CN114441755A - Combined detection structure for double-sample sampling and integrated detection and application thereof - Google Patents

Combined detection structure for double-sample sampling and integrated detection and application thereof Download PDF

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Publication number
CN114441755A
CN114441755A CN202210116208.4A CN202210116208A CN114441755A CN 114441755 A CN114441755 A CN 114441755A CN 202210116208 A CN202210116208 A CN 202210116208A CN 114441755 A CN114441755 A CN 114441755A
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detection
sampling
saliva
sample
pad
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Chinese (zh)
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刘默文
刘杰
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Jiaxing Kangyuan Ketai Technology Development Co ltd
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Jiaxing Kangyuan Ketai Technology Development Co ltd
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Priority to CN202210116208.4A priority Critical patent/CN114441755A/en
Priority to PCT/CN2022/087799 priority patent/WO2023147713A1/en
Publication of CN114441755A publication Critical patent/CN114441755A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983Viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045Devices for taking samples of body liquids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045Devices for taking samples of body liquids
    • A61B10/0051Devices for taking samples of body liquids for taking saliva or sputum samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • G01N33/532Production of labelled immunochemicals
    • G01N33/533Production of labelled immunochemicals with fluorescent label
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/577Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08RNA viruses
    • G01N2333/165Coronaviridae, e.g. avian infectious bronchitis virus

Abstract

The invention discloses a combined detection structure for double-sample sampling and integrated detection, which is a combined set of a saliva sampling structure, a nasal cavity sampling structure and a chromatography detection structure, wherein the nasal cavity sampling structure is not only a collection structure of a nasal cavity object to be detected, but also a detection sample adding structure for detecting saliva and the nasal cavity object to be detected, the saliva sampling structure is not only a collection structure of the saliva object to be detected, but also a solvent liquid phase of the saliva object to be detected and a flowing liquid phase for detecting the object to be detected, and creative multifunctional design is carried out on the sampling structure. The invention can be used for developing various rapid immunoassay products such as colloidal gold, fluorescence immunity, latex microsphere immunity and the like, improves the detection efficiency, convenience and accuracy of the immunoassay products, and has important clinical significance.

Description

Combined detection structure for double-sample sampling and integrated detection and application thereof
The invention relates to the technical field of medical instruments, in particular to a combined detection structure for double-sample sampling and integrated detection and application thereof.
Background
The immunological detection technology is an experimental means for determining antigens, antibodies, immune cells, chemical components and the like by applying the immunological principle, and is widely applied to samples which are derived from human bodies and animal bodies and can be used for disease diagnosis and health detection and samples for environmental, pharmaceutical, food and industrial analysis. Commonly used are immunoturbidimetry, solid-phase enzyme immunoassay, chemiluminescence detection, immunofluorescence labeling, quantum dot immunoassay, colloidal gold immunoassay, spot immunoassay, etc. The development trend of clinical immunoassay technology products at present is high in sensitivity, rapidness, convenience, miniaturization, full quantification and automation, and is perfected through various technical innovations and technical improvements. The point-of-care testing (POCT) is one branch developed most rapidly at present, chromatographic immunoassay is the most common testing method, and the products of the colloidal gold, the fluorescence lateral flow chromatography immunoassay and the latex microsphere immunoassay are widely used, but the adopted methods are generally sampling tests of a single sample. As is known, the detection of a nasal swab or a forenose swab is an important sampling mode for most of respiratory infectious diseases at present, the virus load of a respiratory system is high, but the defects are acceptability and convenience for collection and use, and an extracting solution is required for pretreatment of a sample in the detection process. Saliva is also one of the test samples, but the viral load is lower than that of a nasal swab, and the positive detection rate of a case is influenced. Therefore, the technology for sampling and detecting saliva and nasal cavity double samples is developed, so that the superposition of the virus load in two collected samples can be realized, the saliva is made into an effective solvent for use through the optimization treatment of a detection system, the rapid detection without an extracting solution is further realized, the more excellent accuracy, convenience, rapidity and operational simplicity of the use of a detection reagent are realized, the popularization and the use of clinical detection products are facilitated, the diagnosis and treatment quality is improved, and the important application value is realized.
Disclosure of Invention
Compared with the prior art, the invention has the characteristics of high detection sensitivity, convenience, rapidness, pollution prevention and the like, and improves the detection quality.
In view of the above object, the present invention provides a combined detection structure for dual-sample sampling and integrated detection, which has the following features:
1) the combined detection structure is a combined set of a saliva sampling structure, a nasal cavity sampling structure and a chromatography detection structure;
2) the saliva sampling structure consists of a saliva collecting structure and a saliva collecting tube-like structure, and the saliva collecting structure and the saliva collecting tube-like structure are detachably connected;
3) the nasal cavity sampling structure consists of a sampling head and a sampling handle, and the sampling handle is provided with a sampling connecting structure which is used for fixing the sampling head and is detachably connected with the chromatography detection structure;
4) the chromatography detection structure comprises a detection shell, a detection reagent strip positioned in the detection shell and a detection connection structure positioned at a position corresponding to the starting end of the detection reagent strip.
In the above-mentioned combination detecting structure, the combination detecting structure further has the following features:
1) the combined suit formed by the saliva sampling structure, the nasal cavity sampling structure and the chromatography detection structure is a detachable structure;
2) the saliva sampling structure consists of a funnel-shaped saliva collecting structure with a large upper part and a small lower part and a test tube-shaped saliva collecting tube structure, and a detachable split structure is arranged between the saliva collecting structure and the test tube-shaped saliva collecting tube structure;
3) the nasal cavity sampling structure is an insertion structure that the sampling head is directly connected with the sampling handle and extends out of the sampling handle;
4) the detection reagent strip placed in the detection shell of the chromatography detection structure is directly connected and communicated with the detection connecting structure, and the detection connecting structure comprises a sampling head insertion inlet, an inner connecting structure capable of forming a sample collection channel in detachable connection with the sampling head, and an outer connecting structure capable of forming detachable connection with the sample adding connecting structure;
5) the detection reagent strip comprises a sample pad, a marker combination pad, a nitrocellulose membrane pad and a water absorption pad;
6) the inner connecting structure of the detection connecting structure comprises a cavity structure which can form liquid communication with the detection reagent strip, a detection reagent strip placing layer is arranged at the adjacent part of the inner connecting structure, the detection reagent strip is placed on the inner connecting structure, the sample pad is communicated with the cavity structure through a liquid flow opening, and the inner connecting structure is in liquid communication connection with the detection reagent strip through an insertion inlet of the sampling head, the sample collecting channel and the liquid flow opening of the cavity structure.
In the combined detection structure, the using state structure of the combined detection structure comprises a detection sampling using structure and a detection reaction using structure, wherein the detection sampling using structure is that the nasal cavity sampling structure for collecting the nasal cavity sample collection is placed into the saliva sampling structure for collecting the saliva sample, and is stirred and mixed to form a using state intermediate structure in which a double-sample mixture of the nasal cavity sample and the saliva sample is soaked and adsorbed on the nasal cavity sampling structure; the detection reaction use structure is to soak and adsorb the sampling head of the nasal cavity sampling structure which has the nasal cavity and saliva to be detected and samples, and then starts the use state intermediate structure of the detection reaction.
In the combined detection structure, the detection shell is of an upper and lower pressing type structure and comprises an upper cover and a base, the near end of the detection shell is of a detection connection structure, a support groove for placing a detection reagent strip is arranged on the base, a sample collection channel for squeezing and collecting a sample to be detected is arranged in an inner cavity of the upper cover, the detection reagent strip is arranged on the support groove and sequentially arrayed from near to far in directions of a sample pad, a marker combination pad, a nitrocellulose membrane pad and a water absorption pad, a liquid flow opening is formed in the near end of the sample collection channel and communicated with the sample pad of the detection reagent strip, an observation window is arranged on the upper cover and corresponds to the position of the nitrocellulose membrane pad of the detection reagent strip, and the near end of the pressing type structure is provided with a male-female insertion type connection structure. The detection structure end is male convex, the sampling structure end is female concave, or the detection structure end is female concave, and the sampling structure end is male convex.
Among the above-mentioned combination detection structure, the detection shell is cover barrel-shaped structure, including inner core and outer sleeve, the lateral surface of inner core is equipped with the support groove of placing the detection reagent strip, the inner chamber of inner core is equipped with and is used for the extrusion the sample collection passageway of examining the sample of examining that the sampling head was gathered, the detection reagent strip set up in on the support groove to sample pad, marker combination pad, nitrocellulose membrane pad and the direction of absorbing water pad are arranged by near and far in proper order the sample collection passageway with the near-end of supporting the groove is provided with the liquid stream trompil, communicates with each other with the sample pad of detection reagent strip, the outer sleeve is equipped with the observation window, with the position of the nitrocellulose membrane pad of detection reagent strip is corresponding, the near-end of cover barrel-shaped structure is provided with male-female inserted type detect connection structure. The detection structure end is male convex, the sampling structure end is female concave, or the detection structure end is female concave, and the sampling structure end is male convex.
In the combined detection structure, a plugging structure for preventing liquid phase backflow is arranged at the connecting part of the plug-in structure of the sampling head and the sampling handle, and a piston type movable sealing gasket structure made of elastic materials is preferably selected. The piston type dynamic sealing washer structure made of elastic materials such as rubber washers and silica gel washers is preferred.
In the combined detection structure, the sampling head is inserted into the sample collection channel through the detection connecting structure, extrusion is formed at the far end, and the near end of the outer sleeve structure is provided with a nesting plugging structure which is matched with the sampling structure and used for preventing liquid phase backflow, and a piston type dynamic sealing gasket structure prepared by elastic materials is preferred. The piston type dynamic sealing washer structure made of elastic materials such as rubber washers and silica gel washers is preferred.
In the above-mentioned combined detection structure, the saliva collecting structure is selected from a funnel structure, a folding type opening and closing structure or a telescopic type opening and closing structure.
In the above combined detection structure, the detection reagent strip is selected from at least one of a colloidal gold immunoassay, a fluorescence immunoassay and a latex microsphere immunoassay.
In the above combination detecting structure, the operation of the combination detecting structure comprises the following steps:
1) taking a saliva sampling structure, spitting saliva into a saliva collecting funnel-shaped structure, and collecting a saliva sample through a saliva collecting tube-shaped structure;
2) taking a nasal cavity sampling structure, and extending a sampling head into the nasal cavity to finish sampling;
3) the sampling head of the nasal cavity sampling structure which finishes sampling is placed into a saliva collecting tube sample structure to collect saliva samples, and the saliva samples are repeatedly stirred, uniformly mixed and soaked for absorption;
3) inserting a sampling head containing a double sample of saliva and nasal collection into a sample collection channel through an insertion inlet of the detection connection structure;
4) the liquid phase contained in the sampling head flows into a sample pad of the detection reagent strip through the liquid flow opening of the cavity structure, and then flows through the marker combination pad, the nitrocellulose membrane pad and the water absorption pad to finish detection;
5) the detection results are read from the observation window.
The utility model discloses a chromatography detection structure, including combination detection structure, saliva sampling structure, nasal cavity sampling structure, sampling head, stirring elution, soaking and absorption, combination detection structure's interconnect does saliva sampling structure gathers saliva sample, nasal cavity sampling structure gathers nasal cavity sample, and direct will gather there is nasal cavity sample the sampling head is put into to saliva collection sample in, and stirring elution and soaking absorb on nasal cavity sampling structure's the sampling head, will soak the sampling head that absorbs there are nasal cavity and saliva sample mixture direct through detect connection structure loading extremely in the chromatography detection structure, accomplish application of sample and testing process.
The sampling head is made of water-absorbing and water-insoluble materials, and comprises natural and modified high-molecular super absorbent resin and artificially synthesized water-absorbing resin, such as starch series, cellulose series, other natural product series, polyvinyl acid salt series, polyvinyl alcohol series, polyoxyethylene series and the like.
The combined detection structure comprises a detection assisting liquid phase, and the detection assisting solution is a water quality buffer salt solution of a non-denaturant.
The detection reagent strip is placed in the detection shell by selecting a structure of a sample pad, a marker combination pad, a filtering membrane pad, a nitrocellulose membrane pad and a water absorption paper pad which are sequentially adhered to a PVC negative.
Due to the adoption of the technical scheme, the invention has the following advantages:
1. the invention adopts a rapid detection structure for sampling and detecting saliva and nasal cavity double samples, and collects the saliva and nasal cavity double samples during detection, thereby obviously improving the positive detection rate of cases and the detection sensitivity of diseases, and not like the prior art which can only make articles on the aspect of improving the sensitivity of detection reagents in the market. As is known, the detection of a nasal swab or a forenose swab is an important sampling mode for most of respiratory infectious diseases at present, the virus load of a respiratory system is high, but the defects are acceptability and convenience for collection and use, and an extracting solution is required for pretreatment of a sample in the detection process. Saliva is also one of the test samples, but the viral load is lower than that of a nasal swab, and the positive detection rate of a case is influenced. According to the invention, saliva and nasal cavity double-sample sampling is adopted, so that the superposition of virus loads in two collected samples can be realized, and simultaneously, saliva is made into an effective solvent for use through optimization treatment of a detection system, so that the rapid detection without an extracting solution is realized, and the more excellent accuracy, convenience, rapidity and simplicity in operation of the detection reagent are realized.
2. The nasal cavity sampling structure is not only a collecting structure of a nasal cavity object to be detected, but also a detection sample adding structure for detecting saliva and the nasal cavity object to be detected, the saliva sampling structure is not only a collecting structure of the saliva object to be detected, but also a solvent liquid phase of the nasal cavity object to be detected and a flowing liquid phase for detecting the object to be detected, and creative multifunctional design is carried out on the sampling structure.
3. The saliva sampling structure is a funnel-shaped structure with a collecting pipe, so that saliva directly enters the collecting pipe after being spitted into the funnel, the operation is convenient, and the pollution is avoided.
4. The sampling structure comprises the sampling handle and the sampling head, wherein the sampling head has the double functions of sampling and detecting sample loading, and the sampling structure has the advantages of convenience in acquisition, sample transfer, sample loading safety and the like.
5. The detection connecting structure adopted by the invention is a structure that the sample collecting channel is adjacent to the reagent detection channel, and the starting end of the reagent strip is provided with a traffic structure for liquid phase flow, so that the sampling accuracy is ensured, and the structure and the detection function of the detection reagent strip are not influenced in the sampling process.
6. The invention adopts the detection test strip as a detection part, is suitable for various detection technologies which take lateral flow as main technical characteristics, such as colloidal gold, fluorescence immunoassay, latex microsphere immunoassay and the like, and expands the application range of the detection technology.
7. The invention is provided with the detection assisting liquid phase, can be used for samples with insufficient liquid phase, and improves the detection practicability.
8. The method has simple operation steps, is easy to realize household use or self-detection, is convenient to use, reduces the waste of raw materials, obviously improves the working efficiency, and is applied to various fields of professional and amateur detection.
Drawings
FIG. 1 is a schematic view of the overall structure of the present invention;
FIG. 2 is a schematic view of the connection between the components in the assembled state of the present invention;
FIG. 3 is a schematic diagram of a saliva sampling structure of the present invention;
FIG. 4 is a schematic view of a collapsible saliva sampling structure of the present invention;
FIG. 5 is a schematic diagram of a scalable saliva sampling structure of the present invention;
FIG. 6 is a schematic view of the detachable structure of the present invention in a vertical press-fit type;
FIG. 7 is a schematic view of a vertical press-fit longitudinal section structure according to the present invention;
FIG. 8 is a schematic view of the upper and lower contact type chromatography detection structure of the present invention;
FIG. 9 is a schematic view of a sleeve-like structure of the present invention;
FIG. 10 is a schematic view of a sleeve-like longitudinal section structure of the present invention;
fig. 11 is a schematic view of a sleeve-shaped detachable structure according to the present invention.
The figures are labeled as follows:
a nasal cavity sampling structure 1; a saliva sampling structure 2; a chromatographic detection structure 3; a saliva collecting structure 4; a saliva collecting structure 5; a sampling handle 6; a sampling connection structure 7; a sampling fixing structure 8; a sampling head 9; detecting the connection structure 10; a test reagent strip 11; an observation window 12; a detection housing 13; a detection connection sampling head insertion port 14; a composite sampling use structure 15; a detection reaction using structure 16, a saliva collecting tube cover 17, a foldable saliva collecting structure using state 18, a foldable saliva collecting structure storing state 19, a foldable saliva collecting structure using state 20, a foldable saliva collecting structure storing state 21, an upper and lower pressing type sampling structure handle 22, an upper and lower pressing type sampling fixing structure 23, an upper and lower pressing type detection connecting structure 24, an upper and lower pressing type detection cavity gap structure 25, an upper and lower pressing type sampling connecting structure 26, an upper and lower pressing type detection inner connecting structure 27, an upper and lower pressing type detection liquid flow opening 28, an upper and lower pressing type detection sample collecting channel 29, an upper and lower pressing type detection reagent strip bracket 30, an upper and lower pressing type chromatography detection structure cover 31, a detection reagent strip sample pad 32, a detection reagent strip marker combination pad 33, a detection reagent strip nitrocellulose membrane 34, a detection reagent strip water absorption pad 35, an up-down pressing type chromatography detection structure base 36, a sleeve-shaped detection structure handle 37, a sleeve-shaped detection sampling connection structure 38, a sleeve-shaped sampling fixing structure 39, a sleeve-shaped detection sampling plugging structure 40, a sleeve-shaped detection connection structure 41, a sleeve-shaped detection lacuna structure 42, a sleeve-shaped detection structure inner core 43, a sleeve-shaped detection structure outer sleeve 44, a sleeve-shaped detection reagent strip bracket 45, a sleeve-shaped detection sample acquisition channel 46 and a sleeve-shaped detection structure liquid flow opening 47.
Detailed Description
To further illustrate the technical means and effects of the present invention for achieving the predetermined purpose, the following embodiments are further described with reference to the accompanying drawings, but the present invention is not limited to the following description.
As shown in fig. 1 and 2, the overall structure of the invention comprises a nasal cavity sampling structure 1, a saliva sampling structure 2 and a chromatography detection structure 3, wherein the saliva sampling structure 2 comprises a saliva collecting structure 4 and a saliva collecting structure 5, the saliva collecting structure 4 is a funnel-shaped structure and is downwards connected with the saliva collecting pipe 5 in a detachable manner; the nasal cavity sampling structure 1 comprises a sampling handle 6, a sampling connecting structure 7, a sampling fixing structure 8 and a sampling head 9; the chromatography detection structure 3 comprises a detection shell 13, a detection connecting structure 10, a sampling head insertion opening 14, a detection reagent strip 11 and an observation window 12. During operation, a saliva sampling structure 2 is used for collecting saliva samples from the oral cavity through a saliva collecting structure 4 and collecting the saliva samples into a saliva collecting pipe 5, a nasal cavity sampling structure 1 is used for collecting nasal cavity samples from the nasal cavity through a sampling head 9, the sampling head 9 of the nasal cavity sampling structure 1 with the nasal cavity samples is directly placed into the saliva collecting pipe 5 with the saliva samples, stirring and elution are carried out, and a mixture of the saliva and the nasal cavity samples is soaked and absorbed on the sampling head 9 of the nasal cavity sampling structure 1, and the combined structure of the saliva sampling structure and the nasal cavity samples is also an intermediate state structure 15 when the saliva sampling structure is used, namely the sampling head 9 is soaked in a composite sampling connecting structure 15 in the saliva collecting pipe 5; then the sampling head 9 soaked and absorbed with the mixture of nasal cavity and saliva sample is taken out, and is directly inserted into the detection connecting structure 10 through the sampling head inserting opening 14, the mixed sample is further added to the detection reagent strip 11 in the chromatography detection structure 3, the detection reaction is started, and the detection process is completed, the combination structure of the sampling head 9 and the detection connecting structure is also an intermediate state structure 16 when the detection device is used for detection, namely the sampling head 9 of the nasal cavity sampling structure 1 is inserted into the detection connecting structure 10 through the sampling head inserting opening 14, and forms a stably connected composite detection connecting structure 16; and then the detection result is observed through the observation window 11, so that the integrated operation of double-sample adoption and detection is realized. The structure of the invention is an integrated structure, and double-sample sampling and detection are completed on the same structure.
As shown in fig. 3, 4 and 5, in the saliva collecting structure 4 and the saliva collecting structure 5 of the saliva sampling structure 2 of the present invention, the saliva collecting structure 5 is a tubular structure, and is provided with a saliva collecting tube cover 17 in addition to the saliva collecting tube 5; the saliva collecting structure 4 is a funnel-shaped structure, and the structure comprises a common funnel-shaped structure 4, a foldable opening and closing funnel-shaped structure 18 and a telescopic opening and closing funnel-shaped structure 20, and the detachable connection is formed downwards with the saliva collecting pipe 5. The shape of the general funnel shape 4 is relatively fixed and remains unchanged. The shape of the foldable opening-closing funnel-shaped part 18 comprises a folded storage type 19 and an unfolded using type 18, which are respectively used for transportation, storage and sampling. The shape of the collapsible opening-closing funnel 20 includes a storage type 21 in a folded state and a use type 20 in an unfolded state, which are used for transportation, storage and sampling respectively.
As shown in fig. 6, 7 and 8, the detection housing in the combined detection structure of the present invention is a top-bottom pressing structure, and includes an upper cover, a base, a detection reagent strip and a corresponding sampling structure, wherein the sampling structure includes a sampling handle 22, a sampling connection structure 26, a sampling head fixing structure 23 and a sampling head 9, and the sampling head 9 extends out of the sampling handle 22; the proximal end of the chromatography detection structure is a detection connecting structure 24, a base is provided with a bracket 30 for placing the detection reagent strip 11, the detection reagent strip 11 is arranged on the bracket 30, the directions of a sample pad 32, a marker combination pad 33, a nitrocellulose membrane pad 34 and a water absorption pad 35 are sequentially arranged from near to far, the front side of the detection connecting structure 24 is provided with a sampling head insertion hole 14, the inner cavity of an upper cover is provided with a sample collection channel 29 for squeezing and collecting a sample to be detected, the proximal end of the sample collection channel 29 is provided with a cavity structure 25 of a liquid flow opening 28, the cavity structure is communicated with the sample pad 32 of the detection reagent strip 11 through the liquid flow opening 28, the upper cover is provided with an observation window 12, the position of the nitrocellulose membrane pad 34 of the detection reagent strip 11 corresponds to the position, and the proximal end of the pressure-type detection structure is provided with male-female insertion type connecting structures 24 and 26. The detection structure end is male convex, the sampling structure end is female concave, or the detection structure end is female concave, and the sampling structure end is male convex.
As shown in fig. 9, 10 and 11, the detecting housing in the combined detecting structure of the invention is a sleeve-shaped structure, and includes an inner core, an outer sleeve and a corresponding sampling structure, wherein the sampling structure includes a sampling handle 37, a sampling connecting structure 38, a sampling head fixing structure 39 and a sampling head 9, and the sampling head 9 extends out of the sampling handle 37; the outer side of an inner core 43 of the chromatography detection structure is provided with a bracket 45 for placing a detection reagent strip 11, the inner cavity of the inner core 43 is provided with a sample collection channel 46 for extruding a sample to be detected collected by a sampling head 9, the detection reagent strip 11 is arranged on the bracket 45 and sequentially arranged from near to far in the directions of a sample pad, a marker combination pad, a nitrocellulose membrane pad and a water absorption pad, the proximal ends of the sample collection channel 46 and the bracket 45 are provided with cavity structures 42 of liquid flow open holes 47, the cavity structures are communicated with the sample pad of the detection reagent strip 11 through the liquid flow open holes 47, an outer sleeve 44 is provided with an observation window 12 corresponding to the positions of the cellulose membrane pad 34 of the detection reagent strip 11, the proximal end of a male-female insertion type detection connecting structure 41 is arranged at the proximal end of the male-female insertion type detection connecting structure, and a sampling head insertion hole 14 is arranged at the front side of the detection connecting structure.
Thus, in practical operation, when the rapid detection structure of the invention is a colloidal gold immunoassay structure, the detection reagent strip 11 is a test strip prepared by a colloidal gold method, and a sample pad 32, a colloidal gold binding pad 33 coated with a colloidal gold marker, a nitrocellulose membrane pad 34 coated with a non-marker capture reagent and a water absorbent paper pad 35 are sequentially stuck on a PVC support plate; when the rapid detection structure is a latex microsphere immunoassay structure, the detection reagent strip 11 is a test strip prepared by a latex microsphere immunoassay method, a sample pad 32, a latex microsphere bonding pad 33 coated with a latex microsphere marker, a nitrocellulose membrane pad 34 coated with a non-labeled capture reagent and a water absorption paper pad 35 are sequentially adhered on a PVC support plate, and the rapid detection structure is prepared in a combined set mode of a saliva sampler 2, a nasal cavity sampler 1 and a chromatography detection reagent card 3. When the device is used, the saliva sampler 2, the nasal cavity sampler 1 and the chromatography detection reagent card 3 are taken out of the combined suit, firstly the saliva sampler 2 is taken for collecting saliva, the nasal cavity sampler 1 is taken for collecting a nasal cavity sample, then the sampling head 9 of the nasal cavity collector 1 is placed into the saliva collecting pipe 5, the saliva mixture is stirred, mixed and absorbed onto the sampling head 9, then the sampling head 9 is inserted into the sample collecting channel 29 or 46 through the sampling insertion hole 14 and the internal connecting structure 27 or 41, at the moment, the sampling head 9 is extruded, the collected liquid phase mixed sample flows to the sample pad 32 of the detection reagent strip 11 through the liquid flow opening 28 or 47 of the lacuna structure, the detection reaction is started through the combination pad 33, the nitrocellulose membrane 34 and the absorbent paper pad 35, and then the detection result is read through the observation window.
Experimental study of the invention: the following experiment is illustrative of the detection method of the present invention and its effects, but is not intended to limit the present invention. The experimental methods used in the following experiments are all conventional methods unless otherwise specified. The materials, reagents and the like used are commercially available unless otherwise specified.
Experiment one: immune colloidal gold method new coronavirus antigen rapid detection experiment:
firstly, preparing a detection reagent strip:
preparing a detection reagent strip by adopting a conventional immune colloidal gold detection technology and a double-antibody sandwich method, and preparing a detection kit by adopting the combined detection structure to carry out a new coronavirus antigen detection experiment, wherein a colloidal gold label of a detection line T of the detection reagent strip indicates that an antibody is an anti-new coronavirus S protein monoclonal antibody of 10ug/ml, and colloidal gold particles with the particle size of 50nm are coated on a glass cellulose membrane colloidal gold combination pad; the capture antibody of the detection line T of the detection reagent strip is a 1.0mg/ml paired anti-new coronavirus S protein monoclonal antibody, and the capture antibody is coated on a nitrocellulose membrane; the capture antibody of the quality control line C of the detection reagent strip is a goat anti-mouse IgG polyclonal antibody of 1.0mg/ml, and the capture antibody is coated on a nitrocellulose membrane and used for capturing the colloidal gold labeled anti-new coronavirus S protein monoclonal antibody which is not captured specifically. And respectively sticking a water absorption paper membrane pad and a colloidal gold mark combined membrane pad at two ends of the nitrocellulose membrane printing membrane, and sticking a sample pad at one side of the combined membrane pad. And placing the adhered detection sheet on a strip cutting machine, and cutting into 3.5mm test strips.
Secondly, preparing a combined detection structure:
the upper cover, the base, the nasal cavity sampling structure and the folding saliva sampling structure of the combined detection structure are designed by Solidworks, samples are printed in a 3D mode, a sponge sampling head is pasted on a sampling head fixing structure, a small-sized storage tube for experiments is used as a saliva sampling collecting tube, and a combined detection structure sample is prepared for experiment detection.
Third, experimental method and result:
during the experiment, the prepared detection reagent strip and the combined detection structure are assembled into a detection buckle, the assembled detection buckle is placed into an aluminum amber sealing bag with a drying agent, the sealing is carried out on a sealing machine, and a label is added. Preparing two solutions to be detected, 1) preparing recombinant new coronavirus antigen S protein solutions with different concentrations by using saliva (saliva) of a healthy person; 2) preparing 3 times of the concentration of the recombinant new coronavirus antigen S protein solution with different concentrations in the solution 1) by using non-inactivated virus preservation solution (UTM). Two methods are respectively adopted for detection, wherein the method I comprises the following steps: taking 150ul of solution 1), adding the solution into a test tube, taking a nasal cavity sampling structure, collecting a nasal cavity sample of a healthy person, inserting a sampling head into the solution 1), stirring and absorbing the solution 1), then inserting the sampling head into a detection buckle card through an insertion hole, standing for 20 minutes, observing a detection window, and reading a color development result on a test strip. The second method comprises the following steps: taking 100ul of healthy human saliva without S protein, adding the saliva into a test tube, taking a nasal cavity sampling structure, collecting a healthy human nasal cavity sample, taking 50ul of solution 2) to a sampling head after nasal cavity sampling, inserting the sampling head into blank healthy human saliva, stirring and absorbing the blank healthy human saliva solution, then inserting the sampling head into a detection buckle card through an insertion hole, standing for 20 minutes, observing a detection window, and reading a color development result on a test strip. The quality control line C of the test strip is colored, and the test line T is not colored and is negative; the quality control line C is colored, and the detection line T is also colored and is positive. As a result, positive reactions were observed in the antigen S protein solution at concentrations of 1.0, 0.1 and 0.05ng/ml, while negative reactions were observed at concentrations of 0.01ng/ml and below.
Experiment two: a latex microsphere immunochromatography method for rapid detection of the antigen of the new coronavirus is as follows:
firstly, preparing a detection reagent strip:
preparing a detection reagent strip by adopting a conventional latex microsphere immunochromatography double-antibody sandwich method, and preparing a detection kit by adopting the combined detection structure to perform a new coronavirus antigen detection experiment, wherein latex microspheres are biological red microspheres of 300nm, and a latex microsphere mark indication antibody of a detection line T of the detection reagent strip is an anti-new coronavirus S protein monoclonal antibody of 50ug/ml, and is coated on a glass cellulose membrane combination pad; the capture antibody of the detection line T of the detection reagent strip is a 1.0mg/ml paired anti-new coronavirus S protein monoclonal antibody, and the capture antibody is coated on a nitrocellulose membrane; the capture antibody of the quality control line C of the detection reagent strip is a goat anti-mouse IgG polyclonal antibody of 1.0mg/ml, and the capture antibody is coated on a nitrocellulose membrane and used for capturing latex microspheres marked anti-new coronavirus S protein monoclonal antibodies which are not captured specifically. And respectively sticking a water absorption paper membrane pad and a latex microsphere mark combined membrane pad at two ends of the nitrocellulose membrane printing membrane, and sticking a sample pad at one side of the combined membrane pad. And placing the adhered detection sheet on a strip cutting machine, and cutting into 3.5mm test strips.
Secondly, preparing a combined detection structure:
prepared as in experiment one.
Third, experimental method and result:
during the experiment, the prepared detection reagent strip and the combined detection structure are assembled into a detection buckle, the assembled detection buckle is placed into an aluminum amber sealing bag with a drying agent, the sealing is carried out on a sealing machine, and a label is added. Preparing two solutions to be detected, namely 1) preparing recombinant new coronavirus antigen S protein solutions with different concentrations by using saliva (saliva) of a healthy person; 2) preparing 3 times of the concentration of the recombinant new coronavirus antigen S protein solution with different concentrations in the solution 1) by using non-inactivated virus preservation solution (UTM). Two methods are respectively adopted for detection, wherein the method I comprises the following steps: taking 150ul of solution 1), adding the solution into a test tube, taking a nasal cavity sampling structure, collecting a nasal cavity sample of a healthy person, inserting a sampling head into the solution 1), stirring and absorbing the solution 1), then inserting the sampling head into a detection buckle card through an insertion hole, standing for 20 minutes, observing a detection window, and reading a color development result on a test strip. The second method comprises the following steps: taking 100ul of healthy human saliva without S protein, adding the saliva into a test tube, taking a nasal cavity sampling structure, collecting a healthy human nasal cavity sample, taking 50ul of solution 2) to a sampling head after nasal cavity sampling, inserting the sampling head into blank healthy human saliva, stirring and absorbing the blank healthy human saliva solution, then inserting the sampling head into a detection buckle card through an insertion hole, standing for 20 minutes, observing a detection window, and reading a color development result on a test strip. The quality control line C of the test strip is colored, and the test line T is not colored and is negative; the quality control line C is colored, and the detection line T is also colored and is positive. As a result, positive reactions were observed in the antigen S protein solution at concentrations of 1.0, 0.1 and 0.05ng/ml, while negative reactions were observed at concentrations of 0.01ng/ml and below.

Claims (11)

1. The utility model provides a combination that double-sample sampling and integration detected detects structure which characterized in that:
1) the combined detection structure is a combined set of a saliva sampling structure, a nasal cavity sampling structure and a chromatography detection structure;
2) the saliva sampling structure consists of a saliva collecting structure and a saliva collecting tube-like structure, and the saliva collecting structure and the saliva collecting tube-like structure are detachably connected;
3) the nasal cavity sampling structure consists of a sampling head and a sampling handle, and the sampling handle is provided with a sampling connecting structure which is used for fixing the sampling head and is detachably connected with the chromatography detection structure;
4) the chromatography detection structure comprises a detection shell, a detection reagent strip positioned in the detection shell and a detection connection structure positioned at a position corresponding to the starting end of the detection reagent strip.
2. The composite detection structure of claim 1, wherein:
1) the combined suit formed by the saliva sampling structure, the nasal cavity sampling structure and the chromatography detection structure is a detachable structure;
2) the saliva sampling structure consists of a funnel-shaped saliva collecting structure with a large upper part and a small lower part and a test tube-shaped saliva collecting tube-like structure, and a detachable split-type structure is arranged between the saliva collecting structure and the test tube-shaped saliva collecting tube-like structure;
3) the nasal cavity sampling structure is an insertion structure that the sampling head is directly connected with the sampling handle and extends out of the sampling handle;
4) the detection reagent strip placed in the detection shell of the chromatography detection structure is directly connected and communicated with the detection connecting structure, and the detection connecting structure comprises a sampling head insertion inlet, an inner connecting structure capable of forming a sample collection channel in detachable connection with the sampling head, and an outer connecting structure capable of forming detachable connection with the sample adding connecting structure;
5) the detection reagent strip comprises a sample pad, a marker combination pad, a nitrocellulose membrane pad and a water absorption pad;
6) the inner connecting structure of the detection connecting structure comprises a cavity structure which can form liquid communication with the detection reagent strip, a detection reagent strip placing layer is arranged at the adjacent part of the inner connecting structure, the detection reagent strip is placed on the inner connecting structure, the sample pad is communicated with the cavity structure through a liquid flow opening, and the inner connecting structure is in liquid communication connection with the detection reagent strip through an insertion inlet of the sampling head, the sample collecting channel and the liquid flow opening of the cavity structure.
3. The combined detection structure of claim 1, wherein the usage state structure of the combined detection structure comprises a detection sampling usage structure and a detection reaction usage structure, wherein the detection sampling usage structure is that the nasal cavity sampling structure with the nasal cavity sample collection is placed into the saliva sampling structure with the saliva sample collection, and the nasal cavity sampling structure and the saliva sampling structure are stirred and mixed to form a dual-sample mixture of the nasal cavity sample and the saliva sample to soak the usage state intermediate structure adsorbed on the nasal cavity sampling structure; the detection reaction use structure is to soak and adsorb the sampling head of the nasal cavity sampling structure which has the nasal cavity and saliva to be detected and samples, and then starts the use state intermediate structure of the detection reaction.
4. The combined detecting structure of claim 1, wherein the detecting housing is a top-bottom pressing structure, and comprises an upper cover and a base, the proximal end of the detecting housing is the detecting connecting structure, the base is provided with a bracket for placing a detecting reagent strip, the inner cavity of the upper cover is provided with a sample collecting channel for squeezing and collecting a sample to be detected, the detecting reagent strip is arranged on the bracket and sequentially arranged from near to far in the directions of a sample pad, a marker combining pad, a nitrocellulose membrane pad and a water absorption pad, the proximal end of the sample collecting channel is provided with a liquid flow opening communicated with the sample pad of the detecting reagent strip, the upper cover is provided with an observation window corresponding to the position of the nitrocellulose membrane pad of the detecting reagent strip, and the proximal end of the pressing structure is provided with a male-female insertion type connecting structure.
5. The combined detection structure of claim 1, wherein the detection housing is a sleeve-shaped structure, and comprises an inner core and an outer sleeve, wherein a bracket for placing a detection reagent strip is arranged on the outer side surface of the inner core, a sample collection channel for extruding a sample to be detected collected by the sampling head is arranged in the inner cavity of the inner core, the detection reagent strip is arranged on the bracket and sequentially arranged from near to far in the directions of a sample pad, a marker combination pad, a nitrocellulose membrane pad and a water absorption pad, liquid flow holes are arranged at the proximal ends of the sample collection channel and the bracket and are communicated with the sample pad of the detection reagent strip, the outer sleeve is provided with an observation window corresponding to the position of the nitrocellulose membrane pad of the detection reagent strip, and the proximal end of the sleeve-shaped structure is provided with the detection connection structure of a male-female insertion type.
6. The combination detecting structure of claim 1, wherein the connection portion of the plug-in structure of the sampling head and the sampling handle is provided with a blocking structure for preventing liquid phase from flowing back, preferably a piston type dynamic sealing gasket structure made of elastic material.
7. The combination testing structure of claim 1 or 5, wherein the sampling head is inserted into the sample collection channel through the testing connection structure, and forms a squeeze at the distal end, and the proximal end of the outer sleeve structure has a matching nesting blocking structure for preventing liquid phase backflow, preferably a piston-type dynamic sealing gasket structure made of elastic material.
8. The composite test structure of claim 1, wherein said saliva collecting structure is selected from the group consisting of a funnel structure, a folding structure, and a telescopic structure.
9. The composite test structure of claim 1, wherein said test strip is selected from at least one of a colloidal gold immunoassay, a fluorescence immunoassay, and a latex microsphere immunoassay.
10. The composite detection structure as claimed in claim 1, wherein the operational use of said composite detection structure comprises the steps of:
1) taking a saliva sampling structure, spitting saliva into a saliva collecting funnel-shaped structure, and collecting a saliva sample through a saliva collecting tube-shaped structure;
2) taking a nasal cavity sampling structure, and extending a sampling head into the nasal cavity to finish sampling;
3) the sampling head of the nasal cavity sampling structure which finishes sampling is placed into a saliva collecting tube sample structure to collect saliva samples, and the saliva samples are repeatedly stirred, uniformly mixed and soaked for absorption;
3) inserting a sampling head containing saliva and a double sample of nasal collection into a sample collection channel through an insertion inlet of the detection connecting structure;
4) the liquid phase contained in the sampling head flows into a sample pad of the detection reagent strip through the liquid flow opening of the cavity structure, and then flows through the marker combination pad, the nitrocellulose membrane pad and the water absorption pad to finish detection;
5) the detection results are read from the observation window.
11. Use of the composite test structure of claim 1 in rapid test product development.
CN202210116208.4A 2022-02-07 2022-02-07 Combined detection structure for double-sample sampling and integrated detection and application thereof Pending CN114441755A (en)

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