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.

这个小企业创新研究（SBIR）第一阶段项目的广泛影响/商业潜力将导致一种新型的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）的识别和表征。同分异构体是具有相同组成原子但排列不同的分子。同分异构体及其构象形式的鉴定对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产物往往是彼此的同分异构体。由于这些代谢物中的一些可能是有害的，因此安全性和有效性研究需要仔细的分析“方法开发”工作，以量化它们在临床样品、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，并且需要反复试验，这对监管部门的批准构成了重大瓶颈。拟议的技术旨在提供一种快速而强大的异构体分析仪器，大大降低制药和农用化学品的开发成本，扩大专利独占性销售，同时首次实现对构象的实验鉴定。获取这些新信息有可能改变农化（2022年总可寻址市场（TAM）为2200亿美元）和药物发现（2022年总可寻址市场（TAM）为820亿美元）行业，同时产生新的高薪高科技工作。这个SBIR一期项目建议开发一种新的质谱仪，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，通过它们的电极性的大小来分离它们，而电极性反过来又对分子的3D形状高度敏感。分子可能被磁场推或拉，这取决于它们在磁场中的方向和极性（“偶极矩”）的大小。由于分子同分异构体的重量相同，通过质谱法鉴定它们是复杂的，通常需要耗时的“方法开发”工作。提出的仪器旨在通过使用偶极矩来区分所有同分异构体及其在单一光谱中的构象来减少这项工作-用质量-偶极矩比而不是质量-电荷比标记轴。该技术使用微加工技术将学术文献中描述的先前演示的四极杆装置小型化和平面化，创建了一系列微观四极杆通道。额外的正在申请专利的减速功能，加上速度选择检测，应该会导致比文献设备高2到3个数量级的异构体/构象识别能力。最后，这种通用检测方法将允许连续吞吐量，这是与标准分析仪器接口的理想选择。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。