CN109975265B - A three-dimensional scaling microfluidic device and method for multidirectional induced Dean flow - Google Patents

Abstract

The invention discloses a three-dimensional contraction and expansion microfluidic device and a method for multi-directionally inducing Dean flow, which are suitable for being used in the field of tumor research. The micro-fluidic chip comprises a micro-fluidic chip, wherein a three-dimensional contraction and expansion flow channel is arranged in the micro-fluidic chip, an inlet connector and an outlet connector which are connected with the outside of the micro-fluidic chip are respectively arranged at the head end and the tail end of the three-dimensional contraction and expansion flow channel, an inlet guide pipe is arranged on the inlet connector, and an outlet guide pipe is arranged on the outlet connector; the three-dimensional contraction and expansion flow channel inlet connector is an inlet of a cylindrical space, the outlet connector is an outlet of the cylindrical space, a condensation-expansion structure is arranged between the middle part and the outlet, and a distance is reserved between the condensation-expansion structure and the outlet. The device has a simple structure, overcomes the defect that the existing spiral, asymmetric sine, plane contraction and expansion inertial microfluidic devices can only generate Dean vortex by induction in the cross section transverse direction, and greatly improves the accuracy and sensitivity of flow detection.

Description

A three-dimensional scaling microfluidic device and method for multidirectional induced Dean flow

Technical field:

The patent of the present invention relates to a three-dimensional shrink-expanding microfluidic device and method, which is especially suitable for a three-dimensional shrink-expanding microfluidic device in the field of tumor research that does not require the use of sheath liquid flow and external field force to induce Dean flow in multiple directions. and methods.

Background technique:

With the development of the times, malignant tumors have become a major problem affecting human public health, and the contradiction between people's pursuit of a healthy and happy life and the relative lack of medical diagnosis resources has become increasingly prominent. On-site point-of-care testing (POCT) instruments have unique advantages such as miniaturization of detection devices, simplified operation processes, instant diagnosis results, and civilian testing costs. It has broad application prospects in the fields of accident disasters and promotion of home care diagnosis, and is a powerful tool to solve the above contradictions. Relying on advanced microstructure processing technology, Microfluidic technology precisely controls microliter and milliliter samples through micrometer flow channels, which is the mainstream technology for developing a new generation of POCT instruments.

As one of the important pre-processing units of POCT instruments, the precision of sample pre-focusing will directly restrict the performance indicators of the detection instrument. The existing microfluidic focusing technology can be summarized into the following three categories according to the different control mechanisms: the first category is sheath liquid entrainment technology evolved from traditional macroscopic methods; the second category is based on electricity, magnetism, sound, light Active focusing technology with equal external field; the third type is passive focusing technology based on complex morphological micro-channels to induce fluid and manipulate particles through the action of the fluid itself. For cell detection, an ideal particle focusing device should have the following characteristics: (1) simple operation, (2) no need for sheath flow assistance, (3) narrow focus flow, (4) focusing position far from the wall of the flow channel, and (5) high processing throughput. Although scholars from all over the world have made outstanding achievements in the field of microfluidic focusing, there are still huge challenges in realizing a microfluidic focusing device that can have the above advantages at the same time. Moreover, the particle focusing applied in microfluidic chips is mostly two-dimensional plane state; active focusing technology requires huge and expensive external equipment, and generally has a low flux and is cumbersome to operate. In contrast, as a typical passive focusing technology, Inertial Microfluidic cleverly utilizes the inertial effects of micro-scale fluids (inertial migration and cross-sectional Dean flow) to achieve precise control of particle motion states and equilibrium positions. It has the obvious advantages of simple flow channel structure, no need for sheath liquid flow, no need for external field force and high processing throughput.

However, most of the existing inertial focusing technologies arrange the particles in two or more equilibrium positions, and the focusing equilibrium position is close to the wall of the flow channel. Structures such as asymmetric sinusoidal flow channels can only induce a set of Dean eddy currents in the lateral direction of the main flow channel section, resulting in two equilibrium positions for particle focusing, and the equilibrium positions are close to the wall surface, which is prone to scattering of the detection beam from the wall, which limits the Application of traditional flow cytometry or other optical detection methods. In view of this, the patent of the present invention designs a new three-dimensional shrink-expanded structure, and based on this, proposes a multi-directional induced Dean flow to control the biological particle single-column and cross-sectional center position focusing method, which can provide important sample prediction for the accurate detection of tumor cells in blood. Focusing unit, with a simple flow channel structure and manipulation method to achieve a significant improvement in the accuracy and sensitivity of flow detection.

Invention content:

Purpose of the invention patent: Aiming at the shortcomings of the above technologies, to provide a method that overcomes the shortcomings of the existing inertial microfluidic devices when controlling particle focusing that there are multiple focusing equilibrium positions and the equilibrium positions are close to the wall of the flow channel, so as to realize the flow of biological cells. The single-column precise focusing at the center of the channel section provides a three-dimensional shrink-expanding microfluidic device and method for multi-directional induced Dean flow of an important sample pre-focusing unit for high-precision flow detection.

Technical solution: In order to achieve the above purpose, the three-dimensional constriction-expanding microfluidic device for inducing Dean flow in multiple directions of the present invention includes a microfluidic chip, and the microfluidic chip is provided with a three-dimensional constriction-expansion flow channel, a three-dimensional constriction-expansion flow channel. The head and tail ends of the microfluidic chip are respectively provided with an inlet connector and an outlet connector, which are connected with the outside of the microfluidic chip. The main channel of the rectangular channel structure in the microfluidic chip, the cross section of the main channel is a square or a rectangle whose aspect ratio is not 1, the inlet connector of the main channel is the entrance of the cylindrical space, and the outlet connector of the main channel is The outlet of the cylindrical space, wherein the upstream between the middle part of the main channel and the inlet is a rectangular structure, and the downstream between the middle part of the main channel and the outlet is a polycondensation-expansion structure, and there is a distance between the polycondensation-expansion structure and the outlet.

The polycondensation-expansion structure includes convex structures or concave structures arranged at intervals outside the main channel.

The raised structure includes a raised array II on the top of the main channel, and a raised array I on the side of the main channel, wherein the raised array I and the raised array II are arranged in a one-to-one correspondence on the axial coordinates.

The projection array III is mirrored on the other side of the main channel corresponding to the projection array I, and the projection array III is arranged in a one-to-one correspondence with the projection array I and the projection array II on the axial coordinates.

The convex array III is mirrored on the other side of the main channel corresponding to the convex array I, and the convex array IV is respectively provided on the other surface of the main channel mirrored with the convex array II. Finally, a concave array is formed. The starting array I, the protruding array II, the protruding array III and the protruding array IV are arranged in one-to-one correspondence on the axial coordinates.

The cross-sectional size of the main channel is 200×200 μm; the protrusion array I, protrusion array II, protrusion array III and protrusion array IV are a plurality of rectangular protrusions arranged at intervals, and the size of the rectangular protrusions is 200×50 ×50μm, the spacing between the rectangular protrusions is 50μm.

The recessed structure is a rectangular recess provided on the top of the main channel and the sidewall of one side or the sidewalls of both sides and the bottom.

A method for controlling a three-dimensional shrink-expanded microfluidic device for inducing Dean flow in multiple directions. The dispersed state is sequentially introduced into the three-dimensional constriction-expansion flow channel through the inlet conduit and the inlet connector, and the inertial lift in the rectangular cross-section channel upstream of the main channel in the three-dimensional constriction-expansion flow channel drives the leukocytes and tumor cells to perform lateral migration, thereby connecting leukocytes and tumor cells. The tumor cells are focused to the four equilibrium positions near the center of the four walls of the three-dimensional constriction-expansion channel, and in the middle and downstream of the three-dimensional constriction-expansion channel, the main channel and the side convex array I and the top convex array II together constitute the constriction and expansion structure. , the convex array I located on the side of the main channel induces two Dean vortices that are symmetrical up and down in the lateral direction of the three-dimensional constriction-expansion channel section; the convex array II located at the top of the main channel is in the longitudinal direction of the three-dimensional contraction-expansion channel section. Two Dean vortices with left and right symmetry are induced in the upper direction, and the two Dean vortices generated in the lateral direction and the two Dean vortices generated in the longitudinal direction are coupled with each other to form a new complex Dean flow pattern, so that the white blood cells and tumor cells are in a single row and the center of the section The position-accurate inertial focusing method moves to form a single-row focused particle beam, and an external flow detection device is used to detect the single-row focused particle beam formed at the center of the three-dimensional condensed-expanded flow channel section. The excitation emits emitted light, which is received and recognized by an external flow detection device to complete the accurate counting of tumor cells, and then the focused particle beam is sequentially exported through the outlet, outlet connector, and outlet catheter, and collected by the waste liquid collection device.

Beneficial effects: The present invention can simultaneously induce and generate Dean eddy currents in the lateral and longitudinal directions of the main channel section by arranging raised arrays on the side and top of the main channel. After the multidirectional Dean eddy currents are coupled, a brand-new complex Dean eddy current is formed. The single-row focusing of biological cells can ensure that each cell particle passes through the focus of the excitation beam of the detection system; the focusing position is located at the center of the flow channel section, which can effectively avoid flow The channel wall scatters the beam of the detection system, thereby greatly improving the accuracy and sensitivity of optical detection, and providing an important sample pre-focusing unit for high-precision flow detection; in addition, the invention does not require sheath liquid flow or external field force, low cost, and operation. The advantages of simplicity, easy integration and miniaturization can be widely used in clinical diagnosis, biological research, biochemical analysis and other fields, especially for the early detection of Circulating Tumor Cells (CTCs) in the blood.

Description of drawings:

1 is a schematic structural diagram of a three-dimensional scaling microfluidic device for multidirectional inducing Dean flow of the present invention;

2 is a schematic diagram of a three-dimensional constriction-expansion flow channel structure of a three-dimensional constriction-expansion microfluidic device for multidirectional inducing Dean flow of the present invention;

3 is a schematic diagram of the generation and coupling of the multidirectional Dean flow in the cross-section of the three-dimensional constriction-expansion flow channel of the three-dimensional constriction-expansion microfluidic device of the present invention;

4 is a schematic diagram of the inertial focusing principle of the three-dimensional scaling microfluidic device for multidirectional inducing Dean flow of the present invention;

5 is a schematic structural diagram of a three-dimensional scaling microfluidic device for multidirectional inducing Dean flow according to the present invention;

FIG. 6 is a schematic structural diagram of a three-dimensional scaling microfluidic device for multidirectional inducing Dean flow according to the present invention.

Detailed ways:

The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

As shown in FIG. 1 and FIG. 2 , the three-dimensional condensing and expanding microfluidic device 1 for inducing Dean flow in multiple directions of the present invention includes a microfluidic chip 2, and the microfluidic chip 2 is provided with a three-dimensional condensing and expanding flow channel 5. The head and tail ends of the expansion channel 5 are respectively provided with an inlet connector 4 and an outlet connector 6 which are connected with the outside of the microfluidic chip 2. The inlet connector 4 is provided with an inlet conduit 3, and the outlet connector 6 is provided with an outlet conduit. 7; wherein the three-dimensional constriction and expansion flow channel 5 includes a main channel 52 with a rectangular channel structure arranged in the microfluidic chip 2, the cross section of the main channel 52 is a square or a rectangle with an aspect ratio not equal to 1, and the inlet of the main channel 52 is connected Device 4 is the inlet 51 of the cylindrical space, and the outlet connector 6 of the main channel 52 is the outlet 54 of the cylindrical space, wherein the upstream between the middle part of the main channel 52 and the inlet 51 is a rectangular structure. A polycondensation-expansion structure is provided downstream between the outlets 54 , and a distance is left between the polycondensation-expansion structure and the outlet 54 .

As shown in FIG. 5 , the projection array III 533 is mirrored on the other side of the main channel 52 corresponding to the projection array I 531, and the projection array III 533, the projection array I 531 and the projection array II 532 are on the axial coordinate A corresponding setting.

As shown in FIG. 6 , the convex array III 533 is mirrored on the other side of the main channel 52 corresponding to the convex array I531, and the convex array II 532 is mirrored on the other surface of the main channel 52 with the convex array II 532. Starting from the array IV534, the convex array I531, the convex array II532, the convex array III533 and the convex array IV534 are arranged in one-to-one correspondence on the axial coordinates.

The cross-sectional size of the main channel 52 is 200×200 μm; the protrusion array I531, the protrusion array II532, the protrusion array III533 and the protrusion array IV534 are a plurality of rectangular protrusions arranged at intervals, and the size of the rectangular protrusions is 200× 50×50μm, the spacing between the rectangular bumps is 50μm,

A three-dimensional shrink-expanding microfluidic control method for inducing Dean flow in multiple directions, the steps of which are as follows: tumor cells 9 are fluorescently labeled, and mixed with non-fluorescently labeled background leukocytes 8 to form an initial mixed sample, and the initial mixed sample is randomly dispersed The state sequence is introduced into the three-dimensional constriction and expansion channel 5 through the inlet conduit 3 and the inlet connector 4. As shown in FIG. The tumor cells 9 move laterally, thereby focusing the leukocytes 8 and the tumor cells 9 to four equilibrium positions near the center of the four walls of the three-dimensional constriction-expansion channel 5, and in the middle and downstream of the three-dimensional constriction-expansion channel 5, the main The convex array on the side and the top of the main channel together constitute a shrink-expansion structure. The convex array located on the side of the main channel induces two Dean vortices that are symmetrical up and down in the lateral direction of the cross-section of the three-dimensional contraction-expansion channel 5; the convex array located at the top of the main channel The starting array induces two left-right symmetrical Dean vortices in the longitudinal direction of the cross-section of the three-dimensional constriction-expansion channel 5; as shown in Fig. A new complex Dean flow pattern is formed, so that the leukocytes 8 and tumor cells 9 move in a single-column, precisely focused position of the center of the section by inertial focusing to form a single-column focused particle beam, and an external flow detection device is used to analyze the section of the three-dimensional constriction and expansion channel 5. The single-row focused particle beam formed at the center is detected, and the tumor cells 9 are excited by the fluorescence emitted by the external flow detection device to emit light, which is received and recognized by the external flow detection device. The accurate counting of tumor cells 9 is completed, and then focused The particle beam is sequentially led out through the outlet 54, the outlet connector 6, and the outlet conduit 7, and collected by the waste liquid collection device.

Example 1:

In this embodiment, the three-dimensional shrink-expanding microfluidic device 1 with multi-directional induced Dean flow is prepared by soft lithography process using materials such as polydimethylsiloxane PDMS, polymethyl methacrylate PMMA, polycarbonate PC, etc. The process specifically includes the steps of photolithography SU-8 positive mold, PDMS casting and PDMS-glass bonding, which has the advantages of high processing accuracy; silicone film, polyphthalic acid plastic PET film, and polyvinyl chloride PVC film can also be used. Such materials are prepared by a laser micromachining process, which specifically includes steps such as laser cutting and tearing, plasma surface treatment, bonding, and fixture packaging, and has the advantages of low production cost and short processing cycle. In addition, the flow channel structure in this embodiment can also be made of other materials such as glass, silicon, metal, etc., and is realized by micromachining technologies such as wet/deep reactive ion etching, ultra-precision machining, and photosensitive circuit board etching.

The device described in this embodiment is mainly used for the precise focusing and flow detection of blood cells and circulating tumor cells in blood, and can also be applied to the focusing detection of biological cells in other body fluids such as urine, saliva, pleural effusion, ascites, etc. Efficient inertial manipulation of micro-nanoparticles in other environments.

Figure 3 is a schematic diagram of the principle of multidirectional induced Dean flow in a three-dimensional constriction-expansion channel. In the middle and downstream regions of the three-dimensional shrink-expanded flow channel 5 , the three-dimensional shrink-expand structure is composed of the main flow channel 52 , the convex array I 531 located on the side of the main flow channel 52 , and the convex array II 532 located on the top of the main flow channel 52 . Under this structure, when the fluid flows through, the convex array I531 located on the side can induce a set of up and down symmetrical Dean vortices in the transverse direction of the cross section of the main channel 52; A set of left-right symmetrical Dean vortices are generated in the longitudinal direction of the cross section. By adjusting the parameters such as the main channel 52/convex array I531/convex array II532 and the sample flow rate, the intensity and shape of the two groups of Dean eddy currents can be adjusted. The two sets of Dean eddy currents are superimposed and coupled to each other to generate a complex new model of Dean eddy currents (as shown in the right figure in Figure 3, the cross-sectional flow field simulation of the converging section), which can provide a new method for efficient manipulation of micro-nano particles, enabling It is possible to precisely focus the biological cells in a single row at the center of the cross section of the main channel 52 .

As shown in FIG. 4 , the precise focusing process of leukocytes 8 and tumor cells 9 in the lysed blood in the three-dimensional constriction-expansion channel 5 is shown. After the mixed sample of the non-fluorescent-stained white blood cells 8 and the fluorescent-stained tumor cells 9 is injected from the inlet catheter 3 and the inlet connector 4 , it is in a state of random dispersion at the inlet 51 . Then in the upstream area of the main channel 52, according to the classical theory of inertial control, the inertial lift FL including the wall-induced inertial lift _{F LW} directed to the center of the flow channel and the shear-induced inertial lift F _LS directed to the flow channel wall will migrate laterally, And gradually focus to the four equilibrium positions near the center of the four walls. Then, in the downstream part of the main channel 52, together with the convex array I531 and the convex array II532, a constriction and expansion structure area with three-dimensional polycondensation-expansion characteristics is formed. In addition to the effect, it will also be affected by an additional Dean pulling force F _D. By adjusting the structure size of the flow channel and the flow rate of the sample, the leukocytes 8 and tumor cells 9 can be driven to gradually migrate to the center of the cross-section of the main channel 52, and finally a single column of precise focusing at the center of the flow channel can be achieved. In the detection area between the convex array I 531/convex array II 532 and the outlet 54, the excitation beam of the external optical detection system irradiates the focused particle beam vertically, at this time, the fluorescently stained tumor cells 9 are excited and emit emission light, which is detected by the detection system. Receiving identification; while the white blood cells 8 without fluorescent staining do not excite fluorescence, thereby realizing the detection and counting of tumor cells 9 . Because the three-dimensional constriction-expanding flow channel designed in the present invention can achieve precise focusing in a single row and at the center of the section, the single-row focusing can ensure that each cell particle passes through the focus of the excitation beam of the detection system, and the focusing position is in the center of the flow channel section, which can effectively avoid The flow channel wall scatters the excitation beam of the detection system, so the overall accuracy and sensitivity of the flow detection can be greatly improved.

The three-dimensional constriction-expanding microfluidic device proposed in this embodiment that can induce Dean flow in multiple directions can break through the traditional inertial microfluidic device, which can only induce Dean flow in the transverse direction of the cross-section, resulting in two or more equilibria in particle focusing. Position, and the balance position is close to the limitation of the flow channel wall, realizes the precise focusing of a single beam of biological cells at the center of the flow channel section, and provides an important sample pre-focusing unit for high-precision flow detection. At the same time, the three-dimensional shrink-expanding microfluidic device proposed in this embodiment also has the advantages of simple structure, low processing cost, convenient operation, and high detection throughput, and can also be widely used in clinical diagnosis, biological analysis, biochemical analysis and other fields. It is especially suitable for the early detection of circulating tumor cells in the blood and the sensitivity test of chemotherapeutic drugs at the cytological level.

Embodiment 2, as shown in FIG. 5 , in this embodiment, a convex array III 533 is arranged on the side of the main channel 52 and on the other side opposite to the convex array I 531, and the convex array III 533 is in a mirror image relationship with the convex array I 531. , to induce and couple Dean vortices in three directions, and efficiently manipulate biological cells to achieve precise focusing in a single column at the center of the section.

Embodiment 3, as shown in FIG. 6 , in this embodiment, a convex array IV534 is arranged at the bottom of the main channel 52, and the convex array IV534 is in a mirror image relationship with the convex array II532 to induce Dean eddy currents in four directions. And coupling, efficient control of biological cells to achieve single-line precise focusing at the center of the section.

In some other embodiments, the structures of the convex array I531, the convex array II532, the convex array III533, and the convex array IV534 are composed of rectangular concave structures with concavities arranged in the main flow channel 52, forming a three-dimensional structure in the main flow direction. Polycondensation-expansion feature to induce Dean flow in multiple directions and efficiently manipulate micro-nanoparticles.

Claims (5)

1. A three-dimensional constriction-expansion microfluidic control method for inducing Dean flow in multiple directions, using a controller comprising a microfluidic chip (2), the microfluidic chip (2) being provided with a three-dimensional constriction-expansion flow channel (5), An inlet connector (4) and an outlet connector (6) connected with the outside of the microfluidic chip (2) are respectively provided at the head and tail ends of the condensing and expanding flow channel (5), and an inlet conduit is arranged on the inlet connector (4). (3), the outlet connector (6) is provided with an outlet conduit (7); wherein the three-dimensional constriction and expansion flow channel (5) includes a main channel (52) of a rectangular channel structure arranged in the microfluidic chip (2), The cross section of the main channel (52) is a square or a rectangle whose aspect ratio is not 1, the inlet connector (4) of the main channel (52) is the inlet (51) of the cylindrical space, and the outlet connector of the main channel (52) (6) is the outlet (54) of the cylindrical space, wherein the upstream between the middle part of the main channel (52) and the inlet (51) is a rectangular structure, and the middle part between the main channel (52) and the outlet (54) is a rectangular structure. A polycondensation-expansion structure is arranged downstream, and a distance is left between the polycondensation-expansion structure and the outlet (54); the polycondensation-expansion structure includes a convex structure or a concave structure arranged at intervals on the outside of the main flow channel (52), and the convex structure includes a convex structure in the main flow channel (52). The top of the channel (52) is provided with a convex array II (532), and the side of the main channel (52) is provided with a convex array I (531), wherein the convex array I (531) and the convex array II (532) are on the axis. One-to-one setting to the coordinate; It is characterized in that the steps are as follows: the tumor cells (9) are fluorescently labeled, and mixed with non-fluorescently labeled background leukocytes (8) to prepare an initial mixed sample, and the initial mixed sample is randomly dispersed through the inlet conduit (3) and the inlet in sequence. The connector (4) is introduced into the three-dimensional constriction-expansion flow channel (5), and the inertial lift in the rectangular cross-section channel upstream of the middle main channel (52) of the three-dimensional constriction-expansion flow channel (5) drives the white blood cells (8) and tumor cells (9). ) performs a lateral migration movement, thereby focusing the leukocytes (8) and tumor cells (9) to four equilibrium positions near the center of the four walls of the three-dimensional constriction and expansion channel (5). In the middle and lower reaches, the main channel (52), the side protrusion array I (531), and the top protrusion array II (532) together form a shrink-expansion structure. Two Dean vortices with up and down symmetry are induced in the transverse direction of the cross section of the flow channel (5); the convex array II (532) located at the top of the main flow channel induces left and right symmetry in the longitudinal direction of the cross section of the three-dimensional constricted and expanded flow channel (5). The two Dean vortices generated in the transverse direction and the two Dean vortices generated in the longitudinal direction are coupled with each other to form a new complex Dean flow pattern, so that the white blood cells (8) and the tumor cells (9) are in a single row and cross section. The center position is moved by means of precise inertial focusing to form a single-row focused particle beam, and an external flow detection device is used to detect the single-row focused particle beam formed at the center of the cross-section of the three-dimensional condensed-expanded flow channel (5). The fluorescence emitted by the flow detection device is excited to emit emission light, which is received and recognized by the external flow detection device, and the accurate counting of tumor cells (9) is completed, and then the focused particle beam passes through the outlet (54), the outlet connector (6), The outlet conduits (7) are led out sequentially and collected by the waste liquid collection device. 2. The three-dimensional shrink-expanding microfluidic control method of multi-directional induced Dean flow according to claim 1, characterized in that: in the three-dimensional shrink-expanded microfluidic device of the multi-directional induced Dean flow, in the main channel (52 ) on the other side corresponding to the convex array I (531) is mirrored with a convex array III (533), the convex array III (533) and the convex array I (531) and the convex array II (532) are on the axis One-to-one setting to the coordinates. 3. The three-dimensional shrink-expansion microfluidic control method of multi-directional induced Dean flow according to claim 1, characterized in that: in the three-dimensional shrink-expanded microfluidic device of the multi-directional induced Dean flow, in the main channel (52 ) on the other side corresponding to the convex array I (531) is mirrored with convex array III (533), and on the other side of the main channel (52) mirrored with convex array II (532) The convex array IV (534) finally forms a concave array, and the convex array I (531), the convex array II (532), the convex array III (533) and the convex array IV (534) are on the axial coordinate one by one. corresponding settings. 4 . The three-dimensional scaling microfluidic control method for multidirectional induced Dean flow according to claim 1 , characterized in that: in the three-dimensional scaling microfluidic device for multidirectional induced Dean flow, the main channel ( 52 ) The cross-sectional size is 200×200 μm; the bump array I (531), bump array II (532), bump array III (533) and bump array IV (534) are a plurality of rectangular bumps arranged at intervals , the size of the rectangular protrusions is 200 × 50 × 50 μm, and the spacing between the rectangular protrusions is 50 μm. 5 . The three-dimensional constriction-expanding microfluidic control method for multi-directional induced Dean flow according to claim 1 , wherein in the three-dimensional condensed-expanded microfluidic device for multi-directional induced Dean flow, the concave structure is: 6 . A rectangular recess arranged on the top and one side wall or two side walls and bottom of the main channel (52).

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