WO2020067716A1

WO2020067716A1 - Membrane-based device for liquid fluid pretreatment

Info

Publication number: WO2020067716A1
Application number: PCT/KR2019/012463
Authority: WO
Inventors: 이문근; 김지현; 신설이; 이태재; 이경균; 배남호; 이석재
Original assignee: 한국과학기술원
Priority date: 2018-09-27
Filing date: 2019-09-25
Publication date: 2020-04-02

Abstract

According to the present disclosure, disclosed is a membrane-based device for liquid fluid pretreatment which is manufactured to selectively separate and recover, based on a membrane filter, a specific component from liquid fluids such as blood or fecal liquid samples to be applicable to a variety of diagnoses.

Description

Membrane-based liquid fluid pretreatment device

The present disclosure relates to a device for pretreatment of a liquid fluid based on a membrane. More specifically, the present disclosure is based on a membrane filter, a membrane-based liquid fluid pretreatment designed to selectively separate and recover a specific component from a liquid fluid, such as a liquid sample of blood or feces, to be applied to various diagnosis. Dragon device.

The human body or various animals are continuously exposed to various disease sources (eg, harmful pathogens such as bacteria and viruses), and recently, the damage caused by diseases infected through the respiratory tract is increasing. For example, the severity of acute respiratory infections (SARS) virus, avian influenza virus (e.g., H1N1 influenza virus) have been reported as representative examples of respiratory viral infections.

In order to prevent and treat these diseases, it is essential to diagnose diseases, and various examination or diagnosis methods are applied according to characteristics of individual diseases. To this end, a biological tissue suspected of having a problem is secured and analyzed to directly determine whether a virus is infected or a biological tissue is deformed, or blood or fecal matter (feces) is collected and analyzed to analyze its components. A method of indirectly confirming is used.

First, blood that circulates through blood vessels of a human body or an animal is a liquid that flows in blood vessels, and contains various components such as red blood cells, white blood cells, platelets, and plasma. The blood functions to transport oxygen received from the lungs to tissue cells, release carbon dioxide from the tissues to the body, transport nutrients absorbed from the digestive tract to organs and tissue cells, and to release various unnecessary components to the body. In addition, it has various functions such as transporting hormones secreted from the endocrine glands to target organs and tissues, maintaining a constant body temperature, and killing various bacteria and viruses that have invaded the living body.

The identification of diseases through blood analysis is the most inexpensive, simple, and has the advantage of being able to be achieved in a short time, so it is widely used as a test method primarily performed in the case of the human body. About 42 to 47% of the whole blood is composed of red blood cells, white blood cells and platelets, which are solid components, while the remaining 53 to 58% is composed of plasma, which is a liquid component. Each blood cell has 5 million red blood cells, 8,000 white blood cells, and 300,000 platelets in 1 µl of blood. Plasma is a viscous liquid with a water content of about 90%, the rest consisting of proteins, carbohydrates and fats, and contains traces of vitamins, enzymes, hormones, antibodies and electrolytic substances.

When using blood cells in the examination of disease through whole blood, check the number, shape, size, and amount of hemoglobin of blood cells, and perform it in a way that contrasts with normal cases. Diagnosis of the presence or absence of the disease is made in a manner that contrasts with normal cases. Since plasma contains various nutrients, enzymes, hormones, and antibodies, the types of diseases that can be diagnosed through this are wide. For example, diseases that can be diagnosed by plasma tests include diabetes, hypothyroidism, liver disease, pregnancy, atherosclerosis, myocardial infarction, acute hepatitis, anemia, muscle trauma, mucus edema, viruses, drug addiction, typhoid fever, measles, rubella, etc. Together. As such, the types of diseases that can be diagnosed through plasma are more diverse than those using blood cells.

However, red blood cells in whole blood are easily destroyed in the analysis process, and when components in the blood cells are exposed, they act as obstacles to secure the accuracy of diagnosis. Therefore, in order to increase the reliability of the diagnosis, it may be preferable to use only plasma from which blood cells or the like have been removed from it rather than whole blood. Particularly, the protein chip is a type of biochip that is used to diagnose the presence or absence of a specific protein contained in a blood sample or the amount of a specific protein to diagnose a disease related to the protein, and the protein to be detected mainly exists in plasma. In order to obtain a highly sensitive quantitative result, it is required to separate only plasma components from blood.

On the other hand, in the case of diagnosis of livestock, birds, etc., the diagnosis of feces rather than blood is widely performed. In particular, in the case of avian influenza, it is often difficult to collect the blood by capturing the algae in the field, so the feces left by the algae are used. There is a need to utilize it for diagnosis. However, these excrements contain a significant amount of solids, and thus cannot be used for diagnosis as they are, and are usually mixed in a dilution buffer to perform a diagnostic process. However, it is desirable to obtain a purified sample as much as possible because foreign matter remains in the dilution medium.

As described above, it is advantageous to obtain a liquid sample suitable for point-of-care clinical tests by rapidly pre-treating blood, fecal matter, etc., rather than using them directly for diagnosis.

In this regard, as a method for separating a specific component (e.g., plasma, viral buffer solution) from a liquid fluid (e.g., whole blood, excrement dilution, etc.), active particle separation such as a centrifugal separation method, filter, capillary tube, etc. A passive separation method has been developed (for example, Korean Patent Nos. 0889727 and 177509, WO2004 / 084974, etc.). In particular, a method of separating blood cells by placing a paper, glass fiber, porous medium or membrane on the side or front of the blood flow, and a method of deflecting the flow of blood cells by applying an electrical signal are also known.

However, the separation method developed in the related art has a disadvantage of low separation efficiency due to slow flow in the separation process, so that a syringe pump or the like is attached to the separation device to promote the flow of liquid fluid. Particularly, in the case of a lap-on-a-chip based device, which has recently been spotlighted, membrane filters are mainly applied, but driving power (human hand, negative pressure pump power) is used for sample preparation. Etc.) is required. Therefore, it is more desirable to develop a device for pretreatment of a liquid fluid that can be operated without power and can quickly separate components suitable for a sample from a liquid fluid and can further be manufactured in a small size to maximize portability and convenience. something to do.

In one embodiment of the present disclosure, it is intended to provide a membrane-based device for pre-treatment of a liquid fluid capable of quickly and efficiently separating a sample component in a liquid fluid in a non-powered manner.

In addition, one embodiment of the present disclosure is to provide a membrane-based device for pretreatment of a liquid fluid capable of effectively separating a liquid fluid by a non-powered method while being able to be implemented in a relatively small size compared to the prior art.

According to the first aspect of the present disclosure,

A device for pretreatment of fluid,

A membrane filter for separating the liquid fluid injected into the device while moving in a direction from a contact surface to a transmission surface opposite to the liquid fluid;

A contact structure comprising a receiving chamber of a pre-treatment liquid fluid that is received while contacting the contact surface of a membrane filter of a device in which the liquid fluid is placed upright and flows downward under the application of gravity, and

A recovery structure including a receiving chamber of a liquid fluid after pre-treatment, configured to allow the liquid fluid separated by the membrane filter to flow downward along the permeation surface under the application of gravity;

Including,

Each of the pre-treatment liquid fluid receiving chamber and the pre-treatment liquid fluid receiving chamber is configured to provide a capillary force required for the movement of the liquid fluid, and

The device is provided with a membrane-based device for pretreatment of a liquid fluid, including a collection chamber that communicates with the receiving chamber of the liquid fluid after the pretreatment and provides a collection space of the liquid fluid after the pretreatment.

According to the second aspect of the present disclosure,

(A) a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite thereto;

(B) (b1) A first film having a first through cavity attached to a contact surface of the membrane filter to provide a space for receiving the liquid fluid introduced therein, and a boundary through which the received liquid fluid contacts the membrane filter. Mold structures;

(b2) A film comprising a second through-cavity attached to the first film-like structure, an inlet communicating with the first through-cavity, and a second through-cavity forming a space for accommodating the liquid fluid together with the first through-cavity Mold top structures;

(b3) an outer film structure configured to cover at least a second through cavity attached to the film-like top plate structure to provide a space for moving the introduced liquid fluid by capillary action;

(C) (c1) a second film-like structure attached to the permeable surface of the membrane filter and having a third through cavity bounded to form a space for receiving the separated liquid fluid through the membrane filter; And

(c2) a film-type lower plate structure attached to a lower surface of the second film-like structure, and having a support member supporting a membrane filter through the third through-cavity and a through hole to discharge the separated fluid;

Provided is a device for pretreatment of a film-like liquid fluid comprising a.

According to the third aspect of the present disclosure,

(A ') a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite thereto;

(B ') (b1') is attached to the contact surface of the membrane filter, provides an inlet for the liquid fluid, and provides a space for receiving the introduced liquid fluid and is bounded so that the received liquid fluid contacts the membrane filter. 1 A top plate structure in the form of a plastic molding having a through cavity;

(b2 ') an outer film structure attached to the top plate structure and configured to cover at least a first through cavity to provide a space for moving the introduced liquid fluid by capillary action;

(C ') (c1') Fixing the membrane filter having a second through cavity attached to the permeable surface of the membrane filter and bounded to form a space for receiving the separated liquid fluid through the membrane filter. Adhesive film structure for; And

(c2 ') A lower plate attached to the lower side of the adhesive film structure structure, and having a support member supporting a membrane filter through the second through cavity and first and second through holes to discharge the separated fluid. structure;

Provided is a membrane-based plastic device for pretreatment of a liquid fluid comprising a.

According to the fourth aspect of the present disclosure,

(A ") a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite to it;

(B ") (b1") is provided on the contact surface of the membrane filter to provide a space for receiving the liquid fluid introduced therein and having a first through cavity bounded so that the received liquid fluid contacts the membrane filter. 1 film-like structure;

(b2 ") comprising a second through cavity attached on the first film-like structure, an inlet communicating with the first through cavity, and a second through cavity forming a space for accommodating the liquid fluid together with the first through cavity Top structure;

(C ") (c1") a second film type attached to a permeable surface of the membrane filter and having a third through cavity bounded to form a space for receiving the separated liquid fluid through the membrane filter structure; And

(c2 ") attached to the lower side of the second film-like structure, a supporting member supporting a membrane filter through the third through cavity, a micro-channel for moving the separated liquid fluid, and communicating with the micro-channel A 3D printing type plastic molded lower plate structure having a collection space for collecting the moved liquid fluid;

According to the fifth aspect of the present disclosure,

Providing a liquid fluid as a sample;

Introducing the liquid fluid into the device to perform pretreatment by a membrane filter in the device by using the capillary force and gravity of the microfluid as the driving force in an upright state; And

Recovering the liquid fluid after pre-treatment discharged from the device;

There is provided a method for pre-treatment of a liquid fluid comprising a.

According to an exemplary embodiment, the pre-treatment may further include performing a diagnosis on the liquid fluid.

The device for pre-treatment of a liquid fluid provided in a specific example of the present disclosure is a technique in which a device for separating liquid samples such as blood and animal feces samples has a relatively large volume or requires external driving force. Limitations can be overcome simultaneously. In particular, the members constituting the fluid pretreatment device so as to induce the capillary force of the fluid can be implemented in the form of film-like materials and / or relatively thin plastic moldings (or workpieces thereof), and / or 3D printing moldings, and a simple lamination process By using, it is suitable for commercial scale production or mass production. Moreover, it provides the advantage of pre-processing (separating) the liquid fluid in a short time by using the capillary force of the microfluidic force and the gravitational force of the upright arrangement without supply of an external drive source.

Furthermore, the device for pre-treatment of a liquid fluid according to an embodiment of the present disclosure can quickly perform sample collection and diagnosis as much as it is suitable for directly applying the separated liquid fluid to a diagnostic chip or kit known in the art. It is useful for on-site diagnostics where it is required. Therefore, broad commercialization is expected in the future.

1 is a perspective view showing the appearance of a pretreatment device for liquid fluid according to an exemplary embodiment;

2A and 2B are exploded perspective views of a pretreatment device for liquid fluid according to an exemplary embodiment, and simultaneously forming a support member using a floating cutter to form a second film-like structure, which is formed on a film-like bottom structure. It is a figure showing what is attached;

3 is a top view of a liquid fluid pretreatment device according to an exemplary embodiment;

4 is a side view of a liquid fluid pretreatment device according to an exemplary embodiment;

Fig. 5 is a plan view showing a cut surface of line A-A in Fig. 4;

6 is a perspective view showing the appearance of a membrane-based plastic device according to an exemplary embodiment;

7 is an exploded perspective view of a membrane-based plastic device according to an exemplary embodiment;

8 is a top view of a membrane-based plastic device according to an exemplary embodiment;

9 is a side view of a membrane-based plastic device according to an exemplary embodiment;

FIG. 10 is a view showing a plane cut in the horizontal direction along the line A'-A 'of the membrane-based plastic device shown in FIG. 9;

11 is a perspective view showing the appearance of a membrane-based plastic device according to another embodiment;

12 is an exploded perspective view of a membrane-based plastic device according to another exemplary embodiment;

13 is a top view of a membrane-based plastic device according to another exemplary embodiment;

FIG. 14 shows the fluid flow space in the lower plate structure in the form of a plastic molding as the cut surface of line A ”-A” in FIG. 13;

15 is a perspective view of a lower plate structure with a second support member attached to a membrane-based plastic device according to another exemplary embodiment;

16A and 16B are each a top view and a back view of the pretreatment device for liquid fluid prepared in Example 1;

17A is a photograph showing a change in the amount of recovered plasma separated over time by injecting blood (whole blood) as a liquid fluid (sample) into a pretreatment device of a liquid fluid disposed in an upright state according to Example 2;

17B is a photograph showing a state in which the plasma separated in Example 2 was recovered by a pipette;

Figure 18, in Example 3, spiking the H1N1 virus in urine state in a liquid fluid diluted with feces of chicken in PBS, and then injecting it into a pretreatment device to remove debris contained in the liquid fluid. It is a photograph showing a series of processes;

19 is a photograph showing the appearance of each of the upper and lower structures in the membrane-based plastic device (4 × 8 cm) fabricated in Example 4 and their assembled state;

20 is a photograph showing the process of separating plasma by a membrane-based plastic device in Example 4;

21 is a photograph showing the process of recovering plasma separated by a membrane-based plastic device in Example 4 by a non-powered pump;

FIG. 22 is a photograph showing the top and bottom surfaces of a bottom structure implemented by 3D printing in a membrane-based plastic device (8 × 8 cm) produced in Example 5;

23 is a photograph by step showing the assembly sequence of the membrane-based plastic device produced in Example 5; And

24 is a photograph showing the results of separating plasma from blood using the membrane-based plastic device prepared in Example 5.

The present invention can be achieved by the following description. It should be understood that the following description describes preferred embodiments of the invention, and the invention is not necessarily limited thereto. In addition, the accompanying drawings are intended to aid understanding, and the present invention is not limited thereto, and details regarding individual configurations may be appropriately understood by the specific purpose of related descriptions to be described later.

The terminology used herein may be understood as follows.

“Liquid fluid” may mean a fluid that contains biological cells, tissues, feces, and the like in a liquid medium, and has the same or similar behavior as a liquid fluid. Typically, urine, blood, saliva, semen, feces (feces) diluted with a liquid medium, sputum, cerebrospinal fluid, tears, mucus, amniotic fluid, etc. can be exemplified.

“Blood” may generally mean whole blood, and in some cases, it may also contain additional components, such as saline, nutrients and / or anticoagulants. It may also include pre-treated blood to remove some of the components, such as white blood cells, from the whole blood.

"Channel" is a fluid (especially liquid fluid) as long as it corresponds to a path that moves in a predetermined direction, It is not necessarily limited to the closed form, but may be understood as a concept including the open form.

"Shaping" can mean any technique for manufacturing a specific material (composition, etc.) into a given shape (especially a three-dimensional shape), as is typical polymer (or resin) such as injection molding. It can be understood as a concept including not only molding technology, but also 3D printing.

"3D printing" is a technology that comprehensively manufactures three-dimensional three-dimensional shapes. It is a technical difficulty due to the inefficiency of conventional manufacturing techniques (cutting, casting, forging, etc.) and the application of complex shapes, composite materials, etc. As a manufacturing technique to overcome, it may mean a method of manufacturing a product or a part through continuous lamination of materials based on 3D shape information of an object.

The expressions “on” and “on” can be understood to be used to refer to the concept of relative position. Thus, as well as when other components or layers are present directly in the recited layer, there may be at least one other layer (intermediate or intervening layer) in between, or additional components may be interposed or present. Similarly, the expressions “below”, “below” and “below” and “between” may also be understood as relative concepts of location. In addition, the expression "sequentially" can also be understood as a concept of relative position.

Although the term "contact" means a direct contact between two materials in a narrow sense, it can be understood that in the broad sense, any additional component can be interposed as long as the contact between the component and the liquid flow is made. .

When any component or member is described as being “connected” or “in communication with” another component or member, unless otherwise stated, as well as in direct connection or communication with the other component or member , It may be understood that the case of being connected or connected under the interposition of other components or members is also included.

“Upper surface” or “lower surface” is a term used for convenience in order to indicate a relative arrangement relationship with other members. In this specification, the term “top surface” or “rear surface” is used when the member is placed upright. It can be understood as meaning.

According to one embodiment of the present disclosure, the fluid pretreatment device is largely centered on a membrane filter (specifically a film-type membrane filter), and receives a liquid fluid (or liquid sample) on one side to contact the membrane filter to contact the membrane filter. The contact structure including the receiving chamber of the fluid, and the other side of the membrane filter (ie, the permeating surface) may include a recovery structure including the receiving chamber of the liquid fluid after pretreatment.

In an exemplary embodiment, a member constituting each of the structures constituting the receiving chamber of the liquid fluid before pretreatment and the structures constituting the receiving chamber of the liquid fluid after pretreatment may be a film-like material. According to another exemplary embodiment, at least one of the structures constituting the accommodating chamber of the pre-treatment liquid fluid and the structures constituting the accommodating chamber of the pre-treatment liquid is a member that is a plastic molding (or a workpiece thereof), or in a 3D printing manner. It may include a member that is a manufactured plastic molding.

According to an exemplary embodiment, the membrane filter may typically include a porous membrane having a two-dimensional planar shape, a contact surface in contact with the liquid fluid introduced into the device on a plane basis, and a liquid phase separated through the membrane. A permeate surface is formed through which the fluid escapes.

Membrane filters involve sieving, chemical affinity, and / or immuno-antibody processes, which move the liquid fluid (liquid sample) to be pretreated from the contact surface to the permeate surface facing it. It has the function of separating.

In this connection, the size of the pores in the membrane may vary depending on the liquid fluid to be treated. For example, when blood (whole blood) is used as the liquid fluid and plasma is separated therefrom, blood cells in the blood do not pass through the membrane. However, it is possible to have a pore size range capable of selectively moving only the plasma in the thickness direction. In this case, in consideration of the size (about 2 to 10 μm) of blood cells in the blood, for example, it may be in the range of about 0.1 to 100 μm, specifically about 0.5 to 50 μm, and more specifically about 1 to 20 μm.

According to one embodiment, the material of the membrane filter may be an isotropic membrane, an anisotropic membrane, or a combination thereof. Specifically, as the anisotropic membrane, an asymmetric membrane of the same material and a composite membrane of two or more different materials can be exemplified. According to certain embodiments, anisotropic membranes, specifically asymmetric membranes can be used, for example the upper region of the membrane (area near the contact surface) by thickness has a relatively large pore size, while the lower region ( Area near the transmission surface) may be configured to have a relatively small pore size. Illustratively, the pore size of the upper region in the membrane may range, for example, from about 5 to 100 μm, specifically from about 10 to 50 μm, and more specifically from about 20 to 40 μm, while the pore size of the lower region in the membrane The size can be, for example, in the range of about 0.1 to 5 μm, specifically about 0.5 to 2 μm, more specifically about 0.5 to 1 μm.

According to an exemplary embodiment, it may also exhibit a pattern in which the pore size continuously changes (eg, continuously decreases in pore size) as it progresses from the contact surface of the membrane to the transmission surface. As such, a membrane having an asymmetrical property is used, but in the filtering process, the liquid fluid reduces the pore size in the direction of the membrane filter from the contact surface to the permeation surface. It is believed that the separated liquid fluid can be easily and quickly transported across the membrane.

According to an exemplary embodiment, the material of the membrane may be a polymer, for example, polyolefin, polyester, polyamide, polysulfone, acrylic polymer, polyacrylonitrile, polyaramid, polymer of halogenated olefin, combinations thereof, etc. You can. Specifically, polyethylene, polypropylene, polyethylene terephthalate (PET), nylon (eg, nylon 6, 66, etc.), polyvinylidene difluoride (PVDF) can be exemplified.

According to an alternative embodiment, as a natural polymer, for example, a cellulose derivative, specifically cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, and the like can be used.

According to an exemplary embodiment, the thickness of the film-type membrane filter may be, for example, in the range of about 100 to 1,000 μm, specifically about 200 to 500 μm, and more specifically about 300 to 350 μm. If the thickness of the membrane is too thin, fabrication may not be easy or breakage of the membrane may occur in the pre-treatment process, whereas when it is too thick, the amount of liquid fluid absorbed by the membrane filter increases, limiting the amount of liquid fluid that can be recovered after pretreatment. As long as the problem can be caused, it can be appropriately adjusted within the above-described range in consideration of the amount of liquid fluid to be injected, but is not limited thereto.

On the other hand, in order to form a pattern on the structure of the film member in the device, for example, laser cutting, cutting plotter (floating cutter) processing method, cutting printing method, lathe processing method, etc. may be applied according to a design program. And detailed technical details are known in the art.

In addition, detailed structures, patterns and shapes in the form of plastic moldings (or substrates) may be directly formed by injection molding or casting. Alternatively, it can be formed by processing using a design program and a CNC technique. In addition, the plastic molding of the 3D printing method can be manufactured using a design program and any material capable of 3D printing (eg, photocurable acrylic resin).

According to one embodiment, the liquid fluid pretreatment device can be operated in an upright position, wherein the liquid fluid introduced into the device contacts the contact surface while wetting the contact surface of the membrane filter with gravity in the chamber of the liquid fluid before pretreatment. The liquid fluid is filtered using the capillary force as a driving force in a direction perpendicular to the contact surface of the membrane filter, while moving in the downward direction by the capillary force generated in the horizontal direction. As a result, the liquid fluid is separated while moving in the direction of the permeate surface.

In addition, the liquid fluid (filtered liquid fluid) discharged from the permeate surface through the membrane filter is moved downward under the application of gravity in the receiving chamber of the liquid fluid after pretreatment. At this time, the two chambers formed on both sides of the membrane filter (the receiving chamber of the liquid fluid before pre-treatment and the receiving chamber of the liquid fluid after pre-treatment) can be adjusted in dimensions, geometry, etc. to provide a suitable space for inducing capillary action. Bar, each of the pre-treatment liquid fluid and pre-treatment liquid fluid can be effectively moved using capillary action.

As described above, the liquid fluid after pretreatment (that is, the liquid fluid separated by the membrane filter) may be collected (collected) by using a collection chamber in communication with the receiving (moving) space of the liquid fluid after pretreatment in the device. In this regard, by pre-processing the device in an upright manner, it is possible to achieve the advantage of continuously moving the liquid fluid before and after the pre-treatment to the collection chamber without using external power or power.

According to an exemplary embodiment, a structure in the form of a plastic molding can be introduced into a device for pretreatment of a liquid fluid, in this case, alignment of a pattern for forming a structure that may occur when the entire device is composed of a film-like material. It is possible to alleviate the problems caused by mismatch, and to implement a pre-processing device with fewer members. In addition, when using 3D printing, since a sample movement channel can be implemented inside the device without forming a sample movement channel using a film sheet on the outer surface of the device, the possibility of sample leakage due to deterioration of adhesion between film sheets is fundamentally avoided. Can be removed. Furthermore, in other exemplary embodiments, a sample transfer channel for subsequent sample reaction can be added by forming a connection or connection passage capable of integrating or integrating the pretreatment device with the microfluidic chip between lab-on-a-chip. .

According to an exemplary embodiment, in the case of the absence of a film material in a device for pretreatment of a liquid fluid, the strength measured by ASTM D 882 is, for example, at least about 10 to 30 kgf / mm2, specifically about 15 to 27 kgf / mm2, more specifically about 20 to 25 kgf / mm2. In addition, the ductility of the film as measured by ASTM D 882 may be, for example, at least about 100%, specifically about 110 to 300%, more specifically about 120 to 200%. In addition, the Young modulus of the film as measured by ASTM D 882 is, for example, in the range of about 250 to 500 kgf / mm2, specifically about 300 to 450 kgf / mm2, more specifically about 360 to 430 kgf / mm2 Can be Although the present disclosure is not limited to the mechanical properties described above, it may be desirable to select a film-like member capable of effectively implementing advantages such as good flexibility and reduced volume. According to an exemplary embodiment, the material of such a film-like member is typically polyester (specifically, polyethylene terephthalate (PET)), polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS) ), Polycarbonate (PC), polyurethane, polyvinylidene fluoride, nylon, polymethyl methacrylate (PMMA), polyvinyl chloride (PVC), cyclic olefin copolymer (COC), liquid crystal polymer (LCP), Polyamide (PA), polyimide (PI), poly (phenylene ether) (PPE), polyoxymethylene (POM), polyether ether ketone (PEEK), polyether sulfone (PES), polytetrafluoroethylene ( PTFE), acrylic resin, etc., and at least one of them may be used. More specifically, it may be polyethylene terephthalate (PET), but is not limited thereto.

In addition, the material of the structure in the form of a plastic molding in the device for pretreatment of a liquid fluid is various molding techniques known in the art (for example, injection molding, casting, rolling molding, compression molding, extrusion molding, extrusion blow molding, foam molding, Press, CNC machining, additive manufacturing, etc.), or may be a material capable of forming by 3D printing. For example, plastics that can be produced by molding techniques may be silicone-based polymers, for example, polydimethyl siloxane (PDMS or h-PDMS), polymethylsiloxane, partially alkylated polymethylsiloxane, polyalkylmethylsiloxane, poly Phenylmethylsiloxane, a combination thereof, and the like, and specifically PDMS can be used. In addition, other polymers capable of forming or 3D printing, such as silicone-modified elastomers, thermoplastic elastomers, poly (butylene terephthalate; PBT) polystyrene (PS), polycarbonate (PC), polyolefins (e.g. polyethylene ( PE) and polypropylene (PP)), poly (etheretherketone) (PEEK), poly (etherimide) (PEI), polylactide, polymethylmethacrylate (PMMA), polyurethane thermoplastic elastomer, polyamide ( PA), polyimide (PI), polyester (PET), synthetic rubber, polyisobutylene, and the like, and at least one may be selected. In particular, as a plastic (polymer) material for 3D printing, photocurable resins (specifically, photocurable acrylic resins, acrylonitrile butadiene styrene (ABS), polylactide (PLA), etc.) can be used.

All of the components in the above-described pretreatment device may be the same or different plastic or polymer materials, and in some cases, some of the plurality of layers may be formed of the same or the same material, while the remaining layers may be formed of different materials. . At this time, even if the same or the same plastic material, the physical properties of the individual members may be different.

In addition, an adhesive may be used in the process of laminating a plurality of members, but for quickness and convenience of the process, the member may be formed of an adhesive material (one-sided or double-sided adhesive material), specifically, a double-sided adhesive material. In this connection, in order to mutually attach a plurality of members constituting the pretreatment device, it is possible to induce close adhesion by an adhesive or an adhesive material by applying pressure or pressing.

Hereinafter, a preferred embodiment of the present disclosure will be mainly described. However, the present invention is not necessarily limited thereto.

The first Concrete (For film type liquid fluid pretreatment device )

1 shows the appearance of a liquid fluid pretreatment device according to an exemplary embodiment of the present disclosure.

In the case of the pretreatment device according to the illustrated embodiment, the liquid fluid pretreatment device 100 may be manufactured by using all members as a film-like material and assembling individual members by a lamination process. Therefore, since the pre-processing device 100 may also have a shape similar to that of a two-dimensional film as a whole, the pre-processing device 100 can be manufactured by a lamination process using a film or sheet made of a polymer material, thereby increasing convenience and manufacturing cost. Can be lowered.

2A and 2B are exploded perspective views of a pretreatment device for liquid fluid according to an exemplary embodiment, and simultaneously forming a support member using a floating cutter to form a second film-like structure, which is formed on a film-like bottom structure. It shows what is attached.

In the illustrated embodiment, the membrane filter 111 is a two-dimensional planar structure, and may have an overall pentagonal shape (a shape in which both corner portions of one side are cut out or a rectangular shape in which the top converges in a wedge shape). have. However, the shape of the membrane filter is not limited to this, it can be understood that various modifications are possible.

The membrane filter 111 has a contact surface (the front side of the membrane filter) that comes into contact with the liquid fluid (or a liquid sample) to be pre-treated, and a permeation surface through which the liquid fluid passing through the membrane escapes during filtering (the back side of the membrane filter). Have On the contact surface, a first film-like structure 112 processed in a predetermined pattern is attached. Specifically, the first film-like structure 112 is formed with a first through-cavity 121 and a through-cavity 122 for collecting a first sample, which are separately demarcated within the frame. In the illustrated embodiment, the first through-cavity 121 in the upper region of the first film-like structure 112 and the through-cavity 122 for collecting the first sample are located in the lower region. For example, the first film-like structure 112 may be made of a double-sided adhesive material for easy and effective attachment between the membrane filter 111 positioned below and other film-like members described below.

In this regard, the first through cavity 121 is a member constituting a space in which the liquid fluid introduced into the device 100 is accommodated and moved, that is, a receiving chamber. At this time, the first through cavity 130 typically has a shape corresponding to the membrane filter 111, but is not necessarily the same shape. In addition, when the membrane filter 111 is larger in size than the first through cavity 121, the injected liquid fluid may leak through the side surface of the membrane filter. Accordingly, the membrane filter 111 may have at least the same or smaller size than the first through cavity 121, but must be larger than the third through cavity 130.

In addition, the first sample collection through-cavity 122 may have a size or shape suitable for the space in which the liquid fluid separated by the membrane filter 111 is collected later, that is, corresponding to a member constituting the collection chamber. . In the illustrated example, a pot-shaped cavity is formed that converges gently toward the bottom.

According to an exemplary embodiment, the thickness of the first film-like structure 112 may be determined, for example, within a range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm. have.

Meanwhile, a film-shaped top plate structure 113 may be attached to the first film-type structure 112. According to the illustrated example, the inlet 124 of the liquid fluid is formed in one end region of the top plate structure 113, specifically, the inlet 124 is an area near the top of the film-shaped top plate structure 113 (specifically It may be formed in the center of the upper area converging in a wedge shape). The inlet shape may be of various shapes (eg, circular, elliptical, etc., more specifically circular). In particular, in the case of forming a circular inlet, it is possible to suppress the phenomenon of overflowing to the outside compared to a rectangular inlet when injecting a liquid fluid.

The inlet 124 may preferably have a size sufficient to inject a liquid sample into the receiving space (chamber) of the liquid fluid in the device 100 using a pipette or the like. Illustratively, the size (or diameter) of the inlet 124 may be, for example, in the range of about 1 to 100 mm, specifically about 3 to 50 mm, and more specifically about 5 to 20 mm. Illustratively, the amount of liquid fluid introduced through the inlet 124 may be, for example, in the range of about 0.1 to 10 mL, specifically about 0.5 to 5 mL, and more specifically about 1 to 2 mL.

In the illustrated embodiment, the second through-cavity 123 is formed separately from the inlet 124, and is in communication with the first through-cavity 121 positioned below. That is, the second through-cavity 123 functions as a member constituting the space (or chamber) for receiving the liquid fluid flowing through the inlet 124 in combination with the first through-cavity 121,

In addition, in the region of the film-like upper structure 113 facing the injection hole 124 in the longitudinal direction, and in the lower region, for collecting the second sample in communication with the through cavity 122 for collecting the first sample of the first film structure 112. The through cavity 125 may be formed. In this case, the second sample collection through cavity 125 may correspond to the first sample collection through cavity 122 or may have the same shape.

According to an exemplary embodiment, the thickness of the film-like top plate structure 113 may be determined, for example, within about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

Meanwhile, according to the illustrated embodiment, gravity is applied to the liquid fluid introduced through the injection hole 124 as the device 100 is placed upright. In addition, in order to provide a space (or accommodating chamber) for receiving and moving the liquid fluid before pre-treatment, it is possible to form an outer film structure that is attached to the film-shaped top plate structure 113 and covers at least the second through cavity 123. have.

As described above, by covering the second through cavity 123 with the outer film structure, an environment (or dimension) in which a capillary phenomenon occurs that enables rapid movement of liquid fluid through a space (receiving chamber) formed between the membrane filter and the film structure To form and allow the introduced liquid fluid to reach the moving space or the lower side of the receiving chamber by the capillary force (i.e., the capillary force generated while wetting the microcavity of the membrane filter provides the driving force required for movement) Can do).

However, when the introduced liquid fluid wets the membrane filter 111 and a certain period of time has elapsed, the separated liquid fluid is filtered out from the bottom surface of the membrane filter 111, and at this time, the moving space or the empty space in the receiving chamber Silver is filled with air flowing in from the outside through the injection port (124). Accordingly, a phenomenon in which the liquid fluid is captured or stagnated may occur in the lower portion of the moving space or the receiving chamber that is wet by the liquid fluid.

The outer film structure may be configured using an air permeable film so as to mitigate the stagnation or delay phenomenon of the flow so that the liquid fluid can quickly move in the moving space or the receiving chamber. Specifically, the outer film structure may largely include an air-permeable film fixing tape 114 and an air-permeable film 115. At this time, in the case of the fixing tape 114, the first through-cavity 123 and the second through-collection cavity 125 for collecting the second sample without blocking the inlet 124 of the film-shaped upper plate structure 113 located below A fourth through cavity 126 (in communication) and a through cavity 127 for collecting a fourth sample may be formed.

As an example, a typical example of the air-permeable film may be a hydrophobic filter or the like. Since the air-permeable film is capable of entering and exiting air, it is possible to suppress the stagnation phenomenon of the liquid fluid resulting from the wetting phenomenon of the membrane. In particular, by using the air-permeable film, while the liquid fluid passes through the membrane filter 111, the negative pressure generated at the rear side can be easily eliminated, and as a result, the processing time of the liquid fluid can be shortened. In addition, it is preferable that external air is easily introduced to allow the liquid fluid to pass through the filter in the region near the inlet 124 of the membrane filter 111, as well as in the region relatively far from it, by using an air permeable film. External air may be uniformly introduced through the movement path or the entire surface of the receiving chamber.

According to an exemplary embodiment, the air-permeable film 115 can suppress the inflow and outflow of moisture so that the liquid fluid does not penetrate (wet) the film and escape the outside, while the air can permeate relatively freely. It is desirable to have properties. Therefore, the air permeable film 115 may be a material having a hydrophobic property or a film having a hydrophobic treated material. In this connection, as a material used in hydrophobic treatment, for example, PTFE (Polytetrafluoroethylene) may be exemplified.

According to an exemplary embodiment, the material of the air permeable film 115 may be, for example, polyester, polyolefin, natural fiber (cellulose), or a combination thereof, and may be a nonwoven fabric prepared therefrom. More specifically, the fibers may be in a form that is mechanically entangled by a random web, a mat, or a fusion method of fibers. Of the types exemplified above, polyesters have good water resistance, and polyolefins, especially polypropylene, are inherently hydrophobic. In addition, as described above, an air permeable film may be prepared by applying or treating a hydrophobic material on a nonwoven fabric made of a hydrophilic material.

According to an exemplary embodiment, the thickness of the air permeable film 115 may be, for example, about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm. In addition, the basis weight of the air permeable film 115 may be, for example, in the range of about 50 to 200 g / m 2, specifically about 60 to 170 g / m 2, and more specifically about 80 to 150 g / m 2, which is an example It can be understood for an enemy purpose.

3 is a plan view of a liquid fluid pretreatment device according to an exemplary embodiment.

1 to 3, the lower region of the air permeable film 115 (specifically, the region near the end opposite to the inlet 124) is formed with a liquid fluid outlet 128, which will be described later. As described above, a passage through the membrane filter 111 to communicate with the collection space of the separated liquid fluid is provided to discharge the recovered liquid fluid to the outside. Illustratively, the size (diameter) of the outlet 128 may range, for example, from about 1 to 10 mm, specifically from about 2 to 5 mm, and more specifically from about 3 to 4 mm.

In this regard, in the manufactured state or in a state in which the pretreatment process is in progress, the outlet 128 of the liquid fluid is covered and closed by an outlet cover (one side exhibits adhesion; not shown). This is to prevent the collected liquid fluid from flowing out through the outlet.

On the other hand, as described below, as the pre-processing process proceeds, the liquid fluid after pre-treatment flows into the collection space. At this time, it may be difficult to flow the pre-treatment liquid fluid due to air already present in the collection space. However, according to the illustrated embodiment, air present in the collection space is naturally removed outside the device through the air permeable film 115 covering the fourth sample collection through cavity 127, and as a result, the liquid fluid after pretreatment It does not cause any special problems.

In addition, the fixing tape 114 of the air-permeable film is specifically applicable in the form of a double-sided adhesive tape, and serves to bond the air-permeable film 115 to the film-like top structure 113. As the fixing tape 114 of the air-permeable film, a pressure-sensitive adhesive tape, a thermally active adhesive tape, a chemically active adhesive tape, a photoactive adhesive tape, and the like can be exemplified. Alternatively, the air-permeable film 115 may be attached using an adhesive, not a fixing tape. As such an adhesive, a rubber-based adhesive, an acrylic resin-based adhesive, a silicone-based adhesive, an optical-based adhesive, and a heat-sensitive adhesive may be used. In an exemplary embodiment, the height of the anchoring tape or adhesive layer 114 may range from, for example, about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

In the illustrated embodiment, the sum of the thicknesses of each of the first through cavity 121, the second through cavity 123, and the fourth through cavity 126 forming the moving space (or accommodating chamber) of the liquid fluid is substantially liquid. The height of the fluid's moving space (or receiving chamber) can be determined. However, as the height of the moving space (or the receiving chamber) increases, the capillary force decreases, such that the height of the moving space is, for example, about 0.1 to 10 mm, specifically about 0.5 to 5 mm, and more specifically about 1 to 2 The thickness of each of the first through cavity 121, the second through cavity 123, and the fourth cavity 126 may be adjusted to be in the mm range.

On the other hand, a second film-like structure 116 is attached to the lower surface (rear surface) of the membrane filter 111, that is, the permeable surface, and the second film-like structure 116 is separated by passing through the membrane filter 111. It includes a third through cavity 130 bounded to provide a space for accommodating and moving the liquid fluid, and also separate from the third through cavity 130 to receive the separated liquid fluid through the membrane filter 111. A third through-hole cavity 131 for collecting a sample is defined.

According to the illustrated embodiment, the third through cavity 130 in the second film-like structure 116, similar to the first through cavity 121, has a membrane filter to provide a receiving space for the separated liquid fluid. It may have at least the same or smaller size than (111). In this regard, the lower regions of each of the first film-like structure 112 and the second film-like structure 116 having flexibility based on the membrane filter 111 may be bonded while bending toward the membrane filter 111. In particular, when each of the first film-like structure 112 and the second film-like structure 116 is formed of an adhesive material (single-sided or double-sided adhesive material), the membrane filter 111 is interposed by bonding together with bending. It can be easily fixed. In particular, when the second film-like structure 116 is composed of a double-sided adhesive material, the membrane filter 111 serves to fix the membrane filter 111 to the film-like lower structure 117 via the same, and at the same time, the membrane filter 111 is provided. It is possible to form a moving space (or a recovery chamber) in which the liquid fluid passed through and separated may exist in the form of a thin microfluidic membrane.

In addition, as described above, the third sample collection through cavity 131 functions as a member constituting the collection chamber together with the first sample collection through cavity 122 and the second sample collection through cavity 125. It may be advantageous to have the same shape as these corresponding members.

According to an exemplary embodiment, the thickness of the second film-like structure 116 may be, for example, in the range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

FIG. 4 is a side view of a liquid fluid pretreatment device according to an exemplary embodiment, and FIG. 5 is a plan view showing the cut surface of line AA in FIG. 4, wherein the second film structure 116 and the film-like bottom structure 117 are It shows the combined state.

1 to 5, the film-type lower plate structure 117 is attached to the lower surface of the second film-type structure 116 as described above. In the example shown in FIGS. 2 and 5, the film-like lower plate structure 117 includes a support member 132 for supporting (seating) the membrane filter 111 through the third through cavity 130.

As shown, the support member 132 may have a form in which a plurality of island structures are arranged. The island structure may have various cross-sectional shapes such as a circular shape, a triangular shape, a quadrilateral shape, and an irregular shape, and specifically, it may be advantageous to have a circular cross-section. Illustratively, the cross-sectional size (diameter) of the island structure may range, for example, from about 0.1 to 10 mm, specifically from about 0.5 to 5 mm, and more specifically from about 1 to 3 mm.

Referring to the drawings, a plurality of support members, specifically, three island structures, for example, may be provided in such a manner that they are arranged in a triangular shape, and such arrangements are formed in a plurality at a predetermined distance. In this case, the distance between the arrays may be set within a range of, for example, about 5 to 50 mm, specifically about 7 to 20 mm, and more specifically about 8 to 10 mm along the longitudinal direction (downward direction).

As described above, the reason for forming the support member 132 on the surface of the film-like bottom structure 117 is the fluid due to the capillary phenomenon by maintaining a constant distance between the membrane filter 111 and the film-like bottom structure 117. This is because it is possible to enhance the movement of (separated plasma when the liquid fluid is blood).

2A and 2B, a plurality of island structures 132 may be formed as a support member while forming a cut pattern of the second film-like structure 116 by cutting and processing the film-like sheet. The island structure 132 thus formed may be attached to the film-type lower plate structure 117 by manual or automated methods. In this regard, the height of the support member 132 may be, for example, in the range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm, as described above. When the second film-like structure 116 and the support member 132 are simultaneously formed, the height of the second film-like structure 116 will be substantially the same. Further, according to an exemplary embodiment, the thickness of the film-like lower plate structure 117 may be, for example, in the range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

According to the illustrated embodiment, the film-type lower plate structure 117 may include through holes 129 and 129 'to discharge the liquid fluid from the receiving space after pre-treatment. The size of the through holes 129 and 129 'is not particularly limited as long as the separated liquid fluid can be discharged from the receiving space, for example, about 0.1 to 4 mm, specifically about 0.5 to 3 mm, More specifically, it may range from about 1 to 2 mm.

In addition, the lower surface (rear surface) of the film-type lower plate structure 117 is communicated with a plurality of through-holes each including a first through-hole 129 and a second through-hole 129 'to provide a discharge path for liquid fluid after pre-treatment. The film-type fluid moving channel structure (B) may be provided.

The film-like fluid movement channel structure (B) includes a first sheet 118 formed with a cavity extending in a longitudinal direction on a lower surface (rear surface) of the film-like lower plate structure 117 and a lower surface (rear surface) of the first sheet. The fluid movement channel 133 can be formed by the combination of the second sheet 119 attached to), the fluid movement channel being the first through hole and the second through hole 129 and 129 ', respectively. Can communicate. The cavity formed in the first sheet 118 may have a shape that is drilled at a constant or non-constant distance in the inner direction along the outer edge of the first sheet 118. In the illustrated example, the cavity is formed in a straight pattern, In some cases, it may be a curved pattern (eg, spiral, serpentine, zigzag, etc.). However, a straight line pattern will be preferable in terms of ease of fluid movement. Further, by way of example, the width of the fluid movement channel may be, for example, in the range of about 100 to 2,000 μm, specifically about 200 to 1,500 μm, and more specifically about 500 to 1,000 μm, which will be understood in an exemplary sense. You can.

In addition, an adhesive can be interposed to attach the bonding structure of the first sheet 118 and the second sheet 119 to the lower surface (rear surface) of the film-like lower plate structure 117. It is not limited to a specific kind, as long as it has sufficient adhesiveness. Illustratively, a rubber-based adhesive, an acrylic resin-based adhesive, a silicone-based adhesive, an optical-based adhesive, and a heat-sensitive adhesive may be used. However, as long as the components of the adhesive can contaminate the liquid fluid when exposed to the fluid movement channel 133, it is preferable that the adhesive does not contact the moving liquid fluid as much as possible.

Alternatively, the first sheet 118 can be applied in the form of a double-sided adhesive tape, for example, a pressure-sensitive adhesive tape, a thermally active adhesive tape, a chemically active adhesive tape, a photoactive adhesive tape, and the like.

In addition, the thickness of each of the first sheet 118 and the second sheet 119 may be different or the same, for example, about 20 μm to 1 mm, specifically about 10 to 1000 μm, specifically about 50 to 500 Μm, more specifically about 100 to 300 µm. In particular, the thickness of the first sheet 118 substantially determines the height of the fluid transfer channel 133. However, when the adhesive is used, the height of the adhesive layer also affects the height of the fluid transfer channel, but has a slight effect on the thickness of the first sheet. As described above, the fluid movement channel formed by the two

sheets

118 and 119 may be manufactured in the form of an adhesive film, and the device fabrication may be completed by attaching it to a predetermined portion of the lower surface (rear surface) of the film-like lower structure 117. You can.

According to an exemplary embodiment, the liquid fluid after pre-treatment may be collected by moving to the collection chamber via the fluid transfer channel 133 formed by the two

sheets

118 and 119. At this time, as the film-like members constituting the device 100 are attached to each other, the collection chamber may have a boundary thereof. In the illustrated example, the first sample collection through cavity 122, the second sample collection through cavity 125, the third sample collection through cavity 131, and the fourth sample collection through cavity 127 formed by a combination of It can be a collection space. According to an exemplary embodiment, the receiving volume of the fluid in the collection chamber may range from, for example, about 0.1 to 2 mL, specifically about 0.5 to 1 mL. However, the numerical range may be understood as an exemplary meaning.

According to the illustrated embodiment, the first through hole 129 functions as a passage for communicating the liquid fluid to the fluid moving channel structure B after pretreatment that is discharged from the membrane filter and moves, while the second through hole 129 ') May function as a passage for communicating the fluid movement channel structure (B) to the collection chamber. As such, the liquid fluid separated by the membrane filter 111 may be collected in the collection chamber through the first through hole 129, the fluid transfer channel 133, and the second through hole 129 '.

Thereafter, at least a portion of the liquid fluid after pre-treatment collected in the collection chamber may be collected to the outside by a micropipette (not shown) for diagnostic purposes. For example, in order to collect the liquid fluid after pre-treatment, after the pre-treatment process is completed, the above-described outlet cover may be removed while the upright device is horizontally disposed and collected using a micropipette.

In addition, when the film-like member constituting the collection chamber is composed of a light-transmitting material, in particular, a film-like sheet made of a transparent polymer material, is the device 100 smoothly collected into the collection chamber of the liquid fluid after pre-treatment in an upright arrangement state? Whether or not it can be observed with the naked eye.

On the other hand, in the case of a film-like member (especially a film-like member that forms a space in which the liquid fluid moves after pre-treatment), which provides a surface in which the aqueous liquid fluid contacts, except for a member requiring hydrophobic treatment, such as an air-permeable film, All of them are polymer materials, and their surfaces are hydrophobic (or non-polar) or weakly hydrophilic. Therefore, it is possible to improve the flowability of the aqueous liquid fluid by hydrophilizing the surface of at least one of the polymer materials. Specifically, the hydrophilic surface is a surface that attracts moisture, and the aqueous liquid fluid is spread on the hydrophilic surface. The water drop on the hydrophilic surface has the property of having a low water contact angle at the interface, while the hydrophobic surface exhibits a high water contact angle. For this reason, in the case of a hydrophobic or low hydrophilic surface, the flow characteristics of the aqueous liquid fluid may not be good, which may decrease the flow rate of the fluid, thereby lowering the collection efficiency of the liquid fluid after pretreatment. In this regard, it may be advantageous to improve the flow characteristics of the fluid by, for example, exhibiting a water contact angle of about 60 ° or less, specifically about 40 ° or less, more specifically about 20 ° or less.

To this end, it may be advantageous to use a surface treatment material that can be hydrophilized with organic and / or inorganic materials, in particular that does not substantially react (i.e., be inactive) with liquid fluids after pretreatment. According to an exemplary embodiment, the organic surface treatment is, for example, amine, hydroxy (hydroxy), carbonyl (carbonyl) or epoxy (epoxy) compound having a functional group, a monomer having the functional group, a dimer and Polymers and the like, and these may be used alone or in combination of two or more. In addition, the inorganic surface treatment material is, for example, a metal or non-metal, specifically, one or more metals selected from gold, silver, silicon, aluminum, nickel, iron, copper, manganese, silicon, titanium, chromium, or the like, or the like. It may be an oxide. In some cases, the organic surface treatment and the inorganic surface treatment may be combined, but the organic and inorganic surface treatment agents may be mixed, or one of the organic surface treatment and the inorganic surface treatment may be performed first, and then the remaining surface treatment may be performed.

Organic and / or inorganic materials are sugars such as thermal evaporation, E-beam evaporation, sputtering, chemical vapor deposition (CVD), sol-gel, plasma treatment, liquid chemical treatment, vapor phase chemical treatment, etc. It can be formed by a coating or adhesion method known in the art. According to an exemplary embodiment, the thickness of the organic and / or inorganic coating layer formed on the surface of the polymer material may be selected, for example, in the range of about 1 to 500 nm, specifically about 100 to 200 nm, It can be understood in an exemplary sense. Alternatively, it may be treated with a biological material such as Bovine serum albumin (BSA).

As described above, the device 100 for pre-treatment of a liquid fluid according to this embodiment can be implemented by simply assembling it by constructing a film-like member as a whole, as well as quickly separating and collecting a liquid sample. have. The collected liquid sample can be collected by a micropipette or the like to diagnose various diseases in the field using a diagnostic chip or kit. In particular, the overall thickness of the pretreatment device can be reduced to about 1 to 5 mm, specifically about 3 mm, which is advantageous in terms of portability.

2nd Concrete (Plastic for pretreatment of liquid fluid device )

6 shows the appearance of a liquid fluid pretreatment device according to an exemplary embodiment of the present disclosure.

Referring to the drawings, the liquid fluid pre-treatment device 200 includes a plastic molded structure (or a structure processed thereon) having a predetermined thickness, and other members may be formed of a film-like material as necessary. In addition, individual members may be manufactured by assembling them by a lamination process.

7 is an exploded perspective view of a liquid fluid pretreatment device according to an exemplary embodiment.

In the illustrated embodiment, the membrane filter 211 may have a shape similar to or similar to that shown in the first embodiment. That is, as a two-dimensional planar or film-like structure, the overall shape may be a pentagonal shape (a shape in which both corner portions of one side are cut in a rectangular shape or a rectangular shape in which the top converges in a wedge shape). However, the shape of the membrane filter is not limited to this, it can be understood that various modifications are possible.

The membrane filter 211 includes a contact surface (the front side of the membrane filter) that comes into contact with the liquid fluid (or liquid sample) to be pretreated, and a permeate surface (back side of the membrane filter) through which the liquid fluid passes across the membrane during the filtering process. Have A top plate structure 212 in the form of a plastic molded article processed in a predetermined pattern is positioned on the contact surface. Specifically, the top plate structure 212 includes a first through cavity 221 in which a boundary is defined while a rib member 212 'is formed in a predetermined pattern in a frame, and a through cavity 222 for collecting a first sample. Each is formed. According to the illustrated embodiment, the lip member 212 'can perform the supporting function of the outer film structure, particularly the air permeable film 215, which will be described later, and the air permeable film 215 is wetted and sagged by the liquid fluid ( By suppressing sagging or sagging, it can contribute to securing a sufficient space for accommodating liquid fluid. Further, by way of example, the width of the lip member 212 'may be, for example, in the range of about 1 to 10 mm, specifically about 1 to 5 mm, more specifically about 2 to 4 mm, which is illustratively Can be understood. In addition, the lip member is also not limited to a specific pattern.

In the illustrated embodiment, the first through-cavity 221 in the upper region of the upper plate structure 212 and the through-cavity 222 for collecting the first sample are located in the lower region. In this regard, the lip member 212 'may be in close contact with the membrane 211 during assembly of the device, or the capillary force may be easily formed in a space formed therein by pressing the membrane, as described below. Likewise, it is possible to perform a function of supporting the air permeable film 215.

In the illustrated embodiment, the thickness of the top plate structure 212 is not particularly limited, as long as it can form a capillary force, but is typically about 0.5 to 5 mm, specifically about 1 to 4 mm, more specifically It may range from about 1 to 3 mm. By having a predetermined thickness by such a plastic (polymer) molding, it is possible to alleviate discomfort such as misalignment occurring when a film member is stacked to secure a space required for inducing capillary force and the use of multiple film members.

In this regard, the first through cavity 221 is a member constituting a space in which the liquid fluid introduced into the device 200 is accommodated and moved, that is, a receiving chamber. At this time, the first through cavity 221 typically has a shape corresponding to the membrane filter 211, but is not necessarily the same shape. However, when the membrane filter 211 is larger in size than the first through cavity 221, the injected liquid fluid may leak through the side surface of the membrane filter. Accordingly, the membrane filter 211 may have at least the same or smaller size than the first through cavity 221, but may be advantageously larger than the second through cavity 230 in the adhesive film structure described below.

In addition, the first sample collection through-cavity 222 may have a size or shape suitable for the space in which the liquid fluid separated by the membrane filter 211 is collected, that is, the member constituting the collection chamber. . In the illustrated example, a pot-shaped cavity is formed that converges gently toward the bottom.

On the other hand, the inlet 224 of the liquid fluid is formed in one end region of the top plate structure 212, specifically, the inlet 224 is an area near the top of the top plate structure 212 (specifically the top converging in a wedge shape) Region). As described in the first embodiment, the shape of the inlet may be various shapes (eg, circular, elliptical, etc., more specifically circular), and in particular, when forming a circular inlet, a rectangular inlet when injecting a liquid fluid Compared to the like, the phenomenon of overflowing to the outside can be suppressed.

The inlet 224 may preferably have a size sufficient to inject a liquid sample into the receiving space (chamber) of the liquid fluid in the device 200 using a pipette or the like. Illustratively, the size (or diameter) of the inlet 224 may range, for example, from about 1 to 100 mm, specifically from about 3 to 50 mm, and more specifically from about 5 to 20 mm. Illustratively, the amount of liquid fluid introduced through the inlet 224 may be, for example, in the range of about 0.1 to 10 mL, specifically about 0.5 to 5 mL, and more specifically about 1 to 2 mL. In the illustrated embodiment, the liquid fluid flowing through the injection hole 224 may be accommodated through the space formed by the thickness of the upper plate structure in the form of a plastic molding.

In addition, a first cavity collection through cavity 222 may be formed in the upper plate structure 212 in a region facing the injection hole 224 in the longitudinal direction, that is, in the lower region. In this case, the first sample collection through cavity 222 may correspond to or have the same shape as the second sample collection through cavity 231 in the adhesive film structure described later.

Meanwhile, according to the illustrated embodiment, gravity is applied to the liquid fluid introduced through the injection hole 224 as the device 200 is placed upright. In addition, in order to provide a space (or a receiving chamber) for receiving and moving the liquid fluid before pretreatment, it is attached to the top plate structure 212 in the form of a plastic molding to form an outer film structure covering at least the first through cavity 221. can do.

As described above, an environment (or dimension) in which a capillary phenomenon occurs that covers the first through cavity 221 with an outer film structure and enables rapid movement of liquid fluid through a space (receiving chamber) formed between the membrane filter and the film structure is provided. To form and allow the introduced liquid fluid to reach the moving space or the lower side of the receiving chamber by the capillary force (i.e., the capillary force generated while wetting the microcavity of the membrane filter provides the driving force required for movement) Can do).

However, when the introduced liquid fluid wets the membrane filter 211 and a certain period of time has elapsed, the separated liquid fluid is filtered out from the lower surface of the membrane filter 211, where the moving space or the empty space in the receiving chamber Silver is filled with air flowing in from the outside through the inlet 224. Accordingly, a phenomenon in which the liquid fluid is captured or stagnated may occur in the lower portion of the moving space or the receiving chamber that is wet by the liquid fluid.

The outer film structure may be configured using an air permeable film so as to mitigate the stagnation or delay phenomenon of the flow so that the liquid fluid can quickly move in the moving space or the receiving chamber. Specifically, the outer film structure may largely include an air-permeable film fixing tape 214 and an air-permeable film 215. At this time, in the case of the fixing tape 214, the first through cavity 221 and the lip member 212 'in the top plate structure 212 without blocking the inlet 224 of the top plate structure 212 located below, and A third through cavity 226, a lip member 214 ′ corresponding to each of the first sample collection through holes 222 (in communication), and a third sample collection through cavity 227 may be formed.

Matters such as material, function, hydrophobic treatment and properties (thickness, basis weight, etc.) of the air permeable film 215 are the same as those described in relation to the air permeable film 115 in the first embodiment, and thus detailed description will be omitted. .

According to an exemplary embodiment, an outlet (not shown) of the liquid fluid may be selectively formed in the lower region of the air permeable film 215 (specifically, near the end opposite the inlet 224). In this case, as described below, the passage through the membrane filter 211 communicates with the collection space (collection chamber) of the separated liquid fluid to provide a passage through which the recovered liquid fluid can be discharged (taken out). Illustratively, the size (diameter) of this outlet may range, for example, from about 1 to 10 mm, specifically from about 2 to 5 mm, and more specifically from about 3 to 4 mm.

Fig. 8 is a plan view of a liquid fluid pretreatment device according to an exemplary embodiment.

6 to 8, as the pre-treatment process proceeds, the liquid fluid after the pre-treatment flows into the collection space. At this time, it may be difficult to flow the liquid fluid after the pre-treatment due to air already present in the collection space. However, according to the illustrated embodiment, the air present in the collection space is naturally removed outside the device through the air permeable film 215 covering the third sample collection through cavity 227, and as a result, the liquid fluid after pretreatment It does not cause any special problems.

In addition, the fixing tape 214 of the air-permeable film is specifically applicable in the form of a double-sided adhesive tape, and serves to bond the air-permeable film 215 to the top plate structure 212. In the case of the fixing tape 214, a description of the fixing tape 114 may be applied in the first specific example, so a detailed description thereof will be omitted.

In the illustrated embodiment, the sum of the thicknesses of each of the first through cavities 221 and the third through cavities 226 (substantially the thickness of the first through cavities) forming the moving space (or accommodating chamber) of the liquid fluid is It is possible to substantially determine the height of the moving space (or receiving chamber) of the liquid fluid. However, as the height of the moving space (or the receiving chamber) increases, the capillary force decreases, such that the height of the moving space is, for example, about 0.1 to 10 mm, specifically about 0.5 to 5 mm, and more specifically about 1 to 2 The thickness of each of the first through cavities 221 and the third cavities 226 (substantially, the thickness of the first through cavities) may be adjusted to be in the range of mm.

On the other hand, when the adhesive film structure 216 is attached to the lower surface (rear surface) of the membrane filter 211, that is, the permeable surface, the adhesive film structure 216 is formed of the liquid fluid separated through the membrane filter 211. It includes a second through-cavity 230 bounded to provide a receiving and moving space, and is also demarcated separately from the second through-cavity 230 to accommodate the separated liquid fluid passing through the membrane filter 211 The paper is formed with a through cavity 231 for collecting a second sample.

According to the illustrated embodiment, the second through-cavity 230 in the adhesive film structure 216 is similar to the first through-cavity 221 in order to provide a membrane filter ( It may have at least the same or a smaller size than 211). In this regard, the lower region of the flexible adhesive film structure 216 based on the membrane filter 211 may be bonded while bending toward the membrane filter 211. In particular, when the adhesive film structure 216 is composed of an adhesive material (single-sided or double-sided adhesive material), it can be easily fixed in a state in which the membrane filter 211 is interposed by bonding together with bending. In particular, when the adhesive film structure 216 is composed of a double-sided adhesive material, it serves to fix the membrane filter 211 to the lower plate structure 217 via this, and at the same time, passes through the membrane filter 211 to separate it. The liquid phase fluid may form a moving space (or a recovery chamber) in which a thin microfluidic membrane may exist.

In addition, the second sample collection through-cavity 231 functions as a member constituting the collection chamber together with the first sample collection through-cavity 222 and the third sample collection through-cavity 227, as described above, It may be advantageous to have the same shape as these corresponding members.

According to an exemplary embodiment, the thickness of the adhesive film structure 216 may be, for example, in the range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

Fig. 9 is a side view of a device for pretreatment according to an exemplary embodiment, and Fig. 10 is a view showing a plane cut along the line A'-A 'of the membrane-based plastic device shown in Fig. 9 as an adhesive. It shows the state in which the sex film structure 216 and the lower plate structure 217 are combined.

6 to 10, the lower plate structure 217 is attached to the lower surface of the adhesive film structure 216 as described above. In the example shown in FIGS. 7 and 10, the lower plate structure 217 includes a support member 232 that supports (series) the membrane filter 211 through the second through cavity 230.

In this connection, as the description of the support member 132 described in the first embodiment can be applied, the overlapping description is omitted.

Referring to FIG. 7, a plurality of island structures 232 may be formed as a support member at the same time as forming a cut pattern of the adhesive film structure 216 by cutting plotter processing of the film sheet, and the island structures formed in this way The 232 can be attached to the lower plate structure 217 either manually or in an automated manner. As described above, when the adhesive film structure 216 and the support member 232 are simultaneously formed using a single sheet, the height of the adhesive film structure 216 will be substantially the same.

According to the illustrated embodiment, the lower plate structure 217 extends in the longitudinal direction compared to other members, for example, the upper plate structure 212, the

outer film structures

214, 215, and the adhesive film structure 216, , As a result, the other members are stacked on a part of the surface of the lower plate structure 217 (see FIGS. 6 and 8).

In this regard, the lower plate structure 217 includes at least one first through hole 229 and at least one second through hole 229 ', and at least one third through hole 228 and at least one fourth The through hole 228 'is formed. In the illustrated embodiment, three pairs of first and second through holes 229 and 229 ', and a pair of third and fourth through holes 228 and 228' are formed. The first and second through holes 229 and 229 'are for discharging the liquid fluid from the receiving space after the pretreatment, and the sizes of the first and second through holes 229 and 229' are separated liquid. As long as the fluid can be discharged from the receiving space, it is not particularly limited, and may be, for example, in the range of about 0.1 to 4 mm, specifically about 0.5 to 3 mm, and more specifically about 1 to 2 mm.

In addition, the lower surface of the lower structure 217 (rear) in the first through-hole 229 and the second through-hole (229 ') of a pair of through-holes each of which communicates with each other to provide a discharge path for the liquid after pre-treatment. A film type fluid moving channel structure (B ') may be provided.

The film-like fluid movement channel structure B 'is formed on the lower surface (rear surface) of the first sheet 218 and the lower surface (rear surface) of the first sheet 218 having a cavity extending in the longitudinal direction on the lower surface (rear surface) of the lower plate structure 217. The first fluid movement channel 233 can be formed by the combination of the attached second sheet 219, and the first fluid movement channel is respectively formed with the above-described first and second through holes 229 and 229 '. Can communicate. The cavity formed in the first sheet 218 may have a shape that is drilled at a constant or non-constant distance in the inner direction along the outer edge of the first sheet 218. In the illustrated example, the cavity is formed in a straight line pattern. In some cases, it may be a curved pattern (eg, spiral, serpentine, zigzag, etc.). However, a straight line pattern will be preferable in terms of ease of fluid movement. Further, by way of example, the width of the first fluid movement channel 233 may be, for example, in the range of about 100 to 2,000 μm, specifically about 200 to 1,500 μm, and more specifically about 500 to 1,000 μm. It can be understood in a meaning.

In addition, an adhesive can be interposed to attach the bonding structure between the first sheet 218 and the second sheet 219 to the lower surface (rear surface) of the lower plate structure 217. It is not limited to a specific kind as long as it has sex. Illustratively, a rubber-based adhesive, an acrylic resin-based adhesive, a silicone-based adhesive, an optical-based adhesive, and a heat-sensitive adhesive may be used. However, as long as the components of the adhesive can contaminate the liquid fluid when exposed to the

fluid movement channels

233 and 234, it is preferable to prevent the adhesive from being in contact with the moving liquid fluid as much as possible.

Alternatively, the first sheet 218 can be applied in the form of a double-sided adhesive tape, for example, a pressure-sensitive adhesive tape, a thermally active adhesive tape, a chemically active adhesive tape, a photoactive adhesive tape, and the like.

In addition, the thickness of each of the first sheet 218 and the second sheet 219 may be different or the same, for example, about 20 μm to 1 mm, specifically about 10 to 1000 μm, specifically about 50 to 500 Μm, more specifically about 100 to 300 µm. In particular, the thickness of the first sheet 218 substantially determines the height of the fluid transfer channel 233. However, when the adhesive is used, the height of the adhesive layer also affects the height of the fluid transfer channel, but has a slight effect on the thickness of the first sheet. As such, the first and second

fluid movement channels

233 and 234 formed by the two

sheets

218 and 219 may be manufactured in the form of an adhesive film, and a predetermined portion of the lower surface (rear surface) of the lower structure 217 Device fabrication can be completed by attaching to.

According to an exemplary embodiment, the liquid fluid after pre-treatment may be collected by moving to the collection chamber via the first fluid transfer channel 233 formed by the two

sheets

218 and 219. At this time, as the assembly of the members constituting the device 200 is assembled, the boundary of the collection chamber may be determined. In the illustrated example, it may be a collection space formed by a combination of a first sample collection through cavity 222, a second sample collection through cavity 231 and a third sample collection through cavity 227. According to an exemplary embodiment, the receiving volume of the fluid in the collection chamber may range from, for example, about 0.1 to 2 mL, specifically about 0.5 to 1 mL. However, the numerical range may be understood as an exemplary meaning.

According to the illustrated embodiment, the first through hole 229 functions as a passage for communicating the liquid fluid to the fluid moving channel structure B after pretreatment that is discharged from the membrane filter and moves, while the second through hole 229 ') May function as a passage for communicating the fluid movement channel structure (B) to the collection chamber. As such, the liquid fluid separated by the membrane filter 211 may be collected in the collection chamber through the first through hole 229, the first fluid movement channel 233, and the second through hole 229 '.

On the other hand, as shown, the third and fourth through holes 228 and 228 'formed in the lower plate structure 217 function to connect at least a portion of the liquid fluid to a subsequent process such as diagnosis after pretreatment collected in the collection chamber. To perform. To this end, the third through hole 228 communicates with the collection chamber, and through the second fluid movement channel 234 formed by the first sheet 218 and the second sheet 219, the fourth through hole 228 '). At this time, the fourth through hole 228 'is exposed on the surface of the lower plate structure 217, and provides a connection portion or a connection passage through which the recovered liquid fluid can be discharged to the outside. For example, the sizes (diameter) of the third and fourth through holes 228 and 228 'may be the same or different from those of the first and second through holes. In addition, the dimension of the second fluid channel 234 may be determined within the same dimensional range as the first fluid channel 233 described above, but is not limited thereto. In some cases, the fourth through-hole 228 'is in a closed state by being covered by a hole cover (one side exhibits adhesiveness; not shown) in the fabricated state or in the pre-processing process. . This is to prevent the collected liquid fluid from flowing out through the fourth through hole 228 '.

According to an exemplary embodiment, the fourth through hole 228 ′ may be directly connected to a subsequent device (eg, diagnostic chip), or may discharge the pre-treated fluid to the outside by a micropipette (not shown). have. For example, in order to collect the liquid fluid after pre-treatment, after the pre-treatment process is completed, the above-described cover may be removed while the upright device is horizontally disposed and collected using a micropipette. Alternatively, it may be moved from the collection chamber through the fourth through hole 228 using a non-powered pump or the like. However, as described above, the fluid pre-treated through an outlet (not shown) formed in the air permeable film 215 may be collected using a micropipette or the like.

In addition, when the member constituting the collection chamber is composed of a light-transmitting material, in particular, a transparent polymer material, it is visually observed whether the device 200 is smoothly collected into the collection chamber of the liquid fluid after pre-treatment in an upright arrangement state. can do.

On the other hand, except for members that require hydrophobic treatment, such as air-permeable films, in the case of a member that provides a surface for contact with a liquid-based liquid (especially a member that forms a space in which the liquid-fluid moves after pre-treatment), all are made of a polymer material. Its surfaces may be hydrophobic (or non-polar) or weakly hydrophilic. Therefore, it is possible to improve the flowability of the aqueous liquid fluid by hydrophilizing the surface of at least one of the polymer materials. Details of the hydrophilization treatment are the same as those described in connection with the first specific example, so a separate description is omitted.

On the other hand, in the case of the pre-treatment device 200 according to one embodiment, when injecting a liquid for pre-treatment through the inlet 224, a certain time after the fluid wets the membrane filter 211 (in the case of blood, about After 2 minutes or more), the sample passing through the filter comes out from the bottom surface of the membrane filter, and the empty space in the receiving chamber of the liquid fluid before pre-treatment is filled with air flowing through the inlet. At this time, the wettability of the upper plate structure in the lower receiving chamber region may cause the liquid fluid to be captured. In order to alleviate this phenomenon, when the device is inclined when the pretreatment fluid is introduced through the inlet, the fluid can be easily injected because the injected fluid is easily pushed inward by gravity, and also the membrane filter The time required to wet the can be minimized (for example, within about 2 minutes).

Third Concrete (Plastic for pretreatment of liquid fluid device )

11 is a perspective view showing the appearance of a membrane-based plastic device according to another embodiment of the present disclosure, and FIG. 12 is an exploded perspective view thereof. Hereinafter, descriptions and overlapping descriptions of the members described in the first and second embodiments will be omitted.

Referring to the drawings, the device 300 for pre-treatment of a liquid fluid has a whole swash-shape, specifically a square plane, and the members constituting it are also formed to have a shape corresponding thereto. However, this shape is understood as an exemplary purpose, and is not necessarily limited thereto.

At this time, it should be noted that the lower plate structure 317 is configured in the form of a plastic molded article formed by 3D printing, and unlike the second embodiment, the lower plate structure 317 is not provided with a sample transfer channel on the lower surface of the sample. It means that it is possible to perform both the collection function of the (pre-treated liquid fluid) and the sample transfer channel function.

According to the illustrated embodiment, the first film-like structure 312 processed in a predetermined pattern is attached to the contact surface where the membrane filter 311 contacts the liquid fluid to be pre-treated. Specifically, the first film-like structure 312 is formed with a first through cavity 321 and a first through-hole cavity 322 for collecting samples, which are separately demarcated within the frame. At this time, the first through-cavity 321 in the upper region of the first film-like structure 312 and the through-cavity 322 for collecting the first sample are located in the lower region. Illustratively, the first film-like structure 312 is made of a double-sided adhesive material for easy and effective attachment with the membrane filter 311 located below and other members attached to the upper side, specifically, the upper plate structure 313. You can.

In this regard, optionally, a first support member 332, specifically a plurality of island structures (three pairs of island structures in FIG. 12) may be attached on the contact surface of the membrane filter 311, This may function to support the air permeable film 315, which will be described later. The island structure constituting the first support member 332 may be formed at a number and an array interval capable of smoothly performing a support function, and is not limited to a specific number and an array interval. In this regard, the height of the first support member 332 may be, for example, in the range of about 0.5 to 2 mm, specifically about 1 to 1.8 mm, and more specifically about 1.4 to 1.7 mm, which is illustratively understood. You can.

For example, the first support member 322 may be formed together during cutting plotter processing for pattern formation of the first film-like structure 312, and the island structure 332 formed as described above may be formed on the membrane filter 311. Can be attached manually or in an automated manner. However, since the thickness of the first film-like structure 312 is relatively thin, multiple layers of island structures may be stacked to pre-process a large amount of whole blood to satisfy the height range of the above-described first support member 332. Space can be formed.

Further, the first through cavity 321 is a member that constitutes a space in which the liquid fluid introduced into the device 300 is accommodated and moves, that is, a receiving chamber. At this time, the first through cavity 321 typically has a shape corresponding to the membrane filter 311, but is not necessarily the same shape. However, as described above, when the membrane filter 311 is larger than the first through cavity 321, the injected liquid fluid may leak through the side surface of the membrane filter compared to the first through cavity 321. It may have at least the same or a smaller size, and it may be advantageous to have a larger size than the third through cavity 330 of the second film-like structure 316 described later. According to an exemplary embodiment, the thickness of the first film-like structure 312 may be determined, for example, within a range of about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm. have.

Meanwhile, the top plate structure 313 may be attached to the first film-type structure 312, and the top plate structure may be a film-like material or a plastic molding. According to the illustrated example, a liquid fluid inlet 324 is formed in one end region of the top plate structure 313, and specifically, the inlet 324 may be formed in an area near the top of the top plate structure 313. . This inlet shape may be of various shapes (eg, circular, elongated, elliptical, etc.). More specifically, it may have an elongated oval shape as shown. As described above, the extended oval-shaped inlet may be advantageous in that it is easy to discharge air when injecting a large volume of liquid fluid and can quickly wet a large area membrane filter. In this regard, the size of the injection hole 324 is not particularly limited as long as it has a size sufficient to inject the liquid sample into the receiving space (chamber) of the liquid fluid in the device 300 using a pipette or the like. Illustratively, the amount of liquid fluid introduced through the inlet 324 may be, for example, in the range of about 0.1 to 10 mL, specifically about 0.5 to 5 mL, and more specifically about 1 to 4 mL.

In the illustrated embodiment, the upper plate structure 313 has a second through cavity 323 formed separately from the injection hole 324, and is in communication with the first through cavity 321 located below. That is, the second through cavity 323 functions as a member constituting a space (or chamber) for receiving the liquid fluid flowing through the inlet 324 in combination with the first through cavity 321, and , In the upper plate structure 313, the region in the longitudinal direction opposite to the injection hole 324, the lower region through the first sample collection through cavity 322 of the first film structure 312 in communication with the second sample collection through cavity (322) 325) may be formed. At this time, the second sample collection through-cavity 325 may correspond to the first sample collection through-cavity 322 or may have the same shape. According to the illustrated embodiment, the second through cavity 321 of the upper plate structure 313 is formed with a rib member 313 ′ bounded by a predetermined pattern within the frame. The lip member 313 ′ may support the outer film structure, in particular, the air permeable film 315 together with the first support member 332 described above, and provide a function for facilitating the formation of capillary forces. Illustratively, the width of the lip member 313 'may range from about 0.5 to 5 mm, specifically from about 1 to 4 mm, more specifically from about 1 to 3 mm, but this can be understood as an example. In addition, the pattern of the lip member 313 'is also not particularly limited.

According to an exemplary embodiment, the thickness of the top plate structure 313 may be determined, for example, within about 10 to 1000 μm, specifically about 50 to 500 μm, and more specifically about 100 to 300 μm.

In addition, in the illustrated embodiment, it may include an outer film structure, a fixing tape 314 of the air-permeable film and the air-permeable film 315 on the upper plate structure 313 as described above. At this time, the fixing tape 314 does not block the inlet 324 of the upper plate structure 313 located below, the second through cavity 321, the lip member 313 'of the top plate structure and the through cavity for collecting the second sample 325 includes a fourth through cavity 326 corresponding to each (communicating), a lip member 314 ', and a through cavity 327 for collecting a fourth sample.

According to an exemplary embodiment, an outlet (not shown) of the liquid fluid may be selectively formed in the lower region of the air permeable film 315 (specifically, near the end opposite the inlet 324).

In addition, the fixing tape 314 of the air-permeable film is specifically applicable in the form of a double-sided adhesive tape, and functions to bond the air-permeable film 315 to the top plate structure 313. As the fixing tape 314 of the air-permeable film, a pressure-sensitive adhesive tape, a thermally active adhesive tape, a chemically active adhesive tape, a photoactive adhesive tape, and the like can be exemplified. Alternatively, the air permeable film 315 may be attached using an adhesive, rather than a fixing tape. As such an adhesive, a rubber-based adhesive, an acrylic resin-based adhesive, a silicone-based adhesive, an optical-based adhesive, and a heat-sensitive adhesive may be used. In an exemplary embodiment, the height of the anchoring tape or adhesive layer 314 may be, for example, in the range of about 10 to 1000 μm, specifically about 50 to 500 μm, more specifically about 100 to 300 μm.

In the illustrated embodiment, the sum of the thicknesses of each of the first through cavity 321, the second through cavity 323, and the fourth through cavity 326 forming the moving space (or accommodating chamber) of the liquid fluid is substantially liquid. The height of the fluid's moving space (or receiving chamber) can be determined. However, as the height of the moving space (or the receiving chamber) increases, the capillary force decreases, such that the height of the moving space is, for example, about 0.1 to 10 mm, specifically about 0.5 to 5 mm, and more specifically about 1 to 2 The thickness of each of the first through cavity 321, the second through cavity 323, and the fourth cavity 326 may be adjusted to be in the mm range.

On the other hand, a second film-type structure 316 is attached to the bottom surface (rear surface) of the membrane filter 311, that is, the transmission surface, and the second film-type structure 316 is separated through the membrane filter 311. And a third through cavity 330 bounded to provide a space for receiving and moving liquid fluid. However, in the illustrated embodiment, unlike the above-described first film structure 312, the top structure 313 and the fixing tape 314 of the air permeable film, a through cavity for collecting samples is not formed. This is because a collection chamber (collection space) of the liquid fluid pretreated separately is formed in the lower plate structure 317 formed by 3D printing, as described later. The second film-type structure 316 may be applied with details related to the adhesive film structure 216 of the first embodiment described above except for the shape.

FIG. 13 is a plan view of a membrane-based plastic device according to another exemplary embodiment, and FIG. 14 is a vertical cut along line A ”-A” in FIG. 13, the fluid flow space in the lower structure in the form of a plastic molding. It shows. In addition, a perspective view of a bottom structure with a support member in a membrane-based plastic device according to an exemplary embodiment is shown in FIG. 15.

13 to 15, a lower plate structure 317 in the form of a plastic molding formed by 3D printing is disposed on a lower surface of the second film-type structure 317. According to the illustrated embodiment, the first microchannel and the

second microchannels

333 and 336 and the collection space of the pretreated fluid or the collection chamber 335 are integrally formed inside the lower plate structure 317. In addition, the second support member 332 ′ is formed to maintain a suitable distance for the pre-treated liquid fluid to pass through the space between the membrane filter 311 and the lower plate structure 317 by capillary force. At this time, the second support member may be arranged in the form of a plurality of island structures. Referring to FIG. 15, the second support member 332 ′ may contact the lower surface of the membrane filter 311 to provide a space required to maintain the capillary force, and additionally, the pre-treated fluid can be easily fine patterns, specifically fan Alternatively, a function of uniformly introducing the first fine flow path 333 formed by the radial protrusion pattern may be performed.

At this time, the second support member 332 'may be formed together when the pattern of the second film-type structure 316 is formed, or separately manufactured and attached to the lower plate structure 317, and may also be attached by manual or automated methods. You can.

14 and 15, the pre-processed fluid is collected in the concave portion 334 by moving in a downward direction (downstream direction) through the first micro-channel 333. At this time, the reason for forming the first fine flow path 333 in a fan or radial shape is to strengthen the capillary force for effectively moving the fluid to the collection chamber 335. The dimensions of the protrusion pattern of the first micro-channel 333 (for example, the distance and height between the protrusions) are not particularly limited as long as they provide a function of strengthening and / or maintaining a capillary force. Further, the depth of the recess 334 may be, for example, about 0.5 to 10 mm, specifically about 2 to 8 mm, and more specifically about 4 to 6 mm.

The liquid fluid collected and guided to the recess 334 is transferred to the collection chamber 335 in communication with the recess 334 along the second micro-channel 336. At this time, since the second micro-channel 336 is extended through the protruding jaw 337, the device 300 is pre-treated in a vertically arranged state, so that the protruding jaw 337 is overcome by gravity and capillary force. It is then collected (collected) in a collection chamber 335. According to an exemplary embodiment, each of the size (width) and depth of the collection chamber 335 is, for example, about 5 to 30 mm (specifically about 10 to 25 mm, more specifically about 10 to 15 mm) and about 1 to 10 mm (specifically about 2 to 7 mm, more specifically about 3 to 5 mm).

At this time, when the protruding jaw 337 is disposed horizontally for the purpose of collecting or discharging the pre-treated liquid fluid from the pre-processing device 300 in an upright state, the fluid collected in the collection chamber 335 is reversed and lost. Can be suppressed. At this time, the protruding jaw 337 may be formed in the shape of an arc when observing the plane, but is not limited thereto. In addition, the height of the protruding jaws 337 is not particularly limited, but may be, for example, in the range of about 0.5 to 5 mm, specifically about 1 to 4 mm, and more specifically about 2 to 3 mm.

The fluid collected in the collection chamber 335 may be collected or discharged to the outside using a micropipette or the like, as pre-processed fluid through an outlet (not shown) formed in the air-permeable film. However, according to an exemplary embodiment, a connection hole 338 is formed at a portion of the collection chamber 335, which is in fluid communication with the discharge hole 339 formed on the side of the device, and can be connected to a subsequent process. It can also function as a connection to transfer the pretreated fluid directly to a subsequent process.

As described above, the

plastic devices

200 and 300 for pre-treatment of the liquid fluid according to this embodiment can be implemented not only by a simple assembly method, but also by quickly separating the liquid sample by gravity without inputting a separate driving force. Can be collected. The collected liquid sample is collected by a micropipette or the like, or transferred to a subsequent process through a connection portion or a connection passage (the fourth through hole in the first embodiment, or the discharge hole in the second embodiment) to a diagnostic chip or kit. By doing so, various diseases can be diagnosed in the field. In particular, by appropriately combining the plastic molded member and the film-shaped member in the pretreatment device, it is possible to lower the overall thickness of the device while minimizing misalignment between a plurality of members and improving portability.

According to one embodiment, the liquid fluid to be pretreated may be, for example, blood (whole blood), animal fecal dilution, saliva, urine, or the like. In particular, it is useful for separating plasma from blood or for obtaining a gene-containing liquid sample in which solids are removed from a poultry fecal dilution for detection of a virus such as avian flu.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are provided only to more easily understand the present invention and the present invention is not limited thereto.

Example 1

Preparation of device for pretreatment of film type liquid fluid

The device for pre-treatment of the liquid-state liquid fluid according to the first embodiment (FIGS. 1 to 5) was manufactured in-house, and details of the members constituting the device are as follows.

(i) Membrane filter: Pall's Vivid membrane filter (GR vivid membrane; asymmetric polysulfone-based membrane); thickness 300 µm; width 25.7 mm, total length: 57 mm

(ii) the first film structure 112

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 32 mm and 81.3 mm respectively

-Width and overall length of the first through cavity 121: 26 mm and 57.3 mm, respectively

-Width and overall length of the first cavity for collecting the sample 122: 16 mm and 16 mm, respectively

(iii) Film type top plate structure (113)

-Material: PET resin

-Thickness: 100 μm

-Width and overall length: 32 mm and 81.3 mm respectively

-Width and overall length of the second through cavity 123: 26 mm and 46 mm, respectively

-Width and overall length of the through cavity 125 for collecting the second sample: 16 mm and 16 mm, respectively

-Inlet (124) diameter: 5 mm

(iv) Air-permeable film fixing tape 114

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 28 mm and 72 mm respectively

-Width and overall length of the fourth through cavity 126: 26 mm and 46 mm, respectively

-Width and overall length of the through cavity 127 for collecting the fourth sample: 16 mm and 16 mm, respectively

(v) Air permeable film 115: Air filter

-Thickness: 130 ㎛

-Outlet diameter: 3 mm

(vi) Second film-like structure 116

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 32 mm and 81.3 mm respectively

-Width and overall length of the third through cavity 130: 21 mm and 51 mm, respectively

-Width and overall length of the third sample collection through cavity 131: 16 mm and 16 mm, respectively

(vi) Film-type lower plate structure (117)

-Material: PET resin

-Thickness: 100 μm

-Width and overall length: 32 mm and 81.3 mm respectively

-The size (diameter) and height of the island (round section) structure: 3 mm and 230 μm, respectively

-Distance between arrays of triangular shapes: 13 mm

-Diameter of the first through hole and the second through hole: 1.5 mm

(vii) Fluid movement channel structure

-Material of first and second sheets (119, 119): PVC and PET, respectively

-The thickness of the first and second sheets 118, 119: 230 μm and 100 μm, respectively

-Width and length of the fluid transfer channel 133: 1.5 mm and 11.8 mm, respectively

The pattern of the film member used in the examples was produced using a design program (Autodesk product name: AutoCAD LT 2014) and a floating cutter (Graphtec product name FC4600C-50 PRO). 16A and 16B show external and planar photographs of the fabricated preprocessing device.

Example 2

The pretreatment device prepared according to Example 1 was placed upright, and a blood sample (1.2 mL) was injected through the inlet. At this time, the surface of the remaining film member except the air filter was coated with 0.5% BSA. After the blood sample was injected, the amount of plasma collected in the collection chamber was monitored, and the results are shown in FIGS. 17A and 17B.

According to the figure, about 140 μl of plasma was collected separately after 10 minutes of injecting a blood sample.

Example 3

As shown in FIG. 18, 10 mL of PBS was mixed with about 10 mL of chicken feces in the hood of

bio level

2, and 1 mL of H1N1 virus in the urine state was spiked. Thereafter, in order to remove fecal debris from the liquid sample, the pretreatment was performed in a state of being placed upright as in Example 2 using the device for pretreatment prepared according to Example 1. Virus was detected in the liquid fluid after pre-treatment collected in the collection chamber after 10 minutes. Table 1 below shows the experimental results.

H1N1 바이러스 검출 H1N1 virus detection	CqCq	R² R ²
분변으로부터 분리된 바이러스 Virus isolated from feces	21.8821.88	0.999330.99933
분변으로부터 분리된 바이러스Virus isolated from feces	21.8121.81	0.999260.99926
Negative Control Negative Control	No CqNo Cq	0.999090.99909
Negative Control Negative Control	No CqNo Cq	0.998370.99837

According to the above table, after extracting the RNA by collecting the pre-treated liquid fluid using the pre-processing device prepared according to the present embodiment, and amplified by real-time PCR, H1N1 virus was detected while showing a value of about 22 Cq. . Considering these experimental results, it can be seen that the pretreatment device manufactured according to the embodiment is suitable for pretreatment before diagnosing pathogens (or viruses) from various feces as well as plasma separation from blood.

Example 4

Fabrication of plastic devices for pretreatment of liquid fluids

The plastic device for pretreatment of the liquid fluid according to the second embodiment (FIGS. 6 to 10) was manufactured in-house, and details of the members constituting the pretreatment device are as follows.

(i) Membrane filter 211: Pall's Vivid membrane filter (GR vivid membrane (asymmetric polysulfone-based membrane); thickness 320 µm; width 25.7 mm, total length: 57 mm

(ii) Plastic molded upper plate structure 212

-Material: PC

-Thickness: 3 mm

-Width and overall length: 32 mm and 81.3 mm respectively

-Width and overall length of the first through cavity 221: 26 mm and 57.3 mm, respectively

-Width (size) of the lip member 212 ': 3 mm

-Width and total length of the first sample collection through cavity 222: 16 mm and 16 mm, respectively

-Inlet (224) diameter: 5 mm

(iii) air permeable film fixing tape 214

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 30 mm and 70 mm respectively

-Width and overall length of the third through cavity 226: 26 mm and 57.3 mm, respectively

-Width and overall length of the through cavity 227 for collecting the third sample: 16 mm and 16 mm, respectively

(iv) Air permeable film 215: Air filter

-Thickness: 130 ㎛

-Outlet diameter: 3 mm

(v) adhesive film structure 216

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 32 mm and 81.3 mm respectively

-Width and overall length of the second through cavity 230: 21 mm and 52 mm, respectively

-Width and overall length of the through-cavity 231 for collecting the second sample: 16 mm and 16 mm, respectively

(vi) Bottom structure (217)

-Material: PC

-Thickness: 1 mm

-Width and overall length: 32mm and 113.3mm respectively

-Diameter of the first and second through holes: 1.5 mm

-Diameter of the third and fourth through holes: 1.5 mm

(vii) Fluid movement channel structure

-Materials of the first and second sheets 218 and 219: PET double-sided adhesive film and PET, respectively

-The thickness of the first and second sheets 218, 219: 200 μm and 100 μm, respectively

-Width and length of the first and second fluid movement channels 233 and 234: 1.5 mm and 8.5 mm, respectively

The pattern of the film member used in this example was produced using a design program (Autodesk product name: AutoCAD LT 2014) and a floating cutter (Graphtec product name FC4600C-50 PRO). In addition, the pattern of the top plate structure was formed through CNC machining using a design program. 19 shows the appearances of the upper and lower structures in the membrane-based plastic device (4 × 8 cm) fabricated in this example, and their assembled state in FIG. 19. From the above drawings, it is determined that the use of the upper plate structure as a plastic molding can reduce the number of required members, and alleviate the problem of mismatching that may occur in the lamination process, compared to the case where only the member made of a film material is used.

A plastic device for pretreatment prepared according to this example was placed upright, and a blood sample (2 mL) was injected through the inlet. At this time, the surface of the remaining members except the air filter was coated with 0.5% BSA. After injecting a blood sample and waiting for about 2 minutes to sufficiently soak the blood in the membrane filter, the amount of plasma separated and collected in the collection chamber was monitored, and the results are shown in FIG. 20. According to the figure, about 213 μl of plasma was collected separately after 10 minutes of injecting a blood sample.

In addition, it was confirmed whether the fourth through-hole of the plastic device for pre-treatment and the non-electric power pump can be connected and recovered by a subsequent treatment module. The results are shown in FIG. 21. According to the figure, 185 μl of plasma was recovered by a non-powered pump.

Example 5

Fabrication of plastic devices for pretreatment of liquid fluids

The plastic device for pretreatment of the liquid fluid according to the third embodiment (FIGS. 11 to 15) was manufactured in-house, and details of the members constituting the pretreatment device are as follows.

(i) Membrane filter 311: Pall's Vivid membrane filter (GR vivid membrane (asymmetric polysulfone-based membrane); thickness 320 µm; width 66.6 mm, total length: 49.6 mm

-Size (diameter) and height of the first support member (Ireland (circular cross-section) structure; 332): 3 mm and 1.6 mm, respectively

(ii) first film structure 312

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 70.9 mm and 70.9 mm, respectively

-Width and overall length of the first through cavity 321: 67 mm and 50 mm, respectively

-Width and overall length of the first sample collection through cavity 322: 16 mm and 12 mm, respectively

(iii) Top structure 313

-Material: PET resin

-Thickness: 100 μm

-Width and overall length: 70.9 mm and 70.9 mm, respectively

-Width and overall length of the second through cavity 323: 67 mm and 50 mm, respectively

-Width (size) of the lip member (313 '): 2 mm

-Width and overall length of the through cavity 325 for collecting the second sample: 16 mm and 12 mm, respectively

-Width and length of the inlet 324: 46 mm and 6 mm, respectively

(iv) fixing tape 314 of the air permeable film

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 70.9 mm and 58 mm, respectively

-Width and overall length of the fourth through cavity 326: 67 mm and 50 mm, respectively

-Width (size) of the lip member 314 ': 2 mm

-Width and overall length of the through cavity 327 for collecting the fourth sample: 16 mm and 12 mm, respectively

(v) Air permeable film 315: Air filter

-Thickness: 130 ㎛

-Outlet diameter: 3 mm

(vi) Second film-type structure 316

-Material: PVC resin double-sided adhesive film

-Thickness: 230 μm

-Width and overall length: 66.6 mm and 49.6 mm respectively

-Width and overall length of the third through cavity 330: 62.9 mm and 45.9 mm, respectively

(vii) Bottom Structure (317)

-Material: Photocurable resin (acrylic series)

-Thickness: 6 mm

-Width and overall length: 70.9 mm and 70.9 mm, respectively

-The size (diameter) and height of the island (round section) structure 332 ': 3 mm and 230 μm, respectively.

-Depth (334) depth: 5.2 mm

-Width (diameter) and depth of collection chamber 335: 16 mm and 3.2 mm, respectively

-Height of the protruding jaw (337): 1.3 mm

-Diameter of the connecting hole (338): 1.5 mm

-Diameter of the discharge hole (339): 2.5 mm

The pattern of the film member used in this example was produced using a design program (Autodesk product name: AutoCAD LT 2014) and a floating cutter (Graphtec product name FC4600C-50 PRO). In addition, the lower plate structure was manufactured by integrally molding a pattern through a 3D printer (KINGS product name: KINGS3035) using a design program. The upper and lower surfaces of the lower plate structure in the membrane-based plastic device (8 × 8 cm) produced in this embodiment are shown in FIG. 22. In addition, the assembly sequence of the membrane-based plastic device produced in this example (stacking sequence from the lower plate structure) is shown in FIG. 23.

A plastic device for pretreatment prepared according to this example was placed upright, and a blood sample (5 mL) was injected through the inlet. At this time, the surface of the remaining members except the air filter was coated with 0.5% BSA. After injecting a blood sample and waiting for about 2 minutes to sufficiently soak the blood in the membrane filter, the amount of plasma separated and collected in the collection chamber was monitored, and the results are shown in FIG. 24. According to the figure, about 260 μl of plasma was collected separately after 10 minutes of injecting a blood sample.

Example 6

-1st test

3 mL of a blood sample (bacterial concentration: 10 ⁵ CFU / mL) spiked with bacteria ( E. Coli ) was injected horizontally into the pretreatment device prepared in Example 2, and then about 2 minutes so as to be sufficiently wet with the membrane filter. After waiting for the liver, the cells were switched to an upright state and plasma was separated for 7 minutes, and as a result, 176 μl of plasma was collected.

-2nd test

Plasma separation and collection tests were performed in the same manner as in the first test, and 210 μl of plasma was collected.

In each of the first test and the second test, bacterial separation efficiency was calculated according to the following equation (1).

[Equation 1]

Bacterial separation efficiency (%) = 100-((number of injections-number passed) / number of injections) × 100

As a result of performing the first test and the second test, the average bacteria passing efficiency was about 50%.

Simple modifications or changes of the present invention can be easily used by those skilled in the art, and all such modifications or changes can be considered to be included in the scope of the present invention.

Claims

A device for pretreatment of fluid,

A membrane filter for separating the liquid fluid injected into the device while moving in a direction from a contact surface to a transmission surface opposite to the liquid fluid;

A contact structure comprising a receiving chamber of a pre-treatment liquid fluid that is received while contacting the contact surface of a membrane filter of a device in which the liquid fluid is placed upright and flows downward under the application of gravity, and

A recovery structure including a receiving chamber of a liquid fluid after pre-treatment, configured to allow the liquid fluid separated by the membrane filter to flow downward along the permeation surface under the application of gravity;

Including,

Each of the pre-treatment liquid fluid receiving chamber and the pre-treatment liquid fluid receiving chamber is configured to provide a capillary force required for the movement of the liquid fluid, and

The device comprises a collection chamber that communicates with the receiving chamber of the liquid fluid after the pretreatment and provides a collection space of the liquid fluid after the pretreatment, the membrane-based device for pretreatment of the liquid fluid.
The membrane-based device of claim 1, wherein the contact structure and the recovery structure are both (i) in the form of a film, or (ii) at least one of which comprises a plastic molding.
(A) a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite thereto;

(B) (b1) A first film having a first through cavity attached to a contact surface of the membrane filter to provide a space for receiving the liquid fluid introduced therein, and a boundary through which the received liquid fluid contacts the membrane filter. Mold structures;

(b2) A film comprising a second through-cavity attached to the first film-like structure, an inlet communicating with the first through-cavity, and a second through-cavity forming a space for accommodating the liquid fluid together with the first through-cavity Mold top structures;

(b3) an outer film structure configured to cover at least a second through cavity attached to the film-like top plate structure to provide a space for moving the introduced liquid fluid by capillary action;

(C) (c1) a second film-like structure attached to the permeable surface of the membrane filter and having a third through cavity bounded to form a space for receiving the separated liquid fluid through the membrane filter; And

(c2) a film-type lower plate structure attached to a lower surface of the second film-like structure, and having a support member supporting a membrane filter through the third through-cavity and a through hole to discharge the separated fluid;

Device for pre-treatment of a film-like liquid fluid comprising a.
The method of claim 3, wherein the first film-like structure further comprises a through-cavity for collecting a first sample that is demarcated separately from the first through-cavity to form a collection chamber of the separated liquid fluid. Device for pretreatment of film-like liquid fluid.
The method of claim 3, wherein the film-like top plate structure further comprises a second sample collection through cavity communicating with the first sample collection through cavity to form a collection chamber of liquid fluid separated together with the first sample collection through cavity. Device for pre-treatment of a film-like liquid fluid, characterized in that.
The method of claim 5, wherein the second film-like structure further includes a through-cavity for collecting a third sample forming a collection chamber of liquid fluid separated together with the through-cavity for collecting the first sample and the through-cavity for collecting the second sample. Device for pre-treatment of a film-like liquid fluid, characterized in that.
The device for pre-treatment of a film-like liquid fluid according to claim 3, wherein the outer film structure comprises a fixing tape of an air permeable film and an air permeable film.
The liquid film of claim 7, wherein the fixing tape of the air permeable film includes a fourth through cavity corresponding to the first through cavity and a second through sample collecting cavity, and a through cavity for collecting a fourth sample. Device for pretreatment of fluids.
The device for pre-treatment of a film-like liquid fluid according to claim 3, wherein the support member of the film-like lower plate structure is in a form in which a plurality of island structures are arranged.
According to claim 3, (c3) characterized in that it further comprises a film-type fluid movement channel structure in communication with the through-hole on the lower surface of the film-like bottom structure, to provide a discharge passage for the separated liquid fluid. Device for pretreatment of film-like liquid fluid.
The method of claim 10, wherein the through-hole comprises at least one first through-hole in communication with a space for receiving the separated liquid, and at least one second through-hole in communication with the collection chamber. Device for pretreatment of film-like liquid fluid.
12. The method of claim 11, wherein the film-like fluid movement channel structure is a combination of a first sheet having a cavity extending in a lengthwise direction and a second sheet attached to the rear surface of the first sheet on the lower surface of the film-like lower plate structure. And a fluid movement channel formed by the fluid movement channel, wherein the fluid movement channel is in communication with the first through hole and the second through hole.
The device of claim 12, wherein the collection chamber is configured to collect the separated liquid fluid through the second through hole from the film-type fluid moving channel structure.
The device for pre-treatment of a film-like liquid fluid according to claim 3, wherein the support member provided on the film-like lower plate structure and the second film-like structure are formed by processing a single film-like sheet at a time by a floating cutter. .
The device for pre-treatment of film-like liquid fluid according to claim 3, wherein the height of the space for accommodating the liquid fluid introduced into the device is in the range of 0.1 to 10 mm.
10. The method of claim 9, The cross-sectional size (diameter) of the island structure is 0.1 to 10 mm, the device for pre-treatment of the film-like liquid fluid, characterized in that the arrangement of the plurality of island structures is formed in a plurality at a predetermined distance. .
(A ') a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite thereto;

(B ') (b1') is attached to the contact surface of the membrane filter, provides an inlet for the liquid fluid, and provides a space for receiving the introduced liquid fluid and is bounded so that the received liquid fluid contacts the membrane filter. 1 A top plate structure in the form of a plastic molding having a through cavity;

(b2 ') an outer film structure attached to the top plate structure and configured to cover at least a first through cavity to provide a space for moving the introduced liquid fluid by capillary action;

(C ') (c1') Fixing the membrane filter having a second through cavity attached to the permeable surface of the membrane filter and bounded to form a space for receiving the separated liquid fluid through the membrane filter. Adhesive film structure for; And

(c2 ') A lower plate attached to the lower side of the adhesive film structure structure, and having a support member supporting a membrane filter through the second through cavity and first and second through holes to discharge the separated fluid. structure;

Membrane-based plastic device for pre-treatment of a liquid fluid comprising a.
(A ") a membrane filter having a structure for separating a liquid fluid while moving in a direction from a contact surface to a transmission surface opposite to it;

(B ") (b1") is provided on the contact surface of the membrane filter to provide a space for receiving the liquid fluid introduced therein and having a first through cavity bounded so that the received liquid fluid contacts the membrane filter. 1 film-like structure;

(b2 ") comprising a second through cavity attached on the first film-like structure, an inlet communicating with the first through cavity, and a second through cavity forming a space for accommodating the liquid fluid together with the first through cavity Top structure;

(C ") (c1") a second film type attached to a permeable surface of the membrane filter and having a third through cavity bounded to form a space for receiving the separated liquid fluid through the membrane filter structure; And

(c2 ") attached to the lower side of the second film-like structure, a supporting member supporting a membrane filter through the third through cavity, a micro-channel for moving the separated liquid fluid, and communicating with the micro-channel A 3D printing type plastic molded lower plate structure having a collection space for collecting the moved liquid fluid;

Membrane-based plastic device for pre-treatment of a liquid fluid comprising a.
The method of claim 17, to form a collection chamber of the separated liquid fluid,

The top plate structure further includes a first sample collection through cavity defined by a boundary separately from the first through cavity, and

The adhesive film structure further comprises a second sample collection through cavity for communicating with the first sample collection through cavity to form a separate liquid collection chamber, the membrane-based plastic for pretreatment of liquid fluid. device.
The plastic device for pretreatment of liquid fluid according to claim 17, wherein the outer film structure comprises a fixing tape of an air permeable film and an air permeable film.
21. The method of claim 20, wherein the fixing tape of the air-permeable film includes a first through cavity and a third through cavity corresponding to the through cavity for collecting the second sample and a through cavity for collecting the third sample, and

The third sample collection through-cavity communicates with the first sample collection through-cavity and the second sample collection through-cavity to form a collection chamber of liquid fluid separated therefrom, which is a membrane-based plastic device for pre-treatment of liquid fluid. .
20. The method of claim 19, (c3 ') In order to provide a discharge passage for the separated liquid fluid, the lower plate structure is formed in communication with the at least one first through hole and the at least one second through hole on the lower surface. 1 further comprising a film-type fluid movement channel structure having a fluid movement channel,

The at least one first through-hole communicates with a space for receiving the separated liquid fluid, while the at least one second through-hole communicates with a collection chamber of the separated liquid fluid. Plastic device for pretreatment.
23. The method of claim 22, wherein the lower plate structure further comprises at least one third through hole and at least one fourth through hole, wherein the film-like fluid movement channel structure is the at least one third through hole and the at least one It has a second fluid movement channel in communication with the fourth through hole of,

The at least one third through-hole communicates with the collection chamber of the separated liquid fluid, while the at least one fourth through-hole is exposed to the outside and is configured to provide a connection with a subsequent process. Plastic device for pretreatment.
The plastic device for pre-treatment of liquid fluid according to claim 17, wherein the supporting member of the lower plate structure is in a form in which a plurality of island structures are arranged.
25. The method of claim 24, The film-like fluid movement channel structure is a first sheet formed of a cavity for a first fluid movement channel and a second fluid movement channel in the form of a strip extending on the lower surface of the lower structure, and the first A plastic device for pretreatment of liquid fluid, characterized in that each of the first fluid movement channel and the second fluid movement channel is formed by a combination of a second sheet attached to the back surface of the one sheet.
The plastic device for pre-treatment of liquid fluid according to claim 18, wherein the micro-channel comprises a first micro-channel formed by fan-shaped or radial projection patterns.
27. The method of claim 26, The 3D printing type plastic molded lower plate structure includes a recess formed to collect the separated liquid fluid moving through the fine flow path, the separated liquid fluid is collected space via the recess Plastic device for pre-treatment of a liquid fluid, characterized in that to move to.
The plastic device for pre-treatment of liquid fluid according to claim 27, wherein the 3D printing type plastic molding-type lower plate structure further comprises a prevention jaw for preventing the backflow of the collected liquid fluid.
The plastic device for pre-treatment of liquid fluid according to claim 18, wherein the 3D printing type plastic molded lower plate structure further comprises a discharge passage of the collected liquid fluid.
30. The method according to claim 29, wherein the 3D printing type plastic molded lower plate structure is for pre-treatment of the liquid fluid, characterized in that it further comprises a second micro-channel to guide the separated liquid fluid collected in the recess to move to the collection space. Plastic devices.
a) providing a liquid fluid as a sample;

b) introducing the liquid fluid into the device according to any one of claims 1 to 30 to perform pretreatment by a membrane filter in the device using capillary force and gravity of the microfluid as driving force in an upright state; And

Recovering the liquid fluid after pre-treatment discharged from the device;

Pretreatment method of a liquid fluid comprising a.
32. The method of claim 31, wherein the liquid fluid is a blood or animal fecal dilution.
32. The method of claim 31, further comprising performing a diagnosis on the recovered liquid fluid.