WO2001025138A9 - Modular microfluidic devices comprising sandwiched stencils - Google Patents
Modular microfluidic devices comprising sandwiched stencilsInfo
- Publication number
- WO2001025138A9 WO2001025138A9 PCT/US2000/027366 US0027366W WO0125138A9 WO 2001025138 A9 WO2001025138 A9 WO 2001025138A9 US 0027366 W US0027366 W US 0027366W WO 0125138 A9 WO0125138 A9 WO 0125138A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microfluidic device
- stencil
- microfluidic
- substrate
- substrates
- Prior art date
Links
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B38/00—Ancillary operations in connection with laminating processes
- B32B38/10—Removing layers, or parts of layers, mechanically or chemically
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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- G—PHYSICS
- G01—MEASURING; TESTING
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- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N21/05—Flow-through cuvettes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/447—Systems using electrophoresis
- G01N27/44756—Apparatus specially adapted therefor
- G01N27/44791—Microapparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J2219/0002—Plants assembled from modules joined together
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J2219/00819—Materials of construction
- B01J2219/00824—Ceramic
- B01J2219/00828—Silicon wafers or plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
- B01J2219/00833—Plastic
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
- B01J2219/00835—Comprising catalytically active material
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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- B01J2219/00851—Additional features
- B01J2219/00853—Employing electrode arrangements
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
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- B01J2219/00891—Feeding or evacuation
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00905—Separation
- B01J2219/00912—Separation by electrophoresis
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00952—Sensing operations
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0874—Three dimensional network
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/16—Surface properties and coatings
- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
- B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B2310/00—Treatment by energy or chemical effects
- B32B2310/08—Treatment by energy or chemical effects by wave energy or particle radiation
- B32B2310/0806—Treatment by energy or chemical effects by wave energy or particle radiation using electromagnetic radiation
- B32B2310/0843—Treatment by energy or chemical effects by wave energy or particle radiation using electromagnetic radiation using laser
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0346—Capillary cells; Microcells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N21/05—Flow-through cuvettes
- G01N2021/058—Flat flow cell
Definitions
- the present invention relates generally to modular microfluidic devices and components that can be combined together to form microfluidic devices. More specifically, the present invention relates to modular microfluidic devices comprising layered substrates and sandwiched stencils, and processes for their manufacture.
- microfluidic devices allow, for example, complicated biochemical reactions to be carried out using very small volumes of liquid. These miniaturized devices increase the response time of the reactions, minimize sample volume, and lower reagent cost, among other benefits.
- microfluidic devices have been constructed in a planar fashion using techniques borrowed from the silicon fabrication industry. Representative devices are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). In these publications, microfluidic devices are constructed by using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of this device to provide closure. Miniature pumps and valves can also be constructed to be integral with (e.g., within) such devices.
- a negative mold is first constructed, and plastic or silicone is then poured into or over the mold.
- the mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Anal. Chem. (1998) 70: 4974- 4984; McCormick et al., Anal. Chem. (1997) 69: 2626 -2630), or by building a traditional injection molding cavity for plastic devices.
- Some molding facilities have developed techniques to construct extremely small molds.
- microfluidic devices described by Gonzalez et al. are not truly modular since they are limited to interconnect systems for silicon wafers.
- modular, three-dimensional microfluidic devices which can include various componentry (e.g., valves, filters, etc.).
- One object of the present invention is to provide an inexpensive and robust modular microfluidic device.
- An additional object is to provide a microfluidic device that is rapidly prototyped with minimal tool-up costs.
- the manufacturing cost of the microfluidic devices of the present invention is relatively low, at both high and low production volumes.
- Another object of the present invention is to provide a modular system of microfluidic components that can be combined in various configurations to construct a microfluidic device. In this manner, prototyping and manufacturing can be accomplished in a very rapid manner, since a complete set of generic "building block" components can be constructed in bulk. These components and devices can then be combined in various ways to construct desired microfluidic systems.
- Yet another object of the present invention is to provide an inexpensive means of manufacturing positive or negative molds for the construction of microfluidic replicates.
- An additional object of the present invention is to provide "built-in" (i.e., integrated) electronic components within the microfluidic devices. Specifically, for example, electrodes can be placed within channels and chambers of the microfluidic devices. These electrodes can be used for electrokinetic flow, electrophoresis, electrochemical detection, impedance measurements and temperature sensing, among other functions.
- Another object of the present invention is to provide a microfluidic device comprising valves for the controlled handling and manipulation of fluids.
- Another object of the present invention is to provide a microfluidic device comprising a microstructure capable of filtering a small volume of fluid, especially a fluid comprising biomolecules such as nucleic acids or proteins.
- An additional object of the present invention is to provide a microfluidic device that is chemically compatible with or can accommodate the use of a vast array of liquid reagents or solutions including, but not limited to, organic solvents such as acetonitrile.
- a microfluidic device comprising first and second substrates, and at least one stencil disposed (e.g., sandwiched) between the first and second substrates so as to define one or more sealed microstructures therebetween.
- the stencil is adhered to at least one of the first and second substrates by an adhesive.
- the first and second substrates are substantially planar, and have surfaces complementary with each other so as to better seal microstructures therebetween.
- the first and second substrates preferably are made from Mylar ® , FR-4, polyester, glass, acrylic, polycarbonate or fiberglass.
- the adhesive is preferably a rubber-based adhesive, an acrylic-based adhesive or a gum-based adhesive.
- the stencil is self-adhesive.
- the stencil comprises an adhesive tape, which can be single-sided (i.e., have adhesive on one side) or double-sided (i.e., have adhesive on both sides). Any adhesive tape may be used, including especially commercially available adhesive tapes. Examples of types of adhesive tape include, but are not limited to, pressure-sensitive tapes, temperature- activated (e.g., heat activated) tapes, chemically-activated (e.g., two-part epoxy) tapes and optically-activated (e.g., UV-activated) tapes.
- the adhesive tape comprises a backing material selected from the group consisting of Mylar ® , nylon and polyester, to support the adhesive.
- the stencil and at least one of the first and second substrates are ultrasonically welded together.
- the stencil can be made from polymers, papers, fabrics and foils, among other materials.
- the stencil comprises a polymer selected from the group consisting of Mylar ® , polyesters, polyimides, vinyls, acrylics, polycarbonates, Teflon ® , Kapton ® , polyurethanes, polyethylenes, polypropylenes, polyvinylidene fluorides, polytetrafluoroethylenes, nylons, polyethersulfones, acetal copolymers polyesterimides, polysulfones, polyphenylsulfones, ABS, polyvinylidene fluorides, polyphenylene oxides, and derivatives thereof.
- the microfluidic device preferably includes one or more microstructures comprising a channel or chamber.
- the microstructure is at least partially filled with a filling material, such as a filter material.
- a filling material such as a filter material.
- the filter material may comprise a wide variety of materials capable of specific and non-specific filtering of various size parameters. Any of various chemical, biological and size-exclusion filter materials may be used.
- the filter material is selected from the group consisting of polycarbonates, acrylics, acrylamides, polyurethanes, polyethylenes, polypropylenes, polyvinylidene fluorides, polytetrafluoroethylenes, naphion, nylons and polyethersulfones.
- the filter material may also be selected from the group consisting of agarose, alginate, starch and carrageenan.
- the filter material is Sephadex ® , Sephacil ® or hydroxyapatite.
- the filling material is applied by silk screening, which can reduce the manufacturing time and cost.
- the filling material can also be applied using lithography.
- the filling material is applied using pick-and-place techniques, which are well known in the semiconductor manufacturing industries.
- the microfluidic device includes at least one substrate having one or more apertures, which can be in fluid communication with one or more substrates.
- the microfluidic device may also further comprise one or more valves of various designs. Several valve configurations and componentry are described below.
- the microfluidic device can be used to divide a liquid sample into a plurality of sample. In one embodiment, such splitting of samples is accomplished by using a microstructure comprising one or more forked channels, each preferably having one or more constrictions to control fluid flow therethrough.
- the microfluidic device may further comprise at least one electrode.
- the electrode can be used for detecting or measuring an electrical property of a fluid. Alternatively, the electrode is for promoting electrophoretic or electrokinetic flow.
- the microfluidic device of the present invention may be multi-layered to form a three- dimensional device or system. Therefore, in certain embodiments, the microfluidic device may further comprise one or more additional substrates sealingly engaged thereto.
- the additional substrate(s) are preferably layered or stacked so that microstructures of the various layers are sufficiently aligned as to be functional for the desired application.
- One or more of these additional substrates can comprise a circuit board having on a surface thereof a microstructure. Circuit board substrates useful in the construction of microfluidic devices are described in co- pending United States Patent Application Serial No. (Attorney Docket No. ), the disclosure of which is incorporated herein by reference.
- a microfluidic system comprising a plurality of microfluidic devices may be constructed, wherein at least two of the microfluidic devices are configured to enable fluid communication with each other.
- the microfluidic system can be prepared by layering two or more microfluidic devices to form a three-dimensional microfluidic system.
- the present invention also provides a method for producing a microfluidic device.
- the method comprises the steps of: (a) providing a first substrate; (b) layering on the first substrate one or more panels, each comprising an array of stencils; and (c) layering on the one or more panels a second substrate so as to define a plurality of microstructures therebetween.
- at least one of the first and second substrates has one or more apertures.
- at least one of the panels is aligned with at least one of the first and second substrates so that the apertures are in fluid communication with the microstructures. Such alignment is preferably provided by peg-and-hole alignment.
- the present invention also provides in certain embodiments microfluidic devices prepared according to the foregoing method.
- the present invention also provides a mold prepared using at least a portion of a stencil as a form for defining the mold.
- the mold preferably is made from a silicone material.
- a microfluidic device comprising a microstructure can be prepared using such a mold.
- microstructure refers to microfluidic structures disposed on one or more substrates used to assemble the microfluidic devices of the present invention.
- the term encompasses any of a variety of structures (including, but not limited to, channels and chambers) that are capable of supporting a fluid (i.e., microstructures through or into which fluid(s) are capable of being passed, stored or directed).
- the microstructure boundaries are defined by the outline of the cut-away portion(s) of the sandwiched stencils.
- sealed refers to a microstructure having a sufficiently low unintended leakage rate and/or volume under given flow, fluid identity and pressure conditions.
- the term also encompasses microstructures that have one or more apertures therein through which fluid is intended to pass.
- adheresive refers to any chemical having adhesive properties so as to be effective to adhere the various stencil and/or substrate layers of a microfluidic device of the present invention together to define a sealed microstructure therebetween.
- stencil refers to a material that is preferably substantially planar from which one or more variously shaped and oriented portions are cut or removed.
- the outlines of the cut or removed portions comprise the lateral boundaries of microstructures that are formed upon sandwiching stencil(s) between substrates.
- microfluidic devices described here are "generic" in that they are modular and can be easily reconfigured into or adapted to any design. These devices are capable of being used with a variety of pumping and valving mechanisms, including pressure, peristaltic pumping, electrokinetic flow, electrophoresis, vacuum and the like.
- the microfluidic devices of the present invention are capable of being used in collaboration with optical detection (e.g., fluorescence, phosphorescence, luminescence, absorbance and colorimetry), electrochemical detection, and any of various suitable detection methods. Suitable detection methods will depend on the geometry and composition of the device, The choice of an appropriate detection method for a given application is within the purview of the skilled artisan.
- Figure 1 shows the construction of a microfluidic device comprising a stencil sandwiched between two substrates.
- Figure 1 A is an exploded perspective view showing the individual components of the device, and
- Figure 1 B is a three-dimensional perspective view of the assembled device.
- Figure 2 provides cross-sectional views (A-D) showing a stencil being coated with a sealant coat.
- the adjacent substrate (cover plate) can optionally also be coated with a sealant coat, as in Figure 2D.
- Figure 3 is a cross-sectional view showing a microfluidic device where one sealing coat material is used to coat the stencil and underlying substrate, and a second sealant coat material is used to help seal the substrates together.
- Figure 4 shows the construction of a three-dimensional microfluidic device comprising stencils.
- Figure 4A is an exploded perspective view showing the individual components, and
- Figure 4B is a three-dimensional perspective view of the assembled device.
- Figure 5 shows the construction of another three-dimensional device comprising a stencil.
- Figure 5A is an exploded perspective view showing the individual components
- Figure 5B is a three-dimensional perspective view of the assembled device.
- Figure 6 illustrates the use of silk screening technology to fill or coat specific areas (e.g., filter chambers) of a microfluidic device.
- Figure 6A shows the individual components
- Figure 6B shows an alignment procedure for silk screening a panel of devices.
- Figure 8 is a top view of a microfluidic device comprising forked channels capable of splitting a sample into four approximately equal parts.
- Figure 9 illustrates the components of a microfluidic device that has an integrated (i.e., "built-in") valving mechanism.
- Figure 10 is an exploded view showing an alignment technique using peg-and-hole alignment technology to ensure proper alignment of various layers and componentry of microfluidic devices.
- Figures 11A and 11 B are photomicrographs of a microfluidic device comprising a sandwiched stencil, showing fluid passing therethrough at two stages of operation.
- Figure 12A shows the components of a microfluidic device constructed using 18 stencils.
- Figures 12B and 12C are photomicrographs of such a device with acetonitrile passing through it at two stages of operation.
- Figure 15 is a photomicrograph of a microfluidic device constructed using a stencil comprising a thermal (i.e., temperature-activated) tape.
- Figure 16 shows the construction of a microfluidic device comprising both circuit board- type substrates and stencils.
- Figure 16A illustrates at left an exploded perspective view and at right an assembled perspective view.
- Figure 16B is a photomicrograph of a device as shown in Figure 16A with fluid passing therethrough.
- Figures 17A and 17B are photomicrographs of a microfluidic device comprising forked channels capable of splitting or dividing a fluid sample, at two stages of operation.
- the stencil comprises single-sided or double-sided adhesive tape.
- a portion of the tape (of the desired shape and dimensions) can be cut and removed to form, for example, a channel or chamber.
- the tape stencil can then be placed on a supporting substrate or between substrates.
- stencil layers are stacked on each other. The thickness or height of the channels can be varied by simply varying the thickness of the stencil (e.g., the tape carrier and the adhesive thereon).
- Suitable tapes for use in the present invention can have various methods of curing or activation, including pressure-sensitive tapes, temperature-activated tapes, chemically- activated tapes, optically-activated tapes, among other types of tapes.
- Various adhesives are useful, including, for example, rubber-based adhesives, acrylic-based adhesives, and gum- based adhesives.
- the materials used to carry the adhesive are also numerous. Examples of suitable tape carrier materials include Mylar ® , polyester and nylon. The thickness of the carrier can be varied.
- a probe is used to define the channels and chambers of the stencil.
- the probe is a cutting device mounted to, for example, a computer- controlled plotter. The probe selectively removes shapes from a material to form a stencil defining the lateral boundaries of microstructures (e.g., channels and chambers).
- a heat probe is used to selectively melt or anneal heat-activated adhesive to form microstructures.
- ultrasonic welding is used to create microstructures in layeres stencils. For example, channels can be defined in two stencil layers. These layers can be "melted” together using ultrasonic welding.
- the chemical nature of the stencil material and, thus, the microstructure's chemistry, can be "tuned” for particular applications.
- the stencil material can be hydrophilic, hydrophobic or ionic in nature.
- the stencil material can be flexible.
- the stencil material is selected from the group consisting of vinyl, filter material, paper or fabric, foil, and foam or foam sheets.
- the stencil material is formed from a polymeric material.
- Suitable polymers include, but are not limited, to polycarbonate, acrylic, polyurethane, polyethylene, including high-density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMW), polypropylene (PP), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), nylon, polyethersulfone (PES), acetal copolymers, polyesterimides, polysulfones, polyphenylsulfones, ABS, polyvinylidene fluoride, polyphenylene oxide, and derivatives thereof.
- the polymer is a fluorinated polymer, since fluorinated polymers often have superior resistance to aggressive solvents such as organic solvents.
- the stencil material is a flexible or elastomeric material, such as silicone, viton, or rubber, so as to enable valving and pumping mechanisms. Pressure or mechanical force can be applied to the flexible layer to cause the material to bend and block a channel located above or below it.
- sealant coat material can be chemical and/or biological in nature, and can be hydrophobic or hydrophilic, depending on the application. Solids, liquids, gels and powders, or combinations thereof, can be used. Materials capable of carrying a surface charge can be used, as can neutral species. Specific examples of coating materials suitable for use in the present invention include Teflon ® , Liquin ® , Avatrel ® , silicone, silicone mixtures, epoxies (including solder masks), glue, liquid polymers, polymeric dispersions, plastic, liquid acrylic, paint, metals, oils, waxes, photoresist, varnish, solder and glass.
- the sealant coat material is a fluorinated polymer.
- Fluorinated polymers have excellent resistance to various solvents and chemicals, including organic solvents. Examples include Teflon ® , Avatrel ® , polyvinylidene fluoride (PVDF), THV Fluorothermoplastic (Dyneon, St Paul MN), Hostaflon TF 5035 (Dyneon), among others.
- the various sealant coat material(s) can be deposited using a number of techniques.
- the sealant coat material(s) are spin-deposited onto a given substrate and/or stencil using a spinner or rotator. Specifically, an appropriate amount of a sealant coat material is placed on a substrate or stencil and the entire substrate or stencil is spun to produce a generally uniform sealant coat layer.
- the spin rate is between about 10 rotations per minute (rpm) and about 100,000 rpm. More preferably, the spin rate is about 500-20,000 rpm and, most preferably, is about 1 ,000-20,000 rpm. In order to make the coating thicker, multiple spin-deposition cycles can be used.
- the sealant coat material can be deposited by spraying the sealant coat material onto a surface.
- the sealant coat material can be ultrasonically sprayed through a nozzle or other orifice.
- colloidal dispersions of the sealant coat material are prepared, the concentration being adjusted so that when sprayed onto a surface, a layer of desired thickness results.
- the sealant coat material is sprayed directly onto a surface.
- the sealant coat material is dissolved in an appropriate solvent and then sprayed onto the surface; when the solvent evaporates, the sealant coat material is left behind to form a coating layer.
- the sealant coat material can, alternatively, be applied by dipping a substrate and/or stencil into a volume of the sealant coat material.
- a single dip may produce a coating of a certain thickness; in order to make the coating thicker, multiple dips may be applied.
- the sealant coat material can be brushed onto a surface.
- the sealant coat material can be deposited directly as a colloidal dispersion, or as a material dissolved in a solvent.
- the sealant coat material is stamped onto a surface.
- the sealant coat material is patterned (e.g., by silk screening techniques) onto a surface.
- the sealant coat material can be used to coat only certain selected areas of the surface as defined by the silk screening mask.
- photoresist patterning can be used to achieve liftoff or etch patterning. The photoresist can then be removed to leave a coating only on certain areas of the surface. This procedure can be repeated as desired or necessary using different photoresist patterns and coating materials.
- a variety of thin film deposition techniques can be used to deposit sealant coat materials. Such techniques include, but are not limited to, thermal evaporation, e-beam evaporation, sputtering, chemical vapor deposition, and laser deposition. These and other thin film deposition techniques are well known in the art.
- plating techniques can be used to deposit sealant coat materials. Such plating techniques include, but are not limited to, electroplating of metallic materials and chemical plating.
- silanization reactions can be used to coat the substrates. Silanization is known to minimize adherence of certain biological materials such as nucleic acids and peptides.
- the microstructures are coated with a lipid bilayer or multilayer. In certain embodiments, these molecular monolayers are terminated with a biological molecule that is used to bind a molecule in the solution. Examples include nucleic acid-terminated alkane thiols and protein-terminated silanes.
- a sample is injected into one of the inlet apertures 68 and a reagent is injected into the other of the inlet apertures 68.
- the sample and the reagent mix at the junction of the T-channel and are passed to the adjacent layers below.
- the filter material in filter chamber 78 captures unwanted material(s), and the purified material passes through the outlet aperture.
- the assembled device is shown in Figure 4B.
- FIG 5 An alternate 3-D microfluidic device design is shown in Figure 5.
- the top three layers are identical to those in Figure 4.
- layer 84 is itself a filter material.
- the bottom layer 80 having outlet aperture 81 is the same as in Figure 4.
- the assembled device is shown in Figure 5B.
- Methods of forming apertures include, but are not limited to, mechanical drilling, laser drilling, chemical etching, plasma etching and hole punching.
- components of the device can be constructed from injection molded parts that have integrated or built-in inlet/outlet apertures. Other techniques known in the art for through-hole formation can be employed.
- the sealant coat materials can be chemically bonded to the underlying substrate and to the next layer. Alternatively, non-covalent chemical interactions can be used to hold the substrates together.
- the stencil material can be melted onto the underlying substrate or adhered using an adhesive or some other mechanism, such as heating. In other embodiments, the stencil can be mechanically pressed onto the underlying or adjacent substrate.
- a circuit board substrate having on a surface thereof a microstructure may comprise one or more layers of a microfluidic device.
- the use of circuit board-type substrates, and other substrates having metal laminates, in constructing microfluidic devices is the subject of co- pending United States Patent Application Serial No. (Attorney Docket No. ), the disclosure of which is incorporated herein by reference.
- a microstructure can be filled with any of a variety of filling materials, including reagents or catalysts. These filling materials, in certain embodiments, can be used to perform useful chemical and/or biological reactions.
- the filling materials are filters, which are useful for separating and/or purifying materials.
- filters can be chemical or biological filters, or size-exclusion filters. These filters may bind unwanted material or, alternatively, may bind the material of interest so that it may be eluted off later.
- the filling materials can be hydrophobic or hydrophilic in nature, and can be charged or neutral.
- the filling material may be porous with various pore sizes.
- the filling material used to fill a channel or chamber is polymeric.
- the material used to fill the channel is a carbohydrate, such as agarose, alginate, starch, or carrageenan.
- the polymer may also be an electro-active polymer.
- the filling material is silica gel.
- the filling material is Sephadex ® or Sephacil ® .
- the material used to fill the channel is acrylamide or agarose.
- the material used to fill the channel is hydroxyapatite.
- the filling material is composed of a powder, such as charcoal or porous beads.
- the filling material is a reagent that is to be activated during the use of the device. Two examples are soluble reagents and catalysts.
- the filling material is a paper filter.
- This filter may be a commercially available material that is chemically modified to perform a specific function, such as binding a material or filtering a variety of materials.
- the filling material is placed into the microstructures during the manufacturing process. In this manner, high-throughput techniques can be used to fill the channels. In one embodiment, high-throughput pick-and-place equipment, like that used in the electronics industry, is used to place the filter materials. In one embodiment, the filling material is patterned into the microstructures by, for example, silk screening the material into the channels, or by using lithography, or by mechanically placing the material. Referring to Figure 6A, an "empty" microfluidic device 90 having two filter chambers 91 and 92 is shown. In order to place filter material in the filter chambers 91 and 92, two silk screens 93 and 94 are created. The screen and stencil are formed using materials that are compatible with the filter to be screened.
- a variety of screen materials and stencils can be used.
- One of the screens is aligned, for example, above the device and the first filter material 95 from screen 93 is screened onto the device.
- the second filter material 96 can subsequently be screened onto the device from screen 94 in a similar fashion to create the "completed device 98.
- the viscosity and thickness of the material to be screened is preferably adjusted to properly fill the filter chamber or other filter area. Additionally, the amount of screened-on material should be adjusted so that the chamber fills properly.
- an entire panel of devices can be coated simultaneously.
- stencils are constructed on a panel 111.
- a preferred panel size is approximately 18" by 24"; however, other panel sizes may be used.
- Fiducial marks 114 are placed on the panels for visual or optical alignment. Holes placed in the stencil are used to align the stencil on the various machines used during the device manufacturing process.
- Silk screens 112 and 113 comprising filter material are aligned with the devices on panel 111. A single alignment allows all of the filter chambers (see 115 and 116 denoting the two types of filter chambers on the panel 111) to be filled simultaneously.
- substrates and/or additional stencils may be added to complete a microfluidic system.
- one or more of the layers of a microfluidic device of the present invention can be used as a valve.
- a multi-layer purification device is constructed.
- An inlet aperture 100 and an outlet aperture 101 are constructed in a top substrate layer 102.
- this substrate layer can be a thin piece of acrylic, glass or polycarbonate.
- a stencil forms the next layer below.
- a filter chamber 104 is constructed and filled with an appropriate filter material (not shown) by, for example, silk- screening.
- a T-shaped feature is formed, where one arm of the T is a chamber 105 and the other arm is a channel 103.
- a hole 106 is located at the distal end of the chamber 105.
- Channel 103 is in communication with outlet aperture 101 in the top substrate layer 102.
- the bottom substrate layer 110 of the stack comprises a filter material that allows air to flow but that becomes blocked when liquid comes into contact with it.
- filter materials include X-7744, a 7 ⁇ m pore size T3 sheet from Porex Technologies (Fairburn, GA) and Goretex ® -type materials.
- a sample is injected into the inlet aperture 100.
- the sample flows through the filter material in chamber 104 and into "wide" chamber 105 and "large” hole 106 until sufficient volume has been injected to fill that chamber and hole.
- the fluid flows into "narrow" channel 103 and out through outlet aperture 101.
- Any number of mechanisms can be used to force the fluid to preferentially flow into the larger chamber 105 first. Capillary forces may be taken advantage of.
- the channels may be coated with materials that induce preferential flow.
- a microfluidic device is used to concentrate samples.
- the device is constructed so that the volume of the wide channel/chamber and the large hole is about 2-100,000 times larger than the remaining filter chamber and channel volume.
- a large sample can be injected and washed many times. Then, a very small volume of eluent can be added to remove the sample that had been adhered to the filter material in filter chamber 104.
- valves are constructed by altering the shapes of the channels themselves. Referring to Figure 8B, a device is created having multiple channel splits or forks 120. After each split, the channels are constricted (see 122 in Figure 8B) so that local capillary forces are increased in that region. Further splits can be constructed after the constricted region.
- the fluid typically will prefentailly pass down one of the two channels of the split. However, once the fluid reaches the constriction area, the other of the two channels becomes filled because the capillary forces in this region are much less than in the constricted section. Once both channels are filled, the fluid passes the constriction regions to the next channels, and so on.
- samples can be accurately distributed into approximately equal portions.
- a three-dimensional device using this design should permit samples to be split into many partitions.
- a valve is constructed by altering the outlet apertures for each channel.
- a microfluidic device is constructed that has a large primary channel 125 with a smaller branched channel 126.
- the primary channel 125 terminates in channel 127, which is narrower than channels 125 and 126.
- a cover plate substrate 128 with inlet and outlet apertures positioned at the end of each of the aforementioned channel forms the top substrate layer.
- the surface chemistry of the various channels may be altered in order to achieve the same goal.
- the end of a large channel is coated with a hydrophobic material, while the rest of the channels are hydrophilic.
- water enters the large channel it first passes down the large channel.
- it reaches the area where the channel has been derivatized with hydrophobic terminal groups or coatings surface tension forces the remainder of the water down the smaller, hydrophilic channels.
- Similar techniques can be used with organic solvents. With multi-layered microfluidic devices, alignment of the layers is a consideration.
- a manifold 130 is constructed having dowels 132 of specified diameter.
- a panel 134 of stencils is placed on the manifold 130; alignment is accomplished by aligning holes f35 with the dowels 132.
- An adjacent layer 136 is placed atop panel 134; similarly, alignment is accomplished by aligning holes 137 with the dowels 132.
- Such manifolds can also be used to accommodate silk screens.
- edge alignment is used. The edges of the devices are aligned, which automatically aligns the channels and chambers if the devices are cut to specified dimensions. Alignment can be accomplished mechanically, optically, magnetically, or otherwise.
- a panel of devices is simultaneously aligned and processed.
- the completed panel of structures may then be cut or sectioned into individual devices.
- the component layers are scored into device sections prior to assembly.
- the layers of the device are brought in close proximity, realigned, and then pressed together. In this and other embodiments it may be important to control the humidity and temperature of the environment surrounding the layers. Often, the coating materials and adhesives cause local static interactions between the layers, making alignment difficult.
- the layers can be aligned under water, to minimize the static.
- a small amount of soap is added to the water to prevent immediate adhesion if a slight misalignment occurs.
- the temperature of the local environment surrounding the layers is controlled in order to aid in alignment.
- a press is constructed that has alignment blocks on both the top plate and bottom plate. One layer of the device is placed in the bottom alignment jig, and the next layer is placed in the top alignment jig. The automated press then brings the devices together for adhesion. When the press is expanded, the two layers stay on the bottom block. The next layer can be applied in a similar manner.
- a converter or die-cut printing machine can be used for constructing and layering stencils.
- the materials that form each stencil layer may be loaded in roll format onto the machine. Mechanical die punches are made for each layer. The materials are rolled out, punched, and laminated together in an automated fashion. Companies such as Acutek (Los Angeles, CA) provide services using converters. In a similar manner, a rolling system could be used to fill channels and chambers. The roll of devices can be pulled across an alignment block as described above, and filter material can be added. Again, alignment may be accomplished using a peg-and-hole alignment block. However, other alignment techniques may be used, including optical alignment and precision placement.
- the stencils are not used as the fluidic devices themselves, but rather they (or a portion thereof) are used as forms to define a positive or negative mold.
- Various molding materials can be used, such as moldable polycarbonate or various silicones (see, e.g., Duffy et al.).
- Microfluidic devices can be prepared comprising microstructures formed using such molds.
- a three-dimensional microfluidic device was constructed using double-sided adhesive tape as a stencil.
- a stencil was prepared by cutting a channel from a piece of #444 double-sided transparent polyester film tape (3M, St Paul, MN). This tape stencil was mounted onto a 1/16" thick acrylic sheet having a 0.04" diameter inlet aperture aligned with one end of the stencil channel.
- a 2 mil thick Mylar ® sheet was then layered on the tape stencil; the Mylar ® substrate had a 0.04" diameter aperture aligned with the other end of the stencil channel.
- Another tape stencil comprising a channel was then positioned on the Mylar ® substrate.
- a three-dimensional microfluidic device was constructed as follows. Modular components were constructed by preparing stencils comprising channels by cutting a self- adhesive laminating sheet tape (Avery Dennison, LS10P, 73603) using a computer-controlled plotter modified to have a cutting blade. Seven of these modules were designed so that they could be reconfigured (using simple orientation changes) to construct various microfluidic devices. In this example, two different microfluidic devices were constructed using these modules. In both cases, the first stencil was placed on a 1/16" thick polycarbonate sheet substrate having a drilled 33 mil hole as an inlet aperture.
- the remaining stencils were layered in the order shown in Figure 12A (i.e., 1 ,2,3,4,4,4,5,3,6,7,5,4,3,6,3,5,7,1), so that fluid could pass from one layer to the next at specific locations designated by the round features.
- the final substrate was a piece of Avery Dennison LS10P tape having an outlet aperture. In this 17-layer microfluidic device, fluid enters and exits from the same direction.
- Figures 12B and 12C are photomicrographs of the device with colored acetonitrile passing therethrough at two stages of operation.
- An alternative device was constructed using five of the same modules, but by altering their layering order and orientation to be (1 ,2,3,4,4,4,4,7,1), as shown in Figure 13A.
- Figures 13B and 13C are photomicrographs of the device with colored water passing therethrough at two stages of operation.
- a microfluidic device comprising a filter chamber was constructed.
- a stencil was prepared by cutting a channel out of a 1 mil thick vinyl sheet having adhesive on one side. This stencil was placed on a 1/16" acrylic sheet having an inlet aperture aligned with either end of the filter.
- a silica gel slurry was made by mixing 10 parts of 50 mM NaCI (aq) with 1 part silica gel having a 40 ⁇ m average particle diameter (JT Baker Chemical Co., Phillipsburg NJ). The filter chamber was filled with the slurry by screening it in place.
- a similarly-shaped stencil was prepared by cutting a piece of #444 double-sided tape (3M). The tape stencil was generally aligned with and placed on the vinyl stencil, and an acrylic cover substrate was then placed on the tape stencil. Colored fluid was passed through the device (and the filter chamber) and no leakage was observed.
- a microfluidic device comprising a filter chamber was constructed.
- a stencil was prepared by cutting a channel from a 1 mil thick vinyl sheet having adhesive on one side. This stencil was placed on a 1/16" acrylic sheet having an inlet aperture and an outlet aperture aligned with either end of the filter chamber.
- a sheet of filter paper (Whatman Product # 1070) (Whatman Limited, England) was cut and placed onto the stencil in the filter chamber area. Two outlet apertures were disposed on the opposite side of the filter with a built-in valving mechanism as described above. A 25 ⁇ m pore size Porex filter was used as the valving mechanism. A sample is passed across the filter. The remaining sample and a number of wash cycles are passed through the filter, which then pass into an ante-chamber located beyond the filter chamber.
- FIG. 14 provides three photomicrographs (A-C) of the device at various stages of operation.
- Example 5 A microfluidic device was constructed as follows. A stencil was prepared by cutting a channel from a layer of heat-sealable nylon tape (Product #4220; Bemis Associates, Inc., Shirley, MA), which is 3 mils thick and anneals at 108°C. This stencil was sandwiched between a 2 mil thick Mylar ® substrate and a 1/16" thick polycarbonate substrate having two inlet apertures. An arbor press was fitted with heated aluminum plates. The plates were pre-heated to ⁇ 108°C. The device was placed in the press and compressed, at temperature, for 2-3 seconds to seal the device. Figure 15 is a photomicrograph of the assembled device with fluid passing through it.
- a layer of heat-sealable nylon tape Product #4220; Bemis Associates, Inc., Shirley, MA
- This stencil was sandwiched between a 2 mil thick Mylar ® substrate and a 1/16" thick polycarbonate substrate having two inlet apertures.
- An arbor press was fitted with heated aluminum plates. The plates were pre-
- Example 6 Referring to Figure 7, a microfluidic device designed for biochemical (e.g., protein) purification applications is shown.
- Two apertures 100 and 101 (each 40 mil diameter), representing inlet and outlet apertures, respectively, are drilled in a 1/8" thick polycarbonate substrate 102.
- Stencils are constructed by cutting channels out of a piece of self-adhesive laminating sheet tape (Avery Dennison, LS10P, 73603) using a computer-controlled plotter modified to have a cutting blade (see Figures 12 and 13).
- the filter chamber 104 is then filled with Bio-Gel ® HTP hydroxyapatite (Biorad, Hercules, CA).
- An 80 mil diameter hole 106 is drilled in a 1/8" thick polycarbonate substrate 108, and a sheet of PTFE (25 micron pore size) from Porex Technologies (Fairburn, GA) is used as the bottom substrate 110.
- PTFE 25 micron pore size
- a 100 nl volume of protein solution in 10 mM phosphate buffer is added to the inlet aperture 100.
- the protein binds to the hydroxyapatite filter 104, while the other biomass does not.
- the volume of the chamber 105 and the 80 mil hole 106 is adjusted to accommodate the sample volume (100 nl) plus 4 equivalent washes with buffer (400 nl). Once this amount of fluid has washed the filter 104, 100 nl of higher salt concentration buffer is then injected.
- the molarity of the salt in the elution buffer will differ for different types of proteins; typically, 400 mM phosphate buffer is sufficient.
- This solution elutes the protein off the filter 104.
- the eluent is then collected at the outlet aperture 101.
- the bottom substrate 110 acts as a passive capillary valve by pumping the eluent through the outlet aperture 101 by capillary forces.
- Example 7 A three-dimensional microfluidic device was constructed comprising channels formed using both circuit board substrates and adhesive tape stencils.
- FIG 16A which shows at left an exploded perspective view of the individual components of the device, channels 150 and 151 were formed on a circuit board substrate 160 and coated with a silicone sealant coat.
- Inlet aperture 200 and outlet aperture 201 were formed in the circuit board substrate within channels 150 and 151 , respectively.
- An acrylic cover plate substrate 202 having two apertures 204 and 205, was attached to the top of the coated circuit board channels 150 and 151.
- a roughly horseshoe-shaped channel 206 was constructed in a stencil 208 cut from #444 double sided tape (3M), and the stencil was aligned and adhered to the acrylic substrate 202.
- FIG. 16A is a photomicrograph of a device according to Figure 16A with fluid passing therethrough.
- a device such as this can be used to perform electrophoretic or electrokinetic separation. Electrodes can be provided, for example, at the inlet and outlet apertures to apply the appropriate voltages. Since the optically transparent tape stencil layer 208 extends further than the optically opaque circuit board, analysis of the fluid contained in stencil channel 206 is possible using a variety of optical techniques.
- Example 8 A sample-splitting microfluidic device comprising forked channels was constructed.
- a stencil as shown in Figure 8B was constructed by cutting the outlined area out of a one-sided self-adhesive laminating sheet tape (Avery Dennison, LS10P, 73603) using a computer- controlled plotter modified to have a cutting blade.
- the channels of the device are 25 mils wide.
- the stencil was placed adhesive side down onto a 1/16" thick acrylic substrate having a 33 mil aperture aligned with the inlet aperture of the splitting device (see top of Figure 8).
- FIGS. 17A and 17B are photomicrographs showing water flowing through such a splitting device, at two stages of operation.
- Example 9 A microfluidic device capable of filtering a sample with a built-in valve was constructed. Stencils were constructed by cutting channels out of a self-adhesive laminating sheet tape
- the final device was constructed by placing the silicone replicate onto a 1/16" thick acrylic substrate having apertures drilled at the positions of the silicone wells.
- the tape stencil 252 was mounted to the opposite side of the acrylic substrate, adhesive side down.
- Inlet and outlet apertures were drilled in another acrylic block and a piece of double-sided tape, and were mounted to the opposite ends of the tape stencil.
- Fluid was injected through the device, and no leakage was observed.
- Figure 19C is a photomicrograph of the fluid passing through the silicone replicate. This method of mold creation is very advantageous, since hundreds of molds can be created on a single sheet of vinyl in a few minutes.
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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JP2001528097A JP2003527972A (en) | 1999-10-04 | 2000-10-04 | Modular microfluidic device containing sandwiched stencils |
AU78547/00A AU7854700A (en) | 1999-10-04 | 2000-10-04 | Modular microfluidic devices comprising sandwiched stencils |
EP00968672A EP1222141A1 (en) | 1999-10-04 | 2000-10-04 | Modular microfluidic devices comprising sandwiched stencils |
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PCT/US2000/027366 WO2001025138A1 (en) | 1999-10-04 | 2000-10-04 | Modular microfluidic devices comprising sandwiched stencils |
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JP (1) | JP2003527972A (en) |
AU (1) | AU7854700A (en) |
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-
2000
- 2000-10-04 EP EP00968672A patent/EP1222141A1/en not_active Withdrawn
- 2000-10-04 WO PCT/US2000/027366 patent/WO2001025138A1/en not_active Application Discontinuation
- 2000-10-04 JP JP2001528097A patent/JP2003527972A/en active Pending
- 2000-10-04 AU AU78547/00A patent/AU7854700A/en not_active Abandoned
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WO2001025138A1 (en) | 2001-04-12 |
AU7854700A (en) | 2001-05-10 |
EP1222141A1 (en) | 2002-07-17 |
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