The One-Pot Directed Assembly of Cylinder-Forming Block Copolymer on Adjacent Chemical Patterns for Bimodal Patterning.

The direct self-assembly of cylinder-forming poly(styrene-block-methyl-methacrylate) (PS-b-PMMA) block copolymer is successfully assembled into two orientations, according to the underlying guiding pattern in different areas. Lying-down and perpendicular cylinders are formed, respectively, depending on the design of chemical pattern: sparse line/space pattern or hexagonal dot array. The first chemical pattern composed of prepatterned cross-linked polystyrene (XPS) line/space structure has a period (LS ) equal to twice the intercylinder period of the block copolymer (L0 ). The PS-b-PMMA thin film on the prepared chemical template after thermal annealing forms a lying-down cylinder morphology when the width of the PS strips is less than the width of PS block in the PS-b-PMMA block copolymer. The morphology is only applicable at the discrete thickness of the PS-b-PMMA film. In addition to forming the lying-down cylinders directly on the XPS guiding pattern, the cylinder-forming block copolymer can also be assembled in a perpendicular way on the second guiding pattern (the hexagonal dot array). The block copolymer films are registered into two orientations in a single directed self-assembly process. The features of the assembled patterns are successfully transferred down to the silicon oxide substrate.

Directed self-assembly of solvent-vapor-induced non-bulk block copolymer morphologies on nanopatterned substrates.

We report a study on directed self-assembly (DSA) with solvent annealing to induce the formation of non-bulk block copolymer microdomains on chemical patterns. Ultrathin films of symmetric polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) display morphologies of PMMA dots, stripes, and PS hexagons with increasing exposure time to acetone vapor, a PMMA-selective solvent. All three nanostructures form long-range-ordered and registered arrays on striped chemical patterns with periods (LS) commensurate to the solvated PS-b-PMMA microdomain period (L0,s). Solvent annealing is shown to facilitate DSA on non-regular chemical patterns, on which the local periods are incommensurate to L0,s. DSA with feature density multiplication, via solvent annealing, is also demonstrated.

Programmable nanoparticle ensembles via high-throughput directed self-assembly.

We present a simple and facile strategy for the directed self-assembly of nanoparticles into complex geometries using a minimal set of post guiding features patterned on a substrate. This understanding is based on extensive studies of nanoparticle self-assembly into linear, dense-packed, circular, and star-shaped ensembles when coated onto patterned substrates of predefined post arrays. We determined the conditions under which nanoparticles assemble and "connect" two adjacent post features, thereby forming the desired shapes. We demonstrate that with rational design of the post patterns to enforce the required pairwise interactions with posts, we can create arbitrary arrangements of nanoparticles-for example, to write "IBM" in a deterministic manner. This demonstration of programmable, high-throughput directed self-assembly of nanoparticles shows an alternative route to generate functional nanoparticle assemblies.

Vanillin catabolism in Rhodococcus jostii RHA1.

Genes encoding vanillin dehydrogenase (vdh) and vanillate O-demethylase (vanAB) were identified in Rhodococcus jostii RHA1 using gene disruption and enzyme activities. During growth on vanillin or vanillate, vanA was highly upregulated while vdh was not. This study contributes to our understanding of lignin degradation by RHA1 and other actinomycetes.

Highly selective immobilization of Au nanoparticles onto isolated and dense nanopatterns of poly(2-vinyl pyridine) brushes down to single-particle resolution.

Chemical patterns consisting of poly(2-vinyl pyridine) (P2VP) brushes in a background of a cross-linked polystyrene (PS) mat enabled the highly selective placement of citrate-stabilized Au nanoparticles (NPs) in arrays on surfaces. The cross-linked PS mat prevented the nonspecific binding of Au NPs, and the regions functionalized with P2VP brushes allowed the immobilization of the particles. Isolated chemical patterns of feature sizes from hundreds to tens of nanometers were prepared by standard lithographic techniques. The number of 13 nm Au NPs bound per feature increased linearly with increasing area of the patterns. This behavior is similar to previous reports using 40 nm particles or larger. Arrays of single NPs were obtained by reducing the dimensions of patterned P2VP brushes to below ~20 nm. To generate dense (center-to-center distance = 80 nm) linear chemical patterns for the placement of rows of single NPs, a block-copolymer (BCP)-assisted lithographic process was used. BCPs healed defects associated with the standard lithographic patterning of small dimensions at high densities and led to highly registered, linear, single NP arrays.

New-Onset Atrial Fibrillation Is a Risk Factor of Ischemic Stroke in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) induces atrial fibrillation (AF) and stroke, and COPD with AF increased ischemic stroke (IS) in a cross-sectional study. Therefore, healthcare providers must be concerned and well-informed about this particular situation. For this study, inpatient data were obtained from the Taiwan National Health Insurance Database in 2010. We identified patients who were hospitalized with COPD (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] is 491, 492, and 496). Patients who experienced AF (ICD-9-CM to 427.3) during the same admission or after COPD hospitalization were discharged and defined as new-onset AF. The outcome was IS (ICD-9-CM as 433-437). The factors related to IS after COPD were used for multivariate logistic regression. There were 4177/62,163 (6.72%) patients with incident IS. The risk of IS after COPD hospitalization was shown to have an adjusted odds ratio of 1.749 (95% CI: 1.584-1.93, p < 0.001) for patients with new-onset AF. Other factors included advanced age, atherosclerosis factors, comorbidity severity, sepsis and lower-level hospital admission. In conclusion, COPD patients suffering from new-onset AF had an increased incidence of IS in the population observation study. New-onset AF was an omit risk factor for IS in COPD in the Chinese population.

Ancient genomes from the Himalayas illuminate the genetic history of Tibetans and their Tibeto-Burman speaking neighbors.

Present-day Tibetans have adapted both genetically and culturally to the high altitude environment of the Tibetan Plateau, but fundamental questions about their origins remain unanswered. Recent archaeological and genetic research suggests the presence of an early population on the Plateau within the past 40 thousand years, followed by the arrival of subsequent groups within the past 10 thousand years. Here, we obtain new genome-wide data for 33 ancient individuals from high elevation sites on the southern fringe of the Tibetan Plateau in Nepal, who we show are most closely related to present-day Tibetans. They derive most of their ancestry from groups related to Late Neolithic populations at the northeastern edge of the Tibetan Plateau but also harbor a minor genetic component from a distinct and deep Paleolithic Eurasian ancestry. In contrast to their Tibetan neighbors, present-day non-Tibetan Tibeto-Burman speakers living at mid-elevations along the southern and eastern margins of the Plateau form a genetic cline that reflects a distinct genetic history. Finally, a comparison between ancient and present-day highlanders confirms ongoing positive selection of high altitude adaptive alleles.

Metal nanodot memory by self-assembled block copolymer lift-off.

As information technology demands for larger capability in data storage continue, ultrahigh bit density memory devices have been extensively investigated. To produce an ultrahigh bit density memory device, multilevel cell operations that require several states in one cell have been proposed as one solution, which can also alleviate the scaling issues in the current state-of-the-art complementary metal oxide semiconductor technology. Here, we report the first demonstration of metal nanodot memory using a self-assembled block copolymer lift-off. This metal nanodot memory with simple low temperature processes produced an ultrawide memory window of 15 V at the +/-18 V voltage sweep. Such a large window can be adopted for multilevel cell operations. Scanning electron microscopy and transmission electron microscopy studies showed a periodic metal nanodot array with uniform distribution defined by the block copolymer pattern. Consequently, this metal nanodot memory has high potential to reduce the variability issues that metal nanocrystal memories previously had and multilevel cells with ultrawide memory windows can be fabricated with high reliability and manufacturability.

Exploring Population Structure with Admixture Models and Principal Component Analysis.

Population structure is a commonplace feature of genetic variation data, and it has importance in numerous application areas, including evolutionary genetics, conservation genetics, and human genetics. Understanding the structure in a sample is necessary before more sophisticated analyses are undertaken. Here we provide a protocol for running principal component analysis (PCA) and admixture proportion inference-two of the most commonly used approaches in describing population structure. Along with hands-on examples with CEPH-Human Genome Diversity Panel and pragmatic caveats, readers will learn to analyze and visualize population structure on their own data.

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia.

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time.

One-Step Direct-Patterning Template Utilizing Self-Assembly of POSS-Containing Block Copolymers.

We report the self-assembly of organic-inorganic block copolymers (BCP) in thin-films by simple solvent annealing on unmodified substrates. The resulting vertically oriented lamellae and cylinders are converted to a hard silica mask by a single step highly selective oxygen plasma etching. The size of the resulting nanostructures in the case of cylinders is less than 10 nm.

Assembly of nanocrystal arrays by block-copolymer-directed nucleation.

Growing in line: The surface chemistry of self-assembled nanostructured block copolymers is used to control the sites at which semiconducting metal sulfide nanocrystals nucleate and grow on a surface directly from aqueous solutions. This process is a new and general strategy for the bottom-up assembly of functional nanocrystalline materials for a variety of applications.

Surface Assembly Configurations and Packing Preferences of Fibrinogen Mediated by the Periodicity and Alignment Control of Block Copolymer Nanodomains.

The ability to control the specific adsorption and packing behaviors of biomedically important proteins by effectively guiding their preferred surface adsorption configuration and packing orientation on polymeric surfaces may have utility in many applications such as biomaterials, medical implants, and tissue engineering. Herein, we investigate the distinct adhesion configurations of fibrinogen (Fg) proteins and the different organization behaviors between single Fg molecules that are mediated by the changes in the periodicity and alignment of chemically alternating nanodomains in thin films of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) block copolymer (BCP). Specifically, the adsorption characteristics of individual Fg molecules were unambiguously resolved on four different PS-b-PMMA templates of dsa PS-b-PMMA, sm PS-b-PMMA, com PS-b-PMMA, and PS-r-PMMA. By direct visualization through high resolution imaging, the distinct adsorption and packing configurations of both isolated and interacting Fg molecules were determined as a function of the BCP template-specific nanodomain periodicity, domain alignment (random versus fully aligned), and protein concentration. The three dominant Fg adsorption configurations, SP∥, SP⊥, and TP, were observed and their occurrence ratios were ascertained on each PS-b-PMMA template. During surface packing, the orientation of the protein backbone was largely governed by the periodicity and alignment of the underlying PS-b-PMMA nanodomains whose specific direction was explicitly resolved relative to the polymeric nanodomain axis. The use of PS-b-PMMA with a periodicity much smaller than (and comparable to) the length of Fg led to a Fg scaffold with the protein backbone aligned parallel (and perpendicular) to the nanodomain major axis. In addition, we have successfully created fully Fg-decorated BCP constructs analogous to two-dimensional Fg crystals in which aligned protein molecules are arranged either side-on or end-on, depending on the BCP template. Our results demonstrate that the geometry and orientation of the protein can be effectively guided during Fg self-assembly by controlling the physical dimensions and orientations of the underlying BCP templates. Finally, the biofunctionality of the BCP surface-bound Fg was assessed and the Fg/BCP construct was successfully used in the Ca-P nanoparticle nucleation/growth and microglia cell activation.

Directed self-assembly of block copolymer films on atomically-thin graphene chemical patterns.

Directed self-assembly of block copolymers is a scalable method to fabricate well-ordered patterns over the wafer scale with feature sizes below the resolution of conventional lithography. Typically, lithographically-defined prepatterns with varying chemical contrast are used to rationally guide the assembly of block copolymers. The directed self-assembly to obtain accurate registration and alignment is largely influenced by the assembly kinetics. Furthermore, a considerably broad processing window is favored for industrial manufacturing. Using an atomically-thin layer of graphene on germanium, after two simple processing steps, we create a novel chemical pattern to direct the assembly of polystyrene-block-poly(methyl methacrylate). Faster assembly kinetics are observed on graphene/germanium chemical patterns than on conventional chemical patterns based on polymer mats and brushes. This new chemical pattern allows for assembly on a wide range of guiding periods and along designed 90° bending structures. We also achieve density multiplication by a factor of 10, greatly enhancing the pattern resolution. The rapid assembly kinetics, minimal topography, and broad processing window demonstrate the advantages of inorganic chemical patterns composed of hard surfaces.

Two-dimensional pattern formation using graphoepitaxy of PS-b-PMMA block copolymers for advanced FinFET device and circuit fabrication.

Directed self-assembly (DSA) of lamellar phase block-co-polymers (BCPs) can be used to form nanoscale line-space patterns. However, exploiting the potential of this process for circuit relevant patterning continues to be a major challenge. In this work, we propose a way to impart two-dimensional pattern information in graphoepitaxy-based lamellar phase DSA processes by utilizing the interactions of the BCP with the template pattern. The image formation mechanism is explained through the use of Monte Carlo simulations. Circuit patterns consisting of the active region of Si FinFET transistors, referred to as Si "fins", were fabricated to demonstrate the applicability of this technique to the formation of complex patterns. The quality of the Si fin features produced by this process was validated by demonstrating the first functional DSA-patterned FinFET devices with 29 nm-pitch fins.

Pattern placement accuracy in block copolymer directed self-assembly based on chemical epitaxy.

The realization of viable designs for circuit patterns using the dense features formed by block copolymer directed self-assembly (DSA) will require a precise and quantitative understanding of self-assembled feature registration to guiding templates or chemical prepatterns. Here we report measurements of DSA placement error for lamellar block copolymer domains indexed to specific lines in the surface chemical prepattern for spatial frequency tripling and quadrupling. These measurements are made possible by the use of an inorganic domain-selective prepattern material that may be imaged upon polymer removal after DSA and a prepattern design incorporating a single feature serving as an in situ registration mark that is identifiable by pattern symmetry in both the prepattern and resulting self-assembled pattern. The results indicate that DSA placement error is correlated with average prepattern line width as well as prepattern pitch uniformity. Finally, the magnitude of DSA placement error anticipated for a uniform, optimized prepattern is estimated.

Localization of multiple DNA sequences on nanopatterns.

DNA oligonucleotides of different sequences were patterned at the nanoscale. Areas of positive charge were generated by exposure of insulating substrates, spin-on hydrogen silsesquioxane or vapor-deposited SiO(2) on Si, with ionizing radiation sources used in electron beam and extreme ultraviolet lithography. Au nanoparticles (NPs) with a diameter of 15 nm, carrying covalently bound negatively charged single-stranded DNA oligonucleotides, were site specifically immobilized directly on the exposed regions and presented oligonucleotides for subsequent hybridization. Repeated exposure and deposition of NPs allowed for patterning multiple DNA sequences. Patterns with dimensions as small as 15 nm were fabricated using electron beam lithography. The use of DNA-functionalized NPs rather than just DNA facilitates metrology in scanning electron microscopy and improves the hybridization efficiency of the oligonucleotides on the surface.

Nanofabrication of broad-band antireflective surfaces using self-assembly of block copolymers.

We present a simple and cost-effective method for the fabrication of antireflective surfaces by self-assembly of block copolymers and subsequent plasma etching. The block copolymers create randomly oriented periodic patterns, which are further transferred into fused silica substrates. The reflection on the patterned fused silica surface is reduced to well below 1% in the ultraviolet, visible, and near-infrared ranges by exploiting subwavelength nanostructures with periodicities down to 48 nm. We show that by choosing the appropriate block copolymers and pattern transfer parameters the optical properties of the antireflective surface can be easily tuned, and the spectral measurements verify a significant reduction of the reflectivity by a factor of 10. The experiments, confirmed with simulations based on rigorous diffraction theory, also show that the tapered shape of the nanostructures gives rise to a graded index surface, resulting in a broad-band antireflective behavior.

Molecular transfer printing using block copolymers.

Soft lithographic techniques augment or enhance the capabilities of traditional patterning processes and expand the diversity of materials that can be patterned. Realization of robust parallel techniques for creating chemical patterns at the nanoscale has been challenging. Here we present a method for creating and replicating chemical patterns that uses functionalized homopolymer inks that are preferentially segregated into the nanodomains of phase-separated diblock copolymer films. The inks are transferred by reaction to substrates that are brought into contact with block copolymer films, creating chemical patterns on the substrate that mirror the domain structure present at the film surface with high fidelity and resolution. In addition to printing from self-assembled domain structures, we can also direct the assembly of the block copolymer films from which transfer occurs using lithographically defined masters so as to replicate and transfer patterns of inks with controlled and well-defined geometries. The transferred patterns may be at higher resolution than the lithographically defined master, and the process can be repeated to create multiple copies of identical replicas. Transfer of one ink from one block of the copolymer is also possible, and filling the interspatial regions of the pattern with a second ink provides a pathway toward creating patterns with diverse chemical functionalities.

Directed self-assembly of block copolymers for nanolithography: fabrication of isolated features and essential integrated circuit geometries.

Self-assembling block copolymers are of interest for nanomanufacturing due to the ability to realize sub-100 nm dimensions, thermodynamic control over the size and uniformity and density of features, and inexpensive processing. The insertion point of these materials in the production of integrated circuits, however, is often conceptualized in the short term for niche applications using the dense periodic arrays of spots or lines that characterize bulk block copolymer morphologies, or in the long term for device layouts completely redesigned into periodic arrays. Here we show that the domain structure of block copolymers in thin films can be directed to assemble into nearly the complete set of essential dense and isolated patterns as currently defined by the semiconductor industry. These results suggest that block copolymer materials, with their intrinsically advantageous self-assembling properties, may be amenable for broad application in advanced lithography, including device layouts used in existing nanomanufacturing processes.