Abstract We investigate the utility of a mathematical framework based on discrete geometry to model biological and synthetic self-assembly. Our primary biological example is the self-assembly of icosahedral viruses; our synthetic example is surface-tension-driven self-folding polyhedra. In both instances, the process of self-assembly is modeled by decomposing the polyhedron into a set of partially formed intermediate states. The set of all intermediates is called the configuration space, pathways of assembly are modeled as paths in the configuration space, and the kinetics and yield of assembly are modeled by rate equations, Markov chains, or cost functions on the configuration space. We review an interesting interplay between biological function and mathematical structure in viruses in light of this framework. We discuss in particular: (i) tiling theory as a coarse-grained description of all-atom models; (ii) the building game-a growth model for the formation of polyhedra; and (iii) the application of these models to the self-assembly of the bacteriophage MS2. We then use a similar framework to model self-folding polyhedra. We use a discrete folding algorithm to compute a configuration space that idealizes surface-tension-driven self-folding and analyze pathways of assembly and dominant intermediates. These computations are then compared with experimental observations of a self-folding dodecahedron with side 300 ?m. In both models, despite a combinatorial explosion in the size of the configuration space, a few pathways and intermediates dominate self-assembly. For self-folding polyhedra, the dominant intermediates have fewer degrees of freedom than comparable intermediates, and are thus more rigid. The concentration of assembly pathways on a few intermediates with distinguished geometric properties is biologically and physically important, and suggests deeper mathematical structure.
Given the heterogeneous nature of cultures, tumors, and tissues, the ability to capture, contain, and analyze single cells is important for genomics, proteomics, diagnostics, therapeutics, and surgery. Moreover, for surgical applications in small conduits in the body such as in the cardiovascular system, there is a need for tiny tools that approach the size of the single red blood cells that traverse the blood vessels and capillaries. We describe the fabrication of arrayed or untethered single cell grippers composed of biocompatible and bioresorbable silicon monoxide and silicon dioxide. The energy required to actuate these grippers is derived from the release of residual stress in 3-27 nm thick films, did not require any wires, tethers, or batteries, and resulted in folding angles over 100° with folding radii as small as 765 nm. We developed and applied a finite element model to predict these folding angles. Finally, we demonstrated the capture of live mouse fibroblast cells in an array of grippers and individual red blood cells in untethered grippers which could be released from the substrate to illustrate the potential utility for in vivo operations.
We report on a therapeutic approach using thermo-responsive multi-fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli-responsive poly(N-isopropylacrylamide-co-acrylic acid) hinges. They close above 32?°C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in?vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.
We use micropatterning and strain engineering to encapsulate single living mammalian cells into transparent tubular architectures consisting of three-dimensional (3D) rolled-up nanomembranes. By using optical microscopy, we demonstrate that these structures are suitable for the scrutiny of cellular dynamics within confined 3D-microenvironments. We show that spatial confinement of mitotic mammalian cells inside tubular architectures can perturb metaphase plate formation, delay mitotic progression, and cause chromosomal instability in both a transformed and nontransformed human cell line. These findings could provide important clues into how spatial constraints dictate cellular behavior and function.
Cells live in a highly curved and folded micropatterned environment within the human body. Hence, there is a need to develop engineering paradigms to replicate these microenvironments in order to investigate the behavior of cells in vitro, as well as to develop bioartificial organs for tissue engineering and regenerative medicine. In this chapter, we first motivate the need for such micropatterns based on anatomical considerations and then survey methods that can be utilized to generate curved and folded micropatterns of relevance to 3D cell culture and tissue engineering. The methods surveyed can broadly be divided into two classes: top-down approaches inspired by conventional 2D microfabrication and bottom-up approaches most notably in the self-assembly of thin patterned films. These methods provide proof of concept that the high resolution, precise and reproducible patterning of cell and matrix microenvironments in anatomically relevant curved and folded geometries is possible. A specific protocol is presented to create curved and folded hydrogel micropatterns.
The spontaneous self-organization of conformational isomers from identical precursors is of fundamental importance in chemistry. Since the precursors are identical, it is the multi-unit interactions, characteristics of the intermediates, and assembly pathways that determine the final conformation. Here, we use geometric path sampling and a mesoscale experimental model to investigate the self-assembly of a model polyhedral system, an octahedron, that forms two isomers. We compute the set of all possible assembly pathways and analyze the degrees of freedom or rigidity of intermediates. Consequently, by manipulating the degrees of freedom of a precursor, we were able to experimentally enrich the formation of one isomer over the other. Our results suggest a new approach to direct pathways in both natural and synthetic self-assembly using simple geometric criteria. We also compare the process of folding and unfolding in this model with a geometric model for cyclohexane, a well-known molecule with chair and boat conformations.
Cell encapsulation provides a means to transplant therapeutic cells for a variety of diseases including diabetes. However, due to the large numbers of cells, approximately on the order of a billion, that need to be transplanted for human diabetes therapy, adequate mass transport of nutrients such as oxygen presents a major challenge. Proof-of-concept for the design of a bioartificial endocrine pancreas (BAEP) that is optimized to minimize hypoxia in a scalable and precise architecture is demonstrated using a combination of simulations and experiments. The BAEP is composed of an array of porous, lithographically patterned polyhedral capsules arrayed on a rolled-up alginate sheet. All the important structural variables such as the capsule dimensions, pore characteristics, and spacing can be precisely engineered and tuned. Further, all cells are encapsulated within a single device with a volume not much greater than the total volume of the encapsulated cells, and no cell within the device is located more than 200??m from the surrounding medium that facilitates efficient mass transport with the surroundings. Compared with gel-based encapsulation methods, our approach offers unprecedented precision and tunability of structural parameters as well as the volume of the encapsulated cells and consequently the amount of secreted insulin. Our work highlights the utility of lithography and self-assembly in the fabrication of micro- and nanostructured three-dimensional structures that simulate the function of natural endocrine organs.
Self-folded magnetic microtools with sharp ends are directed at enabling drilling and related incision operations of tissues, ex vivo, in a fluid with a viscosity similar to that of blood. These microtools change their rotation from a horizontal to a vertical one when they are immersed into a rotational magnetic field. Novel self-assembly paradigms with magnetic materials can enable the creation of remotely controlled and mass-produced tools for potential applications in minimally invasive surgery.
The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.
There are numerous techniques such as photolithography, electron-beam lithography and soft-lithography that can be used to precisely pattern two dimensional (2D) structures. These technologies are mature, offer high precision and many of them can be implemented in a high-throughput manner. We leverage the advantages of planar lithography and combine them with self-folding methods(1-20) wherein physical forces derived from surface tension or residual stress, are used to curve or fold planar structures into three dimensional (3D) structures. In doing so, we make it possible to mass produce precisely patterned static and reconfigurable particles that are challenging to synthesize. In this paper, we detail visualized experimental protocols to create patterned particles, notably, (a) permanently bonded, hollow, polyhedra that self-assemble and self-seal due to the minimization of surface energy of liquefied hinges(21-23) and (b) grippers that self-fold due to residual stress powered hinges(24,25). The specific protocol described can be used to create particles with overall sizes ranging from the micrometer to the centimeter length scales. Further, arbitrary patterns can be defined on the surfaces of the particles of importance in colloidal science, electronics, optics and medicine. More generally, the concept of self-assembling mechanically rigid particles with self-sealing hinges is applicable, with some process modifications, to the creation of particles at even smaller, 100 nm length scales(22, 26) and with a range of materials including metals(21), semiconductors(9) and polymers(27). With respect to residual stress powered actuation of reconfigurable grasping devices, our specific protocol utilizes chromium hinges of relevance to devices with sizes ranging from 100 ?m to 2.5 mm. However, more generally, the concept of such tether-free residual stress powered actuation can be used with alternate high-stress materials such as heteroepitaxially deposited semiconductor films(5,7) to possibly create even smaller nanoscale grasping devices.
We describe the self-folding of photopatterned poly (ethylene glycol) (PEG)-based hydrogel bilayers into curved and anatomically relevant micrometer-scale geometries. The PEG bilayers consist of two different molecular weights (MWs) and are photocrosslinked en masse using conventional photolithography. Self-folding is driven by differential swelling of the two PEG bilayers in aqueous solutions. We characterize the self-folding of PEG bilayers of varying composition and develop a finite element model which predicts radii of curvature that are in good agreement with empirical results. Since we envision the utility of bio-origami in tissue engineering, we photoencapsulate insulin secreting ?-TC-6 cells within PEG bilayers and subsequently self-fold them into cylindrical hydrogels of different radii. Calcein AM staining and ELISA measurements are used to monitor cell proliferation and insulin production respectively, and the results indicate cell viability and robust insulin production for over eight weeks in culture.
Self-assembly has emerged as a paradigm for highly parallel fabrication of complex three-dimensional structures. However, there are few principles that guide a priori design, yield, and defect tolerance of self-assembling structures. We examine with experiment and theory the geometric principles that underlie self-folding of submillimeter-scale higher polyhedra from two-dimensional nets. In particular, we computationally search for nets within a large set of possibilities and then test these nets experimentally. Our main findings are that (i) compactness is a simple and effective design principle for maximizing the yield of self-folding polyhedra; and (ii) shortest paths from 2D nets to 3D polyhedra in the configuration space are important for rationalizing experimentally observed folding pathways. Our work provides a model problem amenable to experimental and theoretical analysis of design principles and pathways in self-assembly.
An important feature of naturally self-assembled systems such as leaves and tissues is that they are curved and have embedded fluidic channels that enable the transport of nutrients to, or removal of waste from, specific three-dimensional regions. Here we report the self-assembly of photopatterned polymers, and consequently microfluidic devices, into curved geometries. We discover that differentially photo-crosslinked SU-8 films spontaneously and reversibly curve on film de-solvation and re-solvation. Photolithographic patterning of the SU-8 films enables the self-assembly of cylinders, cubes and bidirectionally folded sheets. We integrate polydimethylsiloxane microfluidic channels with these SU-8 films to self-assemble curved microfluidic networks.
Cell encapsulation therapy (CET) provides an attractive means to transplant cells without the need for immunosuppression. The cells are immunoisolated by surrounding them with a synthetic, semipermeable nanoporous membrane that allows selective permeation of nutrients and therapeutics while isolating the cells from hostile immune components. This communication describes the fabrication and in vitro characterization of lithographically structured and self-folded containers for immunoprotective cell encapsulation. Lithographic patterning ensured identical shapes, sizes, tunable porosity, and precise volumetric control, whereas self-folding enabled transformation of two-dimensional porous membranes into cubes, ensuring that pores were present in all three dimensions for adequate diffusion of O(2) and other nutrients to encapsulated cells. We fabricated containers with varying pore sizes and observed that pores sizes of approximately 78 nm were sufficient to significantly inhibit diffusion of IgG (the smallest antibody) and permit adequate diffusion of insulin, highlighting the possibility to utilize these containers to develop a lithographically structured bioartificial pancreas.
We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.
Because the native cellular environment is 3D, there is a need to extend planar, micro- and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or unfold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano- to centimeter scale polyhedral containers, scaffolds for cell culture and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.
We describe an assembly technique useful for generating ordered arrays of nanowires (NWs) between electrodes via dielectrophoresis (DEP) and an analysis technique useful for extracting quantitative information about the local electric fields and dielectrophoretic forces from video microscopy data. By tuning the magnitude of the applied electric fields such that the attractive forces on the NWs are of the same order of magnitude as the Brownian forces, and by taking advantage of the inter-NW repulsive forces during DEP, NWs can be assembled into parallel arrays with high reproducibility. By employing a particle-tracking code and analysis of NW motion, we demonstrate a method for quantitative mapping of the dielectrophoretic torques and NW-surface interactions as a function of position on the substrate, which allows a more complete understanding of the dynamics of the assembly and the ability to control these parameters for precise assembly.
We describe the spontaneous wrinkling, saddling, and wedging of metallic, annular bilayer nanostructures driven by grain coalescence in one of the layers. Experiments revealed these different outcomes based on the dimensions of the annuli, and we find that the essential features are captured using finite element simulations of the plastic deformation in the metal bilayers. Our results show that the dimensions and nanomechanics associated with the plastic deformation of planar nanostructures can be important in forming complex three-dimensional nanostructures.
We propose the concept of three-dimensional (3D) microwell arrays for cell culture applications and highlight the importance of oxygen diffusion through pores in all three dimensions to enhance cell viability.
We demonstrate a methodology that utilizes the specificity of enzyme-substrate biomolecular interactions to trigger miniaturized tools under biocompatible conditions. Miniaturized grippers were constructed using multilayer hinges that employed intrinsic strain energy and biopolymer triggers, as well as ferromagnetic elements. This composition obviated the need for external energy sources and allowed for remote manipulation of the tools. Selective enzymatic degradation of biopolymer hinge components triggered closing of the grippers; subsequent reopening was achieved with an orthogonal enzyme. We highlight the utility of these enzymatically triggered tools by demonstrating the biopsy of liver tissue from a model organ system and gripping and releasing an alginate bead. This strategy suggests an approach for the development of smart materials and devices that autonomously reconfigure in response to extremely specific biological environments.
Gold (Au) nanoparticles (NPs) have large surface areas and novel optical properties and can be readily functionalized using thiol-based chemistry; hence, they are useful in bioanalytical chemistry. Here, we describe a one-step, plasma-etching process that results in the spontaneous formation of Au NP coated recessed microstructures in silicon (Si). Mechanistically, the plasma etch rate of Si was enhanced in the vicinity of 10-100 nm thick Au patterns resulting in the formation of microwells or microchannels uniformly coated with 20-30 nm sized Au NPs. The methodology provides versatility in the types of microstructures that can be formed by varying the shape and dimensions of the Au patterns and the etch time. We also describe selective binding of antibodies to Au NP coated Si microwells using thiol-based surface modification.
This article investigates the three-dimensional self-assembly of submillimeter scale polyhedra using surface forces. Using a combination of energy landscape calculations and experiments, we investigate the influence of patterns of hydrophobic surfaces on generating defect-free, closed-packed aggregates of polyhedra, with a focus on cubic units. Calculations show that surface patterning strongly affects the interaction between individual units as well as that of the unit with the growing assembly. As expected, an increase in the hydrophobic surface area on each face results in larger global minima. However, it is the distribution of hydrophobic surface area on each cubic face that is strongly correlated to the energetic parameters driving low-defect assembly. For patterns with the same overall area, minimizing the radius of gyration and maximizing the angular distribution leads to steep energy curves, with a lower propensity for entrapment in metastable states. Experimentally, 200-500 microm sized metallic polyhedra were fabricated using a self-folding process, and the exposed surfaces were coated with a hydrophobic polymer. Cubes with surface patterns were agitated to cause aggregative self-assembly. Experimental results were consistent with energy calculations and suggest that geometric patterns with large overall areas, low radii of gyration, and high angular distributions result in efficient and low-defect assembly.
We describe strategies to curve, rotate, align, and bond precisely patterned two-dimensional (2D) nanoscale panels using forces derived from a minimization of surface area of liquefying or coalescing metallic grains. We demonstrate the utility of this approach by discussing variations in template size, patterns, and material composition. The strategy provides a solution path to overcome the limitation of inherently 2D lithographic processes by transforming 2D templates into mechanically robust and precisely patterned nanoscale curved structures and polyhedra with considerable versatility in material composition.
Despite the fact that we live in a 3D world and macroscale engineering is 3D, conventional submillimeter-scale engineering is inherently 2D. New fabrication and patterning strategies are needed to enable truly 3D-engineered structures at small size scales. Here, strategies that have been developed over the past two decades that seek to enable such millimeter to nanoscale 3D fabrication and patterning are reviewed. A focus is the strategy of self-assembly, specifically in a biologically inspired, more deterministic form, known as self-folding. Self-folding methods can leverage the strengths of lithography to enable the construction of precisely patterned 3D structures and "smart" components. This self-assembly approach is compared with other 3D fabrication paradigms, and its advantages and disadvantages are discussed.
The construction of three-dimensional (3D) objects, with any desired surface patterns, is both critical to and easily achieved in macroscale science and engineering. However, on the nanoscale, 3D fabrication is limited to particles with only very limited surface patterning. Here, we demonstrate a self-assembly strategy that harnesses the strengths of well-established 2D nanoscale patterning techniques and additionally enables the construction of stable 3D polyhedral nanoparticles. As a proof of the concept, we self-assembled cubic particles with sizes as small as 100 nm and with specific and lithographically defined surface patterns.
The concept of self-assembly of a two-dimensional (2D) template to a three-dimensional (3D) structure has been suggested as a strategy to enable highly parallel fabrication of complex, patterned microstructures. We have previously studied the surface tension based self-assembly of patterned, microscale polyhedral containers (cubes, square pyramids and tetrahedral frusta). In this paper, we describe the observed hierarchical self-assembly of more complex, patterned polyhedral containers in the form of regular dodecahedra and octahedra. The hierarchical design methodology, combined with the use of self-correction mechanisms, was found to greatly reduce the propagation of self-assembly error that occurs in these more complex systems. It is a highly effective way to mass-produce patterned, complex 3D structures on the microscale and could also facilitate encapsulation of cargo in a parallel and cost-effective manner. Furthermore, the behavior that we have observed may be useful in the assembly of complex systems with large numbers of components.
Microassembly based on origami, the Japanese art of paper folding, presents an attractive methodology for constructing complex three-dimensional (3D) devices and advanced materials. A variety of functional structures have been created using patterned metallic, semiconducting, and polymeric thin films, but have been limited to those that curve in a single direction. We report a design framework that can be used to achieve spontaneous bidirectional folds with any desired angle, and we demonstrate theoretical and experimental realizations of complex 3D structures with +90 degrees , -90 degrees , +180 degrees , and -180 degrees folds. The strategy is parallel, versatile, and compatible with conventional microfabrication.
We describe the fabrication of 3D membranes with precisely patterned surface nanoporosity and their utilization in size selective sampling. The membranes were self-assembled as porous cubes from lithographically fabricated 2D templates (Leong et al., Langmuir 23:8747-8751, 2007) with face dimensions of 200 microm, volumes of 8 nL, and monodisperse pores ranging in size from approximately 10 microm to 100 nm. As opposed to conventional sampling and filtration schemes where fluid is moved across a static membrane, we demonstrate sampling by instead moving the 3D nanoporous membrane through the fluid. This new scheme allows for straightforward sampling in small volumes, with little to no loss. Membranes with five porous faces and one open face were moved through fluids to sample and retain nanoscale beads and cells based on pore size. Additionally, cells retained within the membranes were subsequently cultured and multiplied using standard cell culture protocols upon retrieval.
Nature utilizes self-assembly to fabricate structures on length scales ranging from the atomic to the macro scale. Self-assembly has emerged as a paradigm in engineering that enables the highly parallel fabrication of complex, and often three-dimensional, structures from basic building blocks. Although there have been several demonstrations of this self-assembly fabrication process, rules that govern a priori design, yield and defect tolerance remain unknown. In this paper, we have designed the first model experimental system for systematically analyzing the influence of geometry on the self-assembly of 200 and 500 microm cubes and octahedra from tethered, multi-component, two-dimensional (2D) nets. We examined the self-assembly of all eleven 2D nets that can fold into cubes and octahedra, and we observed striking correlations between the compactness of the nets and the success of the assembly. Two measures of compactness were used for the nets: the number of vertex or topological connections and the radius of gyration. The success of the self-assembly process was determined by measuring the yield and classifying the defects. Our observation of increased self-assembly success with decreased radius of gyration and increased topological connectivity resembles theoretical models that describe the role of compactness in protein folding. Because of the differences in size and scale between our system and the protein folding system, we postulate that this hypothesis may be more universal to self-assembling systems in general. Apart from being intellectually intriguing, the findings could enable the assembly of more complicated polyhedral structures (e.g. dodecahedra) by allowing a priori selection of a net that might self-assemble with high yields.
We demonstrate mass-producible, tetherless microgrippers that can be remotely triggered by temperature and chemicals under biologically relevant conditions. The microgrippers use a self-contained actuation response, obviating the need for external tethers in operation. The grippers can be actuated en masse, even while spatially separated. We used the microgrippers to perform diverse functions, such as picking up a bead on a substrate and the removal of cells from tissue embedded at the end of a capillary (an in vitro biopsy).
We describe a strategy to construct three-dimensional (3D) containers with nanoporous walls by the self-assembly of lithographically patterned two-dimensional cruciforms with solder hinges. The first step involves fabricating two-dimensional (2D) cruciforms composed of six unlinked patterns: each pattern has an open window. The second step entails photolithographic patterning of solder hinges that connect the cruciform. The third step involves the deposition of polystyrene particles within the windows and the subsequent electrodeposition of metal in the voids between the polystyrene particles. Following the dissolution of the particles, the cruciforms are released from the substrate and heated above the melting point of the solder causing the cruciforms to spontaneously fold up into 3D cubic containers with nanoporous walls. We believe these 3D containers with nanoporous side walls are promising for molecular separations and cell-based therapies.
Spatial control of chemical reactions, with micro- and nanometer scale resolution, has important consequences for one pot synthesis, engineering complex reactions, developmental biology, cellular biochemistry and emergent behavior. We review synthetic methods to engineer this spatial control using chemical diffusion from spherical particles, shells and polyhedra. We discuss systems that enable both isotropic and anisotropic chemical release from isolated and arrayed particles to create inhomogeneous and spatially patterned chemical fields. In addition to such finite chemical sources, we also discuss spatial control enabled with laminar flow in 2D and 3D microfluidic networks. Throughout the paper, we highlight applications of spatially controlled chemistry in chemical kinetics, reaction-diffusion systems, chemotaxis and morphogenesis.
Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.
Nanopores with conical geometries have been found to rectify ionic current in electrolytes. While nanopores in semiconducting membranes are known to modulate ionic transport through gated modification of pore surface charge, the fabrication of conical nanopores in silicon (Si) has proven challenging. Here, we report the discovery that gold (Au) nanoparticle (NP)-assisted plasma etching results in the formation of conical etch profiles in Si. These conical profiles result due to enhanced Si etch rates in the vicinity of the Au NPs. We show that this process provides a convenient and versatile means to fabricate conical nanopores in Si membranes and crystals with variable pore-diameters and cone-angles. We investigated ionic transport through these pores and observed that rectification ratios could be enhanced by a factor of over 100 by voltage gating alone, and that these pores could function as ionic switches with high on-off ratios of approximately 260. Further, we demonstrate voltage gated control over protein transport, which is of importance in lab-on-a-chip devices and biomolecular separations.
Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges.
We describe nanoscale tools in the form of autonomous and remotely guided catalytically self-propelled InGaAs/GaAs/(Cr)Pt tubes. These rolled-up tubes with diameters in the range of 280-600 nm move in hydrogen peroxide solutions with speeds as high as 180 ?m s(-1). The effective transfer of chemical energy to translational motion has allowed these tubes to perform useful tasks such as transport of cargo. Furthermore, we observed that, while cylindrically rolled-up tubes move in a straight line, asymmetrically rolled-up tubes move in a corkscrew-like trajectory, allowing these tubes to drill and embed themselves into biomaterials. Our observations suggest that shape and asymmetry can be utilized to direct the motion of catalytic nanotubes and enable mechanized functions at the nanoscale.
This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope (MASCE) carries and releases a large number of thermo-sensitive, untethered micro-grippers (¿-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the ¿-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, sub-millimeter scale tissue sampling -grippers offers a multi-functional strategy for gastrointestinal capsule biopsy.
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