@article{
doi:10.1073/pnas.2220132120,
author = {Michael Schmalz  and Xiao-Xuan Liang  and Ines Wieser  and Caroline Gruschel  and Lukas Muskalla  and Martin Thomas Stöckl  and Roland Nitschke  and Norbert Linz  and Alfred Leitenstorfer  and Alfred Vogel  and Elisa Ferrando-May },
title = {Dissection of DNA damage and repair pathways in live cells by femtosecond laser microirradiation and free-electron modeling},
journal = {Proceedings of the National Academy of Sciences},
volume = {120},
number = {25},
pages = {e2220132120},
year = {2023},
doi = {10.1073/pnas.2220132120},
URL = {https://www.pnas.org/doi/abs/10.1073/pnas.2220132120},
eprint = {https://www.pnas.org/doi/pdf/10.1073/pnas.2220132120},
abstract = {Understanding and predicting the outcome of the interaction of light with DNA has a significant impact on the study of DNA repair and radiotherapy. We report on a combination of femtosecond pulsed laser microirradiation at different wavelengths, quantitative imaging, and numerical modeling that yields a comprehensive picture of photon-mediated and free-electron-mediated DNA damage pathways in live cells. Laser irradiation was performed under highly standardized conditions at four wavelengths between 515 nm and 1,030 nm, enabling to study two-photon photochemical and free-electron-mediated DNA damage in situ. We quantitatively assessed cyclobutane pyrimidine dimer (CPD) and γH2AX-specific immunofluorescence signals to calibrate the damage threshold dose at these wavelengths and performed a comparative analysis of the recruitment of DNA repair factors xeroderma pigmentosum complementation group C (XPC) and Nijmegen breakage syndrome 1 (Nbs1). Our results show that two-photon-induced photochemical CPD generation dominates at 515 nm, while electron-mediated damage dominates at wavelengths ≥620 nm. The recruitment analysis revealed a cross talk between nucleotide excision and homologous recombination DNA repair pathways at 515 nm. Numerical simulations predicted electron densities and electron energy spectra, which govern the yield functions of a variety of direct electron-mediated DNA damage pathways and of indirect damage by •OH radicals resulting from laser and electron interactions with water. Combining these data with information on free electron–DNA interactions gained in artificial systems, we provide a conceptual framework for the interpretation of the wavelength dependence of laser-induced DNA damage that may guide the selection of irradiation parameters in studies and applications that require the selective induction of DNA lesions.}}

@Inbook{Linz2023,
author="Linz, Norbert
and Freidank, Sebastian
and Liang, Xiao-Xuan
and Vogel, Alfred",
editor="Stoian, Razvan
and Bonse, J{\"o}rn",
title="Laser Micro- and Nanostructuring for Refractive Eye Surgery",
bookTitle="Ultrafast Laser Nanostructuring: The Pursuit of Extreme Scales",
year="2023",
publisher="Springer International Publishing",
address="Cham",
pages="1217--1245",
abstract="Every year, more than a million refractive eye operations using femtosecond (fs) laser procedures are performed, and yet the cutting process in corneal tissue remains an area for development. In this chapter, we first review the state of the art of infrared (IR) fs laser dissection in laser in situ keratomileusis (LASIK) and small incision lenticule extraction (SMILE) and formulate the challenges for an improvement of precision and reduction of side effects. Since overcoming these challenges requires better knowledge of the cutting mechanisms, the plasma-mediated corneal dissection process is analyzed by high-speed photography of laser-induced bubble dynamics with up to 50 Mio frames/s, histological analysis of the cuts, and gas chromatography of the dissection products. Based on these results, we show that cutting efficiency and precision are improved through focus shaping by means of a helical phase plate, which converts the linear polarized Gaussian fs laser beam into a Laguerre-Gaussian vortex beam. The focus of the vortex beam has a ring shape with the same length in axial direction as the focus of a Gaussian beam but larger diameter. This greatly facilitates cleavage along the corneal lamellae, enabling cutting with low plasma energy density, higher precision, and fewer mechanical side effects. A shortening of the laser plasma length at constant focusing angle by use of UV-A laser pulses instead of IR pulses further improves precision. To compare the performance of UV and IR Gaussian and vortex beams, the incident and absorbed laser energy needed for easy removal of flaps created in porcine corneas are determined at various pulse durations and the smoothness of cuts is evaluated by scanning electron microscopy. Overall, vortex beams perform better than Gaussian beams for all wavelengths and can be easily implemented in clinical systems. Finally, we discuss a novel concept for refractive correction based on the introduction of refractive index changes in the corneal stroma by localized low-density plasma formation. Experimental findings that UV wavelengths work better for this purpose than IR wavelengths are explained through an analysis of the wavelength dependence of free electron density and energy spectrum that are obtained by numerical simulations.",
isbn="978-3-031-14752-4",
doi="10.1007/978-3-031-14752-4_33",
url="https://doi.org/10.1007/978-3-031-14752-4_33"
}

@article{FU2023106664,
title = {Laser induced spherical bubble dynamics in partially confined geometry with acoustic feedback from container walls},
journal = {Ultrasonics Sonochemistry},
volume = {101},
pages = {106664},
year = {2023},
issn = {1350-4177},
doi = {https://doi.org/10.1016/j.ultsonch.2023.106664},
url = {https://www.sciencedirect.com/science/article/pii/S1350417723003760},
author = {Lei Fu and Xiao-Xuan Liang and Sijia Wang and Siqi Wang and Ping Wang and Zhenxi Zhang and Jing Wang and Alfred Vogel and Cuiping Yao},
keywords = {Laser-induced cavitation, Partial confinement, Acoustic feedback, Elastic wall, Vibrations, Extended Rayleigh-Plesset model},
abstract = {We investigated laser-induced cavitation dynamics in a small container with elastic thin walls and free or partially confined surface both experimentally and by numerical investigations. The cuvette was only 8–25 times larger than the bubble in its center. The liquid surface was either free, or two thirds were confined by a piston-shaped pressure transducer. Different degrees of confinement were realized by filling the liquid up to the transducer surface or to the top of the cuvette. For reference, some experiments were performed in free liquid. We recorded the bubble dynamics simultaneously by high-speed photography, acoustic measurements, and detection of probe beam scattering. Simultaneous single-shot recording of radius-time curves and oscillation times enabled to perform detailed investigations of the bubble dynamics as a function of bubble size, acoustic feedback from the elastic walls, and degree of surface confinement. The bubble dynamics was numerically simulated using a Rayleigh-Plesset model extended by terms describing the acoustically mediated feedback from the bubble’s environment. Bubble oscillations were approximately spherical as long as no secondary cavitation by tensile stress occurred. Bubble expansion was always similar to the dynamics in free liquid, and the environment influenced mainly the collapse phase and subsequent oscillations. For large bubbles, strong confinement led to a slight reduction of maximum bubble size and to a pronounced reduction of the oscillation time, and both effects increased with bubble size. The joint action of breakdown-induced shock wave and bubble expansion excites cuvette wall vibrations, which produce alternating pressure waves that are focused onto the bubble. This results in a prolongation of the collapse phase and an enlargement of the second oscillation, or in time-delayed re-oscillations. The details of the bubble dynamics depend in a complex manner on the degree of surface confinement and on bubble size. Numerical simulations of the first bubble oscillation agreed well with experimental data. They suggest that the alternating rarefaction/compression waves from breakdown-induced wall vibrations cause a prolongation of the first oscillation. By contrast, liquid mass movement in the cuvette corners result in wall vibrations causing late re-oscillations. The strong and rich interaction between the bubble and its surroundings may be relevant for a variety of applications such as intraluminal laser surgery and laser-induced cavitation in microfluidics.}
}

@article{Liang2022,
   author = {Liang, X-X;Linz, N;Freidank, S;Paltauf, G and Vogel, A},
   title = {Comprehensive analysis of spherical bubble oscillations and shock wave emission in laser-induced cavitation},
keywords = {bubble dynamics, cavitation, shock waves},
   journal = {Journal of Fluid Mechanics},
   volume = {940},
   pages = {A5},
   ISSN = {0022-1120},
   DOI = {10.1017/jfm.2022.202},
  
   year = {2022},
   type = {Journal Article}
}

@article{Liang2022,
   author = {Liang, X-X and Vogel, A},
   title = {Probing neuronal functions with precise and targeted laser ablation in the living cortex: comment},
   journal = {Optica},
   volume = {9(8)},
   keywords = {Attenuation coefficient, Femtosecond lasers, Laser ablation, Laser irradiation, Numerical simulation, Thermal effects},
   pages = {868-871},
   DOI = {10.1364/OPTICA.454469},  
   year = {2022},
   type = {Journal Article}
}

@article{Fischer2020,
   author = {Fischer, T;Klinger, A;von Smolinski, D;Orzekowsky-Schroeder, R;Nitzsche, F;Bölke, T;Vogel, A;Hüttmann, G and Gebert, A},
   title = {High-resolution imaging of living gut mucosa: lymphocyte clusters beneath intestinal M cells are highly dynamic structures},
   journal = {Cell and Tissue Research},
   pages = {1-8},
   ISSN = {1432-0878},
   url = {https://doi.org/10.1007/s00441-020-03167-z},
   year = {2020},
   type = {Journal Article}
}

@article{Vogel-2019-1,
   author = {Fischer, T;Klinger, A;Smolinski, D von;Orzekowsky-Schroeder, R;Nitzsche, F;Vogel, A;Hüttmann, G and Gebert, A},
   title = {High-resolution imaging of the living gut mucosa: lymphocyte clusters beneath intestinal M cells are highly dynamic structures},
   journal = {Cell and Tissue Research},
   ISSN = {0302-766X (Print) 
1432-0878 (Online)},
   year = {2019},
   type = {Journal Article}
}

@article{Liang2019,
   author = {Liang, X-X; Zhang, Z and Vogel, A},
   title = {Multi-rate-equation modeling of the energy spectrum of laser-induced conduction band electrons in water},
   journal = {Opt Expr},
   
   
   pages = {4672-4693},
   DOI = {10.1364/OE.27.004672},
   
   year = {2019},
   type = {Journal Article}
}

@inproceedings{Vogel2018,
   author = {Uzunbajakava, N E; Varghese, B; Botchkareva, N V; Verhagen, R and Vogel, A},
   title = {Highlighting the nuances behind interaction of picosecond pulses with human skin: Relating distinct laser-tissue interactions to their potential in cutaneous interventions},
   booktitle = {Progress in Biomedical Optics and Imaging - Proceedings of SPIE},
   volume = {10492} ,
   DOI = {10.1117/12.2307804},
   year = {2018},
date = {2018-20-02},
   type = {Conference Proceedings},
year = { 2018}
}

@article{Wang2016,
   author = {Wang, S. and Huttmann, G. and Scholzen, T. and Zhang, Z. and Vogel, A. and Hasan, T. and Rahmanzadeh, R.},
   title = {A light-controlled switch after dual targeting of proliferating tumor cells via the membrane receptor EGFR and the nuclear protein Ki-67},
   journal = {Sci Rep},
   volume = {6},
   pages = {27032},
   note = {2045-2322
Wang, Sijia
Huttmann, Gereon
Scholzen, Thomas
Zhang, Zhenxi
Vogel, Alfred
Hasan, Tayyaba
Rahmanzadeh, Ramtin
Journal Article
England
Sci Rep. 2016 Jun 1;6:27032. doi: 10.1038/srep27032.},
   abstract = {Using nanotechnology for optical manipulation of molecular processes in cells with high spatial and temporal precision promises new therapeutic options. Especially tumor therapy may profit as it requires a combination of both selectivity and an effective cell killing mechanism. Here we show a dual targeting approach for selective and efficient light-controlled killing of cells which are positive for epidermal growth factor receptor (EGFR) and Ki-67. Liposomes with the covalently linked EGFR antibody Erbitux enabled selective uptake of FITC-labeled Ki-67 antibody TuBB-9 in EGFR-positive cells pre-loaded with the photoactive dye BPD. After irradiation at 690 nm, BPD disrupted the endosomal membranes and delivered the antibodies to the nucleoli of the cells. The second irradiation at 490 nm activated the FITC-labeled TuBB-9, which caused inactivation of the Ki-67 protein and subsequent cell death via apoptosis. Efficient cell killing was possible at nanomolar concentrations of TuBB-9 due to the effective transport by immune liposomes and the high efficacy of the Ki-67 light-inactivation. Delivery of the liposomal constructs and cell destruction correlated well with the EGFR expression pattern of different cell lines (HeLa, OVCAR-5, MCF-7, and human fibroblasts), demonstrating an excellent selectivity.},
   ISSN = {2045-2322},
   DOI = {10.1038/srep27032},
   year = {2016},
   type = {Journal Article}
}

@article{Klinger2017,
   author = {Klinger, A. and Krapf, L. and Orzekowsky-Schroeder, R. and Koop, N. and Vogel, A. and Huttmann, G.},
   title = {Intravital autofluorescence 2-photon microscopy of murine intestinal mucosa with ultra-broadband femtosecond laser pulse excitation: image quality, photodamage, and inflammation},
   journal = {J Biomed Opt},
   volume = {20},
   number = {11},
   pages = {116001},
   ISSN = {1083-3668},
   DOI = {10.1117/1.jbo.20.11.116001},
   year = {2015},
   type = {Journal Article}
}

@article{Wang2015,
   author = {Wang, S. and Huttmann, G. and Zhang, Z. and Vogel, A. and Birngruber, R. and Tangutoori, S. and Hasan, T. and Rahmanzadeh, R.},
   title = {Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67},
   journal = {Mol Pharm},
   note = {1543-8392
Wang, Sijia
Huttmann, Gereon
Zhang, Zhenxi
Vogel, Alfred
Birngruber, Reginald
Tangutoori, Shifalika
Hasan, Tayyaba
Rahmanzadeh, Ramtin
Journal article
Mol Pharm. 2015 Aug 13.},
   abstract = {The selective inhibition of intracellular and nuclear molecules such as Ki-67 holds great promise for the treatment of cancer and other diseases. However, the choice of the target protein and the intracellular delivery of the functional agent remain crucial challenges. Main hurdles are (a) an effective delivery into cells, (b) endosomal escape of the delivered agents, and (c) an effective, externally triggered destruction of cells. Here we show a light-controlled two-step approach for selective cellular delivery and cell elimination of proliferating cells. Three different cell-penetrating nano constructs, including liposomes, conjugates with the nuclear localization sequence (NLS), and conjugates with the cell penetrating peptide Pep-1, delivered the light activatable antibody conjugate TuBB-9-FITC, which targets the proliferation associated protein Ki-67. HeLa cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and the antibody constructs. In the first optically controlled step, activation of BPD at 690 nm triggered a controlled endosomal escape of the TuBB-9-FITC constructs. In more than 75% of Ki-67 positive, irradiated cells TuBB-9-FITC antibodies relocated within 24 h from cytoplasmic organelles to the cell nucleus and bound to Ki-67. After a second light irradiation at 490 nm, which activated FITC, cell viability decreased to approximately 13%. Our study shows an effective targeting strategy, which uses light-controlled endosomal escape and the light inactivation of Ki-67 for cell elimination. The fact that liposomal or peptide-assisted delivery give similar results leads to the additional conclusion that an effective mechanism for endosomal escape leaves greater variability for the choice of the delivery agent.},
   keywords = {endosomal entrapment
liposome
nanotechnology
nuclear localization sequence (NLS)
photodynamic therapy},
   ISSN = {1543-8384},
   DOI = {10.1021/acs.molpharmaceut.5b00260},
   year = {2015},
   type = {Journal Article}
}

@article{Vogel2014,
   author = {Vogel, A and Freidank, S and Linz, N },
   title = {Alternativen zur Femtosekundentechnologie: UV Subnanosekunden-pulse und Ringfoki für LASIK Flaperzeugung (at press)},
   journal = {Ophthalomologe },
   volume = {111},
   number = {6},
   year = {2014},
   type = {Journal Article}
}

@book{Vogel-2011-2,
   author = {Vogel, A and Venugopalan, V.},
   title = {Pulsed laser ablation of tissue},
   publisher = {Springer, Heidelberg, New York},
   edition = {2},
   year = { 2011}
}

@misc{Vogel2008,
   author = {Vogel, A. and Linz, N. and Freidank, S. and Paltauf, G.},
   title = {Femtosecond-laser-induced nanocavitation in water: implications for optical breakdown threshold and cell surgery},
   volume = {100},
   number = {3},
   pages = {23},
   note = {Using Smart Source Parsing
Jan 25;:038102. Epub 2008 Jan},
   abstract = {We determined the bubble radius R_(max) for femtosecond optical breakdown in water at 347, 520, and 1040 nm with an unprecedented accuracy (+/-10 nm). At threshold, R_(max) was smaller than the diffraction-limited focus radius and ranged from 190 nm to 320 nm. The increase of R_(max) with laser energy E_(L) is slowest at 347 nm, providing optimum control of cell surgery. Experimental results agree with a model of bubble formation in heated and thermoelastically stretched liquids. Theory predicts a threshold temperature T_(th) approximately equal to 168 degrees C. For T>300 degrees C, a phase explosion sets in, and R_(max) increases rapidly with E_(L).},
   ISBN = {0031-9007 (Print)
0031-9007 (Linking)},
   year = {2008}
}

@article{Vogel2007-7,
   author = {Vogel, A. and Lorenz, K. and Horneffer, V. and Hüttmann, G. and von Smolinski, D. and Gebert, A.},
   title = {Mechanisms of laser-induced dissection and transport of histologic specimens.},
   journal = {Biophys J},
   volume = {93},
   pages = {4481-4500},
   year = { 2007},
url = { https://doi.org/10.1529/biophysj.106.102277}
}

@article{Horneffer,
   author = {Horneffer, V. and Linz, N. and Vogel, A.},
   title = {Principles of laser-induced separation and transport of living cells},
   journal = {J Biomed Opt},
   volume = {12},
   number = {5},
   pages = {054016},
   note = {Horneffer, Verena
Linz, Norbert
Vogel, Alfred
Evaluation Studies
Research Support, Non-U.S. Gov't
United States
J Biomed Opt. 2007 Sep-Oct;12(5):054016.},
   abstract = {Separation and transport of defined populations of living cells grown on a thin membrane can be achieved by laser microdissection (LMD) of the sample of interest, followed by a laser-induced forward transport process [laser pressure "catapulting" (LPC)] of the dissected cell cluster. We investigate the dynamics of LMD and LPC with focused and defocused UV-A laser pulses by means of time-resolved photography. Catapulting is driven by plasma formation when tightly focused pulses are used, and by confined thermal ablation at the bottom of the sample for defocused catapulting. With both modalities, the initial specimen velocity amounts to about 50 to 60 ms. Time-resolved photography of live cell catapulting reveals that in defocused catapulting, strong shear forces arise when the sample is accelerated out of the culture medium covering the cells. By contrast, pulses focused at the periphery of the specimen cause a fast rotational movement that minimizes the flow of culture medium parallel to the sample surface, and thus the resulting shear stresses. Therefore, the recultivation rate of catapulted cells is much higher when focused pulses are used. Compared to collateral damage by mechanical forces, side effects by heat and UV exposure of the cells play only a minor role.},
   keywords = {Animals
CHO Cells
Cell Separation/ methods
Cricetinae
Cricetulus
Microdissection/ methods
Optical Tweezers
Specimen Handling/ methods},
   year = {2007}
}

@inbook{Vogel2007-4,
   author = {Vogel, A and Horneffer, V. and Lorenz, B. and Linz, N. and Freidank, S. and Hüttmann, G. and Gebert, A.},
   title = {Principles of laser microdissection and catapulting of histologic specimens and live cells},
   booktitle = {Laser Manipulation of Cells and Tissues, Methods in Cell Biology},
   editor = {Berns, M.  and Greulich, K.O.},
   publisher = {Academic Press Elsevier},
   address = {San Diego},
   volume = {82},
   pages = {153-205},
   year = { 2007}
}

@inbook{Vogel2007,
   author = {Vogel, A and Noack, J. and Hüttmann, G. and Paltauf, G.},
   title = {Mechanisms of femtosecond laser nanoprocessing of biological cells and tissues},
   booktitle = {The Eigth International Conference on Laser Ablation (COLA 2005)},
   editor = {Herman, P. and Hess, W .},
   series = {Journal of Physics: Conference Series},
   volume = {59},
   pages = {249-254},
   year = { 2007}
}

@inbook{Vogel2007-5,
   author = {Vogel, A. and Noack, J. and Hüttmann, G. and Linz, N. and Freidank, S. and Paltauf, G.},
   title = {Chapter 18 Femtosecond laser nanosurgery of biological cells and tissues},
   booktitle = {Handai Nanophotonics},
   editor = {Hiroshi Masuhara, Satoshi Kawata and Fumio, Tokunaga},
   publisher = {Elsevier},
   volume = {Volume 3},
   pages = {273-286},
   year = { 2007}
}

@inbook{Vogel2006-2,
   author = {Vogel, A. and Noack, J and Hüttmann, G. and Paltauf, G.},
   title = {Femtosecond plasma-mediated nanosurgery of cells and tissues.},
   booktitle = {Laser Ablation},
   editor = {), Phipps C (Hrsg.},
   publisher = { Springer, Heidelberg},
   pages = {217-262},
   year = { 2006}
}

@article{Vogel2006-1,
   author = {Vogel, A. and Apitz, I. and Freidank, S. and Dijkink, R.},
   title = {Sensitive high-resolution white-light Schlieren technique with a large dynamic range for the investigation of ablation dynamics},
   journal = {Opt. Lett.},
   volume = {31},
   pages = {1812-1814},
   year = { 2006},
url = { https://doi.org/10.1364/OL.31.001812}
}

@inproceedings{Vogel-2006,
   author = {Vogel, A. and Noack, J. and Hüttmann, G. and Linz, N. and Freidank, S. and Paltauf, G.},
   title = {Femtosecond laser nanosurgery of biological cells and tissues},
   booktitle = {4th International Congress on Laser Advanced Materials Processing},
Year = { 2006},
URL = { http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.713.4169&rep=rep1&type=pdf}
}

@article{Brujan,
   author = {Brujan, EA. and Vogel, A .},
   title = {Stress wave emission and cavitation bubble dynamics by nanosecond optical breakdown in a tissue phantom.},
   journal = { J Fluid Mech},
   volume = {558},
   pages = {281-308},
   year = {2006}
}