Single Molecule Instrument for Surface Enhanced Raman Optical Activity of Biomolecules

Stereochemistry is an essential element of our organic life. Only certain enantiomers are useful as drugs for the human body. Raman optical activity (ROA) provides stereochemical information down to the bond levels. Many biomolecules like proteins and DNA can be studied to understand their structural chemistry and structure related dynamics. These methods do not require material in the crystalline form and hence can be very useful tools. However, ROA signals are even weaker than the Raman signals. Using an important biomolecule, we have demonstrated in Phase I that ROA can be enhanced using nanoparticles. Not only did the ROA ratio increase by two orders of magnitude, the measurement time reduced from several hours to 10 seconds. Phase II work will focus on enhancing ROA signals in different subspecies of biomolecules, namely amino acids and proteins, and developing the appropriate colloidal chemistry. Use of nanoparticles is known to enhance Raman signals by several orders of magnitude. Our goal is to achieve similar gains in ROA signals by using a sensitive detection system in combination with improved surface enhanced chemistry and microfluidics-based single-molecule detection techniques. This will result in improved precision of measurement and shorten measurement time.