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）第一阶段项目的更广泛的影响/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（构象异构体）的鉴定和表征。 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业化学工业至关重要，因为许多药物或农业化学化合物的代谢物通常是彼此的异构体。由于这些代谢物中的一些可能是有害的，安全性和有效性研究需要仔细的分析“方法开发”工作，以定量它们在临床样品，土壤和食品中的存在。 不幸的是，目前用于鉴定分子异构体的分析方法繁琐、缓慢，并且涉及试错工作，这对监管批准构成了重大瓶颈。 该技术旨在为异构体分析提供一种快速而强大的仪器，大大降低制药和农业化学品的开发成本，并扩大专利排他性销售，同时首次实现构象异构体的实验鉴定。获得这些新信息有可能改变农用化学品（2022年总可寻址市场（TAM）为2200亿美元）和药物发现（TAM 2022年为820亿美元）部门，同时创造新的高薪高科技工作岗位。 该SBIR第一阶段项目提出开发一种新型的质谱仪，其工作在中性分子而不是离子上。 它使用高电场来操纵和区分分子，通过电极性的大小将它们分开，这反过来又对分子的3D形状高度敏感。 分子可以被场推或拉，这取决于它们在场中的取向和它们的极性大小（“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很复杂，通常需要耗时的“方法开发”工作。拟议的仪器旨在减少这项工作，通过使用偶极矩来区分所有异构体和它们的构象在一个单一的光谱-与轴标记的质量-偶极子矩比，而不是质荷比。该技术使用微加工技术来将先前在学术文献中描述的演示的四极器件进行抛光和平面化，从而创建微观四极通道阵列。额外的正在申请专利的减速功能，加上速度选择性检测，应导致2-3个数量级的异构体/构象异构体的歧视能力超过文献设备。最后，这种通用的检测方法将允许连续的吞吐量，这是与标准分析仪器接口的理想选择。该奖项反映了NSF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。