KR102540452B1 - Microfluidic device with membrane filter attached salt and mounting method of membrane filter - Google Patents

Abstract

An object of the present specification is to provide a method for mounting a membrane filter capable of increasing the flow pressure of a fluid and a microfluidic device including the same. A membrane filter mounting method according to the present specification includes: (a) providing a double-sided adhesive member having an adhesive matrix having adhesive force on both sides and a protective film attached to one of both surfaces having adhesive force; (b) attaching the double-sided adhesive member to one side of a membrane filter having desired filtration characteristics; A partial area of one surface of the membrane filter to which the double-sided adhesive member is attached is exposed, and (c) applying salt to one surface of the membrane filter to which the double-side adhesive member is attached; (d) removing the protective film of the double-sided adhesive member attached to the membrane filter; and (e) attaching the membrane filter to the filter support structure by aligning the membrane filter so that the double-sided adhesive member having the adhesive exposed by removing the protective film corresponds to the filter support structure.

Description

Microfluidic device with membrane filter attached with salt and method for mounting membrane filter

The present invention relates to a biosensor strip, and more particularly, to a method for passing a sample such as blood, urine, saliva, etc. through a membrane filter so that only desired components are passed through a channel.

The content described in this section merely provides background information on the embodiments described herein and does not necessarily constitute prior art.

A measurement method using a sample collection device, so-called sensor strip (or biosensor strip), is used to test a specific characteristic value through a sample such as blood, urine, or saliva. For example, when measuring blood glucose, insert it into the inlet of the blood glucose meter, collect blood from your fingertip, and place a small amount of blood from the fingertip on the sensor strip inserted into the meter, and the blood is automatically sucked into the sensor strip inlet. The value is displayed on the screen of the glucometer.

At this time, a membrane filter is used that filters out blood cell components such as red blood cells and white blood cells from the blood and passes only plasma components. However, when blood passes through a membrane filter, a phenomenon occurs in which the flow pressure of the fluid is lower than the pressure spike. A pressure spike means that an aqueous fluid does not enter if the membrane material is hydrophobic, or the fluid does not leave the membrane if the membrane material is hydrophilic. These pressure spikes occur at the interface between the membrane and the air or between the fluid and the air.

In order to solve the problem that the flow pressure of the fluid is lower than the pressure spike, the prior art has generated positive or negative pressure using a pump. However, the method using a pump basically increases the cost of the sensor strip and has problems in that blood cells are destroyed by pressure and the quality of plasma is deteriorated. Another prior art is to pre-wet the membrane with a solvent such as ethanol or acetone. In the case of this method, the problem of plasma destruction does not occur, but a sealed container is required to prevent evaporation, resulting in increased cost and shortened storage period.

Republic of Korea Patent Registration No. 10-1062356

An object of the present specification is to provide a method for mounting a membrane filter capable of increasing the flow pressure of a fluid and a microfluidic device including the same.

This specification is not limited to the above-mentioned tasks, and other tasks not mentioned will be clearly understood by those skilled in the art from the description below.

A membrane filter mounting method according to the present specification for solving the above problems includes: (a) providing a double-sided adhesive member having an adhesive matrix having adhesive force on both sides and a protective film attached to one of both surfaces having adhesive force; (b) attaching the double-sided adhesive member to one side of a membrane filter having desired filtration characteristics; A partial area of one surface of the membrane filter to which the double-sided adhesive member is attached is exposed, and (c) applying salt to one surface of the membrane filter to which the double-side adhesive member is attached; (d) removing the protective film of the double-sided adhesive member attached to the membrane filter; and (e) attaching the membrane filter to the filter support structure by aligning the membrane filter so that the double-sided adhesive member having the adhesive exposed by removing the protective film corresponds to the filter support structure.

According to one embodiment of the present specification, the shape of the non-exposed region of one surface of the membrane filter to which the double-sided adhesive member is attached may correspond to the shape of the filter support structure.

According to one embodiment of the present specification, in the double-sided adhesive member provided in step (a), the shape of the adhesive matrix may correspond to the shape of the filter support structure.

According to one embodiment of the present specification, step (b) may be a step of attaching a double-sided adhesive member to a region corresponding to the shape of the filter support structure on one surface of the membrane filter.

According to one embodiment of the present specification, in step (b), an area of an exposed region of one surface of the membrane filter may be smaller than an upper area of the filter support structure.

According to one embodiment of the present specification, the step (c) may further include applying and drying the salt by an intermediate mediated diffusion method.

A microfluidic device according to the present specification for solving the above problems includes a microfluidic channel formed inside a body; a sample inlet formed in an area adjacent to one end of the microfluidic channel in the body; a reaction chamber formed in the body and connected to the other end of the microfluidic channel; a membrane filter disposed between the sample inlet and the microfluidic channel and having desired filtration characteristics; a filter support structure formed to support the membrane filter between the membrane filter and the microfluidic channel; In the filter support structure, at least one protruding pattern forms a movement passage so that the fluid separated from the sample injected through the sample inlet gathers into the microfluidic channel, and the upper surface of the at least one protruding pattern and the membrane filter An adhesive member disposed therebetween; including, but a salt matrix may be attached to a region exposed to the movement passage side of a surface of the membrane filter in contact with the filter support structure.

Other specific details of the invention are included in the detailed description and drawings.

According to the present specification, it is possible to prevent a phenomenon in which the flow pressure of the fluid is temporarily lower than the pressure spike. Therefore, the fluid that has passed through the membrane filter can more smoothly move to the microfluidic channel, and a sufficient test can be performed even with a small sample.

The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.

1 is an exploded perspective view to aid understanding of a microfluidic device according to the present specification.
2 is a cross-sectional view of a membrane filter and filter support structure.
3 to 9 are reference views for a method for mounting a membrane filter according to the present specification.
10 to 17 are other embodiments of a method for mounting a membrane filter and a microfluidic device according to the present specification.
18 is a diagram illustrating various exemplary embodiments of a protruding pattern.

Advantages and features of the invention disclosed in this specification, and methods for achieving them, will become clear with reference to the embodiments described below in detail in conjunction with the accompanying drawings. However, the present specification is not limited to the embodiments disclosed below and may be implemented in a variety of different forms, and only the present embodiments make the disclosure of the present specification complete, and are common in the art to which the present specification belongs. It is provided to fully inform the technical person (hereinafter referred to as 'one skilled in the art') of the scope of the present specification, and the scope of rights of the present specification is only defined by the scope of the claims.

Terms used in this specification are for describing the embodiments and are not intended to limit the scope of the present specification. In this specification, singular forms also include plural forms unless specifically stated otherwise in a phrase. As used herein, "comprises" and/or "comprising" does not exclude the presence or addition of one or more other elements other than the recited elements.

Like reference numerals throughout the specification refer to like elements, and “and/or” includes each and every combination of one or more of the recited elements. Although "first", "second", etc. are used to describe various components, these components are not limited by these terms, of course. These terms are only used to distinguish one component from another. Accordingly, it goes without saying that the first element mentioned below may also be the second element within the technical spirit of the present invention.

Unless otherwise defined, all terms (including technical and scientific terms) used in this specification may be used with meanings commonly understood by those skilled in the art to which this specification belongs. In addition, terms defined in commonly used dictionaries are not interpreted ideally or excessively unless explicitly specifically defined.

The spatially relative terms "below", "beneath", "lower", "above", "upper", etc. It can be used to easily describe a component's correlation with other components. Spatially relative terms should be understood as including different orientations of elements in use or operation in addition to the orientations shown in the drawings. For example, if you flip a component that is shown in a drawing, a component described as "below" or "beneath" another component will be placed "above" the other component. can Thus, the exemplary term “below” may include directions of both below and above. Components may also be oriented in other orientations, and thus spatially relative terms may be interpreted according to orientation. Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

1 is an exploded perspective view to aid understanding of a microfluidic device according to the present specification.

Referring to FIG. 1 , a microfluidic device 10 according to the present specification may include an upper housing 100, a membrane filter 200, and a lower housing 300. The upper housing 100 and the lower housing 300 may be made of metal or polymer synthetic resin. The upper housing 100 and the lower housing 300 may be interlocked or coupled by an adhesive to form a body. At this time, the body may have a structure in which the inside is sealed. An inlet 101 and an outlet 102 penetrating the upper housing 100 may be formed at an upper end of the upper housing 100 . The membrane filter 200 may be disposed in a space below the inlet 101 when the upper housing 100 and the lower housing 300 are coupled. To this end, a space in which the membrane filter 200 can be seated may be formed in the upper housing 100 and/or the lower housing 300 . An upper surface of the upper housing 100 and/or the lower housing 300 may have a flow path (hereinafter referred to as 'microfluidic channel') through which microfluid moves. A plurality of sub-channels 301 may be formed in a space where the membrane filter 200 is seated so that the fluid passing through the membrane filter 200 is gathered in the center. The plurality of sub-channels 301 are connected to the main channel 302 formed in the center, and the main channel may lead to the reaction chamber 303. A reaction reagent may be previously applied to the reaction chamber 303 , and a reaction result between the reagent and the sample in the reaction chamber 303 may be detected from the outside. If the reaction chamber 303 can be connected to the discharge channel 304, the end of the discharge channel 304 can be connected to the discharge port 102 formed in the upper housing 100.

The example shown in FIG. 1 is only an example to aid understanding of the microfluidic device 10 according to the present specification. Accordingly, the material, structure, and shape of the bodies 100 and 200 may vary. In addition, the width, shape, and connection point of the microfluidic channels 301 to 304 may vary, and the size, number, and shape of the reaction chamber 303 may also vary. As the main components of the microfluidic device 10 according to the present specification, the microfluidic channels 301 to 304 formed inside the body, the sample inlet 101, the reaction chamber 303, the membrane filter 200, and the filter support structure 305 ). The sample inlet 101 may be formed in an area adjacent to one end of the microfluidic channels 301 to 304 in the body. Accordingly, the sample inlet 101 may be similar to the inlet shown in FIG. 1 , but does not necessarily have to be formed in the upper housing 100 . The reaction chamber 303 may be formed in the body and connected to the other ends of the microfluidic channels 301 to 304. The membrane filter 200 may be disposed between the sample inlet 101 and the microfluidic channels 301 to 304 to have desired filtration characteristics. The membrane filter 200 is for separating a desired component from a sample, and may be various filters widely known to those skilled in the art. For example, the membrane filter 200 can be used for the content disclosed in Korean Patent Registration No. 10-2079783 filed by the present applicant.

The filter support structure 305 may be formed to support the membrane filter 200 between the membrane filter and the microfluidic channel. At this time, the filter support structure 305 has at least one protruding pattern to form a movement passage so that the fluid separated from the sample injected through the sample inlet 101 gathers in the microfluidic channels 301 to 304. there is. A movement path formed by the filter support structure 305 may be a sub-channel 301 shown in FIG. 1 .

2 is a cross-sectional view of a membrane filter and filter support structure.

Referring to FIG. 2 , it can be confirmed that the membrane filter 200 is located at an upper end of the filter support structure 305 . The filter support structure 305 may be formed of at least one protruding pattern 305 , and the membrane filter 200 may be seated on an upper surface of the at least one protruding pattern 305 . At this time, an adhesive member 306 may be disposed between the upper surface of the at least one protruding pattern and the membrane filter. The adhesive member 306 may serve to fix the membrane filter 200 at an upper end of the filter support structure 305 . It is apparent that various materials known to those skilled in the art may be used as the adhesive member 306 .

On the other hand, the filter support structure 305 has at least one protruding pattern to form a movement passage, and the membrane filter 200 has a region exposed to the movement passage side among surfaces in contact with the filter support structure. A salt matrix 307 is attached to the exposed area.

The salt matrix 307 is a micro- or nanoparticle-soluble material that creates hygroscopic and osmotic forces due to the chemical composition of the particles, the pore structure that can be created by the particle size and the space between the particles. Examples of salt matrices include sodium chloride (NaCl), low-viscosity cellulose salts, anhydrous acids (e.g. ethylenediaminetetraacetic acid, EDTA), sugars (e.g. sucrose, dextrose), sugar derivatives (e.g. : Heparin), etc. The salt can have a greater capillary force than the membrane filter below the membrane filter 200, increasing the flow pressure of the fluid above the pressure spike. Accordingly, a phenomenon in which a pressure spike generated at a contact surface between the membrane and the air or between the fluid and air is higher than the flow pressure of the fluid can be solved. On the other hand, the salt matrix is water-soluble and can be dissolved in a fluid, but the influence on the measurement itself can be removed or minimized by separating the reagent and the sample before the reaction step or by measuring the presence of salt in the reaction process.

The salt matrix 307 according to the present specification is attached to the lower surface of the membrane filter 200, but is not attached to the area between the membrane filter 200 and the filter support structure 305, and the lower surface of the membrane filter 200 It is characterized in that it is attached only to the area exposed to the movement passage side 301 of the surface. Hereinafter, a method of attaching salt only to a specific region and mounting the membrane filter 200 to which the salt is attached will be described as described above.

3 to 9 are reference views for a method for mounting a membrane filter according to the present specification.

Referring to FIG. 3 , a membrane filter 200 and a double-sided adhesive member 306 may be provided. The double-sided adhesive member 306 may be in a state in which an adhesive matrix having adhesive strength on both sides and a protective film are attached to one side of both surfaces having adhesive strength.

Referring to FIG. 4 , the double-sided adhesive member 306 may be attached to one surface of the membrane filter 200 . At this time, as shown in FIG. 4 , a partial area of one surface of the membrane filter to which the double-sided adhesive member 306 is attached may be exposed. A shape of an unexposed region of one surface of the membrane filter to which the double-sided adhesive member 306 is attached may correspond to a shape of the filter support structure 305 .

Meanwhile, in the example shown in FIG. 3 , the shape of the adhesive matrix of the double-sided adhesive member 306 corresponds to the shape of the filter support structure 305 . That is, this is an example in which the double-sided adhesive member 306 has a shape corresponding to the filter support structure 305 before being attached to the membrane filter 200 . However, according to another embodiment, the double-sided adhesive member 306 may be attached only to a region corresponding to the shape of the filter support structure 305 on one surface of the membrane filter 200 .

Next, referring to FIG. 5 , salt may be applied to one side of the membrane filter 200 to which the back surface adhesive member 306 is attached. The salt is a substance of the salt matrix described above. At this time, the exposed area of the membrane filter 200 comes into direct contact with the coated salt, and the non-exposed area comes into contact with the double-sided adhesive member 306 . Referring to FIG. 6 , light blue (sky blue) represents salt applied to the exposed area of the membrane filter 200, and dark blue represents salt applied to the double-sided adhesive member 306.

Meanwhile, the salt may be applied by a medium-mediated diffusion method such as mist, spray, or dipping aerosol, and then subjected to a drying process. After the drying process, the salt may be attached to the surface of the membrane filter 200 to form a matrix.

Next, referring to FIG. 7 , the protective film of the double-sided adhesive member 306 attached to the membrane filter 200 may be removed. As a result, the salt applied on the double-sided adhesive member 306 is removed, and only the salt matrix applied on the membrane filter 200 remains.

Next, referring to FIG. 8 , the membrane filter 200 is aligned by aligning the membrane filter 200 such that the double-sided adhesive member 306 with the adhesive exposed by removing the protective film corresponds to the filter support structure. can be attached to.

Finally, referring to FIG. 9, the salt matrix 307 is attached only to a region of one surface of the membrane filter 200 that is not in contact with the filter support structure 305, that is, a region exposed to the movement passage side 301. It can be mounted on the microfluidic device 10 in a state of being.

When the salt adheres to the entire lower portion of the membrane, the salt also exists between the membrane filter 200 and the support structure 305. In this case, the space of the salt may become an obstacle to the adhesive area of the double-sided adhesive member 306, and the separated blood plasma may dissolve the salt in the future and adversely affect the adhesive state.

In addition, as disclosed herein, when salt is attached only to the area exposed to the passageway side 301 instead of the entire lower portion, it can help guide the flow of fluid in a specific direction (main channel) .

In addition, in order for the separated fluid (plasma) to proceed to the main channel 302, the inside of the sub-channel must be filled. When the separated fluid wets the salt matrix on one side of the membrane, at this time, the salt is applied between the bottom of the membrane and the wall of the support structure, so if a droplet is formed in the gap between them, it meets the droplet on the opposite wall. There is a disadvantage in that the subchannel 301 cannot be filled until now. On the other hand, as described herein, when the salt is attached only to the area exposed to the passageway side 301 instead of the entire lower part, the droplet is generated only in the lower part of the membrane without touching the wall surface, and the droplet grows significantly, so that the lower three The speed at which the channel is filled by contacting one of the surfaces and touching the other surface may be increased.

In addition, when blood separation is performed with an enhanced flow by increasing the pressure using a positive pressure pump or a negative pressure pump, hemolysis in which red blood cells are destroyed may occur. However, in the process of separating from the mixture fluid, the flow pressure of the fluid itself is strengthened, so if the pressure spike of the membrane passes without external pressure such as a positive pressure pump or a negative pressure pump, the quality of the resulting fluid (filterate; plasma or serum) can be improved. can Similarly, when separating a mixed solution containing solid particles, a structure such as a membrane or a housing may be damaged due to pressure or a desired separation result may not be obtained. However, when passing without external pressure such as a positive pressure pump or a negative pressure pump, there is an advantage that the internal substrate such as a membrane or a housing does not have to have a configuration corresponding to the strong pressure.

On the other hand, when the membrane is fixed on a protruding or etched lower support structure, that is, when the membrane is fixed to a flat body without a structure and the salt is applied to a part or the entire lower part of the membrane, there is a certain directionality between the lower part of the membrane and the body. Since this does not occur, it may be difficult to enter the fluid into the main channel. However, if the salt is applied to the underside of the membrane, especially around the edges, the separated fluid wets the side of the membrane, which can cause unseparated fluid to flow through the gap between the membrane and the body. That is, the separated fluid may have a specific directionality to flow toward the main channel.

When the salt matrix is attached, the double-sided adhesive member 306 is attached to the exposed surface of the membrane filter 200 so as to more reliably attach only to the area exposed to the passage side of the one surface of the membrane filter 200. The area of the region may be smaller than the top area of the filter support structure 305 . In other words, the area of the face attachment member 306 attached to the membrane filter 200 may be greater than the upper area of the filter support structure 305 .

Meanwhile, FIGS. 10 to 17 are other embodiments of a method for mounting a membrane filter and a microfluidic device according to the present specification. Comparing FIG. 10 with FIG. 1 , it can be seen that the filter support structure shown in FIG. 10 is different from the embodiment shown in FIG. 1 . That is, the embodiment shown in FIG. 10 is an embodiment in which the shape of the filter support structure is simplified to 'a' compared to the embodiment shown in FIG. 1 . 11 corresponds to FIG. 2, FIG. 12 corresponds to FIG. 3, FIG. 13 corresponds to FIG. 4, FIG. 14 corresponds to FIG. 6, FIG. 15 corresponds to FIG. 7, and FIG. 16 corresponds to FIG. 8, and FIG. 17 corresponds to FIG. 10 to 17 show that the membrane filter mounting method and the microfluidic device according to the present specification are not limited by the shape of the filter support structure and/or the size or shape of the moving passage.

18 is a diagram illustrating various exemplary embodiments of a protruding pattern.

Referring to FIG. 18 , it can be seen that protruding patterns on which the membrane filter can be seated are formed in various shapes. The protruding pattern may serve to support the membrane and simultaneously form a moving passage. Therefore, it should be understood that the protruding pattern according to the present specification through the examples is not limited to the examples described above and may have various shapes.

Although the embodiments of this specification have been described with reference to the accompanying drawings, those skilled in the art to which this specification belongs will understand that the present invention can be embodied in other specific forms without changing its technical spirit or essential features. You will be able to. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

10: micro-indwelling device
100: upper housing 200: membrane filter
300: lower housing 301: sub-channel (moving passage side)
302: main channel 303: reaction chamber
304: discharge channel 305: filter support structure (protrusion pattern)
306: adhesive member 307: salt matrix

Claims (7)

(a) providing a double-sided adhesive member having an adhesive matrix having adhesive force on both sides and a protective film attached to one of the two surfaces having adhesive force;
(b) attaching the double-sided adhesive member to one side of a membrane filter having desired filtration characteristics;
A partial area of one surface of the membrane filter to which the double-sided adhesive member is attached is exposed,
(c) applying salt to one side of the membrane filter to which the double-sided adhesive member is attached;
(d) removing the protective film of the double-sided adhesive member attached to the membrane filter; and
(e) attaching the membrane filter to the filter support structure by aligning the membrane filter so that the double-sided adhesive member, from which the protective film is removed and the adhesive is exposed, corresponds to the filter support structure. The method of claim 1,
The membrane filter mounting method, characterized in that the shape of the non-exposed area of one surface of the membrane filter to which the double-sided adhesive member is attached corresponds to the shape of the filter support structure. The method of claim 1,
The double-sided adhesive member provided in step (a),
A membrane filter mounting method, characterized in that the shape of the adhesive matrix corresponds to the shape of the filter support structure. The method of claim 1,
In step (b),
Attaching a double-sided adhesive member to a region corresponding to the shape of the filter support structure among one surface of the membrane filter, a membrane filter mounting method. The method of claim 1,
In the step (b), an area of an exposed area of one surface of the membrane filter is smaller than an upper area of the filter support structure. The method of claim 1,
The step (c) further comprises applying and drying the salt by an intermediate mediated diffusion method. A microfluidic channel formed inside the body;
a sample inlet formed in an area adjacent to one end of the microfluidic channel in the body;
a reaction chamber formed in the body and connected to the other end of the microfluidic channel;
a membrane filter disposed between the sample inlet and the microfluidic channel and having desired filtration characteristics;
It is formed to support the membrane filter between the membrane filter and the microfluidic channel, and a filter support having a plurality of protruding patterns forming a movement passage so that the fluid separated from the sample injected through the sample inlet gathers into the microfluidic channel. structure; and
A microfluidic device comprising an adhesive member disposed only between the upper surface of the plurality of protruding patterns and the membrane filter,
A microfluidic device, characterized in that a salt matrix is attached to a region of the membrane filter exposed only to the movement passage side among surfaces in contact with the filter support structure.

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