使用表面能改性玻璃基板的晶体成核,Crystal Growth & Design

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使用表面能改性玻璃基板的晶体成核
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2017-07-21 00:00:00 , DOI: 10.1021/acs.cgd.7b00574
Kyle A. Nordquist ₁ , Kevin M. Schaab ₁ , Jierui Sha ₁ , Andrew H. Bond ₁

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对玻璃基材的系统表面能修饰可以诱导成核并改善小分子活性药物成分（API）和蛋白质的结晶效果。提出了一个相对广泛的功能探针，其中检查了各种API，蛋白质，有机溶剂，水性介质，表面能基序，结晶方法，形状因数以及平坦和凸起表面能的修饰。复制研究（n≥6）已证明使用两种截然不同的技术从91％的异丙醇中将乙酰水杨酸的结晶起始时间平均缩短了52（4）％（或者52±4％）：大量冷却至0°C（使用平坦的表面能修饰）或从浸入溶液中的具有凸表面能改性的玻璃毛细管内部将微区冷却至4°C。对于thaumatin和牛胰胰蛋白酶，在蒸汽扩散实验中证明结晶开始时间减少32（2）％（n≥15）。已将成核位点阵列设计到经常用于结晶筛选的形状因子上，包括显微镜载玻片，小瓶以及96和384孔高通量筛选板。在包含要结晶的溶质的容器上使用表面能改性进行成核，为结晶研究增加了一层有用的变量，而无需对工作流程或仪器进行重大更改。

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Crystal Nucleation Using Surface-Energy-Modified Glass Substrates

Systematic surface energy modifications to glass substrates can induce nucleation and improve crystallization outcomes for small molecule active pharmaceutical ingredients (APIs) and proteins. A comparatively broad probe for function is presented in which various APIs, proteins, organic solvents, aqueous media, surface energy motifs, crystallization methods, form factors, and flat and convex surface energy modifications were examined. Replicate studies (n ≥ 6) have demonstrated an average reduction in crystallization onset times of 52(4)% (alternatively 52 ± 4%) for acetylsalicylic acid from 91% isopropyl alcohol using two very different techniques: bulk cooling to 0 °C using flat surface energy modifications or microdomain cooling to 4 °C from the interior of a glass capillary having convex surface energy modifications that were immersed in the solution. For thaumatin and bovine pancreatic trypsin, a 32(2)% reduction in crystallization onset times was demonstrated in vapor diffusion experiments (n ≥ 15). Nucleation site arrays have been engineered onto form factors frequently used in crystallization screening, including microscope slides, vials, and 96- and 384-well high-throughput screening plates. Nucleation using surface energy modifications on the vessels that contain the solutes to be crystallized adds a layer of useful variables to crystallization studies without requiring significant changes to workflows or instrumentation.

更新日期：2017-07-21

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