Unmasking the Resolution-Throughput Tradespace of Focused-Ion-Beam Machining.

Focused-ion-beam machining is a powerful process to fabricate complex nanostructures, often through a sacrificial mask that enables milling beyond the resolution limit of the ion beam. However, current understanding of this super-resolution effect is empirical in the spatial domain and nonexistent in the temporal domain. This article reports the primary study of this fundamental tradespace of resolution and throughput. Chromia functions well as a masking material due to its smooth, uniform, and amorphous structure. An efficient method of in-line metrology enables characterization of ion-beam focus by scanning electron microscopy. Fabrication and characterization of complex test structures through chromia and into silica probe the response of the bilayer to a focused beam of gallium cations, demonstrating super-resolution factors of up to 6 ± 2 and improvements to volume throughput of at least factors of 42 ± 2, with uncertainties denoting 95% coverage intervals. Tractable theory models the essential aspects of the super-resolution effect for various nanostructures. Application of the new tradespace increases the volume throughput of machining Fresnel lenses by a factor of 75, enabling the introduction of projection standards for optical microscopy. These results enable paradigm shifts of sacrificial masking from empirical to engineering design and from prototyping to manufacturing.

Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 108 cfu·µg-1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm-1. Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

Size matters--nanotechnology and therapeutics in rheumatology and immunology.

Nanotechnology, or the use of technology at the submicron scale, and its application to medicine (nanomedicine) draws from many ideas and technological advancements across myriad fields of materials technology and has improved biomedical understanding. Nanotechnology puts current materials science on the same physical scale as classic immune mediating substances, including viruses, moieties found on prokaryotic bacteria, and antigen presenting cells. Functionalized nanoparticles, fullerenes, liposomes, nanogels, and virus-like particles, are several examples of nanotechnology that are currently being applied to the treatment of oncologic and infectious diseases. However, the majority of the current commercial utilization of nanomedicine has been directed towards creating improved vaccines in order to prevent infectious diseases. These processes may have direct applications toward the creation of vaccines used to treat autoimmune disease as well. Current therapeutics utilizing nanotechnology, are gaining traction in treatments for gout and rheumatoid arthritis, and experimental animal models have demonstrated success in using the above technologies to improve the effectiveness and safety of current standard treatment of rheumatologic illnesses. Here we review many of the common forms of nanoparticles used in medical applications as well as where they have found a role in rheumatology. Continued technical feasibility, ongoing safety studies, and lingering questions on cost are all issues that have not yet been resolved in regards to widespread application in rheumatology and immunology.

Low Voltage Electrowetting-on-Dielectric Platform using Multi-Layer Insulators.

A low voltage, two-level-metal, and multi-layer insulator electrowetting-on-dielectric (EWD) platform is presented. Dispensing 300pl droplets from 140nl closed on-chip reservoirs was accomplished with as little as 11.4V solely through EWD forces, and the actuation threshold voltage was 7.2V with a 1Hz voltage switching rate between electrodes. EWD devices were fabricated with a multilayer insulator consisting of 135nm sputtered tantalum pentoxide (Ta(2)O(5)) and 180nm parylene C coated with 70nm of CYTOP. Furthermore, the minimum actuation threshold voltage followed a previously published scaling model for the threshold voltage, V(T), which is proportional to (t/ε(r))(1/2), where t and ε(r) are the insulator thickness and dielectric constant respectively. Device threshold voltages are compared for several insulator thicknesses (200nm, 500nm, and 1µm), different dielectric materials (parylene C and tantalum pentoxide), and homogeneous versus heterogeneous compositions. Additionally, we used a two-level-metal fabrication process, which enables the fabrication of smaller and denser electrodes with high interconnect routing flexibility. We also have achieved low dispensing and actuation voltages for scaled devices with 30pl droplets.