Effects of stress and electromigration on microstructural evolution in microbumps of three-dimensional integrated circuits

Due to geometric scaling, the heterogeneous and anisotropic microstructures present in through-silicon vias and microbumps must be considered in the stress management of 3-D integrated circuits. In this paper, a phase field model is developed to investigate the effects of stress and electromigration on microstructural evolution in a Cu/Sn-microbump/Cu structure at 150 °C. External compressive stress is observed to accelerate the growth of Cu3Sn grains and cause the separation of continuous interfacial Cu 6 Sn 5 grains by β-Sn grains, whereas tensile stress promotes the growth of Cu 6 Sn 5 grains and the formation of a continuous Cu 6 Sn 5 layer. The roughness of the β-Sn-Cu 6 Sn 5 interface under compressive stress is greater than that under tensile stress. The morphological evolution of the β-Sn grains is also affected by stress. An external shear or compressive stress favors the growth of the β-Sn grains with their c-axis particular to the Y -direction. Furthermore, the interdiffusion flux driven by electromigration increases the roughness of the interfacial Cu 6 Sn 5 grains at the cathode. The strain caused by electromigration results in larger β-Sn grains, enabling faster interdiffusion along the current direction. The preferential growth of the β-Sn grains under stress or electromigration decreases the shear modulus of microbumps

Multiscale microstructures and microstructural effects on the reliability of microbumps in three-dimensional integration

The dimensions of microbumps in three-dimensional integration reach microscopic scales and thus necessitate a study of the multiscale microstructures in microbumps. Here, we present simulated mesoscale and atomic-scale microstructures of microbumps using phase field and phase field crystal models. Coupled microstructure, mechanical stress, and electromigration modeling was performed to highlight the microstructural effects on the reliability of microbumps. The results suggest that the size and geometry of microbumps can influence both the mesoscale and atomic-scale microstructural formation during solidification. An external stress imposed on the microbump can cause ordered phase growth along the boundaries of the microbump. Mesoscale microstructures formed in the microbumps from solidification, solid state phase separation, and coarsening processes suggest that the microstructures in smaller microbumps are more heterogeneous. Due to the differences in microstructures, the von Mises stress distributions in microbumps of different sizes and geometries vary. In addition, a combined effect resulting from the connectivity of the phase morphology and the amount of interface present in the mesoscale microstructure can influence the electromigration reliability of microbumps

Multiscale microstructures and microstructural effects on the reliability of microbumps in three-dimensional integration

The dimensions of microbumps in three-dimensional integration reach microscopic scales and thus necessitate a study of the multiscale microstructures in microbumps. Here, we present simulated mesoscale and atomic-scale microstructures of microbumps using phase field and phase field crystal models. Coupled microstructure, mechanical stress, and electromigration modeling was performed to highlight the microstructural effects on the reliability of microbumps. The results suggest that the size and geometry of microbumps can influence both the mesoscale and atomic-scale microstructural formation during solidification. An external stress imposed on the microbump can cause ordered phase growth along the boundaries of the microbump. Mesoscale microstructures formed in the microbumps from solidification, solid state phase separation, and coarsening processes suggest that the microstructures in smaller microbumps are more heterogeneous. Due to the differences in microstructures, the von Mises stress distributions in microbumps of different sizes and geometries vary. In addition, a combined effect resulting from the connectivity of the phase morphology and the amount of interface present in the mesoscale microstructure can influence the electromigration reliability of microbumps

A method for quantification of the effects of size and geometry on the microstructure of miniature interconnects

Because the heterogeneity of microstructure has significant effects on the material properties of ultrafine interconnects, it should be quantified, to facilitate high-fidelity prediction of reliability. To address this challenge, a method based on autocorrelation and singular value decomposition is proposed for quantitative characterization of microstructure. The method was validated by developing a quantitative relationship between reported microstructure and tensile strength for SnAgCuRE solders reported in the literature. The method was used to study the effects of size and geometry in ultrafine Sn37Pb interconnects on microstructure and von Mises stress, which were obtained simultaneously by coupling a phase-field model with an elastic mechanical model. By use of this method the degree of heterogeneity of the microstructure in relation to preferred growth directions of the phases was quantified by use of a scalar microstructure index. It was found that microstructure heterogeneity increases with decreasing standoff height, and is higher for hourglass-shaped solder joints. The average von Mises stress was found to be positively related to the microstructure index. The strong correlation between microstructure index and average von Mises stress was confirmed by nonlinear regression analysis using an artificial neural network. This indicates that the mechanical behavior of ultrafine interconnects can be predicted more accurately on the basis of the microstructure index

Effects of the microstructure of copper through-silicon vias on their thermally induced linear elastic mechanical behavior

Through-silicon vias (TSVs) have been investigated extensively in recent years. However, the physical mechanisms behind some of the common problems associated with TSVs, such as the protrusion of Cu vias, are still unknown. In addition, since the dimensions of TSVs have been shrunk to microscopic levels, the sizes of the microstructural features of TSVs are no longer small compared to the dimensions of the vias. Therefore, the role and importance of the microstructural features of TSVs need to be studied to enable more accurate reliability predictions. This study focused on the effects the microstructural features of TSVs, i.e., the Cu grains and their [111] texture, grain size distribution, and morphology, have on the thermally induced linear elastic behavior of the vias. The results of the study indicate that stress distribution in the model that takes into account the Cu grains, whose Young's moduli and Poisson's ratios are set according to their crystallographic orientations, is more heterogeneous than that in a reference model in which the bulk properties of Cu are used. Stresses as high as 250 MPa are observed in the via of the model that takes into consideration the Cu grains, while stresses in the via of the reference model are all lower than 150 MPa. In addition, smaller Cu grains in the vias result in higher stresses; however, the variation in stress owning to changes in the grain size is within 20 MPa. The frequency of the stresses ranging from 80 MPa to 100 MPa was the highest in the stress distribution of the vias, depending on boundary conditions. The stress level in the v ias decreases with the decrease in the number of grains with the [111] texture. Finally, the stress level is lower in the model in which the grain structure is generated using a phase field model and is closer to that of the microstructures present in real materials. © 2014 The Korean Institute of Metals and Materials and Springer Science+Business Media Dordrecht

Rice Protein Peptides Alleviate Dextran Sulfate Sodium-Induced Colitis via the Keap1–Nrf2 Signaling Pathway and Regulating Gut Microbiota

Inflammatory bowel disease (IBD), with increasing incidence, causes a range of gastrointestinal symptoms and brings distress and impact on the health and lives of patients. The aim of this study was to explore the protective effects of industrially produced rice protein peptides (RPP) on dextran sulfate sodium (DSS)-induced acute colitis in mice and the potential mechanisms. The results showed that RPP treatment alleviated the symptoms of colitis in mice, including weight loss, colon shortening, and injury, decreased the level of disease activity index (DAI), regulated the balance of inflammatory factors and oxidation, activated Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway, regulated the expression of related antioxidant proteases, and promoted the expression of intestinal tight junction proteins. In addition, RPP maintained intestinal mucosal barrier function and alleviated acute colitis caused by DSS treatment in mice by increasing the value of F/B, increasing the relative abundance of beneficial bacteria such as Akkermansia, and regulating the level of short-chain fatty acids. In conclusion, RPP alleviated colitis symptoms through the Keap1–Nrf2 signaling pathway and regulating gut microbiota, which had the potential as dietary supplements or functional foods

Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis

<div><p>Objectives</p><p>Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE.</p><p>Methods</p><p>A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results.</p><p>Results</p><p>Nine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17–1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years <i>vs</i>. <2~3 years: OR 0.91 (95% CI 0.25–3.31) <i>vs</i>. 0.91 (0.40–2.07)).There also was considerable heterogeneity between studies.</p><p>Conclusion</p><p>No dysplasia- or cancer-protective effects of PPIs usage in patients with BE were identified by our analysis. Therefore, we conclude that clinicians who discuss the potential chemopreventive effects of PPIs with their patients, should be aware that such an effect, if exists, has not been proven with statistical significance.</p></div

Prognostic Value of HIFs Expression in Head and Neck Cancer: A Systematic Review

<div><p>Background</p><p>Tumor hypoxia plays a fundamental role in resistance to therapy and disease progression. A number of studies have assessed the prognostic role of HIFs expression in head and neck cancer (HNC), but no consistent outcomes are reported.</p><p>Methodology</p><p>A systematical search was performed to search relevant literatures in PubMed, Web of Science and ISI Web of Knowledge databases. The patients’ clinical characteristics and survival outcome were extracted. The correlation between HIFs expression and prognosis was analyzed.</p><p>Principal Findings</p><p>A total of 28 studies assessed the association between HIFs and HNC survival, the result showed that overexpressed HIFs was significantly associated with increase of mortality risk (HR = 2.12; 95% CI: 1.52–2.94; I² 74%). Subgroup analysis on different HIF isoforms with OS indicated that both HIF-1α and HIF-2α were associated with worse prognosis. The pooled HRs were 1.72(95% CI 1.34–2.20; I² 70.7%) and 1.79(95% CI: 1.42–2.27, I² 0%). Further subgroup analysis was performed by different geographical locations, disease subtype, stage, types of variate analysis and cut-off value. The results revealed that overexpressed HIF-1α was significantly associated with poor prognosis in Asian patients (HR = 2.34; 95% CI: 1.76–3.1; I² 48.9%), but not in European patients (HR = 1.13; 95% CI: 0.77–1.66; I² 78.3%). Furthermore, HIF-1α overexpression was significantly associated with worse OS in oral carcinoma(HR = 2.1; 95% CI: 1.11–3.97; I² 81.7%), nasopharyngeal carcinoma(HR = 2.07; 95% CI:1.23–3.49; I² 22.5%) and oropharynx carcinoma(HR = 1.76; 95% CI:1.05–2.97; I² 61%), but not in laryngeal carcinoma(HR = 1.38; 95% CI: 0.87–2.19; I² 62.5%). We also found that the prognostic value of HIF-1α overexpression existed only when using staining and percentage as positive definition (HR = 1.82; 95% CI 1.42–2.33; I² 9.9%).</p><p>Conclusions</p><p>This study showed that overexpressed HIFs were significantly associated with increase of mortality risk. Subgroup analysis revealed that overexpressed HIF-1α was significantly associated with worse prognosis of HNC in Asian countries. Additionally, HIF-1α had different prognostic value in different HNC disease subtypes.</p></div

The use of PPIs and other medication and the incidence of EAC and/or HGD in included studies.

<p>The use of PPIs and other medication and the incidence of EAC and/or HGD in included studies.</p

Forrest plot of Hazard ratio for the association of different HIF isoforms expression with overall survival.

<p>Forrest plot of Hazard ratio for the association of different HIF isoforms expression with overall survival.</p