|PROPOSAL NUMBER:||05-II S2.05-9082|
|PHASE-I CONTRACT NUMBER:||NNA06CA67C|
|PROPOSAL TITLE:||Single Molecule Instrument for Surface Enhanced Raman Optical Activity of Biomolecules|
SMALL BUSINESS CONCERN
(Firm Name, Mail Address, City/State/Zip, Phone)
Radiation Monitoring Devices, Inc.
44 Hunt St
Watertown, MA 02472-4699
PRINCIPAL INVESTIGATOR/PROJECT MANAGER
(Name, E-mail, Mail Address, City/State/Zip, Phone)
44 Hunt Street
Watertown, MA 02472-4699
TECHNICAL ABSTRACT (Limit 2000 characters, approximately 200 words)
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.
POTENTIAL NASA COMMERCIAL APPLICATIONS (Limit 1500 characters, approximately 150 words)
NASA's main interest in determining helicity of biomolecules is for extra-terrestrial life research programs. Indication of prevalence of L or D type biomolecules, their structure and isotope identification, can lead to useful clues of life existence elsewhere in outer space. Surface enhanced Raman optical activity (SEROA) tool will be very useful, especially for unknown biomolecules whose racemic mixtures cannot be easily identified and separated by phase separation techniques. Moreover, trace identification to the order of parts-per-trillion, or structure identification when crystalline structure is non-existent, are also some of the important issues that ROA can address. This instrument can also be useful for marine researchers who study life processes in deep underwater thermal vents. Sensitive Raman measurements with reduced measurement time will be of immense help considering the difficulty in obtaining access to samples. Real-time studies could become possible with the use of appropriate underwater fiber probes with nanoparticle coated films.
POTENTIAL NON-NASA COMMERCIAL APPLICATIONS (Limit 1500 characters, approximately 150 words)
Research can lead to better methods to measure and quantify Raman optical activity (ROA). This technique can augment X-ray diffraction to provide structural information of a biomolecule, which is of prime interest to biomedical researchers and those developing drugs or cures to fight diseases. Many chemical and drug industries employ spectrometer systems to measure circular dichroism. So far, the focus has been on measuring electronic or linear dichroism on a large number of molecules due to the ease of measurement. However, with ROA, a single molecule can be studied. Other benefits include not having to rely on phase separation techniques, which are not easily available for every molecule. Our efforts will pave the way for obtaining improved ROA signals using existing spectrometers with little modification. Knowledge of specific enantiomers can help drug research.
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