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Stable Imaging Arrangement and Fluorescent Microscope




Steven Chu and Alexandros Pertsinidis from Berkeley Lab have invented the first fluorescent microscope capable of measuring distances between individual living biomolecules at subnanometer resolution in real time and in their biological context, e.g., in solution. This represents precision and accuracy levels an order of magnitude greater than the state-of-the-art. The invention is sensitive enough to image individual protein molecules, typically ~5 nm in size, and can therefore provide a molecule-specific overview of the entire protein complex. This information is essential for studying the effect large protein complexes have on biological functions such as cancer cell proliferation and cell-cell communication.

The technology’s subnanometer resolution is a result of superior stability made possible by a novel optical trapping laser that locks the position and orientation of the object under investigation. By suppressing Brownian motion, the tendency of a sample kept in solution to drift in and out of a particular position, the Berkeley Lab invention can resolve distances as small as ~3 nm between fluorescent molecules with a precision and accuracy of <1 nm. Such fine resolution is significantly higher than conventional optical microscopes, which are limited by diffraction to a resolution of ~250 nm, and it surpasses emerging subdiffraction imaging techniques that have only achieved a resolution in the range of 15–20 nm. Additionally, the invention’s programmable feedback control mechanisms, which read and lock onto the coordinates of the fluorescent molecules, are 100 times more stable than those of conventional fluorescent microscopes. The invention can also be used to retrofit any commercial fluorescent microscope.

This novel microscope streamlines the time-consuming process of conventional optical and fluorescent microscopy techniques. By reducing the uncertainty of a distance between two fluorescent molecules to less than a nanometer, the invention minimizes imaging imperfections requiring post-processing corrections, making it possible for the first time to image live multi-component biological complexes in real time.

STATUS: Published Patent Application WO2010/065538 available at Available for licensing or collaborative research.

DEVELOPMENT STAGE: Proven principle. Additional R&D will be required to create an instrument prototype.


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