Long-Throw Microfluidic Actuator

Abstract

A microfluidic device includes a three-dimensional slat structure having a plurality of interstices configured to generate a high power, high flow rate of fluids by electroosmotic flow. The microfluidic device includes a housing for holding and moving fluids through the slat structure, and a plurality of electrodes that generate an electric field within the plurality of interstices.

Claims

1.-56. (canceled)

57. A microfluidic cartridge comprising: a plurality of fluid passageways; at least one junction connecting said plurality of fluid passageways; and at least two fluid transport means, including at least one high-performance fluidic actuator, the at least one high-performance fluidic actuator being a discrete component within the cartridge, and the at least one high-performance fluidic actuator having: a fluid power generation capacity of at least 10.sup.8 watts and capable of sustaining said power for at least 30 seconds; and a response time for fluid power generation of less than 10 seconds.

58. The cartridge of claim 57, wherein said cartridge has a displaced volume less than or equal to five hundred cubic centimeters or less than or equal to fifty cubic centimeters.

59. The cartridge of claim 57, wherein said at least one high-performance fluidic actuator is capable of transducing electrical power into fluidic power.

60. The cartridge of claim 57, wherein said actuator is capable of pressurizing at least 10 microliters of liquid, such that said liquid flows through a fluidic resistance associated with a back pressure of at least 1 kPa at a flow rate of at least 0.1 mL per minute.

61. The cartridge of claim 57, wherein said high-performance actuator is coupled to a pulse generator or other controlled time-varying voltage source and at least one electrode.

62. The cartridge of claim 57, wherein said at least one high-performance fluidic actuator is capable of producing fluidic power through an electrokinetic effect.

63. The cartridge of claim 62, wherein said electrokinetic effect comprises electroosmotic flow.

64. The cartridge of claim 63, wherein said electroosmotic flow is generated within a plurality of slit capillaries within each said at least one fluidic actuator.

65. The cartridge of claim 63, wherein said electroosmotic flow is generated within a bed of packed beads within each said at least one fluidic actuator.

66. The cartridge of claim 63, wherein said electroosmotic flow is generated within a monolithic porous structure within each said at least one fluidic actuator.

67. The cartridge of claim 63, wherein said electroosmotic flow is generated within an array of cylindrical channels within each said at least one fluidic actuator.

68. The cartridge of claim 57, wherein such microfluidic cartridge includes an opening for receiving a starting material into said network of fluid passageways.

69. The cartridge of claim 68, wherein said opening is closed with a plug or a capping element.

70. A system comprising: the microfluidic cartridge of claim 57; and an apparatus comprising a power source and adapted for sourcing electrical power to said microfluidic cartridge.

71. A method, comprising: providing a first fluid to a channel connected to a plurality of fluid passageways, including at least one junction among such fluid passageways, in a microfluidic cartridge, wherein said microfluidic cartridge further comprises at least one high-speed microfluidic actuator, the at least one high-performance fluidic actuator being a discrete component within the cartridge, and the at least one high-performance fluidic actuator having a fluid power generation capacity of at least 10.sup.8 watts and capable of sustaining said power for at least 30 seconds and a response time for power generation of less than 10 seconds; and operating said microfluidic actuators in a time-varying manner, such that said first fluid and a second fluid are introduced into said network of fluid passageways to generate alternating plugs of fluids, wherein a length of each plug volume is less than 5 times the smallest average diameter among such fluid passageways.

72. The method of claim 71, wherein said high-speed microfluidic actuator produces fluid power by an electrokinetic effect.

73. The method of claim 72, wherein said electrokinetic effect is generated by an electroosmotic flow.

74. The method of claim 73, wherein said electroosmotic flow is generated within an array of slits.

75. The method of claim 73, wherein said electroosmotic flow is generated within a packed bead bed.

76. The method of claim 73, where said electroosmotic flow is generated within a monolithic porous structure.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0042] These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, and accompanying drawings, where:

[0043] FIG. 1 illustrates the principle of using electroosmotic flow as the basis of a microfluidic actuator, according to an embodiment of the invention.

[0044] FIG. 2 is an example of a microfluidic actuator shown in isometric section perspective view, according to an embodiment of the invention.

[0045] FIG. 3 is an example of a microfluidic actuator shown in isometric exploded view, according to an embodiment of the invention.

[0046] FIG. 4 is a side view of a microfluidic actuator, according to an embodiment of the invention.

[0047] FIG. 5 illustrates an array of interstices on a microfluidic actuator, according to an embodiment of the invention.

[0048] FIG. 6 is an example of a microfluidic actuator, according to an embodiment of the invention.

[0049] FIG. 7 illustrates the back pressure and flow rate performance among microfluidic actuators according to one embodiment of the invention with comparison to performance of microfluidic actuators described in the prior art.

[0050] FIG. 8 illustrates the electrical resistance across the actuator in the microfluidic device, according to one embodiment of the invention.

[0051] FIG. 9 is an example of a microfluidic cartridge comprising one or more microfluidic actuators of the invention, according to one embodiment of the invention.

[0052] FIG. 10 illustrates an example of alternating plugs of fluids in a fluid passageway, according to one embodiment of the invention.

[0053] FIG. 11 illustrates flow rate and power data for microfluidic actuators as summarized in FIG. 7, according to one embodiment of the invention.

[0054] FIG. 12 illustrates graphs of the flow rate and power data for microfluidic actuators as summarized in FIGS. 7 and 11, according to one embodiment of the invention.

[0055] FIG. 13 illustrates the back pressure and flow rate among first and second generation microfluidic actuators, according to one embodiment of the invention.

[0056] FIG. 14 illustrates the back pressure and flow rate among various microfluidic actuators, according to one embodiment of the invention.

[0057] FIG. 15 illustrates back pressure and flow rate among first generation microfluidic actuators, according to one embodiment of the invention.

[0058] FIG. 16 shows the thermodynamic efficiencies of various microfluidic actuators of the invention, according to one embodiment of the invention.

[0059] FIG. 17 illustrates the back pressure and flow rate for a 1 mm3 mm microfluidic actuator (e.g., a Slit Capillary Array Fluidic Actuator (SCAFA)) using laser-cut, platinum-plated electrodes, according to one embodiment of the invention.

[0060] FIGS. 18A-C illustrate the electric field effects in microfluidic actuators of the invention (SCAFAs), according to one embodiment of the invention.

[0061] FIG. 19 illustrates modeling of microfluidic actuators of the invention (SCAFAs), according to one embodiment of the invention.

[0062] FIGS. 20A-D illustrates additional studies on flow rate and pressure performance using various electrode configurations, according to one embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0063] Electroosmosis is an electrochemical effect in which a fluid phase moves relative to a stationary solid phase. This movement of the fluid phase is associated with the interaction of an imposed electrical field and the mobile ions in the fluid phase of the electrical double layer that forms at many fluid-solid interfaces.

[0064] FIG. 1 illustrates the principle of electroosmotic flow. At the interface between a fluid phase and a solid phase, chemical reactions between the two phases typically result in the formation of a charge double layer, with a net charge at the surface of the solid and net charge of the opposite polarity in the fluid phase. For example, at the interface between an oxygen-containing silicon material 110, such as glass or silica, and a neutral-to-basic aqueous fluid phase, surface silanol groups tend to donate protons to form hydronium ions in the fluid phase, leaving a negative surface charge. An electrical double layer 120 forms as a result. The double layer 120 refers to two parallel layers of charge at the surface, where the first layer comprises ions adsorbed directly onto the object and the second layer composed of ions attracted to the surface charge via a coulomb force, electrically screening the first layer. The second layer is loosely associated with the surface because it is made up of free ions, which are attracted to the surface from within aqueous solution. The surface charge attracts dissolved counter-ions and repels co-ions, resulting in a charge separation. The Debye length is the characteristic thickness of the double layer 120. The term electrokinetic effects is used to describe phenomena associated with the electric double layer [10].

[0065] Electroosmotic flow is a term for bulk fluid flow associated with the body forces on the mobile ions in the diffuse counter-ion layer caused by an externally applied electrical field, and the moving ions drag along bulk liquid through viscous effects. FIG. 1 also shows the direction of electroosmotic flow from low pressure to high pressure, which is in opposition to the direction of the pressure driven flow.

[0066] In an electroosmotic actuator, fluid power associated with electroosmostic flow can do mechanical work on a mass 130 external to the apparatus within which electroosmotic flow is generated.

[0067] Burgeen and Nakache [11] developed a mathematical model which gives the average velocity of electroosmotic flow between two parallel surfaces sufficiently wide and long that flow is approximately one-dimensional. With the flow parallel to the coordinate axis x, for an axial electric field E.sub.x, permittivity , fluid viscosity , and is:

[00001]$\stackrel{\_}{v}=-\frac{a^2}{3.Math.}.Math.\frac{\mathrm{dp}}{\mathrm{dx}}-\frac{\mathrm{.Math.}}{}.Math.E_x\left[1-G\left(,.Math..Math.a\right)\right]$

[0068] where a is one-half the separation distance between the two parallel surfaces, is the fluid viscosity, dp/dx is the pressure gradient counter to the flow, is the fluid permittivity, is the zeta potential, a is an ionic energy parameter, and G is a correction term for the thickness of the double layer. Applying an axial electric field exerts forces on the mobile ions, and electromigration of the mobile ions results in bulk fluid flow through viscous effects. The zeta potential is an empirical parameter characterizing the effect of the surface condition on the electroosmotic flow. The zeta potential is determined from the net excess of surface charge-balancing ions near the surface/fluid interface.

[0069] Definitions

[0070] Terms used in the claims and specification are defined as set forth below unless otherwise specified.

[0071] Electroosmotic flow refers to the movement of liquid induced by an applied potential across a fluid conduit. The fluid conduit can be any porous material, capillary tube, membrane, substrate, microchannel or passageway for allowing the flow of liquid. The electric potential can be applied between any two parallel surfaces.

[0072] A microfluidic actuator refers to a component that converts electrical power or another readily stored or generated form of energy into fluid power, and which can do mechanical work on a mass external to the electroosmotic flow region within the.

[0073] Maximum back pressure is the lowest back pressure at which, for a given working fluid, applied potential, and other parameters, the flow rate Q is zero or negative. For a microfluidic actuator's pressure-curve plotted with the flow rate on the x-axis and the back pressure on the y-axis, the maximum back pressure is the y-intercept of the pressure-flow rate curve.

[0074] A slat refers to a narrow strip of material. The slats may be composed of an insulating material or a semi-conducting core material with surface coatings.

[0075] It must be noted that, as used in the specification and the appended claims, the singular forms a, an and the include plural references unless the context clearly dictates otherwise.

Overview

[0076] The microfluidic device is an apparatus for transducing electrical power into fluid power by means of electroosmosis.

[0077] FIG. 2 shows, in a section isometric perspective view, an example of the microfluidic device 200, according to one embodiment of the invention. The device 200 comprises ports 201a, 201b for receiving fluids and for acting on external masses. Fluid may enter and exit from outside the device 200 via the openings 201a, 201b. There may be fluid passageways that are connected to the device 200 via the openings 201a, 201b, and the fluid passageways may be filled with fluid.

[0078] The device 200 comprises a plurality of slats forming a three-dimensional structure 202, each slat having a first face and a second face and a first sidewall and a second sidewall. The slat structure 202 may also be called an EO flow structure or a slit capillary array (SCA). The separation between the first and second faces of the slats defines a thickness. The slat structure includes a plurality of interstices 203 extending through the slat structure. The plurality of interstices 203 are passageways through which fluid can pass from one side of the slat structure to the other. There may be 10, 15, 20, 25, 30, 35, 40, 45, 50, or more slats, with a corresponding number of interstices. As shown in FIG. 2, the interstices 203 may be approximately uniform in shape. The interstices 203 may also be called slits or slit capillaries. In other embodiments, the slats 202 are wedge-shaped instead of rectangular, and the interstices 203 are arranged radially instead of in rows. In some embodiments, the interstices 203 have straight sides. In other embodiments, the interstices have wavy, curved, or saw-toothed sides. The interstices 202 may be non-uniform in size and shape, although the smaller of the two cross-sectional dimensions will generally be approximately uniform among all the interstices in a particular microfluidic actuator. The slats that comprise the slat structure 202 may be non-uniform in size and shape. In some embodiments, the slats 202 are arranged in a MN array, where there are M rows and N columns of interstices.

[0079] Each interstice 203 has three major dimensions: an in-plane dimension a, a second in-plane dimension b, and a third dimension l that runs the length of the thickness. In some embodiments, the in-plane dimension a is uniform for all of the interstices 203. In other embodiments, the in-plane dimension a is approximately the same for the interstices 203. In another embodiment, dimension a is 1 to 10 microns. In one embodiment, the second in-plane dimension b is twenty, fifty, or hundred times greater than the in-plane dimension a. In another embodiment, dimension b is greater than or equal to 0.5 mm. In yet another embodiment, the thickness dimension l (slat thickness) is between 50 microns and 2 mm in length. The collection of interstices has two major dimensions: a first in-plane dimension F and a second in-plane dimension G, which is also described in FIG. 5. In some embodiments, the ratio of F to G is between 0.2 and 5.

[0080] Whereas the nominal model of electroosmotic flow between two wide parallel slat structures indicates that maximum back pressure is independent of b and maximum flow rate is proportionate to b, it has been experimentally observed that, for b greater than approximately 20, increasing b is associated with increasing and increases in Q.sub.max greater than those. This effect is seen in EO devices with flow area aspect ratio of less than five.

[0081] The slat structure 202 may be assembled from individual slats or produced as a perforated sheet or a perforated block of solid material. In other embodiments, the slat structure 202 is composed of borosilicate glass or silicon. In some embodiments, the slat structure 202 comprises silicon with electrical resistance of at least 1000 ohm-centimeters. In other embodiments, the slat structure is coated with one or more silicon-containing thin films. In other embodiments, the slat structure may be coated with one or more thin films of silicon oxide. In other embodiments, the slat structure 202 may be coated with one or more thin films of silicon nitride. In other embodiments, the slat structure 202 may comprise crystalline silicon. In yet other embodiments, the slat structure 202 is a single-crystal silicon coated with multiple layers of silicon oxide and silicon nitride. In other embodiments, the slat structure is a molded thermoplastic.

[0082] In yet other embodiments, the device 200 includes a conformal insulating layer on at least one of the first and the second faces of the slat structure 202. The insulating layer is capable of reducing the occurrence of an electrochemical reaction between the fluid and the slat structure 202. In other embodiments, the insulating layer is capable of increasing an absolute value of a zeta potential at an interface of the fluid and the slat structure 202.

[0083] In an embodiment, the interstices 203 in the slat structure 202 are made by a photolithographic feature definition process followed by time-multiplexed inductively coupled plasma (TM-ICP) etching, also known as deep-reactive ion enhanced (DRIE) etching [12].

[0084] The microfluidic device 200 also includes a housing 204 enclosing the slat structure 202. The housing 204 has a first structure that defines a first fluid cavity 205a adapted for housing a fluid and in fluidic communication with the either the first face or the second face of the slat structure. The housing 204 has a second structure defining a second fluid cavity 205b adapted for receiving the fluid and in fluidic communication with the other face of the slat structure. The first fluid cavity 205a, the plurality of interstices 203, and the second fluid cavity 205b define a fluid pathway, wherein a lowest flow resistance path from the first fluid cavity 205a to the second fluid cavity 205b is through the plurality of interstices 203 in the slat structure 202.

[0085] The first and second structures may be sealed around the periphery, such that the only path for fluid from one cavity to the other is through the plurality of interstices 203 in the slat structure 202. The first and second structures can be in fluid communication with external passageways by means of the openings 201a and 201b through which fluid may enter and exit from outside the housing. The fluid passageways that are connected to the housing may be filled with fluid.

[0086] In some embodiments, the microfluidic device 200 includes a plurality of gaskets 206a, 206b which seal around the slat array.

[0087] The microfluidic device 200 includes a plurality of electrodes 207a, 207b for generating electric fields within the plurality of interstices 203. In some embodiments, a plurality of gaskets seal 206c, 206d around the plurality of electrodes 207a, 207b. In some embodiments, the slat structure 202, plurality of interstices 203, housing 204 and electrodes 207a, 207b are configured such that when the fluid cavities 205a and 205b and the interstices are wholly filled with a fluid which is substantially spatially uniform in charge density. In other terms, the slat structure 202, plurality of interstices 203, housing 204 and electrodes 207a, 207b are configured such that when the fluid cavities 205a and 205b and the interstices are filled with an aqueous solution and chemical or electrochemical reactions between said aqueous and the electrodes 207a, 207b maintain spatially uniform charge density for a voltage difference V applied across the plurality of electrodes 207a, 207b, such that the average axial electrical field within each interstice is 0.667 V/l. In some embodiments, the distance between each electrode and the corresponding face of the slat structure is less than 1 millimeter.

[0088] In some embodiments, the electrodes 207a, 207b are stainless steel meshes with electroplated platinum. In some embodiments, the electrodes 207a, 207b are drawn platinum wire electrodes. In other embodiments, the electrodes 207a, 207b are silver or silver chloride electrodes and are printed on a surface within a cavity or on the slat structure 202 itself.

[0089] FIG. 3 is an exploded view of a microfluidic device 200, according to one embodiment of the invention, with components as described above in FIG. 2.

[0090] FIG. 4 is a side section view of the device 200, according to one embodiment of the invention, with components as described above in FIG. 2.

[0091] FIG. 5 illustrates the dimensions of the interstices 203, individually and collectively, in the slat structure 202, according to one embodiment of the invention. The first in-plane dimension a and the second in-plane dimension b are shown from an angle facing one of the faces of the slat structure 202. Here, dimension b is shown to be at least 50 times greater than dimension a. The in-plane dimension a can also be characterized by its half-length a (where a= a). Collectively, the plurality of interstices forms a fluid passageway with external dimensions F and G, where the ratio of F to G is between 0.2 and 5.

[0092] In other embodiments, the device 200 may be coupled to a pulse generator programmed to deliver a pattern of voltage pulses to the plurality of electrodes 207a, 207b. The pattern of voltage pulses may repeat at a frequency of 0.5 Hz or faster, at a frequency of 1.0 Hz or faster, at a frequency of 10 Hz or faster, or at a frequency of 100 Hz or faster. In some embodiments, the pattern of voltage pulses is a pulse duration. The pulse duration may be shorter than a period of time corresponding to a 1/pattern repeat frequency. The ratio of time in the on state to time in the off state, or duty cycle, of the pulses may be any value between 0 and 100%.

[0093] In some embodiments, the device 200 has a fluid power generation capacity of at least 10.sup.8 watts. In some embodiments, the device 200 is capable of sustaining power for at least 30 seconds. In other embodiments, the device 200 has a response time for power generation is less than 10 seconds.

[0094] FIG. 6 shows an embodiment of a microfluidic device 600, where the configuration of interstices 604 are positioned in an axial array in the slat structure 602. The electrodes 603a are positioned on either side of the slat structure 602. The microfluidic device 600 includes openings 601a and 601b.

[0095] The following calculations are used to demonstrate the fluidic capacity of the microfluidic device 200.

[0096] In another embodiment, the total flow cross-sectional area (A.sub.SCA) through the interstices of the slat structure 202 is calculated by the following:

A.sub.SCA=A.sub.TOT=n.sub.IAB (Equation 1)

[0097] where the interstices in the slat structure 202 are arranged in a MN array, having M interstices in one in-plane dimension, and N interstices in the second in-plane dimension, and where half-length of the in-plate dimension of the interstice is a and the second in-plate dimension is b.

[0098] The average flow velocity can also be calculated for the microfluidic device 200. It has been shown that a spatially and temporally constant axial electric field E.sub.x within a slit capillary produces electroosmotic flow with an average axial flow velocity U of:

[00002]$\begin{array}{cc}U=-\frac{a_S^2}{3.Math..Math..Math.l_S}.Math..Math..Math.p_S+\frac{\mathrm{.Math.}}{}.Math.E_x\left[1-G\left(,.Math..Math.a_S\right)\right]& \left(\mathrm{Equation}.Math..Math.2\right)\end{array}$

[0099] See R. J. Hunter, Zeta Potential in Colloid Science. San Diego: Academic Press, Inc., 1981; D. Burgreen and F. R. Nakache, Electrokinetic Flow in Ultrafine Capillary Slits, J. Phys. Chemistry, vol. 68, pp. 1084-1091, 1964.

[0100] The slit capillary end-to-end differential pressure ps may be externally imposed and/or arise as a consequence of an external load in series with the slit capillary. For the prescribed values of as <5 m, the thin electric double layer (EDL) assumption is almost always appropriate for the slat structure 202 within the device 200, regardless of the choice of working fluid.

[0101] Furthermore, the flow rate-pressure can be calculated for the microfluidic device 200. The flow rate-pressure relationship is as follows:

[00003]$\begin{array}{cc}Q=A_{\mathrm{SCA}}\left[-\frac{a_S^2}{3.Math..Math..Math.l_S}.Math..Math..Math.p_{\mathrm{SCA}}-\frac{\mathrm{.Math.}}{.Math..Math.l_S}.Math.V_S\right]& \left(\mathrm{Equation}.Math..Math.3\right)\end{array}$

[0102] Previously designed actuators have been designed with an array of openings having dimensions 2 ma4 m, 50 mb200 m, 100 ml500 m arranged in a one-dimensional MN array (200N1000, M=1). These actuators operate at between 100 and 500 volts with a working fluid of deionized water or a similar aqueous solution, generate maximum flow rates on the order of 100 microliters per minute and maximum back pressures on the order of 1 kPa.

[0103] For the microfluidic device 200 of the invention, both P.sub.max and Q.sub.max increase by approximately an order of magnitude. According to Equation 3, Q.sub.max is expected to scale with A.sub.SCA, which in turn increases with increasing m. The increase in P.sub.max demonstrated by the microfluidic device 200 of the invention, however, is not predicted by Equation 4. The spatially complex fluid dynamic effects, electric field effects, or a combination of the two causes the more efficient generation of fluid power in an actuator with M>1.

[0104] FIG. 7 shows a comparison of a microfluidic device 200 of the present invention and a first-generation actuator. The plotted curves show the relationship between back pressure P (the pressure associated with fluidic resistance in the system within which the microfluidic actuator operates) as a function of the flow rate Q through the actuator. First-generation actuators typically produce maximum flow rates Q.sub.max (reagent transport against negligible back pressure) of 10-50 microliters per minute, with maximum back pressure P.sub.max (back pressure at which Q approaches zero) of 200-1000 pascals. The microfluidic actuator 202 of the present invention has a Q.sub.max of 300-800 microliters per minute and P.sub.max of 5-10 kPa. The increase in Qmax is consistent with the greater flow cross-sectional area of the actuator. FIG. 7 illustrates the increased flow rate and back pressure capacity of the microfluidic device 200 of the invention (P.sub.max and Q.sub.max), compared with first-generation microfluidic actuators.

[0105] FIG. 8 provides an illustration of the electrical resistance across the slat structure 202. FIG. 9 illustrates a microfluidic cartridge or processing system 900 that houses the microfluidic actuator 200. One or more microfluidic actuators 200 may be used in the microfluidic cartridge 900.

EXAMPLES

[0106] Below are examples of specific embodiments of the invention. The examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way.

Example 1

Method of Generating a Microfluidic Device

[0107] Methods of the invention include methods of manufacturing a microfluidic device. The method includes generating a slat structure, each slat having a first face and a second face, wherein a separation between the first and second faces defines a thickness and wherein the slat structure comprises a plurality of interstices such that a fluid is capable of flowing through the plurality of interstices. Each of the plurality of interstices has a dimension a across the face of the interstice and a dimension b of the length of the thickness, wherein the dimension b is between 50 microns and 2 mm in length, and is at least fifty times greater than dimension a of the interstice, and wherein the average electrical resistivity of the primary structural material composing the slat structure is at least 1000 ohm-centimeters.

[0108] In one embodiment, the method includes generating a housing enclosing the slat structure, such housing including a first housing structure and a second housing structure. The first housing structure defines a first fluid cavity adapted for housing a fluid and in fluidic communication with one face of the slat structure. The second housing structure defines a second fluid cavity adapted for housing a fluid and in fluidic communication with the other face of the slat structure. In some embodiments, the first fluid cavity, the slat structure and the second fluid cavity define a fluid pathway, wherein the lowest flow resistance path from the first fluid cavity to the second fluid cavity is through the plurality of interstices.

[0109] The method also includes providing a plurality of electrodes for generating an electric field within the plurality of interstices. In some embodiments, the slat structure, the housing and the electrodes are configured such that at least of a maximum voltage difference V applied to the plurality of electrodes occurs between the first face and the second face of the slat structure. In some embodiments, the electric field is perpendicular to the surface of the slat structure.

[0110] The method includes adding a conformal insulating layer to at least one surface of the slat structure, or to the individual slats, to minimize electrical charge transfer between the fluid and the slat structure. The method also includes adding a conformal insulating layer to at least one surface of the slat structure to increase the density of mobile ions within the fluid phase of the electric double layer and to increase the volume of fluid within which the concentration of such mobile ions is sufficiently large to contribute to the generation of electroosmotic flow, such density and distribution effects for mobile ions being describable by an increase in an absolute value of a zeta potential for the interface of a fluid phase and the slat structure surface material. The method also includes coating the slat structure with one or more thin films of silicon. In some embodiments, the thin film comprises silicon oxide. In other embodiments, the method includes coating the slat structure with one or more thin films of silicon nitride. In one embodiment, the slat structure comprises crystalline silicon. The crystalline silicon may have a resistivity of at least 1000 ohm-centimeters.

[0111] In other embodiments, the slats have straight sides. In another embodiment, the sides of the slats are wavy, curved, saw-toothed, or are otherwise non-rectilinear shape.

[0112] In some embodiments, the slat structure is produced by photolithographically patterning a single-crystal silicon wafer, etching a plurality of interstices through bombardment with directional ions, removing a photolithography process residue, producing at least one surface film through deposition or other means, and dicing the wafer. In some embodiments, the method also includes thinning the wafer by means of a chemical-mechanical polishing process. In some embodiments, the method includes oxidizing the etched silicon wafer after etching such that the slats are enlarged through the conversion of silicon to silicon oxide, with a corresponding reduction in the interstice width. In some embodiments, the method includes depositing polysilicon on the wafer after etching such that the slats are enlarged, with a corresponding reduction in the interstice width.

[0113] The method also includes providing a volume of aqueous solution in the housing, such that the volume extends at least 100 microns into the first and second fluid cavities on either side of the slat structure.

[0114] The method also includes programming a pulse generator to deliver a pattern of voltage pulses to the plurality of electrodes. The pattern of voltage pulses may repeat at a frequency of 0.5 Hz or faster, a frequency of 1.0 Hz or faster, or a frequency of 10 Hz or faster. The pattern of voltage pulses repeats at a frequency of 100 Hz or faster. In some embodiments, the pattern of voltage pulses is a pulse duration. In one embodiment, the pulse duration is shorter than a period of time corresponding to a 1/pattern repeat frequency.

Example 2

Microfluidic Cartridge

[0115] The microfluidic device 200 may be housed in a microfluidic cartridge 900, as shown in FIG. 9. In some embodiments, at least two microfluidic devices or actuators are included in the microfluidic cartridge 900. The microfluidic cartridge may also include a plurality of fluid passageways that are fluidly connected to the microfluidic device, openings for receiving fluids, and components for processing, mixing and analyzing fluids.

[0116] Alternating plugs of fluids can be generated from the use of two or more microfluidic devices (or actuators) pressurizing two or more fluids inside the microfluidic cartridge 900. In an example, operating a first microfluidic actuator 200 or a second microfluidic actuator, or both, in a time-varying manner can result in spatially non-uniform distributions of the fluids for the series of cross-sections in the axial direction within the fluid passageway. The first microfluidic actuator 200 can be toggled between an on-state and an off-state with a duty cycle of 50%, and the second microfluidic actuator can be toggled between an on-state and an off-state with a duty cycle of 50%, such that the microfluidic actuators operate 180 degrees out of phase from one another.

[0117] FIG. 10 shows a sequential injection of alternating plugs 1001, 1002 of fluids contained in the fluid passageways. Because of predominance of viscous forces over inertial forces, molecular diffusion can be the primary mechanism by which chemical and biochemical constituents of two fluids intermingle when such fluids are combined within a microfluidic cartridge. Spatially non-uniform distributions of fluids can shorten the distances over which such diffusion takes place, speeding chemical and biochemical reactions. For greater control over differential fluid transport and/or to mix multiple fluids together, multiple microfluidic actuators may be used with multiple channels and junctions for moving and combining fluids. Each microfluidic actuator is fluidly connected to an actuator fluid and generates flow of a processing fluid. For example, two microfluidic actuators can generate mixing of two processing fluids. Next, the mixture can be joined with a third fluid in another fluidic passageway using the fluidic pressure of two additional microfluidic actuators.

[0118] FIG. 10 illustrates a sequential injection of alternating plugs of the fluids followed by pressure-driven flow of the train of plugs through a fluid passageway. Fluid flows in the low Reynolds number regime can be well modeled by assuming the flow velocity at the fluid passageway wall to be zero (the no-slip boundary condition). For a cylindrical passageway, the radial flow velocity profile is parabolic:

[00004]$u\left(r\right)=2.Math.U\left[1-{\left(\frac{r}{a}\right)}^2\right]$

[0119] where U is the average velocity, r is the radial coordinate, and a is the radius of the cylindrical passageway. As the plugs move down the fluid passageway, the parabolic flow profile causes corresponding plug distortion 1001, 1002. Any particles or molecules contained with the fluid plugs can diffuse radially from the distorted plugs. For example, the particles or molecules can diffuse radially outward 1003 from the plug fronts near the fluid passageway centerline and radially inward 1004 from the plug tails near the walls. This phenomenon is known as Taylor dispersion. Similar diffusion effects can arise in non-cylindrical fluid passageways.

[0120] Taylor dispersion between alternating plugs of fluid generated by the microfluidic actuator 200 may be used to mix reagents or molecules within two different fluids. For example, the mixing of fluids may be used to label analytes or molecules or bind target molecules with antibodies or molecular probes.

[0121] FIG. 11 further provides flow rate and power data for microfluidic actuators as summarized in FIG. 7, according to one embodiment of the invention.

[0122] FIG. 12 illustrates graphs of the flow rate and power data for microfluidic actuators as summarized in FIGS. 7 and 11, according to one embodiment of the invention.

[0123] FIG. 13 illustrates the back pressure and flow rate among first and second generation microfluidic actuators, according to one embodiment of the invention.

[0124] FIG. 14 illustrates the back pressure and flow rate among various microfluidic actuators, according to one embodiment of the invention.

[0125] FIG. 15 illustrates back pressure and flow rate among first generation microfluidic actuators, according to one embodiment of the invention.

[0126] FIG. 16 shows the thermodynamic efficiency of microfluidic actuators of the invention, according to one embodiment of the invention.

[0127] FIG. 17 illustrates the back pressure and flow rate for a 1 mm3 mm microfluidic actuator (SCAFA) using laser-cut, platinum-plated electrodes, according to one embodiment of the invention. The process for development of laser-cut, platinum-plated electrodes is as follows:

[0128] 1) Laser cut a 25-micron thick stainless steel sheet to electrode pattern, but held captive in a sheet with ligatures

[0129] 2) Gold strike or flash the stainless steel sheet, proving a gold adhesion layer less than 0.1 micron thick.

[0130] 3) Electroplate 1-2 microns of platinum on top of the gold

[0131] 4) Separate the individual electrodes from the sheet manually

[0132] 5) Laser cut adhesive-backed polyimide to the required insulation area

[0133] 6) Encapsulate the electrodes between the two polyimide insulators

[0134] FIGS. 18A-C illustrate the electric field effects in microfluidic actuators of the invention (Slit Capillary Array Fluidic Actuators (SCAFAs)), according to one embodiment of the invention. The electro-osmotic field (EOF) is associated with the action of an externally imposed electric field on the mobile ions of the fluid phase of the electric double layer. Viscous effects result in bulk flow. In SCAFAs, the bulk flow generated within an internal high field zone creates piston-like action on fluid phases outside the actuatory chip. The high-field zone is designed for efficient EOF generation through choice of surface chemistry optimization and geometry. A parallel arrangement of narrow, deep, closely spaced microchannelsreferred to as a slit capillary arrayformed in single-crystal silicon wafer using photolithography tools can be readily optimized for EOF (Laser, 2006). A common slit capillary array design is shown in FIG. 18A. EOF in a slit capillary can be modeled using parallel-plate flow assumptions (Burgreen and Nakache 1964). For a slit of width 2a, length 11, the general relationship between average velocity v in the slit and the end to end pressure differential p is:

[00005]$\stackrel{\_}{v}=-\frac{a_1^2}{3.Math..Math..Math.l_1}.Math..Math..Math.p_1+\frac{\mathrm{.Math.}}{}.Math.E_x\left[1-G\left(,.Math..Math.a_1\right)\right]$

[0135] where is the fluid viscosity, is the fluid permittivity, E.sub.x is the axial electric field, and is the zeta potential (an empirical parameter related to the double layer thickness and charge distribution). Maximizing E.sub.x for a given applied voltage therefore is an important tool for optimizing both pressure and flow rate performance

[0136] FIG. 18A shows an externally applied electric field can result in bulk fluid motion against a pressure gradient as mobile ions in the fluid phase of the double layer (Laser and Santiago, 2004). The figure shows a schematic of a microfluidic actuator (SCAFA) with inlets, microchannels and electrodes at a height (H) separating them.

[0137] FIG. 18B shows a schematic representation of electric double layer (EDL) formation at a fluid-solid interface. Counter ions in the liquid accumulate in the vicinity of the charged surface.

[0138] FIG. 18C shows a SEM image of the microchannels inside a microfluidic actuator (SCAFA), according to an embodiment of the invention.

[0139] In a typical SCAFA design, EOF is generated within a set of parallel microchannels with approximately rectilinear geometry and minimal microchannel-to-microchannel variation. Numerical simulation is an important tool for optimizing SCAFA design with a minimal number of expensive, labor intensive fabrication iterations. COMSOL Inc.'s electrostatic modeling capabilities were used to study the effect of electrode geometry and position on the average E.sub.x across a variety of slit capillary array designs. Single, double and quadruple platinum electrodes were simulated in an aqueous environment assuming fluid properties consistent with typical SCAFA working fluids. The simulated slit patterns matched the various geometries of the SCAFA designs and a parametric investigation on the electrode height (H) above the slits and lateral distance from the center was performed. FIG. 19 shows electrostatic images in COMSOL showing the 14 mm and 24 mm slit area as well as mesh distribution (Clockwise from bottom left: single wire 14 mm area, double wire 24 mm area, quadruple wire 24 mm area, and quad wire mesh distribution).

[0140] FIGS. 20A-D illustrate additional data from a COMSOL parametric study on flow rate and pressure performance using various electrode configurations, according to one embodiment of the invention. The monotonic decrease in field strength with increasing H is both qualitatively and quantitatively consistent with one-dimensional electrical resistance models for ionic current in the fluid phase. However the pronounced dependence on E.sub.x on multielectrode configuration, particularly at small H, is poorly modeled by simple resistor networks. The simulation indicates that a judicious choice of electrode geometrysuch as the quad electrode configuration described abovecan markedly improve SCAFA flow rate and pressure performance

[0141] FIG. 20A illustrates the fraction of axial electric potential (EP) drop across the slits in the 24 mm slit area SCAFA for single, double, and quadruple electrods versus the height (H) of the electrod above the SCAFA surface. FIG. 20B illustrates the fraction of electric potential drop across the slits multiplied by the respective slit area vs. SCAFA design.

[0142] To test COMSOL model predictions, SCAFAs were tested with a variety of electrode configurations. The experimental setup and key results are shown in FIGS. 20C and 20D. The applied potential is 200 volts and the SCAFAs have 24 mm flow zones. A single wire is the base case. A wire mesh electrode approximated the quad electrode geometry. The flow rate of each triplicate experiment was measured with a Senserion flow meter at 3 relative back pressures. Back pressures were generated by attaching a 0.5 mm diameter coil at 2 lengths inline with the flow path. FIG. 20C shows a measured flow rate of a 24 mm slit area SCAFA with a single wire and wire mesh electrode under three back pressure conditions. Simulated mesh values are calculated from measured SCAFA flow rates with wire electrode multiplied by the simulated quad wire improvement. FIG. 20D shows a schematic of the experimental set up used to perform the experiments.

Example 3

Applications

[0143] The microfluidic device may be used for a wide variety of applications in human health, animal health, food safety, and environmental monitoring involving transport of small amounts of fluids.

[0144] Examples of such applications include the movement of fluids containing samples and reagents for measurement of target species in body fluids, such as diagnosis of infectious and non-infectious disease through detection and quantification of a variety of DNA, RNA, proteins, or other categories of target molecules in tissue samples from patients.

[0145] The microfluidic device may be used in a cartridge to transport or mix fluids containing samples and reagents for the measurement of a target species in environmental samples, such as the detection of chemical or biological contaminants or other materials of interest.

[0146] The microfluidic device may also be used in a cartridge to transport or mix fluids containing samples and reagents for measurement of target species in food samples, such as detection of toxic substances or other materials of interest.

[0147] The microfluidic device may also be used in a cartridge to transport reactants of a chemical synthesis process. For example, two chemical compounds could be combined to produce a compound of pharmaceutical relevance.

[0148] The microfluidic device may be used to transport a material that is toxic or otherwise poorly suitable for direct human handling. For example, pipetting of solutions is associated with risk of aerosolization, which could pose risk of infection to people in the vicinity if the solution contains airborne-transmissible pathogens. The microfluidic device can be used to eliminate a pipetting step.

[0149] The microfluidic device may also be used to reconstitute a material from a dried-down or lyophilized form into a solution form. The microfluidic device can transport a reconstituting solution, such as an aqueous, within a microchannel network to a location where the dried-down or lyophilized material, such as an enzyme, is held. The reconstitution process can include causing the aqueous to flow over the lyophilized material. The reconstitution process can include subjecting the flow to oscillatory or other action to speed reconstitution through disruption of concentration gradients relative to an unperturbed state.

[0150] Other areas of application include drug delivery and other medicinal applications. Various other areas of application include the transport of fluids in miniature power systems, such as fuel cells and solar sterling engines; endoscopic sampling and/or catheter-based sampling; wound care; and use in nebulizers.

[0151] Examples of use of the microfluidic device of the invention in a cartridge are described in U.S. Provisional Application No. 61/771,708, filed on Mar. 1, 2013, which is hereby incorporated in its entirety by reference.

[0152] While the invention has been particularly shown and described with reference to a preferred embodiment and various alternate embodiments, it will be understood by persons skilled in the relevant art that various changes in form and details can be made therein without departing from the spirit and scope of the invention.

[0153] All references, issued patents and patent applications cited within the body of the instant specification are hereby incorporated by reference in their entirety, for all purposes.

REFERENCES

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[0163] Pumps Fabricated From Porous Silicon Membranes, J. Microelectromech. Syst., vol. 15, no. 3, pp. 717-728, June 2006. [0164] [10] R. F. Probstein, Physicochemical Hydrodynamics: An Introduction. John Wiley & Sons, 2005. [0165] [11] D. Burgreen and F. R. Nakache, Electrokinetic Flow in Ultrafine Capillary Slits1, The Journal of Physical Chemistry, vol. 68, no. 5, pp. 1084-1091, 1964. [0166] [12] M. J. Madou, Fundamentals of Microfabrication: The Science of Miniaturization, Second Edition. CRC Press, 2002. [0167] R. J. Hunter, Zeta Potential in Colloid Science, San Diego: Academic Press, Inc., 1981. [0168] D. Burgreen and F. R. Nakache, Electrokinetic Flow in Ultrafine Capillary Slits, J. Phys. Chemistry, vol. 68, pp. 1084-1091, 1964. [0169] D. J. Laser, A. M. Myers, S. Yao, K. F. Bell, K. E. Goodson, J. G. Santiago, and T. W. Kenny, Silicon Electroosmotic Micropumps for IC Thermal Management, Proc. 12th International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers '03), Boston, Mass., Santiago/Stanford [0170] D. J. Laser, Temporal Modulation of Electroosmotic Micropumps, Proc. ASME IMECE, Fluids Engineering in Micro- and Nano-Systems VII, 2006: p. 13960.