Influence of nanoparticle encapsulation and encoding on the surface chemistry of polymer carrier beads

Surface-functionalized polymer beads encoded with molecular luminophores and nanocrystalline emitters such as semiconductor nanocrystals, often referred to as quantum dots (QDs), or magnetic nanoparticles are broadly used in the life sciences as reporters and carrier beads. Many of these applications require a profound knowledge of the chemical nature and total number of their surface functional groups (FGs), that control bead charge, colloidal stability, hydrophobicity, and the interaction with the environment and biological systems. For bioanalytical applications, also the number of groups accessible for the subsequent functionalization with, e.g., biomolecules or targeting ligands is relevant. In this study, we explore the influence of QD encoding on the amount of carboxylic acid (COOH) surface FGs of 2 µm polystyrene microparticles (PSMPs). This is done for frequently employed oleic acid and oleylamine stabilized, luminescent core/shell CdSe QDs and two commonly used encoding procedures. This included QD addition during bead formation by a thermally induced polymerization reaction and a post synthetic swelling procedure. The accessible number of COOH groups on the surface of QD-encoded and pristine beads was quantified by two colorimetric assays, utilizing differently sized reporters and electrostatic and covalent interactions. The results were compared to the total number of FGs obtained by a conductometric titration and Fourier transform infrared spectroscopy (FTIR). In addition, a comparison of the impact of QD and dye encoding on the bead surface chemistry was performed. Our results demonstrate the influence of QD encoding and the QD-encoding strategy on the number of surface FG that is ascribed to an interaction of the QDs with the carboxylic acid groups on the bead surface. These findings are of considerable relevance for applications of nanoparticle-encoded beads and safe-by-design concepts for nanomaterials

Economic predictors of differences in interview faking between countries : economic inequality matters, not the state of economy

Many companies recruit employees from different parts of the globe, and faking behavior by potential employees is a ubiquitous phenomenon. It seems that applicants from some countries are more prone to faking compared to others, but the reasons for these differences are largely unexplored. This study relates country-level economic variables to faking behavior in hiring processes. In a cross-national study across 20 countries, participants (N = 3839) reported their faking behavior in their last job interview. This study used the random response technique (RRT) to ensure participants anonymity and to foster honest answers regarding faking behavior. Results indicate that general economic indicators (gross domestic product per capita [GDP] and unemployment rate) show negligible correlations with faking across the countries, whereas economic inequality is positively related to the extent of applicant faking to a substantial extent. These findings imply that people are sensitive to inequality within countries and that inequality relates to faking, because inequality might actuate other psychological processes (e.g., envy) which in turn increase the probability for unethical behavior in many forms

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61). Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions. Conclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors. Trial registration: ClinicalTrials.gov, Identifier: NCT01915524

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Investigation of Wire Microstructure and Interface Formation during AlSi1 Ultrasonic Wedge-Wedge-Bonding

Für die modellhafte Beschreibung des Drahtbondvorganges in Abhängigkeit von den Bondparametern ist sowohl das Verständnis der werkstoffwissenschaftlichen Zusammenhänge am Interface als auch im Bonddraht von entscheidender Bedeutung. Diese Vorgänge sind sehr eng mit der Oberflächenaktivierung der Fügepartner und der Drahtdeformation in z-Richtung verknüpft. Während der Bondzeit bildet sich am Interface eine intermetallische Phase vom Typ Au8Al3 aus, deren Schichtdicke von der Höhe der Ultraschallenergie beeinflusst wird. Am Ende des Bondprozesses ist das Interface nahezu vollständig mit intermetallischer Phase bedeckt. Entgegen der bisherigen Vorstellungen wird jedoch die Flash-Au-Schicht der Leiterplattenmetallisierung durch die Relativbewegung zwischen Draht und Substrat beim US-Wedge-Wedge-Bonden nicht durchgerieben, sie bleibt als Bestandteil des elektrischen Kontaktes erhalten. Während der Drahtdeformation laufen konkurrierend Ver- und Entfestigungsprozesse im Wedge ab. Damit verbunden sind die Auflösung der Drahttextur und die dynamische Erholung/Rekristallisation des Aluminiumdrahtes unter Einwirkung der Bondparameter. Am Ende des Bondprozesses ist die Härte des Wedges höher als die Härte des Drahtes im Ausgangszustand, jedoch geringer als die Härte des vordeformierten und damit kaltverfestigten Wedges vor Beginn der Ultraschalleinwirkung. Die Höhe der Ultraschallenergie bestimmt die Entfestigung: Je höher die gewählte Ultraschallenergie, umso stärker entfestigt der Wedge während des Drahtbondens. Am Ende der Arbeit wird ein Drahtbondmodell vorgestellt, aus dem Empfehlungen für die Bondparameter und ein Vorschlag für den Aufbau des Bonddrahtes abgeleitet werden.For modelling the wire bond process it is essential to know micro- and nanomaterial processes at the interface and in the bonding wire. These processes are closely related to wire and substrate surface activation and to wire deformation in z-direction. Within the bonding time an Au8Al3 intermetallic phase is grown at the interface. Its thickness is controlled by ultrasonic power. At the end of the bonding process the interface is almost completely covered by intermetallic phase. Contrary to the established assumption, after the wire bond process the 50-100 nm thin flash-Au-layer is an eminent part of the interface structure and the electric contact. The wire deformation is accompanied by competing hardening and softening processes inside the wedge. So the interaction of ultrasonic power and bonding force results in a translation of the wire fibre texture by dynamic recrystallisation of the AlSi1 wedge. At the end of the wire bonding process the wedge is harder than the as-received wire but its hardness is lower than the pre-deformed and cold-worked wire before ultrasonic energy has been acting. The ultrasonic power level determines the degree of wedge softening. The higher the ultrasonic power the more the wedge is softened during the wire bonding process. At the end recommendations for the choice of the bond parameters and a model for an optimised bonding wire are given

Aluminum-Scandium: A Material for Semiconductor Packaging

A well-known aluminum-scandium (Al-Sc) alloy, already used in lightweight sports equipment, is about to be established for use in electronic packaging. One application for Al-Sc alloy is manufacture of bonding wires. The special feature of the alloy is its ability to harden by precipitation. The new bonding wires with electrical conductivity similar to pure Al wires can be processed on common wire bonders for aluminum wedge/wedge (w/w) bonding. The wires exhibit very fine-grained microstructure. Small Al3Sc particles are the main reason for its high strength and prevent recrystallization and grain growth at higher temperatures (>150[1]C). After the wire-bonding process, the interface is well closed. Reliability investigations by active power cycling demonstrated considerably improved lifetime compared with pure Al heavy wires. Furthermore, the Al-Sc alloy was sputter-deposited onto silicon wafer to test it as chip metallization in copper (Cu) ball/wedge bonding technology. After deposition, the layers exhibited fine-grained columnar structure and small coherent Al3Sc particles with dimensions of a few nanometers. These particles inhibit softening processes such as Al splashing in fine wire bonding processes and increase the thickness of remnant Al under the copper balls to 85% of the initial thickness

Alternative Drahtwerkstoffe für den Einsatz im Wedge/Wedge-Bondprozess

Aluminium ist beim Bonden im Ultraschall (US)-Wedge/Wedge-Verfahren sowohl bei Verwendung von dünnen Drähten (25 μm) als auch im Dickdrahtbereich (≥ 100 μm) der dominierende Drahtwerkstoff. Während die Ultraschalldeformation beim Al-Bonden zu einer guten Adaption der Fügepartner am Interface führt, schafft die Oberflächenaktivierung durch die den Al-Draht umgebende natürliche Oxidschicht die erforderlichen Voraussetzungen für die bei der Verschweißung ablaufenden Diffusionsprozesse. Die mit der US-Deformation im Al-Draht einhergehenden mikrostrukturellen Prozesse, besonders die entfestigend wirkenden Gefügeveränderungen, zu denen Aluminium auf Grund materialspezifischer Kennwerte viel stärker als Kupfer neigt, sind somit für die Verbindungsbildung am Interface optimal, können jedoch den Heelbereich des Drahtbonds schwächen und somit zum vorzeitigen Ausfall des Bauteils führen. Es gilt daher, resultierend aus den neu gewonnenen Erkenntnissen der metallkundlichen Vorgänge beim Al-Bonden, die Drähte so zu optimieren, dass diese sowohl durch gute Verschweißbarkeit am Interface als auch durch einen höherfesten Heel und damit längere Lebensdauer gekennzeichnet sind. Vorgestellt und diskutiert werden verschiedene Alternativen und erste Ergebnisse eines neuen Bonddrahtes auf Al-Basis, der aus einer Leichtmetalllegierung besteht, die auch in der Luft- und Raumfahrt eingesetzt wird. Die Methode des fokussierten Elektronenstrahls (FIB) liefert hierzu ausgezeichnete Möglichkeiten, die Gefügestruktur der Drähte, der Metallisierung und das Wachstum intermetallischer Phasen am Interface darzustellen