We employ Field Ion Microscopy and related techniques for fabricating and using electron and ion point sources. Coherent low-energy electron beams are used to acquire electron holograms of individual biological molecules which can be numerically reconstructed. More recently, we combined dedicated electron optical devices with our coherent electron beams to obtain over sampled coherent diffraction patterns from a single molecule. We expect that both methods eventually lead to new tools for structural biology on a single molecule level, free from disturbing radiation damage effects inherent to other radiation with sufficient short wavelengths and thus potential for atomic resolution.
For presenting a fragile single molecule to the coherent electron beam we structure free standing thin films with a focused gallium ion beam. Interfacing single molecules from the liquid phase to such nanometer-sized structures is another pre requisite before imaging by low energy electrons becomes possible. Fluorescent video microscopy allows us to observe and manipulate single DNA molecules already in the liquid phase and to explore the energetics of this important bio-polymer. Molecular biology expertise and tools for anchoring DNA and/or modifying the molecules according to our specific needs for imaging are provided to us by Clondiag Chip Technologies.
|