WO2013066145A1 - A microfluidic system and method thereof - Google Patents

A microfluidic system and method thereof Download PDF

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Publication number
WO2013066145A1
WO2013066145A1 PCT/MY2012/000156 MY2012000156W WO2013066145A1 WO 2013066145 A1 WO2013066145 A1 WO 2013066145A1 MY 2012000156 W MY2012000156 W MY 2012000156W WO 2013066145 A1 WO2013066145 A1 WO 2013066145A1
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WO
WIPO (PCT)
Prior art keywords
chamber
electrostatic
fluid
microfluidic device
curved sidewall
Prior art date
Application number
PCT/MY2012/000156
Other languages
French (fr)
Inventor
Hing Wah Lee
Chia Sheng Daniel Bien
Original Assignee
Mimos Berhad
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Filing date
Publication date
Application filed by Mimos Berhad filed Critical Mimos Berhad
Publication of WO2013066145A1 publication Critical patent/WO2013066145A1/en

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Classifications

    • 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
    • F16K99/0005—Lift valves
    • F16K99/0007—Lift valves of cantilever type
    • 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
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • 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
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • B01F25/4317—Profiled elements, e.g. profiled blades, bars, pillars, columns or chevrons
    • B01F25/43172—Profiles, pillars, chevrons, i.e. long elements having a polygonal cross-section
    • 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
    • B01F25/431—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor
    • B01F25/43197—Straight mixing tubes with baffles or obstructions that do not cause substantial pressure drop; Baffles therefor characterised by the mounting of the baffles or obstructions
    • B01F25/431971—Mounted on the wall
    • 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
    • B01F25/60—Pump mixers, i.e. mixing within a pump
    • 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
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/71805—Feed mechanisms characterised by the means for feeding the components to the mixer using valves, gates, orifices or openings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/75—Discharge mechanisms
    • B01F35/754—Discharge mechanisms characterised by the means for discharging the components from the mixer
    • B01F35/7547—Discharge mechanisms characterised by the means for discharging the components from the mixer using valves, gates, orifices or openings
    • 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
    • B01L3/502738—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
    • 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
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • F04B43/046—Micropumps with piezoelectric drive
    • 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
    • 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
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0042—Electric operating means therefor
    • F16K99/0051—Electric operating means therefor using electrostatic means
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0638—Valves, specific forms thereof with moving parts membrane valves, flap valves

Definitions

  • the present invention relates to a microfluidic device. More particularly, relates to integration and miniaturization of various fluid manipulation components, particularly a multichannel planar pumping unit, a valve and a mixer onto a single chip for microfluidic applications such as clinical genome analysis, macromolecules separation, enzymatic assays, cell-based assays and any operation that involves a minute volume of fluid samples.
  • Microfluidic systems are well known for manipulating and analysis of fluid samples at sub-millimeter scale. To date, intensive investigations and studies have been conducted to miniaturize and integrate various components su ⁇ ch as pumps, ' valves, filters, mixers, and heater on a single device for a variety of biological and chemical applications. These include drug discovery and development, gene sequencing, immunoassays, in vitro fertilization, and peptide analysis.
  • microfluidic systems that are integrated with various manipulation components on a single device, as understood, provides not only the ease of manipulation of fluids within micrometer-sized channels precisely, they also offers several advantages such as low sample volumes, low chemical consumption, ' fast response time, multiple simultaneous assays, and portability. Furthermore, such microfluidic systems provide a platform for a complete on- chip analysis, where sample preparation, pre-treatment , analytical reaction, detection and results, can be performed within the systems.
  • microfluidic pump includes a pumping chamber positioned between an inlet and an outlet; a plurality of moveable fingers positioned in a wall of said pumping chamber, said fingers being arranged in a row along said wall; and a plurality of thermal bend actuators, each actuator being associated with a respective finger such that actuation of said thermal bend actuator causes movement of said respective finger into said pumping chamber, wherein said pump is configured to provide a peristaltic pumping action in said pumping chamber via movement of said fingers.
  • CMOS circuitry that is- configured to either provide a valve action, a mixing action or a pumping action in the device, by altering an actuation sequence of the finger actuators.
  • This disclosed microfluidic system suffers from several limitations.
  • This single inlet and outlet microfluidic device does not allow parallel introduction and simultaneous or subsequent loading of multiple fluid samples into the device. Contamination of fluid samples to be tested or analyzed in the device is often resulted due to a single input channel is used. For example, during a cleaning process, a cleaning solution would have to be introduced through the same inlet port as the sample to be analyzed, and it thus contaminates the sample in the inlet port. Accordingly, it is the primary object of the present invention to overcome the aforementioned drawbacks.
  • the present invention provides a microfluidic device that allows multiple fluid samples to be independently introduced into the device, and thereby preventing contamination of the fluid samples.
  • It is another object of the present invention to provide a miniaturized microfluidic system comprises a multichannel planar pump unit having a pair of electrostatic-driven membrane electrode for manipulating fluid flow and plurality of mixer structures integrated in the pumping chamber thereof.
  • a microfluidic device having a planar pumping unit integrated with a plurality of mixer structures and a pair of electrostatic- driven membrane electrodes that can be served as fluid flow control valves.
  • said microfluidic device comprises a pumping unit having a pump chamber includes an upper wall, a bottom wall, a first curved sidewall having at least two inlets and a second curved sidewall having at least two outlets, wherein the first curved sidewall and the second curved sidewall are placed in an opposing manner; at least two inflow fluid channels connected to said at least two inlets of the pump chamber for introduction of fluids into the chamber; at least two outflow fluid channels connected to said at least two outlets of the pump chamber for withdrawal of fluid from the chamber; a plurality of mixer structures provided within the cavity of the pump chamber for homogenization of fluids; and a pair of electrostatic-driven membrane electrodes (35a, 35b) disposed within the chamber and configured to manipulate fluid flow in the device
  • Figure 1 illustrates a cross-sectional view
  • microfluidic device of a preferred embodiment accordance to the present invention.
  • Figure 2a-2d illustrates the fluid manipulation process adopted by a microfluidic device of a preferred embodiment with accordance to the present invention.
  • FIG. 1 illustrates a cross-sectional view of microfluidic device (10) constructed in accordance to a preferred embodiment of the present invention.
  • Said microfluidic device (10) includes a planar pumping unit having a pump chamber (15) connected to at least two inflow fluid channels
  • the plurality of mixer structures (25) described herein may be constructed in any configuration and of any materials that assists in enhancing interfacial area between the fluids to be mixed and/or expediting the homogenization of fluids within the chamber (15) .
  • Non-limiting example of mixer structures (25) includes a parallel-plate mixer, a Y- mixer, a planar-type mixer, a spiral-shaped mixer, a circular-shaped mixer and a serpentine type mixer.
  • the plurality of mixer structures (25) have a configuration that is in-plane with the pumping unit.
  • the pump chamber (15) includes an upper wall (15a), a bottom wall (15b), a first curved sidewall (15c) having at least two inlets (30a) and a second curved sidewall (15d) having at least two outlets (30b) .
  • Each inlet (30a) disposed through the first curved sidewall (15c) is connected to a corresponding inflow fluid channel (20a) for introduction of fluid into the chamber (15) .
  • each outlet (30b) disposed through the second curved sidewall (15d) directs fluid to exit from the chamber
  • first sidewall (15c) has a cross-section profile resembling an inverted "L"
  • second curved sidewall- (15d), in cross-section has a substantially "L” shaped profile
  • the second (15d) curved sidewalls may have a substantially “L” shaped an inverted “L” shaped, respectively, in the cross-section profile.
  • the pump chamber (15) further includes a pair of electrostatic-driven membrane electrodes that can be served as flow control valves for manipulating fluid flow in the device (10) .
  • Said pair of electrostatic-driven membrane electrodes include a first membrane electrode (35a) and a second membrane electrode (35b), that are spaced apart to one another and are in proximity to the inner surface of their respective sidewalls (15c, 15d) of the pump chamber (15).
  • These membrane electrodes (35a, 35b) are configured in such a manner that allows fluid flow in an open state and stops fluid flow in a closed state.
  • the open state and the closed state of the membrane electrodes (35a, 35b) in accordance to the preferred embodiment, is controlled by application of voltage.
  • the open state of these membrane electrodes (35a, 35b) is defined . by non-deformed or non-deflected state of the membrane electrode, and in other words, such electrode membrane is in its inactivated state with no voltage supply.
  • the membrane electrodes (35a, 35b) upon application of electrical voltage, will be deformed or deflected towards the curvature surface of the sidewalls (15c, 15d) so that they can seal the inlets (30a) and outlets (30b) of the sidewalls (15c, 15d) , and thereby preventing the flow of fluids from the inlets (30a) or out of the pump chamber (15).
  • each membrane electrode (35a, 35b) is controlled by a respective actuator.
  • the deflection angle of the membrane electrodes (35a, 35b) relative to the curvature surface of the sidewalls (15c, 15d) may be varied with different voltage applied thereto.
  • Inlets (30a) or outlets (30b) provided on the curved surface of the sidewalls (15c, 15d) may not be fully sealed if there is low voltage supplied. These unsealed inlets (30a) or outlets (30b) may thus allow fluids to flow from the inflow (20a) or through the outflow fluid channel (20b) that they communicate with.
  • fluids from different inflow channels (20a) can sequentially be introduced into the chamber (15) .
  • fluids from the pump chamber (15) are also allowed to exit the chamber (15) in a sequential manner through the unsealed outlets (30b).
  • the microfluidic device constructed in accordance to the preferred embodiment may allow multiple fluids from different fluid channels to be independently introduced into the chamber.
  • the pump chamber (15) is associated with a pumping structure for fluid pumping operations and such pumping structure may be operatively coupled with the membrane electrodes (35a, 35b) of the chamber (15) for fluid manipulation.
  • Said pumping structure can be driven by, includes but not limited to electrostatic, thermo-pneumatic, piezoelectric, bimetallic, and shape-memory type actuation. It is preferred that a diaphragm pump is employed as the pumping structure in the microfluidic device (10) of the present invention.
  • a second electrostatic-driven membrane electrode (35b) is actuated to a closed state while a first electrostatic-driven membrane electrode (35a) is actuated to a partially open state with a first inlet (30a') being unsealed for permitting a first fluid sample to flow from the connected first inflow fluid channel (20a') into the chamber (15).
  • a diaphragm pump associated with the chamber (15) is also manipulated to assist the first fluid sample from the unsealed first fluid channel (20a') to the chamber (15) .
  • the first electrostatic-driven membrane electrode (35a) is further actuated to unseal a second inlet (30a") for directing a second fluid sample therethrough into the chamber (15) containing the first fluid sample. Both fluid samples are subsequently homogenously mixed by the plurality of mixer structures (25) disposed within the chamber (15).
  • the second membrane electrode (35b) is then actuated to a fully open state, unsealing the outlets (30b), and in the same time, triggering the diaphragm pump to pump the mixture out of the chamber (15) to the outflow fluid channels (20b) through the outlets (30b). This fluid withdrawal operation is shown in Figure 2c.
  • Figure 2d illustrates the cleaning operation adopted by the microfluidic device (10) ⁇ in accordance to the preferred embodiment of the present invention.
  • the first electrostatic-driven membrane electrode (35a) is actuated to a fully open state.
  • Inlets (30a) provided on the first curved sidewalls are no longer sealed by said first membrane electrode (35a) .
  • Cleaning reagent is then introduced into the chamber (15) through the newly unsealed third inlet (20a"' ) . It should be understood that cleaning agent also can be introduced into the chamber (15) from the first (20a') and the second inlets (20") .
  • the diaphragm pump is triggered to reduce pressure in the chamber, resulting cleaning fluid to be introduced therein via the inlets (20a) . Subsequently, actuating the second membrane electrode (35b) to a fully open state and pumping the cleaning reagent out through the unsealed outlets (30b) by means of the diaphragm pump. Cleaning steps as above may be repeated until a desired level of cleaning is obtained. It should be understood that, upon completion of the cleaning, the first membrane electrode (35a) is actuated to its fully closed state, inhibiting cleaning reagent from entering the pump chamber (15) .

Abstract

A microfluidic device (10) comprises a pumping unit having a pump chamber (15) includes an upper wall (15a), a bottom wall (15b), a first curved sidewall (15c) having at least two inlets (30a) and a second curved sidewall (15d) having at least two outlets (30b), wherein the first curved sidewall (15c) and the second curved sidewall (15d) are placed in an opposing manner; at least two inflow fluid channels (20a) connected to said at least two inlets (30a) of the pump chamber (15) for introduction of fluids into the chamber (15); at least two outflow fluid channels (20b) connected to said at least two outlets (30b) of the pump chamber (15) for withdrawal of fluid from the chamber (15); a plurality of mixer structures (25) provided within the cavity of the pump chamber (15) for homogenization of fluids; and a pair of electrostatic-driven membrane electrodes (35a, 35b) disposed within the chamber (15) and configured to manipulate fluid flow in the device.

Description

A Microfluidic System and Method Thereof
Field of Invention
The present invention relates to a microfluidic device. More particularly, relates to integration and miniaturization of various fluid manipulation components, particularly a multichannel planar pumping unit, a valve and a mixer onto a single chip for microfluidic applications such as clinical genome analysis, macromolecules separation, enzymatic assays, cell-based assays and any operation that involves a minute volume of fluid samples.
Background of the Invention
Microfluidic systems are well known for manipulating and analysis of fluid samples at sub-millimeter scale. To date, intensive investigations and studies have been conducted to miniaturize and integrate various components su^ch as pumps, ' valves, filters, mixers, and heater on a single device for a variety of biological and chemical applications. These include drug discovery and development, gene sequencing, immunoassays, in vitro fertilization, and peptide analysis.
Miniaturization of microfluidic systems that are integrated with various manipulation components on a single device, as understood, provides not only the ease of manipulation of fluids within micrometer-sized channels precisely, they also offers several advantages such as low sample volumes, low chemical consumption,' fast response time, multiple simultaneous assays, and portability. Furthermore, such microfluidic systems provide a platform for a complete on- chip analysis, where sample preparation, pre-treatment , analytical reaction, detection and results, can be performed within the systems.
One example of miniaturized microfluidic system comprising microfluidic pumps, mixer or valve, has been disclosed in prior art document, US2009317298. This microfluidic system comprises microfluidic pump includes a pumping chamber positioned between an inlet and an outlet; a plurality of moveable fingers positioned in a wall of said pumping chamber, said fingers being arranged in a row along said wall; and a plurality of thermal bend actuators, each actuator being associated with a respective finger such that actuation of said thermal bend actuator causes movement of said respective finger into said pumping chamber, wherein said pump is configured to provide a peristaltic pumping action in said pumping chamber via movement of said fingers. Such disclosed microfluidic system, further comprises a CMOS circuitry that is- configured to either provide a valve action, a mixing action or a pumping action in the device, by altering an actuation sequence of the finger actuators.
This disclosed microfluidic system suffers from several limitations. This single inlet and outlet microfluidic device does not allow parallel introduction and simultaneous or subsequent loading of multiple fluid samples into the device. Contamination of fluid samples to be tested or analyzed in the device is often resulted due to a single input channel is used. For example, during a cleaning process, a cleaning solution would have to be introduced through the same inlet port as the sample to be analyzed, and it thus contaminates the sample in the inlet port. Accordingly, it is the primary object of the present invention to overcome the aforementioned drawbacks. The present invention provides a microfluidic device that allows multiple fluid samples to be independently introduced into the device, and thereby preventing contamination of the fluid samples.
It is another object of the present invention to provide a miniaturized microfluidic system comprises a multichannel planar pump unit having a pair of electrostatic-driven membrane electrode for manipulating fluid flow and plurality of mixer structures integrated in the pumping chamber thereof.
Other objects of this invention will become apparent on the reading of this entire disclosure.
Summary of the Invention
In one aspect of present invention, disclosed a microfluidic device having a planar pumping unit integrated with a plurality of mixer structures and a pair of electrostatic- driven membrane electrodes that can be served as fluid flow control valves. Suitably, in accordance to a preferred embodiment, said microfluidic device comprises a pumping unit having a pump chamber includes an upper wall, a bottom wall, a first curved sidewall having at least two inlets and a second curved sidewall having at least two outlets, wherein the first curved sidewall and the second curved sidewall are placed in an opposing manner; at least two inflow fluid channels connected to said at least two inlets of the pump chamber for introduction of fluids into the chamber; at least two outflow fluid channels connected to said at least two outlets of the pump chamber for withdrawal of fluid from the chamber; a plurality of mixer structures provided within the cavity of the pump chamber for homogenization of fluids; and a pair of electrostatic-driven membrane electrodes (35a, 35b) disposed within the chamber and configured to manipulate fluid flow in the device.
Brief Description of the Drawings
Other objects, features, and advantages of the invention will be apparent from the following description when read with reference to the accompanying drawings. In the drawings, wherein like reference numerals denote corresponding parts throughout the several views:
Figure 1 illustrates a cross-sectional view
microfluidic device of a preferred embodiment accordance to the present invention; and
Figure 2a-2d illustrates the fluid manipulation process adopted by a microfluidic device of a preferred embodiment with accordance to the present invention.
Detailed Description of the Preferred Embodiments
Figure 1 illustrates a cross-sectional view of microfluidic device (10) constructed in accordance to a preferred embodiment of the present invention. Said microfluidic device (10) includes a planar pumping unit having a pump chamber (15) connected to at least two inflow fluid channels
(20a) and at least two outflow fluid channels (20b) , and a plurality of mixer structures (25) provided within the cavity of the pump chamber (15) for homogenization and/or mixing of fluids introduced from the inflow fluid channels
(20a) .
The plurality of mixer structures (25) described herein may be constructed in any configuration and of any materials that assists in enhancing interfacial area between the fluids to be mixed and/or expediting the homogenization of fluids within the chamber (15) . Non-limiting example of mixer structures (25) includes a parallel-plate mixer, a Y- mixer, a planar-type mixer, a spiral-shaped mixer, a circular-shaped mixer and a serpentine type mixer. However, in order to be integrated with the planar pumping unit, it is preferred that the plurality of mixer structures (25) have a configuration that is in-plane with the pumping unit.
Referring back to Figure 1, the pump chamber (15) includes an upper wall (15a), a bottom wall (15b), a first curved sidewall (15c) having at least two inlets (30a) and a second curved sidewall (15d) having at least two outlets (30b) . Each inlet (30a) disposed through the first curved sidewall (15c) is connected to a corresponding inflow fluid channel (20a) for introduction of fluid into the chamber (15) . Similarly, each outlet (30b) disposed through the second curved sidewall (15d) directs fluid to exit from the chamber
(15) to a corresponding outflow fluid channel (20b) . It should be understood that the curved first sidewall (15c) and the second curved sidewall (15d) are placed in an opposing manner. In this illustrated embodiment, the first curved sidewall (15c) has a cross-section profile resembling an inverted "L", while the second curved sidewall- (15d), in cross-section, has a substantially "L" shaped profile. As will be understood, in an alternative embodiment, the first
(15c) and the second (15d) curved sidewalls may have a substantially "L" shaped an inverted "L" shaped, respectively, in the cross-section profile.
The pump chamber (15) further includes a pair of electrostatic-driven membrane electrodes that can be served as flow control valves for manipulating fluid flow in the device (10) . Said pair of electrostatic-driven membrane electrodes include a first membrane electrode (35a) and a second membrane electrode (35b), that are spaced apart to one another and are in proximity to the inner surface of their respective sidewalls (15c, 15d) of the pump chamber (15). These membrane electrodes (35a, 35b) are configured in such a manner that allows fluid flow in an open state and stops fluid flow in a closed state. The open state and the closed state of the membrane electrodes (35a, 35b) in accordance to the preferred embodiment, is controlled by application of voltage. The open state of these membrane electrodes (35a, 35b) is defined . by non-deformed or non-deflected state of the membrane electrode, and in other words, such electrode membrane is in its inactivated state with no voltage supply. On the contrary, upon application of electrical voltage, the membrane electrodes (35a, 35b) will be deformed or deflected towards the curvature surface of the sidewalls (15c, 15d) so that they can seal the inlets (30a) and outlets (30b) of the sidewalls (15c, 15d) , and thereby preventing the flow of fluids from the inlets (30a) or out of the pump chamber (15).
As illustrated, each membrane electrode (35a, 35b) is controlled by a respective actuator. As will be apparent to one skilled artisan, the deflection angle of the membrane electrodes (35a, 35b) relative to the curvature surface of the sidewalls (15c, 15d) may be varied with different voltage applied thereto. Inlets (30a) or outlets (30b) provided on the curved surface of the sidewalls (15c, 15d) may not be fully sealed if there is low voltage supplied. These unsealed inlets (30a) or outlets (30b) may thus allow fluids to flow from the inflow (20a) or through the outflow fluid channel (20b) that they communicate with. Accordingly, by means of manipulating the voltage supply to these membrane electrodes (35a, 35b), fluids from different inflow channels (20a) can sequentially be introduced into the chamber (15) . Likewise, fluids from the pump chamber (15) are also allowed to exit the chamber (15) in a sequential manner through the unsealed outlets (30b). It is further contemplated that the microfluidic device constructed in accordance to the preferred embodiment may allow multiple fluids from different fluid channels to be independently introduced into the chamber.
Further to the illustrated embodiment, the pump chamber (15), understandably, is associated with a pumping structure for fluid pumping operations and such pumping structure may be operatively coupled with the membrane electrodes (35a, 35b) of the chamber (15) for fluid manipulation. Said pumping structure can be driven by, includes but not limited to electrostatic, thermo-pneumatic, piezoelectric, bimetallic, and shape-memory type actuation. It is preferred that a diaphragm pump is employed as the pumping structure in the microfluidic device (10) of the present invention.
In operation of the microfluidic device (10) constructed in accordance to the preferred embodiment of the present invention, and as be readily seen in Figure 2a, a second electrostatic-driven membrane electrode (35b) is actuated to a closed state while a first electrostatic-driven membrane electrode (35a) is actuated to a partially open state with a first inlet (30a') being unsealed for permitting a first fluid sample to flow from the connected first inflow fluid channel (20a') into the chamber (15). Meanwhile, a diaphragm pump associated with the chamber (15) is also manipulated to assist the first fluid sample from the unsealed first fluid channel (20a') to the chamber (15) . As depicted in Figure 2b, following introduction of said first fluid sample, the first electrostatic-driven membrane electrode (35a) is further actuated to unseal a second inlet (30a") for directing a second fluid sample therethrough into the chamber (15) containing the first fluid sample. Both fluid samples are subsequently homogenously mixed by the plurality of mixer structures (25) disposed within the chamber (15). To withdraw the mixture out from the chamber (15) , the second membrane electrode (35b) is then actuated to a fully open state, unsealing the outlets (30b), and in the same time, triggering the diaphragm pump to pump the mixture out of the chamber (15) to the outflow fluid channels (20b) through the outlets (30b). This fluid withdrawal operation is shown in Figure 2c. Figure 2d illustrates the cleaning operation adopted by the microfluidic device (10) ■ in accordance to the preferred embodiment of the present invention. Referring to this illustrated embodiment, soon after pumping the mixture out of the pump chamber (15), the first electrostatic-driven membrane electrode (35a) is actuated to a fully open state. Inlets (30a) provided on the first curved sidewalls are no longer sealed by said first membrane electrode (35a) . Cleaning reagent is then introduced into the chamber (15) through the newly unsealed third inlet (20a"' ) . It should be understood that cleaning agent also can be introduced into the chamber (15) from the first (20a') and the second inlets (20") .
As described earlier, to direct fluid flows into the chamber, the diaphragm pump is triggered to reduce pressure in the chamber, resulting cleaning fluid to be introduced therein via the inlets (20a) . Subsequently, actuating the second membrane electrode (35b) to a fully open state and pumping the cleaning reagent out through the unsealed outlets (30b) by means of the diaphragm pump. Cleaning steps as above may be repeated until a desired level of cleaning is obtained. It should be understood that, upon completion of the cleaning, the first membrane electrode (35a) is actuated to its fully closed state, inhibiting cleaning reagent from entering the pump chamber (15) . As will be readily apparent to those skilled in the art, the present invention may easily be produced in other specific forms without departing from its essential characteristics. The present embodiments is, therefore, to be considered as merely illustrative and not restrictive, the scope of the invention being indicated by the claims rather than the foregoing description, and all changes which come within therefore intended to be embraced therein.

Claims

Claims
1. A microfluidic device (10), comprising:
a pumping unit having a pump chamber (15) includes an upper wall (15a), a bottom wall (15b), a first curved sidewall ( 15c) having at least two inlets (30a) and a second curved sidewall (15d) having at least two outlets (30b), wherein the first curved sidewall (15c) and the second curved sidewall are placed in an opposing manner;
at least two inflow fluid channels (20a) connected to said at least two inlets of the pump chamber (15) for introduction of fluids into the chamber (15);
at least two outflow fluid channels (20b) connected to said at least two outlets of the pump chamber (15) for withdrawal of fluid from the chamber (15);
a plurality of mixer structures (25) provided within the cavity of the pump chamber (15) for homogenization of fluids; and
a pair of electrostatic-driven membrane electrodes (35a, 35b) disposed within the chamber (15) and configured to manipulate fluid flow in the device by permitting fluid flow in an open state, and inhibiting fluid flow on a closed state, said open state and closed state of the membrane electrodes (35a, 35b) are controlled by application of voltage.
2. A microfluidic device (10) as claimed in Claim 1, wherein said first curved sidewall (15c) may have a cross- section profile resembling an inverted "L", while the second curved sidewall (15d) may have a substantially "L" shaped cross section profile, or vice versa.
3. A microfluidic device (10) as claimed in Claim 1, wherein both pumping unit and plurality of mixer structures have a planar configuration.
4. A microfluidic device (10) as claimed in Claim 1, wherein said pair of electrostatic -driven membrane electrodes (35a, 35b) includes a first electrostatic-driven membrane electrode (35a) disposed in proximity to the inner surface of the first curved sidewall (15c) of the chamber (15), and a second electrostatic-driven membrane electrode (35b) disposed in proximity to the inner surface of the second curved sidewall (15d) of the chamber (15) .
5. A microfluidic device (10) as claimed in Claim 1, said pair of electrostatic-driven electrodes (35a, 35b), when in a closed state, is deformed or deflected in relation to the curvature of the sidewalls so that it can seal the inlets (30a) and outlets (30b) provided at the chamber (15), and thereby inhibits fluid from flowing therethrough.
6. A microfluidic device (10) as claimed in Claim 1, wherein said pair of electrostatic-driven electrodes (35a, 35b), when in an open state, are in a non-deformed or non-deflected condition where the membrane electrodes (35a, 35b) are disposed in such a manner that they are in proximity to the inner surface of the sidewalls (15c, 15d), but do not seal the inlets and outlets provided at the sidewalls of the chamber, so as to allow fluid flow.
7. A microfluidic device (10) as claimed in Claim 1, wherein said pair of electrostatic-driven membrane electrode (35) is configured in such a manner that they allow multiple fluids to be independently introduced into the chamber (15) from different inflow fluid channels (-20a) .
8. A microfluidic device (10) as claimed in Claim 1, wherein said pair of electrostatic-driven membrane electrodes (35) is configured in such a manner that they allow multiple fluids to be introduced into the chamber, and allow fluids to be withdrawn from the chamber in a sequential manner.
9. A microfluidic device (10) as claimed in Claim 1, wherein said pumping unit further includes a diaphragm pump, said diaphragm pump may be actuated by electrostatic, thermo-pneumatic, piezoelectric, bimetallic, and shape- memory type actuation.
10. A method for mixing at least two fluid samples in a minute volume, comprising the steps of:
providing a microfluidic device (10) comprising:
a pumping unit includes a pump chamber (15) having an upper wall (15a), a bottom wall (15b), a first curved sidewall (15c) having at least three inlet (30a) that respectively connected to at least three inflow fluid channels (20a) for introduction of fluids into the chamber (15) and a second curved sidewall (15d) having at least three outflow fluid channels (20b) for withdrawal of fluids from the chamber (15);
a plurality of mixer structures (25) provided within the cavity of the pump chamber (15);
a first electrostatic-driven membrane electrode (35a) and a second electrostatic-driven membrane electrode ( 35b ) disposed in the chamber (15), said first membrane electrode (35a) is placed in proximity to the inner surface of the first curved sidewalls (15c) of the chamber (15), said second membrane electrode (35b) is placed in proximity to the inner surface of the second curved sidewall (15d) of the chamber (15);
a diaphragm pump associated with the chamber (15) and cooperatively coupled with said electrostatic- driven membrane electrodes (35a, 35b) for manipulating fluid flow in the microfluidic device (10) , wherein said electrostatic- driven membrane electrodes (35a, 35b) are configured to permit fluid flow in an open state and to inhibit fluid flow in a closed state;
introducing a first fluid sample into the chamber (15), wherein further comprising:
actuating the second electrostatic-driven membrane electrode ( 35b) to its fully closed state, sealing the outlets (30b) and thus inhibiting fluid flow from the chamber ( 15 ) ;
actuating the first electrostatic-driven membrane electrode ( 35a) to its partially open state with a first corresponding inlet (30a') being unsealed for permitting the first fluid sample to flow from a first inflow fluid channel (20a' ) into the chamber ( 15 ) ; and
simultaneously allowing the diaphragm pump to operate, and thus pumping the first fluid into the chamber (15);
introducing a second fluid samples to the chamber (15), comprising:
actuating the first electrostatic-driven membrane electrode ( 35a ) to its partially open state, unsealing a second inlet (30a"), and thereby allowing the second fluid samples to the chamber (15) from second inflow fluid channel (20b"); and simultaneously allowing the diaphragm pump to operate and thus pumping the second fluid sample into the chamber ( 15 ) ;
homogenously mixing both fluid samples in the chamber (15) by means of a plurality of mixer structures (25 ) disposed therein; and
pumping the homogeneously mixed fluid samples out of the chamber (15) by actuating the second electrostatic-driven membrane electrode (35b) from the closed state to a fully open state, unsealing the outlets (30b) of the chamber ( 15 ), and simultaneously allowing the diaphragm pump to operate so that the fluids can be pumped out through the unsealed outlets ( 30b) .
PCT/MY2012/000156 2011-11-01 2012-06-28 A microfluidic system and method thereof WO2013066145A1 (en)

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