WO2004057386A1 - Amelioration d'une technique de detection par fibres optiques utilisant une fibre optique a ame double - Google Patents

Amelioration d'une technique de detection par fibres optiques utilisant une fibre optique a ame double Download PDF

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Publication number
WO2004057386A1
WO2004057386A1 PCT/US2003/040683 US0340683W WO2004057386A1 WO 2004057386 A1 WO2004057386 A1 WO 2004057386A1 US 0340683 W US0340683 W US 0340683W WO 2004057386 A1 WO2004057386 A1 WO 2004057386A1
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WO
WIPO (PCT)
Prior art keywords
core
fiber
optical fiber
test sample
excitation
Prior art date
Application number
PCT/US2003/040683
Other languages
English (en)
Inventor
Jing Yong Ye
Theodore Norris
James R. Baker
Thommey Thomas
Mon Myaing
Original Assignee
The Regents Of The University Of Michigan
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
Priority claimed from US10/738,828 external-priority patent/US7046888B2/en
Application filed by The Regents Of The University Of Michigan filed Critical The Regents Of The University Of Michigan
Priority to JP2004562329A priority Critical patent/JP2006510906A/ja
Priority to DE10393931T priority patent/DE10393931T5/de
Priority to AU2003301147A priority patent/AU2003301147A1/en
Publication of WO2004057386A1 publication Critical patent/WO2004057386A1/fr

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Classifications

    • 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
    • G02B6/02—Optical fibres with cladding with or without a coating
    • G02B6/02047—Dual mode fibre
    • 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
    • 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
    • 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
    • G02B6/02—Optical fibres with cladding with or without a coating
    • G02B6/02042—Multicore 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
    • G01N21/62—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"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
    • 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
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/069—Supply of sources
    • G01N2201/0696—Pulsed
    • G01N2201/0697—Pulsed lasers
    • 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
    • G02B6/02—Optical fibres with cladding with or without a coating
    • G02B6/02295—Microstructured optical fibre
    • G02B6/02314—Plurality of longitudinal structures extending along optical fibre axis, e.g. holes
    • G02B6/02319—Plurality of longitudinal structures extending along optical fibre axis, e.g. holes characterised by core or core-cladding interface features
    • G02B6/02338—Structured core, e.g. core contains more than one material, non-constant refractive index distribution in core, asymmetric or non-circular elements in core unit, multiple cores, insertions between core and clad
    • 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
    • G02B6/02—Optical fibres with cladding with or without a coating
    • G02B6/02295—Microstructured optical fibre
    • G02B6/02314—Plurality of longitudinal structures extending along optical fibre axis, e.g. holes
    • G02B6/02342—Plurality of longitudinal structures extending along optical fibre axis, e.g. holes characterised by cladding features, i.e. light confining region
    • G02B6/02366—Single ring of structures, e.g. "air clad"

Definitions

  • the present invention relates to fiber optic sensing and, more particularly, to a dual-core fiber for improved detection efficiency relative to conventional single-mode and multi-mode fibers.
  • optical fiber based sensing technology has been rapidly developed and widely used recently in biological and biomedical studies. Many of these studies employ conventional one-photon fluorescence (OPF) measurement techniques.
  • OPF one-photon fluorescence
  • TPF two-photon fluorescence
  • the small nonlinear excitation volume in the close proximity of the fiber tip enables local detection at a specific site.
  • the use of near infrared light allows minimization of photodamage to living cells and drugs, in contrast to excitation by energetic UV photons.
  • the large separation in wavelength between two-photon excitation and fluorescence emission facilitates elimination of detection of background noise.
  • a single laser source may be used to excite a wide variety of fluorophores.
  • Two-photon excitation arises due to the simultaneous absorption of two incident photons by a molecule. This excitation causes a ground-state electron to transition to an excited state of the fluorophore. Because two photons are required for each transition, the probability of excitation is dependent on the square of the instantaneous incident radiation intensity. Thus, an ultra-short-pulsed laser beam is usually needed for efficient excitation.
  • excitation laser beam can be delivered deep into a targeted biological sample through an optical fiber, which otherwise is subject to strong scattering and absorption by biological tissues.
  • bulk optics and laser sources may now be placed remotely from the sample to be tested.
  • an optical fiber having an advantageous construction and method of fiber optic sensing includes a first core and a second core.
  • the second core is generally coaxially disposed within the first core and is sized smaller than the first core.
  • the second core is capable of delivering pulsed laser energy from the laser for nonlinear optical excitation of the test sample. Nonlinear optical feedback signals can then be collected in both the first core and second core for improved detection efficiency relative to conventional single- mode and multi-mode fibers.
  • FIG. 1 is a cross-sectional view illustrating a dual-core optical fiber according to the principles of the present invention
  • FIG. 2 is an end view illustrating the dual-core optical fiber
  • FIG. 3 is a graph showing the calculated result of a two-photon fluorescence detection efficiency comparison between a single-mode fiber and a step-index multimode fiber;
  • FIG. 4 is a graph illustrating experimental results of two-photon fluorescence detection efficiency using different single- and multi-mode fibers
  • FIG. 5 is a graph illustrating the calculated result of an enhancement factor for a two-photon flourescence signal detected with the dual- core optical fiber
  • FIG. 6a is a graph illustrating two-photon flouresence power as a function of the concentrations of G5-FI and G5-FI-FA;
  • FIG. 6b is a graph illustrating a dose-response curve for the binding of G5-FI and G5-FI-FA on KB cells;
  • FIG. 7 is an SEM of a dual-core photonic crystal fiber according to the present invention.
  • FIG. 8 is a graph illustrating two-photon flourescence using a dual-core photonic crystal fiber and a single mode fiber.
  • a dual-core optical fiber is provided in accordance with the principles of the present invention for use with two-photon fluorescence detection to provide excitation and detection of a specimen through a single optical fiber. That is, dual-core optical fiber 10 permits the optimization of both the excitation rate and collection efficiency in a single optical fiber.
  • a laser source 12 is operably coupled to dual- core optical fiber 10 via conventional means. Laser source 12 may be of any conventional design, such as a general pulsed laser.
  • a detection system (not shown) may include a spectrometer and photon counter.
  • the laser source used herein was a Ti:sapphire laser providing 80-fs pulses at 830 nm with an 80-MHz repetition rate.
  • dual-core optical fiber 10 is adapted to deliver ultra short laser pulses from laser source 12 through an inner core 14. It should be appreciated that such delivery of ultra short laser pulses, such as about femtosecond pulses, through inner core 14 is similar to single-mode optical fibers, which maintains single-mode propagation which leads to a high nonlinear optical excitation rate.
  • dual-core optical fiber 10 further includes an outer core 16 disposed about inner core 14 in a coaxial arrangement to receive or collect two-photon fluorescence. Outer core 16 is surrounded by a cladding 18. As the names imply, outer core 16 has a greater radius B relative to radius A of inner core 14 (FIG. 2).
  • the outer core 16 has a large numerical aperture which ensures high collection efficiency. It has been demonstrated that the total detection sensitivity of dual-core optical fiber 10 is significantly enhanced. [0023] In order to appreciate the trade-off between numerical aperture (NA) and the effects of dispersion in determining the signal level, it is necessary to consider the following. In general, the detected two-photon fluorescence power P is given by,
  • n refractive index of the sample
  • A is the laser wavelength
  • a is the radius of the fiber core
  • the ratio between the two-photon fluorescence signal detected through a dual-core fiber and that detected through a conventional single-mode fiber is then calculated.
  • the two-photon fluorescence signal remarkably increases by using dual-core optical fiber 10 with outer core 16 having a high numerical aperture (NA).
  • NA numerical aperture
  • inner core 14 has a radius of 2 ⁇ m and numerical aperture (NA) of 0.11 as a conventional single-mode fiber
  • the refractive index of a sample solution is 1.33
  • the enhancement factor is 39-fold for outer core 16 with a radius of 100 ⁇ m and numerical aperture (NA) of 0.65.
  • the enhancement factor in connection with the present invention is 29-fold when outer core 16 has a radius of 15 ⁇ m and a numerical aperture (NA) of 0.65.
  • NA numerical aperture
  • the present invention was successfully in biosensing the uptake of a targeted dendrimer-based drug delivery agent into cultured KB cells (a sub-line derived from the cervical carcinoma HeLa cell line).
  • the generation 5 dendrimers (G5) used are conjugated both to a fluorescent dye; fluorescein isothiocyanate (FI), for optical sensing of the presence of dendrimers in the cells; and to folic acid (FA), which enables the dendrimers to be selectively taken up by FA-receptor- positive KB cells.
  • FI fluorescein isothiocyanate
  • FA folic acid
  • the binding of G5-FI-FA and control G5-FI dendrimer to KB cells was then investigated.
  • the two-photon fluorescence of standard solutions of G5-FI and G5-FI-FA in the absence of KB cells was measured and exhibited the expected linear concentration dependence as seen in FIG. 6a.
  • the two-photon fluorescence power from cultured KB cell pellets treated with different concentrations of dendrimer solution was then measured.
  • the measured fluorescence was used to determine quantitatively the number of dendrimer molecules bound to the KB cells.
  • FIG. 6b the binding as a function of the concentration used to treat the cells is illustrated.
  • the total G5-FI- FA bound to the KB cells is significantly higher than that for G5-FI, which is expected since the G5-FI is taken into the cells non-specifically. Both the binding parameters and the saturation kinetics are consistent with previous flow cytometric data.
  • the fiber-based biosensing technique appears to be a viable method for real-time in vivo monitoring of uptake of drugs into tumors.
  • Dual-core photonic crystal fiber 100 is just one example of a dual-core fiber.
  • Dual-core photonic crystal fiber 100 is designed to ensure endlessly single mode guidance down the centrally situated core 102.
  • the photonic crystal structure with smaller air holes surrounding the center core is surrounded by a silica web with larger air holes.
  • the PC structure with small air holes acts as an outer core with a very high NA in contrast to the inner solid core. This allows single mode two-photon excitation and multimode collection of two-photon fluorescence.
  • This dual-core fiber can be coupled with a lens, such as a Gradient Index (GRIN) lens, to focus excitation light into a test sample. The excitation light then excites flourescence from the test sample.
  • GRIN Gradient Index
  • the collected fluorescence with the lens normally forms a bigger spot (or a defocused flourescence arrangement) than the excitation beam at the fiber tip due to chromatic aberration (CA).
  • CA chromatic aberration
  • the fluorescence even that being defocused through CA
  • CA chromatic aberration
  • This feature is another advantage of a dual-core fiber over a single-mode fiber; the amount of fluorescence collected into single-mode fiber will be very small, making the single-mode fiber essentially useless in this application, whereas almost all the fluorescence can be collected into the dual-core fiber.
  • the dual-core fiber of the present invention Through the use of the dual-core fiber of the present invention, one can take advantage of the merits of both a single mode and a multimode fibers at the same time, such as high efficiency of nonlinear optical excitation and high fluorescence collection, while simultaneously avoiding the drawbacks of each, such as low collection efficiency of single mode fibers and inefficiency of nonlinear optical excitation with multimode fibers.
  • the description of the invention is merely exemplary in nature and, thus, variations that do not depart from the gist of the invention are intended to be within the scope of the invention. Such variations are not to be regarded as a departure from the spirit and scope of the invention.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Optics & Photonics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention porte sur une fibre optique destinée à être utilisée dans la détection par fibre optique d'un échantillon de test et comprenant une première âme (16) et une seconde âme (14). La seconde âme (14) est généralement placée de manière coaxiale dans la première (16), sa taille étant inférieure à celle de la première. La seconde âme (14) peut délivrer une énergie laser pulsée par le laser (12) afin de générer une excitation optique non linéaire dans l'échantillon de test. Les signaux optiques de réaction non linéaires peuvent être ensuite recueillis dans les première et seconde âmes afin d'améliorer la détection par rapport à l'utilisation de fibres traditionnelles monomodales et multimodales .
PCT/US2003/040683 2002-12-18 2003-12-18 Amelioration d'une technique de detection par fibres optiques utilisant une fibre optique a ame double WO2004057386A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2004562329A JP2006510906A (ja) 2002-12-18 2003-12-18 デュアルコア・ファイバーを用いた光ファイバー・センシング技術の改良
DE10393931T DE10393931T5 (de) 2002-12-18 2003-12-18 Verbesserung der Faseroptischen Messtechnik unter Verwendung einer Doppelkernfaser
AU2003301147A AU2003301147A1 (en) 2002-12-18 2003-12-18 Enhancing fiber-optic sensing technique using a dual-core fiber

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US60/434,604 2002-12-18
US10/738,828 US7046888B2 (en) 2002-12-18 2003-12-17 Enhancing fiber-optic sensing technique using a dual-core fiber
US10/738,828 2003-12-17

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2538220A1 (fr) 2006-02-21 2012-12-26 Trustees Of Tufts College Procédés et réseaux pour la détection d'analytes cibles et détermination de la concentration d'analytes cibles dans une solution
CN110749572A (zh) * 2019-10-29 2020-02-04 广州特种承压设备检测研究院 一种新型石墨烯光纤气体传感器测量系统及其测量硫化氢气体的方法
CN110907410A (zh) * 2018-09-14 2020-03-24 恩德莱斯和豪瑟尔分析仪表两合公司 光学传感器
CN113376136A (zh) * 2021-06-18 2021-09-10 北京航空航天大学 一种基于双芯光子晶体光纤的荧光探测系统和方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5112127A (en) * 1989-11-28 1992-05-12 Eic Laboratories, Inc. Apparatus for measuring Raman spectra over optical fibers
EP1207387A1 (fr) * 2000-11-20 2002-05-22 Institut Curie Dispositif d'imagerie multiphotonique
US20020094528A1 (en) * 2000-11-29 2002-07-18 Salafsky Joshua S. Method and apparatus using a surface-selective nonlinear optical technique for detection of probe-target interations

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5112127A (en) * 1989-11-28 1992-05-12 Eic Laboratories, Inc. Apparatus for measuring Raman spectra over optical fibers
EP1207387A1 (fr) * 2000-11-20 2002-05-22 Institut Curie Dispositif d'imagerie multiphotonique
US20020094528A1 (en) * 2000-11-29 2002-07-18 Salafsky Joshua S. Method and apparatus using a surface-selective nonlinear optical technique for detection of probe-target interations

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2538220A1 (fr) 2006-02-21 2012-12-26 Trustees Of Tufts College Procédés et réseaux pour la détection d'analytes cibles et détermination de la concentration d'analytes cibles dans une solution
CN110907410A (zh) * 2018-09-14 2020-03-24 恩德莱斯和豪瑟尔分析仪表两合公司 光学传感器
CN110907410B (zh) * 2018-09-14 2022-12-27 恩德莱斯和豪瑟尔分析仪表两合公司 光学传感器
CN110749572A (zh) * 2019-10-29 2020-02-04 广州特种承压设备检测研究院 一种新型石墨烯光纤气体传感器测量系统及其测量硫化氢气体的方法
CN113376136A (zh) * 2021-06-18 2021-09-10 北京航空航天大学 一种基于双芯光子晶体光纤的荧光探测系统和方法

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