Circulating tumor cell capturing device
Through the three-layer capture chip structure and fluid dynamic design, combined with specific antibodies, the problems of high cost and low success rate of circulating tumor cells in the prior art are solved, and efficient and stable cell capture effect is achieved.
Patent Information
- Application Number
- CN202422357067.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-26
- Publication Date
- 2025-08-22
- Estimated Expiration
- 2034-09-26
AI Technical Summary
The existing circulating tumor cell capture methods are costly and have low capture success rate, which is prone to tumor cell missing.
Using a three-layer capture chip structure, including upper, middle and lower capture chips, the distribution of multilayer flow channels and capture tanks is used to ensure that circulating tumor cells can be efficiently captured in the multilayer structure through fluid dynamic design and specific antibodies.
It significantly improves the capture efficiency of circulating tumor cells, reduces the possibility of omission, and improves the specificity and reliability of capture.
Smart Images
Figure CN223255213U_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of microfluidics technology, and in particular to a circulating tumor cell capture device. Background Art
[0002] The capture of circulating tumor cells (CTCs) is of great significance in the diagnosis, prognosis, and personalized treatment of cancer. Currently, the most common method for capturing CTCs is to modify a nanostructured substrate with specific biomolecules to specifically identify and capture circulating tumor cells, but this method is relatively expensive. Therefore, in related technologies, it has been proposed to apply microfluidics to the capture design of CTCs. Although this type of technology can reduce costs compared to the use of nanostructured substrates, the success rate of capturing circulating tumor cells is not high, and tumor cells are easily missed. Utility Model Content
[0003] The embodiments of the present application provide a circulating tumor cell capture device to improve the problem of low success rate in capturing circulating tumor cells in circulating tumor cell capture devices in related technologies.
[0004] In a first aspect, an embodiment of the present application provides a circulating tumor cell capture device, comprising:
[0005] an upper layer capture chip, wherein the upper layer capture chip is provided with at least one upper layer flow channel and is connected to an upper layer liquid inlet;
[0006] a middle-layer capture chip, disposed on one side of the upper-layer capture chip and provided with at least one middle-layer flow channel, wherein the middle-layer liquid inlet of the middle-layer flow channel is connected to the upper-layer liquid outlet of the upper-layer flow channel;
[0007] a lower-layer capture chip, which is disposed on a side of the middle-layer capture chip away from the upper-layer capture chip and is provided with at least one lower-layer flow channel, wherein a lower-layer liquid inlet of the lower-layer flow channel is connected to a middle-layer liquid outlet of the middle-layer flow channel;
[0008] Among them, the inner wall of the upper layer flow channel is provided with multiple upper layer capture grooves, the inner wall of the middle layer flow channel is provided with multiple middle layer capture grooves, and the inner wall of the lower layer flow channel is provided with multiple lower layer capture grooves, and the groove sizes of the upper layer capture groove, the middle layer capture groove and the lower layer capture groove are not less than the maximum size of the surface of the circulating tumor cells.
[0009] In some embodiments of the present application, the upper capture chip, the middle capture chip, and the lower capture chip are all rectangular and have the same shape and size;
[0010] The upper layer capture chip comprises four upper layer flow channels, an upper layer liquid inlet and four upper layer liquid outlets, the four upper layer liquid outlets are respectively located at the four corners of the upper layer capture chip, the upper layer liquid inlet is located at the center of the upper layer capture chip, and the two ends of one of the upper layer flow channels are respectively connected to the upper layer liquid inlet and one of the upper layer liquid outlets;
[0011] The middle-layer capture chip comprises four middle-layer flow channels, four middle-layer liquid inlets and one middle-layer liquid outlet. The four middle-layer liquid inlets are respectively located at the four corners of the middle-layer capture chip, and each of the middle-layer liquid inlets is connected to one of the upper-layer liquid outlets. The middle-layer liquid outlet is located at the center of the middle-layer capture chip. Both ends of a middle-layer flow channel are respectively connected to the middle-layer liquid outlets and one of the middle-layer liquid inlets.
[0012] The lower layer capture chip includes four lower layer flow channels, a lower layer liquid inlet and four lower layer liquid outlets. The four lower layer liquid outlets are respectively located at the four corners of the lower layer capture chip. The lower layer liquid inlet is located at the center of the lower layer capture chip and is connected to the middle layer liquid outlet. The two ends of one of the lower layer flow channels are respectively connected to the lower layer liquid inlet and one of the lower layer liquid outlets.
[0013] In some embodiments of the present application, the upper flow channel, the middle flow channel, and the lower flow channel are all serpentine.
[0014] In some embodiments of the present application, the upper capture chip includes an upper substrate and an upper cover plate, the upper substrate is provided with at least one first upper sub-channel and at least one upper liquid outlet, the upper cover plate is provided with at least one second upper sub-channel and the upper liquid inlet, the upper liquid inlet is connected to the second upper sub-channel, the upper liquid outlet is connected to the first upper sub-channel, and the upper cover plate is covered on the upper substrate so that the first upper sub-channel and the second upper sub-channel are aligned and connected to form the upper channel.
[0015] In some embodiments of the present application, the middle-layer capture chip includes a middle-layer substrate and a middle-layer cover plate, the middle-layer substrate is provided with at least one first middle-layer sub-channel and a middle-layer liquid outlet, the middle-layer liquid outlet is connected to the first middle-layer sub-channel, the middle-layer cover plate is provided with at least one second middle-layer sub-channel and at least one middle-layer liquid inlet, the middle-layer liquid inlet is connected to both the second middle-layer sub-channel and the upper-layer liquid outlet, and the middle-layer cover plate is covered on the middle-layer substrate so that the first middle-layer sub-channel and the second middle-layer sub-channel are aligned and connected to form the middle-layer channel.
[0016] In some embodiments of the present application, the lower capture chip includes a lower substrate and a lower cover plate, the lower substrate is provided with at least one first lower sub-channel and at least one lower liquid outlet, the first lower sub-channel is connected to the lower liquid outlet, the lower cover plate is provided with at least one second lower sub-channel and a lower liquid inlet, the lower liquid inlet is connected to the second lower sub-channel, and the lower liquid inlet is also connected to the middle liquid outlet, the lower cover plate is covered on the lower substrate so that the first lower sub-channel and the second lower sub-channel are aligned and connected to form the lower channel.
[0017] In some embodiments of the present application, a plurality of the upper capture grooves are arranged along the upper flow channel array, a plurality of the middle capture grooves are arranged along the middle flow channel array, and a plurality of the lower capture grooves are arranged along the lower flow channel array.
[0018] In some embodiments of the present application, at least a portion of the inner wall of the upper capture groove is provided with an upper capture sub-groove, and the upper capture sub-groove is communicated with the upper capture groove.
[0019] In some embodiments of the present application, specific antibodies are provided in the upper capture tank, the middle capture tank, and the lower capture tank, and the specific antibodies have the property of binding to antigens in the circulating tumor cells.
[0020] In some embodiments of the present application, the specific antibody is an anti-EpCAM antibody.
[0021] It can be seen that the device disclosed in the embodiment of the present application includes three layers of capture chips, namely the upper capture chip, the middle capture chip and the lower capture chip. Based on fluid dynamics, the capture efficiency of circulating tumor cells is significantly improved through the multi-layer structure and the distribution of capture grooves. Each chip is interconnected by a liquid flow channel and is provided with a specific structure to improve the capture rate of circulating tumor cells (CTCs). The upper capture chip is provided with at least one upper flow channel, and a plurality of upper capture grooves are evenly distributed on the inner wall of the flow channel. The groove size of these capture grooves is larger than the maximum surface size of the circulating tumor cells to ensure that tumor cells can enter the capture groove, and small-sized cells can flow out of the capture groove under the action of the flow channel liquid. The inlet of the upper flow channel is the upper liquid inlet, and the outlet is the upper liquid outlet. The fluid first enters the upper flow channel from the upper liquid inlet. When the liquid carrying circulating tumor cells passes through the capture groove, the tumor cells are captured by the specific antibodies in the groove. The middle capture chip is located below the upper capture chip and is connected to the middle liquid inlet through the upper liquid outlet. The middle-layer capture chip is also equipped with at least one middle-layer flow channel, with multiple middle-layer capture grooves on the inner wall of the flow channel. The liquid in the middle-layer flow channel continues to flow through these capture grooves, which are designed to be the same as the upper-layer capture grooves, further ensuring that tumor cells not captured by the upper layer can be captured in the middle layer. The lower-layer capture chip is connected to the lower-layer liquid inlet through the middle-layer liquid outlet, and its structure is similar to that of the upper and middle layers. The lower-layer flow channel is also equipped with multiple capture grooves, with the same size as the upper and middle-layer capture grooves, ensuring the capture of remaining uncaptured tumor cells and improving the capture success rate. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.
[0023] Figure 1 A schematic structural diagram of a circulating tumor cell capture device provided by an embodiment of the present invention (first perspective);
[0024] Figure 2 A schematic structural diagram of an upper capture chip in a circulating tumor cell capture device provided by an embodiment of the present invention;
[0025] Figure 3 A schematic diagram of a structure in which a capture slot is provided on an upper capture chip in a circulating tumor cell capture device provided by an embodiment of the present utility model;
[0026] Figure 4This is a structural schematic diagram of another upper capture chip in a circulating tumor cell capture device provided by an embodiment of the present invention, in which a capture slot is provided.
[0027] Description of reference numerals:
[0028] 1. Upper capture chip; 11. Upper flow channel; 12. Upper liquid inlet; 13. Upper liquid outlet; 14. Upper substrate; 15. Upper cover; 16. Upper capture tank; 161. Upper capture sub-tank; 2. Middle capture chip; 21. Middle substrate; 22. Middle cover; 23. Middle liquid inlet; 24. Middle liquid outlet; 3. Lower capture chip; 31. Lower substrate; 32. Lower cover; 33. Lower liquid inlet; 34. Lower liquid outlet; 4. Specific antibody. DETAILED DESCRIPTION
[0029] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making any creative efforts shall fall within the scope of protection of this application.
[0030] In the description of this application, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or the number of the technical features indicated. Therefore, a feature specified as "first" or "second" may explicitly or implicitly include one or more features. In the description of this application, "plurality" means two or more, unless otherwise specifically specified.
[0031] See Figures 1 to 4 , an embodiment of the present application provides a circulating tumor cell capture device, comprising:
[0032] An upper layer capture chip 1, wherein the upper layer capture chip 1 is provided with at least one upper layer flow channel 11 and is connected to an upper layer liquid inlet 12;
[0033] The middle-layer capture chip 2 is provided on one side of the upper-layer capture chip 1 and is provided with at least one middle-layer flow channel, wherein the middle-layer liquid inlet 23 of the middle-layer flow channel is connected to the upper-layer liquid outlet 13 of the upper-layer flow channel 11;
[0034] The lower capture chip 3 is provided on the side of the middle capture chip 2 away from the upper capture chip 1 and is provided with at least one lower flow channel, wherein the lower liquid inlet 33 of the lower flow channel is connected to the middle liquid outlet 24 of the middle flow channel;
[0035] Among them, the inner wall of the upper layer flow channel 11 is provided with multiple upper layer capture grooves 16, the inner wall of the middle layer flow channel is provided with multiple middle layer capture grooves, and the inner wall of the lower layer flow channel is provided with multiple lower layer capture grooves, and the groove sizes of the upper layer capture groove 16, the middle layer capture groove and the lower layer capture groove are not less than the maximum size of the surface of the circulating tumor cells.
[0036] In the technical solution provided in this application, the device comprises three layers of capture chips: upper capture chip 1, middle capture chip 2, and lower capture chip 3. The chips are interconnected by fluid channels and have specific structures to improve the capture rate of circulating tumor cells (CTCs).
[0037] The upper capture chip 1 is equipped with at least one upper flow channel 11, with multiple upper capture grooves 16 evenly distributed along the inner wall. The groove openings of these capture grooves are larger than the maximum surface dimension of circulating tumor cells to ensure that tumor cells can enter the capture grooves. The inlet of the upper flow channel 11 is the upper liquid inlet 12, and the outlet is the upper liquid outlet 13. The fluid first enters the upper flow channel 11 through the upper liquid inlet 12. As the liquid carrying circulating tumor cells passes through the capture grooves, the tumor cells are captured by the specific antibodies 4 within the grooves.
[0038] The middle capture chip 2 is located below the upper capture chip 1 and is connected to the middle inlet 23 via the upper liquid outlet 13. The middle capture chip 2 also features at least one middle flow channel, the inner wall of which is defined by multiple middle capture grooves. Liquid in the middle flow channel continues to flow through these grooves, which share the same design as the upper capture grooves 16, further ensuring that tumor cells not captured in the upper layer are captured in the middle layer.
[0039] The lower capture chip 3 is connected to the lower inlet 33 via the middle outlet 24, and its structure is similar to that of the upper and middle layers. The lower flow channel also has multiple capture slots, the same size as the upper and middle capture slots, ensuring the capture of any remaining tumor cells.
[0040] The inner wall of the capture groove of each layer of flow channel is provided with a specific antibody 4, which binds to the specific antigen on the surface of circulating tumor cells. This antibody can be an anti-EpCAM antibody, which can effectively bind to the EpCAM antigen on the surface of circulating tumor cells, ensuring efficient capture of CTCs.
[0041] The technical solution provided by this application is based on the principles of fluid dynamics and biochemical recognition. Through a multi-layered structure and the distribution of capture tanks, it significantly improves the efficiency of capturing circulating tumor cells. Specifically, by providing upper, middle, and lower flow channels, the fluid path is extended, allowing the liquid to more fully interact with the antibodies in the capture tanks during flow. Even if the upper flow channel 11 does not completely capture circulating tumor cells, the middle and lower layers still have sufficient opportunities to capture them.
[0042] Specific antibodies 4 modified on the inner wall of the capture tank are capable of recognizing and binding to specific antigens on the surface of circulating tumor cells. By placing antibodies separately within the three-layer flow channel, the specificity and reliability of capture are increased. EpCAM antibodies are specifically targeted to tumor cells. Through the antigen-antibody binding reaction, tumor cells are effectively fixed in the capture tank, reducing the possibility of missing cells.
[0043] In some embodiments, the upper capture chip 1 is rectangular and contains four upper flow channels 11. These four channels are arranged as follows: an upper inlet 12 is located in the center, and four channels extend from the inlet in four different directions to the four corners of the chip, forming an upper outlet 13 at each corner. After entering through the upper inlet 12, the fluid is evenly distributed throughout the four channels, gradually flowing toward each outlet as it passes through the channels. The middle capture chip 2 has a similar structure to the upper chip, also rectangular. Four middle inlets 23 are located at each of its four corners, each connected to the four outlets of the upper chip. Fluid enters the middle chip from the outlet of the upper channel 11 and enters the four middle channels. The middle channels zigzag, guiding the fluid from the four corner inlets to the middle outlet 24 located in the center of the middle chip, completing the secondary capture of the fluid. The lower capture chip 3 is also rectangular and has a similar structure to the upper and middle layers. The lower chip is designed with four lower flow channels, each leading from a lower liquid inlet 33 located at the center of the chip to four lower liquid outlets 34. The flow paths of the lower flow channels form a consistent liquid flow system with the upper and middle layers, ensuring that the liquid can flow smoothly through each layer of flow channels. The flow channels of the upper, middle, and lower capture chips 3 are all arranged in a serpentine pattern, and the shape and size of each layer of flow channels remain consistent, which helps enhance the stability of the fluid flow and avoids turbulence or uneven flow when the fluid enters another layer of chip from one chip.
[0044] Specifically, the flow channels in the upper chip are designed so that liquid originates from a central inlet and diffuses in four directions, reaching outlets at the four corners. This diversion ensures uniform distribution of liquid throughout each channel, ensuring consistent flow rates and flow rates across all channels, thereby avoiding localized excess or excess flow due to uneven flow. The liquid flow path in the middle chip enters from the four inlets and ultimately converges at the central outlet, forming a confluence. This flow pattern effectively recovers uncaptured tumor cells in the upper layer, improving capture efficiency. Rectangular capture chips offer significant advantages in integration and manufacturing. The four corners of the rectangular chip naturally serve as nodes for liquid diversion and confluence, allowing fluid to flow precisely along the designed path. Compared to chips with other shapes (such as circular or irregular shapes), rectangular chips make it easier to achieve precise flow channel arrangement and liquid control, ensuring stable and consistent liquid pressure and flow rate in each channel. Furthermore, the symmetrical structure of the rectangular chip facilitates large-scale production and integration, making it suitable for fluid capture devices of varying sizes.
[0045] In some embodiments, see Figure 1 and Figure 2 The upper capture chip 1 includes two parts: an upper substrate 14 and an upper cover plate 15. At least one first upper sub-channel and at least one upper liquid outlet 13 are provided on the upper substrate 14. The first upper sub-channel is connected to the upper liquid outlet 13, and the liquid is discharged through the upper liquid outlet 13 after passing through the sub-channel. At least one second upper sub-channel and an upper liquid inlet 12 are provided on the upper cover plate 15. The upper liquid inlet 12 is connected to the second upper sub-channel. The design of the cover plate ensures that the liquid can enter the channel system through the liquid inlet. The upper substrate 14 and the upper cover plate 15 are precisely aligned and connected to ensure that the first upper sub-channel is relative to the second upper sub-channel to form a complete upper channel 11. The liquid enters from the upper liquid inlet 12, flows through the second upper sub-channel, and then merges with the first upper sub-channel to form a complete channel. When the liquid flows in the flow channel, it will come into contact with the capture groove on the inner wall of the flow channel, completing the capture operation of circulating tumor cells.
[0046] The middle-layer substrate 21 is provided with at least one first middle-layer sub-channel and a middle-layer liquid outlet 24. The middle-layer liquid outlet 24 is connected to the first middle-layer sub-channel, and the liquid enters the middle-layer liquid outlet 24 through the sub-channel. The middle-layer cover plate 22 is provided with at least one second middle-layer sub-channel and at least one middle-layer liquid inlet 23. The middle-layer liquid inlet 23 is connected to the liquid outlet of the upper-layer chip and is connected to the second middle-layer sub-channel. The middle-layer cover plate 22 and the middle-layer substrate 21 are aligned and connected so that the first middle-layer sub-channel matches the second middle-layer sub-channel to form a middle-layer channel system. The liquid enters the liquid inlet of the middle-layer chip from the liquid outlet of the upper-layer chip and flows into the second middle-layer sub-channel. The liquid then flows in the middle-layer channel, passes through multiple capture tanks to complete the capture operation, and is finally discharged through the middle-layer liquid outlet 24.
[0047] At least one first lower sub-channel and at least one lower liquid outlet 34 are provided on the lower substrate 31. The first lower sub-channel is connected to the lower liquid outlet 34, and the liquid flows out from the liquid outlet after passing through the lower sub-channel. The lower cover plate 32 is provided with at least one second lower sub-channel and a lower liquid inlet 33. The lower liquid inlet 33 is connected to the liquid outlet of the middle chip, and the liquid enters the second lower sub-channel through the lower liquid inlet 33. The lower substrate 31 is aligned with the cover plate to ensure that the first lower sub-channel is aligned with the second lower sub-channel to form a complete lower channel. The liquid enters the lower liquid inlet 33 from the liquid outlet of the middle chip, flows through the second lower sub-channel, and after the capture operation is completed, the liquid is finally discharged from the first lower sub-channel through the lower liquid outlet 34.
[0048] In this embodiment, the flow channel is primarily constructed through the combination of a multi-layer chip's substrate and cover plate. By precisely aligning the substrate and cover plate, a complete flow channel system is formed, ensuring that liquid can flow smoothly through the sub-channels in each chip layer and be captured. Each layer's flow channel consists of two parts: a first sub-channel on the substrate and a second sub-channel on the cover plate. This design not only allows the complex flow channel structure to be manufactured in two parts, reducing the difficulty of single-layer processing, but also forms a complete flow channel system through the alignment of the upper and lower parts, ensuring smooth flow of liquid within each chip layer. Furthermore, the upper and lower flow channels 11 are precisely connected to the lower flow channel via liquid ports, ensuring stable fluid flow between the chip layers and preventing leakage or uneven flow due to structural mismatches. Within each chip layer, liquid enters through the upper inlet 12 or the middle inlet 23, and is gradually distributed and captured through the sub-channels. During liquid flow, the capture tank design ensures full contact between the liquid and the inner wall of the flow channel, thereby ensuring efficient capture of circulating tumor cells in each layer. The separate sub-channel design allows for greater processing flexibility. By aligning the cover and base plates, channels of varying shapes and sizes can be formed. This design approach greatly enhances the adjustability of the channel design, enabling it to adapt to varying fluid flow requirements.
[0049] In some embodiments, the inner wall of the upper flow channel 11 of the upper capture chip 1 is equipped with multiple upper capture grooves 16 distributed along the flow channel array. These grooves are designed to accommodate and capture circulating tumor cells, with the groove opening size no smaller than the maximum diameter of a tumor cell. The capture grooves are evenly spaced, forming a regular array. This array layout ensures that liquid in each area of the flow channel fully contacts the capture grooves, increasing the probability of tumor cell capture. The inner wall of the middle flow channel of the middle capture chip 2 is also equipped with multiple capture grooves, distributed in an array similar to the upper capture grooves 16, with uniform arrangement and consistent spacing. This arrangement of the capture grooves within the middle flow channel ensures that after liquid flows from the upper flow channel 11 into the middle flow channel, it can continue to capture uncaptured tumor cells within the middle flow channel. The inner wall of the lower flow channel of the lower capture chip 3 is also equipped with multiple capture grooves, evenly spaced along the flow channel array. The groove opening size of the capture grooves is consistent with that of the upper and middle layers, ensuring effective capture of circulating tumor cells. The capture trough array is precisely designed across the entire length and width of the flow channel. Each capture trough is evenly distributed along the inner wall of the flow channel, maximizing contact between the capture troughs and the liquid as it flows through the channel, effectively increasing the efficiency of tumor cell capture.
[0050] Furthermore, the upper capture grooves 16 can be respectively provided on the inner walls of the first upper sub-channel and the second upper sub-channel, with multiple upper capture grooves 16 arranged in an array along the extension direction of the upper channel 11. Similarly, the middle capture grooves and the lower capture grooves are also provided on the inner walls of their respective sub-channels, with multiple capture grooves arranged in an array along the extension direction of their respective channels.
[0051] In some embodiments, see Figure 3 or Figure 4 Multiple upper capture grooves 16 are arranged on the inner wall of the upper flow channel 11 of the upper capture chip 1. At least some of the upper capture grooves 16 are provided with a number of upper capture sub-grooves 161 on their inner walls. These sub-grooves directly communicate with the main capture groove, further refining the capture process and increasing the contact area between tumor cells and the capture groove. After circulating tumor cells enter the main capture groove, some may not be fully immobilized due to fluid flow rate or other factors. In this case, the sub-grooves provide additional capture space, allowing these tumor cells to be further immobilized within the groove.
[0052] The size of the capture sub-groove can be smaller than, larger than or equal to the capture groove, which is conducive to accommodating and fixing more circulating tumor cells. The arrangement of the sub-grooves is usually evenly distributed along the inner wall of the main capture groove to maximize the capture efficiency. At the same time, the sub-grooves are connected to the notch of the capture groove, so that the liquid and circulating tumor cells can smoothly enter the sub-grooves to complete the cell capture. When the liquid carries the tumor cells through the upper flow channel 11, the tumor cells first enter the main capture groove. If the tumor cells are not completely fixed in the main groove or may be carried away by the fluid impact, the sub-groove provides them with a second capture opportunity. The setting of the capture sub-groove can increase the area for capturing the tumor while minimizing the area of the inner wall of the flow channel, so that more specific antibodies 4 can be attached to the capture groove and the inner wall of the sub-groove.
[0053] Similarly, at least part of the inner wall of the middle capture groove and at least part of the lower capture groove is also provided with a capture sub-groove. The middle capture sub-groove is connected to the middle capture groove, and the lower capture sub-groove is connected to the lower capture groove. No further details will be given here.
[0054] In summary, the circulating tumor cell capture device provided by the present application achieves efficient and stable capture of circulating tumor cells by optimizing the fluid dynamics design, array capture groove layout and refined capture mechanism of capture sub-grooves. Specifically, the device achieves efficient capture of circulating tumor cells by utilizing a multi-layer structure of upper, middle and lower capture chips 3. Each layer of the chip contains a flow channel system, the inner wall of which is provided with a capture groove, and some capture groove inner walls are also provided with capture sub-grooves to further enhance the capture effect. It is composed of upper, middle and lower capture chips 3, each layer of the chip has an independent flow channel. After entering from the upper chip, the fluid flows through the middle and lower chips in sequence. On the inner wall of the flow channel of each layer of the chip, capture grooves are evenly arranged, and the capture groove size is designed to be no less than the maximum size of the circulating tumor cell to ensure that CTCs can enter and be captured. Some capture groove inner walls are provided with sub-grooves, which are connected to the capture groove, providing additional capture opportunities and further improving the stability and accuracy of capture. The capture tank is equipped with specific antibodies 4, such as anti-EpCAM antibodies, that can recognize and bind to specific antigens on the surface of circulating tumor cells. Through the specific antigen-antibody binding, tumor cells are fixed within the capture tank as they flow through it. Sub-tanks within some capture tanks provide a second chance to capture tumor cells that are not fully captured, further enhancing the accuracy and stability of cell capture.
[0055] The basic concepts have been described above. It will be apparent to those skilled in the art that the detailed disclosure above is merely illustrative and does not limit the present application. Although not explicitly stated herein, those skilled in the art may make various modifications, improvements, and amendments to the present application. Such modifications, improvements, and amendments are suggested in the present application and remain within the spirit and scope of the exemplary embodiments of the present application.
[0056] At the same time, this application uses specific terms to describe the embodiments of this application. For example, "one embodiment," "an embodiment," and / or "some embodiments" refer to a certain feature, structure, or characteristic related to at least one embodiment of this application. Therefore, it should be emphasized and noted that "one embodiment," "an embodiment," or "an alternative embodiment" mentioned twice or multiple times in different locations in this specification does not necessarily refer to the same embodiment. In addition, certain features, structures, or characteristics in one or more embodiments of this application may be appropriately combined.
[0057] Similarly, it should be noted that, in order to simplify the description of this application and thus facilitate understanding of one or more embodiments of the application, the foregoing description of the embodiments of this application sometimes combines multiple features into a single embodiment, figure, or description thereof. However, this disclosure method does not mean that the subject matter of this application requires more features than those recited in the claims. In fact, the features of an embodiment may be fewer than all the features of the individual embodiments disclosed above.
[0058] Each patent, patent application, patent application publication, and other materials, such as articles, books, specifications, publications, and documents, cited in this application is hereby incorporated by reference in its entirety, except for any application history that is inconsistent with or conflicts with this application, and any document (currently or subsequently appended to this application) that limits the broadest scope of the claims of this application. It should be noted that if the descriptions, definitions, and / or terminology used in the accompanying materials are inconsistent with or conflict with the content of this application, the descriptions, definitions, and / or terminology used in this application will control.
[0059] The above are merely preferred embodiments of the present application and are not intended to limit the present application. Those skilled in the art will readily appreciate that various modifications and variations are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.
Claims
1. A circulating tumor cell capture device, characterized in that: include: an upper layer capture chip, wherein the upper layer capture chip is provided with at least one upper layer flow channel and is connected to an upper layer liquid inlet; a middle-layer capture chip, disposed on one side of the upper-layer capture chip and provided with at least one middle-layer flow channel, wherein the middle-layer liquid inlet of the middle-layer flow channel is connected to the upper-layer liquid outlet of the upper-layer flow channel; a lower-layer capture chip, which is disposed on a side of the middle-layer capture chip away from the upper-layer capture chip and is provided with at least one lower-layer flow channel, wherein a lower-layer liquid inlet of the lower-layer flow channel is connected to a middle-layer liquid outlet of the middle-layer flow channel; Among them, the inner wall of the upper layer flow channel is provided with multiple upper layer capture grooves, the inner wall of the middle layer flow channel is provided with multiple middle layer capture grooves, and the inner wall of the lower layer flow channel is provided with multiple lower layer capture grooves, and the groove sizes of the upper layer capture groove, the middle layer capture groove and the lower layer capture groove are not less than the maximum size of the surface of the circulating tumor cells.
2. The circulating tumor cell capture device according to claim 1, characterized in that The upper capture chip, the middle capture chip and the lower capture chip are all rectangular and have the same shape and size; The upper layer capture chip comprises four upper layer flow channels, an upper layer liquid inlet and four upper layer liquid outlets, the four upper layer liquid outlets are respectively located at the four corners of the upper layer capture chip, the upper layer liquid inlet is located at the center of the upper layer capture chip, and the two ends of one of the upper layer flow channels are respectively connected to the upper layer liquid inlet and one of the upper layer liquid outlets; The middle-layer capture chip comprises four middle-layer flow channels, four middle-layer liquid inlets and one middle-layer liquid outlet. The four middle-layer liquid inlets are respectively located at the four corners of the middle-layer capture chip, and each of the middle-layer liquid inlets is connected to one of the upper-layer liquid outlets. The middle-layer liquid outlet is located at the center of the middle-layer capture chip. Both ends of a middle-layer flow channel are respectively connected to the middle-layer liquid outlets and one of the middle-layer liquid inlets. The lower layer capture chip includes four lower layer flow channels, a lower layer liquid inlet and four lower layer liquid outlets. The four lower layer liquid outlets are respectively located at the four corners of the lower layer capture chip. The lower layer liquid inlet is located at the center of the lower layer capture chip and is connected to the middle layer liquid outlet. The two ends of one of the lower layer flow channels are respectively connected to the lower layer liquid inlet and one of the lower layer liquid outlets.
3. The circulating tumor cell capture device according to claim 1, characterized in that The upper flow channel, the middle flow channel and the lower flow channel are all serpentine.
4. The circulating tumor cell capture device according to claim 1, characterized in that The upper capture chip includes an upper substrate and an upper cover plate, the upper substrate is provided with at least one first upper sub-channel and at least one upper liquid outlet, the upper cover plate is provided with at least one second upper sub-channel and the upper liquid inlet, the upper liquid inlet is connected with the second upper sub-channel, the upper liquid outlet is connected with the first upper sub-channel, and the upper cover plate is covered on the upper substrate so that the first upper sub-channel and the second upper sub-channel are aligned and connected to form the upper channel.
5. The circulating tumor cell capture device according to claim 4, characterized in that The middle-layer capture chip includes a middle-layer substrate and a middle-layer cover plate. The middle-layer substrate is provided with at least one first middle-layer sub-channel and a middle-layer liquid outlet, and the middle-layer liquid outlet is connected to the first middle-layer sub-channel. The middle-layer cover plate is provided with at least one second middle-layer sub-channel and at least one middle-layer liquid inlet, and the middle-layer liquid inlet is connected to both the second middle-layer sub-channel and the upper-layer liquid outlet. The middle-layer cover plate is covered on the middle-layer substrate so that the first middle-layer sub-channel and the second middle-layer sub-channel are aligned and connected to form the middle-layer channel.
6. The circulating tumor cell capture device according to claim 5, characterized in that The lower capture chip includes a lower substrate and a lower cover plate, the lower substrate is provided with at least one first lower sub-channel and at least one lower liquid outlet, the first lower sub-channel is connected to the lower liquid outlet, the lower cover plate is provided with at least one second lower sub-channel and a lower liquid inlet, the lower liquid inlet is connected to the second lower sub-channel, and the lower liquid inlet is also connected to the middle liquid outlet, the lower cover plate is covered on the lower substrate so that the first lower sub-channel and the second lower sub-channel are aligned and connected to form the lower channel.
7. The circulating tumor cell capture device according to any one of claims 1 to 6, characterized in that: A plurality of the upper capture grooves are arranged along the upper flow channel array, a plurality of the middle capture grooves are arranged along the middle flow channel array, and a plurality of the lower capture grooves are arranged along the lower flow channel array.
8. The circulating tumor cell capture device according to any one of claims 1 to 6, characterized in that: At least a portion of the inner wall of the upper capture groove is provided with an upper capture sub-groove, and the upper capture sub-groove is communicated with the upper capture groove.
9. The circulating tumor cell capture device according to any one of claims 1 to 8, characterized in that: Specific antibodies are provided in the upper capture tank, the middle capture tank and the lower capture tank. The specific antibodies have the property of binding to antigens in the circulating tumor cells.
10. The circulating tumor cell capture device according to claim 9, characterized in that The specific antibody is an anti-EpCAM antibody.