WO2012156432A1 - Dispositif et sonde pour la détection d'une infection - Google Patents

Dispositif et sonde pour la détection d'une infection Download PDF

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Publication number
WO2012156432A1
WO2012156432A1 PCT/EP2012/059083 EP2012059083W WO2012156432A1 WO 2012156432 A1 WO2012156432 A1 WO 2012156432A1 EP 2012059083 W EP2012059083 W EP 2012059083W WO 2012156432 A1 WO2012156432 A1 WO 2012156432A1
Authority
WO
WIPO (PCT)
Prior art keywords
probe
interaction
activatable
chromophore
moiety
Prior art date
Application number
PCT/EP2012/059083
Other languages
English (en)
Inventor
Hong Zhang
Maurice Aalders
Tom VAN GOOL
Original Assignee
Academisch Medisch Centrum Bij De Universiteit Van Amsterdam
Universiteit Van Amsterdam
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
Application filed by Academisch Medisch Centrum Bij De Universiteit Van Amsterdam, Universiteit Van Amsterdam filed Critical Academisch Medisch Centrum Bij De Universiteit Van Amsterdam
Publication of WO2012156432A1 publication Critical patent/WO2012156432A1/fr

Links

Classifications

    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
    • 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
    • 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
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54346—Nanoparticles
    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/588—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with semiconductor nanocrystal label, e.g. quantum dots
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6432—Quenching
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6484—Optical fibres
    • 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
    • G01N2021/7786—Fluorescence
    • 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
    • G01N2021/7793—Sensor comprising plural indicators

Definitions

  • Such devices may get colonised by pathogenic microorganisms, especially at their outer ends.
  • penetrating devices are changed on a regular basis, generally every three or four days. Replacement of such device is a burden to the patient, is costly, and in itself poses a risk of infection.
  • colonization of pathogens on the surface of the device is a further advantage.
  • the detection at the sub- nanogram per mL level is achieved primarily by adsorption or a surface activity due to a refractive index change.
  • the geometry of the biconically tapered optical sensor affects its
  • Such device relies on natural fluorescence and therefore exhibits low signal-to-noise ratio.
  • the device can only detect at the location of the tapered portion. Further, optical access to opposite ends of the fiber must be available complicating or even preventing use for detection in vivo.
  • US 2009/270269 discloses a sensing system incorporating a nano-scale fluoro-biosensor for detection of specifically targeted bio-contaminants (targets).
  • embodiments use fluorescent nanoparticles such as quantum dots (QD) conjugated to antibody fragments to form a sensor for a specific bio-contaminant based on fluorescent resonance energy transfer (FRET) .
  • QD quantum dots
  • FRET fluorescent resonance energy transfer
  • a quenching dye may be used to label an analog, while a specific antibody is covalently bonded to a hydrophilic QD .
  • Coupling of QD labeled antibodies and quencher labeled analogs provides enough proximity to produce appreciable FRET- based quenching. Any addition of the target displaces the dye- labeled bacteria, eliminating FRET-based quenching and results in a concentration-dependent increase in QD photoluminescence .
  • a target may comprise microbial cells, bacteria, yeast cells, fungi, multicellular organisms, viruses, tumor cells, antibodies, other pathogens etc.
  • the probe may comprise a quenching moiety attached, in particular chemically linked, to the chromophore, having a quenching effect on the chromophore which is configured to be altered, in particular reduced or cancelled by interaction of the target with the interaction moiety.
  • the quenching moiety may be chemically altered, physically altered e.g. by reforming part of the probe such as deformation and/or repositioning part of a protein with respect to the chromophore.
  • the quenching moiety attached, in particular chemically linked, to the chromophore, having a quenching effect on the chromophore which is configured to be altered, in particular reduced or cancelled by interaction of the target with the interaction moiety.
  • the quenching moiety may be chemically altered, physically altered e.g. by reforming part of the probe such as deformation and/or repositioning part of a protein with respect to the chromophore.
  • Absorption and/or emission of such further chromophore may be quenched by a quenching moiety, which may be identical or a different quenching moiety, affected by the target interacting with the interaction moiety.
  • the probe may also comprise a photosensitizer moiety which may be activated by the emission of a chromophore of the activated probe, e.g. for in situ therapy.
  • a chromophore may comprise an inorganic chromophore, which may have increased resistance to
  • the chromophore may be arranged for absorbing light with a near-infrared wavelength in a wavelength range of about
  • 800-2100 nm preferably in a range of about 800-1500 nm, e.g. in a range of about 900-1200 nm such as about 1000 nm, and emitting (near- ) visible light in a wavelength range of about 400-800 nm, preferably in a range of about 500-700 nm, e.g. about 550 nm and/or 650 nm.
  • the near-infrared (NIR) wavelength for absorption and excitation has a relatively large penetration depth in mammalian tissue and induces little to no (auto-) luminescence of the tissue, improving the signal-to-noise ratio.
  • the activatable device may be provided by attaching an activatable probe to the device, e.g. via coating techniques, such as by coating the device with a coating composition
  • the probe further comprises an attachment moiety for attaching the probe to a device, in particular to a device for insertion and/or implanting into a human or animal body.
  • the device and/or the probe may be used for detecting interaction with the probe by a target and in particular binding to and/or colonisation of the device by a target.
  • the device may be inserted in an analyte or in a subjects' body and interaction and/or colonisation may be monitored by monitoring optical alterations of the probe in situ.
  • a device such as an optical fiber may be placed in a blood vessel for an extended period during which period the fiber may "capture" targets out of the blood flowing past it.
  • excitation light can then be transmitted through the fiber 13 and couple to (the chromophore 3 of) the probe 1.
  • the light source may emit white light, which may be filtered, or one or more spectral bands or lines, e.g. originating from one or more light emitting diodes and/or lasers.
  • activatable implant 13B may be tested with an endoscope via an artificial or natural orifice of the body, such as a checking a pacemaker via a port-a-cath, a stomach reduction band via esophagal/stomach endoscopy, and/or a cardial by-pass via a gastroscope. It is further possible to use a fluid column, e.g. a translucent or clear infusion fluid, through an otherwise opaque conduit as the light guide.
  • a fluid column e.g. a translucent or clear infusion fluid
  • Fig. 13 showing intensity in arbitrary units versus wavelength ⁇ in nanometer. Excitation may also be performed with a wavelength of about 810 nm. Further, downconversion processes result in radiative emission around 1520 nm, cf . Fig. 14, showing
  • tissue particular human, tissue.
  • a photosensitizer e.g. Rose Bengal
  • mTHPC 650 nm
  • photofrin 630 nm
  • suitable photosensitizers are e.g. listed on the website http : / /www . photobiology .info/Berg. html .
  • nanoparticle may be tunable by selection of the excitation wavelength.
  • the emitted light can be used for selective
  • the detection may be in vivo and the catheter can remain in the blood vessel until the amount of colonization reaches a critical threshold, (ii) The NIR light excitation and visible light detection configuration can significantly increase the detection sensitivity by minimizing the autofluorescence of the surrounding material, (iii) Destruction of specific targets based on PDT can be carried out after their detection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Biomedical Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Nanotechnology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Materials Engineering (AREA)
  • Plasma & Fusion (AREA)
  • Optics & Photonics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

Cette invention concerne un dispositif activable (15) qui comprend un dispositif (13) et une sonde d'imagerie activable (1) fixée à celui-ci. La sonde comprend un chromophore (3) et un fragment d'interaction (5) lié au chromophore. L'interaction d'une cible (23) avec le fragment d'interaction modifie les propriétés optiques de la sonde. Une sonde d'imagerie activable à fixer au dispositif activable selon l'invention est également décrite.
PCT/EP2012/059083 2011-05-17 2012-05-16 Dispositif et sonde pour la détection d'une infection WO2012156432A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP11166364 2011-05-17
EP11166364.7 2011-05-17

Publications (1)

Publication Number Publication Date
WO2012156432A1 true WO2012156432A1 (fr) 2012-11-22

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017048146A1 (fr) 2015-09-15 2017-03-23 Wrocławskie Centrum Badań Eit+ Sp. Z O.O. Procédé de détection et de sélection de cellules d'hybridome produisant les anticorps souhaités
CN112839573A (zh) * 2018-10-16 2021-05-25 皇家飞利浦有限公司 介入设备的传感器的供能

Citations (9)

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Publication number Priority date Publication date Assignee Title
US20030000443A1 (en) 1999-12-09 2003-01-02 Arctic Cat Inc. Method and system for controlling thrust of watercraft during various steering conditions
WO2005025413A2 (fr) * 2003-09-11 2005-03-24 Theranos, Inc. Dispositif medical permettant de surveiller un analyte et de distribuer des medicaments
US20060147378A1 (en) 2002-09-24 2006-07-06 Ching-Hsuan Tung Azulene dimer-quenched, near-infrared fluorescent probes
WO2006094408A1 (fr) * 2005-03-10 2006-09-14 Universite De Sherbrooke Matrice a points quantiques pour detection rapide et simultanee de differents agents infectieux
WO2008136769A1 (fr) * 2007-05-03 2008-11-13 Nanyang Technological University Système de détection et d'élimination des contaminants en ligne
WO2009045579A2 (fr) 2007-06-14 2009-04-09 The Regents Of The University Of California Sondes d'imagerie multimodes pour imagerie et thérapie in vivo ciblées et non ciblées
WO2009074890A2 (fr) 2007-12-12 2009-06-18 Kimberly-Clark Worldwide, Inc. Dispositifs implantables destinés à une détection d'infection nosocomiale basée sur des fibres optiques
US20090270269A1 (en) 2008-04-28 2009-10-29 Ashok Kumar Nano-scale fluoro-biosensors exhibiting a low false alarm rate for rapid detection of biological contaminants
US20090304551A1 (en) 2006-01-31 2009-12-10 Drexel University Ultra Sensitive Tapered Fiber Optic Biosensor For Pathogens, Proteins, and DNA

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030000443A1 (en) 1999-12-09 2003-01-02 Arctic Cat Inc. Method and system for controlling thrust of watercraft during various steering conditions
US20060147378A1 (en) 2002-09-24 2006-07-06 Ching-Hsuan Tung Azulene dimer-quenched, near-infrared fluorescent probes
WO2005025413A2 (fr) * 2003-09-11 2005-03-24 Theranos, Inc. Dispositif medical permettant de surveiller un analyte et de distribuer des medicaments
WO2006094408A1 (fr) * 2005-03-10 2006-09-14 Universite De Sherbrooke Matrice a points quantiques pour detection rapide et simultanee de differents agents infectieux
US20090304551A1 (en) 2006-01-31 2009-12-10 Drexel University Ultra Sensitive Tapered Fiber Optic Biosensor For Pathogens, Proteins, and DNA
WO2008136769A1 (fr) * 2007-05-03 2008-11-13 Nanyang Technological University Système de détection et d'élimination des contaminants en ligne
WO2009045579A2 (fr) 2007-06-14 2009-04-09 The Regents Of The University Of California Sondes d'imagerie multimodes pour imagerie et thérapie in vivo ciblées et non ciblées
WO2009074890A2 (fr) 2007-12-12 2009-06-18 Kimberly-Clark Worldwide, Inc. Dispositifs implantables destinés à une détection d'infection nosocomiale basée sur des fibres optiques
US20090270269A1 (en) 2008-04-28 2009-10-29 Ashok Kumar Nano-scale fluoro-biosensors exhibiting a low false alarm rate for rapid detection of biological contaminants

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Title
A.D. ELLINGTON; J.W. SZOSTAK: "In vitro selection of RNA molecules that bind specific ligands", NATURE, vol. 346, 1990, pages 818 - 822, XP002547962, DOI: doi:10.1038/346818a0
A.K. SINGH ET AL.: "Development of sensors for direct detection of organophosphates. Part I: immobilization, characterization and stabilization ofacetylcholinesterase and organophosphate hydrolase on silica supports", BIOSENSORS & BIOELECTRONICS, vol. 14, 1999, pages 703 - 713, XP002243724, DOI: doi:10.1016/S0956-5663(99)00044-5
C. TUERK; L. GOLD: "Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophase T4 DNA polymerase", SCIENCE, vol. 249, 1990, pages 505 - 510
KONG X ET AL: "Luminescent upconversion nanoparticle (ULNP) with photosensitizing functions to be used for the diagnosis and therapy of cancer", LUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE; [31660], JOHN WILEY & SONS LTD, GB, vol. 23, no. 2, 17 May 2008 (2008-05-17), pages 77, XP009153028, ISSN: 1522-7235 *
Q.CHEN ET AL.: "Functionalization of upconverted luminescent NaYF4:Yb/Er nanocrystals by folic acid-chitosan conjugates for targeted lung cancer cell imaging", J. MATER. CHEM., 2011
Y. ZHANG ET AL.: "Multi-targeting single fiber-optic biosensor based on evanescent wave and quantum dots", BIOSENSORS & BIOELECTRONICS, vol. 26, 2010, pages 149 - 154, XP027273655

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017048146A1 (fr) 2015-09-15 2017-03-23 Wrocławskie Centrum Badań Eit+ Sp. Z O.O. Procédé de détection et de sélection de cellules d'hybridome produisant les anticorps souhaités
EP3350324A4 (fr) * 2015-09-15 2019-03-20 Wroclawskie Centrum Badan EIT + SP Z O.O. Procédé de détection et de sélection de cellules d'hybridome produisant les anticorps souhaités
CN112839573A (zh) * 2018-10-16 2021-05-25 皇家飞利浦有限公司 介入设备的传感器的供能

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