Research

The research group led by Robert Huber conducts research in the fields of optical coherence tomography (OCT), non-linear imaging and laser physics. Here, work is mainly done on novel pico second lasers and on Fourier domain mode-locked (FDML) lasers. This laser concept was developed by Robert Huber and enables the realization of particularly fast tunable laser light sources. The research focus here is on further technological development, understanding of the physical processes and also on the implementation of FDML lasers for OCT applications. Besides OCT, FDML lasers are also used for nonlinear imaging and spectroscopy.

Another focus is on optical coherence tomography with tunable light sources (swept source OCT, SS-OCT). Here, among other applications, the in-house developed FDML lasers are used for ultrafast imaging to generate cross-sectional images of biological tissues such as skin or eye. Due to the high tuning rate, applications like VR-OCT, which displays entire volumes in a virtual environment with real-time video repetition rates, are possible.

With non-linear optical imaging, the group is pursuing further imaging techniques. Research areas are in time-encoded (TICO) Raman spectroscopy and microscopy, two-photon fluorescence microscopy (TPEF), and two-photon single-pulse fluorescence lifetime imaging (SP-FLIM). These techniques use novel pico second lasers that are also being researched and developed in the group.

Our main research topics:

Publications

2021

Matthias Strauch, Jan Philip Kolb, Christian Rose, Nadine Merg, Jennifer Hundt, Christiane Kümpers, Sven Perner, Sebastian Karpf, and Robert Huber,
Quick sectioning-free H&E imaging of bulk tissue using multiphoton microscopy, in 33rd Congress of the ESP , 2021.
DOI:10.1007/s00428-021-03157-8
Bibtex: BibTeX
@Conference{Strauch2021,
  author    = {M. Strauch, J.P. Kolb, C. Rose, N. Merg, J. Hundt, C. Kümpers, S. Perner, S. Karpf and R. Huber},
  booktitle = {33rd Congress of the ESP},
  title     = {Quick sectioning-free H&E imaging of bulk tissue using multiphoton microscopy},
  year      = {2021},
  keywords  = {AG-Huber_NL},
}
Matthias Strauch, Jan Philip Kolb, Christian Rose, Nadine Merg, Christiane Kümpers, Sven Perner, Jennifer Hundt, Sebastian Karpf, and Robert Huber,
Comparison of Sectioning-free Multiphoton Histology to H&E FFPE imaging, in Virtuelle Pathologietage , 2021.
Bibtex: BibTeX
@Conference{Strauch2021b,
  author    = {M. Strauch, J.P. Kolb, C. Rose, N. Merg, J. Hundt, C. Kümpers, S. Perner, S. Karpf and R. Hubert},
  booktitle = {Virtuelle Pathologietage},
  title     = {Comparison of Sectioning-free Multiphoton Histology to H&E FFPE imaging},
  year      = {2021},
  keywords  = {AG-Huber_NL},
}
Michael Münter, Mario Pieper, Tabea Kohlfaerber, Ernst Bodenstorfer, Martin Ahrens, Christian Winter, Robert Huber, Peter König, Gereon Hüttmann, and Hinnerk Schulz-Hildebrandt,
Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast, Biomed. Opt. Express , vol. 12, pp. 6024-6039, 2021.
DOI:10.1364/BOE.425001
Bibtex: BibTeX
@article{Münter2021,
   author = {M. Münter, M. Pieper, T. Kohlfaerber, E. Bodenstorfer, M. Ahrens, C. Winter, R. Huber, P. König, G. Hüttmann and H. Schulz-Hildebrandt},
   title = {Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast},
   journal = {BiomedOptE},
   volume = {12(10)},
   Keywords = {CMOS cameras,Full field optical coherence tomography,High numerical aperture optics, Image processing,In vivo imaging,Medical imaging,Ag-Huber},
   pages = {6024-6039},
   DOI = {10.1364/BOE.425001},
  
   year = {2021},
   type = {Journal Article}
}

2020

Mark Schmidt, Christin Grill, Robert Huber, and Christian Jirauschek,
Coherence of Fourier Domain Mode-Locked (FDML) Lasers in the Ultra-Stable Regime, in 2020 International Conference Laser Optics (ICLO) , Nov.2020. pp. 1-1.
DOI:10.1109/ICLO48556.2020.9285488
Bibtex: BibTeX
@INPROCEEDINGS{Schmidt2020ICLO,
  author={M. {Schmidt}, C. {Grill}, R. {Huber} and C. {Jirauschek}},
  booktitle={2020 International Conference Laser Optics (ICLO)}, 
  title={Coherence of Fourier Domain Mode-Locked (FDML) Lasers in the Ultra-Stable Regime}, 
  year={2020},
keywords={AG-Huber_FDML},
  volume={},
  number={},
  pages={1-1},
  doi={10.1109/ICLO48556.2020.9285488},
}
Tom Pfeiffer, Madita Göb, Wolfgang Draxinger, Sebastian Karpf, Jan Philip Kolb, and Robert Huber,
Flexible A-scan rate MHz-OCT: efficient computational downscaling by coherent averaging, Biomed. Opt. Express , vol. 11, no. 11, pp. 6799--6811, Nov. 2020. OSA.
DOI:10.1364/BOE.402477
Bibtex: BibTeX
@article{Pfeiffer:20,
author = {T. Pfeiffer, M. G\"{o}b, W. Draxinger, S. Karpf, J.P. Kolb and R. Huber},
journal = {Biomed. Opt. Express},
keywords = {AG-Huber_OCT; High speed imaging; Image quality; Optical coherence tomography; Swept lasers; Swept sources; Systems design},
number = {11},
pages = {6799--6811},
publisher = {OSA},
title = {Flexible A-scan rate MHz-OCT: efficient computational downscaling by coherent averaging},
volume = {11},
month = {Nov},
year = {2020},
doi = {10.1364/BOE.402477},
abstract = {In order to realize adjustable A-scan rates of fast optical coherence tomography (OCT) systems, we investigate averaging of OCT image data acquired with a MHz-OCT system based on a Fourier Domain Mode Locked (FDML) laser. Increased system sensitivity and image quality can be achieved with the same system at the cost of lower imaging speed. Effectively, the A-scan rate can be reduced in software by a freely selectable factor. We demonstrate a detailed technical layout of the strategies necessary to achieve efficient coherent averaging. Since there are many new challenges specific to coherent averaging in swept source MHz-OCT, we analyze them point by point and describe the appropriate solutions. We prove that coherent averaging is possible at MHz OCT-speed without special interferometer designs or digital phase stabilization. We find, that in our system up to \&\#x223C;100x coherent averaging is possible while achieving a sensitivity increase close to the ideal values. This corresponds to a speed reduction from 3.3 MHz to 33 kHz and a sensitivity gain of 20 dB. We show an imaging comparison between coherent and magnitude averaging of a human finger knuckle joint in vivo with 121\&\#x00A0;dB sensitivity for the coherent case. Further, the benefits of computational downscaling in low sensitivity MHz-OCT systems are analyzed.},
}
Matthias Strauch, Jan Philip Kolb, Daniel Weng, Melanie Wacker, Wolfgang Draxinger, Nadine Merg, Jennifer Hundt, Sebastian Karpf, and Robert Huber,
Two-photon microscopy for sectioning-free virtual H&E imaging, in 104. Jahrestagung der Deutschen Gesellschaft fuer Pathologie , 062020.
Weblink: https://www.pathologie-dgp.de/media/Dgp/user_upload/Verhandlungsband_2020_final__kompr._.pdf
Bibtex: BibTeX
@InProceedings{Strauch2020,
  author    = {M. Strauch, J.P. Kolb, D. Weng, M. Wacker, W. Draxinger, N. Merg, J. Hundt, S. Karpf and R. Huber},
  booktitle = {104. Jahrestagung der Deutschen Gesellschaft fuer Pathologie},
  title     = {Two-photon microscopy for sectioning-free virtual {H&E} imaging},
URL = {https://www.pathologie-dgp.de/media/Dgp/user_upload/Verhandlungsband_2020_final__kompr._.pdf},
  year      = {2020},
  keywords  = {AG-Huber_NL},
}
Mark Schmidt, Tom Pfeiffer, Christin Grill, Robert Huber, and Christian Jirauschek,
Self-stabilization mechanism in ultra-stable Fourier domain mode-locked (FDML) lasers, OSA Continuum , vol. 3, no. 6, pp. 1589--1607, 06 2020. Optical Society of America.
DOI:10.1364/OSAC.389972
Bibtex: BibTeX
@article{schmidt2020self,
  title={Self-stabilization mechanism in ultra-stable Fourier domain mode-locked (FDML) lasers},
  author={M. {Schmidt}, T. {Pfeiffer}, C. {Grill}, R. {Huber} and C. {Jirauschek}},
  journal={OSA Continuum},
  volume={3},
  number={6},
  pages={1589--1607},
  year={2020},
keywords={AG-Huber_FDML},
url={https://doi.org/10.1364/OSAC.389972}, 
  publisher=  {Optical Society of America}
}
Matthias Strauch,
Tunable Optics: Spectral Imaging and Surface Manipulation on Liquid Lenses, Delft University of Technology, Delft, 03 2020.
DOI:10.4233/uuid:b61aa64e-cba4-44c0-8d16-93440e028611
Bibtex: BibTeX
@PhdThesis{Strauch2020,
  author      = {M. Strauch},
  title       = {Tunable Optics: Spectral Imaging and Surface Manipulation on Liquid Lenses},
  institution = {Delft University of Technology},
  year        = {2020},
  date        = {2020-03-30},
  type        = {phdthesis},
  subtitle    = {Spectral Imaging and Surface Manipulation on Liquid Lenses},
  language    = {English},
  isbn        = {978-94-028-1994-6},
  pagetotal   = {151},
  doi         = {10.4233/uuid:b61aa64e-cba4-44c0-8d16-93440e028611},
  
  abstract    = {This thesis focusses on two aspects of tunable optics: Fabry-P{\'e}rot interferometers with a variable distance between their mirrors and electrowetting liquid lenses. The need for a device to detect child abuse has motivated us to design and build a camera that can detect the chemical composition of the upper skin layers of a bruise using a self-made Fabry-P{\'e}rot interferometer. The research described in the first part of this thesis has shown that wide-angle spectral imaging can be achieved with compact and cost-effective cameras using Fabry-P{\'e}rot interferometers. Designs with a full field of 90° in which the Fabry-P{\'e}rot interferometer is mounted either in front of an imaging system or behind a telecentric lens system are presented and analysed. The dependency of the spectral resolution on the numerical aperture of the lens system is derived and its value as a design criterion is shown. It is shown that the telecentric camera design is preferable over the collimated design for bruise imaging with a Fabry-P{\'e}rot interferometer.The idea to use a liquid lens for spectral imaging has directed the research towards a new concept of controlling surface waves on the surface of a liquid lens. We investigate and model surface waves because they decrease the imaging quality during fast focal switching. We propose a model that describes the surface modes appearing on a liquid lens and that predicts the resonance frequencies. The effects of those surface modes on a laser beam are simulated using geometrical optics and Fresnel propagation, and the model is verified experimentally. The model of the surface oscillations is used to develop a technique to create aspheric surface shapes on commercially available electrowetting liquid lenses. The surface waves on the liquid lens are described by Bessel functions of which a linear combination can be used to create any circularly symmetrical aspheric lens shape at an instant of time. With these surface profiles, one can realise a large set of circularly symmetrical wavefronts and hence intensity distributions of beams transmitted by the lens. The necessary liquid lens actuation to achieve a desired shape is calculated via a Hankel transform and confirmed experimentally. The voltage signal can be repeated at video rate. Measurements taken with a Mach-Zehnder interferometer confirm the model of the surface waves. The capabilities and limitations of the proposed method are demonstrated using the examples of a Bessel surface, spherical aberration, an axicon, and a top hat structure.},
keywords = {AG-Huber},
  address     = {Delft},
  publisher   = {Delft University of Technology},
  school      = {Delft University of Technology},
}
Paul Strenge, Birgit Lange, Christin Grill, Wolfgang Draxinger, Matteo M. Bonsanto, Christian Hagel, Robert Huber, and Ralf Brinkmann,
Segmented OCT data set for depth resolved brain tumor detection validated by histological analysis, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIV , SPIE, 022020. pp. 82 -- 89.
DOI:10.1117/12.2545659
Bibtex: BibTeX
@inproceedings{Strenge2020,
author = {P. Strenge and B. Lange and C. Grill and W. Draxinger and M. M. Bonsanto and C. Hagel and R. Huber and R. Brinkmann},
title = {{Segmented OCT data set for depth resolved brain tumor detection validated by histological analysis}},
volume = {11228},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIV},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {82 -- 89},
keywords = {AG-Huber_OCT, Optical coherence tomography, OCT, FDML Laser, MHz-OCT, brain tumor, brain imaging, neurosurgery},
year = {2020},

URL = {  https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11228/112282O/Segmented-OCT-data-set-for-depth-resolved-brain-tumor-detection/10.1117/12.2545659.short}
}
Christin Grill, Simon Lotz, Torben Blömker, Dominic Kastner, Tom Pfeiffer, Mark Schmidt, Wolfgang Draxinger, Christian Jirauschek, and Robert Huber,
Beating of two FDML lasers in real time, in Fiber Lasers XVII: Technology and Systems , Liang Dong, Eds. SPIE, 022020. pp. 132 -- 138.
DOI:10.1117/12.2545794
Bibtex: BibTeX
@inproceedings{Grill2020,
author = {C. {Grill}, S. {Lotz}, T. {Blömker}, D. {Kastner}, T. {Pfeiffer}, S. {Karpf}, M. {Schmidt}, W. {Draxinger}, C. 
 {Jirauschek} and R. {Huber}},
title = {{Beating of two FDML lasers in real time}},
volume = {11260},
booktitle = {Fiber Lasers XVII: Technology and Systems},
editor = {Liang Dong},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {132 -- 138},
keywords = {AG-Huber_FDML, FDML laser, fiber lasers, beat signal, OCT, Optical Coherence Tomography, Fourier domain mode locking},
year = {2020},
doi = {10.1117/12.2545794},

}
Leonardo Cecchetti, Tianshi Wang, Ayla Hoogendoorn, Karen T. Witberg, Jurgen M. R. Lighthart, Joost Daemen, Heleen van Beusekom, Tom Pfeiffer, Robert Huber, Jolanda Wentzel, Antonius F. W. van der Steen, and Gijs van Soest,
In-vitro and in-vivo imaging of coronary artery stents with Heartbeat OCT, The International Journal of Cardiovascular Imaging , vol. 36, no. 6, pp. 1021-1029, 02 2020. Springer Science and Business Media LLC.
DOI:10.1007/s10554-020-01796-7
Bibtex: BibTeX
@article{Cecchetti2020,
  doi = {10.1007/s10554-020-01796-7},
  url = {https://doi.org/10.1007/s10554-020-01796-7},
  year = {2020},
  month = feb,
  publisher = {Springer Science and Business Media {LLC}},
  volume = {36},
  number = {6},
  pages = {1021--1029},
  author = {Leonardo Cecchetti and Tianshi Wang and Ayla Hoogendoorn and Karen T. Witberg and Jurgen M. R. Ligthart and Joost Daemen and Heleen M. M. van Beusekom and Tom Pfeiffer and Robert A. Huber and Jolanda J. Wentzel and Antonius F. W. van der Steen and Gijs van Soest},
  title = {In-vitro and in-vivo imaging of coronary artery stents with Heartbeat {OCT}},
  journal = {The International Journal of Cardiovascular Imaging}
}
Matthias Strauch, Jan Philip Kolb, Nadine Merg, Jennifer Hundt, Sebastian Karpf, and Robert Huber,
Evaluation of two-photon fluorescence microscopy for sectioning-free H&E imaging of different tissues, in 32nd Congress of the ESP and XXXIII International Congress of the IAP , 2020.
DOI:10.1007/s00428-020-02938-x
Bibtex: BibTeX
@InProceedings{Strauch2020a,
  author    = {M. Strauch, J.P. Kolb, N. Merg, J. Hundt, S. Karpf and R. Huber},
  booktitle = {32nd Congress of the ESP and XXXIII International Congress of the IAP},
  title     = {Evaluation of two-photon fluorescence microscopy for sectioning-free {H&E} imaging of different tissues},
  year      = {2020},
  keywords  = {AG-Huber_NL},
}

2019

Antonio López-Marín, Geert Springeling, Robert Beurskens, Heleen van Beusekom, Antonius F. W. van der Steen, Arjun D. Koch, Brett E. Bouma, Robert Huber, Gijs van Soest, and Tianshi Wang,
Motorized capsule for shadow-free OCT imaging and synchronous beam control, Opt Lett , vol. 44, no. 15, pp. 3641-3644, 08 2019. Optica Publishing Group.
DOI:10.1364/OL.44.003641
Bibtex: BibTeX
@article{Lopez-Marin:19,
author = {Antonio L\'{o}pez-Mar\'{i}n and Geert Springeling and Robert Beurskens and Heleen van Beusekom and Antonius F. W. van der Steen and Arjun D. Koch and Brett E. Bouma and Robert Huber and Gijs van Soest and Tianshi Wang},
journal = {Opt. Lett.},
keywords = {Image reconstruction; Light beams; Magnetic fields; Optical coherence tomography; Optical imaging; Reflector design},
number = {15},
pages = {3641--3644},
publisher = {Optica Publishing Group},
title = {Motorized capsule for shadow-free OCT imaging and synchronous beam control},
volume = {44},
month = {Aug},
year = {2019},
url = {https://opg.optica.org/ol/abstract.cfm?URI=ol-44-15-3641},
doi = {10.1364/OL.44.003641},
abstract = {We demonstrate a tethered motorized capsule for unobstructed optical coherence tomography (OCT) imaging of the esophagus. By using a distal reflector design, we avoided the common shadow artifact induced by the motor wires. A synchronous driving technique features three types of beam-scanning modes of the capsule, i.e., circumferential beam scanning, localized beam scanning, and accurate beam positioning. We characterized these three modes and carried out ex vivo imaging experiments using the capsule. The results show that the capsule can potentially be a useful tool for diagnostic OCT imaging and OCT-guided biopsy and therapy of the esophagus.},
}
Yoko Miura, Wolfgang Draxinger, Christin Grill, Tom Pfeiffer, Salvatore Grisanti, and Robert Huber,
MHz-OCT for low latency virtual reality guided surgery: first wet lab experiments on ex-vivo porcine eye, in Optical Coherence Imaging Techniques and Imaging in Scattering Media III , Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh, Eds. SPIE, 072019. pp. 110780E.
DOI:10.1117/12.2527123
Bibtex: BibTeX
@inproceedings{10.1117/12.2527123,
author = {Yoko Miura and Wolfgang Draxinger and Christin Grill and Tom Pfeiffer and Salvatore Grisanti and Robert Huber},
title = {{MHz-OCT for low latency virtual reality guided surgery: first wet lab experiments on ex-vivo porcine eye
}},
volume = {11078},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media III},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {110780E},
abstract = {MHz-OCT systems based on FDML swept laser sources combined with the massive parallel processing capabilities of modern computer hardware enable volumetric imaging, processing and stereoscopic display at video rates. The increasing image quality and speed might enable new fields of application where the volumetric OCT completely replaces stereoscopic microscopes instead of being a mere supplement. Aside from the depth resolving capability, a particular advantage is the ability to display a whole image volume from arbitrary points of view without the need to move the actual microscope or to rotate the patient’s eye. Purely digital microscopy is already offered as alternative to traditional through-an-eyepiece surgical microscope. We explore the use of virtual reality to present digital OCT microscopy images to a trained surgeon, carrying out a series of surgical procedures ex-vivo on a porcine eye model.},
keywords = {virtual reality, surgery guidance , real-time OCT, user experience},
year = {2019},
doi = {10.1117/12.2527123},
URL = {https://doi.org/10.1117/12.2527123}
}
Madita Göb, Tom Pfeiffer, and Robert Huber,
Towards combined optical coherence tomography and multi-spectral imaging with MHz a-scan rates for endoscopy, in Optical Coherence Imaging Techniques and Imaging in Scattering Media III , aciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh, Eds. 072019. pp. 110780Y.
DOI:10.1117/12.2526796
Bibtex: BibTeX
@inproceedings{10.1117/12.2526796,
author = {Madita G{\"o}b and Tom Pfeiffer and Robert Huber},
title = {{Towards combined optical coherence tomography and multi-spectral imaging with MHz a-scan rates for endoscopy}},
volume = {11078},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media III},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {110780Y},
abstract = {We demonstrate a preliminary setup of a combined MHz-OCT and RGB narrowband reflection microscope and investigate the performance of the new RGB branch and different display modes of colored OCT data sets.},
keywords = {MHz OCT, multi-spectral imaging, Optical Coherence Tomography, Fourier Domain Mode Locked , FDML, RGB, Color },
year = {2019},
doi = {10.1117/12.2526796},
URL = {https://doi.org/10.1117/12.2526796}
}
Julian Klee, Jan Philip Kolb, Christin Grill, Wolfgang Draxinger, Tom Pfeiffer, and Robert Huber,
Zero roll-off retinal MHz-OCT using an FDML-laser, in Optical Coherence Imaging Techniques and Imaging in Scattering Media III , SPIE, 072019. pp. 110780S.
DOI:10.1117/12.2527034
File: 12.2527034.short
Bibtex: BibTeX
@inproceedings{10.1117/12.2527034,
author = {Julian Klee and Jan Philip Kolb and Christin Grill and Wolfgang Draxinger and Tom Pfeiffer and Robert Huber},
title = {{Zero roll-off retinal MHz-OCT using an FDML-laser}},
volume = {11078},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media III},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {110780S},
abstract = {Optical coherence tomography (OCT) applications like ultra-widefield and full eye-length imaging are of high interest for various diagnostic purposes. In swept-source OCT these techniques require a swept light source, which is coherent over the whole imaging depth. We present a zero roll-off 1060 nm Fourier Domain Mode Locked-Laser (FDML-Laser) for retinal OCT imaging at 1.7 MHz A-scan rate and first long-range imaging results with it. Several steps such as improved dispersion compensation and frequency regulation were performed and will be discussed. Besides virtually no loss in OCT signal over the maximum depth range of 4.6 mm and very good dynamic range was observed. Roll-off measurements show no decrease of the point-spread function (PSF), while maintaining a high dynamic range.},
keywords = {optical coherence tomography, OCT, tunable laser, Fourier Domain Mode Locking, FDML, MHz OCT},
year = {2019},
doi = {10.1117/12.2527034},
URL = {https://doi.org/10.1117/12.2527034}
}
Daniel Weng, Hubertus Hakert, Torben Blömker, Jan Philip Kolb, Matthias Strauch, Matthias Eibl, Philipp Lamminger, Sebastian Karpf, and Robert Huber,
Sub-Nanosecond Pulsed Fiber Laser for 532nm Two-Photon Excitation Fluorescence (TPEF) Microscopy of UV Transitions, in 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , IEEE, 062019. pp. 1-1.
DOI:10.1109/CLEOE-EQEC.2019.8872571
Bibtex: BibTeX
@INPROCEEDINGS{8872571,
  author={Weng, Daniel and Hakert, Hubertus and Blömker, Torben and Kolb, Jan Philip and Strauch, Matthias and Eibl, Matthias and Lamminger, Philipp and Karpf, Sebastian and Huber, Robert},
  booktitle={2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)}, 
  title={Sub-Nanosecond Pulsed Fiber Laser for 532nm Two-Photon Excitation Fluorescence (TPEF) Microscopy of UV Transitions}, 
  year={2019},
  volume={},
  number={},
  pages={1-1},
  abstract={Summary form only given. Two-photon microscopy is a powerful technique for in vivo imaging, due to its high penetration depth and axial sectioning. Usually excitation wavelengths in the near infrared are used. However, most fluorescence techniques for live cell imaging require labeling with exogenous fluorophores. It has been shown that shorter wavelengths can be used to excite the autofluorescence of endogenous proteins, e.g. tryptophan. Recently we demonstrated a fully fiber-based laser source built around a directly modulated, ytterbium amplified 1064 nm laser diode with sub-nanosecond pulses for two-photon imaging [2]. The overall system enables to capture high-speed fluorescence lifetime imaging (FLIM) with single pulse excitation. Here, we extend the spectral range of this laser source by frequency doubling it to 532nm to achieve two-photon excited fluorescence microscopy (TPM) in the ultraviolett (UV) range to harness endogenous autofluorescence. In this presentation we explore first TPM results of tryptophan to investigate signal levels and fi delity before transitioning to biological tissues. It has been shown that TPM of endogenous tryptophan can be used to visualize immune system activity in vivo. Our laser source could be a cheap, flexible and fiber-based alternative to the OPO-based Ti:Sa Lasers currently employed. The basic concept of our design is to shift the wavelength of the pulsed fiber-based master oscillator power amplifier (MOPA) by second-harmonic generation (SHG) using phase-matching in a KTP crystal. This generates a coherent output at 532nm at a maximal peak power of 500W. We achieved a maximum conversion efficiency of about 17%. After the SHG module, the 532nm light is coupled into a single-mode fiber and delivered to a home built microscope. A 40x microscope objective is used to excite the sample and epi-collect the fluorescence. The fluorescence is recorded on a UV-enhanced photomultiplier tube (PMT). For a proof of concept measurement, crystalized tryptophan was imaged. Here we show signals of pure tryptophan, with laser parameters of 1MHz repetition rate and 100ps pulse duration. We used spectral bandpass fi lters in order to detect only fluorescence signal, however, from crystalized tryptophan we observed an unexpected short lifetime. We have recently shown that we can shift our laser output from 1064nm to longer wavelengths. By shifting to 1180nm and frequency doubling to 590nm a more efficient fluorescence excitation of tryptophan can be achieved. In the future we aim at in vivo imaging with our setup.},
  keywords={},
  doi={10.1109/CLEOE-EQEC.2019.8872571},
  ISSN={},
  month={June}}
Jan Philip Kolb, Wolfgang Draxinger, Julian Klee, Tom Pfeiffer, Matthias Eibl, Thomas Klein, Wolfgang Wieser, and Robert Huber,
Live video rate volumetric OCT imaging of the retina with multi-MHz A-scan rates, PLOS ONE , vol. 14, no. 7, pp. e0213144, 03 2019.
DOI:10.1371/journal.pone.0213144
Bibtex: BibTeX
@article{Kolb2019,
   author = {Kolb, J P;Draxinger, W;Klee, J;Pfeiffer, T;Eibl, M;Klein, T;Wieser, W and Huber, R},
   title = {Live video rate volumetric OCT imaging of the retina with multi-MHz A-scan rates},
   journal = {J pone},
 keywords = {AG-Huber_OCT},
   url = {https://doi.org/10.1371/journal.pone.0213144},
   pages = {e0213144},
   ISSN = {1932-6203},
   
   year = {2019},
   type = {Journal Article}
}
Jan Philip Kolb, Daniel Weng, Hubertus Hakert, Matthias Eibl, Wolfgang Draxinger, Tobias Meyer-Zedler, Thomas Gottschall, Ralf Brinkmann, Reginald Birngruber, Jürgen Popp, Jens Limpert, Sebastian Karpf, and Robert Huber,
Virtual HE histology by fiber-based picosecond two-photon microscopy, in Multiphoton Microscopy in the Biomedical Sciences XIX , Ammasi Periasamy; Peter T. C. So; Karsten König, Eds. International Society for Optics and Photonics, 022019. pp. 108822F.
DOI:10.1117/12.2507866
Bibtex: BibTeX
@inproceedings{10.1117/12.2507866,
author = {Jan Philip Kolb and Daniel Weng and Hubertus Hakert and Matthias Eibl and Wolfgang Draxinger and Tobias Meyer and Thomas Gottschall and Ralf  Brinkmann and Reginald Birngruber and J{\"u}rgen Popp and Jens Limpert and Sebastian Nino Karpf and Robert Huber},
title = {{Virtual HE histology by fiber-based picosecond two-photon microscopy}},
volume = {10882},
booktitle = {Multiphoton Microscopy in the Biomedical Sciences XIX},
editor = {Ammasi Periasamy and Peter T. C. So and Karsten K{\"o}nig},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {108822F},
abstract = {Two-Photon Microscopy (TPM) can provide three-dimensional morphological and functional contrast in vivo. Through proper staining, TPM can be utilized to create virtual, HE equivalent images and thus can improve throughput in histology-based applications. We previously reported on a new light source for TPM that employs a compact and robust fiber-amplified, directly modulated laser. This laser is pulse-to-pulse wavelength switchable between 1064 nm, 1122 nm, and 1186 nm with an adjustable pulse duration from 50ps to 5ns and arbitrary repetition rates up to 1MHz at kW-peak powers. Despite the longer pulse duration, it can achieve similar average signal levels compared to fs-setups by lowering the repetition rate to achieve similar cw and peak power levels. The longer pulses lead to a larger number of photons per pulse, which yields single shot fluorescence lifetime measurements (FLIM) by applying a fast 4 GSamples/s digitizer. In the previous setup, the wavelengths were limited to 1064 nm and longer. Here, we use four wave mixing in a non-linear photonic crystal fiber to expand the wavelength range down to 940 nm. This wavelength is highly suitable for imaging green fluorescent proteins in neurosciences and stains such as acridine orange (AO), eosin yellow (EY) and sulforhodamine 101 (SR101) used for histology applications. In a more compact setup, we also show virtual HE histological imaging using a direct 1030 nm fiber MOPA.},
keywords = {Multiphoton Microscopy, Four Wave Mixing, FWM, Histology, Laser, Non Linear Microscopy, Two Photon Microscopy, JenLab Young Investigator Award},
year = {2019},
doi = {10.1117/12.2507866},
URL = {https://doi.org/10.1117/12.2507866}
}
Mark Schmidt, Tom Pfeiffer, Christin Grill, Robert Huber, and Christian Jirauschek,
Coexistence of Intensity Pattern Types in Broadband Fourier Domain Mode Locked (FDML) Lasers, in 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 2019. pp. 1--1.
DOI:10.1109/CLEOE-EQEC.2019.8872381
Bibtex: BibTeX
@inproceedings{schmidt2019coexistence,
  title={Coexistence of Intensity Pattern Types in Broadband Fourier Domain Mode Locked (FDML) Lasers},
  author={Schmidt, M; Pfeiffer, T; Grill, C; Huber, R and Jirauschek, C},
  booktitle={2019 Conference on Lasers and Electro-Optics Europe \& European Quantum Electronics Conference (CLEO/Europe-EQEC)},
  pages={1--1},
  year={2019},
  organization={IEEE},
keywords= { AG-Huber_FDML},
url={  https://ieeexplore.ieee.org/document/8872381}

}
Dominic Kastner, Torben Blömker, Tom Pfeiffer, Christin Grill, Mark Schmidt, Christian Jirauschek, and Robert Huber,
Measurement of Inter-Sweep Phase Stability of an FDML Laser with a 10 kHz Tunable Ring Laser, in 2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference , Optical Society of America, 2019. pp. 1-1.
DOI:10.1109/CLEOE-EQEC.2019.8872860
Bibtex: BibTeX
@inproceedings{Kastner:19,
author = {Kastner, D; Bl\"{o}mker, T; Pfeiffer, T; Grill, C; Schmidt, M; Jirauschek, C and Huber, R},
booktitle = {2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference},
journal = {2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference},
keywords = {Fourier domain mode locking; Image quality; Optical coherence tomography; Phase noise; Ring lasers; Tunable lasers},
pages = {cj_7_5},
publisher = {Optical Society of America},
title = {Measurement of Inter-Sweep Phase Stability of an FDML Laser with a 10 kHz Tunable Ring Laser},
year = {2019},
keywords = {AG-Huber_FDML, AG-Huber_OCT},
doi = { 10.1109/CLEOE-EQEC.2019.8872860},
abstract = {Fourier Domain Mode Locking (FDML) lasers are light sources that generate a sequence of narrowband optical frequency sweeps at the fundamental or harmonic of the cavity repetition rate \[1\]. This frequency swept output can also be considered as a sequence of strongly chirped, long pulses. FDML lasers are mainly used in swept source optical coherence tomography (SS-OCT), a medical imaging technique. The coherence length of the source, i.e. the intra-sweep phase stability of an FDML sweep, is decisive for the image quality and performance of OCT imaging \[2\].},
}
Matthias Strauch, Jan Philip Kolb, Daniel Weng, Melanie Wacker, Wolfgang Draxinger, Sebastian Karpf, and Robert Huber,
Sectioning-Free Virtual H&E Imaging of Tissue Samples with Two-Photon Microscopy, in 31st Congress of the ESP , 2019.
DOI:10.1007/s00428-019-02631-8
Bibtex: BibTeX
@InProceedings{Strauch2019,
  author    = {Strauch, Matthias and Kolb, Jan Philip and Weng, Daniel and Wacker, Melanie and Draxinger, Wolfgang and Karpf, Sebastian and Huber, Robert},
  booktitle = {31st Congress of the ESP},
  title     = {Sectioning-Free Virtual H&E Imaging of Tissue Samples with Two-Photon Microscopy},
  year      = {2019},
  keywords  = {AG-Huber_NL},
}

2018

Josef Maertz, Jan Philip Kolb, Thomas Klein, Kathrin J. Mohler, Matthias Eibl, Wolfgang Wieser, Robert Huber, Siegfried Priglinger, and Armin Wolf,
Combined in-depth, 3D, en face imaging of the optic disc, optic disc pits and optic disc pit maculopathy using swept-source megahertz OCT at 1050 nm, Graefes Arch Clin Exp Ophthalmol , vol. 256, no. 2, pp. 289-298, Dec. 2018.
DOI:10.1007/s00417-017-3857-9
Bibtex: BibTeX
@article{Maertz2018,
   author = {Maertz, J; Kolb, J P; Klein, T; Mohler, K J; Eibl, M; Wieser, W; Huber, R; Priglinger, S and Wolf, A},
   title = {Combined in-depth, 3D, en face imaging of the optic disc, optic disc pits and optic disc pit maculopathy using swept-source megahertz OCT at 1050 nm},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   number = {2},
   pages = {289-298},
   DOI = {10.1007/s00417-017-3857-9},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032262413&doi=10.1007%2fs00417-017-3857-9&partnerID=40&md5=a46c315f12cf5e633ea0f7e644116eb3},
   year = {2018},
   Keywords= {En face imaging, Optical coherence tomography, Swept-source OCT, Megahertz OCT, 3D rendering, Optic disc, Optic disc pit, Optic disc pit maculopathy, AG-Huber_OCT},
   type = {Journal Article}
}
Matthias Eibl, Daniel Weng, Hubertus Hakert, Jan Philip Kolb, Tom Pfeiffer, Jennifer Hundt, Robert Huber, and Sebastian Karpf,
Wavelength agile multi-photon microscopy with a fiber amplified diode laser, Biomedical Optics Express , vol. 9, no. 12, pp. 6273-6282, Nov. 2018. The Optical Society.
DOI:10.1364/BOE.9.006273
Bibtex: BibTeX
@article{Eibl2018,
  doi = {10.1364/boe.9.006273},
  url = {https://doi.org/10.1364/boe.9.006273},
  year = {2018},
  month = nov,
  publisher = {The Optical Society},
  volume = {9},
  number = {12},
  pages = {6273},
  author = {Matthias Eibl and Daniel Weng and Hubertus Hakert and Jan Philip Kolb and Tom Pfeiffer and Jennifer E. Hundt and Robert Huber and Sebastian Karpf},
  title = {Wavelength agile multi-photon microscopy with a fiber amplified diode laser},
  journal = {Biomedical Optics Express}
}

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