microfluidic chip

Abstract

This invention relates to a microfluidic chip, comprising a functional board with an inlet channel, a transition channel, and a sorting channel. One end of the inlet channel is connected to a sample inlet, and the inlet channel has a reciprocating folding structure. One end of the transition channel is connected to the other end of the inlet channel, and the width of the transition channel perpendicular to its extension direction is greater than the width of the inlet channel perpendicular to its extension direction. The sorting channel is connected to the other end of the transition channel, and the width of the sorting channel perpendicular to its extension direction is greater than the width of the transition channel perpendicular to its extension direction. By designing the inlet channel with a reciprocating folding structure, and simultaneously designing a transition channel with a width smaller than the sorting channel but larger than the inlet channel, particles in the sample can inertially aggregate into a band within a shorter channel length before entering the sorting channel, effectively shortening the channel length without affecting the inertial aggregation of circulating tumor cells.

Description

Technical Field

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

[0002] Tumor metastasis occurs when tumor cells detach from the primary or metastatic lesion, circulate in the lymphatic system or peripheral blood, invade distant tissues, and form new tumor foci, ultimately leading to the patient's death. These detached tumor cells are called circulating tumor cells (CTCs). Therefore, by examining the number and types of CTCs in the blood, the dynamic changes in tumor lesions can be monitored, and the effectiveness of treatment can be assessed. Immunophenotyping and genomic sequencing analyses of isolated CTCs can identify drug targets, enabling personalized precision treatment. CTCs are also extremely important for early tumor screening. When tumors are 1-2 millimeters in size, they are difficult to detect using imaging techniques. However, in the early stages of many cancers, a certain number of CTCs are present in the blood. For high-risk patients, regular CTC testing helps in the early detection and treatment of cancer, preventing disease progression. Therefore, the sorting and enrichment of CTCs from the blood is particularly important, although the concentration of CTCs is extremely low.

[0003] Techniques for sorting and enriching circulating tumor cells can be broadly categorized into: immunomagnetic bead method, density gradient centrifugation, membrane filtration, and microfluidic chip technology. Among these, microfluidic chip technology involves introducing samples into the channels of a microfluidic chip and using physical principles to separate different particles within the sample. Microfluidic chip channels can be helical or linear arcuate. However, traditional helical channels are difficult to manufacture and result in larger microfluidic chip sizes; while traditional linear arcuate channels often require longer pipes to allow particles to aggregate inertially, leading to larger microfluidic chip sizes as well. Summary of the Invention

[0004] Therefore, it is necessary to provide a microfluidic chip that can effectively shorten the flow channel length without affecting the inertial aggregation of circulating tumor cells.

[0005] A microfluidic chip includes a functional board, wherein the functional board is provided with:

[0006] An inlet channel, one end of which is used to communicate with a sample inlet, wherein the inlet channel has a reciprocating folding structure;

[0007] A transition channel, one end of which is connected to the other end of the inlet channel, wherein the width of the transition channel perpendicular to its extension direction is greater than the width of the inlet channel perpendicular to its extension direction; and

[0008] The sorting channel is connected to the other end of the transition channel, and the width of the sorting channel perpendicular to its extension direction is greater than the width of the transition channel perpendicular to its extension direction.

[0009] When using the aforementioned microfluidic chip to sort particles such as circulating tumor cells in blood, the sample enters through the inlet channel and flows sequentially into the transition channel and the sorting channel. The inlet channel, connected to the sample inlet, is configured with a reciprocating folding structure to buffer the sample, allowing the velocity of the introduced sample to gradually stabilize within the reciprocating folding structure. Furthermore, the reciprocating folding structure creates multiple bends in the inlet channel. Due to the influence of inertial lift and Dean's drag forces, red blood cells, with their smaller diameter, flow chaotically and disorderly within the inlet channel, while white blood cells and circulating tumor cells, with their larger diameters, initially aggregate into bands under the balance of forces within the inlet channel. The particles then flow into the transition channel, gradually forming a finer aggregation band, which is beneficial for the inertial aggregation of particles. This process is also easier than fabricating spiral pipes or traditional linear arc-shaped channels. The reciprocating folds make the overall channel layout more concentrated, effectively shortening the channel length. Since the width of the sorting channel is often much larger than the width of the inlet channel, a transition channel with a width smaller than the sorting channel allows the sample to transition from the inlet channel to the sorting channel, acting as a buffer. This prevents the sample from suddenly entering a wider channel from a narrower one, disrupting the original particle trajectory and avoiding damage to the original inertial aggregation trajectory. It also avoids the need for the sample to flow through a longer, wider sorting channel before the particles can aggregate close to the inner wall and form a fine band. This microfluidic chip, by designing a reciprocating inlet channel and a transition channel with a width smaller than the sorting channel but larger than the inlet channel, allows particles in the sample to inertially aggregate into a band within a shorter channel length before entering the sorting channel, effectively shortening the channel length without affecting the inertial aggregation of circulating tumor cells.

[0010] In one embodiment, the inlet channel includes an inlet section and a connecting section connected together. The end of the inlet section away from the connecting section is used to communicate with a sample inlet, and the end of the connecting section away from the inlet section is used to communicate with a transition channel. The inlet section has a reciprocating folding structure.

[0011] In one embodiment, the inlet section includes multiple straight pipe sections and multiple bent pipe sections. Two adjacent straight pipe sections are connected by bent pipe sections. The first straight pipe section is used to communicate with the sample inlet, and the last bent pipe section is arranged in a clockwise direction and connected to the connecting section.

[0012] In one embodiment, the straight pipe section between the initial straight pipe section and the final curved pipe section includes alternating long straight pipes and short straight pipes, with both ends of the same long straight pipe connected to two short straight pipes via curved pipe sections arranged in a clockwise direction; or both ends of the same long straight pipe connected to two short straight pipes via curved pipe sections arranged in a counterclockwise direction.

[0013] In one embodiment, the long straight tube and the short straight tube are arranged in parallel along the sample flow direction, and two adjacent long straight tubes and the short straight tube located between the two long straight tubes are arranged at intervals along the width direction of the straight tube segment.

[0014] In one embodiment, the initial straight pipe section is connected to a long straight pipe via a clockwise bend and a counterclockwise bend in sequence; the final straight pipe section is connected to the connecting section via a counterclockwise bend and a clockwise bend in sequence.

[0015] In one embodiment, the connecting segment includes a first straight pipe segment, a first arc segment, a second straight pipe segment, a second arc segment, and a third straight pipe segment connected in sequence. The first straight pipe segment is connected to the last curved pipe segment. The first arc segment is a 90° arc segment arranged in a clockwise direction, and the second arc segment is a 90° arc segment arranged in a clockwise direction.

[0016] In one embodiment, a first region is formed between the extension line of the first straight pipe segment and the extension line of the second straight pipe segment, and the inlet segment folds back and forth within the range of the first region.

[0017] In one embodiment, the transition channel includes alternating first bend units and second bend units, wherein the radius of curvature of the first bend unit is greater than the radius of curvature of the second bend unit.

[0018] The sorting channel includes alternating third and fourth bend units, the radius of curvature of the third bend unit being larger than that of the fourth bend unit, and the last second bend unit connecting to the first third bend unit; wherein the width of the first bend unit perpendicular to its extension direction is 'a', and the width of the third bend unit perpendicular to its extension direction is 'b', where 'a'... <b。

[0019] In one embodiment, the first bending unit includes a first sidewall and a second sidewall disposed opposite to each other, the first sidewall and the second sidewall being asymmetrical curved surfaces; the second bending unit includes a third sidewall and a fourth sidewall disposed opposite to each other, the third sidewall and the fourth sidewall being asymmetrical curved surfaces; the third sidewall is connected to the second sidewall; and the fourth sidewall is connected to the first sidewall.

[0020] The third bend unit includes a fifth sidewall and a sixth sidewall arranged opposite to each other. The fifth sidewall and the sixth sidewall are asymmetrical curved surfaces. The fourth bend unit includes a seventh sidewall and an eighth sidewall arranged opposite to each other. The seventh sidewall and the eighth sidewall are asymmetrical curved surfaces. The fifth sidewall and the eighth sidewall are connected, and the sixth sidewall and the seventh sidewall are connected.

[0021] The first and second bend units protrude in different directions, the third and fourth bend units protrude in different directions, and the first and third bend units protrude in the same direction.

[0022] In one embodiment, the radius of curvature of the third sidewall is smaller than that of the fourth sidewall, and the radius of curvature of the seventh sidewall is smaller than that of the eighth sidewall.

[0023] The radius of curvature of the first sidewall is smaller than that of the second sidewall, and the radius of curvature of the fifth sidewall is larger than that of the sixth sidewall.

[0024] In one embodiment, b is 0.4mm-1.2mm larger than a; or b is 0.7mm-0.9mm larger than a.

[0025] In one embodiment, the functional board is further provided with a first turning channel, a removal channel, and a second turning channel connected in sequence. The end of the first turning channel away from the removal channel flows into the sorting channel. The radius of curvature of the first turning channel is greater than that of the sorting channel. A diversion hole penetrating the wall of the removal channel is provided in the removal channel. A buffer channel communicating with the diversion hole is provided on the side of the functional board opposite to the side where the removal channel is located. The buffer channel has a reciprocating folding structure. The radius of curvature of the second turning channel is greater than that of the removal channel. A deepening channel is excavated on the side of the sorting channel, the first turning channel, the removal channel, and the second turning channel away from the accumulation of circulating tumor cells. An independent recovery channel and a waste liquid channel are provided at the end of the second turning channel away from the removal channel. The recovery channel is connected to the side of the second turning channel near the accumulation of circulating tumor cells. The waste liquid channel is connected to the side of the second turning channel near the deepening channel.

[0026] In one embodiment, the microfluidic chip further includes an upper cover plate and a lower cover plate. The upper cover plate is stacked and connected to one side of the functional board, and the lower cover plate is stacked and connected to the other side of the functional board. The upper cover plate has a sample inlet communicating with the inlet channel, and the lower cover plate has a recovery hole communicating with the recovery channel, a waste liquid hole communicating with the waste liquid channel, and a discharge hole communicating with the buffer channel. The recovery channel and the waste liquid channel both have a reciprocating folding structure. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the top cover of a microfluidic chip in one embodiment;

[0028] Figure 2 This is a schematic diagram of the first side of the functional board of a microfluidic chip in one embodiment;

[0029] Figure 3 This is a schematic diagram of the second side of the functional board of a microfluidic chip in one embodiment;

[0030] Figure 4 This is a schematic diagram of the lower cover plate of a microfluidic chip in one embodiment;

[0031] Figure 5 This is a schematic diagram showing the movement of circulating tumor cells, white blood cells, and red blood cells in a blood sample within the inlet channel.

[0032] Figure 6 This diagram illustrates the movement of circulating tumor cells, white blood cells, and red blood cells in a blood sample within the transition and sorting channels.

[0033] Explanation of reference numerals in the attached figures:

[0034] 01. Red blood cells; 02. White blood cells; 03. Circulating tumor cells; 1. Functional plate; 10. Inlet channel; 11. Sample inlet; 110. Inlet section; 112. Straight tube section; 114. Bend section; 116. Long straight tube; 118. Short straight tube; 120. Connecting section; 121. First straight tube section; 122. First arc-shaped section; 123. Second straight tube section; 124. Second arc-shaped section; 125. Third straight tube section; 210. Transition channel; 13. First bend unit; 13a. First sidewall; 13b. Second sidewall; 14. Second bend unit; 14a. Third sidewall; 14b. Fourth sidewall; 220, sorting channel; 15, third bend unit; 15a, fifth sidewall; 15b, sixth sidewall; 16, fourth bend unit; 16a, seventh sidewall; 16b, eighth sidewall; 30, deepened channel; 40, first turning channel; 50, removal channel; 51, diversion hole; 52, blocking element; 60, second turning channel; 70, recovery channel; 71, first outlet hole; 80, waste liquid channel; 81, second outlet hole; 90, buffer channel; 2, upper cover plate; 21, sample inlet; 3, lower cover plate; 31, recovery hole; 32, waste liquid hole; 33, discharge hole. Detailed Implementation

[0035] 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.

[0036] Please see Figure 1-4 One embodiment provides a microfluidic chip, including a functional board 1. The functional board 1 is provided with an inlet channel 10, a transition channel 210, and a sorting channel 220. Further, the microfluidic chip also includes an upper cover plate 2 and a lower cover plate 3. The upper cover plate 2 is stacked and connected to a first side of the functional board 1, and the lower cover plate 3 is stacked and connected to a second side of the functional board 1. The upper cover plate 2 has a sample inlet 21 communicating with the inlet channel 10.

[0037] Reference Figure 2 , 5 In one embodiment, one end of the inlet channel 10 is used to communicate with the sample inlet 21, and the inlet channel 10 has a reciprocating folding structure. (Refer to...) Figure 2 , 6One end of the transition channel 210 is connected to the other end of the inlet channel 10, and the width of the transition channel 210 perpendicular to its extension direction is greater than the width of the inlet channel 10 perpendicular to its extension direction. The sorting channel 220 is connected to the other end of the transition channel 210, and the width of the sorting channel 220 perpendicular to its extension direction is greater than the width of the transition channel 210 perpendicular to its extension direction.

[0038] When using the aforementioned microfluidic chip to sort particles such as circulating tumor cells 03 in blood, the sample enters through the inlet channel 10 and flows sequentially into the transition channel 210 and the sorting channel 220. The inlet channel 10, which is connected to the sample inlet 21, is configured as a reciprocating folding structure to buffer the sample, allowing the speed of the introduced sample to gradually stabilize within the reciprocating folding structure of the inlet channel 10. Furthermore, the reciprocating folding structure of the inlet channel 10 can form multiple bends. Due to the influence of inertial lift, Dean's drag, and other forces, the smaller diameter of red blood cells 01 flows chaotically and disorderly within the inlet channel 10, while the larger diameters of white blood cells 02 and circulating tumor cells 03, under the balance of forces within the inlet channel 10, will initially aggregate into bands. The particles then flow into the transition channel 210, gradually forming a finer aggregation band, which is beneficial for the inertial aggregation of particles. Moreover, the processing difficulty is easier compared to spiral pipes or traditional linear arc channels. Due to the reciprocating back and forth, the overall channel layout is more concentrated, which can effectively shorten the channel length. Since the width of the sorting channel 220 is often much larger than the width of the inlet channel 10, by setting a transition channel 210 with a width smaller than the sorting channel 220, the sample transitions from the inlet channel 10 to the sorting channel 220, which plays a buffering role. This prevents the sample from suddenly entering a wider channel from a smaller channel, which would disrupt the original movement trajectory of the particles and destroy the original inertial aggregation trajectory of the particles. It also avoids the need to flow through a longer and wider sorting channel 220 before the particles can aggregate close to the inner wall of the channel to form a fine band. This microfluidic chip features an inlet channel 10 with a reciprocating folding structure and a transition channel 210 with a width smaller than the sorting channel 220 but larger than the inlet channel 10. This design facilitates the inertial aggregation of particles in the sample into a band within a shorter channel length before entering the sorting channel 220, effectively shortening the channel length without affecting the inertial aggregation of circulating tumor cells (O3). This microfluidic chip can be used to sort and enrich circulating tumor cells (O3) in blood samples, as well as to sort and enrich other biological particles.

[0039] Reference Figure 2 , 5In one embodiment, the inlet channel 10 includes an inlet section 110 and a connecting section 120 connected together. The end of the inlet section 110 away from the connecting section 120 is used to communicate with the sample inlet 21, and the end of the connecting section 120 away from the inlet section 110 is used to communicate with the transition channel 210. The inlet section 110 has a reciprocating fold structure.

[0040] When a blood sample enters the inlet of the inlet section 110, erythrocytes (01), leukocytes (02), and circulating tumor cells (03) are evenly distributed in the flow channel. Erythrocytes (01) have a diameter of approximately 6-8 μm, leukocytes (02) have a diameter of approximately 8-12 μm, and circulating tumor cells (03) have a diameter of approximately 20-30 μm. As the liquid flows through several bends in the inlet section 110, leukocytes (02) and circulating tumor cells (03) gradually aggregate, while erythrocytes (01) remain evenly distributed. As the liquid flows through the longer connecting section 120, the aggregated band of leukocytes (02) and circulating tumor cells (03) becomes finer. When the liquid flows into the transition channel 210, the aggregated band of leukocytes (02) and circulating tumor cells (03) becomes even finer and closer to the inner wall of the connecting section 120. Setting the inlet section 110 as a reciprocating fold structure not only buffers the inflow of blood samples and makes the liquid flow state more stable, but also facilitates the aggregation of circulating tumor cells O3 and white blood cells O2 in this flow channel as the blood sample flows through the inlet section 110 and the connecting section 120.

[0041] Compared to the transition channel 210 and the sorting channel 220, the inlet channel 10 is an elongated channel. Optionally, the width of the inlet channel 10 is 0.3mm-1.2mm. Preferably, the width of the inlet channel 10 is 0.5mm-0.9mm. Optionally, the depth of the inlet channel 10 is 0.06mm-0.3mm. Preferably, the depth of the inlet channel 10 is 0.1mm-0.2mm. This configuration allows the flow rate of blood samples entering the inlet channel 10 to be relatively stable, while simultaneously allowing circulating tumor cells O3 and leukocytes O2 to initially aggregate into bands, facilitating subsequent sorting of circulating tumor cells O3.

[0042] Specifically, refer to Figure 5In one embodiment, the inlet section 110 includes multiple straight pipe sections 112 and multiple bent pipe sections 114. Two adjacent straight pipe sections 112 are connected by bent pipe sections 114. The initial straight pipe section 112 is connected to the sample inlet 21 through the sample inlet hole 11, and the final bent pipe section 114 is arranged in a clockwise direction and connected to the connecting section 120. This arrangement creates multiple bends in the inlet section 110, gradually stabilizing the blood sample velocity and providing a buffering effect. This facilitates the initial aggregation of leukocytes O2 and circulating tumor cells O3, and the processing is easier compared to spiral pipes, allowing for a smaller overall chip size. The final bent pipe section 114 of the inlet section 110 is arranged in a clockwise direction and connected to the connecting section 120 primarily to ensure that large circulating tumor cells O3 particles always aggregate on the inner wall of the flow channel during subsequent sorting.

[0043] In one embodiment, the straight pipe segment 112 between the initial straight pipe segment 112 and the final curved pipe segment 114 includes alternating long straight pipes 116 and short straight pipes 118. Both ends of the same long straight pipe 116 (e.g., the lower long straight pipe 116) are connected to two short straight pipes 118 via a clockwise curved pipe segment 114. Alternatively, both ends of the same long straight pipe 116 (e.g., the upper long straight pipe 116) are connected to two short straight pipes 118 via a counterclockwise curved pipe segment 114. Clockwise and counterclockwise directions are determined along the sample flow direction. By alternating the long straight pipes 116 and short straight pipes 118, the straight pipe segments 112 are arranged in multiple rows in the direction perpendicular to the sample flow, allowing for a more rational arrangement of the flow channels and facilitating a reduction in the length and width of the chip.

[0044] Furthermore, the long straight tube 116 and the short straight tube 118 are arranged parallel to each other along the sample flow direction. Two adjacent long straight tubes 116 and the short straight tube 118 located between them are spaced apart along the width of the straight tube section 112. The long straight tubes 116 and the short straight tubes 118 are connected by a 180° bend 114. The long straight tubes 116 and the short straight tubes 118 are arranged parallel to each other, forming three rows along the width of the straight tube section 112.

[0045] Specifically, refer to Figure 5 At the very beginning (the inlet end of the inlet section 110), the straight pipe section 112 is connected to a long straight pipe 116 via clockwise and counterclockwise bend sections 114. At the very end, the straight pipe section 112 is connected to the connecting section 120 via counterclockwise and clockwise bend sections 114. When the sample flows into the connecting section 120, it flows clockwise, which facilitates the initial aggregation of circulating tumor cells O3 into a band on one side of the inner wall of the flow channel.

[0046] Reference Figure 2, 5 In one embodiment, the connecting section 120 includes a first straight pipe section 121, a first arc-shaped section 122, a second straight pipe section 123, a second arc-shaped section 124, and a third straight pipe section 125 connected in sequence. The first straight pipe section 121 is connected to the end of the inlet section 110 away from the sample inlet 21. The third straight pipe section 125 is connected to the sorting pipe 20. Specifically, the end of the inlet section 110 is arranged in a clockwise direction and connected to the first straight pipe section 121, so that the circulating tumor cells O3 always accumulate on the inner wall of the flow channel. The connecting section 120 connects the inlet section 110 and the sorting pipe 20. Blood samples flow from the end of the inlet section 110 clockwise through the first straight pipe section 121, the first arc-shaped section 122, the second straight pipe section 123, the second arc-shaped section 124, and the third straight pipe section 125. The bands where leukocytes (O2) and circulating tumor cells (O3) aggregate gradually narrow. When the liquid is in the third straight pipe section 125 and about to enter the sorting pipe 20, the bands where leukocytes (O2) and circulating tumor cells (O3) aggregate become even narrower and closer to the inner wall of the pipe. In one embodiment, the first arc-shaped section 122 is a 90° arc-shaped section arranged clockwise, and the second arc-shaped section 124 is also a 90° arc-shaped section arranged clockwise. The first straight pipe section 121 and the third straight pipe section 125 are spaced vertically, with the third straight pipe section 125 located above the first straight pipe section 121.

[0047] Furthermore, a first region 126 is formed between the extension line of the first straight pipe section 121 and the extension line of the third straight pipe section 125, and the inlet section 110 folds back and forth within the first region. By rationally arranging the positions of each segment of the flow channel, the volume of the chip is fully utilized, which facilitates the miniaturization of the overall chip size and also facilitates the initial aggregation of leukocytes O2 and circulating tumor cells O3 into a band.

[0048] In one embodiment, the transition flow channel 210 includes first elbow units 13 and second elbow units 14 that are alternately arranged, and the radius of curvature of the first elbow units 13 is greater than the radius of curvature of the second elbow units 14. The sorting flow channel 220 includes third elbow units 15 and fourth elbow units 16 that are alternately arranged, and the radius of curvature of the third elbow units 15 is greater than the radius of curvature of the fourth elbow units 16. The second elbow unit 14 at the outermost end is connected to the third elbow unit 15 at the innermost end. The width of the first elbow unit 13 perpendicular to its extending direction is a, and the width of the third elbow unit 15 perpendicular to its extending direction is b, and a < b. The transition flow channel 210 is formed by alternately connecting the first elbow units 13 with a large radius of curvature and the second elbow units 14 with a small radius of curvature, and the sorting flow channel 220 is formed by alternately connecting the third elbow units 15 with a large radius of curvature and the fourth elbow units 16 with a small radius of curvature. The width of the transition flow channel 210 perpendicular to its extending direction mainly refers to the width of the first elbow unit 13 perpendicular to its extending direction, and the width of the sorting flow channel 220 perpendicular to its extending direction mainly refers to the width of the third elbow unit 15 perpendicular to its extending direction. According to factors such as cell diameter, flow channel height and width, and liquid flow rate, through the force analysis of inertial lift, Dean drag, etc., the circulating tumor cells 03 approach the bottom of the inner wall of the sorting flow channel 220, and the white blood cells 02 also gradually approach the bottom of the inner wall of the sorting flow channel 220. Optionally, b is 0.4 mm - 1.2 mm larger than a. Preferably, b is 0.7 mm - 0.9 mm larger than a.

[0049] Refer to Figure 5Furthermore, the first bending unit 13 includes a first sidewall 13a and a second sidewall 13b arranged opposite to each other, the first sidewall 13a and the second sidewall 13b being asymmetrical curved surfaces. The second bending unit 14 includes a third sidewall 14a and a fourth sidewall 14b arranged opposite to each other, the third sidewall 14a and the fourth sidewall 14b being asymmetrical curved surfaces. The third sidewall 14a is connected to the second sidewall 13b, and the fourth sidewall 14b is connected to the first sidewall 13a. The third bending unit 15 includes a fifth sidewall 15a and a sixth sidewall 15b arranged opposite to each other, the fifth sidewall 15a and the sixth sidewall 15b being asymmetrical curved surfaces. The fourth bending unit 16 includes a seventh sidewall 16a and an eighth sidewall 16b arranged opposite to each other, the seventh sidewall 16a and the eighth sidewall 16b being asymmetrical curved surfaces. The fifth sidewall 15a is connected to the eighth sidewall 16b, and the sixth sidewall 15b is connected to the seventh sidewall 16a. The first bend unit 13 and the second bend unit 14 protrude in different directions, the third bend unit 15 and the fourth bend unit 16 protrude in different directions, and the first bend unit 13 and the third bend unit 15 protrude in the same direction. This asymmetric curved surface configuration creates asymmetric inertial aggregation, causing circulating tumor cells to focus at a stable position in the cross-section of the flow channel (bottom of the inner wall of the flow channel) to form a band, resulting in focused flow downstream.

[0050] Reference Figure 5 In one embodiment, the radius of curvature of the third sidewall 14a is smaller than that of the fourth sidewall 14b, and the radius of curvature of the seventh sidewall 16a is smaller than that of the eighth sidewall 16b. In another embodiment, the radius of curvature of the first sidewall 13a is smaller than that of the second sidewall 13b, and the radius of curvature of the fifth sidewall 15a is larger than that of the sixth sidewall 15b. This makes the distance between the first sidewall 13a and the second sidewall 13b smaller than the distance between the fifth sidewall 15a and the sixth sidewall 15b, thus achieving a buffer for the fluid flow from the transition channel 210 to the sorting channel 220.

[0051] Reference Figure 2In one embodiment, the functional plate 1 is further provided with a first turning channel 40, the radius of curvature of the first turning channel 40 being larger than the radius of curvature of the sorting channel 220. The first turning channel 40 flows through the sorting channel 220, and the deepening channel 30 extends correspondingly into the first turning channel 40. Under the action of the deepening channel 30, leukocytes O2 are more evenly distributed in the first turning channel 40, avoiding overlap with circulating tumor cells O3. A first turning channel 40 is connected to the sorting channel 220. Due to the large radius of the first turning channel 40, the relative advantage of inertial lift is greater. When passing through the first turning channel 40, the centrifugal force on the fluid in the middle of the channel is the greatest, thus flowing towards the outer edge of the channel. The fluid velocity near the channel wall is the smallest, and the centrifugal force is also the smallest, thus being squeezed by the middle fluid. Thus, under the action of the first turning channel 40, the circulating tumor cells 03 can be brought as close as possible to the bottom of the inner wall of the channel, preparing for the subsequent sorting of circulating tumor cells 03 and the removal of white blood cells 02.

[0052] Furthermore, referring to Figure 2 In one embodiment, the functional plate 1 is further provided with a removal channel 50, which is connected to the end of the first turning channel 40 away from the sorting channel 220. The deepening channel 30 extends into the removal channel 50 accordingly, and a diversion hole 51 penetrating the wall of the removal channel 50 is provided in the removal channel 50. Blood continues to flow in the removal channel 50, passing through the diversion hole 51. Circulating tumor cells 03 continue to move along the bottom of the inner wall of the removal channel 50. Since white blood cells 02 and red blood cells 01 are relatively evenly distributed in the 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.

[0053] As the liquid flows out of the diversion orifice 51, the flow velocity of the liquid in the flow 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 flow channel. The circulating tumor cells 03 are more likely to approach the diversion orifice 51. By connecting a first bend flow channel 40 with a large radius of curvature before removing the flow channel 50, the circulating tumor cells 03 will flow close to the bottom of the inner wall of the flow channel after passing through the first bend flow channel 40 with a large bend, thus preventing the circulating tumor cells 03 from flowing into the diversion orifice 51 and improving the recovery rate of the circulating tumor cells 03.

[0054] Furthermore, a blocking member 52 is provided in the removal channel 50 corresponding to the inlet of the diversion hole 51, and the blocking member 52 is located on the side of the diversion hole 51 away from the deepened channel 30. The width of the blocking member 52 along the extension direction of the removal channel 50 is greater than the diameter of the diversion hole 51. The blocking member 52 protects the circulating tumor cells 03 from flowing into the diversion hole 51. Since the white blood cells 02 and red blood cells 01 are relatively evenly distributed in the channel, the white blood cells 02 and red blood cells 01 flow out from the diversion hole 51 and flow vertically into the second side of the functional plate 1, flowing into the buffer channel 90.

[0055] In one embodiment, the functional plate 1 is provided with a second turning channel 60, the radius of curvature of the second turning channel 60 being larger than the radius of curvature of the removal channel 50. The second turning channel 60 is connected to the end of the removal channel 50 away from the first turning channel 40, and the deepening channel 30 extends correspondingly into the second turning channel 60. After the blood 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 second turning channel 60, whose radius of curvature is larger than that of the removal channel 50, the movement trajectory of circulating tumor cells O3 can be stabilized, facilitating the subsequent recovery of circulating tumor cells O3.

[0056] Furthermore, the second turning channel 60 has an independent recovery channel 70 and a waste liquid channel 80 at the end away from the removal channel 50. The waste liquid channel 80 is connected to the side of the second turning channel 60 near the deepening channel 30, and the recovery channel 70 is connected to the side of the second turning channel 60 away from the deepening channel 30. Circulating tumor cells 03 flow into the recovery channel 70 adhering to the inner wall of the second turning channel 60, while white blood cells 02 and red blood cells 01 flow into the waste liquid channel 80. In one embodiment, the waste liquid channel 80 and the recovery channel 70 have a reciprocating folding structure, which stabilizes the liquid flow and prevents the liquid from falling from the waste liquid hole 32 and the recovery hole 31, thus affecting the movement trajectory of the circulating tumor cells 03 at the end of the second turning channel 60.

[0057] In one embodiment, reference is made to Figure 2The functional plate 1 is further provided with a first turning channel 40, a removal channel 50, and a second turning channel 60 connected in sequence. The end of the first turning channel 40 away from the removal channel 50 flows into the sorting channel 220, and the radius of curvature of the first turning channel 40 is larger than that of the sorting channel 220. A diversion hole 51 penetrating the wall of the removal channel 50 is provided in the removal channel 50. A buffer channel 90 communicating with the diversion hole 51 is provided on the side of the functional plate 1 opposite to the side where the removal channel 50 is located. The buffer channel 90 has a reciprocating folding structure. The radius of curvature of the second turning channel 60 is larger than that of the removal channel 50. A deepened channel 30 is excavated on the side of the sorting channel 220, the first turning channel 40, the removal channel 50, and the second turning channel 60 away from the aggregation of circulating tumor cells O3. (Refer to...) Figure 6 The deepening channel 30 is located on the side near the eighth sidewall 16b. That is, the deepening channel 30 is located in the sorting channel 220 away from the side where large particles, such as circulating tumor cells 03, tend to aggregate, thus not affecting the trajectory of the circulating tumor cells 03. Optionally, the end of the sorting channel 220 connected to the transition channel 210 does not have the deepening channel 30, while the end away from the transition channel 210 has the deepening channel 30. The second turning channel 60 has an independent recovery channel 70 and a waste liquid channel 80 at the end away from the removal channel 50. The recovery channel 70 is connected to the side of the second turning channel 60 near the aggregation of circulating tumor cells 03, and the waste liquid channel 80 is connected to the side of the second turning channel 60 near the deepening channel 30. The sample passes sequentially through the inlet channel 10, the transition channel 210, the sorting channel 220, the first turning channel 40, the removal channel 50, and the second turning channel 60. Some white blood cells 02 and red blood cells 01 flow into the buffer channel 90 from the diversion hole 51 of the removal channel 50. Due to the setting of the deepening channel 30, the circulating tumor cells 03 inertially gather on the side of the channel away from the deepening channel 30 and finally flow out through the recovery channel 70. Other liquids flow out through the waste liquid channel 80.

[0058] Reference Figure 1-4In one embodiment, the upper cover plate 2 is bonded to the first side of the functional plate 1, and the lower cover plate 3 is bonded to the second side of the functional plate 1, so that the flow channels on the first and second sides of the functional plate 1 form a sealed channel. A sample inlet 21 is provided on the upper cover plate 2, which communicates with the inlet pipe 10 on the first side of the functional plate 1, so that blood samples can be introduced into the microfluidic chip from the sample inlet 21. The lower cover plate 3 is provided with a recovery hole 31, a waste liquid hole 32, and a discharge hole 33. The diversion hole 51 is connected to the discharge hole 33. Some white blood cells O2 and red blood cells O1 flow through the diversion hole 51 to the second side of the functional plate 1 in the removal channel 50, and flow out of the microfluidic chip from the discharge hole 33 of the lower cover plate 3. The recovery channel 70 is connected to the recovery hole 31 through the first outflow hole 71 that penetrates the first side and the second side of the functional plate 1. The sorted circulating tumor cells O3 flow out of the microfluidic chip from the recovery hole 31 of the lower cover plate 3. The waste liquid channel 80 is connected to the waste liquid hole 32 through the second outflow hole 81 that penetrates the first side and the second side of the functional plate 1. The remaining liquid flows out of the microfluidic chip from the waste liquid hole 32 of the lower cover plate 3.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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 microfluidic chip, characterized by, The function plate is provided with: An inlet flow channel, one end of which is used for communicating with the sample inlet, and the inlet flow channel has a reciprocating backfolding structure; A transition flow channel, one end of which is connected with the other end of the inlet flow channel, and the width of the transition flow channel perpendicular to its extension direction is greater than the width of the inlet flow channel perpendicular to its extension direction; and A sorting flow channel, which is connected with the other end of the transition flow channel, and the width of the sorting flow channel perpendicular to its extension direction is greater than the width of the transition flow channel perpendicular to its extension direction. The function plate is further provided with a first turning flow channel, a removal flow channel and a second turning flow channel connected in sequence, one end of the first turning flow channel away from the removal flow channel is in flow communication with the sorting flow channel, the curvature radius of the first turning flow channel is greater than the curvature radius of the sorting flow channel, the removal flow channel is provided with a shunt hole penetrating the wall surface of the removal flow channel, the side of the function plate opposite to the side where the removal flow channel is located is provided with a buffer flow channel in flow communication with the shunt hole, the buffer flow channel has a reciprocating backfolding structure, the curvature radius of the second turning flow channel is greater than the curvature radius of the removal flow channel, the side of the sorting flow channel, the first turning flow channel, the removal flow channel and the second turning flow channel away from the aggregation of circulating tumor cells is provided with a deepened flow channel, one end of the second turning flow channel away from the removal flow channel is provided with a recovery flow channel and a waste liquid flow channel which are independent of each other, the recovery flow channel is in flow communication with the side of the second turning flow channel close to the aggregation of circulating tumor cells, and the waste liquid flow channel is in flow communication with the side of the second turning flow channel close to the deepened flow channel.

2. The microfluidic chip of claim 1, wherein, The inlet flow channel comprises a leading-in section and a connecting section connected with each other, one end of the leading-in section away from the connecting section is used for communicating with the sample inlet, and the connecting section is used for communicating with the transition flow channel, and the leading-in section has a reciprocating backfolding structure.

3. The microfluidic chip of claim 2, wherein, The leading-in section comprises a plurality of straight pipe sections and a plurality of elbow pipe sections, two adjacent straight pipe sections are connected through an elbow pipe section, the first straight pipe section is used for communicating with the sample inlet, and the last elbow pipe section is arranged in a clockwise direction and connected with the connecting section.

4. The microfluidic chip of claim 3, wherein, The straight pipe section between the first straight pipe section and the last elbow pipe section comprises long straight pipes and short straight pipes arranged alternately, and the two ends of each long straight pipe are connected with two short straight pipes through elbow pipe sections arranged in a clockwise direction; or the two ends of each long straight pipe are connected with two short straight pipes through elbow pipe sections arranged in a counterclockwise direction.

5. The microfluidic chip of claim 4, wherein, The long straight pipes and the short straight pipes are arranged in parallel, and adjacent two long straight pipes and the short straight pipe between the two long straight pipes are arranged in a straight pipe section width direction.

6. The microfluidic chip of claim 5, wherein, The first straight pipe section is connected with a long straight pipe through elbow pipe sections arranged in a clockwise direction and elbow pipe sections arranged in a counterclockwise direction in sequence, and the last straight pipe section is connected with the connecting section through elbow pipe sections arranged in a counterclockwise direction and elbow pipe sections arranged in a clockwise direction in sequence.

7. The microfluidic chip of claim 6, wherein, The connecting section comprises a first straight pipe section, a first arc section, a second straight pipe section, a second arc section and a third straight pipe section connected in sequence, the first straight pipe section is connected with the last elbow section, the first arc section is a 90° arc section arranged in a clockwise direction, and the second arc section is a 90° arc section arranged in a clockwise direction.

8. The microfluidic chip of claim 7, wherein, A first area is formed between the extension line of the first straight pipe section and the extension line of the second straight pipe section, and the introduction section reciprocally backfolds in the range of the first area.

9. The microfluidic chip according to any one of claims 1-8, wherein, The transition flow channel comprises first elbow units and second elbow units arranged alternately, the curvature radius of the first elbow unit is greater than that of the second elbow unit; The sorting flow channel comprises third elbow units and fourth elbow units arranged alternately, the curvature radius of the third elbow unit is greater than that of the fourth elbow unit, the last second elbow unit is connected with the first third elbow unit, wherein the width of the first elbow unit perpendicular to its extension direction is a, and the width of the third elbow unit perpendicular to its extension direction is b, and a < b.

10. The microfluidic chip of claim 9, wherein, The first elbow unit comprises oppositely arranged first and second side walls, the first and second side walls are asymmetric curved surfaces, the second elbow unit comprises oppositely arranged third and fourth side walls, the third and fourth side walls are asymmetric curved surfaces, the third side wall is connected with the second side wall, and the fourth side wall is connected with the first side wall; The third elbow unit comprises oppositely arranged fifth and sixth side walls, the fifth and sixth side walls are asymmetric curved surfaces, the fourth elbow unit comprises oppositely arranged seventh and eighth side walls, the seventh and eighth side walls are asymmetric curved surfaces, the fifth side wall is connected with the eighth side wall, and the sixth side wall is connected with the seventh side wall; The first elbow unit and the second elbow unit are protrudingly arranged in different directions, the third elbow unit and the fourth elbow unit are protrudingly arranged in different directions, and the first elbow unit and the third elbow unit are protrudingly arranged in the same direction.

11. The microfluidic chip of claim 10, wherein, The curvature radius of the third side wall is smaller than that of the fourth side wall, and the curvature radius of the seventh side wall is smaller than that of the eighth side wall; The curvature radius of the first side wall is smaller than that of the second side wall, and the curvature radius of the fifth side wall is greater than that of the sixth side wall.

12. The microfluidic chip of claim 9, wherein, b is greater than a by 0.4mm-1.2mm; or b is greater than a by 0.7mm-0.9mm.

13. The microfluidic chip of claim 1, wherein, Further comprising an upper cover plate and a lower cover plate, the upper cover plate is connected with one side of the functional plate, the lower cover plate is connected with the other side of the functional plate, a sample inlet is formed on the upper cover plate and communicates with the inlet flow channel, a recovery hole, a waste liquid hole and a discharge hole are formed on the lower cover plate and communicate with the recovery flow channel, the waste liquid flow channel and the buffer flow channel, and the recovery flow channel and the waste liquid flow channel are reciprocally backfolding structures.

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