Phase II year
2011
(last award dollars: 2013)
This Small Business Innovation Research (SBIR) Phase II project is focused on the creation of a new revolutionary imaging instrumentation that combines vibrational circular dichroism (VCD) spectroscopy with infrared (IR) spectral microscopy. VCD microscopy represents a new class of spectroscopic imaging diagnostic capable of measuring VCD images with millimeter to sub-millimeter spatial resolution. The recent discovery that long-range structural chirality in protein fibrils is characterized by unusually large and distinctive VCD spectra provides the backdrop for this project. None of the currently available techniques can characterize the fibrillation pathway or the final fibril state with the same ease and detail as VCD. VCD microscopy can be thought of as circular polarization contrast microscopy that is sensitive to long-range chiral order in localized regions of biological samples. The broader impacts of this research are studies of the supramolecular chirality of fibrils. This product is not a small improvement of an existing technology but a distinctly new method of studying long-range biochirality that is more sensitive, provides more detail, and is easy and fast to use. A secondary, higher-impact long-term impact will be clinical research laboratories where this innovation can be used for the detection and characterization of amyloids in vivo, i.e. for tissue biopsies, rapid detection of amyloids and drug screening. PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH Kurouski, D., Dukor, R.K., Lu, X., Nafie, L.A., Lednev, I.K.. "Normal and Reversed VCD Supramolecular Chirality of Insulin Fibrils," Biophysical Journal, v.103, 2012, p. 522. Kurouski, D., Dukor, R.K., Lu, X., Nafie, L.A., Lednev, I.K.. "Spontaneous inter-conversion of insulin fibril chirality," Chem. Commun, v.48, 2012, p. 2837