An interview with Sacha De Carlo, Ph.D., Business Development Manager EM, DECTRIS Ltd., Baden
Counting individual photons has revolutionized the way we detect X-rays, and now the technology can do the same for electron microscopy. DECTRIS Business Development Manager EM Sacha De Carlo answers questions about using hybrid pixel detectors in EM applications.
What is Hybrid Photon Counting (HPC)?
The term “hybrid” denotes the presence of two layers as opposed to a monolithic active pixel sensor: a semiconductor layer that is fabricated separately from the readout ASIC (Application-Specific Integrated Circuit) underneath, but physically connected to it by a bump-bonding process.
Hybrid pixel detectors were first introduced to the high-energy physics community in 1985 and were later optimized for X-ray crystallography and related applications, where counting single X-ray photons that impinge on the detector revolutionized the field of protein structure determination at synchrotrons worldwide—and, later, in laboratory X-ray-based techniques.
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Image credits: DECTRIS
How is HPC relevant to electron microscopy?
It turned out that HPC detectors can count electrons very efficiently as well. Single-electron counting is required for near-ideal Detective Quantum Efficiency (DQE), a figure of merit that is often used together with the Modulation Transfer Function (MTF) to assess the quality of a detector. Thus, a near-ideal DQE (i.e. close to 100% efficiency) strongly impacts the quality of the data that the detector generates.
The fact that each pixel is an effective electron counter influences the readout speed, and with dedicated electronic boards, large-area 2D arrays can be made and read out frame by frame, thus reaching up to hundreds of kHz—depending, of course, on the size of the detector array and the bit depth of the data that are being acquired.
What makes HPC better than other technologies for electron microscopy?
Hybrid pixel technology offers several advantages over other detector technologies that are used in Electron Microscopy, namely advantages in dynamic range, speed, and radiation hardness. Monolithic Active Pixel Sensors (MAPS) have revolutionized cryo-electron microscopy in the past few years because, when used with very low electron fluxes (biological macromolecules are beam-sensitive objects, thus “low-dose” exposures are required), they are able to count single electrons, which dramatically improves the detection efficiency, ultimately increasing the signal over the detector’s noise.
With that said, however, the MAPS detectors that are currently on the market are not suitable for materials science, as they saturate too quickly when higher electron fluxes are used. In other words, their dynamic range is rather poor. HPC detectors, by contrast, offer a much higher count-rate capability. Our latest EIGER2 technology, for instance, offers count-rates per pixel that are 4 orders of magnitude better, and with two 16-bit counters per pixel, the dynamic range is much higher, making DECTRIS HPC detectors suitable not only for any diffraction-based study, STEM, or Ptychography, but also for very fast imaging, as required for in-situ TEM imaging.
Its thick sensor makes HPC technology impervious to the direct electron beam, rendering HPC detectors more radiation-hard than MAPS detectors, where a direct diffraction beam is often blocked by the hardware or software to prevent the detector from being damaged.
Can you give examples of the successful use of HPC in electron microscopy?
Since 2016, DECTRIS has collaborated with various academic research groups and industry partners through loaning and testing detector prototypes that were designed specifically for EM. On one hand, it allows our partners to convince themselves of the advantages of our HPC technology, and on the other hand, it allows us to receive immensely valuable feedback to improve our product development and—in the case of newly published data—use as marketing material.
We have worked on several fronts. With Dr. Tim Grüne and Julian Wennmacher, for example, we first demonstrated the suitability and superior performance of our HPC detectors for electron diffraction.
Together with the NION Company (Kirkland, WA, U.S.A.) we demonstrated the suitability of our new EIGER2 detectors for Electron Energy Loss Spectroscopy (EELS), since they allow for fast and simultaneous recording of the intense Zero-Loss peak while maintaining their single-electron counting capabilities throughout the entire energy spectrum.
In collaboration with Drs. Richard Henderson (a 2017 Nobel Prize winner in Chemistry) and Chris Russo, both at the MRC Laboratory of Molecular Biology in Cambridge (U.K.), we provided evidence that HPC technology is also promising for the life science single-particle cryoEM community. Indeed, Drs. Henderson and Russo were able to resolve the structure of a small macromolecule (DPS, 8 nm in diameter) down to a 3.4 Å resolution while using low-electron energy (100 kV). This is very important, as it may be the spark that is needed to move the life science EM community towards a lower cost per structure, thus increasing the potential of expanding single-particle cryoEM to every structural biology lab around the world while keeping very high-end instrumentation concentrated in specialized shared facilities with user access, similar to contemporary synchrotron facilities.
What does the future look like for HPC in electron microscopy?
Given that our pixels can count more than 10 million incoming electrons per second, the future is surely very bright (pun intended). Jokes aside, we are already observing considerable improvements in our new detector technology’s data quality, acquisition speed, and ease of use (along with integration) in various cases, spanning from materials science to life science applications.
What is DECTRIS’ role in these developments?
We are confident that our new developments, which are going well beyond the newly launched EIGER2 product family, will attract much attention from EM manufacturers and their end-users. We are convinced that DECTRIS can become a trusted partner for the EM community while providing reliable and user-friendly detectors that are designed specifically to fulfill and exceed even the highest industry standards.
Where can our readers go to find out more?
About Sacha De Carlo
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Always passionate about electron microscopy, Sacha De Carlo started using it 25 years ago at the University of Lausanne, where he graduated with majors in Biology and Physics in 1998. Intrigued by three-dimensional models of viruses that had been obtained using cryo-electron microscopy, he obtained a Ph.D. in the lab of Nobel Prize winner Prof. Jacques Dubochet (2017, Chemistry). Sacha then continued his academic career in France (IGBMC, Strasbourg) and the U.S., completing postdocs in Berkeley (California) and Boulder (Colorado) which culminated in his obtaining a faculty position at CUNY in New York City.
Sacha left academia in 2011 and switched to industry, when he decided to work for one of the major electron microscope manufacturers, which is based in the Netherlands. There he was in charge of the life science applications team in the EMEAI Nanoport, a center of technical excellence that serves as a demo lab and training center for customers as well as employees.
Born in Locarno (CH), Sacha returned to his home country and joined DECTRIS in June 2016, assuming responsibility for business development in the area of electron microscopy. He is working closely with both the DECTRIS product development team and EM manufacturers to deliver the next generation of direct electron detectors to the EM community.
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