Chemical Imaging of Buried Interfaces in Organic-Inorganic Devices Using Focused Ion Beam-Time-of-Flight-Secondary-Ion Mass Spectrometry

Copyright © 2019 American Chemical Society. Organic-inorganic hybrid materials enable the design and fabrication of new materials with enhanced properties. The interface between the organic and inorganic materials is often critical to the device's performance; therefore, chemical characterization is of significant interest. Because the interfaces are often buried, milling by focused ion beams (FIBs) to expose the interface is becoming increasingly popular. Chemical imaging can subsequently be obtained using secondary-ion mass spectrometry (SIMS). However, the FIB milling process damages the organic material. In this study, we make an organic-inorganic test structure to develop a detailed understanding of the processes involved in FIB milling and SIMS imaging. We provide an analysis methodology that involves a "clean-up" process using sputtering with an argon gas cluster ion source to remove the FIB-induced damage. The methodology is evaluated for two additive manufactured devices, an encapsulated strain sensor containing silver tracks embedded in a polymeric material and a copper track on a flexible polymeric substrate created using a novel nanoparticle sintering technique

A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants

We propose a strategy for creating tuneable 3D printed drug delivery devices. 3D printing offers the opportunity for improved compliance and patient treatment outcomes through personalisation, but bottlenecks include finding formulations that provide a choice of drug loading and release rate, are tuneable and avoid the need for surgical removal. Our solution is to exploit 3D inkjet printing freedoms. We use a reactive prodrug that can polymerize into drug-attached macromolecules during 3D printing, and by tuning the hydrophilicity we can facilitate or hinder hydrolysis, which in turn controls the drug release. To demonstrate this approach, we attach ibuprofen to 2-hydroxyethyl acrylate through a cleavable ester bond, formulate it for inkjet 3D printing, and then print to produce a solid dosage form. This allows a much higher loading than is usually achievable-in our case up to 58 wt%. Of equal importance, the 3D inkjet printing freedoms mean that our drug delivery device is highly tuneable: by selection of spacer monomers to adjust the hydrophilicity; through geometry; by spatially varying the components. Consequently, we create bespoke, hierarchical release systems, from the molecular to macro. This approach represents a new paradigm for the formulation of printable inks for drug-loaded medical devices

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Surface modifications in polymers by ion beams for the study of biocompatibility

Nos dias atuais, grande parte das intervenções cirúrgicas inclui o implante de materiais. Os grandes obstáculos na implantação de próteses em organismos humanos são a coagulação sanguínea em contato com o material devido ao alto grau de ativação plaquetária e a compatibilidade dos tecidos biológicos ao material implantado. Agregando melhorias de propriedades mecânicas a superfícies biocompatíveis, materiais poliméricos apresentam grandes tendências a serem excelentes candidatos a biomateriais para tais aplicações. O objetivo deste trabalho foi realizar modificações superficiais em polímeros através do método de implantação por feixe iônico a fim de se investigar mudanças induzidas em suas propriedades superficiais e estudar possíveis mudanças em sua biocompatibilidade, em específico, sua hemocompatibilidade. Amostras de policarbonato foram irradiadas com feixes de íons de argônio com energia 23 keV e cinco diferentes doses. As superfícies das amostras foram analisadas com medidas de ângulo de contato, microscopia de força atômica, espectroscopia de massa de íons secundários, espectroscopia de fotoelétrons, espectroscopia de retroespalhamento Rutherford, deteção de recuo elástico, espectroscopia de raios-X induzidos por partículas e testes de adesão plaquetária. Os resultados das diferentes técnicas apontaram de forma consistente a uma série de alterações químicas e físicas induzidas nas superfícies das amostras, dentre elas: a perda significativa de hidrogênio nas amostras irradiadas, aumento do grau de reticulação entre as cadeias poliméricas que levou ao aumento de elétron deslocalizados e mudança de coloração, remoção de aditivos, migração à superfície de átomos de argônio implantados e alteração de hidrofilicidade. Ao confrontar todos os resultados obtidos com os resultados dos testes de adesão plaquetária, constatou-se que os efeitos observados aumentam o caráter trombogênico da superfície do policarbonato e que a remoção de aditivos com grupos sulfato e sulfonato após irradiação com argônio teve grande influência em tal aumento.In the current days, a big part of the surgical interventions includes the implant of materials. The great obstacles for prosthesis implantation in living organisms are the blood clotting when in contact to the material due to a high level of platelet activation and the biological tissues compatibility to the implanted material. By joining improvements on mechanical properties to biocompatible surfaces, polymer materials present high tendencies to be excellent biomaterials candidates for such applications. The objective of this work was to perform surface modification in polymers through the ion beam implantation method in order to investigate changes induced in their surface properties and study possible biocompatibility changes. Samples of polycarbonate were irradiated with argon ion beam with 23 keV energy and different doses. The surfaces of the samples were analyzed by contact angle measurements, atomic force microscopy, secondary ion mass spectroscopy, x-ray photoelectron spectroscopy, Rutherford backscattering spectroscopy, elastic recoil detection, particle induced x-ray spectroscopy and platelet adhesion tests. The results from the different techniques pointed consistently to a series of chemical and physical changes induced on the samples\' surfaces, such as: significant loss of hydrogen for the irradiated samples, increase of cross-linking between polymer chains which led to the increase of delocalized electrons and color change, removal of additives, migration of argon atoms to the surface and hydrophilicity changes. By comparing all the obtained results to the platelet adhesion tests results, it was found that the observed effects increase the thrombogenic characteristic of the polycarbonate surface and that the removal of additives with sulfate and sulfonate groups after the argon irradiation had great influence on such increase

A ToF-SIMS/MVA approach to identify phase segregation in blends of incompatible but extremely similar resins

This work presents a data analysis extension to a well-established methodology for the assessment of organic coatings using imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS). Such an approach produced results that can be analysed using a multivariate analysis (MVA) procedure that performs the simultaneous processing of spatially and chemically related datasets. The coatings consist of two commercial resins that yield extremely similar spectra and there are no peaks of sufficient intensity that are uniquely diagnostic of either material to provide an unambiguous identification of each. In order to resolve the problem, in addition to microtome-based sample preparation steps of tapers for the analysis through sample thickness, standard samples in cured and uncured conditions are introduced and measured in the same fashion as the specimens under investigation. The resulting ToF-SIMS imaging datasets have been processed using non-negative matrix factorisation (NMF), which enabled identification of phase separation in the cured coatings

A Study of the Interfacial Chemistry between Polymeric Methylene Diphenyl Di-isocyanate and a Fe-Cr Alloy Surface and Interface Analysis

The interactions of polymeric methylene diphenyl di‐isocyanate (pMDI) and a model Fe–Cr alloy have been studied by X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Films of two different thicknesses have been investigated: one with an extremely thin pMDI layer in which the interfacial chemistry can be probed directly and a thicker one in which sputter profiling using cluster ions is necessary to expose the interface chemistry for direct analysis. Multivariate analysis (MVA), using principal component analysis (PCA) and nonnegative matrix factorisation (NMF), has been used to identify specific ions associated with the interfacial region of the ToF‐SIMS sputter depth profile and chemical species from the XPS sputter depth profile. As an unsupervised method, this avoids an unconscious bias on the part of the analyst. Specific ions associated with pMDI interactions with both Fe and Cr allow the proposal of two complementary reaction mechanisms, supported by the XPS data. A range of cluster ions is used in this investigation, but the bulk of the work used argon clusters for the XPS depth profiles and Buckminster Fullerene projectiles for the ToF‐SIMS analyses. To ensure that such data were directly comparable, the ToF‐SIMS sputter profiles were repeated in a different system of the same type using argon cluster ions

Modulating the Biological Function of Protein by Tailoring the Adsorption Orientation on Nanoparticles

Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important protein-based nanomedicine. In this work, new insights on the effect of the different orientation of cytochrome c (cyt c) bound to gold nanoparticles (GNPs) using various ligands on its apoptotic activity is reported. Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS), electrochemical and circular dichroism (CD) analyses are used to investigate the characteristics of cyt c orientation and structure on functionalized GNPs. These studies indicate that the orientation and position of the heme ring inside the cyt c structure can be altered by changing the surface chemistry on the NPs. A difference in the apoptosis inducing capability because of different orientation of cyt c bound to the GNPs is observed. These findings indicate that the biological activity of a protein can be modulated on the surface of NPs by varying its adsorption orientation. This study will impact on the rational design of new nanoscale biosensors, bioelectronics, and nanoparticle-protein based drugs. Keywords: gold nanoparticles, cytochrome c, orientation, apoptosis, peroxidase activit