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WO2005119328A1 - Source lumineuse amelioree pour microscope a balayage - Google Patents

Source lumineuse amelioree pour microscope a balayage Download PDF

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Publication number
WO2005119328A1
WO2005119328A1 PCT/GB2005/002077 GB2005002077W WO2005119328A1 WO 2005119328 A1 WO2005119328 A1 WO 2005119328A1 GB 2005002077 W GB2005002077 W GB 2005002077W WO 2005119328 A1 WO2005119328 A1 WO 2005119328A1
Authority
WO
WIPO (PCT)
Prior art keywords
light source
microscope
photonic crystal
wavelength
crystal fibre
Prior art date
Application number
PCT/GB2005/002077
Other languages
English (en)
Inventor
Gail Mcconnell
Original Assignee
University Of Strathclyde
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 GB0412470A external-priority patent/GB0412470D0/en
Priority claimed from GB0416441A external-priority patent/GB0416441D0/en
Priority claimed from GB0501218A external-priority patent/GB0501218D0/en
Application filed by University Of Strathclyde filed Critical University Of Strathclyde
Publication of WO2005119328A1 publication Critical patent/WO2005119328A1/fr

Links

Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0032—Optical details of illumination, e.g. light-sources, pinholes, beam splitters, slits, fibers
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/16—Microscopes adapted for ultraviolet illumination ; Fluorescence microscopes

Definitions

  • the present invention relates to the field of laser scanning microscopy.
  • the present invention relates to an improved light source for a laser scanning microscope e.g. a confocal laser scanning microscope (CLSM) or a fluorescence lifetime imaging microscope (FLIM) .
  • a laser scanning microscope e.g. a confocal laser scanning microscope (CLSM) or a fluorescence lifetime imaging microscope (FLIM) .
  • CLSM confocal laser scanning microscope
  • FLIM fluorescence lifetime imaging microscope
  • confocal laser scanning microscopy has become one of the most widely applied and versatile microscopic tools in the fields of biology, medicine, engineering and physics.
  • CLSMs provide a tool that enables minimally intrusive optical sectioning of fluorescently prepared cells and tissue at sub-micron resolutions, as described in J.B. Pawley's text entitled "Handbook of Biological Confocal Microscopy” 2 nd edition (Plenum Press, New York 1995) .
  • CLSMs gas-based laser light sources
  • gas-based laser light sources e.g. a helium-neon or argon ion laser
  • these laser sources exhibit several shortcomings, including stringent maintenance requirements, limited lifetimes, heat generation, large scale and high noise levels .
  • Solid state lasers as described by J.M. Girkin et al "Confocal Microscopy Using An InGaN Violet Laser Diode At 406nm” Optics Express, Volume 7, Page 336- 341 (2000) .
  • solid-state laser sources are more robust than gas laser sources, however they are not wavelength flexible and hence are suitable for use with only a limited range of useful fluorophores that are available within the art.
  • Multi-photon laser scanning microscopy is an alternative technique that is increasingly being employed by those skilled in the art as a complimentary method to confocal laser scanning microscopy techniques.
  • an ultra-short pulsed infrared emitting laser source provides the high peak powers required to instigate simultaneous excitation of multiple electrons within the fluorophore, as taught by D.L. Wokosin et al "All Solid State Ultrafast Lasers Facilitate Multiphoton Excitation Fluorescence Microscopy", IEEE J. Sel Top. Quantum Electronics Volume 2, Page 1051-1065 (1996).
  • several laser sources are therefore often required.
  • FLIM fluorescence lifetime imaging microscopy
  • a pulsed excitation source is required whose excitation wavelength should ideally be well-matched to the absorption wavelength (s) of the sample.
  • the preferred options are either to employ pulsed laser diodes or via multi-photon excitation. In the former case, only a very limited number of discrete, fixed wavelengths are available.
  • multi-photon excitation inherently provides optical sectioning capability, the lower excitation efficiency, limited tuning range (particularly the 1000-1200 nm range) and simultaneous excitation of multiple fluorescent molecules are significant limitations.
  • Optical parametric oscillators have been used to perform both single and multi-photon excited TCSPC FLIM, however, these sources are complex and difficult to operate.
  • a light source for use with a scanning microscope, the light source comprising a coherent light source coupled to a photonic crystal fibre so as to generate a continuum spectrum from the fibre and selection apparatus for selecting a predetermined wavelength range of the generated continuum spectrum.
  • a scanning microscope comprising a coherent light source coupled to a photonic crystal fibre so as to generate a continuum spectrum from the fibre, selection apparatus for selecting a predetermined wavelength range of the generated continuum spectrum, a microscope and scanning means for scanning the spectral output of the " light source over a field of view of the microscope.
  • a first lens couples the coherent light source into the length of photonic crystal fibre.
  • a second lens collimates the continuum spectrum generated by the photonic crystal fibre.
  • the first and second lenses may comprise aspheric anti- reflection coated lenses.
  • the selection apparatus for selecting a predetermined wavelength range of the generated continuum spectrum comprises a bandpass filter.
  • the selection apparatus for selecting a predetermined wavelength range comprises an optical dispersion means.
  • the optical dispersion means comprises an element selected from the group comprising a grating, an electro-optic modulator, an acoustic-optic modulator, a spatial light modulator, a monochrometer, a prism, a fibre, a grism, adaptive optics or one or more chromatic dispersion lenses .
  • the light source further comprises an optical isolator located between the coherent light source and the photonic crystal fibre.
  • the light source further comprises a power control means for controlling the output power of the device.
  • the coherent light source comprises a pulsed single mode laser suitable of generating an output at a wavelength between 720 and 890 nm.
  • the photonic crystal fibre exhibits a zero dispersion wavelength below 720 nm.
  • the photonic crystal fibre exhibits a zero dispersion wavelength of 670 nm.
  • the microscope comprises a confocal laser scanning microscope (CLSM) .
  • the microscope comprises a fluorescence lifetime imaging microscope (FLIM) .
  • a method of generating light for a scanning microscope comprising the steps: 1) Generating a continuum spectrum; and 2) Selecting a portion of the continuum spectrum that corresponds to an optical characteristic of a sample to be tested.
  • the step of generating a continuum spectrum comprises coupling a coherent light source to a photonic crystal fibre wherein the photonic crystal fibre exhibits a zero dispersion wavelength of ⁇ 0 while the coherent light source operates at a wavelength greater than ⁇ 0 .
  • the step of generating a continuum spectrum comprises coupling a coherent light source to a photonic crystal fibre wherein the photonic crystal fibre exhibits a zero dispersion wavelength of ⁇ o while the coherent light source operates at a wavelength of ⁇ 0 .
  • the step of selecting a portion of the continuum spectrum comprises the selection of portion that corresponds to an excitation wavelength of a flurophore located within the sample.
  • Figure 1 provides a schematic representation of a light source, suitable for employment with a scanning microscope, in accordance with an aspect of the present invention
  • Figure 2 presents a sample unfiltered spectral output of the laser source of Figure 1;
  • Figure 3 presents a schematic representation of a confocal laser scanning fluorescence microscope in accordance with an aspect of the present invention
  • Figure 4 presents a: a) fluorescence image; and b) transmission image of a guinea pig detrusor labelled with anti-PGP 9.5 and Alexa 488 obtained employing the confocal laser scanning fluorescence microscope of Figure 3.
  • Figure 5 presents a superimposed fluorescence and transmission image of a guinea pig smooth muscle cell containing flo-4 obtained employing the confocal laser scanning fluorescence microscope of Figure 3 ;
  • Figure 6 presents mean fluorescent intensity signals taken from a control (unloaded) , and ten loaded, smooth muscle cells obtained employing the experimental set up of Figure 5;
  • Figure 7 provides a schematic representation of an alternative embodiment of the light source suitable for employment with a scanning microscope
  • Figure 8 presents a sample non-dispersed spectral output and two dispersed spectral outputs obtained from the laser source of Figure 7 ;
  • Figure 9 presents : a) a fluorescence image of a guinea pig detrusor labelled with anti-PGP 9.5 and Alexa 488; b) a fluorescence image of a guinea pig detrusor labelled with anti-smooth muscle myosin and Alexa 594; and c) a merged representation of the fluroscence images of (a) and (b) obtained employing a confocal laser scanning fluorescence that incorporates the laser source of Figure 7;
  • Figure 10 presents a schematic representation of a fluorescence lifetime imaging microscope in accordance with an aspect of the present invention.
  • Figure 11 presents an Intensity and a TPSPC FLIM image of a mouse fibrosarcoma stained with haematoxin and eosin obtained by employing the fluorescence lifetime imaging microscope of Figure 10.
  • the output radiation generated is then propagated through a Faraday isolator 3 employed to reduce feedback from the subsequent surfaces within the light source 1.
  • PCF 5 is microstructured fibre, known to those skilled in the art of fibre optics. Radiation incident on the PCF 5 is guided by periodically arranged air holes that surround a solid silica core that extends the length of the fibre. This fibre design produces a photonic bandgap in the transverse direction that results in a fibre that is continuously single-mode throughout the visible range, see J.C. Knight et al "All-silica single-mode optical fibre with photonic crystal cladding" Optics Letters, Volume 21, Pages 1547-1549 (1996) .
  • a result of the improved guiding properties of the PCF 5 is that it enables a reduction in the core diameter, down to a few microns, to be achieved.
  • the function of the band pass filter 7 is to provide a means for wavelength selection of the output from the light source 1 while the neutral density filter 8 provides a means for controlling the output power of the device.
  • Figure 2 presents an experimentally measured spectral output 9 for the light source 1 in the absence of the bandpass filter 7 and the neutral density filter 8.
  • the spectral output 9 can be seen to comprise a visible - continuum spectrum that exhibits a measured average output power of ⁇ 51mW.
  • the length of the PCF 5 has been chosen so as to maximise the generation of radiation within the visible wavelength region, thus matching the single-photon excitation wavelengths of many of the fluorophores employed in the art, as described in detail below.
  • Figure 3 presents a schematic representation of the light source 1 incorporated within a CLSM 10.
  • the CLSM 10 can be seen to further comprises a scan head 11 (namely a commercially available Bio-Rad 1024ES) and an inverted microscope 12 (namely a Nikon, TE300) .
  • the function of the scan head 11 and the inverted microscope 12 is to allow the collimated spectral output 9 of the light source 1 to be incident upon a sample contained within the inverted microscope 12.
  • An image of the sample is then obtained by employing the scan-head 11 to scan the spectral output 9 over the field of view of the inverted microscope 12.
  • This optical set up offers great flexibility in image acquisition strategies as is known to those skilled in the art. In particular it enables the production of optical section images, that is images in which light from out-of-focus regions do not contribute to the image.
  • Fluorescence resulting from confocal excitation of the sample 16 is then collected by the objective lens 15 and directed back through the scanning mirror system 14 and the dichroic mirror 13 towards a photomultiplier tube 17.
  • a second optical bandpass filter 18 is then located in front of the photomultiplier tube 17, the function of which is to provide a means for rejecting any light from the light source 1 than may be reflected by the components of the CLSM 10 directly onto the photomultiplier tube 17.
  • An electrical signal generated by the photomultiplier tube 17 is then relayed to a computer processor (not shown) operating image capture software so as to allow for the visualisation of the fluorescently stained regions of the sample 16.
  • the broad spectral output 9 is particularly advantageous in that the light source can readily be employed to stimulate simultaneous or sequential multiple fluorophore excitations, as are commonly required within in the field of confocal laser scanning microscopy.
  • the follow experimental results employ fluorophore transitions that only required single excitations to take place within the samples.
  • Figure 4 presents a typical confocal fluorescence xy cross-section obtained from a thick fixed tissue sample of guinea pig detruser (bladder smooth muscle layer) labelled with anti-PGP 9.5 and Alexa 488.
  • Figure 5 presents similar results for a guinea pig detruser loaded with 2 ⁇ M of Fluo-4 AM.
  • FIG. 4(a) The fluorescence image of Figure 4(a) was obtained at a sample depth of approximately 41 ⁇ M.
  • Figure 4(b) presents the transmission image taken for the same region of the sample. Within the fluorescence image it is possible to observe the fluorescently labelled nerves 19 wrapped around a blood vessel 20 over a partial depth.
  • the CLSM 10 is capable of operating over a total depth of 59 ⁇ m within this particular sample 16. Furthermore, over an image period of several hours, no photobleaching or tissue damage was observed within this sample 16, as is commonly experienced with conventional Kr/Ar laser confocal excitation. A high contrast ratio was also observed with a signal background ratio typically exceeding 100:1, which is again comparable to the excitation results achieved within Kr/Ar laser systems.
  • Figure 5 presents a superimposed fluorescence and transmission images of a guinea pig smooth muscle cell 21. It is noted that a dead cell 22 that also exhibits a fluorescent signal is present below the smooth muscle cell 21. Once more the continual exposure of this sample to radiation over several hours caused no cell damage i.e. membrane, blebbing or shape change or pronounced photobleaching to the sample. A high contrast ratio was again measured as indicated by the comparison of the mean fluorescence intensity signal from the Fluo-4 loaded and control (unloaded) cells, a can be seen in Figure 6.
  • FIG. 7 An alternative embodiment of the light source 23 is now presented within Figure 7.
  • the light source 23 can be seen to comprise common elements with the previously described embodiment presented in Figure 1, therefore for clarity purposes the same reference numerals are employed throughout, as appropriate.
  • the light source 23 again comprises the Ti : Sapphire laser 2 , the Faraday isolator 3 , the first and second anti reflection coated lenses 4 and 6, the length of photonic crystal fibre 5 and the neutral density filter 8 the function of which are as previously described.
  • a different PCF 5 is employed within the light source 23 .
  • the PCF 5 has an overall length of 29cm.
  • the light source 23 differs from the previously described embodiments in that, the bandpass filter 7 is replaced with a 600 lines/mm grating 24 positioned after the neutral density filter 8. Rotation of the grating 24 thus provides a means for changing the angle of dispersion, and hence the wavelength, of the output of the light source 23.
  • the light source 23 can again be employed with the scan- head 11 and the inverted microscope 12 so as to produce a CLSM.
  • a variable aperture is employed between the light source 23 and the scan-head 11 so as to provide a means for regulating the FWHM of the visible continuum propagating into the scan-head 11.
  • the spectral output from the light source 23 in the absence of the grating 25 (at 64mW) and for two separate grating angles is presented in Figure 8.
  • the first grating angle was chosen so as to correspond to the absorption maximum of Alexa 488 (-490 nm) while the second to correspond to the absorption maximum of Alexa 594 (-564 nm) .
  • the laser source output provides spectral coverage of 493 ⁇ 7 nm 26 and 561 ⁇ 8 nm 27, respectively.
  • a 20 ⁇ m- thick fixed tissue sample of guinea pig detrusor (bladder smooth muscle layer) was therefore labelled firstly with anti-PGP 9.5 and Alexa 488 to highlight the nerve structure and secondly with anti-smooth muscle myosin and Alexa 594 to determine the morphology of the smooth muscle layer.
  • the grating and variable width apertures were orientated to deliver 859 ⁇ W and 782 ⁇ W to the sample alternatively, with spectral coverage again of 493 + 7 nm and 561 ⁇ 8 nm, respectively.
  • a 20x/0.75 numerical aperture air objective lens 15 was used to focus the radiation onto the labelled sample.
  • Figure 9 presents a typical CLSFM xy cross-sections of multiple-labelled guinea pig detrusor, obtained at a depth within the sample of approximately 13 ⁇ m, where 9(a) and 9(b) correspond to fluorescence from Alexa 488 and Alexa 594 respectively.
  • the images were taken at a capture rate of 0.95 Hz with a 512x512 pixels box size and were averaged over six consecutive scans, leading to a 2.7 ⁇ s pixel dwell time.
  • a merge of both 9(a) and 9(b) is shown in Figure 9(c) .
  • This composite image clearly indicates the nerve structure and position relative to the smooth muscle layer. Complete optical sectioning of the 20 ⁇ m thick sample was readily achieved.
  • FIG. 10 presents a schematic representation of a fluorescence lifetime imaging microscope 28 that comprises the laser source 1 employed in conjunction with a time correlated single photon counting (TCSPC) module 29 (Becker-Hickl SPC830) .
  • TCSPC time correlated single photon counting
  • the laser source 1 or 23 can easily be adapted so as to be suitable for carry out multiphoton microscopy techniques .
  • the Ti: Sapphire laser 2 wavelength and pulse duration is unaffected and hence is ideal for MPLSM.
  • the resultant white-light supercontinuum source can again capably perform CLSM or FLIM, as previously described.
  • the described apparatus is generally modular in nature. This allows various component elements to be easily interchanged, for example: • the coherent light source is described as a Ti: Sapphire laser however any ultrashort pulsed laser source be alternatively be employed. • the bandpass filter can be replaced with an alternative filtration means such as a prism or a grating combined with a narrow slit; • the grating can be replaced with an alternative optical dispersion means for changing the wavelength of the output of the light source 23 e.g.
  • an electro-optic modulator an acoustic-optic modulator, a spatial light modulator, a monochrometer, a prism, a fibre, a grism, adaptive optics or chromatic dispersion lenses; • an inverted microscope has been described above however it will be readily apparent to those skilled in the art that an upright microscope may equally well be employed; • the light source has been described in connection with a confocal laser scanning microscope and a fluorescence lifetime imaging microscope that are based on detecting the fluorescence of one or more flurophores located within a sample.
  • the same laser source could be used within a laser scanning microscope that is based on the detection light generated by the light source once it has been reflected from, or transmitted by, a particular sample; and • the microscope objective lenses were chosen because of their suitability for use with live cell imaging.
  • other alternative lens systems may be employed so as to achieve the same function.
  • the present invention demonstrates a flexible laser source for a scanning microscope based on laser platform that is also ideally suited to carry out multi-photon laser scanning microscopy.
  • a commercial ultra-short pulsed Ti : Sapphire laser has been employed as a pump source for a photonic crystal fibre so as to generate a visible continuum output spectrum.
  • the wavelength range required to efficiently match the profile of a particular fluorophore is then selected from the visible continuum by either using a conventional and inexpensive optical bandpass filter or an optical dispersion means such as a grating.
  • a significant advantage of the present invention is that it provides a reliable, cost effective, modular system that can be employed to access the whole range of fluorophores currently employed within the field of laser scanning microscopy.
  • the present invention has the added advantage that it employs a laser source that can also be used to perform multi-photon laser scanning microscopy thereby providing a complete laser scanning excitation solution. This has the advantages of reducing costs, maintenance requirements and complexity of the instrumentation while increasing the range of existing flurophores that can be excited.

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  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Microscoopes, Condenser (AREA)

Abstract

L'invention porte sur une source lumineuse (1, 23), idéale pour les microscopes à balayage (10, 28), comportant un laser source (2) couplé à une fibre de cristal photonique (5) de manière à créer un spectre continu partant de la fibre (5), dont on sélectionne une plage de longueurs d'onde à l'aide d'appareils tels qu'un filtre passe-bande (7) ou une grille (24). L'adaptation de la plage de longueurs d'onde aux longueurs des pics d'absorption d'un fluophore particulier rend cette source lumineuse idéale pour les microscopes à balayage, par exemple des types: à laser confocal (10), à laser multiphotonique, ou à imagerie à durée de vie de fluorescence (28).
PCT/GB2005/002077 2004-06-03 2005-05-25 Source lumineuse amelioree pour microscope a balayage WO2005119328A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB0412470.7 2004-06-03
GB0412470A GB0412470D0 (en) 2004-06-03 2004-06-03 Improved confocal laser scanning fluorescence microscope source
GB0416441A GB0416441D0 (en) 2004-07-23 2004-07-23 Improved confocal laser scanning microscope source
GB0416441.4 2004-07-23
GB0501218A GB0501218D0 (en) 2005-01-21 2005-01-21 Improved scanning microscope source
GB0501218.2 2005-01-21

Publications (1)

Publication Number Publication Date
WO2005119328A1 true WO2005119328A1 (fr) 2005-12-15

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PCT/GB2005/002077 WO2005119328A1 (fr) 2004-06-03 2005-05-25 Source lumineuse amelioree pour microscope a balayage

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WO (1) WO2005119328A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102007002203A1 (de) 2007-01-16 2008-07-17 Carl Zeiss Microimaging Gmbh Beleuchtungsvorrichtung und Beleuchtungsverfahren
CN100437323C (zh) * 2007-06-06 2008-11-26 天津大学 双包层大模场面积掺镱光子晶体光纤飞秒激光器
EP2081074A1 (fr) * 2008-01-19 2009-07-22 Fianium Limited Sources d'impulsion optique
US20110292377A1 (en) * 2009-02-02 2011-12-01 Draka Cable Wuppertal Gmbh Fiber optic measuring apparatus
WO2018116302A1 (fr) * 2016-12-22 2018-06-28 Z Square Ltd. Sources d'éclairement d'endoscopes à fibres multicœurs
US10398294B2 (en) 2014-07-24 2019-09-03 Z Square Ltd. Illumination sources for multicore fiber endoscopes
US11038316B2 (en) 2006-01-20 2021-06-15 Nkt Photonics A/S Optical pulse source apparatus with nonlinear fibre and operable to reduce the optical pulse frequency of optical output pulses

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6097870A (en) * 1999-05-17 2000-08-01 Lucent Technologies Inc. Article utilizing optical waveguides with anomalous dispersion at vis-nir wavelenghts
US20020028044A1 (en) * 2000-06-17 2002-03-07 Holger Birk Method and instrument for microscopy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6097870A (en) * 1999-05-17 2000-08-01 Lucent Technologies Inc. Article utilizing optical waveguides with anomalous dispersion at vis-nir wavelenghts
US20020028044A1 (en) * 2000-06-17 2002-03-07 Holger Birk Method and instrument for microscopy

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11038316B2 (en) 2006-01-20 2021-06-15 Nkt Photonics A/S Optical pulse source apparatus with nonlinear fibre and operable to reduce the optical pulse frequency of optical output pulses
WO2008086996A1 (fr) * 2007-01-16 2008-07-24 Carl Zeiss Microimaging Gmbh Dispositif d'éclairage à éléments optiques non linéaires pour produire une lumière laser dans un large domaine spectral avec une densité de puissance spectrale homogène
DE102007002203A1 (de) 2007-01-16 2008-07-17 Carl Zeiss Microimaging Gmbh Beleuchtungsvorrichtung und Beleuchtungsverfahren
CN100437323C (zh) * 2007-06-06 2008-11-26 天津大学 双包层大模场面积掺镱光子晶体光纤飞秒激光器
US10074957B2 (en) 2008-01-19 2018-09-11 Nkt Photonics A/S Variable repetition rate supercontinuum pulses
EP2081074A1 (fr) * 2008-01-19 2009-07-22 Fianium Limited Sources d'impulsion optique
US8848750B2 (en) 2008-01-19 2014-09-30 Fianium Ltd. Optical pulse sources
EP2913701A1 (fr) * 2008-01-19 2015-09-02 Fianium Limited Sources supercontinuum d'impulsion optique
US9531153B2 (en) 2008-01-19 2016-12-27 Fianium Ltd. Apparatus and method for the generation of supercontinuum pulses
US9564731B2 (en) 2008-01-19 2017-02-07 Fianium Ltd. Method for illuminating a sample with supercontinuum pulses
US9570878B2 (en) 2008-01-19 2017-02-14 Fianium Ltd. Method and apparatus for providing supercontinuum pulses
US9774163B2 (en) 2008-01-19 2017-09-26 Nkt Photonics A/S Variable repetition rate and wavelength optical pulse source
US20110292377A1 (en) * 2009-02-02 2011-12-01 Draka Cable Wuppertal Gmbh Fiber optic measuring apparatus
US9354086B2 (en) * 2009-02-02 2016-05-31 Draka Cable Wuppertal Gmbh Fiber optic measuring apparatus
US10398294B2 (en) 2014-07-24 2019-09-03 Z Square Ltd. Illumination sources for multicore fiber endoscopes
WO2018116302A1 (fr) * 2016-12-22 2018-06-28 Z Square Ltd. Sources d'éclairement d'endoscopes à fibres multicœurs

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