WO2018048025A1 - Pattern structure of diagnostic sensor - Google Patents

Pattern structure of diagnostic sensor Download PDF

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Publication number
WO2018048025A1
WO2018048025A1 PCT/KR2016/013698 KR2016013698W WO2018048025A1 WO 2018048025 A1 WO2018048025 A1 WO 2018048025A1 KR 2016013698 W KR2016013698 W KR 2016013698W WO 2018048025 A1 WO2018048025 A1 WO 2018048025A1
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WO
WIPO (PCT)
Prior art keywords
channel
main channel
delay
region
separation
Prior art date
Application number
PCT/KR2016/013698
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French (fr)
Korean (ko)
Inventor
김민곤
송문범
변주영
홍동구
정권영
Original Assignee
주식회사 인지바이오
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Publication of WO2018048025A1 publication Critical patent/WO2018048025A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0663Whole sensors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices

Definitions

  • the present invention relates to a diagnostic sensor for printing an organic compound on paper to form a pattern.
  • the first material and the second material are transferred to the diagnosis area in time by different fluid flows, and in the diagnosis area, the reaction of the second material is induced without disturbing the first supplied material. It is about the pattern structure of the diagnostic sensor that delivers two kinds of materials by time difference and returns them without any repayment.
  • the Telemedicin system has been introduced, which allows a patient or patient to be diagnosed at a remote location at a relatively low cost without visiting a hospital.
  • the diagnosis method can only be very limited, which makes it difficult to make an accurate diagnosis.
  • a biosensor using membrane is used as an immunoassay device that is simple to use, short in execution time, without requiring specialized knowledge or complicated procedures.
  • Analytical devices using these biosensors can generally use an immunochromatographic method that uses a porous membrane as the immobilization matrix for the protein.As the sample containing the analyte is absorbed from the bottom of the membrane strip, capillary The analyte is then immobilized into The transport and reaction between the antigen and the antibody on the solid surface and the unbound components are separated by the fluid flow.
  • This principle-based membrane strip immunochromatography technique uses the lateral flow of the fluid to react the reaction components. By accelerating the delivery of these substances, diagnostics can be completed simply by adding the analyte to the measurement speed and adding the sample.
  • the immunoglobulin-gold label conjugate (Anti-progesterone IgG-gold conjugate) was made. Diagnosis is achieved by passing reactions through the serum albumin conjugate diagnostic line, which results in color development, or by mixing various reaction substances in the sample to make the diagnosis response on the diagnosis line. Diagnostic errors may occur due to low or non-specific reactions.
  • the lateral flow device for multi-component simultaneous quantitative analysis includes: a sample pad for receiving a fluid sample to be analyzed; and placed in contact with the sample pad. Coated with a first binder that binds to different target analytes contained within the fluid sample.
  • a conjugate pad comprising nanospheres; and a patterned sheet disposed in contact with the conjugate pad, the patterned sheet having a branched channel pattern on which the fluid sample can flow, wherein the channel pattern includes:
  • the pattern material is formed by spraying a pattern material on the base member of silver paper using inkjet printing.
  • the above-mentioned document 2 shows a channel in which a channel pattern is branched from one channel to three channels. Fluid sample into one channel. As the process progresses, it is divided into several parts, and each branched channel contains different reaction materials so that multiple diagnosis can be performed at one time.As a result, the detection sensitivity is lowered or non-specific reactions are caused by the interference between materials. The disadvantage that occurred was not solved. Detailed description of the invention
  • the object of the present invention is to provide a pattern structure that can improve detection sensitivity by allowing each reaction to be performed in a substantial manner without interference from other materials.
  • a pattern structure of a diagnostic sensor in which a channel is formed using a printing technique on paper, which is formed to be long in the vertical direction so that fluid flows from the lower part to the upper part.
  • a main channel having a diagnostic region coated with a detection material at an upper end thereof, and having an intersecting area connected to another channel at a middle portion thereof; and a main channel formed side by side on the main channel;
  • a buffer input area into which a buffer is inserted is separated from the area below the delayed fluidized area, and the buffer input area is connected to each other by a delay pad, so that the time delay for transferring the buffer to the main channel is delayed.
  • the separation channel portion is formed separated in communication with the cross-area of the main channel is added to the bottom of the second bending direction angled to the main channel formed; is configured to include a.
  • the first bent portion and the second bent portion may be formed with curved surfaces.
  • the main channel width is formed to be 3 ⁇ 4mm
  • the delay channel is formed in the length between the first bent portion and the joining portion 3 ⁇ 4mm
  • the separation channel is between the second bent portion and the separation portion
  • the length of can be formed into l ⁇ 2mm.
  • the delay channel may include a length of the delayed channel width between the first bent portion and the joining portion.
  • the separation channel may be formed to be 1-1.5 times long, and the separation channel may be spaced apart from the main channel at intervals such that the length between the second bend and the separation part is 0.3 to 0.5 times the main channel width.
  • the intersecting area of the main channel may be formed from a point where the separating part is positioned above the confluence part, and the separating part forms a confluence part or intersects with an extended part of the extended channel.
  • the portion between the confluence portion in the first bent portion of the delay channel and the portion between the separation portion and the second bent portion of the separation channel may be formed in a direction perpendicular to the main channel.
  • the splitter of the splitter channel may have an extended part formed at a lower end of the splitter channel extending from the point opposite to the point where the joining part starts to the second bent part.
  • the delay channel may be formed to have an upward slope in the direction of the joining portion at the first bent portion, and the separation channel may be formed to have an upward slope in the direction of the second bend portion at the separation portion.
  • an additional protrusion protruding in the center direction of the main channel may be further formed on the upper wall of the delay channel communicating with the main channel so that the fluid that joins the delay channel is further introduced into the main channel center direction and flows.
  • the main channel has a length of 2 to 5 mm from the intersection to the bottom thereof.
  • the sample dosing area can be removed and the sample dosing area replaced by a partial overlap of the bond pads at the bottom of the main channel.
  • the main channel is adjacent to the intersection area between the intersection area and the diagnosis area.
  • the top and bottom of the separation zone can be connected.
  • the process of fixing the target material and the immobilized target material react with each other so that the detection process of luminescence or coloration is performed separately.
  • 1 to 7b show a pattern structure according to a preferred embodiment of the present invention.
  • FIG. 8 is a plan view showing various pattern structures according to an embodiment of the present invention.
  • FIG. 9 is a photograph showing a fluid flow process according to various patterns according to an embodiment of the present invention.
  • FIG. 10 is a graph showing the results of measuring the flow rate and flow rate of various delay pads according to the embodiment of the present invention.
  • FIG. 12 is a photograph illustrating a fluid flow process based on a design and time difference using a fluorescent material according to an embodiment of the present invention.
  • FIG. 1 is a plan view showing a pattern structure by printing according to a preferred embodiment of the present invention.
  • the pattern structure according to the present invention (10) is based on paper printing technology.
  • NC membrane Nirocellulose membrane
  • the fabricated pattern structure 10 includes a sample injection zone 21 and a diagnosis zone 22 formed therein.
  • a main channel 20 And a main channel 20, a delay channel 30 for delaying the fluid for a certain time and then joining the main channel, and a separation channel 40 for separating the fluid of the main channel.
  • the main channel 20 is formed to be long in the vertical direction, and at one side thereof.
  • the sample injection zone 21 is formed and the opposite side: a diagnostic zone 22 is formed at the end to allow fluid to flow from the sample injection zone to the diagnostic zone.
  • a search target is provided at the lower end of the main channel.
  • a sample injection zone 21 is formed, and a diagnostic zone 22 in which the detection material is coated on the opposite upper end is formed so that the fluid flows from the lower part to the upper direction.
  • An intersecting region 23 is formed in the middle portion of the section in which the sample introduced into the region 21 flows upward to the capillary phenomenon so as to communicate with another channel. In the intersecting region 23, fluid is introduced from another channel or the main The fluid in the channel is separated and drained.
  • the delay channel 30 is arranged side by side on the lower side of the main channel, and the lower buffer input area 32 into which the buffer is inserted is the main movement area of the delay channel.
  • the delay channel 30 is configured separately from the delay flow region 31.
  • the buffer input area 32 and the delay flow area 31 use separate delay pads 50:
  • Buffer delay pad 50 inserted into buffer input area ⁇ 32
  • Passage increases the flow time and finally joins the main channel 20 with a time difference.
  • the delay channel 30 includes a first bending portion 33 whose upper portion is bent in the main channel direction.
  • the upper end of the delay channel is in communication with the intersecting area 23 of the main channel.
  • the communicating portion of the delay channel and the main channel is called a confluence part 34.
  • the separation channel 40 is arranged side by side with the upper portion of the main channel, the lower portion is bent in the main channel direction by the second bent portion 41, and the lower portion is connected to the intersection region 23 of the main channel.
  • the communicated portion is referred to as a separator 42.
  • the separation channel 40 is formed on one side of the main channel 20, but is located in a direction opposite to the direction in which the delay channel is formed.
  • the first bent portion 33 and the second bent portion 41 are formed in a curved surface to minimize the flow velocity in the process of switching the fluid flow direction as shown in FIG. 2. It is desirable.
  • the main channel 20, the delay channel 30 and the separation channel 40 is formed in a width of 3 to 5mm each formed in the upper and lower portions of the drawing, the first bent portion of the delay channel 30 Between the 33 and the confluence portion 34 is formed in a width of 1.5 ⁇ 2.5mm, and between the second bent portion 41 and the separating portion 42 of the separation channel 40 is formed in a width of 1.5 ⁇ 2.5mm.
  • the width of the main channel, the delay channel, and the separation channel should be less than 3mm.
  • the delay channel 30 is a fluid supplied through the buffer injection region (32)
  • the first bending section 33 breaks the direction toward the main channel 20, and then joins the main channel, and the first bending section, which is a spaced interval between the vertically arranged main channel and the delay channel,
  • the length between the convex part 34 and the convex part 34 is preferably 0.5 to 1 times the width of the main channel width.
  • the length between the first and second bent portions 33 and 34 is less than or equal to 3 mm, and the fluid flowing in the delay channel 30 is joined.
  • the delay channel 30 is less than the channel interval width between the lower portion of the U bend 33 and the delay channel 30 between the confluence portion 34 and the bend portion 33.
  • the meaning of the fluid that is formed in a small width to join the main channel can further increase the force.
  • the width between the confluence 34 and the first bend 33 is 1.5 to 2.5 mm to form a fluid that merges into the main channel.
  • Increasing the force to push the flowing fluid to one side leads to an increase in the flow rate of the fluid flowing through the main channel and the flow rate of the fluid flowing through the confluence of the main channel.
  • the separation channel 40 is disposed between the vertically arranged main channel and the separation channel.
  • the length between the second bent portion 41 and the separating portion 42 may be 1 to 2 mm. If the length between the second bent portion 41 and the separating portion 42 is less than lmm
  • the amount of discharged to the separation channel 40 increases, thereby reducing the amount of sample flow to the diagnostic region 22 located above the main channel.
  • the fluid flowing through the main channel 20 is discharged from the confluence part 34 or pushed toward the separation part 42 by the fluid of the soft channel, and flows in a diagonal direction from the upward flow to the separation part.
  • the length between the second bent portion 41 and the separation portion 42 is longer than 2 mm, the fluid flowing in the diagonal direction strikes the separation channel wall, and then the horizontal direction.
  • this considerable resistance in the process of the flow of the to be done because the inflow into the separation unit is generated such resistance is also fluid entering portion separated delivered: a significant amount by control fluid portion interfere with the entry of the main channel is not divided into separate channels Therefore, it is preferable that the length between the second bend portion 41 and the separation portion 42 is within the range of 1 mm to 2 mm because it affects the diagnosis flowed with the fluid joined in the delay channel.
  • the width between the separation section 42 and the second bent section 41 of the separation channel 40 is formed at a ratio of 0.5 to 1.5 times the width of the main channel, and 4 mm with the main channel 3 to 5 mm. Since the width between the second bent portion and the separating portion is 2 to 6 mm, the width between the second bent portion and the separating portion is preferably 2 mm or less. It is hard to flow into the separation part by being pushed by the fluid joined in the delay channel, and when formed over 6mm
  • the confluence part 34 of the delay channel formed in the intersecting area 23 of the main channel 20 and the separation part 42 of the separation channel are located at positions spaced apart from each other.
  • the fluid of the main channel 20 is introduced from the lower part to the upper part, and must be discharged by the fluid introduced from the confluence part 34 to be separated and discharged to the separating part 42.
  • the confluence part 34 is formed in communication with the main channel 20, and the separation part 42 communicates with the upper part of the confluence part so that the fluid of the main channel located on the condensing part moves in a diagonal direction toward the separation part and discharges. This is done.
  • the forming position of the separating section 42 is formed so that the separating section is formed from the intersection point when the upper side of the main channel side wall consolidation section 34 is extended horizontally so that the vertical flow fluid and the joining section of the main channel are formed.
  • the vertical fluid flows in a diagonal direction so that it is separated and discharged to the separator.
  • the portion between the first bent portion 33 and the confluence portion 34 of the delay channel 30, and the portion between the separation portion 42 and the second bent portion 41 of the separation channel 40 are main Formed in a direction orthogonal to the channel 20, the fluid flowing horizontally at the joining portion can maximize the force that pushes the fluid moving up the main channel to the side.
  • the expansion channel 43 is formed at the bottom of the separation channel 42 of the separation channel so that the moving fluid of the main channel driven by the fluid introduced from the confluence unit can be easily separated.
  • the expansion portion 43 may be introduced into the channel.
  • Expansion can be made to the portion where the second bent portion 41 starts, so that expansion can be made from the position where the fluid push from the confluence portion starts.
  • the upward inclination between the first bend portion 33 and the confluence portion 34 of the phase delay channel, and between the separation portion 42 and the second bend portion 41 of the separation channel can be formed to have.
  • the flow rate of the fluid flowing through the main channel decreases due to the fluid inflow from the delay channel through the confluence part 34.
  • the upward inclination angle formed with the main channel is formed at an angle of 30 or more that can cause side sliding, and prevents a sudden drop in flow rate due to confluence. It can be formed below 60 so that
  • the delay channel 30 further includes a protrusion 35 in which the upper wall forming the confluence part 34 has a predetermined width in the main channel direction, and joins in the delay channel.
  • the protrusion 35 is projected at a ratio of 0.2 to 0.4 times the width of the main channel.
  • sample input to the main channel is separately determined.
  • the sample input area was removed by providing a contact pad (Conjugate pad: 60), and the length from the bottom of the main channel 20 to the conduit 34 of the delay channel 30 was formed shortly. (23) Short formation of the lower part shortens the time that the fluid introduced through the bonding pad 60, which overlaps the lower end of the main channel, enters the intersecting area 23, to the point where the fluid is joined from the delay channel 30. Can further increase the time interval.
  • the widths arranged in the vertical direction in the main channel 20, the delay channel 30, and the separation channel 40 are 4 mm, and are formed between the low 11 bent portion 33 and the confluence portion 34.
  • the delay channel width is 2 mm
  • the separation part 42 is further formed with an expansion part 43 (a part connected from the inner channel inner wall surface facing the lower part of the joining part to the start point of the second bend part) having a 45 inclination.
  • the width of the inlet is increased.
  • the main channel 20 is formed at 3 mm from the lower end to the start point of the confluence part 34, and the delay channel 30 is 3 mm from the beginning of the first bent part 33 to the lower part.
  • the buffer injection zone 32 was separated from the buffer injection zone 32, and the separation width was 1 mm.
  • the buffer injection zone was formed to have a length of 5.5 mm in the upper and lower portions so as to sufficiently absorb the injected solution.
  • the adhesive pad (60; Conjugate pad) is attached to the lower end of the main channel
  • Delayed release pads can be formed into squares with the same width and length as the main channel width. :
  • each of the adhesive pad and the retardation pad can be formed to have a width of 4 mm and a length of 4.5 mm.
  • the asymmetric membrane can be used.
  • Asymmetric super micron polysulfone MMM
  • the separation channel 40 is formed to be 21 mm from the point where the second bent portion 41 is formed to the top, so that the fluid pushed out by the fluid introduced from the delay channel 30 in the cross section 23 is introduced. It was made possible to proceed steadily.
  • the main channel may be positioned at the same horizontal level as that of the separation channel.
  • the main channel 20 may further form a separation region 24 between the intersection region 23 and the top.
  • the separation area 24 is positioned below the diagnosis area 22 through which detection is performed so that channels spaced up and down by an additionally placed adhesive pad 60 are connected to each other.
  • the fluid passing through the intersecting area 23 can be flown to the diagnostic area 22 of the upper part by the adhesive pad 60 by being formed at a point of 4-5 mm from the separating part 4 2.
  • the additional configuration of the delay pad 50 or the adhesive pad 60 in the channel flow section is performed by filtering and removing the precipitate contained in the sample or buffer solution to be added or the precipitate generated during the process. Detection sensitivity
  • the separation region is not limited to 1 or 7 in addition to the pattern 7 applied to the pattern of FIG. 6.
  • the size described in FIG. 7 is for one of the embodiments of the present invention, and the scope of the present invention includes not only the illustrated sizes but also changes of each size in the range of -20 to + 20%. something to do.
  • FIG. 8 is a diagram showing various pattern structures by printing an organic compound on an NC (nitrocellularos) membrane.
  • the vertically arranged portions of the main channel, the delay channel, and the separation channel have a width of 4 mm, and are arranged to be spaced apart from each other by 4 mm.
  • the space between the and separation sections was 2mm wide and formed to have a 45 degree upward slope from the first bend to the low 12 bend.
  • (B) forms a channel pattern in the same manner as in (A), but between the second bend and the separation part
  • the separation channel width was formed to be the same 4mm width as the main channel.
  • a channel pattern 1 turn was formed in the same manner as in (A), but the distance between the vertically arranged separate channel and the main channel was set to 1.5 mm, and the outer angle of the second bent portion was formed as a curved surface.
  • the confluence portion was formed with a protrusion projected to 1.5 mm of the main channel width in the center of the main channel.
  • the vertically arranged portions of the main channel, the delay channel and the separation channel have a width of 4 mm.
  • the separation channel is spaced 1.5 mm apart from the main channel.
  • the width was 2 mm, and horizontally positioned so as to cross the main channel. The inflow to the separation channel was expanded.
  • Asymmetric super micron polysulfone with a pore size of 0.8 // m was used to connect the buffer-to-mip region and the delayed flow region of the delay channel.
  • the main channel has an edible pigment above the sample injection zone.
  • Surfactant (Product name: surfactant 10G from fitzgerald) was applied and dried.
  • the delay channel had food coloring red and 1% (v / v) on the delay pad.
  • a surfactant (product name: surfactant 10G from fitzgerald) was applied and dried.
  • Phosphate Buffered Saline (PBS) * was added to allow fluid to flow upward.
  • FIG. 9 illustrates the steep fluid flow process of the A, B, C, and D patterns of FIG.
  • the red fluid of the delay channel pushes the blue fluid of the main channel (fluid mixed with edible blue), so that a part of the blue fluid is weak. You can see it flowing to the same area.
  • the blue fluid was pushed out to the side so that the blue fluid flowed only into the separation channel, and the D pattern had the best effect.
  • Asymmetric super micron selected from GALL, GX, GR and GF among Vivid as an asymmetric membrane used as a delay pad.
  • the polysulfone was selected as the pore sizes 0.45, 0.8, and 8, respectively, and represented as GR, GX, GF, 0.45, 0.8, and 8, respectively.
  • the lower part of the intersecting area has a length of 3 mm, and the shape of the shape is 6, and the lower part of the main channel has the adhesive pads partially overlapped, and the adhesive pad is the same as the soft pad.
  • the adhesive pad at the bottom of the main channel is composed of lOug / ml STA-650 (Dylight fluorescent dye).
  • the delay pad of the delay channel is 10ug / ml STA-550 (fluorescent dye of Dylight), PVP (Polyvinylpyrrolidone) with lOKDa 1% ( ⁇ / ⁇ ) concentration, 0.5% (v / v) type 3 ⁇ 4 active agent : Surfactant 10G) from fitzgerald was diluted in 1 ⁇ PBS (phosphate buffered saline) buffer and dried at 37 C with a volume of lOul.
  • PBS phosphate buffered saline
  • the adhesive pad placed at the bottom of the main channel and the buffer input area of the delay channel are input by using 1 X PBS buffer, and the time when the fluorescent dye flows out of the delay pad at l ffiin interval (DP flow) and the delay channel.
  • DP flow l ffiin interval
  • the asymmetric membrane of the delay pad is the latest.
  • GF with fluorescent dye and 0.45 were selected, and the final selection of GF with less than 10 minutes in which the existing fluid flowing through the main channel was pushed as a separate channel was selected.
  • Fluorescent dyes from delay pads were applied to selected GF asymmetric membranes.
  • GF was selected as an asymmetric membrane to be used as a delay pad.
  • Asymmetric membrane GF was used as the delay pad and the adhesive pad in the pattern structure of FIG. 6, and the rest was tested in the same conditions as Experimental Example 2, and the fluid flow was measured at 12-minute intervals.
  • the main channel is first driven by fluid in the adhesive pad. Flowed into the upper diagnostic area and passed through the delay pad from 2 minutes elapsed. As the fluid was introduced from the side of the main channel, the fluid that predominantly flowed the main channel began to be pushed to one side. The fluid passing through the adhesive pad pushed to one side was separated into the separation channel, and after 11 minutes had elapsed. In the upper diagnosis area of the main channel, only the fluid flowing from the delay channel was transferred, and the fluid passing through the adhesive pad was separated into the separation channel and flowed.

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Abstract

The present invention relates to a pattern structure of a diagnostic sensor, wherein the pattern is formed by printing an organic mixture on paper. More particularly, the present invention relates to a pattern structure of a diagnostic sensor, wherein the pattern structure enables detection and diagnosis to be performed by transferring two kinds of materials at different times so that the two materials react without interference from each other. For example, a first material and a second material can be transferred to a diagnosis area at different times by different fluid flows, and reaction of the second material can be induced in the diagnosis area without interference from the first material that was supplied earlier.

Description

명세서  Specification
발명의명칭:진단센서의패턴구조 기술분야  Name of invention: Pattern structure technology of diagnostic sensor
[1] 본발명은종이에유기흔합물을인쇄하여패턴을형성하는진단센서의  [1] The present invention relates to a diagnostic sensor for printing an organic compound on paper to form a pattern.
패턴구조에관한것으로,더상세하게는제 1물질과제 2물질이서로다른 유체흐름에의해시간차로진단영역에전달되고,진단영역에서는선행공급된 제 1물질의방해없이제 2물질의반웅을유도할수있는등 2종류의물질을 시간차에의해전달하여서로갚섭없이반웅하여검출및진단이 이루어지도록 하는진단센서의패턴구조에관한것이다.  With regard to the pattern structure, more specifically, the first material and the second material are transferred to the diagnosis area in time by different fluid flows, and in the diagnosis area, the reaction of the second material is induced without disturbing the first supplied material. It is about the pattern structure of the diagnostic sensor that delivers two kinds of materials by time difference and returns them without any repayment.
배경기술  Background
[2] 최근의학과의용공학의발전에:힘입어,다양한질병의원인및치료방법들이 소개됨은물론,각종질병에 대하여보다정확한진단이가능해지고있으며, 보다효과적이고안전한치료방법들이개발되어,질병의치료율이높아지고 있는추세이다.  [2] Recent advances in medical and medical engineering have led to the introduction of various causes and treatments, as well as more accurate diagnosis of various diseases and the development of more effective and safe treatments. The rate of treatment is increasing.
[3] 그럼에도불구하고,이러한질병의진단및치료는주로병원등에서  [3] Nevertheless, the diagnosis and treatment of these diseases is mainly carried out in hospitals.
이루어지게되는바,진단을받고자하는진단대상자의경우,직접 병원등을 방문하지않고서는질병의진찰및진단자체가아예불가능한문제점이 있었으며 ,이로인하여,진단대상자나환자의 입장에서는값비싼검사비 및 치료비를전적으로부담해야하는어려움이따랐다.  In the case of a diagnosis subject who wants to be diagnosed, there was a problem that the diagnosis and diagnosis of the disease could not be avoided without visiting the hospital directly. Therefore, expensive examination and treatment costs for the diagnosis subject or patient It was a total burden.
[4] 최근들어,전자산업및유무선통신망의발전으로인하여,상기와같은  [4] Recently, due to the development of the electronics industry and wired and wireless communication networks,
문제점과어려움을해결하기위한노력의 일환으로원격의료 (Telemedicin) 시스템이소개되고있다.이러한원격의료시스템은직접병원등을방문하지 않고서원격지에서비교적 저렴한비용으로진단대상자또는환자가진단을 받을수있는방식이지만,아직까지는대부분외형적인이상둥에대한진단만이 이루어지고있으며,그진단방법또한매우제한적일수밖에없어,정확한 진단이 행해지기에는많은어려움이따랐다.  As part of our efforts to solve problems and difficulties, the Telemedicin system has been introduced, which allows a patient or patient to be diagnosed at a remote location at a relatively low cost without visiting a hospital. However, until now, most of the external diagnosis has been made, and the diagnosis method can only be very limited, which makes it difficult to make an accurate diagnosis.
[5] 특히,생명에위협이될정도로문제가될수있는질병 (예 :각종암, AIDS등)은 대게병원균등의항원에의해감염및발병하게되는데,이러한질병의경우 신속한진단의선행이요구되는바,각종항원을비롯한바이오물질을진단할 수있는장치의개발이시급한실정이다.  [5] In particular, diseases that may cause problems such as life threats (eg, various cancers, AIDS, etc.) are usually infected and developed by antigens such as pathogens, which require prompt diagnosis. F. It is urgent to develop a device capable of diagnosing biomaterials including various antigens.
[6] 이에,전문지식이나복잡한과정이요구되지않고사용이간편하며수행시간이 짧은면역분석장치로서 ,멤브레인을사용한바이오센서가사용되고있다. ' 이러한바이오센서를이용한분석장치는일반적으로세공성멤브레인을 감웅단백질의고정화모체로사용하는면역크로마토그래픽방법을적용할수 있다.분석물질이포함된시료를멤브레인스트립하단으로부터흡수시키면 세공을통한모세관현상에의해분석물질은고정화된감웅단백질층으로 운반되어고체표면에서항원과항체간의부착반웅이야기되고비결합된 성분들은유체흐름에의해분리된다.이와같은원리에기초한멤브레인스트립 면역크로마토그래피기술은유체의측면흐름 (lateral flow)을이용하여 반웅성분들의물질전달을가속시킴으로써분석물질의측정신속성과단지시료 첨가만으로진단수행이완료€수있다. [6] A biosensor using membrane is used as an immunoassay device that is simple to use, short in execution time, without requiring specialized knowledge or complicated procedures. `` Analytical devices using these biosensors can generally use an immunochromatographic method that uses a porous membrane as the immobilization matrix for the protein.As the sample containing the analyte is absorbed from the bottom of the membrane strip, capillary The analyte is then immobilized into The transport and reaction between the antigen and the antibody on the solid surface and the unbound components are separated by the fluid flow. This principle-based membrane strip immunochromatography technique uses the lateral flow of the fluid to react the reaction components. By accelerating the delivery of these substances, diagnostics can be completed simply by adding the analyte to the measurement speed and adding the sample.
[7] 최근이러한바이오센서는멤브레인위에왁스,파라핀등으로채널등을 [7] Recently, these biosensors use wax, paraffin, etc. on the membrane to feed channels.
프린팅하여제작하는연구가진행되고있으나,이는멤브레인상에다중패턴을 형성할시온도와압력에 영향및유체의흐름에의해영향을받아검출신뢰도가 떨어지는문제가있다.  Although research is being conducted on printing, it has a problem that the reliability of detection decreases due to the influence of temperature and pressure and the flow of fluid when forming multiple patterns on the membrane.
[8] 한국공개특허특 2002-0078032호 (2002.10.18.공개;이하'선행문헌 1'이라 [8] Korean Patent Laid-Open No. 2002-0078032 (published Oct. 18, 2002; hereafter referred to as Priority Document 1).
함)에서는 '비임신진단키트및이를이용한동물의 비임신진단방법'을 제시하였다.상기선행문헌 1의진단키트는,다공이형성된박막형페이퍼의 한쪽말단부에프로게스테론-소혈청알부민결합체 (progesterone-BSA conjugate)가코팅되어 있고,다른한쪽말단부에대조선으로  The non-pregnancy diagnosis kit and the non-pregnancy diagnosis method of an animal using the same are presented in the above-mentioned document. conjugate) and the other end of the
면역글로불린지 (IgG)를고정시킨분석스트립;및항프로게스테론  Assay strips immobilized with immunoglobulin (IgG); and antiprogesterone
면역글로불린지-금라벨접합체 (anti-progesterone IgG-gold conjugate)로 구성되었다.상기선행문헌 1은시료투입위치에반웅물질을미리흔합한시료를 투입하여모세관현상에의해시료가진행되면서프로게스테론-소혈청알부민 결합체인진단선을통과하면서반웅이이루어져발색이 이루어지게함으로써 진단이이루어지도록한것이나,시료에다양한반웅물질을흔합하여 진단선에서의진단반웅이 이루아지므로,물질간간섭에의해검출감도가 낮아지거나비특위적반웅이발생되어진단오류가발생될수있다.  The immunoglobulin-gold label conjugate (Anti-progesterone IgG-gold conjugate) was made. Diagnosis is achieved by passing reactions through the serum albumin conjugate diagnostic line, which results in color development, or by mixing various reaction substances in the sample to make the diagnosis response on the diagnosis line. Diagnostic errors may occur due to low or non-specific reactions.
[9] 한국등록특허제 10-1412777호 (2014.06.20.공개;이하 '선행문헌 2'이라  [9] Korean Patent Registration No. 10-1412777 (published June 20, 2014; hereafter referred to as Priority Document 2)
함)에서는 '다성분동시정량분석용측방유동디바이스'를제시하였다.상기 선행문헌 2의측방유동디바이스는,분석하고자하는유체샘플을수용하는샘플 패드 (sample pad);상기샘플패드와접촉하여배치되며,상가유체샘플내에 포함된서로다른타켓분석물과결합하는제 1바인더가코팅된  The lateral flow device for multi-component simultaneous quantitative analysis is presented. The lateral flow device of the prior document 2 includes: a sample pad for receiving a fluid sample to be analyzed; and placed in contact with the sample pad. Coated with a first binder that binds to different target analytes contained within the fluid sample.
나노스피어 (nanosphere)를포함하는접합체패드 (conjugate pad);및상기접합체 패드와접촉하여배치되며,상기유체샘플이유동할수있는분지된채널 패턴이 형성된패턴시트 (patterned sheet)를포함하되,상기채널패턴은종이 재질의베이스부재 (base member)상에잉크젯프린팅방식을이용하여패턴 물질을분사하여형성된다.상기선행문헌 2는채널패턴이 1개의채널에서 3개의채널로분기되는형태의채널을제시하여유체샘플이 1개의채널로. 진행하면서다수개로분기되어진행하고,각분기된채널에는서로다른 반웅물질을도포하여한번에다수개의진단이가능하게하는것으로,물질간 간섭에의해검출감도가낮아지거나비특위적반웅이발생되어진단오류가 발생되는단점은해소하지못하였다. 발명의상세한설명 A conjugate pad comprising nanospheres; and a patterned sheet disposed in contact with the conjugate pad, the patterned sheet having a branched channel pattern on which the fluid sample can flow, wherein the channel pattern includes: The pattern material is formed by spraying a pattern material on the base member of silver paper using inkjet printing. The above-mentioned document 2 shows a channel in which a channel pattern is branched from one channel to three channels. Fluid sample into one channel. As the process progresses, it is divided into several parts, and each branched channel contains different reaction materials so that multiple diagnosis can be performed at one time.As a result, the detection sensitivity is lowered or non-specific reactions are caused by the interference between materials. The disadvantage that occurred was not solved. Detailed description of the invention
기술적과제  Technical task
[10] 이에본발명의진단센서의패턴구조는, [10] The pattern structure of the diagnostic sensor of the present invention is
[11] 종이에유기물질을프린트하는바이오센서인진단센서분야에서검출에의한 진단영역에전달되는타켓물질이포함된시료나,신호증폭물질을포함하는 다수의반웅물질을시간차에의해전달되도록하여반웅시다른물질에의한 간섭없이각각의반웅이층실하게이루어지도록하여검출감도를향상시킬수 있는패턴구조의제공을목적으로한다.  [11] In the diagnostic sensor field, which is a biosensor for printing organic materials on paper, a sample containing a target material delivered to a detection area by detection, or a plurality of reaction materials including a signal amplification material can be delivered over time. Therefore, the object of the present invention is to provide a pattern structure that can improve detection sensitivity by allowing each reaction to be performed in a substantial manner without interference from other materials.
과제해결수단  Task solution
[12] 상기과제를달성하기위한본발명의진단센서의패턴구조는,  [12] The pattern structure of the diagnostic sensor of the present invention for achieving the above object is
[13] 종이에인쇄기술을이용하여채널을형성한진단센서의패턴구조에 있어서, 상하방향으로길게형성되어하부에서상부로유체가유동되도록하고,하부의 단부에는시료를투입하는시료투입영역이형성되고,상부의단부에는 검출물질이코팅되는진단영역이형성되며,중간부분에는다른채널과 연결되는교차영역이형성된메인채널과;상기메인채널의 일측에나란히 형성되되,주이동영역인지연유동영역과상기지연유동영역하단과이격되어 버퍼가투입되는버퍼투입영역을분리구성하고,지연패드로두영역을연결해 버퍼가메인채널로전달되는시간이지연되도록하고,상부는메인채널 방향으로꺾인제 1절곡부가형성되어상단이메인채널의교차영역에연통되는 합류부가형성된지연채널과;상기메인채널의양측중지연채널과대향되는 측면에나란히형성되되,하부는메인채널방향으로꺾인제 2절곡부가형성되어 하단이메인채널의교차영역에 연통되는분리부가형성된분리채널;을 포함하여구성된다. [13] A pattern structure of a diagnostic sensor in which a channel is formed using a printing technique on paper, which is formed to be long in the vertical direction so that fluid flows from the lower part to the upper part. A main channel having a diagnostic region coated with a detection material at an upper end thereof, and having an intersecting area connected to another channel at a middle portion thereof; and a main channel formed side by side on the main channel; A buffer input area into which a buffer is inserted is separated from the area below the delayed fluidized area, and the buffer input area is connected to each other by a delay pad, so that the time delay for transferring the buffer to the main channel is delayed. A delayed channel having a bent portion formed therein and having a confluence formed therein, the upper portion of which is connected to an intersection region of the main channel; The separation channel portion is formed separated in communication with the cross-area of the main channel is added to the bottom of the second bending direction angled to the main channel formed; is configured to include a.
[14] 상기제 1절곡부와제 2절곡부는절곡된부분이곡면으로형성될수있다.  The first bent portion and the second bent portion may be formed with curved surfaces.
[15] 또한,상기메인채널폭은 3~4mm로형성하고,상기지연채널은제 1절곡부와 합류부사이의길이를 3~4mm로형성하고,상기분리채널은제 2절곡부와분리부 사이의길이를 l~2mm로형성할수있다. In addition, the main channel width is formed to be 3 ~ 4mm, the delay channel is formed in the length between the first bent portion and the joining portion 3 ~ 4mm, the separation channel is between the second bent portion and the separation portion The length of can be formed into l ~ 2mm.
[16] 또한,상기지연채널은제 1절곡부와합류부사이의길이가지연채널폭의The delay channel may include a length of the delayed channel width between the first bent portion and the joining portion.
1-1.5배길이로형성하고,상기분리채널은제 2절곡부와분리부사이의길이.가 메인채널폭의 0.3~0.5배길이로형성되는것을간격으로메인채널과이격될수 있다. The separation channel may be formed to be 1-1.5 times long, and the separation channel may be spaced apart from the main channel at intervals such that the length between the second bend and the separation part is 0.3 to 0.5 times the main channel width.
[17] 또한,상기메인채널의교차영역은분리부를합류부상부에위치시키되,상기 분리부는합류부를형성하는지연채널의연장된부분과교차되는지점으로부터 형성될수있다ᅳ  In addition, the intersecting area of the main channel may be formed from a point where the separating part is positioned above the confluence part, and the separating part forms a confluence part or intersects with an extended part of the extended channel.
[18] 또한,상기지연채널의제 1절곡부에서합류부사이부분과,상기분리채널의 분리부와제 2절곡부사이부분은메인채널과직교되는방향으로형성될수 있다. [19] 또한,상기분리채널의분리부는하단에는합류부가시작되는지점과대향되는 지점으로부터제 2절곡부가시작되는지점까지확관된확관부가형성될수있다. In addition, the portion between the confluence portion in the first bent portion of the delay channel and the portion between the separation portion and the second bent portion of the separation channel may be formed in a direction perpendicular to the main channel. In addition, the splitter of the splitter channel may have an extended part formed at a lower end of the splitter channel extending from the point opposite to the point where the joining part starts to the second bent part.
[20] 또한,상기지연채널은제 1절곡부에서합류부방향으로상향경사를갖도록 형성하고,상기분리채널은분리부에서제 2절곡부방향으로상향경사를갖도록 형성할수있다.  The delay channel may be formed to have an upward slope in the direction of the joining portion at the first bent portion, and the separation channel may be formed to have an upward slope in the direction of the second bend portion at the separation portion.
[21] 또한,상기메인채널과연통된지연채널의상부벽에는메인채널중심방향으로 돌출된돌출부를더형성하여지연채널에서합류하는유체를메인채널 중심방향으로더내입되어유동되도록할수있다.  In addition, an additional protrusion protruding in the center direction of the main channel may be further formed on the upper wall of the delay channel communicating with the main channel so that the fluid that joins the delay channel is further introduced into the main channel center direction and flows.
[22] 또한,상기메인채널은교차영역에서하단까지의길이를 2~5mm로형성해 In addition, the main channel has a length of 2 to 5 mm from the intersection to the bottom thereof.
시료투입영역을제거하고,메인채널하단에접합패드를일부분겹치도록 안치하여시료투입영역을대체하도록할수있다.  The sample dosing area can be removed and the sample dosing area replaced by a partial overlap of the bond pads at the bottom of the main channel.
[23] 또한,상기메인채널은교차영역과진단영역사이에서교차영역과근접한 In addition, the main channel is adjacent to the intersection area between the intersection area and the diagnosis area.
부분에채널을분리시키는분리영역을더형성하고,접합패드에의해  Form a separation area to separate the channel in the portion, and by the bonding pad
분리영역의상하부가연결되도록할수있다.  The top and bottom of the separation zone can be connected.
발명의효과  Effects of the Invention
[24] 상기해결수단에의한본발명의진단센서의패턴구조는,  [24] The pattern structure of the diagnostic sensor of the present invention by the above solving means,
[25] 패턴구조를변경하여시료와반웅물질이시간차를갖으면서검출영역에  [25] By changing the pattern structure, the sample and reaction material have a time difference,
전달되도록함으로써타겟물질의고정화과정과고정화된타겟물질과반웅하여 발광또는발색이이루어지는검출과정이분리하여 이루어지게한것이다.  By transmitting the target material, the process of fixing the target material and the immobilized target material react with each other so that the detection process of luminescence or coloration is performed separately.
[26] 이는시료와반웅물질을동시에검출영역에전달하여각물질간간섭에의해 검출감도가낮아지는기존패턴구조의단점을시간차공급으로개선시킴으로써 검출감도를향상시킬수있고,다양한물질올순차적으로분리공급이 [26] This can improve the detection sensitivity by passing the sample and reaction material to the detection area at the same time and improving the end point of the existing pattern structure whose detection sensitivity is lowered due to the interference between the materials by supplying the time difference, and separating various substances sequentially. Supply
가능함으로흔합공급에의해발생되는비특위적반웅을최소화하여정확하고 정밀한진단이이루어질수있는패턴구조의제공이가능하게되었다.  It is possible to provide a pattern structure in which accurate and precise diagnosis can be made by minimizing non-specific reactions caused by the mixed supply.
도면의간단한설명  Brief description of the drawings
[27] 도 1내지도 7b는본발명의바람직한실시예에따른패턴구조를도시한 1 to 7b show a pattern structure according to a preferred embodiment of the present invention.
평면도.  Floor plan.
[28] 도 8은본발명의실시예에따른다양한패턴구조를나타낸평면도.  8 is a plan view showing various pattern structures according to an embodiment of the present invention.
[29] 도 9는본발명의실시예에따른다양한패턴에따른유체흐름과정을나타낸 사진. 9 is a photograph showing a fluid flow process according to various patterns according to an embodiment of the present invention.
[30] 도 10은본발명의실시예에따른다양한지연패드의유속과유량을측정한 결과를나타낸그래프.  10 is a graph showing the results of measuring the flow rate and flow rate of various delay pads according to the embodiment of the present invention.
[31] 도 11은본발명의실시예에따른선정된지연패드의유속과유량을반복 11 repeats the flow rate and flow rate of a selected delay pad according to an embodiment of the present invention.
실험한결과를나타낸그래프.  Graph showing the results of the experiment.
[32] 도 12는본발명의실시예에따른형광물질을이용하여디자인과시간차이에 의한유체흐름과정을측정한사진. 12 is a photograph illustrating a fluid flow process based on a design and time difference using a fluorescent material according to an embodiment of the present invention.
발명의실시를위한최선의형태 [33] 이하첨부된도면을참조하여본발명을보다상세히설명한다.그러나첨부된 도면은본발명의기술적사상의내용과범위를쉽게설명하기위한예시일뿐, 이에의해본발명의기술적범위가한정되거나변경되는것은아니다.또한 이러한예시에기초하여본발명의기술적사상의범위안에서다양한변형과 변경이가능함은당업자에게는당연할것이다. Best Mode for Carrying Out the Invention [33] The present invention will be described in more detail with reference to the accompanying drawings. However, the accompanying drawings are only illustrative of the technical spirit and scope of the present invention, and the technical scope of the present invention is limited thereto. It will be appreciated by those skilled in the art that various modifications and variations are possible within the scope of the technical idea of the present invention based on these examples.
[34]  [34]
[35] 도 1은본발명의바람직한실시예에따른프린팅에의해패턴구조를도시한 평면도이다.  1 is a plan view showing a pattern structure by printing according to a preferred embodiment of the present invention.
[36] 참조한바와같이본발명에따른패턴구조 (10)는종이에 인쇄기술에의해  [36] As can be seen, the pattern structure according to the present invention (10) is based on paper printing technology.
유기용매를코팅하여형성하는것으로,스크린프린팅등다양한방법에의해 제작될수있다.이때사용되는종이로는유체를유동시키는다양한종류가 사용될수있으며,바람직하게는 NC멤브레인 (Nitrocellulose membrane;  It is formed by coating an organic solvent, and can be produced by various methods such as screen printing. In this case, various kinds of fluid flow can be used, and NC membrane (Nitrocellulose membrane;
'MILLIPORE'사제품 ) -Based(75, 95, 120, 180, 240)s에서선택하여사용한다.  'MILLIPORE' product) -Based (75, 95, 120, 180, 240) s to select and use.
[37] 제작된패턴구조 (10)는시료투입영역 (21)과진단영역 (22)이형성된  [37] The fabricated pattern structure 10 includes a sample injection zone 21 and a diagnosis zone 22 formed therein.
메인채널 (20)과,유체를일정시간지연시킨다음메인채널에합류시키는 지연채널 (30)과,메인채널의유동물질을분리진행시키는분리채널 (40)을 포함하여구성된다.  And a main channel 20, a delay channel 30 for delaying the fluid for a certain time and then joining the main channel, and a separation channel 40 for separating the fluid of the main channel.
[38] 상기메인채널 (20)은상하길이방향으로길게형성된형태로일측에는  The main channel 20 is formed to be long in the vertical direction, and at one side thereof.
시료투입영역 (21)을형성하고대향되는타측:단부에는진단영역 (22)을형성하여 유체가시료투입영역에서진단영역으로유동되도록한다.본발명의도 1에서는 메인채널의하측단부에검색타겟이포함된시료를투입하는  The sample injection zone 21 is formed and the opposite side: a diagnostic zone 22 is formed at the end to allow fluid to flow from the sample injection zone to the diagnostic zone. In FIG. 1, a search target is provided at the lower end of the main channel. To insert a sample containing
시료투입영역 (21)을형성하고,대향되는상측단부에검출물질이코팅되는 진단영역 (22)을형성하여유체가하부에서상부방향으로유동하도록한다.또한, 상기메인채널 (20)은시료투입영역 (21)으로투입된시료가모세관현상으로 상부로유동되는구간중중간부분에교차영역 (23)이형성되어다른채널과 연통되도록한다.상기교차영역 (23)에서는다른채널로부터유체를유입받거나, 메인채널내의유체를분리하여배출시킨다.  A sample injection zone 21 is formed, and a diagnostic zone 22 in which the detection material is coated on the opposite upper end is formed so that the fluid flows from the lower part to the upper direction. An intersecting region 23 is formed in the middle portion of the section in which the sample introduced into the region 21 flows upward to the capillary phenomenon so as to communicate with another channel. In the intersecting region 23, fluid is introduced from another channel or the main The fluid in the channel is separated and drained.
[39] 상기지연채널 (30)은,메인채널의하부측면에나란하배치되는것으로,버퍼가 투입되는하단의버퍼투입영역 (32)은지연채널의주이동영역인  The delay channel 30 is arranged side by side on the lower side of the main channel, and the lower buffer input area 32 into which the buffer is inserted is the main movement area of the delay channel.
지연유동영역 (31)으로부터분리되어구성된다.상기지연채널 (30)의  It is configured separately from the delay flow region 31. The delay channel 30
버퍼투입영역 (32)과지연유동영역 (31)은별도의지연패드 (50)를이용하여:  The buffer input area 32 and the delay flow area 31 use separate delay pads 50:
연결시킴으로써:버퍼투입영역 ί(32)으로투입된버퍼가지연패드 (50)를  By connecting: Buffer delay pad 50 inserted into buffer input area ί 32
통과하면서유동시간이증가되고최종적으로는시간차를갖고메인채널 (20)에 합류하게된다.  Passage increases the flow time and finally joins the main channel 20 with a time difference.
[40] 이러한지연채널 (30)은상부가메인채널방향으로꺾인제 1절곡부 (33)가  [0040] The delay channel 30 includes a first bending portion 33 whose upper portion is bent in the main channel direction.
형성되고,지연채널의상단이메인채널의교차영역 (23)과연통된다.상기 지연채널과메인채널의 연통부분을합류부 (34)라한다.  The upper end of the delay channel is in communication with the intersecting area 23 of the main channel. The communicating portion of the delay channel and the main channel is called a confluence part 34.
[41] [42] 다음으로상기분리채널 (40)은,메인채널의상부와나란히배치되고,하부는 제 2절곡부 (41)에의해메인채널방향으로꺾이고,하단은메인채널의 교차영역 (23)과연통된다.상기 연통된부분을분리부 (42)라한다. [41] Next, the separation channel 40 is arranged side by side with the upper portion of the main channel, the lower portion is bent in the main channel direction by the second bent portion 41, and the lower portion is connected to the intersection region 23 of the main channel. The communicated portion is referred to as a separator 42.
[43] 이러한분리채널 (40)은메인채널 (20)의 일측에형성되되지연채널이 형성된 방향과대향되는방향에위치하여후술되는지연채널 (30)로부터유체가 메인채널로유입되면메인채널 (20)을통해유동하던유체가분리채널 (40)로 밀려나분리되어진행되도록한다.  The separation channel 40 is formed on one side of the main channel 20, but is located in a direction opposite to the direction in which the delay channel is formed. When the fluid is introduced into the main channel from the delay channel 30, the main channel ( 20), the flowing fluid is pushed to the separation channel 40 and separated to proceed.
[44]  [44]
[45] 상기한바와같이게 1절곡부 (33)와제 2절곡부 (41)는도 2를참조한바와같이 유체가유동되는방향을전환하는과정에서유속이저하되는것을최소화하기 위해곡면으로형성하는것이바람직하다.  As described above, the first bent portion 33 and the second bent portion 41 are formed in a curved surface to minimize the flow velocity in the process of switching the fluid flow direction as shown in FIG. 2. It is desirable.
[46]  [46]
[47] [47]
[48] 아울러상기메인채널 (20)과지연채널 (30)및분리채널 (40)은도면의상하로 형성된부분으로각 3~5mm의폭으로형성하고,상기지연채널 (30)의 제 1절곡부 (33)와합류부 (34)사이는 1.5~2.5mm의폭으로형성하고,상기 분리채널 (40)의제 2절곡부 (41)와분리부 (42)사이는 1.5~2.5mm의폭으로 형성한다.  In addition, the main channel 20, the delay channel 30 and the separation channel 40 is formed in a width of 3 to 5mm each formed in the upper and lower portions of the drawing, the first bent portion of the delay channel 30 Between the 33 and the confluence portion 34 is formed in a width of 1.5 ~ 2.5mm, and between the second bent portion 41 and the separating portion 42 of the separation channel 40 is formed in a width of 1.5 ~ 2.5mm.
[49] 상기메인채널과지연채널및분리채널의폭은 3mm이하로형성하면  [49] The width of the main channel, the delay channel, and the separation channel should be less than 3mm.
유동되는속도가증가되어시료투입후반웅개시까지의시간이짧아분리된 환경에서의 2단반웅을시행하기어려우며,각채널의혹이 5mm이상으로 형성하면투입된시료및용액이채널을따라진단영역까지전달되기위해서큰 용량을요구하고있으므로,상기범위로형성하는것이바람직하다.  It is difficult to carry out two-stage reactions in a separated environment because the flow rate increases and the time from the introduction of the sample to the reaction is short.If the channel of each channel is formed to be 5 mm or more, the injected sample and solution are transferred to the diagnosis area along the channel. In order to require large capacity, it is preferable to form the above range.
[50] 또한,상기지연채널 (30)은버퍼투입영역 (32)을통해공급된유체가  In addition, the delay channel 30 is a fluid supplied through the buffer injection region (32)
상부방향으로유동하다가제 1절곡부 (33)에서메인채널 (20)방향으로진행이 꺾인다음메인채널로합류가이루어지는데,수직으로배열된메인채널과 지연채널사이의 이격간격인제 1절곡부 (33)와합류부 (34)사이길이는메인채널 폭에 대해 0.5~1배의 :길이로형성하는것이바람직하다.예컨대메인채널폭이 4mm로형성하면,제 1절곡부 (33)와합류부 (34)사이길이는 3~4mm범위로 형성한다.상기제 1절곡부 (33)와합류부 (34)사이의길이가 3mm이하의길이로 형성되면지연채널 (30)에서유동되는유체가합류부 (34)를통해안정적인 수평층류로전달되지못하여지연채널로유동되는유체와메인채널로유동되는 유체간흔합이발생될수있고,제 1절곡부 (33)와합류부 (34)사이의길이가 4mm 이상으로형성할경우에는안정적인층류상태로메인채널로유입이가능하나 채널구조자체의폭방향사이즈를증가시키는단점이 았으므로,제 1절곡부와 합류부사이의길이는 3~4ram의범위로형성하는것이바람직하다.  Flowing upward, the first bending section 33 breaks the direction toward the main channel 20, and then joins the main channel, and the first bending section, which is a spaced interval between the vertically arranged main channel and the delay channel, The length between the convex part 34 and the convex part 34 is preferably 0.5 to 1 times the width of the main channel width. For example, when the main channel width is formed to be 4 mm, The length between the first and second bent portions 33 and 34 is less than or equal to 3 mm, and the fluid flowing in the delay channel 30 is joined. Failure to pass through the part 34 to a stable horizontal laminar flow can result in a mismatch between the fluid flowing into the delay channel and the fluid flowing into the main channel, and the length between the first bend part 33 and the confluence part 34 In case of forming more than 4mm, it is possible to flow into the main channel in stable laminar flow state, but the width of the channel structure itself is Since a disadvantage that the brushed, it joined to the first bent part of the length thereof vice is preferably formed over 3 ~ 4ram within the range.
[51]  [51]
[52] [53] 또한,상기지연채널 (30)은합류부 (34)와거 1 1절곡부 (33)사이의채널구간폭올 저 U절곡부 (33)와지연채널 (30)하단사이의채널구간폭보다작은폭으로 형성하여메인채널로합류하는유체의미는힘을더욱증대시킬수있다.예컨대 합류부 (34)와제 1절곡부 (33)사이의폭은 1.5~2.5mm로형성하여메인채널로 합류하는유체의유속을증가시켜합류하는유체가기존메인채널을 [52] In addition, the delay channel 30 is less than the channel interval width between the lower portion of the U bend 33 and the delay channel 30 between the confluence portion 34 and the bend portion 33. The meaning of the fluid that is formed in a small width to join the main channel can further increase the force. For example, the width between the confluence 34 and the first bend 33 is 1.5 to 2.5 mm to form a fluid that merges into the main channel. To increase the flow rate of the
주도적으로흐르던유체를일측으로밀어내는힘이증가하도록한다.이때 1.5mm이하로형성할경우메인채널을유동하는유체의유속과합류부를통해 유입하는유체의유속차이가커서미는것이아닌흔합이이루어지는문제점이 있고, 2.5mm이상으로형성할경우에는합류부로유입되는유체의유속아낮아 기존메인채널을유동하는유체를미는힘이낮아지므로상기범위로폭을 형성하는것이바람직하다.  Increasing the force to push the flowing fluid to one side leads to an increase in the flow rate of the fluid flowing through the main channel and the flow rate of the fluid flowing through the confluence of the main channel. In the case of forming more than 2.5 mm, it is preferable to form the width in the above range because the flow velocity of the fluid flowing into the joining portion is low, and the force pushing the fluid flowing through the existing main channel is low.
[54] 상기분리채널 (40)은수직으로배열된메인채널과분리체널사이의  The separation channel 40 is disposed between the vertically arranged main channel and the separation channel.
이격간격인제 2절곡부 (41)와분리부 (42)사이의길미를메인채널폭에대해 The distance between the second bend portion 41 and the separation portion 42, which is the separation interval,
0.3-0.5배의길이로형성할수있다.예컨대메인채널폭이 3~5mm인 4mm내외일 경우제 2절곡부 (41)와분리부 (42)사이의길이는 l~2mm로형성할수있다.상기 제 2절곡부 (41)와분리부 (42)사이의길이가 lmm이하일경우에는 For example, when the main channel width is about 4 mm (3 to 5 mm), the length between the second bent portion 41 and the separating portion 42 may be 1 to 2 mm. If the length between the second bent portion 41 and the separating portion 42 is less than lmm
메인채널 (20)로공급된시료유체가상부로이동되면서분리채널 (40)로 배출되는량이증가되어메인채널상부에위치하는진단영역 (22)으로의시료가 유동되는량이줄어드는단점이 있다.또한,메인채널 (20)을유동하는유체는 합류부 (34)에서배출되는지연채널의유체에의해분리부 (42)방향으로밀려나 상향유동에서대각선방향으로의유동이이루어져분리부를통해  As the sample fluid supplied to the main channel 20 is moved upward, the amount of discharged to the separation channel 40 increases, thereby reducing the amount of sample flow to the diagnostic region 22 located above the main channel. The fluid flowing through the main channel 20 is discharged from the confluence part 34 or pushed toward the separation part 42 by the fluid of the soft channel, and flows in a diagonal direction from the upward flow to the separation part.
분리채널 (40)로분리하여진행된다.이때제 2절곡부 (41)와분리부 (42)사이의 길이가 2mm이상으로길게형성되면대각선방향으로유동되는유체는 분리채널벽에부딪친다음수평방향으로의유동이 이루어지므로분리부 내부로유입되는과정에서상당한저항이발생된다.이러한저항은분리부로 진입하는유체로도전달되 :어유체의진입을일부방해함으로상당량은 분리채널로분리되지않고메인채널을따라지연채널에서합류된유체와함께 유동되어진단에영향을미치게되므로,상가제 2절곡부 (41)와분리부 (42) 사이의길이는 l~2mm범위내로형성하는것이바람직하다. In this case, when the length between the second bent portion 41 and the separation portion 42 is longer than 2 mm, the fluid flowing in the diagonal direction strikes the separation channel wall, and then the horizontal direction. this considerable resistance in the process of the flow of the to be done because the inflow into the separation unit is generated such resistance is also fluid entering portion separated delivered: a significant amount by control fluid portion interfere with the entry of the main channel is not divided into separate channels Therefore, it is preferable that the length between the second bend portion 41 and the separation portion 42 is within the range of 1 mm to 2 mm because it affects the diagnosis flowed with the fluid joined in the delay channel.
[55] 또한,분리채널 (40)의분리부 (42)와제 2절곡부 (41)사이의폭은메인채널의 폭에대해 0.5~1.5배비율로형성하며,메인채널이 3~5mm인 4mm내외의폭으로 형성함으로제 2절곡부와분리부사이의폭은 2~6mm의폭으로형성하는것이 바람직하다.상기제 2절곡부와분리부사이의폭이 2mm이하로형성될경우 메인채널에서흐르는유체가지연채널에서합류된유체에의해밀려나서 분리부로전량유입되기어려우며, 6mm이상으로형성할경우에는  In addition, the width between the separation section 42 and the second bent section 41 of the separation channel 40 is formed at a ratio of 0.5 to 1.5 times the width of the main channel, and 4 mm with the main channel 3 to 5 mm. Since the width between the second bent portion and the separating portion is 2 to 6 mm, the width between the second bent portion and the separating portion is preferably 2 mm or less. It is hard to flow into the separation part by being pushed by the fluid joined in the delay channel, and when formed over 6mm
지연채널에서유체가합류하지않아도메인채널로유동되는유체가분리채널로 진행되는량이증가되어분석물질을포함하는시료의투입량을다량  Even if the fluid does not merge in the delay channel, the amount of fluid flowing into the main channel proceeds to the separate channel, thereby increasing the amount of sample containing the analyte.
요구함으로상기범위로형성하는것이바람직하다ᅳ [57] 아을러상기메인채널 (20)의교차영역 (23)에형성된지연채널의합류부 (34)와 분리채널의분리부 (42)는상하이격된위치에위치되도록한다. It is preferable to form the above range as required. In addition, the confluence part 34 of the delay channel formed in the intersecting area 23 of the main channel 20 and the separation part 42 of the separation channel are located at positions spaced apart from each other.
[58] 즉,메인채널 (20)의유체는하부에서상부로유입되고,합류부 (34)에서유입된 유체에의해밀려나분리부 (42)로분리배출되어야함으로,유체의이동방향에 따라먼저합류부 (34)가메인채널 (20)과연통되어형성되고,합류부보다상부에 분리부 (42)가연통되도록함으로써함류부쪽에위치한메인채널의유체가 분리부쪽인대각선맣향으로이동하여분리배출이 이루어지도록한것이다.  That is, the fluid of the main channel 20 is introduced from the lower part to the upper part, and must be discharged by the fluid introduced from the confluence part 34 to be separated and discharged to the separating part 42. The confluence part 34 is formed in communication with the main channel 20, and the separation part 42 communicates with the upper part of the confluence part so that the fluid of the main channel located on the condensing part moves in a diagonal direction toward the separation part and discharges. This is done.
[59] 이때상기분리부 (42)의 형성위치는메인채널측벽증합류부 (34)의상부측을 수평으로연장했을때의교차되는지점으로부터분리부가형성되도록하여 메인채널의수직유동유체와합류부에서의수평유동유체가동일한유속으로 부딪쳐이동될때수직유동유체가대각선방향으로이동하여분리부로 분리배출이 이루어지도록한다.  At this time, the forming position of the separating section 42 is formed so that the separating section is formed from the intersection point when the upper side of the main channel side wall consolidation section 34 is extended horizontally so that the vertical flow fluid and the joining section of the main channel are formed. When the horizontal fluid flows at and collides at the same flow rate, the vertical fluid flows in a diagonal direction so that it is separated and discharged to the separator.
[60]  [60]
[61] 이와같이상기지연채널 (30)의제 1절곡부 (33)와합류부 (34)사이부분과,상기 분리채널 (40)의분리부 (42)와제 2절곡부 (41)사이부분은메인채널 (20)과 직교되는방향으로형성하여,합류부에서수평으로유입되는유체가 메인채널을상향이동하는유체를측면으로미는힘을최대로높일수있다.  Thus, the portion between the first bent portion 33 and the confluence portion 34 of the delay channel 30, and the portion between the separation portion 42 and the second bent portion 41 of the separation channel 40 are main Formed in a direction orthogonal to the channel 20, the fluid flowing horizontally at the joining portion can maximize the force that pushes the fluid moving up the main channel to the side.
[62] 여기서도 3을참조한바와같이상기분리채널의분리부 (42)하단에는확관이 이루어진확관부 (43)가형성되도록하여,합류부에서유입된유체에밀린 메인채널의 이동유체가용이하게분리채널로유입되도록할수있다.상기 확관부 (43)는합류부 (34)가시작되는지점과대향되는면으로부터  As shown in FIG. 3, the expansion channel 43 is formed at the bottom of the separation channel 42 of the separation channel so that the moving fluid of the main channel driven by the fluid introduced from the confluence unit can be easily separated. The expansion portion 43 may be introduced into the channel.
제 2절곡부 (41)가시작되는부분까지확관이 이루어지도록하여합류부로부터의 유체밀림이시작되는위치부터확관이 이루어지게할수있다.  Expansion can be made to the portion where the second bent portion 41 starts, so that expansion can be made from the position where the fluid push from the confluence portion starts.
[63]  [63]
[64] 아울러도 4를참조한바와같이상가지연채널의제 1절곡부 (33)과합류부 (34) 사이와,상기분리채널의분리부 (42)와제 2절곡부 (41)사이는상향경사를갖도록 형성할수있다.  In addition, as shown in FIG. 4, the upward inclination between the first bend portion 33 and the confluence portion 34 of the phase delay channel, and between the separation portion 42 and the second bend portion 41 of the separation channel. It can be formed to have.
[65] 즉,메인채널 (20)을유동하는유체는하부에서상부로유동이이루어지므로, 합류부 (34)를통한지연채널으로부터의유체유입으로메인채널을유동하는 유체의유속이저하되는것을최소화하기위해수직이아닌경사방향으로 합튜가이루어지게할수있다.이 때상기메인채널과형성하는상향경사 각도로는측면밀림을발생시킬수있는 30 이상의각도로형성하며,합류에 의한유속의급격한저하를방지하도록 60 이하로형성할수있다.  That is, since the fluid flowing through the main channel 20 flows from the lower part to the upper part, the flow rate of the fluid flowing through the main channel decreases due to the fluid inflow from the delay channel through the confluence part 34. In order to minimize, it can be merged in a non-vertical inclination direction, and the upward inclination angle formed with the main channel is formed at an angle of 30 or more that can cause side sliding, and prevents a sudden drop in flow rate due to confluence. It can be formed below 60 so that
[66] 이와같이합류부를형성하는지연채널부위를경사지게형성하면 [66] By forming the confluence or slanting the channel portion in this way
지연채널에서배출되는유체에의해메인채널을상향통과하는유체가측면으로 밀라는정도가낮아짐으로,분리부에서의분리배출이용이하게이루어지지 않을수있다. [67] 따라서,도 5를참조한바와같이지연채널 (30)은합류부 (34)를형성하는 상부벽이메인채널방향으로일정폭돌출된돌출부 (35)를더형성하여, 지연채널에서합류하는유체가메인채널중심방향으로더내입되도록하여 메인채널로유동되는기존유체가측면으로층분히밀려나게할수있다.상기 돌출부 (35)는메인채널폭의 0.2~0.4배비율로돌출된다.상기으2배이하로 돌출되면메인채널중심방향으로내입되는정도가낮아돌출부를형성하는 . 정도가낮고, 0.4배이상으로돌출시키면과도한돌출에의해합류부를통해 메인채널로유입된유체가메인채널의하부에서상부로수직유동하는유체와 흔합되는문제점이발생될수있으므로돌출부는상기범위내로돌출시키는 것이바람직하다. The fluid discharged from the delay channel is less likely to push the main channel upwards to the side, so that separate discharge at the separation part may not be easily achieved. Therefore, as shown in FIG. 5, the delay channel 30 further includes a protrusion 35 in which the upper wall forming the confluence part 34 has a predetermined width in the main channel direction, and joins in the delay channel. By allowing the internal fluid to flow further into the main channel center direction, the existing fluid flowing into the main channel can be evenly pushed to the side. The protrusion 35 is projected at a ratio of 0.2 to 0.4 times the width of the main channel. When protruding below, the degree of penetration into the main channel center direction is low, forming a protruding portion. If the accuracy is low and projected more than 0.4 times, excessive projection may cause a problem that the fluid introduced into the main channel through the confluence may be mixed with the fluid vertically flowing from the bottom of the main channel to the projection. It is desirable.
[68]  [68]
[69] 도 6을참조한바와같이메인채널에대한시료투입을별도의  As shown in FIG. 6, sample input to the main channel is separately determined.
접합패드 (Conjugate pad: 60)에의해제공되도록하여시료투입영역을제거하고, 메인채널 (20)하단으로부터지연채널 (30)합류부 (34)까지의길이를짧게 형성하였다.이와같이메인채널의교차영역 (23)하부를짧게형성하면메인채널 하단에겹쳐서안치되는접합패드 (60)를통해투입되는유체가교차영역 (23)을 진입하는시간을단축시켜지연채널 (30)로부터유체가합류되는시점까지의 시간간격을더욱증대시킬수있다.  The sample input area was removed by providing a contact pad (Conjugate pad: 60), and the length from the bottom of the main channel 20 to the conduit 34 of the delay channel 30 was formed shortly. (23) Short formation of the lower part shortens the time that the fluid introduced through the bonding pad 60, which overlaps the lower end of the main channel, enters the intersecting area 23, to the point where the fluid is joined from the delay channel 30. Can further increase the time interval.
[70] 일예로상기메인채널 (20)과지연채널 (30)및분리채널 (40)에서수직방향으로 배열된폭은 4mm로형성하고,저 11절곡부 (33)와합류부 (34)사이의지연채널 폭은 2mm로형성하고,분리부 (42)는 45 의경사를갖는확관부 (43;합류부 하부와대향되는메인채널내벽면으로부터제 2절곡부시작지점까지연결된 부분)가더형성되어유입부분의폭을증가시켰다.  For example, the widths arranged in the vertical direction in the main channel 20, the delay channel 30, and the separation channel 40 are 4 mm, and are formed between the low 11 bent portion 33 and the confluence portion 34. The delay channel width is 2 mm, and the separation part 42 is further formed with an expansion part 43 (a part connected from the inner channel inner wall surface facing the lower part of the joining part to the start point of the second bend part) having a 45 inclination. The width of the inlet is increased.
[71] 또한,메인채널 (20)은하단에서합류부 (34)시작지점까지 3mm로형성하고, 지연채널 (30)도제 1절곡부 (33)가시작된부분부터하부로 3mm지점을 In addition, the main channel 20 is formed at 3 mm from the lower end to the start point of the confluence part 34, and the delay channel 30 is 3 mm from the beginning of the first bent part 33 to the lower part.
버퍼투입영역 (32)과분리되도록이격시켰고,이격폭은 1mm로하였다.상기 버퍼투입영역은상하 5.5mm의길이로형성하여투입되는용액을층분하게 흡수할수있도록한다.  The buffer injection zone 32 was separated from the buffer injection zone 32, and the separation width was 1 mm. The buffer injection zone was formed to have a length of 5.5 mm in the upper and lower portions so as to sufficiently absorb the injected solution.
[72] 여기서상기메인채널하단에접착되는접착패드 (60; Conjugate pad)와 Wherein the adhesive pad (60; Conjugate pad) is attached to the lower end of the main channel
지연채널의버퍼투입영역 (32)과지연유동영역 (31)을연결하는지연패드 (50; A delay pad 50 connecting the buffer input region 32 and the delayed flow region 31 of the delay channel;
Delayed release pad)는메인채널의폭과동일한폭과길이를갖는정사각형으로 형성할수있다. : Delayed release pads can be formed into squares with the same width and length as the main channel width. :
[73] 또한,접착패드와지연패드로비대칭멤브레인 (Asymmetric Membrane; PALL사 제품)을사용할경우에는길이를다소증가시켜여러침전물의필터링역할을 동시에수행하게할수있다.예컨대메인채널 (20)폭을 4mm로형성하고, 접착패드 (60)와지연패드 (50)를비대칭멤브레인으로사용하면접착패드와 지연패드각각은폭은 4mm로형성하고길이는 4.5mm로형성하여사용할수 있다.여기서상기비대칭멤브레인은혈장및침전물의필터링을위해서는 PALL사제품중 "Vivid GX, Viyid GR, Vivid GF '올선택하여사용할수있고, 반웅물의흐름속도를조절및침전물의필터링을위해서는 PALL사제품중 "포어 (pore)사이즈가 0.45/ffli, 0.8^m, 8/ m인비대칭슈퍼미크론 In addition, when using an asymmetric membrane (Asymmetric Membrane, manufactured by PALL) with an adhesive pad and a delay pad, the length can be slightly increased to perform the filtering role of several sediment at the same time. If it is formed as 4mm, and the adhesive pad 60 and the delay pad 50 are used as asymmetric membranes, each of the adhesive pad and the retardation pad can be formed to have a width of 4 mm and a length of 4.5 mm. Here, the asymmetric membrane can be used. To filter silver plasma and sediment It is possible to select "Vivid GX, Viyid GR, Vivid GF" all of PALL products, and to adjust the flow rate of reaction and filtering of sediment, "Pore size of 0.45 / ffli, 0.8 ^ m, 8 / m asymmetric supermicron
폴리설폰 (Asymmetric super micron polysulfone; MMM)"을선택하는:등 사용목적에따라선택적으로사용할수있다.  Depending on the intended use, such as: "Asymmetric super micron polysulfone (MMM)" can be used.
[74] 또한,상기분리채널 (40)은제 2절곡부 (41)가형성된지점에서상단까지 21mm 로형성하여교차영역 (23)에서지연채널 (30)로부터유입된유체에의해밀려난 유체가유입되어층분히진행될수있게하였다.  In addition, the separation channel 40 is formed to be 21 mm from the point where the second bent portion 41 is formed to the top, so that the fluid pushed out by the fluid introduced from the delay channel 30 in the cross section 23 is introduced. It was made possible to proceed steadily.
[75] 또한,상기메인채널은상단이분리채널과동일한수평상에위치하도록  In addition, the main channel may be positioned at the same horizontal level as that of the separation channel.
연장되어교차영역을통과한유체의유동거리를증가시킬수있다.  It can be extended to increase the flow distance of the fluid through the cross section.
[76]  [76]
[77] 이러한메인채널 (20)은도 7을참조한바와같이교차영역 (23)과상단사이에 분리영역 (24)을더 형성할수있다.  As shown in FIG. 7, the main channel 20 may further form a separation region 24 between the intersection region 23 and the top.
[78] 상기분리영역 (24)은검출이이루어지는진단영역 (22)하부에위치하여추가로 안치되는접착패드 (60)에의해상하이격된채널이연결되도록한다.상기 이격은 1mm내외로형성되며,분리부 (42)로부터상부로 4~5mm지점에 형성하여교차영역 (23)을통과한유체가접착패드 (60)에의해상부의 진단영역 (22)으로유동되게할수있다. The separation area 24 is positioned below the diagnosis area 22 through which detection is performed so that channels spaced up and down by an additionally placed adhesive pad 60 are connected to each other. The fluid passing through the intersecting area 23 can be flown to the diagnostic area 22 of the upper part by the adhesive pad 60 by being formed at a point of 4-5 mm from the separating part 4 2.
[79] 이와같이채널유동구간에지연패드 (50)나접착패드 (60)를추가구성하는것은 투입되는시료또는완충용액에포함되어 있는침전물또는진행과정에서 발생된침전물을필터링하여제거하여진단영역에서의검출감도를 [79] As described above, the additional configuration of the delay pad 50 or the adhesive pad 60 in the channel flow section is performed by filtering and removing the precipitate contained in the sample or buffer solution to be added or the precipitate generated during the process. Detection sensitivity
증가시키거나, .유체의유동속도를조절하기위한것이다.  To increase the flow rate of the fluid.
[80] 따라서,상기분리영역은도 6의패턴에적용한도 7패턴이외에도 1내지Therefore, the separation region is not limited to 1 or 7 in addition to the pattern 7 applied to the pattern of FIG. 6.
5에도적용하여상기효과를제공할수있다. 5 can also be applied to provide the above effects.
[81] 또한,도 7에기재된사이즈는본발명의실시예중하나에 대한것으로,도시된 사이즈뿐만아니라각사이즈를 -20 ~:+20%의범위로변경하여실시하는것도 본발명의범위에포함된다할것이다. In addition, the size described in FIG. 7 is for one of the embodiments of the present invention, and the scope of the present invention includes not only the illustrated sizes but also changes of each size in the range of -20 to + 20%. something to do.
[82]  [82]
[83] [83]
[84] 실시예  [84] Example
[85] 실험예 1)패턴구조에대한유체흐름측정  Experimental Example 1 Fluid Flow Measurement for a Pattern Structure
[86] 도 8은 NC (니트로셀를로스)멤브레인에유기화합물을프린트하여다양한 패턴구조를나타낸도면이다.  FIG. 8 is a diagram showing various pattern structures by printing an organic compound on an NC (nitrocelulos) membrane.
[87] (A)는메인채널과지연채널및분리채널에서수직배치된부분은 4mm의폭을 갖도록하였고,서로 4mm로이격되도록배치하였다.또한,제 1절곡부와합류부 사이와제 2절곡부와분리부사이는 2mm폭으로하였고,제 1절곡부에서 저 12절곡부로 45 로상향경사를갖도록형성하였다. (A) The vertically arranged portions of the main channel, the delay channel, and the separation channel have a width of 4 mm, and are arranged to be spaced apart from each other by 4 mm. The space between the and separation sections was 2mm wide and formed to have a 45 degree upward slope from the first bend to the low 12 bend.
[88] (B)는 (A)와동일하게채널패턴을형성하되제 2절곡부와분리부사이의 분리채널폭을메인채널과동일한 4mm폭으로형성하였다. (B) forms a channel pattern in the same manner as in (A), but between the second bend and the separation part The separation channel width was formed to be the same 4mm width as the main channel.
[89] (C)는 (A)와동일하게채널패 1턴을형성하되,수직배치된분리채널과메인채널 사이의간격을 1.5mm로설정하였고,제 2절곡부의외각을곡면으로형성하였다. 또한,합류부에는메인채널의중심방향으로메인채널폭의 1.5mm로돌출된 돌출부를형성하였다. In (C), a channel pattern 1 turn was formed in the same manner as in (A), but the distance between the vertically arranged separate channel and the main channel was set to 1.5 mm, and the outer angle of the second bent portion was formed as a curved surface. In addition, the confluence portion was formed with a protrusion projected to 1.5 mm of the main channel width in the center of the main channel.
[90] (D)는메인채널과지연채널및분리채널에서수직배치된부분은 4mm의폭을 갖도록하였고,메인채널에대해분리채널은 1.5mm로이격시키고,지연채널은[90] (D) The vertically arranged portions of the main channel, the delay channel and the separation channel have a width of 4 mm. The separation channel is spaced 1.5 mm apart from the main channel.
4mm로이격시켰다.또한,제 1절곡부와합류부사이와제 2절곡부와분리부 사이는 2mm폭으로하였고,수평배치하여매인채널과교차되도록하였다.또한, 분리부하부에는확관부를형성하여분리채널로유입되는부분을확관시켰다. In addition, between the first bent portion and the confluence portion, and between the second bend portion and the separation portion, the width was 2 mm, and horizontally positioned so as to cross the main channel. The inflow to the separation channel was expanded.
[91] 지연채널의버퍼투밉영역과지연유동영역을연결하는지연패드로는포어 사이즈가 0.8//m인비대칭슈퍼미크론폴리설폰 (Asymmetric super micron polysulfone)을사용하였다. Asymmetric super micron polysulfone with a pore size of 0.8 // m was used to connect the buffer-to-mip region and the delayed flow region of the delay channel.
[92]  [92]
[93] 유체흐름을파악하기위해메인채널에는시료투입영역상부에식용색소  [93] In order to understand the fluid flow, the main channel has an edible pigment above the sample injection zone.
blue와 YM h)계면활성제 (제품명: fitzgerald사의 surfactant 10G)를도포한후 건조하였고,지연채널에는지연패드에식용색소 red와 1 %(v/v)  blue and YM h) Surfactant (Product name: surfactant 10G from fitzgerald) was applied and dried. The delay channel had food coloring red and 1% (v / v) on the delay pad.
계면활성제 (제품명: fitzgerald사의 surfactant 10G)를도포한다음건조시켰다.  A surfactant (product name: surfactant 10G from fitzgerald) was applied and dried.
[94] 메인채널의시료투입영역과지연채널의버퍼투입영역에각각 I X  [94] I X in the sample input area of the main channel and the buffer input area of the delay channel, respectively.
PBS(Phosphate Buffered Saline)*투입하여유체가상측으로유동되도록하였다.  Phosphate Buffered Saline (PBS) * was added to allow fluid to flow upward.
[95]  [95]
[96] 도 9은도 8의 A, B, C, D패턴쎄파른유체흐름과정을단계적으로나타낸  FIG. 9 illustrates the steep fluid flow process of the A, B, C, and D patterns of FIG.
사진이다.  It is a photograph.
[97] 4가지패턴모두메인채널의유체가먼저주도적으로흘러메인채널상부의 진단영역으로진행하였고,일전시간지:연후지연패널의유체가메인채널로 공급되어기존메인패널유체를일측으로밀어내어유체유동이 이루어졌다ᅳ [97] All four patterns first flowed in the main channel to the diagnosis area above the main channel, and before the time: after the delay, the fluid from the delay panel was supplied to the main channel to push the existing main panel fluid to one side. Fluid flow has occurred
[98] 이때 A패턴과 B패턴의경우에는지연채널의 red유체 (식용색소 red가흔합된 유체)가메인채널의 blue유체 (식용색소 blue가흔합된유체)를미는힘이 약해서 blue유체일부가같아진단영역으로흘러가는것을확인할수있다. In the case of the A pattern and the B pattern, the red fluid of the delay channel (fluid mixed with edible red) pushes the blue fluid of the main channel (fluid mixed with edible blue), so that a part of the blue fluid is weak. You can see it flowing to the same area.
[99] C패턴과 D패턴의경우에는지연채널에서유입된 red유체가메인채널의  [99] In the case of the C and D patterns, the red fluid introduced from the delay channel is
blue유체를측면으로충분히밀어내어 blue유체가분리채널로만유동됨올알수 있으며, D패턴에서자장좋은효과가나타났다.  The blue fluid was pushed out to the side so that the blue fluid flowed only into the separation channel, and the D pattern had the best effect.
[100] 이와같이 4가지패턴모두지연채널에서유밉된유체에의해메인채널로  [100] In this way, all four patterns were routed from the delay channel to the main channel by the mimicked fluid.
흐르는유체가분리채널로 70~100%까지밀려나서분리진행됨을알수있었다.  It was found that the flowing fluid was pushed out to the separation channel by 70 to 100% and separated.
[101]  [101]
[102] 실험예 2)비대칭멤브레인 (Asymmetric Membrane)의유동측정  Experimental Example 2 Flow Measurement of Asymmetric Membrane
[103] 지연패드로사용되는비대칭멤브레인으로 PALL사제품에서 Vivid중 GX, GR, GF를선정하였고,비대칭슈퍼미크론폴리설폰 (Asymmetric super micron polysulfone)중포어사이즈가 0.45, 0.8, 8인것을선정하여각각 GR, GX, GF, 0.45, 0.8, 8으로나타내었다ᅳ [103] Asymmetric super micron (Asymmetric super micron) selected from GALL, GX, GR and GF among Vivid as an asymmetric membrane used as a delay pad. The polysulfone was selected as the pore sizes 0.45, 0.8, and 8, respectively, and represented as GR, GX, GF, 0.45, 0.8, and 8, respectively.
[104] 선정된각비대칭멤브레인에는실험예 1의 D패턴을적용하되,추가적으로 [104] The D pattern of Experimental Example 1 is applied to each selected asymmetric membrane, but additionally
메인채널에서교차영역하부를 3mm의길이를갖도록하여도 6의형태를갖도록 하였고,메인채널하단은접착패드를일부분겹치게안치되도록하였고, 접착패드는지연패드와동일한제품을사용하였다.  In the main channel, the lower part of the intersecting area has a length of 3 mm, and the shape of the shape is 6, and the lower part of the main channel has the adhesive pads partially overlapped, and the adhesive pad is the same as the soft pad.
[105]  [105]
[106] 메인채널하단의접착패드는,, lOug/ml STA-650(Dylight사의형광염료)와  [106] The adhesive pad at the bottom of the main channel is composed of lOug / ml STA-650 (Dylight fluorescent dye).
lOKDa 1%(ν/ν)농도의 PVP(Polyvmylpyrrolidone), 0.5%(v/v)계면활성계 (제품명: fitzgerald사의 surfactant 10G)를 1 X PBS(phosphate buffered saline)버퍼에 회석하여 lOul의볼륨으로 37 C에서건조하였다.  lOKDa Polyvinylpyrrolidone (PVP) and 0.5% (v / v) surfactant (product name: surfactant 10G from fitzgerald) with 1% (ν / ν) concentration was distilled into 1X PBS (phosphate buffered saline) buffer and converted into lOul volume. Dry at 37 C.
[107] 지연채널의지연패드는, 10ug/ml STA-550(Dylight사의형광염료)와 lOKDa 1%(ν/ν)농도의 PVP(Polyvinylpyrrolidone), 0.5%(v/v)계 ¾활성제 (제품명: fitzgerald사의 surfactant 10G)를 1 X PBS(phosphate buffered saline)버퍼에 희석하여 lOul의볼륨으로 37 C에서건조하였다.  The delay pad of the delay channel is 10ug / ml STA-550 (fluorescent dye of Dylight), PVP (Polyvinylpyrrolidone) with lOKDa 1% (ν / ν) concentration, 0.5% (v / v) type ¾ active agent : Surfactant 10G) from fitzgerald was diluted in 1 × PBS (phosphate buffered saline) buffer and dried at 37 C with a volume of lOul.
[108]  [108]
[109] 메인채널하단에안치된접착패드와,지연채널의버퍼투입영역에는 1 X PBS 버퍼를사용하여투입하고, l ffiin간격으로지연패드로부터형광염료가 흘러나오는시간 (DP flow)과지연채널에서유입된유체에의해메인채널을 유동하는유체가분리채널로밀려나는시간 (Ratio)을측정하여도 10에 나타내었다.  [109] The adhesive pad placed at the bottom of the main channel and the buffer input area of the delay channel are input by using 1 X PBS buffer, and the time when the fluorescent dye flows out of the delay pad at l ffiin interval (DP flow) and the delay channel. The rate at which the fluid flowing through the main channel is pushed to the separation channel by the fluid introduced in Fig. 10 is measured.
[110] 도 10올참조한바와같이지연패드의비대칭멤브레인으로는가장늦게 . 형광염료가흘러나은 GF와 0.45를선택하였고,둘중메인채널을유동하는기존 유체를분리채널로모두밀러네는시간이 10분미만으로나타난 GF를최종 선정하였다.  [10] As shown in FIG. 10, the asymmetric membrane of the delay pad is the latest. GF with fluorescent dye and 0.45 were selected, and the final selection of GF with less than 10 minutes in which the existing fluid flowing through the main channel was pushed as a separate channel was selected.
[111]  [111]
[112] 선정된 GF비대칭멤브레인을대상으로지연패드로부터형광염료가  [112] Fluorescent dyes from delay pads were applied to selected GF asymmetric membranes.
홀러나오는시간 (DP flow)과지연채널에서유입된유체에의해메인채널을 유동하는유체가분리채널로밀려나는시간 (Ratio)을수회반복실험하여도 11에나타내었다.  The repeated outflow experiment (DP flow) and the time in which the fluid flowing through the main channel by the fluid introduced from the delay channel is pushed into the separate channel (Ratio) are shown in Fig. 11 several times.
[113] 반복실험시 5회모두유사한측정값이나타남을알수있어최종적으로  [113] In the repeated experiments, all five measurements showed similar measurement values.
지연패드로사용할비대칭멤브레인으로 GF를선정하였다.  GF was selected as an asymmetric membrane to be used as a delay pad.
[114]  [114]
[115] 실험예 3)패턴의유체흐름확인  Experimental Example 3) Check the fluid flow of the pattern
[116] 도 6의패턴구조에지연패드와접착패드로비대칭멤브레인 GF를사용하였고, 나머지는실험예 2와동일한조건으로실험하여 1분간격으로유체흐름을 측정해도 12에나타내었다.  Asymmetric membrane GF was used as the delay pad and the adhesive pad in the pattern structure of FIG. 6, and the rest was tested in the same conditions as Experimental Example 2, and the fluid flow was measured at 12-minute intervals.
[117] 참조한바와같이메인채널은먼저접착패드의유체가주도적으로유동하여 상부의진단영역으로유동되고, 2분이경과된시점부터지연패드를통과한. 유체가메인채널의측면으로부터유입되면서메인채널을주도적으로유동하던 유체가일측으로밀려나기시작하였다.일측으로밀려난접착패드를통과한 유체는분리채널로분리되어진행하고, 11분이경과된시점에서는메인채널의 상부진단영역에는지연채널에서유입된유체만전달되고,접착패드를통과한 유체는분리채널로분리되어유동되는것을확인할수있었다. As mentioned, the main channel is first driven by fluid in the adhesive pad. Flowed into the upper diagnostic area and passed through the delay pad from 2 minutes elapsed. As the fluid was introduced from the side of the main channel, the fluid that predominantly flowed the main channel began to be pushed to one side. The fluid passing through the adhesive pad pushed to one side was separated into the separation channel, and after 11 minutes had elapsed. In the upper diagnosis area of the main channel, only the fluid flowing from the delay channel was transferred, and the fluid passing through the adhesive pad was separated into the separation channel and flowed.
[118]  [118]
[119] 따라서,진단영역에서로다른물질을순차적으로공급해야정확한검출이 가능한진단방법에적용하여간편한진단이가능하게할수있다.  Therefore, it is necessary to supply different materials in the diagnosis area sequentially so that easy diagnosis can be made by applying a diagnosis method capable of accurate detection.
[120]  [120]

Claims

청구범위 Claim
[청구항 1] 종이에 인쇄기술을이용하여채널을형성한진단센서의 패턴구조에 있어서,  [Claim 1] In the pattern structure of a diagnostic sensor in which a channel is formed using printing technology on paper,
상하방향으로길게형성되어하부에서상부로유체가유동되도록하고, 하부의단부에는시료를투입하는시료투입영역 (21)이형성되고,상부의 단부에는검출물질이코팅되는진단영역 (22)이형성되며,중간부분에는 다른채널과연결되는교차영역 (23)아형성된메인채널 (20)과;;  It is formed long in the vertical direction to flow the fluid from the lower part to the upper part, and the sample input area (21) for introducing the sample is formed at the lower end, the diagnostic region (22) is formed at the upper end is coated with the detection material, An intermediate portion (23) formed in the middle portion of the intersecting region (23) connected to another channel;
상기메인채널의일측에나란히형성되되,주이동영역인 지연유동영역 (31)과상기지연유동영역하단과이격되어버퍼가 : 투입되는버퍼투입영역 (32)을분리구성하고,지연패드 (50)로두영역을 연결해버퍼가메인채널로전달되는시간이지연되도록하고,상부는 메인채널방향으로꺾인제 1절곡부 (33)가형성되어상단이메인채널의 교차영역에연통되는합류부 (34)를갖는지연채널 (30)과; 상기메인채널의 양측중지연채널과대향되는측면에나란히형성되되, 하부는메인채널방향으로꺾인제 2절곡부 (41)가형성되어,하단이 메인채널의교차영역에연통되는분리부 (42)를갖는분리채널 (40);을 포함하여구성되는것을특징으로하는패턴구조.  The delay channel 31 is formed side by side on the main channel, and is separated from the delay flow region 31, which is a main movement region, and the buffer injection region 32 into which the buffer is inserted, spaced apart from the lower end of the delay flow region. It connects the two regions so that the time for the buffer to be transferred to the main channel is delayed, and the upper portion has a first bent portion 33 which is bent in the main channel direction so that the upper portion has a confluence portion 34 which communicates with the cross region of the main channel. Delay channel 30; A second bent part 41 is formed side by side on both sides of the main channel opposite to the delay channel, and the lower part is formed with a second bent part 41 bent in the main channel direction, and the lower part is in communication with the cross section of the main channel. Pattern structure comprising a separate channel (40) having a.
[청구항 2] 제 1항에 있어서,  [Claim 2] The method according to claim 1,
상기제 1절곡부 (33)와제 2절곡부 (41)는절곡된부분이곡면으로형성되는 것을특징으로하는패턴구조.  The first bent portion (33) and the second bent portion (41) is a pattern structure characterized in that the bent portion is formed in a curved surface.
[청구항 3] 제 2항에 있어서,  [Claim 3] The method of claim 2,
상기메인채널폭은 3~4mm이고,  The main channel width is 3 ~ 4mm,
상기지연채널 (30)은저 U절곡부 (33)와합류부 (34)사이의길이가  The delay channel 30 has a length between the low U bend 33 and the confluence 34.
3~4mm이고,  3 ~ 4mm
상기분리채널 (40)은제 2절국부 (41)와분리부 (42)사이의길이가  The separation channel 40 has a length between the second section 41 and the separation section 42.
l~2mm로형성하는것을특징으로하는패턴구조.  Pattern structure characterized by forming from 1 to 2 mm.
[청구항 4] 제 3항에 있어서,  4. The method of claim 3, wherein
상기 메인채널의교차영역 (23)은분리부 (42)를합류부 (34)상부에 위치시키되,상기분리부는합류부를형성하는지연채널 (30)의연장된 부분과교차되는지점으로부터 형성되는것을특징으로하는패턴구조. The intersecting area 23 of the main channel places the separator 42 above the confluence 34, wherein the separator is formed from a point where it forms a confluence or intersects with the extended portion of the extended channel 30. Characterized by a pattern structure.
[청구항 5] 제 4항에 있어서, 5. The method of claim 4,
상기지연채널 (30)의제 1절곡부 (33)와합류부 (34)사이부분과,상기 분리채널 (40)의분리부 (42)와제 2절곡부 (41)사이부분은메인채널과 직교되는방향으로형성되는것을특징으로하는패턴구조.  A portion between the first bent portion 33 and the confluence portion 34 of the delay channel 30 and a portion between the separation portion 42 and the second bent portion 41 of the separation channel 40 are orthogonal to the main channel. Pattern structure characterized by being formed in a direction.
[청구항 6] 계 5항에 있어서,  6. The method of claim 5,
상기분리채널 (40)의분리부 (42)하단에는합류부 (34)가시작되는지점과 대향되는지점으로부터제 2절곡부 (41)가시작되는지점까지확관된 확관부 (43)가형성되는것을특징으로하는패턴구조. The lower part of the separating part 42 of the separating channel 40 extends from the point at which the joining part 34 is started to the point opposite to the point at which the second bent part 41 is started. A pattern structure characterized in that the expansion portion (43) is formed.
[청구항 7] 제 4항에 있어서, 7. The method of claim 4,
상기지연채널 (30)은제 1절곡부 (33)에서합류부 (34)방향으로상향경사를 갖도록형성하고,  The delay channel 30 is formed to have an upward slope in the direction of the joining portion 34 in the first bent portion 33,
상기분리채널 (40)은분리부 (42)에서제 2절곡부 (41)방향으로상향경사를 갖도록형성하는것을특징으로하는패턴구조.  And the separating channel (40) is formed to have an upward slope in the direction of the second bent portion (41) in the separating portion (42).
[청구항 8] 제 4항에 있어서,  8. The method of claim 4,
상기메인채널 (20)과연통된지연채널 (30)의상부벽에는메인채널중심 방향으로돌출된돌출부 (35)를더형성하여지연채널에서합류하는 유체를메인채널중심방향으로내입되어유동되도록한것을특징으로 하는패턴구조.  The upper wall of the delay channel 30 in communication with the main channel 20 is further formed with a projection 35 projecting in the main channel center direction to flow the fluid that joins in the delay channel in the main channel center direction to flow. Pattern structure.
[청구항 9] 제 4항에 있어서,  [Claim 9] The method according to claim 4,
상기메인채널 (20)은교차영역에서하단까지의길이를 2~5mm로형성해 시료투입영역을제거하고,메인채널하단에접합패드 (60)를일부분 겹치도록안치하여시료투입영역을대체하도록한것을특징으로하는 패턴구조.  The main channel 20 has a length from the cross section to the bottom of 2 to 5 mm to remove the sample input region, and to place the bonding pad 60 at the bottom of the main channel to partially overlap the sample input region. Pattern structure.
[청구항 10] 제 4항에있어서,  [Claim 10] In paragraph 4,
상기 메인채널 (20)은교차영역 (23)과진단영역 (22)사이에서교차영역과 근접한부분에채널을분리시키는분리영역 (24)을더형성하고, 접합패드 (60)에의해분리영역의상하부가연결되도록한것을특징으로 하는패턴구조.  The main channel 20 further forms a separation region 24 separating the channel between the intersection region 23 and the diagnosis region 22 in a portion adjacent to the intersection region, and is formed by the bonding pads 60 at the upper and lower portions of the separation region. The pattern structure, characterized by the fact that is connected.
PCT/KR2016/013698 2016-09-07 2016-11-25 Pattern structure of diagnostic sensor WO2018048025A1 (en)

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