SBIR Phase I: A Radio Frequency Quadrupole Stark Decelerator to Identify Isomers and Conformers and Measure their Effective Dipole Moments

Award ID: 2208750

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will lead to a new type of analytical instrument and associated businesses, specializing in the identification and characterization of chemical isomers and their different conformational forms (conformers). Isomers are molecules with the same constituent atoms but arranged differently. The identification of isomers and their conformational forms is of critical importance to pharmaceutical and agrochemical industries since the metabolites of many medications or agrochemical compounds are often isomers of one another. Since some of these metabolites may be harmful, safety and efficacy studies require careful analytical method development work to quantitate their presence in clinical samples, soils, and foodstuffs. Unfortunately, current analytical methods for identifying molecular isomers are cumbersome, slow, and involve trial and error work presenting a significant bottleneck to regulatory approval. The proposed technology seeks to provide a rapid and robust instrument for isomer analysis, dramatically reducing pharmaceutical and agrochemical development costs and extending patent exclusivity sales while enabling the experimental identification of conformers for the first time. Access to this new information has the potential to transform agrochemical ($220 billion total addressable market (TAM) in 2022) and drug discovery ($82 billion TAM 2022) sectors, while generating new well-paying, high-tech jobs. This SBIR Phase I project proposes to develop a novel mass spectrometer that works on neutral molecules rather than ions. It uses high electric fields to manipulate and distinguish molecules, separating them by the magnitude of their electrical polarity which, in turn, is highly sensitive to the molecules 3D shape. Molecules may be pushed or pulled by the fields depending on their orientations in the field and the magnitude of their polarity (dipole moment). Since molecular isomers weigh the same, their identification via mass spectrometry is complicated and typically requires time-consuming method development work. The proposed instrument aims to reduce this work by using dipole moments to distinguish all isomers and their conformers in a single spectrum with an axis labeled by mass-to-dipole-moment ratio, rather than mass-to-charge ratio. This technology uses microfabrication techniques to miniaturize and planarize a previously demonstrated quadrupole device described in the academic literature, creating an array of microscopic quadrupole channels. The additional patent-pending deceleration feature, coupled with velocity selective detection, should result in 2-to-3 orders of magnitude higher isomer/conformer discrimination capabilities over the literature device. Finally, this universal detection methodology will allow for continuous throughput, which is ideal for interfacing with standard analytical instrumentation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Program Director: Benaiah Schrag