Direct Imaging for Electron Microscopy

 

This research developed a new CMOS sensor array for direct electron microscope imaging. It replaces the previous-generation film or scintillating phosphor screen and charged-coupled-device (CCD) combinations, providing several key advantages: It is of higher resolution since it takes images using the electrons directly, without the blurring that a phosphor screen causes. It is faster than typical CCD readout devices, and it is more radiation tolerant. Designs with up to 16 million 5 by 5 micrometer pixels have been created, including on-chip column-parallel analog to digital conversion and fast double-buffered readout. This new instrument will significantly improve the power and resolution of emerging Cryo-EM and other techniques in the study of viruses, proteins and macromolecules.


The above photo shows a 1 M-pixel detector array. Its array of 5x5 micrometer pixels makes a beautifully-colorful diffraction pattern.


Related publications:


  1. •[J51] L. Jin, A.C. Milazzo, S. Kleinfelder, S. Li, P. Leblanc, F. Duttweiler, J.C. Bower, S.T. Peltier, M. Ellisman, N.H. Xuong, “Applications of DirectDetection Device in Transmission Electron Microscopy,” Journal of Structural Biology, Vol 161, no. 3, pp 352-358, March 2008.

  2. •[J50] S. Kleinfelder, S. Li, Y. Chen, “Optimization of monolithic charged-particle sensor arrays,” Nuclear Instruments and Methods in Physics Research A, vol. 579, no. 2, pp. 695-700, Sept. 2007.

  3. •[J49] S. Li, S. Kleinfelder, "Direct charged-particle imaging sensors," Nuclear Instruments and Methods in Physics Research A, vol. 579, no. 1, pp. 227-230, Aug. 2007.

  4. •[J46] A.C. Milazzo, P. Leblanc, F. Duttwieler, Lian-Jin, J. C. Bouwer, S. Peltier, M. Ellisman, F. Bieser, H. S. Matis, H. Wieman, P. Denes, S. Kleinfelder, N-H Xuong, "Active Pixel Sensor Array as a Detector for Electron Microscopy,” Ultramicroscopy, Vol. 104, Issue 2, pp 152-159, September 2005.

  5. •[J44] S. Kleinfelder, F. Bieser, Y. Chen, R. Gareus, H. S. Matis, M. Oldenburg, F. Retiere, H. G. Ritter, H. H. Wieman, E. Yamamoto, "Novel Integrated CMOS Sensor Circuits," IEEE Transactions on Nuclear Science, Vol. 51, No. 5, October 2004.

  6. •[J40] H. S. Matis, F. Bieser, S. Kleinfelder, G. Rai, F. Retiere, H. G. Ritter, K. Singh, S. E. Wurzel, H. Weiman, E. Yamamoto, “Charged Particle Detection using a CMOS Active Pixel Sensor,” IEEE Transactions on Nuclear Science, Vol. 50, No. 4, pages 1020-1025, August 2003.

  7. •[C54] S. Li, H. Matis, S. Kleinfelder, “Monte-Carlo Modeling of Monolithic CMOS Sensors for X-ray and Charged-Particle Imaging,” Proceedings of the SPIE, vol. 6707, 2007.

  8. •[C53] L. Jin, A. Milazzo, S. Kleinfelder, S. Li, P. Leblanc, F. Duttweiler, J. C. Bouwer, S. T. Peltier, M. Ellisman, N. Xuong, “The Intermediate Size Direct Detection Detector for Electron Microscopy,” Proceedings of the SPIE, Vol. 6501, 2007.

  9. •[C51] S. Li, S. Kleinfelder, L. Jin, N. H. Xuong, “A CMOS sensor for nano-imaging,” Proceedings of 2006 IEEE Conference on Nanotechnology, Cincinanati, Ohio, USA, July 2006.

  10. •[C50] S. Li, S. Kleinfelder, “A new direct electron imaging system for biomedical applications,” Proceedings of NanoBio2006: Frontiers in Biomedical Devices Conference, June 8-9, 2006, Irvine, California, USA, in press.

  11. •[C49] S. Li, J. Bouwer, F. Duttweiler, M. Ellisman, L. Jin, P. Leblanc, A. Milazzo, S. Peltier, N. Xuong, S. Kleinfelder, “A new direct detection camera system for electron microscopy,” Proceedings of the SPIE, Electronic Imaging Science and Technology, in press.

  12. •[C45] N. Xuong, A. Milazzo, M. Ellisman, S. Peltier, J. Bouwer, F. Duttweiler, P. Leblanc, J. Matteson, H. Wieman, H. Matis, F. Bieser, P. Denes, S. Kleinfelder, “First use of a high-sensitivity active pixel sensor array as a detector for electron microscopy,” Proceedings of the SPIE, Electronic Imaging Science and Technology, Vol. 5301, pp 242-249, January 2004.

  13. •[P16] N. Xuong, L. Jin, S. Kleinfelder, S. Li, P. Leblanc, F. Duttweiler, J. Bouwer, S. Peltier, A. Milazzo, M. Ellisman, “Future Directions for Camera Systems in Electron Microscopy,” book chapter in "Cellular Electron Microscopy," Volume 79 of Methods in Cell Biology, edited by J. Richard McIntosh, to be published January 2007.

National Institutes of Health, with U.C. San Diego

 
 

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