An inertial microfluidic chip for sorting micro- and nanoparticles

Abstract

The application discloses an inertial microfluidic chip for sorting micro-nano particles, and belongs to the technical field of biomedical engineering, which comprises a substrate, wherein a microchannel is arranged on the substrate; the microchannel forms a flow channel for microfluids to pass through on the substrate; a plurality of expansion structures are arranged on the sidewall of the microchannel; the included angle between the sidewall first contacted with the microfluid and the wall of the flow channel is an acute angle alpha; the shape of the cross section of the expansion structure is a triangle, a trapezoid, a parallelogram, an ellipse, a semi-ellipse or an irregular circular arc; compared with the common right-angle structure, the structure of the application can generate a larger low-pressure area, so that a stronger vortex is formed to capture small-size particles; the vortex generated by the common right-angle structure can usually only affect particles with a size of more than 10 microns, and the acute-angle structure in the application can be applied to the sorting of particles with a size of less than 10 microns.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical engineering, and particularly relates to an inertial microfluidic chip for sorting micro-nano particles. BACKGROUND

[0002] In biological samples, such as blood, there are a large number of various cells, which have different sizes and properties and indicate the health condition of the organism. For example, the number of circulating tumor cells in blood represents the severity of malignant tumors, which plays an important role in the early screening of cancer, drug screening, and monitoring of treatment effect. However, the number of circulating tumor cells in blood is very small compared with other cells, only one circulating tumor cell in one billion blood cells. In addition, there are other smaller particles than circulating tumor cells in biological samples, such as vesicles and cell products, which need to be separated for scientific research. Due to their small size, they are difficult to separate by traditional centrifugation method, so the biomedical field urgently needs a separation method that can realize high throughput, high purity, high recovery rate, and can be used for biological micro-nano particles with small size.

[0003] Microfluidic technology is a new technology that has developed rapidly in recent years, which has the advantages of fast response speed, high sensitivity, low cost, good integration, and is very suitable for meeting the separation needs in biological samples. Microfluidic technology can be divided into active and passive according to the control force. The active type needs to rely on additional driving force, such as electromagnetic force, optical force, acoustic force, to realize the control of particles, while the passive type only relies on the pump to drive the fluid flow to realize the control of fluid. Generally, the active microfluidic technology has the advantages of high precision, good flexibility, real-time control, etc., but it needs more complex external equipment and has low throughput. The passive microfluidic technology does not need extra external equipment, has the advantages of simple structure, reliable performance, easy operation, high throughput, etc., so it has more commercial prospects.

[0004] Among them, the inertial microfluidic chip utilizes the hydrodynamic force generated by fluid inertia to realize high-throughput and high-precision particle sorting, which has attracted widespread attention at home and abroad. However, in the existing inertial microfluidic technology, only larger size particles (>10 μm) can generate force, and it is powerless to differentially sort smaller size particles. SUMMARY

[0005] In order to overcome the shortcomings of the prior art, the purpose of the present application is to provide an inertial microfluidic chip for sorting micro-nano particles, which solves the technical problem that the existing inertial microfluidic technology can only generate force on larger size particles.

[0006] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0007] The application discloses an inertial microfluidic chip for sorting micro-nano particles, comprising a substrate, wherein a microchannel is arranged on the substrate; the microchannel forms a flow channel for microfluid to pass through on the substrate; a plurality of expansion structures are arranged on the side wall of the microchannel; the included angle between the side wall first contacted with the microfluid and the wall of the flow channel is an acute angle alpha;

[0008] The shape of the cross section of the expansion structure is triangular, trapezoidal, parallelogram, elliptical, semi-elliptical or irregular circular arc.

[0009] Further, the width D of the microchannel is 0.02-2mm; the width D of the microchannel is the maximum channel width at the position without the expansion structure 3 on the side wall of the microchannel.

[0010] Further, the acute angle alpha is greater than 5° and less than 90°.

[0011] Further, the ratio of the width D of the microchannel to the maximum width d of the expansion structure is 1: (0.1-10).

[0012] Further, the longest length of the expansion structure is 0.1-100 times of the maximum width d; the spacing between the adjacent expansion structures arranged on the side wall of the microchannel is 0.1-10 times of the maximum value of the longest length of the adjacent expansion structures.

[0013] Further, the material of the microchannel is polydimethylsiloxane, polystyrene, polycarbonate, polymethyl methacrylate or polyvinyl chloride.

[0014] Further, the shape of the microchannel is straight line, wave, arc, spiral line, S shape or ring.

[0015] Further, the plurality of expansion structures are uniformly distributed on the same side wall of the microchannel, staggered arranged on two side walls of the microchannel, oppositely arranged on two side walls of the microchannel or irregularly arranged on the same side wall or two side walls of the microchannel.

[0016] Further, the two ends of the microchannel are respectively provided with an inlet and a plurality of outlets.

[0017] Further, the cross section shape of the microchannel is circular, rectangular or trapezoidal.

[0018] Compared with the prior art, the application has the following beneficial effects:

[0019] This invention discloses an inertial microfluidic chip for sorting micro and nanoparticles. Several abrupt expansion structures are arranged on the sidewalls of a microchannel. Among these structures, the acute-angle structure formed by the angle between the sidewall of the main flow channel and the channel wall generates vortices at the corners. Larger particles are affected by these vortices, causing their flow trajectories to shift towards the vortex, while smaller particles are almost unaffected and continue flowing along their original paths. Thus, particles of different sizes flow along different trajectories to different outlets. Compared to common right-angle structures, acute-angle structures generate a larger low-pressure zone, resulting in stronger vortices to capture smaller particles. Vortices generated by common right-angle structures typically only affect particles larger than 10 μm, while the acute-angle structure of this invention is suitable for sorting particles smaller than 10 μm. Attached Figure Description

[0020] Figure 1 This is a top view of the inertial microfluidic chip of the present invention, which has a linear microchannel, a sudden expansion structure with an α of 45°, and several sudden expansion structures distributed on the same sidewall of the microchannel.

[0021] Figure 2 This is a top view of the inertial microfluidic chip of the present invention, which has a linear microchannel, a sudden expansion structure with an α of 45°, and several sudden expansion structures relatively distributed on the two sidewalls of the microchannel.

[0022] Figure 3 This is a top view of the inertial microfluidic chip of the present invention, which has a spiral microchannel, a sudden expansion structure with an α of 30°, and several sudden expansion structures distributed on the same sidewall of the microchannel.

[0023] Figure 4 This is a top view of the inertial microfluidic chip of the present invention, which has a spiral microchannel, a sudden expansion structure with an α of 30°, and several sudden expansion structures relatively distributed on the two sidewalls of the microchannel.

[0024] Figure 5 This is a schematic diagram of the inertial microfluidic chip of the present invention performing micro-nano particle sorting;

[0025] Wherein: 1-substrate; 2-microchannel; 3-sudden expansion structure; 4-microfluidic flow direction; D-width of microchannel; d-maximum width of sudden expansion structure. Detailed Implementation

[0026] In order to make the person skilled in the art better understand the technical scheme of the present application, the technical scheme in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by the person skilled in the art without creative labor should belong to the protection scope of the present application.

[0027] The application discloses an inertial microfluidic chip for sorting micro-nano particles, comprising a substrate 1, wherein a micro-channel 2 with a width D of 0.02-2 mm is arranged on the substrate 1; the micro-channel 2 forms a flow channel for microfluids to pass through on the substrate 1; a plurality of bulging structures 3 are arranged on the sidewall of the micro-channel 2, the bulging structures 3 make the flow channel suddenly widen, the included angle between the sidewall first contacted with the microfluids and the flow channel wall in the bulging structure 3 is an acute angle α, the acute angle α is greater than 5° and less than 90°; and the shape of the cross section of the bulging structure 3 is triangular, trapezoidal, parallelogram, elliptical, semi-elliptical or irregular circular arc.

[0028] Preferably, the material of the micro-channel 2 comprises but is not limited to polydimethylsiloxane (PDMS), polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (PMMA) and polyvinyl chloride (PVC).

[0029] Preferably, the ratio of the width D of the micro-channel 2 to the maximum width d of the bulging structure is 1: (0.1-10). The longest length of the bulging structure 3 is 0.1-100 times the maximum width d. The spacing between adjacent bulging structures arranged on the sidewall of the micro-channel (2) is 0.1-10 times the maximum value of the longest length of the adjacent bulging structures.

[0030] Preferably, the shape of the micro-channel 2 comprises but is not limited to straight line, wave, arc, spiral line, S shape and ring.

[0031] Preferably, the bulging structures 3 are arranged on the same side of the micro-channel wall in a uniform distribution, staggered on both sides of the micro-channel wall, arranged oppositely on both sides of the micro-channel wall or arranged on both sides or one side of the micro-channel wall in other irregular forms.

[0032] Preferably, the micro-channel 2 is provided with an inlet and a plurality of outlets at both ends respectively, and the cross section of the flow channel comprises but is not limited to a circle, a rectangle and a trapezoid.

[0033] Preferably, the width D of the micro-channel 2 is the maximum channel width without the bulging structure 3.

[0034] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of the invention described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover a non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0035] The present invention will now be described in further detail with reference to the accompanying drawings:

[0036] Example 1

[0037] An inertial microfluidic chip for sorting micro and nanoparticles, such as Figure 1 As shown, the device includes a substrate 1, which is a glass sheet. A linear microchannel 2 formed of polydimethylsiloxane (PDMS) material is disposed on the substrate 1. The microchannel 2 forms a flow channel for the passage of microfluidic fluid on the substrate 1. A sudden expansion structure 3 is disposed on one side wall of the microchannel 2. The angle α between the side wall of the sudden expansion structure 3 that first contacts the microfluidic fluid and the flow channel wall is 45°. The ratio of the width D of the microchannel 2 to the maximum width d of the sudden expansion structure 3 is 1:1.

[0038] Example 2

[0039] like Figure 2 As shown, unlike Embodiment 1, in this embodiment, a protrusion structure 3 is provided on both sidewalls of the microchannel 2, and the rest of the structure is the same as in Embodiment 1.

[0040] Example 3

[0041] An inertial microfluidic chip for sorting micro and nanoparticles, such as Figure 3 As shown, the device includes a substrate 1, which is a glass sheet. A spiral microchannel 2 formed of polydimethylsiloxane (PDMS) material is disposed on the substrate 1. The microchannel 2 forms a flow channel for the passage of microfluidic fluid on the substrate 1. The arrow indicates the flow direction 4. Several abrupt expansion structures 3 are disposed on one side wall of the microchannel 2. The angle α between the side wall of the abrupt expansion structure 3 that first contacts the microfluidic fluid and the flow channel wall is 60°. The ratio of the width D of the microchannel 2 to the maximum width d of the abrupt expansion structure 3 is 4:1.

[0042] Example 4

[0043] like Figure 4As shown, different from example 3, in this example, the microchannel 2 is provided with the enlarged structure 3 on both side walls, and the rest of the structure is the same as example 3.

[0044] Figure 5 As shown, the inertial microfluidic chip with the linear microchannel, the enlarged structure with α of 45°, and the plurality of enlarged structures distributed on the same side wall of the microchannel in example 1 is used for micro-nano particle sorting, it can be seen that the vortex is generated when the microfluid flows through the enlarged structure 3, the relatively large particles are affected by the vortex, and the flow trajectory is offset to the side of the vortex, while the relatively small particles are hardly affected by the vortex, and continue to move along the original path, so that the particles of different sizes flow along different trajectories to different outlets after passing through the enlarged structure.

[0045] The above is only for illustrating the technical idea of the present application, and cannot limit the protection scope of the present application, any modification made according to the technical idea of the present application on the basis of the technical scheme falls into the protection scope of the claims of the present application.

Claims

1. An inertial microfluidic chip for sorting micro / nano particles, characterized in that, Includes a substrate (1), on which a microchannel (2) is provided; the microchannel (2) forms a flow channel for microfluidic passage on the substrate (1); a plurality of abrupt expansion structures (3) are provided on the sidewall of the microchannel (2); the angle between the sidewall of the abrupt expansion structure (3) that first contacts the microfluidic and the flow channel wall is an acute angle α; The cross-sectional shape of the abrupt expansion structure (3) is triangular, trapezoidal, parallelogram, elliptical, semi-elliptical or irregular arc; The width D of the microchannel (2) is 0.02-2mm; the width D of the microchannel (2) is the maximum channel width at the point where there is no protruding expansion structure (3) on the side wall of the microchannel (2); The acute angle α is greater than 5° and less than 90°; The ratio of the width D of the microchannel (2) to the maximum width d of the abrupt expansion structure (3) is 1:(0.1-10). The plurality of abrupt expansion structures (3) are arranged alternately on the two side walls of the microchannel (2), arranged opposite each other on the two side walls of the microchannel (2), or arranged in an irregular form on the two side walls of the microchannel (2).

2. An inertial microfluidic chip for sorting micro / nano particles according to claim 1, characterized in that, The longest length of the abrupt expansion structure (3) is 0.1-100 times the maximum width d; the spacing between adjacent abrupt expansion structures on the sidewall of the microchannel (2) is 0.1-10 times the maximum value of the longest length among the adjacent abrupt expansion structures.

3. An inertial microfluidic chip for sorting micro / nano particles according to claim 1, characterized in that, The material of the microchannel (2) is polydimethylsiloxane, polystyrene, polycarbonate, polymethyl methacrylate or polyvinyl chloride.

4. An inertial microfluidic chip for sorting micro / nano particles according to claim 1, characterized in that, The microchannel (2) can be straight, wavy, arc-shaped, spiral, S-shaped, or ring-shaped.

5. An inertial microfluidic chip for sorting micro / nano particles according to claim 1, characterized in that, The microchannel (2) has an inlet and several outlets at its two ends.

6. An inertial microfluidic chip for sorting micro / nano particles according to claim 1, characterized in that, The cross-sectional shape of the microchannel (2) is circular, rectangular or trapezoidal.

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