Rigid chip for CTC cell enrichment and dyeing integrated equipment

Abstract

The utility model relates to the technical field of medical inspection equipment, in particular to a rigid chip for CTC (circulating tumor cell) cell enrichment and dyeing integrated equipment. Comprising a reagent groove and a rigid chip fixing sheet arranged at the lower end of the reagent groove, a first through hole is formed in the rigid chip fixing sheet, a chip body is placed in the first through hole, the reagent groove is of a sheet structure with a liquid leakage hole longitudinally penetrating through the chip body, and the chip body is made of transparent rigid materials. A plurality of groups of long strip-shaped micropores are uniformly distributed on the chip body; and the micro holes in the chip body comprise transverse holes which are transversely arranged and vertical holes which are longitudinally arranged. The chip is uniform in aperture, strong in selectivity and less in filtrate residue, can effectively avoid the phenomenon of cell stacking or hardening caused by overlarge negative pressure during suction filtration, improves the quality of CTC cell enrichment dyeing, and can be used for automatic detection equipment.

Description

Technical Field

[0001] This utility model relates to the field of medical testing equipment technology, specifically a rigid chip for an integrated CTC cell enrichment and staining device. Background Technology

[0002] CTC, or circulating tumor cell detection, is a newly emerging tumor diagnostic technology that has gained popularity in recent years. Studies have shown that circulating tumor cells can be detected in peripheral blood before solid tumors form, making CTC detection highly suitable for early screening and diagnosis of malignant tumors. Furthermore, CTC detection has shown good results in prognosis, disease progression monitoring, recurrence prediction, postoperative monitoring of small lesions in malignant tumors, and the design and monitoring of targeted drug therapy effects, making it an advanced method for early screening and diagnosis of malignant tumors. However, due to the very low concentration of circulating tumor cells in peripheral blood, the capture and identification of circulating tumor cells in CTC detection presents a significant challenge. Another Chinese patent of the applicant, 2019103326886, discloses an integrated reaction device and method for the enrichment and staining of nucleated cells in body fluids by blotting, authorized publication number CN111855333B. This reaction device includes a microporous membrane with a fixing component, a reaction tank on the fixing component, a top cover on the reaction tank, a liftable platform on one side of the fixing component, and a storage chamber below the fixing component; the storage chamber is filled with an absorbent material. When the cell suspension passes through the microporous membrane, cells larger than the membrane pore size are retained in the reaction vessel and adsorbed onto the membrane surface due to the suction filtration and retention method. Because the water-absorbing substance has a stable suction rate, gentle attraction force, and is slow and essentially pressureless, the cells adhere to the membrane surface. This achieves the capture and enrichment of malignant cells and pathogens in body fluids. The microporous membrane in this device, also called a microfluidic chip, is a key component for enriching circulating tumor cells. Existing microporous membranes all use flexible fiber filter membranes or filter paper as filter media. For example, another Chinese patent of the applicant, 202321916277X, discloses "A Microfluidic Device and Integrated Cell Enrichment and Staining Equipment," with authorization announcement number CN220371064U, in which the microfluidic device includes: a liquid accumulation platform, a filter assembly, and a platform mesh. The liquid accumulation stage has a funnel-shaped internal structure with guide strips protruding from its surface for guiding the filtrate. The filtration assembly is a microfiltration membrane positioned above the liquid accumulation stage for filtering liquid samples. The flexible microfiltration membrane has uneven pore size and significant capillary action, making it easy for filtrate to remain within it. Therefore, auxiliary devices such as a negative pressure pump and absorbent layer are needed below to remove excess filtrate from the microfiltration membrane. Excessive negative pressure can also cause cell stacking or caking. Flexible filter membranes are prone to wrinkles and air bubbles, affecting microscopic observation. Utility Model Content

[0003] To address the problems of the prior art, this invention provides a rigid chip for an integrated CTC cell enrichment and staining device that does not require negative pressure. The filter material has uniform pore size, strong selectivity, and low filtrate residue, which can effectively avoid cell stacking or caking caused by excessive negative pressure during aspiration filtration, thereby improving the quality of CTC cell enrichment and staining and preventing the appearance of air bubbles under the microscope.

[0004] To achieve the above objectives, this utility model provides the following technical solution:

[0005] The rigid chip for CTC cell enrichment and staining integrated device of this utility model includes a reagent tank and a rigid chip fixing plate disposed at the lower end of the reagent tank. The rigid chip fixing plate has a through hole, and the chip body is placed in the through hole. The reagent tank is a sheet-like structure with a leakage hole that runs longitudinally through the chip body. The chip body is made of a transparent rigid material, and multiple sets of elongated micropores are evenly distributed on the chip body. The micropores on the chip body include transversely arranged horizontal holes and longitudinally arranged vertical holes.

[0006] With the above structural design, the rigid chip does not require negative pressure filtration, which can effectively avoid cell stacking or caking caused by excessive negative pressure during filtration; the filter material has uniform pore size and strong selectivity.

[0007] Preferably, the lower surface of the rigid chip fixing sheet is provided with a liquid absorption component, the liquid absorption component including filter paper adhered to the lower surface of the rigid chip fixing sheet and a layer of superabsorbent polymer material disposed between the filter paper and the rigid chip fixing sheet.

[0008] The above structural design utilizes a superabsorbent polymer material to fully absorb various reagents, replacing the traditional filtration components, reducing equipment size and cost. It effectively avoids cell stacking or clumping caused by excessive negative pressure during filtration, preserving the cells' original state as much as possible.

[0009] Preferably, the superabsorbent polymer material layer of the liquid-absorbing component covers the entire through hole one, and a gasket is provided between the lower surface of the rigid chip fixing piece and the liquid-absorbing component, the gasket surrounding the superabsorbent polymer material layer.

[0010] With the above structural design, the gasket fixes the powdered polymer material within the gasket area, preventing the powdered polymer material from being too dispersed and affecting the water absorption effect.

[0011] Preferably, the width of both the horizontal and vertical holes is 0.0075 mm, the length of the horizontal hole is 0.09 mm, and the length of the vertical hole is 0.06 mm.

[0012] By adopting the above structural design, the selectivity of the chip body for cell capture can be improved.

[0013] Preferably, the upper surface of the reagent tank is provided with a funnel-shaped liquid collection tank, and the lower end of the liquid collection tank is connected to the leakage hole.

[0014] The above structural design includes a collection tank for temporary storage of blood and subsequent addition of various reagents.

[0015] Preferably, a drainage channel is provided on the side of the upper end of the liquid collection tank, with the inner end of the drainage channel connected to the liquid collection tank and the outer end connected to the outside of the reagent tank.

[0016] The above structural design facilitates the discharge of residual reagents from the collection tank and leakage hole.

[0017] Preferably, a suction filter chamber is detachably installed at the lower end of the reagent tank via a first slot, the suction filter chamber being a container with an open upper end that receives the leakage hole.

[0018] With the above structural design, the suction chamber can easily collect waste reagents and suction components that pass through the leakage hole.

[0019] Compared with the prior art, the beneficial effects of this utility model are:

[0020] This rigid chip has uniform pore size, high selectivity, and low filtrate residue. It can effectively avoid cell stacking or caking caused by excessive negative pressure during aspiration filtration, maintain the original state of cells as much as possible, improve the quality of CTC cell enrichment staining, avoid the phenomenon of air bubbles under the microscope, and can be used in automated detection equipment. Attached Figure Description

[0021] Figure 1 This is a three-dimensional structural diagram of a reagent tank according to an embodiment of the present invention.

[0022] Figure 2 for Figure 1 A cross-sectional view of the reagent tank.

[0023] Figure 3 This is a schematic diagram of the three-dimensional structure of the chip itself.

[0024] Figure 4 This is a magnified schematic diagram of some of the micropores in the chip body.

[0025] Figure 5 This is a three-dimensional structural diagram of the liquid absorption assembly.

[0026] Figure 6 This is a three-dimensional structural diagram of the filter chamber.

[0027] Figure 7 It is a cross-sectional view of the reagent tank, the chip body, and the suction filter chamber assembled together. Detailed Implementation

[0028] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0029] The rigid chip for the integrated CTC cell enrichment and staining device of this utility model includes a reagent tank 1 and a rigid chip fixing piece 201 disposed at the lower end of the reagent tank 1, such as... Figure 1 , Figure 2 As shown, the reagent tank 1 is a sheet-like structure with a longitudinally penetrating leakage hole 102. The leakage hole 102 can be a cylindrical structure or a square columnar structure. In addition, a liquid collection tank 106 is formed on the upper surface of the reagent tank 1. The liquid collection tank 106 is a funnel-shaped structure that is larger at the top and smaller at the bottom. The lower end of the liquid collection tank 106 is connected to the leakage hole 102. When the reagent tank 1 is placed horizontally, the reagent and other liquids falling through the leakage hole 102 pass through the chip body 2 and collect in the suction filter chamber 4.

[0030] like Figure 3 , Figure 4 As shown, the chip body 2 is preferably made of flexible glass, and multiple sets of elongated micropores are uniformly distributed on the chip body 2. The micropores include horizontally arranged transverse holes 11 and vertically arranged vertical holes 12. The width of both the horizontal holes 11 and the vertical holes 12 is 0.0075 mm, the length of the horizontal hole 11 is 0.09 mm, and the length of the vertical hole 12 is 0.06 mm. The horizontal holes 11 and the vertical holes 12 are arranged perpendicular to each other, with a spacing of 0.03 mm between adjacent horizontal holes 11 and the vertical holes 12 located on the center line of the horizontal holes 11. The distance between the upper ends of the horizontal holes and vertical holes in the same group of holes is 0.015 mm. The large spacing between adjacent vertical holes can effectively prevent cell overlap and prevent the enriched cells from falling onto the horizontal and vertical holes, thus affecting subsequent microscopic observation.

[0031] like Figure 5 , Figure 7 As shown, the lower surface of the rigid chip fixing piece 201 is provided with a liquid absorption component 3. The liquid absorption component 3 includes a filter paper 301 pasted on the rigid chip fixing piece 201 and a polymer water-absorbing material layer 303 disposed between the filter paper 301 and the chip body 1.

[0032] The superabsorbent polymer layer 303 uses powdered superabsorbent resin, a novel functional polymer material. It possesses the ability to absorb hundreds to thousands of times its own weight in water and exhibits excellent water retention. Once it absorbs water and swells into a hydrogel, it is difficult to separate the water even under pressure. Superabsorbent resins are generally polymeric electrolytes containing hydrophilic groups and cross-linked structures. Before absorbing water, the polymer chains entangle and cross-link to form a network structure, achieving overall compactness. Upon contact with water, water molecules permeate into the resin through capillary action and diffusion, while the ionized groups on the chains ionize in the water. The electrostatic repulsion between like ions on the chains causes the polymer chains to extend and swell. Due to the requirement of electroneutrality, counterions cannot migrate to the outside of the resin, and the ion concentration difference between the inside and outside of the resin solution creates reverse osmosis pressure. Under the action of reverse osmosis pressure, water further enters the resin, forming a hydrogel.

[0033] like Figure 7 As shown, a gasket 302 is provided between the lower surface of the rigid chip fixing piece 201 and the liquid absorption component 3, and the gasket 302 surrounds the polymer absorbent material layer 303. The function of the gasket 302 is to fix the powdered polymer material within the range of the gasket 302, preventing the powdered polymer material from being too dispersed and affecting the water absorption effect. Filter paper 301 can be multi-layered. In use, the layer of filter paper 301 furthest from the chip body 2 is fixed to the bottom surface of the rigid chip fixing piece 201. After the polymer absorbent material layer 303 absorbs sufficient reagent, its volume expands, causing the liquid absorption component 3 to detach and fall into the suction chamber 4 under the action of gravity.

[0034] like Figure 1 , Figure 2 As shown, in this embodiment, a diversion groove 105 is provided at two opposite corners along the length of the reagent tank 1. The inner end of the diversion groove 105 is connected to the liquid collection tank 106, and the outer end is connected to the outside of the reagent tank 1.

[0035] like Figure 6 , Figure 7As shown, a suction filter chamber 4 is detachably installed at the lower end of the reagent tank 1 via a first slot 103. The suction filter chamber 4 is a container with an open upper end that receives the leakage hole 102. The edge of the upper port of the suction filter chamber 4 is provided with a claw 401 that matches the first slot 103. In use, the suction filter chamber 4 can be installed at the lower end of the reagent tank 1 simply by inserting the claw 401 into the first slot 103. After installation, the upper opening of the suction filter chamber 4 is directly opposite the leakage hole 102. Waste reagents flowing out of the leakage hole 102 through the chip body 2 and the liquid suction component 3 that falls off the chip body 2 are temporarily stored in the suction filter chamber 4. After the cell enrichment process is completed, the volume and weight of the superabsorbent polymer increase significantly after absorbing water. The filter chamber can prevent the superabsorbent polymer from overflowing after absorbing water, thus reducing pollution to the surrounding environment. It is also because the volume and weight of the superabsorbent polymer increase significantly after absorbing water that the liquid absorption component 3 automatically detaches from the chip fixing slot under the action of gravity, eliminating the need for manual peeling, reducing manual labor and avoiding pollution.

[0036] like Figure 7 As shown, in use, the rigid chip holder 201 is attached to the bottom of the reagent tank 1, the liquid absorption assembly 3 is located below the chip body 2, and the suction chamber 4 is installed below the reagent tank 1. Blood or reagents are poured into the reagent tank 1, collected in the collection tank 106, and then pass through the leakage hole 102 and the chip body 2. The blood or reagents that have passed through the chip body 2 are absorbed by the liquid absorption assembly 3. The liquid absorption assembly contains a superabsorbent polymer material, which expands in volume hundreds of times after absorbing water. After absorbing the liquid, the liquid absorption assembly 3 separates from the rigid chip holder 201. The liquid absorption assembly 3, having fully absorbed the reagent, will finally detach from the chip body 2 and fall into the suction chamber 4.

[0037] Contents not described in detail in this specification are existing technologies known to those skilled in the art. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A rigid chip for an integrated CTC cell enrichment and staining device, comprising a reagent tank (1) and a rigid chip fixing plate (201) disposed at the lower end of the reagent tank (1), characterized in that: The rigid chip holder (201) has a through hole (202) and a chip body (2) is placed in the through hole (202). The reagent tank (1) is a sheet structure with a leakage hole (102) that runs through its body longitudinally. The chip body (2) is made of a transparent rigid material and has multiple sets of elongated micropores evenly distributed on it. The micropores on the chip body (2) include transverse holes (11) and vertical holes (12) arranged longitudinally.

2. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 1, characterized in that: The lower surface of the rigid chip fixing piece (201) is provided with a liquid absorption component (3), which includes a filter paper (301) pasted on the lower surface of the rigid chip fixing piece (201) and a polymer water-absorbing material layer (303) disposed between the filter paper (301) and the rigid chip fixing piece (201).

3. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 2, characterized in that: The polymer absorbent material layer (303) of the liquid absorption component (3) covers the entire through hole (202), and a gasket (302) is provided between the lower surface of the rigid chip fixing piece (201) and the liquid absorption component (3), and the gasket (302) surrounds the polymer absorbent material layer (303).

4. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 1 or 2, characterized in that: The width of both the horizontal hole (11) and the vertical hole (12) is 0.0075 mm, the length of the horizontal hole (11) is 0.09 mm, and the length of the vertical hole (12) is 0.06 mm.

5. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 1 or 2, characterized in that: The reagent tank (1) has a funnel-shaped liquid collection tank (106) on its upper surface, and the lower end of the liquid collection tank (106) is connected to the leakage hole (102).

6. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 5, characterized in that: A flow channel (105) is provided on the side of the upper end of the liquid collection tank (106). The inner end of the flow channel (105) is connected to the liquid collection tank (106), and the outer end is connected to the outside of the reagent tank (1).

7. The rigid chip for the integrated CTC cell enrichment and staining device according to claim 1 or 2, characterized in that: The lower end of the reagent tank (1) is detachably fitted with a suction filter chamber (4) via a first slot (103). The suction filter chamber (4) is a container with an open upper end that receives the leakage hole (102).

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