Abstract
The recent interest in 100 keV cryo-electron microscopy has created a demand for specialized detectors that maximize information per unit dose while remaining cost-effective. We present a hybrid-pixel electron counting detector system tailored for cryo-electron microscopy applications using 100 keV electron energy. The demonstrator uses a 500 μm-thick, chromium-compensated gallium arsenide (high-Z) sensor with a 36 μm pixel pitch arranged in a seamless 1266 × 1057 matrix. Its low-noise front-end electronics achieve a threshold energy as low as 2.5 keV and include an in-pixel hit digitization mechanism. The matrix is read out at a speed of 7.2 kfps and has a counter depth of 1 bit, allowing for an incoming rate of 28 e/s/pix at 5% coincidence loss. The imaging performance is evaluated in standard counting and super-resolution acquisition modes. Thanks to a custom-developed super-resolution algorithm, the detective quantum efficiency at zero-frequency amounts to 0.96 and at the physical Nyquist frequency to 0.56, resulting in an effective pixel size of 27.5 μm. Experimental data are complemented and critically compared with Monte Carlo simulations and analytical models.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
The super-resolution algorithm described in this work is part of a proprietary software package developed by DECTRIS Ltd. While the underlying mathematical principles are summarized in the Methods section and detailed in the provided literature reference, the source code is not publicly available. Requests for access to the algorithm for non-commercial replication purposes may be directed to the corresponding author and will be evaluated on a case-by-case basis.
References
Kühlbrandt, W. The resolution revolution. Science 343, 1443–1444 (2014).
Renaud, J.-P. et al. Cryo-EM in drug discovery: achievements, limitations and prospects. Nat. Rev. Drug Discov. 17, 471–92 (2018).
Callaway, E. Revolutionary cryo-EM is taking over structural biology. Nature 578, 201 (2020).
McMullan, G., Faruqi, A. R., Clare, D. & Henderson, R. Comparison of optimal performance at 300keV of three direct electron detectors for use in low dose electron microscopy. Ultramicroscopy 147, 156–63 (2014).
Deptuch, G. et al. Direct electron imaging in electron microscopy with monolithic active pixel sensors. Ultramicroscopy 107, 674–84 (2007).
Guerrini, N. et al. A high frame rate, 16 million pixels, radiation hard CMOS sensor. J. Instrum. 6, C03003 (2011).
Faruqi, A. R. Direct electron detectors for electron microscopy. Adv. Imaging Electron Phys. 145, 55–93 (2007).
van Schayck, J. P., Zhang, Y., Knoops, K., Peters, P. J. & Ravelli, R. B. G., Integration of an Event-driven Timepix3 Hybrid Pixel Detector into a Cryo-EM Workflow, Microsc. Microanal. 29, 352–363 https://doi.org/10.1093/micmic/ozac009. (2023).
Tate, M. W. et al. High dynamic range pixel array detector for scanning transmission electron microscopy. Microsc. Microanal. 22, 237–249 (2016).
Philipp, H. T. et al. Very-high dynamic range, 10,000 frames/second pixel array detector for electron microscopy. https://doi.org/10.1017/S1431927622000174.
Paton, K. A. et al. Quantifying the performance of a hybrid pixel detector with GaAs:Cr sensor for transmission electron microscopy. Ultramicroscopy 227, 113298 (2021).
McMullan, G. et al. Structure determination by cryoEM at 100 keV, 2023 PNAS, 120 (49) e2312905120, https://doi.org/10.1073/pnas.2312905120.
Peet, M. J., Henderson, R. & Russo, C. J. The energy dependence of contrast and damage in electron cryomicroscopy of biological molecules. Ultramicroscopy 203, 125–31 (2019).
Donath, T. et al. EIGER2 hybrid-photon-counting X-ray detectors for advanced synchrotron diffraction experiments, J. Synchrotron Rad. 30, https://doi.org/10.1107/S160057752300454X (2023).
Motta Alves, G. et al. The Dublin Lens: A Cc =1.0 mm Objective Lens Intended for CryoEM at 100 keV. Methods Microscopy https://doi.org/10.1515/mim-2025-0019 (2025).
Zambon, P. Enhanced DQE and subpixel resolution by single-event processing in counting hybrid pixel electron detectors. A Simul. Study Front. Phys. 11, 1123787 (2023).
Takahashi, T. & Watanabe, S. Recent progress in CdTe and CdZnTe detectors. IEEE Trans. Nucl. Sci. 48, 4 (2001).
van Schayck, J. P. et al. Sub-pixel electron detection using a convolutional neural network. Ultramicroscopy 218, 113091 (2020).
Zambon, P. Modeling the impact of coincidence loss on count rate statistics and noise performance in counting detectors for imaging applications. Front. Phys. 12, 1408430 (2024).
Ramo, S. Current induced by electron motion. Proc. I. R. E 27, 584–5 (1939).
Ponchut, C. et al. Characterisation of GaAs:Cr pixel sensors coupled to Timepix chips in view of synchrotron applications, 19th International Workshop on Radiation Imaging Detectors https://doi.org/10.1088/1748-0221/12/12/C12023 2-6 July (2017).
Zambon, P. Simulation of polarization dynamics in semi-insulating, Cr-compensated GaAs pixelated sensors under high x-ray fluxes. AIP Adv. 11, 075006 (2021).
Zambon, P., Radicci, V., Rissi, M. & Broennimann, C. A fitting model of the pixel response to monochromatic X-rays in photon counting detectors. Nucl. Inst. Methods Phys. Res. A 905, 188–192 (2018).
Ayzenshtat, G. I. et al. GaAs structures for x-ray imaging detectors. Nucl. Instrum. Methods Phys. Res. A 466, 25–32 (2001).
Ferrari, A., Sala, P. R., Fasso, A., Ranft, J. Fluka: a multi-particle transport code (2005). Program version [INFN-TC-05-11] https://doi.org/10.5170/CERN-2005-010 (2005).
Böhlen, T. et al. The FLUKA code: developments and challenges for high energy and medical applications. Nucl. Data Sheets 120, 211–4 (2014).
Stierstofer, K. et al. Modeling the DQE(f) of photon-counting detectors: impact of the pixel sensitivity profile. Phys. Med. Biol. 64, 105008 (2019).
Hovington, P., Drouin, D., Gauvin, E. R. “CASINO: A New Monte Carlo Code in C Language for Electron Beam Interaction - Part I: Description of the Program," Scanning, vol. 19, n. 1, pp. 1–14, https://doi.org/10.1002/sca.4950190101 (1997).
Demers, H. et al. “Three-dimensional electron microscopy simulation with the CASINO Monte Carlo software," Scanning, vol. 33, n. 3, pp. 135–146, https://doi.org/10.1002/sca.20262 (2011).
Bath, M. Evaluating imaging systems: practical applications. Radiat. Prot. Dosim. 139, 26–36 (2010).
McMullan, G. et al. Electron imaging with Medipix2 hybrid pixel detector. Ultramicroscopy 107, 401 (2007).
Acknowledgements
We would like to thank R. Henderson, G. McMullan, and C. Russo from the MRC Laboratory of Molecular Biology, Cambridge (UK), for the many fruitful discussions and for their inspiring role in the 100 keV consortium. We would also like to thank M. Huber from Helbling Group, Zürich (Switzerland), for the careful design of the Faraday cup.
Author information
Authors and Affiliations
Contributions
P.Z. contributed to conceptualization, methodology, software development, investigation, data analysis, and wrote the manuscript. G.V.M. contributed to methodology and investigation. R.S., N. L., and A.D. were responsible for ASIC design. A.J. and P.W. contributed to sensor development and hardware integration. T.S., P.A.J., S.B., and M.M. contributed to hardware integration and technical implementation. S.F.-P. and S.K. contributed to project administration and resources. C.S.-B. provided supervision and project guidance. All authors reviewed and edited the final manuscript.
Corresponding author
Ethics declarations
Competing interests
All authors are employees of DECTRIS Ltd., a commercial manufacturer of detector systems. This represents a financial competing interest as the results presented could potentially influence the commercial value of the company’s products. The authors declare no other financial or non-financial competing interests.
Peer review
Peer review information
Communications Engineering thanks David Pennicard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editors: [Damien Querlioz] and [Wenjie Wang].
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Zambon, P., Montemurro, G.V., Fernandez-Perez, S. et al. A gallium arsenide hybrid-pixel counting detector for 100 keV cryo-electron microscopy. Commun Eng (2026). https://doi.org/10.1038/s44172-026-00607-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s44172-026-00607-6
