WO2006022495A1 - Module de regulation d'ecoulement capillaire et laboratoire sur puce equipe de celui-ci - Google Patents

Module de regulation d'ecoulement capillaire et laboratoire sur puce equipe de celui-ci Download PDF

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Publication number
WO2006022495A1
WO2006022495A1 PCT/KR2005/002752 KR2005002752W WO2006022495A1 WO 2006022495 A1 WO2006022495 A1 WO 2006022495A1 KR 2005002752 W KR2005002752 W KR 2005002752W WO 2006022495 A1 WO2006022495 A1 WO 2006022495A1
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WIPO (PCT)
Prior art keywords
channel
control module
flow control
delay
flow
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Application number
PCT/KR2005/002752
Other languages
English (en)
Inventor
Ji Won Suk
Jae-Young Jang
Eunjeong Lee
Youngduk Kim
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Lg Chem, Ltd.
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Publication date
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Publication of WO2006022495A1 publication Critical patent/WO2006022495A1/fr

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    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/50273—Containers 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 means or forces applied to move the fluids
    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502723—Containers 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 venting arrangements
    • 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
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502746—Containers 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 means for controlling flow resistance, e.g. flow controllers, baffles
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0621—Control of the sequence of chambers filled or emptied
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0463—Hydrodynamic forces, venturi nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the present invention relates to a capillary flow control module and a lab-on- a-chip equipped with the same, and more particularly, a capillary flow control module and a lab-on-a-chip equipped with the same, which can diagnose and analyze a small amount of a sample by transferring and reacting the sample through the natural capillary flow by capillary phenomenon.
  • the technology to transfer and control a small amount of microfluid is a core technology to drive a lab-on-a-chip and can be implemented by various driving methods.
  • Examples of the methods for transferring and controlling microfluid include a pressure-driven method in which pressure is applied to a fluid injection part, an electrophoretic method or an electroosmotic method in which a voltage is applied between micro flow channels to transfer fluid, and a capillary flow method using the capillary phenomenon.
  • the capillary flow method which uses the capillary phenomenon naturally generated in micro flow channels has a merit in that it can spontaneously and promptly transfer a small amount of fluid around a fluid injection part through given channels, without an additional apparatus. Therefore, there have been actively conducted researches for developing a device for transferring microfluid and a lab-on-a-chip using the capillary flow method.
  • the present invention has been made in order to meet such a current trend as described above, and it is an object of the present invention to provide a capillary flow control module and a lab-on-a-chip equipped with the same, which can transfer microfluids by the capillary phenomenon without any additional manipulation and energy.
  • ELISA Enzyme-Linked Immunosorbent Assay
  • the present invention provides a capillary flow control module comprising: a first channel 31 through which a first microfluid flows; a second channel 32 through which a second microfluid flows; a venturi channel 33 formed between the first channel 31 and the second channel 32; at least one flow delay part 34 formed in the venturi channel 33 to delay the flow; and an air exhaust channel 35 connected to the flow delay part 34 to discharge air bubbles between the first microfluid and the second microfluid.
  • the venturi channel 33 has the same cross section shape as that of the first channel 31 and the second channel 32 and the air exhaust channel 35 has a smaller cross section area than that of the venturi channel 33. Also, an angle formed by the wall surface of the air exhaust channel and the wall surface extended from the air exhaust channel at the end of the air exhaust channel 35 is smaller than an angle formed by an inlet zone 11 and a delay boundary zone 13 at the flow delay part 34.
  • the present invention provides a lab-on-a-chip equipped with the capillary flow control module comprising:
  • a capillary flow control module 130 comprising a first channel 131 connected to the A reaction part 120, a second channel 132 connected to the bypass channel 116, at least one first flow delay part 134 formed in a venturi channel 133 disposed between the first channel 131 and the second channel 132 to delay the flow, and an air exhaust channel 135 connected to the first flow delay part 134 to discharge air bubbles between the first microfluid and the second microfluid;
  • the lab-on-a-chip according to the present invention may further comprise a third flow delay part 154 formed in a venturi channel 153 at the end of the B reaction part 150.
  • a second charging part 160 and a third charging part 170 may be connected to the end of the B reaction part 150 via a venturi channel, in which the third charging part 170 is connected to an outlet part 190.
  • a fourth flow delay part 174 formed in a venturi channel is provided between the third charging part 170 and the outlet part 190.
  • the present invention provides a lab-on-a-chip equipped with the capillary flow control module comprising: (a) a divergence channel 215 connected to a fluid injection part 210 containing a microfluid;
  • the present invention may further comprise a fifth flow delay part 274 formed in a venturi channel 273 at the end of the C reaction part 270.
  • the present invention provides a lab-on-a-chip equipped with the capillary flow control module comprising:
  • a sixth flow delay part 284 connected to the C reaction part 270 and an additional sample inlet part 280 to receive another sample; and (o) a detection part 290 connected to the sixth flow delay part 284.
  • the detection part 290 is sequentially connected to first, second, third and fourth outlet parts 300, 303, 306 and 309, a flow stopping part 310 and an air exhaust port 320 via a venturi channel, and a seventh flow delay part 301 and an eighth flow delay part 304 are provided in venturi channels between the first outlet part 300 and the second outlet part 303 and between the third outlet part 306 and the fourth outlet part 309, respectively.
  • the first capillary flow control module 230 comprises a first channel 231 connected to the A reaction part 220, a second channel 232 connected to the first bypass channel 216, a. venturi channel 233 disposed between the first channel 231 and the second channel 232, at least one first flow delay part 234 formed in the venturi channel 233 to delay the flow, and an air exhaust channel 235 connected to the first flow delay part 234 to discharge air bubbles between the first microfluid and the second microfluid.
  • the second capillary flow control module 330 comprises a first channel 331 connected to the first charging part 240, a second channel 332 connected to the second bypass channel 217, a venturi channel 333 disposed between the first channel 331 and the second channel
  • the third capillary flow control module 430 comprises a first channel 431 connected to the B reaction part 250, a second channel 432 connected to the third bypass channel 218, a venturi channel 433 disposed between the first channel 431 and the second channel 432, at least one third flow delay part 434 formed in the venturi channel 433 to delay the flow, and an air exhaust channel 435 connected to the third flow delay part 434 to discharge air bubbles between the first microfluid and the second microfluid.
  • the fourth capillary flow control module 530 comprises a first channel 531 connected to the second charging part 260, a second channel 532 connected to the detection part 290, a venturi channel 533 formed between the first channel 531 and the second channel 532, at least one fourth flow delay part 534 formed in the venturi channel 533 to delay the flow, and an air exhaust channel 535 connected to the fourth flow delay part 534 to discharge air bubbles between the first microfluid and the second microfluid.
  • the fourth capillary flow control module 530 may further comprise a flow stopping part 538 disposed between the second channel 532 and the fourth flow delay part 534 to stop the flow of the fluid.
  • a substrate is previously added to the A reaction part 220, an enzyme-detection antibody complex is previously added to the B reaction part 250 and a capture antibody is previously fixed on the C reaction part 270.
  • an enzyme-detection antibody complex is previously added to the B reaction part 250 and a capture antibody is previously fixed on the C reaction part 270.
  • silver nitrate and hydroquinone as a reducing agent are previously added to the A reaction part 220
  • gold-detection antibody complex is previously added to the B reaction part 250 and capture antibody is previously fixed onto the C reaction part 270.
  • the lab-on-a-chip according to the present invention comprises a signal detection part of the capillary flow control module applicable to the conventional well plate detecting apparatus and thus can detect signals using the convention well plate detecting apparatus.
  • FIG. 1 is a schematic view of an ordinary micro flow channel
  • FIG. 2 is a schematic view of a flow delay model
  • FIG. 3 is a photograph illustrating flow change in the flow delay model of FIG. 2;
  • FIG. 4 shows an air bubble trapped in a micro flow channel when two fluids meet in the micro flow channel;
  • FIG. 5 shows the construction of the capillary flow control module according to the present invention
  • FIG. 6 shows a first embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention
  • FIG. 7 shows a second embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention
  • FIG. 8 shows a third embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention.
  • FIG. 9 shows a fourth embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention.
  • capillary flow control module according to the present invention and the lab-on-a-chip equipped with the same are described in detail, making reference to the attached drawings.
  • capillary flow phenomenon is to be briefly described.
  • FIG. 1 shows a schematic view of an ordinary micro flow channel
  • FIG. 2 shows a schematic view of a flow delay model
  • FIG. 3 shows photographs illustrating flow change in the flow delay model of FIG. 2
  • FIG. 4 shows an air bubble trapped in a micro flow channel when two fluids meet in the micro flow channel.
  • a capillary flow occurs when a gas-liquid interface is curved with a curvature due to discontinuous change of pressure generated on the gas-liquid interface.
  • the interface curvature is produced by a contact angle ( ⁇ ) formed by the gas-liquid interface and a solid wall surface at a triple point, where the gas-liquid interface and the solid wall surface come into contact with each other.
  • ⁇ contact angle
  • the contact angle is defined as an angle between the gas-liquid interface and the wall surface toward the liquid side, in which it is 0 ( ⁇ ⁇ r/2, when the wall surface is more aff ⁇ nitive to the liquid than it is to the gas and ⁇ r/2 ( . ⁇ (. ⁇ , when it is the opposite.
  • Such capillary flow can be delayed by a flow delay model 10, as shown in FIG. 2. That is, when a fluid is introduced to an inlet zone 11, the flow delay takes place in a delay boundary zone 12 which is a boundary zone between the inlet zone 11 and a flow delay zone 13 and this delay effect continues while the fluid passes through the delay boundary zone 12. Then, the capillary flow which has passed through the delay boundary zone 12 flows the flow delay zone 13 and reaches a recovery boundary zone 14 which is a boundary zone between the flow delay zone 13 and a flow recovery zone 15, upon which the interface curvature is increased whereby the fluid recovers its former flow rate. In the flow recovery zone 15, the capillary flow completely recovers its former flow rate and the flow continues.
  • FIG. 3 shows photographs of the actual condition in which the flow is delayed by the flow delay model of FIG. 2. Since the capillary flow was initiated in the inlet part 11, it has taken about 2 minutes and 7.63 seconds for the flow to reach to the next inlet part 11', while it took about only 0.5 second for the flow to pass through the second inlet part H 1 . This is because the capillary flow is delayed in the delay boundary zone 12, the flow delay zone 13 and the recovery boundary zone 14, as shown in FIG. 2.
  • FIG. 5 shows the construction of the capillary flow control module according to the present invention.
  • the capillary flow control module 30 according to the present invention is designed by employing the flow delay model 10 of FIG. 2 to solve the problem associated with the discharge of the air bubble, as shown in FIG. 4.
  • the capillary flow control module 30 comprises a first channel 31 through which a first microfluid flows, a second channel 32 through which a second microfluid flows, a venturi channel 33 formed between the first channel 31 and the second channel 32, at least one flow delay part 34 formed in the venturi channel 33 to delay the flow, and an air exhaust channel 35 connected to the flow delay part 34 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 35 is connected to an external air exhaust port 36.
  • the flow delay part 34 has the same construction as the flow delay model 10, shown in FIG. 2. That is, the flow delay part 34 comprises an inlet zone 11, a delay boundary zone 12, a flow delay zone 13, a recovery boundary zone 14 and a flow recovery zone 15.
  • the capillary flows of the first microfluid and the second microfluid introduced through the first channel 31 and the second channel 32 are delayed by the flow delay part 34, upon which air bubbles existing between the first microfluid and the second microfluid are discharged through the air exhaust channel 35 and the air exhaust port 36, whereby the first microfluid is completely connected to the second microfluid.
  • FIG. 6 shows the first embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention.
  • the first embodiment of the lab-on-a-chip comprises a divergence channel 115 connected to a fluid injection part 110 containing a microfluid, an A reaction part 120 connected to the divergence channel 115 and containing A sample, a bypass channel 116 connected to the divergence channel 115, a capillary flow control module 130 disposed between the A reaction part 120 and the bypass channel 116, a B reaction part 150 containing a B sample, and a first charging part 140 disposed between the B reaction part 150 and the capillary flow control module 130. Also, the B reaction part 150 is connected to a diagnosis/analysis part (K) for diagnosing and analyzing the fluid which has passed through the B reaction part 150.
  • K diagnosis/analysis part
  • the capillary flow control module 130 comprises a first channel 131 connected to the A reaction part 120, a second channel 132 connected to the bypass channel 116, a venturi channel 133 disposed between the first channel 131 and the second channel 132, at least one first flow delay part 134 disposed in the venturi channel 133 to delay the flow, and an air exhaust channel 135 connected to the first flow delay part 134 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 135 is connected to an external air exhaust port 136.
  • a venturi channel 143 is formed between the first charging part 140 and the B reaction part 150 and a second flow delay part 144 is formed in the venturi channel 143.
  • Another venturi channel 153 is formed at the end of the B reaction part 150 and a third flow delay part 154 is formed in the venturi channel 153.
  • the fluid supplied through the fluid injection part 110 is divided into two directions in the divergence channel 115, in which one is transferred to the bypass channel 116 and the other is transferred to the A reaction part 120 to fill up the A reaction part 120.
  • the fluid transferred to the A reaction part 120 dissolves the A sample which has been previously put into the A reaction part 120 and is, then, transferred to the capillary flow control module 130.
  • the flow of the fluid containing the A sample which is transferred to the capillary flow control module 130 is delayed in the first flow delay part 134.
  • the fluid which has been transferred to the bypass channel 116 passes through the second channel 132 of the capillary flow control module 130 and fills up the first charging part 140, in which a part of the fluid is transferred to the first flow delay part 134.
  • air bubbles between the two fluids are discharged out of the air exhaust port 136 through the air exhaust channel 135 connected to the first flow delay part 134 whereby no air bubble is generated.
  • the fluid which has been divided in the divergence channel 115 is united. Therefore, the upper side of the fluid which has passed through the bypass channel 116 contains the A sample.
  • the fluid which has passed through the first charging part 140 and the second flow delay part 144 is introduced to the B reaction part 150 to dissolve the B sample.
  • the flow of the fluid which has been introduced to the B reaction part 150 is delayed while the B sample is being dissolved by the third flow delay part 154 disposed at the end of the B reaction part 150.
  • the fluid is transferred to the diagnosis/analysis part (K) or another capillary flow control module through the third flow delay part 154 and the discharge channel 155.
  • the fluid containing the B sample, the fluid without containing the sample and the fluid containing the A sample are sequentially introduced to the diagnosis/analysis part (K) at an interval of a predetermined time whereby it becomes possible to diagnose and analyze two different types of the A sample and the B sample.
  • FIG. 7 shows the second embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention.
  • the second embodiment differs from the first embodiment in that the end of the B reaction part 150 is connected to a second charging part 160 and a third charging part 170, instead of the diagnosis/analysis part (K) via a venturi channel and the third charging part 170 is connected to an outlet part 190.
  • a fourth flow delay part 174 formed in a venturi channel is disposed between the third charging part 170 and the outlet part 190.
  • a complex of an antigen and a fluorescent dye may be previously added to the A reaction part 120 and a capture antibody may be previously fixed on the B reaction part 150.
  • a buffer solution which has been supplied to the fluid injection part 110, is transferred to the third flow delay part 154 by the flow processes described in FIG. 6. Then, while its flow is delayed by the third flow delay part 154, the buffer solution dissolves the antigen-fluorescent dye complex in the A reaction part 120 and activates the capture antibody of the B reaction part 150.
  • reaction time in the B reaction part 150 is controlled by the flow delay in the fourth flow delay part 174.
  • the fluid delayed by the fourth flow delay part 174 is discharged through the outlet part 190 so that undesired substances in the B reaction part 150 and non-specif ⁇ cally bonded antigen- antibody- fluorescent dye complex can be removed.
  • FIG. 8 shows the third embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention.
  • the third embodiment of the lab-on-a-chip relates to a lab-on-a-chip equipped with the capillary flow control module which can sequentially transfer three different samples and comprises a divergence channel 215 connected to a fluid injection part 210 containing a microfluid, an A reaction part 220 connected to the divergence channel 215 and containing an A sample, a first bypass channel 216 connected to the divergence channel 215, a first capillary flow control module 230 disposed between the A reaction part 220 and the first bypass channel 216, a.
  • first charging part 240 connected to the first capillary flow control module 230, a second capillary flow control module 330 connected to the first charging part 240, a second bypass channel 217 diverged from the first bypass channel 216 and connected to the second capillary flow control module 330, a B reaction part 250 connected to the second capillary flow control module 330 and containing a B sample, a third capillary flow control module 430 connected to the B reaction part 250, a third bypass channel 218 diverged from the second bypass channel 217 and connected to the third capillary flow control module 430, a second charging part 260 connected to the third capillary flow control module 430, and a C reaction part 270 connected to the second charging part 260 and containing a C sample.
  • the first capillary flow control module 230 comprises a first channel 231 connected to the A reaction part 220, a second channel 232 connected to the first bypass channel 216, a venturi channel 233 disposed between the first channel 231 and the second channel 232, at least one first flow delay part 234 formed in the venturi channel 233 to delay the flow, and an air exhaust channel 235 connected to the first flow delay part 234 to discharge air bubbles between the first microfluid and the second microfluid.
  • An external air exhaust port 236 is connected to the air exhaust channel 235.
  • the second capillary flow control module 330 comprises a first channel 331 connected to the first charging part 240, a second channel 332 connected to the second bypass channel 217, a venturi channel 333 disposed between the first channel 331 and the second channel 332, at least one second flow delay part 334 formed in the venturi channel 333 to delay the flow, and an air exhaust channel 335 connected to the second flow delay part 334 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 335 is connected to the air exhaust port 236 diverged from the first capillary flow control module 230.
  • the third capillary flow control module 330 comprises a first channel 431 connected to the B reaction part 250, a second channel 432 connected to the third bypass channel 218, a venturi channel 433 disposed between the first channel 431 and the second channel 432, at least one third flow delay part 434 formed in the venturi channel 433 to delay the flow, and an air exhaust channel 435 connected to the third flow delay part 434 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 435 is connected to the air exhaust port 236 diverged from the first and second capillary flow control modules 230 and 330.
  • a venturi channel 263 is formed between the second charging part 260 and the C reaction part 270 and a fourth flow delay part 264 is formed in the venturi channel 263.
  • Another venturi channel 273 is formed at the end of the C reaction part 270 and a fifth flow delay part 274 is formed in the venturi channel 273.
  • a sample, B sample and C sample are previously added to the A reaction part 220, the B reaction part 250 and the C reaction part 270, respectively.
  • the fluid supplied through the fluid injection part 210 is divided into two directions in the divergence channel 215, in which one is transferred to the first bypass channel 216 and the other is transferred to the A reaction part 220 to fill up the A reaction part 220.
  • the fluid which has been transferred to the first bypass channel 216 passes through the second channel 232 of the first capillary flow control module 230 and fills up the first charging part 240, upon which a part of the fluid is transferred to the first flow delay part 234.
  • the fluid which has diverged from the first bypass channel 216 and passed through the second bypass channel 217 fills up the B reaction part 250 and the second charging part 260 and air is discharged from the second flow delay part 334 and the third flow delay part 434 while the fluid which has reached the third flow delay part 264 is delayed, and then the fluids are united, based on the above-described flow mechanism.
  • the fluids are connected from the A reaction part 220 to the fourth flow delay part 264.
  • the fluid is supplied to the C reaction part 270 to dissolve the C sample while it is delayed by the fifth flow delay part 274.
  • the whole fluid is supplied to the diagnosis/analysis part (K) or another capillary flow control module through the discharge channel 275.
  • the C sample, the B sample and the A sample may be sequentially supplied.
  • FIG. 9 shows the fourth embodiment of the lab-on-a-chip equipped with the capillary flow control module according to the present invention, which is designed for sequential supply and reaction of three different samples, particularly according to the Enzyme-linked immunosorbent assay (ELISA).
  • ELISA Enzyme-linked immunosorbent assay
  • the fourth embodiment of the lab-on-a-chip equipped with the capillary flow control module comprises a divergence channel 215 connected to a fluid injection part 210 containing microfluid, an A reaction part 220 connected to the divergence channel 215 and containing an A sample, a first bypass channel 216 connected to the divergence channel 215, a first capillary flow control module 230 disposed between the A reaction part 220 and the first bypass channel 216, a first charging part 240 connected to the first capillary flow control module 230, a second capillary flow control module 330 connected to the first charging part 240, a second bypass channel 217 diverged from the first bypass channel 216 and connected to the second capillary flow control module 330, a B reaction part 250 connected to the second capillary flow control module 330 and containing a B sample, a third capillary flow control module 430 connected to the B reaction part 250, a third bypass channel 218 diverged from the second bypass channel 217 and connected to the third capillar
  • the second charging part 260 is connected to a fourth capillary flow control module 530 which is connected to a C reaction part 270 containing the C sample.
  • the C reaction part 270 is connected to a sixth flow delay part 284 which is connected to an additional sample inlet part 280 to receive another sample.
  • the sixth flow delay part 284 is sequentially connected to a detection part 290, first, second, third and fourth outlet parts 300, 303, 306 and 309, a flow stopping part 310 and an air exhaust port 320 via a venturi channel.
  • the venturi channels between the first outlet part 300 and the second outlet part 303 and between the third outlet part 306 and the fourth outlet part 309 are provided with a seventh flow delay part 301 and an eighth flow delay part 304, respectively.
  • the first capillary flow control module 230 comprises a first channel 231 connected to the A reaction part 220, a second channel 232 connected to the first bypass channel 216, a venturi channel 233 formed between the first channel 231 and the second channel 232, at least one first flow delay part 234 formed in the venturi channel 233 to delay the flow, and an air exhaust channel 235 connected to the first flow delay part 234 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 235 is connected to an external air exhaust port 236.
  • the second capillary flow control module 330 comprises a first channel 331 connected to the first charging part 240, a second channel 332 connected to the second bypass channel 217, a venturi channel 333 formed between the first channel 331 and the second channel 332, at least one second flow delay part 334 formed in the venturi channel 333 to delay the flow, and an air exhaust channel 335 connected to the second flow delay part 334 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 335 is connected to the air exhaust port 236 diverged from the first capillary flow control module 230.
  • the third capillary flow control module 330 comprises a first channel 431 connected to the B reaction part 250, a second channel 432 connected to the third bypass channel 218, a venturi channel 433 formed between the first channel 431 and the second channel 432, at least one third flow delay part 434 formed in the venturi channel 433 to delay the flow, and an air exhaust channel 435 connected to the third flow delay part 434 to discharge air bubbles between the first microfluid and the second microfluid.
  • the air exhaust channel 435 is connected to the air exhaust port 236 diverged from the first and second capillary flow control modules 230 and 330.
  • the fourth capillary flow control module 530 comprises a first channel 531 connected to the second charging part 260, a second channel 532 connected to the C reaction part 270, a venturi channel 533 formed between the first channel 531 and the second channel 532, at least one fourth flow delay part 534 formed in the venturi channel 533 to delay the flow, and an air exhaust channel 535 connected to the fourth flow delay part 534 to discharge air bubbles between the first microfluid and the second microfluid.
  • a flow stopping part 538 to stop the flow of the fluid from the C reaction part 270 is formed between the second channel 532 and the fourth flow delay part 534.
  • a substrate is previously added to the A reaction part 220, an enzyme- detection antibody complex is previously added to the B reaction part 250, and a capture antibody is previously fixed on the C reaction part 270.
  • the sample which has been introduced from the sample inlet part 280 is supplied to the C reaction part 270 via a sample inlet channel 281.
  • the sample charged in the C reaction part 270 is stopped until a buffer solution supplied from the fluid injection part 210 passes through the fourth flow delay part 534 and reaches the flow stopping part 538, upon which the antigen contained in the sample binds with the capture antibody in the C reaction part 810.
  • the fluid supplied through the fluid injection part 210 is divided into two directions in the divergence channel 215, in which one is transferred to the first bypass channel 216 and the other is transferred to the A reaction part 220 to fill up the A reaction part 220.
  • the buffer solution transferred to the first bypass channel 216 is supplied to the first charging part 240, the B reaction part 250 and the second charging part 260 via the second bypass channel 217 and the third bypass channel 218.
  • the buffer solution supplied to the first and second charging parts 240 and 260, and the B reaction part 250 is delayed and separated by the first flow delay part 234, the second flow delay part 334, the third flow delay part 434 and the fourth flow delay part 534, and dissolves the substrate of the A reaction part 220 and the enzyme-detection antibody complex of the B reaction part 250.
  • the buffer solutions supplied to the reaction part and the charging part are connected to the sample stopped by the first flow stopping part 538.
  • the buffer solution and the sample from the two inlet parts are connected to each other and the effect of the sixth flow delay part 284 is vanished, the fluid fills up the detection part 290 and the first outlet part 300 and is delayed by the seventh flow delay part 301.
  • the substrate and the enzyme-detection antibody complex which are present in the A reaction part 220 and the B reaction part 250 are transferred to the B reaction part 250 and the C reaction part 270, respectively.
  • the enzyme-detection antibody complex and the antigen- capture antibody complex react by antigen-antibody reaction to form enzyme- detection antibody-antigen-capture antibody complex.
  • the fluid fills up the second outlet part 303 and the third outlet part 306 and is delayed again by the eighth flow delay part 304.
  • the substrate in the B reaction part 250 is transferred to the C reaction part 270, in which it chemically reacts by the action of the enzyme existing therein.
  • the fluid which has been delayed by the eighth flow delay part 304 is supplied to the third outlet part 309 and is stopped by the second flow stopping part 310. Meanwhile, the substrate which has chemically reacted in the C reaction part 270 is transferred to the detection part 290, in which it is separated from the enzyme, whereby there is no more chemical reaction by the enzyme.
  • silver nitrate and hydroquinone as a reducing agent are previously supplied to the A reaction part 220, gold-detection antibody complex is previously supplied to the B reaction part 250 and capture antibody is previously fixed onto the C reaction part 270.
  • the antigen of the sample is bonded with the capture antibody in the C reaction part 270 and sequentially, the gold-detection antibody complex in the B reaction part 250 is bonded with the antigen-capture antibody complex in the C reaction part 270 by the antigen-antibody reaction to form gold-detection antibody- antigen-capture antibody complex.
  • the micro flow channel used in the present invention may be formed by covering a plate with a depressed pattern with a flat plate or a plate with a depressed or raised pattern.
  • the plate may be formed of polymers, metals, silicon, glass, PCB (Printed Circuit Board) and the like, preferably materials with polymers.
  • the plate examples include plastics such as PMMA (polymethylmethacrylate), PC (polycarbonate), COC (cycloolefin copolymer), PDMS (polydimethylsiloxane), PA (polyamide), PE (polyethylene), PP (polypropylene), PPE (polyphenylene ether), PS (polystyrene), POM (polyoxymethylene), PEEK (polyetherketone), PTFE (polytetrafluoroethylene), PVC (polyvinylchloride), PVDF (polyvinylidene fluoride), PBT (polybutyleneterephthalate), and FEP (fluorinated ethylenepropylene).
  • the above-listed materials may be largely shaped by replication methods such as injection molding, hot embossing or casting. Particularly, these materials are suitable for production of the micro flow channel according to the present invention due to their inactivity, processability, cheapness and disposability.
  • the method for producing the micro flow channel according to the present invention includes preparing a mold with a raised pattern corresponding to the shape of the micro flow channel, making a plate with a depressed pattern over the mold, adjusting hydrophilicity of the surfaces of each plate and the second plate, and binding the first plate to the second plate.
  • the capillary flow control module has a cross-section of a square but the present invention is not limited thereto.
  • the capillary flow control module may have various shapes such as circle and trapezoid.
  • the capillary flow control module and the lab-on-a- chip equipped with the same As described above, by the capillary flow control module and the lab-on-a- chip equipped with the same according to the present invention, it is possible to connect a plurality of fluids by a specific design of channel configuration based on natural flow due to capillary force without additional manipulation and energy. Also, it is possible to sequentially transfer and diagnose/analyze two or more samples. Further, the capillary flow control module and the lab- on-a-chip equipped with the same according to the present invention can be easily manufactured and used in a simple manner.

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  • Clinical Laboratory Science (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

L'invention concerne un module de régulation d'écoulement capillaire et un laboratoire sur puce équipé de celui-ci, et plus particulièrement un module de régulation d'écoulement capillaire et un laboratoire sur puce équipé de celui-ci qui permettent de diagnostiquer et d'analyser une faible quantité d'un échantillon, par le transfert et la mise en réaction de l'échantillon dans l'écoulement naturel produit par capillarité. Le laboratoire sur puce équipé de ce module fait communiquer une pluralité de fluides par écoulement capillaire naturel sans manipulation ni énergie supplémentaires, dans un canal conçu spécifiquement, et permet de diagnostiquer et d'analyser deux ou davantage d'échantillons différents par transfert séquentiel.
PCT/KR2005/002752 2004-08-21 2005-08-19 Module de regulation d'ecoulement capillaire et laboratoire sur puce equipe de celui-ci WO2006022495A1 (fr)

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US7736890B2 (en) 2003-12-31 2010-06-15 President And Fellows Of Harvard College Assay device and method
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US8394595B2 (en) 2007-10-17 2013-03-12 Electronics And Telecommunications Research Institute Lab-on-a-chip and method of driving the same
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US7736890B2 (en) 2003-12-31 2010-06-15 President And Fellows Of Harvard College Assay device and method
US8574924B2 (en) 2003-12-31 2013-11-05 President And Fellows Of Harvard College Assay device and method
US10082507B2 (en) 2003-12-31 2018-09-25 President And Fellows Of Harvard College Assay device and method
US8394595B2 (en) 2007-10-17 2013-03-12 Electronics And Telecommunications Research Institute Lab-on-a-chip and method of driving the same
US8858897B2 (en) 2007-11-22 2014-10-14 Nanoentek, Inc. Microfluidic chip for analysis for fluid sample
EP2191279A2 (fr) * 2007-11-22 2010-06-02 Digital Bio Technology Co., Ltd. Puce microfluidique permettant l'analyse d'un échantillon fluide
EP2191279A4 (fr) * 2007-11-22 2012-04-25 Digital Bio Technology Co Ltd Puce microfluidique permettant l'analyse d'un échantillon fluide
WO2010006668A1 (fr) * 2008-07-18 2010-01-21 Roche Diagnostics Gmbh Élément de test pour l'analyse d'un analyte présent dans un échantillon de liquide corporel, système d'analyse et procédé de commande du déplacement d'un liquide contenu dans un canal d'un élément de test
EP2145682A1 (fr) * 2008-07-18 2010-01-20 Roche Diagnostics GmbH Elément de test destiné à l'analyse d'un analyte contenu dans un échantillon de liquide corporel, système d'analyse et procédé de commande du mouvement d'un liquide contenu dans un canal d'un élément de test
JP2018185337A (ja) * 2009-07-24 2018-11-22 アコーニ バイオシステムズ インコーポレイテッド フローセルデバイス
US9163279B2 (en) 2009-11-02 2015-10-20 The Secretary Of State For Environment, Food & Rural Affairs, Acting Through The Animal Health And Veterinary Laboratories Agency Device and apparatus
CN102192977A (zh) * 2010-02-10 2011-09-21 富士胶片株式会社 微流体器件
EP2353721A3 (fr) * 2010-02-10 2014-01-08 Fujifilm Corporation Dispositif microfluidique
CN102192977B (zh) * 2010-02-10 2014-10-29 富士胶片株式会社 微流体器件
US10376881B2 (en) 2010-09-07 2019-08-13 Lumiradx Uk Ltd. Assay device and reader
US9919313B2 (en) 2010-09-07 2018-03-20 Lumiradx Uk Ltd. Assay device and reader
US11278886B2 (en) 2010-09-07 2022-03-22 Lumiradx Uk Ltd. Assay device and reader
JP2013541014A (ja) * 2010-10-29 2013-11-07 エフ．ホフマン−ラ ロシュ アーゲー 試料液体を分析するためのマイクロ流体素子
WO2018002668A1 (fr) * 2016-06-30 2018-01-04 Lumiradx Uk Ltd Régulation de fluide
US11000847B2 (en) 2016-06-30 2021-05-11 Lumiradx Uk Ltd. Fluid control
US12076720B2 (en) 2016-06-30 2024-09-03 Lumiradx Uk Ltd. Fluid control
CN111213060A (zh) * 2017-10-11 2020-05-29 麦君宇 微流体计量和输送系统
US11857960B2 (en) 2017-10-11 2024-01-02 Fitbit, Inc. Microfluidic metering and delivery system
CN111213060B (zh) * 2017-10-11 2024-02-09 麦君宇 微流体计量和输送系统

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TWI262096B (en) 2006-09-21
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TW200616705A (en) 2006-06-01

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