Transient thermography for detection of micro-defects in multilayer thin films

Delamination and cracks within the multilayer structure are typical failure modes observed in microelectronic and micro electro mechanical system (MEMS) devices and packages. As destructive detection methods consume large numbers of devices during reliability tests, non-destructive techniques (NDT) are critical for measuring the size and position of internal defects throughout such tests. There are several established NDT methods; however, some of them have significant disadvantages for detecting defects within multilayer structures such as those found in MEMS devices. This thesis presents research into the application of transient infrared thermography as a non-destructive method for detecting and measuring internal defects, such as delamination and cracks, in the multilayer structure of MEMS devices. This technique works through the use of an infrared imaging system to map the changing temperature distribution over the surface of a target object following a sudden change in the boundary conditions, such as the application of a heat source to an external surface. It has previously been utilised in various applications, such as damage assessment in aerospace composites and verification of printed circuit board solder joint manufacture, but little research of its applicability to MEMS structures has previously been reported. In this work, the thermal behaviour of a multilayer structure containing defects was first numerically analysed. A multilayer structure was then successfully modelled using COMSOL finite element analysis (FEA) software with pulse heating on the bottom surface and observing the resulting time varying temperature distribution on the top. The optimum detecting conditions such as the pulse heating energy, pulse duration and heating method were determined and applied in the simulation. The influences of thermal properties of materials, physical dimensions of film, substrate and defect and other factors that will influence the surface temperature gradients were analytically evaluated. Furthermore, a functional relationship between the defect size and the resulting surface temperature was obtained to improve the accuracy of estimating the physical dimensions and location of the internal defect in detection. Corresponding experiments on specimens containing artificially created defects in macro-scale revealed the ability of the thermographic method to detect the internal defect. The precision of the established model was confirmed by contrasting the experimental results and numerical simulations

Non-destructive defect detection for MEMS devices using transient thermography

This paper investigates the use of transient infrared thermography in a transmission mode for subsurface defect detection within thin multilayer structures such as those found in MEMS devices. This was undertaken through the use of finite element analysis based simulations for several sizes of defects and for several combinations of substrate and thin film materials. The maximum temperature difference observable at the sample surface between defective and non-defective regions of the sample was investigated as a function of various parameters of the sample materials and defect geometry

Formation and homogenisation of Sn-Cu interconnects by self-propagated exothermic reactive bonding

We produced SnCu interconnects by self-propagated exothermic reactions using AlNi NanoFoil at ambient conditions, through the instantaneous localised heat across the interfaces between Sn electroplated Cu substrates. This technique presents a great potential for electronics integration with minimal thermal effects to the components. However, the metastable phases resulted from the non-equilibrium interfacial reactions and solidification were inevitable under a highly transient regime due to a drastic heating/cooling (over 107 K/s). In this study, Finite Element Analysis was performed to predict the temperature profiles across bonding interfaces, which were subsequently correlated with the formation and homogenisation of the bonded structures during the bonding and post-bonding ageing process. It has been revealed that, for nano-sized metastable phases, their formation, morphologies and distribution were primarily attributed to the convective mass transportation, liquid-solid inter-diffusion, and directional non-equilibrium solidification of Sn in molten zone of the bonding interfaces. The non-equilibrium phases initially formed in the SnCu interconnects can be homogenised towards the equilibrium status by accelerated ageing. This was achieved through the coalescing and subsequent growth of the original nano-sized metastable phases, as a result of the solid-diffusion of Cu and Ag atoms at intergranular boundary regions of Sn grains, AlNi NanoFoil/Sn. and Cu/Sn interfaces

Sub-ppt Mass Spectrometric Detection of Therapeutic Drugs in Complex Biological Matrixes Using Polystyrene-Microsphere-Coated Paper Spray

Polystyrene (PS) is a class of polymer materials that offers great potential for various applications. However, the applications of PS microspheres in paper spray mass spectrometry are largely underexplored. Herein we prepared a series of PS microspheres via a simple dispersion polymerization and then used them as coating materials for paper spray mass spectrometry (MS) in high-sensitivity analysis of various therapeutic drugs in complex biological matrixes. In the preparation of PS-coated papers, the coating method was found playing a key role in determining the performance of the resulting paper substrate in addition to other parameters (e.g., starch type and amount, PS coating amount, and spray solvent). We also found that as a solvent was applied on PS-coated paper for paper spray, the analytes of interest would be first extracted out and then moved to the tip of paper triangle for spray along with the applied solvent. In the process, the surface energy of PS particles had a strong impact on the desorption performance of analytes from PS-coated paper substrate, and the PS with a high surface energy favored the elution of analytes to allow a high MS sensitivity. When the prepared PS coated paper was used as a substrate for paper spray, it gave high sensitivity in analysis of therapeutic drugs in various biological matrixes such as whole blood, serum, and urine with excellent repeatability and reproducibility. In contrast to uncoated filter paper, an improvement of 10–546-fold in sensitivity was achieved using PS-coated paper for paper spray, and an estimated lower limit of quantitation (LLOQs) in the range of 0.004–0.084 ng mL^–1 was obtained. The present study is significant in exploring the potential of PS for high-sensitivity MS analysis, and it provides a promising platform in the translation of the MS technique to clinical applications

Hydrogen bond network between the C-terminal β-strand of helicase and protease active site in HCV NS3/4A protein (apo).

<p>The protease and helicase domains are shown in cartoon and colored in gray. The six C-terminal residues of the helicase and the protease active site residues are represented by orange and red sticks, respectively. Green dashed lines represent the hydrogen bond.</p

Computational Study on the Inhibitor Binding Mode and Allosteric Regulation Mechanism in Hepatitis C Virus NS3/4A Protein

<div><p>HCV NS3/4A protein is an attractive therapeutic target responsible for harboring serine protease and RNA helicase activities during the viral replication. Small molecules binding at the interface between the protease and helicase domains can stabilize the closed conformation of the protein and thus block the catalytic function of HCV NS3/4A protein via an allosteric regulation mechanism. But the detailed mechanism remains elusive. Here, we aimed to provide some insight into the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A protein by using computational methods. Four simulation systems were investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein in complex with an allosteric inhibitor and the truncated form of the above two systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive state), while the truncated apo protein adopts an open conformation (active state). Further residue interaction network analysis suggests the communication of the domain-domain interface play an important role in the transition from closed to open conformation of HCV NS3/4A protein. However, the inhibitor stabilizes the closed conformation through interaction with several key residues from both the protease and helicase domains, including His57, Asp79, Asp81, Asp168, Met485, Cys525 and Asp527, which blocks the information communication between the functional domains interface. Finally, a dynamic model about the allosteric regulation and conformational changes of HCV NS3/4A protein was proposed and could provide fundamental insights into the allosteric mechanism of HCV NS3/4A protein function regulation and design of new potent inhibitors.</p></div

Distance between the backbone centers of mass of the helicase residues 614–625 and protease residues 103–171, as it varies during apo, inhibitor bound, apo (truncated) and inhibitor bound (truncated) HCV NS3/4A protein simulation.

<p>Distance between the backbone centers of mass of the helicase residues 614–625 and protease residues 103–171, as it varies during apo, inhibitor bound, apo (truncated) and inhibitor bound (truncated) HCV NS3/4A protein simulation.</p

Summary of the shortest path betweenness and closeness centrality of selected residues in the network of HCV NS3/4A protein.

<p>Summary of the shortest path betweenness and closeness centrality of selected residues in the network of HCV NS3/4A protein.</p

Analysis of hydrogen bond network between HCV NS3/4A helicase and protease domains.

<p>Analysis of hydrogen bond network between HCV NS3/4A helicase and protease domains.</p

Additional file 2: of Clinical classification of tissue perfusion based on the central venous oxygen saturation and the peripheral perfusion index

Results: related variables of each subset of patients based on normalized central venous oxygen saturation (ScvO 2 ) (70 %) and critical peripheral perfusion index (PI) (0.6) at 8 h (T8). (DOCX 20 kb