CN109975265B - Three-dimensional contraction and expansion microfluidic device and method for multidirectional induced Dean flow - Google Patents
Three-dimensional contraction and expansion microfluidic device and method for multidirectional induced Dean flow Download PDFInfo
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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
The technical field is as follows:
the invention relates to a three-dimensional shrinking and expanding microfluidic device and a method, in particular to a three-dimensional shrinking and expanding microfluidic device and a method for multidirectional induced Dean flow, which are used under the conditions of no need of sheath liquid flow and no need of external field force in the field of tumor research.
Background art:
with the development of the times, malignant tumors become a great problem affecting the public health of people, and the contradiction between the pursuit of healthy and happy lives of people and the relative shortage of medical diagnosis resources is increasingly prominent. The Point-of-care diagnosing (POCT) instrument has the unique advantages of miniaturization of a detection device, simplification of an operation process, instantaneity of a diagnosis result, civilization of detection cost and the like, has wide application prospects in the fields of perfecting medical construction in resource-deficient areas, coping with sudden accident disasters, promoting home care diagnosis and the like, and is a powerful tool for solving the contradictions. The micro-fluidic (Microfluidic) technology is used for accurately controlling microliter and milliliter-level samples through a micron-sized flow channel by means of an advanced micro-structural processing technology, and is a mainstream technology for developing a new generation of POCT instruments.
The method is characterized in that an ideal particle focusing device has the advantages of ① simplicity in operation, ② no need of sheath fluid assistance, ③ narrow focusing flow beam, ④ focusing position far away from the wall surface of a flow channel and ⑤ high processing flux and the like for cell detection, the realization of the Microfluidic focusing device can simultaneously challenge the advantages of the high-flux sheath fluid introduction of a sheath fluid clamping technology, the application of the high-flux sheath fluid introduction in a Microfluidic chip, the fact that the particles are in a multi-dimensional two-dimensional state, the realization of the high-flux focusing technology, the low-cost active focusing technology, the low-inertia focusing equipment, the simple and low-inertia focusing technology, the simple and low-inertia micro-fluidic particle focusing technology, the simple and low-inertia micro-fluid focusing technology, the low-inertia micro-fluidic chip, the simple and low-inertia micro-fluid focusing technology, the simple and low-micro-fluidic particle focusing technology, and the high-fluid focusing technology.
However, most of the existing inertial focusing technologies arrange particles at two or more balance positions, and the focus balance positions are close to the wall surface of the flow channel, the traditional structures such as a single-side or plane-symmetric double-side contraction and expansion flow channel, a spiral flow channel, an asymmetric sinusoidal flow channel and the like can only induce and generate a group of Dean eddy currents in the transverse direction of the cross section of the main flow channel, so that the particle focusing has two balance positions, and the balance positions are close to the wall surface, which is easy to generate the scattering of the wall surface to the detection light beam, and limits the application of the traditional flow cytometry or other optical detection means. In view of the above, the invention discloses a novel three-dimensional contraction and expansion structure, and accordingly provides a method for focusing a single-row section center position of a multi-directional induced Dean flow control biological particle, which can provide an important sample pre-focusing unit for accurate detection of tumor cells in blood, and greatly improves the flow detection precision and sensitivity by using a simple flow channel structure and a control method.
The invention content is as follows:
the invention has the following patent purposes: aiming at the defects in the technology, the three-dimensional contraction and expansion microfluidic device and the method for multidirectional induction Dean flow of the pre-focusing unit of the important sample for high-precision flow detection are provided, and the defects that a plurality of focusing balance positions exist in the conventional inertial microfluidic device when the particles are controlled to be focused, and the balance positions are close to the wall surface of a flow channel are overcome, so that single-row accurate focusing of biological cells at the central position of the cross section of the flow channel is realized.
The technical scheme is as follows: in order to achieve the purpose, the three-dimensional contraction and expansion microfluidic device for multi-directionally inducing the Dean flow comprises a microfluidic chip, wherein a three-dimensional contraction and expansion flow channel is arranged in the microfluidic chip, an inlet connector and an outlet connector which are connected with the outside of the microfluidic 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 comprises a main flow channel of a rectangular channel structure arranged in the micro-fluidic chip, the cross section of the main flow channel is square or rectangular with the depth-to-width ratio not being 1, an inlet connector of the main flow channel is an inlet of a cylindrical space, an outlet connector of the main flow channel is an outlet of the cylindrical space, the upstream between the middle part of the main flow channel and the inlet is of the rectangular structure, a condensation-expansion structure is arranged at the downstream between the middle part of the main flow channel and the outlet, and a distance is reserved between the condensation-expansion structure and the outlet.
The polycondensation-expansion structure comprises convex structures or concave structures which are arranged at intervals outside the main flow channel.
Protruding structure include be equipped with protruding array II at the sprue top, the side of sprue is equipped with protruding array I, wherein protruding array I sets up with protruding array II on axial coordinate one-to-one.
The other side of the main runner corresponding to the protrusion array I is provided with a protrusion array III in a mirror image mode, and the protrusion array III, the protrusion array I and the protrusion array II are arranged in a one-to-one correspondence mode on an axial coordinate.
The main runner is provided with a protrusion array III on the other surface corresponding to the protrusion array I in a mirror image mode, the other surface provided with a protrusion array II in a mirror image mode on the main runner is provided with a protrusion array IV respectively to finally form a recess array, and the protrusion array I, the protrusion array II, the protrusion array III and the protrusion array IV are arranged on an axial coordinate in a one-to-one correspondence mode.
The cross-sectional dimension of the main flow channel is 200 x 200 μm; the bump arrays I, II, III and IV are a plurality of rectangular bumps arranged at intervals, the size of the rectangular bumps is 200 multiplied by 50 mu m, and the distance between the rectangular bumps is 50 mu m.
The recessed structure is a rectangular recess arranged at the top and a single side wall or two side walls and the bottom of the main flow channel.
A control method of a three-dimensional contraction and expansion microfluidic device for multi-directional induction of Dean flow comprises the following steps: tumor cells are marked by fluorescence and are mixed with non-fluorescence marked background white blood cells to prepare an initial mixed sample, the initial mixed sample is led into a three-dimensional contraction and expansion flow channel in a random dispersion state sequentially through an inlet guide pipe and an inlet connector, the white blood cells and the tumor cells are driven to do transverse migration motion under the action of inertial lift force in a rectangular cross section channel at the upstream of a main flow channel in the three-dimensional contraction and expansion flow channel, so that the white blood cells and the tumor cells are focused to four balance positions close to the centers of four wall surfaces of the three-dimensional contraction and expansion flow channel, a contraction and expansion structure is formed by the main flow channel, a side surface protrusion array I and a top protrusion array II at the middle and downstream of the three-dimensional contraction and expansion flow channel, and two Dean vortexes which are symmetrical up and down are induced and generated by the protrusion array I positioned; the bulge array II positioned at the top of the main runner induces and generates two Dean vortexes which are bilaterally symmetrical in the longitudinal direction of the section of the three-dimensional contraction and expansion runner, the two Dean vortexes generated in the transverse direction and the two Dean vortexes generated in the longitudinal direction are mutually coupled to form a new complex Dean flow mode, so that the leucocytes and the tumor cells move in a single-row and section center position accurate inertial focusing mode to form a single-row focusing particle beam, an external flow detection device is used for detecting the single-row focusing particle beam formed at the section center position of the three-dimensional contraction and expansion flow channel, the tumor cells are excited by fluorescence emitted by the external flow detection device to emit emitted light, and the focused particle beams are received and identified by an external flow type detection device, the accurate counting of the tumor cells is completed, and then the focused particle beams are sequentially led out through an outlet, an outlet connector and an outlet conduit and are collected by a waste liquid collecting device.
Has the advantages that: according to the invention, the side surface and the top of the main runner are simultaneously provided with the protrusion arrays, Dean eddy currents can be simultaneously induced and generated in the transverse and longitudinal directions of the cross section of the main runner, and a brand-new complex Dean eddy current mode is formed after multidirectional Dean eddy current coupling, so that biological cells are efficiently controlled, and the single-row and cross section center position accurate focusing of the biological cells is realized; the single-row focusing of the biological cells can ensure that each cell particle passes through the focus of the excitation beam of the detection system; the focusing position is positioned at the center of the cross section of the flow channel, so that the scattering of the light beam of the detection system by the wall surface of the flow channel can be effectively avoided, the precision and the sensitivity of optical detection are greatly improved, and an important sample pre-focusing unit is provided for high-precision flow detection; in addition, the invention does not need to rely on sheath fluid entrainment or external field force, has the advantages of low cost, simple operation and easy integration and miniaturization, can be widely applied to the fields of clinical diagnosis, biological research, biochemical analysis and the like, and is particularly suitable for the aspect of early detection of Circulating Tumor Cells (CTCs) in blood.
Description of the drawings:
FIG. 1 is a schematic structural diagram of a three-dimensional contraction and expansion microfluidic device for multi-directionally inducing Dean flow according to the present invention;
FIG. 2 is a schematic diagram of a three-dimensional contraction and expansion flow channel structure of a three-dimensional contraction and expansion microfluidic device for multi-directionally inducing Dean flow according to the present invention;
FIG. 3 is a schematic diagram of the generation and coupling of a three-dimensional convergent-divergent flow channel cross section of a three-dimensional convergent-divergent microfluidic device for multi-directionally inducing Dean flow according to the present invention;
FIG. 4 is a schematic diagram of the principle of inertial focusing of a three-dimensional constricting and expanding microfluidic device for multi-directionally inducing Dean flow according to the present invention;
FIG. 5 is a schematic structural diagram of a three-dimensional contraction and expansion microfluidic device for multi-directionally inducing Dean flow according to the present invention;
FIG. 6 is a schematic structural diagram of a three-dimensional contraction and expansion microfluidic device for multi-directional induced Dean flow according to the present invention.
The specific implementation mode is as follows:
the following detailed description of embodiments of the invention refers to the accompanying drawings.
As shown in fig. 1 and fig. 2, the three-dimensional shrinking and expanding microfluidic device 1 for multi-directionally inducing Dean flow of the present invention comprises a microfluidic chip 2, a three-dimensional shrinking and expanding flow channel 5 is arranged in the microfluidic chip 2, an inlet connector 4 and an outlet connector 6 which are connected with the outside of the microfluidic chip 2 are respectively arranged at the head end and the tail end of the three-dimensional shrinking and expanding flow channel 5, an inlet conduit 3 is arranged on the inlet connector 4, and an outlet conduit 7 is arranged on the outlet connector 6; the three-dimensional contraction and expansion flow channel 5 comprises a main flow channel 52 of a rectangular channel structure arranged in the microfluidic chip 2, the cross section of the main flow channel 52 is square or rectangular with the depth-to-width ratio not being 1, an inlet 51 of a cylindrical space is arranged at the position of an inlet connector 4 of the main flow channel 52, an outlet 54 of the cylindrical space is arranged at the position of an outlet connector 6 of the main flow channel 52, the upstream between the middle of the main flow channel 52 and the inlet 51 is of the rectangular structure, a condensation-expansion structure is arranged at the downstream between the middle of the main flow channel 52 and the outlet 54, and a distance is reserved between the condensation-expansion structure and the outlet 54.
As shown in fig. 5, the protrusion array iii 533 is arranged on the other surface of the main flow channel 52 corresponding to the protrusion array i 531 in a mirror image manner, and the protrusion array iii 533, the protrusion array i 531, and the protrusion array ii 532 are arranged in a one-to-one correspondence on the axial coordinate.
As shown in fig. 6, a protrusion array iii 533 is arranged on the other surface of the main flow channel 52 corresponding to the protrusion array i 531 in a mirror image manner, a protrusion array iv 534 is arranged on the other surface of the main flow channel 52 corresponding to the protrusion array ii 532 in a mirror image manner, and the protrusion array i 531, the protrusion array ii 532, the protrusion array iii 533 and the protrusion array iv 534 are arranged in a one-to-one correspondence manner on the axial coordinate.
The cross-sectional dimension of the main flow channel 52 is 200 × 200 μm; the bump arrays I531, II 532, III 533 and IV 534 are a plurality of rectangular bumps arranged at intervals, the size of the rectangular bumps is 200 multiplied by 50 μm, the distance between the rectangular bumps is 50 μm,
a three-dimensional contraction and expansion microflow control method for multidirectional induced Dean flow comprises the following steps: tumor cells 9 are marked by fluorescence and are mixed with non-fluorescence marked background white blood cells 8 to prepare an initial mixed sample, the initial mixed sample is led into a three-dimensional contraction and expansion flow channel 5 through an inlet guide pipe 3 and an inlet connector 4 in a random dispersion state in sequence, as shown in fig. 4, the white blood cells 8 and the tumor cells 9 are driven to do transverse migration motion through the action of inertial lift force in a rectangular cross section channel at the upstream of a main flow channel 52 in the three-dimensional contraction and expansion flow channel 5, so that the white blood cells 8 and the tumor cells 9 are focused to four balance positions close to the centers of four wall surfaces of the three-dimensional contraction and expansion flow channel 5, a contraction and expansion structure is formed by the main flow channel, a side surface convex array and a top convex array at the middle and downstream of the three-dimensional contraction and expansion flow channel 5, and two Dean vortexes which are symmetrical up and down are induced and generated by; the bulge array positioned at the top of the main runner induces and generates two Dean vortexes which are bilaterally symmetrical in the longitudinal direction of the section of the three-dimensional contraction and expansion runner 5; as shown in fig. 4, two Dean vortices generated in the transverse direction and two Dean vortices generated in the longitudinal direction are coupled to each other to form a new complex Dean flow pattern, so that the leukocyte 8 and the tumor cell 9 are inertially focused to form a single-row focused particle beam in a single-row and accurate-focusing manner at the center position of the cross section, the single-row focused particle beam formed at the center position of the cross section of the three-dimensional shrinking and expanding flow channel 5 is detected by using an external flow detection device, the tumor cell 9 is excited by fluorescence emitted from the external flow detection device to emit emitted light, and is received and identified by the external flow detection device, so as to finish accurate counting of the tumor cell 9, and then the focused particle beam is sequentially guided out through an outlet 54, an outlet connector 6 and an outlet duct 7, and is collected by a waste liquid collection device.
Example 1:
in the embodiment, the three-dimensional contraction and expansion microfluidic device 1 for multi-directionally inducing Dean flow is prepared by adopting materials such as polydimethylsiloxane PDMS, polymethyl methacrylate PMMA, polycarbonate PC and the like through a soft lithography processing technology, the technology specifically comprises the steps of photoetching SU-8 male die, PDMS pouring, PDMS-glass bonding and the like, and the three-dimensional contraction and expansion microfluidic device has the advantages of high processing precision and the like; the material such as the silica gel film, the poly terephthalic acid plastic PET film, the polyvinyl chloride PVC film and the like can also be prepared by a laser micromachining process, the process specifically comprises the steps of laser cutting, tearing and forming, plasma surface treatment, bonding, clamp packaging and the like, and the method has the advantages of low manufacturing cost, short processing period and the like. In addition, the flow channel structure in the embodiment can be realized by adopting other materials such as glass, silicon, metal and the like through micro-processing technologies such as wet method/deep reactive ion etching, ultra-precision machining, photosensitive circuit board etching and the like.
The device is mainly used for accurate focusing and flow detection of blood cells and circulating tumor cells in blood, can also be applied to focusing detection of biological cells in other body fluids such as urine, saliva, pleural effusion, ascites and the like, and can also be applied to efficient inertia control of micro-nano particles in other environments.
Fig. 3 is a schematic diagram of the principle of the three-dimensional convergent-divergent flow channel multidirectional induced Dean flow. In the middle and downstream area of the three-dimensional contraction and expansion flow channel 5, a three-dimensional contraction and expansion structure is formed by the main flow channel 52, a protrusion array I531 positioned on the side surface of the main flow channel 52 and a protrusion array II 532 positioned on the top of the main flow channel 52. Under the structure, when a fluid flows through, the convex array I531 positioned on the side surface can induce and generate a group of Dean vortexes which are symmetrical up and down in the transverse direction of the cross section of the main runner 52; the protrusion array II 532 at the top can generate a set of Dean vortexes which are symmetrical left and right in the longitudinal direction of the cross section of the main runner 52. The strength and the appearance of the two sets of Dean vortexes can be adjusted by regulating and controlling the structural size of the main flow channel 52/the protrusion array I531/the protrusion array II 532, the flow rate of a sample and other parameters. The two sets of Dean vortices are mutually superposed and coupled to generate a complex Dean vortex new mode (shown as a convergent section cross section flow field simulation in a right diagram of fig. 3), so that a brand new means can be provided for efficient control of micro-nano particles, and single-row accurate focusing of biological cells at the center of the cross section of the main flow channel 52 becomes possible.
Fig. 4 shows the precise focusing process of the leukocytes 8 and the tumor cells 9 in the lysed blood in the three-dimensional converging-diverging flow channel 5. The mixed sample of the non-fluorescent-stained leukocytes 8 and the fluorescent-stained tumor cells 9 is injected from the inlet catheter 3 and the inlet connector 4, and then is randomly dispersed at the inlet 51. Then in the upstream region of the main runner 52, according to the classical theory of inertial steering, the inertia lift forceF L Wall surface induced inertial lift force containing directional flow channel centerF LW Shear induced inertial lift force directed to wall surface of flow channelF LS The effect migrates laterally and gradually focuses to equilibrium positions around the center of the four walls. Then, a contraction and expansion structure area with three-dimensional condensation-expansion characteristics is formed by the downstream part in the main flow channel 52 together with the protrusion array I531 and the protrusion array II 532, and with the introduction of the multidirectional coupling complex Dean vortex, cell particles receive the action of an inertial lift force and are subjected to additional Dean drag forceF D And (4) acting. By adjusting the structural size of the flow channel and the flow rate of the sample, the leukocyte 8 and the tumor cell 9 can be driven to gradually migrate to the center of the cross section of the main flow channel 52, and finally, the single-row accurate focusing of the center of the flow channel is realized. In bump array I531/bump array II532 and the exit 54, the excitation beam of the external optical detection system is vertically irradiated on the focused particle beam, and the fluorescent-stained tumor cells 9 are excited and emit emission light, which is received and identified by the detection system; and the leucocyte 8 without fluorescent staining does not excite fluorescence, thereby realizing the detection and counting of the tumor cell 9. The three-dimensional contraction and expansion flow channel designed by the invention can realize the accurate focusing of the single-row and cross section center positions, wherein the single-row focusing can ensure that each cell particle passes through the focus of the excitation light beam of the detection system, and the focusing position is positioned in the center of the cross section of the flow channel, so that the scattering of the wall surface of the flow channel to the excitation light beam of the detection system can be effectively avoided, and the accuracy and the sensitivity of flow detection can be greatly improved on the whole.
The three-dimensional shrinking and expanding micro-fluidic device capable of multi-directionally inducing the Dean flow provided by the embodiment can break through the limitation that the traditional inertial micro-fluidic device can only induce and generate the Dean flow in the cross section transverse direction, so that particle focusing exists in two or more balance positions, and the balance positions are close to the wall surface of the flow channel, single-beam accurate focusing of biological cells at the center position of the cross section of the flow channel is realized, and an important sample pre-focusing unit is provided for high-precision flow detection. Meanwhile, the three-dimensional contraction and expansion microfluidic device provided by the embodiment also has the advantages of simple structure, low processing cost, convenience in operation, high detection flux and the like, can be widely applied to the fields of clinical diagnosis, biological analysis, biochemical analysis and the like, and is particularly suitable for the aspects of early detection of circulating tumor cells in blood, sensitivity test of cytological chemotherapy drugs and the like.
In embodiment 2, as shown in fig. 5, in this embodiment, a protrusion array iii 533 is disposed on the other side of the main channel 52 opposite to the protrusion array i 531, and the protrusion array iii 533 and the protrusion array i 531 are in a mirror image relationship, so as to induce Dean eddy current and couple in three directions, and efficiently manipulate the biological cells to realize single-row precise focusing at the center of the cross section.
In other embodiments, the structures of the protrusion array i 531, the protrusion array ii 532, the protrusion array iii 533, and the protrusion array iv 534 are formed by rectangular recessed structures recessed in the main flow channel 52, and a three-dimensional condensation-expansion feature is formed in the main flow direction, so as to induce Dean flow in multiple directions and efficiently control the micro-nano particles.
Claims (5)
1. A three-dimensional contraction and expansion microflow control method for multidirectional induced Dean flow is characterized in that a controller comprises a microfluidic chip (2), a three-dimensional contraction and expansion flow channel (5) is arranged in the microfluidic chip (2), an inlet connector (4) and an outlet connector (6) which are connected with the outside of the microfluidic chip (2) are respectively arranged at the head end and the tail end of the three-dimensional contraction and expansion flow channel (5), an inlet guide pipe (3) is arranged on the inlet connector (4), and an outlet guide pipe (7) is arranged on the outlet connector (6); the three-dimensional contraction and expansion flow channel (5) comprises a main flow channel (52) of a rectangular channel structure arranged in the microfluidic chip (2), the section of the main flow channel (52) is square or rectangular with the depth-to-width ratio not being 1, an inlet (51) of a cylindrical space is arranged at the position of an inlet connector (4) of the main flow channel (52), an outlet (54) of the cylindrical space is arranged at the position of an outlet connector (6) of the main flow channel (52), the upstream between the middle part of the main flow channel (52) and the inlet (51) is of a rectangular structure, a condensation-expansion structure is arranged at the downstream between the middle part of the main flow channel (52) and the outlet (54), and a distance is reserved between the condensation-expansion structure and the outlet (54); the polycondensation-expansion structure comprises convex structures or concave structures arranged at intervals on the outer side of the main flow channel (52), the convex structures comprise convex arrays II (532) arranged at the top of the main flow channel (52), convex arrays I (531) are arranged on the side surface of the main flow channel (52), and the convex arrays I (531) and the convex arrays II (532) are arranged in a one-to-one correspondence mode on an axial coordinate;
the method is characterized by comprising the following steps: tumor cells (9) are marked by fluorescence and are mixed with non-fluorescence marked background white blood cells (8) to prepare an initial mixed sample, the initial mixed sample is led into a three-dimensional contraction and expansion flow channel (5) through an inlet guide pipe (3) and an inlet connector (4) in a random dispersion state in sequence, the white blood cells (8) and the tumor cells (9) are driven to move transversely through the action of inertial lift force in a rectangular cross section channel at the upstream of a main flow channel (52) in the three-dimensional contraction and expansion flow channel (5), so that the white blood cells (8) and the tumor cells (9) are focused to four balance positions close to the centers of four wall surfaces of the three-dimensional contraction and expansion flow channel (5), a contraction and expansion structure is formed by the main flow channel (52), a side surface convex array I (531) and a top convex array II (532) at the middle and downstream of the three-dimensional contraction and expansion flow channel (5), and the convex array I (531) at the side surface of the main flow channel induces and generates two Dean which are symmetrical up and down Swirling; a bulge array II (532) positioned at the top of a main flow channel induces and generates two Dean vortexes which are bilaterally symmetrical in the longitudinal direction of the cross section of a three-dimensional contraction and expansion flow channel (5), the two Dean vortexes generated in the transverse direction and the two Dean vortexes generated in the longitudinal direction are mutually coupled to form a new complex Dean flow mode, so that white blood cells (8) and tumor cells (9) move in a single-row and cross-section center position accurate inertial focusing mode to form a single-row focusing particle beam, an external flow detection device is used for detecting the single-row focusing particle beam formed in the cross section center position of the three-dimensional contraction and expansion flow channel (5), the tumor cells (9) are excited by fluorescence emitted by the external flow detection device to emit emitted light, are received and identified by the external flow detection device to complete accurate counting of the tumor cells (9), and then the focusing particle beam passes through an outlet (54), an outlet connector (6), The outlet conduits (7) are led out in sequence and collected by a waste liquid collecting device.
2. The three-dimensional micro-flow control method for multi-directionally induced Dean flow according to claim 1, wherein: in the three-dimensional contraction and expansion microfluidic device for multi-directional induction of Dean flow, a bulge array III (533) is arranged on the other surface, corresponding to the bulge array I (531), of the main flow channel (52) in a mirror image mode, and the bulge array III (533), the bulge array I (531) and the bulge array II (532) are arranged in a one-to-one correspondence mode on an axial coordinate.
3. The three-dimensional micro-flow control method for multi-directionally induced Dean flow according to claim 1, wherein: in the three-dimensional contraction and expansion microfluidic device for multidirectional induced Dean flow, a bulge array III (533) is arranged on the other surface, corresponding to the bulge array I (531), of a main flow channel (52) in a mirror mode, a bulge array IV (534) is arranged on the other surface, corresponding to the bulge array II (532), of the main flow channel (52) in a mirror mode, and finally a depression array is formed, and the bulge array I (531), the bulge array II (532), the bulge array III (533) and the bulge array IV (534) are arranged on an axial coordinate in a one-to-one correspondence mode.
4. The three-dimensional micro-flow control method for multi-directionally induced Dean flow according to claim 1, wherein: in the three-dimensional contraction and expansion microfluidic device for multidirectional induced Dean flow, the cross section of the main flow channel (52) is 200 multiplied by 200 mu m; the bump arrays I (531), II (532), III (533) and IV (534) are a plurality of rectangular bumps arranged at intervals, the size of the rectangular bumps is 200 multiplied by 50 mu m, and the distance between the rectangular bumps is 50 mu m.
5. The three-dimensional micro-flow control method for multi-directionally induced Dean flow according to claim 1, wherein: in the three-dimensional contraction and expansion microfluidic device for multidirectional induced Dean flow, the concave structure is a rectangular concave arranged at the top and a single side wall or two side walls and the bottom of the main flow channel (52).
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| CN110871137B (en) * | 2019-11-27 | 2021-03-02 | 中国矿业大学 | Small-particle-size fly ash particle sorting spiral runner microfluidic device and method |
| CN111250182B (en) * | 2020-02-11 | 2021-03-19 | 北京理工大学 | High-flux microfluidic electrophoresis screening chip and preparation method and application method thereof |
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| CN114798014A (en) * | 2021-01-29 | 2022-07-29 | 广州万孚生物技术股份有限公司 | Biological particle sorting flow channel and micro-fluidic chip |
| CN115301303B (en) * | 2022-09-15 | 2023-06-16 | 中国矿业大学 | Multicomponent mineral dust sorting microfluidic chip and classification concentration detection method thereof |
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