Emily R. Kinser

Engineering Cellular Response Using Nanopatterned Bulk Metallic Glass

Nanopatterning of biomaterials is rapidly emerging as a tool to engineer cell function. Bulk metallic glasses (BMGs), a class of biocompatible materials, are uniquely suited to study nanopattern–cell interactions as they allow for versatile fabrication of nanopatterns through thermoplastic forming. Work presented here employs nanopatterned BMG substrates to explore detection of nanopattern feature sizes by various cell types, including cells that are associated with foreign body response, pathology, and tissue repair. Fibroblasts decreased in cell area as the nanopattern feature size increased, and fibroblasts could detect nanopatterns as small as 55 nm in size. Macrophages failed to detect nanopatterns of 150 nm or smaller in size, but responded to a feature size of 200 nm, resulting in larger and more elongated cell morphology. Endothelial cells responded to nanopatterns of 100 nm or larger in size by a significant decrease in cell size and elongation. On the basis of these observations, nondimensional analysis was employed to correlate cellular morphology and substrate nanotopography. Analysis of the molecular pathways that induce cytoskeletal remodeling, in conjunction with quantifying cell traction forces with nanoscale precision using a unique FIB-SEM technique, enabled the characterization of underlying biomechanical cues. Nanopatterns altered serum protein adsorption and effective substrate stiffness, leading to changes in focal adhesion density and compromised activation of Rho-A GTPase in fibroblasts. As a consequence, cells displayed restricted cell spreading and decreased collagen production. These observations suggest that topography on the nanoscale can be designed to engineer cellular responses to biomaterials.

Investigation of emerging middle-of-line poly gate-to-diffusion contact reliability issues

The minimum insulator spacing between the polysilicon control gate (PC) and the diffusion contacts (CA) in advanced VLSI circuits is aggressively shrinking due to continuous technology scaling. Meanwhile, rapid adoptions of new materials such as metal gate, epitaxial SiGe source /drain, stress liner, and copper contact together with new device configurations such as raised source/drain and FinFET may further exacerbate the PC-CA dielectric reliability. SRAM yield loss and functional stress failures of both SRAM and DRAM chips due to middle-of-line (MOL) PC-CA shorts and early breakdown have been observed during the course of technology development at 32nm. Therefore, the leakage and breakdown of middle-of-line (MOL) PC-to-CA dielectric is rapidly becoming an emerging reliability issue for a successful technology development. In this paper, a comprehensive investigation of MOL PC-to-CA reliability issues at 32nm technology node was conducted. A new qualification methodology was developed to assure PC-to-CA reliability at an acceptable level.

Guided Evolution of Bulk Metallic Glass Nanostructures: A Platform for Designing 3D Electrocatalytic Surfaces

Electrochemical devices such as fuel cells, electrolyzers, lithium-air batteries, and pseudocapacitors are expected to play a major role in energy conversion/storage in the near future. Here, it is demonstrated how desirable bulk metallic glass compositions can be obtained using a combinatorial approach and it is shown that these alloys can serve as a platform technology for a wide variety of electrochemical applications through several surface modification techniques.

High quality factor metallic glass cantilevers with tunable mechanical properties

The resonant properties of bulk metallic glass (BMG) microcantilevers were studied. Pt57.5Cu14.7Ni5.3P22.5 BMG was used to fabricate the cantilevers, on the wafer scale, using a thermoplastic forming technique. The resonant behaviors of the cantilevers were then measured in air and various vacuum levels and annealing conditions. The quality factors increase predictably after annealing at temperatures below the glass transition temperature (Tg) for different times. The increase of quality factor of annealed cantilevers is attributable to the decrease in internal friction of the BMG due to thermally activated structural relaxation. Annealing above Tg resets the quality factor to values comparable to that of the as-formed cantilever. Therefore, the quality factor and mechanical properties of a cantilever could be tuned by the selection of suitable annealing temperatures and times. The measured quality factors are in excess of 2000 in air and 8100 in vacuum.

Low temperature direct wafer to wafer bonding for 3D integration: Direct bonding, surface preparation, wafer-to-wafer alignment

In this paper the integration challenges related to oxide-oxide bonding for wafer-to-wafer stacking technology are discussed. Furthermore, interface defectivity, wafer-to-wafer alignment and bond strength data are presented.

Regulation of cell-cell fusion by nanotopography

Cell-cell fusion is fundamental to a multitude of biological processes ranging from cell differentiation and embryogenesis to cancer metastasis and biomaterial-tissue interactions. Fusogenic cells are exposed to biochemical and biophysical factors, which could potentially alter cell behavior. While biochemical inducers of fusion such as cytokines and kinases have been identified, little is known about the biophysical regulation of cell-cell fusion. Here, we designed experiments to examine cell-cell fusion using bulk metallic glass (BMG) nanorod arrays with varying biophysical cues, i.e. nanotopography and stiffness. Through independent variation of stiffness and topography, we found that nanotopography constitutes the primary biophysical cue that can override biochemical signals to attenuate fusion. Specifically, nanotopography restricts cytoskeletal remodeling-associated signaling, which leads to reduced fusion. This finding expands our fundamental understanding of the nanoscale biophysical regulation of cell fusion and can be exploited in biomaterials design to induce desirable biomaterial-tissue interactions.

Chip package interaction evaluation for a high performance 65nm and 45nm CMOS Technology in a stacked die package with C4 and wirebond interconnections

An evaluation of 65 nm and 45 nm CMOS technology in a stacked die package is presented. The technology uses SiCOH advanced low K and ultra low K back end of line (BEOL) for high performance. A BEOL specific test vehicle was fabricated in these technologies and both flip chip and wirebond die used in a stacked die configuration. Manufacturability evaluations for bond and assembly processes and materials were performed and reliability studies completed on assembled modules. Results will show that the technologies are reliable in this packaging configuration.

Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass

Mesenchymal stem cell (MSC) differentiation is regulated by surface modification including texturing, which is applied to materials to enhance tissue integration. Here, we used Pt57.5Cu14.7Ni5.3P22.5 bulk metallic glass (Pt-BMG) with nanopatterned surfaces achieved by thermoplastic forming to influence differentiation of human MSCs. Pt-BMGs are a unique class of amorphous metals with high strength, elasticity, corrosion resistance, and an unusual plastic-like processability. It was found that flat and nanopattened Pt-BMGs induced osteogenic and adipogenic differentiation, respectively. In addition, osteogenic differentiation on flat BMG exceeded that observed on medical grade titanium and was associated with increased formation of focal adhesions and YAP nuclear localization. In contrast, cells on nanopatterned BMGs exhibited rounded morphology, formed less focal adhesions and had mostly cytoplasmic YAP. These changes were preserved on nanopatterns made of nanorods with increased stiffness due to shorter aspect ratios, suggesting that MSC differentiation was primarily influenced by topography. These observations indicate that both elemental composition and nanotopography can modulate biochemical cues and influence MSCs. Moreover, the processability and highly tunable nature of Pt-BMGs enables the creation of a wide range of surface topographies that can be reproducibly and systematically studied, leading to the development of implants capable of engineering MSC functions.

Nanopatterned Bulk Metallic Glass Biosensors

Nanopatterning as a surface area enhancement method has the potential to increase signal and sensitivity of biosensors. Platinum-based bulk metallic glass (Pt-BMG) is a biocompatible material with electrical properties conducive for biosensor electrode applications, which can be processed in air at comparably low temperatures to produce nonrandom topography at the nanoscale. Work presented here employs nanopatterned Pt-BMG electrodes functionalized with glucose oxidase enzyme to explore the impact of nonrandom and highly reproducible nanoscale surface area enhancement on glucose biosensor performance. Electrochemical measurements including cyclic voltammetry (CV) and amperometric voltammetry (AV) were completed to compare the performance of 200 nm Pt-BMG electrodes vs Flat Pt-BMG control electrodes. Glucose dosing response was studied in a range of 2 mM to 10 mM. Effective current density dynamic range for the 200 nm Pt-BMG was 10-12 times greater than that of the Flat BMG control. Nanopatterned electrode sensitivity was measured to be 3.28 μA/cm2/mM, which was also an order of magnitude greater than the flat electrode. These results suggest that nonrandom nanotopography is a scalable and customizable engineering tool which can be integrated with Pt-BMGs to produce biocompatible biosensors with enhanced signal and sensitivity.

Electrocatalysts: Guided Evolution of Bulk Metallic Glass Nanostructures: A Platform for Designing 3D Electrocatalytic Surfaces (Adv. Mater. 10/2016).

On page 1940, A. D. Taylor and co-workers demonstrate nanoporous bicontinuous structures using controlled structural evolution of metallic glass. By using techniques such as dealloying, galvanic replacement, and under-potential deposition, bulk-metallic-glass alloys can be pushed beyond their compositional limitations and tuned for a wide variety of interfacial and electrochemical reactions. Examples are illustrated for hydrogen and methanol oxidation, as well as oxygen reduction reactions.