ES2106341T3 - Estructuras de deteccion microfabricadas. - Google Patents

Estructuras de deteccion microfabricadas.

Info

Publication number
ES2106341T3
ES2106341T3 ES93910887T ES93910887T ES2106341T3 ES 2106341 T3 ES2106341 T3 ES 2106341T3 ES 93910887 T ES93910887 T ES 93910887T ES 93910887 T ES93910887 T ES 93910887T ES 2106341 T3 ES2106341 T3 ES 2106341T3
Authority
ES
Spain
Prior art keywords
analyte
link
detection region
detection
sample
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.)
Expired - Lifetime
Application number
ES93910887T
Other languages
English (en)
Inventor
Peter Wilding
Larry J Kricka
Jay N Zemel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Pennsylvania Penn
Original Assignee
University of Pennsylvania Penn
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27542279&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2106341(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from US07/877,536 external-priority patent/US5304487A/en
Priority claimed from US07/877,661 external-priority patent/US5296375A/en
Application filed by University of Pennsylvania Penn filed Critical University of Pennsylvania Penn
Application granted granted Critical
Publication of ES2106341T3 publication Critical patent/ES2106341T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/18—Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/02—Inorganic material
    • B01D71/0213—Silicon
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/7182—Feed mechanisms characterised by the means for feeding the components to the mixer with means for feeding the material with a fractal or tree-type distribution in a surface
    • 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
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/04—Surgical instruments, devices or methods for suturing wounds; Holders or packages for needles or suture materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/028—Microfluidic pore structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40—Static mixers
    • B01F25/41—Mixers of the fractal type
    • 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
    • B01J2219/0059—Sequential processes
    • 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
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00824—Ceramic
    • B01J2219/00828—Silicon wafers or plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00833—Plastic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00889—Mixing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/146—Employing pressure sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Physiology (AREA)
  • Inorganic Chemistry (AREA)
  • Water Supply & Treatment (AREA)
  • Dispersion Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Optical Measuring Cells (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • External Artificial Organs (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Steroid Compounds (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Flow Control (AREA)

Abstract

SE DESCUBREN DISPOSITIVOS PARA DETECTAR LA PRESENCIA DE UN ANALITO PRESELECCIONADO EN UNA MUESTRA FLUIDA. LOS DISPOSITIVOS COMPRENDEN UN SUSTRATO MICROFABRICADO PARA DEFINIR UNA PUERTA (16) DE ENTRADA PARA MUESTRA, Y UN SISTEMA DE FLUJO DE ESCALA INTERMEDIA QUE INCLUYE UN CANAL (20) DE FLUJO DE MUESTRA QUE SE EXTIENDE DESDE LA PUERTA DE ENTRADA. EL SISTEMA DE FLUJO DE MESOESCALA INCLUYE ADEMAS UNA REGION (22) DE DETECCION DE ANALITO EN COMUNICACION FLUIDA CON EL CANAL (20) DE FLUJO QUE COMPRENDE UNA FRACCION DE LIGANTE PARA LIGAR ESPECIFICAMENTE AL ANALITO. LA REGION DE DETECCION ESTA CONSTRUIDA CON UNA DIMENSION DE MESOESCALA SUFICIENTEMENTE PEQUEÑA PARA MEJORAR EL ENLACE DE LA FRACCION LIGANTE Y EL ANALITO. LA FRACCION DE ENLACE PUEDE SER INMOBILIZADA EN LA REGION DE DETECCION. LOS SISTEMAS DE DETECCION MESOESCALA DE LA INVENCION PUEDEN SER USADOS EN UN AMPLIO MARGEN DE APLICACIONES, QUE INCLUYEN LA DETECCION DE CELULAS O MACROMOLECULAS, O PARA SUPERVISAR REACCIONES O CRECIMIENTO DE CULTIVO DE CELULAS.
ES93910887T 1992-05-01 1993-04-29 Estructuras de deteccion microfabricadas. Expired - Lifetime ES2106341T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US87770192A 1992-05-01 1992-05-01
US87770292A 1992-05-01 1992-05-01
US87766292A 1992-05-01 1992-05-01
US07/877,536 US5304487A (en) 1992-05-01 1992-05-01 Fluid handling in mesoscale analytical devices
US07/877,661 US5296375A (en) 1992-05-01 1992-05-01 Mesoscale sperm handling devices

Publications (1)

Publication Number Publication Date
ES2106341T3 true ES2106341T3 (es) 1997-11-01

Family

ID=27542279

Family Applications (2)

Application Number Title Priority Date Filing Date
ES93910887T Expired - Lifetime ES2106341T3 (es) 1992-05-01 1993-04-29 Estructuras de deteccion microfabricadas.
ES93910907T Expired - Lifetime ES2127276T3 (es) 1992-05-01 1993-04-29 Analisis por amplificacion de polinucleotido con la ayuda de un dispositivo microfabricado.

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES93910907T Expired - Lifetime ES2127276T3 (es) 1992-05-01 1993-04-29 Analisis por amplificacion de polinucleotido con la ayuda de un dispositivo microfabricado.

Country Status (10)

Country Link
EP (5) EP0637997B1 (es)
JP (5) JPH07506431A (es)
AT (5) ATE140025T1 (es)
AU (5) AU677197B2 (es)
CA (5) CA2134475C (es)
DE (5) DE69322774T2 (es)
ES (2) ES2106341T3 (es)
GR (2) GR3025037T3 (es)
HK (1) HK16897A (es)
WO (5) WO1993022053A1 (es)

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AU4223593A (en) 1993-11-29
ATE167816T1 (de) 1998-07-15
HK16897A (en) 1997-02-13
AU677781B2 (en) 1997-05-08
AU677197B2 (en) 1997-04-17
JP3207424B2 (ja) 2001-09-10
CA2134476A1 (en) 1993-11-11
EP0637998A1 (en) 1995-02-15
EP0637999B1 (en) 1998-12-23
AU680195B2 (en) 1997-07-24
JP3558294B2 (ja) 2004-08-25
EP0637997B1 (en) 1998-07-01
DE69312483D1 (de) 1997-09-04
DE69303898D1 (de) 1996-09-05
WO1993022421A1 (en) 1993-11-11
WO1993022053A1 (en) 1993-11-11
JPH07506430A (ja) 1995-07-13
ES2127276T3 (es) 1999-04-16
CA2134474A1 (en) 1993-11-11
DE69322774T2 (de) 1999-06-17
EP0637998B2 (en) 2006-04-12
AU677780B2 (en) 1997-05-08
DE69319427T2 (de) 1998-12-10
GR3025037T3 (en) 1998-01-30
CA2134478C (en) 2001-12-18
CA2134477C (en) 1999-07-06
EP0639223A1 (en) 1995-02-22
WO1993022055A2 (en) 1993-11-11
WO1993022054A1 (en) 1993-11-11
CA2134478A1 (en) 1993-11-11
DE69312483T2 (de) 1998-02-12
JPH07506256A (ja) 1995-07-13
CA2134474C (en) 1999-07-06
EP0639223B1 (en) 1996-07-03
JPH07506258A (ja) 1995-07-13
ATE140880T1 (de) 1996-08-15
CA2134475A1 (en) 1993-11-11
ATE155711T1 (de) 1997-08-15
JP3298882B2 (ja) 2002-07-08
EP0637998B1 (en) 1996-07-31
CA2134476C (en) 1999-08-10
DE69303898T3 (de) 2007-01-18
DE69303483T2 (de) 1997-02-06
HK1001305A1 (en) 1998-06-12
AU4222793A (en) 1993-11-29
WO1993022055A3 (en) 1994-03-03
WO1993022058A1 (en) 1993-11-11
CA2134477A1 (en) 1993-11-11
EP0637999A1 (en) 1995-02-15
CA2134475C (en) 1999-07-06
AU674685B2 (en) 1997-01-09
EP0637996A1 (en) 1995-02-15
ATE174813T1 (de) 1999-01-15
EP0637997A1 (en) 1995-02-15
DE69319427D1 (de) 1998-08-06
DE69303898T2 (de) 1997-02-20
AU4222593A (en) 1993-11-29
AU4222393A (en) 1993-11-29
DE69322774D1 (de) 1999-02-04
JPH07506257A (ja) 1995-07-13
JPH07506431A (ja) 1995-07-13
DE69303483D1 (de) 1996-08-08
EP0637996B1 (en) 1997-07-23
GR3029509T3 (en) 1999-05-28
ATE140025T1 (de) 1996-07-15
AU4222693A (en) 1993-11-29

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