved channel, while in the serpentine channel in the prior art, larger particles are focused at the center of the channel, and the particles focused at the center of the channel cannot be separated. Therefore, by using this microfluidic structure, particles of two or more sizes can be inertially focused at different positions, thereby achieving separation.

In addition, the effective flow rate range redundancy of the microfluidic unit of the microfluidic structure is large, so it can be applied to a wider flow rate range; it also has the characteristics of large flow rate, high separation efficiency, simple manufacture, easy operation, and not easily interfered by impurities, which reduces the sensitivity of dependence on the microfluidic structure, making the microfluidic structure have good robustness and a broad application space.

The microfluidic structure and the microfluidic chip provided by the embodiments of the present disclosure are described in detail below with reference to the accompanying drawings.

FIG2A is a schematic diagram of the structure of a microfluidic unit of a microfluidic structure provided in one embodiment of the present disclosure; FIG2B is a schematic diagram of a top view of the microfluidic unit shown in FIG2A. As shown in FIG2A and FIG2B, the microfluidic structure 100 includes at least one microfluidic unit 110, and each microfluidic unit 110 includes a plurality of curved channels 111 and a plurality of turning channels 112. The plurality of curved channels 111 are arranged at intervals along the arrangement direction X, and each turning channel 112 is located between two adjacent curved channels 111 and connects the two adjacent curved channels 111; the two turning channels 112 connected to a curved channel 111 are respectively located at both ends of the curved channel 111. Each curved channel 111 has a first side SN and a second side SN' opposite to each other in the arrangement direction X, and N is the number of curved channels 111 in the microfluidic unit 110; for example, the first curved channel 111 in the arrangement direction X has a first side S1 and a second side S1', and the last curved channel 111 in the arrangement direction X (that is, the sixth curved channel 111) has a first side S6 and a second side S6'. For example, the above-mentioned first side SN and second side SN' may be the left side and the right side of each curved channel 111 in the arrangement direction X. It should be noted that although the number N of curved channels in the microfluidic unit shown in FIGS. 2A and 2B is six, the embodiments of the present disclosure include but are not limited to this.

As shown in FIG. 2A and FIG. 2B , each curved channel 111 is bent toward the first position PN located at the second side SN'. For example, the first curved channel 111 in the arrangement direction X is bent toward the first position P1 located at the second side S1', and the sixth curved channel 111 in the arrangement direction X is bent toward the first position P6 located at the second side S6'. FIG. 2B only shows the first side S1, the second side S1', and the first position P1 of the first curved channel 111 in the arrangement direction X, and the first side S6, the second side S6', and the first position P6 of the sixth curved channel 111. The first side SN, the second side SN', and the first position P1 of other curved channels 111 are similar, and the marking is omitted in the figure.

The multiple curved channels 111 in each microchannel unit 110 of the microchannel structure 100 provided in the embodiment of the present disclosure are arranged at intervals along the arrangement direction X, and each curved channel 111 has a first side SN and a second side SN' opposite to each other in the arrangement direction X, and each curved channel 111 is bent toward the first position PN located on the second side SN'. According to the above theoretical basis, when particles of different sizes are introduced into the curved channel, secondary flow will be generated, and the fluid flowing through the curved channel will experience radial outward centrifugal acceleration, resulting in the formation of two counter-rotating vortices in the upper and lower halves of the curved channel; particles with smaller sizes are more easily entrained by the secondary flow, while particles with larger sizes are concentrated in the inertial equilibrium position. When the particles pass through multiple curved channels 111, the radial outward centrifugal accelerations to which the particles are subjected in each curved channel 111 are all away from the first position PN located on the second side SN'. Therefore, after passing through multiple curved channels 111 that are all bent toward the second side SN', the particles will gradually focus on a position that deviates from the center of the curved channel 111; at the same time, under the action of the secondary flow of the curved channel 111 and the turning channel 112, particles of different sizes deviate from the center of the curved channel 111 to different degrees. Thus, particles of different sizes can be focused on different positions that deviate from the center of the channel, thereby achieving separation of particles of different sizes. Different from the serpentine channels in the prior art, the multiple curved channels 111 in the microfluidic channel structure 100 are all bent toward the first position PN located on the second side SN', so that particles of different sizes can be focused on a position that deviates from the center of the curved channel 111, while in the serpentine channels in the prior art, particles of larger sizes are all focused on the center of the channel, and particles focused on the center of the channel cannot be separated. Therefore, by using the microfluidic channel structure 100, particles of two or more sizes can be inertially focused at different positions, thereby achieving separation.

In addition, the effective flow rate range redundancy of the microfluidic unit 110 of the microfluidic structure 100 is large, so it can be used in a wider flow rate range; it also has the characteristics of large flow rate, high separation efficiency, simple manufacture, easy operation, and not easily interfered by impurities, which reduces the sensitivity of dependence on the microfluidic structure, making the microfluidic structure have good robustness and a broad application space.

In some examples, as shown in FIG2A and FIG2B , the first positions PN of the plurality of curved channels 111 are located on the same side of the plurality of curved channels 111 in the arrangement direction X. That is, the plurality of curved channels 111 of each microfluidic channel unit 110 can be regarded as a whole, and in the arrangement direction X of the plurality of curved channels 111 of the microfluidic channel unit 110, the whole has a first side S0 and a second side S0' opposite to each other, and the first position PN of each curved channel 111 is located on the same side of the whole, for example, it can be located on the first side S0 or the second side S0' of the whole; that is, the first position PN of each curved channel 111 of the microfluidic channel unit 110 does not fall inside the whole.

In some examples, as shown in FIG. 2A and FIG. 2B , the length Len of the plurality of curved channels 111 gradually changes along the arrangement direction X. For example, along the arrangement direction X, the length Len of the plurality of curved channels 111 of each microfluidic unit 110 may gradually decrease or may gradually increase. The disclosed embodiment is not limited to this, and the length Len of the plurality of curved channels 111 of each microfluidic unit 110 may also be the same, or may change alternately, and the length Len of the plurality of curved channels 111 may be set as required.

In some examples, as shown in FIG. 2A and FIG. 2B , each curved channel 111 is an arc-shaped channel, and the first position PN of each curved channel 111 is the center of curvature of the curved channel 111 .

In some examples, the first positions PN of the curved channels 111 are located on the same straight line. Thus, the microchannel structure 100 can make different inertial equilibrium positions of particles of different sizes in the channel more stable, thereby achieving higher separation efficiency and greater redundancy of effective flow rate intervals.

In some examples, as shown in FIG2B , the first positions PN of the plurality of curved channels 111 overlap each other. Thus, the microchannel structure 100 can make different inertial equilibrium positions of particles of different sizes in the channel more stable, thereby achieving higher separation efficiency and greater redundancy of effective flow rate intervals.

In some examples, as shown in FIG. 2A and FIG. 2B , along the arrangement direction X, the lengths of the plurality of curved channels 111 gradually decrease, and among the plurality of curved channels 111, the arc radius of the longest curved channel 111 is r _max , and the value range of the arc radius r _max is 13 mm to 20 mm. The embodiment of the present disclosure does not limit this, for example, the value range of the arc radius r _max may also be 10 mm to 50 mm, for example, the arc radius r _max may be any value between 10 mm and 50 mm.

For example, as shown in FIG. 2A and FIG. 2B , the arc radius r _max may also be the arc radius of the curved channel 111 farthest from the first position PN, or the radius of the first curved channel 111 in the arrangement direction X.

For example, as shown in FIG2A and FIG2B, along the arrangement direction X, the lengths of the plurality of curved channels 111 gradually decrease, and among the plurality of curved channels 111, the arc radius of the shortest curved channel 111 is _rmin , and the value range of the arc radius _rmin is 3 mm to 8 mm. The embodiment of the present disclosure does not limit this, for example, the value range of the arc radius _rmin may also be 1 mm to 20 mm, for example, the arc radius _rmin may be any value between 1 mm and 20 mm.

For example, as shown in FIG. 2A and FIG. 2B , the arc radius r _min may also be the arc radius of the curved channel 111 closest to the first position PN, or the radius of the last curved channel 111 in the arrangement direction X.

In the microfluidic channel structure 100 provided in the embodiment of the present disclosure, different arc radii r _max and arc radii r _min have different effects on the focusing effect. The smaller the radius, the stronger the secondary flow generated by the arc, and the greater the impact on the result. By parameterizing the arc radius r _max and arc radius r _min of the microfluidic channel structure 100, the arc radius r _max and arc radius r _min can be better adjusted and optimized, thereby obtaining an effective improvement scheme, effectively improving the separation effect, and being applicable to a wider flow rate range.

In some examples, as shown in FIG. 2A and FIG. 2B , the number of the plurality of curved channels 111 is N, and the value range of the number N is 4-8; for example, each microchannel unit may include four, five, six, seven or eight curved channels. Thus, after passing through N curved channels 111, the different inertial equilibrium positions of particles of different sizes in the curved channels 111 are more stable, so that a higher separation efficiency can be achieved and a wider range of flow rates can be applied. Of course, the embodiments of the present disclosure are not limited to this, for example, the value range of the number N can also be 2-50. For example, N can be any positive integer between 2 and 50.

In some examples, as shown in FIG. 2A and FIG. 2B , the spacing between two adjacent curved channels 111 is d, and the spacing d may range from 300 μm to 1000 μm. The disclosed embodiment does not limit the range of the spacing d, for example, the spacing d may range from 100 μm to 2000 μm, and the spacing d may be any value between 100 μm and 2000 μm.

For example, as shown in FIG. 2A and FIG. 2B , the intervals d between the plurality of curved flow channels 111 may be equal.

In some examples, as shown in FIG. 2A and FIG. 2B , the plurality of curved channels 111 of the microfluidic channel unit 110 are arc-shaped channels, the first position PN of each curved channel 111 is the center of curvature of the curved channel 111, the plurality of first positions PN of the plurality of curved channels 111 overlap with each other, the lengths of the plurality of curved channels 111 gradually decrease along the arrangement direction X, the plurality of curved channels 111 are equidistantly arranged, and the parameters of the microfluidic channel unit 110 satisfy the following formulas:

(N-1)·d+N·D＝r _max −r _min

Wherein, N is the number of the plurality of curved channels 111, d is the distance between two adjacent curved channels 111, D is the width of the curved channel 111, and among the plurality of curved channels 111, r _max is the arc radius of the curved channel 111 with the longest length, and r _min is the arc radius of the curved channel 111 with the shortest length. The present disclosure is not limited thereto, for example, along the arrangement direction X, the lengths of the plurality of curved channels 111 may not be limited to gradually decreasing, in which case r _max is the arc radius of the curved channel 111 farthest from the first position PN, or the arc radius of the first curved channel 111 in the arrangement direction X, and r _min is the arc radius of the curved channel 111 closest to the first position PN, or the arc radius of the last curved channel 111 in the arrangement direction X. Therefore, the microfluidic unit 110 of the microfluidic structure 100 can be parameterized. By adjusting the values of different parameters, a microfluidic structure 100 suitable for different conditions can be obtained. At the same time, by adjusting the parameters, various parameters can be matched and optimized, and then an effective improvement plan can be obtained, which can effectively improve the separation efficiency and be applicable to a wider flow rate range.

In some examples, as shown in FIG. 2A and FIG. 2B , each turning channel 112 includes an inner wall 112a and an outer wall 112b , the inner wall 112a is disposed opposite to the outer wall 112b , and the inner wall 112a is located on one side of the outer wall 112b close to the interval between two adjacent curved channels 111 .

In some examples, as shown in FIG. 2A and FIG. 2B , the shape of the orthographic projection of the inner sidewall 112a of each turning channel 112 on the reference plane A is a first arc, and the shape of the orthographic projection of the outer sidewall 112b of the turning channel 112 on the reference plane A is a second arc, and the reference plane A is parallel to the arrangement direction X and the extension direction of each curved channel 111. Thus, particles of different sizes can be deviated from the center of the channel to different degrees through each turning channel 112, so that particles of different sizes can be separated, and particles of different sizes can be focused at different positions deviated from the center under the action of the microfluidic channel structure 100.

For example, the radius of the first arc is r _in , and the radius of the second arc is r _out . The curvature radius r _out of the second arc can be approximately equal to the sum of the curvature radius r _in of the first arc and the width of the turning channel 112. For example, the centers of curvature of the first arc and the second arc can coincide. In this case, the width of the turning channel 112 is the same in the extension direction of the turning channel 112. The embodiments of the present disclosure do not limit the parameters of the first arc and the second arc.

In some examples, as shown in FIG. 2A and FIG. 2B , the diameter of the first arc may be equal to the distance d between two adjacent curved channels 111. That is, the first arc is a semicircular arc. Similarly, the second arc may also be a semicircular arc. The embodiments of the present disclosure are not limited to this. For example, the first arc and the second arc may also be inferior arcs or superior arcs.

In some examples, as shown in FIG. 2A and FIG. 2B , the reference straight line L0 is a straight line extending along the arrangement direction X and passing through the plurality of curved channels 111, and among the plurality of turning channels 112 located on the same side of the reference straight line L0, the orthographic projections of the outer sidewall 112b of the first turning channel 112 and the outer sidewall 112b of the last turning channel 112 on the arrangement direction X on the reference plane A are tangent to the first straight line L1. That is, the first straight line L1 is the outer common tangent line of the orthographic projections of the outer sidewall 112b of the first turning channel 112 and the outer sidewall 112b of the last turning channel 112 on the reference plane A.

For example, as shown in FIG. 2A and FIG. 2B , among the plurality of turning channels 112 located on the same side of the reference straight line L0, the outer side wall 112b of the turning channel 112 located between the first turning channel 112 and the last turning channel 112 in the arrangement direction X may also be tangent to the first straight line L1, that is, the outer side walls 112b of the plurality of turning channels 112 located on the same side of the reference straight line L0 have the same external common tangent line, which is the first straight line L1. Of course, the embodiments of the present disclosure include but are not limited to this, the outer side wall 112b of the turning channel 112 located between the first turning channel 112 and the last turning channel 112 in the arrangement direction X may be located on the side of the first straight line L1 close to the reference straight line L0, or at least part of the outer side wall 112b of the turning channel 112 located between the first turning channel 112 and the last turning channel 112 in the arrangement direction X may be located on the side of the first straight line L1 away from the reference straight line L0, that is, beyond the first straight line L1.

In some examples, as shown in Figures 2A and 2B, each microfluidic unit 110 of the microfluidic structure 100 also includes an inlet channel 113 and an outlet channel 114, the inlet channel 113 is connected to the first curved channel 111 in the arrangement direction X; the outlet channel 114 is connected to the last curved channel 111 in the arrangement direction X, the outlet channel 114 and the first straight line L1 are respectively located on both sides of the reference straight line L0, that is, the outlet channel 114 is located on the side of the reference straight line L0 away from the first straight line L1, the side wall of the last curved channel 111 in the arrangement direction X close to the first position P6 and the side wall of the outlet channel 114 close to the first straight line L1 have an intersection Px in their orthographic projections on the reference plane A, the first position P6 of the last curved channel 111 in the arrangement direction X and the intersection Px are located on the second straight line L2, the first straight line L1 and the second straight line L2 have an angle θ, and the value range of the angle θ is 15 degrees to 30 degrees. The angle θ affects the time of the arc for the focusing effect, so that each microchannel unit 110 of the microchannel structure 100 can make the different inertial equilibrium positions of particles of different sizes in the flow channel more stable, and thus the separation efficiency of the microchannel structure 100 is higher and the effective flow rate range redundancy is greater. At the same time, by parameterizing the angle θ, better adjustment and optimization can be made according to particles of different sizes, thereby obtaining an effective improvement plan, effectively improving the separation effect, and being applicable to a wider flow rate range.

For example, the value range of the angle θ may also be 10 degrees to 90 degrees. For example, the angle θ may be any angle between 10 degrees and 90 degrees.

In some examples, as shown in FIG. 2A and FIG. 2B , the orthographic projection of the side wall 114 a of the outlet flow channel 114 close to the first straight line L1 (or close to the reference straight line L0 ) on the reference plane A may coincide with the second straight line L2 .

In some examples, the width of the inlet channel 113 is the same as the width of the curved channel 111. For example, the height of the inlet channel 113 is the same as the height of the curved channel 111.

In some examples, the width of the outlet channel 114 is the same as the width of the curved channel 111. For example, the height of the outlet channel 114 is the same as the height of the curved channel 111.

In some examples, as shown in FIG. 2A and FIG. 2B , among the plurality of turning channels 112 located on the side of the reference straight line L0 away from the first straight line L1, the orthographic projections of the outer sidewall 112b of the first turning channel 112 and the outer sidewall 112b of the last turning channel 112 on the reference plane A in the arrangement direction X are tangent to the third straight line L3. That is, the third straight line L3 is the outer common tangent line of the orthographic projections of the outer sidewalls 112b of the two turning channels 112 on the reference plane A. The third straight line L3 and the first straight line L1 are located on both sides of the reference straight line L0, respectively.

In some examples, the first straight line L1 and the third straight line L3 may be parallel, that is, the angle α between the first straight line L1 and the third straight line L3 is 0 degrees.

In some examples, as shown in FIG. 2A and FIG. 2B , the first straight line L1 and the third straight line L3 may have an angle α, and the angle α of the two first straight lines L1 may range from 15 degrees to 30 degrees. Thus, each microfluidic unit 110 of the microfluidic structure 100 can make the different inertial equilibrium positions of particles of different sizes in the flow channel more stable, and thus the separation efficiency of the microfluidic structure 100 is higher, and the effective flow rate interval redundancy is greater. At the same time, by parameterizing the angle α, it is also possible to make better adjustments and optimizations according to particles of different sizes, thereby obtaining an effective improvement scheme, effectively improving the separation effect, and being applicable to a wider flow rate range. The embodiment of the present disclosure does not limit the value of the angle α, for example, the angle α may also range from 10 degrees to 90 degrees, for example, the angle α may be any value between 10 degrees and 90 degrees.

In some examples, as shown in FIG2A , the height of the plurality of curved channels 111 is h, and the value range of the height h is 10 μm to 100 μm. The embodiment of the disclosure does not limit the value range of the height h, for example, the height h can also be any value from 10 μm to 150 μm.

In some examples, the height h of the curved flow channel 111 can be selected according to the size of the target particles or the particles to be obtained or the desired flow rate of the microfluidic structure 100. For example, according to multiple experiments, the height h of the multiple curved flow channels 111 of the microfluidic structure 100 can satisfy the following empirical formula:

Wherein, a _c is the minimum diameter that can be focused. Therefore, the value range of the height h of the curved flow channel 111 can be preliminarily determined by the value of a _c .

For example, in the embodiment of separating circulating tumor cells, the cutoff diameter of white blood cells is selected to be 8 μm, that is, the value of a _c is 8 μm. The value range of the height h can be confirmed according to the above empirical formula, and then according to the selection of other parameters, the height of the curved flow channel 111 is finally selected to be 75 μm.

In some examples, as shown in FIG2A and FIG2B , the width of the plurality of curved channels 111 is D, and the ratio of the width D to the height h of the curved channel 111 ranges from 1 to 20. Of course, the embodiment of the present disclosure does not limit the range of the ratio of the width D to the height h.

In some examples, as shown in FIG. 2A and FIG. 2B , the width of the plurality of curved channels 111 is D, the ratio of the width D to the height h of the curved channels 111 ranges from 1 to 20, and the height h of the plurality of curved channels ranges from 10 μm to 150 μm.

In some examples, as shown in FIG. 2A and FIG. 2B , the width D of the plurality of curved channels 111 ranges from 10 μm to 800 μm. For example, the width D can also be any value from 10 μm to 800 μm. The present disclosure does not limit the range of the width D. For example, the width D can also range from 10 μm to 1500 μm.

In some examples, the width D of the curved channel 111 can be selected according to the size of the target particles or the particles to be obtained or the desired flow rate of the microfluidic structure 100. For example, in a curved channel 111 with a larger aspect ratio, the inertial lift is too weak in the middle part, making it difficult to focus the particles, while in a curved channel 111 with a smaller aspect ratio, because the selection of height is limited, the applicable Reynolds number range of the microfluidic structure 100 is fixed, so the usable flow rate is lower. An appropriate aspect ratio should be selected to balance the flow rate and focusing effect. For example, in an embodiment of separating circulating tumor cells, the width of the curved channel 111 is selected as 500 μm as the standard width, so that the available flow rate range of the microfluidic structure 100 is within the range of 1-4 mL/min, thereby, the microfluidic structure 100 can be applicable to a wider flow rate range, solving the problem of flow rate sensitivity.

FIG2C is a top view schematic diagram of another microfluidic unit provided in an embodiment of the present disclosure. As shown in FIG2C , the width of the turning channel 112 of the microfluidic unit 110 is not uniform in the extension direction of the turning channel 112. For example, in the extension direction of the turning channel 112, the width of the turning channel 112 first gradually increases and then gradually decreases, and the maximum width of the turning channel 112 is greater than the width of the curved channel 111. Thus, the turning channel 112 of the microfluidic unit 110 can better make particles of different sizes deviate from the center of the channel to different degrees, thereby achieving the separation of particles of different sizes, and further making particles of different sizes focused on different positions deviating from the center under the action of the microfluidic structure 100.

In some examples, as shown in FIG. 2C , the inlet channel 113 of the microfluidic channel unit 110 may be the same as the turning channel 112 , and the outlet channel 114 of the microfluidic channel unit 110 may also be the same as the turning channel 112 .

FIG3A is a top view schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure. As shown in FIG3A , the shape of the positive projection of the inner side wall 112a of the turning channel 112 on the reference plane A is a first straight line segment, and the shape of the positive projection of the outer side wall 112b of the turning channel 112 on the reference plane A is a second straight line segment. Thus, through each turning channel 112, particles of different sizes can be deviated from the center of the channel to different degrees, so that particles of different sizes can be separated, and particles of different sizes can be focused at different positions deviated from the center under the action of the microfluidic structure 100.

For example, the length of the second straight line segment of the same turning channel 112 can be greater than, equal to, or less than the length of the first straight line segment, and the second straight line segment and the first straight line segment of the same turning channel 112 can be parallel, or the straight lines where the two are located have an angle. The disclosed embodiment does not limit the parameters of the first straight line segment and the second straight line segment.

In some examples, as shown in FIG. 3A , the angle between the extension line of the first straight line segment or the second straight line segment and the extension direction of one of the two adjacent curved channels 111 is an acute angle, and the angle between the extension line of the first straight line segment or the second straight line segment and the extension direction of the other of the two adjacent curved channels 111 is an obtuse angle.

In some examples, as shown in FIG3A , the reference straight line L0 is a straight line extending along the arrangement direction X and passing through the plurality of curved flow channels 111, and the plurality of first straight line segments of the plurality of turning flow channels 112 located on the same side of the reference straight line L0 are located on the same straight line. For example, the first straight line segments of all or part of the turning flow channels 112 located on the same side of the reference straight line L0 are located on the same straight line.

In some examples, as shown in Fig. 3A, multiple second straight line segments of multiple diverting channels 112 located on the same side of the reference straight line L0 are located on the same straight line. For example, all or part of the second straight line segments of the diverting channels 112 located on the same side of the reference straight line L0 are located on the same straight line.

In some examples, as shown in FIG3A , among the multiple turning channels 112 located on the same side of the reference straight line L0, the outer sidewall 112b of the first turning channel 112 and the outer sidewall 112b of the last turning channel 112 in the arrangement direction X have their orthographic projections on the reference plane A located on the fourth straight line L4. For example, the outer sidewall 112b of the turning channel 112 located between the first turning channel 112 and the last turning channel 112 in the arrangement direction X may be located on the fourth straight line L4, or may be located on the side of the fourth straight line L4 close to the reference straight line L0, or may be located on the side of the fourth straight line L4 far from the reference straight line L0, that is, beyond the fourth straight line L4.

In some examples, as shown in FIG3A , each microfluidic unit 110 of the microfluidic structure 100 further includes an inlet channel 113 and an outlet channel 114, the inlet channel 113 is connected to the first curved channel 111 in the arrangement direction X; the outlet channel 114 is connected to the last curved channel 111 in the arrangement direction X, the outlet channel 114 and the fourth straight line L4 are respectively located on both sides of the reference straight line L0, that is, the outlet channel 114 is located on the side of the reference straight line L0 away from the fourth straight line L4, the side wall of the last curved channel 111 in the arrangement direction X close to the first position P6 and the side wall 114a of the outlet channel 114 close to the fourth straight line L4 (or close to the reference straight line L0) have an intersection point Px in their orthographic projections on the reference plane A, the first position P6 of the last curved channel 111 in the arrangement direction X and the intersection point Px are located on the second straight line L2, the fourth straight line L4 and the second straight line L2 have an angle β, and the value range of the angle β is 15 to 30 degrees. Thus, each microchannel unit 110 of the microchannel structure 100 can make different inertial equilibrium positions of particles of different sizes in the flow channel more stable, so that the separation efficiency of the microchannel structure 100 is higher and the effective flow rate range redundancy is greater. At the same time, by parameterizing the angle β, better adjustment and optimization can be performed according to particles of different sizes, thereby obtaining an effective improvement plan, effectively improving the separation effect, and being applicable to a wider flow rate range.

For example, the value range of the angle β may also be 10 degrees to 90 degrees. For example, the angle β may be any angle between 10 degrees and 90 degrees.

In some examples, as shown in FIG. 3A , the orthographic projection of the side wall 114 a of the outlet flow channel 114 close to the fourth straight line L4 (or close to the reference straight line L0 ) on the reference plane A may coincide with the second straight line L2 .

In some examples, the width of the inlet channel 113 is the same as the width of the curved channel 111. For example, the height of the inlet channel 113 is the same as the height of the curved channel 111.

In some examples, the width of the outlet channel 114 is the same as the width of the curved channel 111. For example, the height of the outlet channel 114 is the same as the height of the curved channel 111.

In some examples, as shown in FIG3A , among the plurality of turning channels 112 located on the side of the reference straight line L0 away from the fourth straight line L4, the outer sidewall 112b of the first turning channel 112 and the outer sidewall 112b of the last turning channel 112 in the arrangement direction X are projected on the reference plane A on the fifth straight line L5. The fourth straight line L4 and the fifth straight line L5 are located on both sides of the reference straight line L0, respectively. In some examples, the fourth straight line L4 and the fifth straight line L5 may be parallel, that is, the angle γ between the fourth straight line L4 and the fifth straight line L5 is 0 degrees.

In some examples, as shown in FIG. 3A , the fourth straight line L4 and the fifth straight line L5 may have an angle γ, and the value range of the angle γ between the fourth straight line L4 and the fifth straight line L5 may be 15 to 30 degrees. Thus, each microfluidic unit 110 of the microfluidic structure 100 can make the different inertial equilibrium positions of particles of different sizes in the flow channel more stable, and thus the separation efficiency of the microfluidic structure 100 is higher and the effective flow rate interval redundancy is greater. At the same time, by parameterizing the angle γ, better adjustments and optimizations can be made according to particles of different sizes, thereby obtaining an effective improvement plan, effectively improving the separation effect, and being applicable to a wider flow rate range.

For example, the value range of the angle γ may also be 10 degrees to 90 degrees. For example, the angle γ may be any value between 10 degrees and 90 degrees.

FIG3B is a top view schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure. As shown in FIG3B , the reference straight line L0 is a straight line extending along the arrangement direction X and passing through the plurality of curved flow channels 111, and the plurality of second straight line segments of the plurality of turning flow channels 112 located on the same side of the reference straight line L0 are parallel to each other. For example, the second straight line segments of all or part of the turning flow channels 112 located on the same side of the reference straight line L0 are parallel to each other.

In some examples, as shown in Fig. 3B, the first straight line segments of the plurality of diverting channels 112 on the same side of the reference straight line L0 are parallel to each other. For example, the first straight line segments L of all or part of the diverting channels 112 on the same side of the reference straight line L0 are parallel to each other.

In some examples, as shown in Fig. 3B, the second straight line segments of the plurality of diverting channels 112 respectively located on both sides of the reference straight line L0 are parallel to each other. For example, all or part of the second straight line segments of the diverting channels 112 may be parallel to each other.

In some examples, as shown in Fig. 3B, the first straight line segments of the plurality of diverting channels 112 respectively located on both sides of the reference straight line L0 are parallel to each other. For example, all or part of the first straight line segments of the diverting channels 112 may be parallel to each other.

In some examples, as shown in Fig. 3B, the second straight line segments of the plurality of diverting channels 112 located on one side of the reference straight line L0 are located on the same straight line, and the second straight line segments of the plurality of diverting channels 112 located on the other side of the reference straight line L0 are parallel to each other. For example, the first straight line segments of the plurality of diverting channels 112 located on one side of the reference straight line L0 are located on the same straight line, and the first straight line segments of the plurality of diverting channels 112 located on the other side of the reference straight line L0 are parallel to each other.

In some examples, among the second straight line segments of the plurality of turning channels 112 located on the same side of the reference straight line L0 , some of the second straight line segments are parallel to each other, and some of the second straight line segments are located on the same straight line.

Fig. 3C is a top view schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure. As shown in Fig. 3C, the reference straight line L0 is a straight line extending along the arrangement direction X and passing through the plurality of curved channels 111, the plurality of second straight line segments of the plurality of turning channels 112 located on one side of the reference straight line L0 are located on the same straight line, and the plurality of second straight line segments of the plurality of turning channels 112 located on the other side of the reference straight line L0 are located on the same straight line, and the two straight lines are parallel.

FIG3D is a top view schematic diagram of another microchannel unit 110 provided in one embodiment of the present disclosure. As shown in FIG3D , both ends of the multiple second straight segments of the multiple turning channels 112 can be connected to the curved channel 111 through an arc. For example, the multiple first straight segments of the multiple turning channels 112 can also be connected to the curved channel 111 through an arc.

Figure 3E is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3F is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3G is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3H is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3I is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3J is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3K is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure; Figure 3L is a top schematic diagram of another microfluidic unit provided by an embodiment of the present disclosure.

As shown in FIG. 3E to FIG. 3L , by adjusting the arc radius r _max , the arc radius r _min , the number N, the width D, the spacing d, the angle β (or the angle γ), etc., different microfluidic unit 110 can be obtained. The disclosed embodiment is not limited thereto, and other forms of microfluidic unit 110 can also be obtained by adjusting the above parameters (for example, also including the angle θ and the angle α, etc.). Thus, the parameterized adjustment of the microfluidic unit 110 can be achieved. By defining multiple parameters of the microfluidic unit 110, various parameters are matched and optimized, and a parameterized microfluidic unit suitable for different use conditions can be obtained, thereby realizing the controllable modification of the microfluidic unit and the qualitative screening of particles above the cutoff size; and the separation effect of the microfluidic unit 110 can be effectively improved, thereby effectively improving the separation efficiency, and being applicable to a wider range of flow rates.

In some examples, the shape of the orthographic projection of one of the inner wall 112a and the outer wall 112b of the turning channel 112 on the reference plane A may be a straight line segment, and the shape of the orthographic projection of the other of the inner wall 112a and the outer wall 112b of the turning channel 112 on the reference plane A may be an arc.

FIG4 is a distribution simulation diagram of the secondary flow brought by different steering flow channels provided in the embodiment of the present disclosure. As shown in FIG4, different steering flow channels are shown on the left, and the distribution simulation diagram of the secondary flow of the corresponding steering flow channel at the dotted line position when the flow rate is 1 m/s is shown on the right. The color scale in the figure indicates the size of the flow rate. The darker the color, the greater the flow rate. The steering flow channel will affect the overall mode of focusing, and the influence of different steering flow channels on the secondary flow can be simulated using Comsol software. As shown in FIG4, different steering flow channels, for example, the inner wall and the outer wall of the steering flow channel can be arcs or straight line segments. After the particles pass through the steering flow channel, secondary flows can be formed. However, different steering flow channels have different sizes of secondary flows. Different steering flow channels can be selected according to the size of different particles and actual needs. Therefore, under the action of the secondary flow of the steering flow channel, particles of different sizes deviate from the center to different degrees, and under the action of the curved flow channel, particles of different sizes can be focused on different positions deviating from the center of the flow channel, so as to achieve the separation of particles of different sizes.

FIG5 is a schematic top view of a microfluidic structure provided by an embodiment of the present disclosure. As shown in FIG5 , the microfluidic structure 100 also includes a connecting channel 120, and the microfluidic structure 100 includes a plurality of microfluidic units 110, and the connecting channel 120 is located between two adjacent microfluidic units 110, and connects the two adjacent microfluidic units 110. The balance of particles requires a certain distance, and thus, the connection of a plurality of microfluidic units 110 can not only focus particles of two or more sizes at different positions, and achieve the separation of particles of different sizes; but also can make the inertial focusing position of the particles more stable, so that two or more sizes can achieve a stable separation effect, and the separation efficiency is high, thereby further reducing the sensitivity of dependence on the microfluidic structure, so that the microfluidic structure has good robustness.

In addition, the microfluidic structure 100 further increases the redundancy of the effective flow rate range, so that it can be applied to a wider range of flow rates. For example, the stable and available flow rate range reaches 1mL/min, which better solves the problem of flow rate sensitivity; at the same time, the connection of multiple microfluidic units 110 can further increase the flow rate of the microfluidic structure 100, thereby improving the processing efficiency of the microfluidic structure 100, so that it has the characteristics of high throughput and high efficiency. The microfluidic structure 100 is also easy to manufacture, easy to operate, and not easily interfered by impurities, and has a broad application space.

In some examples, as shown in FIG. 5 , the orthographic projection of the connecting flow channel 120 on the reference plane A may be a straight line segment, a circular arc, a broken line segment, etc., which is not limited in the present disclosure.

For example, as shown in FIG. 5 , the connecting channel 120 connects the curved channels 111 of two adjacent micro-channel units 110 .

In some examples, as shown in FIG5 , the multiple microfluidic units 110 of the microfluidic structure 100 are sequentially arranged along the arc a1, and the arc a1 is bent toward the second position PM; the second position PM and the multiple first positions PN of the multiple curved channels 111 of any microfluidic unit 110 are located on the same side of the arc a1. Therefore, sequentially arranging along the arc a1 can not only make the inertial focusing position of particles of different sizes more stable and the separation efficiency high, but also have the effects of small size, high space utilization, high integration, etc.

In some examples, as shown in FIG5 , the plurality of microfluidic units 110 of the microfluidic structure 100 include a first microfluidic unit 110a, a second microfluidic unit 110b, and a third microfluidic unit 110c sequentially arranged in the extending direction of the arc a1, the last curved channel 111 of the first microfluidic unit 110a in its arrangement direction X is connected to the last curved channel 111 of the second microfluidic unit 110b in its arrangement direction X through a connecting channel 120, and the first curved channel 111 of the second microfluidic unit 110b in its arrangement direction X is connected to the first curved channel 111 of the third microfluidic unit 110b in its arrangement direction X through a connecting channel 120. Thus, the plurality of microfluidic units 110 are connected through the connecting channel 120.

In some examples, as shown in FIG. 5 , the lengths of the plurality of curved channels 111 of any microchannel unit 110 of the microchannel structure 100 gradually decrease in the arrangement direction X of the microchannel unit 110 .

In some examples, as shown in FIG. 5 , the second position PM overlaps with the plurality of first positions PN of the plurality of curved channels 111 of any one of the micro-channel units 110 .

In some examples, as shown in Figure 5, the microfluidic structure 100 also includes an inlet 130 and an outlet 140, the inlet 130 is connected to the first microfluidic unit 110 in the extension direction of the arc a1, specifically, it is connected to the first curved channel 111 of the microfluidic unit 110 in its arrangement direction X; the outlet 140 is connected to the last microfluidic unit 110 in the extension direction of the arc a1, specifically, it is connected to the last curved channel 111 of the microfluidic unit 110 in its arrangement direction X.

FIG6A is a top view schematic diagram of another microfluidic structure provided by an embodiment of the present disclosure. As shown in FIG6A , a plurality of microfluidic units 110 can be arranged in sequence along a circumferential line, and two adjacent microfluidic units 110 are connected by a connecting channel 120. Thus, arranging in sequence along a circumferential line can not only make the inertial focusing position of particles of different sizes more stable and the separation efficiency high; it also further improves the space utilization and integration, and further reduces the size of the microfluidic structure under the premise of the same number of microfluidic units.

In some examples, as shown in FIG6A , two different microfluidic units 110 arranged in sequence along a circumferential line constitute a basic microfluidic structure 100a, and multiple basic microfluidic structures 100a are arranged in sequence along a circumferential line, and two adjacent basic microfluidic structures 100a are connected by a connecting channel 120. With such a design, the microfluidic unit 110 can be better arranged, and the space utilization and integration can be further improved. The present disclosure is not limited to this, and the same microfluidic unit 110 can also be arranged in sequence along a circumferential line, or more than two different microfluidic units 110 can be arranged in sequence along a circumferential line.

In some examples, as shown in FIG. 6A , two different microfluidic channel units 110 constituting a basic microfluidic channel structure 100 a have the same structure except for the number N and the arc radius r _max .

In some examples, the multiple microfluidic units 110 in the basic microfluidic structure 100a may not be arranged along a circular line. For example, the multiple microfluidic units 110 in the basic microfluidic structure 100a may be arranged along an arc or in any direction, and then the basic microfluidic structure 100a is arranged in sequence along a circular line.

In some examples, as shown in FIG. 6A , the plurality of microfluidic units 110 include a first microfluidic unit 110a, a second microfluidic unit 110b, and a third microfluidic unit 110c that are sequentially arranged on a circular line, the last curved channel 111 of the first microfluidic unit 110a in its arrangement direction X is connected to the last curved channel 111 of the second microfluidic unit 110b in its arrangement direction X via a connecting channel 120, and the first curved channel 111 of the second microfluidic unit 110b in its arrangement direction X is connected to the first curved channel 111 of the third microfluidic unit 110c in its arrangement direction X via a connecting channel 120.

In some examples, as shown in FIG. 6A , the lengths of the plurality of curved channels 111 of any micro-channel unit 110 gradually decrease in the arrangement direction X of the micro-channel unit 110 .

In some examples, as shown in FIG6A , the center O of the circumference along which the multiple microfluidic units 110 or the multiple basic microfluidic structures 100a are located overlaps with the multiple first positions PN of the multiple curved channels 111 of any microfluidic unit 110. Thus, the space utilization and integration are further improved, and the size of the microfluidic structure is further reduced.

In some examples, as shown in Fig. 6A, the microfluidic channel structure 100 may further include an inlet 130 and an outlet 140. For example, the positions of the inlet 130 and the outlet 140 may be interchanged.

6A , the width of the inlet 130 and the outlet 140 of the microfluidic channel structure 100 is the same as the width of the curved channel 111. For example, the height of the inlet 130 and the outlet 140 of the microfluidic channel structure 100 is the same as the height of the curved channel 111.

FIG6B is an experimental diagram of the focusing position of particles in the microfluidic structure shown in FIG6A as the Reynolds number changes. As shown in FIG6B , the use of fluorescent particles can demonstrate the focusing position or focusing mode of particles as the Reynolds number or flow rate changes. The horizontal axis represents the Reynolds number (Re), and the vertical axis represents the focusing position of the particles in the flow channel of the outlet 140. The middle position of the vertical axis is the center of the flow channel, and the maximum position of the vertical axis is the width of the flow channel. In the experiment, the focusing mode of the particles can be divided into several stages as the Reynolds number (or flow rate) changes:

The first stage is the incomplete focusing stage, that is, when the Reynolds number is small, the particles cannot be completely gathered because the flow rate is too low. The particles are distributed on both sides of the flow channel but the focusing width is large; the second stage is the "double focusing" stage. At a position close to both sides of the flow channel but still with a certain distance, the focusing behavior dominated by the inertial lift makes the particles focus near the equilibrium position; the third stage is the transition stage, that is, the particles gradually transition from the "double focusing" of the previous stage to the "single focusing" of the latter stage. The particles will gradually approach the center from both sides and transform from two focusing flows to one focusing flow. The fourth stage is the "single focusing" stage, that is, the particles are focused into a focusing flow, which is close to the center of the flow channel. For symmetrical structures, the focusing position is at the center, and for asymmetrical structures, the focusing position will be a certain distance from the center; the fifth stage is the defocusing stage. With the increase of the Reynolds number, the influence of the secondary flow on the focusing becomes greater and greater, and it is difficult for the particles to maintain a focused state. In actual experiments, due to the limitations of the interface of the microfluidic structure and the pressure that the injection pump can withstand, the measurement of this part is somewhat difficult.

As shown in Figure 6B, in the first and fifth stages, the particles failed to fully aggregate or were difficult to maintain a focused state, making the measurement of this part somewhat difficult. State 1 to State 4 is the second stage (also known as the "double focusing" stage), State 5 to State 7 is the third stage (also known as the transition stage), and State 8 to State 12 is the fourth stage (single focusing stage). It can be concluded that after the Reynolds number (or flow rate) of the microfluidic structure reaches a certain value, the particles can be focused at a certain position deviating from the center of the flow channel, and the corresponding Reynolds number (or flow rate) has a wide range of values, which can solve the problem of flow rate sensitivity.

Figure 6C is a schematic diagram of the focusing position of three-sized particles of the microfluidic structure shown in Figure 6A when r _min = 2mm, β = 22.5 degrees as the flow rate changes; Figure 6D is a schematic diagram of the focusing position of three-sized particles of the microfluidic structure shown in Figure 6A when r _min = 6.05mm, β = 22.5 degrees as the flow rate changes; Figure 6E is a schematic diagram of the focusing position of three-sized particles of the microfluidic structure shown in Figure 6A when r _min = 12.8mm, β = 22.5 degrees as the flow rate changes; Figure 6F is a schematic diagram of the focusing position of three-sized particles of the microfluidic structure shown in Figure 6A when r _min = 6.05mm, β = 30 degrees as the flow rate changes; Figure 6G is a schematic diagram of the focusing position of three-sized particles of the microfluidic structure shown in Figure 6A when r _min = 6.05mm, β = 45 degrees as the flow rate changes.

As shown in Figures 6C to 6F, using fluorescent particles of different sizes can demonstrate the focusing position or focusing mode of the particles as the Reynolds number or flow rate changes. The horizontal axis represents the flow rate, the vertical axis represents the focusing position of the particles in the flow channel at the outlet 140, the middle position of the vertical axis is the center of the flow channel, and the maximum position of the vertical axis is the width of the flow channel. In order to more clearly show the focusing state, we plotted the focusing positions of particles of different sizes (15μm, 10μm, 7.5μm) in the flow channel based on the half-width at half-height of the particle focus (that is, the half-width at half-height of the fluorescence intensity distribution).

As shown in Figures 6C to 6E, when the angle β is equal to 22.5 degrees, the focusing effect of three sizes of particles (15μm, 10μm, 7.5μm) when the arc radius _rmin is equal to 2mm, 6.05mm, and 12.8mm respectively. When the arc radius _rmin is equal to 6.05mm, the three sizes of particles can be well focused and separated, and after the flow rate is greater than 1.8mL/min, the stable and available flow rate range reaches 1mL/min; when the arc radius _rmin is equal to 2mm, the three sizes of particles can also be well aggregated and separated within the variable flow rate range of 0.5mL/min; the flow rate sensitivity problem (<0.1mL/min) of inertial focusing in the prior art is solved, so the microfluidic structure under this parameter can be applicable to a wider flow rate range, with a simple structure, stable effect and convenient manufacturing. Arcs of different radii have different effects on the focusing effect. The smaller the radius, the stronger the secondary flow generated by the arc, and the greater the impact on the result. Therefore, the influence of the arc with the smallest radius on the result is obvious. The software can be used to simulate the influence of the arc radius _rmin in the microfluidic structure on the focusing state of particles of different sizes, so that the optimal value range can be selected more conveniently and quickly.

As shown in FIG. 6D , FIG. 6F and FIG. 6G , when the arc radius r _min is equal to 6.05 mm, the focusing effect of three sizes of particles (15 μm, 10 μm, 7.5 μm) when the angle β is equal to 22.5 degrees, 30 degrees, and 45 degrees, respectively, when the angle β is equal to 22.5 degrees and 30 degrees, the three sizes of particles can be well focused and separated, and after the flow rate is greater than 1.8 mL/min, the stable and available flow rate range reaches 1 mL/min; therefore, the microfluidic structure under this parameter can be applied to a wider flow rate range, solving the problem of flow rate sensitivity. At the same time, when the angle β is within a certain value range (for example, between 22.5 degrees and 30 degrees), the focusing and separation of particles of three sizes can be achieved, thereby reducing the sensitivity of dependence on the microfluidic structure, making the microfluidic structure have good robustness. The angle β affects the time of the arc for the focusing effect. The larger the angle β, the longer it takes for the particles to pass through the arc, and the greater the impact on the focusing and separation results. The software can be used to simulate the effect of the angle β in the microfluidic structure on the focusing state of particles of different sizes, so that the optimal value range can be selected more conveniently and quickly.

In some examples, other parameters in the microfluidic channel structure may also be adjusted, such as the arc radius r _max , the number N, the width D, the spacing d, etc., so as to achieve parameterization of the microfluidic channel structure.

Figure 7A is a top view schematic diagram of another microfluidic structure provided by an embodiment of the present disclosure; Figure 7B is a top view schematic diagram of the microfluidic structure shown in Figure 7A after being repeated four times; and Figure 7C is an experimental diagram of the particle focusing position of the microfluidic structure shown in Figure 7A at different numbers of repetitions.

In some examples, as shown in FIG. 7A and FIG. 7B , the microfluidic structure 100b shown in FIG. 7A is arranged in sequence along the arc a1 to obtain the microfluidic structure 100c shown in FIG. 7B ; two adjacent microfluidic structures 100b are connected by a connecting channel 120. The center of curvature O of the arc a1 coincides with the first position PN of any microfluidic unit 110 of the microfluidic structure 100c. FIG. 7B is a schematic diagram of the microfluidic structure 100b repeated four times, that is, the number of microfluidic structures 100b is 4. For example, the number of repetitions is represented by q, and when the number of repetitions q takes different values, it corresponds to different microfluidic structures. For example, as shown in FIG. 7B , the repeated microfluidic structures all have an inlet 130 and an outlet 140, and the width and height of the inlet 130 and the outlet 140 are respectively the same as the width and height of the curved channel 111.

In some examples, as shown in FIG7C, the microfluidic structure 100b shown in FIG7A is repeated multiple times, and the focus positions of the outlet 140 of the microfluidic structure 100c of particles of three sizes (15 μm, 10 μm, 7.5 μm) under different repetition numbers q are plotted according to the half-height width of particle focus (i.e., the half-height width of fluorescence intensity), the horizontal axis is the number of repetitions, the vertical axis is the focus position of the particle in the flow channel of the outlet 140, the flow channel width D of the microfluidic structure 100c is 500 μm, and the center position is at the vertical coordinate 250 μm. As shown in FIG7C, when the number of microfluidic structures 100b shown in FIG7A is 4, that is, corresponding to the structure shown in FIG7B, the focus positions of particles of three sizes (15 μm, 10 μm, 7.5 μm) are stably separated, that is, particles of three sizes can be focused at different positions off the center, and can be effectively separated. The equilibrium of the particles requires a certain distance, and thus a series of repetitions of the microfluidic channel structure 100 or the microfluidic channel unit 110 can be performed to achieve a stable separation effect of the particles.

In some examples, by increasing the number of repetitions q, the flow rate of the microfluidic structure 100 can be further increased, thereby improving the processing efficiency of the microfluidic structure 100, thereby having the characteristics of high throughput and high efficiency. For example, the flow rate of a single separation unit of the microfluidic structure 100 can reach 3 mL/min, reaching the maximum processing capacity of the current existing technology.

Fig. 8A is a schematic diagram of another microfluidic structure provided by an embodiment of the present disclosure. As shown in Fig. 8A, a plurality of microfluidic units 110 of the microfluidic structure 100 are arranged in sequence along a first direction Y, and the angle between the arrangement directions X of two adjacent microfluidic units 110 ranges from 0 to 45 degrees.

In some examples, as shown in FIG. 8A , two adjacent microfluidic units 110 include a first microfluidic unit 110a and a second microfluidic unit 110b, and the first microfluidic unit 110a and the second microfluidic unit 110b are adjacent to each other in a first direction Y; the last curved channel 111 of the first microfluidic unit 110a in its arrangement direction X is connected to the first curved channel 111 of the second microfluidic unit 110b in its arrangement direction X through a connecting channel 120.

Fig. 8B is a schematic diagram of a microfluidic structure provided by an embodiment of the present disclosure. As shown in Fig. 8B, the multiple microfluidic units 110 of the microfluidic structure 100 are arranged in sequence along the second direction Z, and the angle between the arrangement directions X of two adjacent microfluidic units 110 ranges from 145 degrees to 180 degrees.

In some examples, as shown in Figure 8B, two adjacent microfluidic units 110 include a first microfluidic unit 110a and a second microfluidic unit 110b, and the first microfluidic unit 110a and the second microfluidic unit 110b are adjacent to each other in the second direction Z; the last curved channel 111 of the first microfluidic unit 110a in its arrangement direction X is connected to the first curved channel 111 of the second microfluidic unit 110b in its arrangement direction X through a connecting channel 120.

At least one embodiment of the present disclosure further provides a microfluidic chip. The microfluidic chip includes any of the above-mentioned microfluidic structures, so that the microfluidic chip can have the beneficial effects corresponding to the beneficial effects of the microfluidic structure, which will not be repeated here.

FIG9A is a schematic diagram of a microfluidic chip provided by an embodiment of the present disclosure; FIG9B is a partially enlarged schematic diagram of the first separation structure shown in FIG9A. As shown in FIG9A and FIG9B, the microfluidic chip 200 includes a microfluidic structure 100 and a first separation structure 210, the microfluidic structure 100 includes an inlet 130 and an outlet 140, the first separation structure 210 includes a first sub-inlet 211 and a plurality of first sub-outlets 212, for example, as shown in FIG9A and FIG9B, the first separation structure 210 includes a first sub-inlet 211 and four first sub-outlets 212, for example, the four first sub-outlets 212 are 212a, 212b, 212c and 212d respectively; the first sub-inlet 211 is connected to the outlet of the microfluidic structure 100. Thus, particles of different sizes can be separated to different first sub-outlets 212 through the first separation structure 210.

For example, as shown in Figures 9A and 9B, the size (width and height) of the inlet 130 of the microfluidic structure 100 is the same as the size (width and height) of the curved channel 111; for example, the size (width and height) of the outlet 140 of the microfluidic structure 100 is the same as the size (width and height) of the curved channel 111; for example, the size (width and height) of the first sub-inlet 211 of the first separation structure 210 is the same as the size (width and height) of the outlet 140 of the microfluidic structure 100.

For example, at least one sub-outlet 212 of the first separation structure 210 can be further connected to a separation structure; for example, the first separation structure can be connected to multiple separation structures in sequence. For example, at least one sub-outlet 212 of the first separation structure 210 can also be connected to multiple separation structures at the same time. Thus, by adding a separation structure, the flow rate and separation efficiency of the microfluidic chip can be further improved. At the same time, by adding a separation structure, the separated particles can also be concentrated to obtain highly concentrated particles.

For example, the first separation structure can further improve the separation efficiency of the microfluidic chip 200 by sequentially connecting multiple separation structures.

FIG. 9C is a schematic diagram of the separation of particles of different sizes in the first separation structure shown in FIG. 9A ; and FIG. 9D is an enrichment diagram of particles of different sizes collected at the four first sub-outlets shown in FIG. 9A . As shown in FIG9C , particles of different sizes are in the focusing position or focusing mode of the microfluidic chip 200, and the three sizes are 15 μm, 10 μm and 7.5 μm, respectively. The secondary flow of the microfluidic structure 100 of the microfluidic chip 200 affects the focusing position of the particles of the three sizes, so that the particles of the three sizes are focused at different positions off the center, thereby achieving effective focusing and separation. As shown in FIG9C , particles of 15 μm are focused at a position close to the center of the flow channel of the outlet 140 of the microfluidic structure 100, particles of 10 μm are focused at a position off the center, and particles of 7.5 μm are focused on both sides farther off the center. After the three different sizes of particles pass through the first sub-inlet 211 and the four first sub-outlets 212 of the first separation structure 210, the separation of the particles is achieved, and the particles of 15 μm flow into the first sub-outlet 212b, the particles of 10 μm flow into the first sub-outlet 212c, and the particles of 7.5 μm flow into the first sub-outlets 212a and 212d. As shown in FIG9D , the enrichment diagram of particles of different sizes collected by three sizes of particles through four first sub-outlets is shown. Thus, the microfluidic chip 200 realizes the separation and collection of particles of different sizes. By statistically analyzing FIG9D , the separation efficiency of particles of different sizes is as high as 99.8%. Thus, by appropriately adjusting the design parameters of the microfluidic structure 100 of the microfluidic chip 200 and the connection mode between the microfluidic units 110 or between the microfluidic structures 100, the design of the microfluidic chip 200 for a specific cutoff diameter (that is, the minimum diameter of the particles to be collected) can be obtained. The focusing position of particles of different sizes is affected by the secondary flow of the microfluidic chip 200, so that particles of different sizes can be focused at different positions of the flow channel within a wide flow rate range, and can be orderly distributed according to the size of different sizes. At the same time, a suitable flow distribution is designed for the multiple first sub-outlets 212 of the first separation structure 210 to collect the desired size interval, and the separation of particles of different sizes can be achieved by matching the outlet flow resistance.

In some examples, as shown in Figures 9A and 9B, the multiple first sub-outlets 212 of the first separation structure 210 of the microfluidic chip 200 can also be designed with appropriate widths, as well as the position of the first separation structure 210 relative to the first sub-inlet 211, so as to collect and separate particles of different sizes focused at different positions, thereby allowing particles of different sizes focused at different positions to flow into different first sub-outlets 212.

In some examples, as shown in FIG9A , the microfluidic chip 200 may further include a filtering structure 230 , which is in communication with the inlet 130 of the microfluidic structure 100 and is configured to have a filtering function. For example, the filtering structure 230 may filter impurities.

Fig. 10A is a schematic diagram of another microfluidic chip provided by an embodiment of the present disclosure. As shown in Fig. 10A, the difference between the microfluidic chip 200 and the microfluidic chip 200 shown in Fig. 9A is that the first separation structure 210 is different. The first separation structure 210 shown in Fig. 10A has three first sub-outlets 212, namely, first sub-outlets 212a, 212b and 212c.

FIG. 10B is a capture efficiency diagram of the target particles in whole blood captured by the microfluidic chip shown in FIG. 10A; FIG. 10C is an enrichment diagram of human breast cancer cells spiked into whole blood at three outlets of the microfluidic chip shown in FIG. 10A. As shown in FIG. 10B, the capture efficiency of the target particles (particle sizes of 10 μm and 15 μm, respectively) in undiluted whole blood was verified using the microfluidic chip 200 shown in FIG. 10A. The particles of the two sizes were collected by the microfluidic chip 200 shown in FIG. 10A at different flow rates (2.4 mL/min, 2.5 mL/min, 2.6 mL/min), and the capture efficiencies of the particles of the two sizes (10 μm, 15 μm) were 75% ± 3% and 81% ± 2%, respectively. Therefore, although the collision between cells in whole blood makes it extremely difficult to focus the target cells, and the focus width of the target particles becomes larger, by using the microfluidic chip 200 shown in Figure 10A, it is also possible to achieve efficient collection of target particles in whole blood, and by setting and matching the flow resistance at the multiple first sub-outlets 212 of the first separation structure 210, the optimal collection interval corresponding to particles of different sizes can be found, thereby effectively separating the target particles in undiluted whole blood and improving the separation efficiency.

In some examples, as shown in Figures 10B and 10C, human breast cancer cells are added to whole blood, and the capture efficiency of human breast cancer cells is verified using the microfluidic chip 200 shown in Figure 10A. At three flow rates (2.4mL/min, 2.5mL/min, 2.6mL/min), the capture efficiency of human breast cancer cells is about 70%, and high-efficiency collection of human breast cancer cells in whole blood can be achieved. As shown in Figure 10C, it is an enrichment diagram of human breast cancer cells at three sub-outlets of the microfluidic chip 200. As shown in the figure, human breast cancer cells are basically collected through the first sub-outlet 212b, with high collection efficiency.

FIG. 11A is a schematic diagram of the structure of another microfluidic chip provided by an embodiment of the present disclosure; FIG. 11B is a schematic diagram of the separation of particles of different sizes at the first separation structure shown in FIG. 11A; FIG. 11C is a schematic diagram of the separation of particles of different sizes at the second separation structure shown in FIG. 11A; and FIG. 11D is a schematic diagram of the separation of particles at the third separation structure shown in FIG. 11A. As shown in FIG. 11A to FIG. 11D, the microfluidic chip 200 includes a filtration structure 230, a microfluidic structure 100, a first separation structure 210, a second separation structure 220, a third separation structure 240, and a plurality of flow channel structures 250. The filtering structure 230 is connected to the inlet 130 of the microfluidic channel structure 100. The first separation structure 210 includes a first sub-inlet 211a and three first sub-outlets 212a, 212b and 212c. The first sub-inlet 211a is connected to the outlet 140 of the microfluidic channel structure 100. The first sub-outlets 212a, 212b and 212c are connected to the flow channel structure 250a, the flow channel structure 250b and the flow channel structure 250c respectively; the first sub-outlet 212c is connected to the second separation structure 220 through the flow channel structure 250c; the second separation structure 220 includes a second sub-inlet 221 and three second sub-outlets 222a, 222b and 222c, and the second sub-inlet 221 is connected to the outlet 140 of the microfluidic channel structure 100. The first sub-outlets 212a, 212b and 212c are connected to the flow channel structure 250a, the flow channel structure 250b and the flow channel structure 250c respectively; the first sub-outlet 212c is connected to the second separation structure 220 through the flow channel structure 250c; the second separation structure 220 includes a second sub-inlet 221 and three second sub-outlets 222a, 222b and 222c. 221 is connected to the outlet of the flow channel structure 250c, the three second sub-outlets 222a, 222b and 222c are respectively connected to the flow channel structure 250d, the flow channel structure 250e and the flow channel structure 250f, and the second sub-outlet 222c is connected to the third separation structure 240 through the flow channel structures 250f and 250g; the third separation structure 240 includes a third sub-inlet 241 and three third sub-outlets 242a, 242b and 242c, the third sub-inlet 241 is connected to the outlet of the flow channel structure 250g, and the three third sub-outlets 242a, 242b and 242c are respectively connected to the flow channel structure 250h, the flow channel structure 250i and the flow channel structure 250j.

In some examples, as shown in Figures 11A to 11D, the flow channel structures 250c, 250f, and 250g may be serpentine flow channels. For example, the flow channel structures 250c, 250f, and 250g may be asymmetric serpentine structures.

In some examples, as shown in FIGS. 11A to 11D , the flow channel structures 250 a , 250 b , 250 d , 250 e , 250 h , 250 i , and 250 j may be configured to match the function of flow resistance.

For example, as shown in FIGS. 11A to 11D , the flow channel structures 250 a , 250 b , 250 d , 250 e , 250 h , 250 i and 250 j may be serpentine structures, zigzag structures, I-shaped structures, etc., and the present disclosure does not limit this.

In some examples, as shown in FIGS. 11A to 11D , particles of different sizes are used in the focusing position or focusing mode of the microfluidic chip 200, and the sizes of the three particles are 15 μm, 10 μm, and 7.5 μm, respectively. The influence of the secondary flow of the microfluidic structure 100 of the microfluidic chip 200 on the focusing position can make the particles of the three sizes focused at different positions off the center, thereby achieving effective focusing and separation. As shown in FIGS. 11A and 11B , particles of 15 μm are focused near the center of the flow channel of the first sub-inlet 211 of the first separation structure 210, particles of 10 μm are focused off the center, and particles of 7.5 μm are focused farther off the center. Through the separation action of the first separation structure 210, particles of 15 μm and 10 μm flow into the first sub-outlet 212c, and particles of 7.5 μm flow into the first sub-outlet 212b.

For example, as shown in FIG. 11A and FIG. 11C , the first sub-outlet 212c can be connected to the flow channel structure 250c, and the flow channel structure 250c is a serpentine flow channel. With the help of the serpentine flow channel structure 250c, the particles collected by the first sub-outlet 212c can be further focused and separated to increase the concentration multiple. For example, the collected particles can be further focused and separated according to the empirical parameters in the serpentine flow channel 250c to increase the concentration multiple. After the 15μm and 10μm particles are further focused and separated through the serpentine flow channel 250c, they flow to the second sub-inlet 221 of the second separation structure 220, the 15μm particles flow into the second sub-outlet 222c, and the 10μm particles flow into the second sub-outlets 222b located on both sides.

For example, as shown in FIG. 11A and FIG. 11D , the second sub-outlet 222c can be connected to the flow channel structure 250f, which is a serpentine flow channel. With the help of the serpentine flow channel structures 250f and 250g, the particles collected by the second sub-outlet 222c can be further focused and separated, so that the concentration multiple can be further improved. After the 15 μm particles are further focused and separated by the serpentine flow channel structures 250f and 250g, they flow to the third sub-inlet 241 of the third separation structure 240, and flow into the third sub-outlet 250j after passing through the third separation structure 240. Through separation by multiple separation structures and further focusing separation by multiple serpentine flow channel structures, the concentration multiple of the particles finally obtained is greatly improved compared with separation by only separation structures; when separation is performed by only separation structures, the concentration multiple can only reach 3-4 times, which is difficult to improve further; the use of the above-mentioned microfluidic chip 200 can not only separate particles of different sizes, but also improve the concentration multiple of particles passing through the serpentine flow channel structure, especially the concentration multiple of particles obtained by the last separation structure is greatly improved, so that the particles can be concentrated at a high concentration. The disclosed embodiment does not limit the serpentine flow channel structure for further focusing separation, for example, it can also be other forms of flow channel structures, and there is no limit on the number of further focusing separations.

In some examples, as shown in FIG. 11A to FIG. 11D, the width D of the curved channel 111 of the microfluidic structure 100 of the microfluidic chip 200 is set to 500 μm, and the flow rate of the first separation structure 210 flowing into the microfluidic chip 200 is between 2-3 mL/min and the flow rate of the second separation structure 220 flowing into the microfluidic chip 200 is between 0.6-0.9 mL/min through the pump. The width of the flow channel structure 250c connected to the first sub-outlet 212c of the first separation structure 210 is 260 μm. Through the 260 μm wide flow channel structure 250c, in a narrow flow rate range, large-sized cells can be focused in the middle of the flow channel, and particles below the target size focused on both sides of the flow channel can be further removed. The flow rate flowing into the third separation structure 240 is between 0.15-0.22 mL/min. In order to further focus and separate the collected particles, the width of the flow channel structure 250g is set to 500 μm, and the symmetry of the particle focusing is destroyed by adjusting the serpentine flow channel structure, so that the particles are focused on a single side of the flow channel and collected through the third sub-outlet 242c. At this time, the concentration multiple of the collected particles is about 80 times.

FIG11E is a schematic diagram of the capture efficiency of target particles using the microfluidic chip shown in FIG11A under different conditions. As shown in FIG11E , using the microfluidic chip 200 shown in FIG11A , the capture efficiency of particles (beads) of different sizes is as high as 99.8%; the capture efficiency of human breast cancer cells (mcf-7) in phosphate buffered saline (PBS) is about 95%; the capture efficiency of human breast cancer cells (mcf-7) in ten-fold diluted blood (10×blood) is about 85%. Therefore, using the microfluidic chip 200, the collection of target particles can be well achieved with high capture efficiency.

Fig. 11F is an enrichment diagram of human breast cancer cells collected in phosphate buffered saline using the microfluidic chip shown in Fig. 11A. As shown in Fig. 11F, using the microfluidic chip 200 shown in Fig. 11A, not only can the human breast cancer cells in the phosphate buffered saline be separated, but also the human breast cancer cells can be concentrated to a high concentration.

FIG11G is a diagram of collecting human breast cancer cells and waste liquid in ten-fold diluted blood using the microfluidic chip shown in FIG11A. As shown in FIG11G, from left to right are the first-level waste liquid of the first separation structure 210, the second-level waste liquid of the second separation structure 220, the third-level waste liquid of the third separation structure 240, and the collected liquid. Using the microfluidic chip 200 shown in FIG11A, not only can the separation of human breast cancer cells in ten-fold diluted blood be achieved, but also the human breast cancer cells can be concentrated to a high concentration.

There are a few points to note about this disclosure:

(1) The drawings of the embodiments of the present disclosure only relate to the structures related to the embodiments of the present disclosure, and other structures may refer to the general design.

(2) The various components or structures in the drawings are not drawn strictly according to scale. For the sake of clarity, the sizes of the various components or structures may be exaggerated or reduced, but these should not be used to limit the scope of the present disclosure.

(3) In the absence of conflict, the embodiments of the present disclosure and the features therein may be combined with each other to obtain new embodiments.

The above are only specific embodiments of the present disclosure, but the protection scope of the present disclosure is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present disclosure, which should be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.

Claims (24)

1. A micro flow channel structure comprising at least one micro flow channel unit, wherein each micro flow channel unit comprises:

the plurality of curved flow channels are distributed at intervals along the arrangement direction; and

A plurality of turning flow passages, each turning flow passage is positioned between two adjacent bending flow passages and communicated with two adjacent bending flow passages,

Wherein two diversion flow passages communicated with one bending flow passage are respectively positioned at two ends of the bending flow passage,

Each of the curved flow passages has opposite first and second sides in the arrangement direction, and each of the curved flow passages is curved toward a first position located at the second side.

2. The micro flow channel structure according to claim 1, wherein a plurality of the first positions of the plurality of curved flow channels are located on the same side of the plurality of curved flow channels in the arrangement direction.

3. The micro flow channel structure according to claim 1, wherein lengths of the plurality of curved flow channels gradually change along the arrangement direction.

4. The micro flow channel structure according to claim 1, wherein each of the curved flow channels is a circular arc-shaped flow channel, and the first position of each of the curved flow channels is a center of curvature of the curved flow channel.

5. The micro flow channel structure according to claim 4, wherein a plurality of the first positions of the plurality of curved flow channels are located on the same straight line.

6. The micro flow channel structure according to claim 4, wherein a plurality of the first positions of the plurality of curved flow channels overlap each other.

7. The micro flow channel structure according to any one of claims 4 to 6, wherein lengths of the plurality of curved flow channels become gradually smaller along the arrangement direction;

Among the plurality of curved flow channels, the arc radius of the curved flow channel with the longest length is r _max, and the value range of r _max is 10mm to 50mm; the arc radius of the curved flow channel with the shortest length is r _min, and the value range of r _min is 1mm to 20mm.

8. The micro flow channel structure according to any one of claims 1 to 6, wherein the number of the plurality of curved flow channels is N, and the value of N ranges from 2 to 50.

9. The micro flow channel structure according to claim 8, wherein the value of N ranges from 4 to 8.

10. The micro flow channel structure according to claim 6, wherein lengths of the plurality of curved flow channels are gradually reduced along the arrangement direction, the plurality of curved flow channels are equidistantly arranged, and the following formula is satisfied between parameters of the micro flow channel unit:

(N-1)·d+N·D＝r_max-r_min

Wherein N is the number of the plurality of curved flow channels, D is the distance between two adjacent curved flow channels, D is the width of each of the plurality of curved flow channels, r _max is the arc radius of the curved flow channel with the longest length, and r _min is the arc radius of the curved flow channel with the shortest length.

11. The micro flow channel structure according to any one of claims 1 to 6, wherein each of the turning flow channels includes an inner side wall and an outer side wall, the inner side wall being disposed opposite to the outer side wall and being located on a side of the outer side wall near a space between two adjacent curved flow channels.

12. The micro flow channel structure according to claim 11, wherein the orthographic projection of the inner side wall on a reference plane is shaped as a first circular arc, the orthographic projection of the outer side wall on the reference plane is shaped as a second circular arc, and the reference plane is parallel to the arrangement direction and the extending direction of each of the curved flow channels.

13. The micro flow channel structure according to claim 12, wherein, among the plurality of diverting flow channels located on the same side of a reference straight line extending in the arrangement direction and passing through the plurality of curved flow channels, an orthographic projection of the outer side wall of the first and last diverting flow channels in the arrangement direction on the reference plane is tangential to a first straight line.

14. The micro flow channel structure of claim 13, further comprising:

an inlet flow passage communicating with a first one of the curved flow passages in the arrangement direction; and

An outlet flow passage communicating with the last one of the curved flow passages in the arrangement direction,

The outlet flow channel and the first straight line are respectively positioned at two sides of a reference straight line extending along the arrangement direction and passing through the plurality of curved flow channels, the orthographic projection of the side wall, close to the first position, of the last curved flow channel in the arrangement direction and the side wall, close to the first straight line, of the outlet flow channel on the reference plane is provided with an intersection point, the first position of the last curved flow channel in the arrangement direction and the intersection point are positioned on a second straight line, the first straight line and the second straight line are provided with an included angle theta, and the value range of the theta is 10-90 degrees.

15. The micro flow channel structure of claim 14, wherein the value of θ ranges from 15 degrees to 30 degrees.

16. The micro flow channel structure according to claim 11, wherein the shape of the orthographic projection of the inner side wall on a reference plane is a first straight line segment, the shape of the orthographic projection of the outer side wall on the reference plane is a second straight line segment, and the reference plane is parallel to the arrangement direction and the extending direction of each of the curved flow channels.

17. The micro flow channel structure according to claim 16, wherein a plurality of the second straight line segments of the plurality of diverting flow channels located on the same side of a reference straight line extending in the arrangement direction and passing through the plurality of curved flow channels are parallel to each other.

18. The micro flow channel structure according to any one of claims 1-6, wherein the ratio of the width to the height of the plurality of curved flow channels is in a range of 1 to 20, and the height of the plurality of curved flow channels is in a range of 10 μm to 150 μm.

19. The micro flow channel structure according to any one of claims 1 to 6, further comprising a connecting flow channel,

The micro-channel structure comprises a plurality of micro-channel units, and the connecting channels are positioned between two adjacent micro-channel units and are communicated with the two adjacent micro-channel units.

20. The micro flow channel structure of claim 19, wherein the plurality of micro flow channel units are arranged in sequence along an arc, the arc being curved toward the second position;

the second position is located on the same side of the arc as the first positions of the curved flow channels of any one of the micro flow channel units.

21. The micro flow channel structure according to claim 20, wherein the plurality of micro flow channel units includes a first micro flow channel unit, a second micro flow channel unit, and a third micro flow channel unit sequentially disposed in an extending direction of the arc line,

The last bending flow channel of the first micro flow channel unit in the arrangement direction is communicated with the last bending flow channel of the second micro flow channel unit in the arrangement direction through the connecting flow channel, and the first bending flow channel of the second micro flow channel unit in the arrangement direction is communicated with the first bending flow channel of the third micro flow channel unit in the arrangement direction through the connecting flow channel.

22. The micro flow channel structure according to claim 21, wherein the second position overlaps with the plurality of first positions of the plurality of curved flow channels of any one of the micro flow channel units.

23. The micro flow channel structure of claim 19, wherein the plurality of micro flow channel units are sequentially arranged along a circumferential line.

24. A micro flow channel chip comprising:

The micro flow channel structure according to any one of claims 1 to 23; and

A first separation structure comprising a first sub-inlet and a plurality of first sub-outlets,

The micro-channel structure comprises an inlet and an outlet, and the first sub-inlet is communicated with the outlet of the micro-channel structure.