Fabrication and applications of the protein patterns

Protein has been widely used for fabricating patterned structures since it is one of the most important macromolecules in living organisms,and protein patterns possess potential applications in many fields such as medical diagnosis,tissue engineering,biosensors,and medical screening.At present,there are two fashions to fabricate protein patterns:one is grafting the protein to the microstructure which is prepared by micro-fabrication techniques;the other one is achieving the patterned protein structures directly.Here we provide an overview on current status of the fabrication techniques and the applications of the protein patterns,and then give an outlook on the development of the fabrication techniques and the prospective applications of the protein patterns in future research.     

蛋白质图案构筑及其应用研究进展

蛋白质作为生物体内一类重要的大分子已被广泛地应用于构筑图案化结构, 所得到的蛋白质图案在医疗诊断、组织工程、生物传感和药物筛选等领域均表现出了巨大的应用价值. 目前, 蛋白质图案的构筑方法主要有两种： （1） 在利用微加工技术制备的微结构上进行蛋白质的后续接枝实现蛋白质图案的构筑; （2） 直接用蛋白质分子构筑图案化结构. 本文对当前常用的蛋白质图案构筑技术进行了综述, 并对蛋白质图案的实际应用进行了总结, 最后对蛋白质图案构筑技术的发展方向以及蛋白质图案的应用前景进行了展望.     

功能性有序微结构的制备及潜在应用

随着科技的发展进步,具有特殊功能的有序微结构日渐引起人们浓厚的研究兴趣,并被广泛应用于微电子器件、微反应器、生物化学传感器以及光学器件等领域.本文总结了我们课题组在微观表面图案化和有序微结构制备及应用方面的研究工作,重点介绍我们在该方向工作的最新进展,并对该领域的发展前景进行了展望.     

Preparation and potential application of functional ordered microstructures

With the development of science and technology,ordered microstructures with special functions have aroused intense research interest.These functional microstructures have been widely used in fields of microelectronic devices,micro-reactors,biochemical sensors and optical devices,etc.This paper summaries our work on preparation and application of microscopic patterned surfaces with ordered microstructures,and looks into the future development of this field.     

Recent Advances on the Abrasion Resistance Enhancements and Applications of Superhydrophobic Materials

Researches on superhydrophobicity have been overwhelming and have shown great advantages in various fields. However, the abrasion resistance of superhydrophobic structures was usually poor, and they were easily damaged by external force or harsh environment, which greatly limited the applications of superhydrophobic surfaces. Much attention has been paid to improving the abrasion resistance of superhydrophobic materials by researchers. In this review, aimed at the advances on improving the abrasion resistance of superhydrophobic surfaces, it was summarized and compared three enhancement strategies including the reasonably design of micro-nano structures, the adoption of adhesives, and the preparation of self-healing surface. Finally, the applications of typical superhydrophobic materials with abrasion resistance were reviewed in various fields. In order to broaden the application fields of superhydrophobic materials, the abarasion resistance should be further improved. Therefore, we proposed the ideas for the future development of superhydrophobic materials with higher abrasion resistance. We hope that this review will provide a new approach to the preparation and development of stable superhydrophobic surfaces with higher abrasion resistance.     

Microstencils for the patterning of nontraditional materials

A microfabrication technique that uses a photolithographically patterned film as a microstencil has been developed. This microstencil has a bilayer structure comprised of parylene and SU-8 films with thicknesses from 4 to 100 microm. The parylene layer enables the microstencil to be mechanically peeled from hydrophilic substrates. Since no chemicals are required to release the microstencil, this technique can be used to pattern chemically and biologically sensitive materials. The amount of material deposited can be automatically controlled by the height of the SU-8 structures or externally controlled by spin coating or other thin film deposition techniques. This patterning method is very versatile and has been used to pattern features as small as 25 by 25 microm on silicon, glass, and polymer substrates. As an initial demonstration, we have patterned wax, cells, proteins, sol, and CYTOP.     

Patterned and controlled polyelectrolyte fractal growth and aggregations

Two-dimensional patterned and controlled polyelectrolyte aggregations (e.g., tree-like ramified structures) created by microcontact printing have been demonstrated and discussed. Polyelectrolyte-micropatterned aggregations on surfaces were controlled by the micropattern size and shape of PDMS stamps. The formation of aggregates was dependent on the ink and surface conditions, and the aggregates consisted of two distinct layers; strongly adsorbed, primary uniform layers and weakly adsorbed, secondary aggregation layers positioned on top of the primary layers. The adsorption of the primary layers was strong enough not to be washed away, while the aggregated secondary layers were easily removed by washing. The aggregation of secondary layers showed typical tree-like ramified structures of fractal growth and aggregation. Directional and confined stamping led to directing and confining the growth of the fractal polyelectrolyte clusters, respectively. The micropatterned primary uniform layers were not removed by extensive washing, and they were identified by selective nickel plating and charged particle selective adsorption in which the surface formed positive and negative micropatterns. These functional and patterned surfaces have great potentials for advanced devices and sensors.     

Recent explorations in electrostatic multilayer thin film assembly

New developments in the area of electrostatic layer-by-layer assembly are reviewed, with emphasis on work in the past two years. Advances in fundamental understanding of polyelectrolyte adsorption is addressed, including the use of new probes and experimental techniques which examine final structure, film interpenetration, and control of thickness. Both theoretical and experimental studies of adsorption of weak polyelectrolytes have been addressed. The role of secondary interactions such as hydrogen bonding or dispersion forces on these parameters is a more recent area of focus. Molecular scale order has been achieved in layered films to produce noncentrosymmetric films; further control of the ordering of molecular side groups in these systems could lead to new and interesting electrical and optical properties. Finally, it has been shown that polyelectrolyte multilayers may be templated onto a number of surfaces; these materials can be patterned onto surfaces to make three dimensional microstructures, or grown on a sacrificial colloidal template to form encapsulant membranes.     

Facile Fabrication of Concentrated Polymer Brushes with Complex Patterning by Photocontrolled Organocatalyzed Living Radical Polymerization

Photocontrolled surface‐initiated reversible complexation mediated polymerization (photo‐SI‐RCMP) was successfully applied to fabricate concentrated polymer brushes with complex patterning structures. Positive‐type patterned polymer brushes were obtained by photo‐SI‐RCMP under visible light (550(±50) nm) using photomasks. A particularly interesting finding was that negative‐type patterned polymer brushes were also obtainable in a facile manner. A nonspecial UV light (250–385 nm) enabled the preparation of pre‐patterned initiator surfaces in a remarkably short time (1 min), leading to negative‐type patterned polymer brushes. Based on this unique selectivity between visible and UV light, the combination of two patterning techniques enabled the preparation of complex patterned brushes, including diblock copolymers, binary polymers, and functional binary polymers, without multistep immobilization of one or more initiators on the surfaces.     

Imaging energy landscapes with concentrated diffusing colloidal probes

The ability to locally interrogate interactions between particles and energetically patterned surfaces provides essential information to design, control, and optimize template directed self-assembly processes. Although numerous techniques are capable of characterizing local physicochemical surface properties, no current method resolves interactions between colloids and patterned surfaces on the order of the thermal energy kT, which is the inherent energy scale of equilibrium self-assembly processes. Here, the authors describe video microscopy measurements and an inverse Monte Carlo analysis of diffusing colloidal probes as a means to image three dimensional free energy and potential energy landscapes due to physically patterned surfaces. In addition, they also develop a consistent analysis of self-diffusion in inhomogeneous fluids of concentrated diffusing probes on energy landscapes, which is important to the temporal imaging process and to self-assembly kinetics. Extension of the concepts developed in this work suggests a general strategy to image multidimensional and multiscale physical, chemical, and biological surfaces using a variety of diffusing probes (i.e., molecules, macromolecules, nanoparticles, and colloids).     

Microcontact click printing for templating ultrathin films of metal-organic frameworks

The controlled growth of metal-organic frameworks (MOFs) over surfaces has been investigated using a variety of surface analytical techniques. The use of microcontact printing to prepare surfaces, patterned with regions capable of nucleating the growth of MOFs, has been explored by employing copper-catalyzed alkyne-azide cycloaddition (CuAAC) to pattern silicon wafers with carboxylic acids, a functional group that has been shown to nucleate the growth of MOFs on surfaces. Upon subjecting the patterned silicon surfaces to solvothermal conditions, MOF thin films were obtained and characterized subsequently by AFM, SEM, and grazing-incidence XRD (GIXRD). Large crystals (～0.5 mm) have also been nucleated, as indicated by the presence of a bas-relief of the original pattern on one surface of the crystal, suggesting that it is possible to transfer the template surface pattern onto a single crystal of a MOF.     

Selective deposition in multilayer assembly: SAMs as molecular templates

Self-assembled monolayers (SAMs) on surfaces may be used as molecular templates for the selective deposition of polymer multilayer films. SAMs of ω-functionalized alkane thiolates are patterned onto gold surfaces with micron scale features using the microcontact printing method; glass substrates can also be patterned with trichloroalkylsilane SAMs. Patterned polymeric monolayer and multilayer films are adsorbed atop the SAM from dilute polymer solutions using ionic macromolecular self-assembly techniques which have been developed recently. The effects of polymer molecular weight and ionic content, as well as the use of a second SAM in the unpatterned regions to promote selectivity are discussed. Surface roughness, selectivity and other film properties are presented. It is demonstrated that this technique can be used successfully in the patterning of micron scale features with multilayers of low molecular weight upon adsorption from dilute solution.     

Recent advances in QSAR and their applications in predicting the activities of chemical molecules, peptides and proteins for drug design

This review is to summarize three new QSAR (quantitative structure-activity relationship) methods recently developed in our group and their applications for drug design. Based on more solid theoretical models and advanced mathematical techniques, the conventional QSAR technique has been recast in the following three aspects. (1) In the fragment-based two dimensional QSAR, or abbreviated as FB-QSAR, the molecular structures in a family of drug candidates are divided into several fragments according to the substitutes being investigated. The bioactivities of drug candidates are correlated with physicochemical properties of the molecular fragments through two sets of coefficients: one is for the physicochemical properties and the other for the molecular fragments. (2) In the multiple field three dimensional QSAR, or MF-3D-QSAR, more molecular potential fields are integrated into the comparative molecular field analysis (CoMFA) through two sets of coefficients: one is for the potential fields and the other for the Cartesian three dimensional grid points. (3) In the AABPP (amino acid-based peptide prediction), the bioactivities of peptides or proteins are correlated with the physicochemical properties of all or partial residues of the sequence through two sets of coefficients: one is for the physicochemical properties of amino acids and the other for the weight factors of the residues. Meanwhile, an iterative double least square (IDLS) technique is developed for solving the two sets of coefficients in a training dataset alternately and iteratively. Using the two sets of coefficients, one can predict the bioactivity of a query peptide, protein, or drug candidate. Compared with the old methods, the new QSAR approaches as summarized in this review possess machine learning ability, can remarkably enhance the prediction power, and provide more structural information. Meanwhile, the future challenge and possible development in this area have been briefly addressed as well.     

Protein adsorption and surface patterning

Surface patterning has become an important discipline of biologically oriented surface science over the past decades. Many methods have been developed that allow the formation of patterns on the micro- and nanoscale. This Opinion discusses the role of protein adsorption in patterning technologies, highlighting how it can be used as an integrated part of the patterning process, how it can be controlled by patterns with appropriate properties, and how it may lead to disruption of formed patterns if not properly accounted for. Recent examples from literature are used to emphasize some of the most interesting developments in the field, such as novel surface chemistries only allowing specific protein adsorption, directed self-sorting adsorption of proteins on patterned surfaces, and control of protein adsorption through nanopatterning.     

Soft lithographic patterning of supported lipid bilayers onto a surface and inside microfluidic channels

We present simple soft lithographic methods for patterning supported lipid bilayer (SLB) membranes onto a surface and inside microfluidic channels. Micropatterns of polyethylene glycol (PEG)-based polymers were fabricated on glass substrates by microcontact printing or capillary moulding. The patterned PEG surfaces have shown 97 +/- 0.5% reduction in lipid adsorption onto two dimensional surfaces and 95 +/- 1.2% reduction inside microfluidic channels in comparison to glass control. Atomic force microscopy measurements indicated that the deposition of lipid vesicles led to the formation of SLB membranes by vesicle fusion due to hydrophilic interactions with the exposed substrate. Furthermore, the functionality of the patterned SLBs was tested by measuring the binding interactions between biotin (ligand)-labeled lipid bilayer and streptavidin (receptor). SLB arrays were fabricated with spatial resolution down to approximately 500 nm on flat substrate and approximately 1 microm inside microfluidic channels, respectively.     

Layer-by-layer assembly as a versatile bottom-up nanofabrication technique for exploratory research and realistic application

The layer-by-layer (LbL) adsorption technique offers an easy and inexpensive process for multilayer formation and allows a variety of materials to be incorporated within the film structures. Therefore, the LbL assembly method can be regarded as a versatile bottom-up nanofabrication technique. Research fields concerned with LbL assembly have developed rapidly but some important physicochemical aspects remain uninvestigated. In this review, we will introduce several examples from physicochemical investigations regarding the basics of this method to advanced research aimed at practical applications. These are selected mostly from recent reports and should stimulate many physical chemists and chemical physicists in the further development of LbL assembly. In order to further understand the mechanism of the LbL assembly process, theoretical work, including thermodynamics calculations, has been conducted. Additionally, the use of molecular dynamics simulation has been proposed. Recently, many kinds of physicochemical molecular interactions, including hydrogen bonding, charge transfer interactions, and stereo-complex formation, have been used. The combination of the LbL method with other fabrication techniques such as spin-coating, spraying, and photolithography has also been extensively researched. These improvements have enabled preparation of LbL films composed of various materials contained in well-designed nanostructures. The resulting structures can be used to investigate basic physicochemical phenomena where relative distances between interacting groups is of great importance. Similarly, LbL structures prepared by such advanced techniques are used widely for development of functional systems for physical applications from photovoltaic devices and field effect transistors to biochemical applications including nano-sized reactors and drug delivery systems.     

Electropatterning—Contemporary developments for selective particle arrangements employing electrokinetics

The selective positioning and arrangement of distinct types of multiscale particles can be used in numerous applications in microfluidics, including integrated circuits, sensors and biochips. Electrokinetic (EK) techniques offer an extensive range of options for label-free manipulation and patterning of colloidal particles by exploiting the intrinsic electrical properties of the target of interest. EK-based techniques have been widely implemented in many recent studies, and various methodologies and microfluidic device designs have been developed to achieve patterning two- and three-dimensional (3D) patterned structures. This review provides an overview of the progress in electropatterning research during the last 5 years in the microfluidics arena. This article discusses the advances in the electropatterning of colloids, droplets, synthetic particles, cells, and gels. Each subsection analyzes the manipulation of the particles of interest via EK techniques such as electrophoresis and dielectrophoresis. The conclusions summarize recent advances and provide an outlook on the future of electropatterning in various fields of application, especially those with 3D arrangements as their end goal.     

Molecular Machines Working on Surfaces and at Interfaces

In the past ten years a great variety of artificial molecular machines have been constructed, and very interesting concepts for controlling molecular‐level movements by external inputs have been developed. Most of the studies, however, have been performed in solution, where the investigated systems contain a huge number of molecules which behave independently from one another because they cannot be addressed individually. Before such systems can find applications in many fields of technology, they must be interfaced with the macroscopic world by ordering them in some way so that they can behave coherently and can be addressed in space. The problem of obtaining ordered arrays of molecular machines can be addressed by a variety of techniques, which include deposition on surfaces, incorporation into polymers, organization at interfaces, and immobilization in membranes or porous materials. In the last few years, the development of scanning‐probe techniques has also enabled direct observation and manipulation of single molecular‐machine molecules on surfaces. Techniques of this kind have opened novel routes to the study of molecular machines, and have also contributed to better understanding the differences between movement at the macroscopic and molecular levels. This paper reviews some recent achievements in the field of molecular machines working on surfaces and at interfaces, as single molecules or ordered arrays. Hybrid natural–artificial machines are also discussed, and the working mechanism of some natural machines is illustrated for the purpose of comparison.     

二维导电金属有机骨架材料

金属有机骨架(MOFs)是由金属离子或簇与有机配体以配位键组装而成的晶态多孔材料,其高的孔隙率及功能可设计性使其广泛应用于各种领域.然而,传统MOFs多数电导率非常低,这严重制约了其在电学相关领域的发展.近年来,导电金属有机骨架尤其是二维导电金属有机骨架(2D ECMOFs)材料因其结构中独特的π-π堆积及π-d共轭作...