US20040178523A1 - Molded waveguides - Google Patents
Molded waveguides Download PDFInfo
- Publication number
- US20040178523A1 US20040178523A1 US10/677,103 US67710303A US2004178523A1 US 20040178523 A1 US20040178523 A1 US 20040178523A1 US 67710303 A US67710303 A US 67710303A US 2004178523 A1 US2004178523 A1 US 2004178523A1
- Authority
- US
- United States
- Prior art keywords
- waveguide
- substrate surface
- cladding
- waveguides
- fluid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00206—Processes for functionalising a surface, e.g. provide the surface with specific mechanical, chemical or biological properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6957—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a device or a kit, e.g. stents or microdevices
-
- 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
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C31/00—Handling, e.g. feeding of the material to be shaped, storage of plastics material before moulding; Automation, i.e. automated handling lines in plastics processing plants, e.g. using manipulators or robots
- B29C31/04—Feeding of the material to be moulded, e.g. into a mould cavity
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C37/00—Component parts, details, accessories or auxiliary operations, not covered by group B29C33/00 or B29C35/00
- B29C37/0053—Moulding articles characterised by the shape of the surface, e.g. ribs, high polish
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C39/00—Shaping by casting, i.e. introducing the moulding material into a mould or between confining surfaces without significant moulding pressure; Apparatus therefor
- B29C39/22—Component parts, details or accessories; Auxiliary operations
- B29C39/24—Feeding the material into the mould
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
- B29C43/02—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of definite length, i.e. discrete articles
- B29C43/021—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of definite length, i.e. discrete articles characterised by the shape of the surface
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C67/00—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00
- B29C67/24—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00 characterised by the choice of material
- B29C67/246—Moulding high reactive monomers or prepolymers, e.g. by reaction injection moulding [RIM], liquid injection moulding [LIM]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29D—PRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
- B29D11/00—Producing optical elements, e.g. lenses or prisms
- B29D11/00009—Production of simple or compound lenses
- B29D11/00317—Production of lenses with markings or patterns
- B29D11/00346—Production of lenses with markings or patterns having nanosize structures or features, e.g. fillers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29D—PRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
- B29D11/00—Producing optical elements, e.g. lenses or prisms
- B29D11/00663—Production of light guides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
- B81C1/00031—Regular or irregular arrays of nanoscale structures, e.g. etch mask layer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C99/00—Subject matter not provided for in other groups of this subclass
- B81C99/0075—Manufacture of substrate-free structures
- B81C99/0085—Manufacture of substrate-free structures using moulds and master templates, e.g. for hot-embossing
-
- 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
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/10—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type
- G02B6/12—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
- G02B6/13—Integrated optical circuits characterised by the manufacturing method
- G02B6/138—Integrated optical circuits characterised by the manufacturing method by using polymerisation
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00382—Stamping
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00414—Means for dispensing and evacuation of reagents using suction
- B01J2219/00416—Vacuum
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00427—Means for dispensing and evacuation of reagents using masks
- B01J2219/0043—Means for dispensing and evacuation of reagents using masks for direct application of reagents, e.g. through openings in a shutter
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00457—Dispensing or evacuation of the solid phase support
- B01J2219/00459—Beads
- B01J2219/00466—Beads in a slurry
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/0061—The surface being organic
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00614—Delimitation of the attachment areas
- B01J2219/00617—Delimitation of the attachment areas by chemical means
- B01J2219/00619—Delimitation of the attachment areas by chemical means using hydrophilic or hydrophobic regions
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/00626—Covalent
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/0063—Other, e.g. van der Waals forces, hydrogen bonding
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00632—Introduction of reactive groups to the surface
- B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00646—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
- B01J2219/00648—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of solid beads
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- 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
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00709—Type of synthesis
- B01J2219/00713—Electrochemical synthesis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C33/00—Moulds or cores; Details thereof or accessories therefor
- B29C33/42—Moulds or cores; Details thereof or accessories therefor characterised by the shape of the moulding surface, e.g. ribs or grooves
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
- B29K2105/0002—Condition, form or state of moulded material or of the material to be shaped monomers or prepolymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
- B29L2011/00—Optical elements, e.g. lenses, prisms
- B29L2011/0016—Lenses
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2201/00—Specific applications of microelectromechanical systems
- B81B2201/02—Sensors
- B81B2201/0214—Biosensors; Chemical sensors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C2201/00—Manufacture or treatment of microstructural devices or systems
- B81C2201/03—Processes for manufacturing substrate-free structures
- B81C2201/034—Moulding
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- 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
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7776—Index
-
- 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
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05K—PRINTED CIRCUITS; CASINGS OR CONSTRUCTIONAL DETAILS OF ELECTRIC APPARATUS; MANUFACTURE OF ASSEMBLAGES OF ELECTRICAL COMPONENTS
- H05K3/00—Apparatus or processes for manufacturing printed circuits
- H05K3/0073—Masks not provided for in groups H05K3/02 - H05K3/46, e.g. for photomechanical production of patterned surfaces
- H05K3/0079—Masks not provided for in groups H05K3/02 - H05K3/46, e.g. for photomechanical production of patterned surfaces characterised by the method of application or removal of the mask
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05K—PRINTED CIRCUITS; CASINGS OR CONSTRUCTIONAL DETAILS OF ELECTRIC APPARATUS; MANUFACTURE OF ASSEMBLAGES OF ELECTRICAL COMPONENTS
- H05K3/00—Apparatus or processes for manufacturing printed circuits
- H05K3/02—Apparatus or processes for manufacturing printed circuits in which the conductive material is applied to the surface of the insulating support and is thereafter removed from such areas of the surface which are not intended for current conducting or shielding
- H05K3/06—Apparatus or processes for manufacturing printed circuits in which the conductive material is applied to the surface of the insulating support and is thereafter removed from such areas of the surface which are not intended for current conducting or shielding the conductive material being removed chemically or electrolytically, e.g. by photo-etch process
- H05K3/061—Etching masks
Definitions
- the present invention relates generally to microprocesses at surfaces, and more particularly to the formation of micropatterned articles such as waveguides, sensors, and switches on substrates from fluid precursors, and mechanisms for micro-scale positioning of biologically active agents at predetermined regions of a surface.
- a well-known method of production of devices, especially in the area of microelectronics, is photolithography.
- a negative or positive resist photoresist
- the resist then is irradiated in a predetermined pattern, and portions of the resist that are irradiated (positive resist) or nonirradiated (negative resist) are removed from the surface to produce a predetermined pattern of resist on the surface.
- the resist may serve as a mask in an etching process in which areas of the material not covered by the resist are chemically removed, followed by removal of resist to expose a predetermined pattern of a conducting, insulating, or semiconducting material.
- the patterned surface is exposed to a plating medium or to metal deposition (for example under vacuum) followed by removal of resist, resulting in a predetermined plated pattern on the surface of the material.
- a plating medium or to metal deposition for example under vacuum
- resist for example under vacuum
- x-ray and electron-beam lithography have found analogous use.
- Photolithographic techniques for fabricating surfaces with positional control of chemical functionalities at submicron resolution is described in an article entitled “Patterning of Self-Assembled Films Using Lithographic Exposure Tools”, by Dressick, et al., Jpn. J. Appl. Phys ., 32, 5829-5839 (December, 1993).
- the technique involves exposure of a self-assembled film to deep UV irradiation through a mask.
- photochemical cleavage of an organic group occurs in exposed regions followed by chemical reactivity selectively at those regions.
- Photolithography has found application in the biological arena as well.
- Sundberg, et al. describe a method for patterning receptors, antibodies, and other macromolecules at precise locations on solid substrates using photolithographic techniques in combination with avidin or streptavidin/biotin interaction in an article entitled “Spatially-Addressable Immobilization of Macromolecules on Solid Supports”, J. Am. Chem. Soc ., 117, 12050-12057 (1995).
- Reactive ion etching is a process that is useful in the semiconductor industry and other arenas for forming very small structures having a very high aspect ratio (a very high height/width ratio of features).
- Reactive ion etching is a dry process in which a gas is accelerated towards a surface to effect etching, in contrast to wet etching processes in which a liquid is simply allowed to contact certain regions of a surface and to chemically react at those regions.
- wet etching processes etching typically takes place not only in a direction perpendicular to the surface, but horizontally, as well. That is, with wet etching it can be difficult to etch relatively precise, vertical channels in a surface. Instead, the sidewalls of the channel are etched horizontally also.
- Reactive ion etching provides an advantageous alternative for etching channels with good, near-vertical sidewalls.
- Reactive ion etching masks should have certain characteristics such as good hardness, inertness to the etchent species, and in many cases electrical insulating properties. Thus, materials suitable for reactive ion etching masks are limited. Many metal masks, such as gold masks, are unsuitable since the metals can sputter easily. Polymeric masks typically degrade under reactive ion etching conditions.
- a typical prior art reactive ion etching mask is made of silica and is formed by creating a layer of silica on a surface and etching the layer selectively to create a silica mask, using photolithography. Such procedures can be costly.
- Waveguides are generally defined by a core, surrounded by a cladding, that acts as a guide of electromagnetic radiation.
- the waveguide can propagate radiation via total internal reflection of the radiation within the core.
- Waveguides have served as important components of sensors and switches, and have been fabricated from a variety of materials including inorganic materials such as glasses and organic materials such as polymers.
- Polymeric waveguides have been fabricated using reactive ion etching, ultraviolet (UV) laser and electron-beam writing, induced dopant diffusion during polymerization (photo-locking and selective polymerization), selective poling of electro-optically active molecules induced by an electric field, and polymerization of self-assembled prepolymers.
- UV ultraviolet
- One common technique for forming polymeric waveguides is injection molding.
- voids in a cladding material can be filled, via injection molding, with a core material.
- problems associated with this technique include softening and deformation of the cladding or substrate under temperatures required for injection molding. Fabrication with precision is compromised, typically.
- a polymeric film is spun onto a substrate and portions of the film are subsequently exposed to light by a photolithographic process, thereby changing the refractive index of a polymeric film and creating a waveguide in the film.
- This technique requires expensive and complicated photolithographic systems for base formation of the waveguide array, and subsequent multi-step processing is required such as removal of the polymeric film from the substrate, lamination processing, curing processing, and other processing steps.
- U.S. Pat. No. 5,136,678 describe fabrication of an optical waveguide array by providing a clad substrate having a number of grooves arranged in lines on a surface of the substrate, the substrate being resistant to a UV-curable resin.
- a UV-curable resin is used to fill the grooves in the substrate and is UV cured to form a core material, and a covering clad portion is formed over the structure of a material that is the same as or close to the material used as the substrate “cladding”.
- U.S. Pat. No. 5,313,545 (Kuo, et al.) describes a technique in which a two-part mold made of stainless steel, aluminum, ceramic, or the like is used to mold a polymeric waveguide core material via injection molding. The mold is opened via removal of the two portions, and the waveguide is placed in a second mold into which is injected a cladding material. Kuo, et al. report that a post-mold curing process is sometimes needed to maximize optical and physical qualities of core regions, support apparatus, and end portions.
- U.S. Pat. No. 5,390,275 (Lebby, et al.) describe a method for manufacturing a molded waveguide.
- a first cladding layer is provided, and channels are formed in the first cladding layer.
- the channels in the first cladding layer are filled with an optically transparent polymer, and a second cladding layer is subsequently affixed over the channels thereby enclosing them.
- U.S. Pat. No. 5,481,633 (Mayer) describes vertical coupling structures in which waveguide patterns include sections that lie in close proximity with other sections, for example one directly above another, such that the distance between coupling portions is very small and coupling between different guides can occur.
- a surface is derivatized with amine linkers that are blocked by a photochemically cleavable protecting group.
- the surface is selectively irradiated to liberate free amines that can be coupled to photochemically blocked building blocks.
- the process is repeated with different regions of the surface being exposed to light and involved in synthesis until a desired array of different compounds, in a grid pattern on the surface, is prepared. Each of these compounds then is assayed simultaneously for binding or activity. Binding “hits” can be identified by the particular location at which binding on the surface occurs.
- the present invention provides techniques for derivatizing surfaces, biologically, chemically, or physically, according to predetermined patterns.
- the derivatized surfaces find a variety of uses in a variety of technical areas, or a structure formed on the surface can be removed from the surface and find utility separate from the surface.
- the invention involves, according to one technique, a method for creating a pattern of a species at a defined region proximate a substrate surface.
- the method involves providing an article having a contoured surface including at least one indentation defining a pattern and forming at a first region proximate the substrate surface, in a pattern corresponding to the indentation pattern, a fluid precursor of the species.
- the fluid precursor is allowed to harden at the first region of the substrate surface in a pattern corresponding to the indentation pattern and in an area including a portion having a lateral dimension of less than about 1 mm.
- a second region proximate the substrate surface, contiguous with the first region, remains free of the species.
- the invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface.
- the method involves positioning an article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a chemically active agent. A chemical reaction involving the chemically active agent then is allowed to take place at the first region proximate the substrate surface.
- the invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface that involves providing an article having a contoured surface including at least one indentation defining a pattern, forming at a first region proximate the substrate surface, in a pattern corresponding to the indentation pattern, a chemically active agent, and allowing a chemical reaction to take place proximate the first region of the substrate surface.
- the chemical reaction takes place in a pattern corresponding to the indentation pattern and in an area including a portion having a lateral dimension of less than about 1 mm.
- a second region proximate the substrate surface, contiguous with the first region remains free of the reaction.
- the invention also provides a method of applying a biochemically active agent to a region proximate a substrate surface.
- An article having a contoured surface, as described above, is used to form, at a first region proximate the substrate surface and in a pattern corresponding to the indentation pattern, a pattern of the biochemically active agent.
- the method can further involve allowing a biochemical interaction involving the biochemically active agent to take place proximate the first region of the substrate surface in a pattern corresponding to the indentation pattern.
- the first region can be defined by an area having a lateral dimension of less than about 1 mm, and a second region proximate the substrate surface, contiguous with the first region, can be left free of the biochemical interaction.
- the biochemically active agent can be a biological binding partner that can be used in subsequent binding with other agents.
- the invention also provides a method of creating a pattern of a species proximate a substrate surface that includes positioning a forming article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a fluid precursor of the species. The fluid precursor is allowed to harden and the forming article is removed from the substrate surface.
- the invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface.
- the method involves transferring a chemically active agent from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface in a pattern corresponding to the indentation pattern.
- a second region proximate the surface, contiguous with the first region, is allowed to remain free of the chemically active agent.
- a chemical reaction involving the chemically active agent can take place at the first region.
- the invention also provides a method of promoting a biochemical interaction at a defined region proximate a substrate surface that involves transferring a biochemically active agent from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface in a pattern corresponding to the application pattern.
- a second region proximate the surface, contiguous with the first region, can remain free of the biochemically active agent.
- a biochemical interaction involving the biochemically active agent can be allowed to take place at the first region.
- the invention also provides a method of applying to a substrate surface a biochemically active agent that involves positioning an article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a biochemically active agent. A biochemical interaction involving the biochemically active agent is allowed to take place at the first region.
- the invention also provides a method for applying essentially instantaneously to a first and a second region proximate a substrate surface separated from each other by an intervening region, distinct first and second chemically active agents, respectively.
- the intervening region is left essentially free of the chemically active agent.
- the method can involve allowing a chemical reaction involving at least one chemically active agent to subsequently take place proximate the first or second region.
- the method also can involve applying essentially instantaneously to the first and second regions distinct first and second biochemically active agents while leaving the intervening region free of the biochemically active agent.
- the invention also provides a method involving applying essentially instantaneously to a first and a second region proximate a substrate surface distinct first and second biochemically active agents, respectively.
- the first and second regions are separated from each other by an intervening region that remains free of biochemically active agent.
- the method can be carried out as well with first and second biochemically active agents that are the same.
- the invention also provides a method involving applying a first reactant to a first region proximate a surface and allowing a first reaction to take place at the first region.
- a second reactant then is applied to a second region proximate the surface that is different from the first region but that includes a portion intersecting the first region.
- the first region is blocked except at the intersecting region during this step, thereby preventing the first reactant from contacting the first region except at the intersecting portion.
- a second reaction is allowed to take place at the second region, thereby creating a first chemical characteristic at the first region except at the intersecting portion, a second chemical characteristic at the second region except at the intersecting portion, and a third chemical characteristic at the intersecting portion.
- the invention also provides a method of establishing a first chemical functionality at a first region proximate a substrate surface and a different chemical functionality at a second region proximate the substrate surface contiguous with the first region.
- the method involves applying to the first region proximate the substrate surface a deprotecting species to chemically deprotect the first region of the substrate surface and thereby render it chemically reactive, while leaving the second region free of deprotection.
- the technique can involve transferring to the second region of the substrate surface a chemical protecting species.
- the method further involves exposing the substrate surface to a chemically or biochemically reactive species that reacts at the first region proximate the substrate surface and does not react at the second region.
- the technique can be used to create a combinatorial library via a series of deprotecting/reacting, re-protecting steps or protecting/reacting/deprotecting steps. Transfer of protecting or deprotecting species to the surface can take place essentially instantaneously.
- the invention also provides a method of creating, on a substrate surface, a patterned, self-assembled monolayer, involving transferring a self-assembled monolayer-forming species from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate the substrate surface.
- a self-assembled monolayer proximate the first region is thereby formed corresponding to the indentation pattern.
- a second region proximate the surface, contiguous with the first region, remains free of the self-assembled monolayer.
- the invention also provides a method involving providing a surface carrying a plurality of chelating agents distributed evenly thereacross and applying to two discrete regions of the surface a metal ion that is coordinated by the chelating agent, while leaving a region intervening the two discrete regions free of the metal ion, thereby creating two discrete regions carrying chelating agents coordinating metal ions.
- the invention also provides a method involving providing a surface carrying an essentially even distribution thereacross of chelating agents coordinating metal ions, and applying to two discrete regions at the surface a biologically active agent, while leaving a region intervening the two discrete regions free of the biologically active agent.
- the invention also provides an article defined by a substrate having a surface and a self-assembled monolayer on the surface.
- the monolayer is formed of at least a first species having a formula X—R—Ch—M, wherein X represents a functional group and R represents a spacer moiety that, together, are able to promote formation at the surface of a self-assembled monolayer.
- Ch represents a chelating agent that coordinates a metal ion.
- M represents a metal ion coordinated to the chelating agent.
- the article further includes a pattern of biological agent coordinated to metal ion at a first region proximate the surface. A second region proximate the surface, contiguous with the first region, remains free of biological agent coordinated to metal ion.
- the invention also provides a method of creating a patterned, self-assembled monolayer on a substrate surface.
- the method involves transferring a self-assembled monolayer-forming species from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface.
- a self-assembled monolayer is thereby formed proximate the first region of the substrate surface corresponding to the indentation pattern.
- a second region proximate the surface, contiguous with the first region, is left free of self-assembled monolayer.
- the self-assembled monolayer can be transferred essentially instantaneously to the first region proximate the substrate surface in this manner.
- the invention also provides a method for providing a surface carrying a plurality of chelating agents distributed evenly thereacross and applying to two discrete regions at the surface a metal ion that is coordinated by the chelating agent. A region intervening the two discrete regions is left free of metal ion.
- the invention also provides a method involving providing a surface that carries, essentially evenly distributed thereacross, chelating agents coordinating metal ions.
- a biochemically active agent is applied to two discrete regions at the surface and a region intervening the two discrete regions remains free of the biochemically active agent.
- the invention also provides an article including a surface and a pathway proximate the surface delineating a pattern at a first region proximate the surface.
- the pattern includes at least one region defining a continuous essentially linear portion of product formed proximate the surface.
- the product is formed in this manner via reaction involving a chemically active agent promoting the reaction that had been transferred proximate the surface from an applicator.
- the linear portion of the product has a dimension parallel to the surface of less than about one millimeter.
- the invention also provides an article as described above, where the pattern is defined by a plurality of microbeads assembled at the surface. Any patterns formed in this manner can have at least one section having a dimension parallel to the surface of less than about one millimeter.
- the fluid precursors, chemically active agents, biochemically active agents, and carriers can be any of a variety of species including prepolymeric species, biological binding partners, inorganic salts, ceramics, metals, catalysts, colloidal activating agents, and the like.
- a variety of combinations of the above-described inventive methods can be carried out, for example formation of a pattern can be carried out via capillary action, instantaneous transfer can take place to form a pattern on a surface having a lateral dimension of less than about 1 mm, and the like.
- Articles formed by the methods above, or by any combination of these methods, and articles formed by other methods are included. The methods can be carried out on essentially planar or non-planar surfaces.
- FIG. 1 illustrates schematically an arrangement for derivatizing a surface in a predetermined pattern according to one embodiment of the invention
- FIG. 2 is a schematic illustration of a technique for transferring a chemically or biochemically active agent or fluid precursor of an article from essentially linear indentations of an applicator defining an indentation pattern to a substrate surface in a pattern corresponding to the indentation pattern;
- FIGS. 3 a - 3 d are photocopies of scanning electron micrographs (SEMs) of patterned polymeric structures formed from hardenable fluid precursors in which the patterned structures remain at the surface (FIGS. 3 a - c ) or are removed from the surface to form a free-standing structure (FIG. 3 d );
- FIGS. 4 a - 4 h are photocopies of SEM images of inorganic and organic microstructures patterned on surfaces in accordance with the invention.
- FIG. 5 is a photocopy of an electron micrograph of microspheres assembled in a predetermined pattern proximate a substrate surface from a fluid precursor in accordance with the invention
- FIGS. 6 a - 6 c are photocopies of SEM images of metallic microstructures formed proximate predetermined regions of a substrate surface in accordance with the invention.
- FIGS. 7 a - 7 c are photocopies of SEM images of a substrate surface derivatized in a pattern with resist followed by lithography to etch the substrate surface in a pattern complementary to the resist pattern;
- FIG. 8 illustrates schematically the formation of a free-standing article from a fluid precursor, using a substrate surface and a forming article including a pattern of indentations in accordance with the invention
- FIGS. 9 a - 9 d are photocopies of SEM images of a free-standing article prepared in accordance with the technique schematically illustrated in FIG. 8 and use of that article as a mask adjacent a substrate surface in vapor deposition of metal (FIG. 9 b ) or creation of a secondary resist formed by a self-assembled monolayer deposited in a pattern complementary to that of the mask, followed by removal of the mask and vapor deposition of metal in a pattern complementary to the secondary resist pattern (FIGS. 9 c - d );
- FIGS. 10 a - 10 c illustrate schematically (FIG. 10 a ), and via photoreproduction of optical micrographs (FIGS. 10 b, c ), a process involving derivatizing a surface with resist via micromolding, a mask so produced, and a substrate surface etched selectively at regions not covered by the mask;
- FIG. 11 illustrates schematically a technique for transfer of a chemically or biochemically active agent or a fluid precursor of an article from an applicator having a discontinuous indentation pattern to regions proximate a substrate surface in a pattern corresponding to the indentation pattern;
- FIG. 12 illustrates schematically the transfer, from an article including an indentation pattern, of a chemically or biochemically active agent or other fluid species to a nonplanar substrate surface in a pattern corresponding to the indentation pattern;
- FIG. 13 illustrates schematically a multi-layered article formed using successive micromolding techniques of the invention that can serve as a waveguide, and is a cross-section through line a-a of FIG. 15;
- FIGS. 14 a - 14 k illustrate schematically the creation of a combinatorial library in accordance with the invention
- FIG. 15 illustrates schematically several techniques of the invention for forming a waveguide array or other structure, from a fluid precursor, on a substrate surface followed by formation of a cladding layer over the waveguide array;
- FIG. 16 illustrates a technique for forming a multi-layer waveguide structure
- FIG. 17 is a schematic illustration of one type of prior art waveguide coupler
- FIG. 18 is a schematic illustration of another type of prior art waveguide coupler, namely an evanescent coupler
- FIG. 19 is a schematic illustration of a coupling region, switch, or sensor using a waveguide array of the present invention.
- FIG. 20 illustrates formation of an interference pattern via coupling among a five-waveguide array in accordance with the invention
- FIG. 21 is a photocopy of a scanning electron micrograph (SEM) image of an unclad array fabricated in accordance with the invention.
- FIG. 22 is a photocopy of an SEM image of a clad array fabricated in accordance with the invention.
- FIG. 23 is a schematic illustration of an optical system used to couple light into waveguide arrays of the invention and to determine interference patterns formed via coupling among the waveguides of the arrays;
- FIGS. 24 a - 24 g show a variety of waveguide arrays and interference patterns of light emerging from various waveguide arrays and created via coupling between waveguides of the arrays;
- FIG. 25 illustrates schematically another technique of the invention for forming a structure from a precursor, on a substrate surface
- FIG. 26 is a photocopy of a SEM image of an aluminosilicate structure that can serve as a waveguide;
- FIG. 27 is a photocopy of a SEM image of a borosilicate structure that can serve as a waveguide.
- FIG. 28 is a photocopy of a SEM image of the structure of FIG. 27 at a different stage of annealing.
- the present invention provides, in one aspect, techniques for placement, at regions proximate a substrate surface, of chemically or biochemically active agents, fluid precursors of articles such as waveguides to be immobilized proximate a substrate surface, and/or other species desirably transferred to a region or regions proximate a substrate surface in a pattern.
- Fluid precursor as used herein, means a material that is fluid enough that it can be formed into a pattern using a forming article, using techniques described herein.
- the invention utilizes an applicator having a pattern of indentations that can be used to transfer such a species from the indentations to a region proximate the substrate surface or that can serve as a mold that when, positioned proximate a substrate surface, can define a region in which such a species is positioned.
- the applicator is used to transfer a fluid precursor from the indentations to a region proximate a substrate surface where the precursor is hardened to the point it is self-supporting and the applicator can be removed. “Self-supporting, in this context, means that the precursor does not lose its form unacceptably upon removal of the forming article and can retain its form during a further hardening procedure.
- the applicator can be used to transfer a fluid precursor to a substrate surface and the applicator can be removed prior to hardening the fluid, but maintaining the fluid within channels defined between indentations in the contoured applicator surface and the substrate surface until the fluid is hardened is preferred, since the ultimate shape of features of the pattern on the substrate is thereby better-controlled.
- FIG. 1 illustrates schematically a technique for derivatizing a substrate surface according to a pattern of, for example, a polymeric article, a pattern of microbeads optionally carrying a chemical or biochemically active species, a catalyst or other activating agent for promoting a chemical reaction such as metal plating at the surface, a fluid carrying a dissolved or suspended species to be deposited or precipitated, or the like.
- a pattern of, for example, a polymeric article optionally carrying a chemical or biochemically active species, a catalyst or other activating agent for promoting a chemical reaction such as metal plating at the surface, a fluid carrying a dissolved or suspended species to be deposited or precipitated, or the like.
- a hardenable prepolymeric fluid that is hardened at the surface to form a patterned polymeric article.
- An article 20 includes an application surface 22 having formed therein a plurality of indentations 24 that together define a linear, patterned array of indentations 24 that are contiguous with a contact surface 26 .
- Article 20 is an applicator used to transfer a species, in a pattern, to a region or regions proximate the substrate surface, or a forming article or micromold placed proximate a substrate surface and used to guide a fluid species so as to position the species in a pattern at a predetermined region or regions proximate the substrate surface.
- proximate is meant to define at a substrate surface, that is, in contact with a substrate surface, or at a position near a substrate surface and fixed relative to the substrate surface.
- a substrate surface carries an adhesion promoter, for example a self-assembled monolayer
- activity at the surface of the self-assembled monolayer is intended to mean activity proximate the substrate surface.
- Fluid precursor 36 can be urged to flow via, for example, pressure applied to the fluid as it is positioned so as to enter the channels, or vacuum created within the channels by, for example, connection of the outlets of the channels to a source of vacuum.
- the fluid can be allowed to flow into the mold via capillary action.
- Capillary filling of the mold is especially useful when the mold is of very small dimension (in particular in the micro scale) and is defined herein to mean that when a fluid precursor is positioned adjacent an opening or channel 32 formed by a portion 34 of the substrate surface and an indentation 24 of article 20 , the fluid precursor will flow into at least a portion of the channel spontaneously.
- the fluid precursor can be hardened before or after removal of applicator 20 from substrate surface 28 (or where the fluid is a carrier of a species to be deposited or precipitated, the fluid can dissipate, i.e., evaporate, be absorbed into applicator 20 , or the like). Where the fluid is viscous enough, or is allowed to reach a particular level of viscosity, the applicator can be removed and the precursor hardened at the surface without unacceptable loss of dimensional integrity.
- the fluid precursor is hardened to the extent that it is self-supporting (dimensionally-stable) prior to removal of Article 20 from the substrate surface.
- the fluid precursor is a solution of monomer in a fluid carrier and is polymerized at the surface with article 20 in place. Article 20 then is removed. A structural article 38 , in a pattern corresponding to the indentation or mold pattern 24 of article 20 , results on substrate surface 28 from the described procedure. According to the description of the process illustrated in FIG. 1, structure 38 is a polymeric structure formed from a fluid prepolymeric precursor.
- the structure 38 formed according to this embodiment is a polymeric structure
- it can be thermally polymerized on substrate surface 28 via application of heat to the substrate and/or article 20 or, if article 20 is removed prior to polymerization, via convective or radiative heat; photopolymerized if substrate 30 and/or article 20 are transparent to radiation, or subsequent to removal of article 20 .
- Free-radical polymerization can be carried out as well.
- All types of polymerization including cationic, anionic, copolymerization, chain copolymerization, cross-linking, and the like can be employed, and essentially any type of polymer or copolymer formable from a fluid precursor can be patterned on surface 28 in accordance with the invention.
- polymers that are suitable include polyurethane, polyamides, polycarbonates, polyacetylenes and polydiacetylenes, polyphosphazenes, polysiloxanes, polyolefins, polyesters, polyethers, poly(ether ketones), poly(alkylene oxides), poly(ethylene terephthalate), poly(methyl methacrylate), polystyrene, and derivatives and block, random, radial, linear, or teleblock copolymers, cross-linkable materials such as proteinaceous material and/or blends of the above. Gels are suitable where dimensionally stable enough to maintain structural integrity upon removal of article 20 from substrate surface 28 .
- Monomers can be used alone, or mixtures of different monomers can be used to form homopolymers and copolymers.
- Non-linear and ferroelectric polymers can be advantageous. Gels are suitable where dimensionally stable enough to maintain structural integrity upon removal of article 20 from substrate surface 28 .
- the particular polymer, copolymer, blend, or gel selected is not critical to the invention, and those of skill in the art can tailor a particular material for any of a wide variety of applications.
- the particular polymer, copolymer, blend, or gel selected is not critical to the invention, and those of skill in the art can tailor a particular material for any of a wide variety of applications.
- a polymerizable or cross-linkable species including an admixed biochemically active agent such as a protein can be made to form a pattern on substrate surface 28 according to the described technique.
- carboxylated DextranTM can carry admixed protein, be introduced into channels 34 , and hardened to form articles 38 .
- the article can be exposed to a medium suspected of containing a biological binding partner of the biochemical agent, and any biochemical binding or other interaction detected via, for example, diffraction, or via a change in coupling between waveguide cores as described more fully below.
- the degree of diffraction can be affected by biological binding between the biological agent compounded within article 38 and an analyte that is a biological binding partner of the compounded agent. Determination of a change in diffraction at surface 28 is indicative of the presence of analyte in the medium brought into contact with article 38 .
- a species such as polymerizable or cross-linkable species can entirely coat surface 28
- article 20 can be placed adjacent surface 28
- a biological agent can be introduced into channels 34 and allowed to admix with the polymerizable or cross-linkable species, and prior to or subsequent to removal of article 20 species on surface 28 can be polymerized or cross-linked. In this manner, a surface having a pattern of biological agent compounded therein is produced, and can serve as a sensor for a biological binding partner of the biological agent via change in refraction or diffraction of light at the surface.
- an electrically-conductive polymer can be selected, and this can have significant application in the microelectronics industry, as would be recognized by one of ordinary skill in the art.
- the invention is intended to encompass creation of a wide variety of structures or patterns of species on substrate surfaces from fluid precursors.
- the precursor can be any fluid that can flow into the mold defined by indentations 24 and portions 34 of substrate surface 28 , and those of ordinary skill in the art can determine, without undue experimentation, which fluids will readily flow into such a mold based upon dimension of the mold and viscosity of the fluid.
- the viscosity of the fluid can be adjusted, by for example diluting or concentrating the fluid, to achieve a level of viscosity suitable for flow into the mold at a desired rate.
- the polarity of the fluid can be tailored as well, with reference to the chemical characteristic of the substrate surface or micromold, to facilitate fluid carrier flow.
- patterned article 38 is not a polymer or cross-linked organic species as described above, but is a non-polymerized organic species that is dissolved or dispersed in a fluid carrier to form fluid precursor 36 which is introduced into mold channels 32 , whereupon the fluid carrier or solvent dissipates (e.g., is removed via evaporation from the mold channels and/or absorption into the substrate or applicator 20 ).
- patterned structure 38 is an inorganic structure, such as a salt or ceramic.
- a salt soluble in a fluid precursor can be prepared as a solution 36 defining a fluid precursor that is introduced into mold channels 32 and precipitated as a patterned salt structure 38 by removal of solvent via evaporation, adsorption, or other physical or chemical change to the surrounding environment.
- Inorganic salts or ceramics can be carried as a suspension in a fluid carrier, flowed into channels 32 , and precipitated or deposited.
- Metals such as those commonly deposited from pastes in accordance with thick-film silk-screening techniques, can be applied to defined regions of substrate surface 28 where a paste is sufficiently fluid, or the paste and/or metal can be carried in a fluid as a suspension or sol in fluid precursor 36 .
- Fluid precursors of inorganic materials such as solutions from which materials can be precipitated, or suspensions from which a fluid carrier can be removed by dissipation or evaporation, can be used to form structures, such as waveguides, from materials such as TiO 2 , TiO 2 /SiO 2 , ZnO, Nb 2 O 5 , Si 3 N 4 , Ta 2 O 5 , HfO 2 , ZrO 2 , or the like.
- Dye-doped fluid precursors can be used, and are advantageous in many situations.
- Another fluid precursor can be a sol-gel precursor, and sol-gel techniques known to those of skill in the art can be used to create the solid structures in patterns, according to the invention.
- Ferroelectric and electrooptic materials and sol-gel processing of a variety of precursors to form a variety of species is well known to those of ordinary skilled in the art and can be applied and exploited by the method of the invention.
- materials such as PbScTaO 3 , (Pb, La)TiO 3 (PLT), LiNbO 3 , KNbO 3 , LiTaO 3 , potassium diphosphate, potassium triphosphate, PbMoO 4 , TeO 2 , Ta 2 O 5 BaTiO 3 , BBO crystals, Ba 1-x Sr x TiO 3 , Pb(Zr, Ti)O 3 , SrTiO 3 , bismuth strontium tantalate, and the like.
- Other sol-gel precursors appropriate for use are precursors of hybrid materials or organically modified ceramics, such as precursors of silicon oxycarbide or ORMOCERs.
- Other sol-gel precursors appropriate for use are described by Brinker and Scherer, in Sol - Gel Science ; Academic Press, San Diego, 1990; Dislich, Transformation of Organometallics into Common and Exotic Materials ; Nijhof, Dordrecht, 1998, volume 141; Pani, et al., J. Am.
- the present invention involves the fabrication and use of reactive ion etch masks from sol-gel precursors.
- Dielectric materials such as aluminia, zirconia, and silica glasses and mixed glasses such as aluminosilicates can be fabricated simply, conveniently, and relatively inexpensively using the techniques of the invention.
- a sol-gel precursor can be formed into a pattern using any of the molding techniques as described herein, with reference for example to FIGS. 1, 2, 8 , 10 , 15 , 16 , and 25 , and can be carried out directly on a surface that is desirably etched via reactive ion etching.
- an article is provided that is desirably etched via reactive ion etching, and a reactive ion etch mask is formed on a surface of the article via molding according to any of the techniques described herein from a precursor of a reactive ion etch mask.
- the reactive ion etch mask is formed from the precursor using the mold defined in part by the forming article of the invention on a first portion of the article surface, in a pattern, while leaving a second portion of the substrate surface free of the mask material.
- the surface of the article then is exposed to reactive ion etch conditions (known to those of ordinary skill in the art, e.g., 0 2 plasma), and etching takes place at the second portion of the substrate surface.
- the first portion of the substrate surface will be a pattern of separated lines or portions that can be isolated or interconnected, and the second portion will be complementary to the first portion.
- the second portion is “free” of reactive ion etch mask when the second portion contains no reactive ion etch mask material or is covered by so little reactive ion etch mask material that exposure to reactive ion etching conditions causes reactive ion etching at the second portion.
- Formation of dielectric, or ceramic materials in accordance with this aspect of the invention can find use not only in reactive ion etching masks but in integrated optics, non-linear optics and other microelectronic arenas as would be understood by those of ordinary skill in the art.
- a biologically active agent can be dissolved or suspended in a fluid carrier as a fluid precursor 36 and introduced into channels 32 adjacent portions 34 of surface 28 and, prior or subsequent to removal of micromold 20 , allowed to engage in a biochemical interaction proximate regions 34 of substrate surface 28 .
- a biochemical agent can include a biotin linker while substrate surface 28 carries immobilized avidin, and biochemical interaction can be allowed to take place at regions 34 of substrate surface 28 in this manner, linking the biochemical agent to the substrate surface at regions 34 .
- Biochemical agents can be immobilized proximate regions 34 of the substrate surface according to other techniques as well.
- a biological agent such as a protein can be non-covalently immobilized at regions 34 of the substrate surface.
- a hydrophobic chemical moiety can be coupled to the biochemical agent at a region of the agent remote from its active site. In this manner, the agent can be hydrophobically coupled to the surface and maintain exposure, away from the surface, of its biochemically active region.
- One of ordinary skill in the art can conduct a simple test to determine whether a biochemical agent is suitable for use with the described technique.
- the binding constant of a candidate biochemical agent for a target species can be determined using standard ELISA techniques.
- the candidate biochemical agent can be hydrophobically immobilized (or immobilized in any other manner described herein or known to those of ordinary skill in the art, for example via a polyamino acid tag coupled to a metal ion immobilized at the surface by a chelating agent) at a variety of surfaces, and then assays can be performed to determine whether the agent has retained its ability to biologically bind to the target species or has been denatured and is unable to bind (this exemplary test is particularly useful in connection with biological agents that, in their native form only, bind target species, but when denatured do not bind the target species).
- Biochemical recognition can be exploited in immobilization of a particular biochemical agent desirably patterned on substrate surface 28 .
- a first agent can be immobilized (for example using hydrophobic coupling) at regions 38 of the substrate surface, and a second agent (which is a biological binding partner of the first agent) then can be immobilized at regions 34 .
- the second step in which the desired agent is immobilized at regions 34 can be carried out with or without micromold 20 proximate the substrate surface.
- Biochemical recognition involving partners also can be exploited to trap biological agents at regions 34 of the substrate surface using other biological agents that have been immobilized at regions 34 .
- Biochemical recognition involving partners such as antibody/antigen, antibody/hapten, enzyme/substrate, enzyme/inhibitor, enzyme/cofactor, biotin/avidin, binding protein/substrate, carrier protein/substrate, lectin/carbohydrate, receptor/hormone, receptor/effector, complementary strands of nucleic acid, repressor/inducer, and the like can be exploited in connection with the technique.
- Those of ordinary skill will recognize a variety of uses for placement of such biochemically active agents at predetermined portions of a substrate surface in a pattern, for example as discussed below with reference to FIG. 14 and as disclosed in co-pending, commonly-owned U.S. Pat. No. 5,512,131 of Kumar, et al. and International Patent Application Publication No. WO 96/29629, both incorporated herein by reference.
- a fluid carrier of the biologically active agent should be selected so as not to detrimentally affect the biochemical activity of the agent.
- a fluid carrier of the biologically active agent should be selected so as not to detrimentally affect the biochemical activity of the agent.
- a fluid carrier should be selected that does not denature the protein or otherwise detrimentally affect the biological binding interaction of the protein that is to be exploited.
- a micromold 20 should be selected and/or fabricated in a manner such that the surfaces of indentations 24 that can come into contact with a biologically active agent will not detrimentally affect the performance of the agent.
- micromold 20 is fabricated from a material that could denature a protein
- the interior surfaces of indentations 24 can be chemically altered, for example via grafting with polyethylene glycol, to render the surfaces non-destructive of the agent.
- fluid precursor 36 carries a suspended or dissolved chemically active agent that is an activating agent as described in a co-pending, commonly owned U.S. application Ser. No. 08/616,692 of Hidber, et al. entitled “Microcontact Printing of Catalytic Colloids”, referenced above.
- a fluid carrier When a fluid carrier is used in this and other embodiments, it can form part of a species or article immobilized proximate the substrate surface or can dissipate, for example via evaporation or adsorption into the applicator or substrate surface, leaving the species carried in the fluid carrier immobilized at the surface.
- a non-limiting list of chemically active agents that can be patterned on a surface in accordance with the invention includes agents as described by Lando (U.S. Pat. Nos. 3,873,359; 3,873,360; and 3,900,614) which can render a substrate surface amenable to metal plating, catalytic activating agents such as finely distributed metal particles and clusters such as conventional metal powders, substrate-fixed metal clusters or multimetallic clusters that are well known as valuable heterogeneous and homogeneous catalysts in organic chemistry, inorganic chemistry, and electrochemistry, etc.
- Lando U.S. Pat. Nos. 3,873,359; 3,873,360; and 3,900,614
- catalytic activating agents such as finely distributed metal particles and clusters such as conventional metal powders, substrate-fixed metal clusters or multimetallic clusters that are well known as valuable heterogeneous and homogeneous catalysts in organic chemistry, inorganic chemistry, and electrochemistry, etc.
- such agents can include those capable of being carried by an applicator, transferred from the applicator to a surface in a form in which it can effect a chemical reaction (such as a metal deposition reaction), and immobilized at the surface with a degree of adhesion and for a period of time sufficient to participate in the desired chemical reaction.
- a chemical reaction such as a metal deposition reaction
- one class of activating agents provided in accordance with the invention are distinguished from prior art agents applied with an applicator such as a stamp, for example as disclosed by Lando (U.S. Pat. Nos.
- the activating agent of the present invention is in a form suitable for effecting reaction such as metal plating or catalytic action when transferred to the surface.
- further chemical reaction at the surface to convert a precursor to a suitable agent, as necessitated in the referenced prior art methods is not required.
- Metal deposition reactions contemplated include electrochemical deposition and electroless deposition, generally involving reduction of a metal cation to create the metal, facilitated in part by the lowering of the electrochemical potential involved in the deposition.
- Activating agents that are finely distributed metal particles and clusters such as conventional metal powders, including substrate-fixed metal clusters or multimetallic clusters are suitable for use as activating agents in accordance with the invention, and are well known as valuable heterogeneous and homogeneous catalysts in organic, inorganic, and electrochemistry.
- exemplary activating agents include one or more metals of periodic table groups Ib, IIb, III, IV, V, VI, VIIb, VIII, lanthanides, and actinides, preferably copper and any metal more noble than copper, in particular Pd, Au, Ag, Pt, and Cu.
- Hydrogenation catalysts for example those effective in hydrogenating olefins or aromatics, as in the partial hydrogenation of benzene to form cyclohexene, with a substrate-fixed ruthenium activating agent or bimetallic activating agent (e.g. Ru/Sn) are contemplated.
- ruthenium activating agent or bimetallic activating agent e.g. Ru/Sn
- Zirconium and titanium catalysts are suitable for use in the invention that catalyze polymerization, such as polymerization of olefins such as ethylene, and these are intended to form part of the invention.
- Other examples of catalytic activating agents include those used in Heck reactions, e.g. in the Pd-catalyzed reaction of bromobenzene and styrene to form stilbene.
- Activating agents that are heterogeneous catalysts are also useful as electrocatalysts in fuel cells (in particular substrate-fixed Pt and Pt/Ru clusters).
- Activating agents prepared according to the invention can be homogeneous catalysts, such as those used in two phase systems (for instance H 2 O/toluene), such as e.g. betaine-stabilized Pd clusters soluble in H 2 O.
- Activating agents that are embedded in polymers can be used to prepare materials for electronic, optical and magnetic applications.
- Suitable embedding polymers include organic polymers, such as poly-p-phenylene-vinylene, polymethyl methacrylate, polysilanes, and polystyrene, or inorganic polymers, such as zeolites, silicates, and metal oxides.
- organic polymers such as poly-p-phenylene-vinylene, polymethyl methacrylate, polysilanes, and polystyrene
- inorganic polymers such as zeolites, silicates, and metal oxides.
- sol-gel process can be used to incorporate metal clusters in amorphous metal oxide materials (e.g. SiO 2 ) as activating agents.
- Soluble metal clusters that are activating agents can also be surface-deposited to prepare novel materials for applications in optics and electronics, e.g. Pd on HOPG (highly oriented pyrolytic graphite).
- HOPG highly oriented pyrolytic graphite
- Particulate activating agents having particle sizes on the order of nanometers are preferred, for example particulate matter having particle size of less than about 100 nm, preferably less than about 50 nm, more preferably less than about 25 nm, and most preferably from about 2 to about 20 nm.
- the size of the particles is not critical except to the extent that where excellent edge resolution of a structure deposited in a reaction involving the particle is desired, the upper limit in size of the particle is reduced.
- colloidal activating agents are colloidal activating agents.
- colloidal activating agent is meant to define particulate matter capable of being involved in a desired chemical reaction, such as a catalytic reaction and including plating of metal at surfaces, that is carried or surrounded by molecules that prevent agglomeration of the individual particles and that render the particulate soluble in, or at least able to be carried in, an organic or aqueous liquid.
- a desired chemical reaction such as a catalytic reaction and including plating of metal at surfaces
- Suitable colloid-forming species and colloids are described in European patent publication no. 672765 by Reetz et al., published Sep. 20, 1995, and incorporated herein by reference.
- the activating agent comprises one or more metals of groups Ib, IIb, III, IV, V, VI, Vllb, VIII, lanthanides, and/or actinides of the periodic table prepared by cathodic reduction in the presence of a stabilizer.
- One method of preparation of such colloids is reduction, optionally with a supporting electrolyte, in organic solvents or in solvent mixtures of organic solvents and/or water within a temperature range of between about ⁇ 78° C. and about 120° C. to form metal colloidal solutions or redispersible metal colloid powders, optionally in the presence of inert substrates and/or soluble metal salts of the respective metals.
- colloids are soluble or redispersible in a suitable fluid that facilitates their application to an applicator such as a stamp.
- an applicator such as a stamp.
- Electrochemical methods are described in EP 672765, referenced above, for synthesis of soluble metal colloids by operating in an inert organic, aprotic solvent, with surface-active colloid stabilizers being added as the supporting electrolyte which will both prevent plating of the metal and protect, or stabilize, small metal nuclei in the cluster stage.
- a metal sheet serves as the anode to be dissolved and a metal or glassy carbon electrode serves as the cathode. After dissolution at the anode, the released metal salts are reduced again at the cathode, with tetraalkylammonium salts serving as stabilizers. Standard organic solvents can be employed.
- Suitable exemplary stabilizers, or carriers, for the colloids, and at the same time as the supporting electrolyte, are quaternary ammonium or phosphonium salts R 1 R 2 R 3 R 4 N + X ⁇ and R 1 R 2 R 3 R 4 P + X ⁇ , respectively.
- R 1 , R 2 , R 3 and R 4 are possible.
- Examples include the symmetrical tetraalkylammonium salts with R 1 ⁇ R 2 ⁇ R 3 ⁇ R 4 ⁇ n-butyl or n-octyl, mixed tetraalkylammonium salts with R 1 ⁇ R 2 ⁇ R 3 ⁇ methyl and R 4 ⁇ cetyl, or chiral tetraalkylammonium salts having four different residues.
- Aryltrialkylammonium salts may also be used.
- Suitable counter ions include various anions, e.g.
- halogenides Cl ⁇ , Br ⁇ , I ⁇
- PF 6 ⁇ hexafluorophosphate
- phosphonium salts including tetraarylphosphonium salts, such as tetraphenylphosphonium bromide.
- tetrabutylammonium chloride bromide or hexafluorophosphate, tetraoctylammonium bromide, or tributylhexadecylphosphonium bromide
- metals any of those listed above, in particular transition metals such as Fe, Co, Ni, Pd, Pt, Ir, Rh, Cu, Ag, or Au, are suitable.
- Suitable solvents are aprotic organic solvents, such as tetrahydrofuran (THF), toluene, acetonitrile (ACN), or mixtures thereof.
- the temperature in the electrolytic cell may be in the range between ⁇ 78° C. and +120° C., preferably 15-30° C. or room temperature.
- a preferred activating agent is a colloidal catalyst that promotes deposition, for example electroless deposition, of a metal at region 34 of substrate surface 28 to which the colloidal catalyst is applied.
- fluid precursor 36 includes a suspension of a colloidal palladium catalyst
- the fluid can be evaporated or adsorbed as described above, resulting in deposition of catalyst at regions 34 of substrate surface 28 .
- an electroless copper plating bath can be introduced into channels 32 and deposition of copper allowed to take place at regions 34 of surface 28 .
- micromold 20 can be removed from surface 28 and the entire surface 28 exposed to an electroless copper plating bath. Copper will plate only at those regions 34 of substrate surface 28 to which colloidal palladium catalyst had been applied.
- Electrochemical metal plating can be carried out as well.
- the chemically active agent of the invention can be any agent that can find use in chemical reaction, attraction, or other interaction proximate a substrate surface.
- agents that can be used in accordance with the invention, including, but not limited to solutions or suspensions of a very small species such as catalytic colloids, monomers, dissolved or suspended salts or ceramics or their precursors or other species.
- a suspension of particulate species in a fluid carrier 36 can be introduced into channels 32 , followed by removal of the fluid carrier via dissipation, as discussed.
- the particulate species can be organic, inorganic, or polymeric material as described above, for example finely-ground polymeric, ceramic, or crystalline material, or can be in the form of microspheres.
- the application of microspheres in a predetermined pattern to a substrate surface can serve a variety of purposes that will be apparent to those of ordinary skill in the art upon reading the present disclosure, in light of the state of the art as set forth in several publications.
- the lattice spacing of the resulting pattern is approximately 900 nanometers with individual trigonal pyramidal peaks.
- a particular concentration of polymeric microspheres in a fluid carrier can be selected without undue experimentation that, when introduced into channels 32 , followed by evaporation of the fluid carrier, would result in a monolayer of microspheres selectively patterned at regions 34 of substrate surface 28 . Removal of micromold 20 , followed by chemical vapor deposition, results in a well-ordered pattern of isolated, nano-scale regions of deposited material within the confines of region 34 of substrate surface 28 .
- Microparticles and microbeads especially polymeric particles and beads such as latex or polystyrene beads, find use in the field of biochemistry as solid supports for biochemical interaction.
- a chemically or biochemically active agent can be coupled to a microbead or microparticle and optionally used in turn to immobilize a second agent that reacts with the immobilized agent, thereby immobilizing the second agent at a region at which the microbead is immobilized. That is, microbeads carrying a particular agent can be immobilized at a surface in a pattern using techniques of the invention and the patterned, immobilized beads can serve as locations for chemical reaction or biochemical interaction on the micro scale, for example as microreactors. Those of ordinary skill will recognize a variety of uses for patterned microparticles or microbeads carrying chemical or biochemical agents such as, for example, biochemical assays.
- the pattern of parallel indentations 24 formed in surface 22 of micromold or applicator 20 is for illustrative purposes only. Any pattern, for example a pattern defined by a single indentation or many indentations, one or more of the indentations defining a non-linear pathway of uniform or non-uniform depth is intended to fall within the scope of the invention. Various patterns are illustrated in subsequent figures.
- the indentation pattern can be of a variety of dimensions and, according to one aspect of the invention, includes a region having a lateral dimension of less than 1 millimeter. “Lateral dimension” is meant to define a dimension parallel to application surface 22 .
- the indentation pattern includes a portion having a lateral dimension of less than about 500 microns or less than about 100 microns, in one set of embodiments more preferably less than about 50, 20, or 10 microns, and more preferably still less than about 5 microns.
- an indentation pattern having a portion including a lateral dimension on the order of 1 micron is provided.
- the dimension of the indentations can be altered, as described in international patent publication number WO 96/29629, published Jun. 26, 1996 of Whitesides, et al., entitled “Microcontact Printing on Surfaces and Derivative Articles”, incorporated herein by reference, by deforming article 20 .
- waveguides are fabricated in accordance with the invention, it is an advantage that, for example, branched sections and/or evanescent coupling sections, as shown in FIGS. 17 and 18 can be included in the pattern.
- branched sections and/or evanescent coupling sections as shown in FIGS. 17 and 18 can be included in the pattern.
- the waveguide will have a width on the order of microns.
- micromold 20 includes an indentation pattern where the indentations have depths and widths on the order of 100 microns to less than 1 micron, controllably.
- article or articles 38 resulting from the technique can have lateral dimensional features that correspond to the lateral dimensional features of indentations 32 of the micromold.
- the fluid precursor need not completely fill channels 32 , and this is preferred according to embodiments in which the lateral dimension of article 38 formed from the fluid precursor is to be minimized.
- fluid precursor 36 is introduced into channels 32 in an amount small enough that the fluid precursor wets only the corners of the channels.
- a fluid precursor, substrate, and micromold are selected such that the fluid precursor will wet the micromold efficiently via capillary action
- the precursor will selectively wet portions of the channels having an interior angle relatively low relative to the rest of the channel (such as comers 40 defined by the abutment of contact surface 26 against substrate surface 28 at the edge of region 34 of the substrate surface).
- a resulting structure can define a pattern having a dimension smaller than that of the lateral dimension of indentation 24 .
- the lateral dimension of structure 38 at its narrowest, is narrower than the narrowest lateral dimension of channel 24 of the micromold, and can have a height significantly less than the height of the channel.
- the lateral dimension of article 38 according to this embodiment can be on the order of less than or equal to about 100 microns or 50 microns, or preferably less than about 20 or 10 microns, more preferably less than about 5 microns or 1 micron, and according to a particularly preferred embodiment less than approximately 0.2 micron.
- any of the species described herein that can be patterned proximate a substrate surface can be patterned so as to have lateral dimensions as described above. This aspect of the invention is illustrated in FIG. 6 c , and discussed below.
- any of the species described herein that can be used to form patterned articles and the like on a substrate surface can be made to coat substrate surface 28 , and then article 20 can be pressed against substrate surface 28 to displace precursor 36 at regions in register with contact surface 26 .
- Precursor 36 will be formed in channels 32 as illustrated in FIG. 1, and procedures described above carried out.
- substrate 30 of the invention can be of the same material as the bulk material of substrate 30 , or a different material.
- Substrates exposing a variety of functional surfaces such as hydrophobic, hydrophilic, and biologically compatible or non-compatible surfaces are known, and are suitable for use with the invention.
- Substrates that are somewhat fluid are known as well, and are acceptable for use in the invention to the extent that a useful pattern can be formed thereupon.
- Article 20 similarly can be formed of essentially any material. For example, ceramic, polymeric, elastomeric, and other materials can be used.
- substrate surface 28 and/or contact surface 26 of article 20 is an elastomer or other conformable material.
- contact surface 26 and more preferably, for ease of fabrication, the entire article 20 is formed of an elastomer.
- an elastomer defines substrate surface 28 or contact surface 26 , or preferably micromold 20
- an optimal seal is created between contact surface 26 and portions of substrate surface 28 adjacent and contiguous with portions 34 that with indentations 24 define channels 32 .
- pressure can be applied to micromold 20 against substrate 30 during micromolding, but according to embodiments in which an elastomer is used as described, pressure need not be applied as the elastomer conforms well to the surface against which it mates thus sealing channels 32 .
- the micromold 20 can be fabricated of an elastomer in a manner analogous to the fabrication of a stamp from an elastomer as described in co-pending, commonly-owned U.S. Pat. No. 5,512,131, issued Apr. 30, 1996 by Kumar, et al, entitled “ Formation of Microstamped Patterns on Surfaces and Derivative Articles ”, and as described in International Patent Publication No. WO 96/29629 of Whitesides, et al., entitled “ Microcontact Printing on Surfaces and Derivative Articles ”, published Jun. 26, 1996, both of which are incorporated herein by reference.
- FIG. 2 illustrates another embodiment of the invention in which, rather than applying article 20 to substrate surface 28 followed by introduction of fluid precursor 36 into channels 32 so defined, article 20 is used as an applicator to transfer a chemically or biochemically active agent (optionally in a fluid carrier), fluid precursor of an article such as microparticles or microbeads in suspension, catalytic colloid, prepolymer fluid, or the like to substrate surface 28 .
- a chemically or biochemically active agent optionally in a fluid carrier
- fluid precursor of an article such as microparticles or microbeads in suspension, catalytic colloid, prepolymer fluid, or the like
- FIG. 15 Described below with reference to FIG. 15 is a set of transfer molding techniques particularly preferred in the fabrication of waveguides and other articles where the final shape of the formed article is essentially identical to the shape of the interior of the mold.
- FIG. 2 and subsequent figures components common to the various figures are given common numerical designation.
- FIG. 2 and subsequent figures components common to the various figures are
- fluid precursor 36 is first applied to indentations 24 of micromold 20 , and then application surface 22 is brought into proximity of substrate surface 28 to allow fluid precursor 36 to be transferred to substrate surface 28 .
- the fluid precursor can be applied to the indentations by bringing the indentations into contact with the fluid precursor and allowing capillary action to cause the indentations to be filled, or the precursor can be applied via micropipetting or the like to the indentations.
- separate fluid species can be applied to separate indentations if desired.
- to select a material exposed by the contoured application surface and the fluid species applied thereto such that the fluid species rapidly is positioned within the indentations, rather than spreading over the entire surface. Those of skill in the art can carry out such selection, using contact angle measurements or the like.
- fluid precursor 36 protrudes from indentations 24 prior to transfer
- application surface 22 need not contact substrate surface 28 for transfer to take place.
- application surface 22 will be brought into contact with substrate surface 28 to transfer a pattern of the fluid precursor 38 to regions proximate the substrate surface in a pattern corresponding to the indentation pattern 24 .
- some fluid precursor remains in indentations 24 , and the fluid precursor transferred to substrate surface 28 has been converted into hardened article 38 .
- the fluid precursor will not result in a hardened article, but will serve to transfer a biochemical agent or chemical agent to a surface. According to the embodiment illustrated in FIG.
- the chemical or biochemical agent, prepolymer, fluid carrier containing a suspension of particulate matter, microbeads, or the like serves to transfer essentially instantaneously the desired species to the surface.
- the pattern of species so transferred can include a single indentation that is of any shape including a non-linear or linear pathway, a plurality of linear indentations as illustrated in FIG. 2, or a plurality of indentations of any shape, one or more indentations having dimensions as described above. Where a plurality of indentations are formed in application surface 22 , each indentation can be made to carry a different chemical or biological agent or precursor.
- distinct first and second species such as distinct first and second chemically or biochemically active agents, precursors, particulate species, or the like can be transferred essentially instantaneously to distinct first and second regions 42 and 44 proximate the substrate surface, in a pattern corresponding to the indentation pattern, and separated from each other by intervening region 46 of the substrate surface that remains free of the agent or precursor.
- FIGS. 3 a - d are photocopies of SEM images of polymeric structures formed on substrates according to the method described above and illustrated in FIG. 1, in which a fluid polymeric precursor was allowed to fill channels formed by indentations in micromold 20 and regions of the substrate.
- FIG. 3 a shows polyurethane articles 48 formed on Si/SiO 2 substrate 50 by capillary filling of a micromold having a surface with indentations placed adjacent substrate 50 . The indentations correspond to the pattern of articles 48 .
- a liquid polyurethane prepolymer was placed adjacent openings of channels formed between the micromold and the substrate surface and filled the channels via capillary action.
- the micromold was made of polydimethylsiloxane (PDMS).
- FIG. 3 b is a top view of a polyurethane article 52 having a complex, interconnected pattern formed on Si/SiO 2 substrate 50 .
- a PDMS micromold having an indentation pattern corresponding to the pattern of article 52 was used, and a liquid polyurethane prepolymer was allowed to fill the mold channels via capillary action.
- FIG. 3 c shows a quasi three-dimensional array of microstructures interconnected through channels. Again, a polyurethane liquid prepolymer was allowed to fill channels formed by a micromold having an indentation pattern corresponding to the pattern of polyurethane article 54 .
- Polyurethane article 54 is formed on a Si/SiO 2 substrate 50 .
- FIG. 3 d shows a free-standing patterned polyurethane article 52 formed by removal of the article from the substrate (FIG. 3 b ).
- FIGS. 4 a - h illustrate structures formed on substrates using the micromolding technique illustrated in FIG. 1 in which liquid precursor 36 is a precursor of inorganic materials. Photocopies of SEM images are shown.
- FIG. 4 a KH 2 PO 4 structures precipitated from aqueous solution on Si/SiO 2 are shown.
- FIG. 4 b shows KH 2 PO 4 structures as well, crystallized more rapidly.
- FIG. 4 c shows Cu(NO 3 ) 2 on the same substrate crystallized from aqueous solution.
- FIG. 4 d shows structures formed of the same material on the same substrate, but crystallized from a much more dilute solution.
- FIG. 4 d illustrates the derivatization in a pattern that is formed within the boundaries of a region of the substrate surface corresponding to the indentation pattern of the micromold, but that does not fill that region.
- FIG. 4 e shows CuSO 4 structure on glass.
- FIG. 4 f shows K 3 Fe(CN) 6 structures on Si/SiO 2 .
- FIG. 4 g shows a fractured view of amaranth on glass. The structures are approximately 0.4 micron in height.
- FIG. 4 h is a section of FIG. 4 g at higher magnification.
- Ceramic structures formed in accordance with the invention can find use, for example, as mechanical ceramics such as abrasion tools.
- Current methodologies involve, typically, chemical vapor deposition to form ceramic patterns having small dimensions for such uses.
- FIG. 5 is a photocopy of an electron micrograph showing a packed, ordered array of polystyrene microspheres 70 on a Si/SiO 2 substrate 72 .
- the ordered array of microspheres was formed by allowing a latex solution containing polystyrene microspheres to fill, via capillary action, channels formed between a micromold and the substrate surface in a pattern corresponding to the pattern of microbeads shown.
- the PDMS micromold was removed following crystallization of the microspheres via dissipation of the fluid carrier.
- FIGS. 6 a - c are photocopies of SEM images of copper structures formed via electroless deposition on Si/SiO 2 substrates.
- a gold surface was provided for the structure in FIG. 6 a .
- a PDMS micromold having an indentation pattern corresponding to the pattern of copper structures illustrated was placed adjacent the gold substrate (as illustrated schematically in FIG. 1) and the channels 32 were filled with a plating bath for electroless deposition of copper, defining a fluid precursor of copper according to one aspect, and a chemically active agent according to another aspect.
- the copper electroless plating solution was allowed to remain in contact with the surface for a period of time sufficient to plate copper structures 74 in a pattern corresponding to the indentation pattern of the micromold, while portions of gold surface 76 corresponding to contact surface 26 of the micromold remained free of copper deposition.
- a PDMS micromold having an indentation pattern corresponding to the pattern of copper structures illustrated was placed adjacent the substrate and the channels 32 were filled with a precursor solution 36 containing catalytic colloids.
- the micromold was removed, and the surface exposed to an electroless copper plating bath.
- copper structures 78 were formed on a Si/SiO 2 substrate 80 coated with a self-assembled monolayer of siloxane on the Si/SiO 2 substrate.
- CH 3 CH 2 O) 3 Si(CH 2 ) 3 NH 2 defined the self-assembled monolayer.
- a micromold having an indentation pattern corresponding to the ultimate copper pattern 78 was placed on the self-assembled monolayer-derivatized silicon substrate.
- FIG. 6 c illustrates an aspect of the invention in which articles of very small lateral dimension can be formed by allowing a small volume of fluid precursor 36 to enter channels 32 defined by the micromold indentations and the substrate surface.
- the substrate was prepared as described in connection with FIG. 6 b .
- a region 82 of the substrate surface corresponds to the indentation pattern of the micromold.
- the fluid precursor 36 wetted only the corners defined between the substrate surface 84 and the micromold channels thus, when the fluid carrier dissipated, the catalytic colloid was solidified only in those portions of the indentation pattern that were wetted, namely, the comers.
- the surface was exposed to an electroless copper plating bath, copper was plated at the regions 86 to which the catalytic colloid had been deposited. A copper pattern of very small lateral dimension resulted.
- FIGS. 7 a - c illustrate the application of a patterned structure to a surface from a fluid precursor using micromolding as illustrated in FIG. 1, followed by use of the structure as a resist in a chemical etch.
- a polymeric structure 88 (polyurethane) was formed from a fluid prepolymer in a pattern corresponding to an indentation pattern on a 200 nm, thermally grown oxide layer 90 of a silicon substrate 92 (FIG. 7 a ).
- FIG. 7 c shows resultant channels 94 anisotropically etched in the silicon substrate between patterned regions of silicon dioxide 90 that correspond to the pattern of polymeric structure 88 formed on the substrate surface via the micromolding technique.
- FIG. 8 illustrates schematically a technique for forming a mask, for use in lithography or the like, via the micromolding technique of the invention.
- a micromold 96 having a molding surface 98 including a plurality of indentations 100 in a grid-like pattern is applied to a surface 102 of a substrate 104 .
- a fluid polymeric precursor 106 is placed adjacent openings of channels formed between the substrate surface and the indentations of the micromold, and allowed to flow, via capillary action, into the channels. Where a PDMS micromold was used, the polymeric precursor could be placed so as to cover all channel openings, and flowed into and made to fill the channels completely. Gas escaped presumably via diffusion through the micromold.
- the micromold was removed.
- the substrate then was separated from the resultant patterned article 108 .
- the patterned article had a “frame” 110 completely surrounding it which could be used for ease of manipulation.
- the frame could be removed as well, to form the article 108 in a pattern corresponding to the indentation pattern of the micromold free of the frame.
- FIGS. 9 a - d are photocopies of SEM images.
- FIG. 9 a shows a polyurethane mask 108 formed as illustrated in FIG. 8, and following formation placed on a Si/SiO 2 substrate 112 .
- FIG. 9 b shows the mask 108 on the substrate 112 following evaporation of gold onto the substrate. A portion of the mask was removed and mask 114 and portions 112 of the substrate not covered by the mask are shown covered with gold. Portions 116 of the substrate that had been covered by mask 108 remain free of gold.
- FIG. 9 a shows a polyurethane mask 108 formed as illustrated in FIG. 8, and following formation placed on a Si/SiO 2 substrate 112 .
- FIG. 9 b shows the mask 108 on the substrate 112 following evaporation of gold onto the substrate. A portion of the mask was removed and mask 114 and portions 112 of the substrate not covered by the mask are shown covered with gold. Portions 116 of the substrate that had been covered by mask 108 remain free
- FIG. 9 c shows a surface having a pattern of isolated regions 118 of gold on a silicon substrate (regions 120 of the silicon substrate not covered by regions 118 of gold can be seen) formed as follows.
- a mask fabricated as described above was placed (with reference to FIG. 8) on a silicon substrate carrying a thin film of gold.
- a self-assembled monolayer-forming species (hexadecanethiol) was exposed to the surface and formed a self-assembled monolayer selectively at regions 118 not covered by the mask.
- the mask then was removed from regions 120 , and the surface exposed to a solution that etched gold, but to which the self-assembled monolayer was resistant.
- FIG. 9 d shows a surface derivatized as described with respect to FIG. 9 c , but the self-assembled monolayer was transferred to regions 118 of the surface by placing a flat PDMS article that had been coated with a self-assembled monolayer-forming species on top of the mask 108 for one minute.
- Mask 108 also could be applied to nonplanar surfaces followed by plating, etching, or the like. It can be advantageous, when transferring mask 108 to a surface having very fine features, such as a surface etched as illustrated in FIG. 7 c , to transfer mask 108 to such a surface by floating it in a fluid that is supported by the surface and allowing the fluid to dissipate or run off.
- etching or plating at a surface can be made to take place selectively at predetermined regions, and this technique can be exploited using the techniques of the present invention as described herein.
- a “protecting species” that is resistant to (for example, incompatible with) a chemical etch can be placed on top of a self-assembled monolayer, followed by etching at regions not covered by the self-assembled monolayer, as described in publication no. WO 96/29629.
- a self-assembled monolayer can be incompatible with an etch and etching can take place without the use of a protecting species.
- the protecting species is compatible with the self-assembled monolayer.
- a protecting species is less compatible with the self-assembled monolayer than with the substrate surface that is exposed at regions intervening the self-assembled monolayer.
- a protecting species is exposed to the surface and when the surface is exposed to an etchant, the surface is etched at regions that had been covered by the self-assembled monolayer.
- FIGS. 10 a - c illustrate formation of a mask 122 on a thin layer 124 of chromium on a glass substrate 126 using the micromolding procedure as illustrated in FIG. 1, followed by etching of chromium at regions 128 not covered by the mask.
- the molding technique described above is used to form a pattern of polyurethane article 122 on chromium 124 leaving region 128 of chromium uncovered.
- FIG. 10 b is an optical micrograph of the chrome mask 130 , top view. The chrome mask 130 was removed from the substrate 126 and placed on a photoresist article.
- FIG. 10 b is an optical micrograph of the chrome mask 130 , top view. The chrome mask 130 was removed from the substrate 126 and placed on a photoresist article.
- 10 c is a photocopy of an SEM image of a pattern that was generated in the photoresist film at regions 132 not protected by the mask.
- Raised portions 134 in a pattern corresponding to the pattern of the chromium mask, and corresponding to the original indentation pattern of the micromold from which the mask 122 was formed, were not ablated in the photolithography process.
- a substrate surface such as a silicon wafer can be spin-coated with photoresist.
- a micromold can be placed adjacent to a photoresist and channels defined thereby filled with a solvent that dissolves photoresist but not the micromold.
- a pattern of the silicon wafer not covered by photoresist, the pattern corresponding to the indentation pattern of the micromold, is thereby produced. Further processing familiar to those of ordinary skill in the art can be carried out.
- FIG. 11 illustrates schematically an applicator 136 that can be used for applying any of the above-described chemically or biochemically active agents, polymeric precursors, fluid precursors of solid structures, fluid carriers of particulate matter, and the like to a substrate surface.
- Applicator 36 includes a plurality of isolated indentations 138 separated from each other by intervening regions of a surface 140 in which the indentations are formed. As illustrated, two of the indentations contain fluid carrier 142 and fluid carrier 144 , respectively. The fluid carriers 142 and 144 can be the same or different.
- a substrate 146 is shown that, for purposes of illustration, includes a self-assembled monolayer 148 formed thereon which can serve as an adhesion promoter.
- Fluid carriers 142 and 144 are transferred to isolated regions proximate the surface of substrate 146 , in particular, regions of the exposed self-assembled monolayer 148 on the surface of substrate 146 .
- the transfer typically takes place by bringing the surface 140 of the applicator into contact with the self-assembled monolayer 148 but, if the fluid carriers 142 and 144 protrude from the indentations, the surface 140 need only be placed in close proximity to the self-assembled monolayer 148 .
- Fluid carriers 142 and 144 can be any of the species described above and, according to a particularly useful embodiment, carry or define a chemically or biochemically active agent that can be used in a subsequent assay or the like.
- a self-assembled monolayer 148 can be a monolayer of a species X—R—Ch as described in U.S. Pat. No. 5,620,850, issued Apr. 15, 1997 to Bamdad, et al., entitled “Molecular Recognition at Surfaces Derivatized with Self-Assembled Monolayers”, incorporated herein by reference.
- X represents a functional group that adheres to a gold surface
- R represents a spacer moiety that promotes formation of a self-assembled monolayer of a plurality of the molecules
- Ch represents a bidentate, tridentate, or quadradentate chelating agent that coordinates a metal ion.
- the chelating agent includes a chelating moiety and a non-chelating linker moiety, such that it can be covalently linked via its linker moiety to the spacer moiety while allowing the chelating moiety to coordinate a metal ion.
- a metal ion is coordinated to the chelating agent, and a binding partner of a target molecule is coordinated to the metal ion.
- This arrangement is facilitated by selecting the chelating agent in conjunction with the metal ion such that the chelating agent coordinates the metal ion without completely filling the ion's coordination sites, allowing the binding partner to coordinate the metal ion via coordination sites not filled by the chelating agent.
- a non-limiting exemplary list of suitable chelating agents includes nitrilotriacetic acid, 2,2′-bis(salicylideneamino)-6,6′-demethyidiphenyl, and 1,8-bis(a-pyridyl)-3,6-dithiaoctane.
- the binding partner can be a biological species that includes a polyamino acid tag, such as a tag made up of at least two histidine residues, that coordinates the metal ion.
- the term “adhere” means to chemisorb in the manner in which, for example, alkyl thiols chemisorb to gold.
- the fluid carriers 142 and 144 can be carriers of a nickel ion, resulting in a surface suitable for capture of a biological binding partner carrying a polyamino acid tag selectively at regions to which carriers 142 and 144 had been applied.
- the fluid carriers 142 and 144 immediately following application of carriers 142 and 144 to the substrate surface, it can be advantageous to expose the surface of substrate 146 to a chelating agent in solution to remove excess nickel ion from the surface. In this way, stray uncoordinated nickel ion does not coordinate to the self-assembled monolayer 148 at regions outside of those regions to which carrier 142 and 144 had been applied.
- the latter-applied chelating agent preferably less-strongly coordinates nickel ion than the chelating agent immobilized at the surface.
- a plurality of isolated regions of self-assembled monolayer 148 include nickel ion. Accordingly, when the surface is exposed to a polyamino acid-tagged biochemically active agent, the biochemically active agent will attach selectively at those regions to which nickel ion had been applied.
- self-assembled monolayer 148 can be a species X—R—Ch—M as described in the above-referenced co-pending application Ser. No. 08/312,388, and the species 142 and 144 can be polyamino acid-tagged biological binding partners, optionally contained in a fluid carrier, that are attached to the surface selectively at those regions corresponding to the indentation pattern of the applicator.
- the separate, isolated regions can include separate, distinct biochemically active agents.
- the procedure can be repeated using fresh substrate surfaces for each step, thus surfaces carrying distinct regions of distinct biochemically active agents can be mass produced.
- cells can be immobilized at a substrate surface in this manner as well.
- Register between the applicator and the substrate surface can be controlled via mechanical, electronic, magnetic, and/or optical apparatus.
- species 142 and 144 or species carried by fluid carriers 142 and 144 can be transferred to a surface carrying a self-assembled monolayer other than the monolayer of X—R—Ch—M as described above.
- a self-assembled monolayer exposing a hydrophobic functionality such as an alkane functionality can be formed on a surface (e.g., hexadecanethiol on gold) and a biochemically or chemically active agent that adheres to a hydrophobic surface can then be applied to the surface in discrete regions or in a pattern as described above.
- the biochemically active agent is a cell or cells, it may be advantageous to coat the hydrophobic surface with a cytophilic species such as laminin.
- Immobilization of cells and other biochemically active species can be carried out without a self-assembled monolayer as well.
- a hydrophobic surface coated with laminin, and free of self-assembled monolayer can serve as a substrate for immobilization of a pattern of cells in accordance with the invention.
- the substrate surface can carry chelating agent immobilized via other than a self-assembled monolayer.
- chelating agents coupled to dextran at a surface can be employed.
- a self-assembled monolayer 148 is illustrated on the surface of substrate 146 , a self-assembled monolayer is not needed according to all embodiments.
- substrate 146 can be adhesive to a species transferred to it from applicator 136 , for example a biochemically or chemically active agent and fluid carriers 142 or 144 , or the like.
- the applicator can be placed in contact with the substrate surface and allowed to remain in place while any species present in the fluid precursor is allowed to harden, the fluid carrier is allowed to dissipate, or the like.
- the species formed proximate the substrate surface in a pattern corresponding to the indentation pattern of the article itself can be a self-assembled monolayer.
- Suitable self-assembled monolayer-forming species are described in U.S. Pat. No. 5,512,131 of Kumar, et al., referenced herein.
- Self assembled monolayers formed of species X—R—Ch, as described above, with or without metal ion and/or biological species coordinated thereto, can be used, as well as other self-assembled monolayer-forming species disclosed in application Ser. No. 08/312,388, by Bamdad, et al., referenced above.
- FIG. 12 illustrates schematically a process for applying a species from indentations in an applicator to a non-planar surface.
- An applicator 136 (shown in cross section) includes a plurality of indentations 138 , each filled with a species 150 . Each of the indentations can be filled with the same fluid or different fluids.
- Species 150 can be any of the above-described fluid precursors, chemically or biochemically active agents, or the like.
- An article 152 having a surface 154 is placed adjacent the application surface of applicator 136 and rolled against the applicator as described in commonly-owned, co-pending U.S. patent application Ser. No.
- nonplanar surfaces having various radii of curvature can be carried out according to the invention, for example, radii of curvature of less than about one centimeter, preferably less than about one millimeter, more preferably less than about 500 microns, more preferably less than about 100 microns, more preferably less than about 50 microns, and according to a particularly preferred embodiment printing can occur on substrates with radii of curvature on the order of about 25 microns or less.
- FIG. 13 illustrates an article 154 created by forming, on a silicon dioxide surface 156 of a silicon substrate 158 , a patterned structure 160 , for example a polymeric structure formed from a prepolymeric fluid using a micromold as illustrated in FIG. 1. Subsequently, a second fluid precursor is positioned so as to cover the patterned structure 160 and allowed to solidify. According to the embodiment illustrated, a fluid precursor was placed atop the patterned structure 160 and a micromold having a complex pattern was placed atop the fluid precursor. The fluid precursor was hardened to form a structure 162 covering and encompassing the patterned structure 160 on the substrate surface.
- a patterned structure 160 for example a polymeric structure formed from a prepolymeric fluid using a micromold as illustrated in FIG. 1.
- a second fluid precursor is positioned so as to cover the patterned structure 160 and allowed to solidify.
- a fluid precursor was placed atop the patterned structure 160 and a micromold having a complex pattern was placed
- the second structure 162 included an exposed surface 164 having a pattern of indentations 165 complementary to the indentation pattern of the second micromold.
- the overall structure when structure 160 differs in refractive index from structure 162 , can serve as a waveguide, the second structure 162 serving as a cladding.
- the contoured surface 164 of cladding 162 is lossy.
- the pattern of surface 164 in most instances, is not important to the waveguide function.
- Waveguides were fabricated from several classes of polymeric materials (epoxies, polyurethanes, and polyacrylates on Si/SiO 2 substrates. Waveguides clad with polymers having slightly lower refractive indices gave single-mode output in the visible and near infrared regions.
- the waveguide was 0.7 centimeters long and the wavelength of light was 0.85 micron. Photocurable polymers are preferred. Waveguides are described in greater detail below.
- FIGS. 14 a - k a schematic illustration of a surface derivatized so as to include discrete regions of differing chemical functionality is shown.
- the article schematically illustrated finds particular use as a combinatorial library.
- An article by Jacobs, et al., entitled “Combinatorial Chemistry-Applications of Light-Directed Chemical Synthesis”, Trends in Biotechnology , volume 12, 19-26 (January, 1994; incorporated by reference above) describes a photolithographic process for forming a combinatorial library. Jacobs, et al. describe derivatizing a substrate with linker molecules that contain amines blocked by a photochemically cleavable protecting group.
- FIGS. 14 a - k illustrate schematically top views of a substrate surface.
- FIGS. 14 a - c illustrate an “orthogonal-stripe” method.
- a plurality of micromolds are fabricated, each of which has a distinct channel pattern.
- Each micromold is fabricated so as to cover substrate surface 166 , or at least enough of substrate surface 166 to define a channel or channels necessary for application of chemically or biochemically active agents to desired regions of the surface.
- the description will assume use of a micromold that completely covers substrate surface 166 , and includes indentations in register with certain portions of substrate surface 166 .
- One micromold includes an indentation in register with a portion of the substrate surface designated “A” in FIG. 14 a and includes a contact surface that contacts the remaining substrate surface at areas designated “B”, “C”, and “D”.
- individual micromolds will be fabricated that include contact surfaces that cover all portions of the substrate except one of the portions “E”, “F”, “G”, or “H”. That is, each micromold forms a channel through which a chemically or biochemically active agent (reactant) can be delivered to the substrate surface at a portion in register with the channel, while remaining portions of the micromold block regions proximate the substrate surface from interaction with the particular chemically or biochemically active agent.
- any combination of micromolds can be used to apply to the surface, in any combination, various chemically or biochemically active agents.
- a micromold having a channel in register with region “A” of the substrate surface is used to apply to the surface a chemically active agent “A” and then, with reference to FIG. 14 b , a micromold is placed adjacent the substrate surface that has an indentation in register with region “E” and is used to apply to region “E” a chemically active agent “E”, the substrate surface will include a region carrying chemically active agent “A” (the region designated “A” in FIG. 14 a ), a region carrying chemically active agent “E” (the region designated “E” in FIG.
- FIGS. 14 d - k a “binary” synthesis technique is described.
- a first micromold having an indentation in register with region “A” and a contact surface in register with region “ ⁇ ” is used to apply to the substrate surface an active agent “A” selectively at region “A”.
- FIG. 14b shows surface 166 including a region “B” in register with an indentation of a second micromold and a region “ ⁇ ” in register with a contact surface of the second micromold, via which an active agent “B” can be applied selectively to region “B” of the substrate surface.
- FIG. 14 d a first micromold having an indentation in register with region “A” and a contact surface in register with region “ ⁇ ” is used to apply to the substrate surface an active agent “A” selectively at region “A”.
- FIG. 14b shows surface 166 including a region “B” in register with an indentation of a second micromold and a region “ ⁇ ” in register with a contact surface of
- 14 f shows surface 166 having portions “C” and “ ⁇ ” that are positionable in register with indentations and contact portions, respectively, of a third micromold to apply an active agent “C” to regions “C”.
- the surface includes portions “D” and “ ⁇ ” that are positionable in register with indentations and contact portions, respectively, of a fourth micromold to transfer agent “D” selectively to regions “D”.
- the binary technique is less labor intensive than the orthogonal-stripe method in that only four transfer or flow steps involving four micromolds are needed to create a grid of sixteen distinct chemically or biochemically functional regions on the substrate surface.
- agent “A” is applied to the left side of the substrate surface 166 and the right side of the substrate surface remains free of agent as illustrated in FIG. 14 h .
- agent “B” is applied to the upper portion of substrate surface using the second micromold.
- four quadrants of the substrate surface carry agent “A” plus agent “B”, agent “B”, agent “A”, and no agent, respectively, as illustrated in FIG. 14 i .
- agent “C” is applied to the left side of the substrate surface 166 and formation of chemically or biochemically active agent “A” via the channel of the first micromold.
- FIG. 14 k After application of agent “D” via the indentations of the fourth micromold, sixteen distinct chemically or biochemically active regions are formed as illustrated in FIG. 14 k , namely “ABCD”, “ABC”, “BCD”, “BC”, “AND”, “AB”, “BD”, “B”, “ACD”, “AC”, “CD”, “C”, “AD”, “A”, “D”, and “ ⁇ ”.
- the register between each micromold and the substrate surface can be controlled by pins in the substrate that engage each micromold, pins in each micromold that engage the substrate surface, an X-Y table that positions the substrate surface identically relative to each micromold, optical, magnetic, or electronic aligning apparatus, or other equivalent apparatus that can align each micromold with the substrate surface. Accurate register at the micron scale is achieved.
- peptides such as new drugs, naturally-occurring chemical and biochemical species, oligonucleotides and the like can be created. Indeed, any of the chemically or biochemically active agents, fluid precursors, prepolymeric fluids, or the like as described above that are transferable from a microapplicator or that can be applied, for example via capillary action, to a surface using a micromold as described above, can find use in the combinatorial arrangement described. Any combination of various agents can be used.
- an article 20 as illustrated in FIG. 2, having a contoured surface 22 including a plurality of protrusions separated by intervening indentations 24 can be used as a stamp for forming a combinatorial library.
- Stamping as described in U.S. Pat. No. 5,512,131 (issued Apr. 30, 1996 to Kumar, et al., referenced above) can be employed.
- the stamp includes a stamping surface defined by the outer surfaces of the protrusions. The process is described with reference to FIGS. 14 d - k .
- a surface 166 carries a protecting group, for example, a self-assembled monolayer exposing outwardly an azide functionality.
- a stamp having a surface including a protrusion in register with area A of surface 166 is prepared by applying to the protrusion a deprotecting species such as a reducing agent for reduction of the azide to a deprotected, reactive amine.
- a deprotecting species such as a reducing agent for reduction of the azide to a deprotected, reactive amine.
- Application of the stamp to surface 166 deprotects the self-assembled monolayer at region A, but leaves the remainder of surface 166 ( ⁇ ) protected. Then, chemical reactivity at region A can take place, followed by reprotection of the entire surface. Then the stamp can be re-oriented, or a second stamp chosen, so that region B is deprotected by contact with a stamping surface (protrusion) of a stamp.
- a stamp having protrusions corresponding to regions C is used to deprotect at regions C, followed by chemical reaction at regions C and re-protection, and the process carried out similarly at regions D (FIG. 14 g ).
- the stamping surface itself without any auxiliary agent carried thereon, can deprotect at regions of surface 166 in register with the stamping surface.
- a stamp having an acidic stamping surface such as a hydrogel loaded with a component of low pH can be used.
- DextranTM carrying polyphosphoric acid can be grafted to a surface of a rigid or elastomeric stamp and used to deprotect surface 166 at regions corresponding to the protrusions or stamping surface.
- Other protecting/deprotecting chemistries such as hydrolysis chemistry can be carried out.
- distinct species can be synthesized and applied to the substrate surface after synthesis.
- a combination of these approaches can be used as well, involving synthesis of building blocks that are assembled according to the prophetic example.
- FIG. 15 illustrates a set of particularly preferred fabrication techniques of the invention in which, rather than applying article 20 to substrate surface 28 followed by introduction of fluid precursor 36 into channels 32 so defined, article 20 is used as an applicator to transfer the fluid precursor to substrate surface 28 .
- article 20 is used as an applicator to transfer the fluid precursor to substrate surface 28 .
- the following description will be made with reference to fabrication of a structure 38 and other structures that are waveguides, from a precursor 36 that will be referred to as a waveguide precursor, although the following description defines one aspect of the invention that is applicable to creation of any of a wide variety of structures described herein and is not limited to waveguides.
- fluid precursor 36 is first applied to indentations 24 of applicator 20 . Excess fluid precursor then can be removed, by scraping, from application surface 22 .
- a block of material similar or identical in composition to that of article 20 can be used to scrape off excess prepolymer.
- the excess precursor can be blown off with a brisk stream of gas such as nitrogen.
- a brisk stream of gas also can be used to remove remaining drops of precursor after the bulk excess of precursor has been scraped away.
- Applicator surface 22 the indentations of which are filled with fluid waveguide precursor 36 , then is placed in contact with surface 28 of substrate 30 .
- Applicator 20 then can be removed, leaving some or all of precursor 36 in contact with surface 28 where it is subsequently made dimensionally stable or, according to preferred embodiments, fluid precursor 36 is hardened to the point that it is dimensionally stable while article 20 remains in place upon substrate surface 28 .
- fluid precursor 36 is a fluid prepolymer, and is heat-curable
- the precursor can be heated, for example, by heating substrate 30 , article 20 , both substrate 30 and article 20 , or applying radiative heat.
- precursor 36 is a photopolymerizable fluid, it can be exposed to electromagnetic radiation that causes polymerization.
- a fluid precursor 36 can be partially or fully polymerized prior to removal of article 20 , so long as it is polymerized to the extent that it is dimensionally stable and self-supporting. In preferred embodiments, as described below, it is often advantageous to only partially polymerize a fluid prepolymeric precursor 36 .
- fluid precursor 36 is a fluid carrier of a suspension
- the fluid carrier can be selected in conjunction with the material of article 20 to allow the fluid to be absorbed into article 20 and thereby dissipated, resulting in deposition of solid material from the suspension as the patterned material on substrate surface 28 .
- fluid precursor 36 is a solution of a dissolved precipitating species
- conditions such as temperature, pH, or the like can be altered to cause precipitation.
- One advantage of the technique of FIG. 15 is that the fluid precursor is in contact with article 20 for only a very brief period of time, thus if article 20 adsorbs or absorbs any components of fluid precursor 36 disadvantageously, such as adsorption of dyes, this is minimized.
- Another advantage is that with a thermally-curable precursor the technique is made much easier since the time required for the process is very fast relative to typically curing times.
- a cladding can be provided upon the waveguide array to form a waveguide assembly 44 by adding a hardenable cladding precursor fluid 40 on top of the array, optionally forming fluid 40 into a desired shape with a desired thickness above and beside the waveguide array by, for example, positioning a cladding mold 42 above the precursor to form the precursor, allowing the cladding precursor to harden (for example, via polymerization) and removing cladding mold 42 to form a cladding 43 that includes a layer of cladding above waveguides 38 .
- a cladding mold 168 can be used which molds cladding precursor 40 between waveguides 38 and laterally of waveguides 38 , but does not allow formation of cladding above the waveguides to form an assembly 172 .
- the cladding mold 168 is a flexible elastomeric mold that conforms to form a mold resting atop waveguide 38 .
- the cladding precursor is allowed to harden, and removal of the mold results in a cladding 170 that fills spaces between waveguide 38 , and extends laterally beyond the lateral-most waveguides such that each side of each waveguide is contacted by cladding, but the top of each waveguide is exposed.
- a waveguide assembly 174 can be formed by applying cladding precursor 40 to waveguides 38 , allowing the cladding precursor to drip off of the waveguides, and hardening the cladding precursor.
- the substrate/waveguide/cladding assembly can be cleaved along lines a-a and b-b to define a waveguide assembly 44 , 172 or 174 having a typical waveguide width x on the order of less than about 100 microns, typically on the order of from about 1 to about 10 microns, more typically from about 2 to about 4 microns, a waveguide height y on the order similar to that of dimension x, more typically slightly less than x, for example about 1 micron, and, in the case of waveguide assembly 44 , an overall assembly height including cladding of a dimension z on the order of dimension y to about 10 times dimension y, for example from about 1 to about 10 microns and a length l of any of a wide variety of lengths on the order of 100 microns to centimeters.
- waveguides can be made as well, for example waveguides having width or height on the order of 200 or 250 microns, with spacing of similar order.
- the cladding height equals the waveguide height, and in the case of 174 the cladding height typically is very slightly greater than the waveguide height.
- Another technique for fabricating a waveguide assembly 172 including waveguides 38 and cladding 170 which contacts the sides, but not the tops of waveguides 38 is as follows. Following fabrication of waveguides 38 , and prior to application of any cladding, a microcontact printing technique as described in international patent publication no. WO 97/07429, of international patent application no.
- PCT/US96/13223 entitled “Patterned Materials Deposition Effected with Microcontact Printing” is carried out to apply a hydrophobic component selectively to the tops, but not the sides of waveguides 38 , followed by addition of a hydrophilic cladding prepolymeric precursor which assembles within and between waveguides 38 , but not atop waveguides 38 , followed by curing of the cladding precursor.
- the particular microcontact printing technique involves coating a flat applicator with a self-assembled monolayer forming molecular species and applying the flat applicator to waveguides 38 such that the applicator contacts only the tops of waveguides 38 .
- any molecular species transferable in this manner can be used to create a hydrophobic functionality atop waveguides 38 such that a hydrophilic prepolymer will assemble between waveguides 38 and laterally on either side, or the opposite can be carried out in which a hydrophilic material is applied to the tops of waveguides 38 and a hydrophobic cladding precursor used to fill spaces between and laterally of the waveguides where the waveguides and surface 28 of substrate 30 is sufficiently hydrophobic.
- surface 28 and waveguides 38 were subjected to oxidizing treatment, and microcontact printing was used to transfer a self-assembled monolayer of a fluorine-terminating molecule to the surface.
- tridecafluoro-1,1,2,2-tetrahydro(o-octyl)-1-trichlorosilane was applied to the tops, but not sides, of waveguides 38 and formed a hydrophobic self-assembled monolayer thereon.
- a hydrophilic cladding precursor in particular a liquid polyurethane prepolymer, was added and assembled between and laterally of waveguides 38 . Curing of the polyurethane cladding precursor, followed by cleaving of the waveguide ends, resulted in a waveguide assembly similar to assembly 172 .
- cladding is added to waveguides 38 to lower the refractive index difference between waveguides 38 and their surrounding environments. Without cladding, waveguides 38 typically are very good performers, but support too many modes. Addition of cladding, which reduces the refractive index difference at the boundaries of waveguides 38 , reduces higher order modes.
- FIG. 13 is essentially identical to a cross-section through line a-a of waveguide assembly 44 of FIG. 15, showing a typical substrate 30 , optional film 31 of an adhesion promoter, native oxide layer, or the like on substrate 30 (the top surface of film 31 defining substrate surface 28 according to this embodiment), array of waveguides 38 , and cladding 43 .
- the waveguide of FIG. 13 differs from waveguides fabricated in accordance with the technique of FIG. 15 in that it includes a contoured cladding surface corresponding to a contoured cladding mold.
- Precursor 36 is a material as described above which can serve as a waveguide. Selection of such materials is within the level of ordinary skill in the art.
- substrate 30 can be essentially any material including those materials described above, but should be optically smooth.
- Substrate surface 28 can be of the same material as the bulk material of substrate 30 , or a different material.
- a non-limiting, exemplary list of substrate materials includes silver, gold, glass, silicon/silicon dioxide, and the like.
- the waveguide pattern can be formed on contoured surfaces, and flexible surfaces. Where substrate 30 is flexible (for example, a polyvinylchloride film) the waveguide can be deformed while guiding light. The utility of this technique will be described more fully below.
- article 20 can be as described above, and preferably is elastomeric.
- Selection of materials for waveguide 38 , cladding 43 , and substrate 30 (and optional film 31 ) can be selected by those of ordinary skill in the art to form a structure that can guide electromagnetic radiation of a desired frequency.
- total internal reflection of electromagnetic radiation will occur within waveguide 38 where the electromagnetic radiation propagating within the waveguide strikes an interior boundary of the waveguide to form an angle ⁇ , with a line normal to the interior boundary, where sin ⁇ is ⁇ (refractive index of the cladding)/(refractive index of the waveguide).
- cladding 43 can be non-existent.
- the cladding can be the environment surrounding the waveguide, such as air.
- waveguides 38 and cladding 43 can be formed from an identical, or nearly identical fluid prepolymer, the degree of polymerization of which can be controlled by the amount of exposure to polymerization conditions such as heat or radiation.
- polymerization is meant to encompass cross-linking. This technique is facilitated by the fact that the refractive index of a solid typically is greater than the refractive index of a liquid of similar composition in that the density of a solid typically is greater than of a liquid. The difference in index of refraction typically decreases with curing time for a polymer. Thus, the difference in refractive index can readily be tailored. This technique provides several advantages that will become apparent from the discussion below.
- prepolymer fluid 36 (with reference to FIG. 15) that is positioned with article 20 against substrate surface 28 and polymerized, for example photopolymerized, followed by addition of a common prepolymer (the same prepolymer) cladding precursor 40 which then can be photopolymerized.
- cladding prepolymer 40 waveguide 38 is cured to a greater extent, and the refractive index difference between cladding 40 and waveguide 38 decreases during curing of cladding 40 .
- One advantage of the transfer technique of FIG. 15 is that it is exceptionally simple experimentally, and very inexpensive. It can readily be used to produce multiple copies of complex microstructures. Another advantage of the technique is that many waveguides can be fabricated essentially simultaneously. Tens or hundreds of applicators 20 can be fabricated from a single master which is, in turn, fabricated from a photolithographically-created surface or the like, and each applicator can be used to fabricate hundreds or thousands of waveguides.
- one molding process as illustrated in FIG. 15 can result in more than 4,000 waveguides.
- FIG. 15 Another advantage of the transfer molding technique of FIG. 15 is that multiple layers of waveguides can be fabricated readily.
- applicator 20 first can be used to transfer fluid waveguide precursor 36 to substrate surface 28 where it is hardened to form waveguide array 38 , as illustrated also in FIG. 15, and then waveguide array 38 on substrate 30 can be placed upside down upon another applicator 20 including indentations filled with fluid waveguide precursor 36 , precursor 36 can be cured, and applicator 20 removed to form a two-layer stacked array 248 .
- the process can be repeated any number of times to form any number of layers of waveguide arrays, as exemplified by stacked waveguide array 250 , with the waveguides arranged in any orientation relative to each other in which support for each layer is provided.
- periodicity in the cladding structure 43 (FIG. 15) can be readily formed, via a cladding mold 42 including a periodically contoured inner surface, or via irradiation of cladding 43 through a mask to cure alternating portions of the cladding to a greater extent relative to intervening portions.
- a grating can be fabricated in the cladding, such as a Bragg grating.
- Gratings also can be fabricated directly in or onto waveguides 38 by using a mold 20 in which the indentations that in part define the mold for the waveguides includes a contoured interior surface.
- Chirped waveguides and other periodic structures can be fabricated in the cladding, or in the waveguide core itself, in this technique. Attenuation can be achieved in this way, and resident cavities can be created.
- FIG. 17 is a schematic illustration of a prior at “Y” coupler including branched portions as shown, for example, in U.S. Pat. No. 5,313,545 (Kuo, et al.), including a coupling region 252 and branching input/output regions 253 , 254 , 255 , and 256 .
- Radiation input from regions 253 and 255 will couple at region 252 and will branch and travel along both branching portions 254 and 256 .
- radiation input from branches 254 and 256 can be made to couple at region 252 and branch into regions 253 and 255 , optionally constructively or destructively interfering to some extent in region 252 .
- FIG. 18 is an illustration of a prior art “evanescent” coupler, the principle of which is used to provide coupling between guides of U.S. Pat. No. 5,481,633 (Mayer).
- This coupler operates on the principle that, depending upon the refractive index between waveguide and surrounding environment (e.g., cladding) the waveguide dimensions (size and shape), the wavelength of light, and separation between waveguides, an “evanescent tail” extends from each waveguide, the energy of the tail decreasing with distance from the guide. Where waveguides are close enough to each other, and the evanescent tail passes into the adjacent waveguide, radiation can leak into the adjacent waveguide and the waveguides couple.
- waveguide 258 includes a coupling portion 260 and non-coupling portions 262 and 264 and waveguide 266 includes a coupling portion 268 and non-coupling portions 270 and 272 .
- coupling portions 260 and 268 are close enough such that the evanescent tail of radiation in each guide passes into the adjacent guide and coupling occurs in these regions.
- non-coupling portions 262 , 264 , 260 , and 272 each are separated from the adjacent waveguide by a distance that does not allow coupling. Coupling thus controllably occurs only at regions 260 and 268 , which thereby defines a coupling junction.
- the prior art arrays of FIGS. 17 and 18 are suitable for many purposes, but, as can be seen, requires significant control and geometry of construction.
- the particular shape of the waveguide required for either of the couplers of FIGS. 17 and 18 is limited also by the fact that curves or comers that form part of the shape of a waveguide should not exceed a maximum amount of sharpness, or the critical angle of total internal reflection will be exceeded and loss of electromagnetic radiation will occur.
- FIG. 19 illustrates an array including essentially parallel waveguides 274 and 276 and cladding 278 which can completely envelope and cover waveguides 274 and 276 , or the like.
- Each of waveguides 274 and 276 and cladding 278 can be formed from an identical prepolymeric precursor with differences in refractive index controlled by different curing times.
- the array of waveguides 274 and 276 and cladding 278 includes central portion 280 and lateral portions 282 and 284 .
- region 280 defines a coupled region of the waveguides that is functionally similar to the coupled portions 260 and 268 of waveguides 258 and 266 of FIG. 18, and coupled portion 252 of the branched structure of FIG. 17. This can be achieved, for example, as follows.
- Waveguides 274 and 276 are fabricated from fluid polymeric precursors as illustrated in FIG. 15, and only partially cured to the extent that they are dimensionally stable. Then, the same polymeric precursor, as a cladding precursor, is placed over waveguides 274 and 276 and cured until dimensionally stable. Where the refractive index difference at this point in the process is great, coupling cannot occur through all of portions 282 , 280 , and 284 of the array. Subsequently, only portion 280 is subjected to additional photopolymerization conditions, resulting in significantly decreased refractive index differences between waveguides 274 and 276 and cladding 278 in that region ( 280 ).
- One advantage of the technique is that coupling can be tailored at any region of the waveguide array where waveguides designed to carry UV or visible light, of the type produced by a red He—Ne laser, are separated more than about 2 microns, for example up to 6 microns, 8 microns, or even 10 microns in region 280 , allowing much simpler fabrication that does not require as much precision.
- the coupling regions of FIG. 18 are defined by their separation distance, which typically must be much smaller than the separation distance allowable for the system of FIG. 19, requiring significantly greater precision and related expense.
- the locations of the regions of coupling between waveguides are tailorable, and the amount of coupling at those locations is controllable. This can be accomplished when waveguides 274 and 276 and cladding 278 are selected such that the refractive index ratio between waveguide and cladding can be changed, reversibly, after fabrication.
- the refractive index of cladding 278 can be changed reversibly based upon exposure to specific electromagnetic radiation (where, for example, cladding 278 is reversibly photosensitive; such materials are known to those of ordinary skill in the art) the array can be fabricated and region 280 irradiated with the specific radiation to cause coupling where no coupling occurs in regions 282 and 284 .
- cladding 278 can be one or more fluids contained in separate chambers that define regions 280 , 282 , and 284 , and the content of the fluid chambers can be controlled to control the refractive index ratio between waveguide and cladding.
- the above technique facilitates a waveguide coupler that can be used at different wavelengths of light. That is, where the refractive index difference at the boundaries of waveguides can be adjusted during use, or between uses, by exposure to different electromagnetic radiation, electric fields, or the like, the waveguide can be adjusted for use with different wavelengths of light. This also can be used to adjust the degree of coupling that occurs during use. For example, coupling could be adjusted from ten percent to fifty percent by exposure to electromagnetic radiation according to this technique.
- cladding 278 is an electro-optical material or other material that can reversibly change refractive index upon exposure to certain electric fields, or is a non-linear optical material (e.g., dye) that changes in refractive index in response to electromagnetic radiation
- the array can be a sensor of that electric field or electromagnetic radiation since exposure to the field or radiation will cause a detectable change in coupling between waveguide 274 and waveguide 276 .
- region 280 can be defined by a cladding that is reversibly electric field sensitive, while sections 282 and 284 are not, thus sensitivity to the specific electric field exists at region 280 only, and coupling at region 280 is indicative of the existence and strength of the field.
- the cladding of region 280 can include, on its exposed surface, a material that is sensitive to a particular analyte such that when the analyte is present, the refractive index of the cladding changes in an amount sufficient to detectably change the coupling characteristic between waveguides 274 and 276 in region 280 .
- region 280 can define a flow chamber about waveguides 274 and 276 such that a desired fluid can be reversibly placed in contact with waveguides 274 and 276 in region 280 .
- the change in the existence of, or concentration of, a particular analyte in the fluid can cause quantitative, or qualitative changes in coupling between guides 274 and 276 at region 280 , resulting in quantitative or qualitative sensing.
- a cation or anion exchange material can be provided that a surface, such as a sulfonic, phenolic, phosphoric, or carboxylic acid group, for capture of ions from solution.
- Chelating agents, kryptands, crown ethers, and the like can be used.
- the array of FIG. 19 can be constructed where, at region 280 (or other or all regions) cladding 278 includes an exposed surface that carries an immobilized biological binding partner of a biological molecule or exposed surfaces of waveguides 274 or 276 carry an immobilized biological binding partner.
- cladding 278 includes an exposed surface that carries an immobilized biological binding partner of a biological molecule or exposed surfaces of waveguides 274 or 276 carry an immobilized biological binding partner.
- the biological molecule can be provided on the cladding.
- a more sensitive sensor can result from a waveguide fabricated, with reference to FIG. 15, including exposed top surfaces.
- a medium suspected of containing the biological molecule is exposed to the surface of cladding 278 , waveguide 274 and/or 276 (at region 280 ) if region 280 carries the biological binding partner exclusively and, if present, the biological molecule binds to its immobilized binding partner, changing the refractive index of cladding 278 (e.g. at region 280 ) and thereby changing the refractive index ratio between the waveguides and cladding in that region, detectably altering coupling.
- cladding 278 form only a very thin layer above waveguides 274 and 276 , such that biological binding at the outermost surface of the cladding produces a greater relative effect in change of refractive index ratio between waveguide and cladding.
- the cladding may be non-existent and the biological molecule can be immobilized directly upon a surface of the waveguide, or the cladding can partially cover the waveguide surface with remaining portions of the waveguide surface carrying the immobilized binding partner.
- biological binding pairs any of a variety of biological binding pairs can be used, one member of the pair immobilized at cladding 278 or waveguides 274 and 276 and the other member being the analyte.
- biological binding pairs is as defined above, referring to a corresponding pair of molecules that exhibit mutual affinity or binding capacity, typically specific or non-specific binding or interaction, including biochemical, physiological, and/or pharmaceutical interactions.
- substrate 30 can be flexible. This facilitates a method involving guiding electromagnetic radiation through a waveguide array of at least two waveguides, simultaneously, while altering the conformation of the waveguides. That is, the substrate carrying a plurality of waveguides can be bent or otherwise deformed during electromagnetic radiation propagation. This can be useful for a variety of purposes, one of which is increased sensitivity in a sensor. Where a sensor is sensitive to changes in a surface of a waveguide or cladding that occur upon exposure to an analyte, as described above, sensitivity can be increased as follows.
- the waveguide can be bent to its limit of maintaining total internal reflection, which is readily determined by bending the waveguide too far and then returning the waveguide to a conformation allowing total internal reflection.
- loss of electromagnetic radiation passing through the waveguide can be indicative of interaction with an analyte, and is made much more sensitive where the waveguide is almost at the limit of maintaining total internal reflection prior to exposure to the analyte.
- an array 286 of waveguides 288 , 290 , 292 , 294 and 296 which are essentially linear and parallel, is illustrated.
- the array is fabricated such that conditions allow coupling between waveguides, as described above, light introduced into waveguide 292 can couple into waveguides 290 and 294 , and from waveguide 290 can couple back into waveguide 292 and into waveguide 288 , and from waveguide 294 can couple back into waveguide 292 and into waveguide 296 .
- an interferometer is created and an interference pattern defined by radiation emerging from each of waveguides 288 - 296 is created and is distinctive based upon spacing of the waveguides, refractive index difference between waveguide and cladding, waveguide dimensions, wavelength of radiation, and propagation length.
- the system of FIG. 20 can serve as a sensor since any change in refractive index differs at the boundaries of one or more waveguides, for example a difference in refractive index of the cladding surrounding waveguides 288 - 296 such as via exposure to an electric field or electromagnetic radiation, exposure to a fluid, or exposure to another analyte as described above will alter the interference pattern emerging from waveguides 288 - 296 .
- PDMS poly(dimethylsiloxane)
- an array of waveguides 38 was formed by filling the relief structure (indentations 24 ) in applicator surface 22 of applicator 20 with a liquid prepolymer (polyurethane, NOA-73, Norland Products New Brunswick, N.J.) and then placing the applicator surface of the filled applicator 20 on substrate surface 28 of a Si( 100 ) wafer 30 supporting a 2 micron-thick layer of SiO 2 .
- the prepolymer was cross-linked in situ by irradiating the system for 1 hour at a distance of 1 centimeter with a 450 W medium-pressure Hg vapor lamp (type 7825-34, Ace Glass, Vineland, N.J.).
- the elastomeric mold (applicator 20 ) was peeled away, leaving an array of waveguide structures 38 on substrate 30 .
- the technique was pattern used to generate waveguides with a variety of widths of 2.0, 2.6, 3.0, and 4.0 microns, and spacings of 2.0, 4.0, and 8.0 microns. All waveguides had the same height of approximately 1 micron.
- the length of the waveguides was determined by the points at which the wafer was fractured. In one set of embodiments the waveguide array was left unclad.
- cladding was made by providing a thick layer of the same liquid prepolymer and applying it to the waveguides, the surfaces of which had been slightly oxidized by exposure for about 10 minutes in a UV-ozone cleaner (models 13550 and 13550-2, Boekel Industries) to render them hydrophilic and improve adhesion.
- the system was heated to 85° C. on a hot plate to decrease the viscosity of the prepolymer, and the excess prepolymer was allowed to drain to one edge.
- the thin layer of prepolymer left on the surface was loosely cross-linked by brief (1 minute) exposure to UV light (365 nm) from a 4 W hand-held lamp (Blak-Ray UV lamp model UVL-21, UVP, San Gabrielle, Calif.).
- the ends of the clad waveguides were squared by cleaving the substrate. After cleaving, the cladding was cured completely (30 seconds) with the 450 W medium-pressure Hg vapor lamp. This procedure allowed the ends of the waveguides to be cleaved when the cladding layer was in the liquid phase, preventing the cladding from deadhering from the guides.
- FIG. 21 is a photocopy of an SEM image of an unclad waveguide array
- FIG. 22 is a photocopy of an SEM image of a clad array, each fabricated according to this technique.
- waveguide width was about 2.6 microns
- waveguide spacing was about 2.0 microns
- waveguide height was about 1.0 microns.
- FIG. 23 is a schematic diagram of apparatus used to couple light into and out of waveguide arrays fabricated as described immediately above.
- Light from a He—Ne laser 298 (633 nm) was first coupled into a single-mode optical fiber 300 which was butt-coupled to the end of waveguides of array 302 (representative of a variety of waveguide arrays fabricated as described immediately above, and tested in accordance with this example) using a precision 3-dimensional translation stage 304 .
- Light also could be coupled into the waveguide array using focusing apparatus. That is, light from a laser could be focused, through a lens arrangement, to the end of waveguides of the array 302 .
- FIGS. 24 a - g show the results of a variety of different waveguide arrays and inputs, and demonstrate tailorable coupling, using the apparatus of FIG. 23 and waveguide arrays fabricated as described above.
- trapezoidal waveguides 38 indicate the positions, in cross-section, of 3 micron-wide waveguides with neighboring waveguides separated by 8 microns. The height of each waveguide was 1 micron.
- Optical fiber 300 was positioned as indicated, in alignment with the central of the 5 waveguides.
- FIG. 24 b is a photocopy of a CCD camera frame grab of the output of the system of FIG. 24 a . A single-mode output occurred, with no evanescent coupling between adjacent waveguides.
- FIG. 24 b is a photocopy of a CCD camera frame grab of the output of the system of FIG. 24 a . A single-mode output occurred, with no evanescent coupling between adjacent waveguides.
- FIG. 24 b is a photocopy of a C
- FIG. 24 c is representative of a second waveguide structure fabricated in accordance with the technique described above, with waveguides separated by 4 microns, rather than 8 microns.
- the UV exposure time for the array of FIG. 24 c was the same as for the array of FIG. 24 a .
- the 4 micron spacing was small enough to allow evanescent coupling between guides and light was observed in 5 adjacent waveguides (FIG. 24 d : photocopy of a CCD camera frame grab of result).
- this output pattern moved in register.
- the reproducibility and symmetry of the pattern established the uniformity of the coupling between the waveguides in the array.
- the low level of light at the exit of the central waveguide was caused by efficient coupling of light from the central waveguide into adjacent waveguides.
- FIG. 24 e demonstrates the ability to modify the coupling between adjacent waveguides by controlling the difference in refractive indices between the guides and their cladding by manipulating exposure time during UV curing.
- FIG. 24 e is a photocopy of a CCD camera frame grab of output of the waveguide of FIG. 24 c (which produced the pattern of FIG. 24 d ) after additional exposure of the array (waveguides plus cladding) under the 450 W medium-pressure Hg vapor lamp. This exposure reduced the index difference between waveguide core and cladding, and increased the coupling between the waveguides. The change is most easily seen in the change in brightness of the center waveguide between FIG. 24 d and FIG. 24 e .
- FIG. 24 e is a photocopy of a CCD camera frame grab of output of the waveguide of FIG. 24 c (which produced the pattern of FIG. 24 d ) after additional exposure of the array (waveguides plus cladding) under the 450 W medium-pressure Hg vapor lamp. This exposure
- the center waveguides formed an interferometer.
- Light from the single waveguide directly addressed by optic fiber 300 was evanescently coupled into nine waveguides and many closed-path interferometers were formed.
- FIG. 24 g shows the output of the array when light was coupled into cladding between the waveguides as shown in FIG. 24 f .
- Two-micron-high clad waveguides of width 2.0, 2.6, 3.0, and 4.0 microns and spacing of 2, 4, and 8 microns were fabricated. These taller waveguides had cross-sections approximately equal to the 3.3 micron mode diameter of the optical fiber 300 , and gave a coupling efficiency of approximately 35% for a 6 millimeter-long waveguide. Propagation loss was measured in these waveguides to be less than 0.6 dB/cm, which is the limit of measurement uncertainty in the system used.
- FIG. 25 illustrates another embodiment of the invention for formation of a structure on a substrate surface using a forming article.
- fluid precursor 36 is first placed on substrate surface 28 , then forming article 20 is brought into contact with fluid precursor 36 and pressed against substrate surface 28 such that the contact surface 26 of the article seals portions of surface 28 that it contacts, thereby forming channels, defined by indentations and portions of substrate surface 28 not contacted by contact surface 26 of the forming article.
- This is another embodiment in which a micromold is created, defined by article 20 and substrate surface 28 .
- the applicator is removed resulting in structure 38 which, depending upon the material selected, can be further cured or sintered and which may shrink in the process.
- a drop of fluid precursor 36 (referring to FIG. 25), was placed on a freshly cleaned substrate and then article 28 was placed face down upon the substrate. A pressure of roughly 10 psi was applied. The area of the patterned surface was typically 1-5 cm 2 with feature sizes in the micron range. Liquid dewetting of the surface upon application of the applicator was carried out to allow contact of the contact surface 26 of article 20 and the substrate in regions where no fluid precursor derived material was desired. Dewetting is driven by both applied pressure and difference of interfacial tension between fluid precursor 36 and contact surface 26 of article 20 .
- S ⁇ LS + ⁇ LE ⁇ ⁇ SE ; ⁇ LS is the liquid-substrate interfacial tension, ⁇ LE is the liquid-elastomer interfacial tension and ⁇ SE is the substrate-elastomer interfacial tension.
- ⁇ SE is fixed, the interfacial tension of the fluid precursor solution was increased in order to accelerate dewetting.
- pressure improves the definition of features, it cannot be increased too much because of the deformations induced in the mold if deformation is not required.
- Diluting fluid precursor with a suitable solvent in the working examples, acetonitrile, a polar solvent with low viscosity and high surface tension that does not s
- a 50-nm thick gold film was prepared on a ⁇ 100> silicon wafer primed with 2 nm of titanium by e-beam evaporation.
- a monolayer of hexadecanethiolate was patterned on the wafer using microcontact printing so that the resulting pattern presented uncovered 2- ⁇ m squares, and the unprotected gold was removed with a cyanide etch.
- the native silica oxide layer was then removed by etching in 2% HF for 30 sec.
- the silicon was etched in a 40% by weight solution of KOH in water and isopropanol; this anisotropic etch generated pyramidal pits.
- the remaining gold was removed with aqua regia.
- the surface of the resulting textured solid was treated by putting the wafer under static vacuum with a drop of (tridecafluoro-1,1,2,2-tetrahydro-octyl)-1-trichlorosilane for 30 min. This compound polymerized on the surface and made a layer that reduced adhesion to the surface.
- the resulting array of silica pyramids prepared by this technique was analyzed via SEM.
- the radius of curvature at the tips of the pyramids was less than 50 nm and the angle of the side of the pyramid was 54-58°. This value is compatible with that obtained with this type of silicon etching. (Barycka, et al., Sensors and Actuators , 1995, A48, 229). This demonstrates that shrinkage taking place during annealing is essentially isotropic.
- the sol-gel precursor was molded against a Si/SiO 2 wafer whose surface had been passivated by silanization. The structure was annealed at 1100° C. It measured 5 ⁇ 5 ⁇ 0.3 mm.
- Optical waveguides of doped silica on Si/SiO 2 were formed.
- the silica was doped with aluminum oxide in order to increase its refractive index.
- Low scattering by the edges of the waveguides can be achieved by an annealing step at a temperature where the viscosity is low enough to allow relaxation of the roughness. In the second working example described below, this temperature was reduced by adding boron oxide to the silica.
- FIGS. 26-29 are photocopies of SEM images of waveguides produced in accordance with this aspect of the invention.
- FIG. 26 is a photocopy of an SEM image of an aluminosilicate waveguide.
- FIGS. 27 and 29 are photocopies of SEM images of borosilicate waveguides.
- FIGS. 27 and 28 show borosilicate lines at different stages of sintering: FIG. 27 shows borosilicate lines after annealing at 800° C. for 10 minutes.
- FIG. 28 shows the lines after annealing at 900° C. for 10 minutes.
- the composition of the glass was found by XPS to be 9% B 2 O 3 and 91% SiO 2 .
- the waveguiding behavior of the aluminosilicate lines was characterized by coupling a 633-nanometer light beam into one end of a 5 mm long line and imaging the other end. The lines appeared to be single mode waveguides with slight coupling between adjacent lines.
- sensors of biological or chemical molecules, or the like that can be made using waveguides fabricated in accordance with the invention.
- sensors of displacement can be provided.
- the waveguide array is subjected to compression or tensile forces in a direction perpendicular to the waveguides, causing the waveguides to move closer to or farther apart from each other, coupling between waveguides will change detectably.
- This can serve as a displacement sensor, pressure sensor, tension sensor, or the like.
- the waveguide array can be arranged to sense a force by being bent, for example to sense a force applied to an edge of the waveguide, and when the waveguide is bent spacing between waveguides will change and the coupling pattern will change.
- Waveguides made of glass as described above may also serve as active devices for integrated optics.
- aluminosilicate waveguides can be doped with rare earth, like neodymium or erbium.
- Doped waveguides can be used as integrated light-amplifiers or lasers when placed in a suitably geometry.
- a regular array of doped waveguides fabricated by this method, when put in a resonant cavity, could exhibit a very interesting behavior where all the lasers would be in phase, leading to a much higher intensity light beam.
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Manufacturing & Machinery (AREA)
- Health & Medical Sciences (AREA)
- Mechanical Engineering (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Analytical Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Robotics (AREA)
- Composite Materials (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Materials Engineering (AREA)
- Crystallography & Structural Chemistry (AREA)
- Optical Integrated Circuits (AREA)
Abstract
Chemically or biochemically active agents or other species are patterned on a substrate surface by providing a micromold having a contoured surface and forming, on a substrate surface, a chemically or biochemically active agent or fluid precursor of a structure. A chemically or biochemically active agent or fluid precursor also can be transferred from indentations in an applicator to a substrate surface. The substrate surface can be planar or non-planar. Fluid precursors of polymeric structures, inorganic ceramics and salts, and the like can be used to form patterned polymeric articles, inorganic salts and ceramics, reactive ion etch masks, etc. at the surface. The articles can be formed in a pattern including a portion having a lateral dimension of less than about 1 millimeter or smaller. The indentation pattern of the applicator can be used to transfer separate, distinct chemically or biochemically active agents or fluid precursors to separate, isolated regions of a substrate surface. Waveguide arrays, combinatorial chemical or biochemical libraris, etc. can be made. Differences in refractive index of waveguide and cladding can be created by subjecting the waveguide and cladding, made of indentical prepolymeric material, to different polymerization or cross-linking conditions. Interferometers are defined by coupling arrays of waveguides, where coupling can be controlled by altering the difference in refractive index between cladding and waveguide at any desired location of the array. Alteration and refractive index can be created photochemically, chemically, or the like. Sensors also are disclosed, including biochemical sensors.
Description
- This application is a divisional of U.S. patent application Ser. No. 09/634,201, filed Aug. 9, 2000 (pending); which is a divisional of U.S. patent application Ser. No. 09/004,583, filed Jan. 8, 1998 (now U.S. Pat. No. 6,355,198); which is a continuation-in-part of U.S. application Ser. No. 08/616,929, filed Mar. 15, 1996 (abandoned); Ser. No. 09/004,583 also claim priority under 35 U.S.C. §119(e) of the benefit of co-pending U.S. provisional application serial No. 60/046,689 filed May 16, 1997, all of which are incorporated herein by reference.
- [0002] Research leading to the invention disclosed and claimed herein was supported in part by the Office of Naval Research, ONR Contract No. N00014-93-I-0498, and by the National Science Foundation, NSF Grant No. PHY 9312572. The U.S. Government may have certain rights to the invention.
- The present invention relates generally to microprocesses at surfaces, and more particularly to the formation of micropatterned articles such as waveguides, sensors, and switches on substrates from fluid precursors, and mechanisms for micro-scale positioning of biologically active agents at predetermined regions of a surface.
- In the fields of chemistry, biology, materials science, microelectronics, and optics, the development of devices that are small relative to the state of the art and conveniently and relatively inexpensively reproduced is important.
- A well-known method of production of devices, especially in the area of microelectronics, is photolithography. According to this technique, a negative or positive resist (photoresist) is coated onto an exposed surface of an article. The resist then is irradiated in a predetermined pattern, and portions of the resist that are irradiated (positive resist) or nonirradiated (negative resist) are removed from the surface to produce a predetermined pattern of resist on the surface. This is followed by one or more procedures. According to one, the resist may serve as a mask in an etching process in which areas of the material not covered by the resist are chemically removed, followed by removal of resist to expose a predetermined pattern of a conducting, insulating, or semiconducting material. According to another, the patterned surface is exposed to a plating medium or to metal deposition (for example under vacuum) followed by removal of resist, resulting in a predetermined plated pattern on the surface of the material. In addition to photolithography, x-ray and electron-beam lithography have found analogous use.
- In an article entitled “Materials for Optical Data Storage”, by Emmelius, et al.,Angewandte Chemie, Int. Ed. (English), 28, 11, 1445-1600 (November, 1989), a review of methods of making CD/ROM, WORM, and EDRAW optical storage disks is presented. According to one method, photolithography is used to create a pattern of protrusions on a surface that can serve as a master for fabrication of articles that have a surface including a series of ridges and protrusions complementary to the photolithographically-produced master. These articles, including microridges and grooves at one surface, can be combined with other materials in a layered structure to form an optical storage device. An article in the Phillips Technical Review,
volume 40, number 10 (1982), entitled “Manufacture of LaserVision Video Disks by a Photopolymerization Process”, by Haverkorn, et al., discusses similar technology. U.S. Pat. Nos. 5,170,461 (Yoon, et al.), U.S. Pat. No. 4,959,252 (Bonnebat, et al.) and U.S. Pat. No. 5,141,785 (Yoshinada, et al.) describe optical elements such as waveguides and optical recording media. Yoshinada, et al. describe a process involving coating a substrate with a polymer or prepolymer, pressing a contoured stamp into the polymer or prepolymer to create a contoured pattern in a surface of the polymer or prepolymer complementary to the contoured surface of the stamp, removing the stamp, and adding a reflective layer to the contoured surface of the polymer or prepolymer for use as an optical device. - Photolithographic techniques for fabricating surfaces with positional control of chemical functionalities at submicron resolution is described in an article entitled “Patterning of Self-Assembled Films Using Lithographic Exposure Tools”, by Dressick, et al.,Jpn. J. Appl. Phys., 32, 5829-5839 (December, 1993). The technique involves exposure of a self-assembled film to deep UV irradiation through a mask. According to one technique, photochemical cleavage of an organic group occurs in exposed regions followed by chemical reactivity selectively at those regions.
- Photolithography has found application in the biological arena as well. Sundberg, et al. describe a method for patterning receptors, antibodies, and other macromolecules at precise locations on solid substrates using photolithographic techniques in combination with avidin or streptavidin/biotin interaction in an article entitled “Spatially-Addressable Immobilization of Macromolecules on Solid Supports”,J. Am. Chem. Soc., 117, 12050-12057 (1995).
- Reactive ion etching is a process that is useful in the semiconductor industry and other arenas for forming very small structures having a very high aspect ratio (a very high height/width ratio of features). Reactive ion etching is a dry process in which a gas is accelerated towards a surface to effect etching, in contrast to wet etching processes in which a liquid is simply allowed to contact certain regions of a surface and to chemically react at those regions. In wet etching processes, etching typically takes place not only in a direction perpendicular to the surface, but horizontally, as well. That is, with wet etching it can be difficult to etch relatively precise, vertical channels in a surface. Instead, the sidewalls of the channel are etched horizontally also. Reactive ion etching provides an advantageous alternative for etching channels with good, near-vertical sidewalls.
- Reactive ion etching masks should have certain characteristics such as good hardness, inertness to the etchent species, and in many cases electrical insulating properties. Thus, materials suitable for reactive ion etching masks are limited. Many metal masks, such as gold masks, are unsuitable since the metals can sputter easily. Polymeric masks typically degrade under reactive ion etching conditions. A typical prior art reactive ion etching mask is made of silica and is formed by creating a layer of silica on a surface and etching the layer selectively to create a silica mask, using photolithography. Such procedures can be costly. In an article entitled “Poly(siloxane)-based Chemically Amplified Resist Convertable into Silica Glass”, by Ito, et al.,Jpn. J. Appl. Phys., 32, 6052-6058 (1993), a poly(siloxane)-based chemically amplified resist is reported. A polymeric glass precursor is converted into silicate glass through a lithographic procedure.
- Waveguides are generally defined by a core, surrounded by a cladding, that acts as a guide of electromagnetic radiation. The waveguide can propagate radiation via total internal reflection of the radiation within the core. Waveguides have served as important components of sensors and switches, and have been fabricated from a variety of materials including inorganic materials such as glasses and organic materials such as polymers. Polymeric waveguides have been fabricated using reactive ion etching, ultraviolet (UV) laser and electron-beam writing, induced dopant diffusion during polymerization (photo-locking and selective polymerization), selective poling of electro-optically active molecules induced by an electric field, and polymerization of self-assembled prepolymers. One common technique for forming polymeric waveguides is injection molding. For example, voids in a cladding material (or substrate) can be filled, via injection molding, with a core material. However, problems associated with this technique include softening and deformation of the cladding or substrate under temperatures required for injection molding. Fabrication with precision is compromised, typically. In an additional prior art technique, a polymeric film is spun onto a substrate and portions of the film are subsequently exposed to light by a photolithographic process, thereby changing the refractive index of a polymeric film and creating a waveguide in the film. This technique requires expensive and complicated photolithographic systems for base formation of the waveguide array, and subsequent multi-step processing is required such as removal of the polymeric film from the substrate, lamination processing, curing processing, and other processing steps.
- U.S. Pat. No. 5,136,678 (Yoshimura) describe fabrication of an optical waveguide array by providing a clad substrate having a number of grooves arranged in lines on a surface of the substrate, the substrate being resistant to a UV-curable resin. A UV-curable resin is used to fill the grooves in the substrate and is UV cured to form a core material, and a covering clad portion is formed over the structure of a material that is the same as or close to the material used as the substrate “cladding”.
- U.S. Pat. No. 5,313,545 (Kuo, et al.) describes a technique in which a two-part mold made of stainless steel, aluminum, ceramic, or the like is used to mold a polymeric waveguide core material via injection molding. The mold is opened via removal of the two portions, and the waveguide is placed in a second mold into which is injected a cladding material. Kuo, et al. report that a post-mold curing process is sometimes needed to maximize optical and physical qualities of core regions, support apparatus, and end portions.
- U.S. Pat. No. 5,390,275 (Lebby, et al.) describe a method for manufacturing a molded waveguide. A first cladding layer is provided, and channels are formed in the first cladding layer. The channels in the first cladding layer are filled with an optically transparent polymer, and a second cladding layer is subsequently affixed over the channels thereby enclosing them.
- U.S. Pat. No. 5,481,633 (Mayer) describes vertical coupling structures in which waveguide patterns include sections that lie in close proximity with other sections, for example one directly above another, such that the distance between coupling portions is very small and coupling between different guides can occur.
- Biological and chemical interactions can be studied on the micro scale using combinatorial chemistry. This technique, as described inChemical & Engineering News, 74, 7, 28-73 (Feb. 12, 1996), involves formation of different biological or chemical species in a grid pattern on a surface and used, for example, to screen compounds for potential biological or chemical activity. An article entitled “Combinatorial Chemistry-Applications of Light-Directed Chemical Synthesis”, by Jacobs, et al., Trends in Biotechnology, 12, 19-26 (January, 1994) describes a photolithographic process used in a spatially-addressable synthesis technique for forming a combinatorial library involving photolithography. A surface is derivatized with amine linkers that are blocked by a photochemically cleavable protecting group. The surface is selectively irradiated to liberate free amines that can be coupled to photochemically blocked building blocks. The process is repeated with different regions of the surface being exposed to light and involved in synthesis until a desired array of different compounds, in a grid pattern on the surface, is prepared. Each of these compounds then is assayed simultaneously for binding or activity. Binding “hits” can be identified by the particular location at which binding on the surface occurs.
- While the above techniques represent, in some cases, useful advances in the art, many of these techniques require relatively sophisticated apparatus, are expensive, and generally consume more reactants and produce more by-products in collateral fabrication steps than is optimal, and/or lack optimal versatility in application. It is an object of the present invention to provide a variety of techniques for modifying a surface chemically and/or biologically at the micro and nanoscale, and to form very small scale structures, including waveguides and masks for etching processes conveniently, inexpensively, and reproducibly.
- The present invention provides techniques for derivatizing surfaces, biologically, chemically, or physically, according to predetermined patterns. The derivatized surfaces find a variety of uses in a variety of technical areas, or a structure formed on the surface can be removed from the surface and find utility separate from the surface. The invention involves, according to one technique, a method for creating a pattern of a species at a defined region proximate a substrate surface. The method involves providing an article having a contoured surface including at least one indentation defining a pattern and forming at a first region proximate the substrate surface, in a pattern corresponding to the indentation pattern, a fluid precursor of the species. The fluid precursor is allowed to harden at the first region of the substrate surface in a pattern corresponding to the indentation pattern and in an area including a portion having a lateral dimension of less than about 1 mm. A second region proximate the substrate surface, contiguous with the first region, remains free of the species.
- The invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface. The method involves positioning an article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a chemically active agent. A chemical reaction involving the chemically active agent then is allowed to take place at the first region proximate the substrate surface.
- The invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface that involves providing an article having a contoured surface including at least one indentation defining a pattern, forming at a first region proximate the substrate surface, in a pattern corresponding to the indentation pattern, a chemically active agent, and allowing a chemical reaction to take place proximate the first region of the substrate surface. The chemical reaction takes place in a pattern corresponding to the indentation pattern and in an area including a portion having a lateral dimension of less than about 1 mm. A second region proximate the substrate surface, contiguous with the first region, remains free of the reaction.
- The invention also provides a method of applying a biochemically active agent to a region proximate a substrate surface. An article having a contoured surface, as described above, is used to form, at a first region proximate the substrate surface and in a pattern corresponding to the indentation pattern, a pattern of the biochemically active agent. The method can further involve allowing a biochemical interaction involving the biochemically active agent to take place proximate the first region of the substrate surface in a pattern corresponding to the indentation pattern. The first region can be defined by an area having a lateral dimension of less than about 1 mm, and a second region proximate the substrate surface, contiguous with the first region, can be left free of the biochemical interaction. The biochemically active agent can be a biological binding partner that can be used in subsequent binding with other agents.
- The invention also provides a method of creating a pattern of a species proximate a substrate surface that includes positioning a forming article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a fluid precursor of the species. The fluid precursor is allowed to harden and the forming article is removed from the substrate surface.
- The invention also provides a method of promoting a chemical reaction at a defined region proximate a substrate surface. The method involves transferring a chemically active agent from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface in a pattern corresponding to the indentation pattern. A second region proximate the surface, contiguous with the first region, is allowed to remain free of the chemically active agent. A chemical reaction involving the chemically active agent can take place at the first region.
- The invention also provides a method of promoting a biochemical interaction at a defined region proximate a substrate surface that involves transferring a biochemically active agent from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface in a pattern corresponding to the application pattern. A second region proximate the surface, contiguous with the first region, can remain free of the biochemically active agent. A biochemical interaction involving the biochemically active agent can be allowed to take place at the first region.
- The invention also provides a method of applying to a substrate surface a biochemically active agent that involves positioning an article proximate a substrate surface and applying, to a first region proximate the substrate surface via capillary action involving the article, a biochemically active agent. A biochemical interaction involving the biochemically active agent is allowed to take place at the first region.
- The invention also provides a method for applying essentially instantaneously to a first and a second region proximate a substrate surface separated from each other by an intervening region, distinct first and second chemically active agents, respectively. The intervening region is left essentially free of the chemically active agent. The method can involve allowing a chemical reaction involving at least one chemically active agent to subsequently take place proximate the first or second region. The method also can involve applying essentially instantaneously to the first and second regions distinct first and second biochemically active agents while leaving the intervening region free of the biochemically active agent.
- The invention also provides a method involving applying essentially instantaneously to a first and a second region proximate a substrate surface distinct first and second biochemically active agents, respectively. The first and second regions are separated from each other by an intervening region that remains free of biochemically active agent. The method can be carried out as well with first and second biochemically active agents that are the same.
- The invention also provides a method involving applying a first reactant to a first region proximate a surface and allowing a first reaction to take place at the first region. A second reactant then is applied to a second region proximate the surface that is different from the first region but that includes a portion intersecting the first region. The first region is blocked except at the intersecting region during this step, thereby preventing the first reactant from contacting the first region except at the intersecting portion. A second reaction is allowed to take place at the second region, thereby creating a first chemical characteristic at the first region except at the intersecting portion, a second chemical characteristic at the second region except at the intersecting portion, and a third chemical characteristic at the intersecting portion.
- The invention also provides a method of establishing a first chemical functionality at a first region proximate a substrate surface and a different chemical functionality at a second region proximate the substrate surface contiguous with the first region. The method involves applying to the first region proximate the substrate surface a deprotecting species to chemically deprotect the first region of the substrate surface and thereby render it chemically reactive, while leaving the second region free of deprotection. Alternatively, the technique can involve transferring to the second region of the substrate surface a chemical protecting species. The method further involves exposing the substrate surface to a chemically or biochemically reactive species that reacts at the first region proximate the substrate surface and does not react at the second region. The technique can be used to create a combinatorial library via a series of deprotecting/reacting, re-protecting steps or protecting/reacting/deprotecting steps. Transfer of protecting or deprotecting species to the surface can take place essentially instantaneously.
- The invention also provides a method of creating, on a substrate surface, a patterned, self-assembled monolayer, involving transferring a self-assembled monolayer-forming species from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate the substrate surface. A self-assembled monolayer proximate the first region is thereby formed corresponding to the indentation pattern. A second region proximate the surface, contiguous with the first region, remains free of the self-assembled monolayer.
- The invention also provides a method involving providing a surface carrying a plurality of chelating agents distributed evenly thereacross and applying to two discrete regions of the surface a metal ion that is coordinated by the chelating agent, while leaving a region intervening the two discrete regions free of the metal ion, thereby creating two discrete regions carrying chelating agents coordinating metal ions.
- The invention also provides a method involving providing a surface carrying an essentially even distribution thereacross of chelating agents coordinating metal ions, and applying to two discrete regions at the surface a biologically active agent, while leaving a region intervening the two discrete regions free of the biologically active agent.
- The invention also provides an article defined by a substrate having a surface and a self-assembled monolayer on the surface. The monolayer is formed of at least a first species having a formula X—R—Ch—M, wherein X represents a functional group and R represents a spacer moiety that, together, are able to promote formation at the surface of a self-assembled monolayer. Ch represents a chelating agent that coordinates a metal ion. M represents a metal ion coordinated to the chelating agent. The article further includes a pattern of biological agent coordinated to metal ion at a first region proximate the surface. A second region proximate the surface, contiguous with the first region, remains free of biological agent coordinated to metal ion.
- The invention also provides a method of creating a patterned, self-assembled monolayer on a substrate surface. The method involves transferring a self-assembled monolayer-forming species from an applicator having a contoured surface including at least one indentation defining an application pattern to a first region proximate a substrate surface. A self-assembled monolayer is thereby formed proximate the first region of the substrate surface corresponding to the indentation pattern. A second region proximate the surface, contiguous with the first region, is left free of self-assembled monolayer. The self-assembled monolayer can be transferred essentially instantaneously to the first region proximate the substrate surface in this manner.
- The invention also provides a method for providing a surface carrying a plurality of chelating agents distributed evenly thereacross and applying to two discrete regions at the surface a metal ion that is coordinated by the chelating agent. A region intervening the two discrete regions is left free of metal ion.
- The invention also provides a method involving providing a surface that carries, essentially evenly distributed thereacross, chelating agents coordinating metal ions. A biochemically active agent is applied to two discrete regions at the surface and a region intervening the two discrete regions remains free of the biochemically active agent.
- The invention also provides an article including a surface and a pathway proximate the surface delineating a pattern at a first region proximate the surface. The pattern includes at least one region defining a continuous essentially linear portion of product formed proximate the surface. The product is formed in this manner via reaction involving a chemically active agent promoting the reaction that had been transferred proximate the surface from an applicator. The linear portion of the product has a dimension parallel to the surface of less than about one millimeter.
- The invention also provides an article as described above, where the pattern is defined by a plurality of microbeads assembled at the surface. Any patterns formed in this manner can have at least one section having a dimension parallel to the surface of less than about one millimeter.
- The fluid precursors, chemically active agents, biochemically active agents, and carriers can be any of a variety of species including prepolymeric species, biological binding partners, inorganic salts, ceramics, metals, catalysts, colloidal activating agents, and the like.
- A variety of combinations of the above-described inventive methods can be carried out, for example formation of a pattern can be carried out via capillary action, instantaneous transfer can take place to form a pattern on a surface having a lateral dimension of less than about 1 mm, and the like. Articles formed by the methods above, or by any combination of these methods, and articles formed by other methods are included. The methods can be carried out on essentially planar or non-planar surfaces.
- FIG. 1 illustrates schematically an arrangement for derivatizing a surface in a predetermined pattern according to one embodiment of the invention;
- FIG. 2 is a schematic illustration of a technique for transferring a chemically or biochemically active agent or fluid precursor of an article from essentially linear indentations of an applicator defining an indentation pattern to a substrate surface in a pattern corresponding to the indentation pattern;
- FIGS. 3a-3 d are photocopies of scanning electron micrographs (SEMs) of patterned polymeric structures formed from hardenable fluid precursors in which the patterned structures remain at the surface (FIGS. 3a-c) or are removed from the surface to form a free-standing structure (FIG. 3d);
- FIGS. 4a-4 h are photocopies of SEM images of inorganic and organic microstructures patterned on surfaces in accordance with the invention;
- FIG. 5 is a photocopy of an electron micrograph of microspheres assembled in a predetermined pattern proximate a substrate surface from a fluid precursor in accordance with the invention;
- FIGS. 6a-6 c are photocopies of SEM images of metallic microstructures formed proximate predetermined regions of a substrate surface in accordance with the invention;
- FIGS. 7a-7 c are photocopies of SEM images of a substrate surface derivatized in a pattern with resist followed by lithography to etch the substrate surface in a pattern complementary to the resist pattern;
- FIG. 8 illustrates schematically the formation of a free-standing article from a fluid precursor, using a substrate surface and a forming article including a pattern of indentations in accordance with the invention;
- FIGS. 9a-9 d are photocopies of SEM images of a free-standing article prepared in accordance with the technique schematically illustrated in FIG. 8 and use of that article as a mask adjacent a substrate surface in vapor deposition of metal (FIG. 9b) or creation of a secondary resist formed by a self-assembled monolayer deposited in a pattern complementary to that of the mask, followed by removal of the mask and vapor deposition of metal in a pattern complementary to the secondary resist pattern (FIGS. 9c-d);
- FIGS. 10a-10 c illustrate schematically (FIG. 10a), and via photoreproduction of optical micrographs (FIGS. 10b, c), a process involving derivatizing a surface with resist via micromolding, a mask so produced, and a substrate surface etched selectively at regions not covered by the mask;
- FIG. 11 illustrates schematically a technique for transfer of a chemically or biochemically active agent or a fluid precursor of an article from an applicator having a discontinuous indentation pattern to regions proximate a substrate surface in a pattern corresponding to the indentation pattern;
- FIG. 12 illustrates schematically the transfer, from an article including an indentation pattern, of a chemically or biochemically active agent or other fluid species to a nonplanar substrate surface in a pattern corresponding to the indentation pattern;
- FIG. 13 illustrates schematically a multi-layered article formed using successive micromolding techniques of the invention that can serve as a waveguide, and is a cross-section through line a-a of FIG. 15;
- FIGS. 14a-14 k illustrate schematically the creation of a combinatorial library in accordance with the invention;
- FIG. 15 illustrates schematically several techniques of the invention for forming a waveguide array or other structure, from a fluid precursor, on a substrate surface followed by formation of a cladding layer over the waveguide array;
- FIG. 16 illustrates a technique for forming a multi-layer waveguide structure;
- FIG. 17 is a schematic illustration of one type of prior art waveguide coupler;
- FIG. 18 is a schematic illustration of another type of prior art waveguide coupler, namely an evanescent coupler;
- FIG. 19 is a schematic illustration of a coupling region, switch, or sensor using a waveguide array of the present invention;
- FIG. 20 illustrates formation of an interference pattern via coupling among a five-waveguide array in accordance with the invention;
- FIG. 21 is a photocopy of a scanning electron micrograph (SEM) image of an unclad array fabricated in accordance with the invention;
- FIG. 22 is a photocopy of an SEM image of a clad array fabricated in accordance with the invention;
- FIG. 23 is a schematic illustration of an optical system used to couple light into waveguide arrays of the invention and to determine interference patterns formed via coupling among the waveguides of the arrays;
- FIGS. 24a-24 g show a variety of waveguide arrays and interference patterns of light emerging from various waveguide arrays and created via coupling between waveguides of the arrays;
- FIG. 25 illustrates schematically another technique of the invention for forming a structure from a precursor, on a substrate surface;
- FIG. 26 is a photocopy of a SEM image of an aluminosilicate structure that can serve as a waveguide;
- FIG. 27 is a photocopy of a SEM image of a borosilicate structure that can serve as a waveguide; and
- FIG. 28 is a photocopy of a SEM image of the structure of FIG. 27 at a different stage of annealing.
- U.S. patent application Ser. No. 09/634,201, filed Aug. 9, 2000 and U.S. patent application Ser. No. 09/004,583, filed Jan. 8, 1998 (now U.S. Pat. No. 6,355,198) and U.S. application Ser. No. 08/616,929, filed Mar. 15, 1996 and U.S. provisional application serial No. 60/046,689 filed May 16, 1997, all are incorporated herein by reference.
- The present invention provides, in one aspect, techniques for placement, at regions proximate a substrate surface, of chemically or biochemically active agents, fluid precursors of articles such as waveguides to be immobilized proximate a substrate surface, and/or other species desirably transferred to a region or regions proximate a substrate surface in a pattern. “Fluid precursor”, as used herein, means a material that is fluid enough that it can be formed into a pattern using a forming article, using techniques described herein. The invention utilizes an applicator having a pattern of indentations that can be used to transfer such a species from the indentations to a region proximate the substrate surface or that can serve as a mold that when, positioned proximate a substrate surface, can define a region in which such a species is positioned. In one set of preferred embodiments the applicator is used to transfer a fluid precursor from the indentations to a region proximate a substrate surface where the precursor is hardened to the point it is self-supporting and the applicator can be removed. “Self-supporting, in this context, means that the precursor does not lose its form unacceptably upon removal of the forming article and can retain its form during a further hardening procedure. Alternatively, the applicator can be used to transfer a fluid precursor to a substrate surface and the applicator can be removed prior to hardening the fluid, but maintaining the fluid within channels defined between indentations in the contoured applicator surface and the substrate surface until the fluid is hardened is preferred, since the ultimate shape of features of the pattern on the substrate is thereby better-controlled.
- FIG. 1 illustrates schematically a technique for derivatizing a substrate surface according to a pattern of, for example, a polymeric article, a pattern of microbeads optionally carrying a chemical or biochemically active species, a catalyst or other activating agent for promoting a chemical reaction such as metal plating at the surface, a fluid carrying a dissolved or suspended species to be deposited or precipitated, or the like. For purposes of illustration, the procedure schematically illustrated in FIG. 1 will be described with respect to a hardenable prepolymeric fluid that is hardened at the surface to form a patterned polymeric article. An
article 20 includes anapplication surface 22 having formed therein a plurality ofindentations 24 that together define a linear, patterned array ofindentations 24 that are contiguous with acontact surface 26.Article 20, according to one embodiment, is an applicator used to transfer a species, in a pattern, to a region or regions proximate the substrate surface, or a forming article or micromold placed proximate a substrate surface and used to guide a fluid species so as to position the species in a pattern at a predetermined region or regions proximate the substrate surface. As used herein, the term “proximate” is meant to define at a substrate surface, that is, in contact with a substrate surface, or at a position near a substrate surface and fixed relative to the substrate surface. For example, if a substrate surface carries an adhesion promoter, for example a self-assembled monolayer, activity at the surface of the self-assembled monolayer is intended to mean activity proximate the substrate surface. When formingarticle 20 is placed proximate asurface 28 of asubstrate 30,contact surface 26 of the article seals portions ofsurface 28 that it contacts, thereby formingchannels 32 defined byindentations 24 andportions 34 ofsubstrate surface 28 not contacted bycontact surface 26. In this manner a micromold is created, which is defined byarticle 20 andsubstrate surface 28. - A fluid36 that, according to the embodiment illustrated, is a precursor of a patterned, polymeric structure (but can be one of a variety of species such as a carrier of a chemically or biochemically active agent, etc., as described herein) is placed adjacent one or more openings of
channels 32 and introduced into the channels and allowed to flowadjacent portions 34 ofsubstrate surface 28 in register withindentations 24.Fluid precursor 36 can be urged to flow via, for example, pressure applied to the fluid as it is positioned so as to enter the channels, or vacuum created within the channels by, for example, connection of the outlets of the channels to a source of vacuum. Alternatively, according to one aspect of the invention, the fluid can be allowed to flow into the mold via capillary action. Capillary filling of the mold is especially useful when the mold is of very small dimension (in particular in the micro scale) and is defined herein to mean that when a fluid precursor is positioned adjacent an opening orchannel 32 formed by aportion 34 of the substrate surface and anindentation 24 ofarticle 20, the fluid precursor will flow into at least a portion of the channel spontaneously. - Subsequent to introduction of the fluid precursor into the mold defined by
channels 32, the fluid precursor can be hardened before or after removal ofapplicator 20 from substrate surface 28 (or where the fluid is a carrier of a species to be deposited or precipitated, the fluid can dissipate, i.e., evaporate, be absorbed intoapplicator 20, or the like). Where the fluid is viscous enough, or is allowed to reach a particular level of viscosity, the applicator can be removed and the precursor hardened at the surface without unacceptable loss of dimensional integrity. In particularly preferred embodiments, the fluid precursor is hardened to the extent that it is self-supporting (dimensionally-stable) prior to removal ofArticle 20 from the substrate surface. - According to one embodiment, the fluid precursor is a solution of monomer in a fluid carrier and is polymerized at the surface with
article 20 in place.Article 20 then is removed. Astructural article 38, in a pattern corresponding to the indentation ormold pattern 24 ofarticle 20, results onsubstrate surface 28 from the described procedure. According to the description of the process illustrated in FIG. 1,structure 38 is a polymeric structure formed from a fluid prepolymeric precursor. - Where the
structure 38 formed according to this embodiment is a polymeric structure, it can be thermally polymerized onsubstrate surface 28 via application of heat to the substrate and/orarticle 20 or, ifarticle 20 is removed prior to polymerization, via convective or radiative heat; photopolymerized ifsubstrate 30 and/orarticle 20 are transparent to radiation, or subsequent to removal ofarticle 20. Free-radical polymerization can be carried out as well. These and other forms of polymerization are known to those of ordinary skill in the art and can be applied to the techniques of the present invention without undue experimentation. All types of polymerization, including cationic, anionic, copolymerization, chain copolymerization, cross-linking, and the like can be employed, and essentially any type of polymer or copolymer formable from a fluid precursor can be patterned onsurface 28 in accordance with the invention. An exemplary, non-limiting list of polymers that are suitable include polyurethane, polyamides, polycarbonates, polyacetylenes and polydiacetylenes, polyphosphazenes, polysiloxanes, polyolefins, polyesters, polyethers, poly(ether ketones), poly(alkylene oxides), poly(ethylene terephthalate), poly(methyl methacrylate), polystyrene, and derivatives and block, random, radial, linear, or teleblock copolymers, cross-linkable materials such as proteinaceous material and/or blends of the above. Gels are suitable where dimensionally stable enough to maintain structural integrity upon removal ofarticle 20 fromsubstrate surface 28. Also suitable are polymers formed from monomeric alkyl acrylates, alkyl methacrylates, alpha-methylstyrene, vinyl chloride and other halogen-containing monomers, maleic anhydride, acrylic acid, acrylonitrile, specifically, methyl methacrylate, imides, carbonates, hexafluoroisopropyl methacrylate, acrylonitrile, bromophenyl acrylates or bromophenyl methacrylates, and the like. Monomers can be used alone, or mixtures of different monomers can be used to form homopolymers and copolymers. Non-linear and ferroelectric polymers can be advantageous. Gels are suitable where dimensionally stable enough to maintain structural integrity upon removal ofarticle 20 fromsubstrate surface 28. The particular polymer, copolymer, blend, or gel selected is not critical to the invention, and those of skill in the art can tailor a particular material for any of a wide variety of applications. The particular polymer, copolymer, blend, or gel selected is not critical to the invention, and those of skill in the art can tailor a particular material for any of a wide variety of applications. - According to one embodiment, a polymerizable or cross-linkable species (optionally in a fluid carrier) including an admixed biochemically active agent such as a protein can be made to form a pattern on
substrate surface 28 according to the described technique. For example, carboxylated Dextran™ can carry admixed protein, be introduced intochannels 34, and hardened to formarticles 38. Where the Dextran™ carries admixed biologically active agent, the article can be exposed to a medium suspected of containing a biological binding partner of the biochemical agent, and any biochemical binding or other interaction detected via, for example, diffraction, or via a change in coupling between waveguide cores as described more fully below. Wherearticle 38 defines diffraction grating, the degree of diffraction can be affected by biological binding between the biological agent compounded withinarticle 38 and an analyte that is a biological binding partner of the compounded agent. Determination of a change in diffraction atsurface 28 is indicative of the presence of analyte in the medium brought into contact witharticle 38. According to another embodiment, a species such as polymerizable or cross-linkable species can entirelycoat surface 28,article 20 can be placedadjacent surface 28, a biological agent can be introduced intochannels 34 and allowed to admix with the polymerizable or cross-linkable species, and prior to or subsequent to removal ofarticle 20 species onsurface 28 can be polymerized or cross-linked. In this manner, a surface having a pattern of biological agent compounded therein is produced, and can serve as a sensor for a biological binding partner of the biological agent via change in refraction or diffraction of light at the surface. - Where electrical conductivity is desired, an electrically-conductive polymer can be selected, and this can have significant application in the microelectronics industry, as would be recognized by one of ordinary skill in the art.
- The invention is intended to encompass creation of a wide variety of structures or patterns of species on substrate surfaces from fluid precursors. The precursor can be any fluid that can flow into the mold defined by
indentations 24 andportions 34 ofsubstrate surface 28, and those of ordinary skill in the art can determine, without undue experimentation, which fluids will readily flow into such a mold based upon dimension of the mold and viscosity of the fluid. In most instances, the viscosity of the fluid can be adjusted, by for example diluting or concentrating the fluid, to achieve a level of viscosity suitable for flow into the mold at a desired rate. The polarity of the fluid can be tailored as well, with reference to the chemical characteristic of the substrate surface or micromold, to facilitate fluid carrier flow. - According to one embodiment of the invention, patterned
article 38 is not a polymer or cross-linked organic species as described above, but is a non-polymerized organic species that is dissolved or dispersed in a fluid carrier to formfluid precursor 36 which is introduced intomold channels 32, whereupon the fluid carrier or solvent dissipates (e.g., is removed via evaporation from the mold channels and/or absorption into the substrate or applicator 20). According to yet another embodiment, patternedstructure 38 is an inorganic structure, such as a salt or ceramic. A salt soluble in a fluid precursor can be prepared as asolution 36 defining a fluid precursor that is introduced intomold channels 32 and precipitated as apatterned salt structure 38 by removal of solvent via evaporation, adsorption, or other physical or chemical change to the surrounding environment. Inorganic salts or ceramics can be carried as a suspension in a fluid carrier, flowed intochannels 32, and precipitated or deposited. Metals, such as those commonly deposited from pastes in accordance with thick-film silk-screening techniques, can be applied to defined regions ofsubstrate surface 28 where a paste is sufficiently fluid, or the paste and/or metal can be carried in a fluid as a suspension or sol influid precursor 36. Those of ordinary skill in the art will recognize that a wide variety of non-electrically conductive, electrically semi-conductive, and electrically-conductive structures can be patterned proximate a substrate surface according to the inventive technique. Fluid precursors of inorganic materials, such as solutions from which materials can be precipitated, or suspensions from which a fluid carrier can be removed by dissipation or evaporation, can be used to form structures, such as waveguides, from materials such as TiO2, TiO2/SiO2, ZnO, Nb2O5, Si3N4, Ta2O5, HfO2, ZrO2, or the like. U.S. Pat. Nos. 5,009,483, 5,369,722, and 5,009,483, each incorporated herein by reference, describe many suitable precursor and waveguide materials. Dye-doped fluid precursors can be used, and are advantageous in many situations. - Another fluid precursor can be a sol-gel precursor, and sol-gel techniques known to those of skill in the art can be used to create the solid structures in patterns, according to the invention. Ferroelectric and electrooptic materials and sol-gel processing of a variety of precursors to form a variety of species is well known to those of ordinary skilled in the art and can be applied and exploited by the method of the invention. For example, materials such as PbScTaO3, (Pb, La)TiO3 (PLT), LiNbO3, KNbO3, LiTaO3, potassium diphosphate, potassium triphosphate, PbMoO4, TeO2, Ta2O5 BaTiO3, BBO crystals, Ba1-xSrxTiO3, Pb(Zr, Ti)O3, SrTiO3, bismuth strontium tantalate, and the like. Other examples of sol-gel precursors that can define fluid precursors of the invention include precursors of multicomponent glasses or ceramics containing at least one oxide, such as silicate glasses or ceramics containing the oxides of aluminum, boron, phosphorus, titanium, zirconium, sodium, etc. Other sol-gel precursors appropriate for use are precursors of hybrid materials or organically modified ceramics, such as precursors of silicon oxycarbide or ORMOCERs. Other sol-gel precursors appropriate for use are described by Brinker and Scherer, in Sol-Gel Science; Academic Press, San Diego, 1990; Dislich, Transformation of Organometallics into Common and Exotic Materials; Nijhof, Dordrecht, 1998, volume 141; Pani, et al., J. Am. Ceram. Assoc., 1994, 77, 1242; Ramamurthi, et al., Mat. Res. Soc. Symp. Proc., 1992, 271, 351; Peiying, et al., Sensors and Actuators, 1995, A49, 187; Rao, J. Electrochem. Soc., 1996, 143, 189; Li, et al., Solar Energy Materials and Solar Cells, 1995, 39, 179, each of which is incorporated herein by reference. Where a sol-gel precursor is used, a hydrolysis and polycondensation reaction takes place, preferably a two-step reaction. The working examples described herein use tetramethylorthosilicate as the main constituent in glasses formed according to this reaction. Other alkoxides react similarly. Sol-gel precursors that include mixtures of glasses or glasses that are mixtures of compounds. These structures can be deposited in any pattern that corresponds to an indentation pattern formable in an applicator or
micromold 20 and can include dimensions through a wide range as described below. - The present invention, according to one aspect, involves the fabrication and use of reactive ion etch masks from sol-gel precursors. Dielectric materials such as aluminia, zirconia, and silica glasses and mixed glasses such as aluminosilicates can be fabricated simply, conveniently, and relatively inexpensively using the techniques of the invention. A sol-gel precursor can be formed into a pattern using any of the molding techniques as described herein, with reference for example to FIGS. 1, 2,8, 10, 15, 16, and 25, and can be carried out directly on a surface that is desirably etched via reactive ion etching. That is, an article is provided that is desirably etched via reactive ion etching, and a reactive ion etch mask is formed on a surface of the article via molding according to any of the techniques described herein from a precursor of a reactive ion etch mask. The reactive ion etch mask is formed from the precursor using the mold defined in part by the forming article of the invention on a first portion of the article surface, in a pattern, while leaving a second portion of the substrate surface free of the mask material. The surface of the article then is exposed to reactive ion etch conditions (known to those of ordinary skill in the art, e.g., 02 plasma), and etching takes place at the second portion of the substrate surface. Typically, the first portion of the substrate surface will be a pattern of separated lines or portions that can be isolated or interconnected, and the second portion will be complementary to the first portion. The second portion is “free” of reactive ion etch mask when the second portion contains no reactive ion etch mask material or is covered by so little reactive ion etch mask material that exposure to reactive ion etching conditions causes reactive ion etching at the second portion.
- Formation of dielectric, or ceramic materials in accordance with this aspect of the invention can find use not only in reactive ion etching masks but in integrated optics, non-linear optics and other microelectronic arenas as would be understood by those of ordinary skill in the art.
- According to yet another embodiment, a biologically active agent can be dissolved or suspended in a fluid carrier as a
fluid precursor 36 and introduced intochannels 32adjacent portions 34 ofsurface 28 and, prior or subsequent to removal ofmicromold 20, allowed to engage in a biochemical interactionproximate regions 34 ofsubstrate surface 28. For example, a biochemical agent can include a biotin linker while substrate surface 28 carries immobilized avidin, and biochemical interaction can be allowed to take place atregions 34 ofsubstrate surface 28 in this manner, linking the biochemical agent to the substrate surface atregions 34. Biochemical agents can be immobilizedproximate regions 34 of the substrate surface according to other techniques as well. For example, wheresubstrate surface 28 exposes a hydrophobic functionality, a biological agent such as a protein can be non-covalently immobilized atregions 34 of the substrate surface. To control orientation of a protein or other biochemical agent immobilized at a substrate surface via hydrophobic interaction, a hydrophobic chemical moiety can be coupled to the biochemical agent at a region of the agent remote from its active site. In this manner, the agent can be hydrophobically coupled to the surface and maintain exposure, away from the surface, of its biochemically active region. One of ordinary skill in the art can conduct a simple test to determine whether a biochemical agent is suitable for use with the described technique. The binding constant of a candidate biochemical agent for a target species can be determined using standard ELISA techniques. Then, the candidate biochemical agent can be hydrophobically immobilized (or immobilized in any other manner described herein or known to those of ordinary skill in the art, for example via a polyamino acid tag coupled to a metal ion immobilized at the surface by a chelating agent) at a variety of surfaces, and then assays can be performed to determine whether the agent has retained its ability to biologically bind to the target species or has been denatured and is unable to bind (this exemplary test is particularly useful in connection with biological agents that, in their native form only, bind target species, but when denatured do not bind the target species). - Biochemical recognition can be exploited in immobilization of a particular biochemical agent desirably patterned on
substrate surface 28. For example, a first agent can be immobilized (for example using hydrophobic coupling) atregions 38 of the substrate surface, and a second agent (which is a biological binding partner of the first agent) then can be immobilized atregions 34. The second step in which the desired agent is immobilized atregions 34 can be carried out with or withoutmicromold 20 proximate the substrate surface. Biochemical recognition involving partners also can be exploited to trap biological agents atregions 34 of the substrate surface using other biological agents that have been immobilized atregions 34. Biochemical recognition involving partners such as antibody/antigen, antibody/hapten, enzyme/substrate, enzyme/inhibitor, enzyme/cofactor, biotin/avidin, binding protein/substrate, carrier protein/substrate, lectin/carbohydrate, receptor/hormone, receptor/effector, complementary strands of nucleic acid, repressor/inducer, and the like can be exploited in connection with the technique. Those of ordinary skill will recognize a variety of uses for placement of such biochemically active agents at predetermined portions of a substrate surface in a pattern, for example as discussed below with reference to FIG. 14 and as disclosed in co-pending, commonly-owned U.S. Pat. No. 5,512,131 of Kumar, et al. and International Patent Application Publication No. WO 96/29629, both incorporated herein by reference. - According to embodiments in which the biochemical activity of a biologically active agent can be detrimentally affected by environmental factors, a fluid carrier of the biologically active agent should be selected so as not to detrimentally affect the biochemical activity of the agent. For example, if a protein is to be patterned on the surface and used in an interaction that cannot take place (or takes place at an unacceptably low level) when the protein is denatured, a fluid carrier should be selected that does not denature the protein or otherwise detrimentally affect the biological binding interaction of the protein that is to be exploited. Additionally, a
micromold 20 should be selected and/or fabricated in a manner such that the surfaces ofindentations 24 that can come into contact with a biologically active agent will not detrimentally affect the performance of the agent. For example, ifmicromold 20 is fabricated from a material that could denature a protein, then if used with the protein the interior surfaces ofindentations 24 can be chemically altered, for example via grafting with polyethylene glycol, to render the surfaces non-destructive of the agent. - According to yet another embodiment,
fluid precursor 36 carries a suspended or dissolved chemically active agent that is an activating agent as described in a co-pending, commonly owned U.S. application Ser. No. 08/616,692 of Hidber, et al. entitled “Microcontact Printing of Catalytic Colloids”, referenced above. When a fluid carrier is used in this and other embodiments, it can form part of a species or article immobilized proximate the substrate surface or can dissipate, for example via evaporation or adsorption into the applicator or substrate surface, leaving the species carried in the fluid carrier immobilized at the surface. - A non-limiting list of chemically active agents that can be patterned on a surface in accordance with the invention includes agents as described by Lando (U.S. Pat. Nos. 3,873,359; 3,873,360; and 3,900,614) which can render a substrate surface amenable to metal plating, catalytic activating agents such as finely distributed metal particles and clusters such as conventional metal powders, substrate-fixed metal clusters or multimetallic clusters that are well known as valuable heterogeneous and homogeneous catalysts in organic chemistry, inorganic chemistry, and electrochemistry, etc. With reference to the application of Hidber, et al., such agents can include those capable of being carried by an applicator, transferred from the applicator to a surface in a form in which it can effect a chemical reaction (such as a metal deposition reaction), and immobilized at the surface with a degree of adhesion and for a period of time sufficient to participate in the desired chemical reaction. As such, one class of activating agents provided in accordance with the invention are distinguished from prior art agents applied with an applicator such as a stamp, for example as disclosed by Lando (U.S. Pat. Nos. 3,873,359, 3,873,360, and 3,900,614), in that the activating agent of the present invention is in a form suitable for effecting reaction such as metal plating or catalytic action when transferred to the surface. According to preferred embodiments, further chemical reaction at the surface to convert a precursor to a suitable agent, as necessitated in the referenced prior art methods, is not required. Metal deposition reactions contemplated include electrochemical deposition and electroless deposition, generally involving reduction of a metal cation to create the metal, facilitated in part by the lowering of the electrochemical potential involved in the deposition.
- Activating agents that are finely distributed metal particles and clusters, such as conventional metal powders, including substrate-fixed metal clusters or multimetallic clusters are suitable for use as activating agents in accordance with the invention, and are well known as valuable heterogeneous and homogeneous catalysts in organic, inorganic, and electrochemistry. Exemplary activating agents include one or more metals of periodic table groups Ib, IIb, III, IV, V, VI, VIIb, VIII, lanthanides, and actinides, preferably copper and any metal more noble than copper, in particular Pd, Au, Ag, Pt, and Cu. Hydrogenation catalysts for example those effective in hydrogenating olefins or aromatics, as in the partial hydrogenation of benzene to form cyclohexene, with a substrate-fixed ruthenium activating agent or bimetallic activating agent (e.g. Ru/Sn) are contemplated. Zirconium and titanium catalysts, among others, are suitable for use in the invention that catalyze polymerization, such as polymerization of olefins such as ethylene, and these are intended to form part of the invention. Other examples of catalytic activating agents include those used in Heck reactions, e.g. in the Pd-catalyzed reaction of bromobenzene and styrene to form stilbene. Activating agents that are heterogeneous catalysts are also useful as electrocatalysts in fuel cells (in particular substrate-fixed Pt and Pt/Ru clusters). Activating agents prepared according to the invention can be homogeneous catalysts, such as those used in two phase systems (for instance H2O/toluene), such as e.g. betaine-stabilized Pd clusters soluble in H2O. Activating agents that are embedded in polymers can be used to prepare materials for electronic, optical and magnetic applications. Suitable embedding polymers include organic polymers, such as poly-p-phenylene-vinylene, polymethyl methacrylate, polysilanes, and polystyrene, or inorganic polymers, such as zeolites, silicates, and metal oxides. The well-known sol-gel process can be used to incorporate metal clusters in amorphous metal oxide materials (e.g. SiO2) as activating agents.
- Soluble metal clusters that are activating agents can also be surface-deposited to prepare novel materials for applications in optics and electronics, e.g. Pd on HOPG (highly oriented pyrolytic graphite).
- Particulate activating agents having particle sizes on the order of nanometers are preferred, for example particulate matter having particle size of less than about 100 nm, preferably less than about 50 nm, more preferably less than about 25 nm, and most preferably from about 2 to about 20 nm. The size of the particles is not critical except to the extent that where excellent edge resolution of a structure deposited in a reaction involving the particle is desired, the upper limit in size of the particle is reduced.
- Especially preferred as activating agents in accordance with the invention are colloidal activating agents. As used herein, colloidal activating agent is meant to define particulate matter capable of being involved in a desired chemical reaction, such as a catalytic reaction and including plating of metal at surfaces, that is carried or surrounded by molecules that prevent agglomeration of the individual particles and that render the particulate soluble in, or at least able to be carried in, an organic or aqueous liquid. Suitable colloid-forming species and colloids are described in European patent publication no. 672765 by Reetz et al., published Sep. 20, 1995, and incorporated herein by reference. According to one embodiment the activating agent comprises one or more metals of groups Ib, IIb, III, IV, V, VI, Vllb, VIII, lanthanides, and/or actinides of the periodic table prepared by cathodic reduction in the presence of a stabilizer. One method of preparation of such colloids is reduction, optionally with a supporting electrolyte, in organic solvents or in solvent mixtures of organic solvents and/or water within a temperature range of between about −78° C. and about 120° C. to form metal colloidal solutions or redispersible metal colloid powders, optionally in the presence of inert substrates and/or soluble metal salts of the respective metals. These colloids are soluble or redispersible in a suitable fluid that facilitates their application to an applicator such as a stamp. The following articles, incorporated herein by reference, describe as well exemplary activating agents suitable for use in connection with the invention. Vargo, et al., “Adhesive Electroless Metallization of Fluoropolymeric Substrates”Science, 262, 1711-1712 (Dec. 10, 1993); Bönnemann, et al., “Preparation and Catalytic Properties of NR4 + Stabilized Palladium Colloids”,
Applied Organometallic Chemistry 8, 361-378 (1994); Reetz, et al., “Size-Selective Synthesis of Nanostructured Transition Metal Clusters” J. Am. Chem. Soc. 116, 7401-7402 (1994); Reetz, et al., “Visualization of Surfactants on Nanostructured Palladium Clusters by a Combination of STM and High-Resolution TEM”, Science, 267, 367-369 (Jan. 20, 1995); and Meldrum, et al., “Formation of Thin Films of Platinum, Palladium, and Mixed Platinum Palladium Nonocrystallites by the Langmuir Monolayer Technique” Chem. Mater., 7, 111-116 (1995). - Electrochemical methods are described in EP 672765, referenced above, for synthesis of soluble metal colloids by operating in an inert organic, aprotic solvent, with surface-active colloid stabilizers being added as the supporting electrolyte which will both prevent plating of the metal and protect, or stabilize, small metal nuclei in the cluster stage. A metal sheet serves as the anode to be dissolved and a metal or glassy carbon electrode serves as the cathode. After dissolution at the anode, the released metal salts are reduced again at the cathode, with tetraalkylammonium salts serving as stabilizers. Standard organic solvents can be employed.
- Suitable exemplary stabilizers, or carriers, for the colloids, and at the same time as the supporting electrolyte, are quaternary ammonium or phosphonium salts R1R2R3R4N+X− and R1R2R3R4P+X−, respectively. A wide variety of combinations of R1, R2, R3 and R4 are possible. Examples include the symmetrical tetraalkylammonium salts with R1═R2═R3═R4═n-butyl or n-octyl, mixed tetraalkylammonium salts with R1═R2═R3═methyl and R4═cetyl, or chiral tetraalkylammonium salts having four different residues. Aryltrialkylammonium salts may also be used. Suitable counter ions include various anions, e.g. halogenides (Cl−, Br−, I−), hexafluorophosphate (PF6 −), carboxylates R′CO2 −(R′=alkyl, aryl), or sulfonates R″S0 3 −(R′=alkyl, aryl). A similar variety of phosphonium salts may be used, including tetraarylphosphonium salts, such as tetraphenylphosphonium bromide. Preferably, tetrabutylammonium chloride, bromide or hexafluorophosphate, tetraoctylammonium bromide, or tributylhexadecylphosphonium bromide can be employed. As metals, any of those listed above, in particular transition metals such as Fe, Co, Ni, Pd, Pt, Ir, Rh, Cu, Ag, or Au, are suitable. Suitable solvents are aprotic organic solvents, such as tetrahydrofuran (THF), toluene, acetonitrile (ACN), or mixtures thereof. The temperature in the electrolytic cell may be in the range between −78° C. and +120° C., preferably 15-30° C. or room temperature.
- A preferred activating agent is a colloidal catalyst that promotes deposition, for example electroless deposition, of a metal at
region 34 ofsubstrate surface 28 to which the colloidal catalyst is applied. For example, wherefluid precursor 36 includes a suspension of a colloidal palladium catalyst, the fluid can be evaporated or adsorbed as described above, resulting in deposition of catalyst atregions 34 ofsubstrate surface 28. Subsequently, an electroless copper plating bath can be introduced intochannels 32 and deposition of copper allowed to take place atregions 34 ofsurface 28. Alternatively, micromold 20 can be removed fromsurface 28 and theentire surface 28 exposed to an electroless copper plating bath. Copper will plate only at thoseregions 34 ofsubstrate surface 28 to which colloidal palladium catalyst had been applied. Electrochemical metal plating can be carried out as well. The chemically active agent of the invention can be any agent that can find use in chemical reaction, attraction, or other interaction proximate a substrate surface. Those of ordinary skill in the art will recognize a variety of agents that can be used in accordance with the invention, including, but not limited to solutions or suspensions of a very small species such as catalytic colloids, monomers, dissolved or suspended salts or ceramics or their precursors or other species. - According to yet another embodiment of the invention a suspension of particulate species in a
fluid carrier 36 can be introduced intochannels 32, followed by removal of the fluid carrier via dissipation, as discussed. The particulate species can be organic, inorganic, or polymeric material as described above, for example finely-ground polymeric, ceramic, or crystalline material, or can be in the form of microspheres. The application of microspheres in a predetermined pattern to a substrate surface can serve a variety of purposes that will be apparent to those of ordinary skill in the art upon reading the present disclosure, in light of the state of the art as set forth in several publications. An article by Lenzmann, et al., entitled “Thin-Film Micropatterning Using Polymer Microspheres”, Chem. Mater., 6, 156-159 (1994), incorporated herein by reference, describes formation of densely-packed monolayers of monodisperse polystyrene microspheres deposited on a glass substrate. The spheres serve as a mask for zinc sulfide deposition on the substrate as a thin film by thermal evaporation in vacuum. The mask (microspheres) are removed from the substrate surface after evaporative deposition leaving behind a surface with zinc sulfide features located in the interstitial spaces of the densely-packed spheres. For 2-micron diameter spheres, the lattice spacing of the resulting pattern is approximately 900 nanometers with individual trigonal pyramidal peaks. According to the present invention, a particular concentration of polymeric microspheres in a fluid carrier can be selected without undue experimentation that, when introduced intochannels 32, followed by evaporation of the fluid carrier, would result in a monolayer of microspheres selectively patterned atregions 34 ofsubstrate surface 28. Removal ofmicromold 20, followed by chemical vapor deposition, results in a well-ordered pattern of isolated, nano-scale regions of deposited material within the confines ofregion 34 ofsubstrate surface 28. - An article by Dushkin, et al. entitled “Colored Multilayers From Transparent Submicrometer Spheres”,Langmuir, 9, 3695-3701 (1993), incorporated herein by reference, discusses optical phenomena associated with polymeric beads at surfaces. Ordered multilayers are formed by evaporating the water carrier from polystyrene latex suspensions of diameter smaller than the wavelength of visible light. The spheres exhibit color when illuminated with polychromatic light. Accordingly, arrangement of a pattern of microspheres at
regions 34 ofsubstrate surface 28 in accordance with the invention can result in various radiative and calorimetric phenomena. An article by Hayashi, et al. entitled “Imaging by Polystyrene Latex Particles”, Journal of Colloid and interface Science, 144, 2, 538-547 (July, 1991), incorporated herein by reference, describes microarrays of identical images produced by polydispersed polystyrene particles at a surface. Microparticles and microbeads, especially polymeric particles and beads such as latex or polystyrene beads, find use in the field of biochemistry as solid supports for biochemical interaction. For example, a chemically or biochemically active agent can be coupled to a microbead or microparticle and optionally used in turn to immobilize a second agent that reacts with the immobilized agent, thereby immobilizing the second agent at a region at which the microbead is immobilized. That is, microbeads carrying a particular agent can be immobilized at a surface in a pattern using techniques of the invention and the patterned, immobilized beads can serve as locations for chemical reaction or biochemical interaction on the micro scale, for example as microreactors. Those of ordinary skill will recognize a variety of uses for patterned microparticles or microbeads carrying chemical or biochemical agents such as, for example, biochemical assays. - The pattern of
parallel indentations 24 formed insurface 22 of micromold orapplicator 20 is for illustrative purposes only. Any pattern, for example a pattern defined by a single indentation or many indentations, one or more of the indentations defining a non-linear pathway of uniform or non-uniform depth is intended to fall within the scope of the invention. Various patterns are illustrated in subsequent figures. The indentation pattern can be of a variety of dimensions and, according to one aspect of the invention, includes a region having a lateral dimension of less than 1 millimeter. “Lateral dimension” is meant to define a dimension parallel toapplication surface 22. According to preferred embodiments, the indentation pattern includes a portion having a lateral dimension of less than about 500 microns or less than about 100 microns, in one set of embodiments more preferably less than about 50, 20, or 10 microns, and more preferably still less than about 5 microns. According to a particularly preferred embodiment, an indentation pattern having a portion including a lateral dimension on the order of 1 micron is provided. The dimension of the indentations can be altered, as described in international patent publication number WO 96/29629, published Jun. 26, 1996 of Whitesides, et al., entitled “Microcontact Printing on Surfaces and Derivative Articles”, incorporated herein by reference, by deformingarticle 20. Where waveguides are fabricated in accordance with the invention, it is an advantage that, for example, branched sections and/or evanescent coupling sections, as shown in FIGS. 17 and 18 can be included in the pattern. Those of ordinary skill in the art can select suitable dimensions, depending upon the frequency of electromagnetic radiation being guided. Typically, the waveguide will have a width on the order of microns. The technique can be carried out wheremicromold 20 includes an indentation pattern where the indentations have depths and widths on the order of 100 microns to less than 1 micron, controllably. - Where
micromold 20 is placed adjacent a substrate surface and a fluid precursor fillschannels 32, article orarticles 38 resulting from the technique can have lateral dimensional features that correspond to the lateral dimensional features ofindentations 32 of the micromold. - According to another embodiment, the fluid precursor need not completely fill
channels 32, and this is preferred according to embodiments in which the lateral dimension ofarticle 38 formed from the fluid precursor is to be minimized. According to this embodiment,fluid precursor 36 is introduced intochannels 32 in an amount small enough that the fluid precursor wets only the corners of the channels. When a fluid precursor, substrate, and micromold are selected such that the fluid precursor will wet the micromold efficiently via capillary action, when a small amount of fluid precursor is supplied to the mold channel or channels, the precursor will selectively wet portions of the channels having an interior angle relatively low relative to the rest of the channel (such ascomers 40 defined by the abutment ofcontact surface 26 againstsubstrate surface 28 at the edge ofregion 34 of the substrate surface). When the fluid precursor wets the comers selectively and the fluid is hardened, evaporated, or adsorbed, a resulting structure can define a pattern having a dimension smaller than that of the lateral dimension ofindentation 24. According to this embodiment the lateral dimension ofstructure 38, at its narrowest, is narrower than the narrowest lateral dimension ofchannel 24 of the micromold, and can have a height significantly less than the height of the channel. The lateral dimension ofarticle 38 according to this embodiment can be on the order of less than or equal to about 100 microns or 50 microns, or preferably less than about 20 or 10 microns, more preferably less than about 5 microns or 1 micron, and according to a particularly preferred embodiment less than approximately 0.2 micron. According to this aspect, any of the species described herein that can be patterned proximate a substrate surface can be patterned so as to have lateral dimensions as described above. This aspect of the invention is illustrated in FIG. 6c, and discussed below. - In an alternate technique, any of the species described herein that can be used to form patterned articles and the like on a substrate surface (such as fluid precursor36) can be made to
coat substrate surface 28, and thenarticle 20 can be pressed againstsubstrate surface 28 to displaceprecursor 36 at regions in register withcontact surface 26.Precursor 36 will be formed inchannels 32 as illustrated in FIG. 1, and procedures described above carried out. - Any suitable material can define
substrate 30 of the invention.Substrate surface 28 can be of the same material as the bulk material ofsubstrate 30, or a different material. Substrates exposing a variety of functional surfaces such as hydrophobic, hydrophilic, and biologically compatible or non-compatible surfaces are known, and are suitable for use with the invention. Substrates that are somewhat fluid are known as well, and are acceptable for use in the invention to the extent that a useful pattern can be formed thereupon.Article 20 similarly can be formed of essentially any material. For example, ceramic, polymeric, elastomeric, and other materials can be used. According to a preferred embodiment,substrate surface 28 and/orcontact surface 26 ofarticle 20 is an elastomer or other conformable material. Preferably,contact surface 26 and more preferably, for ease of fabrication, theentire article 20, is formed of an elastomer. When an elastomer definessubstrate surface 28 orcontact surface 26, or preferably micromold 20, an optimal seal is created betweencontact surface 26 and portions ofsubstrate surface 28 adjacent and contiguous withportions 34 that withindentations 24 definechannels 32. This results in optimal confinement offluid precursor 36 tochannels 32. According to the invention pressure can be applied tomicromold 20 againstsubstrate 30 during micromolding, but according to embodiments in which an elastomer is used as described, pressure need not be applied as the elastomer conforms well to the surface against which it mates thus sealingchannels 32. Themicromold 20 can be fabricated of an elastomer in a manner analogous to the fabrication of a stamp from an elastomer as described in co-pending, commonly-owned U.S. Pat. No. 5,512,131, issued Apr. 30, 1996 by Kumar, et al, entitled “Formation of Microstamped Patterns on Surfaces and Derivative Articles”, and as described in International Patent Publication No. WO 96/29629 of Whitesides, et al., entitled “Microcontact Printing on Surfaces and Derivative Articles”, published Jun. 26, 1996, both of which are incorporated herein by reference. - FIG. 2 illustrates another embodiment of the invention in which, rather than applying
article 20 tosubstrate surface 28 followed by introduction offluid precursor 36 intochannels 32 so defined,article 20 is used as an applicator to transfer a chemically or biochemically active agent (optionally in a fluid carrier), fluid precursor of an article such as microparticles or microbeads in suspension, catalytic colloid, prepolymer fluid, or the like tosubstrate surface 28. Described below with reference to FIG. 15 is a set of transfer molding techniques particularly preferred in the fabrication of waveguides and other articles where the final shape of the formed article is essentially identical to the shape of the interior of the mold. In FIG. 2 and subsequent figures, components common to the various figures are given common numerical designation. In FIG. 2,fluid precursor 36 is first applied toindentations 24 ofmicromold 20, and thenapplication surface 22 is brought into proximity ofsubstrate surface 28 to allowfluid precursor 36 to be transferred tosubstrate surface 28. The fluid precursor can be applied to the indentations by bringing the indentations into contact with the fluid precursor and allowing capillary action to cause the indentations to be filled, or the precursor can be applied via micropipetting or the like to the indentations. In this way, separate fluid species can be applied to separate indentations if desired. In can be advantageous, with these techniques, to select a material exposed by the contoured application surface and the fluid species applied thereto such that the fluid species rapidly is positioned within the indentations, rather than spreading over the entire surface. Those of skill in the art can carry out such selection, using contact angle measurements or the like. - Where
fluid precursor 36 protrudes fromindentations 24 prior to transfer,application surface 22 need not contactsubstrate surface 28 for transfer to take place. Typically, however,application surface 22 will be brought into contact withsubstrate surface 28 to transfer a pattern of thefluid precursor 38 to regions proximate the substrate surface in a pattern corresponding to theindentation pattern 24. As illustrated, some fluid precursor remains inindentations 24, and the fluid precursor transferred tosubstrate surface 28 has been converted into hardenedarticle 38. However, according to several embodiments discussed above, the fluid precursor will not result in a hardened article, but will serve to transfer a biochemical agent or chemical agent to a surface. According to the embodiment illustrated in FIG. 2, the chemical or biochemical agent, prepolymer, fluid carrier containing a suspension of particulate matter, microbeads, or the like serves to transfer essentially instantaneously the desired species to the surface. As with all embodiments of the invention, the pattern of species so transferred can include a single indentation that is of any shape including a non-linear or linear pathway, a plurality of linear indentations as illustrated in FIG. 2, or a plurality of indentations of any shape, one or more indentations having dimensions as described above. Where a plurality of indentations are formed inapplication surface 22, each indentation can be made to carry a different chemical or biological agent or precursor. According to that embodiment, when application surface 22 of the micromold is brought into contact withsubstrate surface 28, distinct first and second species such as distinct first and second chemically or biochemically active agents, precursors, particulate species, or the like can be transferred essentially instantaneously to distinct first andsecond regions region 46 of the substrate surface that remains free of the agent or precursor. - FIGS. 3a-d are photocopies of SEM images of polymeric structures formed on substrates according to the method described above and illustrated in FIG. 1, in which a fluid polymeric precursor was allowed to fill channels formed by indentations in
micromold 20 and regions of the substrate. FIG. 3a showspolyurethane articles 48 formed on Si/SiO2 substrate 50 by capillary filling of a micromold having a surface with indentations placedadjacent substrate 50. The indentations correspond to the pattern ofarticles 48. A liquid polyurethane prepolymer was placed adjacent openings of channels formed between the micromold and the substrate surface and filled the channels via capillary action. The micromold was made of polydimethylsiloxane (PDMS). FIG. 3b is a top view of apolyurethane article 52 having a complex, interconnected pattern formed on Si/SiO2 substrate 50. A PDMS micromold having an indentation pattern corresponding to the pattern ofarticle 52 was used, and a liquid polyurethane prepolymer was allowed to fill the mold channels via capillary action. FIG. 3c shows a quasi three-dimensional array of microstructures interconnected through channels. Again, a polyurethane liquid prepolymer was allowed to fill channels formed by a micromold having an indentation pattern corresponding to the pattern ofpolyurethane article 54.Polyurethane article 54 is formed on a Si/SiO2 substrate 50. FIG. 3d shows a free-standingpatterned polyurethane article 52 formed by removal of the article from the substrate (FIG. 3b). - FIGS. 4a-h illustrate structures formed on substrates using the micromolding technique illustrated in FIG. 1 in which
liquid precursor 36 is a precursor of inorganic materials. Photocopies of SEM images are shown. In FIG. 4a, KH2PO4 structures precipitated from aqueous solution on Si/SiO2 are shown. FIG. 4b shows KH2PO4 structures as well, crystallized more rapidly. FIG. 4c shows Cu(NO3)2 on the same substrate crystallized from aqueous solution. FIG. 4d shows structures formed of the same material on the same substrate, but crystallized from a much more dilute solution. FIG. 4d illustrates the derivatization in a pattern that is formed within the boundaries of a region of the substrate surface corresponding to the indentation pattern of the micromold, but that does not fill that region. A series of isolated regions of product on the order of 4 microns in lateral dimension are shown. FIG. 4e shows CuSO4 structure on glass. FIG. 4f shows K3Fe(CN)6 structures on Si/SiO2. FIG. 4g shows a fractured view of amaranth on glass. The structures are approximately 0.4 micron in height. FIG. 4h is a section of FIG. 4g at higher magnification. - Ceramic structures formed in accordance with the invention can find use, for example, as mechanical ceramics such as abrasion tools. Current methodologies involve, typically, chemical vapor deposition to form ceramic patterns having small dimensions for such uses.
- FIG. 5 is a photocopy of an electron micrograph showing a packed, ordered array of
polystyrene microspheres 70 on a Si/SiO2 substrate 72. The ordered array of microspheres was formed by allowing a latex solution containing polystyrene microspheres to fill, via capillary action, channels formed between a micromold and the substrate surface in a pattern corresponding to the pattern of microbeads shown. The PDMS micromold was removed following crystallization of the microspheres via dissipation of the fluid carrier. - FIGS. 6a-c are photocopies of SEM images of copper structures formed via electroless deposition on Si/SiO2 substrates. For the structure in FIG. 6a, a gold surface was provided. A PDMS micromold having an indentation pattern corresponding to the pattern of copper structures illustrated was placed adjacent the gold substrate (as illustrated schematically in FIG. 1) and the
channels 32 were filled with a plating bath for electroless deposition of copper, defining a fluid precursor of copper according to one aspect, and a chemically active agent according to another aspect. The copper electroless plating solution was allowed to remain in contact with the surface for a period of time sufficient to platecopper structures 74 in a pattern corresponding to the indentation pattern of the micromold, while portions ofgold surface 76 corresponding to contactsurface 26 of the micromold remained free of copper deposition. For the structure illustrated in FIGS. 6b-c, a PDMS micromold having an indentation pattern corresponding to the pattern of copper structures illustrated was placed adjacent the substrate and thechannels 32 were filled with aprecursor solution 36 containing catalytic colloids. The solvent in which the catalytic colloids dissipated, resulting in formation of the catalytic colloids as a chemically active agent formed on regions of the substrate surface corresponding to the indentation pattern of the micromold. The micromold was removed, and the surface exposed to an electroless copper plating bath. Specifically, in FIG. 6b,copper structures 78 were formed on a Si/SiO2 substrate 80 coated with a self-assembled monolayer of siloxane on the Si/SiO2 substrate. CH3CH2O)3Si(CH2)3NH2 defined the self-assembled monolayer. A micromold having an indentation pattern corresponding to theultimate copper pattern 78 was placed on the self-assembled monolayer-derivatized silicon substrate. A DMF solution containing palladium colloids as afluid precursor 36 was allowed to fill the channels. Dissipation of DMF resulted in the chemically active agent (specifically, palladium colloid) forming structures in a pattern corresponding topattern 78. The substrate was exposed to an electroless copper plating bath to plate copper at patternedregion 78. FIG. 6c illustrates an aspect of the invention in which articles of very small lateral dimension can be formed by allowing a small volume offluid precursor 36 to enterchannels 32 defined by the micromold indentations and the substrate surface. The substrate was prepared as described in connection with FIG. 6b. Aregion 82 of the substrate surface corresponds to the indentation pattern of the micromold. Thefluid precursor 36 wetted only the corners defined between thesubstrate surface 84 and the micromold channels thus, when the fluid carrier dissipated, the catalytic colloid was solidified only in those portions of the indentation pattern that were wetted, namely, the comers. When the surface was exposed to an electroless copper plating bath, copper was plated at theregions 86 to which the catalytic colloid had been deposited. A copper pattern of very small lateral dimension resulted. - FIGS. 7a-c illustrate the application of a patterned structure to a surface from a fluid precursor using micromolding as illustrated in FIG. 1, followed by use of the structure as a resist in a chemical etch. A polymeric structure 88 (polyurethane) was formed from a fluid prepolymer in a pattern corresponding to an indentation pattern on a 200 nm, thermally grown
oxide layer 90 of a silicon substrate 92 (FIG. 7a). Following exposure of the substrate to a solution (aqueous HF/NH4F for about 2 minutes) that etches silicon dioxide, but to which thepolymeric structure 88 was resistant, the silicon dioxide layer was removed at regions of the substrate intervening the regions covered by the patternedstructure 88, that is, regions that had been contacted bycontact surface 26 of the micromold (FIG. 7b). Subsequently, the substrate surface was exposed to a solution (400 ml H2O, 92 g KOH, 132 ml 2-propanol for about 15 minutes at 65° C.) that etches silicon, but to which silicon dioxide is resistant. FIG. 7c shows resultant channels 94 anisotropically etched in the silicon substrate between patterned regions ofsilicon dioxide 90 that correspond to the pattern ofpolymeric structure 88 formed on the substrate surface via the micromolding technique. - FIG. 8 illustrates schematically a technique for forming a mask, for use in lithography or the like, via the micromolding technique of the invention. A
micromold 96 having amolding surface 98 including a plurality ofindentations 100 in a grid-like pattern is applied to asurface 102 of asubstrate 104. A fluidpolymeric precursor 106 is placed adjacent openings of channels formed between the substrate surface and the indentations of the micromold, and allowed to flow, via capillary action, into the channels. Where a PDMS micromold was used, the polymeric precursor could be placed so as to cover all channel openings, and flowed into and made to fill the channels completely. Gas escaped presumably via diffusion through the micromold. Once the polymeric precursor was hardened, via thermal or photolytic polymerization or the like, the micromold was removed. The substrate then was separated from the resultantpatterned article 108. The patterned article had a “frame” 110 completely surrounding it which could be used for ease of manipulation. The frame could be removed as well, to form thearticle 108 in a pattern corresponding to the indentation pattern of the micromold free of the frame. - The
article 108 could be used as a mask, for example as illustrated in FIGS. 9a-d, which are photocopies of SEM images. FIG. 9a shows apolyurethane mask 108 formed as illustrated in FIG. 8, and following formation placed on a Si/SiO2 substrate 112. FIG. 9b shows themask 108 on thesubstrate 112 following evaporation of gold onto the substrate. A portion of the mask was removed andmask 114 andportions 112 of the substrate not covered by the mask are shown covered with gold.Portions 116 of the substrate that had been covered bymask 108 remain free of gold. FIG. 9c shows a surface having a pattern ofisolated regions 118 of gold on a silicon substrate (regions 120 of the silicon substrate not covered byregions 118 of gold can be seen) formed as follows. A mask fabricated as described above was placed (with reference to FIG. 8) on a silicon substrate carrying a thin film of gold. A self-assembled monolayer-forming species (hexadecanethiol) was exposed to the surface and formed a self-assembled monolayer selectively atregions 118 not covered by the mask. The mask then was removed fromregions 120, and the surface exposed to a solution that etched gold, but to which the self-assembled monolayer was resistant. The self-assembled monolayer then was removed, resulting in theregions 118 of gold that had been protected by the secondary, self-assembled monolayer resist, isolated byregions 120 of the silicon substrate. FIG. 9d shows a surface derivatized as described with respect to FIG. 9c, but the self-assembled monolayer was transferred toregions 118 of the surface by placing a flat PDMS article that had been coated with a self-assembled monolayer-forming species on top of themask 108 for one minute. -
Mask 108 also could be applied to nonplanar surfaces followed by plating, etching, or the like. It can be advantageous, when transferringmask 108 to a surface having very fine features, such as a surface etched as illustrated in FIG. 7c, to transfermask 108 to such a surface by floating it in a fluid that is supported by the surface and allowing the fluid to dissipate or run off. - As described in international patent publication number WO 96/29629, published Jun. 26, 1996 of Whitesides, et al., referenced above, etching or plating at a surface can be made to take place selectively at predetermined regions, and this technique can be exploited using the techniques of the present invention as described herein. Additionally, where a self-assembled monolayer is patterned, a “protecting species” that is resistant to (for example, incompatible with) a chemical etch can be placed on top of a self-assembled monolayer, followed by etching at regions not covered by the self-assembled monolayer, as described in publication no. WO 96/29629. Of course, a self-assembled monolayer can be incompatible with an etch and etching can take place without the use of a protecting species. The protecting species, according to this embodiment, is compatible with the self-assembled monolayer. According to another embodiment, a protecting species is less compatible with the self-assembled monolayer than with the substrate surface that is exposed at regions intervening the self-assembled monolayer. According to this embodiment, after patterning of a self-assembled monolayer a protecting species is exposed to the surface and when the surface is exposed to an etchant, the surface is etched at regions that had been covered by the self-assembled monolayer.
- FIGS. 10a-c illustrate formation of a
mask 122 on athin layer 124 of chromium on aglass substrate 126 using the micromolding procedure as illustrated in FIG. 1, followed by etching of chromium atregions 128 not covered by the mask. In FIG. 10a, the molding technique described above is used to form a pattern ofpolyurethane article 122 onchromium 124 leavingregion 128 of chromium uncovered. The surface was exposed to an etchant (400 ml H2O, 24 ml of 63% HNO3, 62 g NH4NO3.Ce(NO3)3 for about 1 minute) that removes chromium but to which thepolymeric article 122 is resistant. The result was aglass substrate 126 having thereon apatterned mask 130 defined by chromium protected from the etch bymask 122 in the pattern corresponding to mask 122 (and the pattern corresponding to the indentation pattern of the micromold). FIG. 10b is an optical micrograph of thechrome mask 130, top view. Thechrome mask 130 was removed from thesubstrate 126 and placed on a photoresist article. FIG. 10c is a photocopy of an SEM image of a pattern that was generated in the photoresist film atregions 132 not protected by the mask. Raisedportions 134, in a pattern corresponding to the pattern of the chromium mask, and corresponding to the original indentation pattern of the micromold from which themask 122 was formed, were not ablated in the photolithography process. - According to another embodiment a substrate surface such as a silicon wafer can be spin-coated with photoresist. A micromold can be placed adjacent to a photoresist and channels defined thereby filled with a solvent that dissolves photoresist but not the micromold. A pattern of the silicon wafer not covered by photoresist, the pattern corresponding to the indentation pattern of the micromold, is thereby produced. Further processing familiar to those of ordinary skill in the art can be carried out.
- FIG. 11 illustrates schematically an
applicator 136 that can be used for applying any of the above-described chemically or biochemically active agents, polymeric precursors, fluid precursors of solid structures, fluid carriers of particulate matter, and the like to a substrate surface.Applicator 36 includes a plurality ofisolated indentations 138 separated from each other by intervening regions of asurface 140 in which the indentations are formed. As illustrated, two of the indentations containfluid carrier 142 andfluid carrier 144, respectively. Thefluid carriers substrate 146 is shown that, for purposes of illustration, includes a self-assembledmonolayer 148 formed thereon which can serve as an adhesion promoter.Fluid carriers substrate 146, in particular, regions of the exposed self-assembledmonolayer 148 on the surface ofsubstrate 146. The transfer typically takes place by bringing thesurface 140 of the applicator into contact with the self-assembledmonolayer 148 but, if thefluid carriers surface 140 need only be placed in close proximity to the self-assembledmonolayer 148. -
Fluid carriers monolayer 148 can be a monolayer of a species X—R—Ch as described in U.S. Pat. No. 5,620,850, issued Apr. 15, 1997 to Bamdad, et al., entitled “Molecular Recognition at Surfaces Derivatized with Self-Assembled Monolayers”, incorporated herein by reference. These species have the general formula as above where X represents a functional group that adheres to a gold surface, R represents a spacer moiety that promotes formation of a self-assembled monolayer of a plurality of the molecules, and Ch represents a bidentate, tridentate, or quadradentate chelating agent that coordinates a metal ion. The chelating agent includes a chelating moiety and a non-chelating linker moiety, such that it can be covalently linked via its linker moiety to the spacer moiety while allowing the chelating moiety to coordinate a metal ion. According to a preferred aspect of the invention a metal ion is coordinated to the chelating agent, and a binding partner of a target molecule is coordinated to the metal ion. This arrangement is facilitated by selecting the chelating agent in conjunction with the metal ion such that the chelating agent coordinates the metal ion without completely filling the ion's coordination sites, allowing the binding partner to coordinate the metal ion via coordination sites not filled by the chelating agent. A non-limiting exemplary list of suitable chelating agents includes nitrilotriacetic acid, 2,2′-bis(salicylideneamino)-6,6′-demethyidiphenyl, and 1,8-bis(a-pyridyl)-3,6-dithiaoctane. The binding partner can be a biological species that includes a polyamino acid tag, such as a tag made up of at least two histidine residues, that coordinates the metal ion. In this context the term “adhere” means to chemisorb in the manner in which, for example, alkyl thiols chemisorb to gold. - In this case the
fluid carriers carriers carriers substrate 146 to a chelating agent in solution to remove excess nickel ion from the surface. In this way, stray uncoordinated nickel ion does not coordinate to the self-assembledmonolayer 148 at regions outside of those regions to whichcarrier monolayer 148 include nickel ion. Accordingly, when the surface is exposed to a polyamino acid-tagged biochemically active agent, the biochemically active agent will attach selectively at those regions to which nickel ion had been applied. - According to another embodiment, self-assembled
monolayer 148 can be a species X—R—Ch—M as described in the above-referenced co-pending application Ser. No. 08/312,388, and thespecies applicator 136 in register with a plurality of reservoirs of distinct (different) biochemically active agents to position distinct biochemically active agents in the respective indentations of the applicator, then placing the applicator adjacent the surface ofsubstrate 146 to transfer distinct biochemically active agents to distinct, isolated regions of the surface. The procedure can be repeated using fresh substrate surfaces for each step, thus surfaces carrying distinct regions of distinct biochemically active agents can be mass produced. In addition to the species described above, cells can be immobilized at a substrate surface in this manner as well. Register between the applicator and the substrate surface can be controlled via mechanical, electronic, magnetic, and/or optical apparatus. - According to another embodiment,
species fluid carriers - Immobilization of cells and other biochemically active species can be carried out without a self-assembled monolayer as well. For example, a hydrophobic surface coated with laminin, and free of self-assembled monolayer, can serve as a substrate for immobilization of a pattern of cells in accordance with the invention.
- According to this and other embodiments, the substrate surface can carry chelating agent immobilized via other than a self-assembled monolayer. For example, chelating agents coupled to dextran at a surface, as is known, can be employed. Although a self-assembled
monolayer 148 is illustrated on the surface ofsubstrate 146, a self-assembled monolayer is not needed according to all embodiments. For example,substrate 146 can be adhesive to a species transferred to it fromapplicator 136, for example a biochemically or chemically active agent andfluid carriers - In accordance with all embodiments of the invention, such as those illustrated in FIGS. 1, 2, and11, the species formed proximate the substrate surface in a pattern corresponding to the indentation pattern of the article itself can be a self-assembled monolayer. Suitable self-assembled monolayer-forming species are described in U.S. Pat. No. 5,512,131 of Kumar, et al., referenced herein. Self assembled monolayers formed of species X—R—Ch, as described above, with or without metal ion and/or biological species coordinated thereto, can be used, as well as other self-assembled monolayer-forming species disclosed in application Ser. No. 08/312,388, by Bamdad, et al., referenced above.
- FIG. 12 illustrates schematically a process for applying a species from indentations in an applicator to a non-planar surface. An applicator136 (shown in cross section) includes a plurality of
indentations 138, each filled with aspecies 150. Each of the indentations can be filled with the same fluid or different fluids.Species 150 can be any of the above-described fluid precursors, chemically or biochemically active agents, or the like. Anarticle 152 having asurface 154 is placed adjacent the application surface ofapplicator 136 and rolled against the applicator as described in commonly-owned, co-pending U.S. patent application Ser. No. 08/397,635 by Whitesides, et al., entitled “Microcontact Printing on Surfaces and Derivative Articles”, and Internation Patent Application Publication No. WO 96/29629, both incorporated herein by reference. As thearticle 152 includingnonplanar surface 154 is rolled against theapplicator 136,species 150 is transferred to surface 154 in a pattern corresponding to the indentation pattern of the applicator. The indentation pattern can be any pattern as described above, for example individual, isolated regions or one or more continuous linear or non-linear indentations. The indentation or indentations can be of one or more depths. Application to nonplanar surfaces having various radii of curvature can be carried out according to the invention, for example, radii of curvature of less than about one centimeter, preferably less than about one millimeter, more preferably less than about 500 microns, more preferably less than about 100 microns, more preferably less than about 50 microns, and according to a particularly preferred embodiment printing can occur on substrates with radii of curvature on the order of about 25 microns or less. - FIG. 13 illustrates an
article 154 created by forming, on asilicon dioxide surface 156 of asilicon substrate 158, apatterned structure 160, for example a polymeric structure formed from a prepolymeric fluid using a micromold as illustrated in FIG. 1. Subsequently, a second fluid precursor is positioned so as to cover the patternedstructure 160 and allowed to solidify. According to the embodiment illustrated, a fluid precursor was placed atop the patternedstructure 160 and a micromold having a complex pattern was placed atop the fluid precursor. The fluid precursor was hardened to form astructure 162 covering and encompassing the patternedstructure 160 on the substrate surface. Thesecond structure 162 included an exposedsurface 164 having a pattern ofindentations 165 complementary to the indentation pattern of the second micromold. The overall structure, whenstructure 160 differs in refractive index fromstructure 162, can serve as a waveguide, thesecond structure 162 serving as a cladding. Thecontoured surface 164 ofcladding 162 is lossy. The pattern ofsurface 164, in most instances, is not important to the waveguide function. Waveguides were fabricated from several classes of polymeric materials (epoxies, polyurethanes, and polyacrylates on Si/SiO2 substrates. Waveguides clad with polymers having slightly lower refractive indices gave single-mode output in the visible and near infrared regions. A typical waveguide structure exhibiting single-mode behavior consisted of a trapezoidal waveguide (nguide=1.545) clad in a polymeric slab with ncladding=1.52. The waveguide was 0.7 centimeters long and the wavelength of light was 0.85 micron. Photocurable polymers are preferred. Waveguides are described in greater detail below. - Referring now to FIGS. 14a-k, a schematic illustration of a surface derivatized so as to include discrete regions of differing chemical functionality is shown. The article schematically illustrated finds particular use as a combinatorial library. An article by Jacobs, et al., entitled “Combinatorial Chemistry-Applications of Light-Directed Chemical Synthesis”, Trends in Biotechnology, volume 12, 19-26 (January, 1994; incorporated by reference above) describes a photolithographic process for forming a combinatorial library. Jacobs, et al. describe derivatizing a substrate with linker molecules that contain amines blocked by a photochemically cleavable protecting group. Specific sites on this synthesis surface are photo-deprotected by illumination through a photolithographic mask. Those regions exposed to light are deprotected, and may then be coupled to amino acids of interest using standard peptide-synthesis conditions. The process is repeated using new masks until an array of compounds of the desired length and composition are built up. The patterns of photolysis and order of addition of amino acids define the products and their locations on the solid support. The present invention can find application in combinatorial library synthesis with a minimum of expense and equipment. Those of ordinary skill in the art will recognize that any of a wide variety of chemically and biologically active agents can be used in accordance with the procedure discussed below and illustrated in FIGS. 14a-k. The criteria for selection of such agents is similar to selection criteria for those agents described above that can be positioned on a substrate surface using a forming article or
micromold 20. In a manner analogous to the procedure of Jacobs, et al., wet chemical protecting groups can be utilized in accordance with the present invention rather than photochemically cleavable protecting groups. Orthogonal-stripe methods and binary synthesis of combinatorial libraries in accordance with the invention, with reference to FIGS. 14a-k, are described below in the prophetic example. - The following prophetic example involves the creation of a combinatorial library on a substrate surface using the micromold of the invention. With optional reference to Jacobs, et al., “Combinatorial Chemistry-Applications of Light-Directed Chemical Synthesis”,Trends in Biotechnology, 12, 19-26 (January, 1994) and Chemical & Engineering News, 74, 7, 28-73 (Feb. 12, 1996), those of ordinary skill in the art can follow the teachings herein to form a combinatorial library inexpensively.
- Reference will be made to FIGS. 14a-k, which illustrate schematically top views of a substrate surface. FIGS. 14a-c illustrate an “orthogonal-stripe” method. According to the technique, a plurality of micromolds are fabricated, each of which has a distinct channel pattern. Each micromold is fabricated so as to cover
substrate surface 166, or at least enough ofsubstrate surface 166 to define a channel or channels necessary for application of chemically or biochemically active agents to desired regions of the surface. For purposes of illustration, the description will assume use of a micromold that completely coverssubstrate surface 166, and includes indentations in register with certain portions ofsubstrate surface 166. One micromold includes an indentation in register with a portion of the substrate surface designated “A” in FIG. 14a and includes a contact surface that contacts the remaining substrate surface at areas designated “B”, “C”, and “D”. With reference to FIG. 14b, individual micromolds will be fabricated that include contact surfaces that cover all portions of the substrate except one of the portions “E”, “F”, “G”, or “H”. That is, each micromold forms a channel through which a chemically or biochemically active agent (reactant) can be delivered to the substrate surface at a portion in register with the channel, while remaining portions of the micromold block regions proximate the substrate surface from interaction with the particular chemically or biochemically active agent. Any combination of micromolds can be used to apply to the surface, in any combination, various chemically or biochemically active agents. For example, with reference to FIG. 14a, if a micromold having a channel in register with region “A” of the substrate surface is used to apply to the surface a chemically active agent “A” and then, with reference to FIG. 14b, a micromold is placed adjacent the substrate surface that has an indentation in register with region “E” and is used to apply to region “E” a chemically active agent “E”, the substrate surface will include a region carrying chemically active agent “A” (the region designated “A” in FIG. 14a), a region carrying chemically active agent “E” (the region designated “E” in FIG. 14b), and at the region where the regions “A” and “E” intersect both chemically active agents will have been applied (upper left comer of the substrate surface as viewed in FIG. 14c). It can be seen that, if all combinations of micromolds and chemically active agents are employed, the result will be a grid on the substrate of each combinatorial permutation of the chemically active agents each confined to a separate region of the substrate surface (FIG. 14c). As is apparent to those of ordinary skill in the art, the order of application of active agent to the various regions of the substrate surface can be used to tailor the synthesis of the individual species at the various locations on the substrate surface. - With reference to FIGS. 14d-k, a “binary” synthesis technique is described. In FIG. 14d, a first micromold having an indentation in register with region “A” and a contact surface in register with region “Ø” is used to apply to the substrate surface an active agent “A” selectively at region “A”. FIG. 14b shows
surface 166 including a region “B” in register with an indentation of a second micromold and a region “Ø” in register with a contact surface of the second micromold, via which an active agent “B” can be applied selectively to region “B” of the substrate surface. FIG. 14f showssurface 166 having portions “C” and “Ø” that are positionable in register with indentations and contact portions, respectively, of a third micromold to apply an active agent “C” to regions “C”. In FIG. 14g the surface includes portions “D” and “Ø” that are positionable in register with indentations and contact portions, respectively, of a fourth micromold to transfer agent “D” selectively to regions “D”. The binary technique is less labor intensive than the orthogonal-stripe method in that only four transfer or flow steps involving four micromolds are needed to create a grid of sixteen distinct chemically or biochemically functional regions on the substrate surface. - After application of the first micromold and formation of chemically or biochemically active agent “A” via the channel of the first micromold, agent “A” is applied to the left side of the
substrate surface 166 and the right side of the substrate surface remains free of agent as illustrated in FIG. 14h. After application of agent “B” to the upper portion of substrate surface using the second micromold, four quadrants of the substrate surface carry agent “A” plus agent “B”, agent “B”, agent “A”, and no agent, respectively, as illustrated in FIG. 14i. After application of agent “C” via the channels of the third micromold, eight regions of distinct chemical or biochemical functionality exist on the surface as illustrated in FIG. 14j. After application of agent “D” via the indentations of the fourth micromold, sixteen distinct chemically or biochemically active regions are formed as illustrated in FIG. 14k, namely “ABCD”, “ABC”, “BCD”, “BC”, “AND”, “AB”, “BD”, “B”, “ACD”, “AC”, “CD”, “C”, “AD”, “A”, “D”, and “Ø”. The register between each micromold and the substrate surface can be controlled by pins in the substrate that engage each micromold, pins in each micromold that engage the substrate surface, an X-Y table that positions the substrate surface identically relative to each micromold, optical, magnetic, or electronic aligning apparatus, or other equivalent apparatus that can align each micromold with the substrate surface. Accurate register at the micron scale is achieved. - Those of ordinary skill in the art have the ability to select, without experimentation or with only routine experimentation, chemically or biochemically active agents that can be used to create a myriad of chemically active or biochemically active combinatorial libraries according to the technique of the invention. It can be useful to first
coat substrate surface 166 with a common chemical linker functionality coupled to a chemical protecting group, apply a first micromold to the substrate surface, first deprotect at the region in register with the channel, then carry out a synthesis step at that region and reprotect, then remove the first micromold and apply a second, different micromold, again deprotect at the portion of the substrate surface in register with the channel of the second micromold, carry out a second synthesis step, and reprotect, etc. Libraries of peptides, synthetic molecules such as new drugs, naturally-occurring chemical and biochemical species, oligonucleotides and the like can be created. Indeed, any of the chemically or biochemically active agents, fluid precursors, prepolymeric fluids, or the like as described above that are transferable from a microapplicator or that can be applied, for example via capillary action, to a surface using a micromold as described above, can find use in the combinatorial arrangement described. Any combination of various agents can be used. - As an alternative embodiment to that described above, an
article 20 as illustrated in FIG. 2, having a contouredsurface 22 including a plurality of protrusions separated by interveningindentations 24 can be used as a stamp for forming a combinatorial library. Stamping as described in U.S. Pat. No. 5,512,131 (issued Apr. 30, 1996 to Kumar, et al., referenced above) can be employed. The stamp includes a stamping surface defined by the outer surfaces of the protrusions. The process is described with reference to FIGS. 14d-k. Asurface 166 carries a protecting group, for example, a self-assembled monolayer exposing outwardly an azide functionality. A stamp having a surface including a protrusion in register with area A of surface 166 (FIG. 14d) is prepared by applying to the protrusion a deprotecting species such as a reducing agent for reduction of the azide to a deprotected, reactive amine. Application of the stamp to surface 166 deprotects the self-assembled monolayer at region A, but leaves the remainder of surface 166 (Ø) protected. Then, chemical reactivity at region A can take place, followed by reprotection of the entire surface. Then the stamp can be re-oriented, or a second stamp chosen, so that region B is deprotected by contact with a stamping surface (protrusion) of a stamp. Chemical reaction then is carried out a region B, and the surface re-protected. With reference to FIG. 14f, a stamp having protrusions corresponding to regions C is used to deprotect at regions C, followed by chemical reaction at regions C and re-protection, and the process carried out similarly at regions D (FIG. 14g). According to a preferred embodiment, the stamping surface itself, without any auxiliary agent carried thereon, can deprotect at regions ofsurface 166 in register with the stamping surface. For example, a stamp having an acidic stamping surface such as a hydrogel loaded with a component of low pH can be used. For example, Dextran™ carrying polyphosphoric acid can be grafted to a surface of a rigid or elastomeric stamp and used to deprotectsurface 166 at regions corresponding to the protrusions or stamping surface. Other protecting/deprotecting chemistries such as hydrolysis chemistry can be carried out. - According to another embodiment, rather than building a combinatorial library through step-by-step synthesis of various species at various distinct regions proximate a substrate surface, distinct species can be synthesized and applied to the substrate surface after synthesis. A combination of these approaches can be used as well, involving synthesis of building blocks that are assembled according to the prophetic example.
- FIG. 15 illustrates a set of particularly preferred fabrication techniques of the invention in which, rather than applying
article 20 tosubstrate surface 28 followed by introduction offluid precursor 36 intochannels 32 so defined,article 20 is used as an applicator to transfer the fluid precursor tosubstrate surface 28. The following description will be made with reference to fabrication of astructure 38 and other structures that are waveguides, from aprecursor 36 that will be referred to as a waveguide precursor, although the following description defines one aspect of the invention that is applicable to creation of any of a wide variety of structures described herein and is not limited to waveguides. In FIG. 15,fluid precursor 36 is first applied toindentations 24 ofapplicator 20. Excess fluid precursor then can be removed, by scraping, fromapplication surface 22. For example, a block of material similar or identical in composition to that ofarticle 20 can be used to scrape off excess prepolymer. Alternatively, with appropriate structures, the excess precursor can be blown off with a brisk stream of gas such as nitrogen. A brisk stream of gas also can be used to remove remaining drops of precursor after the bulk excess of precursor has been scraped away.Applicator surface 22, the indentations of which are filled withfluid waveguide precursor 36, then is placed in contact withsurface 28 ofsubstrate 30.Applicator 20 then can be removed, leaving some or all ofprecursor 36 in contact withsurface 28 where it is subsequently made dimensionally stable or, according to preferred embodiments,fluid precursor 36 is hardened to the point that it is dimensionally stable whilearticle 20 remains in place uponsubstrate surface 28. Wherefluid precursor 36 is a fluid prepolymer, and is heat-curable, the precursor can be heated, for example, byheating substrate 30,article 20, bothsubstrate 30 andarticle 20, or applying radiative heat. Whereprecursor 36 is a photopolymerizable fluid, it can be exposed to electromagnetic radiation that causes polymerization. Afluid precursor 36 can be partially or fully polymerized prior to removal ofarticle 20, so long as it is polymerized to the extent that it is dimensionally stable and self-supporting. In preferred embodiments, as described below, it is often advantageous to only partially polymerize a fluidprepolymeric precursor 36. - Where
fluid precursor 36 is a fluid carrier of a suspension, the fluid carrier can be selected in conjunction with the material ofarticle 20 to allow the fluid to be absorbed intoarticle 20 and thereby dissipated, resulting in deposition of solid material from the suspension as the patterned material onsubstrate surface 28. Wherefluid precursor 36 is a solution of a dissolved precipitating species, conditions such as temperature, pH, or the like can be altered to cause precipitation. One advantage of the technique of FIG. 15 is that the fluid precursor is in contact witharticle 20 for only a very brief period of time, thus ifarticle 20 adsorbs or absorbs any components offluid precursor 36 disadvantageously, such as adsorption of dyes, this is minimized. Another advantage is that with a thermally-curable precursor the technique is made much easier since the time required for the process is very fast relative to typically curing times. - Following solidification of
fluid precursor 36 to form an array ofwaveguides 38, solidification taking place to the extent that waveguide 38 is dimensionally stable,article 20 is removed fromsubstrate 30. Following this step, or other steps for forming an array ofwaveguides 38 on substrate surface 28 (e.g. as described with reference to FIG. 1), a cladding can be provided upon the waveguide array to form awaveguide assembly 44 by adding a hardenablecladding precursor fluid 40 on top of the array, optionally formingfluid 40 into a desired shape with a desired thickness above and beside the waveguide array by, for example, positioning acladding mold 42 above the precursor to form the precursor, allowing the cladding precursor to harden (for example, via polymerization) and removingcladding mold 42 to form acladding 43 that includes a layer of cladding abovewaveguides 38. In another embodiment acladding mold 168 can be used whichmolds cladding precursor 40 betweenwaveguides 38 and laterally ofwaveguides 38, but does not allow formation of cladding above the waveguides to form anassembly 172. This can be accomplished where thecladding mold 168 is a flexible elastomeric mold that conforms to form a mold resting atopwaveguide 38. The cladding precursor is allowed to harden, and removal of the mold results in acladding 170 that fills spaces betweenwaveguide 38, and extends laterally beyond the lateral-most waveguides such that each side of each waveguide is contacted by cladding, but the top of each waveguide is exposed. In another embodiment awaveguide assembly 174 can be formed by applyingcladding precursor 40 towaveguides 38, allowing the cladding precursor to drip off of the waveguides, and hardening the cladding precursor. - In each case, subsequently, the substrate/waveguide/cladding assembly can be cleaved along lines a-a and b-b to define a
waveguide assembly waveguide assembly 44, an overall assembly height including cladding of a dimension z on the order of dimension y to about 10 times dimension y, for example from about 1 to about 10 microns and a length l of any of a wide variety of lengths on the order of 100 microns to centimeters. Larger waveguides can be made as well, for example waveguides having width or height on the order of 200 or 250 microns, with spacing of similar order. In the case ofwaveguide assembly 172 the cladding height equals the waveguide height, and in the case of 174 the cladding height typically is very slightly greater than the waveguide height. - Another technique for fabricating a
waveguide assembly 172, includingwaveguides 38 andcladding 170 which contacts the sides, but not the tops ofwaveguides 38 is as follows. Following fabrication ofwaveguides 38, and prior to application of any cladding, a microcontact printing technique as described in international patent publication no. WO 97/07429, of international patent application no. PCT/US96/13223 entitled “Patterned Materials Deposition Effected with Microcontact Printing” is carried out to apply a hydrophobic component selectively to the tops, but not the sides ofwaveguides 38, followed by addition of a hydrophilic cladding prepolymeric precursor which assembles within and betweenwaveguides 38, but not atopwaveguides 38, followed by curing of the cladding precursor. The particular microcontact printing technique involves coating a flat applicator with a self-assembled monolayer forming molecular species and applying the flat applicator towaveguides 38 such that the applicator contacts only the tops ofwaveguides 38. Any molecular species transferable in this manner can be used to create a hydrophobic functionality atopwaveguides 38 such that a hydrophilic prepolymer will assemble betweenwaveguides 38 and laterally on either side, or the opposite can be carried out in which a hydrophilic material is applied to the tops ofwaveguides 38 and a hydrophobic cladding precursor used to fill spaces between and laterally of the waveguides where the waveguides andsurface 28 ofsubstrate 30 is sufficiently hydrophobic. In one technique,surface 28 andwaveguides 38 were subjected to oxidizing treatment, and microcontact printing was used to transfer a self-assembled monolayer of a fluorine-terminating molecule to the surface. Specifically, tridecafluoro-1,1,2,2-tetrahydro(o-octyl)-1-trichlorosilane was applied to the tops, but not sides, ofwaveguides 38 and formed a hydrophobic self-assembled monolayer thereon. A hydrophilic cladding precursor, in particular a liquid polyurethane prepolymer, was added and assembled between and laterally ofwaveguides 38. Curing of the polyurethane cladding precursor, followed by cleaving of the waveguide ends, resulted in a waveguide assembly similar toassembly 172. - In typical embodiments, cladding is added to
waveguides 38 to lower the refractive index difference betweenwaveguides 38 and their surrounding environments. Without cladding,waveguides 38 typically are very good performers, but support too many modes. Addition of cladding, which reduces the refractive index difference at the boundaries ofwaveguides 38, reduces higher order modes. - FIG. 13 (discussed above) is essentially identical to a cross-section through line a-a of
waveguide assembly 44 of FIG. 15, showing atypical substrate 30, optional film 31 of an adhesion promoter, native oxide layer, or the like on substrate 30 (the top surface of film 31 definingsubstrate surface 28 according to this embodiment), array ofwaveguides 38, andcladding 43. The waveguide of FIG. 13 differs from waveguides fabricated in accordance with the technique of FIG. 15 in that it includes a contoured cladding surface corresponding to a contoured cladding mold.Precursor 36 is a material as described above which can serve as a waveguide. Selection of such materials is within the level of ordinary skill in the art. - In embodiments of the invention involving waveguide fabrication,
substrate 30 can be essentially any material including those materials described above, but should be optically smooth.Substrate surface 28 can be of the same material as the bulk material ofsubstrate 30, or a different material. A non-limiting, exemplary list of substrate materials includes silver, gold, glass, silicon/silicon dioxide, and the like. The waveguide pattern can be formed on contoured surfaces, and flexible surfaces. Wheresubstrate 30 is flexible (for example, a polyvinylchloride film) the waveguide can be deformed while guiding light. The utility of this technique will be described more fully below. In embodiments of the invention involving waveguide fabrication,article 20 can be as described above, and preferably is elastomeric. - Selection of materials for
waveguide 38, cladding 43, and substrate 30 (and optional film 31) can be selected by those of ordinary skill in the art to form a structure that can guide electromagnetic radiation of a desired frequency. As is known, total internal reflection of electromagnetic radiation will occur withinwaveguide 38 where the electromagnetic radiation propagating within the waveguide strikes an interior boundary of the waveguide to form an angle θ, with a line normal to the interior boundary, where sin θ is ≧(refractive index of the cladding)/(refractive index of the waveguide). Those of ordinary skill in the art can select materials to form theoverall system 44 that will serve as a waveguide. In one set of embodiments cladding 43 can be non-existent. That is, the cladding can be the environment surrounding the waveguide, such as air. In some embodiments it is useful to have a cladding defined by a material filling the indentations between and defined bywaveguides 38, where the top surfaces ofwaveguides 38 are exposed to ambient conditions. The difference in index of refraction between waveguide and cladding, and waveguide and the substrate, typically is from about 0.01 to about 0.001. These and other embodiments can be useful as sensors, etc., and are described more fully below. - It is one feature of the invention that waveguides38 and
cladding 43 can be formed from an identical, or nearly identical fluid prepolymer, the degree of polymerization of which can be controlled by the amount of exposure to polymerization conditions such as heat or radiation. For purposes of the invention, “polymerization” is meant to encompass cross-linking. This technique is facilitated by the fact that the refractive index of a solid typically is greater than the refractive index of a liquid of similar composition in that the density of a solid typically is greater than of a liquid. The difference in index of refraction typically decreases with curing time for a polymer. Thus, the difference in refractive index can readily be tailored. This technique provides several advantages that will become apparent from the discussion below. One advantage is simplicity, since in this embodiment only a single prepolymer fluid need be used, first as prepolymer fluid 36 (with reference to FIG. 15) that is positioned witharticle 20 againstsubstrate surface 28 and polymerized, for example photopolymerized, followed by addition of a common prepolymer (the same prepolymer)cladding precursor 40 which then can be photopolymerized. During polymerization (curing) ofcladding prepolymer 40,waveguide 38 is cured to a greater extent, and the refractive index difference betweencladding 40 andwaveguide 38 decreases during curing ofcladding 40. One advantage of using identical, or nearly identical fluid prepolymers both forwaveguides 38 andcladding 43, the difference in refractive index being due to different curing times, is that any batch-to-batch difference between polymers is unimportant as the amount of exposure to polymerization conditions is the only important feature. That is, the relative refractive index change in material, during curing, is what is important, and conditions do not need to be adjusted because of slight variation in material composition. - One advantage of the transfer technique of FIG. 15 is that it is exceptionally simple experimentally, and very inexpensive. It can readily be used to produce multiple copies of complex microstructures. Another advantage of the technique is that many waveguides can be fabricated essentially simultaneously. Tens or hundreds of
applicators 20 can be fabricated from a single master which is, in turn, fabricated from a photolithographically-created surface or the like, and each applicator can be used to fabricate hundreds or thousands of waveguides. For example, where anapplicator 20 having a dimension perpendicular to the linear dimension ofindentations 24 of approximately 3 centimeters is used, andindentations 24 each are of approximately 2 microns in width and spaced approximately 2 microns from each other, one molding process as illustrated in FIG. 15 can result in more than 4,000 waveguides. - Another advantage of the transfer molding technique of FIG. 15 is that multiple layers of waveguides can be fabricated readily. With reference to FIG. 16,
applicator 20 first can be used to transferfluid waveguide precursor 36 tosubstrate surface 28 where it is hardened to formwaveguide array 38, as illustrated also in FIG. 15, and then waveguidearray 38 onsubstrate 30 can be placed upside down upon anotherapplicator 20 including indentations filled withfluid waveguide precursor 36,precursor 36 can be cured, andapplicator 20 removed to form a two-layerstacked array 248. The process can be repeated any number of times to form any number of layers of waveguide arrays, as exemplified by stackedwaveguide array 250, with the waveguides arranged in any orientation relative to each other in which support for each layer is provided. - Yet another advantage is that periodicity in the cladding structure43 (FIG. 15) can be readily formed, via a
cladding mold 42 including a periodically contoured inner surface, or via irradiation ofcladding 43 through a mask to cure alternating portions of the cladding to a greater extent relative to intervening portions. In this manner, a grating can be fabricated in the cladding, such as a Bragg grating. Gratings also can be fabricated directly in or ontowaveguides 38 by using amold 20 in which the indentations that in part define the mold for the waveguides includes a contoured interior surface. Chirped waveguides and other periodic structures can be fabricated in the cladding, or in the waveguide core itself, in this technique. Attenuation can be achieved in this way, and resident cavities can be created. - Another feature of the present invention is the ability to fabricate waveguide couplers, easily and conveniently, regardless of the local geometry of the waveguide. FIG. 17 is a schematic illustration of a prior at “Y” coupler including branched portions as shown, for example, in U.S. Pat. No. 5,313,545 (Kuo, et al.), including a
coupling region 252 and branching input/output regions regions region 252 and will branch and travel along both branchingportions branches region 252 and branch intoregions region 252. - FIG. 18 is an illustration of a prior art “evanescent” coupler, the principle of which is used to provide coupling between guides of U.S. Pat. No. 5,481,633 (Mayer). This coupler operates on the principle that, depending upon the refractive index between waveguide and surrounding environment (e.g., cladding) the waveguide dimensions (size and shape), the wavelength of light, and separation between waveguides, an “evanescent tail” extends from each waveguide, the energy of the tail decreasing with distance from the guide. Where waveguides are close enough to each other, and the evanescent tail passes into the adjacent waveguide, radiation can leak into the adjacent waveguide and the waveguides couple. In the prior art array of FIG. 18,
waveguide 258 includes acoupling portion 260 andnon-coupling portions waveguide 266 includes acoupling portion 268 andnon-coupling portions coupling portions non-coupling portions regions - The particular shape of the waveguide required for either of the couplers of FIGS. 17 and 18 is limited also by the fact that curves or comers that form part of the shape of a waveguide should not exceed a maximum amount of sharpness, or the critical angle of total internal reflection will be exceeded and loss of electromagnetic radiation will occur.
- The invention provides a solution to this problem, as illustrated in FIG. 19 which illustrates an array including essentially
parallel waveguides cladding 278 which can completely envelope and coverwaveguides waveguides cladding 278 can be formed from an identical prepolymeric precursor with differences in refractive index controlled by different curing times. The array ofwaveguides cladding 278 includescentral portion 280 andlateral portions waveguides cladding 278, withincentral portion 280 is relatively small, while the refractive index ratio between the waveguides and the cladding inlateral portions waveguides portion 280, but does not occur inlateral portions region 280 defines a coupled region of the waveguides that is functionally similar to the coupledportions waveguides portion 252 of the branched structure of FIG. 17. This can be achieved, for example, as follows.Waveguides waveguides portions only portion 280 is subjected to additional photopolymerization conditions, resulting in significantly decreased refractive index differences betweenwaveguides cladding 278 in that region (280). The result is that, inregions region 280 coupling occurs. One advantage of the technique is that coupling can be tailored at any region of the waveguide array where waveguides designed to carry UV or visible light, of the type produced by a red He—Ne laser, are separated more than about 2 microns, for example up to 6 microns, 8 microns, or even 10 microns inregion 280, allowing much simpler fabrication that does not require as much precision. In contrast, the coupling regions of FIG. 18 are defined by their separation distance, which typically must be much smaller than the separation distance allowable for the system of FIG. 19, requiring significantly greater precision and related expense. - In another embodiment of the invention the locations of the regions of coupling between waveguides are tailorable, and the amount of coupling at those locations is controllable. This can be accomplished when
waveguides cladding 278 are selected such that the refractive index ratio between waveguide and cladding can be changed, reversibly, after fabrication. For example, where the refractive index ofcladding 278 can be changed reversibly based upon exposure to specific electromagnetic radiation (where, for example, cladding 278 is reversibly photosensitive; such materials are known to those of ordinary skill in the art) the array can be fabricated andregion 280 irradiated with the specific radiation to cause coupling where no coupling occurs inregions region 280, andregion 282 can be exposed to the specific radiation resulting in coupling withinregion 282 where no coupling occurs inregions regions - The above technique facilitates a waveguide coupler that can be used at different wavelengths of light. That is, where the refractive index difference at the boundaries of waveguides can be adjusted during use, or between uses, by exposure to different electromagnetic radiation, electric fields, or the like, the waveguide can be adjusted for use with different wavelengths of light. This also can be used to adjust the degree of coupling that occurs during use. For example, coupling could be adjusted from ten percent to fifty percent by exposure to electromagnetic radiation according to this technique.
- The geometrical tailorability of refraction index ratio between cladding and waveguide facilitates the creation of a variety of switches and sensors. With reference to FIG. 19, where
cladding 278 is an electro-optical material or other material that can reversibly change refractive index upon exposure to certain electric fields, or is a non-linear optical material (e.g., dye) that changes in refractive index in response to electromagnetic radiation, the array can be a sensor of that electric field or electromagnetic radiation since exposure to the field or radiation will cause a detectable change in coupling betweenwaveguide 274 andwaveguide 276. In one arrangement,region 280 can be defined by a cladding that is reversibly electric field sensitive, whilesections region 280 only, and coupling atregion 280 is indicative of the existence and strength of the field. - As an example of a sensor of a chemical or biological species in accordance with the invention, the cladding of
region 280 can include, on its exposed surface, a material that is sensitive to a particular analyte such that when the analyte is present, the refractive index of the cladding changes in an amount sufficient to detectably change the coupling characteristic betweenwaveguides region 280. As one example,region 280 can define a flow chamber aboutwaveguides waveguides region 280. The change in the existence of, or concentration of, a particular analyte in the fluid (such as a salt or other refractive index-altering substance) can cause quantitative, or qualitative changes in coupling betweenguides region 280, resulting in quantitative or qualitative sensing. For example, a cation or anion exchange material can be provided that a surface, such as a sulfonic, phenolic, phosphoric, or carboxylic acid group, for capture of ions from solution. Chelating agents, kryptands, crown ethers, and the like can be used. - As another example, the array of FIG. 19 can be constructed where, at region280 (or other or all regions) cladding 278 includes an exposed surface that carries an immobilized biological binding partner of a biological molecule or exposed surfaces of
waveguides cladding 278,waveguide 274 and/or 276 (at region 280) ifregion 280 carries the biological binding partner exclusively and, if present, the biological molecule binds to its immobilized binding partner, changing the refractive index of cladding 278 (e.g. at region 280) and thereby changing the refractive index ratio between the waveguides and cladding in that region, detectably altering coupling. As mentioned, where a cladding completely coverswaveguides cladding 278 form only a very thin layer abovewaveguides waveguides - As mentioned above,
substrate 30 can be flexible. This facilitates a method involving guiding electromagnetic radiation through a waveguide array of at least two waveguides, simultaneously, while altering the conformation of the waveguides. That is, the substrate carrying a plurality of waveguides can be bent or otherwise deformed during electromagnetic radiation propagation. This can be useful for a variety of purposes, one of which is increased sensitivity in a sensor. Where a sensor is sensitive to changes in a surface of a waveguide or cladding that occur upon exposure to an analyte, as described above, sensitivity can be increased as follows. The waveguide can be bent to its limit of maintaining total internal reflection, which is readily determined by bending the waveguide too far and then returning the waveguide to a conformation allowing total internal reflection. Where the interaction of an analyte with the waveguide decreases the difference in refractive index between waveguide and cladding, loss of electromagnetic radiation passing through the waveguide can be indicative of interaction with an analyte, and is made much more sensitive where the waveguide is almost at the limit of maintaining total internal reflection prior to exposure to the analyte. In another example, where coupling between waveguides is highly dependent upon the conformation of the waveguides, altering the conformation of the waveguides (facilitated with a flexible substrate) can result in operation very near the limits of coupling where exposure to an analyte will relatively more greatly affect coupling. - Referring now to FIG. 20, an
array 286 ofwaveguides waveguide 292 can couple intowaveguides waveguide 290 can couple back intowaveguide 292 and intowaveguide 288, and fromwaveguide 294 can couple back intowaveguide 292 and intowaveguide 296. The result is that an interferometer is created and an interference pattern defined by radiation emerging from each of waveguides 288-296 is created and is distinctive based upon spacing of the waveguides, refractive index difference between waveguide and cladding, waveguide dimensions, wavelength of radiation, and propagation length. The system of FIG. 20 can serve as a sensor since any change in refractive index differs at the boundaries of one or more waveguides, for example a difference in refractive index of the cladding surrounding waveguides 288-296 such as via exposure to an electric field or electromagnetic radiation, exposure to a fluid, or exposure to another analyte as described above will alter the interference pattern emerging from waveguides 288-296. - A series of working examples were conducted relating to waveguides. With the exception of cross-linking of the polymer, synthesis was conducted in a class-100 clean room. A poly(dimethylsiloxane) (PDMS) elastomeric mold, or applicator, 20 (sylgard 184, Dow Corning, Silicone Elastomer: curing agent=15:1) was cast from a photoresist pattern made in a standard photolithographic process (Kumar, et al., Langmuir, 10, 1498 (1994)). With reference to FIG. 15, an array of
waveguides 38 was formed by filling the relief structure (indentations 24) inapplicator surface 22 ofapplicator 20 with a liquid prepolymer (polyurethane, NOA-73, Norland Products New Brunswick, N.J.) and then placing the applicator surface of the filledapplicator 20 onsubstrate surface 28 of a Si(100)wafer 30 supporting a 2 micron-thick layer of SiO2. The prepolymer was cross-linked in situ by irradiating the system for 1 hour at a distance of 1 centimeter with a 450 W medium-pressure Hg vapor lamp (type 7825-34, Ace Glass, Vineland, N.J.). After UV exposure, the elastomeric mold (applicator 20) was peeled away, leaving an array ofwaveguide structures 38 onsubstrate 30. The technique was pattern used to generate waveguides with a variety of widths of 2.0, 2.6, 3.0, and 4.0 microns, and spacings of 2.0, 4.0, and 8.0 microns. All waveguides had the same height of approximately 1 micron. The length of the waveguides was determined by the points at which the wafer was fractured. In one set of embodiments the waveguide array was left unclad. In embodiments in which cladding was applied, cladding was made by providing a thick layer of the same liquid prepolymer and applying it to the waveguides, the surfaces of which had been slightly oxidized by exposure for about 10 minutes in a UV-ozone cleaner (models 13550 and 13550-2, Boekel Industries) to render them hydrophilic and improve adhesion. The system was heated to 85° C. on a hot plate to decrease the viscosity of the prepolymer, and the excess prepolymer was allowed to drain to one edge. The thin layer of prepolymer left on the surface was loosely cross-linked by brief (1 minute) exposure to UV light (365 nm) from a 4 W hand-held lamp (Blak-Ray UV lamp model UVL-21, UVP, San Gabrielle, Calif.). The ends of the clad waveguides were squared by cleaving the substrate. After cleaving, the cladding was cured completely (30 seconds) with the 450 W medium-pressure Hg vapor lamp. This procedure allowed the ends of the waveguides to be cleaved when the cladding layer was in the liquid phase, preventing the cladding from deadhering from the guides. - FIG. 21 is a photocopy of an SEM image of an unclad waveguide array, and FIG. 22 is a photocopy of an SEM image of a clad array, each fabricated according to this technique. In each case waveguide width was about 2.6 microns, waveguide spacing was about 2.0 microns, and waveguide height was about 1.0 microns.
- FIG. 23 is a schematic diagram of apparatus used to couple light into and out of waveguide arrays fabricated as described immediately above. Light from a He—Ne laser 298 (633 nm) was first coupled into a single-mode
optical fiber 300 which was butt-coupled to the end of waveguides of array 302 (representative of a variety of waveguide arrays fabricated as described immediately above, and tested in accordance with this example) using a precision 3-dimensional translation stage 304. Light also could be coupled into the waveguide array using focusing apparatus. That is, light from a laser could be focused, through a lens arrangement, to the end of waveguides of thearray 302. Using this apparatus, light was selectively coupled into individual waveguides in the array, or into the cladding between or above the waveguides. The output light from the waveguides was imaged with amicroscope objective 305 and recorded on aCCD camera 306. The shapes and intensities of the outputs of the individual waveguides could easily be observed (in the absence of the objective 305 the far field patterns from adjacent waveguides overlapped). - FIGS. 24a-g show the results of a variety of different waveguide arrays and inputs, and demonstrate tailorable coupling, using the apparatus of FIG. 23 and waveguide arrays fabricated as described above. In FIG. 24a,
trapezoidal waveguides 38 indicate the positions, in cross-section, of 3 micron-wide waveguides with neighboring waveguides separated by 8 microns. The height of each waveguide was 1 micron.Optical fiber 300 was positioned as indicated, in alignment with the central of the 5 waveguides. FIG. 24b is a photocopy of a CCD camera frame grab of the output of the system of FIG. 24a. A single-mode output occurred, with no evanescent coupling between adjacent waveguides. FIG. 24c is representative of a second waveguide structure fabricated in accordance with the technique described above, with waveguides separated by 4 microns, rather than 8 microns. The UV exposure time for the array of FIG. 24c was the same as for the array of FIG. 24a. However, the 4 micron spacing was small enough to allow evanescent coupling between guides and light was observed in 5 adjacent waveguides (FIG. 24d: photocopy of a CCD camera frame grab of result). Additionally, as the input optical fiber was moved to adjacent waveguides, this output pattern moved in register. The reproducibility and symmetry of the pattern established the uniformity of the coupling between the waveguides in the array. The low level of light at the exit of the central waveguide was caused by efficient coupling of light from the central waveguide into adjacent waveguides. - FIG. 24e demonstrates the ability to modify the coupling between adjacent waveguides by controlling the difference in refractive indices between the guides and their cladding by manipulating exposure time during UV curing. FIG. 24e is a photocopy of a CCD camera frame grab of output of the waveguide of FIG. 24c (which produced the pattern of FIG. 24d) after additional exposure of the array (waveguides plus cladding) under the 450 W medium-pressure Hg vapor lamp. This exposure reduced the index difference between waveguide core and cladding, and increased the coupling between the waveguides. The change is most easily seen in the change in brightness of the center waveguide between FIG. 24d and FIG. 24e. In FIG. 24d, the light coupled out of the center waveguide into the adjacent waveguides. In FIG. 24e, the light coupled from the adjacent waveguides back into the center waveguide. Thus, the center waveguides formed an interferometer. Light from the single waveguide directly addressed by
optic fiber 300 was evanescently coupled into nine waveguides and many closed-path interferometers were formed. - FIG. 24g shows the output of the array when light was coupled into cladding between the waveguides as shown in FIG. 24f. No waveguide output was observed and very little light was observed from the output of the cladding. This demonstrated that the excitation of multiple waveguides as shown in FIGS. 12d-e was the result of coupling from propagating waveguide mode to propagating waveguide mode, not from cladding modes to waveguide modes. This interpretation was supported by numerical simulations.
- Two-micron-high clad waveguides of width 2.0, 2.6, 3.0, and 4.0 microns and spacing of 2, 4, and 8 microns were fabricated. These taller waveguides had cross-sections approximately equal to the 3.3 micron mode diameter of the
optical fiber 300, and gave a coupling efficiency of approximately 35% for a 6 millimeter-long waveguide. Propagation loss was measured in these waveguides to be less than 0.6 dB/cm, which is the limit of measurement uncertainty in the system used. - To demonstrate essentially instantaneous formation of plural waveguide arrays, a waveguide fabrication technique was carried out as described above. An array of about 1,000 3-centimeter-long, two-micron-wide, one-micron-high waveguides were formed over a 0.8 by 3 square centimeter area in a single step taking only five minutes. The parallelism of this procedure makes it a tremendously useful technique for the fabrication of complex but low-cost integrated optical devices.
- FIG. 25 illustrates another embodiment of the invention for formation of a structure on a substrate surface using a forming article. In the technique illustrated,
fluid precursor 36 is first placed onsubstrate surface 28, then formingarticle 20 is brought into contact withfluid precursor 36 and pressed againstsubstrate surface 28 such that thecontact surface 26 of the article seals portions ofsurface 28 that it contacts, thereby forming channels, defined by indentations and portions ofsubstrate surface 28 not contacted bycontact surface 26 of the forming article. This is another embodiment in which a micromold is created, defined byarticle 20 andsubstrate surface 28. In FIG. 25, following hardening offluid precursor 36 to the point that it is essentially self-supporting (if it is not so hardened prior to forming with article 20), the applicator is removed resulting instructure 38 which, depending upon the material selected, can be further cured or sintered and which may shrink in the process. - In the working examples described below, a drop of fluid precursor36 (referring to FIG. 25), was placed on a freshly cleaned substrate and then
article 28 was placed face down upon the substrate. A pressure of roughly 10 psi was applied. The area of the patterned surface was typically 1-5 cm2 with feature sizes in the micron range. Liquid dewetting of the surface upon application of the applicator was carried out to allow contact of thecontact surface 26 ofarticle 20 and the substrate in regions where no fluid precursor derived material was desired. Dewetting is driven by both applied pressure and difference of interfacial tension betweenfluid precursor 36 andcontact surface 26 ofarticle 20. More precisely, the dewetting speed is proportional to S where S=γLS+γLE−γSE; γLS is the liquid-substrate interfacial tension, γLE is the liquid-elastomer interfacial tension and γSE is the substrate-elastomer interfacial tension. (F. Brochard-Wyart, P.-G. de Gennes, J. Phys.: Condens. Matter, 1994, 6, A9). Since γSE is fixed, the interfacial tension of the fluid precursor solution was increased in order to accelerate dewetting. Although pressure improves the definition of features, it cannot be increased too much because of the deformations induced in the mold if deformation is not required. Diluting fluid precursor with a suitable solvent (in the working examples, acetonitrile, a polar solvent with low viscosity and high surface tension that does not swell the mold) allowed satisfactory dewetting for all patterns used. - Gelation occurred within about an hour, although the mold and structure were allowed to remain undisturbed for about 12 h to allow reasonable consolidation. Gelling time can, however, be decreased by raising pH of the precursor to about 4-5 before casting, and some structures were produced in less than 30 minutes using this technique.
- Working examples of molding of sol-gel fluid precursors using a forming article of the invention were carried out. In this set of examples, silicon wafers (Silicon Sense, Massachusetts) were cleaned briefly in an oxygen plasma cleaner before use. Tetramethyl-orthosilicate and di-sec-butoxyaluminoxytriethoxysilane (United Chemicals), titanium isopropoxide and boron triethoxide (Aldrich), oxalic acid and acetonitrile (Fisher) were used as received. Patterned Solid: A silica sol-gel precursor was molded against a silicon wafer that had been patterned by anisotropic etching with square pyramidal pits. A 50-nm thick gold film was prepared on a <100> silicon wafer primed with 2 nm of titanium by e-beam evaporation. A monolayer of hexadecanethiolate was patterned on the wafer using microcontact printing so that the resulting pattern presented uncovered 2-μm squares, and the unprotected gold was removed with a cyanide etch. (A. Kumar, G. M. Whitesides,Applied Physics Letters 1993, 63, 2002). The native silica oxide layer was then removed by etching in 2% HF for 30 sec. The silicon was etched in a 40% by weight solution of KOH in water and isopropanol; this anisotropic etch generated pyramidal pits. The remaining gold was removed with aqua regia. The surface of the resulting textured solid was treated by putting the wafer under static vacuum with a drop of (tridecafluoro-1,1,2,2-tetrahydro-octyl)-1-trichlorosilane for 30 min. This compound polymerized on the surface and made a layer that reduced adhesion to the surface.
- A mixture of 6.5 g TMOS and 1.5 g of water acidified to pH=1 by adding oxalic acid was stirred for 1 min and left at room temperature for 1 h (sol A). The mold was prepared by putting a 1 cm2 piece of the textured wafer in a plastic petri dish. Just before casting in the mold, 5 drops of aqueous ammonia (pH=11) were added to 3 g of sol A. The wafer was covered with 0.5 ml of this solution. The preparation was then placed in a closed 100 cm3 container for 24 h. The solid structure was not adhering to the mold at this point and was carefully removed. It was then dried slowly at room temperature for a week, then at 60° C. for 2 days. It was finally annealed at 1100° C. for 10 h.
- The resulting array of silica pyramids prepared by this technique was analyzed via SEM. The radius of curvature at the tips of the pyramids was less than50nm and the angle of the side of the pyramid was 54-58°. This value is compatible with that obtained with this type of silicon etching. (Barycka, et al., Sensors and Actuators, 1995, A48, 229). This demonstrates that shrinkage taking place during annealing is essentially isotropic. The sol-gel precursor was molded against a Si/SiO2 wafer whose surface had been passivated by silanization. The structure was annealed at 1100° C. It measured 5×5×0.3 mm.
- Optical waveguides of doped silica on Si/SiO2 were formed. The silica was doped with aluminum oxide in order to increase its refractive index. Low scattering by the edges of the waveguides can be achieved by an annealing step at a temperature where the viscosity is low enough to allow relaxation of the roughness. In the second working example described below, this temperature was reduced by adding boron oxide to the silica.
- Specifically, 0.5 g of di-sec-butoxyaluminoxytriethoxysilane was added to 3 g of sol A. After stirring for 6 h, 3 g of acetonitrile were added to the clear solution (sol B). A solution of 0.8 g of trimethylborate in 3 g of acetonitrile was added to 3 g of sol A and left at room temperature for 1 h (sol C).
- One drop of the solution (sol B or C) was placed on a freshly cleaned silicon wafer bearing a 2-μm thick thermal oxide layer. A 1-cm2 elastomeric forming article having a protrusion pattern complementary to the final pattern of the waveguide (illustrated schematically in FIG. 25) was immediately pressed against the surface. The whole structure was placed in a closed 100-cm3 container with one drop of aqueous ammonia (30%). After 18 h, the mold was removed and the structure was consolidated by annealing for 3 h at 1100° C. (for sol B) and 15 min at 800° C. or 900° C. (for sol C).
- FIGS. 26-29 are photocopies of SEM images of waveguides produced in accordance with this aspect of the invention. FIG. 26 is a photocopy of an SEM image of an aluminosilicate waveguide. FIGS. 27 and 29 are photocopies of SEM images of borosilicate waveguides. FIGS. 27 and 28 show borosilicate lines at different stages of sintering: FIG. 27 shows borosilicate lines after annealing at 800° C. for 10 minutes. FIG. 28 shows the lines after annealing at 900° C. for 10 minutes. Whereas pure sintering seemed to occur at 800° C., the cross section of the lines changed dramatically after annealing at 900° C., due to the melting of the glass, resulting in smoother edges. The composition of the glass was found by XPS to be 9% B2O3 and 91% SiO2. The waveguiding behavior of the aluminosilicate lines was characterized by coupling a 633-nanometer light beam into one end of a 5 mm long line and imaging the other end. The lines appeared to be single mode waveguides with slight coupling between adjacent lines.
- Described above are a variety of sensors of biological or chemical molecules, or the like, that can be made using waveguides fabricated in accordance with the invention. In another set of embodiments, sensors of displacement can be provided. For example, with reference to FIG. 24, where the waveguide array is subjected to compression or tensile forces in a direction perpendicular to the waveguides, causing the waveguides to move closer to or farther apart from each other, coupling between waveguides will change detectably. This can serve as a displacement sensor, pressure sensor, tension sensor, or the like. The waveguide array can be arranged to sense a force by being bent, for example to sense a force applied to an edge of the waveguide, and when the waveguide is bent spacing between waveguides will change and the coupling pattern will change. Waveguides made of glass as described above may also serve as active devices for integrated optics. For instance, aluminosilicate waveguides can be doped with rare earth, like neodymium or erbium. Doped waveguides can be used as integrated light-amplifiers or lasers when placed in a suitably geometry. A regular array of doped waveguides fabricated by this method, when put in a resonant cavity, could exhibit a very interesting behavior where all the lasers would be in phase, leading to a much higher intensity light beam.
Claims (11)
1. A method comprising:
forming at least one waveguide, and a cladding contacting the waveguide, each from a common prepolymer, the waveguide and cladding having a refractive index difference.
2. A method as in claim 1 , involving exposing a portion of the common prepolymer to a first amount of polymerizing energy to form the at least one waveguide and exposing a second amount of a common prepolymer to a second amount of polymerizing energy to form the cladding.
3. A method as in claim 2 , wherein the polymerizing energy is electromagnetic radiation.
4. A method as in claim 1 , comprising:
curing an array of at least two essentially parallel lines of a fluid prepolymer to a first extent to form at least two essentially parallel lines of polymeric material cured to a first extent;
contacting the at least two lines of cured polymeric material with a portion of the fluid prepolymer and curing the portion to a second extent to form a portion of the polymeric material cured to the second extent contacting the lines of polymeric material cured to the first extent.
5. A method comprising:
forming a waveguide and cladding; and
altering a refractive index ratio between a waveguide and cladding.
6. A method as in claim 5 , the waveguide and cladding each being formed of a polymeric material.
7. A method as in claim 5 , the waveguide and cladding each defining a polymeric material formed from a common prepolymeric material.
8. A method as in claim 5 , the altering step involving curing the waveguide and cladding, together, after formation.
9. A method comprising:
simultaneously deforming at least two guided, propagating electromagnetic waves.
10. A method comprising:
introducing electromagnetic radiation into a first waveguide, allowing the electromagnetic radiation to couple from the first waveguide into a second waveguide, and allowing the electromagnetic radiation to couple from the second waveguide into a third waveguide.
11. A method comprising:
forming a waveguide array of at least two waveguides having a coupling characteristic between them;
guiding electromagnetic radiation using the waveguide array by introducing the electromagnetic radiation into the array and causing the radiation to be essentially totally internally reflected within pathways of the array; and
altering the coupling characteristic of a section of the array including at least a portion of each waveguide to alter the coupling characteristic of the waveguides relative to each other.
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/677,103 US20040178523A1 (en) | 1996-03-15 | 2003-10-01 | Molded waveguides |
US12/001,564 US20080116608A1 (en) | 1996-03-15 | 2007-12-12 | Molded waveguides |
US12/398,132 US8012382B2 (en) | 1996-03-15 | 2009-03-04 | Molded waveguides |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61692996A | 1996-03-15 | 1996-03-15 | |
US4668997P | 1997-05-16 | 1997-05-16 | |
US09/004,583 US6355198B1 (en) | 1996-03-15 | 1998-01-08 | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US09/634,201 US6660192B1 (en) | 1996-03-15 | 2000-08-09 | Molded waveguides |
US10/677,103 US20040178523A1 (en) | 1996-03-15 | 2003-10-01 | Molded waveguides |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/634,201 Division US6660192B1 (en) | 1996-03-15 | 2000-08-09 | Molded waveguides |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/001,564 Division US20080116608A1 (en) | 1996-03-15 | 2007-12-12 | Molded waveguides |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040178523A1 true US20040178523A1 (en) | 2004-09-16 |
Family
ID=26724198
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/004,583 Expired - Lifetime US6355198B1 (en) | 1996-03-15 | 1998-01-08 | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US09/634,201 Expired - Lifetime US6660192B1 (en) | 1996-03-15 | 2000-08-09 | Molded waveguides |
US10/016,614 Expired - Lifetime US6752942B2 (en) | 1996-03-15 | 2001-10-30 | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US10/677,103 Abandoned US20040178523A1 (en) | 1996-03-15 | 2003-10-01 | Molded waveguides |
US12/001,564 Abandoned US20080116608A1 (en) | 1996-03-15 | 2007-12-12 | Molded waveguides |
US12/398,132 Expired - Fee Related US8012382B2 (en) | 1996-03-15 | 2009-03-04 | Molded waveguides |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/004,583 Expired - Lifetime US6355198B1 (en) | 1996-03-15 | 1998-01-08 | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US09/634,201 Expired - Lifetime US6660192B1 (en) | 1996-03-15 | 2000-08-09 | Molded waveguides |
US10/016,614 Expired - Lifetime US6752942B2 (en) | 1996-03-15 | 2001-10-30 | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/001,564 Abandoned US20080116608A1 (en) | 1996-03-15 | 2007-12-12 | Molded waveguides |
US12/398,132 Expired - Fee Related US8012382B2 (en) | 1996-03-15 | 2009-03-04 | Molded waveguides |
Country Status (1)
Country | Link |
---|---|
US (6) | US6355198B1 (en) |
Cited By (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070210483A1 (en) * | 2004-05-04 | 2007-09-13 | Lee Hong H | Mold made of amorphous fluorine resin and fabrication method thereof |
WO2007146848A2 (en) * | 2006-06-09 | 2007-12-21 | Lam Research Corporation | Surface modification of interlayer dielectric for minimizing contamination and surface degradation |
US20080294236A1 (en) * | 2007-05-23 | 2008-11-27 | Boston Scientific Scimed, Inc. | Endoprosthesis with Select Ceramic and Polymer Coatings |
US20090016672A1 (en) * | 2007-07-13 | 2009-01-15 | Oliver Schmidt | Producing Fluidic Waveguides |
US20090016690A1 (en) * | 2007-07-13 | 2009-01-15 | Oliver Schmidt | Producing Sandwich Waveguides |
US20090048659A1 (en) * | 2007-08-17 | 2009-02-19 | Boston Scientific Scimed, Inc. | Medical devices having sol-gel derived ceramic regions with molded submicron surface features |
US20090060434A1 (en) * | 2007-09-03 | 2009-03-05 | Fuji Xerox Co., Ltd. | Waveguide device |
US20090202737A1 (en) * | 2008-02-07 | 2009-08-13 | Nitto Denko Corporation | Manufacturing method of optical waveguide for touch panel |
US20090232966A1 (en) * | 2008-03-17 | 2009-09-17 | Kalyankar Nikhil D | Stamp Usage To Enhance Surface Layer Functionalization And Selectivity |
US20100019401A1 (en) * | 2008-07-28 | 2010-01-28 | Nitto Denko Corporation | Method for manufacturing optical waveguide |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US8066763B2 (en) | 1998-04-11 | 2011-11-29 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8221822B2 (en) | 2007-07-31 | 2012-07-17 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
US20120188746A1 (en) * | 2011-01-21 | 2012-07-26 | Lg Innotek Co., Ltd. | Optical Member, Display Device Having the Same and Method of Fabricating the Same |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US8353949B2 (en) | 2006-09-14 | 2013-01-15 | Boston Scientific Scimed, Inc. | Medical devices with drug-eluting coating |
US8373860B2 (en) | 2008-02-01 | 2013-02-12 | Palo Alto Research Center Incorporated | Transmitting/reflecting emanating light with time variation |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8449603B2 (en) | 2008-06-18 | 2013-05-28 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8574615B2 (en) | 2006-03-24 | 2013-11-05 | Boston Scientific Scimed, Inc. | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8629981B2 (en) | 2008-02-01 | 2014-01-14 | Palo Alto Research Center Incorporated | Analyzers with time variation based on color-coded spatial modulation |
US8723140B2 (en) | 2011-08-09 | 2014-05-13 | Palo Alto Research Center Incorporated | Particle analyzer with spatial modulation and long lifetime bioprobes |
US8771343B2 (en) | 2006-06-29 | 2014-07-08 | Boston Scientific Scimed, Inc. | Medical devices with selective titanium oxide coatings |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
US8821799B2 (en) | 2007-01-26 | 2014-09-02 | Palo Alto Research Center Incorporated | Method and system implementing spatially modulated excitation or emission for particle characterization with enhanced sensitivity |
US8828521B2 (en) * | 2007-08-09 | 2014-09-09 | International Business Machines Corporation | Corrugated interfaces for multilayered interconnects |
US8900292B2 (en) | 2007-08-03 | 2014-12-02 | Boston Scientific Scimed, Inc. | Coating for medical device having increased surface area |
US8920491B2 (en) | 2008-04-22 | 2014-12-30 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
US8932346B2 (en) | 2008-04-24 | 2015-01-13 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
US9029800B2 (en) | 2011-08-09 | 2015-05-12 | Palo Alto Research Center Incorporated | Compact analyzer with spatial modulation and multiple intensity modulated excitation sources |
US9164037B2 (en) | 2007-01-26 | 2015-10-20 | Palo Alto Research Center Incorporated | Method and system for evaluation of signals received from spatially modulated excitation and emission to accurately determine particle positions and distances |
US9284409B2 (en) | 2007-07-19 | 2016-03-15 | Boston Scientific Scimed, Inc. | Endoprosthesis having a non-fouling surface |
WO2020149931A1 (en) * | 2019-01-15 | 2020-07-23 | Massachusetts Institute Of Technology | Integrated freeform optical couplers |
Families Citing this family (413)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR876M (en) | 1960-10-12 | 1961-10-16 | ||
US5776748A (en) * | 1993-10-04 | 1998-07-07 | President And Fellows Of Harvard College | Method of formation of microstamped patterns on plates for adhesion of cells and other biological materials, devices and uses therefor |
US8128856B2 (en) * | 1995-11-15 | 2012-03-06 | Regents Of The University Of Minnesota | Release surfaces, particularly for use in nanoimprint lithography |
US20080217813A1 (en) * | 1995-11-15 | 2008-09-11 | Chou Stephen Y | Release surfaces, particularly for use in nanoimprint lithography |
US6355198B1 (en) | 1996-03-15 | 2002-03-12 | President And Fellows Of Harvard College | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US7282240B1 (en) | 1998-04-21 | 2007-10-16 | President And Fellows Of Harvard College | Elastomeric mask and use in fabrication of devices |
EP2360271A1 (en) | 1998-06-24 | 2011-08-24 | Illumina, Inc. | Decoding of array sensors with microspheres |
US6334960B1 (en) * | 1999-03-11 | 2002-01-01 | Board Of Regents, The University Of Texas System | Step and flash imprint lithography |
KR100335070B1 (en) * | 1999-04-21 | 2002-05-03 | 백승준 | Method for forming micro pattern on substrate by using compression patterning technique |
US20030124509A1 (en) * | 1999-06-03 | 2003-07-03 | Kenis Paul J.A. | Laminar flow patterning and articles made thereby |
US7082093B1 (en) * | 1999-07-15 | 2006-07-25 | D Data Inc. | Optical data storage system having combined fluorescent three-dimensional information carrier |
US7432634B2 (en) | 2000-10-27 | 2008-10-07 | Board Of Regents, University Of Texas System | Remote center compliant flexure device |
US7323143B2 (en) * | 2000-05-25 | 2008-01-29 | President And Fellows Of Harvard College | Microfluidic systems including three-dimensionally arrayed channel networks |
US6645432B1 (en) * | 2000-05-25 | 2003-11-11 | President & Fellows Of Harvard College | Microfluidic systems including three-dimensionally arrayed channel networks |
US6686184B1 (en) * | 2000-05-25 | 2004-02-03 | President And Fellows Of Harvard College | Patterning of surfaces utilizing microfluidic stamps including three-dimensionally arrayed channel networks |
SG142150A1 (en) * | 2000-07-16 | 2008-05-28 | Univ Texas | High-resolution overlay alignment systems for imprint lithography |
US6696220B2 (en) * | 2000-10-12 | 2004-02-24 | Board Of Regents, The University Of Texas System | Template for room temperature, low pressure micro-and nano-imprint lithography |
WO2002006902A2 (en) * | 2000-07-17 | 2002-01-24 | Board Of Regents, The University Of Texas System | Method and system of automatic fluid dispensing for imprint lithography processes |
US20050160011A1 (en) * | 2004-01-20 | 2005-07-21 | Molecular Imprints, Inc. | Method for concurrently employing differing materials to form a layer on a substrate |
AU2001275984A1 (en) * | 2000-07-20 | 2002-02-05 | President And Fellows Of Harvard College | Self-assembled electrical networks |
US7301199B2 (en) * | 2000-08-22 | 2007-11-27 | President And Fellows Of Harvard College | Nanoscale wires and related devices |
US20060175601A1 (en) * | 2000-08-22 | 2006-08-10 | President And Fellows Of Harvard College | Nanoscale wires and related devices |
TWI292583B (en) * | 2000-08-22 | 2008-01-11 | Harvard College | Doped elongated semiconductor articles, growing such articles, devices including such articles and fabicating such devices |
CA2422762A1 (en) | 2000-09-18 | 2002-03-21 | President And Fellows Of Harvard College | Differential treatment of selected parts of a single cell with different fluid components |
JP3922338B2 (en) * | 2000-09-20 | 2007-05-30 | セイコーエプソン株式会社 | Substrate manufacturing method and manufacturing apparatus |
US20060005657A1 (en) * | 2004-06-01 | 2006-01-12 | Molecular Imprints, Inc. | Method and system to control movement of a body for nano-scale manufacturing |
US20050274219A1 (en) * | 2004-06-01 | 2005-12-15 | Molecular Imprints, Inc. | Method and system to control movement of a body for nano-scale manufacturing |
DE60135775D1 (en) | 2000-12-11 | 2008-10-23 | Harvard College | DEVICE CONTAINING NANOSENSORS FOR THE DETECTION OF AN ANALYTE AND METHOD FOR THE PRODUCTION THEREOF |
US20020115977A1 (en) * | 2000-12-15 | 2002-08-22 | Topolkaraev Vasily A. | Disposable products having materials having shape-memory |
US6731843B2 (en) * | 2000-12-29 | 2004-05-04 | Intel Corporation | Multi-level waveguide |
WO2002086333A1 (en) | 2001-04-25 | 2002-10-31 | President And Fellows Of Harvard College | Fluidic switches and method for controlling flow in fluidic systems |
US6964793B2 (en) * | 2002-05-16 | 2005-11-15 | Board Of Regents, The University Of Texas System | Method for fabricating nanoscale patterns in light curable compositions using an electric field |
US7622129B1 (en) | 2002-08-05 | 2009-11-24 | Purdue Research Foundation | Nano-structured polymers for use as implants |
US7833283B2 (en) * | 2001-08-16 | 2010-11-16 | Purdue Research Foundation | Material and method for promoting tissue growth |
US20030044481A1 (en) * | 2001-08-28 | 2003-03-06 | Beaudry Wallace J. | Cast ceramic edge or embossed surface for a cutting die |
US7001541B2 (en) * | 2001-09-14 | 2006-02-21 | Inphase Technologies, Inc. | Method for forming multiply patterned optical articles |
US7666579B1 (en) * | 2001-09-17 | 2010-02-23 | Serenity Technologies, Inc. | Method and apparatus for high density storage of analog data in a durable medium |
GB2379995B (en) * | 2001-09-21 | 2005-02-02 | Kamelian Ltd | An optical coupling |
WO2003035932A1 (en) * | 2001-09-25 | 2003-05-01 | Minuta Technology Co., Ltd. | Method for forming a micro-pattern on a substrate by using capillary force |
US6936181B2 (en) * | 2001-10-11 | 2005-08-30 | Kovio, Inc. | Methods for patterning using liquid embossing |
US7224868B2 (en) * | 2001-10-24 | 2007-05-29 | Massachusetts Institute Of Technology | Radiation-free optical cavity |
US6903815B2 (en) * | 2001-11-22 | 2005-06-07 | Kabushiki Kaisha Toshiba | Optical waveguide sensor, device, system and method for glucose measurement |
US20060199260A1 (en) * | 2002-05-01 | 2006-09-07 | Zhiyu Zhang | Microbioreactor for continuous cell culture |
US20040077075A1 (en) * | 2002-05-01 | 2004-04-22 | Massachusetts Institute Of Technology | Microfermentors for rapid screening and analysis of biochemical processes |
WO2003096123A1 (en) * | 2002-05-08 | 2003-11-20 | Agency For Science, Technology And Research | Reversal imprint technique |
JP3945322B2 (en) | 2002-06-27 | 2007-07-18 | 富士ゼロックス株式会社 | Optical element and manufacturing method thereof |
JP2004086144A (en) * | 2002-06-27 | 2004-03-18 | Fuji Xerox Co Ltd | Method for manufacturing macromolecular optical waveguide |
JP2006507921A (en) | 2002-06-28 | 2006-03-09 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Method and apparatus for fluid dispersion |
JP3858995B2 (en) * | 2002-07-02 | 2006-12-20 | オムロン株式会社 | Manufacturing method of optical waveguide device |
US7179079B2 (en) * | 2002-07-08 | 2007-02-20 | Molecular Imprints, Inc. | Conforming template for patterning liquids disposed on substrates |
US7019819B2 (en) | 2002-11-13 | 2006-03-28 | Molecular Imprints, Inc. | Chucking system for modulating shapes of substrates |
US7442336B2 (en) | 2003-08-21 | 2008-10-28 | Molecular Imprints, Inc. | Capillary imprinting technique |
US7077992B2 (en) | 2002-07-11 | 2006-07-18 | Molecular Imprints, Inc. | Step and repeat imprint lithography processes |
WO2004010552A1 (en) | 2002-07-19 | 2004-01-29 | President And Fellows Of Harvard College | Nanoscale coherent optical components |
JP2004069743A (en) * | 2002-08-01 | 2004-03-04 | Fuji Xerox Co Ltd | Manufacture method for macromolecular optical waveguide |
US6916584B2 (en) * | 2002-08-01 | 2005-07-12 | Molecular Imprints, Inc. | Alignment methods for imprint lithography |
JP4007113B2 (en) * | 2002-08-01 | 2007-11-14 | 富士ゼロックス株式会社 | Polymer optical waveguide with alignment mark and manufacturing method of laminated polymer optical waveguide |
JP2004069955A (en) * | 2002-08-06 | 2004-03-04 | Fuji Xerox Co Ltd | Method for manufacturing macromolecular optical waveguide |
US7901630B2 (en) * | 2002-08-20 | 2011-03-08 | Illumina, Inc. | Diffraction grating-based encoded microparticle assay stick |
US7923260B2 (en) | 2002-08-20 | 2011-04-12 | Illumina, Inc. | Method of reading encoded particles |
US7164533B2 (en) * | 2003-01-22 | 2007-01-16 | Cyvera Corporation | Hybrid random bead/chip based microarray |
US20050227252A1 (en) * | 2002-08-20 | 2005-10-13 | Moon John A | Diffraction grating-based encoded articles for multiplexed experiments |
US7872804B2 (en) * | 2002-08-20 | 2011-01-18 | Illumina, Inc. | Encoded particle having a grating with variations in the refractive index |
US7441703B2 (en) * | 2002-08-20 | 2008-10-28 | Illumina, Inc. | Optical reader for diffraction grating-based encoded optical identification elements |
US7399643B2 (en) * | 2002-09-12 | 2008-07-15 | Cyvera Corporation | Method and apparatus for aligning microbeads in order to interrogate the same |
US7900836B2 (en) * | 2002-08-20 | 2011-03-08 | Illumina, Inc. | Optical reader system for substrates having an optically readable code |
CA2496296A1 (en) * | 2002-08-20 | 2004-03-04 | Cyvera Corporation | Diffraction grating-based encoded micro-particles for multiplexed experiments |
US7508608B2 (en) * | 2004-11-17 | 2009-03-24 | Illumina, Inc. | Lithographically fabricated holographic optical identification element |
EP1535241A1 (en) * | 2002-08-20 | 2005-06-01 | Cyvera Corporation | Diffraction grating-based optical identification element |
US6911385B1 (en) * | 2002-08-22 | 2005-06-28 | Kovio, Inc. | Interface layer for the fabrication of electronic devices |
US7071088B2 (en) * | 2002-08-23 | 2006-07-04 | Molecular Imprints, Inc. | Method for fabricating bulbous-shaped vias |
US6858174B2 (en) * | 2002-09-03 | 2005-02-22 | Ceramatec, Inc. | Process for casting ceramic materials |
AU2003303950A1 (en) * | 2002-09-06 | 2004-11-23 | Derek. J. Hansford | Microfabrication of polymer microparticles |
CN1329111C (en) * | 2002-09-09 | 2007-08-01 | 国际商业机器公司 | Printing method using rubber stamp |
WO2004025561A1 (en) * | 2002-09-12 | 2004-03-25 | Cyvera Corporation | Chemical synthesis using diffraction grating-based encoded optical elements |
US7092160B2 (en) * | 2002-09-12 | 2006-08-15 | Illumina, Inc. | Method of manufacturing of diffraction grating-based optical identification element |
US20100255603A9 (en) * | 2002-09-12 | 2010-10-07 | Putnam Martin A | Method and apparatus for aligning microbeads in order to interrogate the same |
AU2003278827A1 (en) * | 2002-09-12 | 2004-04-30 | Cyvera Corp. | Method and apparatus for labelling using diffraction grating-based encoded optical identification elements |
CA2498913A1 (en) * | 2002-09-12 | 2004-03-25 | Cyvera Corporation | Assay stick comprising coded microbeads |
CA2499046A1 (en) * | 2002-09-12 | 2004-03-25 | Cyvera Corporation | Diffraction grating-based encoded micro-particles for multiplexed experiments |
US8062573B2 (en) * | 2002-09-16 | 2011-11-22 | Theraject, Inc. | Solid micro-perforators and methods of use |
US7029529B2 (en) * | 2002-09-19 | 2006-04-18 | Applied Materials, Inc. | Method and apparatus for metallization of large area substrates |
KR101000043B1 (en) * | 2002-09-20 | 2010-12-09 | 도판 인사츠 가부시키가이샤 | Optical wave guide and method of manufacturing the same |
JP2004109927A (en) * | 2002-09-20 | 2004-04-08 | Fuji Xerox Co Ltd | Method of manufacturing polymer optical waveguide |
JP3969263B2 (en) * | 2002-09-20 | 2007-09-05 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
US7329545B2 (en) | 2002-09-24 | 2008-02-12 | Duke University | Methods for sampling a liquid flow |
US6911132B2 (en) | 2002-09-24 | 2005-06-28 | Duke University | Apparatus for manipulating droplets by electrowetting-based techniques |
US8349241B2 (en) * | 2002-10-04 | 2013-01-08 | Molecular Imprints, Inc. | Method to arrange features on a substrate to replicate features having minimal dimensional variability |
DE10248924A1 (en) * | 2002-10-17 | 2004-04-29 | C. & E. Fein Gmbh & Co Kg | power tool |
US20040250683A1 (en) * | 2002-10-18 | 2004-12-16 | Innovative Construction And Building Materials, Llc | Advanced filtration devices and methods |
JP2004144987A (en) * | 2002-10-24 | 2004-05-20 | Fuji Xerox Co Ltd | Manufacturing method of polymeric optical waveguide |
CA2504842A1 (en) * | 2002-11-05 | 2004-05-21 | Jingjiao Guan | Self-folding polymer microparticles |
US7641840B2 (en) * | 2002-11-13 | 2010-01-05 | Molecular Imprints, Inc. | Method for expelling gas positioned between a substrate and a mold |
US6929762B2 (en) * | 2002-11-13 | 2005-08-16 | Molecular Imprints, Inc. | Method of reducing pattern distortions during imprint lithography processes |
US6900126B2 (en) * | 2002-11-20 | 2005-05-31 | International Business Machines Corporation | Method of forming metallized pattern |
JP4581328B2 (en) * | 2002-11-28 | 2010-11-17 | 富士ゼロックス株式会社 | Polymer optical waveguide and optical element manufacturing method |
JP4534415B2 (en) * | 2002-11-29 | 2010-09-01 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
US20040112862A1 (en) * | 2002-12-12 | 2004-06-17 | Molecular Imprints, Inc. | Planarization composition and method of patterning a substrate using the same |
US6871558B2 (en) * | 2002-12-12 | 2005-03-29 | Molecular Imprints, Inc. | Method for determining characteristics of substrate employing fluid geometries |
AU2003300371A1 (en) * | 2002-12-20 | 2004-07-22 | Minerva Biotechnologies Corporation | Optical devices and methods involving nanoparticles |
WO2004067191A2 (en) | 2003-01-29 | 2004-08-12 | President And Fellows Of Harward College | Alteration of surface affinities |
EP1443344A1 (en) * | 2003-01-29 | 2004-08-04 | Heptagon Oy | Manufacturing micro-structured elements |
US20040168613A1 (en) * | 2003-02-27 | 2004-09-02 | Molecular Imprints, Inc. | Composition and method to form a release layer |
JP2004280009A (en) * | 2003-03-19 | 2004-10-07 | Toppan Printing Co Ltd | Optical waveguide and its manufacturing method |
US7122079B2 (en) * | 2004-02-27 | 2006-10-17 | Molecular Imprints, Inc. | Composition for an etching mask comprising a silicon-containing material |
US7179396B2 (en) * | 2003-03-25 | 2007-02-20 | Molecular Imprints, Inc. | Positive tone bi-layer imprint lithography method |
US7186656B2 (en) * | 2004-05-21 | 2007-03-06 | Molecular Imprints, Inc. | Method of forming a recessed structure employing a reverse tone process |
US7323417B2 (en) * | 2004-09-21 | 2008-01-29 | Molecular Imprints, Inc. | Method of forming a recessed structure employing a reverse tone process |
US7993412B2 (en) * | 2003-03-27 | 2011-08-09 | Purdue Research Foundation | Nanofibers as a neural biomaterial |
US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
GB0307428D0 (en) * | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
EP3616781A1 (en) * | 2003-04-10 | 2020-03-04 | President and Fellows of Harvard College | Formation and control of fluidic species |
US7396475B2 (en) * | 2003-04-25 | 2008-07-08 | Molecular Imprints, Inc. | Method of forming stepped structures employing imprint lithography |
US7618510B2 (en) * | 2003-05-23 | 2009-11-17 | The Regents Of The University Of Michigan | Imprinting polymer film on patterned substrate |
JP4175183B2 (en) * | 2003-06-04 | 2008-11-05 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
JP4265293B2 (en) * | 2003-06-11 | 2009-05-20 | 富士ゼロックス株式会社 | Method of manufacturing polymer optical waveguide integrated with mold and connector |
JP3952995B2 (en) * | 2003-06-13 | 2007-08-01 | セイコーエプソン株式会社 | Method for forming optical waveguide |
US20050160934A1 (en) * | 2004-01-23 | 2005-07-28 | Molecular Imprints, Inc. | Materials and methods for imprint lithography |
US7307118B2 (en) * | 2004-11-24 | 2007-12-11 | Molecular Imprints, Inc. | Composition to reduce adhesion between a conformable region and a mold |
US7157036B2 (en) * | 2003-06-17 | 2007-01-02 | Molecular Imprints, Inc | Method to reduce adhesion between a conformable region and a pattern of a mold |
US7879696B2 (en) * | 2003-07-08 | 2011-02-01 | Kovio, Inc. | Compositions and methods for forming a semiconducting and/or silicon-containing film, and structures formed therefrom |
US7150622B2 (en) * | 2003-07-09 | 2006-12-19 | Molecular Imprints, Inc. | Systems for magnification and distortion correction for imprint lithography processes |
JP2005043652A (en) * | 2003-07-22 | 2005-02-17 | Fuji Xerox Co Ltd | Method for manufacturing polymer optical waveguide and apparatus for manufacturing the same |
JP4561059B2 (en) * | 2003-07-24 | 2010-10-13 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
JP4144468B2 (en) * | 2003-07-25 | 2008-09-03 | 富士ゼロックス株式会社 | Multilayer polymer optical waveguide and method for manufacturing the same |
JP4140475B2 (en) * | 2003-07-25 | 2008-08-27 | 富士ゼロックス株式会社 | Master for producing polymer optical waveguide and method for producing polymer optical waveguide |
EP2662136A3 (en) * | 2003-08-27 | 2013-12-25 | President and Fellows of Harvard College | Method for handling and mixing droplets |
US20060057729A1 (en) * | 2003-09-12 | 2006-03-16 | Illumina, Inc. | Diffraction grating-based encoded element having a substance disposed thereon |
ATE551383T1 (en) * | 2003-09-23 | 2012-04-15 | Univ North Carolina | PHOTOHARDENABLE PERFLUORUM POLYETHERS FOR USE AS NEW MATERIALS IN MICROFLUIDIC DEVICES |
US7136150B2 (en) * | 2003-09-25 | 2006-11-14 | Molecular Imprints, Inc. | Imprint lithography template having opaque alignment marks |
US20050069644A1 (en) * | 2003-09-29 | 2005-03-31 | National Taiwan University | Micro-stamping method for photoelectric process |
US8211214B2 (en) * | 2003-10-02 | 2012-07-03 | Molecular Imprints, Inc. | Single phase fluid imprint lithography method |
US7090716B2 (en) * | 2003-10-02 | 2006-08-15 | Molecular Imprints, Inc. | Single phase fluid imprint lithography method |
US7261830B2 (en) * | 2003-10-16 | 2007-08-28 | Molecular Imprints, Inc. | Applying imprinting material to substrates employing electromagnetic fields |
US20050084804A1 (en) * | 2003-10-16 | 2005-04-21 | Molecular Imprints, Inc. | Low surface energy templates |
JP4453335B2 (en) * | 2003-10-22 | 2010-04-21 | 富士ゼロックス株式会社 | Optical circuit pattern and method for producing polymer optical waveguide |
US20050106321A1 (en) * | 2003-11-14 | 2005-05-19 | Molecular Imprints, Inc. | Dispense geometery to achieve high-speed filling and throughput |
US20050098534A1 (en) * | 2003-11-12 | 2005-05-12 | Molecular Imprints, Inc. | Formation of conductive templates employing indium tin oxide |
EP1542074A1 (en) * | 2003-12-11 | 2005-06-15 | Heptagon OY | Manufacturing a replication tool, sub-master or replica |
US9040090B2 (en) * | 2003-12-19 | 2015-05-26 | The University Of North Carolina At Chapel Hill | Isolated and fixed micro and nano structures and methods thereof |
EP3242318A1 (en) * | 2003-12-19 | 2017-11-08 | The University of North Carolina at Chapel Hill | Monodisperse micro-structure or nano-structure product |
JP2005181662A (en) * | 2003-12-19 | 2005-07-07 | Fuji Xerox Co Ltd | Method for manufacturing macromolecular optical waveguide |
US20050136500A1 (en) * | 2003-12-19 | 2005-06-23 | Kimberly-Clark Worldwide; Inc. | Flow-through assay devices |
KR100610230B1 (en) * | 2003-12-31 | 2006-08-08 | 주식회사 루밴틱스 | Fabrication of polymer waveguide using uv-molding method |
US20050156353A1 (en) * | 2004-01-15 | 2005-07-21 | Watts Michael P. | Method to improve the flow rate of imprinting material |
JP4196839B2 (en) * | 2004-01-16 | 2008-12-17 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
JP4225207B2 (en) * | 2004-01-23 | 2009-02-18 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
US20090227107A9 (en) * | 2004-02-13 | 2009-09-10 | President And Fellows Of Havard College | Nanostructures Containing Metal Semiconductor Compounds |
CN101189271A (en) * | 2004-02-13 | 2008-05-28 | 北卡罗来纳大学查珀尔希尔分校 | Functional materials and novel methods for the fabrication of microfluidic devices |
US7433123B2 (en) | 2004-02-19 | 2008-10-07 | Illumina, Inc. | Optical identification element having non-waveguide photosensitive substrate with diffraction grating therein |
US8076386B2 (en) * | 2004-02-23 | 2011-12-13 | Molecular Imprints, Inc. | Materials for imprint lithography |
US7906180B2 (en) | 2004-02-27 | 2011-03-15 | Molecular Imprints, Inc. | Composition for an etching mask comprising a silicon-containing material |
US20050189676A1 (en) * | 2004-02-27 | 2005-09-01 | Molecular Imprints, Inc. | Full-wafer or large area imprinting with multiple separated sub-fields for high throughput lithography |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
JP4517704B2 (en) * | 2004-04-06 | 2010-08-04 | 富士ゼロックス株式会社 | Method for producing polymer optical waveguide |
US7140861B2 (en) * | 2004-04-27 | 2006-11-28 | Molecular Imprints, Inc. | Compliant hard template for UV imprinting |
JP2005321560A (en) * | 2004-05-07 | 2005-11-17 | Fuji Xerox Co Ltd | Polymer optical waveguide module with light receiving/emitting element |
US20050253307A1 (en) * | 2004-05-11 | 2005-11-17 | Molecualr Imprints, Inc. | Method of patterning a conductive layer on a substrate |
US20050272179A1 (en) * | 2004-05-24 | 2005-12-08 | Andrew Frauenglass | Three-dimensional lithographic fabrication technique |
US7504268B2 (en) * | 2004-05-28 | 2009-03-17 | Board Of Regents, The University Of Texas System | Adaptive shape substrate support method |
US20050275311A1 (en) * | 2004-06-01 | 2005-12-15 | Molecular Imprints, Inc. | Compliant device for nano-scale manufacturing |
US20050276919A1 (en) * | 2004-06-01 | 2005-12-15 | Molecular Imprints, Inc. | Method for dispensing a fluid on a substrate |
JP4792028B2 (en) * | 2004-06-03 | 2011-10-12 | モレキュラー・インプリンツ・インコーポレーテッド | Fluid distribution and drop-on-demand distribution technology in nanoscale manufacturing technology |
US20070228593A1 (en) * | 2006-04-03 | 2007-10-04 | Molecular Imprints, Inc. | Residual Layer Thickness Measurement and Correction |
WO2006107312A1 (en) * | 2004-06-15 | 2006-10-12 | President And Fellows Of Harvard College | Nanosensors |
CN100489578C (en) * | 2004-06-25 | 2009-05-20 | 欧姆龙株式会社 | Film optical waveguide and method for manufacture thereof, and electronic instrument device |
JP2006011210A (en) * | 2004-06-29 | 2006-01-12 | Fuji Xerox Co Ltd | Polymer optical waveguide module with light emitting element and light receiving element for use in monitor |
US7655470B2 (en) | 2004-10-29 | 2010-02-02 | University Of Chicago | Method for manipulating a plurality of plugs and performing reactions therein in microfluidic systems |
US9477233B2 (en) | 2004-07-02 | 2016-10-25 | The University Of Chicago | Microfluidic system with a plurality of sequential T-junctions for performing reactions in microdroplets |
US7785526B2 (en) * | 2004-07-20 | 2010-08-31 | Molecular Imprints, Inc. | Imprint alignment method, system, and template |
WO2006020363A2 (en) * | 2004-07-21 | 2006-02-23 | Illumina, Inc. | Method and apparatus for drug product tracking using encoded optical identification elements |
US7709247B2 (en) * | 2004-08-04 | 2010-05-04 | Intel Corporation | Methods and systems for detecting biomolecular binding using terahertz radiation |
US7309225B2 (en) * | 2004-08-13 | 2007-12-18 | Molecular Imprints, Inc. | Moat system for an imprint lithography template |
US7939131B2 (en) * | 2004-08-16 | 2011-05-10 | Molecular Imprints, Inc. | Method to provide a layer with uniform etch characteristics |
US7205244B2 (en) * | 2004-09-21 | 2007-04-17 | Molecular Imprints | Patterning substrates employing multi-film layers defining etch-differential interfaces |
US7547504B2 (en) * | 2004-09-21 | 2009-06-16 | Molecular Imprints, Inc. | Pattern reversal employing thick residual layers |
US20060062922A1 (en) * | 2004-09-23 | 2006-03-23 | Molecular Imprints, Inc. | Polymerization technique to attenuate oxygen inhibition of solidification of liquids and composition therefor |
US7968287B2 (en) * | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
US20060138083A1 (en) * | 2004-10-26 | 2006-06-29 | Declan Ryan | Patterning and alteration of molecules |
JP2006125999A (en) * | 2004-10-28 | 2006-05-18 | Denso Corp | Collision detection sensor |
JP2006126568A (en) * | 2004-10-29 | 2006-05-18 | Fuji Xerox Co Ltd | Method for manufacturing polymer optical waveguide device |
US8329202B2 (en) | 2004-11-12 | 2012-12-11 | Depuy Products, Inc. | System and method for attaching soft tissue to an implant |
US7604173B2 (en) * | 2004-11-16 | 2009-10-20 | Illumina, Inc. | Holographically encoded elements for microarray and other tagging labeling applications, and method and apparatus for making and reading the same |
AU2005307746B2 (en) * | 2004-11-16 | 2011-05-12 | Illumina, Inc. | And methods and apparatus for reading coded microbeads |
US7630067B2 (en) * | 2004-11-30 | 2009-12-08 | Molecular Imprints, Inc. | Interferometric analysis method for the manufacture of nano-scale devices |
US20070231421A1 (en) * | 2006-04-03 | 2007-10-04 | Molecular Imprints, Inc. | Enhanced Multi Channel Alignment |
US7292326B2 (en) * | 2004-11-30 | 2007-11-06 | Molecular Imprints, Inc. | Interferometric analysis for the manufacture of nano-scale devices |
WO2006060757A2 (en) * | 2004-12-01 | 2006-06-08 | Molecular Imprints, Inc. | Eliminating printability of sub-resolution defects in imprint lithography |
KR20070086766A (en) * | 2004-12-01 | 2007-08-27 | 몰레큘러 임프린츠 인코퍼레이티드 | Methods of exposure for the purpose of thermal management for imprint lithography processes |
US8154002B2 (en) * | 2004-12-06 | 2012-04-10 | President And Fellows Of Harvard College | Nanoscale wire-based data storage |
US7281919B2 (en) | 2004-12-07 | 2007-10-16 | Molecular Imprints, Inc. | System for controlling a volume of material on a mold |
US20060140843A1 (en) * | 2004-12-23 | 2006-06-29 | In-Kyung Sung | Macroporous structures for heterogeneous catalyst support |
KR100682919B1 (en) * | 2005-01-20 | 2007-02-15 | 삼성전자주식회사 | Pattern forming method of fine metal thin layer, biomolecular fixing substrate and biochip using the same |
WO2006081558A2 (en) | 2005-01-28 | 2006-08-03 | Duke University | Apparatuses and methods for manipulating droplets on a printed circuit board |
US7636999B2 (en) * | 2005-01-31 | 2009-12-29 | Molecular Imprints, Inc. | Method of retaining a substrate to a wafer chuck |
US20060177535A1 (en) * | 2005-02-04 | 2006-08-10 | Molecular Imprints, Inc. | Imprint lithography template to facilitate control of liquid movement |
US7635263B2 (en) * | 2005-01-31 | 2009-12-22 | Molecular Imprints, Inc. | Chucking system comprising an array of fluid chambers |
WO2006084202A2 (en) * | 2005-02-03 | 2006-08-10 | The University Of North Carolina At Chapel Hill | Low surface energy polymeric material for use in liquid crystal displays |
KR100696254B1 (en) | 2005-02-23 | 2007-03-21 | 박철민 | The patterning method of nanosized blockcopolymer micelle |
US20070054119A1 (en) * | 2005-03-04 | 2007-03-08 | Piotr Garstecki | Systems and methods of forming particles |
AU2006220816A1 (en) * | 2005-03-04 | 2006-09-14 | President And Fellows Of Harvard College | Method and apparatus for forming multiple emulsions |
US20060222762A1 (en) * | 2005-03-29 | 2006-10-05 | Mcevoy Kevin P | Inorganic waveguides and methods of making same |
US7575707B2 (en) | 2005-03-29 | 2009-08-18 | University Of Washington | Electrospinning of fine hollow fibers |
US20060231195A1 (en) * | 2005-04-15 | 2006-10-19 | Klaser Technology Inc. | Method for forming fine lines on gas permeable and moisture absorptive material |
US20070228608A1 (en) * | 2006-04-03 | 2007-10-04 | Molecular Imprints, Inc. | Preserving Filled Features when Vacuum Wiping |
KR20080023303A (en) * | 2005-05-18 | 2008-03-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | Fabrication of conductive pathways, microcircuits and microstructures in microfluidic networks |
US20100227382A1 (en) * | 2005-05-25 | 2010-09-09 | President And Fellows Of Harvard College | Nanoscale sensors |
US20060266916A1 (en) * | 2005-05-25 | 2006-11-30 | Molecular Imprints, Inc. | Imprint lithography template having a coating to reflect and/or absorb actinic energy |
WO2006132659A2 (en) * | 2005-06-06 | 2006-12-14 | President And Fellows Of Harvard College | Nanowire heterostructures |
KR20060131551A (en) * | 2005-06-16 | 2006-12-20 | 엘지.필립스 엘시디 주식회사 | Electrode structure of flexible display device and method of fabrication thereof |
KR101264673B1 (en) * | 2005-06-24 | 2013-05-20 | 엘지디스플레이 주식회사 | method for fabricating detail pattern by using soft mold |
US8808808B2 (en) | 2005-07-22 | 2014-08-19 | Molecular Imprints, Inc. | Method for imprint lithography utilizing an adhesion primer layer |
US8557351B2 (en) | 2005-07-22 | 2013-10-15 | Molecular Imprints, Inc. | Method for adhering materials together |
US7759407B2 (en) * | 2005-07-22 | 2010-07-20 | Molecular Imprints, Inc. | Composition for adhering materials together |
WO2007133235A2 (en) * | 2005-08-08 | 2007-11-22 | Liquidia Technologies, Inc. | Micro and nano-structure metrology |
EP1922364A4 (en) | 2005-08-09 | 2010-04-21 | Univ North Carolina | Methods and materials for fabricating microfluidic devices |
US20070074635A1 (en) * | 2005-08-25 | 2007-04-05 | Molecular Imprints, Inc. | System to couple a body and a docking plate |
US7665981B2 (en) * | 2005-08-25 | 2010-02-23 | Molecular Imprints, Inc. | System to transfer a template transfer body between a motion stage and a docking plate |
US20070064384A1 (en) * | 2005-08-25 | 2007-03-22 | Molecular Imprints, Inc. | Method to transfer a template transfer body between a motion stage and a docking plate |
KR100758699B1 (en) * | 2005-08-29 | 2007-09-14 | 재단법인서울대학교산학협력재단 | Method for forming high aspect ratio nanostructure and method for forming nano pattern using the same |
CN101687094B (en) * | 2005-09-06 | 2012-09-26 | 谢拉杰克特股份有限公司 | Solid solution perforator containing drug particle and/or drug-adsorbed particles |
US7670534B2 (en) | 2005-09-21 | 2010-03-02 | Molecular Imprints, Inc. | Method to control an atmosphere between a body and a substrate |
US7623624B2 (en) * | 2005-11-22 | 2009-11-24 | Illumina, Inc. | Method and apparatus for labeling using optical identification elements characterized by X-ray diffraction |
US7803308B2 (en) * | 2005-12-01 | 2010-09-28 | Molecular Imprints, Inc. | Technique for separating a mold from solidified imprinting material |
US7906058B2 (en) | 2005-12-01 | 2011-03-15 | Molecular Imprints, Inc. | Bifurcated contact printing technique |
US7650050B2 (en) * | 2005-12-08 | 2010-01-19 | Alstom Technology Ltd. | Optical sensor device for local analysis of a combustion process in a combustor of a thermal power plant |
US7670530B2 (en) * | 2006-01-20 | 2010-03-02 | Molecular Imprints, Inc. | Patterning substrates employing multiple chucks |
CN101535021A (en) * | 2005-12-08 | 2009-09-16 | 分子制模股份有限公司 | Method and system for double-sided patterning of substrates |
US20070266801A1 (en) * | 2005-12-16 | 2007-11-22 | Alireza Khademhosseini | Reversible Sealing of Microfluidic Arrays |
US20070138699A1 (en) * | 2005-12-21 | 2007-06-21 | Asml Netherlands B.V. | Imprint lithography |
EP1984738A2 (en) | 2006-01-11 | 2008-10-29 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US20070195127A1 (en) * | 2006-01-27 | 2007-08-23 | President And Fellows Of Harvard College | Fluidic droplet coalescence |
KR101530379B1 (en) * | 2006-03-29 | 2015-06-22 | 삼성전자주식회사 | Method for Producing Silicon Nanowire Using Porous Glass Template and Device Comprising Silicon Nanowire Formed by the Same |
US8142850B2 (en) | 2006-04-03 | 2012-03-27 | Molecular Imprints, Inc. | Patterning a plurality of fields on a substrate to compensate for differing evaporation times |
US7802978B2 (en) | 2006-04-03 | 2010-09-28 | Molecular Imprints, Inc. | Imprinting of partial fields at the edge of the wafer |
US8850980B2 (en) | 2006-04-03 | 2014-10-07 | Canon Nanotechnologies, Inc. | Tessellated patterns in imprint lithography |
KR20090003153A (en) | 2006-04-03 | 2009-01-09 | 몰레큘러 임프린츠 인코퍼레이티드 | Method of concurrently patterning a substrate having a plurality of fields and alignment marks |
US7830575B2 (en) * | 2006-04-10 | 2010-11-09 | Illumina, Inc. | Optical scanner with improved scan time |
KR100869066B1 (en) * | 2006-04-17 | 2008-11-17 | 한국기술산업 (주) | Bio-chip of pattern-arranged in line, method for manufacturing the same, and method for detecting an analyte bound in the same |
US8012395B2 (en) * | 2006-04-18 | 2011-09-06 | Molecular Imprints, Inc. | Template having alignment marks formed of contrast material |
US7547398B2 (en) * | 2006-04-18 | 2009-06-16 | Molecular Imprints, Inc. | Self-aligned process for fabricating imprint templates containing variously etched features |
WO2007124007A2 (en) * | 2006-04-21 | 2007-11-01 | Molecular Imprints, Inc. | Method for detecting a particle in a nanoimprint lithography system |
EP2481815B1 (en) * | 2006-05-11 | 2016-01-27 | Raindance Technologies, Inc. | Microfluidic devices |
US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
US20070269924A1 (en) * | 2006-05-18 | 2007-11-22 | Basf Aktiengesellschaft | Patterning nanowires on surfaces for fabricating nanoscale electronic devices |
US8215946B2 (en) | 2006-05-18 | 2012-07-10 | Molecular Imprints, Inc. | Imprint lithography system and method |
JP2009540333A (en) | 2006-06-12 | 2009-11-19 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | Nanosensors and related technologies |
US20080181958A1 (en) * | 2006-06-19 | 2008-07-31 | Rothrock Ginger D | Nanoparticle fabrication methods, systems, and materials |
US7625515B2 (en) * | 2006-06-19 | 2009-12-01 | Iowa State University Research Foundation, Inc. | Fabrication of layer-by-layer photonic crystals using two polymer microtransfer molding |
JP2008004200A (en) | 2006-06-23 | 2008-01-10 | Fujifilm Corp | Manufacturing method of master recording medium, magnetic transfer method using manufactured master recording medium and manufacturing method of magnetic recording medium |
US20080145627A1 (en) * | 2006-07-03 | 2008-06-19 | Arryx, Inc. | Nanoscale masking and printing using patterned substrates |
EP3536396B1 (en) | 2006-08-07 | 2022-03-30 | The President and Fellows of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
WO2008033303A2 (en) | 2006-09-11 | 2008-03-20 | President And Fellows Of Harvard College | Branched nanoscale wires |
US8287895B1 (en) | 2008-04-24 | 2012-10-16 | Hrl Laboratories, Llc | Three-dimensional biological scaffold compromising polymer waveguides |
US8017193B1 (en) | 2008-08-06 | 2011-09-13 | Hrl Laboratories, Llc | Monomeric formulation for making polymer waveguides |
US7382959B1 (en) | 2006-10-13 | 2008-06-03 | Hrl Laboratories, Llc | Optically oriented three-dimensional polymer microstructures |
US8197930B1 (en) | 2007-05-10 | 2012-06-12 | Hrl Laboratories, Llc | Three-dimensional ordered open-cellular structures |
WO2008060455A2 (en) | 2006-11-09 | 2008-05-22 | Nanosys, Inc. | Methods for nanowire alignment and deposition |
US20080110557A1 (en) * | 2006-11-15 | 2008-05-15 | Molecular Imprints, Inc. | Methods and Compositions for Providing Preferential Adhesion and Release of Adjacent Surfaces |
WO2008127314A1 (en) | 2006-11-22 | 2008-10-23 | President And Fellows Of Harvard College | High-sensitivity nanoscale wire sensors |
US20100190654A1 (en) * | 2006-12-05 | 2010-07-29 | Liquidia Technologies , Inc. | Nanoarrays and methods and materials for fabricating same |
US8772046B2 (en) | 2007-02-06 | 2014-07-08 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
FI20075153A0 (en) | 2007-03-02 | 2007-03-02 | Valtion Teknillinen | Capillary transport of nano- or microparticles to form an ordered structure |
WO2008109176A2 (en) | 2007-03-07 | 2008-09-12 | President And Fellows Of Harvard College | Assays and other reactions involving droplets |
WO2008115530A2 (en) * | 2007-03-20 | 2008-09-25 | Nano Terra Inc. | Polymer composition for preparing electronic devices by microcontact printing processes and products prepared by the processes |
WO2008118861A2 (en) * | 2007-03-23 | 2008-10-02 | The University Of North Carolina At Chapel Hill | Discrete size and shape specific organic nanoparticles designed to elicit an immune response |
US7776927B2 (en) * | 2007-03-28 | 2010-08-17 | President And Fellows Of Harvard College | Emulsions and techniques for formation |
US7872563B2 (en) * | 2007-04-09 | 2011-01-18 | The Board Of Trustees Of The University Of Illinois | Variably porous structures |
US8592221B2 (en) | 2007-04-19 | 2013-11-26 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US7892610B2 (en) * | 2007-05-07 | 2011-02-22 | Nanosys, Inc. | Method and system for printing aligned nanowires and other electrical devices |
WO2009011808A1 (en) * | 2007-07-13 | 2009-01-22 | President And Fellows Of Harvard College | Droplet-based selection |
US8883291B2 (en) * | 2007-08-07 | 2014-11-11 | President And Fellows Of Harvard College | Metal oxide coating on surfaces |
WO2009021233A2 (en) * | 2007-08-09 | 2009-02-12 | Advanced Liquid Logic, Inc. | Pcb droplet actuator fabrication |
GB0717054D0 (en) * | 2007-09-01 | 2007-10-17 | Eastman Kodak Co | Patterning method |
US8814556B2 (en) * | 2007-09-28 | 2014-08-26 | Toray Industries, Inc | Method and device for manufacturing sheet having fine shape transferred thereon |
SG153674A1 (en) * | 2007-12-11 | 2009-07-29 | Nanyang Polytechnic | A method of doping and apparatus for doping |
CN101946010B (en) | 2007-12-21 | 2014-08-20 | 哈佛大学 | Systems and methods for nucleic acid sequencing |
JP4974917B2 (en) * | 2008-01-29 | 2012-07-11 | 新光電気工業株式会社 | Manufacturing method of optical waveguide |
US8802027B2 (en) * | 2008-03-28 | 2014-08-12 | President And Fellows Of Harvard College | Surfaces, including microfluidic channels, with controlled wetting properties |
JP5160941B2 (en) * | 2008-04-17 | 2013-03-13 | 日東電工株式会社 | Manufacturing method of optical waveguide module |
JP5584202B2 (en) * | 2008-05-21 | 2014-09-03 | セラジェクト, インコーポレイテッド | Method for manufacturing solid solution punch patch and use thereof |
JP2011525811A (en) * | 2008-06-27 | 2011-09-29 | マサチューセッツ インスティテュート オブ テクノロジー | Microfluidic droplets for metabolic engineering and other applications |
US8990096B2 (en) * | 2008-07-11 | 2015-03-24 | Michael W. Shore | Distributing alternatively generated power to a real estate development |
US12038438B2 (en) | 2008-07-18 | 2024-07-16 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
EP4047367A1 (en) | 2008-07-18 | 2022-08-24 | Bio-Rad Laboratories, Inc. | Method for detecting target analytes with droplet libraries |
DE102008038993B4 (en) * | 2008-08-13 | 2011-06-22 | Karlsruher Institut für Technologie, 76131 | Optical element and method for its production |
KR101004769B1 (en) * | 2008-09-09 | 2011-01-04 | 서울대학교산학협력단 | Optofluidic Lithography System and a Manufacturing Method of Three-Dimensional Microstructures |
WO2010033200A2 (en) | 2008-09-19 | 2010-03-25 | President And Fellows Of Harvard College | Creation of libraries of droplets and related species |
KR101017403B1 (en) * | 2008-11-06 | 2011-02-28 | 한국기계연구원 | Patterning method of nanoink using nano-imprint lithography |
US8195023B1 (en) | 2008-12-18 | 2012-06-05 | Hrl Laboratories, Llc | Functionally-graded three-dimensional ordered open-cellular microstructure and method of making same |
EP2373812B1 (en) | 2008-12-19 | 2016-11-09 | President and Fellows of Harvard College | Particle-assisted nucleic acid sequencing |
US20100207301A1 (en) * | 2009-02-17 | 2010-08-19 | Suh Kahp Yang | Method of forming fine channel using electrostatic attraction and method of forming fine structure using the same |
JP5435824B2 (en) | 2009-02-17 | 2014-03-05 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | Method for fabricating a microstructure |
CN102405098A (en) | 2009-03-13 | 2012-04-04 | 哈佛学院院长等 | Scale - up of flow - focusing microfluidic devices |
WO2010104604A1 (en) | 2009-03-13 | 2010-09-16 | President And Fellows Of Harvard College | Method for the controlled creation of emulsions, including multiple emulsions |
US8852523B1 (en) | 2009-03-17 | 2014-10-07 | Hrl Laboratories, Llc | Ordered open-cellular materials for mass transfer and/or phase separation applications |
US8528589B2 (en) | 2009-03-23 | 2013-09-10 | Raindance Technologies, Inc. | Manipulation of microfluidic droplets |
US20120034390A1 (en) * | 2009-04-20 | 2012-02-09 | Suh Kahp Yang | Method of forming hierarchical microstructure using partial curing |
US20110266724A1 (en) * | 2009-05-08 | 2011-11-03 | Hoowaki, Llc | Method for manufacturing microstructured metal or ceramic parts from feedstock |
WO2010138132A1 (en) * | 2009-05-26 | 2010-12-02 | The Board Of Trustees Of The University Of Illinois | Casting microstructures into stiff and durable materials from a flexible and reusable mold |
US9400219B2 (en) * | 2009-05-19 | 2016-07-26 | Iowa State University Research Foundation, Inc. | Metallic layer-by-layer photonic crystals for linearly-polarized thermal emission and thermophotovoltaic device including same |
JP5498058B2 (en) * | 2009-05-22 | 2014-05-21 | 東京エレクトロン株式会社 | Conductive film manufacturing method and manufacturing apparatus, and conductive film |
WO2010138506A1 (en) | 2009-05-26 | 2010-12-02 | Nanosys, Inc. | Methods and systems for electric field deposition of nanowires and other devices |
EP4019977A1 (en) | 2009-06-26 | 2022-06-29 | President and Fellows of Harvard College | Fluid injection |
US20120211084A1 (en) | 2009-09-02 | 2012-08-23 | President And Fellows Of Harvard College | Multiple emulsions created using jetting and other techniques |
WO2011038228A1 (en) | 2009-09-24 | 2011-03-31 | President And Fellows Of Harvard College | Bent nanowires and related probing of species |
WO2011042564A1 (en) | 2009-10-09 | 2011-04-14 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US9056289B2 (en) | 2009-10-27 | 2015-06-16 | President And Fellows Of Harvard College | Droplet creation techniques |
WO2011079176A2 (en) | 2009-12-23 | 2011-06-30 | Raindance Technologies, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
WO2011100604A2 (en) | 2010-02-12 | 2011-08-18 | Raindance Technologies, Inc. | Digital analyte analysis |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
JP2013525087A (en) | 2010-03-17 | 2013-06-20 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | Melt emulsification |
US9499813B2 (en) | 2010-06-10 | 2016-11-22 | President And Fellows Of Harvard College | Systems and methods for amplification and phage display |
JP5337114B2 (en) * | 2010-07-30 | 2013-11-06 | 株式会社東芝 | Pattern formation method |
US9695390B2 (en) | 2010-08-23 | 2017-07-04 | President And Fellows Of Harvard College | Acoustic waves in microfluidics |
US8399305B2 (en) * | 2010-09-20 | 2013-03-19 | Stats Chippac, Ltd. | Semiconductor device and method of forming dam material with openings around semiconductor die for mold underfill using dispenser and vacuum assist |
WO2012045012A2 (en) | 2010-09-30 | 2012-04-05 | Raindance Technologies, Inc. | Sandwich assays in droplets |
JP2012099178A (en) * | 2010-11-02 | 2012-05-24 | Hoya Corp | Imprint mold for bit-patterned medium manufacturing, and manufacturing method thereof |
WO2012109600A2 (en) | 2011-02-11 | 2012-08-16 | Raindance Technologies, Inc. | Methods for forming mixed droplets |
US8742406B1 (en) | 2011-02-16 | 2014-06-03 | Iowa State University Research Foundation, Inc. | Soft lithography microlens fabrication and array for enhanced light extraction from organic light emitting diodes (OLEDs) |
WO2012112804A1 (en) | 2011-02-18 | 2012-08-23 | Raindance Technoligies, Inc. | Compositions and methods for molecular labeling |
WO2012151497A1 (en) * | 2011-05-04 | 2012-11-08 | The University Of Akron | Suppression of dewetting of polymer films via inexpensive soft lithography |
US10427125B2 (en) * | 2011-05-09 | 2019-10-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Methods for performing patterned chemistry |
KR20140034242A (en) | 2011-05-23 | 2014-03-19 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | Control of emulsions, including multiple emulsions |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
EP3709018A1 (en) | 2011-06-02 | 2020-09-16 | Bio-Rad Laboratories, Inc. | Microfluidic apparatus for identifying components of a chemical reaction |
EP3120923A3 (en) | 2011-07-06 | 2017-03-01 | President and Fellows of Harvard College | Article comprising a particle having a shell and a fluid |
US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
US9539773B2 (en) | 2011-12-06 | 2017-01-10 | Hrl Laboratories, Llc | Net-shape structure with micro-truss core |
EP2795300A1 (en) | 2011-12-21 | 2014-10-29 | Imec | Optical fluorescence-based chemical and biochemical sensors and methods for fabricating such sensors |
CH705944A2 (en) * | 2011-12-22 | 2013-06-28 | Swatch Group Res & Dev Ltd | Method for manufacturing component e.g. anchor pallet, of timepiece, involves modifying structure of zone of substrate by laser so as to make zone more selective, and chemically engraving zone to selectively manufacture component |
US9017806B2 (en) | 2012-03-23 | 2015-04-28 | Hrl Laboratories, Llc | High airflow micro-truss structural apparatus |
IL220657A (en) | 2012-06-26 | 2015-09-24 | Zdf Ltd | Coated optical fibres having improved features |
US9951386B2 (en) | 2014-06-26 | 2018-04-24 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10273541B2 (en) | 2012-08-14 | 2019-04-30 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10400280B2 (en) | 2012-08-14 | 2019-09-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US20150376609A1 (en) | 2014-06-26 | 2015-12-31 | 10X Genomics, Inc. | Methods of Analyzing Nucleic Acids from Individual Cells or Cell Populations |
US20140155295A1 (en) | 2012-08-14 | 2014-06-05 | 10X Technologies, Inc. | Capsule array devices and methods of use |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US9701998B2 (en) | 2012-12-14 | 2017-07-11 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10323279B2 (en) | 2012-08-14 | 2019-06-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10752949B2 (en) | 2012-08-14 | 2020-08-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10221442B2 (en) | 2012-08-14 | 2019-03-05 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US9952388B2 (en) | 2012-09-16 | 2018-04-24 | Shalom Wertsberger | Nano-scale continuous resonance trap refractor based splitter, combiner, and reflector |
US9823415B2 (en) | 2012-09-16 | 2017-11-21 | CRTRIX Technologies | Energy conversion cells using tapered waveguide spectral splitters |
US9112087B2 (en) * | 2012-09-16 | 2015-08-18 | Shalom Wretsberger | Waveguide-based energy converters, and energy conversion cells using same |
EP2931919B1 (en) | 2012-12-14 | 2019-02-20 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10533221B2 (en) | 2012-12-14 | 2020-01-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10130459B2 (en) * | 2013-01-11 | 2018-11-20 | Bvw Holding Ag | Bio-selective surface textures |
CN108753766A (en) | 2013-02-08 | 2018-11-06 | 10X基因组学有限公司 | Polynucleotides bar code generating at |
TW201503266A (en) * | 2013-03-08 | 2015-01-16 | Nat Univ Corp Univ Kobe | A method for forming an organic semiconductor thin film |
US10179952B2 (en) * | 2013-03-08 | 2019-01-15 | Rutgers, The State University Of New Jersey | Patterned thin films by thermally induced mass displacement |
FR3005316B1 (en) * | 2013-05-03 | 2015-04-17 | Biomerieux Sa | DEVICE AND METHOD FOR DISTRIBUTING A SUSPENSION OF MICROORGANISMS |
US10395758B2 (en) | 2013-08-30 | 2019-08-27 | 10X Genomics, Inc. | Sequencing methods |
US20160090488A1 (en) * | 2013-09-09 | 2016-03-31 | FunNano USA, Inc. | Mesh-like micro- and nanostructure for optically transparent conductive coatings and method for producing same |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
EP3065712A4 (en) | 2013-11-08 | 2017-06-21 | President and Fellows of Harvard College | Microparticles, methods for their preparation and use |
US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US9824068B2 (en) | 2013-12-16 | 2017-11-21 | 10X Genomics, Inc. | Methods and apparatus for sorting data |
US9738013B1 (en) | 2013-12-19 | 2017-08-22 | Hrl Laboratories, Llc | Multi-chemistry microlattice structures and methods of manufacturing the same |
EP3090063B1 (en) | 2013-12-31 | 2019-11-06 | Bio-Rad Laboratories, Inc. | Method for detection of latent retrovirus |
US9771998B1 (en) | 2014-02-13 | 2017-09-26 | Hrl Laboratories, Llc | Hierarchical branched micro-truss structure and methods of manufacturing the same |
JP6018237B2 (en) * | 2014-02-14 | 2016-11-02 | アークレイ株式会社 | Chip manufacturing method including microchannel and chip manufactured thereby |
CA2943624A1 (en) | 2014-04-10 | 2015-10-15 | 10X Genomics, Inc. | Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same |
US10258987B2 (en) | 2014-06-26 | 2019-04-16 | President And Fellows Of Harvard College | Fluid infection using acoustic waves |
EP4235677A3 (en) | 2014-06-26 | 2023-11-22 | 10X Genomics, Inc. | Processes and systems for nucleic acid sequence assembly |
KR101645533B1 (en) * | 2014-07-18 | 2016-08-08 | 연세대학교 산학협력단 | Apparatus and method for etching substrate, stamp for etching substrate and method for manufacturing the same |
US9733429B2 (en) | 2014-08-18 | 2017-08-15 | Hrl Laboratories, Llc | Stacked microlattice materials and fabrication processes |
EP3212807B1 (en) | 2014-10-29 | 2020-09-02 | 10X Genomics, Inc. | Methods and compositions for targeted nucleic acid sequencing |
US9975122B2 (en) | 2014-11-05 | 2018-05-22 | 10X Genomics, Inc. | Instrument systems for integrated sample processing |
SG11201705615UA (en) | 2015-01-12 | 2017-08-30 | 10X Genomics Inc | Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same |
WO2016115273A1 (en) | 2015-01-13 | 2016-07-21 | 10X Genomics, Inc. | Systems and methods for visualizing structural variation and phasing information |
AU2016219480B2 (en) | 2015-02-09 | 2021-11-11 | 10X Genomics, Inc. | Systems and methods for determining structural variation and phasing using variant call data |
AU2016222719B2 (en) | 2015-02-24 | 2022-03-31 | 10X Genomics, Inc. | Methods for targeted nucleic acid sequence coverage |
US10697000B2 (en) | 2015-02-24 | 2020-06-30 | 10X Genomics, Inc. | Partition processing methods and systems |
JP2018520512A (en) * | 2015-06-25 | 2018-07-26 | エーファウ・グループ・エー・タルナー・ゲーエムベーハー | Method for producing a structure on a substrate surface |
LT3341116T (en) | 2015-08-27 | 2022-05-25 | President And Fellows Of Harvard College | Sorting method using acoustic waves |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
AU2016338907B2 (en) | 2015-10-13 | 2022-07-07 | President And Fellows Of Harvard College | Systems and methods for making and using gel microspheres |
EP3162549B1 (en) * | 2015-10-28 | 2023-06-21 | Baden-Württemberg Stiftung gGmbH | Method and device for forming an optical element with at least one functional area, and use of the device |
CN115369161A (en) | 2015-12-04 | 2022-11-22 | 10X 基因组学有限公司 | Methods and compositions for nucleic acid analysis |
WO2017138984A1 (en) | 2016-02-11 | 2017-08-17 | 10X Genomics, Inc. | Systems, methods, and media for de novo assembly of whole genome sequence data |
US11925933B2 (en) | 2016-04-15 | 2024-03-12 | President And Fellows Of Harvard College | Systems and methods for the collection of droplets and/or other entities |
WO2017197338A1 (en) | 2016-05-13 | 2017-11-16 | 10X Genomics, Inc. | Microfluidic systems and methods of use |
US10908431B2 (en) | 2016-06-06 | 2021-02-02 | Shalom Wertsberger | Nano-scale conical traps based splitter, combiner, and reflector, and applications utilizing same |
US11607658B2 (en) | 2016-07-08 | 2023-03-21 | President And Fellows Of Harvard College | Formation of colloids or gels within droplets |
US10725373B1 (en) * | 2016-10-21 | 2020-07-28 | Iowa State University Research Foundation, Inc. | Nano-patterning methods including: (1) patterning of nanophotonic structures at optical fiber tip for refractive index sensing and (2) plasmonic crystal incorporating graphene oxide gas sensor for detection of volatile organic compounds |
US10502550B2 (en) * | 2016-12-21 | 2019-12-10 | Kennametal Inc. | Method of non-destructive testing a cutting insert to determine coating thickness |
US10011872B1 (en) | 2016-12-22 | 2018-07-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10815525B2 (en) | 2016-12-22 | 2020-10-27 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
WO2018140966A1 (en) | 2017-01-30 | 2018-08-02 | 10X Genomics, Inc. | Methods and systems for droplet-based single cell barcoding |
EP3370058A1 (en) * | 2017-03-01 | 2018-09-05 | Danmarks Tekniske Universitet | Planar waveguide device with nano-sized filter |
CN110870018A (en) | 2017-05-19 | 2020-03-06 | 10X基因组学有限公司 | System and method for analyzing a data set |
US10844372B2 (en) | 2017-05-26 | 2020-11-24 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
EP4230746A3 (en) | 2017-05-26 | 2023-11-01 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
ES2755184T3 (en) * | 2017-06-29 | 2020-04-21 | Univ Aix Marseille | Micro-transfer molding process and modeled substrate obtainable therefrom |
CN111051523B (en) | 2017-11-15 | 2024-03-19 | 10X基因组学有限公司 | Functionalized gel beads |
US10829815B2 (en) | 2017-11-17 | 2020-11-10 | 10X Genomics, Inc. | Methods and systems for associating physical and genetic properties of biological particles |
SG11202009889VA (en) | 2018-04-06 | 2020-11-27 | 10X Genomics Inc | Systems and methods for quality control in single cell processing |
EP3654075A1 (en) * | 2018-11-13 | 2020-05-20 | Koninklijke Philips N.V. | Structured grating component, imaging system and manufacturing method |
CN109795062B (en) * | 2018-12-20 | 2020-03-17 | 西安交通大学 | Preparation method for processing shark skin-imitated surface by mask |
CN109931859B (en) * | 2019-04-10 | 2021-05-14 | 重庆理工大学 | Linear displacement sensor with complementary coupling structure |
FI129419B (en) | 2019-05-07 | 2022-02-15 | Teknologian Tutkimuskeskus Vtt Oy | Polarization rotators |
JP7263966B2 (en) | 2019-08-02 | 2023-04-25 | 富士通オプティカルコンポーネンツ株式会社 | optical device |
US11701658B2 (en) | 2019-08-09 | 2023-07-18 | President And Fellows Of Harvard College | Systems and methods for microfluidic particle selection, encapsulation, and injection using surface acoustic waves |
JP7276001B2 (en) * | 2019-08-27 | 2023-05-18 | 富士通オプティカルコンポーネンツ株式会社 | optical device |
KR102600749B1 (en) * | 2021-09-24 | 2023-11-09 | 울산과학기술원 | Microfluidic module and method for fabricating the microfluidic module |
KR102558147B1 (en) * | 2021-09-24 | 2023-07-20 | 울산과학기술원 | Microfluidic film and method for fabricating the microfluidic film |
CN115073022A (en) * | 2022-07-11 | 2022-09-20 | 诺丁汉大学卓越灯塔计划(宁波)创新研究院 | Reaction tank for optical fiber decoating and surface treatment and flow tank for packaging optical fiber module |
Citations (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3873360A (en) * | 1971-11-26 | 1975-03-25 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US3873359A (en) * | 1971-11-26 | 1975-03-25 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US3900614A (en) * | 1971-11-26 | 1975-08-19 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US4098922A (en) * | 1976-06-07 | 1978-07-04 | Western Electric Company, Inc. | Method for depositing a metal on a surface |
US4100037A (en) * | 1976-03-08 | 1978-07-11 | Western Electric Company, Inc. | Method of depositing a metal on a surface |
US4192764A (en) * | 1977-11-03 | 1980-03-11 | Western Electric Company, Inc. | Stabilizing composition for a metal deposition process |
US4258001A (en) * | 1978-12-27 | 1981-03-24 | Eastman Kodak Company | Element, structure and method for the analysis or transport of liquids |
US4322457A (en) * | 1978-01-25 | 1982-03-30 | Western Electric Co., Inc. | Method of selectively depositing a metal on a surface |
US4472458A (en) * | 1982-01-27 | 1984-09-18 | Bayer Aktiengesellschaft | Process for the production of metallized semiconductors |
US4508755A (en) * | 1983-03-30 | 1985-04-02 | Northern Telecom Limited | Method of applying a layer of conductive ink |
US4555414A (en) * | 1983-04-15 | 1985-11-26 | Polyonics Corporation | Process for producing composite product having patterned metal layer |
US4637904A (en) * | 1983-11-14 | 1987-01-20 | Rohm And Haas Company | Process for molding a polymeric layer onto a substrate |
US4690715A (en) * | 1982-06-18 | 1987-09-01 | American Telephone And Telegraph Company, At&T Bell Laboratories | Modification of the properties of metals |
US4710401A (en) * | 1984-09-04 | 1987-12-01 | Rockwell International Corporation | Method of printing electrically conductive images on dielectric substrates |
US4728591A (en) * | 1986-03-07 | 1988-03-01 | Trustees Of Boston University | Self-assembled nanometer lithographic masks and templates and method for parallel fabrication of nanometer scale multi-device structures |
US4802951A (en) * | 1986-03-07 | 1989-02-07 | Trustees Of Boston University | Method for parallel fabrication of nanometer scale multi-device structures |
US4869778A (en) * | 1987-07-20 | 1989-09-26 | Gardoc, Inc. | Method of forming a patterned aluminum layer and article |
US4959252A (en) * | 1986-09-29 | 1990-09-25 | Rhone-Poulenc Chimie | Highly oriented thermotropic optical disc member |
US5073495A (en) * | 1988-10-21 | 1991-12-17 | Large Scale Biology Corporation | Apparatus for isolating cloned vectors and cells having a recovery device |
US5079600A (en) * | 1987-03-06 | 1992-01-07 | Schnur Joel M | High resolution patterning on solid substrates |
US5087510A (en) * | 1990-03-22 | 1992-02-11 | Monsanto Company | Electrolessly deposited metal holograms |
US5141785A (en) * | 1989-04-13 | 1992-08-25 | Canon Kabushiki Kaisha | Recording medium |
US5170461A (en) * | 1991-12-11 | 1992-12-08 | Hoechst Celanese Corp. | Polymeric electrooptic waveguide devices using a polymeric substrate |
US5227474A (en) * | 1987-02-13 | 1993-07-13 | Abbott Laboratories | Bifunctional chelating agents |
US5258024A (en) * | 1989-05-12 | 1993-11-02 | Essilor International (Compaigne Generale D'optique) | Method of manufacture of a lens of transparent polymer having a modulated refractive index |
US5259926A (en) * | 1991-09-24 | 1993-11-09 | Hitachi, Ltd. | Method of manufacturing a thin-film pattern on a substrate |
US5345869A (en) * | 1990-02-12 | 1994-09-13 | Alcan International Limited | Lithographic plate, and method for making, having an oxide layer derived from a type A sol |
US5385116A (en) * | 1992-03-24 | 1995-01-31 | Sumitomo Electric Industries, Ltd. | Method for producing organic crystal film |
US5439829A (en) * | 1991-01-30 | 1995-08-08 | Eli Lilly And Company | Immobilization of biologically active molecules by changing the Oxidation state of a chelated transition metal ion |
US5471455A (en) * | 1994-05-17 | 1995-11-28 | Jabr; Salim N. | High density optical storage system |
US5484324A (en) * | 1988-08-25 | 1996-01-16 | Daicel Chemical Industries, Ltd. | Stamper for injection molding |
US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US5534101A (en) * | 1994-03-02 | 1996-07-09 | Telecommunication Research Laboratories | Method and apparatus for making optical components by direct dispensing of curable liquid |
US5620850A (en) * | 1994-09-26 | 1997-04-15 | President And Fellows Of Harvard College | Molecular recognition at surfaces derivatized with self-assembled monolayers |
US5807906A (en) * | 1995-02-27 | 1998-09-15 | Essilor International-Compagnie Generale D'optique | Process for obtaining a transparent article with a refractive index gradient |
US5976826A (en) * | 1993-10-04 | 1999-11-02 | President And Fellows Of Harvard College | Device containing cytophilic islands that adhere cells separated by cytophobic regions |
US5989835A (en) * | 1997-02-27 | 1999-11-23 | Cellomics, Inc. | System for cell-based screening |
US6103479A (en) * | 1996-05-30 | 2000-08-15 | Cellomics, Inc. | Miniaturized cell array methods and apparatus for cell-based screening |
US6355198B1 (en) * | 1996-03-15 | 2002-03-12 | President And Fellows Of Harvard College | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US6766817B2 (en) * | 2001-07-25 | 2004-07-27 | Tubarc Technologies, Llc | Fluid conduction utilizing a reversible unsaturated siphon with tubarc porosity action |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE671444A (en) * | 1964-10-28 | 1900-01-01 | ||
US3907624A (en) * | 1968-08-28 | 1975-09-23 | Henry County Plywood Corp | Panel with decorative integral shaped edge and method of forming same |
JPH0627742B2 (en) | 1982-12-21 | 1994-04-13 | コムテツク リサ−チ ユニツト リミテツド | Assay method and apparatus therefor |
US4731155A (en) * | 1987-04-15 | 1988-03-15 | General Electric Company | Process for forming a lithographic mask |
JPH02165933A (en) | 1988-12-20 | 1990-06-26 | Seiko Epson Corp | Manufacture of microlens array |
US5096401A (en) * | 1989-06-26 | 1992-03-17 | Canon Kabushiki Kaisha | Apparatus for producing a substrate sheet for optical recording media |
DE4115414C2 (en) * | 1991-05-10 | 1995-07-06 | Meinhard Prof Dr Knoll | Process for the production of miniaturized chemo- and biosensor elements with an ion-selective membrane as well as carriers for these elements |
JP3239598B2 (en) | 1994-02-25 | 2001-12-17 | キヤノン株式会社 | Method for manufacturing diffractive optical element |
EP0672765B1 (en) | 1994-03-14 | 1999-06-30 | Studiengesellschaft Kohle mbH | Electrochemical reduction of metal salts as a method of preparing highly dispersed metal colloids and substrate fixed metal clusters by electrochemical reduction of metal salts |
WO1996029629A2 (en) | 1995-03-01 | 1996-09-26 | President And Fellows Of Harvard College | Microcontact printing on surfaces and derivative articles |
AU6774996A (en) | 1995-08-18 | 1997-03-12 | President And Fellows Of Harvard College | Self-assembled monolayer directed patterning of surfaces |
US5772905A (en) * | 1995-11-15 | 1998-06-30 | Regents Of The University Of Minnesota | Nanoimprint lithography |
DE69707853T2 (en) | 1996-03-15 | 2002-06-27 | President And Fellows Of Harvard College, Cambridge | METHOD FOR SHAPING OBJECTS AND MICROSTRUCTURING SURFACES BY MOLDING WITH CAPILLARY EFFECT |
US5827780A (en) * | 1996-04-01 | 1998-10-27 | Hsia; Liang Choo | Additive metalization using photosensitive polymer as RIE mask and part of composite insulator |
-
1998
- 1998-01-08 US US09/004,583 patent/US6355198B1/en not_active Expired - Lifetime
-
2000
- 2000-08-09 US US09/634,201 patent/US6660192B1/en not_active Expired - Lifetime
-
2001
- 2001-10-30 US US10/016,614 patent/US6752942B2/en not_active Expired - Lifetime
-
2003
- 2003-10-01 US US10/677,103 patent/US20040178523A1/en not_active Abandoned
-
2007
- 2007-12-12 US US12/001,564 patent/US20080116608A1/en not_active Abandoned
-
2009
- 2009-03-04 US US12/398,132 patent/US8012382B2/en not_active Expired - Fee Related
Patent Citations (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3873359A (en) * | 1971-11-26 | 1975-03-25 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US3900614A (en) * | 1971-11-26 | 1975-08-19 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US3873360A (en) * | 1971-11-26 | 1975-03-25 | Western Electric Co | Method of depositing a metal on a surface of a substrate |
US4100037A (en) * | 1976-03-08 | 1978-07-11 | Western Electric Company, Inc. | Method of depositing a metal on a surface |
US4098922A (en) * | 1976-06-07 | 1978-07-04 | Western Electric Company, Inc. | Method for depositing a metal on a surface |
US4192764A (en) * | 1977-11-03 | 1980-03-11 | Western Electric Company, Inc. | Stabilizing composition for a metal deposition process |
US4322457A (en) * | 1978-01-25 | 1982-03-30 | Western Electric Co., Inc. | Method of selectively depositing a metal on a surface |
US4258001A (en) * | 1978-12-27 | 1981-03-24 | Eastman Kodak Company | Element, structure and method for the analysis or transport of liquids |
US4472458A (en) * | 1982-01-27 | 1984-09-18 | Bayer Aktiengesellschaft | Process for the production of metallized semiconductors |
US4690715A (en) * | 1982-06-18 | 1987-09-01 | American Telephone And Telegraph Company, At&T Bell Laboratories | Modification of the properties of metals |
US4508755A (en) * | 1983-03-30 | 1985-04-02 | Northern Telecom Limited | Method of applying a layer of conductive ink |
US4555414A (en) * | 1983-04-15 | 1985-11-26 | Polyonics Corporation | Process for producing composite product having patterned metal layer |
US4637904A (en) * | 1983-11-14 | 1987-01-20 | Rohm And Haas Company | Process for molding a polymeric layer onto a substrate |
US4710401A (en) * | 1984-09-04 | 1987-12-01 | Rockwell International Corporation | Method of printing electrically conductive images on dielectric substrates |
US4728591A (en) * | 1986-03-07 | 1988-03-01 | Trustees Of Boston University | Self-assembled nanometer lithographic masks and templates and method for parallel fabrication of nanometer scale multi-device structures |
US4802951A (en) * | 1986-03-07 | 1989-02-07 | Trustees Of Boston University | Method for parallel fabrication of nanometer scale multi-device structures |
US4959252A (en) * | 1986-09-29 | 1990-09-25 | Rhone-Poulenc Chimie | Highly oriented thermotropic optical disc member |
US5227474A (en) * | 1987-02-13 | 1993-07-13 | Abbott Laboratories | Bifunctional chelating agents |
US5079600A (en) * | 1987-03-06 | 1992-01-07 | Schnur Joel M | High resolution patterning on solid substrates |
US4869778A (en) * | 1987-07-20 | 1989-09-26 | Gardoc, Inc. | Method of forming a patterned aluminum layer and article |
US5484324A (en) * | 1988-08-25 | 1996-01-16 | Daicel Chemical Industries, Ltd. | Stamper for injection molding |
US5073495A (en) * | 1988-10-21 | 1991-12-17 | Large Scale Biology Corporation | Apparatus for isolating cloned vectors and cells having a recovery device |
US5141785A (en) * | 1989-04-13 | 1992-08-25 | Canon Kabushiki Kaisha | Recording medium |
US5258024A (en) * | 1989-05-12 | 1993-11-02 | Essilor International (Compaigne Generale D'optique) | Method of manufacture of a lens of transparent polymer having a modulated refractive index |
US5345869A (en) * | 1990-02-12 | 1994-09-13 | Alcan International Limited | Lithographic plate, and method for making, having an oxide layer derived from a type A sol |
US5087510A (en) * | 1990-03-22 | 1992-02-11 | Monsanto Company | Electrolessly deposited metal holograms |
US5439829A (en) * | 1991-01-30 | 1995-08-08 | Eli Lilly And Company | Immobilization of biologically active molecules by changing the Oxidation state of a chelated transition metal ion |
US5259926A (en) * | 1991-09-24 | 1993-11-09 | Hitachi, Ltd. | Method of manufacturing a thin-film pattern on a substrate |
US5170461A (en) * | 1991-12-11 | 1992-12-08 | Hoechst Celanese Corp. | Polymeric electrooptic waveguide devices using a polymeric substrate |
US5385116A (en) * | 1992-03-24 | 1995-01-31 | Sumitomo Electric Industries, Ltd. | Method for producing organic crystal film |
US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US5976826A (en) * | 1993-10-04 | 1999-11-02 | President And Fellows Of Harvard College | Device containing cytophilic islands that adhere cells separated by cytophobic regions |
US5534101A (en) * | 1994-03-02 | 1996-07-09 | Telecommunication Research Laboratories | Method and apparatus for making optical components by direct dispensing of curable liquid |
US5471455A (en) * | 1994-05-17 | 1995-11-28 | Jabr; Salim N. | High density optical storage system |
US5620850A (en) * | 1994-09-26 | 1997-04-15 | President And Fellows Of Harvard College | Molecular recognition at surfaces derivatized with self-assembled monolayers |
US5807906A (en) * | 1995-02-27 | 1998-09-15 | Essilor International-Compagnie Generale D'optique | Process for obtaining a transparent article with a refractive index gradient |
US6355198B1 (en) * | 1996-03-15 | 2002-03-12 | President And Fellows Of Harvard College | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US20020066978A1 (en) * | 1996-03-15 | 2002-06-06 | Enoch Kim | Method of forming articles including waveguides via capillary micromolding and microtransfer molding |
US6660192B1 (en) * | 1996-03-15 | 2003-12-09 | Harvard College | Molded waveguides |
US6103479A (en) * | 1996-05-30 | 2000-08-15 | Cellomics, Inc. | Miniaturized cell array methods and apparatus for cell-based screening |
US5989835A (en) * | 1997-02-27 | 1999-11-23 | Cellomics, Inc. | System for cell-based screening |
US6766817B2 (en) * | 2001-07-25 | 2004-07-27 | Tubarc Technologies, Llc | Fluid conduction utilizing a reversible unsaturated siphon with tubarc porosity action |
Cited By (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8066763B2 (en) | 1998-04-11 | 2011-11-29 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US7588710B2 (en) * | 2004-05-04 | 2009-09-15 | Minuta Technology Co., Ltd. | Mold made of amorphous fluorine resin and fabrication method thereof |
US20070210483A1 (en) * | 2004-05-04 | 2007-09-13 | Lee Hong H | Mold made of amorphous fluorine resin and fabrication method thereof |
US8574615B2 (en) | 2006-03-24 | 2013-11-05 | Boston Scientific Scimed, Inc. | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
WO2007146848A2 (en) * | 2006-06-09 | 2007-12-21 | Lam Research Corporation | Surface modification of interlayer dielectric for minimizing contamination and surface degradation |
WO2007146848A3 (en) * | 2006-06-09 | 2008-03-06 | Lam Res Corp | Surface modification of interlayer dielectric for minimizing contamination and surface degradation |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
US8771343B2 (en) | 2006-06-29 | 2014-07-08 | Boston Scientific Scimed, Inc. | Medical devices with selective titanium oxide coatings |
US8353949B2 (en) | 2006-09-14 | 2013-01-15 | Boston Scientific Scimed, Inc. | Medical devices with drug-eluting coating |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US8821799B2 (en) | 2007-01-26 | 2014-09-02 | Palo Alto Research Center Incorporated | Method and system implementing spatially modulated excitation or emission for particle characterization with enhanced sensitivity |
US9164037B2 (en) | 2007-01-26 | 2015-10-20 | Palo Alto Research Center Incorporated | Method and system for evaluation of signals received from spatially modulated excitation and emission to accurately determine particle positions and distances |
US9638637B2 (en) | 2007-01-26 | 2017-05-02 | Palo Alto Research Center Incorporated | Method and system implementing spatially modulated excitation or emission for particle characterization with enhanced sensitivity |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US20080294236A1 (en) * | 2007-05-23 | 2008-11-27 | Boston Scientific Scimed, Inc. | Endoprosthesis with Select Ceramic and Polymer Coatings |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US20090016672A1 (en) * | 2007-07-13 | 2009-01-15 | Oliver Schmidt | Producing Fluidic Waveguides |
US20090016690A1 (en) * | 2007-07-13 | 2009-01-15 | Oliver Schmidt | Producing Sandwich Waveguides |
US7522811B2 (en) | 2007-07-13 | 2009-04-21 | Palo Alto Research Center Incorporated | Producing sandwich waveguides |
US7529438B2 (en) | 2007-07-13 | 2009-05-05 | Palo Alto Research Center Incorporated | Producing fluidic waveguides |
US9284409B2 (en) | 2007-07-19 | 2016-03-15 | Boston Scientific Scimed, Inc. | Endoprosthesis having a non-fouling surface |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US8221822B2 (en) | 2007-07-31 | 2012-07-17 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
US8900292B2 (en) | 2007-08-03 | 2014-12-02 | Boston Scientific Scimed, Inc. | Coating for medical device having increased surface area |
US8828521B2 (en) * | 2007-08-09 | 2014-09-09 | International Business Machines Corporation | Corrugated interfaces for multilayered interconnects |
US9089080B2 (en) | 2007-08-09 | 2015-07-21 | International Business Machines Corporation | Corrugated interfaces for multilayered interconnects |
US20090048659A1 (en) * | 2007-08-17 | 2009-02-19 | Boston Scientific Scimed, Inc. | Medical devices having sol-gel derived ceramic regions with molded submicron surface features |
US20090060434A1 (en) * | 2007-09-03 | 2009-03-05 | Fuji Xerox Co., Ltd. | Waveguide device |
US7747128B2 (en) * | 2007-09-03 | 2010-06-29 | Fuji Xerox Co., Ltd. | Waveguide device |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US8629981B2 (en) | 2008-02-01 | 2014-01-14 | Palo Alto Research Center Incorporated | Analyzers with time variation based on color-coded spatial modulation |
US8373860B2 (en) | 2008-02-01 | 2013-02-12 | Palo Alto Research Center Incorporated | Transmitting/reflecting emanating light with time variation |
US20090202737A1 (en) * | 2008-02-07 | 2009-08-13 | Nitto Denko Corporation | Manufacturing method of optical waveguide for touch panel |
US8231813B2 (en) * | 2008-02-07 | 2012-07-31 | Nitto Denko Corporation | Manufacturing method of optical waveguide for touch panel |
CN101533127A (en) * | 2008-02-07 | 2009-09-16 | 日东电工株式会社 | Method of manufacturing optical waveguide for touch panel |
US8580344B2 (en) | 2008-03-17 | 2013-11-12 | Intermolecular, Inc. | Stamp usage to enhance surface layer functionalization and selectivity |
US20090232966A1 (en) * | 2008-03-17 | 2009-09-17 | Kalyankar Nikhil D | Stamp Usage To Enhance Surface Layer Functionalization And Selectivity |
US8920491B2 (en) | 2008-04-22 | 2014-12-30 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
US8932346B2 (en) | 2008-04-24 | 2015-01-13 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
US8449603B2 (en) | 2008-06-18 | 2013-05-28 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US20100019401A1 (en) * | 2008-07-28 | 2010-01-28 | Nitto Denko Corporation | Method for manufacturing optical waveguide |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US8852469B2 (en) * | 2011-01-21 | 2014-10-07 | Lg Innotek Co., Ltd. | Optical member, display device having the same and method of fabricating the same |
US20120188746A1 (en) * | 2011-01-21 | 2012-07-26 | Lg Innotek Co., Ltd. | Optical Member, Display Device Having the Same and Method of Fabricating the Same |
US10066810B2 (en) | 2011-01-21 | 2018-09-04 | Lg Innotek Co., Ltd. | Optical member, display device having the same and method of fabricating the same |
US8723140B2 (en) | 2011-08-09 | 2014-05-13 | Palo Alto Research Center Incorporated | Particle analyzer with spatial modulation and long lifetime bioprobes |
US9029800B2 (en) | 2011-08-09 | 2015-05-12 | Palo Alto Research Center Incorporated | Compact analyzer with spatial modulation and multiple intensity modulated excitation sources |
WO2020149931A1 (en) * | 2019-01-15 | 2020-07-23 | Massachusetts Institute Of Technology | Integrated freeform optical couplers |
US11378733B2 (en) | 2019-01-15 | 2022-07-05 | Massachusetts Institute Of Technology | Integrated freeform optical couplers |
Also Published As
Publication number | Publication date |
---|---|
US20080116608A1 (en) | 2008-05-22 |
US8012382B2 (en) | 2011-09-06 |
US20020066978A1 (en) | 2002-06-06 |
US6660192B1 (en) | 2003-12-09 |
US6752942B2 (en) | 2004-06-22 |
US20090166903A1 (en) | 2009-07-02 |
US6355198B1 (en) | 2002-03-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8012382B2 (en) | Molded waveguides | |
CA2248576C (en) | Method of forming articles and patterning surfaces via capillary micromolding | |
EP0812434B1 (en) | Microcontact printing on surfaces and derivative articles | |
Lopez | Materials aspects of photonic crystals | |
US6180239B1 (en) | Microcontact printing on surfaces and derivative articles | |
Moon et al. | Chemical aspects of three-dimensional photonic crystals | |
US5900160A (en) | Methods of etching articles via microcontact printing | |
Xia et al. | A facile approach to directed assembly of patterns of nanoparticles using interference lithography and spin coating | |
US7875197B2 (en) | Methods of etching articles via microcontact printing | |
Werts et al. | Nanometer scale patterning of Langmuir− Blodgett films of gold nanoparticles by electron beam lithography | |
Blättler et al. | Nanopatterns with biological functions | |
US5512131A (en) | Formation of microstamped patterns on surfaces and derivative articles | |
CA2282713C (en) | Gel sensors and methods of making thereof | |
CA2329412C (en) | Elastomeric mask and use in fabrication of devices, including pixelated electroluminescent displays | |
Jeong et al. | Proximity injection of plasticizing molecules to self-assembling polymers for large-area, ultrafast nanopatterning in the sub-10-nm regime | |
WO1996029629A9 (en) | Microcontact printing on surfaces and derivative articles | |
Lin et al. | Multilength-scale chemical patterning of self-assembled monolayers by spatially controlled plasma exposure: nanometer to centimeter range | |
Xia et al. | Formation of hierarchical nanoparticle pattern arrays using colloidal lithography and two-step self-assembly: Microspheres atop nanospheres | |
CA2681374A1 (en) | Mechanical process for creating particles in a fluid | |
EP1339550B1 (en) | A process and an apparatus for the formation of patterns in films using temperature gradients | |
Davydovich et al. | Coordinated Responsive Arrays of Surface-Linked Polymer Islands CORALs | |
Blanco et al. | Photonic crystals: fundamentals and applications | |
Ma et al. | Curved Microwell Arrays Created by Diffusion-Limited Chemical Etching of Artificially Engineered Solids | |
Li et al. | Chemical/Electrochemical Corrosion-Created Dynamic Metal Ion Gradients Enable the Assembly of Colloidal Particles | |
Mrksich et al. | SYMPOSIUM Z |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: PRESIDENT AND FELLOWS OF HARVARD COLLEGE, MASSACHU Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KIM, ENOCH;XIA, YOUNAN;MRKSICH, MILAN;AND OTHERS;REEL/FRAME:021764/0060;SIGNING DATES FROM 19980817 TO 19981005 |