Device for detecting multiple analytes in liquid sample through transverse flow

Abstract

The present invention provides a device for detecting a substance to be analyzed in a fluid sample, the device comprising: a housing having an upper card and a lower card, the lower card being provided with a support structure for supporting a lateral flow test element, the lateral flow test element being provided for detecting a substance to be analyzed in a liquid sample, the supporting structure comprises an applying pad for receiving a liquid sample, the supporting structure comprises a supporting mechanism for supporting the whole sample applying pad, and the partial structure for supporting the sample applying pad is inclined.

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 analytes in liquid samples in the field of rapid diagnosis, such as urine and saliva collection, and particularly to a detection device for detecting multiple analytes in the same sample by lateral flow. 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] In the field of in vitro diagnosis (IVD), chromatography technology is often used to diagnose and test diseases and other items. For example, immunocolloidal gold test paper, dry chemical test paper, immunofluorescence test paper, etc. all use the principle of chromatography to pre-treat the sample, then react with the reagent, and finally obtain the diagnosis result reflecting whether the disease is present. The working process of the fluorescent immunochromatographic test paper is as follows: after the sample (whole blood, plasma, etc.) is dripped into the sample pad, the liquid flows to the absorbent filter paper end; the sample is processed in the sample pad, red blood cells are filtered, interference substances are removed, etc.; the sample flows through the binding pad, antigen-antibody immunobinds, and carries fluorescent groups, and when it flows through the nitrocellulose membrane, it specifically binds to the antigen-antibody pre-bound on it. The fluorescent groups gathered on the test line and the control line can reflect the test results, and other unbound interference substances are absorbed by the absorbent filter paper. Due to the characteristics of simple operation, strong specificity, high sensitivity, and quantification, the fluorescent immunochromatographic technology has been widely used in the field of POCT detection in recent years. However, in recent decades, most immunochromatographic test cards can only be a single card with a single test paper for single item detection. However, with the development of medical technology, the diagnosis of diseases requires the simultaneous detection of multiple targets for more accurate judgment, such as myocardial 3-joint test, myocardial 5-joint test, etc. In some cases, it is necessary to detect the status of multiple organs at the same time to determine the disease, such as cardiopulmonary 5-joint test, etc.

[0004] 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.

[0005] Lateral flow assay device may include a housing having a sample port and a result window downstream of the sample port, and optionally a control window downstream of the result window. The sample port is suitable for receiving a certain amount of liquid buffer or a sample applied thereto, and it spans the lateral flow path via the lateral flow test strips in the housing, extending from the sample port to a downstream position. The housing may be formed by any suitable material, and examples thereof include molded plastics, and preferably have sufficient rigidity to provide support and stability to one or more lateral flow paths accommodated therein. Adhesive may be assembled on the housing surface, wherein the adhesive faces the lateral flow matrix to help maintain the lateral flow matrix in the housing in the appropriate position.

[0006] WO2007 / 063423 discloses a kind of lateral flow device, wherein shell also comprises one or more pressure bars, support and / or dowel pin for multiple layers and strip are arranged in shell and maintained in the proper position of assembly device.For example, described shell top can be provided with the pressure bar that is used for the upstream part of lower wick to be remained on buffer hole proper position and the pressure bar that is used for the downstream end of lower wick and the upstream end of main strip to be kept in contact with each other and remain on the proper position in assembly device.In one embodiment, these pressure bars can be formed with shell top as a whole, for example when shell top is formed by molded plastic.Alternatively, one or more pressure bars can be provided as independent element.

[0007] WO2020 / 143219 also describes that applying a sample can detect multiple analyzed substances, but the design of the device is more complicated, with a multi-layer stepped mechanism in the sample application area to receive liquid samples or buffers. In addition, each step is designed at a different height. In fact, it is difficult to maintain consistency for each product in specific production. The main reason may be that the use of absorbent materials to form a stepped structure of different heights cannot achieve batch consistency. Although multiple items or analyzed substances can be detected at the same time, the structural design is complicated.

[0008] WO2008 / 110044 also discloses a device for testing multiple analytes by applying a sample once. However, when the sample application hole is as wide as the arrangement of the test strip, the amount of sample applied needs to be relatively large, and it is not easy to contact the sample on each test strip at the same time, resulting in inaccurate test results and large time differences in the obtained test results. Although it is also disclosed that the small application holes are radially distributed on the test strip, so that the sample can be applied once to test multiple different test strips, it still has an impact on the accuracy of the test.

[0009] The above lateral flow devices have the following defects: (1) the structure design is complex and the manufacturing cost is high; (2) most of them require professional training to operate, and if they are operated by unprofessional personnel, it will often cause inaccurate detection; (3) although they are operated by professionally trained personnel, they will still cause inaccurate detection results. In view of the technical problems of some of the above traditional products, it is necessary to improve them and provide other ways to solve the shortcomings of existing traditional technologies. Summary of the invention

[0010] In order to overcome the defects of the prior art, the purpose of the present invention is to provide a device for detecting analytes in fluid samples. In particular, it is desired to apply a liquid sample once to detect multiple analytes at the same time. In particular, applying a sample once allows the sample to be evenly distributed on two test strips. Through the lateral immunoassay device of the present invention, once a sample is applied, the sample on each lateral flow test strip is basically evenly distributed. In addition, even if an excessive amount of sample is applied, the test result will not be affected, which is particularly suitable for home self-testing.

[0011] In order to solve this problem, the present invention provides a detection device, which includes an upper card and a lower card, wherein the lower card has a support structure for supporting a lateral flow test element, and a plurality of test elements are arranged on the support structure, wherein each test element can detect different analyzed substances in the sample.

[0012] In some embodiments, the structure supporting the test element has a detection area, a marking area and a sample application area for supporting the test element. In some embodiments, the structure supporting the sample application area is configured as a first support area and a second support area, and the second support area is configured as an inclined configuration. In some embodiments, the first support area and the structure supporting the marking area are at the same horizontal position. The second support area is lower than the first support area and is configured as a gradually decreasing inclined configuration.

[0013] In some embodiments, the lower card has a plurality of structures for supporting the test strips, and these structures all have a detection area, a marking area, and a sample application area for supporting the test element. Moreover, each supporting structure has a structure for supporting the sample application area, and the structure is arranged as a first supporting area and a second supporting area, and the second supporting area is arranged obliquely. In some embodiments, each first supporting area and the structure for supporting the marking area are at the same horizontal position. Each second supporting area is lower than the first supporting area and is arranged obliquely and gradually lowered. The plurality of structures can be two or more.

[0014] In some embodiments, the multiple inclined or sloped structures are located in a fluid diversion area, and after the fluid enters the area, it flows to the sample application area of ​​each test strip. In other words, the area supporting sample application with multiple inclined or sloped structures of the present invention is located in a fluid sub-area, and fluid enters the area, and the fluid flows to each test element in the area. In some embodiments, a flow guide element is also provided in the fluid diversion area, and the flow guide element covers the sample application area. In some embodiments, the flow guide element covers the sample application area located on the second slope support structure.

[0015] In some ways, in order to allow part of the sample application area of ​​the test element to cover the surface of the second support structure, a layer is set on the corresponding upper card, and the layer can be applied to part of the sample application area so that the area covers the surface of the second support structure. Similarly, when there is a flow guide element, the flow guide element is also allowed to cover the sample application area. It can be understood that in the liquid diversion area, there are multiple support structures with inclined surfaces, and the multiple support structures are all inclined in the diversion area. On the upper surface of the support area of ​​each inclined surface, part of the sample application area of ​​the lateral flow test strip is covered. In this way, if there are 2 inclined surface areas, the sample application areas of 2 test strips are covered, and if there are three, the sample application areas of three test elements are covered. In this way, when the fluid sample first contacts the sample application area on the inclined surface, it then flows upward to the sample application area on the surface of the first support structure by relying on the capillary force of the sample application area, and then flows to the support mark area structure at the same horizontal plane as the first support structure, and then flows to the detection area. In this way, when the guide element covers the sample application area located on the inclined surface, the fluid applied on the guide element will flow to the sample application area on each test strip, so that there is a portion of the liquid sample on each test element, so that multiple tests can be completed by applying the same liquid sample.

[0016] In some embodiments, in order to allow the fluid to flow smoothly and relatively evenly to each test element on the multiple test elements, a plurality of guide strips are arranged on the surface of the guide element, and these guide strips can allow the fluid to flow along the guide strips to the sample application area of ​​the test element. In some embodiments, the guide strips are arranged on the upper card. In some embodiments, the upper card is provided with a sample loading hole, and the sample loading hole is arranged on the guide element. The sample loading hole is located in the middle position of the inclined support structure. In some embodiments, the guide strips are distributed on both sides of the sample loading hole. The guide strips are raised ribs arranged on the inner surface of the upper card, which guide the flow of the liquid on the one hand, and are applied to the guide element on the other hand, so that the guide element is fixed in the diversion area.

[0017] In some embodiments, a positioning pin is provided near the guide strip of the upper card, and the positioning pin is applied on the surface of the guide element, so that the partial application area of ​​the test element is close to the surface of the inclined support structure, and the lower surface of the guide element is close to the surface of the sample application area. In this way, the partial sample application area of ​​the test strip is presented in a gradually lowered position relative to other areas, such as the marking area and the detection area. In this way, when the liquid sample is applied to the gradually lowered position or the liquid sample guided by the guide element flows from a low position to a high position and then flows in parallel, it can not only improve the sensitivity of the detection, but also allow the liquid sample to have a delayed flow effect, which can give the liquid sufficient time to dissolve the dry marking material in the marking area. In some embodiments, the positioning pin is provided on the front side of the guide strip and is located above the sample application area. When the upper card is installed on the lower card, the positioning pin is applied to the guide element to fix the guide element on the partial sample application area, and the partial sample application area is covered on the surface of the gradually inclined support structure.

[0018] In some embodiments, the sample diversion area is located in a rectangular area, and the structure of the inclined support part sample application area is located on both sides of the rectangular area. In some embodiments, it is located on both sides of the short side of the rectangular area. In some embodiments, a limiting structure is set on both sides of the first support area to limit the left and right movement of the test strip. In some embodiments, the rectangular area has a three-sided raised fence, which forms a liquid diversion area, and the fence area includes the above-mentioned inclined support part liquid application area. In some embodiments, the limiting structure is located on the line connecting the other long sides of the rectangular area. In some embodiments, a plurality of protrusions are set on the short side, and the protrusions contact the edge of the sample application area of ​​the test element.

[0019] In some embodiments, the test element includes a detection area, a marking area and a liquid sample application area, and the detection area is a nitrocellulose film on which antibodies or antibody fragments are fixed. The marking area includes a marking pad, on which antibodies or antibody fragments are coupled with colored particles. In some embodiments, one end of the marking pad is overlapped on one end of the nitrocellulose membrane. In some embodiments, a blank pad is also arranged on the marking pad and the nitrocellulose membrane, and the blank pad is treated with a reagent for improving flow properties. In some embodiments, the sample application pad is located at the end of the test element, and the water-absorbing pad is located at the other end of the test element. In some embodiments, part of the sample application pad is covered on the inclined support structure. In some embodiments, the angle between the inclined support surface and the bottom surface of the lower card is 20-30 degrees.

[0020] Beneficial Effects

[0021] By adopting the above structure, the influence of a large amount of liquid sample on the accuracy of the test result can be reduced, and the test result can be obtained quickly, which is particularly suitable for self-testing by women at home. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is a top view of the structure of the test element in the detection device housing in a specific embodiment of the present invention).

[0023] Figure 2 It is a schematic diagram of the three-dimensional structure of the test element of the present invention.

[0024] Figure 3A It is a schematic diagram of the decomposed structure of two flow-guiding elements for detecting different analytes in a specific embodiment of the present invention.

[0025] Figure 3B It is a schematic structural diagram of a combination of two flow guide elements for detecting different analytes in a specific embodiment of the present invention.

[0026] Figure 4 It is a schematic diagram of a test element and a support structure supporting the test element in a specific embodiment of the present invention (part of the sample application pad is located on the slope and does not cover the slope).

[0027] Figure 5 It is a schematic diagram of a test element and a support structure supporting the test element in a specific embodiment of the present invention (part of the sample application pad is covered on the slope, and the guide element is also located on the slope and covers part of the sample application pad).

[0028] Figure 6 It is a schematic diagram of the lower card structure of the detection device in a specific implementation manner of the present invention.

[0029] Figure 7 It is a schematic diagram of the structure of an upper card of a detection device in a specific implementation manner of the present invention.

[0030] Figure 8 The present invention Figure 6 An enlarged schematic diagram of a portion of the structure of the upper shell in a specific implementation manner is shown.

[0031] Fig. 9 It is a schematic diagram of the exploded structure of the detection device, the test strip and the flow-guiding element in a specific embodiment of the present invention.

[0032] Fig.10 This is a schematic diagram of the structure in which the test element and the flow guiding element are located in the lower card in a specific embodiment of the present invention.

[0033] Fig.11 This is a schematic diagram of the lower card structure of the detection device in another specific embodiment of the present invention.

[0034] Fig.12 This is a schematic diagram of the upper card structure of a detection device in another specific embodiment of the present invention.

[0035] Detailed description

[0036] 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.

[0037] Detection

[0038] 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.

[0039] sample

[0040] 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.

[0041] 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.

[0042] In some embodiments, the sample application area of ​​the test element of the present invention does not need to be manually applied with a fluid sample, but is in contact with a flow guide element, allowing the liquid sample guided by the flow guide element to flow into the sample application area, and then into the marking area, and then be assayed or tested. The following is further described in detail in conjunction with specific implementation examples.

[0043] Downstream and Upstream

[0044] Downstream or upstream is divided according to the direction of liquid flow. Generally, liquid or fluid flows from the upstream to the 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, the fluid can flow from the guide element to the sample application area or sample application pad of the two test elements, and then the liquid flowing to the sample application pad flows to the downstream marking pad, and then mixes with the marked marking substance, and then flows to the downstream detection pad through the transition pad. On the detection pad, the test area is located upstream of the test result control area, and finally flows to the absorption pad on the downstream absorption 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 upstream of the marking area of ​​the test element. The specific structure of the test element is as follows. Figure 1-2 The structure shown in FIG20. When part of the sample application pad is located on the inclined surface and its position is lower than the marking pad, the liquid on the sample pad mainly flows from bottom to top by capillary force, while the liquid on the surface of the application pad may flow downward due to gravity.

[0045] Gas connection or liquid connection

[0046] 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.

[0047] Test components

[0048] The so-called "test element" here 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. This detection can be based on any technical principle, whether 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. In the present invention, the test element and "lateral flow test element, or test strip" can be used interchangeably to express the same meaning.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] The various zones of the test paper or the lateral flow test strip of the present invention can be arranged in the following manner: a sample application area 205, a marking area 204, a detection area 202, and the detection area includes a test result area 206 and a test result control area 207. The control area is located after or downstream of the detection area. All zones can be arranged on a test paper using only one material. Different materials can also be used in different zones. Each zone can be directly in contact with the liquid sample, or different zones can be arranged according to the direction of flow of the liquid sample, and the end of each zone is connected to the front end of another zone 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.

[0054] 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.

[0055] 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 application area 205, a marking area 204, and a detection area 202. The sample collection area includes a sample receiving pad or a sample application pad, and the marking area includes a marking pad. It can also include a water absorption area 201 to absorb the liquid sample from the nitrocellulose membrane, and the water absorption area can include a water absorption pad. In some embodiments, the marking area includes color particles coupled to antibodies, and the color particles can be latex particles, gold particles, or dyes. The detection area 202 includes necessary chemical substances that can detect whether the analyzed substance is contained, such as immunoreagents or enzyme chemical reagents. The sample application area or application pad 205 of the present invention does not directly receive the sample, but contacts the guide element 30 to receive the liquid sample guided by the guide element. Therefore, part of the sample application area of ​​the present invention is covered by the guide element 30 (such as Figure 3B ). In some methods, such as Figure 2 As shown, a transition pad 203 is also provided between the marking pad and the detection pad of the test strip, and the transition pad is to delay the speed of the liquid on the marking pad flowing to the detection pad, so that the liquid sample can be in contact with the dry marking substance on the marking pad for a longer time, so as to obtain a more adequate reaction or allow the dry marking substance to be fully dissolved by the liquid sample. The commonly used detection reagent strip is a nitrocellulose membrane reagent strip, that is, the detection area 202 includes a nitrocellulose membrane, and the specific binding molecules are fixed on the nitrocellulose membrane to display the result area 206 (T-line) of the detection; it can also be a cellulose acetate membrane or a nylon membrane, etc.; of course, the downstream of the detection area can also include a detection result control area 207 (C-line), usually, the control area and the detection area appear in the form of a horizontal line, which is a detection line or a control line. Such a detection reagent strip is a traditional reagent strip, and of course, it can also be other types of reagent strips that use capillary action for detection. In addition, generally, the test strips carry dry chemical reagent components, such as fixed antibodies or other reagents. When the liquid encounters the liquid, the liquid flows along the test strip by capillary action. As the liquid flows, the dry reagent components are dissolved in the liquid, and then the liquid is processed in the next area to react with the dry reagent in the area, so as to perform the necessary test. The liquid flows mainly by capillary action. Here, they can all be applied to the detection device of the present invention, or be set 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.

[0056] In addition to the above-mentioned test strips or lateral flow test strips themselves being used to contact the liquid sample to test whether the liquid sample contains the substance to be analyzed. The test element of the present invention itself can be used as a detection device to detect the substance to be analyzed in the sample, so the detection device itself is equivalent to the test element. For example, after the fluid sample is mixed with the processing liquid, it is directly detected by the test element. There will be a detailed description below. When describing the receiving device to process the fluid sample, the test element can be used alone for detection. .

[0057] Analyte

[0058] 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.

[0059] 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 cactus) and substances related to physiological characteristics in urine samples, such as pH and specific gravity. Any other clinical chemical analysis can be detected using the lateral flow detection format in conjunction with the device of the present invention. It is also possible to detect the presence of viral antigens, such as new crown antigens and influenza antigens.

[0060] Housing containing the test element

[0061] 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 support 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 supporting or accommodating the test element. In some embodiments, the shell or carrier of the present invention includes a slot structure, 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.

[0062] In some ways, such as Figure 4-5As shown, it is a schematic diagram of the principle structure of the detection device of the present invention, including a test element 20 located on a support carrier, and the support carrier structure is generally located on a housing, such as a lower housing. The support structure has a support area for supporting the sample application area 205 of the test strip. Generally, the sample application area is a sample application pad 2051, which is a glass fiber sample application pad, and the support supporting the sample application pad includes a first support area 60 and a second support area 61, and the two support areas are arranged together to support the entire sample application pad 2051, wherein the second support area gradually tilts along one end of the first support area to form a section of a tilted support area 61 with a gradually decreasing height, and the surface of the tilted support area covers part of the sample application pad 2052. In this way, the entire sample application pad is divided into two parts by the sample support structure, one part covers the surface of the tilted support area 61. The other part covers the first support area 60. The first support area also covers the marking pad and part of the sample application area 2052, so the marking pad, part of the sample application pad, and the detection pad are on the same horizontal plane, and part of the application pad is on the slope. Of course, the sample application pad described here is generally bonded to a non-absorbent backing, so the sample application pad does not directly cover the surface of the second support area, but indirectly covers the surface of the second support structure through the backing. Similarly, nitrocellulose as a detection pad, a marking pad with a marking substance, and an absorbent pad can all be bonded to a non-absorbent backing. In some embodiments, when it is desired to apply a sample once and to perform simultaneous testing of multiple test elements, a guide element 30 is further provided, which covers part of the sample application area 2015, 205 of the first test element 20 and the second test element 21, so that the guide element connects the two test elements and forms a fluid connection between the two test elements. In some embodiments, the guide element covers the inclined sample application areas of the two test elements (such as Figure 5 As shown). It can also be understood that the flow-guiding element 30 also covers the surface of the inclined second support area 61, rather than directly covering it, but by covering the surface of the sample application area 2052. When two test elements are connected, the two test elements are arranged in parallel, and the sample application areas covered by the flow-guiding element 30 are respectively located in the inclined second support area. It is easy to understand that when two test strips are used, two support structures supporting the test strips are arranged in parallel, and the support structure includes an inclined support portion sample application pad. In some embodiments, a sample application area 40 is set in the middle position of the flow-guiding area, and the fluid sample can be directly applied to the application area of ​​the flow-guiding element. The fluid sample flows from both sides of the flow-guiding element to the two test elements to perform detection of different analyzed substances ( Figure 3B ).

[0063] In conventional devices like this, a common problem is that due to the material of the flow-guiding element itself, the capillary fibers that make up the flow-guiding element are not evenly distributed, and when the liquid is transmitted by capillary force, there is naturally a speed difference. At the same time, the thickness of the flow-guiding element is not uniform. In this way, when the fluid is applied to the application area 40, the fluid flowing to the two test elements is not evenly distributed. For example, when 1 ml of liquid sample is applied, only 0.2 ml of liquid may flow to the test element 20, and the other 0.8 ml flows to the test element 21 (in some extreme cases). In this way, the liquid on the test element 20 is not enough to complete the entire test, and there is too much liquid sample on the test element 21, which also affects the final test result, such as the flood phenomenon. Therefore, in order to overcome the problem of uneven distribution of fluid samples, a slope structure is set, and it is found that the problem of uneven distribution can be significantly improved. In addition, there is a certain distance between the two test elements, and the area for applying the fluid is directly located on the flow-guiding element, and the area for applying the fluid is not directly on the sample application areas 2015 and 205 of the test element. When the liquid is applied to the sample receiving area of ​​the flow-guiding element, the liquid flows from the middle to both sides, and the liquid flows upward on the inclined surface. If there is too much liquid, it will flow from the middle position to the area below the flow-guiding element, and will not flow too much onto the test strip. At the same time, an inclined slope structure is set. Due to the effect of the liquid's own gravity, the speed at which the liquid flows on the flow-guiding element is slowed down, so that the amount of liquid flowing to the sample application area of ​​the test strip can maintain a stable content. Here, the sample application area of ​​the test strip is shorter than that of a general test strip, and the amount of liquid required is relatively less. The liquid flowing to the sample application pad quickly flows to the marking pad, so not too much sample is required to flow onto the test element. About 10-50 microliters is sufficient for each test strip. Generally, the sample application pad is a whole component, and the inclined surface is set in this way, which is equivalent to folding the sample reagent pad. For example, at the fold 2054, on the one hand, the part 2052 of the sample application pad is fixed on the inclined surface, and on the other hand, the sample reagent pad is pressed in the downstream area of ​​the fold 2054. The folded structure will also slow down the flow of the liquid. In this way, when there is a sufficient amount of sample and the sample reagent pad itself is short, the folding and the slope setting can reduce the overall flow rate of the liquid, so that the liquid flow speed can be kept consistent within a very short distance, and there is more time for the dry marker substance downstream to contact and dissolve, and at the same time, the analyzed substance in the sample reacts with the marker substance, thereby enhancing the sensitivity.

[0064] In some embodiments, in order to allow the liquid dripped on the sample receiving area 40 of the sample guide element 30 to flow more quickly to the test elements connected on both sides, a guide strip is also provided on the guide element. When the guide strip is pressed on the surface of the guide element 30, on the one hand, the guide element is only attached to the sample application pad 2052 of the test element, and at the same time, the sample application pad is only attached to the inclined support surface. The guide strip itself is not absorbent, such as some plastic strips, but when it contacts the surface of the guide element, a capillary structure is formed. Relying on the capillary structure, the liquid sample from the sample application area of ​​the guide element can flow quickly to the test strips 21, 20 distributed on both sides. These guide strips can be located on the upper card, which has a hole for applying the sample, and the hole is located on the sample receiving area 40 of the guide element 30, and the guide strips can be distributed on both sides of the sample loading hole of the upper card, and the guide strips are also located on the upper card. When the upper card is combined with the lower card, the sample loading hole for applying the sample covers the sample receiving area 40 of the guide element, and the guide strips distributed on both sides of the hole are pressed on the surface of the guide element 30.

[0065] Generally, each sample application pad, marking pad, transition pad, test pad and absorbent pad of a test strip are bonded to a rigid backing paper. The check has a certain rigidity and is vertical in its natural state. Each of the above pads is absorbent and has a thin wall. When the sample application area on the backing is bent, it is easy to return to its original straight state (such as Figure 4 In the present invention, it is always desirable to allow part of the sample application area or the application pad to be bent and covered on the surface of the support structure 61. To achieve this purpose, a protruding fixing nail is provided on the inner surface of the upper shell, and the length of the nail protrudes from the inner surface of the upper cover, and then when the upper and lower cards are combined with the lower card, the length of the nail is from the inner surface to the surface at the middle position of the inclined surface ( Figure 5 The fixing nail can be applied to the guide element and also to the sample absorption pad, so that part of the sample absorption pad is closely attached to the inclined surface of the support area 61. The sample application area 2052 of the test element is always kept at an inclined angle relative to the position of the other part of the sample application pad 2053, or the sample application pad is bent to form two parts. The fixing nail method is the simplest to implement. Of course, glue is applied on the inclined surface, so that part of the sample application pad 2053 is bonded to the surface of the inclined surface, and glue is also applied on the surface of the support area 61, so that a bend can be formed, but the operation process is very complicated and not conducive to automatic production.

[0066] In some embodiments, the present invention provides a device, which includes an upper shell 100 and a lower shell 200. The lower shell 200 contains a support structure for supporting horizontal test elements 21, 20, and the support structure is used to place the test elements. The support element includes a support structure unit 110 for supporting absorbent paper, a support structure unit 117 for supporting a detection pad, a support structure unit 108 for supporting a label pad, and a support structure unit 180 for supporting a sample application pad. In some embodiments, the position of a portion of the support structure 106, 105 for supporting the sample application pad is lower than the support structure 107 for supporting another portion of the sample application pad. It can also be considered that the test element provided includes a sample application pad 205, a label pad 2041, a detection pad 207 and an absorbent pad 201, and the sample application pad 205 is in a folded form. In some embodiments, the end of the sample reagent pad to the fold 2054 is inclined, or the end to the fold is sequentially increased. In some embodiments, in order to achieve a state where part of the sample application pad is tilted, a support structure 180 supporting the sample application area is provided on the bottom of the lower card, and the structure has a part that is tilted, so that part of the sample application pad is covered on the tilted support structure surface, thereby making part of the sample application pad also tilted. Figure 6As shown, the support structure shown includes two symmetrically arranged support bars 107, 180 arranged in parallel, and each support bar has an inclined surface 106, 105 at the end, and the two inclined surfaces 106, 105 have the same angle and are arranged in parallel. When the lateral flow strip is placed on the support structure, the end with the sample application area contacts a pair of limiting structures 128, 129, and the end with the water absorption pad contacts the limiting structure 112, so that the length of the entire reagent strip is determined by the distance between the raised limiting structures 129 and 112. At this time, the entire test strip is located on the support structure, the water absorption pad is located on the water absorption area support structure 110, and the detection pad, such as the area of ​​nitrocellulose membrane, is located on the support structure 117 supporting the detection pad, and the area with the marking pad and the area with the sample application pad are simultaneously located on the support structure 108. One end of the end of the support structure is inclined, that is, it is hoped that part of the sample application pad is covered on the inclined support structure surface 105, 106. In some embodiments, the length of the entire inclined surface 106, 105 is approximately 1 / 3, or 1 / 2 of the length of the entire sample application pad. In this way, the sample application pad portion of the test element is on the same horizontal plane as the marking pad, while the sample application pad at the end portion is located on the inclined surface, and there is a fold 190 between the inclined surface and the plane of the marking pad. In some embodiments, the sample application pad located on the inclined surface is used to receive liquid samples. The so-called sample application pad here is not used to directly apply samples, and can be understood as receiving liquid samples, such as receiving samples from the guide element, rather than being used to directly receive applied samples. Figure 6As shown in FIG8 , two inclined structures are provided in the lower card, and a pair of structures for supporting the test strips are also provided. In this way, two reagent strips can be placed in the lower card at the same time, and each reagent strip can detect the analyte. The analyte detected by each test strip is different. For example, one is for detecting the new crown antigen and the other is for detecting the influenza antigen. However, it can include multiple parallel support structures, and multiple test strips can be placed. The sample application or receiving pads of these tests are covered by the flow guide element and are fluidically connected. In some embodiments, a sample diversion area 104 is provided in the lower card, and the area is a rectangular area, and the area is surrounded by three walls 192, 122, and 191 protruding upward from the bottom 193 of the lower card, and no wall is provided on the side opposite to the wall 192, so that the sample application area support structure supporting the test strip extends into the diversion area 104, and the inclined support structure is located in the diversion area, including a pair of parallel inclined surfaces 105, 106 located in the diversion area 104, and at the same time, the end of the inclined surface is located near the limiting structure 129, and the limiting structure is formed by a pair of protruding structures 129, 130 from the inner wall of the wall 192. In addition to limiting the end of the sample application pad, the grooves formed between the protruding structures can also play a role in drainage. In some embodiments, the inclination angle 132 is between 25-35 degrees, and the angle represents the height of the inclined surface.

[0067] In some embodiments, when two test strips are placed on the support structure, a flow guide element 30 is provided at the end of the sample application pads of the two test strips, and the size of the flow guide element 30 is comparable to the size of the sample diversion area 104 (e.g., Fig.10 Therefore, the guide element covers part of the sample application pads of the two test elements. In particular, the width of the guide element is the same as the length of the inclined surfaces 106 and 105. In this way, when a certain pressure is applied to the guide element, part of the sample reagent pad can be covered on the inclined surfaces 106 and 105, so that the guide element and part of the sample reagent pad are inclined. Figure 8It can be seen that the test strips are distributed on both sides close to the liquid diversion area 104. The two test strips have a certain distance in the sample diversion area and are not close together. In some embodiments, the guide element is provided with a sample receiving area 40, which is located in the middle of the two test strips. It can also be considered that the application receiving area 40 is located in the center of the guide element. In this way, from the perspective of physical structure, the liquid from the guide element can flow to the two test elements, and it is hoped that the volume of liquid flowing to each test strip is equal. In some embodiments, the sample application area of ​​the guide element corresponds to the sample application hole 204 of the upper shell 200, so that the applied liquid sample flows directly to the sample receiving area 40 of the guide element, and then is diverted to the two test strips through the application pad. The sample receiving area 40 on the guide element 30 is set in the middle position, and its advantages are mainly reflected in the following aspects: one is, from Figure 8 It can be known that there is a blank area between the two test strips, and due to the effect of the support structure, a low-lying area 193 is relatively formed in the diversion area 104. When applying the sample through the sample loading hole 204 of the upper card, if the amount of sample applied is relatively large, the excess sample will flow along the inclined guide element to the low-lying area 193 for collection. These low-lying liquids are far away from the test strips and will not flow onto the test strips. In addition, due to the blocking effect of the raised support structure, the flooding caused by the large amount of liquid flowing to the sample application pad is reduced. This is because the guide element is also rectangular and is also in an inclined position, and the area for receiving liquid is located in the center. Part of the liquid flows laterally relative to the lower card along the capillary action of the guide element ( Fig.10 ), thereby flowing to the test elements on both sides, while the excess liquid flows along the longitudinal direction of the guide element (along the longitudinal direction of the lower card) ( Fig.10The direction of the arrow) directly flows to the low-lying side, and will not flow to the test strip. The flow-guiding element is a rectangular setting, and the distance directly flowing to the test element is long, and the distance end flowing to the low-lying place is conducive to the flow of excess liquid, so that the lateral flow mainly relies on capillary force to flow. This is mainly considered that these detection devices are operated by people without any experience. The most common problem for inexperienced people is that the amount of liquid applied is too much. Originally, 2-3 drops, about 40-30 microliters, are required, but the amount of liquid often applied will be 50-500 microliters, and sometimes, 1 ml will be applied. With this arrangement, the excess sample will flow to the low-lying place in the diversion area 104 and gather, and the normal sample will flow to the inclined sample application area on the lateral flow element set on both sides, which is greatly improved compared with the traditional detection of multiple analytes detected by one sample. In addition, when the sample amount is appropriate, the appropriate sample amount will flow from the sample receiving area 40 to both sides along the flow-guiding element, and flow to the sample application areas of the two test strips respectively. In addition, part of the sample application area of ​​the test strip is at an inclined angle, and another part of the sample application pad is at the same horizontal position as the marking pad and other detection pads, and the inclined sample application pad is at a low position, while the marking pad is at a high position. When the liquid sample flows onto the inclined sample reagent pad, the liquid actually flows from a low position to a high position. When the sample application pad is very short, it is hoped that the liquid will flow more slowly on the test strip. The liquid flows from a low position to a high position, and gravity will naturally cause it to flow more slowly. In this way, when the liquid flows to the marker area, the liquid has more time to contact the dry marker substance. In this way, if the sample contains the substance to be analyzed, the dissolved marker substance will have more time to react with the substance to be analyzed and combine more fully. Another advantage is that if too much sample is diverted from the flow guide element 30 to the sample application area, which often occurs in actual operation, the flow guide element is only 10-12 mm long and about 1-2 mm thick. The entire saturated liquid is about 10-15 microliters. If there is too much liquid, the excessive liquid will flow to the sample application area. Under the condition of an inclined angle, the excessive liquid will flow from the surface of the sample application area to a low position (the effect of gravity), and cannot flow to a high position, and the liquid flowing to the high position will rely entirely on capillary force. When the liquid flows onto some water-absorbing materials with capillary action, it is generally hoped that the liquid will move forward by capillary action. This is the basic principle and property of the horizontal detection test strip. However, if there is too much liquid, part of the liquid will rely on capillary action to move from upstream to downstream, but the other part of the liquid on the surface of the water-absorbing material (the capillary has been completely wetted) is actually flowing naturally, so the flow rate is naturally faster than the flow relying on capillary action.In actual testing, if the amount of sample added is too large, such a problem will occur, and such a problem will cause the surface liquid to reach the reagent area in advance, especially the detection area on the detection pad. If the dry reagent, such as antibody or antigen, is treated on it and wetted in advance, the capillary force is lost, and the subsequent marker substance or marker mixture loses the capillary action and continues to move or moves to the detection area more difficult, resulting in erroneous results. For example, when the liquid flows to the sample application area, if there is too much liquid, part of the liquid flows through the capillary force, and the other part may be located on the surface of the application area and flow directly (not relying on the capillary force), and the flow speed is fast. In lateral flow detection, it is not expected that the liquid will flow directly on the surface, but it is expected to flow by the capillary force itself, so that the test results can be more accurate. Because the surface flow also flows fast, some areas downstream are wetted in advance, and the liquid of the dry reagent flowing through the capillary force flows slowly, wetting the downstream area in advance (the capillary force is lost or weakened), and the reagent behind cannot continue to move or the power of movement is damaged, resulting in the liquid with the reagent being unable to flow or the amount of flow is small, and the amount of binding in the detection area is small, affecting the accuracy of the result. In fact, although the guide element is directly used to receive the liquid sample, there is still such a problem that a part of the liquid relies on capillary action to flow. If the amount of liquid is large, part of the liquid sample flows directly from the surface of the guide element. The speed of the liquid flowing on the surface is also faster than the speed of the capillary flow, resulting in too much liquid flowing to the sample reagent pad. Similarly, too much liquid is applied to the sample pad, resulting in inaccurate detection results. The present invention adopts an inclined guide element, and the excess part of the liquid can be directly along the longitudinal direction of the lower card (. Fig.10 The so-called "low-lying area" in the diversion area 104 can be formed by setting holes or depressions on the inner surface of the lower card to collect liquid, or it can be formed by the position of the support structure relative to the inner plane, and the low-lying area is formed at the bottom of the diversion area, and it does not need to be deliberately made.

[0068] In order to ensure that excess liquid in the flow guiding element 30 can flow to low-lying areas, protrusions are provided on the surrounding walls 192, 122, 191 of the liquid diversion area 104. These protrusions can fix the flow guiding element so that the flow guiding element does not contact the surrounding walls. There are grooves 1231 between two protrusions. These grooves can actually drain excess liquid samples to low-lying areas. For example, Figure 8In the embodiment, projections 125, 124, 123 are arranged on the wall 122 of the diversion area, and there is a groove between each two projections. The surface of the projection directly contacts the cross section of the diversion element and also directly contacts the side 290 (i.e., the side of the thickness of the test element) of the sample application area of ​​the test element. On the one hand, the test element is fixed differently, and on the other hand, if there is excess liquid, it flows to the low-lying area through the groove instead of flowing onto the test element. The other wall 191 also adopts such a design, for example, some projections are arranged, and there are grooves between the projections for draining excess liquid samples. A similar structure is also arranged at the position of the wall 192 of the diversion area 104 corresponding to the end of the test strip sample application area, with projection pairs 129, 130 or projections 128, 1281, and grooves 198 and 199 are arranged before the projection pairs. The purpose of these projections is to prevent the test element from directly contacting the wall, and the grooves are used to remove excess liquid from the test or diversion element, mainly to remove excess liquid on the diversion element. In some embodiments, positioning pins 127, 126 are provided near the support structure, and the positioning pins are located next to the support structure, mainly to accurately position the test strip on the support structure. In lateral flow detection, the cooperation between the upper shell and the lower shell also has a significant impact on the specificity and sensitivity of the test strip detection, especially some structures that affect the flow of liquid directly affect the detection performance of the test strip.

[0069] In some ways, in order to fix part of the sample application area of ​​the test element in an inclined state through some structures of the upper card, or to cover part of the sample reagent area on the surface 105, 106 of the inclined support mechanism, a fixing needle 206, 205 structure is provided on the upper card, and the length of the needle is basically enough to allow the fixing needle to contact the inclined surface when the upper card and the lower card are assembled, so that the fixing pin presses the flow-guiding element to make the flow-guiding element in an inclined state, and also puts part of the sample application area in an inclined position. The fixing needle here can be understood as "pressing, applying pressure", that is, applying pressure to the flow-guiding element and part of the sample to cover the inclined support structure. This is because, generally when producing lateral flow test strips, the sample application pad 205, the marking pad 204, the transition pad 203 (if necessary), the test pad 207, and the absorbent pad 201 are generally bonded to a rigid cardboard. As above, the sample application pad is a whole, such as a piece of glass fiber bonded to the cardboard. In this way, when the test strip is placed on the support structure of the lower card, part of the sample application area does not naturally cover the inclined surface (such as Figure 4), when the guide element is covered on part of the sample application pads of the two test elements, it will not naturally cover the inclined surface, so it is necessary to apply a certain amount of pressure to overcome the reverse elastic force of the cardboard card and make the guide element and part of the sample application surface in an inclined position. In some embodiments, guide strips 208, 207 are set on both sides of the sample application hole 204 of the upper card. The guide strips are raised from the inner surface of the upper card, and the surface of the guide strips also contacts the sample guide element 30, basically along the Fig.10 The guide strip is pressed on the surface of the guide element in the direction of the transverse arrow. The function of the guide strip is to allow the liquid on the guide element to flow to the sample application area of ​​the test element as quickly as possible, especially to the inclined sample application area.

[0070] In some embodiments, some pressing marking pads and transition pads, as well as the places where the sample application pad and the marking pad overlap, are also provided in the upper card, so that each reagent pad can smoothly carry out the fluid of the liquid. The pressing bar is pressed on the place where the marking pad 204 and the transition pad 203 overlap, which can also slow down the flow of the liquid, thereby extending the contact time between the liquid and the dry marking pad and increasing the reaction time. In addition, these pressing bars also allow the test element to be tightly attached to the support structure, so that each area (marking, part of the sample application area, and the test area) are located at the same horizontal plane. The upper card also includes windows 214, 215 for reading or observing the test results on the detection pad. In some embodiments, some rivets are also provided in the upper card.

[0071] 202, 201, 211, 210, 213, 212, these rivets correspond to the rivet holes 102, 103, 108, 118, 119, 120 in the lower card respectively, and these rivets cooperate with the rivet holes to allow the upper card and the lower card to be assembled and fixed in a certain position. Such fixation allows the test strip to be in a fixed position between the upper and lower cards. At the same time, combined with the fixing needles 206, 205 and the guide strips 208, 207 above, part of the sample application area is close to the surface 105, 106 of the inclined support structure, so that the guide strip is in contact with the surface of the guide element, and the sample application hole 204 is located on the sample receiving area 40 at the center of the guide element.

[0072] In some other embodiments, the present invention provides a detection device, which includes an upper card 800 and a lower card 900. The lower card includes a test element support structure, and the support structure includes a structure 810 supporting a water-absorbing pad, a structure 801 supporting a detection pad, a structure supporting a marking pad, and a structure 806 supporting a portion of a sample application pad. When two test strips are used for detection, the sample application areas of the two test strips (the sample area 806 of the first test strip and the sample application area 805 of the second test strip) are cross-stacked in a diversion area 808. The support structure intersects near the sample application area, and has a liquid diversion area 808 at the intersection. The diversion area and the portion of the sample application pad are overlapped in a common area 804. The overlapped common area 804 is used to receive liquid samples. In this way, different analyzed substances can be detected by applying a sample at one time. Figure 11-12 As shown, the lower card 800 includes a supporting structure 801 for supporting the first test strip, and a common area 804 for supporting the supporting part sample application pad with the second test strip is provided on the region 803 of the application pad for supporting the first reagent strip of the sample on the supporting structure, and the part of the first application pad and the second reagent strip of the part application pad are arranged on the common area 804, and are in an overlapping position in the common area. In some ways, the sample application pad is generally a layer of 1-2 mm thick glass fiber (the part of the sample area lacks lining at this time), and two layers are cross-overlapped on the common area 804, and when the upper card is assembled with the lower card, the sample application hole of the upper card is located at the center of the intersection area, and a part of the application hole is located on the application pad of the overlapping area, and the non-overlapping sample application area on the two test strips is evenly or equally divided and covered by the application hole. Like this, the liquid sample from the application hole can evenly contact the sample application area of ​​the two test strips, thereby allowing the substantially equal volume of the sample obtained. Similarly, there is a fixing needle 901 on the upper card, which is located in the overlapping area 804 of the sample reagent pad, so that the sample application pad is fixed in different positions. The upper card is also provided with pressing bars 903, 904 to apply pressure to the overlapping area of ​​the marking pad and the sample pad. At the same time, two windows 906, 905 are provided corresponding to the detection area of ​​the test strip.

[0073] Example 1 Lateral flow detection of saliva novel coronavirus antigens and influenza A and B antigens by immunoassay provided by the present invention Preparation of the device

[0074] The lateral flow detection device for detecting COVID-19 antigens and influenza A+B antigens in saliva by immunoassay prepared in this embodiment is as follows Figure 1, 3, 9-10, including a first test strip 21, according to the liquid flow direction, from upstream to downstream, there are sample application pad 205, marking area 204, test area 206, test area control area 207 (the two areas are located on the nitrocellulose membrane 202), the marking pad has a first antibody that specifically binds to the new coronavirus antigen and coupled gold particles, and a second antibody that specifically binds to the new coronavirus antigen is fixed on the test area. Then there is a transition pad 203 downstream of the marking pad, according to Figure 2 The second test strip 20 for influenza detection has the same structure as the first test strip, except that the first antibody mixture that specifically binds to influenza A+B antigens is processed in the test area, and the second antibody that specifically binds to influenza A or B antigens is processed on the label, and both are coupled to gold particles.

[0075] Here, the sample application pad of the test strip has a length of 14 mm and a width of 4 mm. The width of the test strip is 4 mm and the thickness is 2 mm. The length of the flow guide element is 17 mm and the width is 6 mm. Therefore, the width of the sample application area covered by the flow guide element on each test strip is 6 mm, and the width of the sample application area not covered by the flow guide element between two test strips is 9 mm. The distance between the two test strips is approximately 9 mm. The inclined length of the sample application pad of the supporting part arranged on the lower plate is 6 mm. The upper card and the lower card are assembled together so that the sample application hole is located in the center of the flow guide element. The distance between the two test strips is 9 mm. According to the following Fig.10 The layout is shown in the figure, and then the card is covered to form a complete test device. The length of the liquid diversion area of ​​the lower card is equivalent to the length of the guide element, which is also 19 mm long, 7 mm wide, and 4 mm deep, while the height of the support structure is also about 4 mm, thus forming a low-lying area, the depth of which is about 4 mm.

[0076] The antibody is coupled to the labeled particles (such as gold particles, latex particles or dyes, or other colored labeled substances), and then the labeled mixture is sprayed on a polyester film through a spraying device to form a labeled pad. The labeled substance on the labeled pad can flow with the flow of the liquid; the detection area uses a nitrocellulose membrane, and the antibody 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.

[0077] The positive COVID-19 samples and the positive A+B saliva fire extinguishing sample mixture were used for the test. The lateral flow test results of these samples were all positive, and the color depth was at the level of G3 (COVID-19 positive, influenza positive) (using the standard color card configured in the laboratory for comparison, G3 is positive, less than G3 is negative, and greater than G3 is positive). The negative control uses a blank PBS solution.

[0078] Implementation Example 2: Different from Implementation Example 1, the traditional setting method is adopted on the lower card. There is no inclined supporting structure. Instead, a structure setting at the same height as the supporting structure at the marking pad is adopted. In this implementation example, the fixing nails on the upper card are missing, and other structures are retained. Implementation Examples 1 and 2 do not set a groove structure around the wall, but there is a diversion area.

[0079] Implementation Example 3: Compared with Implementation Example 1, groove structures are set on the three walls of the diversion area. The specific number is the same as Figure 8 The numbers shown are the same and the structure is the same.

[0080] Experimental process: Assemble different experimental groups and implement the devices of Example 1-2, each with 20 samples, and then use the configured standard products for indoor testing. The experimental method is to use a pipette to absorb 40 μl, 50 μl, 100 μl, 200 μl, 500 μl, and 1000 μl of negative and positive samples, and then apply them to the sample receiving area of ​​the guide element through the sample loading hole on the upper card, and observe the test results after 5 minutes.

[0081] Table 1: Positive sample results

[0082]

[0083] Note: G3 is a positive result. If there is no C line, it means the test result is invalid. If there is no T line, it means it does not match the actual result.

[0084] By observing the flow of each test device in Examples 1-3, it was found that when the sample applied was above 200 ml, the number of T lines that did not appear increased. It was observed that these samples flowed to the nitrocellulose membrane in advance to wet the T line, and then the flow of the liquid with color particles was blocked. The liquid with color particles flowed out from the marking pad and began to contact the nitrocellulose membrane, which caused the failure of the detection. When the amount of liquid was 500 microliters, there was a T line without C line in Example 1. It may be that the amount of liquid was too large, the T line appeared, but the C line did not appear, indicating that the particle marker did not flow to the C line, so it was considered to be an invalid structure, while there were 4 invalid results in Example 2. When the sample volume increased to 1 ml, Example 1 still had an invalid result, but Example 2 lacked 8 invalid results, and 2 could not be judged. However, compared with Example 3, the volume range of the liquid from 10 microliters to 1 ml can be effectively detected, indicating that such a design can control the amount of liquid within the range of 10-1 ml, and the detection structure is not affected by the volume of the liquid. This is actually meaningful for the OCT market's self-testing. Many people who have not received professional training are not subject to many restrictions, at least not on the amount of liquid samples, and can be relatively free, making home self-testing products more practical.

[0085] Table 2: Negative control PBS solution

[0086]

[0087] From the negative results, both implementation examples 1 and 3 can obtain correct results, while implementation example 2 still has different numbers of invalid results.

[0088] 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 shell having an upper card and a lower card, a support structure for supporting a lateral flow test element is arranged on the lower card, the lateral flow test element is arranged to detect an analyte in a liquid sample, the lateral flow test element includes an application pad for receiving the liquid sample, the support structure includes a support mechanism for supporting the entire sample application pad, wherein a part of the structure supporting the sample application pad is inclined.

2. The device according to claim 1, wherein the test element further comprises a marking pad and a test pad, wherein the marking pad is located downstream of the pad for receiving the liquid sample, and the structure supporting the other part of the sample application pad is in a substantially horizontal position with the structure supporting the marking pad.

3. The device according to claim 2, wherein the inclined support structure is located lower than the support structure supporting the marking pad.

4. According to the device according to claim 3, the lateral flow element includes a first lateral flow element containing a first sample receiving pad and a second lateral flow element containing a second sample receiving pad, and the partially inclined structure supporting the sample applying pad includes a first inclined support structure and a second inclined support structure, wherein a portion of the first sample receiving pad is covered on the first inclined support structure, and a portion of the second sample receiving pad is covered on the second inclined support structure.

5. According to the device of claim 4, the first inclined support structure and the second inclined support structure are arranged in parallel and there is a distance between them.

6. The device according to claim 5, further comprising a liquid guiding element, the guiding element being made of a water-absorbing material, and the guiding element covering a portion of the first sample receiving pad and a portion of the second sample receiving pad.

7. The device according to claim 6, wherein the lower card further comprises a liquid sample diversion area, the first inclined support structure and the second inclined support structure are located in the diversion area, and the first inclined support structure and the second inclined support structure are distributed at both ends of the diversion area.

8. The device according to claim 7, wherein the guide element is parallel to the first inclined support structure and the second inclined support structure, or the guide element is also arranged to be inclined.

9. The device according to claim 7, wherein: An area for receiving liquid samples is arranged at the center of the flow-guiding element, and the area is located between the first inclined support structure and the second inclined support structure.

10. The device according to claim 6, wherein the diversion area includes a low-lying area, and the liquid from the inclined guide element can flow to the low-lying area and gather.

11. The device according to claim 10, wherein the upper card comprises a hole for dripping a liquid sample, and the hole is located on the sample receiving area on the flow guide element.

12. The device according to claim 11, wherein both sides of the sample loading hole of the upper card further include guide strips, and the guide strips are in contact with the surface of the guide element.

13. The device according to claim 12, wherein the guide strip is located in contact with the guide elements on the first inclined support structure and the second inclined support structure.

14. The device according to claim 13, wherein the upper card further comprises a pressing pin, and the pressing pin is arranged on the flow guiding element on the first inclined supporting structure and the second inclined supporting structure, so that the flow guiding element covers the sample application pad.

15. The device according to claim 14, wherein the diversion area is surrounded by a wall, and a plurality of grooves are arranged on the inner surface of the wall, and the grooves can allow the liquid in the guide element to flow into the grooves, such as the low-lying area at the bottom of the diversion area.

16. According to the device of claim 15, the sample application pad has a length of 14 mm and a width of 4 mm, the guide element has a length of 17 mm and a width of 6 mm, so the width of the guide element covering the sample application area of ​​each test strip is 6 mm, and the distance between the two test strips is 9 mm.

17. The device according to claim 2, wherein a transition pad is further provided downstream of the marking pad, and the transition pad is located between the detection pad and the marking pad.

18. According to the device of claim 4, the first horizontal test element is used to test the new coronavirus antigen, and the second test element is used to test the influenza antigen.

19. The device according to claim 2, wherein the upper card further comprises a window for exposing a detection area of ​​the test element.

20. The device according to claim 1, wherein the liquid sample is blood, saliva, nasal secretions, laryngeal secretions or urine.

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