Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design

All biological phenomena depend on molecular recognition, which is either intermolecular like in ligand binding to a macromolecule or intramolecular like in protein folding. As a result, understanding the relationship between the structure of proteins and the energetics of their stability and binding with others (bio)molecules is a very interesting point in biochemistry and biotechnology. It is essential to the engineering of stable proteins and to the structure-based design of pharmaceutical ligands. The parameter generally used to characterize the stability of a system (the folded and unfolded state of the protein for example) is the equilibrium constant (K) or the free energy (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o)) terms. These parameters are temperature dependent through the heat capacity change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be derived from spectroscopic experiments, using the van't Hoff method, or measured directly using calorimetry. Along with isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) is a powerful method, less described than ITC, for measuring directly the thermodynamic parameters which characterize biomolecules. In this article, we summarize the principal thermodynamics parameters, describe the DSC approach and review some systems to which it has been applied. DSC is much used for the study of the stability and the folding of biomolecules, but it can also be applied in order to understand biomolecular interactions and can thus be an interesting technique in the process of drug design.

Inversion of light scattering data by singular system analysis

We consider the problem of inverting experimental data obtained in light scattering experiments described by linear theories. We discuss applications to particle sizing and we describe fast and easy-to-implement algorithms which permit the extraction, from noisy measurements, of reliable information about the particle size distribution. © 1987, SPIE.

[Book review] Peter Reimann and Hans Spada (eds), Learning in Humans and Machines: Towards an Interdisciplinary Learning Science

Review of: Peter Reimann and Hans Spada (eds), Learning in Humans and Machines: Towards an Interdisciplinary Learning Science, Pergamon. (1995). ISBN: 978-0080425696

Low Reynolds number turbulence models for accurate thermal simulations of electronic components

The electronics industry and the problems associated with the cooling of microelectronic equipment are developing rapidly. Thermal engineers now find it necessary to consider the complex area of equipment cooling at some level. This continually growing industry also faces heightened pressure from consumers to provide electronic product miniaturization, which in itself increases the demand for accurate thermal management predictions to assure product reliability. Computational fluid dynamics (CFD) is considered a powerful and almost essential tool for the design, development and optimization of engineering applications. CFD is now widely used within the electronics packaging design community to thermally characterize the performance of both the electronic component and system environment. This paper discusses CFD results for a large variety of investigated turbulence models. Comparison against experimental data illustrates the predictive accuracy of currently used models and highlights the growing demand for greater mathematical modelling accuracy with regards to thermal characterization. Also a newly formulated low Reynolds number (i.e. transitional) turbulence model is proposed with emphasis on hybrid techniques.

Turbulence modelling and its impact on CFD predictions for cooling of electronic components

This paper will discuss Computational Fluid Dynamics (CFD) results from an investigation into the accuracy of several turbulence models to predict air cooling for electronic packages and systems. Also new transitional turbulence models will be proposed with emphasis on hybrid techniques that use the k-ε model at an appropriate distance away from the wall and suitable models, with wall functions, near wall regions. A major proportion of heat emitted from electronic packages can be extracted by air cooling. This flow of air throughout an electronic system and the heat extracted is highly dependent on the nature of turbulence present in the flow. The use of CFD for such investigations is fast becoming a powerful and almost essential tool for the design, development and optimization of engineering applications. However turbulence models remain a key issue when tackling such flow phenomena. The reliability of CFD analysis depends heavily on the turbulence model employed together with the wall functions implemented. In order to resolve the abrupt fluctuations experienced by the turbulent energy and other parameters located at near wall regions and shear layers a particularly fine computational mesh is necessary which inevitably increases the computer storage and run-time requirements. The PHYSICA Finite Volume code was used for this investigation. With the exception of the k-ε and k-ω models which are available as standard within PHYSICA, all other turbulence models mentioned were implemented via the source code by the authors. The LVEL, LVEL CAP, Wolfshtein, k-ε, k-ω, SST and kε/kl models are described and compared with experimental data.

Accuracy of turbulence models and CFD for thermal characterisation of electronic systems

A major percentage of the heat emitted from electronic packages can be extracted by air cooling whether by means of natural or forced convection. This flow of air throughout an electronic system and the heat extracted is highly dependable on the nature of turbulence present in the flow field. This paper will discuss results from an investigation into the accuracy of turbulence models to predict air cooling for electronic packages and systems.

Investigation into the performance of turbulence models for fluid flow and heat transfer phenomena in electronic applications

Computational Fluid Dynamics (CFD) is gradually becoming a powerful and almost essential tool for the design, development and optimization of engineering applications. However the mathematical modelling of the erratic turbulent motion remains the key issue when tackling such flow phenomena. The reliability of CFD analysis depends heavily on the turbulence model employed together with the wall functions implemented. In order to resolve the abrupt changes in the turbulent energy and other parameters situated at near wall regions a particularly fine mesh is necessary which inevitably increases the computer storage and run-time requirements. Turbulence modelling can be considered to be one of the three key elements in CFD. Precise mathematical theories have evolved for the other two key elements, grid generation and algorithm development. The principal objective of turbulence modelling is to enhance computational procedures of efficient accuracy to reproduce the main structures of three dimensional fluid flows. The flow within an electronic system can be characterized as being in a transitional state due to the low velocities and relatively small dimensions encountered. This paper presents simulated CFD results for an investigation into the predictive capability of turbulence models when considering both fluid flow and heat transfer phenomena. Also a new two-layer hybrid kε / kl turbulence model for electronic application areas will be presented which holds the advantages of being cheap in terms of the computational mesh required and is also economical with regards to run-time.

Electronic packaging and reduction in modelling time using domain decomposition

The domain decomposition method is directed to electronic packaging simulation in this article. The objective is to address the entire simulation process chain, to alleviate user interactions where they are heavy to mechanization by component approach to streamline the model simulation process.

Lifetime assessment of electronic components for high reliability aerospace applications

This paper details a modelling approach for assessing the in-service (field) reliability and thermal fatigue life-time of electronic package interconnects for components used in the assembly of an aerospace system. The Finite Element slice model of a Plastic Ball Grid Array (PBGA) package and suitable energy based damage models for crack length predictions are used in this study. Thermal fatigue damage induced in tin-lead solder joints are investigated by simulating the crack growth process under a set of prescribed field temperature profiles that cover the period of operational life. The overall crack length in the solder joint for all different thermal profiles and number of cycles for each profile is predicted using a superposition technique. The effect of using an underfill is also presented. A procedure for verifying the field lifetime predictions for the electronic package by using reliability assessment under Accelerated Thermal Cycle (ATC) testing is also briefly outlined.

Decision support systems for eco-friendly electronic products

This paper discusses an optimisation based decision support system and methodology for electronic packaging and product design and development which is capable of addressing in efficient manner specified environmental, reliability and cost requirements. A study which focuses on the design of a flip-chip package is presented. Different alternatives for the design of the flip-chip package are considered based on existing options for the applied underfill and volume of solder material used to form the interconnects. Variations in these design input parameters have simultaneous effect on package aspects such as cost, environmental impact and reliability. A decision system for the design of the flip-chip that uses numerical optimisation approach is used to identify the package optimal specification which satisfies the imposed requirements. The reliability aspect of interest is the fatigue of solder joints under thermal cycling. Transient nonlinear finite element analysis (FEA) is used to simulate the thermal fatigue damage in solder joints subject to thermal cycling. Simulation results are manipulated within design of experiments and response surface modelling framework to provide numerical model for reliability which can be used to quantify the package reliability. Assessment of the environmental impact of the package materials is performed by using so called Toxic Index (TI). In this paper we demonstrate the evaluation of the environmental impact only for underfill and lead-free solder materials. This evaluation is based on the amount of material per flip-chip package. Cost is the dominant factor in contemporary flip-chip packaging industry. In the optimisation based decision support system for the design of the flip-chip package, cost of materials which varies as a result of variations in the design parameters is considered.

"System in package technology" - design for manufacture challenges

Purpose – To present key challenges associated with the evolution of system-in-package technologies and present technical work in reliability modeling and embedded test that contributes to these challenges. Design/methodology/approach – Key challenges have been identified from the electronics and integrated MEMS industrial sectors. Solutions to optimising the reliability of a typical assembly process and reducing the cost of production test have been studied through simulation and modelling studies based on technology data released by NXP and in collaboration with EDA tool vendors Coventor and Flomerics. Findings – Characterised models that deliver special and material dependent reliability data that can be used to optimize robustness of SiP assemblies together with results that indicate relative contributions of various structural variables. An initial analytical model for solder ball reliability and a solution for embedding a low cost test for a capacitive RF-MEMS switch identified as an SiP component presenting a key test challenge. Research limitations/implications – Results will contribute to the further development of NXP wafer level system-in-package technology. Limitations are that feedback on the implementation of recommendations and the physical characterisation of the embedded test solution. Originality/value – Both the methodology and associated studies on the structural reliability of an industrial SiP technology are unique. The analytical model for solder ball life is new as is the embedded test solution for the RF-MEMS switch.

Thermal-mechanical modelling of power electronic module packaging

In this paper the reliability of the isolation substrate and chip mountdown solder interconnect of power modules under thermal-mechanical loading has been analysed using a numerical modelling approach. The damage indicators such as the peel stress and the accumulated plastic work density in solder interconnect are calculated for a range of geometrical design parameters, and the effects of these parameters on the reliability are studied by using a combination of the finite element analysis (FEA) method and optimisation techniques. The sensitivities of the reliability of the isolation substrate and solder interconnect to the changes of the design parameters are obtained and optimal designs are studied using response surface approximation and gradient optimization method

Wire bond reliability for power electronic modules - effect of bonding temperature

In this paper, thermal cycling reliability along with ANSYS analysis of the residual stress generated in heavy-gauge Al bond wires at different bonding temperatures is reported. 99.999% pure Al wires of 375 mum in diameter, were ultrasonically bonded to silicon dies coated with a 5mum thick Al metallisation at 25degC (room temperature), 100degC and 200degC, respectively (with the same bonding parameters). The wire bonded samples were then subjected to thermal cycling in air from -60degC to +150degC. The degradation rate of the wire bonds was assessed by means of bond shear test and via microstructural characterisation. Prior to thermal cycling, the shear strength of all of the wire bonds was approximately equal to the shear strength of pure aluminum and independent of bonding temperature. During thermal cycling, however, the shear strength of room temperature bonded samples was observed to decrease more rapidly (as compared to bonds formed at 100degC and 200degC) as a result of a high crack propagation rate across the bonding area. In addition, modification of the grain structure at the bonding interface was also observed with bonding temperature, leading to changes in the mechanical properties of the wire. The heat and pressure induced by the high temperature bonding is believed to promote grain recovery and recrystallisation, softening the wires through removal of the dislocations and plastic strain energy. Coarse grains formed at the bonding interface after bonding at elevated temperatures may also contribute to greater resistance for crack propagation, thus lowering the wire bond degradation rate

Predicting the reliability of power electronic modules

This paper discusses the reliability of an IGBT power electronics module. This work is part of a major UK funded initiative into the design, packaging and reliability of power electronic modules. The predictive methodology combines numerical modeling techniques with experimentation and accelerated testing to identify failure modes and mechanisms for these type of power electronic module structures. The paper details results for solder joint failure substrate solder. Finite element method modeling techniques have been used to predict the stress and strain distribution within the module structures. Together with accelerated life testing, these results have provided a failure model for these joints which has been used to predict reliability of a rail traction application