Direct visualization of nanoparticle morphology in thermally sintered nanoparticle ink traces and the relationship among nanoparticle morphology, incomplete polymer removal, and trace conductivity.

A key challenge encountered by printed electronics is that the conductivity of sintered metal nanoparticle (NP) traces is always several times smaller than the bulk metal conductivity. Identifying the relative roles of the voids and the residual polymers on NP surfaces in sintered NP traces, in determining such reduced conductivity, is essential. In this paper, we employ a combination of electron microscopy imaging and detailed simulations to quantify the relative roles of such voids and residual polymers in the conductivity of sintered traces of a commercial (Novacentrix) silver nanoparticle-based ink. High resolution transmission electron microscopy imaging revealed details of the morphology of the inks before and after being sintered at 150 °C. Prior to sintering, NPs were randomly close packed into aggregates with nanometer thick polymer layers in the interstices. The 2D porosity in the aggregates prior to sintering was near 20%. After heating at 150 °C, NPs sintered together into dense aggregates (nanoaggregates or NAgs) with sizes ranging from 100 to 500 nm and the 2D porosity decreased to near 10%. Within the NAgs, the NPs were mostly connected via sintered metal bridges, while the outer surfaces of the NAgs were coated with a nanometer thick layer of polymer. Motivated by these experimental results, we developed a computational model for calculating the effective conductivity of the ink deposit represented by a prototypical NAg consisting of NPs connected by metallic bonds and having a polymer layer on its outer surface placed in a surrounding medium. The calculations reveal that a NAg that is 35%-40% covered by a nanometer thick polymeric layer has a similar conductivity compared to prior experimental measurements. The findings also demonstrate that the conductivity is less influenced by the polymer layer thickness or the absolute value of the NAg dimensions. Most importantly, we are able to infer that the reduced value of the conductivity of the sintered traces is less dependent on the void fraction and is primarily attributed to the incomplete removal of the polymeric material even after sintering.

Numerical Study of the Coalescence and Mixing of Drops of Different Polymeric Materials.

In this study, we employ direct numerical simulation (DNS) to investigate the solutal hydrodynamics dictating the three-dimensional coalescence of microscopic, identical-sized sessile drops of different but miscible shear-thinning polymeric liquids (namely, PVAc or polyvinyl acetate and PMMA or polymethylmethacrylate), with the drops being in partially wetted configuration. Despite the ubiquitousness of the interaction of different dissimilar droplets in a variety of engineering problems ranging from additive manufacturing to understanding the behavior of photonic crystals, coalescence of drops composed of different polymeric and non-Newtonian materials has not been significantly explored. Interaction of such dissimilar droplets often involves simultaneous drop spreading, coalescence, and mixing. The mixing dynamics of the dissimilar drops are governed by interphase diffusion, the residual kinetic energy of the drops stemming from the fact that coalescence starts before the spreading of the drops have been completed, and the solutal Marangoni convection. We provide the three-dimensional velocity fields and velocity vectors inside the completely miscible, dissimilar coalescing droplets. Our simulations explicate the relative influence of these different effects in determining the flow field at different locations and at different time instances and the consequent mixing behavior inside the interacting drops. We also show the non-monotonic (in terms of the direction of migration) propagation of the mixing front of the miscible coalescing drops over time. We also establish that the overall mixing (on either side of the mixing front) speeds up as the Marangoni effects dictate the mixing. We anticipate that our study will provide an important foundation for studying miscible multi-material liquid systems, which will be crucial for applications such as inkjet or aerosol jet printing, lab-on-a-chip, polymer processing, etc.

Coalescence of Microscopic Polymeric Drops: Effect of Drop Impact Velocities.

In this paper, we employ the direct numerical simulation (DNS) method for probing three-dimensional, axisymmetric coalescence of microscale, power-law-obeying, and shear-thinning polymeric liquid drops of identical sizes impacting a solid, solvophilic substrate with a finite velocity. Unlike the cases of drop coalescence of Newtonian liquid drops, coalescence of non-Newtonian polymeric drops has received very little attention. Our study bridges this gap by providing (1) the time-dependent, three-dimensional (3D) velocity field and 3D velocity vectors inside two coalescing polymeric drops in the presence of a solid substrate and (2) the effect of the drop impact velocity (on the solid substrate), quantified by the Weber number (We), on the coalescence dynamics. Our simulations reveal that the drop coalescence is qualitatively similar for different We values, although the velocity magnitudes involved, the time required to attain different stages of coalescence, and the time needed to attain equilibrium vary drastically for finitely large We values. Finally, we provide detailed simulation-based, as well as physics-based, scaling laws describing the growth of the height and the width of the bridge (formed due to coalescence) dictating the 3D coalescence event. Our analyses reveal distinct scaling laws for the growth of bridge height and width for early and late stages of coalescence as a function of We. We also provide simulation-based coalescence results for the case of two unequal sized drops impacting on a substrate (nonaxisymmetric coalescence) as well as results for axisymmetric coalescence for drops of different rheology. We anticipate that our findings will be critical in better understanding events such as inkjet or aerosol jet polymer printing, dynamics of polymer blends, and many more.

N-Hydroxyformamide LpxC inhibitors, their in vivo efficacy in a mouse Escherichia coli infection model, and their safety in a rat hemodynamic assay.

UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase (LpxC), the zinc metalloenzyme catalyzing the first committed step of lipid A biosynthesis in Gram-negative bacteria, has been a target for antibacterial drug discovery for many years. All inhibitor chemotypes reaching an advanced preclinical stage and clinical phase 1 have contained terminal hydroxamic acid, and none have been successfully advanced due, in part, to safety concerns, including hemodynamic effects. We hypothesized that the safety of LpxC inhibitors could be improved by replacing the terminal hydroxamic acid with a different zinc-binding group. After choosing an N-hydroxyformamide zinc-binding group, we investigated the structure-activity relationship of each part of the inhibitor scaffold with respect to Pseudomonas aeruginosa and Escherichia coli LpxC binding affinity, in vitro antibacterial potency and pharmacological properties. We identified a novel, potency-enhancing hydrophobic binding interaction for an LpxC inhibitor. We demonstrated in vivo efficacy of one compound in a neutropenic mouse E. coli infection model. Another compound was tested in a rat hemodynamic assay and was found to have a hypotensive effect. This result demonstrated that replacing the terminal hydroxamic acid with a different zinc-binding group was insufficient to avoid this previously recognized safety issue with LpxC inhibitors.

Pharmacokinetic/Pharmacodynamic Determination and Preclinical Pharmacokinetics of the ß-Lactamase Inhibitor ETX1317 and Its Orally Available Prodrug ETX0282.

Increasingly resistant Enterobacteriaceae have emerged as a health threat in both hospital and community settings. Infections of the urinary tract, once often treated with oral agents in the community, are requiring increased hospitalization and use of intravenously administered agents for effective treatment. These isolates often carry extended spectrum ß-lactamases (ESBLs) and carbapenemases that necessitate the need for an inhibitor to cover a broad range of ß-lactamases. ETX1317 is a novel diazabicyclooctane class serine ß-lactamase inhibitor that restores the antibacterial activity of several classes of ß-lactams, including third-generation cephalosporins such as cefpodoxime. ETX1317 is currently being developed as an orally available prodrug, ETX0282, to be administered with cefpodoxime proxetil (CPDP). The combination has demonstrated oral efficacy in murine models of infection. Pharmacokinetics established in preclinical species and pharmacokinetic/pharmacodynamic attributes suggest the orally administered combination ETX0282 + CPDP could serve as an effective treatment option against contemporary ESBL and carbapenemase-producing Enterobacteriaceae.

Pharmacokinetics and Tolerability of Intravenous Sulbactam-Durlobactam with Imipenem-Cilastatin in Hospitalized Adults with Complicated Urinary Tract Infections, Including Acute Pyelonephritis.

Durlobactam (DUR; ETX2514) is a novel ß-lactamase inhibitor with broad-spectrum activity against Ambler class A, C, and D ß-lactamases. Durlobactam restores the in vitro activity of sulbactam (SUL) against members of the Acinetobacter baumannii-A. calcoaceticus complex (ABC). Sulbactam (SUL)-durlobactam (SUL-DUR) is under development for the treatment of ABC infections. Eighty patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), were randomized 2:1 to receive SUL-DUR at 1 g/1 g intravenously (i.v.) or placebo every 6 h (q6h) for 7 days and background therapy with imipenem-cilastatin (IMI) at 500 mg i.v. q6h to evaluate the tolerability of SUL-DUR in hospitalized patients. Patients with bacteremia could receive up to 14 days of therapy. SUL-DUR tolerability and the values of various pharmacokinetic (PK) parameters were determined. Efficacy was recorded at the test-of-cure (TOC) visit. SUL-DUR was well tolerated, with no serious adverse events (AEs) being reported. Headache (5.7%), nausea (3.8%), diarrhea (3.8%), and vascular pain (3.8%) were the most common drug-related AEs with SUL-DUR and were mostly of mild or moderate severity. The PK profile of DUR and SUL in hospitalized patients was consistent with observations in healthy volunteers. Overall success in the microbiological modified intent-to-treat (m-MITT) population was similar between the groups, as would be expected with IMI background therapy in all patients (overall success at the TOC visit, 76.6% [n = 36] with SUL-DUR and 81.0% [n = 17] with placebo). SUL-DUR in combination with IMI was well tolerated in patients with cUTIs. The pharmacokinetics of SUL-DUR observed in hospitalized patients was similar to that observed in healthy volunteers. (This study has been registered at ClinicalTrials.gov under identifier NCT03445195.).

Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

High-quality uniform dry transfer of graphene to polymers.

In this paper we demonstrate high-quality, uniform dry transfer of graphene grown by chemical vapor deposition on copper foil to polystyrene. The dry transfer exploits an azide linker molecule to establish a covalent bond to graphene and to generate greater graphene-polymer adhesion compared to that of the graphene-metal foil. Thus, this transfer approach provides a novel alternative route for graphene transfer, which allows for the metal foils to be reused.

Mechanisms of controlled release from silk fibroin films.

The controlled release of fluorescein-iso-thio-cyanate (FITC)-labeled dextrans from methanol-treated and untreated silk fibroin films was modeled to characterize the release kinetics and mechanisms. Silk films were prepared with FITC-dextrans of various molecular weights (4, 10, 20, 40 kDa). Methanol treatment was used to promote crystallinity. The release data were assessed with two different models, an empirical exponential equation commonly fit to release data and a mechanism-based semiempirical model derived from Fickian diffusion through a porous film. The FITC-dextran release kinetics were evaluated as a function of molecular weight and compared between the untreated- and methanol-treated films. For the empirical model, the estimated values of the model parameters decreased with the molecular weight of the analyte and showed no significant difference between untreated- and methanol-treated films. For the diffusion-based model, the estimated diffusion coefficient was smaller for the methanol-treated films than for the untreated films. Also, the diffusion coefficient was observed to decrease linearly with increasing molecular weight of the analyte. The percent of FITC-dextran loading entrapped and not released was less for the methanol-treated films than for untreated films and linearly increased with molecular weight. A linear regression was fit to the relationship between molecular weight and the percent of entrapped FITC-dextran particles. Using these defined linear relationships, we present an updated version of the diffusion model for simulating release of FITC-dextran of varied molecular weights from methanol-treated and untreated silk films.

Formation of silicon-based molecular electronic structures using flip-chip lamination.

We report the fabrication of molecular electronic test structures consisting of Au-molecule-Si junctions by first forming omega-functionalized self-assembled monolayers on ultrasmooth Au on a flexible substrate and subsequently bonding to Si(111) with flip-chip lamination by using nanotransfer printing (nTP). Infrared spectroscopy (IRS), spectroscopic ellipsometry (SE), water contact angle (CA), and X-ray photoelectron spectroscopy (XPS) verified the monolayers self-assembled on ultrasmooth Au were dense, relatively defect-free, and the -COOH was exposed to the surface. The acid terminated monolayers were then reacted with a H-terminated Si(111) surface using moderate applied pressures to facilitate the interfacial reaction. After molecular junction formation, the monolayers were characterized with p-polarized backside reflection absorption infrared spectroscopy (pb-RAIRS) and electrical current-voltage measurements. The monolayer quality remains largely unchanged after lamination to the Si(111) surface, with the exception of changes in the COOH and Si-O vibrations indicating chemical bonding. Both vibrational and electrical data indicate that electrical contact to the monolayer is formed while preserving the integrity of the molecules without metal filaments. This approach provides a facile means to fabricate high-quality molecular junctions consisting of dense monolayers chemically bonded to metal and silicon electrodes.