Circulating tumor cell sorting microfluidic chip

Abstract

The application relates to a circulating tumor cell sorting microfluidic chip, which comprises a functional plate, a sorting flow channel for gathering circulating tumor cells into a band is arranged on the first side of the functional plate, a shunt hole penetrating the wall surface of the sorting flow channel is arranged in the sorting flow channel, a blocking piece is arranged at the inlet of the shunt hole in the sorting flow channel, and the blocking piece is located at the side of the shunt hole close to the gathering of circulating tumor cells. Part of red blood cells and white blood cells are discharged through the shunt hole arranged in the sorting flow channel, the circulating tumor cells are blocked by the blocking piece, the circulating tumor cells are prevented from flowing into the shunt hole, the proportion of the circulating tumor cell content in the liquid downstream of the shunt hole is increased, and the recovery rate of the circulating tumor cells can be effectively improved.

Description

Technical Field

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

[0002] Cancer is the second leading cause of death worldwide, affecting one in six people. Tumor metastasis is responsible for 90% of cancer deaths. The process of metastasis involves tumor cells detaching from the primary or metastatic lesion, circulating in the lymphatic system or peripheral blood, invading distant tissues, forming new tumor foci, and ultimately leading to 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 treatment effectiveness 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 cancer screening. Tumors measuring 1-2 millimeters are difficult to detect with imaging techniques. However, a certain number of CTCs are present in the blood at the early stages of many cancers. For high-risk patients, regular CTC testing helps in early detection and treatment of cancer, preventing disease progression. Therefore, sorting and enriching circulating tumor cells from blood is particularly important. However, the content of circulating tumor cells is extremely low, usually 1-10 circulating tumor cells per milliliter of blood, millions of white blood cells per milliliter, and billions of red blood cells per milliliter. Sorting and enriching circulating tumor cells is as difficult as finding a needle in a haystack.

[0003] To achieve the sorting of circulating tumor cells, traditional techniques employ helical channels on microfluidic chips, but these channels are difficult to manufacture and require large dimensions. Conventional linear arc-shaped channels utilize asymmetric inertial focusing and Dean's vortex principle to aggregate and recover circulating tumor cells, but the recovery rate is low. Summary of the Invention

[0004] Therefore, it is necessary to provide a circulating tumor cell sorting microfluidic chip to address the above problems, which can effectively improve the recovery rate of circulating tumor cells.

[0005] A circulating tumor cell sorting microfluidic chip includes a functional board. A sorting channel for aggregating circulating tumor cells into a band is provided on a first side of the functional board. A diversion hole penetrating the wall of the sorting channel is provided in the sorting channel. A blocking member is provided in the sorting channel corresponding to the inlet of the diversion hole, and the blocking member is located on the side of the diversion hole closer to the aggregation of circulating tumor cells.

[0006] When a blood sample is diluted and introduced into a sorting channel, due to the influence of inertial lift, Dean's drag, and other forces, red blood cells, white blood cells, and circulating tumor cells will move relative to each other in the cross-section of the sorting channel under the balance of forces. When they reach the equilibrium position of the cross-section, the larger white blood cells and circulating tumor cells will stabilize at a certain position in the cross-section, forming a focused flow. Because white blood cells and circulating tumor cells have different diameters, they will gather at different positions in the cross-section of the sorting channel. A diversion hole is provided in the sorting channel, penetrating the wall of the sorting channel, and a blocking element is provided in the sorting channel corresponding to the entrance of the diversion hole. The blocking element is located on the side of the diversion hole closer to the gathering of circulating tumor cells. The blocking element can block the focused circulating tumor cells from flowing into the diversion hole. The circulating tumor cells flow downstream of the sorting channel along the blocking element, while white blood cells and red blood cells are more evenly distributed in the sorting channel. Some white blood cells and red blood cells flow out of the sorting channel from the diversion hole. This circulating tumor cell (CTC) sorting microfluidic chip pre-emptively removes some red blood cells and white blood cells through diversion orifices in the sorting channel. Furthermore, it utilizes blocking elements to prevent CTC cells from flowing into the diversion orifices, thus increasing the proportion of CTC cells in the downstream liquid and effectively improving the CTC recovery rate. In addition, this CTC sorting microfluidic chip only aggregates CTC cells, excluding white blood cells and red blood cells. This allows for miniaturization of the chip's overall size, while allowing for larger channel heights and widths. Blood samples can be diluted significantly, resulting in higher liquid flow rates and reduced sorting time.

[0007] In one embodiment, the width of the blocking member along the extension direction of the sorting channel is greater than the diameter of the diversion hole.

[0008] In one embodiment, the blocking member protrudes from the wall of the sorting channel, and the side of the blocking member near the accumulation of circulating tumor cells is an arc-shaped wall, and the bending direction of the arc-shaped wall is consistent with the bending direction of the side wall of the sorting channel near the accumulation of circulating tumor cells.

[0009] In one embodiment, the blocking member and the functional plate are integrally formed, and the middle part of the blocking member on the side away from the arc-shaped wall is arranged around the outer periphery of the side corresponding to the diversion hole.

[0010] In one embodiment, a plurality of diversion holes are sequentially provided along the extension direction of the sorting channel, and a plurality of buffer channels with a reciprocating folding structure are provided on the second side of the functional board, and the buffer channels are connected to the diversion holes one by one.

[0011] In one embodiment, along the sample flow direction, the length of the buffer channel corresponding to the upstream diversion orifice is greater than the length of the other buffer channels.

[0012] In one embodiment, along the sample flow direction, the plurality of diversion holes are gradually positioned toward the side where circulating tumor cells accumulate in the sorting channel.

[0013] In one embodiment, the proportion of liquid flowing out of the buffer channel is 30%-70%; or the proportion of liquid flowing out of the buffer channel is 45%-60%.

[0014] In one embodiment, the first side of the functional panel is further provided with a turning channel connected to the end of the sorting channel. The radius of curvature of the turning channel is greater than that of the sorting channel. The end of the turning channel away from the sorting channel is provided with an independent recovery channel and a waste liquid channel. The recovery channel is connected to the side of the turning channel near the accumulation of circulating tumor cells, and the waste liquid channel is connected to the side of the turning channel away from the accumulation of circulating tumor cells.

[0015] In one embodiment, the ratio of liquid flowing out of the waste liquid channel to liquid flowing out of the recovery channel is 45%-65%: 3%-20%; or the ratio of liquid flowing out of the waste liquid channel to liquid flowing out of the recovery channel is 50%-60%: 5%-10%.

[0016] In one embodiment, the sorting channel is a sinusoidal arc-shaped channel, and both the waste liquid channel and the recovery channel have a meandering structure.

[0017] In one embodiment, the circulating tumor cell sorting microfluidic chip further includes an upper cover plate and a lower cover plate. The upper cover plate has a sample inlet communicating with the sorting channel. The upper cover plate is stacked and connected to a first side of the functional plate. The lower cover plate has a recovery hole, a waste liquid hole, and a discharge hole. The lower cover plate is stacked and connected to a second side of the functional plate. The recovery channel communicates with the recovery hole, the waste liquid channel communicates with the waste liquid hole, and the buffer channel communicates with the discharge hole. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the sorting channel of a circulating tumor cell sorting microfluidic chip in one embodiment;

[0019] Figure 2 This is a schematic diagram of the top cover of a circulating tumor cell sorting microfluidic chip in one embodiment;

[0020] Figure 3 This is a schematic diagram of the first side of the functional board of a circulating tumor cell sorting microfluidic chip in one embodiment;

[0021] Figure 4This is a schematic diagram of the second side of the functional board of a circulating tumor cell sorting microfluidic chip in one embodiment;

[0022] Figure 5 This is a schematic diagram of the lower cover plate of a circulating tumor cell sorting microfluidic chip in one embodiment.

[0023] Explanation of reference numerals in the attached figures:

[0024] 01. Red blood cells; 02. White blood cells; 03. Circulating tumor cells; 1. Functional plate; 10. Inlet channel; 20. Aggregation channel; 30. Deepening channel; 40. Reversing channel; 50. Sorting channel; 51. Diverting orifice; 52. Blocking element; 522. Arc wall; 60. Turning channel; 70. Recovery channel; 71. First outlet orifice; 80. Waste liquid channel; 81. Second outlet orifice; 90. Buffer channel; 2. Top cover plate; 21. Sample inlet; 3. Bottom cover plate; 31. Recovery orifice; 32. Waste liquid orifice; 33. Discharge orifice. Detailed Implementation

[0025] 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.

[0026] Please see Figure 1-5 One embodiment provides a circulating tumor cell sorting microfluidic chip, including a functional board 1. Further, the circulating tumor cell sorting 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. A sample inlet 21 is provided on the upper cover plate 2.

[0027] Reference Figure 1 , 2 In one embodiment, the first side of the functional plate 1 is provided with a sorting channel 50 for aggregating circulating tumor cells 03 into a band. A diversion hole 51 penetrating the wall of the sorting channel 50 is provided in the sorting channel 50, and a blocking member 52 is provided at the inlet of the diversion hole 51, with the blocking member 52 located on the side of the diversion hole 51 closer to the aggregating circulating tumor cells 03. Figure 1 The image shows the movement of circulating tumor cells, white blood cells, and red blood cells in the sorting channel of a blood sample under magnification.

[0028] A diluted blood sample is introduced into the sorting channel 50 through sample inlet 21. Due to the influence of inertial lift, Dean's drag, and other forces, under the equilibrium of forces in the sorting channel 50, red blood cells 01, white blood cells 02, and circulating tumor cells 03 will move relative to each other in the cross-section of the sorting channel 50. When they reach the equilibrium position in the cross-section, the larger-diameter white blood cells 02 and circulating tumor cells 03 will stabilize at a certain position in the cross-section, forming a focused flow. Because the white blood cells 02 and circulating tumor cells 03 have different diameters, they will accumulate at different positions in the cross-section of the sorting channel 50, thus being separated by the sorting flow. A diversion hole 51 is provided in the sorting channel 50, penetrating the wall of the sorting channel 50. A blocking member 52 is provided in the sorting channel 50 at the entrance of the diversion hole 51, and the blocking member 52 is located on the side of the diversion hole 51 near the aggregation of circulating tumor cells 03. The blocking member 52 can block the focused circulating tumor cells 03 from flowing into the diversion hole 51. The circulating tumor cells 03 flow along the blocking member 52 to the downstream of the sorting channel 50. The white blood cells 02 and red blood cells 01 are relatively evenly distributed in the sorting channel 50, and some white blood cells 02 and red blood cells 01 flow out of the sorting channel 50 from the diversion hole 51. This circulating tumor cell (CTC) sorting microfluidic chip pre-emptively discharges some red blood cells (01) and white blood cells (02) through a diversion orifice 51 in the sorting channel 50. Furthermore, a blocking element 52 prevents CTCs (03) from flowing into the diversion orifice 51, thus increasing the proportion of CTCs (03) in the liquid downstream of the diversion orifice 51 and effectively improving the recovery rate of CTCs (03). In addition, this CTC sorting microfluidic chip only aggregates CTCs (03), not white blood cells (02) or red blood cells (01). This allows for miniaturization of the chip's overall size, while allowing for larger channel heights and widths, enabling significant dilution of blood samples and resulting in higher liquid flow rates and reduced sorting time.

[0029] Reference Figure 1 , 2 In one embodiment, the width of the blocking member 52 along the extension direction of the sorting channel 50 is greater than the diameter of the diversion orifice 51. This allows the blocking member 52 to block the aggregated circulating tumor cells 03 over a longer distance in the direction of sample flow, so that the circulating tumor cells 03 flow downstream along the side of the blocking member 52 away from the diversion orifice 51.

[0030] Reference Figure 1 , 2In one embodiment, the blocking member 52 protrudes from the wall of the sorting channel 50, meaning the height of the blocking member 52 is higher than other parts of the sorting channel 50, blocking the circulating tumor cells 03 between them and the diversion hole 51, preventing the circulating tumor cells 03 from flowing out of the diversion hole 51. The side of the blocking member 52 near the aggregation of the circulating tumor cells 03 is an arc-shaped wall 522, and the curvature direction of the arc-shaped wall 522 is consistent with the curvature direction of the side wall of the sorting channel 50 near the aggregation of the circulating tumor cells 03. The arc-shaped wall 522 of the blocking member 52 near the aggregation of the circulating tumor cells 03 matches the aggregation zone of the circulating tumor cells 03, ensuring that the influence of the blocking member 52 on the aggregation of the circulating tumor cells 03 is consistent, avoiding disturbance to the aggregation of the circulating tumor cells 03, allowing the circulating tumor cells 03 to flow downstream along the arc-shaped wall 522 of the blocking member 52.

[0031] In one embodiment, the blocking member 52 and the functional plate 1 are integrally formed, and the blocking member 52 is formed by removing the protruding portion reserved during the opening of the flow channel 50. The middle part of the side of the blocking member 52 away from the arc-shaped wall 522 is arranged around the outer periphery of the corresponding side of the diversion hole 51. White blood cells O2 and red blood cells O1 flowing towards the diversion hole 51 are blocked by the side wall of the blocking member 52 away from the arc-shaped wall 522 and eventually flow into the diversion hole 51.

[0032] Reference Figure 1 , 2 3. In one embodiment, a plurality of diversion holes 51 are sequentially provided along the extension direction of the sorting channel 50, and a plurality of buffer channels 90 with a reciprocating folding structure are provided on the second side of the functional plate 1. The buffer channels 90 are connected to the diversion holes 51 one by one. The multiple diversion holes 51 along the liquid flow direction remove white blood cells O2 and red blood cells O1 multiple times, which is beneficial to the subsequent recovery of circulating tumor cells O3. The buffer channels 90 are designed with a reciprocating folding structure to stabilize the liquid state flowing out of the sorting channel 50 and avoid the remaining liquid in the sorting channel 50 from being disturbed by shaking, which would affect the subsequent recovery of circulating tumor cells O3. A blocking member 52 is provided at the inlet of each corresponding diversion hole 51 in the sorting channel 50, and the blocking member 52 is located on the side of the diversion hole 51 near the aggregation of circulating tumor cells 03. The width of the blocking member 52 along the extension direction of the sorting 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, while 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 and into the buffer channel 90.

[0033] In one embodiment, along the sample flow direction, the length of the buffer channel 90 corresponding to the upstream diversion orifice 51 is greater than the length of the other buffer channels 90. (Refer to...) Figure 3It can be seen that the length of the buffer channel 90 corresponding to the upstream diversion orifice 51 is longer than that of the others. Since the amount of liquid flowing into the upstream diversion orifice 51 is relatively more than that of the other diversion orifices 51, the buffer channel 90 is designed to be longer so that more liquid can flow out, making the outflowing liquid tend to be stable and avoiding affecting the flow rate of the subsequent liquid and disrupting the flow of circulating tumor cells 03.

[0034] Reference Figure 1 In one embodiment, along the sample flow direction, the plurality of diversion holes 51 are gradually positioned closer to the side of the sorting channel 50 where circulating tumor cells 03 are aggregated. (Refer to...) Figure 5 Along the sample flow direction, the distance L between the plurality of diversion holes 51 and the sidewall of the corresponding sorting channel 50 where circulating tumor cells 03 are concentrated gradually decreases. As the liquid is discharged, white blood cells 02 and red blood cells 01 gradually flow towards the side where circulating tumor cells 03 are concentrated. Correspondingly, along the sample flow direction, the diversion holes 51 are set towards the side where circulating tumor cells 03 are concentrated to facilitate the outflow of white blood cells 02 and red blood cells 01 from the subsequent diversion holes 51.

[0035] In one embodiment, the proportion of liquid flowing out of the buffer channel 90 is 30%-70%. Preferably, the proportion of liquid flowing out of the buffer channel 90 is 45%-60%. The length of the buffer channel 90 can control the amount of liquid discharged. The length of the buffer channel 90, combined with the position of the diversion orifice 51, adjusts the amount of white blood cells O2 and red blood cells O1 removed and regulates the movement trajectory of circulating tumor cells O3. In one embodiment, the proportion of white blood cells O2 and red blood cells O1 removed by the diversion orifice 51 is 30%-70%, preferably 45%-60%. Similarly, the proportion of liquid flowing out of the diversion orifice 51 is 30%-70%, with an optimal range of 45%-60%. This setting ensures that the liquid outflow is less than 70%, and the final flow rate is reduced by no more than 70%, avoiding affecting the original movement trajectory of the circulating tumor cells O3 and making it difficult to recover some of the circulating tumor cells O3.

[0036] Reference Figure 2In one embodiment, the first side of the functional plate 1 is further provided with a turning channel 60 connected to the end of the sorting channel 50, and the radius of curvature of the turning channel 60 is larger than that of the sorting channel 50. At the end of the turning channel 60 away from the sorting channel 50, there are independent recovery channels 70 and waste liquid channels 80. The recovery channel 70 is connected to the side of the turning channel 60 near the aggregation of circulating tumor cells O3, and the waste liquid channel 80 is connected to the side of the turning channel 60 away from the aggregation of circulating tumor cells O3. 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 turning channel 60, whose radius of curvature is larger than that of the sorting channel 50, the movement trajectory of the circulating tumor cells O3 can be stabilized, facilitating the subsequent recovery of the circulating tumor cells O3. Circulating tumor cells 03 flow into the recovery channel 70, adhering closely to the inner wall of the 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 movement trajectory of the circulating tumor cells 03 at the end of the turning channel 60 from being affected by the subsequent outflow and drop of the liquid.

[0037] In one embodiment, the ratio of liquid flowing out of the waste liquid channel 80 to the liquid flowing out of the recovery channel 70 is 45%-65%: 3%-20%; or the ratio is 50%-60%: 5%-10%. By adjusting the length and depth of the waste liquid channel 80 and the recovery channel 70, their volume ratio can be adjusted, thereby regulating the removal ratio of leukocyte O2 and erythrocyte O1. In one embodiment, the liquid flowing out of the waste liquid channel 80 accounts for 45%-65%, preferably 50%-60%. The liquid flowing out of the recovery channel 70 accounts for 3%-20%, preferably 5%-10%. The liquid collected from the recovery orifice 31 shows a circulating tumor cell O3 recovery rate of over 90%, and a leukocyte O2 and erythrocyte O1 removal rate of over 90%. Returning the recovered liquid to the chip for repeated filtration can further improve the removal rate of white blood cells (O2) and red blood cells (O1), and increase the purity of the recovered circulating tumor cells (O3).

[0038] The volume of the recovery channel 70 for circulating tumor cells (O3) is very small, while the volume of the waste liquid channel 80 is very large. Therefore, white blood cells (O2) and red blood cells (O1) can be indirectly removed during the recovery of tumor cells. Because this chip has a high recovery rate for circulating tumor cells (O3), it can be filtered multiple times. Thus, the overall reduction in circulating tumor cells (O3) is relatively small, and white blood cells (O2) are almost completely removed after multiple filtrations.

[0039] In one embodiment, the sorting channel 50 is a sinusoidal 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 in the direction perpendicular to the fluid flow, 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 of the particles in the curved 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 asymmetrical sorting channel 50.

[0040] Reference Figure 2-5 In 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 sorting flow channel 50 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 02 and red blood cells 01 flow through the diversion hole 51 to the second side of the functional plate 1 in the sorting 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 03 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.

[0041] Reference Figure 2In one embodiment, the functional board 1 is further provided with an inlet channel 10, an aggregation channel 20, and a reversing channel 40 connected in sequence. The end of the reversing channel 40 is connected to the sorting channel 50. Blood samples flow into the inlet channel 10 through the sample inlet 21, then flow through the aggregation channel 20 and the reversing channel 40 in sequence, and then enter the sorting channel 50. The inlet channel 10 has a reciprocating folding structure, which serves to buffer the samples entering the circulating tumor cell O3 sorting microfluidic chip. The aggregation channel 20 is an asymmetric arc-shaped channel, which serves to aggregate the circulating tumor cells O3. A reversing channel 40 is connected between the sorting channel 50 and the aggregation channel 20. Due to the large radius of the reversing channel 40, the relative advantage of inertial lift is greater. When passing through the reversing channel 40, the centrifugal force on the fluid in the middle of the channel is the greatest, so it flows 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, so it is squeezed by the middle fluid. Thus, under the action of the reversing flow channel 40, the circulating tumor cells 03 can be brought as close as possible to the bottom of the inner wall of the flow channel, which prepares for the subsequent sorting of the circulating tumor cells 03 and the removal of leukocytes 02 through the sorting flow channel 50.

[0042] Furthermore, a deepened flow channel 30 is provided on the side of the aggregation channel 20, reversing flow channel 40, sorting flow channel 50, and turning flow channel 60 away from the aggregation of circulating tumor cells 03. The deepened flow channel 30 is set along the sample flow direction, which disrupts the liquid flow state near the side where the deepened flow channel 30 is located, changes the inertial lift and Dean drag, and breaks the original balance. This allows leukocytes 02 to generate a disordered movement state, thereby making the distribution of leukocytes 02 in the fine screening channel 20 more uniform, avoiding the overlap of leukocyte 02 aggregates with circulating tumor cells 03. Similarly, erythrocytes 01 are also distributed more uniformly, ensuring that they do not interfere with the aggregation of circulating tumor cells 03 and preventing leukocytes 02 from aggregating at the bottom of the inner wall of the fine screening channel 20. This facilitates the subsequent separation of circulating tumor cells 03 from leukocytes 02 and is beneficial for the recovery of circulating tumor cells 03.

[0043] The material of the circulating tumor cell sorting microfluidic chip in the above embodiments is not limited and can be made of PMMA, PC, ABS, glass, etc. This chip is reusable, requires no antigens or antibodies, and does not require magnetic beads, thus greatly reducing costs.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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 for sorting circulating tumor cells, characterized in that, The device includes a functional plate, on the first side of which is provided a sorting channel for aggregating circulating tumor cells into a band. A diversion hole is provided in the sorting channel, penetrating the wall of the sorting channel. A blocking member is provided in the sorting channel corresponding to the entrance of the diversion hole, and the blocking member is located on the side of the diversion hole closer to the aggregation of circulating tumor cells. The width of the blocking member along the extension direction of the sorting channel is greater than the diameter of the diversion hole; The blocking member protrudes from the wall of the sorting channel. The side of the blocking member near the accumulation of circulating tumor cells is an arc-shaped wall, and the bending direction of the arc-shaped wall is consistent with the bending direction of the side wall of the sorting channel near the accumulation of circulating tumor cells. The blocking component and the functional plate are integrally formed, and the middle part of the blocking component on the side away from the arc wall is arranged around the outer periphery of the corresponding side of the diversion hole; The first side of the functional panel is also provided with a turning channel connected to the end of the sorting channel. The radius of curvature of the turning channel is greater than that of the sorting channel. The end of the turning channel away from the sorting channel is provided with an independent recovery channel and a waste liquid channel. The recovery channel is connected to the side of the turning channel near the accumulation of circulating tumor cells, and the waste liquid channel is connected to the side of the turning channel away from the accumulation of circulating tumor cells.

2. The circulating tumor cell sorting microfluidic chip according to claim 1, characterized in that, Multiple flow dividers are sequentially provided along the extension direction of the sorting channel, and multiple buffer channels with a reciprocating folding structure are provided on the second side of the functional board. The buffer channels are connected to the flow dividers one by one.

3. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, Along the sample flow direction, the length of the buffer channel corresponding to the upstream diversion orifice is greater than the length of other buffer channels.

4. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, Along the sample flow direction, the multiple diversion holes are gradually positioned closer to the side where circulating tumor cells accumulate in the sorting channel.

5. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, The proportion of liquid flowing out of the buffer channel is 30%-70%.

6. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, The ratio of liquid flowing out of the waste liquid channel to liquid flowing out of the recovery channel is 45%-65%: 3%-20%; or the ratio of liquid flowing out of the waste liquid channel to liquid flowing out of the recovery channel is 50%-60%: 5%-10%.

7. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, The sorting channel is a sinusoidal arc-shaped channel, and both the waste liquid channel and the recovery channel have a meandering structure.

8. The circulating tumor cell sorting microfluidic chip according to claim 2, characterized in that, It also includes an upper cover plate and a lower cover plate. The upper cover plate has a sample inlet that communicates with the sorting channel. The upper cover plate is stacked and connected to the first side of the functional plate. The lower cover plate has a recovery hole, a waste liquid hole and a discharge hole. The lower cover plate is stacked and connected to the second side of the functional plate. The recovery channel communicates with the recovery hole, the waste liquid channel communicates with the waste liquid hole, and the buffer channel communicates with the discharge hole.

9. The circulating tumor cell sorting microfluidic chip according to claim 8, characterized in that, The upper cover plate is bonded to the first side of the functional panel, and the lower cover plate is bonded to the second side of the functional panel.

10. The circulating tumor cell sorting microfluidic chip according to claim 8, characterized in that, The functional board is also provided with an inlet channel, a gathering channel and a reversing channel connected in sequence, and the end of the reversing channel is connected to the sorting channel.

Images