Laser Manipulation and Cellular Engineering

Objectives

The aims of the RG Cell Surgery and the professorship "Biophotonics" are the study and development of optical tools for the manipulation of cells and cellular functions. Optical techniques allow the achievement of highly localized effects within cells, which can be simultaneously used for high resolution imaging.

Research Focus

The focus of the professorship "Biophotonics" within the RG Cell Surgery are the use of photonic technologies in the field of regenerative medicine and biology. Using linear and nonlinear imaging modalities, like laser microscopy, tissue samples of up to several millimeters thickness can be imaged non-invasively, even in vivo imaging at the subcellular level is possible. By using further (nonlinear) effects a precise manipulation or ablation of cells or tissue structures can be achieved, for example for cell surgery or cell transfection. Using plasmonic effects induced in nanoparticles as gold nanoparticles (GNP) or gold nanorods, markers for higher contrast in diagnostics or biotechnologies or even selective therapy can be employed. Furthermore, the group applies genetic methods, like optogenetic modification of cells, to achieve optically controlled cell function, like contraction, signaling or gene expression.

Collaborations

  • R. Zweigerdt, REBIRTH Unit Mass Production of Pluripotent Stem Cells, Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, Characterization of stem cell clusters by scanning laser technologies, optogenetic manipulation of cardiomyocytes.
  • I. Gruh, REBIRTH Unit Myocardial Tissue Engineering, Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, Optogenetic manipulation of heart muscle tissues.
  • U. Martin, REBIRTH Unit iPSCs for Disease Modelling, Drug Screening and Cell Therapy, Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, optical characterization and mnaipiulation of stem cells and iPS cells or iPS cell derivatives.
  • A. Haverich, Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, in vivo imaging of cardiovascular constructs and vessels in vivo, development of optical imaging in lung researchM
  • R. Förster, REBIRTH Unit Regenerative Immuology, Use of GNOME lasertransfection and CRISPR Cas9 in the mouse model
  • T. Scheper, REBIRTH Unit Production and purification of recombinant proteins
  • M. Ochs, REBIRTH Unit Quantitative Microscopy in regeneration, application of optical tomography for lung imaging
  • J. Bode, Institute for Experimental Hematology, MHH: Transfektion von murinen haematopetischen Stammzellen (HSC), um eine weniger toxische und effizientere Alternative zur Elektroporation zu etablieren. 
  • S. Barcikowski, Universität Duesseldorf: Development of new nanoparticles and systems (AuNP) for cellular manipulations.
  • A. Schambach, REBIRTH Unit Regenerative Gene Therapy, MHH: Application of optical methods for genetic manipulations of cells and tissues.
  • M. Stiesch, Clinic for Dental Prosthetics, Hannover Medical School, optical imaging of cells and tissues as well as implants.
  • L. Kahrs, T. Ortmaier, Institute of Mechatronic Systems (imes), Leibniz University Hannover, Imaged guided surgery, controlled by OCT.
  • A. Ngezahayo, Institute of Biophysics, Leibniz University Hannove, , optical application of various systems in cell biology and electrophysiology, development of optogenetic tools in cell biology.
  • P.  Sasse, T. Fleischmann, University Bonn, Optogenetic applications
  • M. Terakawa, Keio University, Biopolymers for optical applications in medicine

Further Research Projects

  • Principal investigator in the German Center for Lung Research (DZL, BREATH)
  • Coordinator BMBF project “BioPACE” funded by the BMBF
  • Board member of the excellence clusters REBIRTH and H4a
  • Various projects related to cell characterization, cell manipulation, tissue imaging and imaged guided surgery

    Awards

    • Fellow of the Fellow of SPIE
    • Distinguished Guest Professor (Global), Keio University, Tokyo, Japan (2018-2019)

    Teaching

    Lectureship in the Physics courses at Leibniz University (Experimental Physics, Nonlinear Optics, Lasermedicine, Biophotonics, Microscopy etc.), lectureship in HBRS, lectureship in biomedical engineering courses.

    Publications

    2013 - ongoing

    2017

    Saklayen N, Kalies S, Madrid M, Nuzzo V, Huber M, Shen W, Sinanan-Singh J, Heinemann D, Heisterkamp A, Mazur E. Analysis of poration-induced changes in cells from laser-activated plasmonic substrates. Biomed Opt Express. 2017/10/31 ed2017. p. 4756-71.

    Saklayen N, Huber M, Madrid M, Nuzzo V, Vulis DI, Shen W, Nelson J, McClelland AA, Heisterkamp A, Mazur E. Intracellular Delivery Using Nanosecond-Laser Excitation of Large-Area Plasmonic Substrates. ACS Nano. 2017;11(4):3671-80. Epub 2017/03/16.

    Doll K, Fadeeva E, Schaeske J, Ehmke T, Winkel A, Heisterkamp A, Chichkov BN, Stiesch M, Stumpp NS. Development of Laser-Structured Liquid-Infused Titanium with Strong Biofilm-Repellent Properties. ACS Appl Mater Interfaces. 2017;9(11):9359-68. Epub 2017/02/24.

    Gentemann L, Kalies S, Coffee M, Meyer H, Ripken T, Heisterkamp A, Zweigerdt R, Heinemann D. Modulation of cardiomyocyte activity using pulsed laser irradiated gold nanoparticles. Biomed Opt Express. 2017;8(1):177-92.

    2016

    Krawinkel J, Torres-Mapa ML, Werelius K, Heisterkamp A, Ruttermann S, Romanos GE, Gerhardt-Szep S. Gold Nanoparticle-Mediated Delivery of Molecules into Primary Human Gingival Fibroblasts Using ns-Laser Pulses: A Pilot Study. Materials. 2016;9(5).

    Krawinkel J, Torres-Mapa ML, Mhatre E, Kovacs AT, Heisterkamp A. Structural damage of Bacillus subtilis biofilms using pulsed laser interaction with gold thin films. J Biophotonics. 2016.

    Krawinkel J, Richter U, Torres-Mapa ML, Westermann M, Gamrad L, Rehbock C, Barcikowski S, Heisterkamp A. Optical and electron microscopy study of laser-based intracellular molecule delivery using peptide-conjugated photodispersible gold nanoparticle agglomerates. J Nanobiotechnology. 2016;14:2.

    Ishii A, Ariyasu K, Mitsuhashi T, Heinemann D, Heisterkamp A, Terakawa M. Biodegradable microsphere-mediated cell perforation in microfluidic channel using femtosecond laser. J Biomed Opt. 2016;21(5):55001.

    2015

    Seiler TG, Ehmke T, Fischinger I, Zapp D, Stachs O, Seiler T, Heisterkamp A. Two-Photon Fluorescence Microscopy for Determination of the Riboflavin Concentration in the Anterior Corneal Stroma When Using the Dresden Protocol. Invest Ophthalmol Vis Sci. 2015;56(11):6740-6.

    Schomaker M, Heinemann D, Kalies S, Willenbrock S, Wagner S, Nolte I, Ripken T, Murua Escobar H, Meyer H, Heisterkamp A. Characterization of nanoparticle mediated laser transfection by femtosecond laser pulses for applications in molecular medicine. J Nanobiotechnology. 2015;13:10.

    Antonopoulos GC, Steltner B, Heisterkamp A, Ripken T, Meyer H. Tile-Based Two-Dimensional Phase Unwrapping for Digital Holography Using a Modular Framework. PloS one. 2015;10(11):e0143186.

    Ehmke T., Knebl A., Heisterkamp A. Four-wave mixing microscopy: A high nonlinear imaging method Multiphoton Microscopy. Biomedical Sciences XV. 2015

    Seiler TG, Ehmke T, Fischinger I, Zapp D, Stachs O, Seiler T, Heisterkamp A. Two-Photon Fluorescence Microscopy for Determination of the Riboflavin Concentration in the Anterior Corneal Stroma When Using the Dresden Protocol. Invest Ophthalmol Vis Sci. 2015;56(11):6740-6. Epub 2015/11/17.

    Schomaker M, Killian D, Willenbrock S, Heinemann D, Kalies S, Ngezahayo A, Nolte I, Ripken T, Junghanss C, Meyer H, Murua Escobar H, Heisterkamp A. Biophysical Effects in Off-Resonant Gold Nanoparticle Mediated (Gnome) Laser Transfection of Cell Lines, Primary- and Stem Cells Using Fs Laser Pulses. J Biophotonics. 2015;8(8):646-58.

    Schomaker M, Heinemann D, Kalies S, Willenbrock S, Wagner S, Nolte I, Ripken T, Murua Escobar H, Meyer H, Heisterkamp A. Characterization of Nanoparticle Mediated Laser Transfection by Femtosecond Laser Pulses for Applications in Molecular Medicine. J Nanobiotechnology. 2015;13:10.

    Ehmke T, Knebl A, Reiss S, Fischinger IR, Seiler TG, Stachs O, Heisterkamp A. Spectral Behavior of Second Harmonic Signals from Organic and Non-Organic Materials in Multiphoton Microscopy. AIP Adv. 2015;5(8):084903.

    2014

    Kalies S, Heinemann D, Schomaker M, Murua Escobar H, Heisterkamp A, Ripken T, Meyer H. Plasmonic Laser Treatment for Morpholino Oligomer Delivery in Antisense Applications. J Biophotonics. 2014;7(10):825-33.

    Kalies S, Birr T, Heinemann D, Schomaker M, Ripken T, Heisterkamp A, Meyer H. Enhancement of Extracellular Molecule Uptake in Plasmonic Laser Perforation. J Biophotonics. 2014;7(7):474-82.

    Gamrad L, Rehbock C, Krawinkel J, Tumursukh B, Heisterkamp A, Barcikowski S. Charge Balancing of Model Gold-Nanoparticle-Peptide Conjugates Controlled by the Peptide’s Net Charge and the Ligand to Nanoparticle Ratio. The Journal of Physical Chemistry C. 2014;118(19):10302-13.

    Ehmke T, Nitzsche TH, Knebl A, Heisterkamp A. Molecular Orientation Sensitive Second Harmonic Microscopy by Radially and Azimuthally Polarized Light. Biomed Opt Express. 2014;5(7):2231-46.

    Eberhard J, Loewen H, Kruger A, Donner S, Stumpp N, Patzlaff M, Stachs O, Reichard M, Ripken T, Heisterkamp A, Stiesch M. Non-Invasive in Vivo Imaging by Confocal Laser Scanning Microscopy of Gingival Tissues Following Natural Plaque Deposition. J Clin Periodontol. 2014;41(4):321-6.

    2013

    Mitchell CA, Kalies S, Cizmar T, Heisterkamp A, Torrance L, Roberts AG, Gunn-Moore FJ, Dholakia K. Femtosecond Optoinjection of Intact Tobacco by-2 Cells Using a Reconfigurable Photoporation Platform. PLoS One. 2013;8(11):e79235.

    Heinemann D, Schomaker M, Kalies S, Schieck M, Carlson R, Murua Escobar H, Ripken T, Meyer H, Heisterkamp A. Gold Nanoparticle Mediated Laser Transfection for Efficient Sirna Mediated Gene Knock Down. PLoS One. 2013;8(3):e58604. Epub 2013/03/29.

    Donner S, Muller O, Witte F, Bartsch I, Willbold E, Ripken T, Heisterkamp A, Rosenhahn B, Kruger A. In Situ Optical Coherence Tomography of Percutaneous Implant-Tissue Interfaces in a Murine Model. Biomed Tech (Berl). 2013;58(4):359-67.

    Burmeister F, Richter S, Richter D, Voigtlander C, Heisterkamp A, Nolte S. Breakthroughs in Photonics 2012: Femtosecond-Laser Nanomachining. Photonics Journal, IEEE. 2013;5(2):0700506-.

    Aper T, Teebken OE, Kruger A, Heisterkamp A, Hilfiker A, Haverich A. Development of Implantable Autologous Small-Calibre Vascular Grafts from Peripheral Blood Samples. Zentralbl Chir. 2013;138(2):173-9.

    2006 - 2012

    2012

    Heinemann D, Schomaker M, Schieck M, Ripken T, Meyer H, Heisterkamp A. Efficient siRNA transfection in cell lines and primary neuronal cells by gold nanoparticle mediated laser transfection. Histology and histopathology. 2012;27(Supplement 1):48.

    Schomaker M, Heinemann D, Killian D, Willenbrock S, Ripken T, Junghanss C, Nolte I, Meyer H, Murua Escobar H, Heisterkamp A. Establishment of a non-viral, gold nanoparticle mediated laser transfection method for gene therapeutic approaches. Histology and histopathology. 2012;27(Supplement 1):102-3.

    Willenbrock S, Braun O, Baumgart J, Lange S, Junghanss C, Heisterkamp A, Nolte I, Bullerdiek J, Murua Escobar H. Tnf-Alpha Induced Secretion of Hmgb1 from Non-Immune Canine Mammary Epithelial Cells (Mth53a). Cytokine. 2012;57(2):210-20.

    Rendall HA, Marchington RF, Praveen BB, Bergmann G, Arita Y, Heisterkamp A, Gunn-Moore FJ, Dholakia K. High-Throughput Optical Injection of Mammalian Cells Using a Bessel Light Beam. Lab Chip. 2012;12(22):4816-20.

    Kellner M, Heidrich M, Beigel R, Lorbeer RA, Knudsen L, Ripken T, Heisterkamp A, Meyer H, Kuhnel MP, Ochs M. Imaging of the Mouse Lung with Scanning Laser Optical Tomography (Slot). J Appl Physiol (1985). 2012;113(6):975-83.

    2011

    Schomaker M, Baumgart J, Motekaitis D, Heinemann D, Krawinkel J, Pangalos M, Bintig W, Boulais E, Lachaine R, St.-Louis Lalonde B, Ngezahayo A, Meunier M, Heisterkamp A, editors. Mechanisms of Gold Nanoparticle Mediated Ultrashort Laser Cell Membrane Perforation. 2011.

    Pospiech M, Emons M, Kuetemeyer K, Heisterkamp A, Morgner U. Superresolved Femtosecond Laser Nanosurgery of Cells. Biomed Opt Express. 2011;2(2):264-71.

    Muller O, Donner S, Klinder T, Dragon R, Bartsch I, Witte F, Kruger A, Heisterkamp A, Rosenhahn B. Model Based 3d Segmentation and Oct Image Undistortion of Percutaneous Implants. Med Image Comput Comput Assist Interv. 2011;14(Pt 3):454-62.

    Lorbeer RA, Heidrich M, Lorbeer C, Ramirez Ojeda DF, Bicker G, Meyer H, Heisterkamp A. Highly Efficient 3d Fluorescence Microscopy with a Scanning Laser Optical Tomograph. Opt Express. 2011;19(6):5419-30.

    Kuetemeyer K, Lucas-Hahn A, Petersen B, Niemann H, Heisterkamp A. Femtosecond Laser-Induced Fusion of Nonadherent Cells and Two-Cell Porcine Embryos. J Biomed Opt. 2011;16(8):088001.

    Kuetemeyer K, Kensah G, Heidrich M, Meyer H, Martin U, Gruh I, Heisterkamp A. Two-Photon Induced Collagen Cross-Linking in Bioartificial Cardiac Tissue. Opt Express. 2011;19(17):15996-6007.

    Kensah G, Gruh I, Viering J, Schumann H, Dahlmann J, Meyer H, Skvorc D, Bar A, Akhyari P, Heisterkamp A, Haverich A, Martin U. A Novel Miniaturized Multimodal Bioreactor for Continuous in Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation. Tissue Eng Part C Methods. 2011;17(4):463-73.

    Kalies S, Kuetemeyer K, Heisterkamp A. Mechanisms of High-Order Photobleaching and Its Relationship to Intracellular Ablation. Biomed Opt Express. 2011;2(4):805-16.

    Heinemann D, Schomaker M, Motekaitis D, Krawinkel J, Killian D, Escobar HM, Junghanß C, Heisterkamp A, editors. Gold Nanoparticle Mediated Cell Manipulation Using Fs and Ps Laser Pulses for Cell Perforation and Transfection. 2011.

    Heidrich M, Kuhnel MP, Kellner M, Lorbeer RA, Lange T, Winkel A, Stiesch M, Meyer H, Heisterkamp A. 3d Imaging of Biofilms on Implants by Detection of Scattered Light with a Scanning Laser Optical Tomograph. Biomed Opt Express. 2011;2(11):2982-94.

    2010

    Kuetemeyer K, Rezgui R, Lubatschowski H, Heisterkamp A. Influence of Laser Parameters and Staining on Femtosecond Laser-Based Intracellular Nanosurgery. Biomed Opt Express. 2010;1(2):587-97.

    Kuetemeyer K, Lucas-Hahn A, Petersen B, Lemme E, Hassel P, Niemann H, Heisterkamp A. Combined Multiphoton Imaging and Automated Functional Enucleation of Porcine Oocytes Using Femtosecond Laser Pulses. J Biomed Opt. 2010;15(4):046006.

    Baumgart J, Bintig W, Ngezahayo A, Lubatschowski H, Heisterkamp A. Fs-Laser-Induced Ca2+ Concentration Change During Membrane Perforation for Cell Transfection. Opt Express. 2010;18(3):2219-29.

    2009

    Ngezahayo A, Baumgart J, Przemeck S, Kutemeyer K, Kruppe L, Witte F, Bintig W, Lubatschowski H, Heisterkamp A: Intracellular manipulation of single cells using ultrashort laser pulses: mitochondria and cytoskeleton, Eur Cell Biol. 2009;88(Suppl. 59), 76-76.

    Schomaker M, Baumgart J, Ngezahayo A, Bullerdiek J, Nolte I, Murua-Escobar H, Lubatschowski H, Heisterkamp A, editors. Nanoparticle Mediated Laser Cell Perforation. 2009.

    Schomaker M, Baumgart J, Ngezahayo A, Bullerdiek J, Nolte I, Murua Escobar H, Lubatschowski H, Heisterkamp A, editors. Plasmonic Perforation of Living Cells Using Ultrashort Laser Pulses and Gold Nanoparticles. 2009.

    Kütemeyer K, Lucas-Hahn A, Petersen B, Hassel P, Lemme E, Niemann H, Heisterkamp A, editors. Femtosecond Laser Based Enucleation of Porcine Oocytes for Somatic Cell Nuclear Transfer. 2009.

    Kuetemeyer K, Baumgart J, Lubatschowski H, Heisterkamp A. Repetition Rate Dependency of Low-Density Plasma Effects During Femtosecond-Laser-Based Surgery of Biological Tissue. Applied Physics B. 2009;97(3):695-9.

    Baumgart J, Kuetemeyer K, Bintig W, Ngezahayo A, Ertmer W, Lubatschowski H, Heisterkamp A. Repetition Rate Dependency of Reactive Oxygen Species Formation During Femtosecond Laser-Based Cell Surgery. J Biomed Opt. 2009;14(5):054040.

    2008

    Baumgart J, Bintig W, Ngezahayo A, Willenbrock S, Murua Escobar H, Ertmer W, Lubatschowski H, Heisterkamp A. Quantified Femtosecond Laser Based Opto-Perforation of Living Gfshr-17 and Mth53 a Cells. Opt Express. 2008;16(5):3021-31.

    2007

    Heisterkamp A, Baumgart J, Martin U, Ngezahayo A, Murua Escobar H, Nolte I, Lubatschowski H, Laser nanosurgery for stem cell research, Proceedings of LIM, 2007.

    Heisterkamp A, Baumgart J, Maxwell IZ, Ngezahayo A, Mazur E, Lubatschowski H. Fs-Laser Scissors for Photobleaching, Ablation in Fixed Samples and Living Cells, and Studies of Cell Mechanics. Methods Cell Biol. 2007;82:293-307.

    Baumgart J, Bintig W, Ngezahayo A, Ertmer W, Lubatschowski H, Heisterkamp A, editors. Live Cell Opto-Injection by Femtosecond Laser Pulses. 2007.

    Arnold CL, Heisterkamp A, Ertmer W, Lubatschowski H. Computational Model for Nonlinear Plasma Formation in High Na Micromachining of Transparent Materials and Biological Cells. Opt Express. 2007;15(16):10303-17.

    Arnold CL, Ertmer W, Lubatschowski H, editors. Modeling of Ultrashort Pulse Propagation and Nonlinear Plasma Formation in Transparent Kerr Media Using Realistic Initial Conditions. 2007.

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