WO2003000392A2 - Method and apparatus for controlling fluid flow rate in a microfluidic circuit - Google Patents

Method and apparatus for controlling fluid flow rate in a microfluidic circuit Download PDF

Info

Publication number
WO2003000392A2
WO2003000392A2 PCT/US2002/019482 US0219482W WO03000392A2 WO 2003000392 A2 WO2003000392 A2 WO 2003000392A2 US 0219482 W US0219482 W US 0219482W WO 03000392 A2 WO03000392 A2 WO 03000392A2
Authority
WO
WIPO (PCT)
Prior art keywords
fluid
flow
microfluidic channel
flow rate
ofthe
Prior art date
Application number
PCT/US2002/019482
Other languages
French (fr)
Other versions
WO2003000392A3 (en
Inventor
Bernard H. Weigl
Ronald L. Bardell
Thomas E. Schulte
Original Assignee
Micronics, Inc.
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 Micronics, Inc. filed Critical Micronics, Inc.
Priority to EP02753344A priority Critical patent/EP1419004A2/en
Priority to JP2003507029A priority patent/JP2004536699A/en
Publication of WO2003000392A2 publication Critical patent/WO2003000392A2/en
Publication of WO2003000392A3 publication Critical patent/WO2003000392A3/en

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • 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
    • B01L3/502738—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 integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433—Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • B01F25/4331—Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/3039—Micromixers with mixing achieved by diffusion between layers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/451—Magnetic mixers; Mixers with magnetically driven stirrers wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502776—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 multiphase flow arrangements specially adapted for focusing or laminating flows
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F15—FLUID-PRESSURE ACTUATORS; HYDRAULICS OR PNEUMATICS IN GENERAL
    • F15C—FLUID-CIRCUIT ELEMENTS PREDOMINANTLY USED FOR COMPUTING OR CONTROL PURPOSES
    • F15C3/00—Circuit elements having moving parts
    • F15C3/04—Circuit elements having moving parts using diaphragms
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F15—FLUID-PRESSURE ACTUATORS; HYDRAULICS OR PNEUMATICS IN GENERAL
    • F15C—FLUID-CIRCUIT ELEMENTS PREDOMINANTLY USED FOR COMPUTING OR CONTROL PURPOSES
    • F15C3/00—Circuit elements having moving parts
    • F15C3/06—Circuit elements having moving parts using balls or pill-shaped disks
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0017—Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0028—Valves having multiple inlets or outlets
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
    • G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
    • G01N27/06—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/44—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement
    • B01F31/441—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement performing a rectilinear reciprocating movement
    • 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
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • 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
    • B01L2300/0822—Slides
    • 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
    • B01L2300/0887—Laminated structure
    • 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
    • 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
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal 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
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • 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
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic 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
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

  • This invention generally relates to microfluidics, and more particularly to controlling a flow of a fluid in a microfluidic circuit.
  • Microfluidics relates to systems that exploit physical properties and flow characteristics of fluids within micro-sized channels of capillary dimensions.
  • fluids having different viscosities that flow next to each other take up different amounts of space within a channel, either by having a different cross-sectional area or different relative volumes within the channel.
  • pressure-controlled microfluidic circuits including, for example, gravity- fed circuits
  • fluids having different viscosities and flowing next to each other take up the same amount of space, but flow at different volume flow rates.
  • this phenomenon presents a problem for cases in which a constant or accurate flow rate is required, or in which the position ofthe interface between two fluids next to each other must be known.
  • fluids having non-dissolved particles dispersed within them show a flow behavior that is different from that of a particle-free fluid, even if the viscosities ofthe fluids are similar.
  • particle-laden fluids may also take up different amounts of space in volume-controlled circuits, or have different flow rates in pressure-controlled circuits.
  • the particles themselves may be uncontrollably forced to different areas ofthe channel by any of these forces, whereas the fluids in which they are contained would remain in place.
  • Figure 1 is a graph illustrating a parabolic flow rate distribution in a microchannel having two side walls each defining an internal surface.
  • Figure 2 depicts one embodiment of an injection structure suitable for the invention.
  • Figures 3-5 illustrate various alternative cross-sections of inlets to a microfluidic channel.
  • Flow rate is a function of cross-sectional area of a fluid within a channel, and the rate of speed with which the fluid travels through the channel.
  • Several other factors affecting a fluid's flow rate include the fluid's viscosity, or property of resistance to flow, the composition and configuration ofthe channel, and the presence of other adjacently flowing fluids. In general, the effect of a fluid's viscosity on flow rate is more pronounced closer to internal surfaces ofthe channel, usually defined by the channel walls.
  • Figure 1 illustrates this property, in which a flow speed of a fluid with a l ⁇ iown viscosity has a parabolic distribution 100 within a microchannel, the flow being slower at and near the walls 103 ofthe channel and faster toward the center ofthe channel.
  • a center region 101 ofthe parabolic distribution 100 is substantially flat, representing a constant or near- constant flow rate across the region.
  • a fluid sample 102 that requires a constant or accurate flow rate is sheathed in a second fluid 104.
  • the fluid sample 102, or first fluid is injected as a flow into the channel, preferably within a small, center portion ofthe entire stream in the area 101 in which flow rate is constant.
  • the first fluid can have an unknown or variable viscosity that would otherwise inhibit a constant or accurate flow rate.
  • the second fluid 104 sheaths the first fluid 102 and has a known viscosity, such that the second fluid has a constant or accurately known flow rate at the interface with the first fluid 102. Accordingly, the first fluid 102 will maintain substantially the same constant or accurate flow rate as the second fluid at the interface.
  • the first fluid 102 if containing non-dissolved particles, is also protected against forces which can affect the flow rate and direction ofthe first fluid, or any non-dissolved particles dispersed therein. These forces are substantially perpendicular to the direction ofthe flow ofthe first fluid 102. Being susceptible to these forces, the non-dissolved particles can be moved, altering the flow ofthe first fluid 102. These forces include, but not limited to, hydrodynamic shear stress, hydrodynamic shear lift, and elastic collision of particles.
  • Figure 2 is a two-dimensional cross-sectional view of an injection structure 200 consistent with a device known as a "T"-Sensor, which includes a microfluidic channel 201 having side walls 203 that define an internal surface.
  • the microfluidic channel 201 has a primary inlet 202 for receiving a first fluid flow, and secondary inlets 204 for receiving one or more second fluid flows.
  • secondary inlets 204 are depicted as separate, but could form different parts of one inlet in a three-dimensional configuration.
  • the second fluid sheaths the first fluid, to isolate the first fluid from the side walls 203 ofthe channel 201.
  • the first fluid has an unknown or variable viscosity, which has minimal effect on the flow rate ofthe first fluid since the first fluid will flow at substantially the same rate as the second fluid where the two fluids interface, at 205.
  • the second fluid has a known viscosity selected for achieving a particular flow rate at the interface 205.
  • Figure 2 The structure 200 shown in Figure 2 is shown as two-dimensional for example only, and not limitation. In a third-dimensional, many different cross- sectional profiles can be used.
  • Figures 3-5 show several embodiments of inlets or injectors to a microfluidic channel. Many other embodiments are possible within the scope ofthe invention.
  • Figure 3 is a cross-section of a circular arrangement 300 of inlets. The arrangement includes a first inlet 302 for providing a first fluid, and a second inlet 304 for providing a second fluid that sheaths the first fluid. In the arrangement shown, the second inlet 304 circumscribes the first inlet 302, at least in close proximity to the channel.
  • Figure 4 shows a similar arrangement 400 in which the first inlet 402 and the second inlet 404 are rectangular. It should be understood that, in any embodiment, the second inlet need not necessarily conform to the exact shape ofthe first inlet. Thus, with reference to Figure 4, the second inlet 404 could be a different shape, i.e. rounded, than the first inlet 402.
  • the second fluid is preferably provided by the second inlet 404 to sheath, or surround, the first fluid, or at least isolate the first fluid from contact with an internal surface ofthe channel.
  • Figure 5 shows an alternative embodiment of an arrangement 500 in which a second inlet 504 only partially surrounds the first inlet 502. In such an arrangement, effects ofthe viscosity ofthe first fluid can be mitigated at the channel wall 503 not completely interceded with the second fluid, by a a coating 505 on the wall 503.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Fluid Mechanics (AREA)
  • Theoretical Computer Science (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Electrochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

A method and apparatus are disclosed for controlling a flow rate of a fluid sample having an unknown or variable viscosity. The fluid sample is provided as a first fluid flow to a microfluidic channel. A second fluid is provided to the channel as a sheath around the first fluid. In one embodiment, the second fluid is injected between the first flow and an internal surface of the channel. In another embodiment, the second fluid completely circumscribes the first fluid as a parallel or sheath flow. The second fluid has a known viscosity selected for achieving a flow rate. The first fluid flow at the same rate as the achieved flow rate of the second fluid.

Description

METHOD AND APPARATUS FOR CONTROLLING FLUID FLOW RATE
IN A MICROFLUIDIC CIRCUIT
STATEMENT OF RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No.
60/213,865, filed June 23, 2000 and entitled "MICROFLUIDIC SYSTEMS AND METHODS," which is incorporated herein in its entirety. This application also relates to U.S. Patent Application No. 09/428,807, filed October 28, 1999 and entitled "SHEATH FLOW ASSEMBLY," which is incorporated by reference herein for all purposes.
BACKGROUND OF THE INVENTION
[0002] This invention generally relates to microfluidics, and more particularly to controlling a flow of a fluid in a microfluidic circuit. Microfluidics relates to systems that exploit physical properties and flow characteristics of fluids within micro-sized channels of capillary dimensions.
[0003] In volume-controlled microfluidic circuits, fluids having different viscosities that flow next to each other take up different amounts of space within a channel, either by having a different cross-sectional area or different relative volumes within the channel. Similarly, in pressure-controlled microfluidic circuits, including, for example, gravity- fed circuits, fluids having different viscosities and flowing next to each other take up the same amount of space, but flow at different volume flow rates. For fluids which have an unknown or varying viscosity, this phenomenon presents a problem for cases in which a constant or accurate flow rate is required, or in which the position ofthe interface between two fluids next to each other must be known.
[0004] Furthermore, fluids having non-dissolved particles dispersed within them show a flow behavior that is different from that of a particle-free fluid, even if the viscosities ofthe fluids are similar. Depending on a variety of forces that may occur between the particles, between the particles and the fluid, and other forces applied to the particles by the hydrodynamic shear stress and flow profile within a microchannel, such particle-laden fluids may also take up different amounts of space in volume-controlled circuits, or have different flow rates in pressure-controlled circuits. In addition, the particles themselves may be uncontrollably forced to different areas ofthe channel by any of these forces, whereas the fluids in which they are contained would remain in place.
BRIEF DESCRIPTION OF THE DRAWING
[0005] Figure 1 is a graph illustrating a parabolic flow rate distribution in a microchannel having two side walls each defining an internal surface.
[0006] Figure 2 depicts one embodiment of an injection structure suitable for the invention.
[0007] Figures 3-5 illustrate various alternative cross-sections of inlets to a microfluidic channel.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0008] Flow rate is a function of cross-sectional area of a fluid within a channel, and the rate of speed with which the fluid travels through the channel. Several other factors affecting a fluid's flow rate include the fluid's viscosity, or property of resistance to flow, the composition and configuration ofthe channel, and the presence of other adjacently flowing fluids. In general, the effect of a fluid's viscosity on flow rate is more pronounced closer to internal surfaces ofthe channel, usually defined by the channel walls. Figure 1 illustrates this property, in which a flow speed of a fluid with a lαiown viscosity has a parabolic distribution 100 within a microchannel, the flow being slower at and near the walls 103 ofthe channel and faster toward the center ofthe channel. [0009] With reference to Figure 1, it is shown that a center region 101 ofthe parabolic distribution 100 is substantially flat, representing a constant or near- constant flow rate across the region. In accordance with the invention, a fluid sample 102 that requires a constant or accurate flow rate is sheathed in a second fluid 104. The fluid sample 102, or first fluid, is injected as a flow into the channel, preferably within a small, center portion ofthe entire stream in the area 101 in which flow rate is constant. The first fluid can have an unknown or variable viscosity that would otherwise inhibit a constant or accurate flow rate. The second fluid 104 sheaths the first fluid 102 and has a known viscosity, such that the second fluid has a constant or accurately known flow rate at the interface with the first fluid 102. Accordingly, the first fluid 102 will maintain substantially the same constant or accurate flow rate as the second fluid at the interface.
[0010] The first fluid 102, if containing non-dissolved particles, is also protected against forces which can affect the flow rate and direction ofthe first fluid, or any non-dissolved particles dispersed therein. These forces are substantially perpendicular to the direction ofthe flow ofthe first fluid 102. Being susceptible to these forces, the non-dissolved particles can be moved, altering the flow ofthe first fluid 102. These forces include, but not limited to, hydrodynamic shear stress, hydrodynamic shear lift, and elastic collision of particles.
[0011] Many different microfluidic structures and injection mechanisms can be employed to sheath a fluid sample with a fluid of known viscosity for achieving a constant and/or accurate flow rate for the fluid sample. U.S. Patent Nos. 5,932,100 to Yager et al., 5,948,684 to Weigl et al, and 6,159,739 to Weigl et al., the contents of which are incorporated by reference herein in their entirety, describe various structures, mechanisms and methods for sheathing a fluid within another fluid. [0012] Figure 2 is a two-dimensional cross-sectional view of an injection structure 200 consistent with a device known as a "T"-Sensor, which includes a microfluidic channel 201 having side walls 203 that define an internal surface. The microfluidic channel 201 has a primary inlet 202 for receiving a first fluid flow, and secondary inlets 204 for receiving one or more second fluid flows. Those having the requisite skill in the art will recognize that secondary inlets 204 are depicted as separate, but could form different parts of one inlet in a three-dimensional configuration.
[0013] The second fluid sheaths the first fluid, to isolate the first fluid from the side walls 203 ofthe channel 201. The first fluid has an unknown or variable viscosity, which has minimal effect on the flow rate ofthe first fluid since the first fluid will flow at substantially the same rate as the second fluid where the two fluids interface, at 205. The second fluid has a known viscosity selected for achieving a particular flow rate at the interface 205.
[0014] The structure 200 shown in Figure 2 is shown as two-dimensional for example only, and not limitation. In a third-dimensional, many different cross- sectional profiles can be used. Figures 3-5 show several embodiments of inlets or injectors to a microfluidic channel. Many other embodiments are possible within the scope ofthe invention. Figure 3 is a cross-section of a circular arrangement 300 of inlets. The arrangement includes a first inlet 302 for providing a first fluid, and a second inlet 304 for providing a second fluid that sheaths the first fluid. In the arrangement shown, the second inlet 304 circumscribes the first inlet 302, at least in close proximity to the channel.
[0015] Figure 4 shows a similar arrangement 400 in which the first inlet 402 and the second inlet 404 are rectangular. It should be understood that, in any embodiment, the second inlet need not necessarily conform to the exact shape ofthe first inlet. Thus, with reference to Figure 4, the second inlet 404 could be a different shape, i.e. rounded, than the first inlet 402. The second fluid is preferably provided by the second inlet 404 to sheath, or surround, the first fluid, or at least isolate the first fluid from contact with an internal surface ofthe channel. [0016] Figure 5 shows an alternative embodiment of an arrangement 500 in which a second inlet 504 only partially surrounds the first inlet 502. In such an arrangement, effects ofthe viscosity ofthe first fluid can be mitigated at the channel wall 503 not completely interceded with the second fluid, by a a coating 505 on the wall 503.
[0017] Other embodiments, combinations and modifications of this invention will occur readily to those of ordinary skill in the art in view of these teachings. Therefore, this invention is to be limited only by the following claims, which include all such embodiments and modifications when viewed in conjunction with the above specification and accompanying drawings.
WHAT IS CLAIMED IS:

Claims

1. A method of controlling a flow of a fluid sample, comprising: providing a first fluid as a flow in a microfluidic channel; and sheathing the first fluid with a second fluid having a known viscosity, such that the first fluid has a flow rate that is substantially equal to a flow rate ofthe second fluid at the interface with the first fluid.
2. The method of claim 1, further comprising contacting the first fluid with the second fluid.
3. The method of claim 1 , wherein the first fluid and the second fluid flow in contact with each other.
4. The method of claim 1, wherein sheathing the first fluid includes injecting the second fluid into the channel at least partially around the first fluid.
5. The method of claim 4, wherein the second fluid is injected on either side ofthe first fluid in a two-dimensional sheath flow.
6. The method of claim 4, wherein the second fluid completely surrounds the first fluid in a three-dimensional sheath flow.
7. The method of claim 6, wherein the three-dimensional sheath flow has a rounded cross-sectional profile.
8. The method of claim 6, wherein the three-dimensional sheath flow has a squared cross-sectional profile.
9. The method of claim 1, wherein the second fluid is configured to minimize contact ofthe first fluid with an internal surface ofthe microfluidic channel.
10. The method of claim 10, wherein the second fluid is configured to insulate the first fluid from contact with an internal surface ofthe microfluidic channel.
11. A method of controlling a flow of a fluid sample, comprising:
• providing a first fluid as a flow in a microfluidic channel, the first fluid having an unknown or variable viscosity; and sheathing the first fluid with a second fluid having a known viscosity, such that the first fluid has a flow rate that is substantially equal to a flow rate ofthe second fluid at the interface with the first fluid.
12. The method of claim 11 , wherein the known viscosity of the second fluid is adapted for maintaining a particular flow rate for the first fluid in the microfluidic channel.
13. An apparatus for controlling a flow of a fluid samples in a microfluidic channel, comprising: a first fluid, provided as a flow in the microfluidic channel; a second fluid, provided as a flow between an internal surface ofthe channel and the first fluid, the second fluid having a lαiown viscosity tailored to achieve a constant flow rate at a the interface with the first fluid, such that the first fluid achieves substantially the constant flow rate independent of a viscosity associated with the first fluid.
14. The apparatus of claim 13, wherein the second fluid sheaths the first fluid.
15. A method of controlling a flow of a fluid sample, comprising: providing a first fluid as a flow in a microfluidic channel; and providing a second fluid as a flow in the microfluidic channel between the first fluid and an internal surface ofthe channel, the second fluid having a known viscosity, such that the first fluid has a flow rate that is substantially equal to a flow rate ofthe second fluid at the interface with the first fluid.
16. The method of claim 15, wherein the second fluid sheaths the first fluid.
17. A system for performing a microfluidic process, comprising: a microfluidic channel, having a first inlet for receiving a first fluid flow and a second inlet for receiving a second fluid flow in between the first fluid flow and an internal surface ofthe channel, the second fluid having a viscosity that is selected for achieving a particular, constant flow rate at the interface with the first fluid, such that the first fluid flow achieves a flow rate that is substantially equal to the flow rate ofthe second fluid at the interface with the first fluid.
18. The system of claim 17, wherein the second inlet surrounds the first inlet.
19. The system of claim 17, wherein the first and/or the second inlets are squared.
20. The system of claim 17, wherein the first and/or second inlets are rounded.
21. The system of claim 17, wherein the first fluid has an unknown or variable viscosity.
22. A method of controlling a flow of a fluid sample, comprising: injecting a first fluid into a microfluidic channel; and injecting a second fluid into the channel adjacent to the first fluid, the second fluid having a known viscosity, such that the first fluid has a flow rate that is substantially equal to a flow rate ofthe second fluid at the interface between the first and second fluid.
23. The method of claim 22, wherein inj ecting the second fluid further includes forming a sheath around the first fluid with the second fluid.
24. The method of claim 23, wherein the second fluid insulates the first fluid from contact with an internal surface ofthe microfluidic channel.
25. A method of controlling a flow of a fluid sample, comprising: providing a first fluid as a flow in a microfluidic channel, the first fluid containing non-dissolved particles that are susceptible to forces which affect the flow ofthe first fluid; and sheathing the first fluid within a second fluid having a controlled flow, so as to substantially insulate the first fluid from the forces.
26. The method of claim 25, wherein the forces include hydrodynamic shear stress within the microfluidic channel.
27. The method of claim 25, wherein the second fluid has a lαiown viscosity selected for achieving a particular flow profile within the microfluidic channel.
28. A method of controlling a flow of a fluid sample, comprising: providing a first fluid as a flow in a microfluidic channel, the first fluid containing non-dissolved particles that are susceptible to forces which affect the flow of said non-dissolved particles within said microfluidic channel; and sheathing the first fluid within a second fluid having a controlled flow, so as to substantially insulate said first fluid from the forces.
29. A method of controlling a flow of a fluid sample, comprising: providing a first fluid as a flow in a microfluidic channel, the first fluid containing non-dissolved particles that are susceptible to forces which are substantially perpendicular to the direction of flow within said microfluidic channel; and sheathing the first fluid within a second fluid having a controlled flow, so as to substantially insulate said first fluid from the forces.
30. The method of claim 29, wherein the forces include hydrodynamic shear stress within the microfluidic channel.
31. The method of claim 29, wherein the forces include hydrodynamic shear lift within the microfluidic channel.
32. The method of claim 29, wherein the forces include elastic collisions of particles within the microfluidic channel.
PCT/US2002/019482 2001-06-25 2002-06-20 Method and apparatus for controlling fluid flow rate in a microfluidic circuit WO2003000392A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP02753344A EP1419004A2 (en) 2001-06-25 2002-06-20 Method and apparatus for controlling fluid flow rate in a microfluidic circuit
JP2003507029A JP2004536699A (en) 2001-06-25 2002-06-20 Method and apparatus for controlling fluid flow rate in a microfluidic circuit

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/888,727 US20010055546A1 (en) 2000-06-23 2001-06-25 Method and apparatus for controlling fluid flow rate in a microfluidic circuit
US09/888,727 2001-06-25

Publications (2)

Publication Number Publication Date
WO2003000392A2 true WO2003000392A2 (en) 2003-01-03
WO2003000392A3 WO2003000392A3 (en) 2004-03-18

Family

ID=25393764

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/019482 WO2003000392A2 (en) 2001-06-25 2002-06-20 Method and apparatus for controlling fluid flow rate in a microfluidic circuit

Country Status (4)

Country Link
US (1) US20010055546A1 (en)
EP (1) EP1419004A2 (en)
JP (1) JP2004536699A (en)
WO (1) WO2003000392A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10028067C1 (en) * 2000-04-14 2001-08-23 Danfoss As Method for the optical analysis of a fluid
GB2395196B (en) * 2002-11-14 2006-12-27 Univ Cardiff Microfluidic device and methods for construction and application
US20060076295A1 (en) 2004-03-15 2006-04-13 The Trustees Of Columbia University In The City Of New York Systems and methods of blood-based therapies having a microfluidic membraneless exchange device
ATE510605T1 (en) * 2003-03-14 2011-06-15 Univ Columbia SYSTEMS AND METHODS FOR BLOOD BASED THERAPY USING A MEMBRANELESS MICROFLUID EXCHANGE DEVICE
US7155082B2 (en) * 2004-04-12 2006-12-26 Colorado School Of Mines Switchable microfluidic optical waveguides
FR2879290B1 (en) * 2004-12-10 2007-02-02 Rhodia Chimie Sa METHOD AND INSTALLATION FOR DETERMINING RHEOLOGICAL CHARACTERISTICS OF A FLUID, AND METHOD OF IDENTIFYING SAME
CA2652173A1 (en) 2006-05-22 2007-11-29 Edward F. Leonard Systems and methods of microfluidic membraneless exchange using filtration of extraction fluid outlet streams
CA2714594A1 (en) 2008-02-04 2009-08-13 Edward F. Leonard Fluid separation devices, systems and methods
US8861904B2 (en) 2009-10-30 2014-10-14 Cornell University Optofluidic apparatus, method, and application
EP2502075B1 (en) * 2009-11-16 2015-07-15 Silicon Biodevices, Inc. Filtration device for assays
DE102010039031A1 (en) * 2010-08-06 2012-02-09 Krones Aktiengesellschaft Method and device for determining the viscosity
CN102886236B (en) * 2012-10-31 2014-06-04 厦门大学 Driving method of micro-channel inner fluid with nano scale
EP3787794A1 (en) * 2018-04-30 2021-03-10 United Therapeutics Corporation Apparatus and method for controlling fluid flow

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989001590A1 (en) * 1987-08-10 1989-02-23 Australian Commercial Research & Development Limit Pipeline transportation of natural or industrial aqueous slurries
US5948684A (en) * 1997-03-31 1999-09-07 University Of Washington Simultaneous analyte determination and reference balancing in reference T-sensor devices
US6200814B1 (en) * 1998-01-20 2001-03-13 Biacore Ab Method and device for laminar flow on a sensing surface

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6454945B1 (en) * 1995-06-16 2002-09-24 University Of Washington Microfabricated devices and methods
CA2222126A1 (en) * 1995-06-16 1997-01-03 Fred K. Forster Microfabricated differential extraction device and method
US5747349A (en) * 1996-03-20 1998-05-05 University Of Washington Fluorescent reporter beads for fluid analysis
US6159739A (en) * 1997-03-26 2000-12-12 University Of Washington Device and method for 3-dimensional alignment of particles in microfabricated flow channels
CA2320296A1 (en) * 1998-05-18 1999-11-25 University Of Washington Liquid analysis cartridge

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989001590A1 (en) * 1987-08-10 1989-02-23 Australian Commercial Research & Development Limit Pipeline transportation of natural or industrial aqueous slurries
US5948684A (en) * 1997-03-31 1999-09-07 University Of Washington Simultaneous analyte determination and reference balancing in reference T-sensor devices
US6200814B1 (en) * 1998-01-20 2001-03-13 Biacore Ab Method and device for laminar flow on a sensing surface

Also Published As

Publication number Publication date
WO2003000392A3 (en) 2004-03-18
US20010055546A1 (en) 2001-12-27
JP2004536699A (en) 2004-12-09
EP1419004A2 (en) 2004-05-19

Similar Documents

Publication Publication Date Title
US20010055546A1 (en) Method and apparatus for controlling fluid flow rate in a microfluidic circuit
US7134453B2 (en) Microfluidic switch for stopping a liquid flow during a time interval
US7189580B2 (en) Method of pumping fluid through a microfluidic device
US8652852B2 (en) Method of pumping fluid through a microfluidic device
EP0956449B1 (en) Microejection pump
EP1967267B1 (en) Microfluidic valve filler and valve unit including the same
US20030196714A1 (en) Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
US7837948B2 (en) Phase transition type valve and method of manufacturing the same
US20010017158A1 (en) Magnetically actuated fluid handling devices for microfluidic applications
ZA200603614B (en) Multilayer hydrodynamic sheath flow structure
EP2738431A1 (en) Fluid treatment apparatus and method for treating fluid
EP2662135A3 (en) Method for mixing droplets in a microchannel
EP2686595B1 (en) Microfluidic valve and microfluidic platform
CA2864641C (en) Centrifugal microfluidic mixing apparatus and method
US20210114022A1 (en) Microfluidic serial dilution platform based well-plate using an oil-free immiscible phase driven by manual or electronic pipettors
DE102019209746A1 (en) Microfluidic device for processing and aliquoting a sample liquid, method and control device for operating a microfluidic device and microfluidic system for performing an analysis of a sample liquid
AU2021254626A1 (en) An arrangement for mixing fluids in a capillary driven fluidic system
DE102008001312A1 (en) Packing and dispenser system for formulation of multi-constituent viscous substances, has dosing pumps attached to components and exhibiting sucking side that communicates with storage vessels, and check valves provided in inlet of mixer
EP0672834B1 (en) Micro fluid manipulator
EP4106919B1 (en) A microfluidic system and a method for providing a sample fluid having a predetermined sample volume
KR20200024392A (en) Micromixer
DE102022101339A1 (en) ENERGY DISIPATIVE NOZZLES FOR DROP-ON-DEMAND PRINTING AND PROCESSES THEREOF
EP3946732A1 (en) Microdroplet retention arrangement
KR101902847B1 (en) Microvalve
WO2013051924A1 (en) A microfluidic mixer

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2003507029

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2002753344

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002753344

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 2002753344

Country of ref document: EP