CN1828301B - A device that displays test results of specimens with intuitive symbols - Google Patents

Abstract

The device comprises: a sample application zone, a reagent zone, a detection zone with positive and negative contrast zones and the combination zone for detected target, and a reagent strip. Wherein, the positive contrast zone comprises one or more material to show the first color on dried condition and the second color when on wet condition. If there is detected target in sample, the interactive action of the combination zone and contrast zone forms the legible symbols.

Description

A device that displays test results of specimens with intuitive symbols

technical field

The invention belongs to medical diagnostic items, specifically a detection device that can quickly detect whether a sample contains an analyte.

Background technique

In any test, positive and negative control experiments are very important components. In immunological tests, these control tests are usually completed by combining immunological principles to form controls, and the results of control tests can be displayed as colored lines on the test strip. These types of control tests are effective in determining whether the detection device is functioning properly, but additional costs are incurred in the manufacture of this part of the device and in performing these control tests, especially as the specific binding molecules used in the control tests require very delicate techniques to be produced. In addition, these controlled trials can lead to misinterpretation of the test results by ordinary users without special training. Therefore, it is necessary to use a better method and device for sample collection and testing to make the test results more intuitive and allow ordinary users without special training to easily interpret the results.

Contents of the invention

The present invention provides a device for detecting an analyte in a liquid sample and indicating to the user the presence or absence of the analyte with a recognizable symbol. A specific solution is that the present invention provides a reagent strip, which includes a sample receiving area, a reagent area and a detection area. There are positive, negative control areas and analyte binding areas in the detection area. The positive control zone contains one or more components that exhibit a first color when dry and a second color when wet. The analyte binding region contains binding molecules that can capture the analyte, and the labeled analyte can also be captured. The interaction of the analyte binding zone and the positive control zone to produce a recognizable symbol indicates the test result. A specific solution is that the positive control area is displayed in the shape of a minus sign in the reagent strip, the control area includes one or more components, and the positive control area will change from white to red after adding a certain aqueous solution. In this particular protocol, the assay begins with the strip dry, and both the positive control area and the strip are white. Therefore, the positive control area is not visible when we look at the test area before adding the sample. When a liquid sample is added, the sample flows through the detection zone of the strip, wetting the positive control zone and causing the positive control zone to change from white to red. This way the minus sign in the detection zone becomes clearly visible. If the sample does not contain the analyte, only a minus sign is displayed in the test area, informing the user of a negative test result. However, if the sample contains an analyte, the labeled analyte is captured by the binding molecules of the analyte-binding region and accumulates continuously, showing a color, the color of the analyte-binding region and the minus sign (positive control region ) can interact to produce a plus sign, informing the user of a positive test result. The reported symbol can choose any recognizable symbol. Such as plus and minus signs, but also "X" or other symbols with special meaning.

First, the present invention provides a device for detecting the presence or absence of a certain analyte in a sample. The device includes a reagent strip that allows the liquid sample to flow freely, a sample application area is specially used to add the liquid sample, a detection area contains a positive control area, and the positive control area contains one or more components that can Shows first color when dry and second color when wet. The detection zone also has an analyte binding zone containing specific binding molecules. The device also has one or more reagent zones containing assays.

In one embodiment, one or more of the ingredients comprise a colorless or lightly colored base dye. The reagent strip can be a nitrocellulose test strip, and the positive control zone can be in the shape of a minus sign on the test strip. The analyte binding region can be divided into two regions, which contain molecules or molecular conjugates that specifically bind the analyte to bind the analyte, and these two regions are located on both sides of the positive control region. These two areas should be aligned so that when the positive control area becomes wet and the sample contains the analyte, the positive control area and the analyte binding area form a recognizable symbol. This recognizable symbol can be a plus sign or any other recognizable symbol. Many examples of colorless or lightly colored base dyes can be found in US Patent No. 5,130,290.

In another embodiment, the positive control area further comprises positive control filaments comprising one or more water-sensitive dyes. "Water sensitive" means a color change when exposed to aqueous solutions. The specific binding molecule can be an antibody or antibody fragment, and the water-sensitive dye can also include one or more components containing a base dye. In one embodiment, the analyte is human chorionic gonadotropin (hCG). The positive control zone can be delimited by one or more positive control filaments within the detection zone, and the positive control zone is devoid of many components of the specific binding pair.

In another embodiment, the analyte binding region further comprises a specific binding molecule for binding the analyte and a label providing a detectable signal. The label can be a colored microparticle, such as a dextran-containing microparticle. The analyte binding area can be arranged in strip form along the latitude direction of the central axis of the test paper, and also contains binding molecules that can specifically bind the analyte. The positive control zone may consist of two zones flanking the analyte binding zone. The positive control region and the analyte binding region interact to form a recognizable symbol.

In another aspect, the invention provides methods of determining whether a liquid sample contains an analyte. The method entails placing a liquid sample on a device as described herein and allowing the liquid sample to flow through the device and through one or more reagent zones so that if the sample contains an analyte, the reagent and sample can react to form Detectable reaction product. Flowing a liquid sample through the detection zone wets the color-changing substances, which display one color when dry and a second color when wet. The analyte in the sample is retained in the analyte binding zone as the sample flows through the detection zone. Observation of the detection zone of the device can confirm the presence or absence of the analyte in the liquid sample.

In a specific embodiment, one or more components are contained on a positive control filament. The positive control zone may contain positive control filaments containing one or more components that are wetted when the fluid sample flows through the detection zone, causing the one or more components on the filament to exhibit a second color. The analyte binding area may form a strip along the latitude direction of the longitudinal axis of the test paper, and contain specific binding molecules, which can bind the analyte or the analyte with a labeled substance.

In another embodiment, the detection device is a test strip made of water-absorbent material, and the positive control areas are arranged in the shape of a minus sign along the longitude direction of the longitudinal axis of the water-absorbent material. The analyte binding zone, however, includes two regions located on either side of the positive control zone. The analyte binding region and the positive control region interact to produce a recognizable symbol. The analyte binding area can be a bar perpendicular to the longitudinal axis of the test strip, and the analyte binding area has specific binding molecules, which can combine with the analyte and produce a label.

In another embodiment, the analyte in the sample is labeled with a detectable label as it passes through the reagent zone, and the labeled analyte is retained in the analyte binding zone as the sample passes through the detection zone.

In another aspect, the invention provides kits for determining whether a sample contains an analyte. As described herein, kits include a device of the invention and instructions for use. The test device in the kit can be used to detect HCG in urine. In another embodiment, the device can also be used to detect luteinizing hormone (LH) or ovarian stimulating hormone (FSH) in body fluid, and the instructions in the kit describe how to use the device to detect these substances.

The introduction of the present invention described above is not exhaustive, and other features and advantages of the present invention will be elaborated in the following description and claims.

Description of drawings

FIG. 1A provides us with a perspective view of one embodiment of the device of the present invention, including a reagent strip 20 . The reagent strip 20 includes a sample application area 25 , a reagent area 30 , and a detection area 32 . The detection zone contains a positive control zone 45 shown in the shape of a minus sign. In this embodiment, the positive control zone 45 is printed or coated on the nitrocellulose membrane 35 . The detection zone also includes an analyte detection zone 40 and a negative control zone 12 . Arrows indicate the direction of sample flow.

FIG. 1B provides us with a perspective view of another embodiment of the present invention. The reagent strip 20 is composed of multiple substances cross-linked with each other. The positive control area 45 shows the shape of a minus sign, which can be engraved on the nitrocellulose membrane, or can be printed, painted or drawn on the nitrocellulose membrane.

FIG. 2A is another analytical view of the present invention, where the positive control zone includes a filament 50 . One or more components that cause the positive control zone to exhibit a first color when dry and a second color when wet are located on or contained within the filament. In this embodiment, the filaments are embedded in grooves 55 in the nitrocellulose membrane.

Figure 2B illustrates what is shown in Figure 2A. In this particular illustration, the positive control zone comprises filaments 50 on top of the nitrocellulose membrane, and one or more components are located on or contained within the filaments.

Figure 2C illustrates that of Figure 2B, except that the filament 50 is located beneath the nitrocellulose membrane. When the filament is wet, it (takes on the second color) can be visually observed in the detection zone.

Figure 3A shows an exploded view of another embodiment of the device of the present invention. In this embodiment, the positive control zone is delimited by filaments 50 located beneath the nitrocellulose membrane. In this embodiment, the filament tongue-like protrudes from the positive control area 52 and fits into the groove 85 of the support layer 80 .

Figure 3B illustrates the specific content of the positive control area in Figure 3A. Filament 50 is a tongue protruding from positive control segment 52 . The filaments (colored parts) have one or more components on them that cause them to change from a first color to a second color when wet. The filaments are embedded in grooves 85 carved into the support layer 80 .

Fig. 4A is also another analytical diagram of the present invention. In this analytical view, the filaments 50 are located in the matrix beneath the nitrocellulose membrane 35, and the test strip also includes a bottom support 60. The interaction between the filament 50 and the reagent zone 30 is through a liquid. In a particular embodiment, the cover block 2 can be used to facilitate contact between the sample block, the reagent block and the nitrocellulose membrane located below the cover block.

FIG. 4B illustrates an embodiment of the present invention in which grooves 51 are engraved on the bottom support 60 . The filaments 50 are embedded in the grooves, and the nitrocellulose membrane 35 is on top of the grooves.

Figure 4C illustrates the display of test results before use (Figure 4Ci), when the test result is negative (Figure 4Cii) and when the test result is positive (Figure 4Ciii).

Fig. 5A is also an exploded view of another embodiment of the present invention. In this embodiment, filaments 50 protrude from positive control block 52 and lie beneath nitrocellulose membrane 35 . In this particular scheme, we can clearly see a support layer 54 positioned between the positive control block 52 , the filament 50 and the nitrocellulose membrane 35 .

Figure 5B provides an assembled perspective view of the device of Figure 5A.

FIG. 6A is a cross-sectional view of another embodiment of the device in which there are two positive control segments 52 and two filaments 50 . Moreover, in this figure, there is also a support layer 80 with a groove 85 whose size and shape can just embed two filaments 50 . Figure 6B provides an assembled perspective view of the device shown in Figure 6A. In the figure, an arbitrary sample acquisition block is indicated by a dotted line.

Detailed ways

In the following detailed description, reference texts accompanying the legends are a part hereof, and are presented by way of illustration of certain embodiments in which the invention may be practiced. We do not exclude that the present invention can implement other specific solutions and change the structure of the present invention without departing from the scope of use of the present invention.

Test Device In one embodiment, the device of the present invention uses a test strip to detect the presence of an analyte in a liquid sample. These devices communicate test results to the user in the form of a recognizable symbol formed by the combination of visual signals generated by the positive control zone and the analyte binding zone. One embodiment of device 10 is illustrated in FIG. 1A . The detection device contains a reagent strip 20 through which a liquid sample can flow. The reagent strip comprises a sample application zone 25 for applying a liquid sample to the device, a reagent zone 30 and a detection zone 32 . The reagent area 30 contains the reagents required to perform the assay. There may be more than one reagent zone on the test strip as required by the particular test to be performed. The detection zone 32 includes a positive control zone 45 , an analyte binding zone 40 and a negative control zone 12 . The negative control area is colorless when the test is performed normally. In this particular scheme, the negative control zone 12 is easily indicated by those zones surrounding the plus sign, because those zones surrounding the plus sign will display the plus sign when the sample contains the analyte (e.g., when the plus sign number is selected as the recognizable symbol)

Figure 1B illustrates another embodiment of the present invention. In this embodiment, reagent strip 20 is composed of multiple overlapping materials, including a sample application block 25 , a reagent block 30 , a nitrocellulose strip 35 and an absorbent block 14 . The detection zone 32 is located on the nitrocellulose strip. A positive control zone and a negative control zone are located within the detection zone. The absorbent block provides an absorbent receiving area that absorbs the liquid sample, thus facilitating the flow of liquid through the matrix until the end of the test. In various embodiments, the individual components of the matrix may be bound together by one or more binding substances (not illustrated).

In another embodiment of the invention ( FIG. 4 a ), positive control filaments 50 are treated with water-sensitive ink and positioned between strips of nitrocellulose 35 and a bottom support layer 60 . In this embodiment the filament 50 is made of absorbent paper impregnated with a water sensitive agent. The filament 50 intersects the analyte binding zone so that when a positive result occurs, the positive control zone and the analyte bind and interact to form a plus sign. In this embodiment, one end of the filament 50 is positioned under the nitrocellulose strip 35 and the other end interacts with the fluid in the reagent block 30 or sample application block 25 . "Positive control filament" means a structure in the device that contains one or more substances that cause it to exhibit a first color when dry and a second color when wet. The filaments do not need to have a specific shape, but in this device are usually long strips that can be seen with the naked eye in the detection zone. The shape of the filament depends on the recognizable symbol used in the test. The filament can be an extension of another structure in the device, or it can be a separate structure in the device.

In another embodiment (FIG. 4b) the filaments are embedded in grooves 51 carved into the backing layer 60, which also intersect the analyte binding region, thus forming a plus sign when the sample contains an analyte.

In another version ( FIG. 5 ) the positive control filament 50 is an extension of the positive control block 52 . The filaments 50 extend below the nitrocellulose membrane and intersect the analyte binding zone 40 to form a plus sign when the sample contains the analyte and a minus sign when the sample does not contain the analyte. In this embodiment, the filament 50 is impregnated with a color-changing reagent, and the filament 50 interacts with the fluid in the positive control block 52 , as well as with the fluid in the reagent zone 30 and the sample application zone 25 . Thus, when a liquid sample is added to the sample application area 25, the positive control block 52 becomes wet, thereby producing a color change reaction. The interaction of the filament 50 and the analyte binding region forms a recognizable symbol.

In the embodiment depicted in FIG. 6 , the device includes an additional support layer 80 that can support the filament 50 . The filaments 50 are inserted into grooves 85 carved into the support layer 80 . Backing 60 may be attached (eg, adhered) to support layer 80 .

The test strip contained in the device of the present invention and the bracket for placing the test strip are the main parts of the device and can be used for specific tests. The holder can be a hollow plastic structure with windows for viewing the test results and adding the sample to the sample application area. Another design is that the device is a test strip, without the support. The support may also be located at only one end of the test strip, allowing the user to remove the test strip and without contaminating the device, the sample application area is immersed in the sample solution.

In some designs, the device may include a control line in addition to the positive control area. In these designs, the control line can be displayed upstream or downstream of the positive control area. Positive results are determined not only by recognizable symbols displayed in the test zone, but also by comparing the analyte-binding zone with the control line. In some tests, comparing the relative intensities of the two lines can determine whether the test is positive or negative. In this particular design, the analyte is luteinizing hormone (LH).

Matrix Material In one embodiment, the test strip contains an absorbent material that provides a matrix material to support fluid flow. "Matrix material" means a material that supports the flow and transport of liquids. In one embodiment, the matrix material is a water-absorbing material. Fluid flow through the device is accomplished by capillary movement. In different embodiments, the matrix material can be a strip of a single material (Figure 1A), or it can be composed of multiple water-absorbing materials that interact in a liquid (Figure 1B), and "water-absorbing" materials refer to Those substances that can stably absorb water and allow water to be transported therein by the action of capillary movement. Examples of absorbent materials include nitrocellulose, filter paper, fiberglass, polyester and other suitable materials.

Sample application area The sample application area may include a buffer to dissolve the sample, or it may simply be a site on the matrix where the sample is added, but may also contain other reagents for performing the assay. For example, in those embodiments where "scavenger" antibodies are useful, the "scavenger" antibody may be placed on the sample application area, reagent area, or other area of the substrate. The sample application area thus also becomes the reagent area. A liquid sample is convenient to use when performing the test, but it can also dry out on the test strip, and the test can only be started by adding water, buffers, and other reagents to dissolve the sample. The sample itself may be a liquid sample, or a solid sample that has been dissolved or prepared as a liquid.

Reagents The reagents contained in the reagent area are removable. Some reagents are capable of attaching to the label and binding to the target analyte in the sample to form a labeled analyte. The sample application area and/or the reagent area may also contain buffers for dissolving the sample and adjusting the pH value required for the particular assay. In one embodiment, the reagent zone comprises a specific binding molecule (eg, an antibody or antibody fragment) linked to a label. The label can be any suitable label, such as gold sol, fluorescent dye or water soluble dye. The specific binding molecule can specifically bind to one or more epitopes of the target analyte, thereby labeling the analyte.

Detection area The detection area of the device includes a positive control area, a negative control area and an analyte binding area. The negative control zone is located within the detection zone and is not part of the positive control zone, nor is it a part of the analyte binding zone. If a signal from the detectable label is detected in this region, a false negative control has been generated and the assay is invalid. In some specific schemes, the detection area is a rectangular or square area on the water-absorbent substrate, surrounding the positive control area and the analyte binding area, distributed along the longitude direction of the test strip, and further separated by the line protruding from the side of the test strip. surrounded by. The detection zone may also include a plastic portion placed thereon to provide a window for viewing the detection zone only. The detection zone involves the entire structure of the device. Therefore, whether it is a structure located on the matrix, in the matrix or under the matrix, or the display result of the positive or negative analyte test result, as long as it can be observed in the detection zone when dry or wet, it can be included in the detection zone. Inside.

positive control area

Positive control areas may be displayed as one or more areas on the device that contain one or more color changing components that display a first color when dry and a second color when wet. The positive control area may be a strip distributed along the longitude direction of the longitudinal axis of the reagent strip. The streaks can be revealed by one of the color-changing ingredients. In another embodiment, the color changing component can be attached to a substrate or to a backing or other support that can reveal a positive control zone. For example, the color changing component may be attached to a substance of the substrate or backing or other support, or may be attached directly to these structures. In one embodiment, the color changing component can be attached to a protein that is itself attached to the nitrocellulose portion of the matrix.

)支撑，或者被含有黏合剂的背衬物60支撑，没有分离的背衬物。在这个具体方案中，基质材料也可以包括试剂区块30，样品应用区块25和吸收区块58。基质成分相互邻接，并且有少许相互重叠，因此加入的样品可以持续从样品应用区块流到吸收区块。检测区包含被分析物结合区40和阳性对照细丝50。细丝上包含一种或者多种成分，可以在干的时候显示第一种颜色，在湿的时候显示第二中颜色。这一种或者多种成分可能是墨水或者染料。在这个具体方案中有一个大小和形状刚好可以插入细丝的凹槽55被刻在硝化纤维膜上。凹槽55可能被刻在硝化纤维膜上。换句话说，如果有背衬物，凹槽也可能被刻穿入硝化纤维膜的背衬物。在制造试验条的过程中，细丝位于硝化纤维膜的凹槽中。试剂可以在刻出凹槽或将细丝嵌入凹槽之前或者之后加入到被分析物结合区。In some embodiments, the positive control area is delineated by a positive control filament. The filaments may be made of any suitable material that includes a color changing component, so that the filaments can display a second color when wet. In some examples, the filaments are made of paper or other fibrous or fibrous material that can carry liquid. The filaments can be part of the matrix due to their ability to carry fluid. Figure 2A shows a matrix composed of various hygroscopic substances. The substrate is supported by a backing 60 which in one embodiment contains an adhesive. Adhesives help hold the parts of the matrix together, maintaining fluid flow between the parts. Various adhesives are conveniently used, such as medical glue or tape and double-sided tape. In the embodiment illustrated in FIG. 2A , strip 35 of nitrocellulose is positioned on top of backing 60 . In various embodiments the nitrocellulose strip 35 can be backed by its own backing (e.g.,

) supported, or supported by a backing 60 containing an adhesive, without a separate backing. In this embodiment, the matrix material may also comprise reagent block 30 , sample application block 25 and absorbent block 58 . The matrix components are adjacent to each other and slightly overlap each other, so that the added sample can continue to flow from the sample application block to the absorption block. The detection zone comprises an analyte binding zone 40 and a positive control filament 50 . The filaments contain one or more ingredients that can develop a first color when dry and a second color when wet. The one or more components may be ink or dye. In this embodiment a groove 55 just sized and shaped to insert the filament is carved into the nitrocellulose membrane. Grooves 55 may be engraved on the nitrocellulose membrane. In other words, grooves may also be carved into the backing of the nitrocellulose membrane, if any. During the manufacture of the test strips, the filaments are located in the grooves of the nitrocellulose membrane. Reagents may be added to the analyte binding zone either before or after scoring the grooves or inserting the filaments into the grooves.

Figures 2B and 2C show the specific scheme involved. In the embodiment illustrated in Figure 2B, the filaments are located on top of the nitrocellulose membrane rather than in the grooves of the nitrocellulose membrane. In the embodiment illustrated in Figure 2C, the filaments are located beneath the nitrocellulose layer. The filaments may be located between the nitrocellulose membrane and its backing layer (if present), or between the nitrocellulose membrane and the bonded backing layer (when the nitrocellulose membrane does not have its own backing layer). When wet, the nitrocellulose membrane is translucent or transparent so that the wet colored filaments 50 can be clearly seen through the nitrocellulose membrane.

)和/或一种透明的支持物54(图5和图6)可以被用来防止样品溢出到细丝外。More embodiments of the device are illustrated in FIGS. 3-6 , where the filaments are shown in the shape of positive control filaments 50 protruding from positive control block 52 . Referring to FIG. 3A , the filament 50 is embedded in a groove 85 on a support layer 80 (eg, a strip of plastic). Positive control filament 50 may comprise a dye having one or more components that exhibit a first color when dry and a second color when wet. A nitrocellulose membrane may be positioned over the support layer 80 and the positive control block 52, so that when the positive control block 52 becomes wet after adding the sample, the liquid sample flows through the positive control filament 50, causing the filament to change from its first color. into the second color. In one embodiment, when we use a dye containing one or more components, the filaments can be clearly transformed from white (first color) to red (second color). When the filaments change to the second color, we can observe the filament color through the covering nitrocellulose membrane, which is also wetted by the sample. A backing for a nitrocellulose membrane (e.g.,

) and/or a transparent support 54 (Figures 5 and 6) can be used to prevent the sample from spilling out of the filament.

Various absorbent materials can be used as positive control filaments and/or positive control blocks (when used), which can be made from the same material. Any material capable of transporting liquids can be used. Liquids can flow through the material through capillary movement. In one embodiment, the positive control block or positive control filament is a polyester fiber membrane. Film thicknesses between 0.6-1.0 mm are useful, but other thicknesses can be used if desired. This material has a natural property of absorbing water, and in this particular case, a 60mm x 10mm polyester membrane can absorb 0.6 +/- 0.15 grams of water. Useful polyester fibers are capillary motility materials available from Filtrona Fibertec( ^TM ) (Colonial Heights, VA). Of course other water absorbent materials are also useful in the present invention. For example, surface-active media, which are often used in filtration and utilize amine and carboxyl groups on the surface of fibers as substrates for many linking substances, can also be used as water-absorbing materials. Such materials also function well in the present invention as absorbent materials when placed on a sheet or strip and are also commercially available under Filtrona Fibertec ^(TM) . Among other embodiments, cotton is used, and other substances are used. Polyester is another useful water-absorbing material, and we can conveniently obtain polyester according to the technical methods of detergents, proteins and buffers.

symbol

The identifiable symbol is formed by the interaction of the positive control zone and the analyte binding zone in the device. The positive control area can be delineated by a part of the symbols, and interact with the symbols displayed in the analyte binding area, and the shapes are glued to each other to form a recognizable symbol. The symbol can optionally present one identifiable symbol for a negative result and another identifiable symbol for a positive result, where the positive control region and the analyte binding region interact to form a identifiable symbol. The positive control zone contains one or more components that can display a first color when wet and a second color when wet. The symbol (or part of the symbol) can be glued and applied by printing or painting on the substrate (the adhesive material is accompanied by one or more components, which can display the first color when dry and the second color when wet. The method on the color) forms the positive control area, or is formed by other methods. This symbol may be formed on, under or in the middle of the nitrocellulose membrane, or between the nitrocellulose membrane and its backing.

In various specific scenarios, the "identifiable symbol" can be a plus sign, a minus sign, a dash, a bar, an "X", or another technically or verbally conveyed special meaning of the test result. symbol. Any meaningful symbol can be used, such as letters of the Roman alphabet, numbers, mathematical operators, scientific symbols, or letters of another language or alphabet system, such as Chinese, Japanese, or Arabic. For example, the minus sign is convenient for negative results because it is a meaningful and easily recognizable symbol. Other symbols such as "X", "O", zero, "Y", "N", "Z", or arrows may also be used. These symbols can be easily read and understood by untrained users. When the same color is used for one or more components that can change the color and the boundary of the positive control area, the positive control area and the analyte binding area interact to form a recognizable symbol when a positive result is obtained. When the symbol is a minus sign, its edges can be square or rounded.

Figure 4C, i-iii exemplifies a specific scheme in which the identifiable symbols are a plus sign and a minus sign, indicating positive and negative test results, respectively. As shown in Figure 4Ci, prior to use, no symbols are observed in the detection zone 32. If there is no analyte in the sample, the positive control area 45 displays a minus sign, indicating a negative result (Fig. 4Cii). When there is an analyte in the sample, the positive control area interacts with the analyte binding area 40 to display a plus sign (see FIG. 4Ciii), indicating a positive result.

Discoloration substance

US Patent No. 5,130,290 to Tanimoto describes a number of color changing compositions which are hereby referred to as a whole, including tables, figures and claims. In one embodiment, these components can be combined to form an ink or other water-sensitive colored dye that is applied to a substrate (eg, a piece of paper or a portion of a test device). In some embodiments, the color-changing substance includes a colorless or light-colored base dye, which is a color-changing substance that develops a color upon contact with the dye, photosensitizer, and binder. Various dyes, color changing substances, photosensitizers and binders can be combined in various ratios to form a color changing ink, and many examples of suitable ingredients and combinations of ingredients are described in US Patent No. 5,130,290. One or more components can be briefly described as a water-sensitive ink. This ink or other water-sensitive layer materials can be purchased from Kanzaki Paper Co., Ltd. in Tokyo, Japan, Beijing Chuangxin Chengye Technology Co., Ltd. (Address: #02-4-2, Yungang South Lane, Fengtai District, Beijing, China ) or Shenzhen Huiju Technology Co., Ltd. in Shenzhen, China. Examples of colorless and light-colored base dyes include triarylmethane dyes, diphenylmethane dyes, diazine dyes, lactam dyes and fluorescein dyes. Examples of discoloration substances include 4-tert-butylphenol, butylphenol, α-naphthol, β-naphthol, 4-acetylphenol. Examples of photosensitizers include polyethyleneimine, polyethylene glycol, anionic surfactants, and nonpolar surfactants. Examples of binders include starch, hydroxycellulose, methylcellulose, ethylcellulose, carboxymethylcellulose, gelatin, gum arabic and water-soluble polymers. Additional examples can be found in US Patent No. 5,130,290.

In one embodiment, one or more components of the ink can appear white when dry and red when wet. In other embodiments, the material appears orange or blue when wet. But the material is optional so we can produce as many different colors as we want. White or colorless ink can be engraved, stamped, painted or otherwise applied to the detection zone or positive control filament of the device. When using a positive control filament, the filament cannot be seen by the user prior to use because it is the same color as the matrix and is located in or under the nitrocellulose membrane, or in another layer of fluid-carrying matrix. As the sample flows through the positive control zone, one or more components in the ink become wet and turn red, causing the positive control zone to appear in the shape of a minus sign. In other embodiments, the first color of the positive control zone may be a color other than white, and the device changes from the first color to the second color. As long as the composition of that color is available, we can choose it as the first and second color.

analyte binding region

The analyte binding zone is located on the matrix so that it can interact with the positive control zone to produce a identifiable symbol when the fluid sample contains the analyte of interest. The labeled reagent of the reagent zone can bind (directly or indirectly) to the target analyte, thereby labeling the target analyte with a detectable label as the sample flows through the matrix. The analyte binding region also includes a reagent that can bind to the analyte associated site. The moiety may be an immunological antigen of the analyte itself or a reagent that binds the analyte (eg, a reagent that binds the analyte as it passes through the reagent zone) Determine base. In various embodiments, the reagent that binds to the analyte may be an antibody, a fragment or portion of an antibody, a derivative of an antibody of a different species than the antibody that binds to the analyte binding region (or wherein fragment), or another component of a specific binding pair, for example, avidin, streptavidin, or biotin that can bind to the analyte-binding moiety.

In a specific scheme, the analyte binding area is located on both sides of the positive control area, so when the sample contains the analyte, the analyte is marked and retained in the analyte binding area, and the positive control The zones interact to form a recognizable symbol and display a positive test result. In another embodiment, the analyte binding zone is a strip extending latitudinal along the longitudinal axis of the test strip, comprising an analyte-specific binding molecule, or a molecule that binds the analyte Complex. In either instance, as the labeled analyte in the sample flows through the detection zone, it accumulates in the analyte binding zone and produces a detectable color in the analyte binding zone. The colors of the analyte binding zone and the positive control zone interact to form recognizable symbols. In some embodiments, the label is a colored particle, possibly dextran particles, gold sol, or other labeled particles, and these labels can be any suitable label that provides a detectable signal.

Reagent area

A label that binds the target analyte provides an observable detection signal that produces an analyte-binding region that interacts with the positive control region to form an identifiable symbol when the sample contains the analyte. The analyte-specific binding molecules carry the label of the reagent zone. When the specific binding molecule captures the analyte and the labeled analyte is bound in the analyte binding region, this region is observed due to the accumulation of the marker in this region. An analyte-specific binding molecule refers to a binding molecule that binds to the analyte and does not bind strongly to any other molecule in the sample. An analyte-specific binding molecule may also bind to a molecule that indicates or correlates with the presence of the analyte in the sample. By strong binding is meant binding to such an extent that the test results are altered or made inconspicuous. In some embodiments, the specific binding molecule may be an antibody or an antibody fragment (e.g., the Fab region of an antibody), an antigen, a ligand-binding receptor or receptor fragment, Either a component of a biotin-streptavidin binding pair or other type of binding pair.

The reagent zone thus provides a label, and when the sample flows through the reagent zone, the analyte binds the label to produce a detectable signal. A "labeled area" refers to a site on a substrate that contains a substance that labels an analyte that may be present in a sample. A reagent zone is therefore a marker zone. A "label" may be any suitable label that produces a detectable signal. For example, labels can be soluble particles, fluorescent particles, chemiluminescent particles, metals or alloys (eg, colloidal gold), or vesicles, especially liposomes, containing visible dyes. Hydrophobic sols are also useful. Hydrophobic organic dyes or pigments are insoluble or only to a limited extent soluble in water. The markers can also be polymeric particles, such as colored polystyrene particles (eg, spherical). Other useful particulate markers include ferritin, phycoerythrin, phycobilin-proteins, precipitated or soluble metals or alloys, fungal, algal, or bacterial pigments or derivatives such as bacterial chlorophyll or other plant raw material. In certain embodiments, the markers are colored particles, such as dextran particles. In other embodiments, the label and dye used as positive controls are chosen to be the same color to enhance the interaction of the two signals to produce a single distinct symbol on or within the substrate.

In other embodiments, the label may be a labeled specific binding molecule (eg, an antibody) for the analyte. For example, in one embodiment, the analyte of interest is human chorionic gonadotropin (hCG) and the label that binds hCG is a gold sol labeled anti-hCG antibody. When the sample reaches the reagent area (or marking block), the hCG in the sample is bound by the gold sol-labeled anti-hCG antibody. The labeled antibody does not interfere with the binding of the capture molecule in the analyte binding region to the labeled hCG. For example, a label can bind one portion of the analyte and a capture molecule can bind another portion of the analyte or bind the label. The hCG-anti-hCG antibody-gold complex moves downstream of the matrix. When the complex reaches the analyte binding region, it combines with the capture molecule to form gold-anti-hCG anti-hCG-anti-hCG antibody. The capture molecule may be another specific binding molecule for hCG, or a specific binding molecule that binds the hCG analyte half. When the gold-anti-hCG specific binding molecule-hCG-anti-hCG specific binding molecule complex binds to the analyte-binding region, the analyte-binding region is stained by the gold label on the complex and Zone gold marks become visible to the naked eye. In a specific embodiment, the specific binding molecule is an antibody or antibody fragment. The label and capture binding molecules are capable of binding to different epitopes on the analyte. In one embodiment, the labeled specific binding molecule binds β-hCG and the capture binding molecule binds α-hCG.

"Antibody" means an immunoglobulin, whether natural or partially or fully synthetic. The term also includes derivatives of antibodies in which the binding ability is retained, as well as any protein containing a binding domain that is homologous or substantially homologous to that of an immunoglobulin. These proteins may be derived from natural substances, or may be partially or fully synthesized. An antibody may be monoclonal or polyclonal. An antibody may be a member of any immunoglobulin class, including any of the human immunoglobulin classes: IgG, IgM, IgA, IgD, IgG, and IgE. An "antibody fragment" is a derivative of an antibody or a portion of an antibody that is less than the full length. Antibody fragments are capable of retaining at least one significant site of the binding ability of the full-length antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab') ₂ , scFv, Fv, dsFv dimers, and Fd fragments.

Antibody fragments can be produced by any means. For example, antibody fragments can be produced by enzymatic or chemical cleavage of an intact antibody, or by recombination from genes encoding partial antibody sequences. In other words, antibody fragments can be partially or fully recombinantly produced. Antibody fragments may be any single chain antibody fragments. In other words, antibody fragments may comprise multiple peptide chains that are interconnected, eg, by disulfide bonds. Antibody fragments can also be any multimolecular complex. A functional antibody fragment generally comprises at least about 50 amino acids, and more antibody fragments generally comprise at least about 200 amino acids.

Single-chain Fvs (scFvs) are recombinant antibody fragments consisting only of variable light ( _VL ) and variable heavy ( _VH ) chains covalently bound to each other as polypeptide chains. One of VL and _VH has _an amino terminal region. Polypeptide chains are variable in length and composition, the length of which allows the two variable domains to bridge to each other without seriously affecting the arrangement of atoms. Polypeptide chains are usually composed primarily of stretches of glycine and serine residues with some interspersed glutamic and lysine residues to increase their solubility. "Dimer" refers to a dimer of single-chain Fvs. Dimeric monomers generally contain shorter peptide chains than most single-chain Fvs, and they show a tendency to form dimers.

An "Fv" fragment consists of a _VH and a _VL domain non-covalently linked to each other. The term "dsFv" herein refers to an Fv comprising an intermolecular disulfide bond that stabilizes the _VH - _VL pair. A "F(ab') ₂ " fragment is a fragment of an antibody, essentially identical to that obtained by digestion of an immunoglobulin (usually IgG) with pepsin at pH 4.0-4.5. This fragment can also be synthesized recombinantly. A "Fab'" fragment is an antibody fragment that is essentially identical to a fragment obtained by reducing the disulfide bond connecting the two heavy chains of the F(ab') ₂ fragment. Fab' fragments can also be synthesized recombinantly. A "Fab" fragment is an antibody fragment essentially identical to that obtained by papain digestion of an immunoglobulin (usually IgG). Fab fragments can also be synthesized recombinantly. The heavy chain fragment on the Fab fragment is the Fd fragment.

Before using the device, it is not possible for the user to see the analyte binding zone. In a specific protocol, the test result will be displayed with a plus sign or a minus sign, depending on whether the analyte is present in the sample. When the sample does not contain the analyte, the positive control area displays a minus sign because one or more components can change from a first color to a second color (eg, from white to red). If the sample contains an analyte, the analyte reacts with the labeled reagent zone reagent and is captured by specific binding molecules at the analyte binding zone. In a specific embodiment, the analyte binding region is two regions located on both sides of the positive control region and distributed along the latitudinal direction of the test strip. "Latitudinal" means the direction perpendicular to the flow of fluid through the device, and generally also refers to the direction perpendicular to the full length of the test strip. The positive control zone and the analyte binding zone interact to produce a recognizable symbol. In one embodiment, the positive control region is capable of interacting with the analyte binding region to display a plus sign, but the analyte binding region is also capable of interacting with the positive control region to form other recognizable symbols.

In another embodiment, the analyte binding zone is one zone across the test strip and the positive control zone is two sites on either side of the analyte binding zone. Therefore, the positive control zone is located at two locations in the longitudinal direction on the test strip, and the analyte binding zone is located on the top of the positive control zone or between the positive control zones. In different embodiments, these zones may or may not overlap. One or more components used on the positive control zone or filament can be selected to be of the same color so that the positive control zone and the analyte binding zone form a single symbol when interacting. Thus, the positive test symbol is displayed as a plus sign, and the negative test symbol is displayed as a minus sign.

In yet another embodiment, a plus sign is formed by the positive control zone and the analyte detection zone, which may or may not overlap. In this particular protocol, the analyte binding zone on the test strip is displayed first, followed by the positive control zone, such that it displays a plus sign for a positive result and a minus sign for a negative result.

In another embodiment, the positive control zone is positioned on the side of the test strip and the analyte binding zone is positioned longitudinally thereof. In this positioning, the sign of the positive result is still a plus sign, and the sign of the negative result is still a minus sign. Compared with other schemes, the only positioning is different.

In a related embodiment, the positive control zone consists of a plurality of strips (not a single strip) aligned in a row, which are adjacent to and perpendicular to the analyte detection zone so as to form a plus sign. Conversely, the analyte binding zone can consist of a plurality of aligned strips perpendicular to and adjacent to the positive control zone, which together form a plus sign.

In another embodiment, the test area and the positive control area interact to form an "X". In this particular protocol, the test zone and positive control zone are positioned at an angle to the direction of sample flow. In a further embodiment, the test and positive control areas are configured to interact exactly to form a "Y".

Analyte type

Any analyte can be analyzed with the present invention. Examples of analytes that can be reliably detected by the present invention include (but are not limited to) human chorionic gonadotropin (hCG), luteinizing hormone (LH), ovarian stimulating hormone (FSH), hepatitis C virus (HCV), hepatitis B Virus (HBV), HBsAg, HIV and any drugs of abuse. Analytes can be detected in any liquid or liquefied sample, such as urine, saliva, saliva, blood, plasma, or serum. Other examples of analytes are creatinine, bilirubin, nitrite, proteins (non-specific), blood, leukocytes, glucose, heavy metals and toxins, bacterial components (e.g., specific coli 0157:H7, Staphylococcus aureus, Salmonella, Clostridium perfringens, Campylobacter, Listeria monocytogenes, Vibrio enteritidis, or Bacillus cereus). Any other analyte suitable for the lateral flow assay format can be detected with the device.

Types of Samples Any type of sample can be tested with the device of the present invention, including bodily fluids (eg, urine and other bodily fluids, as well as clinical samples). Liquid samples may be derived from solid or semi-solid samples, including feces, biological tissue, and food samples. These solid and semi-solid samples can be converted into liquid samples by any suitable method, such as mixing, crushing, macerating, incubating, dissolving or enzymatically dissolving solid samples in a suitable liquid (for example, water, phosphate buffer or other buffers). "Biological samples" include samples derived from living animals, plants, and food, and also include urine, saliva, blood and blood components, cerebrospinal fluid, vaginal swabs, semen, feces, sweat, secretions, tissues, organs, tumors, Tissue and organ cultures, cell cultures and conditioned media therein, whether human or animal. Food samples included processed food ingredients and final products, meat, cheese, wine, milk and drinking water. Plant samples include samples derived from any plant, plant tissue, plant cell culture and conditioned media therein. "Environmental samples" are those samples derived from the environment (eg, samples of lake water or other bodies of water, sewage samples, soil samples, groundwater samples, seawater samples, waste water samples). Sewage and related wastes can also be included in environmental samples.

Instructions

The invention also provides methods of detecting the presence of an analyte in a liquid sample using the device of the invention. The method steps include placing a liquid sample on the sample application area of the device of the invention and then flowing the liquid sample through the test strip. A liquid sample can be placed on the sample application area by any easily practicable method, for example by using a dropper.

Referring to Figures 1-3, after a liquid or liquefied sample is added to the sample application zone 25, the sample begins to flow through the matrix and into the reagent strip. Reagents necessary for the assay and/or labeling the analyte interact with the sample as the sample enters the reagent zone 30 . The analyte in the sample is thus labeled with a detectable label, in this case an antibody to the analyte carrying gold sol particles. As the sample flows through the device, the analyte in the liquid sample is labeled with a detectable label and retained in the analyte binding zone of the detection zone. The analyte binding domain comprises a member of a specific binding pair of a half body associated with the analyte, in this example an antibody that binds directly to an epitope of the analyte. Additionally, the color-changing component on the positive control filament becomes wet when the liquid sample flows through the positive control zone, and the filament changes from a first color (eg, white) to a second color (eg, red).

The positive control filament and detectable label can be chosen to be the same color so that when the labeled analyte binds to the analyte binding zone, the interaction of the positive control zone and the analyte control zone occurs in the detection zone. An identifiable symbol, in this case a "+" sign. In this example, gold sol appears red when it accumulates in the analyte-binding region, interacting with the red positive control filament to form a "+" sign.

In the absence of analyte in the sample, the initial symbol (minus sign in the positive control area) is clearly visible in the test area, and a minus sign is displayed in the test area at the end of the test to indicate a negative result of the test.

test kit

Another part of the invention is the kit of the invention for determining the presence or absence of an analyte in a fluid, and instructions for using the device. The test kit of the present invention can be packed in any form according to the needs of customers.

In one embodiment, the test strip can be designed as a "mid-stream urine" fertility test device, comprising a box into which the test strip can be placed, a gauze that can be attached to the sample application area on the test strip and a device for detecting the target prolific hormone. Reagent liquid association, such as human chorionic gonadotropin (hCG), luteinizing hormone (LH) or ovarian stimulating hormone (FSH). There is a window juxtaposed with the detection area on the box, and the test results can be seen. In some embodiments, a midstream urine pregnancy test kit device includes one or more individually packaged devices and a set of instructions. The instructions explain how to perform the test and interpret the results. For example, a patient provides a urine sample at the sample collection site of a urine testing device, the device transports the urine to the sample application section of the device, and the fluid flows through the reagent and detection areas of the device. If the test result is negative (no pregnancy), the color-changing component of the positive control area becomes wetted with the sample to a second color, showing a minus sign. If the test result is positive (pregnant), the color changing component of the positive control zone and the color of the analyte binding zone interact to form a plus sign.

In each specific protocol, the kit contains 4 or more or contains 6 or more ovulation test devices, and 1 or more pregnancy test devices and a booklet with instructions on how to use the device to determine the time of peak luteinizing hormone and how to Instructions for using the device to perform a pregnancy test. The device can be any of the specific solutions described here. The device can also be designed as a "test card" for professional laboratories.

In another embodiment, the kit comprises a test strip of the invention. In one embodiment, the test strips can be designed for pregnancy testing and packaged in a case containing 15 or more or 20 or more test strips and an instruction sheet.

experiment

In order to better illustrate the beneficial effect of sub-invention, experiment description is now given

Experiment 1: Construction of hCG test device

This example describes a specific implementation of the device of the present invention for the detection of hCG in urine.

Reagent strips are manufactured according to professional methods, except where otherwise noted. Referring to FIG. 6 , the positive control area is formed by placing the positive control filaments 50 in grooves 85 carved on the support layer 80 for accommodating the filaments. Positive control filament 50 is an extension of positive control block 52 . As depicted in Figure 6, in this particular embodiment, the filaments and control blocks are bilayered. Filaments were 0.9mm x 10mm paper discs and had been previously treated with 3 μl of water-sensitive ink (purchased from Beijing Chuangxin Chengye Technology Co., Ltd., Beijing, China, under the name of water-sensitive ink), and Let dry at room temperature until it turns white.

Goat anti-αhCG IgG (4.0 mg/ml) was applied to the analyte-binding zone on the nitrocellulose strip. Viewing the device from above, the analyte-binding zone was located on both sides of the positive control filament, so when a positive test result was generated Observers see a plus sign. The reagent area contains gold sol-labeled mouse anti-βhCG IgG. The various parts of the test device are stacked on top of each other. An anti-human IgG (1.3 mg/ml) was optionally added using a microprocessor-controlled microsyringe as a control line for the second procedure distal to the nitrocellulose membrane.

Use of this device

After the test strips were constructed, we tested the test strips with hCG positive and negative urine. We obtained three batches of urine samples that contained amounts of pregnancy-indicating hCG and thus correlated with positive or negative populations. The first batch included 200 urine samples. The second and third batches each included 60 urine samples.

In each example using the device and method of the present invention, the detection results of 100% of the urine samples can correctly reflect their objective conditions, and the specificity reaches more than 99.9%.

The invention described by way of example herein can be used as long as each part is available, and its limitations are not specifically stated here. The terms and expressions used to describe the device in this article are not the only constant, and we have no intention to use these terms and expressions to exclude any expressions with the same meaning that describe the structure or characteristics of the device. We agree that in this article Various expressions within the scope of the claimed invention. Therefore, we believe that although the invention has been clearly demonstrated herein with various specific solutions and arbitrary characterizations, changes in the expression of the designs disclosed herein also require the recourse to those skilled in the art, and these Changes are to be made in accordance with the accompanying statement of the invention.

The contents of articles, patents, patent applications, and all other documents, as well as useful electronic information mentioned and cited herein are combined and must be referenced as a complete content, and any part of it published must be specifically identified. at this point. Applicants have the right to incorporate into this application the information and material of any and all of these articles, patents, patent applications, or other documents as part of the disclosure of this patent specification.

Claims (26)

1. A detection device is used to detect whether a sample contains an analyte, and the detection device comprises: A reagent strip supporting the flow of a liquid sample; the strip has a liquid sample application zone; a detection zone containing a positive control zone, an analyte binding zone, and one or more zones containing the reaction reagents necessary to perform the test; The analyte binding zone comprises a specific binding molecule, and the positive control zone comprises a water-absorbing strip made of a water-absorbing material, the water-absorbing strip containing A substance of one color which, when wet, exhibits one or more components of a second color. 2. The detection device of claim 1, wherein said one or more components comprise at least one base dye. 3. The detection device according to claim 1, wherein the reagent strip in the described device is a nitrocellulose test strip, and the positive control area is formed by a minus sign shape on the test strip. 4. The detection device according to claim 3, wherein the analyte binding region is composed of two positions located on both sides of the positive control region, which contains a specific binding molecule that can bind to the analyte The positive control area and the analyte binding area interact to form a recognizable symbol when the sample contains the analyte and wets the positive control area. 5. The detection device according to claim 3, wherein the identifiable symbol is a plus sign, an "X" shape, a "Y" shape or an "N" shape. 6. The detection device of claim 3, wherein said absorbent strip comprises a positive control filament, and said filament comprises one or more components of a water sensitive dye. 7. The detection device of claim 3, wherein said specific binding molecule is an antibody or antibody fragment, and said one or more components comprise a base dye. 8. The detection device according to claim 7, wherein the analyte is human chorionic gonadotropin or luteinizing hormone. 9. The detection device according to claim 6, wherein the positive control area is composed of one or more positive control filaments in the detection area, and the positive control area does not include components of specific binding pairs. 10. The detection device according to claim 3, wherein the analyte binding region further comprises a specific binding molecule capable of specifically binding the analyte, and further comprises a label capable of Generate detectable information. 11. The detection device of claim 10, wherein said marker comprises a colored particle. 12. The detection device according to claim 11, wherein the colored particles are dextran particles. 13. The detection device according to claim 1, wherein the analyte-binding region is perpendicular to the longitudinal axis of the reagent strip in the form of a strip, and further comprises a specific binding molecule that binds the analyte, The positive control zone consists of two regions flanking the analyte, the positive control zone and the analyte binding zone interact to form a recognizable symbol. 14. The detection device according to claim 1, wherein the first color is white, light or colorless, and the second color is red. 15. The detection device according to claim 1, wherein the reagent strip is a test strip made of a water-absorbing material; the positive control area is composed of a minus-shaped object parallel to the longitudinal axis of the water-absorbing material ; The analyte binding area is composed of areas on both sides of the positive control area, and the analyte binding area and the positive control area interact to form a recognizable symbol. 16. The detection device according to claim 15, wherein the analyte binding region is perpendicular to the longitudinal axis of the test strip in the form of a strip, wherein the analyte binding region comprises a specific binding molecule, Enables the analyte to bind the label. 17. The detection device according to claim 16, wherein if the detection sample contains an analyte, when the analyte passes through the reagent area, it is labeled by the label to form a labeling complex, and when the analyte is combined The labeled complex is accumulated on the analyte-binding region. 18 . The detection device according to claim 1 , wherein the positive control area includes a water-sensitive substance that changes color when exposed to water and forms an identifiable water-sensitive substance. 19. The detection device according to claim 1, characterized in that, the detection device comprises a water-absorbent matrix material that supports liquid flow, and a groove corresponding to the shape of the water-absorbent strip is provided on the matrix material, The absorbent strip is placed in the groove. 20. The detection device of claim 1, wherein the detection device comprises a matrix material supporting liquid flow, the absorbent strip is disposed beneath the matrix material, the matrix material exhibits a Opaque, transparent or translucent when wet. 21. The detection device according to claim 1, wherein the positive control area further comprises a positive control block, and a water-absorbent strip protrudes from the positive control block in a tongue shape. 22. The detection device according to claim 21, characterized in that, the detection device further comprises a support layer with a groove, and the tongue-shaped protruding water-absorbent strip is embedded in the groove. 23. The detection device according to claim 1, further comprising a bottom support, a groove is formed on the bottom support, and the water-absorbing strip is inserted into the groove. 24. The detection device of claim 1, further comprising a water-absorbing matrix material that supports liquid flow, a positive control block, and a support layer, the support layer being located in the positive control block , above the water-absorbing strip, and below the water-absorbing matrix material. 25. The detection device according to any one of claims 1 to 24, characterized in that there are two absorbent strips. 26. The detection device according to any one of claims 1 to 24, characterized in that the absorbent strip is made of paper or other fibrous or fibrous material capable of carrying liquid.

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