原子力显微镜在蛋白质晶体生长研究中的应用

原子力显微镜(AFM)的发明是二十几年来表面扫描和成像技术领域中重要的进展之一,由于具有原子级的分辨率,并可在液态环境中进行实时扫描,AFM已成为蛋白质晶体界面研究的有效工具之一.本文将讨论AFM在蛋白质晶体研究中取得的成果,包括在晶体形核、晶体生长及晶体缺陷研究等方面的最新进展.     

直拉单晶硅生长过程中固液界面形状研究

本文采用晶体生长软件CGSim对直拉单晶硅生长过程中固液界面进行了研究。讨论了不同晶体等径长度下固液界面形状的特点,模拟了晶体生长界面的变化过程;与此同时对不同晶体拉速、晶转、埚转对固液界面形状的影响进行研究,根据模拟结果确定影响固液界面的最优拉速、晶转及埚转。     

晶体生长理论的发展趋势与界面相模型

简要介绍了前人提出的晶体生长理论的要点及其优点与不足之处；在此基础之上提出了晶体生长理论的发展趋势及晶体生长所面临的基本科学总则王码电脑公司软件中心；通过分析研究，作者认为晶体生长过程中，介于晶体相与环境相之间的界面相起着重要的作用；重点论述了界面相中的界面层、吸附层和过渡层与晶体生长的关系。并进一步提出了晶体生长的界面相模型。     

硅锌矿结晶釉的结晶研究——釉熔体中球粒体结晶动力学探讨

对结晶釉中的硅锌矿结构性质和结晶习性的研究证明釉中硅锌矿是沿c轴方向发育生长的纤维状或针状晶体。 对结晶釉中硅锌矿的热力学稳定性和釉熔体中的相平衡关系进行了讨论。确定了釉中硅锌矿的形成条件和釉料组成范围。 本文着重研究釉熔体中硅锌矿的结晶动力学。在釉中,硅锌矿具有球粒体性质。用电炉和高温热台显微镜测定了釉熔体中硅锌矿的均相成核曲线和晶体生长曲线,并且用高温X射线衍射仪直接测定釉中硅锌矿的等温结晶曲线。根据结晶动力学理论,对釉中硅锌矿的均相成核和生长机理以及结晶机理作了研究。研究发现,釉中硅锌矿的均相成核是非热因的,晶体生长是受扩散过程控制的,总的结晶是由非热因成核、扩散过程和界面反应三个因素共同导致的。 此外,还发现硅锌矿的均相成核速率和晶体生长速度均与ZnO含量成正比。     

聚氧乙烯超薄膜等温结晶过程的研究

利用原子力显微镜(AFM)研究了不同温度的聚氧乙烯(PEO)超薄膜等温结晶过程。结果表明:超薄膜晶体形貌具有生长控制因素的依赖性;当晶体生长同时受到表面成核和熔体扩散控制时,各方向生长速率明显不同,且在晶体形成过程中,先发生液相-固相转变,后发生固相-固相转变。     

Nd∶KGd(WO_4)_2激光晶体生长

以K2 W2 O7为助熔剂 ,采用熔盐顶部籽晶 (TSSG)法生长出尺寸为 2 3mm× 2 0mm× 19mm的Nd∶KGd(WO4) 2 激光晶体 .比较了K2 WO4和K2 W2 O7两种助熔剂的性能及对晶体生长的影响 ,认为K2 W2 O7熔点较低可以有效地降低晶体生长温度 ,有利于控制晶体生长和生长环境 .进行了KGd(WO4) 2 -KNd(WO4) 2 系统二元相图的研究 ,认为两者互溶性好 ,有利于晶体生长 ,并且Nd3+ 易于以化学剂量比取代Gd3+ .采用XRD、偏光显微镜及TG -DTA对晶体性能进行了研究 ,实验表明所生长的晶体为高温相的 β -Nd∶KGW .用光学显微镜对晶体表面裂纹、生长条纹、生长丘、生长台阶和包裹物等缺陷进行了观察 ,认为它们形成的原因是由于晶体生长工艺不稳定 ,温度梯度过大 ,拉速和降温速率过快     

Nd: KGd (WO4)2激光晶体生长

以K2W2O7为助熔剂,采用熔盐顶部籽晶(TSSG)法生长出尺寸为23mm×20mm×19mm的NdKGd(WO4)2激光晶体.比较了K2WO4和K2W2O7两种助熔剂的性能及对晶体生长的影响,认为K2W2O7熔点较低可以有效地降低晶体生长温度,有利于控制晶体生长和生长环境进行了KGd(WO4)2-KNd(WO4)2系统二元相图的研究,认为两者互溶性好,有利于晶体生长,并且Nd3+易于以化学剂量比取代Gd3+采用XRD、偏光显微镜及TG-DTA对晶体性能进行了研究,实验表明所生长的晶体为高温相的β-NdKGW.用光学显微镜对晶体表面裂纹、生长条纹、生长丘、生长台阶和包裹物等缺陷进行了观察,认为它们形成的原因是由于晶体生长工艺不稳定,温度梯度过大,拉速和降温速率过快.     

聚氧乙烯薄膜的结晶形态研究

以不同相对分子质量的聚氧乙烯(PEO)为研究对象,采用差示扫描量热仪、偏光显微镜和原子力显微镜研究了影响PEO薄膜结晶的主要因素。结果表明:影响PEO结晶的主要因素是结晶温度,PEO在25℃形成球晶,温度升高时,晶体尺寸亦略微增加,黑十字消光现象明显,且可观察到环形裂纹;结晶温度较低时,片晶生长先由成核生长机理控制,而后由扩散生长机理控制,结晶温度较高时,片晶生长主要由成核机理控制;相对分子质量对晶体尺寸有一定影响,但不影响结晶形态,随着相对分子质量的增加,PEO薄膜的片晶形成由成核机理控制转变成扩散机理控制,PEO晶体从Flat-on结构逐渐转变为Edge-on结构。     

负离子配位多面体生长基元与晶体的结晶习性

研究了晶体中负离子配位多面体的结晶方位与晶体形貌之间的关系。根据对溶液（水热、溶剂）中结构的测定，发现有与晶体中负离子配位体相同的结构基元存在，提出晶体生长基元为负离子配位多面体的生长模型。生长基元往界面上叠合是生长基元与晶体界面上负离子配位多面体的结合反应。文中列举了ＢａＴｉＯ３，ＬＢＯ和ＫＴＰ晶体的结晶习性与形成机理。     

原子力显微镜在质子交换膜燃料电池表/界面现象中的应用

综述了原子力显微镜（AFM）的技术特点及其在质子交换膜燃料电池（PEMFCs）表/界面现象研究中的应用,总结了利用AFM多种模式表征质子交换膜和催化层的表面性质、界面结构、质子传导机理以及电化学活性方面的研究进展。除此之外,AFM可以在燃料电池工作条件下对电化学反应过程进行监控, 实时观察PEMFCs中的电化学行为,是研究PEMFCs中质子传导机理和电化学活性的一种有效手段。AFM研究对质子交换膜的合成与改性具有一定的指导意义,同时也为催化剂等其他关键材料的制备提供了参考,为PEMFCs中电化学反应过程的研究开辟了更多的方向,具有良好的发展前景。     

Polymorphism of D-mannitol: Crystal structure and the crystal growth mechanism

The polymorphism of D-Mannitol(mannitol) is reviewed in this paper. It was found that the structure of the stable form is consistent in most literatures, but different authors have given different information about the two metastable forms. Therefore the commonly used nomenclature of mannitol was summarized based on the crystal unit cell parameters with the help of X-ray powder diffraction. Moreover, the crystal growth mechanism of mannitol polymorphs was summarized. Considering the lack of kinetic data for the metastable form especially, a reported method was attempted to apply to δ mannitol in an aqueous cooling crystallization process based on the induction time previously measured, and it was identified that the growth of the δ form follows the two-dimensional(2D) nucleationmediated mechanism. The results also indicate that the method based on induction time and supersaturation should have the potential to be expanded to the metastable polymorphs for the growth property study in a bulk system.     

熔融结晶洗涤分离过程的传递行为

通过对熔融结晶洗涤分离的操作模式和提纯机理进行分析,按照滤饼洗涤原理建立了流体流动模型,得到晶层内的压力分布。同时对晶层进行质量和热量衡算,建立了传质和传热模型,求得了晶层内杂质浓度分布和温度分布表达式。分布表达式表明了压力、浓度、温度与之相关的参数的关系,这个结果对熔融结晶洗涤分离过程的参数确定和操作过程的进一步实验研究具有重要的应用价值。     

Recent advances of pharmaceutical crystallization theories

As a technology of separation and purification, crystallization plays a vital role in diverse industries such as inorganic salt, pharmaceutical, and food industries, which has a huge impact on purity, crystal polymorph, crystal morphology, and particle size distribution of final products. In the past few decades, with the rapid advancement of experimental approaches and molecular simulation methods, considerable advances in the interpretation of crystallization mechanisms have been obtained, promoting the investigation and understanding of crystallization theories greatly. In this review, the advances of pharmaceutical crystallization theories in recent years from the perspectives of nucleation and crystal growth are summarized and discussed. Two thermodynamic models that are helpful in the study of the crystallization mechanisms will be introduced. In this section, the perturbed-chain statistical associating fluid theory (PC-SAFT) and a chemical-potential-gradient model will be introduced, which have been successfully applied in pharmaceutical solubility prediction, the research of dissolution mechanism as well as dissolution kinetics analysis. These two models are expected to be applied to the study of pharmaceutical crystallization process and mechanism. Furthermore, molecular simulation based on the interaction between particles can provide structural information, thermodynamics, and dynamics properties of complex systems at the molecular level, like intermolecular interaction and surface adsorption energies. Application and some shortcomings of molecular simulation, especially molecular dynamics simulation, in the field of pharmaceutical crystallization will be expounded.     

Analysis of Surface Features on Single Crystals of Synthetic Garnets

Surface features observed on the faces of synthetic garnets grown from lead oxide-lead fluoride melts are described and interpreted in terms of growth processes. The growth processes involve (1) nucleation of new growth layers at corners and edges between crystal faces and (2) propagation of layers associated with growth systems located on the crystal faces. Growth systems on the faces of crystals that terminated growth at about 1000°C appear as growth hillocks. Continuing growth to lower temperatures produces large vicinal faces, which result from the propagation of polygonized growth steps associated with a single, dominant growth system. Growth steps on the vicinal faces in turn possess faces that are parallel to the nearest adjacent crystal faces. Growth spirals have been observed on the faces of crystals that were grown slowly by evaporation of flux. Several observations, including the presence of growth spirals, the nature and location of line imperfections and hollow tubes, and the etching behavior of crystal faces and polished sections, are interpreted as evidence in favor of a latter-stage growth mechanism that involves the propagation of steps associated with screw dislocations.     

Fractal crystal growth of poly(ethylene oxide) crystals from its amorphous monolayers

The fractal crystal growth process of the PEO monolayer with a molecular weight and a distribution has been followed on the substrate of the silicon wafer using AFM equipped with a hot stage. A depletion zone between the ramified crystals and the viscous amorphous layer was found in the AFM height images. The formation of the depletion zone shows that the molecules have to “break up” with the amorphous layer and then diffuse through the depletion zone to join the crystals. The diffusion process further means the diffusion-controlled mechanism resulting in the fractal crystal pattern with a fractal dimension D_f ≈ 1.63. The linear feature of the crystal pattern radius growth with time means that the surface kinetic process plays a key role in the crystal growth.     

Structural analysis of poly(butylene adipate) banded spherulites from their biodegradation behavior

Poly(butylene adipate) (PBA) has been reported to have polymorphic crystal structures and only the mixture of two crystal modifications (α and β crystals) forms banded spherulites. However, how the two crystals coexist in banded spherulites remains to be solved. In this work, the morphological structure of PBA banded spherulites was analyzed from their biodegradation behavior by means of polarized optical microscopy (POM), scanning electron microscopy (SEM), atomic force microscopy (AFM) and wide-angle X-ray diffraction (WAXD). It was found that the banded spherulites were made up of alternate flat-on and edge-on domains in lamellar crystals along the radiating direction. To determine the distribution of two crystal modifications in banded spherulites and the interrelationships between the alternate domains with polymorphic crystal structures, the relative contents of two crystal modifications in banded spherulites were first quantified, and their changes were then correlated to the morphological changes of banded spherulites in the course of biodegradation in terms of the difference in biodegradation kinetics of two crystal modifications. It was found that the flat-on domains show a slower crystal growth rate but a faster biodegradation rate than the edge-on domains. The analysis indicates that the flat-on domains in spherulites are composed of α crystals, while the edge-on domains are composed of β crystals. The primary growth mechanism of PBA banded spherulite was proposed based on the difference in crystallization heat and kinetics of two crystal modifications.     

Kinetics of precipitation of surfactants. III. Atomic force microscopy of precipitate crystals

The overall time required for precipitation to occur can increase dramatically for surfactant mixtures compared to single components. Atomic force microscopy (AFM) has been used in this study to examine the precipitated surfactant crystals, which gives insight into both the thermodynamics and kinetics of surfactant precipitation. Calcium dodecyl sulfate, Ca(DS)₂ shows regular, layered growth that is consistent with a screw-dislocation crystallization mechanism. Calcium octylbenzene sulfonate, Ca(OBS)₂, forms crystals with uneven, jagged edges. At high magnification, the head groups of both Ca(DS)₂ and Ca(OBS)₂ show hexagonal packing. For mixtures that have surprisingly slow precipitation kinetics, the jagged Ca(OBS)₂ crystals were observed to grow on the layered Ca(DS)₂ crystals. Other surfactant mixtures that exhibited a stepwise rate curve formed crystals with incomplete layers and holes that are not observed with pure surfactants. In general, this type of crystal formation can occur when an impurity is present, which in this case is most likely the second surfactant. This work indicates that interruption of crystal growth by crystallization of a dissimilar supersaturated surfactant onto the first crystal is one explanation for the slower precipitation of surfactant mixtures compared to single surfactants. Entrapment of the nonprecipitating surfactant (inclusion) in the forming crystal of the precipitating surfactant in mixed surfactant systems is another mechanism responsible for the reduction in precipitation rate.     

Optimization and control of crystal shape and size in protein crystallization process

Large molecule protein crystals have shown significant benefits in the delivery of biopharmaceuticals to achieve high stability, high concentration of active pharmaceutical ingredients (API), and controlled release of API. However, among the about 150 biopharmaceuticals on the market by 2004, only insulin has been marketed in crystalline form. A major technological challenge is that protein crystallization has a very complicated environment and is affected by many factors. There is currently a lack of knowledge on large scale production of protein crystals. In contrast to the majority of previous work on protein crystallization that was centered on single crystal scale, the current research is focused on computational study of protein crystallization at process scale, investigating the growth behavior of a population of crystals in a crystallizer. Using a newly developed morphological population balance model that can simulate the multidimensional size distributions of a population of crystals, known as shape distribution, an optimization technique is applied to optimize the growth of individual faces with the aim of obtaining desired crystal shape and size distributions. Using a target shape as the objective function, optimal temperature and supersaturation profiles leading to the desired crystal shape were derived. Genetic algorithm was investigated and found to be an effective optimization technique for the current application. Since tracking an optimum temperature or supersaturation trajectory can be easily implemented by manipulating the coolant flowrate in the reactor jacket, the methodology provides a feasible closed-loop mechanism for protein crystal shape tailoring and control.     

聚集结晶动力学研究方法的改进

在Hounslow工作的基础上,推导了新的聚集机理,改进了聚集模型。通过粒数衡算和质量衡算,结合改进的聚集模型建立了聚集结晶动力学辨识的新方法。文中以头孢哌酮钠结晶过程为例,应用新方法确定了该物系的晶体生长、聚集以及成核动力学。结果表明新方法研究聚集结晶动力学具有一定的可靠性。     

Growth of thin epitaxial films

A new theoretical model for prediction of the mechanism of growth of thin epitaxial films is developed. The model is not based on the classical nucleation theory as this is the case of the approach of Bauer to the problem. The thermodynamic conditions for occurrence of island growth, layer-by-layer growth, multilayer growth and Stranski—Krastanov mechanism consisting of layer-by-layer growth followed by islands are found. The influence of the lattice misfit and the surface alloying on the mode of growth is discussed. The effect of the crystallographic orientation of the substrate is also studied. The theoretical results are applied to the case of electrocrystallization of metals on single crystal metal substrates. A comparison with experimental data is carried out whenever possible.