3-D Imaging and Mass Spectrometry of Mammalian Cells

Background:
The National Cancer Institute's Cell Biology Laboratory is seeking statements of capability or interest from parties interested in collaborative research and/or partnership agreements to further develop and commercialize tools for three-dimensional mapping of cells and tissues at nanometer resolution for applications in cytology, oncology, cell biology and other fields that require in-depth understanding of cellular mechanisms.

Understanding the hierarchical organization of molecules, multi-protein assemblies, organelles and networks within the interior of a eukaryotic cell is a challenge of fundamental interest in biology. There is a genuine need for tools that can rapidly provide high resolution 3-D images of the interior of eukaryotic cells combined with proteomic information. One such technology is Ion Abrasion Scanning Electron Microscopy (IA-SEM). IA-SEM combines the imaging power of scanning electron microscopes with the capability of focused ion beams to abrade the surface of bulk specimens in a controlled manner.

Technology:
Available for licensing and commercial development is a new automated approach to cellular imaging that combines methods for 3D visualization of cellular organelles and protein expression at nanometer (nm) resolution using Ion Abrasion Scanning Electron Microscopy (IA-SEM) with novel approaches for determining spatial distribution of ion, metabolite and protein composition. A variety of strategies are under development to explore 3D distribution of cellular components with the goal of establishing rapid diagnostic methods for determining protein, metabolite and drug localization in the sub-cellular space. This information is vital in the identification of drug targets as well in the drug discovery process.

Value Proposition:

• Ability to rapidly create three-dimensional cellular images .
• Ability to map cells and tissues at nanometer resolution.

Further R&D Needed:
Development of commercially-viable three-dimensional protein mapping

R&D Status:
Pilot experiments are ongoing for the development and optimization of the technology using commercially available components. Clinical applications for the diagnosis of tissue specimens are also being explored.

IP Status:
U.S. Provisional Applications 60/970,070 and 60/974,686 filed Sept. 2007.

Publications:

1. Heymann, J., Hayles, M., Gestmann, I., Giannuzzi, L., Lich, L., and Subramaniam, S. (2006) Site-specific 3D Imaging of Cells and Tissues With a Dual Beam Microscope J. Struct. Biol. 155, 63-73.
2. J Heymann et al. 3D imaging of melanoma cells using automated "ion abrasion scanning electron microscopy". Microsc Microanal. 2007 Aug;13(Suppl 2):360-361.

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #613 KH

Updated 03/27/2008