KR102399034B1 - Composition for Coronavirus Diagnosis and Use thereof - Google Patents

Abstract

The present invention relates to a composition for diagnosing coronavirus and a use thereof. According to the present invention, it is possible to detect coronavirus (SARS-CoV-2) with high sensitivity and specificity. In one embodiment of the present invention, an antibody specifically binds to spike protein or nucleocapsid protein on the surface of SARS-CoV-2.

Description

Composition for Coronavirus Diagnosis and Use thereof

The present invention relates to a composition for diagnosing coronavirus and its use.

Corona 19 (COVID-19, 2019-nCoV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) is a new virus first reported in Wuhan City, Hubei Province, China in December 2019. It is a non-segmented positive-strand RNA virus) and has been reported to have a 50-200 nm diameter and 9-12 nm spike protein. In addition, as a result of phylogenetic analysis, it was confirmed that it was the closest to the SARS-associated coronavirus. The name of Corona 19 (COVID-19) refers to an infectious disease, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) refers to the name of the virus and was named separately.

COVID-19 enters the lungs through ACE2 receptors and is known to cause respiratory syndromes such as cough, shortness of breath, and pneumonia, and the transmission route is reported through droplet contact. The global fatality rate is 4.3%, but a specific antiviral drug has not yet been developed, so only conservative treatments such as replenishment of fluids and antipyretics are being performed.

Corona 19 is known to be transmitted when droplets of an infected person penetrate the respiratory tract or the mucous membranes of the eyes, nose, and mouth. are putting all their effort into

A system that can quickly and in real time identify the health abnormality of the subject to be analyzed at the access facility is required. It has to be quarantined in some facilities until it is released, which is economically and socially expensive, such as quarantine facilities and diagnosis time.

Korean Utility Model Document No. 20-2011-0006452 (June 29, 2011)

According to the present invention, it is an object of the present invention to provide a composition for diagnosis of coronavirus (SARS-CoV-2).

Another object of the present invention is to provide a medical device capable of detecting coronavirus (SARS-CoV-2) with high sensitivity and specificity.

In addition, a cut portion is formed on the sample collection swab, and the extraction buffer is composed of a mixed solution of predetermined substances having a predetermined concentration, thereby providing a medical device capable of detecting coronavirus with high precision even with a small amount of sample. that has its purpose

Another object of the present invention is to provide a medical device with improved detection sensitivity by increasing antigen-antibody interaction time by providing a reserve pad in a diagnostic kit in which a test line and a control line are formed.

Another object of the present invention is to provide a medical device in which a protective film in the form of a transparent film is attached to the result confirmation unit to prevent foreign substances from being introduced into the diagnostic kit and to visually check the diagnostic result from the outside.

Another object of the present invention is to provide a medical device in which the sample dropper is provided in a form capable of accommodating a solution of a predetermined volume or more, so that the solution containing the sample is prevented from leaking to the outside even when an appropriate amount of solution is introduced.

An embodiment of the present invention for solving the above problems, SARS-coronavirus-2 (SARS-CoV-2) on the surface of the spike protein (Spike protein) or nucleocapsid protein (nucleocapsid protein) specifically Antibodies that bind are provided.

In addition, the present invention provides an antibody that specifically binds to a spike protein or a nucleocapsid protein on the surface of SARS-CoV-2 is immobilized, and the immobilized antibody Mouse monoclonal anti-Chicken IgY immobilized more downstream, provided upstream from the immobilized antibody, and specifically binding to other spike proteins or nucleocapsid proteins on the SARS-coronavirus-2 surface, Gold(III) chloride Trihydrate conjugated mAb anti-COVID19 antibody and Gold (III) chloride trihydrate conjugated Purified chicken IgY, which is provided upstream from the mouse monoclonal anti-Chicken IgY, and specifically binds to the Mouse monoclonal anti-Chicken IgY, corona virus A medical device for diagnosing infection is provided.

In one embodiment, the SARS-coronavirus-2 extraction further comprises an extraction tube 210 accommodated in the extraction, the extraction buffer, the extraction buffer accommodated in the extraction tube 210 is 0.18M to Tris at a concentration of 0.22M, Tw-80 at a concentration of 0.45% to 0.55%, Polidocanol at a concentration of 1.35% to 1.65%, NaCl at a concentration of 0.45M to 0.55M, Casein at a concentration of 0.45% to 0.55%, 0.018% to 0.022% concentration It may be a solution containing sodium azide and Proclin 300 at a concentration of 0.045% to 0.055%.

In one embodiment, a sample collection swab 100 configured to collect a sample from a collection target, is coupled to the opening 211 of the extraction tube 210, and passes through the nozzle cap 220 having a filter and the filter and then the test device 500 into which the solution discharged through the outlet 221 of the nozzle cap 220 is added, and the sample collection swab 100 is placed in the extraction buffer accommodated in the extraction tube 210. The supported and collected specimen may be eluted in the extraction buffer.

In one embodiment, the sample collection swab 100 includes a first head portion 111 that is bent and extended as the diameter increases, and a second head portion that has the same diameter and extends from the first head portion 111 . (112), a third head part 113 bent and extended from the second head part 112 while decreasing in diameter, and a fourth head part bent and extended from the third head part 113 while increasing in diameter from the third head part 113 The head 110, including a 114, is located on one side of the handle 120 and the handle 120 extending with a predetermined length and thickness from the fourth head portion 114 of the head 110, It may include a cutout 130 having a thinner thickness than the handle 120 .

In one embodiment, the test device 500 is a backing card 310 made of polyethylene material, placed on the backing card 310, and a test line 321 to which a mouse monoclonal anti COVID19 antibody is fixed. And, at the first end in the longitudinal direction of the membrane 320 made of a cellulose membrane material with a control line 322 having a mouse monoclonal anti-Chicken IgY immobilized thereon, the membrane 320 and at least A reserve pad 330 made of a polyester material laminated on the membrane 320 to partially overlap, at the second end in the longitudinal direction of the membrane 320 opposite to the first end, at least partially overlaps the membrane 320 A moisture absorption pad 340 made of a glass fiber material laminated on the membrane 320 so as to face the membrane 320 with the reserve pad 330 interposed therebetween, and at least with the reserve pad 330 . As a conjugate pad 350 laminated on the reserve pad 330 to partially overlap, a polyester material equipped with Gold(III) chloride trihydrate conjugated mAb anti-COVID19 antibody and Gold(III) chloride trihydrate conjugated Purified chicken IgY It faces the reserve pad 330 with the conjugate pad 350 and the conjugate pad 350 interposed therebetween, and is laminated on the conjugate pad 350 so as to at least partially overlap the conjugate pad 350 . A diagnostic kit 300 including a sample pad 360 made of a glass fiber material may be further included.

In one embodiment, a PVC material that covers the diagnostic kit 300 so that the first area where the test line 321 and the control line 322 are formed and the second area that is at least a part of the sample pad 360 are exposed A housing 400 may be further included.

In one embodiment, the housing 400 includes a lower housing 401 that covers a lower portion of the diagnostic kit 300 and an upper housing 402 that covers an upper portion of the diagnostic kit, and the upper The housing 402 includes a first opening 411 through which the first region is exposed, a first inclined portion 412 inclined upward from the first opening 411 toward the outside of the diagnostic kit 300, the A first extension portion 413 extending from the first inclined portion 412 to the outside of the diagnostic kit 300 in parallel to the ground and a first extension portion 413 extending upwardly from the first extension portion 413 and perpendicular to the ground. It may include a result confirmation unit 410 including one step portion 414 .

In an embodiment, the upper housing 402 includes a second opening 421 through which the second region is exposed, and extends from the second opening 421 while being bent toward the outside of the diagnostic kit 300 . A second inclined portion 422 , a second extension portion 423 extending parallel to the ground from the second inclined portion 422 toward the outside of the diagnostic kit 300 , a lower side from the second extension portion 423 . a second stepped portion 424 extending perpendicular to the ground toward the It may further include a sample dropper 420 including a third stepped portion 426 extending vertically from the ground toward the upper side from 425 .

In addition, the present invention is a medical device for diagnosing infection using an antibody that specifically binds to the nucleocapsid protein of SARS-CoV-2 (SARS-CoV-2). As the collection swab 100 , the curved first head portion 111 , the second head portion 112 connected to the first head portion 111 , and the third having a reduced diameter from the second head portion 112 . A head 110 including a head portion 113 , a handle 120 extending with a predetermined length and thickness from the head 110 , and located on one side of the handle 120 , thinner than the handle 120 . A sample collection swab 100 including a thick cut portion 130, an extraction buffer for extracting the SARS-coronavirus-2 from the sample collected by the sampling swab 100 is accommodated, and the sample collection A swab 100 is loaded in the extraction buffer and the sample collected is eluted in the extraction buffer, the extraction tube 210, coupled to the opening 211 of the extraction tube 210, and a nozzle cap equipped with a filter ( 220) and an inspection device 500 into which the solution discharged through the outlet 221 of the nozzle cap 220 is injected after passing through the filter, and the inspection device 500 is provided with the solution , a diagnostic kit 300 including a test line 321 whose color develops depending on whether or not the SARS-coronavirus-2 is included in the injected solution, and a control line 322 that always develops color according to the development of the injected solution 300 and the diagnosis A housing 400 covering the diagnostic kit 300 such that the first area where the test line 321 and the control line 322 are formed and the second area that is at least a part of the sample pad 360 of the kit 300 are exposed. ), wherein the diagnostic kit 300 includes a backing card 310, a membrane 320 placed on the backing card 310 and formed with the test line 321 and the control line 322, the membrane Part 1 of 320 A first material that is provided in a minute and is fixed to the test line 321 and the SARS-coronavirus-2 and contains a chromogenic material, and a material fixed to the control line 322 and specific The conjugate pad 350 is provided with a second material that is positively combined and includes a color developing material, and is provided in the first portion of the conjugate pad 350, and the solution discharged through the outlet 221 is injected. a sample pad 360 and a moisture absorption pad 340 provided in a second portion of the membrane 320 opposite to the first portion, wherein the housing 400 includes a first area to be exposed. A result confirmation unit 410 including a first opening 411, a first inclined portion 412 inclined upwardly from the first opening 411 outward, and a second opening through which the second area is exposed ( 421), a second inclined portion 422 curved outwardly from the second opening 421, a second extension portion 423 extending outwardly from the second inclined portion 422 parallel to the ground, and and a sample dropper 420 including a second step portion 424 extending downward from the second extension portion 423, and the material fixed to the test line 321 is the SARS-coronavirus When the SARS-coronavirus-2 is contained in the solution injected into the sample pad 360 by binding specifically to -2, color is developed at the test line 321, and when not included, color is not formed. , The material fixed to the control line 322 is specifically combined with the second material to provide a medical device for diagnosing corona virus infection, in which color develops at all times in the control line 322 .

In one embodiment, the material immobilized on the control line 322 is Mouse monoclonal anti-Chicken IgY, the first material is Gold(III) chloride trihydrate conjugated mAb anti-COVID19 antibody, and the second material is the Mouse It may be Gold(III) chloride trihydrate conjugated Purified chicken IgY that specifically binds to monoclonal anti-Chicken IgY.

In one embodiment, the extraction buffer accommodated in the extraction tube 210 is 0.18M to 0.22M concentration of Tris, 0.45% to 0.55% concentration of Tw-80, 1.35% to 1.65% concentration of Polidocanol, 0.45M to 0.55 It may be a solution comprising NaCl at a concentration of M, Casein at a concentration of 0.45% to 0.55%, sodium azide at a concentration of 0.018% to 0.022%, and Proclin 300 at a concentration of 0.045% to 0.055%.

In one embodiment, the nozzle cap 220, a coupling portion coupled to the extraction tube 210, a step portion larger than the coupling portion while being connected to the coupling portion, and the outlet 221 connected from the step portion Including, an inner diameter of the upper portion of the extraction tube 210 in which the opening 211 is formed may be greater than the outer diameter of the coupling portion and smaller than the outer diameter of the stepped portion.

In one embodiment, the first head portion 111 is bent as the diameter increases,

The second head part 112 continues with the same diameter from the first head part 111, and the third head part 113 is bent while decreasing in diameter from the second head part 112, The head 110 may further include a fourth head part 114 that is curved while increasing in diameter from the third head part 113 .

In one embodiment, the backing card 310 is made of a polyethylene material, the membrane 320 is made of a cellulose membrane material, and the moisture absorption pad 340 is made of a glass fiber material. , the conjugate pad 350 is made of a polyester material, the sample pad 360 is made of a glass fiber material, and the diagnostic kit 300 is formed in the first part of the membrane 320. , may further include a polyester reserve pad 330 laminated on the membrane 320 to at least partially overlap the membrane 320 .

In one embodiment, in the first part of the membrane 320 , the membrane 320 partially overlaps the reserve pad 330 , and the reserve pad 330 in the first part of the reserve pad 330 . is partially overlapped with the conjugate pad 350 , and in a first portion of the conjugate pad 350 , the conjugate pad 350 partially overlaps the sample pad 360 , and In the second part, the membrane 320 may partially overlap the moisture absorption pad 340 .

In one embodiment, the cross-section of the end of the second portion of the sample pad 360 may be spaced apart from the cross-section of the end of the first portion of the membrane 320 .

In one embodiment, the housing 400 may be made of a PVC material.

In an embodiment, the second inclined portion 422 may include a curved surface in which an angle formed with the ground increases.

In an embodiment, the shape formed by the edge of the second opening 421 and the shape formed by the inner or outer edge of the second extension part 423 may correspond to each other.

In an embodiment, the result confirmation unit 410 includes a first extension 413 extending outward from the first inclined portion 412 in parallel with the ground and from the first extension 413 . It may further include a first step portion 414 extending perpendicularly to the ground toward the upper side.

In one embodiment, the sample dropper 420 includes a depression 425 extending outward from the second step 424 in parallel with the ground and upward from the depression 425 on the ground. It may further include a third step portion 426 extending perpendicular to the.

The medical device for diagnosing coronavirus infection according to the present invention is capable of detecting coronavirus with high sensitivity and specificity.

In addition, since a cut portion is formed on the sample collection swab and the extraction buffer is composed of a mixed solution of predetermined substances having a predetermined concentration, it is possible to detect the coronavirus with high precision even with a small amount of sample.

In addition, in the diagnostic kit in which the test line and the control line are formed, by providing a reserve pad, the antigen-antibody interaction time is increased, thereby improving detection sensitivity.

In addition, a protective film in the form of a transparent film is attached to the result confirmation unit to prevent the introduction of foreign substances into the diagnostic kit, and it is possible to visually check the diagnostic results from the outside.

In addition, the sample dropper is provided in a form capable of accommodating a solution of a predetermined capacity or more, so that the solution containing the sample is prevented from leaking to the outside even if an appropriate amount or more of the solution is introduced.

1 is a view showing a state in which a diagnostic kit and a housing of a medical device for diagnosing coronavirus infection according to an embodiment of the present invention are combined.
FIG. 2 is a diagram for describing the diagnostic kit of FIG. 1 in more detail.
3 is a view for explaining a sample collection swab of a medical device for diagnosing coronavirus infection according to an embodiment of the present invention.
4 is a view for explaining an extraction tube and a nozzle cap of a medical device for diagnosing coronavirus infection according to an embodiment of the present invention.

In some cases, well-known structures and devices may be omitted or shown in block diagram form focusing on core functions of each structure and device in order to avoid obscuring the concept of the present invention.

Throughout the specification, when a part is said to "comprising or including" a certain component, it does not exclude other components unless otherwise stated, meaning that other components may be further included. do. In addition, terms such as “…unit”, “…group”, and “module” described in the specification mean a unit that processes at least one function or operation, which may be implemented as hardware or software or a combination of hardware and software. there is. Also, "a or an", "one", "the" and like related terms are used differently herein in the context of describing the invention (especially in the context of the following claims). Unless indicated or clearly contradicted by context, it may be used in a sense including both the singular and the plural.

In describing the embodiments of the present invention, if it is determined that a detailed description of a well-known function or configuration may unnecessarily obscure the gist of the present invention, the detailed description thereof will be omitted. In addition, the terms to be described later are terms defined in consideration of functions in an embodiment of the present invention, which may vary according to intentions or customs of users and operators. Therefore, the definition should be made based on the content throughout this specification.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

1. Description of medical devices for diagnosing coronavirus infection

Referring to FIG. 1 , a medical device for diagnosing coronavirus infection according to an embodiment of the present invention includes a sample collection swab 100 , an extraction tube 210 , a nozzle cap 220 , and a test device 500 .

The sample collection swab 100 is a part configured to collect a sample from the subject to be analyzed.

Referring to FIG. 3 , the sample collection swab 100 may be provided in the form of a swab, and includes a head 110 , a handle 120 , and a cutting unit 130 .

The head 110 is a portion from which a sample is collected. Referring to FIG. 3 , the first head portion 111 bent and extended as the diameter increases, and the second head extending with the same diameter from the first head portion 111 . Part 112, the third head part 113 bent and extended from the second head part 112 while decreasing in diameter, and the fourth head part bent and extended with increasing diameter from the third head part 113 ( 114).

The head 110 is preferably made of a material that is in contact with the sample and can accommodate the sample in contact with a predetermined capacity or more.

In addition, the head 110 has a length of 13.5 mm to 16.5 mm, more specifically, may have a length of 15 mm so that a sufficient amount of the sample can be accommodated in the head 110 .

In addition, the head 110 may have a thickness of 3.96 mm to 4.84 mm, more specifically, a thickness of 4.4 mm.

The handle 120 has a predetermined length and thickness from the fourth head portion 114 of the head 110 and extends in one direction. The subject to be collected is operated so that the head 110 is inserted into the oral cavity or nasal cavity while holding the handle 120 with their hand. The handle 120, even when the head 110 is inserted up to the sample collection site, the handle 120 may have a length positioned outside the oral cavity or nasal cavity, for example, 67.5 mm to 82.5 mm, more specifically 75 mm. can have a length.

In addition, the handle 120 may have a thickness of 3.96 mm to 4.84 mm, more specifically, a thickness of 4.4 mm.

The cut portion 130 is formed on one side of the handle 120 , and is a portion formed to have a thinner thickness than the handle 120 .

For example, the cut portion 130 may be formed at a position separated from the head 110 by 40.5 mm to 49.5 mm, more specifically, at a position separated by 45 mm.

Since the cut portion 130 is formed to have a thinner thickness than the handle 120, the sample collection swab 100 on which the sample collection has been completed is loaded in the extraction buffer of the extraction tube 210 to be described later, and then the cut portion 130 is located on the handle ( 120), the part of the handle 120 located at the rear end of the cutting part 130 is separated from the sample collection swab 100. The nozzle cap 220 may be coupled to the extraction tube 210 while the configuration including the head 110 is supported in the extraction buffer inside the extraction tube 210, and as the sample is loaded in the extraction buffer for a long time, , it has the advantage that it is possible to extract a large amount of sample into the extraction buffer.

The extraction tube 210 has an opening 211 formed in the upper portion, and has a space in which an extraction buffer for extracting a sample from the sample collection swab 100 is accommodated. The nozzle cap 220 is installed through the open opening 211 (refer to FIG. 4).

The extraction tube 210 may be made of a soft material, and a user who wants to inject the extraction solution accommodated in the extraction tube 210 into the test device 500 controls the time and degree of pressurization of the extraction tube 210 . By doing so, it is possible to control the amount of the extract injected into the test device (500).

The extraction buffer accommodated in the inner space of the extraction tube 210 may have a capacity of 315 μl to 385 μl, and more specifically, it may have a capacity of 350 μl.

Extraction buffer is 0.18M to 0.22M concentration, specifically 0.2M concentration of Tris, 0.45% to 0.55% concentration, specifically 0.5% concentration of Tw-80, 1.35% to 1.65% concentration, specifically 1.5% concentration of Polidocanol, NaCl at a concentration of 0.45M to 0.55M, specifically NaCl at a concentration of 0.5M, Casein at a concentration of 0.45% to 0.55%, specifically at a concentration of 0.5%, Sodium azide at a concentration of 0.018% to 0.022%, specifically 0.02% concentration, and 0.045% to 0.055 % concentration, specifically, may include Proclin 300 at a concentration of 0.05%.

The nozzle cap 220 is coupled to the opening 211 of the extraction tube 210 , and a filter is provided therein. When the extraction buffer accommodated in the extraction tube 210 is discharged to the outside through the outlet 221 , foreign substances It is possible to remove

The test device 500 is configured to display a different result depending on whether a solution containing a sample is injected, and whether or not the injected solution contains coronavirus and the amount of the injected solution.

Referring to FIG. 1 , a test device 500 includes a diagnostic kit 300 and a housing 400 .

The diagnostic kit 300 is configured to show different results depending on the substance contained in the solution, and the housing 400 is configured to surround the outside of the diagnostic kit 300 , the test device 500 . It constitutes the exterior of the diagnosing kit 300 and gives durability to the diagnostic kit 300 .

First, the configuration of the diagnostic kit 300 according to the embodiment of the present invention will be described in detail with reference to FIG. 2 .

The diagnostic kit 300 includes a backing card 310 , a membrane 320 , a reserve pad 330 , a moisture absorption pad 340 , a conjugate pad 350 , and a sample pad 360 .

The backing card 310 is provided under the diagnostic kit 300 , serves as a support for the diagnostic kit 300 , and extends over the entire length of the diagnostic kit 300 . For example, the backing card may be made of polyethylene.

The membrane 320 is placed on the backing card 310 , and a test line 321 and a control line 322 are formed. Depending on whether the test line 321 and the control line 322 are colored, the solution injected into the test device 500 is diagnosed.

For example, the membrane 320 may be made of a cellulose membrane.

1±0.2 μg of mouse monoclonal anti-COVID19 antibody is immobilized on the test line 321 , and 1±0.2 μg of mouse monoclonal anti-Chicken IgY is immobilized on the control line 322 .

The reserve pad 330 is laminated on the membrane 320 so as to at least partially overlap the membrane 320 in the longitudinal direction at the first end of the membrane 320 in the longitudinal direction.

For example, the reserve pad 330 may be made of polyester.

In the present invention, since the reserve pad 330 is provided, the antigen-antibody interaction time is increased, and thus the detection sensitivity of the diagnostic kit 300 can be improved.

The moisture absorption pad 340 is laminated on the membrane 320 so as to at least partially overlap the membrane 320 in the longitudinal direction at the second end in the longitudinal direction of the membrane 320 opposite to the first end.

For example, the moisture absorption pad 340 may be made of glass fiber.

The moisture absorption pad 340 provides a force to allow the solution injected into the sample pad 360 to develop into the moisture absorption pad 340 .

The conjugate pad 350 is stacked on the reserve pad 330 so as to face the membrane 320 with the reserve pad 330 interposed therebetween, and to at least partially overlap the reserve pad 330 in the longitudinal direction.

For example, the conjugate pad 350 may be made of polyester.

The conjugate pad 350 includes a first material that specifically binds to a material fixed to the test line 321 and a coronavirus (SARS-COV-2 (2019-Ncov) nccp 43326/2020/Korea), and a control line A second material that specifically binds to the immobilized material is provided at 322 .

Here, a concept in which a material is provided in the conjugate pad 350 and a material is fixed in the membrane 320 are different. The provision of the material means that the solution injected into the sample pad 360 is developed in the direction of the moisture absorption pad 340 and can move together in the development direction, but that the material is fixed does not move together even if the solution is developed. It means to be fixed in place.

More specifically, the conjugate pad 350 includes a mouse monoclonal anti COVID19 antibody fixed to the test line 321 and binding moieties that specifically bind to the coronavirus, and Gold(III) chloride trihydrate containing a coloring material. Gold (III) chloride trihydrate containing a binding moiety that specifically binds to the conjugated mAb anti-COVID19 antibody (first substance) and the mouse monoclonal anti-Chicken IgY immobilized on the control line (322) and containing a chromogenic substance Conjugated Purified chicken IgY (second substance) is provided.

That is, when the solution injected into the sample pad 360 contains coronavirus, the coronavirus specifically binds to the first material provided in the conjugate pad 350 , and the first material-coronavirus conjugate is the solution. As it unfolds, it moves toward the membrane 320 .

At the same time, the second material provided in the conjugate pad 350 also moves toward the membrane 320 as the solution is developed.

Since the material (Mouse monoclonal anti-COVID19 antibody) fixed to the test line 321 of the membrane 320 specifically binds to the coronavirus, when the developed solution contains the coronavirus, the test line 321 is captured by the immobilized material. At this time, since the material captured by the test line 321 is the first material - coronavirus - the test line fixing material, the color is developed by the coloring material included in the first material. If the solution injected into the sample pad 360 does not contain the coronavirus, even if the solution is developed to the membrane 320 , since the solution is not captured by the material fixed to the test line 321 , separate color development is not performed. does not

That is, when color development is made on the test line 321, it can be determined that the corona virus infection is positive, and when the color is not developed, it can be determined that the corona virus infection is negative.

The material (Mouse monoclonal anti-Chicken IgY) fixed to the control line 322 of the membrane 320 specifically binds to the second material provided in the conjugate pad 350 , and the second material is a solution of the membrane 320 . ) as it develops, so it is always captured by the material immobilized on the control line 322 , regardless of whether the coronavirus is contained in the solution. Since the second material includes a color developing material, the control line 322 is always colored.

If the control line 322 does not develop color, it means that the second material provided on the conjugate pad 350 is not properly developed, so it may be determined as an inspection error and may require re-inspection.

The sample pad 360 faces the reserve pad 330 with the conjugate pad 350 interposed therebetween, and is laminated on the conjugate pad 350 to at least partially overlap the conjugate pad 350 in the longitudinal direction.

For example, the sample pad 360 may be made of glass fiber.

The solution that has passed through the filter of the nozzle cap 220 is injected into the sample pad 360 . When the solution is injected into the sample pad 360 , the injected solution develops in the direction of the moisture absorption pad 340 to cause a reaction between the conjugate pad 350 and the membrane 320 .

The housing 400 is configured to surround the outside except for some areas of the diagnostic kit 300 .

Referring to FIG. 1 , the housing 400 is a diagnostic kit such that the first area where the test line 321 and the control line 322 of the diagnostic kit 300 are formed and the second area that is at least a part of the sample pad 360 are exposed. configured to cover 300 .

Only when the first area is exposed to the outside is it possible to visually check whether the color of the test line 321 and the control line 322 is developed from the outside, and only when the second area is exposed to the outside is the sample pad 360 containing the sample. This is because it is possible to inject the solution.

The housing 400 may be made of PVC to have a predetermined rigidity. The lower housing 401 covers the lower part of the diagnostic kit 300 and the lower housing 401 while covering the upper part of the diagnostic kit 300 . and an upper housing 402 coupled thereto.

First, the configuration of the upper housing 402 to expose the first area of the diagnostic kit 300 to the outside will be described in detail.

Referring to FIG. 1 , in the upper housing 402 , a first opening 411 for exposing the first area is formed, and the first inclination is inclined upward from the first opening 411 toward the outside of the diagnostic kit 300 . A first extension 413 extending from the first inclined portion 412 to the outside of the diagnostic kit 300 in parallel to the ground, and perpendicular to the ground from the first extension 413 upwards It has a result confirmation unit 410 including an extended first stepped portion 414 .

A protective film in the form of a film may be attached to the result confirmation unit 410 to prevent foreign substances from being introduced into the diagnostic kit 300 . For the protective film, for example, a transparent film is applied so that it is possible to visually check whether the inspection line 321 and the control line 322 are colored from the outside, but foreign substances may not be introduced into the diagnostic kit 300 .

As the result confirmation unit 410 includes the configuration of the first opening 411 , the first inclined portion 412 , the first extended portion 413 , and the first stepped portion 414 , the protective film may be attached thereto. By providing an area (in one example, the protective film may be attached to the first extension), it is possible to provide adhesion stability of the protective film.

Next, the configuration of the upper housing 402 to expose the second area of the diagnostic kit 300 to the outside will be described in detail.

Referring to FIG. 1 , the upper housing 402 has a second opening 421 through which the second region is exposed, and a second inclined portion extending from the second opening 421 to the outside of the diagnostic kit 300 while being bent outward ( 422), a second extension portion 423 extending parallel to the ground from the second inclined portion 422 toward the outside of the diagnostic kit 300, and extending perpendicularly to the ground from the second extension portion 423 downward The second step portion 424, the depression portion 425 extending parallel to the ground from the second step portion 424 toward the outside of the diagnostic kit 300, and extending perpendicularly to the ground from the depression portion 425 toward the top It has a sample dripping part 420 including a third stepped part 426.

The sample dropper 420 passes through the filter of the nozzle cap 220 and is configured to inject a solution containing the sample.

Even if the solution is injected into the sample pad 360 , the injected solution may not be absorbed into the sample pad 360 within a short time. In order to prevent the solution not put into the sample pad 360 from leaking to the outside and becoming contaminated, the configuration of the second inclined part 422 and the second extension part 423 was designed. Due to the above configuration, a space in which a solution of a predetermined volume can be accommodated is formed, and the problem that the injected solution is absorbed by the sample pad 360 and leaked to the outside while it is developed is prevented.

In the test device 500 according to the present invention, it is recommended to inject an appropriate amount of solution (for example, the amount of 4 drops of solution that has passed through the nozzle cap), but depending on the operator, a larger amount of solution may be added.

When a larger amount of solution than the accommodating space formed due to the configuration of the second inclined part 422 and the second extension part 423 is input, the solution may leak out of the diagnostic kit 300 , so in the present invention, the second By forming another accommodating space composed of the stepped portion 424, the recessed portion 425 and the third stepped portion 426, the solution is accommodated in the accommodating space even if a solution of more than an appropriate capacity is introduced and designed so that it does not leak to the outside. Thus, external contamination can be minimized.

2. Validation Experiment

2-1. Preparation of antibodies

Antibodies fixed to the test line 321 and the control line 322 of the membrane 320 and antibodies provided in the conjugate pad 350 were prepared as described in Table 1 below.

No. Ingredient name Information One Mouse monoclonal anti-COVID19 antibody (mAb anti-COVID19 antibody) Source: Mouse
Isotype: IgG
Immunogen: Recombinant COVID-19 nucleocapsid protein
(ACCESSION No.: NC_045512/
Strain: Wuhan-Hu-1) 2 Mouse monoclonal anti-chicken IgY antibody (mAb anti-Chicken IgY) Source: Mouse
Isotype: IgG
Immunogen: Purified chicken IgY 3 Mouse monoclonal anti-COVID19 antibody (mAb anti-COVID19 antibody) Source: Mouse
Isotype: IgG
Immunogen: Recombinant COVID-19 necleocapsid protein
(ACCESSION No.: NC_045512/
Strain: Wuhan-Hu-1) 4 Purified Chicken IgY Source: Chicken
Isotype: IgY
Purified: protein

2-2. Assessing Analytical Sensitivity (Limit of Detection)

A 13-step concentration sample of 1 Х10 ^5.2 ~ 4.87 Х 10 ^0.2 TCID ⁵⁰ /ml made by serial dilution of SARS-CoV-2 (2019-nCoV) virus was prepared, and the sample was tested with an RT-PCR product approved for emergency use. Thus, the Ct value at each concentration was confirmed.

As a result of confirming the minimum detection limit showing a positive rate of 95% or more by repeating 5 times for each concentration with 1 lot product and then repeating 20 times at 3 concentrations near the minimum detection limit, as shown in Table 2 below, 3.12 Х 10 ^2.2 TCID ⁵⁰ / ml (Ct value of RdRp gene: 23.37). The positive rate at this concentration was 100%.

Virus name density Ct value SARS-CoV-2 (2019-nCOV) NCCP 43326/2020/Korea 3.12 X 10 ^2.2 TCID ₅₀ /ml 23.37

2-3. Assessing Analytical Specificity (Interference)

In order to confirm the analytical specificity (interference), as a result of repeating the test three times with negative and low-concentration positive standards and the samples with the interference substances in Tables 3 and 4 added to the corresponding standards, interference was observed up to the following concentrations It didn't happen.

Exogenous factor Factor Interfering substances Concentration Relevant medicines Zanamivir (Influenza) 5 mg/ml Oseltamivir (Influenza) 10 mg/ml Artemether-lumefantrine (Malaria) 50 uM Doxycycline hyclate (Malaria) 70 uM Quinine (Malaria) 150 uM Lamivudine (Retroviral medication) 1 mg/ml Ribavirin (HCV) 1 mg/ml Daclatasvir (HCV) 1 mg/ml Anti-inflammatory medication Acetaminophen 200 uM Acetylsalicylic acid 3.7 mM Ibuprofen 2.5 mM antibiotic Mupirocin 10 mg/ml Tobramycin 5 ug/ml Erythromycin (antibiotic) 81.6 uM Ciprofloxacin (antibiotic) 31 uM Nasal sprays or drops Neo-Synephrine (Phenylephrine) 10% (v/v) Afrin Nasal Spray (Oxymetazoline) 10% (v/v) Saline Nasal Spray 10% (v/v) Rhinocort (Nasal corticosteroids - Budesonide) 10% (v/v) Homeopathic allergy
relief
medicine Homeopathic Zicam Allergy Relief Nasal Gel 5% (v/v) Sodium Cromoglycate 20 mg/ml Olopadine Hydrochloride 10 mg/ml Oral anesthetic Anbesol (Benzocaine 20%) 5% (v/v) Throat lozenges Strepsils (flurbiprofen 8.75mg) 5% (w/v, 50mg/ml) Thoat candy (mint) 5% (w/v, 50mg/ml) Others Mucin: bovine submaxillary gland,
type IS 100 μg/ml Biotin 100 μg/ml

Endogenous factor Factor Interfering substances Concentration Autoimmune
disease Human anti-mouse antibody 802 ng/ml 375 ng/ml 317 ng/ml 69 ng/ml 727.5 ng/ml Rheumatoid factor 3,480 IU/mL Serum protein Whole Blood (human), EDTA anticoagulated 10% (w/w) Human serum albumin 60 mg/ml

2-4. Assessing Analytical Specificity (Crossover)

In order to confirm the analytical specificity (crossover), a cross-reaction was observed only in SARS-CoV as a result of repeated tests of negative and low-concentration positive standards and samples in which the crossover material in Table 5 was added to the standard material three times.

Potential cross reacting substance strain Tier/value
(Potential cross reacting substance) SARS-coronavirus Urbani 3.5 μg/ml MERS-Coronavirus Florida/USA-2_SaudiArabia_2014 4 X 10 ⁴ TCID ₅₀ /ml Human Coronavirus 229E 1 X 10 ^4.5 TCID ₅₀ /ml OC43 1 X 10 ⁵ TCID ₅₀ /ml NL63 1 X 10 ⁴ TCID ₅₀ /ml HKU1 1 μg/ml Influenza A H1N1 Denver 3 X 10 ⁵ TCID ₅₀ /ml H1N1 WS/33 3 X 10 ⁵ TCID ₅₀ /ml H1N1 Pdm-09 3 X 10 ⁵ TCID ₅₀ /ml H1N1 New Caledonia 3 X 10 ⁵ TCID ₅₀ /ml H1N1 New Jersey 3 X 10 ⁵ TCID ₅₀ /ml Influenza B Nevada/03/2011 3 X 10 ⁵ TCID ₅₀ /ml B/Lee/40 2.5 X 10 ⁴ TCID ₅₀ /ml B/Taiwan/2/62 3 X 10 ⁵ TCID ₅₀ /ml Respiratory syncytial virus Type A 3 X 10 ⁵ TCID ₅₀ /ml Type B 3 X 10 ⁵ TCID ₅₀ /ml Human Metapneumovirus (hMPV) hMPV 3 Type B1/
Peru2-2002 1 X 10 ⁵ TCID ₅₀ /ml hMPV 3 Type A1/
IA10-2003 1 X 10 ⁵ TCID ₅₀ /ml Parainfluenza virus Type 1 1 X 10 ⁵ TCID ₅₀ /ml Type 2 1 X 10 ⁵ TCID ₅₀ /ml Type 3 1 X 10 ⁵ TCID ₅₀ /ml Type 4A 1 X 10 ⁵ TCID ₅₀ /ml Rhinovirus A16 1 X 10 ⁵ TCID ₅₀ /ml Type B42 1 X 10 ⁴ TCID ₅₀ /ml Mycobacterium tuberculosis K 5 X 10 ⁴ TCID ₅₀ /ml Erdman 5 X 10 ⁴ TCID ₅₀ /ml HN878 5 X 10 ⁴ TCID ₅₀ /ml CDC1551 5 X 10 ⁴ TCID ₅₀ /ml H37Rv 5 X 10 ⁴ TCID ₅₀ /ml adenovirus Type 1 4 X 10 ⁵ TCID ₅₀ /ml Type 3 4 X 10 ⁵ TCID ₅₀ /ml Type 5 4 X 10 ⁵ TCID ₅₀ /ml Type 7 4 X 10 ⁵ TCID ₅₀ /ml Type 8 4 X 10 ⁵ TCID ₅₀ /ml Type 11 4 X 10 ⁵ TCID ₅₀ /ml Type 18 4 X 10 ⁵ TCID ₅₀ /ml Type 23 4 X 10 ⁵ TCID ₅₀ /ml Type 55 4 X 10 ⁵ TCID ₅₀ /ml Human immunodeficiency virus lysate BaL 10 μg/ml Haemophilus influenzae NCTC 4560 5 X 10 ⁴ cells/ml Mycoplasma pneumoniae Mutant 22 5 X 10 ⁴ cells/ml FH strain of Eaton Agent [NCTC 10119] 5 X 10 ⁴ cells/ml M129-B7 5 X 10 ⁴ cells/ml Streptococcus pneumoniae 4752-98 [Maryland(D1)6B-17] 5 X 10 ⁴ cells/ml 178 [Poland 23F-16] 5 X 10 ⁴ cells/ml 262 [CIP 104340] 5 X 10 ⁴ cells/ml Slovakia 14-10 [29055] 5 X 10 ⁴ cells/ml Streptococcus pyrogens Typing strain T1 [NCIB 11841, SF 130] 5 X 10 ⁴ cells/ml Legionella pneumophila Bloomington-2 5 X 10 ⁴ cells/ml Los Angeles-1 5 X 10 ⁴ cells/ml 82A3105 5 X 10 ⁴ cells/ml Candida albicans 3147 5 X 10 ⁴ cells/ml Bordetela pertussis NCCP 13671 5 X 10 ⁴ cells/ml Moraxella catarrhalis N9 5 X 10 ⁴ cells/ml Pseudomonas aeruginosa R. Hugh 813 5 X 10 ⁴ cells/ml Staphylococcus epidermidis FDA strain PCI 1200 5 X 10 ⁴ cells/ml Streptococcus salivarius S21B [IFO 13956] 5 X 10 ⁴ cells/ml Chlamydia pneumonia TWAR strain TW-183 1 X 10 ⁵ cells/ml Pooled human nasal wash N/A N/A

2-5. Check precision (repeatability)

As a result of testing negative and low/medium/high-concentration positive samples at one location, one tester tested twice a day twice a day for 20 days with a single lot product, the results of each sample were 100% consistent.

No. Sort Total Agreement One high positive 80/80 100% 2 Medium positive 80/80 100% 3 Low positive 80/80 100% 4 negative 80/80 100%

2-6. Check precision (reproducibility)

① Lot-to-Lot reproducibility

As a result of testing negative and low/medium/high-concentration positive samples at one location by one tester with 3 lot products, the test was repeated twice a day for 5 days. As a result, the results for each sample were 100% consistent.

No. Specimen No. lot 1 lot 2 Lot 3 Total One high positive 20/20 20/20 20/20 60/60 (100%) 2 Medium positive 20/20 20/20 20/20 60/60 (100%) 3 Low positive 20/20 20/20 20/20 60/60 (100%) 4 negative 20/20 20/20 20/20 60/60 (100%)

② Between site reproducibility

As a result of testing negative and low/medium/high-concentration positive samples at 3 locations, one tester tested twice a day for 5 days with a single lot product, the results were 100% consistent with each sample.

No. Specimen No. Site 1 Site 2 Site 3 Total One high positive 20/20 20/20 20/20 60/60 (100%) 2 Medium positive 20/20 20/20 20/20 60/60 (100%) 3 Low positive 20/20 20/20 20/20 60/60 (100%) 4 negative 20/20 20/20 20/20 60/60 (100%)

③ Between operators reproducibility

As a result of testing negative and low/medium/high-concentration positive samples at one place by 3 testers using 1 lot of product, the test was repeated twice a day for 5 days. As a result, the results of each sample were 100% consistent.

No. Specimen No. operator 1 operator 2 operator 3 Total One high positive 20/20 20/20 20/20 60/60 (100%) 2 Medium positive 20/20 20/20 20/20 60/60 (100%) 3 Low positive 20/20 20/20 20/20 60/60 (100%) 4 negative 20/20 20/20 20/20 60/60 (100%)

2-7. Clinical sensitivity and specificity (nasal smear)

The clinical performance test of the present invention was conducted from November 30 to December 11, 2020 in Berlin, Germany, with confirmed contact with a confirmed SARS-CoV-2 infection, those with suspicious symptoms, fever, damage to taste or smell, etc. This study was conducted prospectively on 145 suspected SARS-CoV-2 infection patients (40 positive, 105 negative) who showed symptoms of

In this test, positive test was conducted within 7 days after symptom onset, and negative test was conducted on humans within 10 days after symptom onset, and participants ranged in age from 18 to 68 years old.

After filling out the consent form, the study subjects directly performed from nasal smear sampling to clinical performance test product evaluation and result reading using the provided instructions. CoV-2 gene test reagent (RT-PCR) was tested.

The results of calculating the clinical sensitivity and specificity of the kit used in the present invention by comparing the results of an individual's self-test with nasal smears and RT-PCR test results of nasopharyngeal smears collected by experts are as follows.

RT-PCR product results positivity voice Total STANDARD Q COVID-19 Ag Home Test positivity 33 0 33 voice 7 105 112 Total 40 105 145

- Clinical sensitivity: 82.5% (33/40) [95% CI: 68.1% - 91.3%]

- Clinical specificity: 100.00% (105/105) [95% CI: 96.5% - 100%]

As confirmed in Table 10, it can be seen that the clinical sensitivity is 82.5% and the specificity is 100%, which shows a very good result, and it can be seen that the result does not indicate a cross-reaction between viral infections, other This suggests that it is possible to specifically detect only the desired SARS-coronavirus-2 (SARS-CoV-2) with high sensitivity without detecting the virus.

In the above, the present specification has been described with reference to the embodiments shown in the drawings so that those skilled in the art can easily understand and reproduce the present invention, but these are merely exemplary, and those skilled in the art can make various modifications and equivalent other modifications from the embodiments of the present invention. It will be appreciated that embodiments are possible. Therefore, the protection scope of the present invention should be defined by the claims.

100: sample collection swab
110: head
111: first head portion
112: second head part
113: third head part
114: fourth head part
120: handle
130: cut part
210: extraction tube
211: opening
220: nozzle cap
221: outlet
300: diagnostic kit
310: backing card
320: membrane
321: inspection line
322: Chosun Line
330: reserve pad
340: moisture absorption pad
350: conjugate pad
360: sample pad
400: housing
401: lower housing
402: upper housing
410: result confirmation unit
411: first opening
412: first inclined portion
413: first extension
414: first step part
420: sample droplet
421: second opening
422: second inclined portion
423: second extension
424: second step portion
425: depression
426: third step part

Claims (13)

As a medical device for diagnosing infection using an antibody that specifically binds to the nucleocapsid protein of SARS-CoV-2,
A sample collection swab 100 for collecting a sample from a collection target, wherein a bent first head portion 111, a second head portion 112 connected to the first head portion 111, and the second head portion 112 ), including a third head part 113 having a reduced diameter from the head 110, the handle 120 extending with a predetermined length and thickness from the head 110, and the handle 120 is located on one side , A sample collection swab 100, including a cut portion 130 that is thinner than the handle 120;
An extraction buffer for extracting the SARS-coronavirus-2 from the sample collected by the sample collection swab 100 is accommodated, and the sample collection swab 100 is loaded in the extraction buffer and the collected sample is extracted Extraction tube 210, eluted in the buffer;
a nozzle cap 220 coupled to the opening 211 of the extraction tube 210 and having a filter; and
and an inspection device 500 into which the solution discharged through the outlet 221 of the nozzle cap 220 is injected after passing through the filter; and
The inspection device 500,
A diagnostic kit ( 300); and
A housing that covers the diagnostic kit 300 so that the first area where the test line 321 and the control line 322 are formed and the second area that is at least a part of the sample pad 360 of the diagnostic kit 300 are exposed (400); including;
The diagnostic kit 300 includes:
backing card 310;
a membrane 320 placed on the backing card 310 and formed with the test line 321 and the control line 322;
A first material provided on the first portion of the membrane 320 and fixed to the test line 321 and a first material that specifically binds to the SARS-coronavirus-2 and contains a chromogenic material, and the control line ( a conjugate pad 350 having a second material that specifically binds to the material fixed to 322 and includes a color developing material;
a sample pad 360 provided in the first part of the conjugate pad 350 and into which the solution discharged through the outlet 221 is put; and
Including; and a moisture absorption pad 340 provided on the second portion of the membrane 320 opposite to the first portion,
The housing 400 is
a result confirmation unit 410 including a first opening 411 through which the first region is exposed, and a first inclined portion 412 inclined upwardly from the first opening 411 to the outside; and
A second opening 421 through which the second region is exposed, a second inclined portion 422 curved outwardly from the second opening 421 , and a ground surface from the second inclined portion 422 outwardly and a sample dropper 420 including a second extension portion 423 extending in parallel and a second step portion 424 extending downward from the second extension portion 423,
The material fixed to the test line 321 specifically binds to the SARS-coronavirus-2, and when the SARS-coronavirus-2 is included in the solution injected into the sample pad 360, the test line 321 ), and if not included, color development does not occur.
The material fixed to the control line 322 is specifically bound to the second material to always develop color in the control line 322,
Medical device for diagnosis of corona virus infection.
According to claim 1,
The material fixed to the control line 322 is Mouse monoclonal anti-Chicken IgY,
The first material is a Gold (III) chloride trihydrate conjugated mAb anti-COVID19 antibody,
The second material is Gold (III) chloride trihydrate conjugated Purified chicken IgY that specifically binds to the Mouse monoclonal anti-Chicken IgY,
Medical device for diagnosis of corona virus infection.
3. The method of claim 2,
Extraction buffer accommodated in the extraction tube 210 is 0.18M to 0.22M concentration of Tris, 0.45% to 0.55% concentration of Tw-80, 1.35% to 1.65% concentration of Polidocanol, 0.45M to 0.55M concentration of NaCl, 0.45 A solution comprising Casein at a concentration of % to 0.55%, Sodium azide at a concentration of 0.018% to 0.022%, and Proclin 300 at a concentration of 0.045% to 0.055%,
Medical device for diagnosis of corona virus infection.
According to claim 1,
The nozzle cap 220,
A coupling portion coupled to the extraction tube 210, a step portion larger than the coupling portion while being connected to the coupling portion, and the outlet 221 connected from the step portion,
The inner diameter of the upper extraction tube 210 in which the opening 211 is formed is larger than the outer diameter of the coupling portion, smaller than the outer diameter of the stepped portion,
Medical device for diagnosis of corona virus infection.
According to claim 1,
The first head portion 111 is bent as the diameter increases,
The second head part 112 has the same diameter and continues from the first head part 111,
The third head part 113 is bent while decreasing in diameter from the second head part 112,
The head 110 further includes a fourth head portion 114 curved while increasing in diameter from the third head portion 113,
Medical device for diagnosis of corona virus infection.
6. The method of claim 5,
The backing card 310 is made of a polyethylene material,
The membrane 320 is made of a cellulose membrane material,
The moisture absorption pad 340 is made of a glass fiber (Glass fiber) material,
The conjugate pad 350 is made of a polyester material,
The sample pad 360 is made of a glass fiber material,
The diagnostic kit 300 is
In the first part of the membrane 320, a polyester reserve pad 330 laminated on the membrane 320 to at least partially overlap the membrane 320, further comprising:
Medical device for diagnosis of corona virus infection.
7. The method of claim 6,
In the first part of the membrane 320 , the membrane 320 partially overlaps the reserve pad 330 ,
In a first portion of the reserve pad 330 , the reserve pad 330 partially overlaps the conjugate pad 350 ,
In a first portion of the conjugate pad 350 , the conjugate pad 350 partially overlaps the sample pad 360 ,
In the second part of the membrane 320 , the membrane 320 partially overlaps the moisture absorption pad 340 ,
Medical device for diagnosis of corona virus infection.
According to claim 1,
a cross-section of the end of the second portion of the sample pad (360) is spaced apart from the cross-section of the end of the first portion of the membrane (320);
Medical device for diagnosis of corona virus infection.
7. The method of claim 6,
The housing 400 is made of PVC material,
Medical device for diagnosis of corona virus infection.
According to claim 1,
The second inclined portion 422 includes a curved surface in which the angle formed with the ground increases,
Medical device for diagnosis of corona virus infection.
According to claim 1,
The shape formed by the edge of the second opening 421 and the shape formed by the inner or outer edge of the second extension part 423 correspond to each other,
Medical device for diagnosis of corona virus infection.
10. The method of claim 9,
The result confirmation unit 410,
a first extension portion 413 extending outwardly parallel to the ground from the first inclined portion 412; and
Further comprising; a first step portion 414 extending perpendicular to the ground from the first extension portion 413 upward
Medical device for diagnosis of corona virus infection.
13. The method of claim 12,
The sample dropper 420 is,
a recessed portion 425 extending parallel to the ground from the second step portion 424 outward; and
A third step portion 426 extending perpendicularly to the ground from the depression 425 upwards
Medical device for diagnosis of corona virus infection.

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