Detection device for detecting analyte in fluid sample

Abstract

The invention provides a detection device, which comprises a test element and a shell for accommodating the test element, the shell is formed by folding a card made of a paper material, the test element is positioned in the shell, and the detection or test of an analyzed substance in a sample is carried out by enabling the shell to be in different change states.

Description

Technical Field

[0001] The present invention relates to a device for collecting liquid samples and a detection device, in particular to a device for detecting substances to be analyzed in liquid samples in the field of rapid diagnosis, such as urine and saliva collection. Background Art

[0002] The following background technology introduction is merely an introduction to some background common sense and does not constitute any limitation to the present invention.

[0003] At present, detection devices for detecting whether a sample contains the substance to be analyzed are widely used in hospitals or homes. These detection devices for rapid diagnosis include one or more detection reagent strips, such as early pregnancy tests, drug abuse tests, etc. This rapid diagnosis detection device is very convenient and can obtain test results on the detection reagent strip in one minute, or at most ten minutes. Drug testing is widely used and is often used in drug control departments, public security bureaus, drug rehabilitation centers, physical examination centers, national conscription physical examination offices and other institutions. Drug tests are of various types and frequent. Some require sample collection, and then require professional testing agencies or testing laboratories to conduct tests. Some require on-site, such as roadside, timely completion of testing. For example, people who drive after taking drugs (referred to as "drug driving") need to be tested on-site and then obtain the test results in a timely manner.

[0004] For example, the detection of saliva samples is gradually accepted and welcomed by detection institutions or detection personnel based on the convenience of collection. Various sample collection and testing devices for clinical or home use are available and described in some documents. For example, U.S. Patent No. 5,376,337 discloses a saliva sampling device, in which a filter paper is used to collect saliva from the mouth of the subject and transfer the saliva to the indicator reagent. U.S. Patent Nos. 5,576,009 and 5,352,410 each disclose a syringe-type fluid sampling device.

[0005] For example, in the patent application in the United States, application number: 14 / 893,461, application publication number: US2016 / 0121322A1, a sample detection device is disclosed. The patent only discloses some basic detection schemes and principles, but the actual realization of a specific product is relatively difficult. For example, how the cover body combination and the detection combination are coordinated, how the washing head for absorbing saliva is compressed, how it moves, and how it is effectively mixed with the liquid, the actual effect is not ideal.

[0006] In vitro tests for early pregnancy testing have been relatively mature, but there are still many drawbacks, such as the long testing time. In addition, such tests are usually performed by the tester himself, and there are still many defects, such as easy mistakes in operation, resulting in inaccurate test results. This is why it is hoped that existing OCT products can be improved to shorten the time it takes for the test results to appear, and at the same time, the products can adapt to the operating habits of different operators.

[0007] In view of the technical problems of some of the above-mentioned traditional products, it is necessary to improve them and provide other ways to solve the shortcomings of existing traditional technologies. Summary of the invention

[0008] In view of the above situation, in order to overcome the defects of the prior art, the purpose of the present invention is to provide a device for detecting the analyzed substance in a fluid sample, which is particularly a device for women to detect HCG and LH, and can quickly obtain test results, reduce the inaccuracy of results due to large amounts of liquid, and adapt to operations of different operators.

[0009] This is because, when women are testing for early pregnancy or ovulation, they directly apply urine to the test device, especially to the guide element, so that the guide element guides the urine to the test element for testing. Usually, women urinate directly on the guide element. At this time, they hold the test element with their hands, and then place the guide element under the urethra to let the urine directly fall on the guide element. Due to the personal habits of the operator, each person holds the angle of the hand differently. The amount of urine collected on the guide element ranges widely, from 1 ml to 200 ml, or more, such as 500 ml. In addition, urine can also be poured on places other than the guide element, such as the surface of the device. The liquid required on the test element is generally not very large, far less than the liquid collected on the guide element. The above factors will affect the accuracy of the final result. For example, the window on the surface of the device is where the test results can be read by the naked eye, and the test results are displayed through the test area.

[0010] In order to solve this problem, the present invention provides a detection device, which is particularly suitable for detecting HCG, LH and other analytes in urine, allowing the operator to directly urinate into the device to detect the analytes in the urine.

[0011] On the one hand, the present invention provides a device for detecting an analyte in a fluid sample, the device comprising: a label pad containing a marker substance and a lateral flow test element of a nitrocellulose membrane containing a detection area, one end of the label pad is superimposed on the nitrocellulose membrane; wherein a layer of non-absorbent transparent film is covered on the detection area. The film can prevent the nitrocellulose membrane from contacting the liquid sample in advance and getting wet in advance. Generally, the nitrocellulose membrane hopes that the liquid from the sample application area passes through the label pad and then flows to the nitrocellulose membrane to wet the test area thereon, and does not want the liquid to directly contact the test area in advance and wet the test area.

[0012] In some embodiments, a non-absorbent transparent film is covered on the entire nitrocellulose. In some embodiments, the first end of the non-absorbent transparent film is directly or indirectly bonded to the first end of the nitrocellulose film, and the second end of the non-absorbent transparent film is free and located near the second end of the marker pad superimposed on the nitrocellulose film. In some embodiments, the second end of the non-absorbent transparent film is not bonded to the second end of the nitrocellulose film. In some embodiments, the test element also includes an absorbent pad located on the first end of the nitrocellulose film, and the first end of the non-absorbent transparent film is bonded to the filter paper. In some embodiments, the bonding is bonded to the filter paper by glue, and in some embodiments, it is bonded to the filter paper by a self-adhesive adhesive covering the filter paper. Here, the nitrocellulose film has a first end and a second end, the first end is superimposed with the absorbent pad, and the second end is superimposed with the marker pad, and the second end of the non-absorbent film is free and not bonded to the second end. Here, "free" means that the non-absorbent transparent film is not fixed on the second end of the nitrocellulose film or the marking pad. The advantage is that the thickness of the filter paper is generally higher than that of the NC, and one end of the non-absorbent film is superimposed on the filter paper. The non-absorbent transparent film is covered on the NC film in the form of a slope. When the upper and lower cards are assembled, the pressing ring under the window gives pressure to the transparent film. When the upper and lower cards are assembled, the film is generally given pressure, which allows the film to have free elasticity and can be conveniently covered on the test area. If both ends are fixed, when the upper and lower cards are assembled, when the non-absorbent film is under pressure, the non-absorbent film will generally shrink. If it is bonded to the marking point, it may shrink and damage the marking pad, which affects the solubility and fluidity of the marking material on the marking pad in the subsequent test liquid. In addition, the other end is in a free state, which allows the non-absorbent film to better fit the surface of the NC film. The advantage of being more in line with the surface of the NC membrane is that the sample colloidal gold solution is evenly chromatographed on the NC membrane and the background is clear.

[0013] In some embodiments, the device further comprises an upper shell and a shell connected to a lower shell; the test element is located between the upper shell and the lower shell, the shell has an opening at one end, and the opening includes a portion of a flow guide element, wherein one end of the flow guide element contacts the marking area, so that the liquid sample from the flow guide element can flow directly to the marking area. In some embodiments, the upper shell has a window area where the test result on the test area can be read by naked eyes, and the non-water-absorbent transparent film is located between the test area and the window area. Alternatively, the non-water-absorbent transparent film is located between the nitrocellulose film and the window area, or the window area is covered with a layer of non-water-absorbent transparent film, or one side of the non-water-absorbent transparent film covers the nitrocellulose film and the other side covers the window. In this way, even if the liquid sample is received from the window in advance or the liquid sample enters from the window and enters the test area in advance, the test area will not be wetted in advance, thereby avoiding invalid test results. This is because, when conducting the test, the operator urinates on the water absorption backflow flow element of the test device, and may also urinate on the window. If the window is not covered with a lid, the nitrocellulose membrane is directly exposed and can contact the liquid sample. The sample flowing into the flow guide element is later than the liquid introduced from the window. In this way, the nitrocellulose membrane is wetted in advance, and the dry film loses its capillary action, which ultimately affects the test results. If the test area on the film is wetted in advance, it will directly lead to test failure. In some methods, one end of the non-absorbent film is bonded to the filter paper, while the other end is not bonded to or in contact with the film, so as not to affect the fluidity of the liquid from the backflow element. If both ends of the non-absorbent film are bonded to the film, or one end is bonded to the marking pad superimposed on the film, the liquid flow of the marking pad will be slowed down. At the same time, it is hoped that the non-absorbent film is directly covered on the nitrocellulose film to protect the cellulose film from damage. Therefore, the other end is in a free state, so that during assembly, the edge of the window can be pressed on the non-diluted aqueous film, and the non-absorbent transparent film is only covered on the nitrocellulose film.

[0014] In some embodiments, the other end of the flow guiding element is used to receive the urine sample. In some embodiments, the other end of the flow guiding element is directly placed near the female urethra to directly receive the urine sample from the urethra.

[0015] In some embodiments, the test element is in the lower housing, and the lower housing has a groove for accommodating the test element. In some embodiments, the upper housing has a cavity for retaining a fluid sample, and the cavity can accommodate a liquid sample on the surface of the guide element. Here, the cavity for retaining the liquid sample has an opening, and the opening is covered by the guide element, so that the liquid on the surface of the guide element will flow into the cavity. Therefore, in some embodiments, the cavity is one or more grooves, and these grooves have openings, and these openings cover the surface of the guide element. In some embodiments, these cavities for retaining liquid samples are cavities of non-capillary structure, which are retained in the cavity without flowing by relying on the surface tension between the liquid and the cavity. Therefore, these cavities can be treated with hydrophilic materials. Of course, if these cavities have capillary forces, the liquid samples are retained by these cavities and cannot flow, thereby reducing the content or volume of the liquid on the surface of the guide element. In some embodiments, the cavity or groove is formed or separated by a pressing strip, and the surface of the pressing strip covers the surface of the guide element, so that excess liquid will flow into the cavity. One function of the pressing strip is to block the flow rate of the liquid on the surface of the guide element, and to allow the liquid to enter the cavity. At this time, the cavity can be a non-capillary function. Generally, the guide element has an upper surface for receiving the liquid sample, and part of the guide element is located in the shell, and the other part of the guide element extends outside to receive the liquid.

[0016] In some embodiments, the device further comprises a blocking element for blocking the liquid at the end of the liquid outlet of the flow-guiding element from flowing to the marking area, and the blocking element is arranged in the housing, wherein the end of the liquid outlet of the flow-guiding element contacts the blocking element. The blocking element can be a structure of any shape, such as a sheet structure, which allows the liquid outlet of the flow-guiding element to contact, so that the liquid flowing into the flow-guiding element is blocked by the blocking element, slowing down the speed of the liquid flowing out of the end, and allowing the liquid to flow out of the side of the flow-guiding element, thus slowing down the flow rate of the liquid and reducing the amount of the liquid. In some embodiments, the blocking element is arranged at the end of the fluid retention cavity or the end of the retention cavity area, so as to prevent the liquid on the flow-guiding element from directly flowing into the marking pad on the test element, and allow the liquid to flow into the retention cavity. In some embodiments, the blocking element is arranged on the upper housing, and a notch is provided in the lower housing, and a blank area of ​​a portion of the marking pad is provided on the notch, and the end of the flow-guiding element is located on the blank area and directly contacts the blank area. In some embodiments, when the upper shell and the lower shell are assembled together, the blocking element is inserted into the recess and contacts the end of the guide element.

[0017] In some embodiments, the test element further includes a sample application pad partially overlapping a blank area on the marking pad, and the flow guide element is overlapped on the sample application pad, wherein the flow rate of the liquid in the flow guide element is greater than the flow rate of the liquid in the sample application pad.

[0018] In some embodiments, the test element further includes a sample application pad partially superimposed on the blank area on the marking pad, and the flow guide element is superimposed on the application pad, wherein the liquid from the flow guide element partially flows into the sample application pad and partially flows directly into the sample marking pad, wherein the time when the liquid from the flow guide element directly flows into the marking pad is earlier than the time when the liquid on the sample application pad flows into the marking pad. In this way, the liquid from the test strip has two flow paths, one is the liquid sample directly from the flow guide element, and the other is the liquid sample from the sample application pad. We hope that the liquid sample from the flow guide element contacts the marking pad first, and the liquid sample from the sample application pad is used as the subsequent liquid sample, so that the test result can appear in a very short time, and at the same time reduce the occurrence of false negatives. Of course, if there is no sample application pad, and only the liquid from the flow guide element is allowed to flow directly into the marking pad, the structural design of the present invention can also obtain the test result as soon as possible, and reduce the number of false negative or invalid test results.

[0019] In some embodiments, the marking pad includes a first marking pad and a second marking pad, wherein the first marking pad is located upstream of the second marking pad, and the liquid outlet end of the flow-guiding element is superimposed on the first marking pad. The present invention uses two marking pads to detect the same analyte, which can improve the sensitivity of detection. Compared with the traditional method of using one marking pad, the sensitivity of the present invention is improved and the detection time is shortened. In some embodiments, the first marking pad includes a blank area without a surface substance and an area containing a marker, the second marking pad includes a blank area without a marker and an area containing a marker, and the end of the flow-guiding element is superimposed on the blank area of ​​the first marking pad. In some embodiments, the nitrocellulose membrane includes a test result area, on which a second antibody that specifically binds to the analyte is fixed, and the area containing the marker includes a first antibody that specifically binds to the analyte coupled to latex or gold particles.

[0020] In some embodiments, the length of the marking pad composed of the first marking pad and the second marking pad is 15 mm, the distance between the liquid outlet end of the guide element and the marking area of ​​the first marking pad is 2 mm, and the distance between the end of the second marking pad and the test area is 7 mm. In this way, the distance that the entire liquid flows on the test strip is 24 mm, and the test result can be obtained within a very short distance, and the test result is basically controlled within 2 minutes. In some embodiments, the length of the guide element is 40 mm, the length of the guide element located in the shell is 13 mm, and the thickness of the guide element is 3 mm.

[0021] In some embodiments, the second antibody specifically captures HCG antigen, the first antibody specifically binds to HCG antigen, and the sample is a urine sample. In some embodiments, the marker on the first label pad is a first antibody that binds to HCG in urine and is coupled to gold particles, and the marker on the second label pad is a first antibody that specifically binds to HCG in urine and is coupled to latex particles. These markers are all in a dry state and can flow to the test result area with the liquid and bind to the antibody fixed on the test result area.

[0022] In some embodiments, the marking pad includes a first marking pad and a second marking pad, wherein the first marking pad is located upstream of the second marking pad, and the liquid outlet end of the flow-guiding element is superimposed on the first marking pad. In some embodiments, the first marking pad includes a blank area without a marking substance and an area containing a marking substance, and the second marking pad includes a blank area without a marking substance and an area containing a marking substance, and the end of the flow-guiding element is superimposed on the blank area of ​​the first marking pad. In some embodiments, the length of the marking pad composed of the first marking pad and the second marking pad is 15 mm, the distance between the liquid outlet end of the flow-guiding element and the marking area of ​​the first marking pad is 2 mm, the distance between the second marking pad and the test area is 7 mm, the length of the sample application pad is 15 mm, the length of the flow-guiding element is 40 mm, of which the length located in the shell is 13 mm.

[0023] Beneficial Effects

[0024] By adopting the above structure, the influence of a large amount of liquid samples on the accuracy of the test results can be reduced, and the test results can be obtained quickly, which is particularly suitable for women at home to self-test the concentration or content of urine HCG or LH. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a schematic diagram of the positional relationship between the test element and the flow guide element in the detection device housing in a specific embodiment of the present invention (including the sample application pad 201).

[0026] Figure 2AIt is a schematic diagram of the structure of the flow guiding element and the test element of the present invention, wherein the blocking element 900 is located at the end of the flow guiding element, and the end of the flow guiding element is directly overlapped with the blank area of ​​the first marking pad 202.

[0027] Figure 2B It is a schematic diagram of the assembly structure of each pad of the present invention.

[0028] Figure 3 It is a schematic diagram of the three-dimensional structure of a detection device in a specific embodiment of the present invention.

[0029] Figure 4 It is a schematic structural diagram of an upper shell body containing a test element on a lower shell body in a specific embodiment of the present invention.

[0030] Figure 5 It is a schematic diagram of the longitudinal section structure of the detection device in the assembled state in a specific embodiment of the present invention.

[0031] Figure 6 It is a schematic diagram of the longitudinal section structure of the assembled state of the detection device in a specific embodiment of the present invention.

[0032] Figure 7 It is a schematic structural diagram of an upper shell and a lower shell in a specific implementation manner of the present invention.

[0033] Figure 8 It is a schematic diagram of the enlarged structure of the liquid retention cavity or area of ​​the upper shell in a specific embodiment of the present invention.

[0034] Fig. 9 It is a schematic diagram of the operating state of the detection device receiving the urine sample and the operating state of the guide element receiving the urine sample in a specific embodiment of the present invention.

[0035] Fig.10 This is a schematic diagram of the operating state of the detection device receiving a urine sample in another specific embodiment of the present invention, and a schematic diagram of the operating state of the guide element receiving a urine sample.

[0036] Fig.11 It is a schematic diagram of the longitudinal section structure of the assembled detection device in a specific embodiment of the present invention.

[0037] Fig.12 This is a schematic diagram of an exploded three-dimensional structure of a detection device in another specific embodiment of the present invention.

[0038] Fig.13 In another specific embodiment of the present invention, the lower shell of the detection device contains a test element and a flow guide element, and is a schematic diagram of the exploded three-dimensional structure of the upper shell.

[0039] Fig.14It is a schematic structural diagram of an upper shell and a lower shell in another specific embodiment of the present invention.

[0040] Fig.15 It is a structural schematic diagram of a cavity for retaining liquid in an upper shell in a specific embodiment of the present invention.

[0041] Fig.16 It is a top view and a schematic diagram of the cross-sectional structure of the assembled detection device in a specific embodiment of the present invention.

[0042] Fig.17 It is a top view of the structure of the test element in a specific implementation of the present invention.

[0043] Fig.18 It is a schematic diagram of a three-dimensional structure in a specific implementation manner of the present invention.

[0044] Fig.19 It is a schematic diagram of a three-dimensional structure in which the test strip is arranged in the upper and lower shells, wherein the test strip is located in the groove of the lower card.

[0045] Fig. 20 It is a schematic structural diagram of a specific embodiment of the present invention, in which a test area is located on a nitrocellulose film and a non-hydroscopic transparent film covers the test area on the nitrocellulose film. Detailed description

[0046] The structures involved in the present invention or the technical terms used are further explained below. If not specifically specified, they are understood and interpreted according to the general terms commonly used in the art.

[0047] Detection

[0048] Detection means to test or examine a substance or material for the presence or absence of a substance or material, such as, but not limited to, a chemical substance, an organic compound, an inorganic compound, a metabolite, a drug or a drug metabolite, an organic tissue or a metabolite of an organic tissue, a nucleic acid, a protein, or a polymer. In addition, detection means to test the amount of a substance or material. Furthermore, assay also means immunoassay, chemical assay, enzyme assay, etc.

[0049] sample

[0050] The sample of the detection device of the present invention includes biological fluid (such as case fluid or clinical sample). Liquid sample or fluid sample can be derived from solid or semi-solid sample, including excrement, biological tissue and food sample. Solid or semi-solid sample can be converted into liquid sample by any appropriate method, such as mixing, crushing, macerating, incubating, dissolving or digesting solid sample by enzymolysis in a suitable solution (such as water, phosphate solution or other buffer solution). "Biological sample" includes samples derived from animals, plants and food, such as urine, saliva, blood and its components, cerebrospinal fluid, vaginal secretions, sperm, feces, sweat, secretions, tissues, organs, tumors, tissue and organ cultures, cell cultures and media derived from humans or animals. Preferably, the biological sample is urine, and preferably, the biological sample is saliva. Food samples include food processed substances, final products, meat, cheese, wine, milk and drinking water. Plant samples include any plant, plant tissue, plant cell culture and media. An "environmental sample" is derived from the environment (eg, a liquid sample from a lake or other body of water, a sewage sample, a soil sample, groundwater, seawater, and a wastewater sample). An environmental sample may also include sewage or other wastewater.

[0051] By using a suitable detection device of the present invention, any analyte can be detected. The present invention is preferably used to detect drug molecules in saliva and urine. Of course, the sample detected by the detection device of the present invention can be any form of sample above, whether it is solid or liquid at the beginning, as long as these liquids or liquid samples can be absorbed by the sample application area of ​​the test element. The sample application area here is generally prepared by water-absorbing materials, and through the capillary or other characteristics of the absorbing element material, it can absorb liquid samples or fluid samples and allow the fluid sample sample application area to flow. The material of the fluid sample sample application area can be any material that can absorb liquid, such as sponge, filter paper, polyester fiber, gel, non-woven fabric, cotton, polyester film thin, yarn, etc. Of course, the fluid sample sample application area is not necessarily prepared by a material with water-absorbing properties, and can be prepared by a non-water-absorbing material, but there are holes, threads, and caves on the absorbing element, and samples can be collected on these structures. These samples are generally solid or semi-solid samples, and these samples are filled between the threads, holes, or holes to collect samples. Of course, optionally, the fluid sample application area can be composed of some non-absorbent fibers and hairs, and these materials are used to scrape a solid, semi-solid or liquid sample, so that these samples are retained on the fluid sample application area. When detection is required, a buffer solution is applied to the sample application area to dissolve the sample, so that the dissolved sample flows on the test element or detection element.

[0052] In some embodiments, the sample application area of ​​the test element of the present invention does not need to manually apply the fluid sample, but contacts the guide element, allowing the liquid sample guided by the guide element to flow into the sample application area, and then flows into the marking area, and then is assayed or tested. The following is further detailed description in conjunction with specific implementation examples. In some embodiments, the liquid sample guided by the guide element flows directly to the marking area without passing through the sample application area. In some embodiments, part of the sample that flows into the marking area comes from the sample application area, and part of the sample comes directly from the guide area. In some embodiments, the sample in the sample application area comes from the guide element. In some embodiments, the guide element is used to receive a fluid sample. For example, when a woman is tested, she urinates directly on the guide element, and then observes the test results.

[0053] Downstream and Upstream

[0054] Downstream or upstream is divided according to the direction of liquid flow, generally liquid or fluid flows from upstream to downstream area. The downstream area receives liquid from the upstream area, and the liquid can also flow along the upstream area to the downstream area. Here it is generally divided according to the direction of liquid flow. For example, on some materials that use capillary force to promote the flow of liquid, the liquid can overcome gravity and flow in the opposite direction of gravity. At this time, the upstream and downstream are still divided according to the flow direction of the liquid. For example, in the detection device of the present invention, after the guide element receives the fluid sample, such as the urine sample directly from the tester, the fluid can flow from the guide element to the marking area, such as the first gold particle marking area, and then flow to the second latex marking area, and then flow to the detection area, such as the test result area and the test result control area. At this time, the liquid flows into the first marking area in the guide element, then flows to the second marking area, and then flows to the test result area. The flow from the guide area to the test area is from upstream to downstream. During the circulation process, it passes through the first marking area and the second marking area in sequence. There is a detection area and a test result control area on the test area. The test area can be a polyester fiber film, and the guide element can be glass fiber, polyester sheet, or polyester film. At this time, the guide element is located upstream of the test element marking area. The specific structure of the test element is as follows: Figure 1 -The structure shown in 20 shown in 2.

[0055] Gas connection or liquid connection

[0056] Gas connectivity or liquid connectivity means that liquid or gas can flow from one place to another, and some physical structures may be used to guide the flow process. The so-called passing through physical structures generally refers to the liquid passing through the surface of these physical structures, or the internal space of these structures and passively or actively flowing to another place. Passive flow is generally caused by external forces, such as flow under capillary action, air pressure, etc. The flow here can also be the liquid or gas due to its own action (gravity or pressure), or it can be passive flow. The fluid under the action of air pressure can be a flow in the same direction, or it can be a flow in the opposite direction, or it can be caused by the action of air pressure to cause the fluid to flow from one position to another. The connectivity here does not mean that liquid or gas must exist. It only indicates the connection relationship or state between two objects in some cases. If there is liquid, it can flow from one object to another. This refers to the state of connection between two objects. On the contrary, if there is no liquid connection or gas connection between the two objects, if there is liquid in or on one object, the liquid cannot flow into or on another object. Such a state is non-connected, non-liquid or gas connected.

[0057] Test components

[0058] Here, the so-called "test element" refers to an element that can detect whether a fluid sample or a fluid sample (liquid sample or liquid sample) contains an analyte of interest. Such detection can be based on any technical principle, such as immunology, chemistry, electricity, optics, molecular science, nucleic acid, physics, etc. The test element can be a lateral flow test strip, which can detect a variety of analytes. Of course, other suitable test elements can also be used in the present invention.

[0059] Various test elements can be combined and applied to the present invention. One form is a test strip. The test strip used to analyze the analyte in the sample (such as drugs or metabolites indicating physical conditions) can be in various forms, such as immunoassays or chemical analysis. The test strip can adopt a non-competitive or competitive analysis mode. The test strip generally comprises a water-absorbing material with a sample application area, a reagent area and a test area. Add a fluid or liquid sample to the sample application area and flow to the reagent area through capillary action. In the reagent area, if the analyte is present, the sample combines with the reagent. Then the sample continues to flow to the detection area. Other reagents, such as molecules that specifically bind to the analyte, are fixed in the detection area. These reagents react with the analyte in the sample (if present) and bind the analyte to the area, or bind to a reagent in the reagent area. The marker used to display the detection signal is present in the reagent area or a separate labeling area.

[0060] The typical non-competitive assay format is that if the sample contains the analyte, a signal is generated, and if it does not contain the analyte, no signal is generated. In a competitive assay, if the analyte is not present in the sample, a signal is generated, and if the analyte is present, no signal is generated.

[0061] The test element can be a test paper, which can be made of absorbent or non-absorbent materials. The test paper can include multiple materials for liquid sample delivery. One material of the test paper can be covered on another material, such as filter paper covered on a nitrocellulose membrane. One area of ​​the test paper can be made of one or more materials, while another area can be made of one or more different materials. The test paper can be adhered to a certain support or hard surface to increase the strength of holding the test paper.

[0062] The analyte is detected through a signal generating system, such as by using one or more enzymes that react specifically with the analyte, and by using the method of fixing the specific binding substance on the test paper as described above, to fix the composition of one or more signal generating systems on the analyte detection area of ​​the test paper. The substance that generates the signal can be in the sample addition area, the reagent area, or the detection area, or on the entire test paper, and the substance can be filled with one or more materials of the test paper. A solution containing the signal substance is added to the surface of the test paper or one or more materials of the test paper are immersed in a solution containing the signal substance. The test paper to which the solution containing the signal substance is added is dried.

[0063] The various areas of the test paper can be arranged in the following manner: sample application area 201, reagent areas 202, 204, detection area 207, the detection area includes a test result area 206 and a test result control area 210. The control area is located after the detection area. All areas can be arranged on a test paper using only one material. Different areas can also use different materials. Each area can be directly in contact with the liquid sample, or different areas can be arranged according to the direction of flow of the liquid sample, and the end of each area is connected to the front end of another area and overlapped. The material used can be a material with good water absorption such as filter paper, glass fiber or nitrocellulose membrane. The test paper can also be in other forms.

[0064] The commonly used reagent strip is a nitrocellulose membrane reagent strip, that is, the detection area includes a nitrocellulose membrane (NC), and specific binding molecules are fixed on the nitrocellulose membrane to display the detection results; it can also be a cellulose acetate membrane or a nylon membrane, etc. For example, the following patents describe reagent strips or devices containing reagent strips: US 4857453; US 5073484; US 5119831; US ​​5185127; US 5275785; US 5416000; US 5504013; US 5602040; US 5622871; US5654162; US 5656503; US 5686315; US 5766961; US ​​5770460; US 5916815; US 5976895; US6248598; US 6140136; US 6187269; US 6187598; US 6228660; US 6235241; US The test strips and similar devices with test strips disclosed in the above patent documents can be applied to the test element or detection device of the present invention to detect the analyte, such as the analyte in the sample.

[0065] The test strip used in the present invention may be a so-called lateral flow test strip. The specific structure and detection principle of these test strips are well known to those skilled in the art. Figure 1 - Figure 2), including a sample collection area or a sample application area 201, a marking area (202, 204), and a detection area 207. The sample collection area includes a sample receiving pad, the marking area includes a marking pad, and the water absorption area may include a water absorption pad, wherein the detection area includes necessary chemical substances that can detect whether the analyzed substance is contained, such as immune reagents or enzyme chemical reagents. The sample application area or application pad 201 of the present invention does not directly receive the sample, but contacts the guide element to receive the liquid sample guided by the guide element. Therefore, the sample application area of ​​the present invention is covered by the guide element (such as Figure 1 ); Of course, if Figure 2AAs shown, the test strip lacks a sample application area. The commonly used test strip is a nitrocellulose membrane test strip, that is, the test area 207 includes a nitrocellulose membrane, and a specific binding molecule is fixed on the nitrocellulose membrane to display the result area 206 (T-line) of the test; it can also be a cellulose acetate membrane or a nylon membrane, etc.; of course, the downstream of the test area can also include a test result control area 210 (C-line), usually, the control area and the test area appear in the form of a horizontal line, which is a test line or a control line. Such a test strip is a traditional test strip, and of course, it can also be other types of test strips that utilize capillary action to detect. In addition, the general test strip carries dry chemical reagent components, such as fixed antibodies or other reagents. When encountering liquid, the liquid flows along the test strip with capillary action, and as it flows, the dry reagent components are dissolved in the liquid, so that the dry reagent in the next area is processed to react, thereby performing necessary detection. The flow of liquid is mainly carried out by capillary action. Here, they can all be applied to the detection device of the present invention, or be arranged in the detection chamber to contact the liquid sample, or be used to detect the presence or amount of the analyzed substance in the liquid sample entering the detection chamber.

[0066] In some ways, such as Figure 17-19 As shown, the present invention provides a test element, the test element 901 includes a sample application area 902, a first marking area 903, a second marking area 904, and a test area 905, the test area has a detection area 909, and the detection area downstream has a test result control area 1000. The test area 905 can be set on a nitrocellulose film, and the film has a detection area 909 and a test result control area 1000. In the two areas, the detection area is fixed with antibodies, which can bind to the analyzed substance, generally in the form of a line, usually called a T line, and the test result control area 1000 is an area used to verify whether the test result is valid. If it is usually presented in a line, it is called a C line. The post-test area, especially including the detection area 909 and the test result control area 1000, corresponds to the window area of ​​the upper card, and the detection area 909 and the test result control area 1000 are exposed through the window area 401, so that the test result on the test area can be directly observed by the naked eye. The exposure is directly exposed to the air. Generally, according to the normal working mode, the urine is directly received by the backflow element 10, for example, it is directly placed near the female urethra. When the female urinates, the urine is directly poured onto the flow guide element 10. The urine received by the flow guide element flows in the following order: first, it flows to the first marking area 903, then to the second marking area 904, then to the nitrocellulose membrane, and then passes through the detection area 909, the detection result control area 1000, and then flows into the water absorbent pad 907. Fig. 9As shown in Figure 10, if during the test, when the liquid sample is poured onto the guide element 10, part of the liquid enters the test area through the window, or flows into the nitrocellulose plastic film, naturally, the liquid will first wet the nitrocellulose membrane, that is, the liquid on the guide element 10 has not yet reached the nitrocellulose plastic film, and the liquid passing through the window wets the nitrocellulose membrane in advance, especially the test area in advance, so that the test area becomes wet from a dry state, and the capillary force is lost. In this way, even if the subsequent liquid flows through the test area, it will directly affect the binding ability of the test area. Sometimes, if a lot of liquid enters the test area from the window, the liquid may flow to both sides of the test area, one side flows to the water-absorbing area 907, and the other side flows over the marking area, which will hinder the liquid in the marking area from flowing to the test area, and the test area cannot complete the test, causing the test to fail. Therefore, if a layer of non-absorbent transparent film is covered on the test area 905, the liquid from the window can be prevented from contacting the test area, and the test area will not be wetted in advance, ensuring that the test is carried out according to the normal process. Therefore, if Figure 17-19 As shown, a non-absorbent transparent film 906 is covered on the test area, and the film covers the test area or the test area on the nitrocellulose film. Generally, the test area is only located on a portion of the nitrocellulose film.

[0067] The detection area 207 is also covered with a non-absorbent transparent film, such as PP, PV and other plastic films, so that when urine is tested, Figure 9-10As shown, even if liquid is received through the window 401 for reading the test results, the test area will remain dry to receive the liquid backflowed by the backflow element, allowing the liquid to pass through the backflow element and the marking area normally, and then flow to the test area 207. On the contrary, if there is no covering of the transparent film, the liquid can wet the test area 207 in advance, and after the test is wetted, the test area loses the capillary force, and on the one hand, the liquid in the marking area and the backflow area cannot flow smoothly to the test area, thereby failing the inversion test. In some methods, the non-absorbent cover is on the test area but is not bonded to the test area, for example, a layer of glue is coated on the non-absorbent film, and the transparent film is bonded to the test area, which will also affect the test results. This is because the test area is generally also an absorbent film, generally a nitrocellulose film, which has many micropores to allow antibodies or antigens to be fixed on the film. If the transparent film is bonded to the test area with glue, on the one hand, it will affect the fluidity of the liquid in the test area, and on the other hand, the glue will affect the binding of the antibody and antigen (subsequent experimental data will prove this). The third aspect is that the number of processing steps increases, and the operation must be very careful, otherwise the carrier of the test area, such as the nitrocellulose film, will be damaged. The film is very fragile and very easy to be damaged. In reality, some manufacturers that supply nitrocellulose plastic film have a transparent non-absorbent film as a substrate on one side of the film, which only serves as a support to protect the nitrocellulose film (NC). Then, the antibody or antigen can be fixed on the other side by a tool. However, the purpose of the substrate is to protect the film. Our invention team tried to use such a film to perform the test area of ​​the present invention, with the side with the substrate facing up and facing the window, and the side with the antibody facing down. The effect was not ideal. Although the problem of premature wetting may be solved, the flow of liquid and the display of test results are very unclear and difficult to achieve. Therefore, by covering the front side of the nitrocellulose plastic film (the side where the antibody is processed) with another layer of non-absorbent transparent film, it is possible to achieve the problem of not affecting the test results and avoiding the problem of premature wetting of the test area.

[0068] In some embodiments, the nitrocellulose membrane includes two ends, the first end is connected or overlapped with a marking pad, such as the second marking pad 904, and the second end is overlapped with one end of the absorbent paper 907. The filter paper provides the power of capillary action, allowing the liquid to flow from the backflow element 10 through the marking pads 903, 904 to the nitrocellulose membrane and pass through the test area located on the membrane, the test area has a detection area 909, a detection result control area 1000, and then flows to the absorbent area. Therefore, in some embodiments, one end of the non-absorbent transparent film is covered on one end of the absorbent paper 907 and bonded to the absorbent paper, and the other end is used as a free end, so that the non-absorbent transparent film can be attached to the NC film, and the liquid can flow more evenly on the NC film and the background can be cleaner. However, the width of the transparent absorbent film can be slightly larger than the width of the nitrocellulose film (such as Fig.18 As shown). For the convenience of the team leader, the two ends of the transparent film can be firstly put in such a way that one end 9061 overlaps with one end of the filter paper and the other end is free 9062, and then a layer of adhesive layer 908 is covered on the filter paper. The adhesive layer has adhesive glue, which is bonded to one end of the non-transparent water-absorbing film 906 through the glue, so that it is fixed on one end of the filter paper, and the other end naturally covers the end of the nitrocellulose film near the marking pad. When assembling, first provide as shown in FIG. Fig.17Such a test strip is then placed in the groove of the lower plate 9011, and then the test area or the nitrocellulose plastic film faces the area of ​​the window 401, and then the upper cover or upper card 9012 is covered, and there is a circular protrusion 4011 below the window area, and the edge of the protrusion has a pressing edge 4012, and the pressing edge 4012 surrounds the entire window area 401. When the upper cover 9012 is covered on the lower cover 9011, the pressing edge contacts the upper or front side 9063 of the non-hydroscopic transparent film 905, and the bottom side 9064 of the film contacts the nitrocellulose film and covers the test area. When assembled, although the non-hydroscopic film is subjected to pressure, it can be flexible because one end is free. In addition, the non-hydroscopic film can be more closely attached to the surface of the NC film, improving the fluidity of the liquid, making the background more rapid, and making the lines near the cut-off value clearer. Then the cap 2000 is covered on the channel flow element 10 to form a complete test device. In fact, the pressing edge 4012 and the transparent non-absorbent film form an area, which is directly connected to the outside atmosphere. The results of the test area can be observed through the window. Moreover, when directly receiving the sample, the liquid may splash into the window area. Even if liquid enters the window area, it will not contact the absorbent nitrocellulose film below, and thus will not wet the test area in advance, thereby ensuring the accuracy of the test results. In some embodiments, the pressing edge forms a closed ring structure, that is, the entire window is uninterruptedly surrounded by the pressing edge, which ensures that even if liquid enters the window area, it will not flow around. Of course, if the transparent film is relatively wide, if liquid enters the window, the liquid will flow along the transparent film into the groove of the lower plate. At this time, even if the pressing ring is not in close contact with the transparent film, the function of the present invention will be achieved. Fig. 20 As shown, an opaque non-absorbent film 906 covers the nitrocellulose film 905, on which a test area is set, the area includes a test line 909 and a test result control line 1000. If the test line has a line, it indicates a positive result, and if it does not, it indicates a negative result. If liquid enters the window 401, the liquid flows out from the two sides 9066, 9065 of the non-absorbent transparent film on the window area, specifically into the groove under the lower card 9011, and does not flow onto the test area (such as Fig. 20 direction of the arrow).

[0069] In addition to the above-mentioned test strip or lateral flow test strip itself being used to contact the liquid sample to test whether the liquid sample contains the analyte. The test element of the present invention itself can be used as a detection device to detect the analyte in the sample, so the detection device itself is equivalent to the test element. For example, after the fluid sample is mixed with the treatment liquid, the test element is directly used for detection. There will be a specific description below. When describing the receiving device to process the fluid sample, the test element can be used alone for detection. In the present invention, the test strip only includes a marking area and a test area, and does not include a sample application area 201. In some embodiments, the marking area on the invented test element includes a first marking area and a second marking area, and the two marking areas include a marked substance, such as a color particle mark or a coupled antibody, which can specifically bind to the analyte in the sample. In some embodiments, the first marking area is located upstream of the second marking area, and the color particles coupled to the antibody in each marking area are different. In some embodiments, the color particles can be latex particles, gold particles, or dye particles.

[0070] Analyte

[0071] Examples of analytes that can be used in the present invention include some small molecules, including drugs (such as drugs of abuse). "Drugs of abuse" (DOA) refer to the use of drugs for non-medical purposes (usually to paralyze nerves). Abuse of these drugs can cause physical and mental damage, dependence, addiction and / or death. Examples of drug abuse include cocaine; amphetamine AMP (for example, Black Beauty, White Amphetamine Pills, Dextroamphetamine, Dextroamphetamine Pills, Beans); methamphetamine MET (crank, methamphetamine, crystal, speed); barbiturates BAR (such as Valium, Roche Pharmaceuticals, Nutley, New Jersey); sedatives (i.e., sleeping aids); lysergic acid diethylamide (LSD); depressants (downers, goofballs, barbs, blue devils, yellow jackets, methaqualone); tricyclic antidepressants (TCA, i.e. imipramine, amitriptyline and doxepin); MDMA; PCP; THC, pot, dope, hash, weed, etc.); opiates (i.e. morphine MOP or opium, cocaine COC, heroin, hydroxydihydrocodeinone); antianxiety drugs and sedatives and hypnotics. Antianxiety drugs are a class of drugs mainly used to reduce anxiety, tension, fear, stabilize mood, and have Drugs with hypnotic and sedative effects include benzodiazepines BZO (benzodiazepines), atypical BZs, fused diazepine NB23Cs, benzodiazepines, ligands of BZ receptors, open-ring BZs, diphenylmethane derivatives, piperazine carboxylates, piperidine carboxylates, quinazolinones, thiazine and thiazole derivatives, other heterocyclics, imidazole-type sedatives / analgesics (such as oxycodone OXY, methadone MTD), propylene glycol derivatives-carbamates, aliphatic compounds, anthracene derivatives, etc. The detection device of the present invention can also be used to detect drugs that are for medical purposes but are prone to overdose, such as tricyclic antidepressants (imipramine or analogs) and acetaminophen, etc. These drugs will be metabolized into small molecules after being absorbed by the human body. These small molecules exist in body fluids such as blood, urine, saliva, sweat, etc., or some body fluids contain the above-mentioned small molecules.

[0072] For example, the analytes detected by the present invention include, but are not limited to, creatinine, bilirubin, nitrite, protein (non-specific), hormones (e.g., human chorionic villus stimulating hormone, progesterone hormone, follicle stimulating hormone, etc.), blood, white blood cells, sugars, heavy metals or toxins, bacterial substances (such as proteins or sugar substances for specific bacteria, such as Escherichia coli 0157: H7, Staphylococcus, Salmonella, Clostridium, Campylobacter, L.monocytogenes, Vibrio, or Bacillus cereus) and substances related to physiological characteristics in urine samples, such as pH and specific gravity. Any other clinical

[0073] Chemical analysis can be performed using lateral flow detection in conjunction with the device of the present invention.

[0074] The sample of the present invention can be urine, and the substance to be analyzed can be HCG, LH and other substances, which are used to test ovulation period or early pregnancy test.

[0075] Housing containing the test element

[0076] In some specific embodiments, the test element can also be arranged on some carrier elements, so that the carrier element contains the test element to complete the detection and analysis of the analyzed substance in the fluid sample. Therefore, in some embodiments, the detection device includes a carrier, and the test element is arranged on the carrier. In some embodiments, the carrier of the present invention is used to carry and accommodate the test element. The carrier element itself does not participate in the direct detection function, but serves as a carrier or shell for carrying or accommodating the test element. In some embodiments, the shell or carrier of the present invention includes a slot structure 901, which is used to limit the position of the test element on the carrier. The slot structure here can be one or more. A test element is arranged in each slot, and the test element can be used to test the amount or existence of the analyzed substance in the sample.

[0077] In some ways, such as Figure 3-8 As shown, the detection device includes a test element 20 therein, and the detection device is composed of a lower shell 40 and a lower shell 50, which can also be called an upper plate and a lower plate. Figure 3 As shown, the detection device comprises an upper shell 40 and a lower shell 50. The lower shell has a slot body on which the test element 20 is placed. The slot body has several support bars. The overall width of the slot body is consistent with the beginning of the test element. Then the upper shell is covered to form the detection device. Figure 5As shown, the width of the groove 516 of the lower shell 50 is consistent with the width of the test element, and a plurality of support bars are arranged on the groove, some of which are parallel to the reagent strip, and some are perpendicular to the reagent strip. For example, at one end of the shell, there are three support bars 517, 518, 519 which are perpendicular to the longitudinal direction of the reagent strip. These three support bars correspond to the three pressure bars 480, 481 on the upper shell 40 (one of the pressure bars is not shown), and are used to press several areas on the test strip or the overlapping places of several reagent pads, so that the reagent on the reagent pad can be released evenly. In addition, the phenomenon of "flooding" can also be prevented, which will be explained or illustrated in detail in conjunction with the implementation examples below.

[0078] In some embodiments, there is an area in the lower shell for placing the flow guide element 10. One end of the flow guide element is placed on the area, and the other end extends out of the shell to receive the fluid sample. The upper shell also has an area 406. When the latches 405, 402, 404, 403 of the upper shell are combined with the sockets 505, 502, 503, 504 of the lower shell 50, one end of the flow guide element is now in the area. The area 406 of the upper shell is located on the upper surface 108 of the flow guide element, and the area of ​​the lower shell is located under the lower surface of the flow guide element. In this way, part of the flow guide element is located in the shell, and the part extending from the shell is used to receive the liquid sample. In particular, it is used to receive female urine, especially directly used to receive female urine. The flow guide element has two functions, one is to directly receive female urine, and the other is to transmit to the test element 10 to detect the presence or quantity of the analyzed substance in the urine, such as HCG, LH. Such an area is set on the lower shell 50, which can also be used as a sample application area for placing the test element. The area is provided with support bars 506, 515, which are used to support the sample application area 201. A partition is set between the support area of ​​the sample application area and the reagent area or marker area 203, 204 for supporting the test strip. A recess or notch 509 is set in the middle of the partition. The notch or partition separates the marker area from the sample application area. The partition is divided into two parts 507, 508 by the notch 509. The width of the notch or recess is consistent with the width of the test strip. The width of the sample application area on the support test element 20 is smaller than the width of the guide element. When the guide element is placed on the application area 201 of the support test element, the guide element 10 covers the sample application area or the sample application pad 201, but the liquid outlet end of the guide element is in overlapping contact with the marker pad 202. It can be understood that the test element is an integral structure, which is placed in the slot 501 of the lower shell after being assembled. The part of the test element passes through the notch 509, and the sample application pad 201 is located in the area where the support bars 506, 515 of the lower shell are located. Then, the flow guide element 10 is placed at the front end of the partition, so that the end 104 (liquid outlet end) of the flow guide element contacts the front surface of the partitions 507, 508. In some embodiments, the width of the notch 509 is consistent with the width of the test element, but the width of the flow guide element is greater than the width of the test element, so the end of the flow guide element or the liquid outlet end 104 is restricted by the partitions 507, 508, so that the end surface 108 of the flow guide element is tightly close to the partition. In this way, part of the liquid from the flow guide element 10 will flow to the sample application area 201 of the test element, and then flow to the marking pad through the sample application area, and the other part of the liquid will flow directly from the flow guide element to the marking pad.Therefore, when the test strip is placed in the lower housing slot 516, if there is no sample application pad 201, the blank area of ​​the marking pad 202 will slightly pass through the recess 506, about 1-2 mm, so that the liquid outlet end 104 of the guide element will contact the marking pad, so that the liquid can flow directly onto the marking pad.

[0079] In this embodiment, since the aperture of the flow-guiding element is relatively large and the liquid is the first to directly contact the flow-guiding element, there is also more liquid on the flow-guiding element. The liquid first flows from the liquid outlet 104 of the flow-guiding element to the marking pad, contacts the marking reagent on the marking pad and dissolves. The dissolved marking reagent flows forward, and then the liquid from the sample application area flows to the marking area, contacts the marking reagent and dissolves the marking reagent. The liquid of the sample application pad 201 (if any) also flows in from the flow-guiding element, which can speed up the flow of the liquid and shorten the distance the liquid flows. In this way, for example, Figure 1 , the end 104 of the guide element is also superimposed on the marking area, so that the liquid can flow in advance, can reach the test area (T line) faster, and can obtain the test results earlier. Therefore, in one method, the liquid from the guide element 10 reaches the marking area earlier than the liquid from the sample application pad 201 or in advance. In other words, the liquid received by the marking pad is earlier from the liquid from the guide element than from the sample application pad. One way to improve it is that the guide element has a large pore size and is loose, while the sample application pad has a small pore size and a tight texture, so that the liquid flow rate will be different. In some methods, the flow rate of the liquid in the guide element is greater than the flow rate in the sample application pad. The liquid here can be a urine sample. In this way, as two liquids with different flow rates reach the test element, the liquid can flow on the test element in advance, accelerating the wetting of the dry reagent (labeling substance) under the action of the liquid sample, allowing the analyte in the liquid sample to react with the labeling substance. It is known in the art that surface reactions can only be carried out when wet, for example, the labeled-conjugated antibody can specifically bind to the analyte, such as HCG or LH.

[0080] In some embodiments, the test element may not contain the sample application area 201. In this way, the test element only contains the marking area and the test area. The end (mark) of the test element is limited by the partition. It can be understood that the marking area can only reach the notch 509 at most, or extend a little bit. For example, the blank area 209 of the first marking pad extends out of the notch 509 by 1-3 mm, and the extended 1-3 mm is covered by the guide element. The lower shell used to support the end of the guide element does not contain any components on the test strip, does not contain the liquid application pad 201, but only contains the guide element, and the end 104 of the guide element is in contact with the blank 209 end of the marking area. In this way, the liquid from the guide element can flow directly to the marking pad to release the solution of the marking substance on the marking pad, thereby completing the detection. In this way, the liquid will not flow to the sample application area on the test strip, and the liquid on the guide element will not be diverted. This can also shorten the distance that the liquid flows on the test strip and speed up the display of the test results.

[0081] The marking area of ​​the test strip includes a first marking pad 202 and a second marking pad 204. The first marking pad 202 has a reagent area 203 with a mark and a blank area 209 without a mark. When the flow guide element covers the application area 201, the end of the flow guide element also indirectly covers the blank area 209 without any reagent by covering the application area (e.g., Figure 2A and 2B ). In this way, the liquid of the flow-guiding element can also flow directly to the blank area 209 on the marking pad 202. If there is a sample application area 201, the flow-guiding element covers the sample application area, and then one end of the application area covers the blank area 209 without any labeling reagent. Therefore, one end 104 of the flow-guiding element 10 indirectly covers the blank area 209 of the marking pad by covering the application area 201, so that part of the liquid of the flow-guiding element flows to the sample application area, and part of it flows directly to the blank area 209 of the marking area. As mentioned above, the flow speed of the liquid on the flow-guiding element is faster than that of the liquid in the application area, and the flow-guiding element is the first to contact the liquid, so the liquid from the flow-guiding element flows to the marking area first.

[0082] In some embodiments, the test strip includes a sample application area 201, which is superimposed with a blank area 209 of the first marking area 202, and the first marker area 206 of the first marking area is superimposed on the blank area 208 of the second marking area 204, and the area 205 containing the second marker substance on the second marking area is superimposed on the test area 207, and the test area is located on the nitrocellulose film. The test area includes a test result area 206 and a test result control area 210. Generally, the test result area is in the shape of a line, such as the T line 206, and the control area is also in the shape of a line, referred to as the C line 210. Antibodies are processed on the T line and the C line, and these antibodies are fixed. The T line is used to capture the analyzed substance, and the antibodies on the C line area are used to capture the labeled substance. Generally, the appearance of the C line indicates that the test result is valid, and the color depth of the T line indicates the content of the analyzed substance and whether the analyzed substance exists.

[0083] In some methods, the first marker substance and the second marker substance are respectively an antibody labeled with gold particles and an antibody labeled with latex particles, and the antibodies are both directed against the same analyte. For example, if you want to test HCG in urine, the first marker substance is labeled with a first anti-HCG antibody coupled with gold particles, and the second marker substance is a first anti-HCG antibody coupled with latex particles. The antibody here can be mouse anti-HCG or sheep anti-HCG, and the second anti-HCG antibody is fixed on the T line. The first antibody and the second antibody bind to different sites on HCG respectively. Of course, it is understandable that the first marker substance and the second marker substance are both labeled with gold particles or latex particles, but they are coupled with antibodies against the same analyte.

[0084] In some methods, the marker also includes a first antibody against human IgG, and a second antibody that captures human IgG is fixed on the C line. Regardless of whether the analyte is in the urine, the C line will appear. However, if there is a flooding phenomenon, C sometimes does not appear. The present invention is to solve this problem by making structural improvements, reducing the flooding phenomenon, and allowing the device to quickly produce results within 2 minutes, for example, the results will appear between 1 minute and 2 minutes, so that the test results can be known earlier.

[0085] There are generally several ways to quickly get test results or make the color line appear faster in the T-line area. For example, on the one hand, the distance that the liquid flows on the test strip needs to be shortened (especially the distance from the marked area to the test result area (the position of the T line) is as short as possible, so that the sample liquid can reach the marked area at the fastest speed. On the other hand, if the amount of liquid is large, the flow rate will also be accelerated, and the liquid flow rate will be accelerated, so that the test results can appear earlier. However, it is difficult to achieve in actual conditions. The liquid path flows a short distance. It is not easy to make the dry reagent dissolve the liquid sample quickly and react fully in a short distance. On the other hand, if the amount of liquid is large, although this will also speed up the flow rate, when the amount of liquid is large, a flood phenomenon will occur, that is, the liquid will not actually flow out of the test strip. Instead of flowing through the marking pads on the test element, the liquid quickly flows through the surface of these marking pads and wets the test area in advance, so that the marking substance to be dissolved later is not easy to reach the test area, so that the test result will not be displayed on the test area (the area has been wetted). When the above two aspects are needed, it is hoped to find a balance between them, so that the flow distance of the liquid is shortened, but it does not affect the reaction of the reagent and the reaction needs to be sufficient. If the amount of liquid is increased, but not too much, it is avoided that too much liquid causes a negative flood phenomenon, and ultimately the detection cannot be effectively performed. This is exactly the problem that the present invention hopes to solve. If there is too much liquid on the test element, the flow rate is too fast, or the speed of the liquid flowing on the surface of the test element is greater than the speed of the liquid flowing in the test by capillary action, it will lead to inaccurate test results.

[0086] In the detection of lateral flow test, the liquid is allowed to flow by relying on capillary force, and the reaction between the reagents during the flow process results in the result, such as the reaction of the binding of antibodies and antigens. If the liquid flows quickly from the surface of the test strip (basically not relying on capillary force), it cannot effectively dissolve the dry reagent on the test strip, and wets the downstream area in advance, such as flowing quickly from the surface of the marking area (when the amount of liquid is large), the liquid on the surface of the marking pad has not yet dissolved the dry reagent on the marking area, and reaches the test area, such as the nitrocellulose membrane, and wets the nitrocellulose membrane in advance. The reagents coming later or the solution dissolved with the reagents cannot flow or reach the test area, and cannot cause the required reaction, and naturally the detection cannot be effectively completed. This is because, after being wetted in advance, the capillary force of the area disappears or decreases, and the subsequent liquid cannot continue to flow under the capillary action. If the nitrocellulose membrane is wetted in advance, the subsequent solution with the labeled substance cannot continue to flow under the capillary action of the nitrocellulose membrane, and may not flow to the detection area, which ultimately leads to the failure of the test. For example, the T line does not show color, or the T line does not show color (when the sample is positive), and even the downstream C line does not show color, resulting in an invalid structure. This is not due to insufficient amount of liquid, but too much.

[0087] In order to reduce the distance that the liquid flows, one solution of the present invention is to allow the liquid outlet end 104 of the flow guiding element 10 to directly overlap with the blank area 209 of the marking area (such as Figure 2A ), and the length of the marking area is 10-20 mm, and the distance between the marking area and the T line is 6-10 mm. The distance that the liquid flows on the test strip is about 16-30 mm. This distance is relatively short, and the time when the result appears on the T line is relatively fast. This method has been explained above. If there is no sample application area on the test element, the liquid on the guide element will flow directly to the marking area, so that the liquid can reach the test strip faster. If the test element contains a sample application area 201, the application area is made shorter, such as within 10 mm, and the end 104 of the guide element is also allowed to contact the marking pad, so that at least part of the liquid reaches the marking pad first. Traditional test elements need to pass through the sample application area and then flow to the marking area. The length of the application area can reach 20-80 mm in some cases. It flows through the application area and then flows to the marking area. The total flow distance is 40-120 mm. Generally, the result can be judged after 5 minutes.

[0088] Another solution is to hope that the liquid flows within such a short distance. If the labeling reagent is distributed in one area, the amount of labeling will be relatively large. When the liquid passes through, the dry labeling substance needs to be dissolved in the liquid and flow with the liquid to obtain accurate test results. If the liquid flows a short distance, it is hoped that the labeling substance will be quickly dissolved and carried away by the liquid. When the content of the labeling substance is high, the dry labeling substance cannot be fully dissolved in the liquid, and the labeling substance cannot fully react with the analyzed substance in the sample, resulting in inaccurate test results, such as false negative results. In order to overcome this problem, the present invention processes the marking substance on two marking pads 202, 204 respectively. The two marking pads are superimposed on each other and separated by a blank area 208, for example, 2-3 mm. The fluid flows on the two markings. Since the marking substance is processed on the two marking pads, the marking substance in each area is not much. The material of the traditional marking area is shared by two marking areas, which allows the liquid to be more fully in contact with the dry marking substance during the flow process. In this way, the solution can dissolve more marking substances in a very short distance, and the accuracy or sensitivity of the detection is improved. In particular, for the detection of early pregnancy HCG, it is hoped that the earlier the detection, the better, so that the result can be known in advance, and it will not affect the accuracy of the detection.

[0089] The third aspect is to maximize the amount of liquid flowing onto the test element. The flow rate of the liquid can be accelerated, but a flood cannot occur. This ensures that the test results appear in a very short time. Otherwise, invalid results will occur. For example, for positive urine (HCG), the T line does not appear, or both the T and C lines do not appear, or the T line appears but the C line does not appear, and the result is an invalid result.

[0090] In order to give the test results as soon as possible in a short time, it is necessary to make the liquid flow on the test element as soon as possible. Increasing the amount of liquid is another solution, which will inevitably bring other negative effects. For example, if the amount of liquid is relatively large, in the traditional test device, the liquid guided by the guide element generally needs to pass through the test element's relatively long sample pad 201 and then rely on the capillary action of the sample pad to let the liquid flow to the marking area, so that the amount of liquid can be controlled, but the disadvantage is that it takes a long time. In the present invention, the liquid can flow directly from the guide element to the marking pad, reducing the flow time of the liquid through the application pad, and allowing the liquid to enter the marking pad in advance. However, the volume of the liquid flowing from the guide element is far greater than the volume of the traditional sample application area, and the flow rate is fast, which requires additional control of the guide element to reduce negative unfavorable factors while controlling the amount of liquid. The present invention has been improved in structure to avoid the flood phenomenon caused by excessive liquid, resulting in abnormal test results. In addition, the guide element is blocked by the liquid to gradually reduce the flow rate of the liquid. Another problem is that currently, women can test their pregnancy at home by themselves. When using the flow guide element 10, women directly hold one end of the test device with their hands, such as Figure 9-10 The place indicated by 100 is then allowed to allow the other end 103 (exposed) of the guide element 10 to receive the urine sample, which is generally located below or near the urethra. When a woman urinates, she urinates directly onto the guide element for testing. One end of the guide element here is located in the shell and directly connected to the marking pad, and the other end extends out of the shell to receive the urine sample. For many home testing devices, although the operator has an instruction manual explaining how to operate, they generally do not read the instruction manual carefully. Even if they have read the instruction manual, sometimes the operation will be inappropriate. In addition, this type of test hopes that women will urinate directly on the guide element when urinating. First of all, the angle at which women hold the test device is different ( Figure 9-10 ).for example Fig. 9 The test device is shown positioned just below the urethra. Fig.10It is shown that the device is tilted, and the guide element is closer to the urethra. Second, when urine is poured onto the guide element, the amount is relatively large. It is difficult for the tester to control the amount of urine directly. In fact, the tester is allowed to release urine in a relatively natural situation. There is no special regulation for the amount. Third, the duration of each person is different. From the above aspects, the amount of liquid is usually much larger than the required volume for the test. In addition, the angle of operation of each person is different. The urine may directly face the inlet 701 of the shell, so that the urine directly enters the shell through the inlet. The inlet here is the mechanical gap between the shell and the guide element. This gap is generally 1-2 mm. Sometimes, the gap is wider, so that urine does not pass through the guide element and directly enters the shell from the gap. These liquids may flow directly to the test strip at a relatively fast speed. In addition, urine can be directly poured onto the shoulder 417, and then the urine flows back into the gap 701. These urines will be collected on the upper surface 108 of the guide element 10.

[0091] The amount of urine is usually excessive. At this time, there is a lot of liquid on the flow-guiding element, and part of the liquid 301 enters the flow-guiding element (such as Figure 1 ), enters the housing through the flow guide element, and another part of the liquid 302 may flow directly through the surface of the flow guide element (upper surface 102, 108), and directly enter the housing from the surface (such as Figure 1 Schematic diagram of the test strip) and flows to the marking pad 202. The liquid flowing from the surface has no resistance, so it flows faster than the liquid flowing from the inside of the guide element, and can reach the marking area in advance. However, if too much liquid reaches the marking area, it will cause a flood on the test strip. In addition, the liquid in the guide element can flow to the marking pad from the end 104 (liquid outlet end) or from the place in contact with the end ( Figure 2A-2B ),like Figure 2B Arrows indicate the direction of liquid flow.

[0092] Therefore, in order to avoid the negative impact on the test results caused by large amounts of liquid and fast flow rates under different conditions, the present invention provides a space for excess liquid to be retained when the flow-guiding element enters the shell. The excess liquid can flow into the space, thereby reducing the amount of liquid entering the test strip from the surface of the flow-guiding element. These reserved spaces are spaces outside the space where the reagent strip is located. There is no reagent strip in these cavities or spaces that retain liquid, or part of the test strip will not be in the space, so the retained liquid will not be contacted by the test strip. Figure 4, 5 and 6, the space for retaining liquid is set on the upper shell (there is no test strip on the upper shell, and the test strip of the present invention is set on the lower shell), and the upper shell includes transverse grooves 491, 470, 417, 418; these grooves are formed by the grooves between the raised beadings 492, 450, 412, 451, 460, and specifically, there is a gap between the beading 492 and the beading 450, so as to form the recessed groove 491. Since the beading 492 is at the outermost side and is arched, the recess or groove 491 has two parts. The recess or groove 470 between the beadings 450 and 412, the groove 417 between the beading 412 and the beading 451, and the recess 418 between the beadings 451 and 460. These grooves are vertical to the guide element, and the pressure strips have flat surfaces. When the upper shell and the lower shell are combined, these flat surfaces are in contact with the upper surface 108 of the guide element, and the grooves with openings also cover the surface of the guide element (such as Figure 6,11,7), these strips perpendicular to the guide element (or arranged horizontally) cover the upper surface 108 of the guide element 10. On the one hand, the strips slow down the flow rate of the liquid on the surface of the guide element, mainly to slow down the flow rate of the liquid on the surface of the guide element, and the grooves formed by the strips accommodate excess liquid, which can enter the space divided by these strips and be retained inside. These liquids will not be moved in the communication or cavity due to surface tension, and are also limited by the strips, so the liquid is not easy to flow. These grooves or spaces can be multiple or one, and these spaces are all covered on the upper side 108 of the guide element. Such an effect is particularly useful for urine that directly splashes into the gap 701 between the shell and the guide element. The urine can be retained by the liquid retention space or retention cavity and the grooves to reduce the liquid from flowing directly onto the marking pad 202. In some embodiments, in order to strengthen the position fixation of the flow-guiding element, a plurality of raised pressing pins 416 are also provided in these grooves. These pressing pins are also directly pressed on the surface of the flow-guiding element, which not only fixes the position of the flow-guiding element and prevents it from falling off from the shell, but also limits the flow of liquid. The liquid entering the groove is restricted by the pressing pins 416, and the flow is reduced. After many clinical trials, we found that keeping the volume of the retention space at 0.5-1 ml is sufficient to reduce the excess liquid to the marking area. With such a volume, part of the liquid on the surface of the flow-guiding element is allowed to pass through the barriers 492, 450, 412, 451, 460 one by one, and then the excess liquid is retained in these groove spaces. The above structural design and the blocking of the pressing pin 416 slow down the flow rate of the liquid, so that it flows to the marking pad and can contact and wet the substance on the marking pad in advance. The liquid inside the flow-guiding element can continue to flow to the marking pad due to its slow flow rate, so the amount of liquid is appropriate, and the liquid can fully wet the marking substance and flow to the downstream of the test area. If the volume of the reserved space is too small, it cannot retain more liquid, so the liquid flows to the marking pad. If the amount of liquid is too much, it will cause a flood and cause the test to fail. If the reserved space is too large, more shell space is required. In addition, in multiple clinical tests of the flow-guiding element, the collected liquid is about 1-2 ml, and 0.5-1 ml is retained. The sample volume that enters the test strip is about 0.5-1 ml, which can complete the flow and test of the test strip.

[0093] In some embodiments, the upper shell further includes some grooves 415, 420 arranged longitudinally with the guide element 10. The grooves are distributed near the longitudinal edges of the guide element. Figure 6It can be seen that the width of the guide element is equal to the distance defined by the two sides 413, 414 on the shell, the width of the longitudinal groove is the width set by the sides indicated by 422, 421, and the distance between the widest sides of the longitudinal groove is greater than the side defining the width of the guide element, so that the liquid from the edge of the guide element will be received or contained or retained by the longitudinal grooves 415, 420. The area where these transverse grooves and longitudinal grooves are formed is lower than the edge area as a whole, and the edge area is provided with latches 405, 404, 402, 403 to cooperate with the sockets in the edge area of ​​the lower shell, so that the upper shell and the lower shell are assembled together. In this way, the excess liquid from the guide element will be retained by these receiving chambers, and the receiving chambers rely on capillary force or the surface tension of the liquid itself to retain the liquid without being moved. The above transverse grooves or small gaps, as well as the longitudinal grooves can be called capillary grooves or capillary spaces, which can retain liquid and make it difficult to flow. Of course, many capillary channels can be provided, and these capillary channels can also retain excess liquid on the guide element, but the cost of providing capillary channels on the shell is relatively high, so some non-capillary grooves, caves, and cavities can be provided to accommodate excess liquid.

[0094] The above is to reduce the liquid from the surface of the flow-guiding element entering the marking area of ​​the test strip, while the below is to reduce or slow down the liquid from the flow-guiding element flowing into the marking area of ​​the test element.

[0095] Therefore, in some embodiments, a blocking piece 409 is provided on the housing as a blocking element. The partition structure blocks the end of the flow-guiding element, thereby reducing the flow of liquid to the marking area. Usually, the blocking piece 409 is a raised blocking piece and is located on the upper housing. Usually, the flow-guiding element 10 has a certain thickness, which is 2-3 times the thickness of the test element. Because the aperture of the flow-guiding element is large, the liquid flows quickly, while the texture of the marking pad is tight and the aperture is small, and the liquid flows slowly on it. In this way, the liquid directly coming out of the end 104 of the flow-guiding element will have an impact on the marking pad. If there is too much liquid, the excess liquid will flow directly from the surface of the mark quickly, and arrive at the test area in advance to wet the test area in advance, which will also cause a flood phenomenon and affect the accuracy of the test. In order to avoid such a problem, a notch 509 is also provided on the lower card 50. The notch divides the partition into two parts, and the blocking piece 409 is directly connected to the notch, thereby resisting the end 104 of the flow-guiding element, such as the blocking element described in 900 of Figure 2 (Figure 2 is a principle structure). In this way, the end of the flow-guiding element rests on the surface of the blocking sheet 409. If excess liquid flows out from the end (in the flow-guiding element), it will be blocked by the blocking sheet 409, and the excess liquid will flow into the receiving area of ​​the lower shell 50. Some of the liquid will also flow into the cavity near the blocking sheet 409 (for example, the cavity of the upper shell, such as the cavity shown in 418 and 417). This structural arrangement allows the liquid on the flow-guiding element to flow through the inside of the flow-guiding element to the maximum extent, and then allows the liquid to flow to the marking pad from the place in contact with the marking pad to the maximum extent ( Figure 2A The liquid flows in the direction of the arrow, and then when it flows to the end, the liquid is blocked to reduce the flow rate of the liquid, and can smoothly reach the marked area, thereby reducing the inaccuracy of the test results caused by excessive liquid flowing onto the test strip. This is because the end of the flow-guiding element 10 is directly connected to the marking pad, and the distance between the end and the marking area of ​​the marking pad is very close. The urine flowing into the end can flow directly to the area with the marking substance on the marking pad, so the amount and flow rate of the liquid flowing into the end must also be controlled.

[0096] In some embodiments, the liquid flows directly from the flow-guiding element to the marking area, and the distance between the marking area and the T-line area on the test area is relatively short. In order to improve the sensitivity of the detection, more time is given to the liquid to contact the dry marking substance on the marking area, and the analyzed substance in the liquid reacts with the marking substance. Some blocking structures are also set on the upper shell. These blocking structures are sheet-shaped and have a certain thickness, such as 1-2 mm thick. When these sheet-shaped structures are connected to the upper shell 40 and the lower shell, the first barrier pressure sheet 480 is applied to the overlapping part of the first marking pad and the second marking pad, and the second barrier pressure sheet 481 is applied to the second marking pad and the test pad (the overlapping part of the nitrocellulose membrane). Since a blank area of ​​the marking pad is set at the notch 509, when the blocking sheet 409 blocks the end of the flow-guiding element, it also exerts a certain pressure on the blank area of ​​the marking pad. The liquid of the marking pad flows from the upstream to the downstream of the blank area where the blocking sheet contacts. The blocking sheet 409 also has the effect of extending the flow rate. When the sample application pad 201 is provided, the blocking sheet 409 is applied to the overlapped portion of the sample application pad and the first marking pad. The blocking sheets arranged on the marking pad can slow down the flow of the liquid on the one hand, and on the other hand, block the excess liquid, especially the liquid that flows rapidly from the surface of the marking pad (these liquids cannot carry sufficient marking substances or have little dissolved marking substances), so that the test area cannot be wetted in advance, and the solution carrying or dissolving the marking substances can wet the test area as much as possible, thereby improving the accuracy of the detection.

[0097] In some other implementation examples, for example, Figure 12-16As shown, the test element is installed between the upper shell 70 and the lower shell 80. The upper shell has a window 701 for displaying the test results, and the window corresponds to the test area on the test element. The test element also has a first marking area 202 and a second marking area 204, as well as a sample application area 201, and the sample application area is covered by the flow guide element 10. There is also a sample retention area 706 on the upper shell, and the retention area is recessed in the entire area, relative to the two side edges 711, 712 and the edge 710 for covering the test strip, and the outlet corresponds to the edge shown in 710. This recessed area is a cavity for containing liquid as a whole. When the upper shell and the lower shell are assembled, the two side edges 711, 712 of the upper shell and the two side edges 811, 812 of the lower shell are combined through the pins and the sockets, so that each edge is in contact and sealed. The guide element is squeezed in the middle of the edge 810 of the lower shell and the edge 710 of the upper shell through the pin and the plug hole, so that the liquid on the surface of the guide element can be blocked by the edges 810 and 710. The excess liquid will stay in the recessed area 706, thereby preventing more liquid from entering the test element 20. There are multiple small holes 708 in the recessed area 706, and these small holes can also accommodate liquid. Of course, these small holes can rely on surface tension, so that the liquid is not easy to flow.

[0098] Example 1 Preparation of the immunoassay lateral flow detection device for detecting urine HCG provided by the present invention

[0099] The lateral flow detection device for detecting urine HCG by immunoassay prepared in this embodiment is as follows Figure 3-11 As shown, the test strip includes, according to the liquid flow direction, from upstream to downstream, the flow guide element (flow guide pad 10, length 40 mm, thickness 3 mm, width 11 mm, material is macroporous fiber absorbent paper), the first marking area (first marking pad), the second marking area (second marking pad), the test area, the test area control area (the two areas are located on the nitrocellulose membrane), the other end of the nitrocellulose membrane is overlapped by filter paper as an absorbent pad, wherein the first marking area and the second marking area are made of polyester film as the material, the first marking area is sprayed with the first antibody of HCG labeled with gold particles, and the second marking area is sprayed with the second antibody of HCG labeled with latex particles, and both marking pads have blank areas without labeled substances. The distance between the liquid outlet end of the flow guide element and the area with labeled substances in the first marking area is 2 mm, and the overlapping length is 2 mm; the length of the flow guide element is 40 mm, the width is 11 mm, and the width of the marking pad and the detection pad is 7 mm. The length of the first marking pad with marking substance is 9 mm (the area with marking substance is 5 mm, and the blank area is 4 mm), the length of the second marking pad with marking substance is 8 mm (the length of the area with marking substance is 4 mm, and the blank area is 4 mm), and the distance between the end of the second marking pad and the test area (T line) is 7 mm.

[0100] The labeling area is made into a labeling pad, including antibodies coupled to labeling particles (such as gold particles, latex particles or dyes, or other colored labeling substances), and then the labeling mixture is sprayed on a polyester film through a spraying device to form a labeling pad. The labeling substance on the labeling pad can flow with the flow of the liquid; the detection area uses a nitrocellulose membrane, and the antibody or antigen of the detection line is dissolved with a buffer solution PBS, and then a film dot device is used to draw a line on the nitrocellulose membrane, and then the nitrocellulose membrane is placed in an oven to dry for use. The antibodies processed on the membrane are generally immobile.

[0101] The length of the guide element located in the shell is 13 mm. It is located below the groove channel in the shell (upper shell), covered by the channel of the upper shell, and also covered by the pressure strip on the upper surface of the guide element. In addition, the edges on both sides of the guide element also contain grooves (415, 420) with a width of 2 mm and a length of 11 mm. These transverse grooves or grooves on both sides are also used to store excess samples. In short, it is hoped that the liquid flowing onto the test element only passes through the liquid in the guide element, and it is not hoped that the liquid that is not in the guide element will flow onto the test element. This is because if too much liquid flows into the test element, it will cause flooding or inaccurate testing, and false negative results. The "in the guide element" mentioned above refers to the liquid entering the guide element and the liquid that will enter the guide element. Non-in the guide element means that the liquid is applied to the guide element, part of the liquid enters the guide element, and the other part of the liquid flows on the specific surface of the guide element.

[0102] After the preparation of the guide pad, the first and second marking pads, and the detection pad are completed respectively, they are assembled. The assembly method is as follows: the area of ​​the marking substance of the first marking pad (gold particles) is superimposed on the blank area of ​​the second marking pad, and the guide element is directly superimposed on the blank area of ​​the first marking pad. Therefore, the length of the marking area formed by the two marking pads is 15 mm, and the length from the end of the guide element to the T line is approximately: 24 mm in length. The area of ​​the second marking pad containing the marking substance is overlapped on the nitrocellulose membrane. The length of the nitrocellulose membrane is 2.5 cm and the width is 7 mm. The upper shell and the lower shell are arranged according to Figure 4-5 Assembled together to form the final product, such as Fig. 9 , wherein the several blocking pressing sheets (2) of the upper shell are pressed respectively on the overlapping part of the first marking pad and the second marking pad, and on the overlapping part of the second marking pad and the nitric acid film, and the partition sheet 409 of the flow guiding element is close to the end 104 of the flow guiding element 10. There is no sample application area or application pad 201 here.

[0103] The test is conducted with standard products, which contain 20ug / L, 30ug / L, and 50ug / L of HCG (human chorionic gonadotropin). Here, if it is 20ug / L, the test result should be negative, with no T line, and the valid result is the presence of C line, 30 and 50ug / L are positive, with T line, but the C line should appear in all samples to be considered a valid result.

[0104] Embodiment 2: Different from Embodiment 1, the test element also contains a sample application pad, and the application pad 201 is located below the flow guide element. The length of the application pad is 15 mm, 12 mm of which is covered by the flow guide pad, and the other 3 mm is covered on the second marking pad. The water outlet end of the flow guide element covers the sample application pad, and the water outlet end 104 of the flow guide element covers the sample application pad, but the distance between the end and the first marking pad is the same as in Embodiment 1, which is also 2 mm. In this way, part of the liquid from the flow guide element flows to the marking pad, and reaches the marking pad earlier, and part flows to the sample application pad 201, and then flows from the application pad to the marking pad.

[0105] Embodiment 3: On the upper shell, where the flow guide element is provided, no cavity is provided, and a flat structure is provided, and the flat structure covers the surface of the flow guide element. The rest is the same as Embodiment 1.

[0106] Embodiment 4: A detection device without the blocking piece 409, and without the blocking piece to block the end of the flow-guiding element. The other structures are the same as those of embodiment 1.

[0107] Example 5: It only contains one marking pad. The marked amount is the sum of the two marked amounts in the example. Gold particles and latex can be mixed and sprayed on a marking pad. The rest is the same as Example 1.

[0108] Example 6: The other aspects are the same as Example 1. A non-absorbent transparent film is covered on the nitrocellulose film. The film does not contain any glue layer. The total length of the film is 2.5 cm. One end of the film is superimposed on the filter paper pad, and the other end is free. Then the upper and lower shells are covered to assemble into a test device. The window area of ​​the device is completely covered on the transparent non-absorbent film, and the window directly protects the test area (the area where the T and C lines are located) from the atmosphere. There is no object covering or closing the window, such as a transparent plastic cover. A clinical experiment was conducted using this setting, and women who were 6-7 weeks pregnant were tested at home using the device of this example to examine the test results. Two groups were set up, each with 20 people. Each woman was tested twice a day. One group was the device of Example 1, and the other was the device of Example 6. The test results were recorded. The test results were as follows: the device of Example 1 had 15 positive results and 5 invalid results (no T and C lines appeared), while the device of Example 6 and the device of Example 1 had 19 positive results and 1 negative result (misjudged due to unclean background). The testers were interviewed and found that the invalid results were because the urine directly splashed onto the window and wet the test area during the operation, resulting in invalid results. The test device of Example 6 had 20 positive results and a clean background, which means that in actual operation, even if the urine entered the window, it would not affect the test results, and the background was clean.

[0109] Experimental process: Assemble different experimental groups, implement the devices of Examples 1-5, each with 20 samples, and then use the configured standard products for indoor testing. The test method is to use a pipette to suck 50 ml of sample each time, and then quickly apply it to the guide element to simulate the action of female urination for testing, and observe whether the T line and C line appear in 2 minutes.

[0110] Table 1: 2-minute experimental results

[0111]

[0112] Note: A negative result for a positive sample here means that there is no T line, but there is a C line. An invalid result means that the C line does not appear.

[0113] At 2 minutes, the test results of Example 1 have 20 positive results, indicating that Example 1 can complete the test in the process of simulating female urination in the laboratory, and only one is a false negative. The positive detection rate in Example 2 is slightly reduced, indicating that when there is a sample application pad, the positive detection rate is relatively reduced, and there is 1 false negative, which may be due to the fact that there is still a lot of liquid. Example 3 is a structure that does not accommodate excess samples on the flow guide element. For the positive standard of 30ug / L, there are 15 positives, 2 false negatives, and then 3 invalid results. It can be explained that there may be too much liquid, which flows into the marking area and causes a torrent. 2 T lines do not appear, and the other 3 Cs have no lines. The marker is not fully dissolved, so the T line does not appear to be visible to the naked eye. When there is no blocking fast, the amount of liquid is also relatively large, with 4 wrong results (Example 4), while for Example 5, there are only 14 positives, indicating that the sensitivity is reduced. Compared with 50ug / L in the sample, the positive rate of Example 5 is improved, but there are still 3 false negatives. This shows that two marker pads can improve the sensitivity of detection. For negative samples, invalid results were obtained in Examples 3 and 4, while for positive samples with high concentrations, invalid results were obtained in Examples 3-4, and false negatives also occurred. This may be caused by too much liquid flowing over the surface of the marker pad without fully dissolving the marker substance.

[0114] The above five examples were used to conduct clinical trials. 100 women who were confirmed to be pregnant were selected for the clinical trials. The HCG content of these pregnant women was above 50ug / L. The operation was carried out according to the instructions, that is, urinating naturally on the diversion element. The results were read at 2 minutes and 5 minutes. The results are as follows:

[0115]

[0116] From the clinical trial, in the positive female, the device of the present invention can correctly detect that only one result is invalid, and for example 2, 2 of the 3 invalid results are false negatives, and for implementation examples 3-4, there are more invalid results, and the results of false negatives increase, which shows that the amount of liquid is more, too much urine flows on the test strip, and the marked area is not fully dissolved and flows downstream, thereby causing the appearance of false negatives (the T line has no lines or the lines are very shallow and invisible). For implementation example 5, the marking pad is a marking pad, and 90 positive results and 10 negative results (false negatives) are obtained. In this example, when the HCG of urine is equal to or less than 20ug / L, it should be a negative result. The clinical results are all the results filled in by the tester himself, and the results of the laboratory are obtained by the experimenter judging the results according to the instructions.

[0117] All patents and publications mentioned in the present specification indicate that these are public technologies in the field and can be used in the present invention. All patents and publications cited here are also listed in the references, just as each publication is specifically cited separately. The present invention described here can be implemented in the absence of any one or more elements, one or more restrictions, and such restrictions are not specifically stated here. For example, in each example here, the terms "comprising", "substantially consisting of..." and "consisting of..." can be replaced by the other two terms of one of the two. The so-called "one" here only means "one", but does not exclude that it only includes one, and can also mean that it includes more than two. The terms and expressions used here are descriptive and not limited by them. There is no intention to indicate that these terms and explanations described in this book exclude any equivalent features, but it can be known that any appropriate changes or modifications can be made within the scope of the present invention and the claims. It can be understood that the embodiments described in the present invention are some preferred embodiments and features, and any person skilled in the art can make some changes and variations based on the essence of the present invention, and these changes and variations are also considered to belong to the scope of the present invention and the scope limited by the independent claims and the appended claims.

Claims

1. A device for detecting an analyte in a fluid sample, the device comprising: A lateral flow test element comprises a marking pad containing a marking substance and a nitrocellulose membrane containing a detection area, wherein one end of the marking pad is superimposed on the nitrocellulose membrane; wherein the nitrocellulose is also covered with a transparent non-absorbent film, which prevents the nitrocellulose membrane from being prematurely wetting by the liquid sample during the test.

2. The device according to claim 1, wherein the non-absorbent film is wider than the nitrocellulose film.

3. The device according to claim 1, wherein one end of the non-absorbent film is bonded to the first end of the nitrocellulose film, and the other end is movably covered on the second end of the nitrocellulose film, wherein: The second end of the nitrocellulose membrane is superimposed with the label pad.

4. The device according to claim 1, wherein the test element further comprises a water-absorbent pad, wherein the water-absorbent pad is superimposed on a first end of the nitrocellulose membrane, and one end of the non-water-absorbent membrane is superimposed on the filter paper pad.

5. The device according to claim 4, wherein one end of the non-absorbent film superimposed on the filter paper pad is bonded to the filter paper pad.

6. The device according to claim 5, wherein the bonding is performed by adhesive bonding covering the filter paper.

7. The device according to claim 6, further comprising a housing including an upper housing and a lower housing; wherein, The test element is located between the upper shell and the lower shell, one end of the shell has an opening, and the opening includes a portion of a flow-guiding element, wherein the liquid outlet end of the flow-guiding element contacts the marking pad on the test element in the shell, so that the liquid sample from the flow-guiding element can flow directly to the marking area.

8. The device according to claim 7, wherein the upper shell further comprises a window for observing the test area, and the non-water-absorbent transparent film is located between the window and the window area.

9. The device according to claim 8, wherein the test element is located in the groove of the lower shell, and the upper shell comprises a fluid retention chamber for receiving a portion of the liquid sample from the surface of the guide element.

10. The device according to claim 9, wherein the retaining chamber has an opening, the flow-guiding element has an upper surface for receiving the liquid sample, and the opening is partially covered by the upper surface of the flow-guiding element.

11. The device according to claim 10, wherein the retaining cavity is composed of a partition cavity formed by a raised plastic strip set on the inner surface of the shell, and the surface of the pressing strip is in contact with the upper surface of the guide element.

12. The device according to claim 11, wherein the retaining chamber comprises one or more non-capillary grooves or non-capillary cavities.

13. The device according to claim 12, further comprising a blocking element for blocking the liquid at the end of the liquid outlet of the flow-guiding element from flowing to the marking area, wherein the blocking element is arranged in the housing, The end of the liquid outlet of the flow-guiding element contacts the blocking element.

14. The device according to claim 13, wherein the blocking element is disposed at the end of the fluid retaining chamber to prevent the liquid on the flow-guiding element from directly flowing onto the marking pad on the test element, thereby allowing the liquid from the liquid outlet end to flow into the retaining chamber.

15. The device according to claim 14, wherein the blocking element is arranged on the upper shell, and a recess is provided on the lower shell, a blank area of ​​a portion of the marking pad is provided on the recess, and an end of the guide element is located on the blank area and directly contacts the blank area.

16. The device according to claim 15, wherein: When the upper shell and the lower shell are assembled together, the blocking element is inserted into the recess and contacts the end of the flow guide element.

17. The device according to claim 16, wherein the test element further comprises a sample application pad partially overlapping a blank area on the marking pad, and the part of the flow guide element covers the application pad, wherein: The flow rate of the liquid in the flow guide element is greater than the flow rate of the liquid in the sample application pad.

18. The device according to claim 17, wherein the test element further comprises a sample application pad partially superimposed on the blank area on the marking pad, and the part of the flow guide element is superimposed on the application pad, wherein: Part of the liquid from the guide element flows into the sample application pad, and part of the liquid flows directly into the marking pad, wherein the liquid from the guide element flows directly into the marking pad earlier than the liquid on the sample application pad flows into the marking pad.

19. The device according to claim 18, wherein the marking pad comprises a first marking pad and a second marking pad, wherein: The first marking pad is located upstream of the second marking pad, and the liquid outlet end of the flow guiding element is superimposed on the first marking pad.

20. According to the device of claim 19, the first marking pad includes a blank area without marking substance and an area containing marking substance, the second marking pad includes a blank area without marking substance and an area containing marking substance, and the end of the guide element is superimposed on the blank area of ​​the first marking pad.

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