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.

这项小型企业创新研究（SBIR）I期项目的更广泛的影响/商业潜力将导致一种新型的分析工具和相关业务，专门研究化学异构体及其不同构象形式（构象异构体）的识别和表征。异构体是具有相同成分原子但排列不同的分子。鉴定异构体及其构象形式对于药物和农业化学产业至关重要，因为许多药物或农业化合物的代谢物通常是彼此的异构体。由于这些代谢产物中的某些可能是有害的，因此安全性和有效的研究需要仔细的分析“方法开发”工作，以量化其在临床样品，土壤和食品中的存在。不幸的是，当前用于识别分子异构体的分析方法很麻烦，缓慢，并且涉及反复试验 - 呈现出明显的瓶颈来进行调节批准。拟议的技术旨在为异构体分析提供快速而健壮的工具，从而大大降低药物和农业化学开发成本并扩大专利的排他性销售 - 同时首次实现了对构体的实验性识别。访问这些新信息有可能改变农业化学（2022年的2200亿美元总可寻址市场（TAM））和药物发现（820亿美元TAM 2022）部门，同时产生了新的高薪高科技工作。 SBIR I期项目的项目提案要开发出一种用于中性分子而不是离子的新型质谱仪。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，这反过来又对分子的3D形状高度敏感。田地可以根据田间的方向和极性的大小（“偶极力矩”）推动或拉出分子。由于分子异构体的重量相同，因此它们通过质谱的识别很复杂，通常需要耗时的“方法开发”工作。该提出的仪器旨在通过使用偶极矩在单个频谱中区分所有异构体及其构象异构体，该仪器以质量到偶极运动比例标记，而不是质量与电荷比，以区分所有异构体及其构象异构体。该技术使用微型制造技术将学术文献中描述的先前证明的四倍器设备进行微型化和平衡，从而创建了一系列的微型四杆渠道。额外的申请专利减速功能，再加上速度选择性检测，应导致2至3个数量级高的异构体/构象异构体辨别能力，而不是文献设备。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触的理想选择。本奖反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，通过评估被认为是宝贵的支持。