Device for detecting multiple analysis target substances in liquid sample using lateral flow assay

Abstract

To provide a device for detecting analysis target substances in a fluid sample.SOLUTION: A device includes a housing having an upper card and a lower card. A support structure for supporting a lateral flow assay element is provided on the lower card. The lateral flow assay element is arranged so as to detect analysis target substances in a liquid sample. The lateral flow assay element includes a sample injection pad for receiving the liquid sample. The support structure includes a support mechanism for supporting the sample injection pad. Here, a portion of the structure for supporting the sample injection pad is inclined.SELECTED DRAWING: Figure 7

Description

[Technical field]

[0001] The present invention relates to devices for collecting and detecting liquid samples, particularly in the field of rapid diagnostics, for detecting analytes in liquid samples, such as devices for collecting and detecting urine, saliva, and more particularly devices for detecting multiple analytes in a single liquid sample in a lateral flow assay. [Background technology]

[0002] The following background art introduction is merely an introduction to some background general knowledge and does not limit the present invention.

[0003] In the field of in vitro diagnosis (IVD), chromatography technology is often used to detect and diagnose diseases, etc., such as immunocolloidal gold test paper, dry chemical test paper, immunofluorescence test paper, etc., first pretreat the sample according to the principle of chromatography technology, then react with reagents, and finally obtain a diagnosis result that reflects whether there is a disease. Here, the working process of the fluorescent immunochromatography test paper is as follows: After the sample (whole blood, plasma) is dropped onto the sample pad, the liquid flows to the end of the absorbent filter paper, the sample is processed in the sample pad, red blood cells are filtered, interfering substances, etc. are removed, the sample flows through the binding pad, the antigen-antibody is immuno-bound with the fluorescent group, and when it flows through the nitrocellulose membrane, it specifically binds with the antigen-antibody pre-bound thereon, and the fluorescent dye gathered on the test line and control line can reflect the test result, and the absorbent filter paper absorbs other unbound interfering substances. Fluorescence immunochromatography technology has the characteristics of being easy to operate, highly specific, highly accurate, and quantifiable, and therefore has been widely used in the POCT detection field in recent years. However, in recent decades, the majority of immunochromatography test cards only consist of a single test card with a single test paper to detect a single item. However, with the development of medical technology, in the diagnosis of diseases, it is necessary to simultaneously detect multiple targets, such as the three-item composite detection of myocardium and the five-item composite detection of myocardium, in order to make a more accurate judgment. In order to judge diseases, it may be necessary to simultaneously detect the status of multiple organs, such as the five-item composite detection of the heart and lungs.

[0004] Currently, detection devices for detecting whether a sample contains an analyte are widely used in hospitals or homes, and these rapid diagnostic detection devices include one or more detection reagent strips, such as early pregnancy detection, drug abuse, etc. These rapid diagnostic detection devices are very convenient, and the detection results can be obtained in one minute with the detection reagent strip, or up to about 10 minutes. Drug detection is widely used and is always used in institutions such as drug control departments, police stations, drug addiction treatment centers, health examination centers, and national conscription health examination centers. Drug detection is diverse and frequent. Some need to collect samples and then be detected by specialized detection organizations or testing laboratories. In order to complete the test in real time, it may be necessary to conduct on-site testing such as roadside testing, for example, drivers who have smoked drugs (abbreviated as drug driving) need to be detected on-site and the detection results obtained in real time.

[0005] The lateral flow assay device may include a housing having a sample port, a result window downstream of the sample port, and optionally a control window downstream of the result window. The sample port is adapted to receive a metered amount of liquid buffer or other sample injected therein, which overlies a lateral flow pathway through a lateral flow test strip within the housing and extends to a location downstream from the sample port. The housing may be manufactured of any suitable material, such as molded plastic, and preferably provides support and stability to one or more lateral flow pathways contained therein. An adhesive may be assembled to a surface of the housing, where the adhesive faces the lateral flow array, to maintain the lateral flow array in place in the housing.

[0006] Patent application WO2007 / 063423 discloses a lateral flow device, in which the housing further comprises one or more pressure bars, supports and / or positioning pins for arranging the layers and strips in the housing and maintaining them in the proper position in the assembly device. For example, the top of the housing is provided with a pressure bar for maintaining the upstream part of the lower liquid intake core in the proper position of the buffer hole, and a pressure bar for maintaining the downstream end of the lower liquid intake core and the upstream end of the main strip in contact with each other and maintaining them in the proper position in the assembly device. In one embodiment, when the top of the housing is made of molded plastic, these pressure bars can be integrally molded with the top of the housing. Preferably, one or more pressure bars are provided as independent elements.

[0007] Patent application WO2020 / 143219 also discloses a device that can detect analytes by injecting one sample, but the device is more complicated in design, and the sample injection area has a multi-layered step mechanism for receiving liquid samples or buffer solutions, and each step has a different height. In fact, in a particular production, it is difficult to maintain the consistency of each product, mainly because the use of water-absorbing materials forms step structures with different heights, making it impossible to achieve batch consistency. Although multiple items or analytes can be detected simultaneously, the structural design is complicated.

[0008] Patent application WO2008 / 110044 also discloses a device for detecting multiple analytes with one sample injection, but if the width of the sample hole and the arranged test strip are the same, the injected sample volume will be large, and it is not easy to contact each test strip with the sample at the same time, resulting in inaccurate test results and a large time difference between the obtained test results. It also discloses that small injection holes are radially distributed on the test strip so that one sample can be detected on multiple different test strips, but it still affects the detection accuracy.

[0009] The above lateral flow devices have the following defects: (1) the structural design is complicated, and the manufacturing cost is high; (2) in most cases, professional training is required for operation, and if untrained personnel operate it, the detection will be inaccurate; and (3) even if it is operated by professionally trained personnel, it still produces inaccurate detection results. In order to improve the technical problems of some of the above conventional products and make up for the shortcomings of the conventional technology, an alternative is provided. Summary of the Invention

[0010] In order to overcome the deficiencies of the prior art, the object of the present invention is to provide an apparatus for detecting analytes in a fluid sample, which is expected to detect multiple analytes with a single injection of a liquid sample, and in particular, to distribute the sample evenly on two test strips with a single injection of the sample. With the lateral flow immunoassay device, with a single injection of the sample, the sample on each lateral flow test strip is uniformly allocated, and even if an excess sample is injected, the detection result is not affected, so that it is particularly suitable for home testing.

[0011] To solve this problem, the present invention provides a detection device, which includes an upper card and a lower card, the lower card having a support structure for supporting a multilayer flow assay element, and the support structure is provided with a plurality of test elements, wherein each test element is capable of detecting a different analyte in a sample.

[0012] In some embodiments, the structure for supporting a test element includes a detection region, a marker region, and a sample injection region for supporting a test element. In some embodiments, the structure for supporting the sample injection region is arranged as a first support region and a second support region, and the second support region is provided at an incline. In some embodiments, the first support region and the structure for supporting the marker region are at the same horizontal position. The second support region is provided at an incline, lower than the first support region, and gradually lowers.

[0013] In some embodiments, the bottom card has a plurality of structures for supporting test strips, each of which has a detection region, a marker region, and a sample injection region for supporting a test element. Each of the support structures has the structure for supporting the sample injection region, each of which is arranged as a first support region and a second support region, and the second support region is provided at an incline. In some embodiments, each of the first support regions and the structure for supporting the marker region are at the same horizontal position. Each of the second support regions is lower than the first support region and is provided at an incline so as to gradually decrease in height. By multiple is meant two or more.

[0014] In some embodiments, the plurality of structures having a slope or incline are located in a fluid diversion region, where the fluid enters and then flows to the sample injection region of each test strip. That is, the plurality of slopes or inclines of the present invention for assisting sample injection are located in a fluid diversion region, where the fluid enters and then flows to each test element. In some embodiments, a guide element is further provided in the fluid diversion region, where the guide element covers the sample injection region. In some embodiments, the guide element covers the sample injection region located on the second inclined support structure.

[0015] In some embodiments, the corresponding upper card is provided with a push bar so that a part of the sample injection area of ​​the test element covers the surface of the support structure, and the push bar applies pressure to a part of the sample injection area, so that the area covers the surface of the second support structure. Similarly, when a guide element is provided, the guide element also covers the sample injection area. Note that in the liquid diversion area, there are a plurality of support structures with inclined surfaces, and the plurality of support structures are inclined in the diversion area, and a part of the sample injection area of ​​the lateral flow test strip covers the upper surface of the support area of ​​each inclined surface. In this way, when there are two inclined surface areas, the sample injection areas of two test strips are covered, and when there are three inclined surface areas, the sample injection areas of three test strips are covered. In this way, the fluid sample first contacts the sample injection area on the inclined surface, and then flows upward to the sample injection area on the surface of the first support structure due to the capillary action force of the sample injection area, and then flows to the structure that is located in the same horizontal plane as the first support structure and supports the marker area, and finally flows to the detection area. In this way, when the guide element covers the sample injection area located on the inclined surface, the fluid dripped onto the guide element flows to the sample injection area in each test strip, so that each test element has a portion of liquid sample, and one injection of the liquid sample can complete several detections.

[0016] In some embodiments, the surface of the guide element is provided with a number of guide strips to allow the fluid to flow smoothly and uniformly into each of the test elements, and the fluid flows along these guide strips to the sample injection area of ​​the test element. In some embodiments, the guide strips are provided on the upper card. In some embodiments, the upper card is provided with a sample injection hole, and the sample injection hole is provided on the guide element. The sample injection hole is located at the middle position of the inclined support structure. In some embodiments, the guide strips are distributed on both sides of the sample injection hole. The guide strips are provided on protruding ribs on the inner surface of the upper card, which not only guide the flow of the liquid but also apply pressure to the guide element to fix the guide element in the flow division area.

[0017] In some embodiments, a positioning pin is provided near the guide strip of the upper card, and the positioning pin applies pressure to the surface of the guide element, so that a part of the injection area of ​​the test element is in close contact with the surface of the inclined support structure, and the lower surface of the guide element is in close contact with the surface of the sample injection area. In this way, the part of the sample injection area of ​​the test strip is gradually lowered compared to the marker area and the detection area. In this way, the liquid sample is injected into the gradually lowered position, or the guide element guides the liquid to flow from the lower position to the higher position, and then the liquid flows in parallel, thus improving the detection accuracy, and the liquid sample has a delayed flow effect, giving the liquid enough time to dissolve the dried marker material in the marker area. In some embodiments, the positioning pin is provided on the front side of the guide strip and located above the sample injection area, and when the upper card is attached to the lower card, the positioning pin applies pressure to the guide element to fix the guide element to the part of the sample injection area, and this part of the sample injection area covers the gradually inclined surface of the support structure.

[0018] In some embodiments, the sample diversion area is located in a rectangular area, and the sloped structures supporting a portion of the sample injection area are located on either side of the rectangular area. In some embodiments, they are located on either side of the short sides of the rectangular area. In some embodiments, a limiting structure is provided on either side of the first support area to limit left and right movement of the test strip. In some embodiments, the rectangular area has a three-sided protruding enclosure that forms a liquid diversion area, and the enclosure area includes the sloped structures supporting a portion of the liquid injection area. In some embodiments, the limiting structure is located at a tie line of the other long side of the rectangular area. In some embodiments, the short side is provided with a plurality of protrusions, which contact the edge of the sample injection area of ​​the test element.

[0019] In some embodiments, the test element includes a detection area, a marker area, and a liquid sample injection area, and an antibody or antibody fragment is immobilized on the nitrocellulose membrane in the detection area. The marker area includes a marker pad, and the marker pad has an antibody or antibody fragment, to which colored particles are coupled. In some embodiments, one end of the marker pad is spliced ​​onto one end of the nitrocellulose membrane. In some embodiments, the marker pad and the nitrocellulose membrane are provided with a blank pad, and the blank pad has a reagent that improves flow performance. In some embodiments, the sample injection pad is located at the end of the test element, and the absorbent pad is located at the other end of the test element. In some embodiments, a portion of the sample injection pad covers the support structure of the bevel. In some embodiments, the included angle between the support surface of the bevel and the bottom surface of the lower card is 20 to 30 degrees. Effect of the Invention

[0020] The above structure can reduce the impact of large amounts of liquid sample on the accuracy of the test results, while at the same time providing rapid test results, which is especially suitable for self-testing by women at home. [Brief description of the drawings]

[0021] [Figure 1] FIG. 2 is a top view of the structure of a test element in the housing of a detection device according to one particular embodiment of the present invention. [Diagram 2] FIG. 2 is a perspective view of a test element of the present invention. [Figure 3A] FIG. 2 is a schematic diagram of an exploded view of two devices and a guide element for detecting different analytes according to one particular embodiment of the present invention. [Figure 3B] FIG. 1 is a schematic diagram of a combined structure of two devices and guide elements for detecting different analytes according to one particular embodiment of the present invention. [Figure 4]FIG. 2 is a schematic diagram of a test element and a support structure for supporting the test element according to one particular embodiment of the present invention (with a portion of the sample injection area located in but not covering the gradient). [Diagram 5] Schematic diagram of a test element and a support structure for supporting the test element according to one particular embodiment of the present invention (part of the sample injection area is located on a slope and the guide element is also located on a slope to cover part of the sample injection pad). [Figure 6] FIG. 2 is a structural schematic diagram of the lower card of the detection device according to one particular embodiment of the present invention; [Figure 7] FIG. 2 is a structural schematic diagram of an upper card of a detection device according to one particular embodiment of the present invention; [Figure 8] 7 is an enlarged view of a portion of the structure of the upper housing according to one particular embodiment shown in FIG. 6 of the present invention. [Figure 9] 1 is an exploded schematic diagram of a detection device, a test strip, and a guide element according to one particular embodiment of the present invention. [Figure 10] FIG. 1 is a structural schematic diagram when a test element and a guide element are located on a lower card according to one particular embodiment of the present invention. [Figure 11] FIG. 13 is a structural schematic diagram of the lower card of the detection device according to another particular embodiment of the present invention. [Figure 12] FIG. 13 is a structural schematic diagram of an upper card of a detection device according to another particular embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Detailed Description

[0023] The structures according to the present invention or the technical terms used therein will be further explained below, and unless otherwise specified, they shall be understood and interpreted according to general terms commonly used in the art.

[0024] detection

[0025] "Detection" refers to chemical testing for the presence or absence of a substance or material, or testing for the presence or absence of a substance or material, including, but not limited to, a chemical, an organic compound, an inorganic compound, a metabolite, a drug or drug metabolite, an organic tissue or a metabolite of an organic tissue, a nucleic acid, a protein, or a polymer. "Detection" also refers to testing the amount of a substance or material. "Chemical testing" also refers to immunodetection, chemical detection, enzyme detection, and the like.

[0026] sample The sample of the detection device of the present invention includes biological liquids (e.g., case liquids or clinical samples). It can be any liquid or fluid sample and can be taken from solid or semi-solid samples, such as excrement, biological tissues, food samples, etc. The solid or semi-solid sample can be converted into a liquid sample in any suitable manner, such as mixing, stamp-grinding, maceration, incubation, dissolution, or enzymatic digestion of the solid sample in a suitable solution (e.g., phosphate solution or other buffer solution). "Biological samples" include animal, plant and food samples, such as human or animal urine, saliva, blood and its components, spinal fluid, vaginal secretions, sperm, feces, sweat, secretions, tissues, organs, tumors, tissue and organ cultures, cell cultures and media. A preferred biological sample is urine, and preferably the biological sample is saliva. "Food samples" include materials for food processing, finished products, cheese, liquor, milk and drinking water. "Plant samples" include any plant, plant tissue, plant cell culture and media. An "environmental sample" is one taken from the environment (e.g., liquid samples from lakes and other bodies of water, wastewater samples, soil samples, groundwater, seawater, and wastewater samples). An "environmental sample" can include wastewater or other wastewater.

[0027] A suitable detection device of the present invention can be used to detect any analyte. Preferably, the present invention can be used to detect small drug molecules in saliva, urine. Of course, the detection device of the present invention can be used to detect any of the above-mentioned forms of samples, whether initially solid or liquid, as long as the liquid or liquid sample can be absorbed by the sample injection area of ​​the test element. The sample injection area used herein is generally made of a water-absorbent material, and the capillary or other properties of the material of the absorbent element allow the liquid or fluid sample to be absorbed, so that the fluid sample flows through the sample injection area. The material of the fluid sample injection area can be any material capable of absorbing liquid, such as sponge, filter paper, polyester fiber, gel, non-woven fabric, cotton, polyester film, thread, etc. Of course, the material of the fluid sample injection area does not have to be made of a material with water absorption, and can be made of a non-water-absorbent material, but the absorbent element has holes, threads, holes, and these structures can collect samples, and these samples are generally solid or semi-solid samples, and these samples are filled between the threads, into the holes or holes to collect the samples. Of course, optionally the fluid sample injection area may be comprised of some non-absorbent fibers, hairs, which may hold solid, semi-solid or liquid samples when scraped off of these materials, and when detection is required, a buffer solution is added to the sample injection area to dissolve the sample, which then flows to the test or detection element.

[0028] In some embodiments, there is no need to manually inject a fluid sample into the sample injection area of ​​the test element of the present invention, which contacts the guide element, and under the action of the guide element, the liquid sample flows into the sample injection area, then into the marker area, and finally into the chemical examination or test. The present invention will be further described below with reference to specific examples.

[0029] Downstream and Upstream Downstream and upstream are divided according to the flow direction of the liquid, and generally, the liquid or fluid flows from the upstream to the downstream region. The downstream region is located to receive the liquid from the upstream region, and the liquid can also flow along the upstream region to the downstream region. Here, generally, the liquid is divided according to the flow direction of the liquid, for example, in some materials that utilize capillary force to promote the flow of the liquid, the liquid can overcome gravity and flow in the opposite direction to gravity, in this case, the upstream and downstream are 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 flows from the guide element to the sample injection region or sample injection pad of the two test elements, and then the liquid tau that flows into the sample injection pad flows into the downstream marker pad, then mixes with the marked marker substance, and flows through the transition pad to the downstream test pad, and in the test pad, the test region is located upstream of the test result control region, and finally flows into the absorption pad in the downstream absorption region. The test region can be a polyester fiber thin film, and the guide element can be a glass fiber, a polyester sheet, or a polyester thin film. In this case, the guide element is located upstream of the marker region of the test element. A specific structure of the test element is the structure shown by 20 in Figures 1 and 2. When a part of the sample injection pad is located on a slope and its position is lower than the marker pad, the liquid located on the sample injection pad flows from bottom to top mainly due to capillary action force, and the liquid located on the surface of the sample injection pad flows downward due to the action of gravity.

[0030] Gas or liquid communication Gas communication or liquid communication refers to a liquid or gas being able to flow from one location to another, passing through a physical structure that plays a guiding role in the flow process. The so-called "passing through a physical structure" refers to being passively or actively guided to another location through the surface of these physical structures or the internal space of these structures, where passive generally refers to flow by capillary action, flow by external force such as air pressure action, etc. As used herein, "flow" may refer to a liquid or gas being applied by its own action (gravity or pressure), or may be a passive flow, and the air pressure action of the fluid may be a forward flow, a reverse flow, or the air pressure action may encourage the fluid to flow from one location to another. As used herein, "communication" does not mean the presence of liquid and gas, but only indicates a connection relationship or state between two objects in some cases, and when a liquid exists, it can flow from one object to another object. As used herein, this refers to a state of connection between two objects; conversely, if there is no gas or liquid communication between two objects, and liquid is in or on one object, the liquid cannot flow into or on the other object, this state is a non-communicating, non-liquid or gas communication state.

[0031] Test element The so-called "test element" refers to an element for detecting whether a fluid sample or specimen (liquid sample or specimen) contains an analyte of interest, and this detection can be based on any technical principle, such as immunological, chemical, electrical, optical, molecular, nucleic acid, physical, etc. The test element can be selected as a lateral flow detection test strip, which can detect several analytes. Of course, other suitable test elements can also be used in the present invention. In the present invention, the terms test element, "lateral flow assay element or test strip" are used interchangeably, since they mean the same thing.

[0032] Various test elements can be combined and used in the present invention. One form is a detection test strip. Detection test strips for analyzing analytes in a sample (e.g., illegal drugs or metabolites indicative of a disease state) can be in various forms, such as immunoassays or chemical assays. Detection test strips can analyze in a non-competitive or competitive mode. In general, a detection test strip comprises an absorbent material with a sample injection area, a reagent area and a test area. A fluid or liquid sample is injected into the sample injection area and flows into the reagent area by capillary action. In the reagent area, if the analyte is present, the sample binds to the reagent. The sample then flows into the test area. Other reagents, such as molecules that specifically bind to the analyte, are immobilized in the detection area. These reagents react with the analyte in the sample (if present) and bind to the analyte in that area or bind to one of the reagents in the reagent area. A marker for indicating a detection signal is present in the reagent area or in a separate marker area.

[0033] In a typical non-competitive assay mode, a sample produces a signal if it contains the analyte and produces no signal if it does not contain the analyte, whereas in a competitive mode, a sample produces a signal if it does not contain the analyte and produces no signal if it does contain the analyte.

[0034] The test element may be a detection strip, and may be selected from absorbent or non-absorbent materials. The detection strip may include several materials for transporting liquid samples. One of the detection strip materials may be coated with another type of material, for example, a filter paper may be coated with a nitrocellulose membrane. One area of ​​the detection strip may be selected from one or more materials, and another area may be selected from one or more different materials. In order to improve the pinch strength of the detection strip, the detection strip may be attached to a support or hard surface.

[0035] The analyte is detected by a signal generating system, for example, by using one or more enzymes that react specifically with the analyte, or the method of immobilizing a specific binding substance on the detection test strip as described above, and a combination of one or more signal generating systems is immobilized in the detection area of ​​the detection test strip for the analyte. The substance that generates the signal can be in the sample injection area, the reagent area, or the detection area, or throughout the detection test strip, and the substance can flow sufficiently into one or more materials of the detection test strip. A solution containing the signal substance is injected onto the surface of the test strip, or one or more materials of the test strip are immersed in the solution containing the signal substance. The test strip to which the solution containing the signal substance has been applied is then dried.

[0036] The detection test strip or each area of ​​the lateral flow test strip of the present invention can be arranged according to the order of sample injection sample 205, marker area 204, detection area 202, and the detection area includes a test result area 206 and a detection result control area 207. The control area is located after or downstream of the detection area. All areas may be arranged on one test strip using only one material. Different areas may use different materials. Each area can be in direct contact with the liquid sample, or the different areas are arranged according to the flow direction of the liquid sample, connecting and overlapping the end of each area with the front end of another area. The materials used may be materials with good water absorption, such as filter paper, glass fiber, nitrocellulose membrane, etc. The detection test strip can use other forms.

[0037] Generally, a typical reagent strip is a nitrocellulose membrane reagent strip, i.e., the detection area includes a nitrocellulose membrane (NC) and shows the detection result by immobilizing a specific binding molecule on the nitrocellulose membrane, which may also be a cellulose acetate membrane or a nylon membrane, etc. For example, the following patent applications describe reagent strips or devices equipped with reagent strips: US 4857453, US 5073484, US 5119831, US 5185127, US 5275785, US 5416000, US 5504013, US 5602040, US 5622871, US 5654162, US 5656503, US 5686315, US 5766961, US 5770460, US 5916815, US 5976895, US 6248598, US 6140136, US 6187269, US 6187598, US 6228660, US 6235241, US 6306642, US 6352862, US No. 6,372,515, US 6,379,620 and US 6,403,383. The test strips and similar devices comprising test strips disclosed in the above patent applications may all be adapted for use in the test element of the present invention for detecting an analyte, such as detecting an analyte in a sample.

[0038] The detection reagent strip used in the present invention may be a normal lateral flow test strip, and the specific structure and detection principle of these detection reagent strips are well known to those skilled in the art. A normal detection reagent strip (FIGS. 1-2) includes a sample inlet region 205, a marker region 204, and a detection region 202, the sample collection region includes a sample receiving pad or a sample injection pad, and the marker region includes a marker pad. It may further include an absorbent region 201 for absorbing the liquid sample from the nitrocellulose membrane, and the absorbent region may include an absorbent pad. In some embodiments, the marker region includes colored particles coupled with an antibody, and the colored particles may be latex particles, gold particles, or dyes. The detection region 202 includes the necessary chemicals that can detect whether the analyte is contained, which are, for example, immunological reagents or enzyme chemical reagents. The sample injection region or sample injection pad 205 of the present invention does not directly accept the sample, but contacts the guide element 30 and accepts the liquid sample guided by the guide element. Thus, the guide element 30 covers a part of the sample injection area of ​​the present invention (FIG. 3B). In some embodiments, as shown in FIG. 2A, a transition pad 203 is also provided between the marker pad and the test pad of the test strip, which can slow down the flow of the liquid in the marker pad through the test pad, and the contact time between the liquid sample and the dried marker substance in the marker pad is longer, so that the reaction can be sufficiently carried out or the dried marker substance can be sufficiently dissolved in the liquid sample. Generally, a typical detection reagent strip is a nitrocellulose membrane reagent strip, that is, the detection area 202 includes a nitrocellulose membrane and an area 206 (T-line) that shows the detection result by immobilizing a specific binding molecule on the nitrocellulose membrane, and can also be a cellulose acetate membrane or a nylon membrane, etc., and of course, the downstream of the detection area further includes a detection result control area 207 (C-line), and usually the horizontal line that appears in the control area and the detection area is the detection line or the control line.Such a detection reagent strip may be a conventional reagent strip, or of course, another type of reagent strip that utilizes capillary action for detection. A typical detection reagent strip has dry chemical reagent components, such as immobilized antibodies or other reagents, and if there is liquid, the liquid flows along the reagent strip by capillary action, and in the flow, the dry reagent components dissolve in the liquid, thus processing the reaction of the dry reagent in the area in the next area and performing the required detection. The flow of the liquid is mainly performed by capillary action. Here, any of them can be applied to the detection device of the present invention, or placed in the detection cavity for contacting with the liquid sample, or used to detect the presence or amount of the analyte in the liquid sample that has entered the detection cavity.

[0039] Except for using the above test strip or lateral flow test strip itself to contact a liquid sample and test whether the liquid sample contains an 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 here is equivalent to the test element. For example, the fluid sample is mixed with a processing liquid and then directly detected by the test element. In the following specific description, when the receiving device processes the fluid sample, the test element can be used independently for detection.

[0040] Analyte Examples of analytes according to the present invention include a number of small molecule substances, including illegal drugs (e.g., drugs of abuse). "Drugs of Abuse (DOA)" refers to the use of drugs for non-medical purposes (usually acting to paralyze the nerves). Abuse of these drugs can lead to physical and mental damage, compulsive use, addiction, and / or death. Examples of drugs of abuse include cocaine, amphetamines AMP (e.g., black beauties, white amphetamine tablets, dextroamphetamine, dextroamphetamine tablets, Beans), methamphetamines MET (crank, N-methylamphetamine, crystal, speed), barbiturates BAR (e.g., Valium, Roche Pharmaceuticals, Nutley, New Jersey), sedatives (i.e., sleep aids), lysergic acid diethylamide (LSD), depressants (downers, goofballs, barbs, blue devils, yellow jackets, methaqualone), tricyclic antidepressants (TCAs, i.e. imipramine, amitriptyline, and doxepin), methylenedioxymethamphetamine (MDMA), phencyclidine (PCP), tetrahydrocannabinol (THC, pot, dope, hash, weed, etc.), opiates (i.e. morphine (MOP), or opium, cocaine (COC), heroin, oxycodone), anxiolytics, and sedative-hypnotics. Anxiolytics are drugs that primarily reduce anxiety, tension, and fear, stabilize emotions, and have a hypnotic and sedative effect, while benzodiazepines are drugs that primarily reduce anxiety, tension, and fear, stabilize emotions, and have a hypnotic and sedative effect. These include benzodiazepines (BZO), atypical BZ drugs, fused diazepines (NB23C), benzodiazepines, BZ receptor ligands, ring-opened BZ drugs, diphenylmethane derivatives, piperazine carboxylates, piperidine carboxylates, quinazolinones, thiazine and thiazole derivatives, other heterocyclic drugs, imidazole sedatives and analgesics (e.g., oxycodone OXY, methadone MTD), propylene glycol derivatives (urethane drugs), aliphatic compounds, anthracene derivatives, etc. The detection device of the present invention can also be used to detect overdoses of drugs that are easy to take but belong to medical uses, such as tricyclic antidepressants (imipramine or similar) and acetaminophen.After being absorbed into the human body, these drugs are metabolized into low molecular weight substances, and these low molecular weight substances are contained in body fluids such as blood, urine, saliva, and sweat, or are contained as part of the body fluids.

[0041] For example, analytes detected by the present invention include, but are not limited to, creatinine, bilirubin, nitrite, protein (non-specific), hormones (e.g., human chorionic gonadotropin, progesterone, follicle maturation hormone, etc.), blood, white blood cells, sugars, heavy metals or toxins, bacterial substances (e.g., proteins and carbohydrates for specific bacteria, such as E. coli 0157:H7, Staphylococcus aureus, Salmonella, Clostridium spp., Campylobacter spp., L. monocytogenes, Vibrio spp., or Bacillus cereus), and substances related to physiological properties such as pH and specific gravity in urine samples. Any other clinical chemical analysis can be detected by combining the lateral flow assay detection means with the device of the present invention. Also, the presence of viral antigens such as novel coronavirus antigens and influenza antigens can be detected.

[0042] Housing with test element In some embodiments, the test element may be placed on some support elements, such support elements containing the test element, and complete the detection and chemical testing of the analyte in the fluid sample. Thus, in some embodiments, the detection device includes a support, and the support is provided with the test element. In some embodiments, the support of the present invention is for supporting and housing the test element, and the support element itself does not participate in the function of direct detection, but is used as a support or housing for the supported and housed test element. In some embodiments, the housing or support of the present invention includes a channel structure, which is used to define the position of the test element on the support. The channel structure of this specification can be one or more. A test element is provided in each channel, and the test element can be used to test the number or presence of the analyte in the sample.

[0043] In some embodiments, Figs. 4-5 are structural schematic diagrams of the principle of the detection device of the present invention, the device includes a test element 20 located on a support, the support structure is generally located in a housing such as a lower housing. The support structure has a support area for supporting a sample injection area 205 of a test strip. Generally, the sample injection area is a sample injection pad 2051, which is a glass fiber sample injection pad, and the support structure for supporting the sample injection pad includes a first support area 60 and a second support area 61, the two support areas are arranged to support the entire sample injection pad 2051, where the second support area gradually slopes along one end of the first support area to form an inclined support area 61 with a gradually decreasing height, and the surface of the inclined support area 61 covers a part of the sample injection pad 2052. Thus, the sample injection pad is divided into two parts by the sample support structure, one part covers the surface of the inclined support area 61. The other part covers the first support area 60. The marker pad and a part of the sample injection area 2052 also cover the first support area, so that the marker pad, a part of the sample injection pad and the test pad are located in the same horizontal plane, and the other part of the sample injection pad is located in a slope. Of course, the sample injection pads described herein are generally attached to a non-bibulous backing, so that the sample injection pad does not directly cover the surface of the second support area, but indirectly covers the surface of the second support structure by the backing. Similarly, nitrocellulose can be attached to a non-bibulous backing as the detection pad, the marker pad with the marker substance and the bibulous pad. In some embodiments, when a single injection of sample is expected to detect multiple test elements simultaneously, the arrangement of the guide element 30 is necessary, which is connected to the two test elements to cover a part of the sample injection areas 2015, 205 of the first test element 20, the second test element 21, and a fluid passage is formed between the two test elements. In some embodiments, the guide element covers the inclined sample injection areas (FIG. 5) of the two test elements.It should be noted that the guide element 30 also covers the surface of the inclined second support area 61, but not directly, but covers the surface of the sample injection area 2052, and when two tests are connected, two test elements are provided in parallel, and the sample injection areas covered by the guide element 30 are located in the inclined second support area, respectively, and further, when two test strips are used, the support structures for supporting the two test strips are provided in parallel, and the support structures include a structure for supporting a part of the sample injection pad at an angle. In some embodiments, the sample injection area 40 is provided at the middle position of the guide area, and the fluid sample can be directly injected into the injection area of ​​the guide element, and the fluid sample flows from both sides of the guide element to the two test elements, thereby performing the detection of different analytes (FIG. 3B).

[0044] In the conventional similar devices, there are the following common problems: Due to the material of the guide element itself, the capillary fibers constituting the guide element are not uniformly distributed, and when the liquid is transported by the capillary action force, there is a speed difference, and at the same time, the thickness of the guide element is not consistent, so that the fluid injected into the injection region 40 and flowing into the two test elements is not uniformly distributed, for example, when 1 milliliter of liquid sample is injected, only 0.2 milliliters of liquid may flow into the test element 20, and the remaining 0.8 milliliters may flow into the test element 21 (in some extreme cases), thus the liquid in the test element 20 is not enough to complete the detection, and the liquid sample in the test element 21 is too much, which also affects the final detection result, for example, the flooding phenomenon occurs. Therefore, in order to overcome the problem of the uneven distribution of the fluid sample, the slope structure is arranged, which can significantly improve the problem of the uneven distribution of the fluid sample. In addition, there is a certain distance between the two test elements, the fluid injection area is directly located on the guide element, and the fluid injection area is not directly located on the sample injection area 2015 and 205 of the test element, when the liquid is injected into the sample receiving area of ​​the guide element, the liquid flows from the middle to both sides, the liquid flows upwards while located on the slope, if there is too much liquid, it flows from the middle to the lower area of ​​the guide element, and does not flow too much into the test strip; at the same time, in the inclined gradient structure, the flow speed of the liquid in the guide element is slowed down by the action of the gravity of the liquid itself, so the amount of liquid flowed into the sample injection area of ​​the test strip is stable; here, the sample injection area of ​​the test strip is shorter than the normal test strip, so the amount of liquid required is less, and the liquid flowed into the sample injection pad flows quickly to the marker pad, so not much sample is needed to flow into the test element, about 10 to 50 microliters per test strip is enough.A typical sample injection pad is an integrated member, and thus arranging the slope is the same as folding the sample injection pad, for example, the folding portion 2054, by fixing a portion 2052 of the sample injection pad to the slope, and by pressing the sample injection pad in the downstream region of the folding portion 2054, the folding structure slows down the flow rate of the liquid, so that when the sample is sufficient, the length of the sample injection pad itself is small, and the sample injection pad is folded to arrange a gradient, which slows down the flow rate of the liquid, so that the flow rate of the liquid matches over a short distance, and the liquid has more time to contact and dissolve with the dried marker substance downstream, and at the same time, the analyte of the sample reacts with the marker substance, improving accuracy.

[0045] In some embodiments, the guide element is further provided with a guide strip so that liquid dropped into the sample receiving area 40 of the sample guide element 30 can flow quickly to the test elements connected to both sides, and when the guide strip is pressed against the surface of the guide element 30, the guide element is brought into close contact only with the sample injection pad 2052 of the test element, and at the same time, the sample injection pad is brought into close contact only with the inclined support surface. The guide strip itself, such as a plastic strip, is not water-absorbent, but when it comes into contact with the surface of the guide element, a capillary structure is formed, which allows the liquid sample from the sample injection area of ​​the guide element to flow quickly to the test strips 21, 20 distributed on both sides. These guide strips may be located on an upper card, which has a sample injection hole that is located in the sample receiving area 40 of the guide element 30, with the guide strips distributed on both sides of the sample injection hole on the upper card, and the guide strips also located on the upper card, such that when the upper and lower cards are combined, the sample injection hole covers the sample receiving area 40 of the guide element, and the guide strips distributed on both sides of the hole are pressed into the surface of the guide element 30.

[0046] Each sample injection pad, marker pad, transition pad and water-absorbent pad of a typical reagent strip are all attached to a rigid paper backing, which has a certain rigidity and is vertical under natural conditions, and each of the above pads has water-absorbency, and when its wall becomes thin and a part of the sample injection area located on the backing is bent, it easily returns to the original vertical state (FIG. 4). In the present invention, it is expected that a part of the sample injection area or the sample injection pad will bend and cover the surface of the support structure 61. To achieve this purpose, the inner surface of the upper housing is provided with a protruding fixed nail, the length of which protrudes from the inner surface of the upper cover, and when the upper card and the lower card are combined, it can contact from the inner surface to the surface at the middle position of the slope (the position indicated by the arrow in FIG. 5), and thus the fixed nail applies pressure to the guide element and further applies pressure to the sample absorption pad, so that a part of the sample absorption pad is in close contact with the slope of the support area 61. A part of the sample injection area 2052 of the test element always maintains a tilt angle with respect to the position of the other part of the sample injection pad 2053, or the sample injection pad is bent to form two parts. The fixing nail method is the simplest, and naturally, adhesive is applied to the inclined surface, a part of the sample injection pad 2053 is attached to the surface of the inclined surface, and adhesive is also applied to the surface of the support area 61, thus forming a bend, but the operation process is complicated and disadvantageous to automated production.

[0047] In some embodiments, the present invention provides a device, which includes an upper housing 100 and a lower housing 200. The lower housing 200 includes a support structure for supporting a lateral flow assay element 20, 21, which is used to place a test element. The support structure includes a support structure unit 110 for supporting an absorbent paper, a support structure unit 117 for supporting a test pad, a support structure unit 108 for supporting a marker pad, and a support structure unit 180 for supporting a sample injection pad. In some embodiments, the support structures 106, 105 for supporting a part of the sample injection pad are located lower than the support structure 107 for supporting another part of the sample injection pad. Further, the provided test element includes a sample injection pad 205, a marker pad 2041, a test pad 207, and an absorbent pad 201, the sample injection pad 205 being in a folded form, and in some embodiments, the portion of the sample injection pad from the end to the folded portion 2054 is inclined, or the portion from the end to the folded portion 2054 is gradually higher. In some embodiments, in order to make the sample injection pad inclined, a support structure 180 for supporting the sample injection area is provided at the bottom of the lower card, the structure is partially inclined, and when a portion of the sample injection pad covers the surface of the inclined support structure, the portion of the sample injection pad is also inclined. 6, the support structure includes two support strips 107, 108 arranged symmetrically in parallel, each end of the support strip has a slope 106, 105, the angle of the two slopes 106, 105 is the same and arranged in parallel, when the lateral flow strip is placed on the support structure, one end with the sample injection area contacts a pair of limiting structures 128, 129, and the end with the absorbent pad contacts the limiting structure 112, thus the length of the reagent strip is determined by the distance between the protruding limiting structures 129 and 112. In this case, the whole test strip is placed on the support structure, the absorbent pad is placed on the support structure 110 of the absorbent area, the test pad, for example, the area of ​​nitrocellulose membrane is placed on the support structure 117 for supporting the test pad, and the area with the marker pad and the area with the sample injection pad are simultaneously placed on the support structure 108.The reason why one end of the support structure is inclined is that the sample injection pad is expected to cover the inclined surface 105, 106 of the support structure. In some embodiments, the total length of the inclined surface 106, 105 is about 1 / 3 or 1 / 2 of the total length of the sample injection pad. Thus, a part of the sample injection pad of the test element and the marker pad are located on the same horizontal plane, and a part of the sample injection pad of the end is located on the inclined surface, and the plane of the inclined surface and the marker pad have a folding region 190. In some embodiments, the sample injection pad located on the inclined surface is used to receive a liquid sample, and the so-called sample injection pad is not used to directly inject a sample, but is used to receive a liquid sample, for example, to receive a sample from a guide element and not directly receive an injected sample. As shown in Figures 6 and 8, the lower card is provided with two inclined structures and also provided with a pair of structures for supporting a test strip. In this way, the lower card may have two reagent strips arranged thereon, each capable of detecting an analyte, and the analytes detected in each test strip may be different, for example, one used to detect a novel coronavirus antigen and the other an influenza antigen, but may also include multiple parallel support structures to accommodate multiple test strips, and the sample injection pads or receiving pads for these tests are all connected by the covering of the guide element. In some embodiments, the lower card is provided with a sample diversion area 104, which is a rectangular area consisting of three enclosures 192, 122, 191 protruding upward from the bottom 193 of the lower card, with no enclosure on the opposite side of the enclosure 192, a support structure for supporting the sample injection area of ​​the test strip extends to the diversion area 104, and a slanted support structure is located within the diversion area, and a pair of slanted surfaces 105, 106 are also located in the diversion area 104, with the ends of the slanted surfaces being located near a limiting structure 129, which is a pair of structures 129, 130 formed by the inner wall of the enclosure 192 protruding outward, which structures limit the ends of the sample injection pad, and at the same time, the grooves formed between the protruding structures can also drain liquid.In some embodiments, the slope angle 132 ranges from 25 to 35, with the angle indicating the height of the slope.

[0048] In some embodiments, when two test strips are placed on the support structure, the guide element 30 is placed at the end position of the sample injection pads of the two test strips, and the dimension of the guide element 30 is the same as the dimension of the sample diversion 104 (FIG. 10), and thus the guide element covers a part of the sample injection 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, 105, so that after applying a certain pressure to the guide element, a part of the sample injection pad covers the inclined surfaces 106, 105, and as a result, both the guide element and the sample injection pad exhibit an inclination angle. As can be seen from FIG. 8, the test strips are distributed on both sides of the liquid diversion region 104, and the two test strips have a certain distance from the sample diversion region and are not close to each other. In some embodiments, the guide element is provided with a sample receiving region 40, which is located at the middle position of the two test strips, and the sample receiving region 40 is regarded as the center position of the guide element. Thus, from the viewpoint of physical structure, the liquid from the guide element can flow to two test elements, and it is expected that the volume of liquid flowing to each test strip is equal. In some embodiments, the sample injection area of ​​the guide element corresponds to the sample injection hole 204 of the upper housing 200, thus guiding the injected liquid sample to the sample receiving area 40 of the guide element, and then splitting it to two test strips by the sample injection pad. The sample receiving area 40 in the guide element 30 is provided at the middle position, and its advantages are as follows: As can be seen from FIG. 8, there is a blank area between the two test strips, and a recessed portion 193 is formed in the splitting area 104 due to the action of the support structure. When the sample is injected through the sample injection hole 204 in the upper card, if the amount of injected sample is large, the excess sample will be collected in the recessed areas 193 along the inclined guide element, and the liquid in these recessed areas will be far away from the test strip, so that it will not flow to the test strip, but will flow to the sample injection pad due to the obstruction effect of the protruding support structure due to the large amount of liquid, thereby reducing the occurrence of the flooding phenomenon. The reason is as follows.The guide element is rectangular and inclined, the liquid receiving area is in the center position, some liquid flows along the guide element under the action of capillary in the transverse direction to the lower card (direction indicated by the arrow in FIG. 10) and flows to the test elements on both sides, and the excess liquid flows along the longitudinal direction of the guide element (longitudinal direction of the lower card) (direction indicated by the arrow in FIG. 10) to the recessed area and does not flow to the test strip, the guide element is rectangular, the distance when flowing directly to the test element is long, and the distance when flowing to the recessed area is short, which is favorable for the flow of excess liquid, and the transverse flow mainly depends on the capillary action force. It is mainly considered that those detection devices are operated by inexperienced people, and the most common problem for inexperienced people is that the amount of liquid injected is too much, and although 2-3 drops, about 40-30 microliters, are required, the usual injection amount is 50-500 microliters, and in some cases 1 milliliter is injected. When arranged in this manner, excess sample collects in the recessed portion in the splitting region 104, and normal sample flows to the inclined sample injection regions of the lateral flow assay elements on both sides, which is a significant improvement over the conventional detection of multiple analytes in one sample. If the amount of sample is appropriate, the appropriate amount of sample flows from the sample receiving region 40 along the guide element to both sides and flows into the sample injection regions of the two test strips, respectively. Note that a part of the sample injection region of the test strip has an inclination angle, and another part of the sample injection region is at the same horizontal position as the marker pad and other test pads, and the position of the inclined sample injection pad is low, but the position of the marker pad is high. When the liquid sample flows into the inclined sample injection pad, the liquid actually flows from the low position to the high position, and if the sample injection pad is short, the flow rate of the liquid in the test strip is expected to be slow, and the liquid flows from the low position to the high position, and the flow rate is slowed under the action of gravity. In this way, when the liquid flows into the marker area, the contact time between the liquid and the dried marker material is increased, and thus, if the sample contains an analyte, the dissolved marker material has more time to react with the analyte and bind to it.During practical operation, it often happens that too much sample flows from the guide element 30 to the sample injection area, in this case, the length of the guide element is only 10-12 mm, the thickness is about 1-2 mm, and the total saturated liquid is about 10-15 microliters, when there is too much liquid, the excess liquid flows into the sample injection area, when there is an inclination angle, the excess liquid flows from the surface of the sample injection area to the lower position (gravity action) and does not flow to the higher position, the liquid flowing to the higher position is entirely dependent on the capillary action force. When liquid flows into a water-absorbing material with capillary action, it is expected that the liquid will move forward by capillary action, which is the basic principle and attribute of the lateral flow test strip, but when there is too much liquid, some liquid will move from upstream to downstream by capillary action, but the other part of the liquid located on the surface of the water-absorbing material (the capillary has been completely wetted) will actually flow naturally, and the flow rate is faster than the flow rate by capillary action. During actual detection, this problem occurs when the amount of sample injected is too large, so that the liquid on the surface reaches the reagent area early, especially the detection area in the test pad, and if this detection area has dried reagents such as antibodies or antigens and becomes wet early, the capillary action is completely lost, and the subsequent marker substance or marker mixture continues to move due to the loss of capillary action or is difficult to move to the detection area, resulting in erroneous results. For example, when liquid flows into the sample injection area, if there is too much liquid, some liquid will flow by capillary action force, and other liquid will flow directly on the surface of the injection area (not dependent on capillary action force), resulting in a faster flow rate; in the lateral flow assay, it is not expected to flow directly on the surface, but is expected to flow naturally by capillary action force, thus the accuracy of the detection result is higher. Because the flow rate of the liquid flowing on the surface is fast, it wets some downstream areas early, and the flow rate of the liquid dissolved in the dried reagent that flows due to capillary action is slowed down, causing the downstream areas to be wet early (the capillary action is completely lost or reduced), and the subsequent reagent cannot move or loses its ability to move, resulting in the liquid carrying the reagent not flowing or flowing at a low rate, and the amount of binding in the detection area being reduced, which affects the accuracy of the results.In fact, the guide element is used to directly receive the liquid sample, but there are problems: some liquid flows by capillary action, and when the amount of liquid is large, some liquid sample flows directly on the surface of the guide element, and the speed of the liquid flowing on the surface is faster than the speed of the flow by capillary action, so that the excess liquid flows into the sample injection pad, and too much liquid flowing into the sample injection pad will cause inaccurate detection results. The present invention uses an inclined guide element, and the remaining liquid flows into the recessed area of ​​the diversion area along the vertical direction of the lower card (arrow in FIG. 10). Here, the "recessed area" of the diversion area 104 may be a hole or recess arranged on the inner surface of the lower card to collect the liquid, or the position of the support structure is higher than the inner surface, and the recessed area is formed by the position of the bottom surface of the diversion area, and does not need to be intentionally manufactured.

[0049] In order to ensure that excess liquid in the guide element 30 flows to the recessed area, the enclosures 192, 122, 191 around the liquid splitting area 104 are all provided with protrusions, which fix the guide element so that it does not contact the enclosure, and between two protrusions there is a groove 1231, which can actually drain excess liquid sample to the recessed area. For example, in FIG. 8, the enclosure 122 of the guide area is provided with protrusions 125, 124, 123, and between two protrusions there is a groove, and the surface of the protrusion is in direct contact with the cross section of the guide element and directly contacts the side surface 290 of the sample injection area of ​​the test element (i.e. the thick side of the test element), thus fixing the test element, and excess liquid flows to the recessed area through the groove, but does not flow to the test element. The enclosure 191 also adopts this design, for example, several protrusions are provided, and between the protrusions there is a groove for draining excess liquid sample. At the end of the sample injection area of ​​the corresponding test strip in the enclosure 192 of the flow splitting area 104, a similar structure is arranged, which includes a pair of protrusions 129, 130 or protrusions 128, 1281, and grooves 198 and 199 between the pair of protrusions. These protrusions are arranged to prevent the test element from directly contacting the enclosure, and the grooves are mainly used to drain excess liquid from the test element or the guide element, and are mainly used to drain excess liquid in the guide element. In some embodiments, positioning pins 127, 126 are provided near the support structure, which are located near the support structure and are mainly used to accurately position the test strip on the support structure. In lateral flow assays, the cooperation between the upper and lower housings also has a significant impact on the specificity and accuracy of detection by the test strip, and in particular, some structures that affect the flow of liquid directly affect the detection performance of the test strip.

[0050] In some embodiments, in order to fix the sample injection area of ​​the test element in an inclined state by some structures of the upper card or cover the sample injection area on the surface 105, 106 of the inclined support structure, the upper card is provided with a structure of fixed needles 206, 205, the length of which is basically such that the fixed needles contact the inclined surface when the upper card and the lower card are assembled, thus the fixed needles push the guide element to make the guide element in an inclined state and at the same time make the sample injection area in an inclined position. Here, the fixed needle means "to push, apply pressure" and is used to apply pressure to the guide element and a part of the sample to cover them on the inclined support structure. The reason is as follows. Typically, when manufacturing a lateral flow test strip, the sample injection pad 205, marker pad 204, transition pad 203 (if necessary), test pad 207, and absorbent pad 201 are glued to a rigid cardboard; similarly, the sample injection pad is integrally molded, for example, a piece of glass fiber glued to the cardboard; thus, the test strip is placed on the support structure of the lower card, and part of the sample injection area is not naturally covered by the slope (Figure 4); when the guide element is covered to part of the sample injection pad of the two test elements, rather than naturally covering the slope, in this case, a certain pressure needs to be applied to overcome the repulsive force of the cardboard and bring the guide element and the sample injection surface into an inclined position. In some embodiments, guide strips 208, 207 are provided on both sides of the sample injection hole 204 of the upper card, which protrude from the inner surface of the upper card, and the surface of the guide strip also contacts the sample guide element 30 and is pressed against the surface of the guide element basically along the direction of the horizontal arrow in Figure 10, and the function of the guide strip is to flow the liquid in the guide element as quickly as possible to the sample injection area of ​​the test element, in particular the inclined sample injection area.

[0051] In some embodiments, the top card further includes a pressing marker pad, a transition pad, and an overlapping area between the sample injection pad and the marker pad, so that the liquid can flow smoothly to each sample injection pad. When the pressing bar presses the overlapping area between the marker pad 204 and the transition pad 203, it can slow down the flow rate of the liquid, extend the contact time between the liquid and the dry marker pad, and increase the reaction time. These pressing bars also make the test element in close contact with the support structure, and each area (marker area, sample injection area, test area) is located at the same horizontal plane. The top card further includes windows 214, 215 for reading and observing the test results on the test pads. In some embodiments, the upper card is further provided with several rivets 202, 201, 211, 210, 213, 212, which correspond to the rivet holes 102, 103, 108, 118, 119, 120 in the lower card, respectively, and by engaging these rivets with the rivet holes, the upper card and the lower card are assembled and fixed, so that the test strip is in a fixed position between the upper card and the lower card, and at the same time, by cooperation of the above-mentioned fixed needles 206, 205 and guide strips 208, 207, the sample injection area is in close contact with the surfaces 105, 106 of the inclined support structure, the guide strip is in contact with the surface of the guide element, and the sample injection hole 204 is located in the sample receiving area 40 at the center position of the guide element.

[0052] 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 support structure for the test element, the support structure includes a structure 810 for supporting an absorbent pad, a structure 801 for supporting a test pad, a structure for supporting a marker pad, and a structure 806 for supporting a part of a sample injection pad, and when detecting with two test strips, the sample injection areas of the two test strips (the sample area 806 of the first test strip and the sample injection area 805 of the second test strip) are overlapped across a diversion area 808, the support structures cross near the sample injection areas, and at the crossing site, there is a liquid diversion area 808, and the diversion area and the sample injection pad overlap at a common area 804. The overlapping common area 804 is used to receive a liquid sample. In this way, a single injection of the sample can detect different analytes. 11-12, the lower card 800 includes a support structure 801 for supporting a first reagent strip, and a region 803 of the injection pad of the sample of the support structure supporting the first reagent strip has a common region 804 for supporting a part of the sample injection pad of the second reagent strip, and a part of the sample injection pad of the first reagent strip and a part of the sample injection pad of the second reagent strip are provided at the overlapping position of the common region 804. In some embodiments, the sample injection pad is generally a glass fiber layer (in this case, a part of this region is unlined) having a thickness of 1-2 millimeters, and the two glass fiber layers overlap crosswise at the common region 804, and when the upper card and the lower card are assembled, the sample injection hole of the upper card is at the center position of the crossing region, and a part of the sample injection hole is located in the sample injection pad of the overlapping region, and the sample injection hole covers the non-overlapping sample injection regions of the two test strips uniformly or equidistantly. In this way, the liquid sample from the sample injection hole can uniformly contact the sample injection areas of the two test strips such that the obtained sample volumes are substantially equal.Similarly, the upper card also has a fixed needle 901, which is located in the overlapping area 804 of the sample test pad to fix the sample injection pad in a fixed position, and the upper card is further provided with push bars 903, 904 for applying pressure to the overlapping area of ​​the marker pad and the sample injection pad, and at the same time, two windows 906, 905 corresponding to the detection areas of the test strip are further provided. Example 1: Fabrication of a lateral flow detection device for detecting SARS-CoV-2 antigens and influenza A and B antigens in saliva using the immunoassay provided by the present invention

[0053] As shown in Figures 1, 3, 9 and 10, the lateral flow detection device for detecting SARS-CoV-2 antigens and influenza A+B antigens in saliva by immunoassay manufactured according to this embodiment includes a first test strip 21, which, according to the flow direction of the liquid, from upstream to downstream, is a sample injection pad 205, a marker pad 204, a test area 206 and a control area 207 (the test area 206 and the control area 207 are located on the nitrocellulose membrane 202), in which the marker pad has a first antibody specifically bound to the SARS-CoV-2 antigen and coupled gold particles, and the test area has a second antibody specifically bound to the SARS-CoV-2 antigen immobilized. Then, downstream of the marker pad, there is a transition pad 203, which is assembled according to the overlapping manner in Figure 2 to form a test strip for detecting SARS-CoV-2 antigens. The second test strip 20 for detecting influenza is identical in structure to the first test strip, except that only the test area is treated with a primary antibody mixture that specifically binds to influenza A+B antigens, and a secondary antibody specific for influenza A or B antigens is treated with a marker, all of which are coupled to gold particles.

[0054] Here, the sample injection pad of the test strip is 14 mm long and 4 mm wide, and the test strip is 4 mm wide and 2 mm thick. The guide element is 17 mm long and 6 mm wide, so that the width of the guide element covering the sample injection area of ​​each test strip is 6 mm, the width of the guide element not covering the sample injection area between the two test strips is 9 mm, and the distance between the two test strips is 9 mm. The length of the inclined surface provided on the lower plate to support a part of the sample injection pad is 6 mm. The upper card and the lower card are assembled, the sample injection hole is at the center position of the guide element, and the distance between the two test strips is 9 mm. The arrangement is as shown in FIG. 10, and then the upper card is put together to form the completed test device. The length of the liquid distribution area of ​​the lower card is the same as the length of the guide element, which is 19 mm, its width is 7 mm, its depth is 4 mm, and the height of the support structure is also about 4 mm, thus forming a recessed area, the depth of which is about 4 mm.

[0055] The marker area includes antibodies coupled to marker particles (e.g., gold particles, latex particles or dyes, or other colored marker substances), then the marker mixture is sprayed onto a polyester membrane by a spray device to produce a marker pad, in which the marker substance in the marker pad flows along with the liquid flow, and the detection area uses a nitrocellulose membrane, dissolving the antibody of the detection line in a buffer solution PBS, then drawing a line on the nitrocellulose membrane using a dot membrane device, then putting the nitrocellulose membrane into an oven to dry, in preparation for use, the antibodies processed on the membrane generally do not migrate.

[0056] A mixture of a positive novel coronavirus sample and a positive A+B saliva inactivated sample is used, and the lateral flow test results of these samples are positive, with the color intensity at the level of G3 (positive for novel coronavirus, positive for influenza) (compared to the standard color card arranged in the laboratory, G3 is positive, less than G3 is negative, and more than G3 is positive). A blank PBS solution is used as the negative control. Example 2

[0057] The differences from Example 1 are as follows: the lower card uses a conventional placement means, does not have an inclined support structure, but uses a structure with the same height as the support structure of the marker pad; in this example, the fixing nails in the upper card are eliminated, and other structures remain; in Examples 1 and 2, there is no groove structure around the enclosure, but there is a diversion area. Example 3

[0058] Compared with Example 1, three enclosed groove structures are added in the diversion area, and the specific number is the same as that shown in FIG. 8, and the structure is also the same.

[0059] The test process is as follows: In the different test groups, 20 samples are provided for each of the devices of Example 1 and Example 2, and then the standard samples are placed for laboratory testing. The test method is as follows: For each device, 40 microliters, 50 microliters, 100 microliters, 200 microliters, 500 microliters, and 1000 microliters of negative and positive samples are respectively aspirated by a pipettor, and then injected into the sample receiving area of ​​the guide element through the sample injection hole of the upper card, and the detection result is observed after 5 minutes.

[0060] Table 1. Results of positive samples JPEG2025007516000002.jpg167170

[0061] Note: G3 is a positive result, no C line means the test result is invalid, no T line means it does not match the actual result.

[0062] As can be seen from the flow conditions of each detection device in Examples 1 to 3, when the injected sample is 200 milliliters, the number of T lines does not increase, and all of these samples flow into the nitrocellulose membrane early to wet the T lines, and then the flow of the liquid with colored particles is blocked, and the liquid with colored particles flows out of the marker pad and begins to contact the nitrocellulose membrane, resulting in detection failure. When the amount of liquid is 500 microliters, in Example 1, only one has no C line and a T line, and because the amount of liquid is too large, the T line is shown, but the C line is not shown, indicating that the particle marker does not flow into the C line, which is considered to be an invalid structure; in Example 2, there are four invalid results; when the amount of sample is increased to 1 milliliter, in Example 1, there is one invalid result remaining, but in Example 2, there are eight invalid results, and two cannot be determined. For example 3, the liquid volume of 10 microliters to 1 milliliter can be effectively detected, which indicates that this design can control the amount of liquid in the range of 10 microliters to 1 milliliter, and the detection structure is not affected by the volume of liquid. It is practically meaningful for self-testing in the OCT market, and there will be less restrictions on people without professional training, and at least the amount of liquid sample is not limited and can be relatively freely used, so that the product for home testing will be more practical in practice.

[0063] Table 2 Positive control PBS solution JPEG2025007516000003.jpg172170

[0064] In terms of the negative results, both Example 1 and Example 3 can obtain accurate results, while Example 2 still has a different number of invalid results.

[0065] All patent applications and publications mentioned in the specification of the present invention indicate that they are techniques disclosed in the technical field and that the present invention can be used. All patent applications and publications cited in this specification are also incorporated by reference as if each publication were specifically and independently cited. The present invention described herein can be realized in the absence of one or more elements, one or more limitations, which are not specifically described herein. For example, the terms "comprise", "consist essentially of" and "consist of" in each example of the present specification can be replaced with the remaining two terms out of the three. In this specification, the so-called "one" only means "one", but does not exclude the inclusion of only one, and can also indicate the inclusion of two or more. The terms and expressions used in this specification are for the purpose of explanation and not for limitation, and there is no intention to indicate that the interpretation of these terms described in this specification excludes equivalent features, but it is understood that any suitable change or modification can be made within the scope of the present invention and claims. It should be noted that the embodiments described by the present invention are preferred embodiments and features, and therefore those skilled in the art may make some modifications and changes according to the essence of the description of the present invention, and these modifications and changes are also considered to be within the scope of the present invention and limited by the independent claims and dependent claims.

Claims

1. 1. An apparatus for detecting an analyte in a fluid sample, comprising: The device includes a housing having an upper card and a lower card; The lower card is provided with a support structure for supporting the lateral flow assay element; the lateral flow assay element is configured to detect an analyte in a liquid sample; the lateral flow assay element includes a sample application pad for receiving a liquid sample; and a support mechanism for supporting the sample application pad; An apparatus wherein a portion of the structure supporting the sample application pad is tilted.

2. The assay element further comprises a marker pad and a test pad; the marker pad is located downstream of a sample injection pad for receiving a liquid sample; The apparatus of claim 1 , wherein the structure supporting the remaining portion of the sample application pad and the structure supporting the marker pad are in a substantially horizontal position.

3. The apparatus of claim 2 , wherein the position of the inclined support structure is lower than the position of a support structure for supporting a marker pad.

4. the lateral flow assay element includes a first lateral flow assay element having a first sample receiving pad, and a second lateral flow assay element having a second sample receiving pad; the structure supporting the sample injection pad and having a portion that is inclined includes a first inclined support structure and a second inclined support structure; 4. The apparatus of claim 3, wherein a portion of the first sample receiving pad covers the first angled support structure and a portion of the second sample receiving pad covers the second angled support structure.

5. The first tilted support structure and the second tilted support structure are provided in parallel, The apparatus of claim 4 , wherein there is a gap therebetween.

6. The apparatus further comprises a liquid guiding element; 6. The device of claim 5, wherein the guide element is made of a bibulous material, the guide element covering a portion of the first sample receiving pad and a portion of the second sample receiving pad.

7. the bottom card further comprises a liquid sample diversion area; the first and second tilted support structures are located within the flow split region; The apparatus of claim 6 , wherein the first and second tilted support structures are distributed on opposite ends of the flow diverter region.

8. 8. The apparatus according to claim 7, wherein the guide element is parallel to the first and second tilted support structures or the guide element is also provided at an angle.

9. a region for receiving a liquid sample is provided at a central position of the guide element; The apparatus of claim 7 , wherein the region is located between a first tilted support structure and a second tilted support structure.

10. The device according to claim 7 , wherein the flow dividing region includes a recessed region, and liquid in the inclined guide element flows into and collects in the recessed region.

11. 11. The device of claim 10, wherein the upper card includes a hole for dropping a liquid sample, the hole being located in a sample receiving area in a guide element.

12. The device of claim 11 , wherein both sides of the sample injection hole of the upper card further comprise guide strips, the guide strips contacting a surface of the guide element.

13. The apparatus of claim 12 , wherein the guide strip contacts guide elements located on a first tilted support structure and a second tilted support structure.

14. 14. The apparatus of claim 13, wherein the upper card further comprises a push needle, the push needle being provided on guide elements of the first tilted support structure and the second tilted support structure so that the guide elements cover the sample injection pad.

15. The device according to claim 14, wherein the diversion area is made of an enclosure, the inner surface of which is provided with one or more grooves, for example, through which liquid in the guide element can flow to reach a recessed area at the bottom of the diversion area.

16. 16. The device of claim 15, wherein the sample injection pad is 14 millimeters long and 4 millimeters wide, and the guide element is 17 millimeters long and 6 millimeters wide, such that the width of the guide element covering the sample injection area of ​​each test strip is 6 millimeters and the distance between the two test strips is 9 millimeters.

17. 3. The apparatus of claim 2, further comprising a transition pad downstream of the marker pad, the transition pad being located between the test pad and the marker pad.

18. 5. The device of claim 4, wherein the first lateral flow assay element is used to test for a novel coronavirus antigen and the second lateral flow assay element is used to test for an influenza antigen.

19. The device of claim 2 , wherein the top card further comprises a window for exposing a detection area of ​​an assay element.

20. The device of claim 1 , wherein the liquid sample is blood, saliva, nasal fluid, laryngeal fluid or urine.

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