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Bright sub-20-nm cathodoluminescent nanoprobes for electron microscopy

Journal Article · · Nature Nanotechnology
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  1. Stanford Univ., CA (United States)
  2. Univ. of California, Berkeley, CA (United States)
  3. Stanford Univ., CA (United States); Georgia Inst. of Technology, Atlanta, GA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Stanford Univ., CA (United States); Hunan Univ., Changsha (China)
  6. Stanford Univ., CA (United States); Stellenbosch Univ. (South Africa)
  7. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  8. IBM Research, San Jose, CA (United States)

Electron microscopy has been integral in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. In this report, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results indicate that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible.

Research Organization:
Energy Frontier Research Centers (EFRC) (United States). Light-Material Interactions in Energy Conversion (LMI); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH), National Science Foundation (NSF)
Grant/Contract Number:
AC02-05CH11231; SC0001293
OSTI ID:
1542401
Journal Information:
Nature Nanotechnology, Journal Name: Nature Nanotechnology Journal Issue: 5 Vol. 14; ISSN 1748-3387
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (39)

Solid-to-Hollow Single-Particle Manipulation of a Self-Assembled Luminescent NaYF 4 :Yb,Er Nanocrystal Monolayer by Electron-Beam Lithography journal September 2009
Efficiency of Cathodoluminescence Emission by Nitrogen-Vacancy Color Centers in Nanodiamonds journal April 2017
Lanthanide upconversion nanoparticles and applications in bioassays and bioimaging: A review journal June 2014
Saturated Reconstruction of a Volume of Neocortex journal July 2015
Multicolor Electron Microscopy for Simultaneous Visualization of Multiple Molecular Species journal November 2016
A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy journal July 2017
Distinguishing signal from autofluorescence in cryogenic correlated light and electron microscopy of mammalian cells journal January 2018
Enhanced biological cathodoluminescence journal April 2008
Cathodoluminescence-Activated Nanoimaging: Noninvasive Near-Field Optical Microscopy in an Electron Microscope journal April 2015
Optimal Sensitizer Concentration in Single Upconversion Nanocrystals journal April 2017
A Generalized Ligand-Exchange Strategy Enabling Sequential Surface Functionalization of Colloidal Nanocrystals journal February 2011
Cathodoluminescence in a Scanning Transmission Electron Microscope: A Nanometer-Scale Counterpart of Photoluminescence for the Study of II–VI Quantum Dots journal November 2013
Controlled Synthesis and Single-Particle Imaging of Bright, Sub-10 nm Lanthanide-Doped Upconverting Nanocrystals journal February 2012
Recent advances in the optimization and functionalization of upconversion nanomaterials for in vivo bioapplications journal December 2013
Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy journal October 2012
Multiplexed ion beam imaging of human breast tumors journal March 2014
Correlative super-resolution fluorescence and metal-replica transmission electron microscopy journal January 2014
Directed evolution of APEX2 for electron microscopy and proximity labeling journal November 2014
Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics journal February 2015
Ultrahigh-throughput single-molecule spectroscopy and spectrally resolved super-resolution microscopy journal August 2015
Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots journal September 2005
Engineering bright sub-10-nm upconverting nanocrystals for single-molecule imaging journal March 2014
Tunable lifetime multiplexing using luminescent nanocrystals journal December 2013
Upconversion luminescence imaging of cells and small animals journal September 2013
Preparation of core-shell NaGdF4 nanoparticles doped with luminescent lanthanide ions to be used as upconversion-based probes journal June 2014
Chunkflow: hybrid cloud processing of large 3D images by convolutional nets journal March 2021
High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling journal August 2017
Correlative light and electron microscopy using cathodoluminescence from nanoparticles with distinguishable colours journal November 2012
Combinatorial approaches for developing upconverting nanomaterials: high-throughput screening, modeling, and applications journal January 2015
Intensities of Crystal Spectra of Rare‐Earth Ions journal August 1962
Upconverting core-shell nanocrystals with high quantum yield under low irradiance: On the role of isotropic and thick shells journal November 2015
An efficient and user-friendly method for the synthesis of hexagonal-phase NaYF 4 :Yb, Er/Tm nanocrystals with controllable shape and upconversion fluorescence journal July 2008
Optical Absorption Intensities of Rare-Earth Ions journal August 1962
Optical excitations in electron microscopy journal February 2010
Multicolor Cathodoluminescence Microscopy for Biological Imaging with Nanophosphors journal November 2011
Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. journal December 1978
Effect of particle size on labeling density for catalase in protein A-gold immunocytochemistry. journal January 1988
Dynamic autofluorescence imaging of intracellular components inside living cells using direct electron beam excitation journal January 2014
Optical excitations in electron microscopy text January 2009

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ColorEM: analytical electron microscopy for element-guided identification and imaging of the building blocks of life journal August 2018

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