Systems and Methods for Kinetic Measurement and Structure Determination of Macromolecules

Invention Summary:

Microscopic images of cellular structure in biological samples can reveal important information regarding biological processes and cellular architecture. A correlative approach (CLEM), which uses both optical and electron microscopy, produces the most comprehensive results. For example, light microscopy information can be used to identify areas of biological importance and their dynamics within a sample. Then, electron microscopy can be used to resolve structural details within those areas at high-resolution. Currently available CLEM methods are used for localization of fluorescently labeled molecules in vitrified samples using light/fluorescent microscopy, and then for correlation of light and electron microscopy images.

A Rutgers researcher has combined single-molecule (sm) techniques with cryo-electron microscopy (cryo-EM) to yield a new heretofore unknown method and device for single-molecule Correlative Light and Electron Microscopy (sm-CLEM). This novel method is applicable to the structure-function study of different biological systems, for instance: (i) real-time measurements of protein kinetics or cellular dynamics with subsequent high-resolution structure determination, (ii) analysis of structural heterogeneity of the multiprotein complexes, which are potential drug targets, (iii) time-resolved interactions of drugs with their targets at high-resolution.  So far, these systems have not been suitable for high-resolution structure determination due to unresolved sample heterogeneity. 

Market Applications: 

  • Product: optical and electron microscopy equipment.
  • Commercial application: microscope accessories/stages and supplies.
  • Market: pharmaceutical industry, biotechnology, academic research, life sciences.


  • Enables fluorescence and label-free microscopy of macromolecular complexes, cells or tissues at high resolution with medium throughput.
  • Enables structure determination of transient kinetic states of molecular complexes with medical importance, which are otherwise not accessible for structural studies.
  • Overcomes measurement limitations related to the intrinsic dynamics and heterogeneity of molecular complexes.
  • Increased resolution.

Intellectual Property & Development Status: Patent pending. Available for licensing and/or collaboration.

Patent Information: