Split type immunochromatographic detection device and immunochromatographic detection method

Abstract

The present invention provides a split immunochromatographic detection device and an immunochromatographic detection method. The split immunochromatographic detection device includes a first part and a second part. The first part includes a first shell and a sample pad disposed in the first shell and partially exposed from the first shell, the first shell is provided with a first liquid adding part, and the first liquid adding part is at least used to add a chromatographic fluid. The second part includes a second shell and a test strip disposed in the second shell. Among them, the first part is independent of the second part and can be connected to the second part in a detachable manner; when the first part is connected to the second part, the split immunochromatographic detection device can absorb the chromatographic fluid through the first liquid adding part, and the sample pad is in contact with the test strip. According to the solution of the present invention, the function of the sample pad is maximized, the steps of the sample pretreatment process and the consumables used are simplified, and the sensitivity and accuracy of the immunochromatographic detection are improved.

Description

Technical Field

[0001] The present invention relates to the field of detection technology, and in particular to a split-type immunochromatographic detection device and an immunochromatographic detection method. Background Art

[0002] Existing immunochromatographic detection devices generally include a base plate, on which a sample pad, a chromatographic membrane and a water-absorbing pad are sequentially overlapped. Immunochromatographic detection generally includes a sample pretreatment process and a chromatography process. Generally, the sample is pretreated, and the target object is converted into a test liquid (including a sample liquid and a chromatographic liquid) by various means, and then the sample pad at the front end of the immunochromatographic detection device is used to absorb the liquid and divert it to the chromatographic membrane for immune recognition. Therefore, the sample pad only plays a drainage role in the current immunochromatographic detection device. When necessary, some ingredients, such as SDS (sodium dodecyl sulfate), etc., will be soaked on the sample pad and dried to change its hydrophilicity and hydrophobicity, causing a change in flow rate, but the potential of the sample pad as a sample pretreatment tool has not been brought into play.

[0003] During the detection process, the commonly used sample pretreatment process includes steps such as extraction, concentration, enrichment and purification of the sample liquid. For simpler matrices, such as water, if the capture unit (antibody, nucleic acid aptamer, small molecule) used for detection is high, extraction can be exempted and direct sampling and detection can be performed; or if the capture unit has a strong anti-matrix effect and high sensitivity, it can also be directly detected in the obtained liquid sample. However, in most cases, due to the presence of more interfering substances in the matrix, in order to achieve more sensitive and accurate detection, sample pretreatment is generally required to remove the interfering substances and purify and concentrate the target. Sample pretreatment generally uses nitrogen / air purging, solid phase extraction, dialysis, ultrafiltration, etc., which requires consumables such as ultrafiltration columns, solid phase extraction columns, dialysis membranes, and equipment such as purging machines, centrifuges, and stirrers. The process also requires more manual operations and time, which is inconvenient. After the sample pretreatment process is completed, the obtained solution can be subjected to immunochromatography.

[0004] Therefore, it is necessary to provide a split-type immunochromatographic detection device and an immunochromatographic detection method to at least partially solve the problems existing in the prior art. Summary of the invention

[0005] In order to solve the above technical problems, the present invention proposes a split immunochromatographic detection device and an immunochromatographic detection method, aiming to solve the problem that the sample pretreatment process of immunochromatographic detection in the prior art has many steps and consumables and is inconvenient to use.

[0006] In a first aspect, a split-type immunochromatographic detection device is provided. The split-type immunochromatographic detection device comprises a first part and a second part. The first part comprises a first shell and a sample pad disposed in the first shell and partially exposed from the first shell, the first shell being provided with a first liquid adding portion, the first liquid adding portion being at least used for adding a chromatographic fluid. The second part comprises a second shell and a test strip disposed in the second shell. The first part is independent of the second part and can be connected to the second part in a detachable manner; when the first part is connected to the second part, the split-type immunochromatographic detection device can absorb the chromatographic fluid through the first liquid adding portion, and the sample pad is in contact with the test strip.

[0007] Preferably, the first shell is provided with a first clamping portion on the outer side, and the second shell is provided with a second clamping portion cooperating with the first clamping portion on the inner side, and when the first part is connected with the second part, the first clamping portion is clamped with the second clamping portion.

[0008] Preferably, the first shell includes a first upper cover, a first lower cover, a first sample pad protection block arranged at one end of the first upper cover, and a second sample pad protection block arranged at one end of the first lower cover, a portion of the sample pad is arranged between the first sample pad protection block and the second sample pad protection block, and the length of the first sample pad protection block is greater than or equal to the length of the sample pad extending out of the first upper cover, and the length of the second sample pad protection block is less than the length of the sample pad extending out of the first lower cover.

[0009] Preferably, the first shell further includes a third sample pad protection block arranged at the other end of the first upper cover and a fourth sample pad protection block arranged at the other end of the first lower cover, a portion of the sample pad is arranged between the third sample pad protection block and the fourth sample pad protection block and the sample pad can be exposed through the third sample pad protection block or the fourth sample pad protection block to absorb the chromatography fluid.

[0010] Preferably, the first liquid adding portion is arranged on the first upper cover, and the upper surface of the second shell is provided with a second liquid adding portion; when the first part is connected to the second part, the second liquid adding portion is located above the first liquid adding portion.

[0011] Preferably, the first liquid adding portion includes a liquid adding recess and an injection hole provided at the bottom of the liquid adding recess.

[0012] Preferably, the lower surface of the first sample pad protection block and / or the upper surface of the second sample pad protection block are provided with one or more first supporting members contacting with the sample pad and used for supporting the sample pad.

[0013] Preferably, a pressing structure is provided on the inner upper surface of the second shell, and when the first part is connected to the second part, the pressing structure presses the first sample pad protection block and the sample pad downwards, so that the sample pad and the test strip fit tightly.

[0014] Preferably, the first upper cover is provided with a plurality of first connecting members on the inner surface, and the first lower cover is provided with a plurality of second connecting members cooperating with the first connecting members and a sample pad positioning structure for positioning the sample pad on the inner surface; and / or the second shell includes a second upper cover and a second lower cover, the second upper cover is provided with a third clamping portion on the side edge and a plurality of third connecting members on the inner surface, the second lower cover is provided with a fourth clamping portion cooperating with the third clamping portion on the side edge and a plurality of fourth connecting members cooperating with the third connecting members on the inner surface.

[0015] Preferably, the second shell is provided with a mounting groove on the inner lower surface thereof, the shape of which matches the test strip, the test strip is installed in the mounting groove, and the second shell is provided with one or more second support members on the inner upper surface thereof for supporting the test strip.

[0016] Preferably, a heating element is arranged inside the first part, and the heating element is arranged above and / or below the sample pad.

[0017] In a second aspect of the present invention, an immunochromatographic detection method is provided. The immunochromatographic detection method uses the above-mentioned split immunochromatographic detection device. The immunochromatographic detection method includes: performing sample pretreatment through the independent first part; connecting the first part with the second part so that the sample pad contacts the test strip; and absorbing the chromatography liquid through the first liquid adding part to perform chromatography detection.

[0018] According to the solution of the present invention, by making the first part with the sample pad independent of the second part with the test strip, the independent first part is used for sample pretreatment, so that the target object is enriched and concentrated on the sample pad, thereby maximizing the use of the function of the sample pad, simplifying the steps and consumables used in the sample pretreatment process, and improving the sensitivity and accuracy of immunochromatographic detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Non-limiting and non-exhaustive embodiments of the present invention are described, by way of example, with reference to the following drawings, in which:

[0020] Figure 1 is a three-dimensional schematic diagram of a split-type immunochromatographic detection device according to an embodiment of the present invention;

[0021] Figure 2 yes Figure 1 An exploded perspective view of the first part of the split-type immunochromatographic detection device shown in FIG.

[0022] Figure 3a , 3b and 3c are Figure 2 A top view, a bottom view and a front side view of the first part shown in FIG.

[0023] Figure 4a yes Figure 2 A perspective view of a first upper cover of a first housing of the first part shown in FIG.

[0024] Figure 4b yes Figure 2 A perspective view of a first lower cover of a first housing of a first part shown in FIG.

[0025] Figure 5 yes Figure 1 An exploded perspective view of the first part of the split-type immunochromatographic detection device shown in FIG.

[0026] Figure 6 yes Figure 1 An exploded perspective view of the second part of the split-type immunochromatographic detection device shown in FIG.

[0027] Figure 7 yes Figure 6 A bottom perspective view of the second upper cover of the second part shown in FIG.

[0028] Figure 8 is a three-dimensional diagram of a first part of a split-type immunochromatographic detection device according to another embodiment of the present invention; and

[0029] Fig. 9 It is a schematic flow chart of an immunochromatographic detection method according to an embodiment of the present invention. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0031] In a first aspect of the present invention, a split-type immunochromatographic detection device is provided. Figure 1 1 is a three-dimensional schematic diagram of a split-type immunochromatographic detection device 10 according to an embodiment of the present invention. Figure 2 yes Figure 1 FIG. 2 is an exploded perspective view of the first part 100 of the split-type immunochromatographic detection device 10 . Figure 3a , 3band 3c are Figure 2 1 and 2 , show a top view, a bottom view and a front side view of the first part 100 . Figure 4a yes Figure 2 1 is a perspective view of the first upper cover 111 of the first shell 110 of the first part 100. Figure 4b yes Figure 2 1 is a perspective view of the first lower cover 112 of the first shell 110 of the first part 100 shown in FIG. Figure 5 yes Figure 1 FIG. 2 is an exploded perspective view of the first part 100 of the split-type immunochromatographic detection device 10 . Figure 6 yes Figure 1 FIG. 2 is an exploded perspective view of the second part 200 of the split-type immunochromatographic detection device 10 . Figure 7 yes Figure 6 FIG. 2 is a bottom perspective view of the second upper cover 211 of the second part 200 shown in FIG. Figure 8 1 is a three-dimensional diagram of a first part 100 ′ of a split-type immunochromatographic detection device according to another embodiment of the present invention.

[0032] The following will first combine Figures 1 to 7 A split-type immunochromatographic detection device 10 according to an embodiment of the present invention is described in detail.

[0033] like Figure 1 , Figure 2 and Figure 6 As shown, the split-type immunochromatographic detection device 10 includes a first part 100 having a sample pad 120 and a second part 200 having a test strip 220 . Figure 1 The first part 100 and the second part 200 are shown in a connected state, but the first part 100 and the second part 200 are independent parts. When necessary, for example, when the first part 100 is required to perform sample pretreatment, the first part can be disassembled from the second part 200. That is, the first part 100 of the split-type immunochromatographic detection device 10 is independent of the second part 200 and can be connected to the second part 200 in a detachable manner.

[0034] By making the first part 100 with the sample pad 120 independent of the second part 200 with the test strip 220, the sample pre-treatment is performed using the independent first part 100, and the sample liquid containing the sample can be adsorbed onto the sample pad 120 of the first part 100, and then concentrated in volume by drying, evaporation, heating and drying, etc., so that the liquid adsorbed by the sample pad can be concentrated on the sample pad at a volume multiple times larger than that of the sample pad liquid, thereby aggregating the target on the sample pad and increasing the concentration. After being subsequently connected to the second part 200 with the test strip 220, the concentration of the target in the chromatography process can be greatly increased, thereby improving the detection sensitivity.

[0035] Specifically, Figure 2 As shown, the first part 100 includes a first shell 110, a sample pad 120 as described above, and a first liquid adding part 130. The sample pad 120 is arranged in the first shell 110. A portion of the sample pad 120 (for example, one end close to the test strip 120) is exposed from the first shell 110 so that it can contact the test strip 120 when the first part 100 is connected to the second part 200 to perform chromatographic detection. The portion of the sample pad 120 exposed from the first shell 110 can also be used to adsorb the sample liquid. The first shell 110 can protect the sample pad 120 to prevent the sample pad 120 from being contaminated during operation, and make the first part 100 more convenient to use. The first liquid adding part 130 is opened in the upper surface of the first shell 110 and is configured to at least be used to add chromatography liquid. It should be noted that, if necessary, the sample liquid can also be added dropwise through the first liquid adding part 130. In this embodiment, as Figure 3a As shown, the first liquid adding part 130 includes a liquid adding recess 131 and an injection hole 132 disposed at the bottom of the liquid adding recess 131. The horizontal cross-sections of the liquid adding recess 131 and the injection hole 132 may be any suitable shape such as a circle, a square, etc. Preferably, the injection hole 132 is disposed at the center of the bottom of the liquid adding recess 131. The liquid adding recess 131 is configured to store the test liquid when the test liquid is added, so that the test liquid flows into the injection hole 132 along the bottom of the liquid adding recess 131, thereby reducing the waste of the test liquid.

[0036] like Figure 6As shown, the second part 200 includes a second housing 210, a test strip 220 as described above, and a second liquid adding part 230. The test strip 220 is arranged in the second housing 210, and the second housing 210 can protect the test strip 220 to prevent the test strip 220 from being contaminated during operation, and make the second part 200 more convenient to use. Specifically, the test strip 220 is installed at the inner lower surface of the second housing 210, and the test strip 220 includes a bottom plate (not shown), an absorbent pad 221 and a chromatographic membrane 222, and the absorbent pad 221 and the chromatographic membrane 222 are overlapped on the bottom plate, and the absorbent pad 221 and the chromatographic membrane 222 are arranged facing upward. Preferably, the chromatographic membrane 222 is a nitrocellulose (NC) membrane, which is a carrier of the quality control line (C line) and the detection line (T line), and the place where the immune reaction occurs. Additionally, the test strip 220 also includes a nano gold particle pad or a fluorescent microsphere pad. The second liquid adding part 230 is opened in the upper surface of the second housing 210 and is configured to be used for adding the chromatographic liquid. When the first part 100 is connected to the second part 200, the second liquid adding part 230 is located above the first liquid adding part 130 to avoid the second liquid adding part 230 being blocked by the first housing 110, so that when the chromatographic liquid is added, the chromatographic liquid can pass through the second liquid adding part 230 and the first liquid adding part 130 to reach the sample pad 120, that is, the chromatographic liquid is absorbed by the second liquid adding part 230 and the first liquid adding part 130. Preferably, the second liquid adding part 230 coincides with the liquid adding concave part 131 (if any) of the first liquid adding part 130, and the liquid can pass through the second liquid adding part 230 and flow into the injection hole 132 along the bottom of the liquid adding concave part 131 of the first liquid adding part 130. The specific antibody is fixed on the NC membrane in the form of a strip. After the target is enriched and concentrated on the sample pad 120 by using the first part 100 for sample pretreatment, the first part 100 is connected to the second part 200, and the chromatography liquid is added through the second liquid adding part 230 and the first liquid adding part 130. The chromatography liquid flows from the sample pad 120 to the nanogold particle pad or the fluorescent microsphere pad, dissolves the labeled reagent on the nanogold particle pad or the fluorescent microsphere pad, and reacts with each other. When it moves to the area of ​​the fixed antibody, the complex of the target and the labeled reagent specifically binds to it and is intercepted, and gathers on the detection line, and an intuitive color development result is obtained through a visually observable marker. In this embodiment, the second shell 210 is provided with an observation window 240 on the upper surface, and the observation window 240 is configured to observe the color change of the chromatography membrane 222 of the test strip 220 during the chromatography process. In other embodiments not shown in the present invention, the second shell 210 may not include an observation window, but may be made of a transparent material so that the tester can observe the color change of the chromatographic membrane 222 of the test strip 220 during the chromatography process through the transparent second shell 210.

[0037] In this embodiment, the first housing 110 of the first part 100 is provided with a first clamping portion 140 on the outer side. Figures 2 to 5 The second housing 210 of the second part 200 is provided with a second clamping portion 250 on the inner side thereof that cooperates with the first clamping portion 140, as shown in FIG. Figure 6 to Figure 7 As shown. When the first part 100 is connected to the second part 200, the first clamping portion 140 is clamped with the second clamping portion 250, and the sample pad 120 is in contact with the test strip 220 (specifically, in contact with the chromatographic membrane 222 of the test strip 220). Since the sample pad 120 is in contact with the chromatographic membrane 222 of the test strip 220, the sample liquid and the chromatographic liquid on the sample pad 120 can flow onto the chromatographic membrane 222 of the test strip 220 to perform chromatographic detection. In the present embodiment, the first clamping portion 140 is a protrusion and the second clamping portion 250 is a recess. Alternatively, the first clamping portion 140 can also be a recess and the second clamping portion 250 is a protrusion accordingly. In other embodiments not shown in the present invention, the first part 100 can also be connected to the second part 200 in other ways, such as interference fit, lock connection, etc.

[0038] In this embodiment, if Figures 2 to 5 As shown, the first housing 110 includes a first upper cover 111 and a first lower cover 112, and the first liquid adding part 130 as described above can be arranged on the first upper cover 111. In addition, the first housing 110 also includes a first sample pad protection block 121 arranged at one end of the first upper cover 111 and a second sample pad protection block 122 arranged at one end of the first lower cover 112, and a part of the sample pad 120 is arranged between the first sample pad protection block 121 and the second sample pad protection block 122. The sample pad protection block is used to protect the sample pad 120 from being bent or damaged during production, transportation, and use, and to support the sample pad 120 during use. The length of the first sample pad protection block 121 is greater than or equal to the length of the sample pad 120 extending out of the first upper cover 111, and the purpose is: when the sample pad 120 is placed in the sample cup to absorb the sample liquid, the first sample pad protection block 121 can effectively support the sample pad and bear the weight of the entire first part 100, thereby preventing the sample pad 120 from bending and deforming. The length of the second sample pad protection block 122 is less than the length of the sample pad 120 extending out of the first lower cover 112, so that the second sample pad protection block 122 will not completely cover the sample pad 120, and a portion of the sample pad 120 can be exposed from the first shell 110. The purpose is: when the sample pad 120 is placed in the sample cup to absorb the sample liquid, the portion of the sample pad 120 exposed outside the second sample pad protection block 122 can fully contact with the sample liquid, thereby improving the absorption efficiency of the sample liquid.

[0039] Preferably, if Figure 4a and Figure 4bAs shown, one or more first supporting members 160 are provided on the lower surface of the first sample pad protection block 121 and / or the upper surface of the second sample pad protection block 122, and the first supporting member 160 contacts the sample pad 120 and is used to support the sample pad 120. In this embodiment, the first supporting member 160 may be a protrusion, which also serves to separate the first sample pad protection block 121 and / or the second sample pad protection block 122 from the sample pad 120, thereby preventing the sample liquid from flowing into the interior of the first housing 110 along the ends of the first sample pad protection block 121 and the second sample pad protection block 122 close to the first upper cover 111 and the first lower cover 112, thereby preventing the interior of the first housing 110 from being contaminated, and ensuring that the sample liquid is better adsorbed on the sample pad 120, and the target can be better concentrated and enriched on the sample pad 120.

[0040] In this embodiment, if Figure 6 to Figure 7 As shown, the second housing 210 includes a second upper cover 211 and a second lower cover 212. The second housing 210 is provided with a mounting groove 261 on the inner lower surface thereof, the shape of which matches the test strip 220, and the test strip 220 is installed in the mounting groove 261, wherein the absorbent pad 221 and the chromatographic membrane 222 are arranged facing upward. Accordingly, the second housing 210 is provided with one or more second support members 262 on the inner upper surface thereof for supporting the test strip 220. Specifically, the mounting groove 261 is provided on the inner surface of the second lower cover 212, and the second support member 262 is arranged on the inner surface of the second upper cover 211.

[0041] In the traditional two-step chromatography detection device, after the sample liquid is concentrated, it is added to a gold cup containing gold nanoparticles, and then inserted into the chromatography detection device for chromatography. In order to ensure the smooth progress of the chromatography process, several times (generally 3-5 times) of the liquid volume is usually added to the gold cup. Due to the limited amount of liquid adsorbed by the sample pad, there will be residual liquid in the gold cup, that is, part of the sample liquid containing the target object is not effectively utilized, which dilutes the target object in disguise. Moreover, the amount of liquid adsorbed by the sample pad from the gold cup will be different each time due to the influence of environmental humidity, which will affect the repeatability of the chromatography detection device. In the present invention, after the sample pad is combined with the test strip, the chromatographic liquid is directly added to the sample pad through the second liquid adding part and the first liquid adding part, and the required liquid volume is less (the concentration of the target object can be increased), and all liquids will be chromatographed, that is, all liquids are effective chromatography liquids, and the repeatability will be better.

[0042] Preferably, a pressing structure 270 is provided on the inner upper surface of the second housing 210. Figure 7As shown, the pressing structure 270 is disposed on the inner surface of the second upper cover 211. When the first part 100 is connected to the second part 200, the portion of the sample pad 120 exposed to the first housing 110 through the second sample pad protection block 122 contacts the test strip 220 (specifically, contacts the chromatographic membrane 222 of the test strip 220) above the test strip 220 (specifically, above the chromatographic membrane 222 of the test strip 220). The pressing structure 270 of the second part 200 presses the first sample pad protection block 121 of the first part 100 downwardly and then presses the sample pad 120 below the first sample pad protection block 121 to bend the sample pad 120, so that the sample pad 120 is closely matched with the test strip 220 (specifically, closely matched with the chromatographic membrane 222 of the test strip 220), so as to better realize the chromatographic flow of the test liquid from the sample pad 120 to the chromatographic membrane 222 of the test strip 220.

[0043] In an embodiment not shown in the present invention, the length of the first sample pad protection block 121 may also be less than the length of the sample pad 120 extending out of the first upper cover 111, and the length of the second sample pad protection block 122 is correspondingly greater than or equal to the length of the sample pad 120 extending out of the first lower cover 112, and the sample pad 120 is exposed from the upper first sample pad protection block 121. In this case, in the second part 200, the second liquid adding part 230 is arranged in the same manner as in the aforementioned embodiment, that is, the second liquid adding part 230 is still arranged in the upper surface of the second housing 210, so that the chromatographic liquid can pass through the second liquid adding part 230 and the first liquid adding part 130 to reach the sample pad 120, but the test strip 220 is installed on the inner upper surface of the second housing 210, and the absorbent pad 221 and the chromatographic membrane 222 are arranged facing downward. Accordingly, the second part 200 is provided with a pressing structure, which is arranged on the inner lower surface of the second housing 210. When the first part 100 is connected to the second part 200, the portion of the sample pad 120 exposed from the first housing 110 through the first sample pad protection block 121 contacts the test strip 220 (specifically, contacts the chromatographic membrane 222 of the test strip 220) below the test strip 220 (specifically, below the chromatographic membrane 222 of the test strip 220). The pressing structure of the second part 200 presses the second sample pad protection block 122 of the first part 100 upwards and then presses the sample pad 120 above the second sample pad protection block 122 to bend the sample pad 120, so that the sample pad 120 is closely matched with the test strip 220 (specifically, closely matched with the chromatographic membrane 222 of the test strip 220), so as to better realize the chromatographic flow of the test liquid from the sample pad 120 to the chromatographic membrane 222 of the test strip 220. Correspondingly, the observation window 240 can be opened on the lower surface of the second shell 210. After the chromatography liquid is added through the second liquid adding part 230 and the first liquid adding part 130, the split immunochromatographic detection device 10 can be turned over to observe the color change of the chromatography membrane 222 of the test strip 220 through the observation window 240.

[0044] Preferably, if Figure 4a and Figure 4bAs shown, the first upper cover 111 is provided with a plurality of first connecting members 181 on the inner surface, and the first lower cover 112 is provided with a plurality of second connecting members 182 matched with the first connecting members 181 on the inner surface. The first connecting members 181 and the second connecting members 182 are configured to combine the first upper cover 111 with the first lower cover 112 in a detachable manner, so that the sample pad 120 can be directly taken out from the first housing 110 when the sample pad 120 absorbs the sample liquid, and the sample pad 120 is assembled into the first housing 110 after the sample liquid is absorbed. The first lower cover 112 is also provided with a sample pad positioning structure 171 for positioning the sample pad 120 on the inner surface. The sample pad positioning structure 171 can be a U-shaped member, and the sample pad 120 is positioned in the opening of the U-shaped member. Alternatively, in other embodiments not shown in the present invention, the sample pad positioning structure for positioning the sample pad 120 can also be provided on the inner surface of the first upper cover 111.

[0045] Preferably, if Figure 6 to Figure 7 As shown, the second upper cover 211 is provided with a plurality of third connecting members 291 on the inner surface, and the second lower cover 212 is provided with a plurality of fourth connecting members 292 on the inner surface that cooperate with the third connecting members 291. The third connecting members 291 and the fourth connecting members 292 are configured to enable the second upper cover 211 to be detachably combined with the second lower cover 212. Preferably, the second upper cover 211 is provided with a third clamping portion 281 on the side edge, and the second lower cover 212 is provided with a fourth clamping portion 282 on the side edge that cooperates with the third clamping portion 281, and the third clamping portion 281 and the fourth clamping portion 282 are configured to strengthen the combination of the second upper cover 211 and the second lower cover 212.

[0046] Preferably, if Figures 1 to 5 As shown, the first upper cover 111 and / or the first lower cover 112 is provided with one or more ventilation holes 150, and the ventilation holes 150 are configured to help the solvent on the sample pad 120 to evaporate, accelerate the enrichment and concentration of the target on the sample pad 120, and thus improve the sensitivity and accuracy of immunochromatographic detection.

[0047] Preferably, if Figure 5 As shown, a heating element 190 is disposed inside the first part 100, and the heating element 190 is disposed above and / or below the sample pad 120 and is configured to heat the sample pad 120. The heating element 190 can be a heating source that can generate heat itself, or a heat conductor that heats the sample pad 120 by conducting heat from other heat sources. The number of heating elements 190 can be one or more. In the embodiment shown in the present invention, there are two heating elements 190, namely a first heating element 191 located above the sample pad 120 and a second heating element 192 located below the sample pad 120. Figure 4a , Figure 4b and Figure 5 As shown, a first heating element positioning structure 173 for positioning the first heating element 191 is provided on the inner surface of the first upper cover 111, and a second heating element positioning structure 174 for positioning the second heating element 192 is provided on the inner surface of the first lower cover 112. In this embodiment, the first heating element positioning structure 173 includes two parallel strips 1731, and a ridge 1732 extending along the height direction of the strip 1731 is provided on the inner side of each strip 1731, and a protrusion 1733 extending inward is provided at the end of each strip 1731 away from the sample pad protection block; the second heating element positioning structure 174 includes two parallel strips 1741, and a ridge 1742 extending along the height direction of the strip 1741 is provided on the inner side of each strip 1741, and a columnar member 1744 is provided between the two strips 1741. The first heating element 191 is provided with a hollow portion 1911 for allowing liquid to pass through, and the second heating element 192 is provided with a hole 1921 for combining with the columnar element 1744 of the second heating element positioning structure 174 . When the first part 100 with the heating element 190 is assembled, the protrusions 1733 of the first heating element positioning structure 173 abut against the two sides of the U-shaped sample pad positioning structure 171, the second heating element 192 is arranged in the second heating element positioning structure 174, the columnar member 1744 of the second heating element positioning structure 174 passes through the hole 1921 of the second heating element 192, and the ridge 1742 abuts against the second heating element 192; the first heating element 191 is arranged in the first heating element positioning structure 173, the ridge 1732 abuts against the first heating element 191, the sample pad 120 is arranged between the first heating element 191 and the second heating element 192, and the end of the sample pad 120 away from the sample pad protection block is inserted into the opening of the U-shaped sample pad positioning structure 171, and the hollow portion 1911 of the first heating element 191 at least partially overlaps with the injection hole 132, so that the liquid can flow to the sample pad 120 through the injection hole 132 and the hollow portion 1911.

[0048] In other embodiments not shown in the present invention, multiple heating elements are arranged above and / or below the sample pad in an interval manner along the length direction of the sample pad (from one end of the sample pad for contacting the test strip to the other end), and the multiple heating elements are capable of heating different parts of the sample pad to different temperatures.

[0049] In this embodiment, the heating element 190 is in the shape of a square plate. However, in other embodiments not shown in the present invention, the heating element 190 may also be in any other suitable shape, and the corresponding positioning structure for positioning the heating element 190 may also be in any other suitable structure.

[0050] By setting a heating element 190 for heating the sample pad 120, the cross-sectional / instant binding concentration of the immunochromatography target can be improved. The solvent containing the target is volatilized during the crawling process of the sample pad 120, and finally concentrated in a relatively narrow three-dimensional space. When the chromatography fluid is added later, the concentration of the target on the cross section can be effectively improved, thereby improving the sensitivity of the detection. By setting different temperature points, combining the heating area and the number of heating points, the speed and amount of liquid volatilization are controlled, so that the sample liquid is evaporated at a determined position, thereby achieving the target point concentration, making it shorter in the subsequent chromatography process. In addition, we found that some impurities (such as pigments) can enhance their ability to adhere to the sample pad after heating and volatilization. Then, when the immunochromatography device is assembled and the chromatography fluid is dripped, the impurities fail to climb onto the NC membrane, thereby achieving the separation of the target and the impurities, making the test results more accurate.

[0051] The following will be combined Figure 8 The first part 100 ′ of the split-type immunochromatographic detection device according to another embodiment of the present invention is described in detail.

[0052] like Figure 8 As shown, the first part 100' has a structure similar to the first part 100, and the first part 100' includes a first shell 110', a sample pad 120' and a first liquid adding part 130', and the sample pad 120' is arranged in the first shell 110'. The first shell 110' includes a first upper cover 111', a first lower cover 112', a first sample pad protection block 121' arranged at one end of the first upper cover 111', and a second sample pad protection block 122' arranged at one end of the first lower cover 112'. The structures of the first sample pad protection block 121' and the second sample pad protection block 122' are similar to those of the first sample pad protection block 121 and the second sample pad protection block 122, and are not repeated here.

[0053] The first part 100' is different from the first part 100 in that the first housing 110' further includes: a third sample pad protection block 123', which is disposed at the other end of the first upper cover 111'; and a fourth sample pad protection block 124', which is disposed at the other end of the first lower cover 112', and a portion of the sample pad 120' is disposed between the third sample pad protection block 123' and the fourth sample pad protection block 124'. The sample pad 120' can be exposed through the third sample pad protection block 123' or the fourth sample pad protection block 124' to absorb the chromatography liquid. Specifically, in this embodiment, the length of the fourth sample pad protection block 124' is greater than or equal to the length of the end of the sample pad 120' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' extending out of the first lower cover 112', the purpose is: the fourth sample pad protection block 124' is used to help the sample pad 120' to be positioned during production, to protect the sample pad 120' from being bent during production, transportation, and use, especially when the end of the first part 100' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' is inserted into the nanoparticle cup containing the labeled antigen and antibody When the fourth sample pad protection block 124' can effectively support the sample pad 120' and bear the weight of the entire first part 100', thereby preventing the sample pad 120' from bending and deforming; the length of the third sample pad protection block 123' is less than the length of the end of the sample pad 120' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' extending out of the first upper cover 111', the purpose is: to enable the sample pad 120' to be exposed outside the third sample pad protection block 123' and the fourth sample pad protection block 124' and form a first liquid adding part 130' in the first shell 110' for absorbing the chromatography liquid. When the end of the first part 100' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' is inserted into the nanoparticle cup containing labeled antigens and antibodies, the part of the sample pad 120' exposed outside the third sample pad protection block 123' and the fourth sample pad protection block 124' can fully contact with the liquid, thereby improving the liquid absorption efficiency. That is, in this embodiment, the first liquid adding part 130 ′ is formed by the third sample pad protection block 123 ′ or the fourth sample pad protection block 124 ′.

[0054] Preferably, the end of the fourth sample pad protection block 124' away from the first lower cover 112' is provided with a notch 1241, and the notch 1241 can promote the sample pad 120' to absorb the solution in the cup. Correspondingly, the end of the sample pad 120' close to the notch 1241 can be provided with a protrusion (not shown), which extends into the notch 1241 and is flush with the notch 1241.

[0055] In an embodiment not shown in the present invention, the length of the third sample pad protection block 123' may also be greater than or equal to the length of the end of the sample pad 120' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' extending out of the first upper cover 111'. Correspondingly, the length of the fourth sample pad protection block 124' may also be less than the length of the end of the sample pad 120' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' extending out of the first lower cover 112'.

[0056] Preferably, the ends of the first part 100' close to the third sample pad protection block 123' and the fourth sample pad protection block 124' may also be provided with protective covers (not shown), and the protective covers are configured to protect the ends of the sample pad 120' exposed outside the third sample pad protection block 123' and the fourth sample pad protection block 124' from contamination during sample pre-treatment using the first part 100', and the first part 100' is also more convenient to hold.

[0057] The second part (not shown) according to the present embodiment has a structure similar to the second part 200. The difference between the second part of the present embodiment and the second part 200 of the aforementioned embodiment is that the second part of the present embodiment does not need to be provided with a second liquid adding part. When in use, after the sample pre-treatment is performed by using the independent first part 100' to achieve enrichment and concentration of the target on the sample pad, the first part 100' is connected to the second part so that the sample pad 120' contacts the test strip (specifically, contacts the chromatographic membrane of the test strip), and then the end of the first part 100' having the first liquid adding part 130' is inserted into the nanoparticle cup containing the labeled antigen and antibody, so as to perform chromatographic detection.

[0058] According to a second aspect of the present invention, an immunochromatographic detection method is provided, which uses the split immunochromatographic detection device 10 as described above. Fig. 9 FIG. 1 is a schematic flow chart of an immunochromatographic detection method according to an embodiment of the present invention. Fig. 9 As shown, the immunochromatographic detection method comprises:

[0059] Step S310: performing sample pretreatment through the independent first part 100;

[0060] Step S320: connecting the first part 100 and the second part 200 so that the sample pad 120 contacts the test strip 220 (specifically, contacts the chromatographic membrane 222 of the test strip 220); and

[0061] Step S330 : Absorbing the chromatography liquid via the first liquid adding part 130 to perform chromatography detection.

[0062] The step of performing sample pretreatment through the independent first part 100 may be performed by performing sample pretreatment on the sample pad 120 of the first part 100 and then installing the sample pad 120 that has undergone sample pretreatment in the first shell 110, or the sample pretreatment may be performed directly through the entire first part 100.

[0063] Several specific embodiments of using the split-type immunochromatographic detection device 10 of the present invention to perform immunochromatographic detection will be described below.

[0064] Example 1

[0065] Add sodium silicate (0.4 g / mL) ethanol aqueous solution to a 50 ml beaker, and slowly drip ammonia (0.1 mol / L). While dripping ammonia, soak the sample pad in the solution and wait for the reaction for 4 hours. After the reaction, take out the sample pad, dry it at 90 degrees Celsius, and place the dried sample pad in the first shell of the first part to form the first part of the split immunochromatographic detection device for detecting malachite green.

[0066] Example 2

[0067] Detection of malachite green in shrimp. Take out the split immunochromatographic detection device of the present invention. Add 2 grams of shrimp to a 15 ml centrifuge tube, add 3 ml of acetonitrile, vortex for 3 minutes, and centrifuge at 4000 rpm for 3 minutes to make an acetonitrile solution. Add 50 μL of acetonitrile solution to the first liquid addition part of the first part, let it dry for 3 minutes, and repeat the addition 4 times. After drying, connect the first part and the second part. Add 80 μL of chromatography solution to the second liquid addition part of the second part, and observe the results after 3 minutes.

[0068] Example 3

[0069] Detection of methamidophos in tea leaves. Take out the split immunochromatographic detection device of the present invention. Add 1 gram of tea leaves to a 15 ml centrifuge tube, add 3 ml of 50% ethanol water, soak for 10 minutes, vortex for 3 minutes, and then centrifuge at 4000 rpm for 4 minutes to form a sample solution. Take 500 μL of the sample solution and add it to the sample cup. Put the sample cup into the heater, put the first part into the sample cup, and control the heater to heat at 70 degrees for 10 minutes. Take out the first part, insert it into the second part, and combine it in place. Add 80 μL of 0.1M pH7 phosphate buffered saline (PBS) to the second liquid adding part of the second part for chromatography, and observe the results through the observation window after 5 minutes.

[0070] The beneficial effects of the present invention are as follows: by separating the sample pad for absorbing the sample liquid from the test strip part of the immunochromatographic detection device as an independent sample pretreatment part, the target object is enriched and concentrated, and then combined with the test strip part to realize the immunochromatographic process, which can effectively reduce the use of sample pretreatment consumables and related pretreatment solutions in the detection process. Consumables such as SPE columns are reduced, and the solid phase extraction and adsorption processes can be completed on the sample pad. The pretreatment solution only needs to be absorbed and evaporated on the sample pad, and the amount of sample required is less, which is more environmentally friendly.

[0071] The loss of samples in sample pretreatment consumables can be effectively reduced, and all targets can be effectively transferred to the sample pad. During the pretreatment process, the transfer of samples usually needs to be carried out in different consumables, and also needs to go through processes such as drying and solid phase extraction, and the samples usually cannot be completely transferred. Reducing the use of consumables, the sample can be directly added to the sample pad, reducing the loss of the sample, and all targets are effectively transferred to the sample pad, which is an effective way to improve the recovery rate. And less liquid can be used to achieve the same target concentration on the test strip.

[0072] The sample can be effectively concentrated on the sample pad to improve the detection sensitivity. The sample liquid containing the sample can be adsorbed onto the sample pad, and then concentrated in volume by drying, evaporation, heating and drying, etc., so that the liquid adsorbed by the sample pad can be concentrated on the sample pad at a volume multiple times larger than that on the sample pad, thereby aggregating the target on the sample pad and increasing the concentration. After being connected to the test strip part, the concentration of the target in the chromatography process can be greatly increased, thereby improving the detection sensitivity.

[0073] The sample liquid can be separated and purified on the sample pad to reduce the influence of the matrix on the immunochromatography. The sample pad can be modified to be endowed with different physical and chemical capabilities, producing selective adsorption for different large and small molecules, thereby achieving separation and purification of the target and matrix in the sample liquid. In particular, after the sample pad is modified to obtain adsorption capacity for the matrix, when the subsequent chromatography fluid is added, the matrix will remain on the sample pad, and the target can be effectively chromatographed, thereby reducing interference in the chromatography process and increasing accuracy.

[0074] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0075] Although the present invention has been described in conjunction with the embodiments, it should be understood by those skilled in the art that the above description and the accompanying drawings are only exemplary and non-restrictive, and the present invention is not limited to the disclosed embodiments. Various modifications and variations are possible without departing from the spirit of the present invention.

Claims

1. A split type immunochromatographic detection device, characterized in that: include: Part I and Part II; The first part includes a first shell and a sample pad disposed in the first shell and partially exposed from the first shell, the first shell is provided with a first liquid adding portion, and the first liquid adding portion is at least used for adding a chromatography liquid; The second part includes a second housing and a test strip disposed in the second housing; Wherein, the first part is independent of the second part and can be connected to the second part in a detachable manner; when the first part is connected to the second part, the split-type immunochromatographic detection device can absorb the chromatography liquid through the first liquid adding part, and the sample pad is in contact with the test strip; The first housing comprises a first upper cover, a first lower cover, a first sample pad protection block arranged at one end of the first upper cover, and a second sample pad protection block arranged at one end of the first lower cover, a portion of the sample pad is arranged between the first sample pad protection block and the second sample pad protection block, and a length of the first sample pad protection block is greater than or equal to a length of the sample pad extending out of the first upper cover, and a length of the second sample pad protection block is less than a length of the sample pad extending out of the first lower cover; A heating element is arranged inside the first part, and the heating element is arranged above and / or below the sample pad.

2. The split-type immunochromatographic detection device according to claim 1, characterized in that: The first shell is provided with a first clamping portion on the outer side, and the second shell is provided with a second clamping portion cooperating with the first clamping portion on the inner side. When the first part is connected with the second part, the first clamping portion is clamped with the second clamping portion.

3. The split-type immunochromatographic detection device according to claim 1, characterized in that: The first shell also includes a third sample pad protection block arranged at the other end of the first upper cover and a fourth sample pad protection block arranged at the other end of the first lower cover, a portion of the sample pad is arranged between the third sample pad protection block and the fourth sample pad protection block and the sample pad can be exposed through the third sample pad protection block or the fourth sample pad protection block to absorb the chromatography fluid.

4. The split-type immunochromatographic detection device according to claim 1, characterized in that: The first liquid adding part is arranged on the first upper cover, and the second liquid adding part is opened on the upper surface of the second shell; when the first part is connected with the second part, the second liquid adding part is located above the first liquid adding part.

5. The split-type immunochromatographic detection device according to claim 4, characterized in that: The first liquid adding portion includes a liquid adding recess and an injection hole provided at the bottom of the liquid adding recess.

6. The split-type immunochromatographic detection device according to claim 1, characterized in that: The lower surface of the first sample pad protection block and / or the upper surface of the second sample pad protection block are provided with one or more first supporting members contacting with the sample pad and used for supporting the sample pad.

7. The split-type immunochromatographic detection device according to claim 1, characterized in that: A pressing structure is provided on the inner upper surface of the second shell. When the first part is connected to the second part, the pressing structure presses the first sample pad protection block and the sample pad downwards, so that the sample pad and the test strip fit tightly.

8. The split-type immunochromatographic detection device according to claim 1, characterized in that: The first upper cover is provided with a plurality of first connecting members on the inner surface, and the first lower cover is provided with a plurality of second connecting members cooperating with the first connecting members and a sample pad positioning structure for positioning the sample pad on the inner surface; and / or The second shell includes a second upper cover and a second lower cover, the second upper cover is provided with a third clamping portion on the side edge and a plurality of third connecting members on the inner surface, the second lower cover is provided with a fourth clamping portion on the side edge that cooperates with the third clamping portion and a plurality of fourth connecting members on the inner surface that cooperate with the third connecting member.

9. The split-type immunochromatographic detection device according to claim 1 or 2, characterized in that: The second shell has a mounting groove on its inner lower surface, the shape of which matches the test strip, and the test strip is installed in the mounting groove. The second shell has one or more second support members on its inner upper surface for supporting the test strip.

10. An immunochromatographic detection method, characterized in that: The immunochromatographic detection method uses the split-type immunochromatographic detection device according to any one of claims 1 to 9, wherein the immunochromatographic detection method comprises: Perform sample preparation by independently performing the first part; connecting the first portion to the second portion such that the sample pad is in contact with the test strip; and The chromatography liquid is absorbed through the first liquid adding part to perform chromatography detection.

Images