Structural Biology on the Truly Single Molecule Level

EPSI - Electron Point Source Instruments, a Zurich based company, aims at developing the first tool for structural analysis of individual biomolecules at atomic resolution. The goal of EPSI is to develop a low-voltage electron microscopy technology based on the quantum mechanical wave nature of electrons. Since coherent low-energy electrons do not impose radiation damage to biological molecules, EPSI aims at realizing the very first tool for structural analysis on individual biomolecules at atomic resolution. The business idea of EPSI is to offer the structural decoding to pharmaceutical companies, academic and government institutions and thus provide support for their intentions like rational drug design or the like.

The technological lead of EPSI is based on the unique innovations listed below:

  • Atomic dimension source for low-energy electrons for coherent imaging analogous to a Laser in coherent light optics but with wavelengths reduced by a factor of ten thousands
  • A technology to manufacture micron-sized electron lenses exhibiting reduced lens aberrations by a factor of thousand
  • A technology to manufacture ultraclean freestanding graphene, an atomically thin two-dimensional material, serving as the ultimate electron microscopy slide for depositing and imaging individual biomolecules
  • Novel algorithms and associated numerical routines for phase retrieval in holography and coherent diffraction

Low-energy electrons are the only radiation with Angstrom wavelength that does not cause damage to biological molecules; a unique feature of slow electrons. To present individual molecules to the coherent electron wave front, a patented method of obtaining ultraclean freestanding graphene is vital to fix a protein in space for structural analysis. By combining low-energy electron holography and coherent diffraction, more than half a million unit cells of graphene could thus be imaged in one shot demonstrating 2 Angstrom resolution inherent to our novel technology. In contrast to conventional structural biology tools, all relying on averaging over many molecules, our technology will now make it possible to image individual molecules.
To summarize, the coherence of electron point source beams, miniaturized electron optics, ultraclean graphene to fix a protein in space and novel reconstruction algorithms will be unique features of EPSI with unprecedented performance compared to existing technologies. These key assets of EPSI shall ensure the realization of the first instrumentation for routine structural biology at the truly single molecule level. We expect a breakthrough in the respective markets since single protein structural analysis at atomic resolution has always been aspired in the pharmaceutical industry having regard to rational drug design. In particular those proteins that do not readily crystallize or where knowledge of conformational changes within the protein is of importance will now also be accessible for structural analysis on the atomic scale.

Further reading:

  • Imaging proteins at the single-molecule lev - link
  • New Scientist: First ever pictures of single proteins thanks to graphene sheet - link
  • List of projects and publications related to Low-Energy Electron Holography, Coherent Diffraction and related subjects - link

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