Particle enrichment micro-flow control chip structure

Abstract

The utility model discloses a particle enrichment micro-flow control chip structure, which comprises a chip shell, the spiral guide groove drum is detachably arranged in the chip shell and comprises a drum body, a first connector arranged at the first axial end of the drum body and a second connector arranged at the second axial end of the drum body, and a spiral guide groove extending in the axial direction is formed in the drum body; the flexible pipe is wound in the spiral guide groove, a feeding port is formed in one end of the flexible pipe, and a discharging port is formed in the other end of the flexible pipe; the particle separation component is connected to the discharge port, a main channel, a cell discharge channel communicated with the main channel and a waste liquid discharge channel communicated to the main channel are arranged in the particle separation component, the cell discharge channel is close to the radial inner side of the spiral guide groove drum, and the waste liquid discharge channel is close to the radial outer side of the spiral guide groove drum. And the waste liquid discharge channel is close to the radial outer side of the spiral guide groove drum. The particle enrichment micro-flow control chip structure provided by the utility model can improve the separation efficiency and is suitable for separation of cells with different sizes.

Description

A microfluidic control chip structure for particle enrichment Technical Field

[0001] This invention belongs to the field of microparticle enrichment technology, and specifically relates to a microfluidic control chip structure for microparticle enrichment. Background Technology

[0002] Stem cell transplantation, as a core treatment in regenerative medicine, relies heavily on the viability and purity of the transplanted cells for its efficacy. While cryopreservation is essential for maintaining cell viability during clinical-grade stem cell preparation, residual cryopreservation solution significantly hinders the safety of clinical applications. Currently, the widely used cryopreservation system containing 5-10% dimethyl sulfoxide (DMSO) poses significant clinical risks: studies have shown that DMSO at room temperature disrupts the lipid bilayer structure of cell membranes, leading to abnormal calcium ion influx and activation of the caspase apoptosis pathway. Therefore, the International Society for Cell Therapy (ISCT) has listed residual cryopreservation solution as a key indicator for the quality control of cell products.

[0003] Traditional centrifugation for liquid removal has revealed significant drawbacks in clinical applications, including cell loss due to repeated washing, cytoskeleton damage induced by centrifugation shear force, and the risk of exogenous contamination introduced during the process. While microfluidic technology can achieve gentle separation through laminar flow, existing PDMS chips have inherent limitations: the solidified channels are prone to blockage due to cell adhesion, especially when processing high-concentration frozen-recovered samples; and the fixed curvature channels are difficult to adapt to the size differences of stem cells from different sources. These bottlenecks severely limit the clinical translation of the technology. Summary of the Invention

[0004] The purpose of this invention is to provide a microfluidic control chip structure for particle enrichment, which can achieve the separation requirements of different cell sizes by adjusting the channel curvature or size.

[0005] Based on the above problems, the technical solution provided by this utility model is as follows:

[0006] A microfluidic control chip structure for particle enrichment includes:

[0007] Chip casing;

[0008] A spiral guide groove cylinder, which is detachably disposed inside the chip housing, includes a cylinder body, a first connector disposed at the first axial end of the cylinder body, and a second connector disposed at the second axial end of the cylinder body. The cylinder body is provided with a spiral guide groove extending along the axial direction.

[0009] A flexible tube is wound inside the spiral guide groove, with one end of the flexible tube being a feed inlet and the other end being a discharge outlet;

[0010] A particle separation component is connected to the discharge port. The particle separation component has a main channel, a cell discharge channel connected to the main channel, and a waste liquid discharge channel connected to the main channel. The cell discharge channel is close to the radial inner side of the spiral guide cylinder, and the waste liquid discharge channel is close to the radial outer side of the spiral guide cylinder.

[0011] In some embodiments, the main channel, cell discharge channel, and waste liquid discharge channel are connected in a Y-shape, the cell discharge channel is connected to a cell discharge tube, and the waste liquid discharge channel is connected to a waste liquid discharge tube.

[0012] In some embodiments, the inlet end of the waste liquid discharge channel is provided with several interception columns for intercepting particles.

[0013] In some embodiments, the cylinder is a hollow structure, with one axial end of the cylinder serving as the temperature control medium inlet and the other axial end serving as the temperature control medium outlet.

[0014] In some embodiments, the first connector includes a first end cap extending radially outward from the cylinder and a plurality of first positioning blocks disposed circumferentially on the first end cap.

[0015] The second connector includes a second end cap extending to the radial outer side of the cylinder, a positioning boss disposed at the lower end of the second end cap, and a plurality of second positioning blocks disposed in the circumferential direction of the positioning boss. The outer diameter of the positioning boss is smaller than that of the second end cap, and the outer diameter of the second end cap is the same as that of the first end cap.

[0016] In some embodiments, the chip casing is a hollow cuboid structure, with a chip inlet at the upper end and a chip positioning port at the lower end.

[0017] The inner diameter of the chip inlet is adapted to the outer diameter of the first end cap, and the inner wall of the chip inlet is provided with a plurality of positioning slots that match the plurality of first positioning blocks.

[0018] The inner diameter of the chip positioning port matches the positioning boss, and several positioning steps are provided in the circumferential direction to match the several second positioning blocks.

[0019] In some embodiments, the chip casing has an opening at the front end, and the opening has a transparent viewing window.

[0020] In some embodiments, the second end cap is provided with a plurality of support ribs arranged at intervals in the circumferential direction. The support ribs extend along the axial direction of the cylinder and are spaced apart from the first end cap. There is a gap between the support ribs and the spiral guide groove.

[0021] In some embodiments, the gap is 1.5 to 2 times the outer diameter of the flexible tube.

[0022] In some embodiments, the chip housing sidewall is provided with a through groove for the particle separation component to extend out and a through hole for the feed end of the flexible tube to extend out.

[0023] Compared with the prior art, the advantages of this utility model are:

[0024] 1. The detachable spiral guide tube allows for adjustment of the channel curvature radius to accommodate the separation needs of different cell sizes;

[0025] 2. The spiral radius of the planar spiral channel is continuously changing, which causes the Dean resistance of the fluid flow to continuously change, and the equilibrium position of the particles to continuously change slightly. In this invention, the spiral channel adopts a three-dimensional design, which can enhance the TP effect (tubular pinch effect), so that the cells form a stable spatial focusing zone under the Dean vortex: cells larger than the critical diameter are enriched on the inner side of the channel near the center of the spiral curvature, while small molecules and other harmful substances form a cell-free layer on the outer side. This design effectively reduces the cell loss rate. Attached Figure Description

[0026] To more clearly illustrate the technical solutions of the embodiments of this utility model, the drawings used in the following description of the embodiments will be briefly introduced. The drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 is a schematic diagram of an embodiment of a microfluidic control chip structure for microparticle enrichment according to the present invention.

[0028] Figure 2 is a schematic diagram of the spiral guide groove cylinder in an embodiment of this utility model;

[0029] Figure 3 is a schematic diagram of the particle separation component in an embodiment of this utility model;

[0030] Figure 4 is a magnified view of part A in Figure 3;

[0031] in:

[0032] 1. Chip casing; 1-1. Chip inlet; 1-2. Chip positioning port; 1-3. Positioning bayonet; 1-4. Positioning step; 1-5. Through slot; 1-6. Through hole;

[0033] 2. Spiral guide groove cylinder; 2-1. Cylinder body; 2-1a. Spiral guide groove; 2-2. First connector; 2-2a. First end cap; 2-2b. First positioning block; 2-3. Second connector; 2-3a. Second end cap; 2-3b. Positioning boss; 2-3c. Second positioning block; 2-4. Support rib;

[0034] 3. Flexible pipes;

[0035] 4. Particle separation component; 4-1. Separation body; 4-2. Cover plate; 4-3. Main channel; 4-4. Cell discharge channel; 4-5. Waste liquid discharge channel; 4-6. Interception column; 4-7. Cell discharge tube; 4-8. Waste liquid discharge tube;

[0036] 5. Transparent viewing window. Detailed Implementation

[0037] The above solution will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrating the present invention and are not intended to limit the scope of the present invention. The implementation conditions used in the embodiments can be further adjusted according to the conditions of specific manufacturers, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0038] Figure 1 shows a schematic diagram of the structure of an embodiment of the present invention, which provides a microfluidic control chip structure for particle enrichment, including a chip shell 1, a spiral guide tube 2 detachably disposed in the chip shell 1, a flexible tube 3 wound around the spiral guide tube 2, and a particle separation component 4 connected to the flexible tube 3.

[0039] The flexible tube 3 is made of a flexible polymer with an inner diameter of 190–300 μm, such as polytetrafluoroethylene. The biocompatibility design of the flexible tube 3 can avoid cell damage, and its smooth inner surface can effectively prevent cell aggregation and blockage, significantly improving cell enrichment efficiency.

[0040] The spiral guide tube 2 includes a tube body 2-1, a first connector 2-2 disposed at a first axial end of the tube body 2-1, and a second connector 2-3 disposed at a second axial end of the tube body 2-1. A spiral guide groove 2-1a extending axially is provided on the tube body 2-1. The spiral guide tube 2 and the chip housing 1 are detachably connected via the first connector 2-2 and the second connector 2-3. The spiral guide groove 2-1a has an arc-shaped cross-section to accommodate the flexible tubing 3.

[0041] The cylinder 2-1 has a hollow structure, with one axial end serving as the inlet for the temperature-controlled medium and the other axial end serving as the outlet for the temperature-controlled medium. By introducing a temperature-controlled medium, such as water, into the cylinder 2-1, the cell temperature can be adjusted to meet the requirements of cell separation.

[0042] The first connector 2-2 includes a first end cap 2-2a extending radially outward from the cylinder 2-1 and a plurality of first positioning blocks 2-2b disposed circumferentially on the first end cap 2-2a. The number of first positioning blocks 2-2b is at least two to ensure structural stability; in this example, four are provided. The second connector 2-3 includes a second end cap 2-3a extending radially outward from the cylinder, a positioning boss 2-3b disposed at the lower end of the second end cap 2-3a, and a plurality of second positioning blocks 2-3c disposed circumferentially on the positioning boss 2-3b. The number of second positioning blocks is at least two to ensure structural stability; in this example, four are provided. The outer diameter of the positioning boss 2-3b is smaller than that of the second end cap 2-3a, while the outer diameters of the first end cap 2-2a and the second end cap 2-3a are the same.

[0043] The chip casing 1 has a hollow cuboid structure. A chip inlet 1-1 is provided at the upper end of the chip casing 1, and a chip positioning port 1-2 is provided at the lower end of the chip casing 1. In order to cooperate with the spiral guide tube 2, the inner diameter of the chip inlet 1-1 is set to fit the first end cap 2-2a. At the same time, the inner wall of the chip inlet 1-1 is provided with positioning slots 1-3 that match a number of first positioning blocks 2-2b. The first end cap 2-2a and the second end cap 2-3a can pass through the chip inlet 1-1 to enter the chip casing 1, and the first positioning blocks 2-2b can be locked in the positioning slots 1-3. The inner diameter of the chip positioning port 1-2 is matched with the positioning boss 2-3b, and several positioning steps 1-4 are provided in the circumferential direction to match several second positioning blocks 2-3c. The positioning boss 2-3b can extend into the chip positioning port 1-2, and the second end cap 2-3a abuts against the upper end of the chip positioning port 1-2. The second positioning blocks 2-3c can be fixed on the positioning steps 1-4, thereby realizing the detachable connection between the spiral guide tube 2 and the chip shell 1.

[0044] To facilitate observation of the cells inside the flexible tube 3, an opening is provided at the front end of the chip shell 1, and a transparent observation window 5 is provided at the opening. The transparent observation window 5 can be fixed to the chip shell 1 by existing snap-fit ​​devices or by a hinge. In this example, the dimensions of the transparent observation window 5 are 50mm × 50mm. The dimensions of the chip shell 1 can be appropriately enlarged, with the length, width, and height ranging from a few centimeters. The specific dimensions can be set according to the actual situation, and this utility model does not impose any limitations.

[0045] To improve structural stability, as shown in Figure 2, several support ribs 2-4 are spaced apart circumferentially on the second end cap 2-3a. The support ribs 2-4 extend axially along the cylinder 2-1 and are spaced apart from the first end cap 2-2a, so that the flexible tube 3 can be wound around the spiral guide groove 2-1a on the cylinder 2-1 through this gap. At the same time, there is a gap between the support ribs 2-4 and the spiral guide groove 2-1a, which is 1.5 to 2 times the outer diameter of the flexible tube 3, to ensure radial support of the flexible tube 3.

[0046] To further optimize the implementation effect of this utility model, the chip shell 1 is provided with a through groove 1-5 for the particle separation component 4 to extend out and a through hole 1-6 for the feed end of the flexible tube 3 to extend out.

[0047] As shown in Figure 3, the particle separation component 4 includes a separation main body 4-1 and a cover plate 4-2 disposed on the upper end of the separation main body 4-1. The separation main body 4-1 is provided with a main channel 4-3 connected to the discharge port, a cell discharge channel 4-4 connected to the main channel 4-3, and a waste liquid discharge channel 4-5 connected to the main channel 4-3. The cell discharge channel 4-4 is close to the radial inner side of the spiral guide cylinder 2, and the waste liquid discharge channel 4-5 is close to the radial outer side of the spiral guide cylinder 2, so as to separate and discharge the cells separated by the spiral channel. Preferably, the main channel 4-3, the cell discharge channel 4-4, and the waste liquid discharge channel 4-5 are connected in a Y-shape. The cell discharge channel 4-4 is connected to a cell discharge pipe 4-7, and the waste liquid discharge channel 4-5 is connected to a waste liquid discharge pipe 4-8.

[0048] To further optimize the implementation effect of this utility model, as shown in Figure 4, several intercepting columns 4-6 are provided at the inlet end of the waste liquid discharge channel 4-5 to intercept particles, so as to prevent particles from being discharged from the waste liquid discharge channel 4-8.

[0049] The working principle of this utility model is as follows:

[0050] Based on the equivalent particle size of the target cells, the spiral guide tube 2 is selected with a spiral curvature that matches the enrichment requirements of the target particle size. According to the required lateral migration path length of the target cells, the number of turns of the flexible tube 3 on the spiral guide tube 2 is adjusted, for example, 10-15 turns. The cell stock solution is injected into the inlet of the flexible tube 3, and the flow rate is adjusted to make the Reynolds number Re=1~10. The cell stock solution moves in the flexible tube 3 and is migrated to the preset position under the combined action of Dean flow shear force and inertial lift. The enriched cells are discharged through the cell discharge channel 4-7 on the particle separation component 4, and the remaining liquid is discharged through the waste liquid discharge channel 4-8.

[0051] In summary, this control chip can improve separation efficiency and adjust the curvature of the spiral channel to meet the separation needs of cells of different sizes.

[0052] The above examples are only for illustrating the technical concept and features of this utility model, and are intended to enable those skilled in the art to understand the content of this utility model and implement it accordingly. They should not be used to limit the scope of protection of this utility model. All equivalent changes or modifications made in accordance with the spirit and essence of this utility model should be included within the scope of protection of this utility model.

Claims

1. A microfluidic control chip structure for particle enrichment, characterized in that, include: Chip casing; A spiral guide tube, detachably disposed within the chip housing, includes a tube body, a first connector disposed at a first axial end of the tube body, and a second connector disposed at a second axial end of the tube body. The tube body is provided with a spiral guide groove extending axially. A flexible tube is wound within the spiral guide groove, with one end of the flexible tube being a feed inlet and the other end being a discharge outlet. A particle separation component is connected to the discharge outlet. The particle separation component is provided with a main channel, a cell discharge channel communicating with the main channel, and a waste liquid discharge channel communicating with the main channel. The cell discharge channel is located near the radially inner side of the spiral guide tube, and the waste liquid discharge channel is located near the radially outer side of the spiral guide tube.

2. The microfluidic control chip structure for particle enrichment according to claim 1, characterized in that: The main channel, cell discharge channel, and waste liquid discharge channel are connected in a Y-shape. The cell discharge channel is connected to a cell discharge tube, and the waste liquid discharge channel is connected to a waste liquid discharge tube.

3. The microfluidic control chip structure for particle enrichment according to claim 2, characterized in that: The inlet end of the waste liquid discharge channel is equipped with several interception columns for intercepting particles.

4. The microfluidic control chip structure for particle enrichment according to claim 1, characterized in that: The cylinder has a hollow structure, with one axial end serving as the temperature control medium inlet and the other axial end serving as the temperature control medium outlet.

5. The microfluidic control chip structure for particle enrichment according to claim 1, characterized in that: The first connector includes a first end cap extending to the radial outer side of the cylinder and a plurality of first positioning blocks disposed in the circumferential direction of the first end cap; the second connector includes a second end cap extending to the radial outer side of the cylinder, a positioning boss disposed at the lower end of the second end cap and a plurality of second positioning blocks disposed in the circumferential direction of the positioning boss, wherein the outer diameter of the positioning boss is smaller than that of the second end cap, and the outer diameter of the second end cap is the same as that of the first end cap.

6. The microfluidic control chip structure for particle enrichment according to claim 5, characterized in that: The chip shell has a hollow cuboid structure. The upper end of the chip shell is provided with a chip inlet and the lower end is provided with a chip positioning port. The inner diameter of the chip inlet is adapted to the outer diameter of the first end cap. The inner wall of the chip inlet is provided with a plurality of positioning slots that match the plurality of first positioning blocks. The inner diameter of the chip positioning port matches the positioning boss and is provided with a plurality of positioning steps in the circumferential direction that match the plurality of second positioning blocks.

7. The microfluidic control chip structure for particle enrichment according to claim 5, characterized in that: The chip casing has an opening at the front end, and a transparent viewing window is provided on the opening.

8. The microfluidic control chip structure for particle enrichment according to claim 5, characterized in that: The second end cap is provided with a plurality of support ribs arranged at intervals in the circumferential direction. The support ribs extend along the axial direction of the cylinder and are spaced apart from the first end cap. There is a gap between the support ribs and the spiral guide groove.

9. The microfluidic control chip structure for particle enrichment according to claim 8, characterized in that: The gap is 1.5 to 2 times the outer diameter of the flexible tube.

10. The microfluidic control chip structure for particle enrichment according to claim 1, characterized in that: The chip casing sidewall is provided with a through groove for the particle separation component to extend out and a through hole for the feed end of the flexible tube to extend out.

Images