A microfluidic chip with self-adjustable microchannel height

Abstract

The present invention belongs to the technical field of in vitro diagnosis and immunoassay, and particularly relates to a microfluidic chip with self-adjustable flow channel height. It includes a substrate, a liquid guiding rail, and a pressing column. A microfluidic channel with self-adjustable height is arranged on the substrate. The microfluidic channel is formed by placing a slender liquid guiding rail on the upper surface of the substrate. The liquid guiding rail is a flexible thin film liquid guiding rail, and both sides in the width direction of the liquid guiding rail are open; one end of the liquid guiding rail is covered by a pressing column at the upper part as the end, and the other end is the starting end for adding sample liquid; a marking area is arranged near the starting end, and a detection area is arranged in the middle between the liquid guiding rail and the substrate; it also includes a housing clamped to the circumferential direction of the substrate. The present invention can use a plastic film coil to make the liquid guiding rail, a plastic plate to make the substrate, and the housing is made by ordinary injection molding process, without the need for precision processing, and the cost is low. The microfluidic channel of the present invention has a small height, requires a small amount of sample liquid, and the height of the microfluidic channel will be automatically adjusted according to different sample liquids to make the sample liquid flow smoothly, with strong applicability.

Description

Technical Field

[0001] The present invention belongs to the technical field of in vitro diagnosis and immunoassay, and particularly relates to a microfluidic chip with self-adjusting flow channel height. Background Art

[0002] Microfluidic technology belongs to the rapidly developing field of medical diagnosis and uses microscale fluid systems for biological and chemical testing. This technology can precisely control the movement of liquids in a microscale space and has significant advantages over traditional diagnostic methods. In medical diagnosis, microfluidic technology has a wide range of applications, including the rapid and accurate detection of infectious diseases, the analysis of blood, urine, saliva, and other body fluid samples, and the detection of gene mutations. This technology achieves high-precision, high-sensitivity, and specific analysis by precisely controlling the flow and mixing of liquids in a controlled environment. Microfluidic technology can be integrated into portable, low-cost devices, enabling medical professionals to obtain results on-site and make diagnoses in real time. In addition, microfluidic technology has the potential to greatly reduce the cost and time of diagnostic tests, and thus has broad prospects for application in resource-limited environments.

[0003] In the micron-scale range, the behavior of fluids is very different from that in the macroscale. In a microscale system, the surface area-to-volume ratio is much higher than in a large-scale system, surface effects become more important, and inertial forces can be neglected compared to viscous forces. This leads to unique fluid phenomena such as capillary flow, surface-tension-driven liquid flow, and the liquid flow exhibits laminar flow without forming vortices.

[0004] A microfluidic immunoassay chip uses microchannels and chambers to perform biochemical reactions at the microscale, and uses specific antibodies to detect or quantitatively measure target analytes in biological samples, such as the presence or concentration of a certain protein. Its basic principle is as follows: capture antibodies are implanted at designated positions on the surface of the microchannel or microcavity, and this position is called the detection point; a labeled antibody with a marker is placed in the area near the inlet in the microchannel, and this area is called the labeling area; after the analyte to be detected in the sample flows into the labeling area and mixes and binds with the labeled antibody, the analyte to be detected is labeled; when the sample solution flows through the detection point in the microchannel, the capture antibody selectively binds to the labeled analyte to be detected and retains it at the detection point, and other molecules become waste liquid and are washed away, while the marker generates a measurable signal at the detection point position; by comparing the signal generated by the marker with the calibration curve generated by the target analyte with a known concentration, the concentration of the analyte to be detected in the sample is determined.

[0005] Such as Figure 1As shown, the common microfluidic channels in the prior art are slender pipes that are open at both ends and sealed in the middle. The microfluidic channels confine the sample liquid to flow in a tiny space through the seal. The cross-section of the microfluidic channel can be different shapes such as circles and squares. One dimension of the microfluidic channel must be below 100 microns. The manufacturing techniques include photolithography, soft printing, microfabrication, precision mold injection molding, etc. They can be made of materials such as glass, silicon, and polymer polymers. However, no matter which manufacturing process, such as Figure 2 the grooving method and the sandwich method shown, require multi-layer material bonding to achieve a long and narrow microfluidic channel.

[0006] For immunological detection chips, the shape of the cross-section of the microfluidic channel is mostly rectangular, and the height of the channel is a micron-level dimension. The existing processing technology has great processing difficulty and high mass production cost, which are reflected in: 1. The water molecule is only 0.28 nanometers in size. Even a 0.1-micron gap at the bonding interface will cause liquid leakage in the microfluidic channel. Because the smaller the gap, the greater the capillary force, and the capillary force of the gap is much greater than the capillary force of the microfluidic channel itself. 2. The microfluidic channel requires micron-level precision and has high requirements for the mechanical stability and thermal stability of the material. Different thicknesses of the adhesive will change the height of the channel. It can be obtained from the Hagen-Poiseuille equation that the height of the microfluidic channel has a great influence on the sample volume, sample flow rate, and flow velocity, directly affecting the reaction time and reaction concentration. 3. The manufacturing cost of an injection mold with micron-level precision is very high. Summary of the Invention

[0007] Aiming at the deficiencies of the above-mentioned prior art, the present invention proposes a microfluidic chip with self-adjustable microfluidic channel height, as follows:

[0008] It includes a substrate, a liquid guiding rail, and a pressing column. A microfluidic channel with self-adjustable height is added on the substrate. Each microfluidic channel is formed by placing a slender liquid guiding rail on the upper surface of the substrate. The liquid guiding rail is a flexible thin film liquid guiding rail, and both sides of the width direction of the liquid guiding rail are open; one end of the liquid guiding rail is covered with a pressing column at the upper part as the end, and the other end is the starting end for adding the sample liquid; a marking area is set near the starting end, and a detection area is set in the middle between the liquid guiding rail and the substrate.

[0009] Preferably, the substrate is a rigid flat polymer material substrate, and the liquid guiding rail is made of PET (polyethylene terephthalate) or PC (polycarbonate) film.

[0010] Preferably, the flexible thin film liquid guiding rail is 0.02-0.1 mm thick, 2-5 mm wide, and the length is more than 5 times the width.

[0011] When the detection object is a common sample liquid (non-whole blood):

[0012] Preferably, two identical, spaced, and longitudinally extending slender holes are cut in the middle of the flexible film, and a liquid guide track is formed between the two slender holes. The slender holes do not penetrate the entire length of the flexible film.

[0013] Among them, the liquid guide track is sequentially divided into sections AB, BC, CD, and DE along the direction of sample liquid flow. The BC and DE sections are parallel to the substrate surface. The AB section forms a straight uphill slope, and the CD section forms an arc-shaped downhill slope. An inlet is provided on the AB section. The BC section forms a marking area, and the DE section forms a detection area. The other areas of the flexible film are tiled on the substrate in the same manner as the DE section. The areas of the flexible film before and after the DE section and away from the marking area form a waste liquid area.

[0014] Preferably, an independent strip-shaped flexible film liquid guide track is cut. The liquid guide track is sequentially divided into sections AB, BC, CD, and DE along the direction of sample liquid flow. The BC and DE sections are parallel to the substrate surface. The AB section forms a straight uphill slope, and the CD section forms an arc-shaped downhill slope. An inlet is provided on the AB section. The BC section forms a marking area, and the front part of the DE section forms a detection area, and the rear part forms a waste liquid area.

[0015] Among them, a cellulose membrane is laid under the waste liquid area at the end of the flexible film liquid guide track. The thickness of the membrane is less than the height h of the microchannel. The cellulose membrane extends outside the flexible film liquid guide track. A water-absorbing cotton is pressed on the end of the flexible film liquid guide track and the exposed cellulose membrane. The density of the water-absorbing cotton is greater than that of the cellulose membrane.

[0016] Preferably, the height of the BC section is between 0.2 mm and 0.5 mm.

[0017] Preferably, the width of the AB section is large to facilitate the processing of an inlet with a sufficient diameter. The width of the BC section is small at both ends, and both sides at both ends are processed into inwardly concave arcs.

[0018] Preferably, it further includes a housing. The housing is snap-connected to the circumference of the substrate in the form of an end cover. The cross-section of the housing is U-shaped.

[0019] Preferably, a limiting bone and a pressing column protrude downward from the inner top surface of the housing. The limiting bone is located directly above the BC section. The pressing column is located at the end of the inner top surface of the housing, and the lower part directly presses on the end of the flexible film liquid guide track or the water-absorbing cotton.

[0020] Preferably, a funnel-shaped sample addition hole is provided on the housing directly above the AB section, and a viewing window is provided on the housing directly above the detection area.

[0021] Preferably, the bottom of the funnel-shaped sample addition hole is flush with the bottom of the limiting bone. The bottom of the limiting bone is as close as possible to the BC section of the liquid guide track and is arranged at intervals along the liquid guiding direction of the flexible film liquid guide track.

[0022] Preferably, the outer shell is a plastic shell processed by an injection molding process.

[0023] When the test object is whole blood sample fluid:

[0024] Preferably, two identical, spaced, longitudinally extending slender holes are cut out in the middle of the flexible film, and a liquid guide rail is formed between the two slender holes, and the slender holes do not penetrate the entire length of the flexible film.

[0025] Among them, the flexible film liquid guide rail is laid flat, an anticoagulant blood filtering cotton is arranged at the starting end of the liquid guide rail, a labeled antibody is arranged below the anticoagulant blood filtering cotton, and the starting section of the flexible film liquid guide rail is located below the anticoagulant blood filtering cotton and on the side of the labeled antibody; a detection area and a waste liquid area are also arranged along the flowing direction of the sample liquid on the flexible film liquid guide rail, and other areas of the flexible film are also laid flat on the substrate to form a waste liquid area in the same way.

[0026] Preferably, an independent strip-shaped flexible film liquid guide rail is cut out, the flexible film liquid guide rail is laid flat, an anticoagulant blood filtering cotton is arranged at the starting end of the liquid guide rail, a labeled antibody is arranged below the anticoagulant blood filtering cotton, and the starting section of the flexible film liquid guide rail is located below the anticoagulant blood filtering cotton and on the side of the labeled antibody; a detection area and a waste liquid area are also arranged along the flowing direction of the sample liquid on the flexible film liquid guide rail.

[0027] Among them, a cellulose membrane is laid under the waste liquid area at the end of the flexible film liquid guide rail, the thickness of the membrane is less than the height h of the microchannel, the cellulose membrane extends outside the flexible film liquid guide rail, and a water-absorbing cotton is pressed on the end of the flexible film liquid guide rail and the exposed cellulose membrane, and the density of the water-absorbing cotton is greater than that of the cellulose membrane.

[0028] Preferably, the anticoagulant blood filtering cotton is a fiber cotton with a lower density, and an anticoagulant and a hemoglobin antibody are added to the fiber cotton.

[0029] Preferably, it further includes an outer shell, the outer shell is clamped to the circumference of the substrate in the form of an end cover, and the cross section of the outer shell is U-shaped.

[0030] Preferably, a limiting bone and a pressing column protrude downward from the inner top surface of the outer shell, the pressing column is located at the end of the inner top surface of the outer shell, and the lower part directly presses on the end of the flexible film liquid guide rail or the water-absorbing cotton.

[0031] Preferably, a funnel-shaped sample adding hole is arranged on the outer shell directly above the anticoagulant blood filtering cotton, and a perspective window is arranged on the outer shell directly above the detection area.

[0032] Preferably, the bottom of the funnel-shaped sample adding hole is closely attached to the upper part of the blood filtering cotton, the bottom of the limiting bone is lower than the bottom of the funnel-shaped sample adding hole and higher than the bottom of the anticoagulant blood filtering cotton, and the funnel-shaped sample adding hole and the limiting bone are arranged at intervals along the flowing direction of the flexible film liquid guide rail.

[0033] Preferably, the outer shell is a plastic outer shell processed by an injection molding process.

[0034] A microfluidic chip with self-adjustable microchannel height obtained by the above technical solution has the following beneficial effects:

[0035] 1. The microchannel of the present invention is formed by disposing an open flexible thin film liquid guiding rail on a substrate. The height of the microchannel can be self-adjusted. The consistency of the height h of the microchannel only depends on the consistency of the thickness of the flexible thin film liquid guiding rail and the flatness of the substrate. There is a large supply of films with good thickness consistency and plastic sheets with good flatness on the market, and the price is very low.

[0036] The microfluidic chip of the present invention can use a ready-made plastic film roll to make the liquid guiding rail and a plastic sheet to make the substrate, without precise processing. The outer shell can be made by an ordinary injection molding process. Therefore, the manufacturing cost will be lower than that of the microfluidic chips made by the existing grooving method and sandwich method, and the manufacturing precision requirements are low.

[0037] 2. According to experiments, when the membrane is made of 0.05 mm thick PET and water is used as the sample liquid, the height of the microchannel is about 18 microns. It is very difficult for the microchannel of the microfluidic chip made by the existing process to reach this scale. And a small microchannel height requires a small amount of sample liquid. Therefore, the microfluidic chip of the present invention has great advantages in the detection of trace samples.

[0038] 3. The height of the microchannel of the present invention can be self-adjusted. If the sample liquid is a liquid with larger molecules and higher viscosity, such as blood, according to the principle of fluid mechanics, the height of the microchannel will also be automatically adjusted to allow the sample liquid to flow smoothly, which cannot be achieved in a chip with a fixed-height microchannel. Description of the Drawings

[0039] Figure 1 is a cross-sectional view and a front view of a general microchannel structure in the prior art;

[0040] Figure 2 is a cross-sectional view of a microchannel made by the grooving method and the sandwich method in the prior art;

[0041] Figure 3 is a top view of the microfluidic chip in Embodiment 1 of the present invention;

[0042] Figure 4 is Figure 3 a cross-sectional view along the length direction of the liquid guiding rail;

[0043] Figure 5 is Figure 3 a cross-sectional view along the width direction of the liquid guiding rail;

[0044] Figure 6It is a schematic diagram of the working principle of the microfluidic chip in the first embodiment of the present invention (longitudinal sectional view);

[0045] Figure 7 It is a schematic diagram of the working principle of the microfluidic chip in the first embodiment of the present invention (transverse sectional view);

[0046] Figure 8 It is a schematic diagram of the force balance when the microfluidic chip in the first embodiment of the present invention is working;

[0047] Figure 9 It is a longitudinal sectional view of the microfluidic chip in the second embodiment of the present invention;

[0048] Figure 10 It is a top view of the diaphragm in the second embodiment of the present invention;

[0049] Figure 11 It is one of the longitudinal sectional views of the substrate and the flexible thin film liquid guide rail in the second embodiment of the present invention;

[0050] Figure 12 It is a top view of the outer shell in the second embodiment of the present invention;

[0051] Figure 13 It is the second longitudinal sectional view of the substrate and the flexible thin film liquid guide rail in the second embodiment of the present invention;

[0052] Figure 14 It is the second top view of the substrate and the flexible thin film liquid guide rail in the second embodiment of the present invention along the length direction;

[0053] Figure 15 It is a longitudinal sectional view of the microfluidic chip in the third embodiment of the present invention;

[0054] In the figure: substrate 1, flexible thin film liquid guide rail 2, top pressure column 3, sample liquid 4; marking area 5, detection area 6, waste liquid area 7, liquid inlet 8, outer shell 9, limiting bone 10, perspective window 11, sample addition hole 12, marking antibody 13, capture antibody 14, cellulose membrane 15, absorbent cotton 16, anticoagulant blood-filtering cotton 17. Detailed implementation manners

[0055] It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other. Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art to which the present invention belongs. The test reagents used in the following embodiments are all conventional biochemical reagents unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.

[0056] The present invention will be further explained below with reference to the embodiments and the drawings. It can be understood that the present invention is not limited to the specific implementation manners described.

[0057] Example 1

[0058] As Figure 3-5 shown, the microfluidic chip with self-adjustable microchannel height of the present invention includes a substrate 1, a flexible thin-film liquid guide rail 2 and a top pressure column 3. The substrate 1 is a rigid flat polymer material substrate (such as an acrylic plate); an open and self-adjustable height microchannel is disposed on the substrate 1, and each microchannel is formed by placing a slender liquid guide rail 2 on the upper surface of the substrate 1; the liquid guide rail 2 is a flexible thin film, specifically a polymer material thin film, preferably a PET or PC thin film. The thickness of the flexible thin-film liquid guide rail 2 does not exceed 0.1 mm (it can be 0.02 - 0.1 mm), the width is between 2 - 5 mm, and the length is more than 5 times the width; there is a gap with a height of h between the flexible thin-film liquid guide rail 2 placed on the upper surface of the substrate 1 and the upper surface of the substrate 1 to form a microchannel with a height of h, and the height h is in the micron level; one end of the liquid guide rail 2 is covered and pressed by the top pressure column 3, which is the end, and the other end lies flat naturally under the action of gravity, which is the starting end, and the starting end is the sample liquid adding end; between the flexible thin-film liquid guide rail 2 and the substrate 1, a labeled antibody 13 is disposed near the starting end, and a capture antibody 14 is disposed in the middle part.

[0059] As a further optimization of this embodiment, the liquid guide rail 2 can be straight or curved in the length direction. The curved liquid guide rail can increase the effective length of the flow channel, reduce the flow rate, and is beneficial to mixing.

[0060] As a further optimization of this embodiment, the top pressure column 3 presses one end of the flexible thin-film liquid guide rail 2 against the substrate 1.

[0061] The liquid guide rail 2 of the present invention is a flexible thin-film material and will lie flat on the substrate 1 under the action of gravity. However, the seemingly flat substrate 1 and the flexible thin-film liquid guide rail 2 are not flat at the nano and micron scales, and there will be a gap h (microchannel height h) of 1 micron to several microns between them, that is, the flexible thin-film liquid guide rail 2 lying flat on the substrate 1 under the action of gravity is not absolutely closely attached to the substrate 1.

[0062] When the sample liquid 4 contacts the starting end of the flexible thin-film liquid guide rail 2, the sample liquid 4 will be sucked into the gap h under the capillary action. Since the liquid guide rail 2 is a flexible material of flexible thin film, under the pressure generated by the capillary effect (the capillary action will generate pressure on the water in the slit), the part with the sample liquid 4 will be slightly lifted, and the end of the flexible thin-film liquid guide rail 2 is pressed by the top pressure column 3, and the gap at the end will remain the smallest. According to the Young-Laplace Equation, the pressure difference ΔP inside and outside the liquid interface is inversely proportional to the gap h (see the following formula (1)), so the sample liquid 4 will continuously flow towards the end under the pulling of the capillary action (see Figure 6)。 And because the sample liquid 4 is attracted by the adhesion force on the lower surface of the flexible thin-film liquid guide rail 2 (the surface of the thin film is hydrophilic, and when it comes into contact with the liquid, it will generate intermolecular attraction to the water molecules in the liquid, and there is also attraction between the liquid molecules, so the liquid will gather under the thin film), when the sample liquid 4 flows, it will form a slender microchannel along the lower surface of the flexible thin-film liquid guide rail 2, and will not spread to both sides (see Figure 7 )。

[0063]

[0064] In the formula, γ is the surface tension coefficient, and θ is the contact angle between the liquid surface and the tube wall.

[0065] The stable microchannel height h must make the pressure difference between the sample liquid 4 and the atmosphere balance with the gravity and stress of the flexible thin-film liquid guide rail 2 (that is, water pressure - air pressure = gravity + bending stress, see Figure 8 )。 Assuming that the toughness of the flexible thin-film liquid guide rail 2 is proportional to the thickness, combining the Young-Laplace equation and Hooke's Law, the microchannel height can be deduced

[0066]

[0067] In the formula, l is the length of the flexible thin-film liquid guide rail, t is the thickness of the flexible thin-film liquid guide rail, σ is the stress coefficient of the flexible thin-film liquid guide rail, ρ is the density of the flexible thin-film liquid guide rail, and g is the acceleration due to gravity.

[0068] Taking the partial derivative of the above formula (2) can derive: And when l is long enough, It can be seen that the microchannel height h is inversely related to the thickness t and directly related to the length l. When l is long enough, the length no longer affects the microchannel height. For the given sample liquid 4 and the thin-film material properties of the flexible thin-film liquid guide rail 2, the microchannel height h is completely determined by the hydrodynamics theory, and the requirements for the processing technology are not so high.

[0069] Embodiment 2

[0070] In order to improve the working stability of the microfluidic chip in Embodiment 1, the technical solution of Embodiment 2 of the present invention is as follows:

[0071] As Figure 9-12As shown in the figure, the microfluidic chip with self-adjustable microchannel height of the present invention includes a substrate 1, a flexible thin film, and a housing 9. A flexible thin film is placed on the substrate 1. Two identical, spaced, and longitudinally extending slender holes are cut out in the middle of the flexible thin film by die-cutting. The width of the slender holes is not less than 1 mm. A liquid guide rail 2 is formed between the two slender holes. An open microchannel with self-adjustable height is formed between the liquid guide rail 2 and the substrate 1. Along the flowing direction of the sample liquid 4, the liquid guide rail 2 is successively provided with three inflection points B, C, and D, with A and D at the head and tail respectively. That is, the liquid guide rail 2 is successively divided into sections AB, BC, CD, and DE along the flowing direction of the sample liquid 4. The BC and DE sections are parallel to the surface of the substrate 1. The AB section forms a straight uphill, and the CD section forms an arc-shaped downhill section. The center point of the arc is far from the substrate 1, that is, the BC section is higher than the CD section. An inlet 8 is provided on the AB section. The BC section forms a marking area 5. The DE section forms a detection area. The other areas of the flexible thin film are laid flat on the substrate 1 in the same way as the DE section. The flexible thin film forms a waste liquid area 7 in the areas before and after the DE section and far from the marking area 5.

[0072] The housing 9 is snap-connected to the circumference of the substrate in the form of an end cap. The cross-section of the housing 9 is generally U-shaped. Along the guiding direction of the liquid on the flexible thin film liquid guide rail 2, a limiting bone 10 and a pressing column 3 protrude downward from the inner top surface of the housing 9. The limiting bone 10 is located directly above the BC section. A funnel-shaped sample adding hole 12 is provided on the housing 9 directly above the AB section. The bottom of the funnel-shaped sample adding hole 12 is flush with the bottom of the limiting bone 10 and is spaced along the guiding direction of the liquid on the flexible thin film liquid guide rail 2. That is, a groove is provided between the bottom of the funnel-shaped sample adding hole 12 and the limiting bone 10. The groove can prevent the gap between the limiting bone 10 and the flexible thin film liquid guide rail 2 from absorbing the sample liquid from the sample adding hole 12. The bottom of the limiting bone 10 is as close as possible to the BC section of the liquid guide rail. A perspective window 11 is provided on the housing 9 directly above the detection area 6. The pressing column 3 is located at the end of the inner top surface of the housing 9, and the lower part presses on the end of the flexible thin film liquid guide rail 2.

[0073] A labeled antibody 13 is placed under the marking area 5, and a number of capture antibodies 14 are placed under the detection area 6.

[0074] As a further optimization of this embodiment, the housing 9 is made of a plastic housing and processed by an injection molding process.

[0075] As a further optimization of this embodiment, the width of the AB section is large to facilitate the processing of an inlet 8 with a sufficient diameter. The width of the BC section is small at both ends, and both sides at both ends are processed into inwardly concave arcs.

[0076] When a liquid flows in a microchannel with a height less than 100 microns, the flow is laminar. Laminar flow is stable but not conducive to liquid mixing. Since the labeled antibody 13 needs to be fully mixed with the sample solution, the labeling area 5 cannot be a microchannel. The height of the microchannel in the labeling area 5 needs to be designed between 200 microns and 0.5 mm. The labeled antibody 13 is also an obstacle in the microchannel. When the sample solution flows in and encounters the obstacle, eddy currents will be generated, which helps the sample solution to mix with the dissolved labeled antibody.

[0077] As Figure 13-14 described, in order to improve the recovery of waste liquid, a new way of setting the waste liquid area is provided. First, an independent flexible film liquid guide rail 2 is made. An open and self-adjustable height microchannel is formed between the liquid guide rail 2 and the substrate 1. The liquid guide rail 2 is sequentially provided with three inflection points B, C, and D along the flowing direction of the sample liquid 4, with A and D at the head and tail respectively. That is, the liquid guide rail 2 is sequentially divided into AB, BC, CD, and DE segments along the flowing direction of the sample liquid 4. The BC and DE segments are parallel to the surface of the substrate 1. The AB segment forms a straight uphill, and the CD segment forms an arc downhill. The center point of the arc is far from the substrate 1, that is, the BC segment is higher than the CD segment. An inlet 8 is provided on the AB segment. The BC segment forms the labeling area 5. The front part of the DE segment forms a detection area, and the rear part forms a waste liquid area.

[0078] A cellulose membrane 15 is laid under the waste liquid area at the end of the flexible film liquid guide rail 2. The thickness of the membrane is less than the height h of the microchannel. The cellulose membrane 15 extends outside the flexible film liquid guide rail 2. A water-absorbing cotton 16 is pressed on the end of the flexible film liquid guide rail 2 and the exposed cellulose membrane 15. The density of the water-absorbing cotton is greater than that of the cellulose membrane. The water-absorbing cotton 16 is located under the top pressure column 3. When the thickness of the water-absorbing cotton 16 is large enough, it can also play the role of the top pressure column by itself, or the thickness of the water-absorbing cotton is directly set to the inner top surface of the housing 9. This method has two more processes, but the water absorption capacity of the waste liquid area is large, and the chip can be made narrower, which is suitable for chips that require a large sample addition volume.

[0079] Embodiment III

[0080] This Embodiment III is particularly suitable for the case where the sample liquid is whole blood. When the sample liquid is whole blood, it first needs to be anticoagulated and the red blood cells need to be filtered out. Therefore, it is necessary to adjust the sample addition and labeling methods, such as Figure 15As shown, the substrate 1 and the outer shell 9 (except for the bottom height of the limiting bone) in the third embodiment are arranged in the same way as in the second embodiment. The arrangement of the flexible thin-film liquid guide rail 2 is adjusted. The arrangements of the waste liquid area and the detection area are the same as those in the second embodiment (both of the two waste liquid area arrangement methods are acceptable). The difference from the second embodiment is only that the flexible thin-film liquid guide rail 2 is not bent but laid flat on the substrate 1 along the flowing direction of the sample liquid 4. An anticoagulant blood-filtering cotton 17 is arranged at the bottom of the funnel-shaped sample adding hole 12. A labeled antibody 13 is arranged below the anticoagulant blood-filtering cotton 17. The anticoagulant blood-filtering cotton 17 and the labeled antibody 13 are vertically collinear at the center, and the circumferential size of the anticoagulant blood-filtering cotton 17 is larger than that of the labeled antibody 13. The circumferential range of the anticoagulant blood-filtering cotton 17 is smaller than that of the limiting bone 10 and does not exceed the groove between the bottom of the funnel-shaped sample adding hole 12 and the limiting bone 10. The starting section of the flexible thin-film liquid guide rail 2 is located below the anticoagulant blood-filtering cotton 17 and at the side of the labeled antibody 13. The bottom of the funnel-shaped sample adding hole is tightly attached to the upper part of the blood-filtering cotton. The bottom of the limiting bone is lower than the bottom of the funnel-shaped sample adding hole and higher than the bottom of the anticoagulant blood-filtering cotton. There is a spacing of about 0.1 mm between the bottom of the limiting bone and the BC section of the liquid guide rail. Among them, the anticoagulant blood-filtering cotton is a fiber cotton with a lower density. An anticoagulant and a hemoglobin antibody are added to the fiber cotton. After the sample adding to the blood-filtering cotton is supersaturated, the plasma will precipitate from the lower side. After the plasma is mixed with the labeled antibody, it is sucked in by the capillary force of the flexible thin-film liquid guide rail 2.

[0081] The above technical solutions only reflect the preferred technical solutions of the technical solutions of the present invention. Some possible changes made by those skilled in the art to some parts thereof all reflect the principles of the present invention and fall within the protection scope of the present invention.

Claims

1. A microfluidic chip with self-adjustable microchannel height, characterized in that It includes a substrate, a liquid guiding rail, and a pressing column. A microchannel with adjustable height is placed on the substrate. The microchannel is formed by placing a slender liquid guiding rail on the upper surface of the substrate. The liquid guiding rail is a flexible film liquid guiding rail, and both sides in the width direction of the liquid guiding rail are open. One end of the liquid guiding rail is covered by a pressing column at the upper part as the end, and the other end is the starting end for adding sample liquid. A marking area is set near the starting end, and a detection area is set in the middle between the liquid guiding rail and the substrate.

2. The microfluidic chip according to claim 1, wherein The liquid guiding rail has a thickness of 0.02 - 0.1 mm, a width of 2 - 5 mm, and a length greater than 5 times the width.

3. The microfluidic chip according to claim 1 or 2, characterized in that, Two spaced and slender holes extending along the length direction are cut out in the middle of the flexible film, and the liquid guiding rail is formed between the two slender holes. The slender holes do not penetrate the entire length of the flexible film.

4. The microfluidic chip according to claim 3, characterized in that, The liquid guiding rail is sequentially divided into sections AB, BC, CD, and DE along the flowing direction of the sample liquid. Sections BC and DE are parallel to the surface of the substrate. Section AB forms a straight uphill, and section CD forms an arc downhill. An inlet is provided on section AB. Section BC forms a marking area. Section DE forms a detection area. Other areas of the flexible film are tiled on the substrate in the same way as section DE. The areas of the flexible film before and after section DE and away from the marking area form waste liquid areas.

5. The microfluidic chip according to claim 1 or 2, characterized in that, The liquid guiding rail is an independent long strip. The liquid guiding rail is sequentially divided into sections AB, BC, CD, and DE along the flowing direction of the sample liquid. Sections BC and DE are parallel to the surface of the substrate. Section AB forms a straight uphill, and section CD forms an arc downhill. An inlet is provided on section AB. Section BC forms a marking area. The front part of section DE forms a detection area, and the rear part forms a waste liquid area.

6. The microfluidic chip according to claim 5, wherein A cellulose membrane is laid under the waste liquid area at the end of the liquid guiding rail. The thickness of the membrane is less than the height of the microchannel. The cellulose membrane extends outside the liquid guiding rail. An absorbent cotton is pressed on the end of the liquid guiding rail and the exposed cellulose membrane. The density of the absorbent cotton is greater than that of the cellulose membrane.

7. The microfluidic chip according to any one of claims 1-2, 4, and 6, characterized in that It further includes a housing, which is clamped to the circumference of the substrate in the form of an end cover. The cross-section of the housing is U-shaped.

8. The microfluidic chip according to claim 7, characterized in that, A limiting bone and a pressing column protrude downward from the top surface inside the housing. The limiting bone is located directly above section BC. The pressing column is located at the end of the top surface inside the housing, and the lower part directly presses on the end of the liquid guiding rail or the absorbent cotton.

9. The microfluidic chip according to claim 8, wherein A funnel-shaped sample adding hole is provided on the housing directly above section AB, and a perspective window is provided on the housing directly above the detection area.

10. The microfluidic chip according to claim 9, wherein The bottom of the funnel-shaped sample adding hole is flush with the bottom of the limiting bone and is arranged at intervals along the guiding direction of the liquid guiding rail. The bottom of the limiting bone is close to section BC.

11. The microfluidic chip according to claim 3, characterized in that, The liquid guiding rail is laid flat. An anticoagulant blood filtering cotton is provided at the starting end of the liquid guiding rail. A labeled antibody is provided under the anticoagulant blood filtering cotton. The starting section of the liquid guiding rail is located under the anticoagulant blood filtering cotton and on the side of the labeled antibody. The liquid guiding rail is also provided with a detection area and a waste liquid area along the flowing direction of the sample liquid. Other areas of the flexible film are also laid flat on the substrate to form waste liquid areas in the same way.

12. The microfluidic chip according to claim 1 or 2, characterized in that, The liquid guiding rail is an independent long strip. The liquid guiding rail is laid flat. An anticoagulant blood filtering cotton is provided at the starting end of the liquid guiding rail. A labeled antibody is provided under the anticoagulant blood filtering cotton. The starting section of the liquid guiding rail is located under the anticoagulant blood filtering cotton and on the side of the labeled antibody. The liquid guiding rail is also provided with a detection area and a waste liquid area along the flowing direction of the sample liquid.

13. The microfluidic chip according to claim 12, characterized in that, A cellulose membrane is laid under the waste liquid area at the end of the liquid guiding rail. The thickness of the membrane is less than the height of the microchannel. The cellulose membrane extends outside the liquid guiding rail. An absorbent cotton is pressed on the end of the liquid guiding rail and the exposed cellulose membrane. The density of the absorbent cotton is greater than that of the cellulose membrane.

14. The microfluidic chip according to claim 11 or 13, characterized in that, The anticoagulant blood filtering cotton is a fiber cotton with a relatively low density, and an anticoagulant and a hemoglobin antibody are added to the fiber cotton.

15. The microfluidic chip according to claim 11 or 13, characterized in that, It further includes a housing, which is clamped to the circumference of the substrate in the form of an end cover, and the cross section of the housing is U-shaped.

16. The microfluidic chip according to claim 15, wherein, A limiting bone and a pressing column protrude downward from the inner top surface of the housing. The pressing column is located at the end of the inner top surface of the housing, and the lower part directly presses on the end of the liquid guiding rail or the absorbent cotton.

17. The microfluidic chip according to claim 16, wherein, A funnel-shaped sampling hole is provided on the housing directly above the anticoagulant blood filtering cotton, and a perspective window is provided on the housing directly above the detection area.

18. The microfluidic chip according to claim 17, wherein, The bottom of the funnel-shaped sampling hole is in close contact with the upper part of the blood filtering cotton. The bottom of the limiting bone is lower than the bottom of the funnel-shaped sampling hole and higher than the bottom of the anticoagulant blood filtering cotton. The funnel-shaped sampling hole and the limiting bone are arranged at intervals along the liquid guiding direction of the liquid guiding rail.

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