WO2012064172A1 - Canal microfluidique et procédés d'élimination des bulles du fluide dans le canal microfluidique - Google Patents

Canal microfluidique et procédés d'élimination des bulles du fluide dans le canal microfluidique Download PDF

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Publication number
WO2012064172A1
WO2012064172A1 PCT/MY2011/000083 MY2011000083W WO2012064172A1 WO 2012064172 A1 WO2012064172 A1 WO 2012064172A1 MY 2011000083 W MY2011000083 W MY 2011000083W WO 2012064172 A1 WO2012064172 A1 WO 2012064172A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluid
bubbles
sharp protuberance
microfluidic channel
primary
Prior art date
Application number
PCT/MY2011/000083
Other languages
English (en)
Inventor
Hing Wah Lee
Chia Sheng Daniel Bien
Original Assignee
Mimos Berhad
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mimos Berhad filed Critical Mimos Berhad
Publication of WO2012064172A1 publication Critical patent/WO2012064172A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • 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
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • G01N2035/1018—Detecting inhomogeneities, e.g. foam, bubbles, clots

Definitions

  • the present invention provides a microfluidic channel and methods of removing bubbles from fluid in the microfluidic channel.
  • Microfluidic channel have been extensively used in chemical analysis systems and BioMEMS applications for fluid transport. It is a technique for applications such as drug delivery, cell manipulation or chemical and biological sensing.
  • One of the main issues during manipulation and dosing of the small amounts of fluids in microfluidic channel is the formation of bubbles inside the fluid flow path at the reaction or mixing chamber within the microfluidic channel.
  • bubbles are very stable and are very hard to be naturally broken.
  • the bubbles expand when they are in contact with each other to form bigger bubbles. This creates an air lock condition which causes clogging of the microfluidic channel when the size of the bubbles is almost equal to the microfluidic channel or at the fluid entry point or fluid exit point.
  • US20070167797 describes an ultrasound imaging system that transmits a broad beam of ultrasound into tissues that are perfused with blood containing microbubbles.
  • the ultrasound has an intensity that is sufficient to destroy the microbubbles in the tissues.
  • This prior art requires high external power.
  • US5831727 describes an apparatus that includes a plurality of chambers having an open top. Each chamber directs the moving liquid stream upwardly through an area of reduced diameter and then downwardly to an opening into an adjacent chamber. The bubbles are thereby urged upwardly to the top of the liquid where they burst and are vented to the atmosphere.
  • US5228889 describes a device comprising a channel of varying section for the liquid, the channel having a high point for collecting bubbles under gravity, and means for dynamically concentrating bubbles upstream from the high point, said means being constituted by a curved length of the channel situated upstream from the high point.
  • the bubbles are broken due to collision and they are collected and broken at the top of reservoir or fluid chamber only.
  • the invention discloses a microfluidic channel and methods to puncture and remove the bubbles along the fluid flow path without requiring external power.
  • the advantage of this invention is that the disclosed apparatus and method are able to prevent clogging of the microfluidic channel by removing bubbles in the fluid flow path.
  • a device for eliminating bubbles from fluid in a microfluidic channel is disclosed. Also disclosed are the methods for eliminating bubbles from fluid in microfluidic channel.
  • a device for eliminating bubbles from fluid in a microfluidic channel includes: a) a fluid entry point;
  • a method for eliminating bubbles from fluid in microfluidic channel including: a) flowing of fluid in a microfluidic channel through a fluid entry point;
  • a device for eliminating bubbles from fluid in a microfluidic channel includes: a) a fluid entry point;
  • a method for eliminating bubbles from fluid in a microfluidic channel including: a) flowing of fluid in a microfluidic channel through a fluid entry point;
  • FIG 1 illustrates isometric view of microfluidic channel with enclosed sharp protuberances.
  • FIG 2 illustrates A-A cross-sectional view of microfluidic channel with enclosed sharp protuberances.
  • FIG 3 illustrates top view of microfluidic channel with enclosed sharp protuberances.
  • FIG 4 illustrated an embodiment of this invention.
  • FIG 5 illustrates an exemplary case using an embodiment of the invention.
  • FIG 6 (a) and (b) illustrates exemplary situations using an embodiment of the invention.
  • FIG 7 (a), (b), (c) and (d) illustrates exemplary of sharp protuberance arrays.
  • FIG 1 , 2 and 3 illustrates the view of the embodiment in different directions.
  • FIG 1 illustrates the isometric view of microfluidic channel (104) with enclosed primary and secondary sharp protuberances (103), (106).
  • FIG 2 illustrates the A-A cross-sectional view of microfluidic channel (104) and
  • FIG 3 illustrates the top view of the microfluidic channel (104).
  • microfluidic channel (104) bubbles will be formed due to the existence of air or gases inside the fluid in which equilibrium state is achieved between their outward air pressure and the inward surface tension of the fluid.
  • the sharp protuberances (103), (106) edges break the molecular bond holding the structure of bubbles causing the bubbles to collapse and disintegrate.
  • the primary sharp protuberance (103) punctures the bigger bubbles into smaller ones.
  • Air vent (102) removes the smaller bubbles created after the large bubbles are broken by primary sharp protuberance (103) so that it will not come in contact with other bubbles and expand into bigger bubble.
  • the secondary sharp protuberance (106) punctures the escaped bubbles that were not removed by the air vent (102). After the bubbles are broken, the fluid exits through fluid exit (101 ).
  • FIG 4 illustrates the formation of microfluidic channel (104) with base (501 ) and a cover (502) wherein the cover (502) is located on top of the base (502).
  • the primary sharp protuberance (103) and secondary sharp protuberance (106) are fabricated on the base (501 ) while the cover (502) is formed by silicon or glass substrates.
  • the cover encapsulates the base (501 ) through bonding processes such as anodic, adhesives or fusion.
  • FIG 5 illustrates an exemplary implementation situation using the microfluidic channel (104) with enclosed sharp protuberance (103), (106) in a microfluidic mixing process.
  • the invention resides within a microfluidic system which includes microfluidic mixer (601 ), microvalves (602), micropump (603), fluid reservoir (604) and outlet reservoir (606).
  • Sample and reagent fluid will flow from reservoir (604) and pass through micropump (603) into microfluidic channel (104) and microfluidic mixer (601 ) during pumping.
  • the sample and reagent starts to mix in the microfluidic mixer (601 ) and generate byproducts in the form of gaseous bubbles.
  • the bubbles formed will flow with the fluid through microfluidic channel (104).
  • the bubbles will come in contact with primary sharp protuberance (103), and secondary sharp protuberance (106) inside the microfluidic channel (104) within the microfluidic mixer (601 ).
  • the primary and secondary sharp protuberances (103), (106) will easily break the molecular bonding of the bubbles causing the bubbles to collapse and disintegrate into smaller bubbles.
  • the fluid flows output is through outlet reservoir (606).
  • FIG 6 (a) and (b) illustrates exemplary situations of using the microfluidic channel to puncture bubbles.
  • Fluid enters the microfluidic channel (104) through fluid entry (100).
  • Figure 6 (a) illustrates puncturing of the bigger bubbles by primary sharp protuberance (103).
  • Figure 6 (b) illustrates air vent (102) removing the smaller bubbles created after the large bubbles are broken by primary sharp protuberances (103).
  • the secondary sharp protuberance (106) punctures the escaped bubbles that were not trapped by the air vent (102). After the bubbles are punctured, the fluid exits through fluid exit (101 ).
  • FIG 7 (a), (b), (c) and (d) illustrates different types of sharp protuberances arrays. Bubbles which are not broken by a single sharp protuberance (103), (106) might merge to form bigger bubbles and clog the fluid flow passage. Arrays of sharp protuberances is utilised to offer higher effectiveness of bubble puncturing process.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Hematology (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Micromachines (AREA)

Abstract

L'invention divulgue un appareil et des procédés de crevaison de bulles du fluide dans un canal microfluidique (104). La protubérance pointue primaire (103) crève les bulles les plus grandes. Le conduit d'aération (102) piège et élimine les bulles créées après que les bulles les plus grandes ont été rompues par la protubérance pointue primaire (103). La protubérance pointue secondaire (106) crève les bulles qui se sont échappées sans avoir été rompues par la protubérance pointue primaire (103) ou non éliminées par le conduit d'aération (102). Un ensemble de diverses protubérances pointues peut être intégré à l'intérieur du canal microfluidique (104) pour crever les bulles sur le passage du flux de fluide.
PCT/MY2011/000083 2010-11-08 2011-06-07 Canal microfluidique et procédés d'élimination des bulles du fluide dans le canal microfluidique WO2012064172A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MYPI2010005233 2010-11-08
MYPI2010005233 MY150793A (en) 2010-11-08 2010-11-08 A microfluidic channel and methods of removing bubbles from fluid in the microfluidic channel

Publications (1)

Publication Number Publication Date
WO2012064172A1 true WO2012064172A1 (fr) 2012-05-18

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WO (1) WO2012064172A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014039514A2 (fr) * 2012-09-05 2014-03-13 President And Fellows Of Harvard College Élimination de bulles dans des systèmes microfluidiques
US20180015464A1 (en) * 2016-07-12 2018-01-18 EMULATE, Inc. Removing bubbles in a microfluidic device

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050247198A1 (en) * 2004-05-07 2005-11-10 Kent Fraser C Method and apparatus for removing gas bubbles from a liquid
US20090269767A1 (en) * 2008-04-10 2009-10-29 C/O Valtion Teknillinen Tutkimuskeskus Microfluidic chip devices and their use
WO2009148448A1 (fr) * 2008-06-05 2009-12-10 Hewlett-Packard Development Company, L.P. Réduction de gouttelettes d'encre générées par l'éclatement de bulles dans un révélateur d'encre

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050247198A1 (en) * 2004-05-07 2005-11-10 Kent Fraser C Method and apparatus for removing gas bubbles from a liquid
US20090269767A1 (en) * 2008-04-10 2009-10-29 C/O Valtion Teknillinen Tutkimuskeskus Microfluidic chip devices and their use
WO2009148448A1 (fr) * 2008-06-05 2009-12-10 Hewlett-Packard Development Company, L.P. Réduction de gouttelettes d'encre générées par l'éclatement de bulles dans un révélateur d'encre

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9962698B2 (en) 2012-09-05 2018-05-08 President And Fellows Of Harvard College Removing bubbles in microfluidic systems
WO2014039514A3 (fr) * 2012-09-05 2014-06-19 President And Fellows Of Harvard College Élimination de bulles dans des systèmes microfluidiques
WO2014039514A2 (fr) * 2012-09-05 2014-03-13 President And Fellows Of Harvard College Élimination de bulles dans des systèmes microfluidiques
US10661275B2 (en) 2016-07-12 2020-05-26 EMULATE, Inc. Removing bubbles in a microfluidic device
GB2555892B (en) * 2016-07-12 2021-03-31 Emulate Inc Removing bubbles in a microfluidic device
US10335788B2 (en) 2016-07-12 2019-07-02 EMULATE, Inc. Removing bubbles in a microfluidic device
JP2019525836A (ja) * 2016-07-12 2019-09-12 エミュレイト， インコーポレイテッド マイクロ流体デバイスにおける気泡の除去
EP3484620A4 (fr) * 2016-07-12 2020-02-19 Emulate, Inc. Élimination des bulles dans un dispositif microfluidique
US20180015464A1 (en) * 2016-07-12 2018-01-18 EMULATE, Inc. Removing bubbles in a microfluidic device
US10913063B2 (en) 2016-07-12 2021-02-09 EMULATE, Inc. Removing bubbles in a microfluidic device
GB2555892A (en) * 2016-07-12 2018-05-16 Emulate Inc Removing bubbles in a microfluidic device
US10974242B2 (en) 2016-07-12 2021-04-13 EMULATE, Inc. Removing bubbles in a microfluidic device
US11065620B2 (en) 2016-07-12 2021-07-20 EMULATE, Inc. Removing bubbles in a microfluidic device
US11141727B2 (en) 2016-07-12 2021-10-12 EMULATE, Inc. Removing bubbles in a microfluidic device
JP2022020693A (ja) * 2016-07-12 2022-02-01 エミュレイト， インコーポレイテッド マイクロ流体デバイスにおける気泡の除去
JP7301928B2 (ja) 2016-07-12 2023-07-03 エミュレイト， インコーポレイテッド マイクロ流体デバイスにおける気泡の除去
EP4325111A3 (fr) * 2016-07-12 2024-05-01 Emulate, Inc. Élimination de bulles dans un dispositif microfluidique

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