The Q-SORT project is working on developing a new generation of electron microscopes – so-called “Quantum Sorters”, able to probe delicate specimens with extremely low sample damage. The potential benefits of such tools include, but are not limited to, the ability to determine protein structures that could lead to new drug designs for healthcare and next-generation biomedicine.

For decades scientists, art-science buffs, and the wider public have marvelled at the beautiful worlds revealed by electron microscopy – from the hideous beauty of an insect’s mouthparts to the shimmering world of meta-materials at the molecular level. Modern machines can now fire powerful electron beams to produce images with single-atom resolution.

But electron microscopes are much more than simple imagers. Scientists can in fact use them to determine the composition of a sample or to probe its magnetic, mechanical, structural, or electronic properties. Their flexibility as tools of investigation has also made them precious allies for testing fundamental physics.

Electron microscopy is thus fundamental to unveil the smallest secrets of the natural world. (For an easy introduction to electron microscopy, see for example https://www.fei.com/introduction-to-electron-microscopy/history/and the following pages.)

One important issue in modern electron microscopy is that electron beams can damage samples as they strike them. This so-called “dose problem” is particularly serious when the sample is very delicate, like a protein for example. When imaging samples, the dose problem forces scientists to seek an awkward trade-off between resolution and sample integrity. Careful specimen handling is key in important research fields, such as biology and biochemistry, that typically feature delicate samples, due to their organic chemical make-up.

Q-SORT aims to develop radically new techniques to explore and study fragile specimens at the microscopic level, uncovering an array of information that was previously hidden.

Q-SORT exploits TEM (transmission electron microscopy), a technique in which a beam of electrons is passed through an ultra-thin slice of specimen to form an image on a CCD camera.

Unlike previous incarnations of this technology, Q-SORT takes advantage of recently-developed techniques that allow scientists to shape electron beams according to their needs: electron beams can be structured either by means of nanofabricated electron holograms or via electrostatic (or magnetostatic) lenses. These novel devices can also split the beam in its component quantum states, thus turning the TEM into what project scientists call a “quantum state sorter” or “quantum sorter”. These sorters can probe the properties of samples with very few electrons, allowing scientists to answer tricky questions about the specimens with maximum efficiency and extremely low damage.

The advantage of the sorter, compared to ‘traditional’ forms of TEM, stems from the idea of re-thinking the set-up of the electron microscope in order to optimise the extraction from the sample of a specific quantity of interest. This is achieved through the operation of sorting specific electron quantum states out of the electron beam, after it has interacted with the sample. Knowledge of this decomposition provides useful and often unique information about the sample.

Q-SORT’s primary goal is to develop and validate tools and techniques enabling researchers to perform quantum sorting. The Project is also pursuing their application to a selected number of systems of interest.

The successful marriage of the Sorter to cryomicroscopy is especially exciting. Cryomicroscopy is a technique generally used for biological specimens, in which a flash-frozen solution is fed into a TEM. In cryomicroscopy the techniques developed by Q-SORT can be used to recognise protein structures, symmetries, and orientations. These proteins can be cell-signalling molecules, or parts of membranes, which ultimately provide researchers with knowledge of how cells and tissues function. The new information gathered from quantum sorting could eventually be applicable in drug design for healthcare and next-generation biomedicine. Progress in the development of cryomicroscopy led to the Nobel Prize for Chemistry in 2017. Application of the Sorter to cryoTEM is one of the four objectives of Q-SORT.

Moreover, the Sorter is a multipurpose tool which will be useful in many other fields besides biochemistry. This new paradigm in measurement should allow researchers to map magnetism down to the atomic scale. It should also afford the investigation of various types of exotic electronic excitations (e.g. plasmons) in materials. Probing magnetic spin properties and the physics of plasmons is part of the four-fold goal of Q-SORT.

Besides the above three examples, the concept of a quantum sorter that extracts hidden information with maximum efficiency is of potential use in a variety of other applications and systems.

SCIENCE AND APPLICATIONS OF COHERENT ELECTRON BEAM MANIPULATION

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