WO2017165535A1 - Integrated dielectric elastomeric actuators - Google Patents

Integrated dielectric elastomeric actuators Download PDF

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Publication number
WO2017165535A1
WO2017165535A1 PCT/US2017/023612 US2017023612W WO2017165535A1 WO 2017165535 A1 WO2017165535 A1 WO 2017165535A1 US 2017023612 W US2017023612 W US 2017023612W WO 2017165535 A1 WO2017165535 A1 WO 2017165535A1
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Prior art keywords
fluidic channel
compliant
electrode
fluid
microfluidic
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PCT/US2017/023612
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French (fr)
Inventor
Christopher T. Culbertson
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Kansas State University Research Foundation
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Publication of WO2017165535A1 publication Critical patent/WO2017165535A1/en

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    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04BPOSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006Micropumps
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273Containers 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
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04BPOSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/04Pumps for special use
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0003Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0026Valves using channel deformation
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0034Operating means specially adapted for microvalves
    • F16K99/0042Electric operating means therefor
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0034Operating means specially adapted for microvalves
    • F16K99/0042Electric operating means therefor
    • F16K99/0049Electric operating means therefor using an electroactive polymer [EAP]
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0034Operating means specially adapted for microvalves
    • F16K99/0055Operating means specially adapted for microvalves actuated by fluids
    • F16K99/0061Operating means specially adapted for microvalves actuated by fluids actuated by an expanding gas or liquid volume
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/088Channel loops
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials
    • B01L2300/123Flexible; Elastomeric
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0082Microvalves adapted for a particular use
    • F16K2099/0084Chemistry or biology, e.g. "lab-on-a-chip" technology
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0082Microvalves adapted for a particular use
    • F16K2099/0094Micropumps

Definitions

  • the present invention is generally directed toward integrated dielectric elastomeric actuators that can be incorporated within a microfluidic device.
  • the actuators function as valves that are operable to collapse a fluidic channel formed in a compliant material.
  • the plurality of actuators make up a pump capable of providing a motive force for a fluid flowing within the fluidic channel.
  • the actuators, and/or pump made from a plurality of actuators can be used within a point-of-care device for the detection of an analyte within a fluid sample.
  • Actuators are becoming an increasingly popular component of micro-Total Analysis Systems ( ⁇ -TAS, or microfluidic devices). Their popularity stems from the desire to fully integrate multiple fluid-handling architectures on a single device in order to perform multi-step analyses.
  • ⁇ -TAS micro-Total Analysis Systems
  • devices that incorporate pneumatic, thermopneumatic, piezoelectric, shape memory alloy, electrothermal, electrochemical, electrostatic, or magnetic actuation have been constructed. The majority of these actuation systems derive their function from the reversible deflection of a polymer membrane, which produces a volume change in a portion of the native channel network.
  • these miniaturized actuators have found use as microvalves and micropumps.
  • a microfluidic actuator comprises a compliant electrode layer, a fluidic channel layer, a fixed electrode and an insulative layer interposed between the fluidic channel layer and the fixed electrode.
  • the compliant electrode layer comprises a liquid compliant electrode.
  • the fluidic channel layer comprises a fluidic channel defined at least in part by a compliant material.
  • the compliant material is interposed between the liquid compliant electrode and the fluidic channel.
  • the fixed electrode comprises a conductive material carried by a substrate, and the insulative layer comprises an insulating material.
  • a microfluidic pump comprising a fluidic channel layer comprising a fluidic channel defined at least in part by a compliant material.
  • the pump also comprises a compliant electrode layer comprising at least first and second liquid compliant electrodes that are spaced apart and overlie the fluidic channel.
  • the pump further comprises at least one fixed electrode affixed to a substrate and in registry with the first and second liquid compliant electrodes.
  • the pump also comprises an insulative layer comprising an insulating material. The insulating material is interposed between the fluidic channel layer and the at least one fixed electrodes.
  • a device for analysing a fluid specimen includes a fluid-analysis loop comprising a fluidic channel layer.
  • the fluidic channel layer comprises a fluid inlet, a fluid outlet, and a fluidic channel interconnecting the fluid inlet and fluid outlet.
  • the fluidic channel is defined at least in part by a compliant material and configured to conduct the fluid specimen through the device.
  • the device also includes at least one microfluidic pump comprising a compliant electrode layer, a least one fixed electrode, and an insulative layer.
  • the compliant electrode layer has at least first and second liquid compliant electrodes that are spaced apart and overlie the fluidic channel.
  • the at least one fixed electrode is affixed to a substrate and is in registry with the first and second liquid compliant electrodes.
  • the insulative layer comprises an insulating material that is interposed between the fluidic channel layer and the at least one fixed electrode.
  • the device further comprises at least one biosensor located between the fluid inlet and fluid outlet and operable to detect the presence or absence of an analyte within the fluid specimen flowing within the fluidic channel.
  • a method of moving a fluid within a fluidic channel on a microfluidic device comprises the steps of introducing a fluid into the fluidic channel and actuating a microfluidic pump contained within the microfluidic device.
  • the fluidic channel is formed within a fluidic channel layer on the device.
  • the fluidic channel layer comprises a compliant material.
  • the microfluidic pump comprises a compliant electrode layer having at least first, second, and third liquid compliant electrodes that are spaced apart and overlying the fluidic channel, at least one fixed electrode affixed to a substrate and in registry with the first, second, and third liquid compliant electrodes, and an insulative layer comprising an insulating material.
  • the insulating material is interposed between the fluidic channel layer and the at least one fixed electrode.
  • Figure 1A is a schematic illustration of an integrated dielectric elastomeric actuator constructed in accordance with one embodiment of the present invention
  • Fig. IB is schematic illustration of the cross section of two actuator embodiments, one embodiment comprising an insulating layer and showing the actuator in "valve open” and “valve closed” configurations, and one embodiment in which the insulating layer comprises a high-dielectric coating over the fixed electrode;
  • Fig. 2 is a schematic illustration of the operation of a microfluidic pump comprising three actuators arranged in series;
  • Fig. 3 is a schematic diagram of a point-of-care device comprising a plurality of integrated actuators for the detection of an analyte present in a fluid sample.
  • EAPs electroactive polymers
  • An EAP is an organic polymer that can be physically deformed in the presence of an electric field, i.e. an electromechanical transducer. These electromechanical transducers exist in multiple forms, depending upon the type of EAP used. Types of EAPs include conducting polymers, ionic polymer-metal composites (EVIPCs), carbon nanotubes (CNTs), ferroelectric polymers and dielectric elastomers (DEs). Regardless of the exact identity of the EAP, an actuator can be formed by sandwiching a thin EAP film between two electrodes.
  • EAPs electroactive polymers
  • At least one of the electrodes has some degree of compliance, i.e. be able to move and stretch.
  • an electric field is applied across the EAP, opposite charges accumulate on each electrode surface. Due to the presence of these opposing charges on the electrodes, Maxwell stress is generated and it acts on the EAP film in two ways. First, unlike charges on the opposite surfaces of the EAP create an attractive force perpendicular to the plane of the film, which seeks to compress the polymer. Second, the presence of like charges on the surface of each electrode produces a repulsive force in the plane of the film, which acts to stretch the polymer.
  • s z is the thickness strain
  • Y is the Young's modulus of the EAP
  • J 7 is the potential drop across the EAP film
  • zo is the original thickness of the EAP film.
  • the Hookean model predicts elastomer response only at infinitesimal strains (typically less than 10%). At finite strains, the Hookean model breaks down for DEs since they tend to become "harder” for increasingly compressive stresses.
  • the Neo-Hookean, Mooney-Rivlin and Ogden models have been developed. These models take into account the fact that the elasticity of an elastomer changes as the amount of strain that it experiences increases.
  • the behavior of elastomers in response to stress is often described using the Mooney-Rivlin model.
  • the strain in a system that is immobilized in one dimension can be calculated from:
  • T xx and T zz are the stress tensors in their respective Cartesian planes, Ci and C2 are constants, and a is the stretch ratio.
  • the difference between the stress tensors T xx and T zz represents the total stress on the elastomer, which is defined as:
  • Equations (1) and (4) are equivalent.
  • elastomers are used frequently as electroactive actuators.
  • Other elastomeric materials may be used, e.g. acrylics, urethanes, fluoroelastomers, and polybutadienes. With a Poisson's ratio extremely close to 0.5, silicone elastomers are also virtually incompressible.
  • the z-directional compression is accompanied by an equivalent amount of extension in the x a d y planes of the film.
  • DEs typically require large operating voltages (10 2 to 10 3 V) to produce significant strains, their flexibility, ruggedness, scalability, low cost and ease of fabrication further increase the feasibility of incorporating these materials on commercial devices.
  • DE actuators are gaining interest for use in the development of robotics, pumps, motors, acoustics, medical prosthetics, micro air vehicles (MAVs) and haptic devices.
  • FIG. 1A An exemplary actuator 10 is shown in Fig. 1A.
  • Actuator 10 is constructed on a substrate 12, which is preferably a rigid support upon which the various feature or layers making up actuator 10 can be applied.
  • the substrate 12 can comprise glass (i.e., silicon dioxide), one or more plastics, or mixtures thereof.
  • the substrate 12 can have any width, length, and thickness suitable for use in a microfluidic device.
  • Formed on or otherwise carried by substrate 12 is fixed, noncompliant electrode 14.
  • Electrode 14 is generally planar and can be formed from any electrically conducting materials known in the art.
  • Exemplary materials that may be used in forming electrode 14 include, but are not limited to, solid conductive materials such as one or more metals, graphitic carbon, indium tin oxide, barium (strontium) titanates, or mixtures thereof. Additionally, the electrode 14 can be incorporated on the substrate layer 12 employing methods known in the art, such as photolithography and wet chemical processing (etching).
  • Insulative layer 16 is applied over electrode 14 and/or substrate layer 12.
  • Insulative layer 16 comprises an insulating, or non-conductive, material.
  • insulating material is also noncompliant.
  • Exemplary insulating materials that comprise insulative layer 16 include poly(dimethylsiloxane) (PDMS), a poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof.
  • the insulative layer 16 has an average material thickness of from about 5 to about 100 ⁇ , from about 10 to about 75 ⁇ , or from about 20 to about 50 ⁇ . As illustrated in Fig.
  • insulative layer 16 has an average material thickness of 30 ⁇ .
  • the insulative layer comprises a high dielectric coating 16a that is applied over the fixed electrode 14. This design decreases the distance between the electrodes making up actuator 10, which allows for lower voltage actuation of actuator 10.
  • Exemplary high dielectric coatings include various silicones, acrylics, cellulose acetate, barium (or strontium) titanate, silicon or titanium oxides, or perovskite materials that have significantly high electrical breakdown potentials than PDMS or other types of elastomers.
  • such surfaces have functionalities that make them suitable for modification and the attachment of sensing species for point of care devices, such as those described below.
  • a fluidic channel layer 18 is located over insulative layer 16 and comprises a fluidic channel 20 formed therein.
  • the fluidic channel layer 18 generally comprises a compliant material, and in particular an electroactive polymer.
  • the electroactive polymer is selected from the group consisting of poly(dimethylsiloxane) (PDMS), a poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof.
  • PDMS poly(dimethylsiloxane)
  • a fluorosilicone an acrylic polymer
  • fluidic channel layer 18 comprises the same or a different material than insulative layer 16.
  • the fluidic channel layer 18 has an average material thickness of from about 10 to about 100 ⁇ , from about 25 to about 80 ⁇ , or from about 40 to about 60 ⁇ . As illustrated in Fig. 1A, fluidic channel layer 18 has an average thickness of 50 ⁇ .
  • the fluidic channel 20 generally comprises an elongate void region that is cooperatively defined by the fluidic channel layer 18 and the insulative layer 16, and is configured to conduct a fluid, which can be a gas, liquid or supercritical fluid, for example. As illustrated in Fig. 1A, fluidic channel 20 is hemicylindrical (half of a right circular cylinder), although other configurations such as right rectangular cylinders may also be used.
  • the fluidic channel 20 is formed within fluidic channel layer 18 by molding PDMS or other likewise material against a negative mastermold of the channel manifold. Layer 18 is then joined (adhered) to layers 22 and 16. The joining can be reversible or irreversible. Reversible joining occurs due to contact adhesion forces. In irreversible joining, differing ratios of PDMS prepolymer curing agents are used. In general if a 5: 1 A:B curing ratio for layer 18 is used, then a 30: 1 A:B ratio for layers 22 and 16 can be used.
  • the fluidic channel 20 can have any dimensions suitable for permitting the flow of a fluid on a microfluidic device.
  • the fluidic channel 20 can have average widths of from about 5 to about 150 ⁇ , from about 15 to about 100 ⁇ , or from about 30 to about 750 ⁇ . In certain embodiments, the fluidic channel 20 may have an average depth of from about 5 to about 100 ⁇ , from about 10 to about 50 ⁇ , or from about 15 to about 35 ⁇ . As illustrated in Fig. 1A, the fluidic channel 20 has an average width of 50 ⁇ and an average depth of 25 ⁇ .
  • a compliant electrode layer 22 is located over fluidic channel layer 18.
  • a liquid compliant electrode 24 is formed within layer 22 by molding in a similar manner as to how the fluidic channel 20 is molded.
  • the compliant electrode layer 22 comprises a compliant material, and in certain embodiments, the compliant material comprises a silicone elastomer. In preferred embodiments, the silicone elastomer comprises poly(dimethylsiloxane). In certain embodiments, the compliant electrode layer 22 has an average material thickness of from about 100 ⁇ to about 1 cm, from about 500 ⁇ to about 5 mm, or from about 1 mm to about 3 mm. .
  • the liquid compliant electrode 24 generally comprises a pumping channel 26 formed within the compliant electrode layer 22 that is filled with a conductive liquid.
  • the pumping channel 26 is cooperatively defined by the compliant electrode layer 22 and the fluidic channel layer.
  • Exemplary conductive liquids that can be used in the compliant electrode 24 include any aqueous solution, conducting organic liquid, liquid metal, and ionic-liquid.
  • the compliant electrode it is preferred that the compliant electrode not comprise a carbon grease electrode.
  • the pumping channel 26 has a length, or longest dimension, that is greater than the average width of the fluidic channel 20. As explained below, this configuration ensures that the fluidic channel can be completely collapsed upon expansion of the compliant electrode 24.
  • the pumping channel 26 has an average length of from about 10 to about 200 ⁇ , from about 25 to about 150 ⁇ , or from about 50 to about 125 ⁇ .
  • the length of the pumping channel 26 depicted in Fig. 1A is 90 ⁇ .
  • the liquid compliant electrode 24 is also oriented to be in general registry, or alignment, with the fixed electrode, which are separated by at least the fluidic channel layer 18 and the insulative layer 16 thereby forming a capacitor-like structure. It is noted that because in certain embodiments fixed electrode 14 is noncompliant, compliant electrode 24 is the only electrode fabricated from a compliant material for any particular actuator 10.
  • Figure IB depicts the operation of actuator 10.
  • the fluidic channel 20 is sandwiched between the liquid compliant electrode 24 and the fixed electrode 14.
  • the electrodes 14 and 24 are connected to a voltage source 28, and once a switch 30, e.g., an optodiode, is closed the force generated between the two electrodes causes the compliant electrode 24 to change shape.
  • a switch 30, e.g., an optodiode e.g., an optodiode
  • the fluidic channel layer 18 must change shape.
  • the easiest path for relieving the stress induced by the electric field is to compress the fluidic channel thus collapsing or pinching off the channel between the two electrodes. This effectively forms a valve that is capable of controlling the flow of a liquid within the fluidic channel 20.
  • Connections to electrical power supplies can be made using small, flexible wires or pins.
  • the capacitance of the actuator 10 is low and so little power is required to drive the valve. This allows high voltage/low current power supplies to be used for actuation, such as computer USB ports. In such designs, a single power supply can be used with several high voltage switches. Such switches can work at speeds of over a kHz.
  • a plurality of actuators 10 can be arranged in series along a common fluidic channel thereby creating a peristaltic pump capable of moving a fluid within the fluidic channel.
  • Figure 2 illustrates one such pump 32 made in accordance with the present invention and comprising three compliant electrodes.
  • the uppermost image of Fig. 2 depicts a switch-open configuration for each of compliant electrodes 24a, 24b, and 24c and the fixed electrode 14.
  • the fixed electrode 14 may cover the entire bottom plane of the device and serve as a ground plane or high voltage plane.
  • the actuators 10 are then actuated by applying a potential to the compliant electrodes 24a, 24b, 24c or grounding them if they are otherwise floating.
  • all of the compliant electrodes 14a, 24b, 24c can be grounded and a plurality of fixed electrodes can be patterned individually on the substrate 12.
  • the actuators 10 could be individually actuated either through switching the ground electrodes from floating to grounded or by applying a potential to one of more of the fixed electrodes.
  • a single fixed electrode 14 is shown.
  • separate fixed electrodes to be utilized with a respective compliant electrode.
  • the bottom two images depict closure of switches 30a and 30b, respectively.
  • the pump 32 and actuators 10 can be used in the construction of various devices for analysing a fluid specimen.
  • the device is utilized to detect the presence of one or more analytes in a fluid specimen.
  • One such device includes point-of-care (POC) systems that can be used for disease diagnosis.
  • POC point-of-care
  • One embodiment of such a POC device 34 is shown in Fig. 3.
  • two recirculating microfluidic loops are used to first concentrate a biologically significant molecule or species, e.g. exosome, from a biological sample, e.g. blood, sputum, nasal lavage, etc. and then to detect the biological marker(s) using a variety of sensing platforms (moieties).
  • the fluid-analysis loop can have a volume (i.e., the volume of fluid carried within the fluidic channel contained in the loop) that is much smaller than the volume of the analyte-concentrating loop.
  • the fluid-analysis loop can have a volume that is about 100 to about 1000 times smaller than that of the analyte-concentrating loop.
  • the analyte-concentrating loop LOOP1 can have a volume of 15 ⁇ _, and the fluid-analysis loop can have a volume of 50 nL.
  • a volume of several mL of biological fluid cam be loaded into the loop displacing a sterile PBS type buffering system.
  • the fluid is first loaded into an input reservoir in communication with a fluidic channel inlet 36.
  • Valves VI and V3 are opened while valves V2, V4, and V5 are closed.
  • the pump PI in the analyte- concentrating loop LOOP1 is opened and the sample is drawn into the loop as the PBS is displaced and sent to a waste outlet 38. Once LOOP1 is filled.
  • Valves VI and V3 are closed and valve V2 is opened.
  • the sample is then recirculated over the capture pad CP1 by pump PI until a sufficient quantity of the analyte (species, exosome, etc.) is captured.
  • the capture may be attained using a variety of affinity agents including but not limited to antibodies, aptamers, peptide aptamers, Fab fragments, etc.
  • pump PI is stopped.
  • the captured analyte is directed through a fluid-analysis loop LOOP2. Valves V4, V5, V7 and V8 are opened. Pump PI valves are closed along with valve V6.
  • Fluid-analysis loop LOOP2 is then actuated to pull lysis buffer out of side channel SC3, over the capture pad CP1 and into fluid-analysis loop LOOP2.
  • the concentrated analytes released from CP1 flow through fluid-analysis loop LOOP2 displacing the sterile PBS solution in that loop.
  • the displaced sterile PBS exits through side channel SC4.
  • valves V5 and V8 are closed and valves V6 and V7 are opened. This allows the recirculation of the analytes in LOOP2 over the biosensor pads 40.
  • the recirculation of the fluid specimen continues to occur until a sufficient quantity of analyte (e.g., biomarkers), if present, are captured by biosensor pads 40 to produce a detectable signal.
  • analyte e.g., biomarkers
  • the actuators 10 of the present invention permit microfluidic devices such as POC device 34 to be constructed without check valves and with reduced dead volume within the pumps, unlike previous microfluidic devices. This construction makes the devices much easier and less expensive to manufacture and improves operational performance.

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Abstract

Integrated dielectric elastomeric actuators are provided that can be incorporated within a microfluidic device. The individual actuators function as valves that are operable to collapse a fluidic channel formed in a compliant material. A plurality of actuators can be arranged in series and selectively actuated to form a peristaltic pump that is capable of providing a motive force for a fluid flowing within the fluidic channel. The actuators, which operate as valves, and pumps can be used within a point-of-care device for the detection of an analyte within a fluid sample.

Description

INTEGRATED DIELECTRIC ELASTOMERIC ACTUATORS
RELATED APPLICATIONS
The present application claims the benefit of U.S. Provisional Patent Application No. 62/312,978, filed March 24, 2016, which is incorporated by reference herein in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
This invention was made with government support under Grant Nos. CHE- 1411993 and CHE-0548046 awarded by the National Science Foundation. The government has certain rights in the invention. BACKGROUND OF THE INVENTION
Field of the Invention
The present invention is generally directed toward integrated dielectric elastomeric actuators that can be incorporated within a microfluidic device. In certain embodiments, the actuators function as valves that are operable to collapse a fluidic channel formed in a compliant material. When a plurality of actuators are formed in series and selectively actuated, the plurality of actuators make up a pump capable of providing a motive force for a fluid flowing within the fluidic channel. The actuators, and/or pump made from a plurality of actuators, can be used within a point-of-care device for the detection of an analyte within a fluid sample.
Description of the Prior Art
Actuators are becoming an increasingly popular component of micro-Total Analysis Systems (μ-TAS, or microfluidic devices). Their popularity stems from the desire to fully integrate multiple fluid-handling architectures on a single device in order to perform multi-step analyses. To date, devices that incorporate pneumatic, thermopneumatic, piezoelectric, shape memory alloy, electrothermal, electrochemical, electrostatic, or magnetic actuation have been constructed. The majority of these actuation systems derive their function from the reversible deflection of a polymer membrane, which produces a volume change in a portion of the native channel network. Thus, these miniaturized actuators have found use as microvalves and micropumps. However, each of the aforementioned actuation methods commonly suffer from a variety of problems, including complicated and expensive fabrication techniques, a dependence upon large, off-chip equipment, high power consumption, slow response times and limited effectiveness. Exemplary electroactive polymer devices are disclosed in U.S. Patent Application Publication Nos. 2008/0245985, 2009/0151422, and 2012/0273702.
SUMMARY OF THE INVENTION
According to one embodiment of the present invention there is provided a microfluidic actuator. The microfluidic actuator comprises a compliant electrode layer, a fluidic channel layer, a fixed electrode and an insulative layer interposed between the fluidic channel layer and the fixed electrode. The compliant electrode layer comprises a liquid compliant electrode. The fluidic channel layer comprises a fluidic channel defined at least in part by a compliant material. The compliant material is interposed between the liquid compliant electrode and the fluidic channel. The fixed electrode comprises a conductive material carried by a substrate, and the insulative layer comprises an insulating material.
According to another embodiment of the present invention there is provided a microfluidic pump. The microfluidic pump comprises a fluidic channel layer comprising a fluidic channel defined at least in part by a compliant material. The pump also comprises a compliant electrode layer comprising at least first and second liquid compliant electrodes that are spaced apart and overlie the fluidic channel. The pump further comprises at least one fixed electrode affixed to a substrate and in registry with the first and second liquid compliant electrodes. The pump also comprises an insulative layer comprising an insulating material. The insulating material is interposed between the fluidic channel layer and the at least one fixed electrodes.
According to yet another embodiment of the present invention there is provided a device for analysing a fluid specimen. The device includes a fluid-analysis loop comprising a fluidic channel layer. The fluidic channel layer comprises a fluid inlet, a fluid outlet, and a fluidic channel interconnecting the fluid inlet and fluid outlet. The fluidic channel is defined at least in part by a compliant material and configured to conduct the fluid specimen through the device. The device also includes at least one microfluidic pump comprising a compliant electrode layer, a least one fixed electrode, and an insulative layer. The compliant electrode layer has at least first and second liquid compliant electrodes that are spaced apart and overlie the fluidic channel. The at least one fixed electrode is affixed to a substrate and is in registry with the first and second liquid compliant electrodes. The insulative layer comprises an insulating material that is interposed between the fluidic channel layer and the at least one fixed electrode. The device further comprises at least one biosensor located between the fluid inlet and fluid outlet and operable to detect the presence or absence of an analyte within the fluid specimen flowing within the fluidic channel.
According to still another embodiment of the present invention there is provided a method of moving a fluid within a fluidic channel on a microfluidic device. The method comprises the steps of introducing a fluid into the fluidic channel and actuating a microfluidic pump contained within the microfluidic device. The fluidic channel is formed within a fluidic channel layer on the device. The fluidic channel layer comprises a compliant material. The microfluidic pump comprises a compliant electrode layer having at least first, second, and third liquid compliant electrodes that are spaced apart and overlying the fluidic channel, at least one fixed electrode affixed to a substrate and in registry with the first, second, and third liquid compliant electrodes, and an insulative layer comprising an insulating material. The insulating material is interposed between the fluidic channel layer and the at least one fixed electrode. Upon actuation of the microfluidic pump, fluid within the fluidic channel is caused to flow toward a fluid outlet of the device.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1A is a schematic illustration of an integrated dielectric elastomeric actuator constructed in accordance with one embodiment of the present invention;
Fig. IB is schematic illustration of the cross section of two actuator embodiments, one embodiment comprising an insulating layer and showing the actuator in "valve open" and "valve closed" configurations, and one embodiment in which the insulating layer comprises a high-dielectric coating over the fixed electrode;
Fig. 2 is a schematic illustration of the operation of a microfluidic pump comprising three actuators arranged in series; and
Fig. 3 is a schematic diagram of a point-of-care device comprising a plurality of integrated actuators for the detection of an analyte present in a fluid sample.
DETAILED DESCRIPTION OF THE PREFERRED EMB ODFMENT
Actuators in accordance with certain embodiments of the present invention rely upon the behavior of electroactive polymers (EAPs). An EAP is an organic polymer that can be physically deformed in the presence of an electric field, i.e. an electromechanical transducer. These electromechanical transducers exist in multiple forms, depending upon the type of EAP used. Types of EAPs include conducting polymers, ionic polymer-metal composites (EVIPCs), carbon nanotubes (CNTs), ferroelectric polymers and dielectric elastomers (DEs). Regardless of the exact identity of the EAP, an actuator can be formed by sandwiching a thin EAP film between two electrodes. In particular embodiments of this "capacitor" configuration, at least one of the electrodes has some degree of compliance, i.e. be able to move and stretch. As an electric field is applied across the EAP, opposite charges accumulate on each electrode surface. Due to the presence of these opposing charges on the electrodes, Maxwell stress is generated and it acts on the EAP film in two ways. First, unlike charges on the opposite surfaces of the EAP create an attractive force perpendicular to the plane of the film, which seeks to compress the polymer. Second, the presence of like charges on the surface of each electrode produces a repulsive force in the plane of the film, which acts to stretch the polymer.
Since it functions as a capacitor, the resultant physical deformation of the EAP- electrode unit is greatly dependent upon the electrical properties of the EAP film. This is because the total amount of electrical energy stored in the charged capacitor provides an upper limit to the amount of mechanical work that can be done on the EAP. The amount of Maxwell stress (pressure, p) generated between the two electrodes depends upon the electric field across the EAP (E) as defined by the following equation: p = ks^E (1) where k is the dielectric constant of the EAP and aDis the permittivity of free space. However, the actual magnitude of the EAP's physical response to the stress depends upon its physical properties. This is a very complex response that is dependent upon many variables that relate to the mechanical properties of the EAP. Previously, linear Hookean models have been used to describe both a loading stress and Maxwell stress in elastomeric materials. The amount of strain perpendicular to the plane of the film due to Maxwell stress using this linear model has been defined as:
(2)
Figure imgf000006_0001
where sz is the thickness strain, Y is the Young's modulus of the EAP, J7 is the potential drop across the EAP film and zo is the original thickness of the EAP film. The Hookean model, however, predicts elastomer response only at infinitesimal strains (typically less than 10%). At finite strains, the Hookean model breaks down for DEs since they tend to become "harder" for increasingly compressive stresses. In order to describe the nonlinear behavior of elastomeric materials under unidirectional stress (both tension and compression), the Neo-Hookean, Mooney-Rivlin and Ogden models have been developed. These models take into account the fact that the elasticity of an elastomer changes as the amount of strain that it experiences increases.
The behavior of elastomers in response to stress is often described using the Mooney-Rivlin model. The strain in a system that is immobilized in one dimension can be calculated from:
(3)
T xx - T zz = \ 2 +
Figure imgf000006_0002
where Txx and Tzz are the stress tensors in their respective Cartesian planes, Ci and C2 are constants, and a is the stretch ratio. The difference between the stress tensors Txx and Tzz represents the total stress on the elastomer, which is defined as:
Figure imgf000007_0001
where the term on the left is a physical load placed on the polymer and the term on the right is the Maxwell stress. For systems with negligible loads, Equations (1) and (4) are equivalent.
Since they possess a high dielectric strength and have a low Young's modulus, elastomers (a type of DE) are used frequently as electroactive actuators. Other elastomeric materials, however, may be used, e.g. acrylics, urethanes, fluoroelastomers, and polybutadienes. With a Poisson's ratio extremely close to 0.5, silicone elastomers are also virtually incompressible. Thus, when an elastomer is subjected to Maxwell stress, the z-directional compression is accompanied by an equivalent amount of extension in the x a d y planes of the film. Overall, the physical properties of elastomers endow the actuation unit with low power consumption, high energy densities, response times on the order of 10 - 1000 and non-hysteretic voltage cycling. While DEs typically require large operating voltages (102 to 103 V) to produce significant strains, their flexibility, ruggedness, scalability, low cost and ease of fabrication further increase the feasibility of incorporating these materials on commercial devices. Currently, DE actuators are gaining interest for use in the development of robotics, pumps, motors, acoustics, medical prosthetics, micro air vehicles (MAVs) and haptic devices.
Certain embodiments of the present invention pertain to a dielectric actuator that allows the easy fabrication of both valves and pumps on microfluidic devices. An exemplary actuator 10 is shown in Fig. 1A. Actuator 10 is constructed on a substrate 12, which is preferably a rigid support upon which the various feature or layers making up actuator 10 can be applied. In certain embodiments, the substrate 12 can comprise glass (i.e., silicon dioxide), one or more plastics, or mixtures thereof. The substrate 12 can have any width, length, and thickness suitable for use in a microfluidic device. Formed on or otherwise carried by substrate 12 is fixed, noncompliant electrode 14. Electrode 14 is generally planar and can be formed from any electrically conducting materials known in the art. Exemplary materials that may be used in forming electrode 14 include, but are not limited to, solid conductive materials such as one or more metals, graphitic carbon, indium tin oxide, barium (strontium) titanates, or mixtures thereof. Additionally, the electrode 14 can be incorporated on the substrate layer 12 employing methods known in the art, such as photolithography and wet chemical processing (etching).
An insulative layer 16 is applied over electrode 14 and/or substrate layer 12. Insulative layer 16 comprises an insulating, or non-conductive, material. In certain embodiments, insulating material is also noncompliant. Exemplary insulating materials that comprise insulative layer 16 include poly(dimethylsiloxane) (PDMS), a poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof. In certain embodiments, the insulative layer 16 has an average material thickness of from about 5 to about 100 μπι, from about 10 to about 75 μπι, or from about 20 to about 50 μιη. As illustrated in Fig. 1A, insulative layer 16 has an average material thickness of 30 μιη. In alternative embodiments, such as depicted in the lower left schematic illustration of Fig. IB, the insulative layer comprises a high dielectric coating 16a that is applied over the fixed electrode 14. This design decreases the distance between the electrodes making up actuator 10, which allows for lower voltage actuation of actuator 10. Exemplary high dielectric coatings include various silicones, acrylics, cellulose acetate, barium (or strontium) titanate, silicon or titanium oxides, or perovskite materials that have significantly high electrical breakdown potentials than PDMS or other types of elastomers. In addition, such surfaces have functionalities that make them suitable for modification and the attachment of sensing species for point of care devices, such as those described below.
A fluidic channel layer 18 is located over insulative layer 16 and comprises a fluidic channel 20 formed therein. The fluidic channel layer 18 generally comprises a compliant material, and in particular an electroactive polymer. In particular embodiments, the electroactive polymer is selected from the group consisting of poly(dimethylsiloxane) (PDMS), a poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof. In certain embodiments, fluidic channel layer 18 comprises the same or a different material than insulative layer 16. In certain embodiments, the fluidic channel layer 18 has an average material thickness of from about 10 to about 100 μπι, from about 25 to about 80 μπι, or from about 40 to about 60 μιη. As illustrated in Fig. 1A, fluidic channel layer 18 has an average thickness of 50 μιη. The fluidic channel 20 generally comprises an elongate void region that is cooperatively defined by the fluidic channel layer 18 and the insulative layer 16, and is configured to conduct a fluid, which can be a gas, liquid or supercritical fluid, for example. As illustrated in Fig. 1A, fluidic channel 20 is hemicylindrical (half of a right circular cylinder), although other configurations such as right rectangular cylinders may also be used. The fluidic channel 20 is formed within fluidic channel layer 18 by molding PDMS or other likewise material against a negative mastermold of the channel manifold. Layer 18 is then joined (adhered) to layers 22 and 16. The joining can be reversible or irreversible. Reversible joining occurs due to contact adhesion forces. In irreversible joining, differing ratios of PDMS prepolymer curing agents are used. In general if a 5: 1 A:B curing ratio for layer 18 is used, then a 30: 1 A:B ratio for layers 22 and 16 can be used. The fluidic channel 20 can have any dimensions suitable for permitting the flow of a fluid on a microfluidic device. In one or more embodiments, the fluidic channel 20 can have average widths of from about 5 to about 150 μπι, from about 15 to about 100 μπι, or from about 30 to about 750 μπι. In certain embodiments, the fluidic channel 20 may have an average depth of from about 5 to about 100 μπι, from about 10 to about 50 μπι, or from about 15 to about 35 μπι. As illustrated in Fig. 1A, the fluidic channel 20 has an average width of 50 μπι and an average depth of 25 μπι.
A compliant electrode layer 22 is located over fluidic channel layer 18. A liquid compliant electrode 24 is formed within layer 22 by molding in a similar manner as to how the fluidic channel 20 is molded. The compliant electrode layer 22 comprises a compliant material, and in certain embodiments, the compliant material comprises a silicone elastomer. In preferred embodiments, the silicone elastomer comprises poly(dimethylsiloxane). In certain embodiments, the compliant electrode layer 22 has an average material thickness of from about 100 μπι to about 1 cm, from about 500 μπι to about 5 mm, or from about 1 mm to about 3 mm. . The liquid compliant electrode 24 generally comprises a pumping channel 26 formed within the compliant electrode layer 22 that is filled with a conductive liquid. In certain embodiments, the pumping channel 26 is cooperatively defined by the compliant electrode layer 22 and the fluidic channel layer. Exemplary conductive liquids that can be used in the compliant electrode 24 include any aqueous solution, conducting organic liquid, liquid metal, and ionic-liquid. In certain embodiments, it is preferred that the compliant electrode not comprise a carbon grease electrode. In certain embodiments, the pumping channel 26 has a length, or longest dimension, that is greater than the average width of the fluidic channel 20. As explained below, this configuration ensures that the fluidic channel can be completely collapsed upon expansion of the compliant electrode 24. In particular embodiments, the pumping channel 26 has an average length of from about 10 to about 200 μπι, from about 25 to about 150 μπι, or from about 50 to about 125 μπι. The length of the pumping channel 26 depicted in Fig. 1A is 90 μπι. The liquid compliant electrode 24 is also oriented to be in general registry, or alignment, with the fixed electrode, which are separated by at least the fluidic channel layer 18 and the insulative layer 16 thereby forming a capacitor-like structure. It is noted that because in certain embodiments fixed electrode 14 is noncompliant, compliant electrode 24 is the only electrode fabricated from a compliant material for any particular actuator 10.
Figure IB depicts the operation of actuator 10. As can be seen, the fluidic channel 20 is sandwiched between the liquid compliant electrode 24 and the fixed electrode 14. The electrodes 14 and 24 are connected to a voltage source 28, and once a switch 30, e.g., an optodiode, is closed the force generated between the two electrodes causes the compliant electrode 24 to change shape. As the dielectric or insulative layer 16 is not compressible, the fluidic channel layer 18 must change shape. The easiest path for relieving the stress induced by the electric field is to compress the fluidic channel thus collapsing or pinching off the channel between the two electrodes. This effectively forms a valve that is capable of controlling the flow of a liquid within the fluidic channel 20.
Connections to electrical power supplies can be made using small, flexible wires or pins. The capacitance of the actuator 10 is low and so little power is required to drive the valve. This allows high voltage/low current power supplies to be used for actuation, such as computer USB ports. In such designs, a single power supply can be used with several high voltage switches. Such switches can work at speeds of over a kHz.
A plurality of actuators 10 (i.e., at least two) can be arranged in series along a common fluidic channel thereby creating a peristaltic pump capable of moving a fluid within the fluidic channel. Figure 2 illustrates one such pump 32 made in accordance with the present invention and comprising three compliant electrodes. The uppermost image of Fig. 2 depicts a switch-open configuration for each of compliant electrodes 24a, 24b, and 24c and the fixed electrode 14. The fixed electrode 14 may cover the entire bottom plane of the device and serve as a ground plane or high voltage plane. The actuators 10 are then actuated by applying a potential to the compliant electrodes 24a, 24b, 24c or grounding them if they are otherwise floating. Alternatively, all of the compliant electrodes 14a, 24b, 24c can be grounded and a plurality of fixed electrodes can be patterned individually on the substrate 12. In this configuration the actuators 10 could be individually actuated either through switching the ground electrodes from floating to grounded or by applying a potential to one of more of the fixed electrodes. Note, in this embodiment, a single fixed electrode 14 is shown. However, it is within the scope of the present invention for separate fixed electrodes to be utilized with a respective compliant electrode. The bottom two images depict closure of switches 30a and 30b, respectively. In most cases the first valve, comprising compliant electrode 24a, will remain actuated while the second valve, comprising compliant electrode 24b, is actuated to ensure that the flow moves from left to right in the channel 20 depicted in Fig. 2. The sequence is repeated as long as flow is desired. A typical pumping sequence in terms of the relative states of the 3 valves depicted in Fig. 2 is as follows: 101, 100,110,010,011, 001, wherein 1 = a collapsed fluidic channel 20 between the respective liquid compliant electrode 24a, 24b, 24c, and the fixed electrode 14, and 0 = an open fluidic channel between the respective liquid compliant electrode 24a, 24b, 24c and the fixed electrode 14.
The pump 32 and actuators 10 can be used in the construction of various devices for analysing a fluid specimen. Specifically, the device is utilized to detect the presence of one or more analytes in a fluid specimen. One such device includes point-of-care (POC) systems that can be used for disease diagnosis. One embodiment of such a POC device 34 is shown in Fig. 3. In this device, two recirculating microfluidic loops are used to first concentrate a biologically significant molecule or species, e.g. exosome, from a biological sample, e.g. blood, sputum, nasal lavage, etc. and then to detect the biological marker(s) using a variety of sensing platforms (moieties). However, it is within the scope of the present invention for a device to be constructed that utilizes a single fluid-analysis loop for use in applications where no pre-concentration of the particular analyte is required. In certain embodiments in which a first, analyte-concentrating loop and second, fluid-analysis loop are employed, the fluid-analysis loop can have a volume (i.e., the volume of fluid carried within the fluidic channel contained in the loop) that is much smaller than the volume of the analyte-concentrating loop. In particular embodiments, the fluid-analysis loop can have a volume that is about 100 to about 1000 times smaller than that of the analyte-concentrating loop. With respect to the POC device 34 illustrated in Fig 3, the analyte-concentrating loop LOOP1 can have a volume of 15 μΙ_, and the fluid-analysis loop can have a volume of 50 nL.
In the first loop a volume of several mL of biological fluid cam be loaded into the loop displacing a sterile PBS type buffering system. The fluid is first loaded into an input reservoir in communication with a fluidic channel inlet 36. Valves VI and V3 are opened while valves V2, V4, and V5 are closed. The pump PI in the analyte- concentrating loop LOOP1 is opened and the sample is drawn into the loop as the PBS is displaced and sent to a waste outlet 38. Once LOOP1 is filled. Valves VI and V3 are closed and valve V2 is opened. The sample is then recirculated over the capture pad CP1 by pump PI until a sufficient quantity of the analyte (species, exosome, etc.) is captured. The capture may be attained using a variety of affinity agents including but not limited to antibodies, aptamers, peptide aptamers, Fab fragments, etc. Once the analyte has been captured and concentrated on CP1, pump PI is stopped. Next, the captured analyte is directed through a fluid-analysis loop LOOP2. Valves V4, V5, V7 and V8 are opened. Pump PI valves are closed along with valve V6. Pump P2 is then actuated to pull lysis buffer out of side channel SC3, over the capture pad CP1 and into fluid-analysis loop LOOP2. The concentrated analytes released from CP1 flow through fluid-analysis loop LOOP2 displacing the sterile PBS solution in that loop. The displaced sterile PBS exits through side channel SC4. After filling fluid-analysis loop LOOP2 with the concentrated analyte, valves V5 and V8 are closed and valves V6 and V7 are opened. This allows the recirculation of the analytes in LOOP2 over the biosensor pads 40. The recirculation of the fluid specimen continues to occur until a sufficient quantity of analyte (e.g., biomarkers), if present, are captured by biosensor pads 40 to produce a detectable signal.
In certain embodiments, the actuators 10 of the present invention permit microfluidic devices such as POC device 34 to be constructed without check valves and with reduced dead volume within the pumps, unlike previous microfluidic devices. This construction makes the devices much easier and less expensive to manufacture and improves operational performance.

Claims

I claim:
1. A microfluidic actuator comprising:
a compliant electrode layer comprising a liquid compliant electrode; a fluidic channel layer comprising a fluidic channel defined at least in part by a compliant material, the compliant material being interposed between the liquid compliant electrode and the fluidic channel; a fixed electrode comprising a conductive material carried by a substrate; and
an insulative layer comprising an insulating material, the insulating
material being interposed between the fluidic channel layer and the fixed electrode.
2. The microfluidic actuator of claim 1, wherein the compliant electrode layer comprises a silicone elastomer
3. The microfluidic actuator of claim 2, wherein the silicone elastomer comprises poly(dimethylsiloxane).
4. The microfluidic actuator of claim 1, wherein the liquid compliant electrode comprises a member selected from the group consisting of aqueous solutions, ionic liquids, liquid metals, conducting organic liquids or solutions.
5. The microfluidic actuator of claim 1, wherein the compliant electrode layer has an average thickness of from about 100 μπι to about 5 mm.
6. The microfluidic actuator of claim 1, wherein the fluidic channel layer comprises an electroactive polymer.
7. The microfluidic actuator of claim 6, wherein the electroactive polymer is selected from the group consisting of poly(dimethylsiloxane), a poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof.
8. The microti uidic actuator of claim 1, wherein the fixed electrode comprises a solid conductive material.
9. The microfluidic actuator of claim 8, wherein the fixed electrode comprises at least one material selected from the group consisting of one or more metals, carbon graphite, indium tin oxide, barium (strontium) titanates, or mixtures of two or more thereof.
10. The microfluidic actuator of claim 1, wherein the insulative layer comprises a noncompliant material.
11. The microfluidic actuator of claim 1 , wherein the insulative layer is selected from the group consisting of poly(dimethylsiloxane), a
poly(dimethylsiloxane)/poly(ethylene oxide) copolymer, a fluorosilicone, an acrylic polymer, and mixtures of two or more thereof.
12. The microfluidic actuator of claim 1, wherein the insulative layer comprises a high dielectric constant dielectric material.
13. The microfluidic actuator of claim 12, wherein the dielectric material is coated over the fixed electrode.
14. The microfluidic actuator of claim 1, wherein the liquid compliant electrode expands in a direction toward the fluidic channel upon application of a voltage across the liquid compliant electrode and the fixed electrode thereby compressing the fluidic channel layer and collapsing the fluidic channel.
15. The microfluidic actuator of claim 1, wherein the substrate comprises a material selected from the group consisting of silicon dioxide, one or more rigid plastics, and mixtures thereof.
16. A microfluidic pump comprising:
a fluidic channel layer comprising a fluidic channel defined at least in part by a compliant material;
a compliant electrode layer comprising at least first and second liquid compliant electrodes that are spaced apart and overlying the fluidic channel;
at one fixed electrodes affixed to a substrate and in registry with the first and second liquid compliant electrodes; and an insulative layer comprising an insulating material, the insulating
material being interposed between the fluidic channel layer and the at least one fixed electrode.
17. The microfluidic pump of claim 16, wherein the pump further comprises a third liquid compliant electrode in registry with the at least one fixed electrode.
18. The microfluidic pump of claim 17, wherein each liquid compliant electrode expands in a direction toward the fluidic channel upon application of a voltage across each liquid compliant electrode and the at least one fixed electrode thereby compressing the fluidic channel layer and collapsing the fluidic channel.
19. The microfluidic pump of claim 18, wherein selective application of a voltage across one or more of the liquid compliant electrodes and the at least one fixed electrode and the resulting collapse of the fluidic channel therebetween provides a motive force for a flow of a fluid present within the fluidic channel.
20. A device for analyzing a fluid specimen comprising a fluid- analysis loop, the fluid-analysis loop comprising:
a fluidic channel layer comprising fluid inlet, a fluid outlet, and a fluidic channel interconnecting the fluid inlet and fluid outlet, the fluidic channel being defined at least in part by a compliant material and configured to conduct the fluid specimen through the device;
at least one microfluidic pump comprising- a compliant electrode layer having at least first and second liquid compliant electrodes that are spaced apart and overlying the fluidic channel;
at least one fixed electrode affixed to a substrate and in registry with the first and second liquid compliant electrodes; and an insulative layer comprising an insulating material, the insulating material being interposed between the fluidic channel layer and the at least one fixed electrode; and
at least one biosensor located between the fluid inlet and fluid outlet and operable to detect the presence or absence of an analyte within the fluid specimen flowing within the fluidic channel.
21. The device of claim 20, wherein the device further comprises at least one valve located upstream or downstream from the microfluidic pump, wherein the valve comprises a valve liquid compliant electrode formed in the compliant electrode layer and overlying the fluidic channel and in registry with the at least one fixed electrode.
22. The device of claim 20, wherein the device comprises an analyte- concentrating loop located upstream from and fluidly connected with the fluid-analysis loop, wherein the analyte-concentrating loop comprises an analyte capture pad configured to remove at least a portion of the analyte from an analyte-containing fluid being flowed through the analyte-concentrating loop.
23. The device of claim 22, wherein the analyte-concentrating loop comprises at least one microfluidic pump configured to effect a flow of the analyte- containing fluid within the analyte-concentrating loop.
24. The device of claim 23, wherein the at least one microfluidic pump of the analyte-concentrating loop comprises at least first and second liquid compliant electrodes that are spaced apart and overlying a fluidic channel of the analyte- concentrating loop, and are in registry with the at least one fixed electrode.
25. The device of claim 22, wherein the device comprises a valve capable of isolating the analyte-concentrating loop from the fluid-analysis loop when the valve is in the valve-closed configuration and capable of permitting fluid communication between the analyte-concentrating loop and the fluid-analysis loop when the valve is in the valve-open configuration.
26. A method of moving a fluid within a fluidic channel on a microfluidic device comprising:
introducing a fluid into the fluidic channel, the fluidic channel being
formed within a fluidic channel layer on the device, the fluidic channel layer comprising a compliant material; and
actuating a microfluidic pump contained within the microfluidic device, the microfluidic pump comprising- a compliant electrode layer having at least first, second, and third liquid compliant electrodes that are spaced apart and overlying the fluidic channel;
at least one fixed electrode affixed to a substrate and in registry with the first, second, and third liquid compliant electrodes; and
an insulative layer comprising an insulating material, the insulating material being interposed between the fluidic channel layer and the at least one fixed electrode, wherein actuation of the microfluidic pump causes the fluid within the fluidic channel to flow toward a fluid outlet of the device.
27. The method of claim 26, wherein the actuation of the microfluidic pump causes at least one of the first, second, and third liquid compliant electrodes to expand thereby collapsing the fluidic channel between a said at least one liquid compliant electrode and the at least one fixed electrode.
28. The method of claim 27, wherein the actuation order of the first, second, and third pairs of liquid compliant electrodes is 101,100, 110,010,011, 001, wherein 1 = a collapsed fluidic channel between the respective liquid compliant electrode and the at least one fixed electrode, and 0 = an open fluidic channel between the respective liquid compliant electrode and the at least one fixed electrode.
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