Water-sulfur-rich, oxidised adakite magmas are likely porphyry copper progenitors.

The world's largest current Cu resource is volcanic arc-hosted, porphyry copper deposits. Whether unusual parental magmas or fortuitous combinations of processes accompanying emplacement of common parental arc magmas (e.g., basalt) is required for ore deposit formation, remains unclear. Spatial and tectonic associations of adakite (andesite with high La/Yb, Sr/Y) with porphyries exist, but genetic links are debated. Delayed saturation with Cu-bearing sulfides consequent to elevated redox state seems essential for late-stage exsolution of Cu-bearing hydrothermal fluids. Partial melting of igneous layers of subducted, hydrothermally altered oceanic crust in the eclogite stability field are invoked to account for andesitic compositions, residual garnet signatures, and the putative oxidised character of adakites. Alternative petrogeneses include partial melting of lower crustal, garnet-bearing sources and extensive intra-crustal amphibole fractionation. Here we demonstrate mineral-hosted, adakite glass (formerly melt) inclusions in lavas erupted subaqueously in the New Hebrides arc are oxidised relative to island arc (and mid-ocean ridge) basalts, are H2O-S-Cl-rich, and moderately enriched in Cu. Polynomial fitting of chondrite-normalised, rare earth element abundance patterns shows the precursors of these erupted adakites were unequivocally derived from partial melting of subducted slab, and represent optimal porphyry copper progenitors.

Tetherless thermobiochemically actuated microgrippers.

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).

Three-dimensional fabrication at small size scales.

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.

Size selective sampling using mobile, 3D nanoporous membranes.

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.

Hierarchical self-assembly of complex polyhedral microcontainers.

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.

Self-loading lithographically structured microcontainers: 3D patterned, mobile microwells.

We demonstrate mass-producible, mobile, self-loading microcontainers that can be used to encapsulate both non-living and living objects, thus forming three-dimensionally patterned, mobile microwells.

Pick-and-place using chemically actuated microgrippers.

In this communication, we demonstrate the concept of single-use, chemically triggered, reversible tools in the form of mobile grippers that can be used to manipulate micro-objects. Both the closing and opening of the mobile grippers are triggered by chemicals, namely acetic acid (CH(3)COOH) and hydrogen peroxide (H(2)O(2)), respectively. The grippers close and open en masse based on chemically triggered, mechanical property changes within trilayer joints patterned within the gripper, and no external power is needed for operation. We describe the actuation of the gripper using a multilayer thin film model and demonstrate the utility of the gripper by picking-and-placing 200 microm diameter tubes and beads. Our pick-and-place microgripper is a first step toward the development of functional Micro Chemo-Mechanical Systems (MCMS), which are actuated by chemistry as opposed to electricity [as in Micro Electro-Mechanical Systems (MEMS)].

3D lithographically fabricated nanoliter containers for drug delivery.

Lithographic patterning offers the possibility for precise structuring of drug delivery devices. The fabrication process can also facilitate the incorporation of advanced functionality for imaging, sensing, telemetry and actuation. However, a major limitation of present day lithographic fabrication is the inherent two-dimensionality of the patterning process. We review a new approach to construct three dimensional (3D) patterned containers by lithographically patterning two dimensional (2D) templates with liquefiable hinges that spontaneously fold upon heating into hollow polyhedral containers. The containers have finite encapsulation volumes, can be made small enough to pass through a hypodermic needle, and the 3D profile of the containers facilitates enhanced diffusion with the surrounding medium as compared to reservoir systems fabricated in planar substrates. We compare the features of the containers to those of present day drug delivery systems. These features include ease of manufacture, versatility in size and shape, monodisperse porosity, ability for spatial manipulation and remote triggering to release drugs on-demand, the incorporation of electronic modules, cell encapsulation, biocompatibility and stability. We also review possible applications in drug delivery and cell encapsulation therapy (CET). The results summarized in this review suggest a new strategy to enable construction of "smart", three dimensional drug delivery systems using lithography.

Cell viability and noninvasive in vivo MRI tracking of 3D cell encapsulating self-assembled microcontainers.

Several molecular therapies require the implantation of cells that secrete biotherapeutic molecules and imaging the location and microenvironment of the cellular implant to ascertain its function. We demonstrate noninvasive in vivo magnetic resonance imaging (MRI) of self-assembled microcontainers that are capable of cell encapsulation. Negative contrast was obtained to discern the microcontainer with MRI; positive contrast was obtained in the complete absence of background signal. MRI on a clinical scanner highlights the translational nature of this research. The microcontainers were loaded with cells that were dispersed in an extracellular matrix, and implanted both subcutaneously and in human tumor xenografts in SCID mice. MRI was performed on the implants, and microcontainers retrieved postimplantation showed cell viability both within and proximal to the implant. The microcontainers are characterized by their small size, three dimensionality, controlled porosity, ease of parallel fabrication, chemical and mechanical stability, and noninvasive traceability in vivo.

Compactness determines the success of cube and octahedron self-assembly.

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.

MRI of regular-shaped cell-encapsulating polyhedral microcontainers.

We devised cubic and pyramidal microcontainers for cell encapsulation. While the cube is easier to manipulate, the pyramid offers a higher surface area-to-volume ratio and may therefore provide the encapsulated cells with increased access to nutrients. To discern the microcontainers' implant location and environment, and to aid in image-guided therapy, we showed noninvasive detection of microcontainers using MRI. Diamagnetic microcontainers were imaged using the radio frequency (RF) shielding effect, with negative contrast localized to the interior of the microcontainers. For applications in which it is difficult to distinguish the microcontainers from other hypointensities, positive contrast can be used to discern them. We showed positive-contrast MRI of a diamagnetic microcontainer. To image microcontainers that are smaller than the spatial resolution of MRI, we performed in vivo negative-contrast MRI of a ferromagnetic microcontainer. As opposed to the diamagnetic microcontainer, the ferromagnetic microcontainer created a region of MRI contrast several times larger than the microcontainer's dimensions.

Surface tension-driven self-folding polyhedra.

We discuss finite element simulations and experiments involving the surface tension-driven self-folding of patterned polyhedra. Two-dimensional (2D) photolithographically patterned templates folded spontaneously when solder hinges between adjacent faces were liquefied. Minimization of interfacial free energy of the molten solder with the surrounding fluidic medium caused the solder to ball up, resulting in a torque that rotated adjacent faces and drove folding. The simulations indicate that the folding process can be precisely controlled, has fault tolerance, and can be used to fold polyhedra composed of a variety of materials, ranging in size from the millimeter scale down to the nanometer scale. Experimentally, we have folded metallic, arbitrarily patterned polyhedra ranging in size from 2 mm to 15 microm.

Spatially controlled chemistry using remotely guided nanoliter scale containers.

In this communication we describe a new chemical encapsulation and release platform using 3D microfabricated nanoliter scale containers with controlled porosity. The containers can be fabricated of magnetic materials that allow them to be remotely guided using magnetic fields. The favorable attributes of the containers that include a versatile highly parallel fabrication process, precisely engineered porosity, isotropic/anisotropic chemical release profiles, and remote magnetic guiding provide an attractive platform for engineering spatially controlled chemical reactions in microfluidic systems.

Self-assembled three dimensional radio frequency (RF) shielded containers for cell encapsulation.

This paper describes the construction of three dimensional (3D) encapsulation devices in large numbers, using a novel self-assembling strategy characterized by high mechanical stability, controlled porosity, extreme miniaturization, high reproducibility and the possibility of integrating sensing and actuating electromechanical modules. We demonstrated encapsulation of microbeads and cells within the containers, thereby demonstrating one possible application in cell encapsulation therapy. Magnetic resonance (MR) images of the containers in fluidic media suggest radio frequency (RF) shielding and a susceptibility effect, providing characteristic hypointensity within the container, thereby allowing the containers to be easily detected. This demonstration is the first step toward the design of 3D, micropatterned, non-invasively trackable, encapsulation devices.