BrightSpec Inc. NIH SBIR Application Project Summary Novel Sample Introduction Methodologies for Molecular Rotational Resonance (MRR) Spectroscopy NIH SBIR Direct to Phase II BrightSpec, Inc. Project Summary This project proposes to develop a new analyte sampling technique for Molecular Rotational Resonance (MRR) spectrometers for the volatilization of solid phase analytes. The proposed system, Laser Induced Acoustic Desorption (LIAD), will enable a large number of important compounds to be accessible by MRR, enhancing our understanding in several important areas of research and accelerating pharmaceutical development. The resulting expansion of sampling range and corresponding utility of this valuable technique will greatly accelerate the adoption of MRR in important areas of research and development. MRR is a spectroscopic technique for unambiguous structure determination and quantitation of small molecules, which has been used for decades in academic research laboratories, but only recently commercialized after the recent achievement of several groundbreaking innovations. MRR excels in structural and isomeric analysis, providing a detail of information like nuclear magnetic resonance (NMR), but at a much lower cost and faster speed, with reduced method development. Through working on a final piece of the puzzle, the development of new sampling techniques, BrightSpec seeks to unlock the full analytical potential of this powerful analytical technique to broaden its use throughout a range of applications, including metabolomics, drug discovery, natural product analysis, and the monitoring of environmental pollutants. BrightSpec has evaluated several sampling techniques for volatilization of solid samples and Laser Induced Acoustic Desorption (LIAD) was determined to be uniquely suitable for incorporation with MRR, as the sensitivity of results with these instruments can be adversely affected by the presence of solvents. BrightSpec has evaluated several sampling techniques for volatilization of solid samples and Laser Induced Acoustic Desorption (LIAD was determined to be uniquely suitable for combination with MRR, as the sensitivity of results with these instruments can be adversely affected by the presence of solvents. The project would be conducted by BrightSpec in collaboration with Kenttämaa Labs at Purdue University, which has been developing the LIAD technique for use with mass spectrometry for over 20 years and holds several LIAD-related patents. A proof-of-concept prototype LIAD-MRR instrument has been used to demonstrate the viability of coupling the two techniques. This preliminary work has de-risked this proposed Phase II project, which involves refinement of the prototype to develop a product with the necessary sensitivity, speed, and ease-of-use to facilitate commercial adoption. The resulting product will then be tested thoroughly on relevant samples in market areas where LIAD-MRR is expected to have the greatest impact. Several pro...