A Metal Reducing Enzymatic Tag for Optical and Electron Microscopy

Colorado State University Background
In academic research and pharmaceutical R&D, there is a demand for high resolution, non-disruptive imaging modalities. Contrast ultimately defines the ability to distinguish a component of interest from background. The development of a cloneable, consistently sized, nanoparticle tag for microscopy represents a significant advancement in the field allowing for greater contrast and improved imaging throughout multiple modalities. Growing markets for both optical and electron microscopy represent significant opportunities for this technology. Higher throughput modalities such as flow cytometry are also experiencing significant growth, and this technology represents a significant improvement over the state of the art available to these three markets. Together these markets are projected to exceed a $10 billion valuation by 2020.
Technology Overview

A clonable marker for electron and optical microscopy. 
Allows for high resolution imaging using non-disruptive modalities
Can be readily adapted to flow cytometry
Potential to provide a platform for radio frequency interactions with a protein of interest.
Immediately applicable markets: academic research, pharmaceutical R&D

This technology, when paired with modern imaging techniques, can provide significant improvements in the targeted imaging of specific proteins or protein complexes. This can help elucidate interactions, localization, and functionality. This has the potential to be heavily utilized in academic and industry research for in vivo single cell-imaging via electron and optical microscopy. Conceivably, this technology can be packaged as a kit for utilization in microscopy. The MRE (metal reducing enzyme) that produces a “cloneable tag” could be provided as a plasmid to be inserted into a protein of interest by insertion into the genome of an organism. Upon insertion, the “cloneable tag” will allow for utilization of multiple microscopy modalities to assess biologic location and function of target proteins. This can provide high resolution 3D imaging, on the scale of single cells, as well as at the tissue and organism level. Further applications include remote perturbation of biologic function through radio frequency. This is achieved by utilizing inorganic nanoparticle antennae to locally produce heat and influence biological mechanisms.

Further Details
Thomas W. Ni, Lucian C. Staicu, Richard S. Nemeth, Cindi L. Schwartz, David Crawford, Jeffrey D. Seligman, William J. Hunter, Elizabeth A. H. Pilon-Smits and Christopher J. Ackerson. Progress toward cloneable inorganic nanoparticles. Nanoscale, 7, 17320-17327. 

Highly localized and specific signal enables high contrast, low background imaging at higher resolutions than current state of the art
Minimally disruptive sample preparation. Sample only needs treatment with an inorganic salt bath
Placement of clonable nanoparticles on proteins of interest allows for cryo-EM reconstruction of proteins that cannot be purified, a significant advantage over current methods.
The metal-reducing capabilities of the tagged proteins enable visualizations of protein functions and localizations within a whole organism via CT scanning. This application would require some adaptation of the technology, and FDA clearance, but would allow expansion into the medical imaging market, valued at $34 billion4.
Allows for atomic placement within biomolecular models.
These cloneable nanoparticles allow for unambiguous correlation of discrete protein densities with x-ray structures and making placement of atomic structures within cells possible.

The MRE can be utilized as a radio frequency receptive antenna, which would allow directed heat delivery and control of function to specific proteins. This has potential applications in personalized medicine, cancer biotherapies, and gene therapies if the technology can be adapted and approved for clinical trials.


Commercial partner for kit generation for microscopy techniques
Licensing partner

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