Patterned glycine crystals nucleated on functionalized metallic square islands. This approach can be used to fabricate particles with micron dimensions and screen solid forms under different conditions. The size of the glycine crystals is controlled by the dimensions of the islands. High energy metastable beta-glycine crystallizes on small metallic islands, whereas for large islands, the polymorphic outcome becomes biased toward the alpha-form.

Minimally invasive repair of pectus excavatum based on a novel morphology-tailored, patient-specific approach is effective for quality repair of the full spectrum of pectus excavatum, including asymmetry and adult patients. Continuous technical refinements have significantly decreased the complication rates and postoperative morbidity.

This study demonstrates the effect of the solution pH on the polymorphic outcome of glycine by evaporation-driven crystallization from aqueous solution. More than 2000 solution droplets under identical conditions were generated using a patterned self-assembled monolayers (SAMs) substrate. Each droplet on the substrate serves as an independent crystallization trial. Glycine nucleated inside the droplets through solvent evaporation, and their polymorphic forms were identified via Raman microscopy. Three different polymorphic forms of glycine (R-, β-, and γ-forms) simultaneously crystallized at all conditions employed. The probability of producing the thermodynamically stable γ-glycine from acidic (pH 3.40) or basic solution (pH 10.10) droplets significantly increased when compared with neutral aqueous solution (pH ∼ 6.00) droplets.

Multiple crystal forms can concomitantly nucleate on patterned substrates. This technique can particularly be attractive to screen for polymorphs as elusive, metastable solid forms are favored with the creation of high supersaturation and can be stabilized due to the minimal volumes generated.

The primary goal of crystallization process is to generate particles with controlled size, shape and solid form, and the desired chemical purity. Many different types of approaches including molecular level strategies have been devised and employed to control the final structure of crystals. One promising approach is the utilization of self-assembled monolayers (SAMs) as templates. Recently, we reported that single glycine crystals can nucleate on patterned metallic square islands, with the size and morphology of the particles controlled by the dimensions of the islands or the concentration of the solution. Herein, the effect of the solution concentration on the polymorphic outcome of glycine crystals confined to hydrophilic metallic islands is investigated. Furthermore, we examine how variations in the solvent evaporation rate can impact the polymorph distribution of glycine.

In this study, we demonstrate how increasing the number of crystallization trials can help crystallize polymorphs which may not be obtained in a fewer number of trials due to statistical reasons. Crystallization experiments were conducted using patterned substrates of self-assembled monolayers (SAMs) with solutions of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (known as ROY for its red, orange, and yellow crystals) in dimethylsulfoxide (DMSO). The patterned bifunctional surface was immersed and slowly withdrawn from undersaturated solutions. The solution preferentially wetted the metallic islands, and as the solvent evaporated, ROY crystals exclusively nucleated on the lyophilic metallic islands. Raman microscopy was utilized to characterize the crystalline form on each metallic island. In one of the experiments, over 10 000 islands were analyzed, and we calculated the probability of crystallizing a particular polymorph on an island. We were able to crystallize six of the seven stable polymorphs of ROY using this method, including form YT04, which to the best of our knowledge, has never been obtained from solution crystallization.

Small droplets of supersaturated hen egg white lysozyme (HEWL) solution were exposed to intense linearly polarized laser pulses with different wavelengths, intensities, and pulse durations. Laser irradiation under some conditions significantly increased the number of droplets in which crystals were observed in a given time period, compared with nonirradiated samples. As a general rule, nonphotochemical laser induced nucleation (NPLIN) in lysozyme solutions was more effective with shorter aging time, 532-nm wavelength, higher peak intensity, and shorter pulse duration. Bovine pancreatic trypsin (BPT) was also examined using NPLIN, showing the potential application of NPLIN to other proteins.

The pharmaceutical industry has great interest in organic molecular nanosized crystals because their enhanced solubility and dissolution rate can potentially enhance drug bioavailability. In this work, patterned engineered surfaces were used to crystallize glycine with a lateral dimension below 200 nm in a confined volume while controlling supersaturation. Bifunctional patterned surfaces with hydrophilic islands, as small as 500 nm, surrounded by hydrophobic regions were prepared using lithography and self assembled monolayers. Individual glycine crystals under 200 nm were formed from the confined solutions wetting each hydrophilic island, while supersaturation was controlled by slow antisolvent diffusion. Individual crystals were characterized with AFM and Raman spectroscopy and determined to be the metastable beta form. The solubility enhancement as a function of crystal size was measured, and the solubility of crystals with a radius of 100 nm or less was estimated.