Bioparticle sorting flow channel and microfluidic chip

Abstract

The present application relates to a kind of biological particle sorting flow channel and microfluidic chip, biological particle sorting flow channel includes first flow channel unit, the first flow channel unit includes oppositely arranged first side wall and second side wall, the first side wall and second side wall are asymmetric curved surface, the first flow channel unit near one side of first side wall or second side wall is excavated with deepening flow channel, the deepening flow channel is along the first flow channel unit extension direction setting.Set with asymmetric curved surface first flow channel unit, form focusing flow, deepening flow channel is along the first flow channel unit extension direction setting, break the liquid flow state near the first flow channel unit near deepening flow channel, so that inertial lift force and dean drag change, destroy original balance, so that the particle such as leukocyte near deepening flow channel side can produce disorderly movement state, avoid leukocyte aggregate band and circulating tumor cell overlap, benefit the recovery of circulating tumor cell.

Description

Technical Field

[0001] This invention relates to the field of biological particle sorting technology, and in particular to a biological particle sorting channel and microfluidic chip. Background Technology

[0002] Inertial focusing microfluidics is increasingly being applied in cell sorting within the biomedical industry, such as for sorting circulating tumor cells (CTCs) from blood. Tumor metastasis occurs when tumor cells detach from the primary or metastatic lesion, circulate in the lymphatic system or peripheral blood, and invade distant tissues, forming new tumor foci and ultimately leading to patient death. These detached tumor cells are called circulating tumor cells (CTCs). The concentration of CTCs is extremely low, typically 1-10 per milliliter of blood, compared to millions of white blood cells and billions of red blood cells per milliliter. Sorting and enriching CTCs is extremely difficult, like finding a needle in a haystack. In traditional linear arc-shaped focusing processes, CTCs tend to overlap with white blood cells, hindering their sorting. Summary of the Invention

[0003] Therefore, it is necessary to provide a biological particle sorting channel and microfluidic chip to address the above problems, which can effectively avoid the overlap of circulating tumor cells and white blood cells and facilitate the sorting of circulating tumor cells.

[0004] A biological particle sorting channel includes a first channel unit, the first channel unit including a first sidewall and a second sidewall disposed opposite to each other, the first sidewall and the second sidewall being asymmetrical curved surfaces, and a deepened channel being excavated on one side of the first channel unit near the first sidewall or the second sidewall, the deepened channel being disposed along the extending direction of the first channel unit.

[0005] When samples such as blood are passed into the aforementioned biological particle sorting channel for particle sorting, a first channel unit with an asymmetric curved surface is used. Due to the influence of inertial lift, Dean's drag, and other forces, the particles in the sample, such as white blood cells and circulating tumor cells in blood, will undergo relative movement within the cross-section of the first channel unit. When each particle reaches its equilibrium position within the cross-section, it will stabilize at that position, thus focusing the particles at a stable location within the cross-section, forming a focused flow that flows downstream. Because the diameters of particles such as white blood cells and circulating tumor cells are different, they will aggregate at different positions within the cross-section of the first channel unit. However, some particles, such as white blood cells and circulating tumor cells, will inertially aggregate in closely clustered zones. Recently, a deepened flow channel was excavated in the first flow channel unit near the first or second sidewall (such as the side away from the aggregation of circulating tumor cells). The deepened flow channel is set along the extension direction of the first flow channel unit, which disrupts the liquid flow state near the deepened flow channel in the first flow channel unit. This changes the inertial lift and Dean drag, and disrupts the original balance. As a result, particles such as leukocytes near the deepened flow channel can generate a disordered movement state, avoiding the overlap of leukocyte aggregates and circulating tumor cells. This ensures that the aggregation of circulating tumor cells is not interfered with, and also prevents leukocytes from aggregating on the same side of the circulating tumor cells. This makes it easier to separate the circulating tumor cells from the leukocytes in the future, and facilitates the recovery of the circulating tumor cells.

[0006] In one embodiment, the biological particle sorting channel further includes a second channel unit connected to the first channel unit. The radius of curvature of the second channel unit is smaller than that of the first channel unit. The deepened channel extends into the second channel unit. The second channel unit includes a third sidewall and a fourth sidewall disposed opposite to each other. The third sidewall and the fourth sidewall are asymmetrical curved surfaces. The third sidewall is connected to the second sidewall, and the fourth sidewall is connected to the first sidewall.

[0007] In one embodiment, the biological particle sorting channel includes a plurality of first channel units and a plurality of second channel units, wherein the first channel units and the second channel units are alternately arranged.

[0008] In one embodiment, the biological particle sorting channel further includes a third channel unit connected to the last second channel unit. The radius of curvature of the third channel unit is greater than that of the first channel unit. The deepened channel extends into the third channel unit, and the third channel unit is rotated 90° relative to the first channel unit. The third channel unit includes a fifth sidewall and a sixth sidewall arranged opposite to each other. The fifth and sixth sidewalls are asymmetrical curved surfaces. The fifth sidewall is connected to the end of the third sidewall away from the second sidewall, and the sixth sidewall is connected to the end of the fourth sidewall away from the first sidewall.

[0009] In one embodiment, the biological particle sorting channel further includes multiple fourth channel units and multiple fifth channel units. The radius of curvature of the fourth channel units is smaller than that of the fifth channel units, and the radius of curvature of the third channel units is larger than that of the fifth channel units. The fourth and fifth channel units are alternately arranged, and the deepening channel extends correspondingly into the fourth and fifth channel units. The third channel unit is rotated 90° relative to the fifth channel unit, and the fourth channel unit includes a seventh sidewall and an eighth sidewall arranged opposite to each other. The seventh and eighth sidewalls are asymmetrical curved surfaces. The fifth flow channel unit includes a ninth and tenth sidewalls arranged opposite each other. The ninth and tenth sidewalls are asymmetrical curved surfaces. The eighth sidewall is connected to the ninth sidewall, and the seventh sidewall is connected to the tenth sidewall. The seventh sidewall of the foremost fourth flow channel unit is connected to the end of the fifth sidewall away from the third sidewall. The eighth sidewall of the foremost fourth flow channel unit is connected to the end of the sixth sidewall away from the fourth sidewall. At least one of the fifth flow channel units has a flow divider hole that penetrates the wall of the fifth flow channel unit.

[0010] In one embodiment, a blocking member is provided in the fifth flow channel unit corresponding to the inlet of the diversion hole, and the blocking member is located on the side of the diversion hole away from the deepened flow channel. The width of the blocking member along the extension direction of the fifth flow channel unit is greater than the diameter of the diversion hole.

[0011] In one embodiment, the biological particle sorting channel further includes a sixth channel unit connected to the fourth channel unit at the far end. The radius of curvature of the sixth channel unit is greater than that of the fifth channel unit. The deepened channel extends into the sixth channel unit. The sixth channel unit is rotated 90° relative to the fifth channel unit and protrudes in the opposite direction to the third channel unit. The sixth channel unit includes an eleventh sidewall and a twelfth sidewall that are opposite to each other. The eleventh sidewall and the twelfth sidewall are asymmetrical curved surfaces. The eleventh sidewall is connected to the end of the eighth sidewall away from the ninth sidewall, and the twelfth sidewall is connected to the end of the seventh sidewall away from the tenth sidewall.

[0012] In one embodiment, the depth of the deepened channel is 50μm-200μm; or the depth of the deepened channel is 70μm-120μm.

[0013] In one embodiment, the radius of curvature of the first sidewall is greater than or less than the radius of curvature of the second sidewall, and the first sidewall and the second sidewall protrude toward the same side.

[0014] And / or, the radius of curvature of the third sidewall is smaller than the radius of curvature of the fourth sidewall, and the third sidewall and the fourth sidewall protrude toward the same side;

[0015] And / or, the radius of curvature of the fifth sidewall is smaller than the radius of curvature of the sixth sidewall, and the fifth sidewall and the sixth sidewall protrude toward the same side;

[0016] And / or, the radius of curvature of the seventh sidewall is smaller than the radius of curvature of the eighth sidewall, and the seventh sidewall and the eighth sidewall protrude toward the same side;

[0017] And / or, the radius of curvature of the ninth sidewall is smaller than the radius of curvature of the tenth sidewall, and the ninth sidewall and the tenth sidewall protrude toward the same side;

[0018] And / or, the radius of curvature of the eleventh sidewall is smaller than the radius of curvature of the twelfth sidewall, and the eleventh sidewall and the twelfth sidewall protrude toward the same side.

[0019] A microfluidic chip includes a functional board, and the first side of the functional board is provided with the biological particle sorting channel.

[0020] A microfluidic chip includes a functional board, a first side of which is provided with the biological particle sorting channel, and a second side of which is provided with a buffer channel with a reciprocating folding structure, the buffer channel being connected to the diversion hole. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of a biological particle sorting channel in one embodiment;

[0022] Figure 2 This is a schematic diagram of the first side of the functional board of a microfluidic chip in one embodiment;

[0023] Figure 3 This is a schematic diagram of the second side of the functional board of a microfluidic chip in one embodiment;

[0024] Figure 4 for Figure 2 A schematic sectional view along section line AA;

[0025] Figure 5 This is a schematic diagram of the top cover of a microfluidic chip in one embodiment;

[0026] Figure 6 This is a schematic diagram of the lower cover plate of a microfluidic chip in one embodiment.

[0027] Explanation of reference numerals in the attached figures:

[0028] 01. Red blood cells; 02. White blood cells; 03. Circulating tumor cells; 1. Biological particle sorting channel; 10. First channel unit; 110. First sidewall; 120. Second sidewall; 2. Deepened channel; 20. Second channel unit; 210. Third sidewall; 220. Fourth sidewall; 30. Third channel unit; 310. Fifth sidewall; 320. Sixth sidewall; 40. Fourth channel unit; 410. Seventh sidewall; 420. Eighth sidewall; 50. Fifth channel unit; 510. Ninth sidewall; 520. Tenth sidewall; 51. Diverter hole; 52. Blocking element; 60 1. Sixth flow channel unit; 610. Eleventh sidewall; 620. Twelfth sidewall; 70. First connecting unit; 710. Thirteenth sidewall; 720. Fourteenth sidewall; 80. Second connecting unit; 810. Fifteenth sidewall; 820. Sixteenth sidewall; 3. Buffer flow channel; 4. Inlet flow channel; 5. Recovery flow channel; 501. First outlet hole; 6. Waste liquid flow channel; 601. Second outlet hole; 11. Functional plate; 101. Sample inlet hole; 22. Upper cover plate; 201. Sample inlet; 33. Lower cover plate; 301. Recovery hole; 302. Waste liquid hole; 303. Discharge hole. Detailed Implementation

[0029] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0030] Please see Figure 1 , 2 One embodiment provides a microfluidic chip, including a functional board 11, wherein a biological particle sorting channel 1 is provided on a first side of the functional board 11.

[0031] Reference Figure 1 In one embodiment, the biological particle sorting channel 1 includes a first channel unit 10, the first channel unit 10 including a first sidewall 110 and a second sidewall 120 disposed opposite to each other, the first sidewall 110 and the second sidewall 120 being asymmetrical curved surfaces, and a deepened channel 2 being excavated on the side of the first channel unit 10 near the first sidewall 110 or the second sidewall 120, the deepened channel 2 being disposed along the extending direction of the first channel unit 10.

[0032] Figure 1This is a schematic diagram of the structure of the biological particle sorting channel 1. The diagram shows an enlarged view of the motion state of circulating tumor cells, white blood cells, and red blood cells in different channel units of the biological particle sorting channel 1. When a sample, such as blood, is introduced into the biological particle sorting channel 1 for particle sorting, the first channel unit 10 with an asymmetric curved surface is set up. Due to the influence of inertial lift, Dean's drag, etc., the particles in the sample, such as white blood cells O2 and circulating tumor cells O3 in blood, will undergo relative movement in the cross-section of the first channel unit 10. When each particle moves to the equilibrium position of the cross-section, the particle will stabilize at this position, thus focusing the particles at a stable position in the cross-section, forming a focused flow that flows downstream. Because the diameters of the particles, such as white blood cells O2 and circulating tumor cells O3 in blood, are different, they will aggregate at different positions in the cross-section of the first channel unit 10. However, some particles, such as white blood cells O2 and circulating tumor cells O3, are inertially aggregated in very close zones. A deepened flow channel 2 is excavated on the side of the channel unit 10 near the first sidewall 110 or the second sidewall 120 (such as the side away from the aggregation of circulating tumor cells 03). The deepened flow channel 2 is set along the extension direction of the first channel unit 10, which disrupts the liquid flow state of the first channel unit 10 near the deepened flow channel 2, changes the inertial lift and Dean drag, and disrupts the original balance. This allows particles such as leukocytes 02 near the deepened flow channel 2 to generate a disordered movement state, avoids the overlap of the leukocyte 02 aggregate and the circulating tumor cells 03, ensures that the aggregation of circulating tumor cells 03 is not interfered with, and also prevents leukocytes 02 from aggregating on the same side of the circulating tumor cells 03. This facilitates the subsequent separation of the circulating tumor cells 03 from the leukocytes 02 and is conducive to the recovery of the circulating tumor cells 03.

[0033] In one embodiment, the biological particle sorting channel 1 further includes a second channel unit 20 connected to the first channel unit 10. The radius of curvature of the second channel unit 20 is smaller than that of the first channel unit 10. The deepened channel 2 extends into the second channel unit 20. The second channel unit 20 includes a third sidewall 210 and a fourth sidewall 220 disposed opposite to each other. The third sidewall 210 and the fourth sidewall 220 are asymmetrical curved surfaces. The third sidewall 210 is connected to the second sidewall 120, and the fourth sidewall 220 is connected to the first sidewall 110. A second flow channel unit 20 with a radius of curvature smaller than that of the first flow channel unit 10 is connected to the first flow channel unit 10. At the same time, the flow channel 2 is deepened and extended into the second flow channel unit 20. This further adjusts the focusing and equilibrium position of the particles, so that the particles gather into a band at the equilibrium position of the cross section of the biological particle sorting flow channel 1 under the combined effect of the first flow channel unit 10 with a large radius of curvature and the second flow channel unit 20 with a small radius of curvature.

[0034] Reference Figure 1, 2 Furthermore, the biological particle sorting channel 1 includes multiple first channel units 10 and multiple second channel units 20, which are alternately arranged. By alternately connecting multiple first channel units 10 and multiple second channel units 20 to form a wave-shaped channel, the particles are physically acted upon, which helps to reduce the length of the channel and achieve the effect of inertial focusing into a band.

[0035] Reference Figure 1 , 2 In one embodiment, the biological particle sorting channel 1 further includes a third channel unit 30 connected to the last second channel unit 20. The radius of curvature of the third channel unit 30 is larger than that of the first channel unit 10. The deepening channel 2 extends into the third channel unit 30, and the third channel unit 30 is rotated 90° relative to the first channel unit 10. The third channel unit 30 includes a fifth sidewall 310 and a sixth sidewall 320 arranged opposite each other. The fifth sidewall 310 and the sixth sidewall 320 are asymmetrical curved surfaces. The fifth sidewall 310 is connected to the end of the third sidewall 210 away from the second sidewall 120, and the sixth sidewall 320 is connected to the end of the fourth sidewall 220 away from the first sidewall 110. The deepening channel 2 extends into the third channel unit 30, and under the action of the deepening channel, the leukocytes O2 are more evenly distributed in the third channel unit 30, avoiding overlap with circulating tumor cells O3. At the very end, the second flow channel unit 20 connects to a third flow channel unit 30 rotated 90°. Due to the larger radius of the third flow channel unit 30, the relative advantage of inertial lift is greater. When passing through the third flow channel unit 30, the centrifugal force experienced by the fluid in the middle of the channel is the greatest, causing it to flow towards the outer edge of the channel. The fluid velocity near the channel wall is the lowest, and the centrifugal force experienced is also the smallest, thus being squeezed by the middle fluid. Therefore, under the action of the third flow channel unit 30, circulating tumor cells 03 can adhere to the bottom of the inner wall of the channel to the maximum extent, preparing for subsequent sorting of circulating tumor cells 03 and removal of leukocytes 02.

[0036] Furthermore, referring to Figure 1 , 2In one embodiment, the biological particle sorting channel 1 further includes multiple fourth channel units 40 and multiple fifth channel units 50. The radius of curvature of the fourth channel unit 40 is smaller than that of the fifth channel unit 50, and the radius of curvature of the third channel unit 30 is larger than that of the fifth channel unit 50. The fourth channel units 40 and the fifth channel units 50 are alternately arranged, and the deepening channel 2 extends correspondingly into the fourth channel units 40 and the fifth channel units 50. The third channel unit 30 is rotated 90° relative to the fifth channel unit 50. The fourth flow channel unit 40 includes a seventh sidewall 410 and an eighth sidewall 420 arranged opposite to each other. The seventh sidewall 410 and the eighth sidewall 420 are asymmetrical curved surfaces. The fifth flow channel unit 50 includes a ninth sidewall 510 and a tenth sidewall 520 arranged opposite to each other. The ninth sidewall 510 and the tenth sidewall 520 are asymmetrical curved surfaces. The eighth sidewall 420 is connected to the ninth sidewall 510. The seventh sidewall 410 of the foremost fourth flow channel unit 40 is connected to the end of the fifth sidewall 310 away from the third sidewall 210. The eighth sidewall 420 of the foremost fourth flow channel unit 40 is connected to the end of the sixth sidewall 320 away from the fourth sidewall 220. At least one of the fifth flow channel units 50 has a flow divider hole 51 that penetrates the wall of the fifth flow channel unit. The sample flows sequentially from the third flow channel unit 30 into the alternately arranged fourth flow channel unit 40 and fifth flow channel unit 50. The fourth flow channel unit 40, the fifth flow channel unit 50, and the third flow channel unit 30 are arranged at 90°. In this way, the fourth flow channel unit 40 and the fifth flow channel unit 50 are alternately connected to form a wave-shaped flow channel, which further sorts the particles, which helps to reduce the length of the flow channel and achieve the effect of inertial focusing into a band. A diversion hole 51 is opened in at least one fifth flow channel unit 50, penetrating the wall of the fifth flow channel unit. Larger particles, such as circulating tumor cells 03, continue to move along the bottom of the inner wall of the fifth flow channel unit 50 (the side away from the deepened flow channel 2). Since smaller particles, such as white blood cells 02 and red blood cells 01, are more evenly distributed in the flow channel, some white blood cells 02 and red blood cells 01 flow out from the diversion hole 51, which facilitates the subsequent recovery of circulating tumor cells 03.

[0037] Meanwhile, as the liquid flows out of the diversion hole 51, the flow velocity of the liquid in the channel will decrease relatively, and the trajectory of the circulating tumor cells 03 will change slightly, making them more likely to move away from the inner wall of the channel. The circulating tumor cells 03 are more likely to approach the diversion hole 51. By connecting a third channel unit 30 with a large radius of curvature before the fourth channel unit 40 and the fifth channel unit 50, the circulating tumor cells 03 will flow close to the bottom of the inner wall of the channel after passing through the large bend of the third channel unit 30, thus preventing the circulating tumor cells 03 from flowing into the diversion hole 51 and improving the recovery rate of the circulating tumor cells 03.

[0038] Reference Figure 1 , 2 In one embodiment, a blocking member 52 is provided in the fifth flow channel unit 50 corresponding to the inlet of the diversion hole 51. The blocking member 52 is located on the side of the diversion hole 51 away from the deepening flow channel 2, and the width of the blocking member 52 along the extension direction of the fifth flow channel unit 50 is greater than the diameter of the diversion hole 51. By providing a blocking member 52 on the side away from the deepening flow channel 2, particles focused on that side, such as circulating tumor cells O3, are prevented from flowing into the diversion hole 51. Furthermore, the width of the blocking member 52 along the extension direction of the fifth flow channel unit 50 is greater than the diameter of the diversion hole 51, allowing the blocking member 52 to block focused particles on the side away from the deepening flow channel 2 for a longer distance along the particle flow direction. Since white blood cells O2 and red blood cells O1 are relatively evenly distributed in the flow channel, white blood cells O2 and red blood cells O1 flow out from the diversion hole 51.

[0039] Reference Figure 3 In one embodiment, the second side of the functional plate 11 is provided with a buffer channel 3 that communicates with the diversion hole 51. The buffer channel 3 has a reciprocating folding structure to stabilize the state of the outflowing liquid and prevent the flow of the remaining liquid in the biological particle sorting channel 1 from being disturbed by shaking, which would affect the subsequent recovery of circulating tumor cells 03.

[0040] Reference Figure 1 , 2 Furthermore, in one embodiment, the biological particle sorting channel 1 further includes a sixth channel unit 60 connected to the last fourth channel unit 40. The radius of curvature of the sixth channel unit 60 is larger than that of the fifth channel unit 50. The deepened channel 2 extends into the sixth channel unit 60, which is rotated 90° relative to the fifth channel unit 50. The sixth channel unit 60 protrudes in the opposite direction to the third channel unit 30. The sixth channel unit 60 includes an eleventh sidewall 610 and a twelfth sidewall 620 arranged opposite to each other. The eleventh sidewall 610 and the twelfth sidewall 620 are asymmetrical curved surfaces. The eleventh sidewall 610 is connected to the end of the eighth sidewall 420 away from the ninth sidewall 510, and the twelfth sidewall 620 is connected to the end of the seventh sidewall 410 away from the tenth sidewall 520. After the blood sample flows through the diversion orifice 51, the content of white blood cells O2 and red blood cells O1 gradually decreases, and the flow rate also gradually decreases. By connecting the sixth flow channel unit 60, which has a radius of curvature greater than that of the fourth flow channel unit 40 and the fifth flow channel unit 50, the movement trajectory of circulating tumor cells O3 can be stabilized, which facilitates the subsequent recovery of circulating tumor cells O3.

[0041] Reference Figure 4Optionally, the depth h of the biological particle sorting channel 1 relative to the first side of the functional plate is 100μm-200μm. Preferably, the depth h of the biological particle sorting channel 1 relative to the first side of the functional plate is 110μm-150μm. In one embodiment, the depth H of the deepening channel 2 is 50μm-200μm, that is, the depth of the deepening channel 2 is 50μm-200μm deeper than the biological particle sorting channel 1. Preferably, the depth of the deepening channel 2 is 70μm-120μm, that is, the depth of the deepening channel 2 is 70μm-120μm deeper than the biological particle sorting channel 1. This ensures that circulating tumor cells 03 can flow as close as possible to the bottom of the inner wall of the flow channel in each flow channel unit of the biological particle sorting channel 1, while disturbing and deepening the liquid flow state on one side of the flow channel 2, so as to avoid the overlap of the band of leukocyte 02 aggregates and circulating tumor cells 03, which would affect the recovery rate and purity of the subsequent circulating tumor cells 03.

[0042] Reference Figure 2 In one embodiment, one end of the sixth flow channel unit 60 is provided with an independent recovery flow channel 5 and a waste liquid flow channel 6. The recovery flow channel 5 is connected to the side of the sixth flow channel unit 60 away from the deepening flow channel 2 (the side where circulating tumor cells 03 focus), and the waste liquid flow channel 6 is connected to the side of the sixth flow channel unit 60 closer to the deepening flow channel 2. Circulating tumor cells 03 flow into the recovery flow channel 5 while adhering to the inner wall of the sixth flow channel unit 60, while white blood cells 02 and red blood cells 01 flow into the waste liquid flow channel 6. In one embodiment, the waste liquid flow channel 6 and the recovery flow channel 5 have a reciprocating folding structure, which stabilizes the liquid flow and prevents the subsequent outflow and drop of liquid from affecting the movement trajectory of the circulating tumor cells 03 at the end of the biological particle sorting flow channel 1.

[0043] Reference Figure 1 , 2Furthermore, in one embodiment, the biological particle sorting channel 1 further includes alternatingly connected first connecting unit 70 and second connecting unit 80. The radius of curvature of the first connecting unit 70 is greater than that of the second connecting unit 80. The first connecting unit 70 includes a thirteenth sidewall 710 and a fourteenth sidewall 720 arranged opposite to each other. The thirteenth sidewall 710 and the fourteenth sidewall 720 are asymmetrical curved surfaces. The second connecting unit 80 includes a fifteenth sidewall 810 and a sixteenth sidewall 820 arranged opposite to each other. The fifteenth sidewall 810 and the sixteenth sidewall 820 are asymmetrical curved surfaces. The fourteenth sidewall 720 is connected to the fifteenth sidewall 810, and the thirteenth sidewall 710 is connected to the sixteenth sidewall 820. The first sidewall 110 of the foremost first channel unit 10 is connected to the sixteenth sidewall 820 of the last second connecting unit 80, and the second sidewall 120 of the foremost first channel unit 10 is connected to the fifteenth sidewall 810 of the last second connecting unit 80. The first connecting unit 70 and the second connecting unit 80 are alternately connected to form a wave-shaped channel. The width of the first connecting unit 70 perpendicular to its extension direction is smaller than the width of the first flow channel unit 10 perpendicular to its extension direction. To avoid the sudden increase in the width of the flow channel when the blood sample enters the biological particle sorting flow channel 1 from the inlet flow channel 4, which would disrupt the original movement trajectory of the circulating tumor cells 03 and prevent damage to the original movement trajectory of the circulating tumor cells 03 against the inner wall, a transition is set between the first connecting unit 70 and the second connecting unit 80, which are smaller than the width of the first flow channel unit 10. This serves as a buffer, preventing the circulating tumor cells 03 from needing to flow through more wave-shaped first flow channel units 10 and second flow channel units 20 before they can aggregate into a thin band close to the inner wall of the flow channel. This also shortens the length of the biological particle sorting flow channel 1.

[0044] Reference Figure 1 Optionally, the first flow channel unit 10 and the second flow channel unit 20 located near the first connecting unit 70 may not have a deepening flow channel 2. This allows the sample to flow stably from the first connecting unit 70 and the second connecting unit 80 into the first flow channel unit 10 and the second flow channel unit 20 without the deepening flow channel 2, avoiding interference with the focusing trajectory of the circulating tumor cells 03. Alternatively, the first flow channel unit 10 and the second flow channel unit 20 located away from the first connecting unit 70 may have a deepening flow channel 2. In this case, the circulating tumor cells 03 are located at the bottom of the flow channel, while the leukocytes 02 have not yet focused at the bottom of the flow channel. The deepening flow channel 2 disrupts the focusing trajectory of the leukocytes 02, causing them to flow towards the side of the deepening flow channel 2, thus avoiding overlap with the circulating tumor cells 03.

[0045] Reference Figure 2Furthermore, in one embodiment, the first side of the functional plate 11 is also provided with an inlet channel 4. One end of the inlet channel 4 is provided with a sample inlet hole 101, and the other end is connected to the first connecting unit 70 of the biological particle sorting channel 1. The inlet channel 4 has a reciprocating folding structure. When the sample enters the inlet end of the inlet channel 4, the red blood cells O1, white blood cells O2, and circulating tumor cells O3 in the sample are evenly distributed in the channel. The diameter of red blood cells O1 is about 6-8 μm, the diameter of white blood cells O2 is about 8-12 μm, and the diameter of circulating tumor cells O3 is about 20-30 μm. When the liquid flows through several bends of the inlet channel 4, the white blood cells O2 and circulating tumor cells O3 slowly aggregate, while the red blood cells O1 are still evenly distributed. As the liquid flows through a longer inlet channel 4, the band of white blood cells O2 and circulating tumor cells O3 aggregates becomes finer. When the liquid flows into the biological particle sorting channel 1, the band of white blood cells O2 and circulating tumor cells O3 aggregates becomes even finer and closer to the inner wall of the inlet channel 4. Setting the inlet channel 4 as a reciprocating fold structure can not only buffer the inflow of blood samples, but also make the liquid flow state more stable, which makes it easier for circulating tumor cells O3 and white blood cells O2 to aggregate into a band in the inlet channel 4.

[0046] Compared to the biological particle sorting channel 1, the inlet channel 4 is a long and narrow channel. Optionally, the width of the inlet channel 4 is 0.3mm-1.2mm. Preferably, the width of the inlet channel 4 is 0.5mm-0.9mm. Optionally, the depth of the inlet channel 4 is 0.06mm-0.3mm. Preferably, the depth of the inlet channel 4 is 0.1mm-0.2mm. This configuration makes the flow rate of blood samples entering the inlet channel 4 more stable, while allowing circulating tumor cells O3 and leukocytes O2 to initially aggregate into a band, facilitating subsequent sorting of circulating tumor cells O3. In other embodiments, for buffering purposes, the inlet channel 4 can also be configured as a reciprocating "S" shape or a spiral shape, etc.

[0047] Reference Figure 1 Optionally, the radius of curvature of the first sidewall 110 is smaller or larger than the radius of curvature of the second sidewall 120, and the first sidewall 110 and the second sidewall 120 protrude towards the same side. Thus, the first flow channel unit 10 forms an asymmetrical arc-shaped flow channel. In one embodiment, the radius of curvature of the first sidewall 110 is larger than the radius of curvature of the second sidewall 120, and the radius of curvature of the thirteenth sidewall 710 of the first connecting unit 70 is smaller than the radius of curvature of the fourteenth sidewall 720, so that the width of the first connecting unit 70 perpendicular to its extension direction is smaller than the width of the first flow channel unit 10 perpendicular to its extension direction.

[0048] In one embodiment, the radius of curvature of the third sidewall 210 is smaller than that of the fourth sidewall 220, and the third sidewall 210 and the fourth sidewall 220 protrude toward the same side. Thus, the second flow channel unit 20 forms an asymmetrical arc-shaped flow channel, enabling connection between adjacent first flow channel units 10 and improving particle sorting.

[0049] In one embodiment, the radius of curvature of the fifth sidewall 310 is smaller than that of the sixth sidewall 320, and the fifth sidewall 310 and the sixth sidewall 320 protrude toward the same side. Thus, the third flow channel unit 30 forms an asymmetrical arc-shaped flow channel, and during the 90° rotation of the biological particle sorting flow channel 1, the circulating tumor cells 03 are closer to the bottom of the flow channel interior.

[0050] In one embodiment, the radius of curvature of the seventh sidewall 410 is smaller than that of the eighth sidewall 420, and the seventh sidewall 410 and the eighth sidewall 420 protrude toward the same side. Thus, the fourth flow channel unit 40 forms an asymmetrical arc-shaped flow channel to connect adjacent fifth flow channel units 50, while simultaneously improving particle sorting.

[0051] In one embodiment, the radius of curvature of the ninth sidewall 510 is smaller or larger than the radius of curvature of the tenth sidewall 520, and the ninth sidewall 510 and the tenth sidewall 520 protrude toward the same side. Thus, the fifth flow channel unit 50 forms an asymmetrical arc-shaped flow channel, while simultaneously improving particle sorting and facilitating the focusing of circulating tumor cells 03 onto one side of the tenth sidewall 520.

[0052] In one embodiment, the radius of curvature of the eleventh sidewall 610 is smaller than that of the twelfth sidewall 620, and the eleventh sidewall 610 and the twelfth sidewall 620 protrude toward the same side. Thus, the sixth flow channel unit 60 forms an asymmetrical arc-shaped flow channel, and during the 90° rotation of the biological particle sorting flow channel 1, the circulating tumor cells 03 are closer to the bottom of the flow channel, facilitating subsequent recovery of the circulating tumor cells 03 along the side closer to the twelfth sidewall 620.

[0053] The biological particle sorting channel 1 is an asymmetrical arc-shaped channel. When the fluid flows in the arc-shaped channel, the parabolic flow has the highest velocity in the middle of the channel. At the bend in the channel, the fluid in the middle of the microchannel experiences the greatest centrifugal force due to its maximum velocity, causing it to flow towards the outer wall of the arc-shaped channel. The fluid near the channel wall has the lowest velocity and experiences the least centrifugal force, thus being compressed by the high-velocity fluid in the middle. To maintain mass conservation throughout the fluid, a pair of counter-rotating and symmetrical vortices are formed perpendicular to the fluid flow direction, located at the upper and lower parts of the channel cross-section, respectively, thus generating a secondary flow of Dean's vortices. Dean's vortices exert a drag force on the particles in the fluid, known as Dean's drag. In the arc-shaped channel, the flowing particles are simultaneously subjected to inertial lift and Dean's drag; the relative magnitudes of these two forces determine the focusing flow pattern of the particles in the arc-shaped channel. In this embodiment, due to the effects of inertial lift and Dean drag, circulating tumor cells 03 are focused into a band on the inner wall of the biological particle sorting channel 1.

[0054] Reference Figure 2-6 In one embodiment, the microfluidic chip further includes an upper cover plate 22 and a lower cover plate 33. The upper cover plate 22 is bonded to a first side of the functional plate 11, and the lower cover plate 33 is bonded to a second side of the functional plate 11, so that the flow channels on the first and second sides of the functional plate 11 form a sealed channel. A sample inlet 201 is provided on the upper cover plate 22, which communicates with the sample inlet hole 101 of the inlet flow channel 4 on the first side of the functional plate 11, so that blood samples can be introduced into the microfluidic chip from the sample inlet 201. The lower cover plate 33 is provided with a recovery hole 301, a waste liquid hole 302, and a discharge hole 303. The diversion hole 51 is connected to the discharge hole 303. Some white blood cells O2 and red blood cells O1 flow from the diversion hole 51 to the second side of the functional plate 11 and flow out of the microfluidic chip from the discharge hole 303 of the lower cover plate 33. The recovery channel 5 is connected to the recovery hole 301 through the first outflow hole 501 that penetrates the first side and the second side of the functional plate 11. The sorted circulating tumor cells O3 flow out of the microfluidic chip from the recovery hole 301 of the lower cover plate 33. The waste liquid channel 6 is connected to the waste liquid hole 302 through the second outflow hole 601 that penetrates the first side and the second side of the functional plate 11. The remaining liquid flows out of the microfluidic chip from the waste liquid hole 302 of the lower cover plate 33.

[0055] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," and "circumferential" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0056] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0057] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0058] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "over," and "on top" of the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0059] It should be noted that when an element is referred to as being "fixed to" or "set on" another element, it can be directly on the other element or there may be an intervening element. When an element is considered to be "connected to" another element, it can be directly connected to the other element or there may be an intervening element. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used herein are for illustrative purposes only and do not represent the only possible implementation.

[0060] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0061] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A bio-particle sorting flow channel, characterized by, The first flow channel unit includes a first sidewall and a second sidewall disposed opposite to each other. The first sidewall and the second sidewall are asymmetrical curved surfaces. A deepened flow channel is excavated on the side of the first flow channel unit near the first sidewall or the second sidewall. The deepened flow channel is disposed along the extension direction of the first flow channel unit. It also includes a second flow channel unit that communicates with the first flow channel unit. The radius of curvature of the second flow channel unit is smaller than that of the first flow channel unit. The deepened flow channel extends into the second flow channel unit. The second flow channel unit includes a third sidewall and a fourth sidewall that are disposed opposite to each other. The third sidewall and the fourth sidewall are asymmetrical curved surfaces. The third sidewall is connected to the second sidewall, and the fourth sidewall is connected to the first sidewall. It includes multiple first flow channel units and multiple second flow channel units, with the first flow channel units and second flow channel units alternately arranged; the depth of the deepened flow channel is 50μm-200μm.

2. The biological particle sorting channel according to claim 1, characterized in that, It also includes a third flow channel unit that communicates with the last second flow channel unit. The radius of curvature of the third flow channel unit is greater than that of the first flow channel unit. The deepened flow channel extends into the third flow channel unit, and the third flow channel unit is rotated 90° relative to the first flow channel unit. The third flow channel unit includes a fifth sidewall and a sixth sidewall that are arranged opposite to each other. The fifth sidewall and the sixth sidewall are asymmetrical curved surfaces. The fifth sidewall is connected to the end of the third sidewall away from the second sidewall, and the sixth sidewall is connected to the end of the fourth sidewall away from the first sidewall.

3. The biological particle sorting channel according to claim 2, characterized in that, It also includes multiple fourth flow channel units and multiple fifth flow channel units. The radius of curvature of the fourth flow channel unit is smaller than that of the fifth flow channel unit, and the radius of curvature of the third flow channel unit is larger than that of the fifth flow channel unit. The fourth and fifth flow channel units are alternately arranged, and the deepened flow channel extends into the fourth and fifth flow channel units accordingly. The third flow channel unit is rotated 90° relative to the fifth flow channel unit. The fourth flow channel unit includes a seventh sidewall and an eighth sidewall arranged opposite each other. The wall is an asymmetrical curved surface. The fifth flow channel unit includes a ninth side wall and a tenth side wall arranged opposite each other. The ninth side wall and the tenth side wall are asymmetrical curved surfaces. The eighth side wall is connected to the ninth side wall. The seventh side wall is connected to the end of the fifth side wall away from the third side wall. The eighth side wall is connected to the end of the sixth side wall away from the fourth side wall. At least one of the fifth flow channel units has a flow-diverting hole that penetrates the wall surface of the fifth flow channel unit.

4. The biological particle sorting channel according to claim 3, characterized in that, The fifth flow channel unit is provided with a blocking member at the inlet of the diversion hole, and the blocking member is located on the side of the diversion hole away from the deepened flow channel. The width of the blocking member along the extension direction of the fifth flow channel unit is greater than the diameter of the diversion hole.

5. The biological particle sorting channel according to any one of claims 3-4, characterized in that, It also includes a sixth flow channel unit that communicates with the fourth flow channel unit at the very end. The radius of curvature of the sixth flow channel unit is greater than that of the fifth flow channel unit. The deepened flow channel extends into the sixth flow channel unit. The sixth flow channel unit is rotated 90° relative to the fifth flow channel unit and protrudes in the opposite direction to the third flow channel unit. The sixth flow channel unit includes an eleventh sidewall and a twelfth sidewall that are arranged opposite each other. The eleventh sidewall and the twelfth sidewall are asymmetrical curved surfaces. The eleventh sidewall is connected to the end of the eighth sidewall away from the ninth sidewall, and the twelfth sidewall is connected to the end of the seventh sidewall away from the tenth sidewall.

6. The biological particle sorting channel according to claim 5, characterized in that, The depth of the deepened flow channel is 70μm-120μm.

7. The biological particle sorting channel according to claim 5, characterized in that, The radius of curvature of the first sidewall is greater than or less than the radius of curvature of the second sidewall, and the first sidewall and the second sidewall protrude toward the same side; And / or, the radius of curvature of the third sidewall is smaller than the radius of curvature of the fourth sidewall, and the third sidewall and the fourth sidewall protrude toward the same side; And / or, the radius of curvature of the fifth sidewall is smaller than the radius of curvature of the sixth sidewall, and the fifth sidewall and the sixth sidewall protrude toward the same side; And / or, the radius of curvature of the seventh sidewall is smaller than the radius of curvature of the eighth sidewall, and the seventh sidewall and the eighth sidewall protrude toward the same side; And / or, the radius of curvature of the ninth sidewall is smaller than the radius of curvature of the tenth sidewall, and the ninth sidewall and the tenth sidewall protrude toward the same side; And / or, the radius of curvature of the eleventh sidewall is smaller than the radius of curvature of the twelfth sidewall, and the eleventh sidewall and the twelfth sidewall protrude toward the same side.

8. A microfluidic chip, characterized in that, It includes a functional board, and the first side of the functional board is provided with a biological particle sorting channel as described in any one of claims 1-7.

9. A microfluidic chip, characterized in that, The device includes a functional board, wherein a first side of the functional board is provided with a biological particle sorting channel as described in any one of claims 3-7, and a second side of the functional board is provided with a buffer channel having a reciprocating folding structure, the buffer channel being connected to the diversion hole.

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