Single Molecule Holography Realized

I am very grateful that I could join, maybe one of the most exciting experimental efforts recently. It goes back to Denis Gabor, the inventor of holography, who really proposed an idea to improve electron microscopy (D. Gabor, A New Microscopic Principle, Nature 161, 777-778 (1948)).

Above is shown what Gabor suggested. A coherent point emitter shines electrons onto a suspended object and the a screen record the pattern that is formed by the unscattered wave interfering with the scattered part of the beam. The pattern is called the hologram. In it each point of the object creates an image that looks like a Fresnel lens. This kind of lens illuminated with light bundles it into one point again, by diffraction not refraction. And this is how the holographic image can be reconstructed, a hologram is illuminated with again coherent light and the object reappears.

Gabors idea was realized with light once the laser was invented (image below). For a holographic electron microscope there was no source and no sample holder at the time. These problems have now been solved and I had to chance to take part in the endeavor and deposit folded proteins onto the sample holder of freestanding graphene to be imaged in the holographic microscopy, with the images nowadays reconstructed in-silico.

Scheme of the holographic microscope. Below, a hologram and the reconstructed image of the protein BSA (scalebar 2nm).

Hans-Werner Finks group at the University of Zuerich built the holographic microscope for electrons. The emitter is a very sharp metal tip, the sample holder is ultrapure, freestanding graphene. And the molecule is placed on the surface with preparative mass spectrometry, hence with my ion beam deposition instrument.

Just now we published this in PNAS:

J.-N. Longchamp, S. Rauschenbach, S. Abb, C. Escher, T. Latychevskaia, K. Kern & H.-W. Fink: Imaging Proteins at the Single Molecule Level. Proc. Natl. Acad. Sci. U.S.A. doi:10.1073/pnas.1614519114 (2017)

and there was a nice accompanying article, nicely explaining the implications:

F. Forneris & A. Mattevi: Expanding the structural biology toolbox with single-molecule holography. Proc. Natl. Acad. Sci. U.S.A. (2017)

And also a few other outlets reported

NZZ article

MPG press release



Sequence Controlled Self-Assembly

Look at this molecular network. It is so nice. And it is quite large too. The pores are more than 2nm wide. Each hexagon is build from 6 dimers of Angiotensin II. Please look in our latest publication for the precise structure (

The idea to build these networks and tailor their structure and ultimately their properties is around for a while. However, when you only have the molecule, it is next to impossible to predict the structure or the properties you will get. This gets even worse, of the molecules are large and functional. And then, in addition, the synthesis get more and more complicated, if for instance one would want to include a small modification.


Not so with peptides. Here you can order a sequence online and because the synthesis is universal and done by robots, they are quite cheap. In our paper we saw that we can do a similar trick as nature: We change the sequence and get a different structure. Not too surprising, true, but we can now work a lot of different sequences and maybe finally learn how to design molecular networks.

see also:

electrospray ion beam deposition (ES-IBD) source (short version)

Our experiment consists of two parts: (1) the deposition source and (2) the tunneling microscope with the sample preparation.

Here I briefly introduce the deposition source, that we use to deposit nonvolatile molecules onto surfaces in ultrahigh vacuum (UHV). It is a differentially pumped apparatus consisting of six differential pumping stages starting at 0.1 mbar and reaching to 1e-11 mbar in the UHV deposition chamber.

Scheme of the ES-IBD setup

Fig. 1: Scheme of the ES-IBD setup

everything starts with the spray source (1) at ambient pressure. Sometimes we use curtain gas (2) to dry the droplets and help the electrospray desolvation. The ions enter the vacuum trough a capillay (3). In the first and second vacuum chamber they are bundeled by RF ion optics, one ion funnel (4) and one quadrupole (5). The next quadrupole (6) in in high vacuum, so no more collimation is possible, but we use it for mass selection. Further throughout the machine we use electrostatic lenses (7) to focus the beam through the apertures (8). We have a time-of-flight (TOF) mass spectrometer (9) to measure the chemical composition and then we can deposit: in high vacuum (10) for ex situ analysis, in a vacuum suitcase (11) to transfer the sample to another UHV instrument, and finally in UHV (12) to move the sample in our own STM.

More details in the future.