GOALI: CDS&E: Sensitively Quantifying Trace Crystallinity and Crystal Form within Pharmaceutical Formulations

目标：CDS

• 批准号: 1710475
• 负责人: Garth Simpson
• 金额: $ 43.8万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710475&HistoricalAwards=false
• 关键词: GOALI; CDS& Sensitively; Quantifying; Trace

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, and co-funding from the Division of Industrial Innovation and Partnerships, Professors Simpson and Bouman at Purdue University, Dr. Danzer at AbbVie, and Dr. Gualtieri at Formulatrix are working on advancing spectroscopic imaging methods for probing polymorph crystals. polymorph crystal forms are ubiquitous in chemistry. In food science, the crystallinity of starches within potatoes and pasta directly dictate bioavailability of the stored energy content. In renewable energy, biochemical degradation of biomass is greatly affected by the degree of crystallinity. Biomineralization also relies on careful control over crystal phase, often resulting in selection of metastable structures. In pharmaceutical materials, physical solid state form can profoundly affect bioavailability and drug efficacy. Reliably measurement and monitoring of how crystal forms and transforms requires tools capable of reporting crystalline content at low levels. With the support of this grant, Professors Simpson and Bouman work closely with their industrial partners to develop fast and sensitive imaging tools to do just that. Through close partnership with AbbVie and Formulatrix, the developed approach is expected to bring impacts in pharmaceutical formulations development and other areas, such as pretreatment of biomass for energy conversion and artificial biomineralization. In addition to working with their undergraduate and graduate students closely on the project, professor Simpson also organizes an intensive summer short-course program on nonlinear optics that more than 160 students have participated in the past ten years. Professor Simpson plans now to produce short videos on the topics discussed at the short course program and makes it available to a much broader audience through YouTube. In the present work, Professors Simpson, Bouman, and their groups work on reducing the detection limits of Raman spectroscopy by several orders of magnitude to enable analysis of glassy metastable assemblies, targeting detection limits in the parts per million (ppm) regime. Three complementary approaches are pursued to achieve this objective, all of which center on signal to noise enhancement through background reduction. In the first, SHG is used to rapidly identify regions of interest for targeted Raman analysis, building on the inherent speed and selectivity of SHG for chiral crystals. In addition, a dynamic sampling strategy is adopted for analysis of the SHG-inactive components of formulations, in which spatially sparse sampling informed by the preceding set of outcomes is used for efficient hyperspectral imaging reconstruction. Finally, a spectral sparse sampling strategy for beam-scanning imaging using a photomultiplier tube array allows low-noise measurements for hyperspectral Raman imaging. Complementing these spectral characterization approaches, triboluminescence detection will be developed for fast screening. All efforts greatly benefit from close partnership between collaborators working in pharmaceutical formulations development (AbbVie) and instrumentation companies (Formulatrix) positioned to transition innovations in the research laboratory to viable commercial products. While the primary focus of the work is on metastable systems of relevance to industrial collaborators, the results of this work provides a foundation for expansion to other metastable biological assemblies, including pretreatment of biomass for energy conversion, crystallinity in edible products, and fundamentals of biomineralization. Professor Simpson organizes a week- long intensive program, Chautauqua on Nonlinear Optics for graduate student from research groups worldwide. The program focuses on in-depth understanding of the theoretical and practical fundamentals of nonlinear optics and aims to build a community operating within a common framework for performing and interpreting nonlinear optical measurements.

在化学系化学测量和成像项目的支持下，以及工业创新与合作司的共同资助下，普渡大学的 Simpson 和 Bouman 教授、AbbVie 的 Danzer 博士以及 Formulatrix 的 Gualtieri 博士正在开展工作先进的光谱成像方法用于探测多晶型晶体。多晶型物晶体形式在化学中普遍存在。在食品科学中，土豆和面食中淀粉的结晶度直接决定了所储存能量的生物利用度。在可再生能源中，生物质的生化降解很大程度上受结晶度的影响。生物矿化还依赖于对晶相的仔细控制，通常导致亚稳态结构的选择。在药物材料中，物理固态形式可以深刻影响生物利用度和药物功效。可靠地测量和监测晶体的形成和转变需要能够报告低水平晶体含量的工具。在这笔赠款的支持下，辛普森教授和布曼教授与工业合作伙伴密切合作，开发快速、灵敏的成像工具来实现这一目标。 通过与艾伯维和 Formulatrix 的密切合作，开发的方法预计将对药物配方开发和其他领域产生影响，例如用于能量转换和人工生物矿化的生物质预处理。 除了与本科生和研究生在该项目上密切合作外，辛普森教授还组织了一个关于非线性光学的夏季强化短期课程，在过去十年中已有 160 多名学生参加了该课程。辛普森教授现在计划就短期课程计划中讨论的主题制作短片，并通过 YouTube 向更广泛的受众开放。 在目前的工作中，Simpson、Bouman 教授及其团队致力于将拉曼光谱的检测限降低几个数量级，以便能够分析玻璃状亚稳态组件，目标是将检测限控制在百万分之几 (ppm) 范围内。为了实现这一目标，我们采用了三种互补的方法，所有这些方法都以通过降低背景来增强信噪比为中心。首先，基于倍频对于手性晶体的固有速度和选择性，倍频用于快速识别目标拉曼分析的感兴趣区域。此外，采用动态采样策略来分析配方中的SHG非活性成分，其中根据前面一组结果通知的空间稀疏采样用于有效的高光谱成像重建。最后，使用光电倍增管阵列进行光束扫描成像的光谱稀疏采样策略可以实现高光谱拉曼成像的低噪声测量。作为这些光谱表征方法的补充，摩擦发光检测将被开发用于快速筛选。所有努力都极大受益于药物配方开发合作者 (AbbVie) 和仪器公司 (Formulatrix) 之间的密切合作，这些公司致力于将研究实验室的创新转化为可行的商业产品。虽然这项工作的主要重点是与工业合作者相关的亚稳态系统，但这项工作的结果为扩展到其他亚稳态生物组件提供了基础，包括用于能量转换的生物质预处理、可食用产品的结晶度以及生物矿化的基础知识。 辛普森教授为来自世界各地的研究小组的研究生组织了为期一周的非线性光学肖托夸强化课程。该计划侧重于深入了解非线性光学的理论和实践基础知识，旨在建立一个在通用框架内运行的社区，以执行和解释非线性光学测量。

项目成果

Spatial encoded polarization dependent nonlinear optical analysis for local tensors imaging of collagenous tissue

用于胶原组织局部张量成像的空间编码偏振相关非线性光学分析

• DOI: 10.1117/12.2510049
• 发表时间: 2019-02
• 期刊: Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XXVI
• 作者: Ding, Changqin;Ulcickas, James R.;Deng, Fengyuan;Simpson, Garth;Brown, Thomas G.;Wilson, Tony
• 通讯作者: Wilson, Tony

Multi-photon excited Fourier-transform fluorescence recovery after photobleaching (FT-FRAP) with patterned illumination

光漂白后多光子激发傅里叶变换荧光恢复 (FT-FRAP) 与图案照明

• DOI: 10.1117/12.2545908
• 发表时间: 2020-02
• 期刊: Multi-photon excited Fouriertransform fluorescence recovery after photobleaching (FT-FRAP
• 作者: Geiger, Andreas C.;Smith, Casey J.;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.

Defense against adversarial spectroscopic attacks (Conference Presentation)

防御对抗性光谱攻击（会议演示）

• DOI: 10.1117/12.2518922
• 发表时间: 2019-05
• 期刊: Defense against adversarial spectroscopic attacks
• 作者: Smith, Casey;Liu, Youlin;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.

Spectral classification by generative adversarial linear discriminant analysis

通过生成对抗性线性判别分析进行谱分类

• DOI: 10.1016/j.aca.2023.341129
• 发表时间: 2023-06
• 期刊: Analytica Chimica Acta
• 影响因子: 6.2
• 作者: Cao, Ziyi;Zhang, Shijie;Liu, Youlin;Smith, Casey J.;Sherman, Alex M.;Hwang, Yechan;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.

Multiagent Consensus Equilibrium in Molecular Structure Determination

分子结构测定中的多主体一致性平衡

• DOI: 10.1021/acs.jpca.0c07282
• 发表时间: 2020-10
• 期刊: The Journal of Physical Chemistry A
• 作者: Ulcickas, James R.W.;Cao, Ziyi;Rong, Jiayue;Bouman, Charles A.;Slipchenko, Lyudmila V.;Buzzard, Gregery T.;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.