Crystal Growth of Aspirin Using a Temperature-Controlled Microfluidic Device

Identifying the most appropriate polymorph of active pharmaceutical ingredients is one of the important steps in drug development, since their bioactivities are largely dependent on their solid forms. However, the sample preparation for the characterization of crystal forms is time-consuming and requires large quantities of sample. Here, we introduce a microfluidic device-based method to prepare a sub-millimeter-sized single aspirin crystal from a small quantity of material. For the crystal preparation, a device equipped with a solution flow system and temperature controller was placed under the microscope. To use the device, concentration–temperature phase diagrams were generated, and regions where dominant nucleation or crystal growth with specific directions were clearly determined. By observing time-dependent changes of crystal number and size with solution temperature, a pathway to grow a single crystal of aspirin was determined and applied to prepare a sub-millimeter-sized crystal from 250 μg of aspirin. The obtained crystal was sufficiently large for single-crystal X-ray diffraction analysis, which usually requires 10 mg to 1 g of material per crystallization experiment. Thus, this method can be adapted as an efficient approach to uncovering the crystallization process to obtain required crystal forms with minimal sample consumption

A Bioinspired Coprecipitation Method for the Controlled Synthesis of Magnetite Nanoparticles

Nature often uses precursor phases for the controlled development of crystalline materials with well-defined morphologies and unusual properties. Mimicking such a strategy in in vitro model systems would potentially lead to the water-based, room-temperature synthesis of superior materials. In the case of magnetite (Fe₃O₄), which in biology generally is formed through a ferrihydrite precursor, such approaches have remained largely unexplored. Here we report on a simple protocol that involves the slow coprecipitation of Fe^III/Fe^II salts through ammonia diffusion, during which ferrihydrite precipitates first at low pH values and is converted to magnetite at high pH values. Direct coprecipitation often leads to small crystals with superparamagnetic properties. Conversely, in this approach, the crystallization kineticsand thereby the resulting crystal sizescan be controlled through the NH₃ influx and the Fe concentration, which results in single crystals with sizes well in the ferrimagnetic domain. Moreover, this strategy provides a convenient platform for the screening of organic additives as nucleation and growth controllers, which we demonstrate for the biologically derived M6A peptide