WO2020067716A1 - Dispositif à base de membrane pour le prétraitement de fluide liquide - Google Patents

Dispositif à base de membrane pour le prétraitement de fluide liquide Download PDF

Info

Publication number
WO2020067716A1
WO2020067716A1 PCT/KR2019/012463 KR2019012463W WO2020067716A1 WO 2020067716 A1 WO2020067716 A1 WO 2020067716A1 KR 2019012463 W KR2019012463 W KR 2019012463W WO 2020067716 A1 WO2020067716 A1 WO 2020067716A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid fluid
film
cavity
fluid
membrane filter
Prior art date
Application number
PCT/KR2019/012463
Other languages
English (en)
Korean (ko)
Inventor
이문근
김지현
신설이
이태재
이경균
배남호
이석재
Original Assignee
한국과학기술원
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020180115148A external-priority patent/KR102121953B1/ko
Priority claimed from KR1020190108962A external-priority patent/KR102319984B1/ko
Application filed by 한국과학기술원 filed Critical 한국과학기술원
Publication of WO2020067716A1 publication Critical patent/WO2020067716A1/fr

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Definitions

  • 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.
  • disease sources eg, harmful pathogens such as bacteria and viruses
  • SARS acute respiratory infections
  • avian influenza virus e.g., H1N1 influenza virus
  • 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.
  • 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 ⁇ l 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.
  • diseases that can be diagnosed through this are wide.
  • 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.
  • the types of diseases that can be diagnosed through plasma are more diverse than those using blood cells.
  • 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.
  • 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.).
  • 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.
  • 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.
  • a syringe pump or the like is attached to the separation device to promote the flow of liquid fluid.
  • 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.
  • 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.
  • 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.
  • a device for pretreatment of fluid is provided.
  • 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;
  • 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
  • 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.
  • 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;
  • (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;
  • (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;
  • a device for pretreatment of a film-like liquid fluid comprising a.
  • (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.
  • a membrane-based plastic device for pretreatment 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.
  • (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;
  • a membrane-based plastic device for pretreatment of a liquid fluid comprising a.
  • the pre-treatment may further include performing a diagnosis on the liquid fluid.
  • the device for pre-treatment of a liquid fluid 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.
  • 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.
  • 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.
  • the device for pre-treatment of a liquid fluid 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.
  • FIG. 1 is a perspective view showing the appearance of a pretreatment device for liquid fluid according to an exemplary embodiment
  • FIGS. 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;
  • FIG. 3 is a top view of a liquid fluid pretreatment device according to an exemplary embodiment
  • FIG. 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;
  • FIG. 6 is a perspective view showing the appearance of a membrane-based plastic device according to an exemplary embodiment
  • FIG. 7 is an exploded perspective view of a membrane-based plastic device according to an exemplary embodiment
  • FIG. 8 is a top view of a membrane-based plastic device according to an exemplary embodiment
  • FIG. 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;
  • FIG. 11 is a perspective view showing the appearance of a membrane-based plastic device according to another embodiment
  • FIG. 12 is an exploded perspective view of a membrane-based plastic device according to another exemplary embodiment
  • FIG. 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;
  • FIG. 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
  • FIG. 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;
  • Example 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;
  • Example 23 is a photograph by step showing the assembly sequence of the membrane-based plastic device produced in Example 5.
  • 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.
  • 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.
  • Chromer 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.
  • Shape 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.
  • on and “on” can be understood to be used to refer to the concept of relative position.
  • the expressions “below”, “below” and “below” and “between” may also be understood as relative concepts of location.
  • the expression “sequentially” can also be understood as a concept of relative position.
  • 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. .
  • “Upper surface” or “lower surface” is a term used for convenience in order to indicate a relative arrangement relationship with other members.
  • the term “top surface” or “rear surface” is used when the member is placed upright. It can be understood as meaning.
  • 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.
  • 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.
  • 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.
  • 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.
  • the size of the pores in the membrane may vary depending on the liquid fluid to be treated.
  • blood whole blood
  • plasma plasma is separated therefrom
  • blood cells in the blood do not pass through the membrane.
  • a pore size range capable of selectively moving only the plasma in the thickness direction.
  • the size (about 2 to 10 ⁇ m) of blood cells in the blood for example, it may be in the range of about 0.1 to 100 ⁇ m, specifically about 0.5 to 50 ⁇ m, and more specifically about 1 to 20 ⁇ m.
  • the material of the membrane filter may be an isotropic membrane, an anisotropic membrane, or a combination thereof.
  • anisotropic membrane an asymmetric membrane of the same material and a composite membrane of two or more different materials can be exemplified.
  • 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.
  • the pore size of the upper region in the membrane may range, for example, from about 5 to 100 ⁇ m, specifically from about 10 to 50 ⁇ m, and more specifically from about 20 to 40 ⁇ m, 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 ⁇ m, specifically about 0.5 to 2 ⁇ m, more specifically about 0.5 to 1 ⁇ m.
  • 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.
  • the pore size continuously changes eg, continuously decreases in pore size
  • 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.
  • 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.
  • a polymer for example, polyolefin, polyester, polyamide, polysulfone, acrylic polymer, polyacrylonitrile, polyaramid, polymer of halogenated olefin, combinations thereof, etc.
  • PVDF polyvinylidene difluoride
  • 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.
  • the thickness of the film-type membrane filter may be, for example, in the range of about 100 to 1,000 ⁇ m, specifically about 200 to 500 ⁇ m, and more specifically about 300 to 350 ⁇ m. 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.
  • plastic moldings may be directly formed by injection molding or casting. Alternatively, it can be formed by processing using a design program and a CNC technique.
  • 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).
  • 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.
  • the liquid fluid is separated while moving in the direction of the permeate surface.
  • 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.
  • the two chambers formed on both sides of the membrane filter 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.
  • 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.
  • a collection chamber in communication with the receiving (moving) space of the liquid fluid after pretreatment in the device.
  • 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.
  • 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.
  • 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. .
  • 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.
  • 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%.
  • 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
  • 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.
  • 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.
  • PET polyethylene terephthalate
  • PE polyethylene
  • PP polypropylene
  • 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.
  • 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.
  • PDMS polydimethyl siloxane
  • h-PDMS polydimethyl siloxane
  • polymethylsiloxane partially alkylated polymethylsiloxane
  • polyalkylmethylsiloxane poly Phenylmethylsiloxane
  • PDMS polyphenylmethylsiloxane
  • other polymers capable of forming or 3D printing such as silicone-modified elastomers, thermoplastic elastomers, poly (butylene terephthalate; PBT) polystyrene (PS), polycarbonate (PC), polyolefin
  • PE polyethylene
  • PP polypropylene
  • PEEK poly (etheretherketone)
  • PEI poly (etherimide)
  • PMMA polymethylmethacrylate
  • PA polyamide
  • PA polyimide
  • PET polyester
  • synthetic rubber polyisobutylene, and the like, and at least one may be selected.
  • photocurable resins specifically, photocurable acrylic resins, acrylonitrile butadiene styrene (ABS), polylactide (PLA), etc.
  • ABS acrylonitrile butadiene styrene
  • PLA polylactide
  • 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.
  • 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.
  • an adhesive material one-sided or double-sided adhesive material
  • a double-sided adhesive material specifically, a double-sided adhesive material.
  • the first Concrete (For film type liquid fluid pretreatment device )
  • FIG. 1 shows the appearance of a liquid fluid pretreatment device according to an exemplary embodiment of the present disclosure.
  • 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.
  • FIGS. 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.
  • 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.
  • 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).
  • a first film-like structure 112 processed in a predetermined pattern is attached.
  • 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.
  • 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.
  • 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.
  • 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.
  • the first through cavity 130 typically has a shape corresponding to the membrane filter 111, but is not necessarily the same shape.
  • 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.
  • 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. .
  • a pot-shaped cavity is formed that converges gently toward the bottom.
  • the thickness of the first film-like structure 112 may be determined, for example, within a range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m. have.
  • a film-shaped top plate structure 113 may be attached to the first film-type structure 112.
  • 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.
  • 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.
  • 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.
  • 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,
  • the through cavity 125 may be formed.
  • the second sample collection through cavity 125 may correspond to the first sample collection through cavity 122 or may have the same shape.
  • the thickness of the film-like top plate structure 113 may be determined, for example, within about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • gravity is applied to the liquid fluid introduced through the injection hole 124 as the device 100 is placed upright.
  • a space or accommodating chamber
  • 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).
  • 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.
  • the outer film structure may largely include an air-permeable film fixing tape 114 and an air-permeable film 115.
  • 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.
  • 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.
  • 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.
  • PTFE Polytetrafluoroethylene
  • 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.
  • the thickness of the air permeable film 115 may be, for example, about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • 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.
  • FIG 3 is a plan view of a liquid fluid pretreatment device according to an exemplary embodiment.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a pressure-sensitive adhesive tape 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.
  • the air-permeable film 115 may be attached using an adhesive, not a fixing tape.
  • 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.
  • the height of the anchoring tape or adhesive layer 114 may range from, for example, about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • 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.
  • 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.
  • 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).
  • 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.
  • the membrane filter 111 is interposed by bonding together with bending. It can be easily fixed.
  • 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.
  • 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.
  • the thickness of the second film-like structure 116 may be, for example, in the range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • FIG. 4 is a side view of a liquid fluid pretreatment device according to an exemplary embodiment
  • 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.
  • the film-type lower plate structure 117 is attached to the lower surface of the second film-type structure 116 as described above.
  • 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.
  • 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.
  • 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.
  • a plurality of support members 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.
  • 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).
  • 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).
  • 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.
  • the height of the support member 132 may be, for example, in the range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m, as described above.
  • 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.
  • the thickness of the film-like lower plate structure 117 may be, for example, in the range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • 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.
  • 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.
  • 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.
  • the width of the fluid movement channel may be, for example, in the range of about 100 to 2,000 ⁇ m, specifically about 200 to 1,500 ⁇ m, and more specifically about 500 to 1,000 ⁇ m, which will be understood in an exemplary sense. You can.
  • 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.
  • 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.
  • 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.
  • each of the first sheet 118 and the second sheet 119 may be different or the same, for example, about 20 ⁇ m to 1 mm, specifically about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, more specifically about 100 to 300 ⁇ m.
  • the thickness of the first sheet 118 substantially determines the height of the fluid transfer channel 133.
  • 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.
  • 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.
  • 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.
  • the collection chamber may have a boundary thereof.
  • 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.
  • 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.
  • 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.
  • 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 '.
  • 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.
  • a micropipette for diagnostic purposes.
  • the above-described outlet cover may be removed while the upright device is horizontally disposed and collected using a micropipette.
  • 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.
  • a film-like member 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • BSA Bovine serum albumin
  • the device 100 for pre-treatment of a liquid fluid 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.
  • 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.
  • FIG. 6 shows the appearance of a liquid fluid pretreatment device according to an exemplary embodiment of the present disclosure.
  • 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.
  • FIG. 7 is an exploded perspective view of a liquid fluid pretreatment device according to an exemplary 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).
  • 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.
  • a top plate structure 212 in the form of a plastic molded article processed in a predetermined pattern is positioned on the contact surface.
  • 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.
  • 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.
  • 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.
  • the lip member is also not limited to a specific pattern.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the first through cavity 221 typically has a shape corresponding to the membrane filter 211, but is not necessarily the same shape.
  • 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.
  • 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. .
  • a pot-shaped cavity is formed that converges gently toward the bottom.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • gravity is applied to the liquid fluid introduced through the injection hole 224 as the device 200 is placed upright.
  • 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.
  • 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.
  • the capillary force i.e., the capillary force generated while wetting the microcavity of the membrane filter provides the driving force required for movement
  • 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.
  • the outer film structure may largely include an air-permeable film fixing tape 214 and an air-permeable film 215.
  • 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. .
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • a description of the fixing tape 114 may be applied in the first specific example, so a detailed description thereof will be omitted.
  • 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 may be adjusted to be in the range of mm.
  • the adhesive film structure 216 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.
  • 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).
  • 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.
  • 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.
  • the adhesive film structure 216 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.
  • 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.
  • the thickness of the adhesive film structure 216 may be, for example, in the range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • Fig. 9 is a side view of a device for pretreatment according to an exemplary embodiment
  • 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.
  • the lower plate structure 217 is attached to the lower surface of the adhesive film structure 216 as described above.
  • the lower plate structure 217 includes a support member 232 that supports (series) the membrane filter 211 through the second through cavity 230.
  • 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.
  • the height of the adhesive film structure 216 will be substantially the same.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • the width of the first fluid movement channel 233 may be, for example, in the range of about 100 to 2,000 ⁇ m, specifically about 200 to 1,500 ⁇ m, and more specifically about 500 to 1,000 ⁇ m. It can be understood in a meaning.
  • 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.
  • 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.
  • 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.
  • each of the first sheet 218 and the second sheet 219 may be different or the same, for example, about 20 ⁇ m to 1 mm, specifically about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, more specifically about 100 to 300 ⁇ m.
  • the thickness of the first sheet 218 substantially determines the height of the fluid transfer channel 233.
  • 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.
  • 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.
  • 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.
  • the boundary of the collection chamber may be determined.
  • 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.
  • 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.
  • 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.
  • 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 '.
  • 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.
  • 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 ').
  • 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.
  • 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.
  • 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.
  • 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 '.
  • 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).
  • a subsequent device eg, diagnostic chip
  • the above-described cover may be removed while the upright device is horizontally disposed and collected using a micropipette.
  • it may be moved from the collection chamber through the fourth through hole 228 using a non-powered pump or the like.
  • 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.
  • 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.
  • the pre-treatment device 200 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.
  • the fluid 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).
  • FIG. 11 is a perspective view showing the appearance of a membrane-based plastic device according to another embodiment of the present disclosure
  • FIG. 12 is an exploded perspective view thereof.
  • 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.
  • this shape is understood as an exemplary purpose, and is not necessarily limited thereto.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the first through cavity 321 typically has a shape corresponding to the membrane filter 311, but is not necessarily the same shape.
  • 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.
  • the thickness of the first film-like structure 312 may be determined, for example, within a range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m. have.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the pattern of the lip member 313 ' is also not particularly limited.
  • the thickness of the top plate structure 313 may be determined, for example, within about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, and more specifically about 100 to 300 ⁇ m.
  • the illustrated embodiment 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • the air permeable film 315 may be attached using an adhesive, rather than a fixing tape.
  • 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.
  • the height of the anchoring tape or adhesive layer 314 may be, for example, in the range of about 10 to 1000 ⁇ m, specifically about 50 to 500 ⁇ m, more specifically about 100 to 300 ⁇ m.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the second support member may be arranged in the form of a plurality of island structures. Referring to FIG.
  • 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.
  • 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.
  • 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.
  • 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 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.
  • the device 300 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.
  • 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).
  • the protruding jaw 337 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.
  • the protruding jaw 337 may be formed in the shape of an arc when observing the plane, but is not limited thereto.
  • 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.
  • 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.
  • 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.
  • 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.
  • various diseases can be diagnosed in the field.
  • 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.
  • the liquid fluid to be pretreated may be, for example, blood (whole blood), animal fecal dilution, saliva, urine, or the like.
  • blood whole blood
  • animal fecal dilution saliva, urine, or the like.
  • 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.
  • 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.
  • Membrane filter Pall's Vivid membrane filter (GR vivid membrane; asymmetric polysulfone-based membrane); thickness 300 ⁇ m; width 25.7 mm, total length: 57 mm
  • Air permeable film 115 Air filter
  • the thickness of the first and second sheets 118, 119 230 ⁇ m and 100 ⁇ m, 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.
  • 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.
  • 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.
  • 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.
  • Membrane filter 211 Pall's Vivid membrane filter (GR vivid membrane (asymmetric polysulfone-based membrane); thickness 320 ⁇ m; width 25.7 mm, total length: 57 mm
  • Air permeable film 215 Air filter
  • the thickness of the first and second sheets 218, 219 200 ⁇ m and 100 ⁇ m, 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).
  • 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 ⁇ l of plasma was collected separately after 10 minutes of injecting a blood sample.
  • 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.
  • Membrane filter 311 Pall's Vivid membrane filter (GR vivid membrane (asymmetric polysulfone-based membrane); thickness 320 ⁇ m; width 66.6 mm, total length: 49.6 mm
  • Air permeable film 315 Air filter
  • 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).
  • 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.
  • the assembly sequence of the membrane-based plastic device produced in this example 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 ⁇ l of plasma was collected separately after 10 minutes of injecting a blood sample.
  • Plasma separation and collection tests were performed in the same manner as in the first test, and 210 ⁇ l of plasma was collected.
  • Bacterial separation efficiency (%) 100-((number of injections-number passed) / number of injections) ⁇ 100
  • the average bacteria passing efficiency was about 50%.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

Selon la présente invention, celle-ci concerne un dispositif à base de membrane pour le prétraitement de fluide liquide qui est fabriqué pour séparer et récupérer sélectivement, sur la base d'un filtre à membrane, un constituant spécifique contenu dans des fluides liquides tels que des échantillons liquides de sang ou fécaux devant être appliqué à divers diagnostics.
PCT/KR2019/012463 2018-09-27 2019-09-25 Dispositif à base de membrane pour le prétraitement de fluide liquide WO2020067716A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2018-0115148 2018-09-27
KR1020180115148A KR102121953B1 (ko) 2018-09-27 2018-09-27 멤브레인을 기반으로 하는 액상 유체 전처리용 디바이스
KR10-2019-0108962 2019-09-03
KR1020190108962A KR102319984B1 (ko) 2019-09-03 2019-09-03 액상 유체 전처리용 멤브레인 기반 플라스틱 디바이스

Publications (1)

Publication Number Publication Date
WO2020067716A1 true WO2020067716A1 (fr) 2020-04-02

Family

ID=69952227

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2019/012463 WO2020067716A1 (fr) 2018-09-27 2019-09-25 Dispositif à base de membrane pour le prétraitement de fluide liquide

Country Status (1)

Country Link
WO (1) WO2020067716A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080027392A (ko) * 2005-07-14 2008-03-26 나노디텍 코포레이션 미세유체장치와 미세유체장치의 제작 및 사용방법
JP2008076306A (ja) * 2006-09-22 2008-04-03 Sumitomo Bakelite Co Ltd マイクロ流路デバイス
KR20150133774A (ko) * 2013-03-15 2015-11-30 테라노스, 인코포레이티드 시료 수집 및 시료 분리용 방법과 기기
US20160274010A1 (en) * 2013-12-03 2016-09-22 The University Of Tokyo Separation unit, separation method, fluid device, and composite fluid device and kit
US20170268967A1 (en) * 2016-03-16 2017-09-21 Cellmax, Ltd. Collection of suspended cells using a transferable membrane

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080027392A (ko) * 2005-07-14 2008-03-26 나노디텍 코포레이션 미세유체장치와 미세유체장치의 제작 및 사용방법
JP2008076306A (ja) * 2006-09-22 2008-04-03 Sumitomo Bakelite Co Ltd マイクロ流路デバイス
KR20150133774A (ko) * 2013-03-15 2015-11-30 테라노스, 인코포레이티드 시료 수집 및 시료 분리용 방법과 기기
US20160274010A1 (en) * 2013-12-03 2016-09-22 The University Of Tokyo Separation unit, separation method, fluid device, and composite fluid device and kit
US20170268967A1 (en) * 2016-03-16 2017-09-21 Cellmax, Ltd. Collection of suspended cells using a transferable membrane

Similar Documents

Publication Publication Date Title
WO2014104830A1 (fr) Dispositif de disque d'amplification d'acide nucléique faisant intervenir un composite polymère thermosensible et méthode d'analyse mettant en œuvre celui-ci
JP4312950B2 (ja) 微小流体分析モジュール
EP2633328A2 (fr) Système automatisé de pcr en temps réel pour l'analyse de divers échantillons biologiques
WO2023277247A1 (fr) Appareil d'extraction de génome comprenant un couvercle d'écoulement
CN110312176B (zh) 麦克风组件
WO2011136624A2 (fr) Dispositif de purification automatique d'échantillon biologique à unité d'application de champ magnétique, procédé pour extraire une substance cible d'un échantillon biologique, et procédé d'expression et de purification de protéine
WO2020067716A1 (fr) Dispositif à base de membrane pour le prétraitement de fluide liquide
US8562114B2 (en) Inkjet ejector having an improved filter
US20020124896A1 (en) Modular microfluidic systems
JP4367055B2 (ja) マイクロチップ基板の接合方法およびマイクロチップ
KR20120016199A (ko) 세포를 분리하기 위한 미세유체 디바이스
WO2012144794A2 (fr) Procédé de fabrication d'un dispositif de microvanne monté sur un laboratoire sur puce, et dispositif de microvanne fabriqué par ledit procédé
US20030132162A1 (en) Underdrain for filtration membrane
WO2023277245A1 (fr) Dispositif d'extraction de génome présentant une structure à double chambre dans laquelle une chambre externe et une chambre interne sont combinées
WO2022145983A1 (fr) Structure de diagnostic mobile
JP2009503489A (ja) 電子的機能および流体機能をもつバイオ医療装置のための相互接続およびパッケージング方法
WO2020027500A1 (fr) Puce fluidique modulaire et système d'écoulement de fluide la comprenant
JPH11147318A (ja) インクジェットプリントヘッド用アクチュエータの熱処理方法およびインクジェットプリントヘッドの製造方法
AU2018303111B2 (en) Modules for transferring magnetic beads, automated system comprising the same and method for nucleic acid extraction using the same
WO2023277248A1 (fr) Dispositif d'extraction de génome doté d'une structure à double chambre à chambre externe et chambre à billes combinées
WO2023017894A1 (fr) Dispositif d'extraction de génome comprenant une pince de sécurité couplée à une chambre interne
WO2023204432A1 (fr) Cartouche de biocapteur et système de biocapteur la comprenant
WO2020106004A1 (fr) Dispositif microfluidique ayant une structure séparable utilisant un film mince
WO2023214843A1 (fr) Cartouche de détection d'acide nucléique
WO2020055152A1 (fr) Dispositif de mesure de vitesse d'écoulement jetable présentant une sensibilité prédéterminée à un changement de pression à l'aide de divers types de films ultra-minces, et dispositif microfluidique permettant l'élimination de micro-bulles à l'intérieur d'un canal à l'aide de motifs de support faisant saillie depuis un film ultra-mince poreux et procédé de fabrication correspondant

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19867522

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19867522

Country of ref document: EP

Kind code of ref document: A1