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Welcome to our website! The goal of our research is to develop new tools for biomedical imaging, using advanced lasers and optical technology. Our projects range from the development of table-top soft-X-ray imaging to the construction of miniature high-resolution microscopes for cellular imaging. Check out the 'Research' section for more details on our ongoing projects.

Latest news

ARCNL

In 2014, the Advanced Research Center for Nanolithography (ARCNL) has started. ARCNL is a new, public-private funded research center founded on the initiative of ASML, in collaboration with FOM, NWO, UvA, and VU University. The focus of ARCNL is to perform cutting-edge fundamental science relating to nanolithography. I will become group leader of the 'EUV Generation and Imaging' Group at ARCNL, in collaboration with Prof. Kjeld Eikema.

There are several exciting job opportunities for PhDs and postdocs. Check out the ARCNL website for details.


Lensless imaging with ultra-broadband high-harmonic sources

We developed a method that enables efficient lensless imaging with ultra-broadband light sources, using coherent pairs of pulses. This method works well with visible light sources, but especially with table-top extreme-ultraviolet radiation sources such as produced by high-harmonic generation. We recently published the paper on this invention in Light: Science and Applications!


Miniature phase contrast microscopes in Optics Letters

Our paper on the development of miniature lensless microscopes for live cell imaging has been published in Optics Letters! Check out the paper for some high-res quantitative phase images of live neurons, recorded using only a few laser diodes and a camera.


FOM Valorisation grant

February 2014: together with Prof. Kjeld Eikema, I was awarded a Valorisation grant from FOM. This grant provides 50 kE in funding for our project entitled "Compact lensless microscopes for quantitative phase contrast imaging". Check out the press release here.


FOM Projectruimte Grant

January 2014: I received a 400 kE 'Projectruimte' grant from FOM (Foundation for Fundamental Research on Matter), for my proposal entitled "Beyond optical microscopy: Phase-contrast imaging of cells with a table-top soft-X-ray Microscope"!


Our research is centered around the theme of biophotonics and medical imaging. The aim is to improve microscopy and biomedical imaging by using advanced lasers and optical techniques. To this end, we work on a variety of projects that are all linked to this theme:

 

Soft-X-ray imaging with a table-top high-harmonic source

There is a great need for imaging systems with a resolution that surpasses the diffraction limit of optical microscopes. Such a device would enable visualization of many fine details in cells, for instance. We are working on the development of a compact soft-X-ray microscope, to enable cellular imaging with ultra-high resolution. While soft-X-ray microscopy is already being developed at synchrotrons and XFELs, it would be highly advantageous to have the ability of doing soft-X-ray imaging with a compact device in a laboratory environment.

To this end, we are constructing a table-top soft-X-ray source based on high-harmonic generation (HHG), and are working on novel imaging methods that allow imaging with such sources. Since good-quality imaging optics for soft-X-rays are not (yet) available, we are focusing on so-called lensless imaging techniques: in lensless imaging, a diffraction pattern rather than an image of an object is recorded. In specific cases, an image of the object can then be reconstructed numerically, either through holographic detection or iterative phase retrieval algorithms.

A major limiting factor for coherent diffractive imaging is the ultra-broadband spectrum that is typically emitted by a HHG source, as a finite spectrum results in a blurry diffraction pattern. We have recently developed a method that enables spectrally resolved imaging with a HHG source (already down to 47 nm wavelength), while using the full source spectrum efficiently. We recently published our paper on these results in the new journal from the Nature Publishing Group, Light: Science and Applications. The online version can be found here! This project is a collaboration with the group of Prof. Kjeld Eikema.

 

Ultrafast laser development and optical parametric chirped pulse amplification

Since we need a HHG-based soft-X-ray source for the imaging project, we are currently developing a high-intensity laser system based on optical parametric chirped pulse amplification (OPCPA). In the past we have pioneered ultrafast OPCPA development, resulting in the first demonstration of multi-terawatt sub-3-cycle laser pulses. See the 'Publications' section for our papers on the subject.

Currently, we are setting up a new system, based on similar OPCPA technology, but now using a new pump laser approach based on quasi-CW diode pumped Nd:YAG amplifiers. This pulsed diode pumping approach enables much higher repetition rates than our previous, flashlamp-pumped amplifier system. The final OPCPA output will again produce terawatt peak power few-cycle pulses, but this time at a repetition rate of 300 Hz.

The Nd:YAG pump laser is now fully operational, and our paper describing it has recently been accepted by Optics Letters.

 

Lensless imaging and miniaturized microscopes

Besides soft-X-ray imaging and large laser systems, we are also working on the development of lensless imaging methods in small-scale imaging devices. A major advantage of lensless imaging is that the actual microscope hardly contains any components anymore (basically only the light source, the sample and a camera are really needed), which means that the device can be kept extremely compact and cost-effective.

We are now introducing some of our lensless imaging concepts, which we originally developed for soft-X-ray microscopy, into an optical imaging device for live cell imaging. First results are highly encouraging: we find that by recording diffraction patterns at a few different wavelengths of the light, we can retrieve the phase in a very robust way, without the need for support constraints or moving objects in the microscope. We have applied this method to image live neurons in a culture dish, and we obtain quantitative phase contrast images of the cells at sub-2-micron spatial resolution, using a very small and robust lensless microscope. We have recently published these results in Optics Letters, the paper can be found here.

 

Nonlinear microscopy and biological imaging

In previous projects, I have been involved in the development of new imaging methods for biological microscopy. We have built a new type of microscope that enables single-shot, quantitative phase contrast imaging of live cells using off-axis holography with white light. Off-axis holography is very convenient for rapid imaging, as it enables direct separation of the holographic signal by spatial Fourier filtering. However, due to the short coherence length of broadband sources, such an off-axis geometry usually results in a very limited field-of-view. By implementing a controlled pulse front tilt onto the reference beam, we have been able to reconstruct high-resolution phase images of live cells over a large field of view, in a single shot and without the need for moving parts in the setup. We have published these results in Biomedical Optics Express.

I have also been involved in the development of nonlinear microscopy methods aimed at live brain imaging. We discovered that third-harmonic generation (THG) microscopy is an excellent method for live brain imaging with cellular resolution. A more detailed explanation of this project, including some cool pictures, can be found here, as well as in our paper in PNAS.

 

Coherent control and precision spectroscopy (PI Kjeld Eikema)

A major workhorse of precision spectroscopy has always been Doppler-free two-photon excitation in a gas cell, using counter-propagating photons to excite an atomic or molecular transition in such a way that the Doppler shift is canceled. However, when such an experiment is combined with direct frequency comb spectroscopy, the extremely short pulse duration results in a very poor spatial overlap between the counter-propagating pulses. Since the individual pulses do excite the transition with full Doppler broadening, the ratio between Doppler-free and Doppler-broadened signal becomes very low.

I have been involved in a series of experiments conducted by Kjeld Eikema's group, where we showed that coherent control techniques can be used to turn off this single-sided excitation, while the Doppler-free signal remains at full strength. In addition, complex spatially localized excitation patterns can be engineered, effectively allowing spatial coherent control.Furthermore, high-resolution Doppler-free spectroscopy can now be performed using direct frequency comb excitation, which has many advantages for e.g. XUV spectroscopy. These results were recently published in Nature Photonics (check out the January 2013 cover!) and PRL.

Full publication list (most recent first)

    Front page Light: Science and Applications
  1. S. Witte, V.T. Tenner, D.W.E. Noom, K.S.E. Eikema,
    Lensless diffractive imaging with ultrabroadband table-top sources: from infrared to extreme-ultraviolet wavelengths,
    Light: Science and Applications 3, e163 (2014).

  2. D.W.E. Noom, K.S.E. Eikema, S. Witte,
    Lensless phase contrast microscopy based on multiwavelength Fresnel diffraction,
    Optics Letters 39, 193-196 (2014).

  3. D.W.E. Noom, S. Witte, J. Morgenweg, R.T. Altmann, K.S.E. Eikema,
    High energy, high repetition rate picosecond pulses from a quasi-CW diode pumped Nd:YAG system,
    Optics Letters 38, 3021-3023 (2013).

  4. I. Barmes, S. Witte, K.S.E. Eikema,
    High-precision spectroscopy with counterpropagating femtosecond pulses,
    Physical Review Letters 111, 023007 (2013).

    Front page Light: Science and Applications
  5. I. Barmes, S. Witte, K.S.E. Eikema,
    Spatial and spectral coherent control with frequency combs,
    Nature Photonics 7, 38-42 (2013).

  6. S. Witte, A. Plauska, M.C. Ridder, L. van Berge, H.D. Mansvelder, M.L. Groot,
    Short-coherence off-axis holographic phase microscopy of live cell dynamics,
    Biomedical Optics Express 3, 2184 (2012).

  7. D. Hickstein, P. Ranitovic, S. Witte, X.M. Tong, Y.Huismans, P. Arpin, X. Zhou, K.E. Keister, C.W. Hogle, B. Zhang, C. Ding, P. Johnsson, N. Toshima, M.J.J. Vrakking, M.M. Murnane, H.C. Kapteyn,
    Direct visualization of laser-driven electron multiple-scattering and tunneling distance in strong-field ionization,
    Physical Review Letters 109, 073004 (2012).

  8. S. Witte, K.S.E. Eikema,
    Ultrafast optical parametric chirped-pulse amplification (Invited paper),
    IEEE. J. Sel. Topics Quantum Electron. 18, 296 (2011).

  9. S. Witte, A. Negrean, J.C. Lodder, C.P.J. de Kock, G.T. Silva, H.D. Mansvelder, M.L. Groot,
    Label-free live brain imaging and targeted patching with third-harmonic generation microscopy,
    Proc. Natl. Acad. Sci. USA 108, 5970-5975 (2011).

      Highlighted in:
      • The Scientist, Nov 2011, “Brainspotting”
      • SciBX 4 (15), “Third-harmonic generation microscopy for guiding brain surgery”
      • This week in PNAS, April 12 2011, “Live brain imaging without labels”

  10. S. Witte, M. Baclayon, E.J.G. Peterman, R.F.G. Toonen, H.D. Mansvelder, M.L. Groot,
    Single-shot two-dimensional full-range optical coherence tomography achieved by dispersion control,
    Opt. Express 17, 11335-113349 (2009).

  11. D.Z. Kandula, A. Renault, C. Gohle, A.L. Wolf, S. Witte, W. Hogervorst, W. Ubachs, K.S.E. Eikema,
    Ultrafast double-pulse parametric amplification for precision Ramsey metrology,
    Opt. Express 16, 7071-7082 (2008).

  12. A. Renault, D.Z. Kandula, S. Witte, A.L. Wolf, R.T. Zinkstok, W. Hogervorst, K.S.E. Eikema,
    Phase stability of ultrabroadband parametric amplification,
    Opt. Lett. 32, 2363-2365 (2007).

  13. S. Witte, R.Th. Zinkstok, W. Hogervorst, K.S.E. Eikema,
    Numerical simulations for performance optimization of a few-cycle terawatt NOPCPA system,
    Appl. Phys. B 87, 677-684 (2007).

  14. S. Witte, R.Th. Zinkstok, A.L. Wolf, W. Hogervorst, W. Ubachs, K.S.E. Eikema,
    A source of 2 terawatt, 2.7 cycle laser pulses based on noncollinear optical parametric chirped pulse amplification,
    Opt. Express 14, 8168-8177 (2006).

  15. R.Th. Zinkstok, S. Witte, W. Ubachs, W. Hogervorst, K.S.E. Eikema,
    Frequency comb laser spectroscopy in the vacuum-ultraviolet region,
    Phys. Rev. A 73, 061801 (2006).

  16. S. Hannemann, E.J. Salumbides, S. Witte, R.Th. Zinkstok, E.-J. van Duijn, K.S.E. Eikema, W. Ubachs,
    Frequency metrology on the EF 1Σ+g ß X 1Σ+g (0,0) transition in H-2, HD, and D-2,
    Phys. Rev. A 74, 062514 (2006).

  17. S. Hannemann, E.J. Salumbides, S. Witte, R.Th. Zinkstok, K.S.E. Eikema, W. Ubachs,
    Frequency metrology on the Mg 3s2 1S à 3s4p 1P line for comparison with quasar data,
    Phys. Rev. A 74, 012505 (2006).

  18. S. Witte, R.Th. Zinkstok, W. Hogervorst, K.S.E. Eikema,
    Generation of few-cycle terawatt light pulses using optical parametric chirped pulse amplification,
    Opt. Express 13, 4903-4908 (2005).

  19. S. Witte, R.Th. Zinkstok, W. Ubachs, W. Hogervorst, K.S.E. Eikema,
    Deep-ultraviolet quantum interference metrology with ultrashort laser pulses,
    Science 307, 400-403 (2005).

      Also see Perspective by Thomas Udem, “Short and sharp – Spectroscopy with frequency combs”, Science 307, 364 (2005)

  20. R.Th. Zinkstok, S. Witte, W. Hogervorst, K.S.E. Eikema,
    High-power parametric amplification of 11.8-fs laser pulses with carrier-envelope phase control,
    Opt. Lett. 30, 78-80 (2005).

  21. S. Witte, R.Th. Zinkstok, W. Hogervorst, K.S.E. Eikema,
    Control and precise measurement of carrier-envelope phase dynamics,
    Appl. Phys. B 78, 5-12 (2004).

  22. J. Mes, E.-J. van Duijn, R.Th. Zinkstok, S. Witte, W. Hogervorst,
    Third-harmonic generation of a continuous-wave Ti:Sapphire laser in external resonant cavities,
    Appl. Phys. Lett. 82, 4423-4425 (2003).

  23. S. Witte, E.-J. van Duijn, R.Th. Zinkstok, W. Hogervorst,
    High-resolution LIF measurements on hyperfine structure and isotope shifts in various states of Lu I using the second and third harmonic of a cw Ti:sapphire laser,
    Eur. Phys. J. D 20, 159-164 (2002).

  24. R.Th. Zinkstok, E.-J. van Duijn, S. Witte, W. Hogervorst,
    Hyperfine structure and isotope shift of transitions in Yb I using UV and deep-UV cw laser light and the angular distribution of fluorescence radiation,
    J. Phys. B 35, 2693-2701 (2002).

  25. E.-J. van Duijn, S. Witte, R.Th. Zinkstok, W. Hogervorst,
    Hyperfine structure and isotope shift measurements on 4d10 1S0 à 4d95p J = 1 transitions in Pd I using deep-UV cw laser spectroscopy,
    Eur. Phys. J. D 19, 25-29 (2002).

Current composition of the research team

Dr. Stefan Witte - Group leader

Daniel Noom, M.Sc. - PhD student

Dirk Boonzajer Flaes, M.Sc. - PhD student

Matthijs Jansen, B.Sc. - Masters student

Martijn Stoffels, B.Sc. - Masters student

Elias Labordus - Bachelors student


On the topic of X-ray microscopy, I collaborate with Prof. Dr. Kjeld Eikema, who heads the Ultrafast Laser Physics and Precision Metrology Group at VU University Amsterdam


Short CV of Dr. Stefan Witte


Former members and group alumni

Vasco Tenner - M.Sc. degree June 2013 (cum laude). Present: PhD student at Leiden University.

Martijn Stoffels - B.Sc. project April 2013

Menno Pleijster - B.Sc. project Feb 2012

Are you interested in our work and would you like to know more? Don't hesitate to contact me by email: stefan.witte<at>vu.nl (replace <at> by @).

 

Further contact Details:

Dr. Stefan Witte

Biophotonics and Medical Imaging
Department of Physics and Astronomy
VU University Amsterdam
De Boelelaan 1081
1081 HV Amsterdam
The Netherlands

Office
Room T0.61
Phone +31-(0)20-598 1508

Laser Lab
Room KA 1.91a
Phone +31-(0)20-598 7446

 

 

Links
Faculty of Sciences
Department of Physics
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Section Biophotonics and Medical Imaging - VU University Amsterdam

Address: De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands
Telephone:+31(0)205981508 Fax:+31(0)205987992