Biological Nanoimaging

These pages represent the research interests of the biological nanoimaging research group at the Institute of Photonics Technology, the Department of Physical Chemisty at the FSU, Jena and the Randall Division of Cell and Molecular Biophysics, King's College London headed by Rainer Heintzmann.
The research focuses on developing (often high-resolution) techniques to measure multidimensional information in small biological objects such as cells, cellular organelles, molecules or other structures of interest.

Molecules interact in living cells at specific places (e.g. inside organelles) and often at well defined times (e.g. after stimulation with other molecules). Much biological research is now focused onto unravelling these details. Luckily there are a number of physical effects, which can be used to tell things apart, when one or multiple molecules are fluorescing (either by themselves or by having a specific fluorescent molecule (fluorophore) attached to them).
For a nice demonstration on different biological objects and their sizes, click here.

Recently a number of molecules have been found that can be switched between different fluorescent states by illumination at separate wavelengths. The transitions between the states can be driven into saturation. The arising non-linear dependencies offer the unique possibility of a theoretically unlimited optical resolution. Part of our work focuses on an experimental demonstration of high resolution based on these effects. To this aim we employ an imaging mode in which the sample is illuminated with a grid of very fine lines. This technique is called structured illumination microscopy (SIM).
This is an example comparing stuctured illumiination (left) and standard imaging (right) of muscle myofibrils acquired by Liisa Hirvonen in collaboration with Elisabeth Ehler.

Selected Recent Publications

  • M. Walde, J. Moneypenny, R. Heintzmann, G.E. Jones, S. Cox. Vinculin binding angle in podosomes revealed by high resolution microscopy. PLoS One e88251-1, 2014.
  • K. Wicker, R. Heintzmann.Resolving a misconception about structured illumination. Nature Photonics 342, 2014.
  • K. Wicker, O. Mandula, G. Best, R. Fiolka, R. Heintzmann. Phase optimisation for structured illumination microscopy. Optics Express 2032, 2013.
  • S. Cox, E. Rosten, J. Monypenny, T. Jovanovic-Talisman, D. T. Burnette, J. Lippincott-Schwartz, G. E. Jones und R.Heintzmann. Bayesian localization microscopy reveals nanoscale podosome dynamics.  Nature Methods 9, 195-200 , 2012.
  • R. Heintzmann, Correcting distorted optics: back to the basics, Nature Methods 7, 108-110, 2010.
  • R. Heintzmann, M.G.L. Gustafsson, The requirements for sub-diffraction resolution in continuous samples, Nature Photonics 3, 362-364, 2009.
  • A. Hoppe, S. L. Shorte, J. A. Swanson, R. Heintzmann, D-FRET Reconstruction Microscopy for Analysis of Dynamic Molecular Interactions in Live Cells, Biophysical Journal 95, 400-418, 2008.
  • K. Wicker and R. Heintzmann, Interferometric resolution improvement for confocal microscopes, Optics Express 15, 12206- 12216, 2007.
  • R. Heintzmann and P.A. Benedetti, High-Resolution Image Reconstruction in Fluorescence Microscopy with Patterned Excitation, Applied Optics, 45, 5037-5045, 2006.
  • D.S. Lidke, P. Nagy, R. Heintzmann, D.J. Arndt-Jovin, J.N. Post, H. Grecco, E.A. Jares-Erijman and T.M. Jovin. Quantum dot ligands provide new insights in receptor-mediated signal transduction. Nature Biotechnology, 22, 198-203, 2004.
  • R. Heintzmann., K.A. Lidke and T.M. Jovin. Double-pass Fourier transform imaging spectroscopy. Optics Express. 12, 753-763, 2004.
  • R. Heintzmann and C. Cremer. Axial tomographic confocal fluorescence microscopy, J. Microsc., 206, 7-23, 2002.
  • R. Heintzmann, T.M. Jovin and C. Cremer. Saturated patterned excitation microscopy (SPEM) - a novel concept for optical resolution improvement. J. Opt. Soc. Am. A, 19, 1599-1609, 2002.