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

SBIR 第一阶段：射频四极 Stark 减速器，用于识别异构体和构象异构体并测量其有效偶极矩

• 批准号: 2208750
• 负责人: Demitri Balabanov
• 金额: $ 25.6万
• 依托单位: MOIRES INSTRUMENTS, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208750&HistoricalAwards=false
• 关键词: SBIR; Phase; Radio; Frequency; Quadrupole

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 molecule’s 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.

该小企业创新研究 (SBIR) 第一阶段项目的更广泛影响/商业潜力将带来新型分析仪器和相关业务，专门从事化学异构体及其不同构象形式（构象异构体）的识别和表征。 异构体是具有相同组成原子但排列不同的分子。异构体及其构象形式的鉴定对于制药和农用化学工业至关重要，因为许多药物或农用化学化合物的代谢物通常是彼此的异构体。由于其中一些代谢物可能有害，因此安全性和功效研究需要仔细的分析“方法开发”工作，以定量它们在临床样本、土壤和食品中的存在。 不幸的是，目前用于识别分子异构体的分析方法繁琐、缓慢，并且涉及反复试验——给监管审批带来了重大瓶颈。 拟议的技术旨在为异构体分析提供快速而强大的仪器，大幅降低制药和农用化学品的开发成本并扩大专利独占销售，同时首次实现构象异构体的实验鉴定。获取这些新信息有可能改变农用化学品（2022 年总目标市场 (TAM) 为 2200 亿美元）和药物发现（2022 年 820 亿美元 TAM）行业，同时创造新的高薪高科技就业机会。 该 SBIR 第一阶段项目提议开发一种新型质谱仪，适用于中性分子而不是离子。 它使用高电场来操纵和区分分子，通过其电极性的大小将它们分开，而电极性的大小又对分子的 3D 形状高度敏感。 分子可能被场推动或拉动，具体取决于分子在场中的方向和极性的大小（“偶极矩”）。 由于分子异构体的重量相同，因此通过质谱法对其进行鉴定非常复杂，并且通常需要耗时的“方法开发”工作。所提出的仪器旨在通过使用偶极矩来区分单个光谱中的所有异构体及其构象异构体来减少这项工作 - 轴由质量偶极矩比而不是质荷比标记。该技术使用微加工技术对学术文献中描述的先前演示的四极设备进行小型化和平面化，从而创建一系列微观四极通道。正在申请专利的附加减速功能与速度选择性检测相结​​合，异构体/构象异构体辨别能力应比文献设备高 2 到 3 个数量级。最后，这种通用检测方法将允许连续吞吐量，非常适合与标准分析仪器连接。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。