超快激光调控晶体形核与生长过程研究进展

Significance Crystallization has applications in biomedicine, structural analysis, and other related fields. For example, single crystal X-ray diffraction (XRD) is a common method for the structural analysis of biomacromolecules. Polymorph crystallization is also of significance in the pharmaceutical industry. These applications require the number, size, and polymorph of the crystals to be determined. Conventionally, crystals are obtained by evaporation of a solution or via a batch cooling process. However, the complex nature of the crystallization process means that precise control of crystallization is difficult. The crystallization process consists of two main stages: nucleation and crystal growth. When the concentration of a solute exceeds its solubility, the supersaturated solution is in a metastable zone. When the solute concentration reaches the supersaturation limit, nucleation occurs. The nucleus will then grow into larger crystals when the concentration drops back to the solubility level. In recent years, various methods have been studied for controlling crystal nucleation and growth processes, including those involving lasers, ultrasonics, and electromagnetic fields (Table 1, Table 2). Among these methods, ultrafast laser, because of its ultrashort pulse width and ultrahigh peak intensity, interacts uniquely with the solution and crystals. It has advantages including limited thermal effects and can be applied to many materials. Therefore, the ultrafast laser method has been applied for the control of the crystallization process. In this review, we introduce the research progress of ultrafast laser-controlled crystallization. Many different methods and mechanisms of laser-induced nucleation and crystallization are discussed. Studies on effective control of the crystallization process will not only benefit the biomedical industry, but also shed new light on current academic crystallography research. Progress The ultrafast laser-controlled crystallization process can be categorized into several different types depending on stage of crystallization where the laser is involved (Fig. 1). Ultrafast laser interaction with a supersaturated solution will induce the nucleation of crystals. Many different mechanisms contribute to this process, including laser heating of the substrate, formation of cavitation bubbles, and the electromagnetic effect. Local heating of the substrate or laser-induced cavitation in solution increases the local concentration and results in nucleation. Laser irradiation with lower power leads to electromagnetic field interactions with the solution or the heating of impurities within the solution. These methods are collectively known as non-photochemical laser induced nucleation (NPLIN) since the laser is not directly absorbed by the solution. The electromagnetic effects, including polarization and Kerr effects, reduce the energy barrier and enhance the nucleation rate (Fig. 2). Through these methods, researchers are able to enhance the nucleation probability, and control the number and size of the crystals. Most importantly, the spatial selectivity of laser radiation allows local nucleation while the global concentration is lower than the supersaturation limit. This means fewer initial nuclei compared to spontaneous nucleation, which further results in crystals with large size and high quality. Ultrafast laser irradiation can also influence the polymorph of nucleation and enhance the ratio of metastable crystal phases (Fig. 4). This is useful in biomedical research and within the pharmaceutical industry. After the crystal nucleus dissolves out from the solution, laser interaction with the crystals or the surrounding solution can influence the crystal growth process. Laser irradiation of the solution can be performed to change the growth rate of crystals through a laser trapping phenomenon. For some organic materials, laser trapping increases the concentration at the focal point and accelerates the crystal growth. For some other materials, such as proteins, the electromagnetic field will keep the molecules and clusters in a low energy state and restrain the crystal growth. In addition to the control of the entire crystal growth rate, the growth of a specific crystal face can also be promoted. Ultrafast laser ablation on a crystal surface alters the growth mode and enhances the growth speed of the specific crystal face(Fig. 5). This will be helpful in obtaining single crystals with ideal size and shape, which is crucial in single-crystal XRD and other biomedical applications. Ultrafast laser processing on crystal surfaces can also be performed to achieve micropatterning on single crystals. Ultrafast laser ablation has high precision and has a limited thermal effect on the surrounding materials because of the nonlinear absorption effect and non-thermal ablation process. Therefore, it is suitable for the processing of thermally sensitive materials, including proteins, amino acids, and other biomaterials. Arbitrary micropatterns such as microarrays can be achieved on the surface of single protein crystals without thermal damage using femtosecond laser processing. Ultrafast laser cleaving of protein crystals can be performed to fabricate crystal seeds with high quality. Micropatterning on single crystals has potential applications in the fabrication of biological devices. Conclusion and Prospect In conclusion, ultrafast laser can be used to control the nucleation and crystal growth processes. This approach is applicable for many biomedical fields because it can control crystallization and has limited thermal effects. Ultrafast laser control of the crystallization process still poses challenges such as lack of mechanism understanding and limits in practical applications. Future studies on its mechanism and cross-disciplinary collaboration will enhance the significance and application prospect of this method.