Single-crystal X-ray diffraction analysis (SCXRD) constitutes a universal approach for the elucidation of molecular structure and the study of crystalline forms. However, the discovery of viable crystallization conditions remains both experimentally challenging and resource intensive in both time and the quantity of analyte(s). We report a robot-assisted, high-throughput method for the crystallization of organic-soluble small molecules in which we employ only micrograms of analyte per experiment. This allows hundreds of crystallization conditions to be screened in parallel with minimal overall sample requirements. Crystals suitable for SCXRD are grown from nanoliter droplets of a solution of analyte in organic solvent(s), each of which is encapsulated within an inert oil to control the rate of solvent loss. This encapsulated nanodroplet crystallization methodology can also be used to search for new crystal forms, as exemplified through both our discovery of a new (13^th) polymorph of the olanzapine precursor ROY and SCXRD analysis of the “uncrystallizable” agrochemical dithianon.

单晶X射线衍射分析（SCXRD）构成了阐明分子结构和研究晶体形式的通用方法。然而，发现可行的结晶条件在时间和分析物的数量上仍然是实验上的挑战和资源密集的。我们报告了一种用于有机可溶性小分子结晶的机器人辅助高通量方法，其中每个实验仅使用微克分析物。这样可以并行筛选数百个结晶条件，而总样品需求最少。适用于SCXRD的晶体是从分析物在一种或多种有机溶剂中的纳升液滴生长而来的，每种液滴都封装在一种惰性油中，以控制溶剂流失的速率。^th）奥氮平前体ROY的多晶型物和“不可结晶的”农药二噻酮的SCXRD分析。