Spontaneous and nonphotochemical laser-induced nucleation in levitated supersaturated microdroplets

该项目研究了悬浮过饱和微滴的自发成核和激光诱导成核，这些微滴的直径范围约为5到50 ìm，对应的体积范围为0.065到65 pL。微滴的小体积可以实现比散装溶液更高的过饱和，为亚稳态多晶的形成创造有利条件。这种微液滴提供了一种消除杂质诱导的非均相结晶的方法，为通过使用表面活性剂分子创建设计界面来研究多晶控制提供了独特的机会。本课题的主要目的是研究悬浮过饱和微滴自发成核和激光诱导成核过程中有机化合物的多晶型控制，以及微滴体积与表面活性剂的关系。表面活性剂将作为特定多晶型成核的设计模板。预计这些研究将揭示不寻常的甚至未知的多晶型和水合物，它们将通过潮解点、拉曼光谱和重量变化来识别。该项目汇集了独特的专业知识：Garetz在激光材料相互作用领域，Arnold在微滴悬浮领域，与Michael Ward在结晶和多态性领域合作。它与Garetz早期在激光诱导成核方面的工作有很大的不同，因为所有的实验都将在有限体积的微滴中进行，而且许多实验将使用表面活性剂。在这些新条件下，由于微液滴的表面积体积比更大，并且外来成核杂质的干扰最小，预计表面活性剂单层对成核的影响将比块状结晶介质更大。虽然其他研究小组已经研究了表面单分子层对多态性的影响或受限体积对多态性的影响，但本文提出的研究是独一无二的，它将这两个参数同时结合到一个超净环境中的单个实验中，以允许独立控制每个参数的方式。更广泛的影响：虽然晶体材料的成核已经研究了几十年，但它仍然是一个知之甚少的现象，只有通过新的和创新的方法才能解开。如果这个项目成功，它将为探索无数有机化合物的成核、结晶和多态性提供相当大的机会，这些有机化合物因其商业应用而令人感兴趣。新的多晶体代表着新的材料。本提案中开发的方法可能为发现新的多态性提供一种独特的方法，这在新药开发中至关重要。如果这个项目成功，它可能会改变制药行业发现新多态性的方式。本提案的两位pi都有丰富的指导本科生的经验，并且拟议的研究适合通过夏季研究实习进行这种培训，本提案要求为此提供资金。

0932810GaretzThis project investigats both spontaneous and laser-induced nucleation in levitated supersaturated microdroplets having diameters ranging from about 5 to 50 ìm, that corresponds to a range of volumes from 0.065 to 65 pL. The small volumes achievable in microdroplets allow the attainment of significantly higher supersaturations than in bulk solutions, creating conditions favorable for the creation of metastable polymorphs. Such microdroplets provide a means of eliminating impurity induced heterogeneous crystallization, providing a unique opportunity to study polymorph control by creating designer interfaces using surfactant molecules. The principal aim of this projectl is to study polymorph control of organic compounds in the spontaneous and laser induced nucleation of levitated supersaturated microdroplets, as a function of microdroplet volume, with and without surfactants. Surfactants will serve as designer templates for nucleation of specific polymorphs. It is anticipated that these studies will reveal unusual and even unknown polymorphs and hydrates, which will be identified by deliquescence points, Raman spectra and weight changes. The project brings together a unique combination of expertise: Garetz in the area of laser-material interactions, and Arnold in the area of microdroplet levitation, in collaboration with Michael Ward in the area of crystallization and polymorphism. It differs significantly from Garetz's earlier work on laser-induced nucleation, in that all experiments will be carried out in the confined volumes of microdroplets, and many will employ surfactants. Under these novel conditions, it is anticipated that surfactant monolayers will exert a greater influence on nucleation compared to bulk crystallization media owing to the greater surface area volume ratio in microdroplets and the minimization of interference from adventitious nucleation impurities. While other research groups have studied the effects of surface monolayers on polymorphism or the effects of confined volumes on polymorphism, the research proposed herein is unique in simultaneously combining these two parameters into a single experiment in an ultraclean environment, in a manner that allows independent control of each parameter. Broader Impact: Although nucleation of crystalline materials has been investigated for decades, it remains a poorly understood phenomenon that will only be unraveled through new and innovative methods. If this project succeeds it will open considerable opportunities for exploring the nucleation, crystallization, and polymorphism of innumerable organic compounds that are interesting because of their commercial applications. New polymorphs represent new materials. The methodology developed in this proposal may provide a unique approach to the discovery of new polymorphs, which is of vital importance in the development of new pharmaceuticals. If this project is successful, it could potentially transform the way new polymorphs are discovered in the pharmaceutical industry. Both PIs of this proposal have considerable experience mentoring undergraduate students, and the proposed research lends itself to such training through summer research internships, funding for which is requested in this proposal.