KR20230094051A - Diagnosis strip - Google Patents

Abstract

The present invention relates to a diagnostic strip, comprising: a housing having an accommodation space therein, and having a first inlet and a second inlet spaced apart from each other on an upper surface of the housing in communication with the accommodation space and an external space; and a second inlet located inside the housing. A membrane pad disposed at the lower end of the inlet, an absorbent pad contacting the membrane pad, fixed to and moving on a sliding member capable of moving outwardly of the housing, disposed above the absorbent pad and in contact with the membrane pad A sample pad in which contact is released according to the movement of the sliding member, a first water-soluble polymer coating layer formed on a portion in contact with the sample pad to prevent absorption of the sample solution, and a washing input through the second inlet A second water-soluble polymer coating layer that blocks absorption and diffusion of the sample solution may be included at the injection site of the solution.

Description

Diagnostic strip {Diagnosis strip}

The present invention relates to a diagnostic strip, and more particularly, to a diagnostic strip capable of removing a background signal when washed using a washing solution.

Many diagnostic strips have been developed and used to quickly and accurately measure the concentration or presence of analytes in bodily fluids, such as blood and urine, in the field. Immunosensor strips and DNA sensor strips based on biospecific binding This has recently been developed.

The diagnostic strip using nanoparticles based on the lateral flow immunoassay method is the most common disposable point-of-care diagnostic strip. Nanoparticles agglomerate by antigen binding to form a band, so positive/negative can be judged with the naked eye. However, there is a limit in the sensitivity of the analysis that occurs in the process of visually observing the formation of bands in the case of low concentration antigen analysis. There is a way to improve the sensitivity so that bands can be visually distinguished at low concentrations, but there are limitations in terms of materials. In addition, there is a method of improving sensitivity by analyzing images through fluorescence or light emission, but there is a problem that is not suitable for a disposable point-of-care diagnostic kit because an additional image analysis device is required. In addition, the colored band can be analyzed as a general optical or fluorescence image and the result can be digitized, but there is a problem in that an additional image analysis device is required.

In order to analyze low-concentration antigens, high-sensitivity electrochemical analysis was attempted to be grafted onto lateral flow immunoassay. is necessarily accompanied by a washing step to remove and a certain amount of substrate dispensing step thereafter.

The washing step is for washing unreacted substances non-specifically attached to the membrane pad, and the degree of removal of unreacted substances by washing is determined according to the degree of absorption of the sample solution in the membrane pad in the previous step.

1 is a comparison diagram of washing degree according to various conditions.

In i) of FIG. 1, an example of normal washing is shown.

First, the sample solution (L1) is absorbed into the membrane pad (1) through the sample pad (2), and the washing solution (W1) is injected into the membrane pad (1) on the opposite side of the input portion of the sample solution (L1) to the membrane pad. Remove unreacted substances adhering to (1).

At this time, when the absorption and diffusion of the sample solution (L1) is made in the entire membrane pad (1) (ii in FIG. 1), the unreacted material is not completely removed, and the washing solution (W1) is introduced into the membrane pad Complete removal of unreacted substances is achieved only when the sample solution (L1) is not absorbed and diffused in the partial region of (1).

In iii) of FIG. 1, the input positions of the sample solution L1 and the washing solution W1 are the same, and the positions of the sample pad 2 and the absorbent pad 3 are opposite, but this is a classical structure. Also, it is difficult to completely remove unreacted substances.

1 iv) has a structure in which the input positions of the sample solution (L1) and the washing solution (W1) are changed using another absorbent pad (3-1). In this case, the sample pad (2) and the absorbent pad (3) Since the sample solution is absorbed and diffused throughout the membrane pad 1 by this, it is difficult to completely remove unreacted substances.

Therefore, there is a demand for development of a diagnostic strip capable of removing unreacted substances.

Japanese Patent Laid-open No. 6190395 ("Method and composition for detecting multiple subjects with a single signal", Invisible Central, 2017 08 10) Republic of Korea Patent Registration No. 10-1768876 (“Antigen detection device and use thereof”, Invisible Central, 2017 08 10) Republic of Korea Patent Registration No. 10-1742958 (“Strip sensor module, on-site inspection device for molecular diagnosis based on strip sensor using strip sensor module”, Genet Bio Co., Ltd., 2017 05 29)

A technical problem to be achieved by the present invention is to provide a diagnostic strip capable of preventing a sample solution from being absorbed and diffused throughout the membrane pad.

The diagnostic strip of the present invention includes a housing having an accommodation space therein, and a first inlet and a second inlet spaced apart from each other on an upper surface of the housing in communication with the accommodation space and the external space; a membrane pad disposed on the membrane pad, an absorbent pad that is fixed to and moved to a sliding member that is in contact with the membrane pad and is movable in an outward direction of the housing; A sample pad whose contact is released as the sliding member moves, and a second water-soluble polymer coating layer that is partially located on the membrane pad at the input position of the washing solution introduced through the second inlet to block absorption and diffusion of the sample solution can include

In an embodiment of the present invention, a first water-soluble polymer coating layer formed on a portion of the membrane pad contacting the absorption pad to prevent absorption of the sample solution may be further included.

In an embodiment of the present invention, the first water-soluble polymer coating layer and the second water-soluble polymer coating layer may be polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone, or polyethylene glycol.

In an embodiment of the present invention, a waterproof layer positioned between the absorbent pad and the sample pad may be further included.

In an embodiment of the present invention, a portion of the sample pad may be positioned above the absorption pad with the waterproof layer interposed therebetween, and the other portion may protrude toward the top of the membrane pad.

In an embodiment of the present invention, the area of the sample pad protruding toward the upper side of the membrane pad may be pressed by a pressing member extending downward from an inner upper part of the housing in an initial state to contact the membrane pad.

In an embodiment of the present invention, while the sample pad is moved by the sliding member, contact with the membrane pad may be released by separating from the pressing member.

The present invention has an effect of enabling more accurate diagnosis by preventing the absorption and diffusion of the sample solution at the position where the washing solution is introduced, thereby preventing the degradation of the analysis signal due to the absorption and diffusion of the sample solution.

1 is a comparative example of conditions for effective cleaning of a membrane pad.
2 is a cross-sectional configuration diagram of a diagnostic strip according to a preferred embodiment of the present invention.
3 to 5 are explanatory diagrams showing position changes of some components according to use conditions of the present invention, respectively.

Advantages and features of the present invention and methods for achieving them will become clear with reference to the detailed description of the following embodiments in conjunction with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various different forms, and only the present embodiments make the disclosure of the present invention complete and those skilled in the art in the art to which the present invention belongs It is provided to fully inform the person of the scope of the invention, and the invention is defined only by the claims. Like reference numerals designate like elements throughout the specification.

Hereinafter, the configuration and operation of a diagnostic strip according to a preferred embodiment of the present invention will be described with reference to the drawings.

2 is a cross-sectional configuration diagram of a diagnostic strip according to a preferred embodiment of the present invention.

Referring to FIG. 2 , the diagnostic strip 1 of the present invention is a diagnostic kit for general users to conveniently measure the concentration or presence of an analyte present in bodily fluids such as blood or urine, and quickly and accurately analyze it in the field.

The diagnostic strip 1 of the present invention includes a housing 10, a membrane pad 20 located inside the housing 10, a sample pad 30, an absorbent pad 40, and a sliding member 50. .

In particular, the membrane pad 20 includes a first water-soluble polymer coating layer 70 formed on a contact portion with the absorbent pad 40 and a second water-soluble polymer coating layer 80 formed on an area where the washing solution W1 is injected. It is composed by

Specifically, in the diagnostic strip 1 of the present invention, an accommodation space 11 is formed inside, and the first inlet 12 and the second inlet are spaced apart from each other by communicating the accommodation space 11 and the external space on the upper surface. The housing 10 forming the housing 13, the membrane pad 20 exposed to the second inlet 13 and disposed in the accommodating space 11, and at least one surface of the membrane pad 20 in the accommodating space 11 A sample pad 30 disposed in contact with and absorbing the sample solution L1 introduced into the first inlet 12, and the sample pad 30 is located in contact with the upper surface, and a portion of the lower surface is the membrane pad An absorbent pad 40 in contact with a part of the upper surface of the 20, and a sliding member holding the absorbent pad 40, extending in the horizontal direction, and protruding outwardly through at least a portion of the side surface of the housing 10 ( 50), the electrode part 60 located at the center of the upper surface of the membrane pad 20, and the first water-soluble polymer coating layer 70 formed on the contact portion of the membrane pad 20 with the absorbent pad 40 , and a second water-soluble polymer coating layer 80 formed on a partial region of the membrane pad 20 located on the lower side of the second inlet 13.

Hereinafter, the configuration and operation of the diagnostic strip 1 of the present invention configured as described above will be described in more detail.

First, the housing 10 forms the main body of the diagnostic strip 1, and may be formed in a rectangular parallelepiped shape to form the accommodation space 11 therein.

The housing 10 accommodates the membrane pad 20 , the sample pad 30 , the absorbent pad 40 and the sliding member 50 in the accommodation space 11 .

The housing 10 may be separated vertically so that each component accommodated in the accommodation space 11 can be easily disposed.

On the upper surface of the housing 10, the first inlet 12 and the second inlet 13 are spaced apart from each other, and the arrival confirmation port 14 is formed between the first inlet 12 and the second inlet 13. can

The first inlet 12 and the second inlet 13 are through-holes for introducing the sample solution L1, the washing solution W1, and the reaction solution L2 into the receiving space 11, respectively.

A pressing member 15 is formed in the housing 10 to press the end of the sample pad 30 so that one end of the sample pad 30 comes into contact with the membrane pad 20 .

The membrane pad 20 is disposed in the inner accommodating space 11 of the housing 10 and is fixed to the bottom surface of the lower side of the second inlet 13 . The end of the membrane pad 20 is in a dried state, and absorbs a cleaning solution to be described later through the dried surface.

The membrane pad 20 may include a nitrocellulose (NC) pad 21 and extends along the longitudinal direction of the housing 10 .

At least a portion of the membrane pad 20 is pre-treated with a capture antibody that specifically binds to a specific target antigen, and the detection antibody and capture material that secondarily bind to the antigen bound to the capture antibody are not limited to antibodies. , proteins, carbohydrates, nucleotides, aptamers, and the like.

The membrane pad 20 may be formed by combining a cover capable of reducing the interaction between the fluid in the nitrocellulose pad 21 and the housing 10, for example, the nitrocellulose pad 21 and polyethylene tere It may be formed by combining polyethylene terephthalate (PET) 22.

The membrane pad 20 may be formed of a member that minimizes an interaction such as a corrosion reaction by a fluid, and may be a member having an adhesive formed on its lower surface.

In particular, the membrane pad 20 may include a water-soluble polymer coating layer partially coated with a water-soluble polymer.

As the water-soluble polymer, polyvinyl alcohol (PVA) may be used. In addition, polyacrylic acid (PAA), polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) may be used.

PVA is easy to form a film and has excellent adhesion, so it is easy to form the first water-soluble polymer coating layer 70 and the second water-soluble polymer coating layer 80 on a part of the membrane pad 20 .

The role of the first water-soluble polymer coating layer 70 is to prevent the sample solution L1 from being absorbed into the absorption pad 40 for a certain period of time, and the second water-soluble polymer coating layer 80 prevents the sample solution L1 from being absorbed into the absorption pad 40 for a certain period of time. ) is prevented from being absorbed and diffused into the membrane pad 20, so that the sample solution L1 is not absorbed at the washing solution W1 input position of the membrane pad 20 at the time when the washing solution W1 is injected. is to keep

This is effective in removing unreacted substances previously described with reference to FIG. 1 .

The membrane pad 20 has one end capable of absorbing the sample solution L1 injected from the first inlet 12 from the sample pad 30, and the sample solution L1 moves along the longitudinal direction so that the arrival confirmation port 14 ), it is possible to absorb the washing solution (W1) and the reaction solution (L2) introduced into the second inlet (13) from the other end.

At this time, the second water-soluble polymer coating layer 80 is dissolved and removed, washed by the washing solution W1 injected into the membrane pad 20, and absorbs the reaction solution L2 to generate an electrical signal from the electrode unit 60. will cause

More specifically, the second water-soluble polymer coating layer 80 prevents the sample solution L1 from being absorbed to the dried end of the membrane pad 20 . As described above, the dried end of the membrane pad 20 is for absorbing the washing solution (W1), and when the dried end absorbs the sample solution (L1), the washing solution (W1) is not absorbed well. do.

Accordingly, the sample solution L1 is prevented from overflowing to the left end of the membrane pad 20 by using the second water-soluble polymer coating layer 80 .

The membrane pad 20 is characterized in that one side is pre-treated with a capture antibody that specifically binds to a predetermined antigen. The membrane pad 20 is not limited to antibodies, and may be composed of proteins, carbohydrates, nucleotides, aptamers, and the like. Membrane pad 20 can be described as an example in which capture is pre-coated on one side, and capture and detector may not be limited to materials called antibodies.

A reaction occurring on the surface of the membrane pad 20 through the electrode unit 60 can be quantitatively analyzed by electrochemical analysis. Meanwhile, the electrode unit 60 is disposed on the upper surface of the membrane pad 20 , and the sample pad 30 contacting and separated from the membrane pad 20 is disposed on one side of the membrane pad 20 .

The electrode part 60 obtains a signal from a reaction in which the reaction solution injected into the second inlet 13 and absorbed by the membrane pad 20 is oxidized/reduced by the enzyme of the detection antibody. It may be placed in close contact with the upper surface of the membrane pad 20 positioned between the absorbent pads 40 .

The electrode unit 60 includes a substrate on which electrodes are patterned, and may have two or three electrodes patterned thereon. For example, the electrode unit 60 includes a counter electrode, a working electrode, and a reference electrode, and is disposed on the upper surface of the membrane pad 20 to face the pressing member. It can be. The electrode unit 60 reacts with the solution introduced through the first inlet 12 and the second inlet 13 to cause an oxidation/reduction reaction, thereby analyzing the concentration or presence of the analyte contained in the solution. .

The washing solution (W1) may be, for example, a washing buffer containing a portion of a surfactant such as tween, and the reaction solution (L2) may contain a substrate that reacts with an enzyme (peroxidase, phosphatase, etc.) bound to the detection antibody. A solution is an example. The sample solution L1, the washing solution W1, and the reaction solution L2 may be introduced through the first inlet 12 and the second inlet 13 to be opposite to each other. The first inlet 12 and the second inlet 13 are characterized in that non-specific reactions can be minimized by implementing the input directions in which the sample solution (L1), the washing solution (W1), and the reaction solution (L2) are injected in opposite directions. there is.

The arrival check hole 14 is a through-hole for confirming that the sample solution L1 injected into the first inlet 12 has reached a specific position by riding the membrane pad 20, and includes the first inlet 12 and the second inlet. (13) can be located between.

The arrival confirmation hole 14 is spaced apart from the first inlet 12 and the second inlet 13, but may be formed at a position adjacent to the second inlet 13 rather than the first inlet 12.

In the present invention, one side of the absorbent pad 40 is coupled to the sliding member 50 and moves along with the movement of the sliding member 50 . In addition, a waterproof layer 41 is formed on the upper surface of the absorbent pad 40 .

The sample solution L1 absorbed by the sample pad 30 is prevented from being directly absorbed by the absorbent pad 40 by the waterproof layer 41 .

A part of the sample pad 30 is fixed to an upper part of the waterproof layer 41, and another part of the sample pad 30 protrudes from a part of the side of the absorbent pad 40, and the housing 10 is in an initial state. It is pressed by the pressing member 15 and comes into contact with a part of the membrane pad 20 .

In such a structure, a change in the structure according to the use state of the present invention and an action according to the change will be described in more detail.

3 to 5 are explanatory diagrams showing position changes of some components according to use conditions of the present invention, respectively.

First, referring to FIG. 3 , the sample solution L1 is injected through the first inlet 12 in the installation state of FIG. 2 .

The injected sample solution L1 is absorbed into the sample pad 30 positioned below the first inlet 12 and is absorbed and diffused toward the membrane pad 20 in contact with the sample pad 30 .

At this time, since the absorbent pad 40 is also in contact with the membrane pad 20, the sample solution L1 can be absorbed into the absorbent pad 40, but the absorbent pad 40 is not in contact with the membrane pad 20. Since the first water-soluble polymer coating layer 70 is formed, absorption of the sample solution L1 into the absorbent pad 40 is prevented.

In addition, the sample solution L1 is easily diffused along the membrane pad 20 up to the second water-soluble polymer coating layer 80 by the second water-soluble polymer coating layer 80, but at the rear end of the second water-soluble polymer coating layer 80. It does not spread to the membrane pad 20 where it is located.

In this state, when the sample solution L1 is confirmed through the arrival confirmation port 14, the sliding member 50 is first pulled outward so that the absorbent pad 40 and the sample pad 30 are connected to the electrode unit 60. ) in the direction away from

At this time, as shown in FIG. 4 , the end of the sample pad 30 is released from being pressed by the pressing member 15 and the contact with the membrane pad 20 is released. The absorbent pad 40 maintains contact with the first water-soluble polymer coating layer 70 formed on the membrane pad 20 .

Part or all of the first water-soluble polymer coating layer 70 is dissolved by the sample solution L1 absorbed by the membrane pad 20, so that a part of the absorbent pad 40 directly contacts the membrane pad 20.

Therefore, from this time, the absorption action by the absorption pad 40 is performed.

In addition, part or all of the second water-soluble polymer coating layer 80 is also dissolved in the sample solution L1.

Then, the washing solution (W1) and the reaction solution (L2) are sequentially introduced through the second inlet (13).

The injected washing solution W1 completely dissolves the second water-soluble polymer coating layer 80 and then diffuses toward the absorption pad 40 to remove unreacted substances. Therefore, the present invention can increase the removal rate of unreacted substances.

That is, a more accurate diagnosis is possible by preventing absorption and diffusion of the sample solution at the position where the washing solution is introduced, and removing a background signal without a non-specific reaction.

Thereafter, the introduced reaction solution L2 is absorbed by the membrane pad 20 and partially absorbed by the absorption pad 40 after passing through the electrode unit 60 .

The absorbent pad 40 serves to help the reaction solution L2 spread.

In this state, as shown in FIG. 5 , the sliding member 50 is further pulled outward to move the absorbent pad 40 so as not to come into contact with the membrane pad 20 .

If the absorbent pad 40 remains in contact with the membrane pad 20, the flow of the reaction solution L2 by the absorbent pad 40 continues to occur during the electrochemical measurement process in the electrode unit 60. Since the analytes pass through the electrode part 60 and are absorbed into the absorption pad 40, stable signal acquisition may be difficult. Therefore, by separating the absorption pad 40 to prevent the flow of the reaction solution (L2), it is possible to obtain a stable signal.

In the above embodiments, the introduction of the washing solution (W1) and the reaction solution (L2) has been described, and this is done either manually or automatically by using an automatic introduction device. can be put into

Although the embodiments of the present invention have been described with reference to the accompanying drawings, those skilled in the art to which the present invention pertains know that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. You will understand. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

1: diagnostic strip 10: housing
11: receiving space 12: first inlet
13: second inlet 14: arrival confirmation
15: pressing member 20: membrane pad
30: sample pad 40: absorbent pad
50: sliding member 60: electrode part
70: first water-soluble polymer coating layer 80: second water-soluble polymer coating layer

Claims (7)

A housing that forms an accommodation space therein, and forms a first inlet and a second inlet spaced apart from each other by communicating the accommodation space and the external space on an upper surface of the housing;
a membrane pad disposed at the lower end of the second inlet inside the housing and absorbing the washing solution by drying the end of the second inlet;
an absorbent pad that is in contact with the membrane pad and is fixed to a sliding member that is movable in an outward direction of the housing;
a sample pad disposed above the absorbent pad and released from contact with the membrane pad as the sliding member moves;
A diagnostic strip comprising a second water-soluble polymer coating layer positioned on a portion of the membrane pad at an input position of the washing solution introduced through the second inlet to block absorption and diffusion of the sample solution to an end of the dried membrane pad. According to claim 1,
The diagnostic strip further comprises a first water-soluble polymer coating layer formed on a portion of the membrane pad in contact with the absorbent pad to prevent absorption of the sample solution. According to claim 2,
The first water-soluble polymer coating layer and the second water-soluble polymer coating layer,
A diagnostic strip characterized in that it is polyvinyl alcohol, polyacrylic acid, polyvinylpyrrolidone or polyethylene glycol. According to claim 1,
The diagnostic strip further comprises a waterproof layer positioned between the absorbent pad and the sample pad. According to claim 4,
The sample pad,
A portion is located on top of the absorbent pad with the waterproof layer interposed therebetween;
The other part of the diagnostic strip is characterized in that it protrudes toward the upper side of the membrane pad. According to claim 5,
The diagnostic strip of claim 1 , wherein an area of the sample pad protruding toward the upper side of the membrane pad is pressed by a pressing member extending downward from an inner upper part of the housing in an initial state and comes into contact with the membrane pad. According to claim 6,
While the sample pad is moved by the sliding member, the diagnostic strip is separated from the pressing member and contact with the membrane pad is released.

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