bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the Stress-Strain and Creep Behavior of Underfill Encapsulants With Aging
Authors: Lin Chang , Suhling Jeffrey C. , Lall Pradeep
Published: January 2011

Microelectronic encapsulants exhibit evolving properties that change significantly with environmental exposures such as isothermal aging and thermal cycling. Such aging effects are exacerbated at higher temperatures typical of thermal cycling qualification tests for harsh environment electronic packaging. In this work, measurements of material behavior changes occurring in flip chip underfill encapsulants exposed to isothermal aging have been performed. A novel method has been developed to fabricate freestanding underfill uniaxial test specimens so that they accurately reflect the encapsulant layer present in flip chip assemblies. Using the developed specimen preparation procedure, isothermal aging effects have been characterized at several elevated temperatures (+ 80, +100, + 125, and +150 °C). Samples have been aged at the four temperatures for periods up to 6 months. Stress-strain and creep tests have been performed on non-aged and aged samples, and the changes in mechanical behavior have been recorded for the various aging temperatures and durations of isothermal exposure. Empirical models have been developed to predict the evolution of the material properties (modulus, strength) and the creep strain rate as a function of temperature, aging time, and aging temperature. The evaluated underfill illustrated softening behavior at temperatures exceeding 100 °C, although the documented Tg ranged from 130–150 °C. The obtained results showed an obvious enhancement of the underfill mechanical properties as a function of the aging temperature and aging time. Both the effective elastic modulus (initial slope) and ultimate tensile strength (highest stress before failure) increase monotonically with the amount of isothermal aging or aging temperature, regardless of whether the aging temperature is below, at, or above the Tg of the material. From the creep results, it was seen that at a given time, the creep strains were much lower for the aged samples relative to the non-aged samples. Thermal aging has a significant effect on the secondary creep rate, which decreases with both the aging temperature and the aging time. Up to a 100X reduction in the creep rate was observed, and the major changes occurred during the first 50 days of the isothermal aging.
Operational Benefits of Real-Time Monitoring and Visualization in Data Centers
Authors: Cader Tahir , Sharma Ratnesh , Bash Cullen , Fox Les , Bhatia Vaibhav , Mekanapurath Mohandas
Published: January 2011

The 2007 US EPA report to Congress (US EPA, 2007) on the state of energy consumption in data centers brought to light the true energy inefficiencies built into today’s data centers. Marquez et al. (2008) conducted an initial analysis on the productivity of a Pacific Northwest National Lab computer using The Green Grid’s Data Center Energy Productivity metric (The Green Grid, 2008). Their study highlights how the Top500 ranking of computers disguises the serious energy inefficiency of today’s High Performance Computing data centers. In the rapidly expanding Cloud Computing space, the race will be won by the providers that deliver the lowest cost of computing — such cost is heavily influenced by the operational costs incurred by data centers. As a means to address the urgent need to lower the cost of computing, solution providers have been intensely focusing on real-time monitoring, visualization, and control/management of data centers. The monitoring aspect involves the widespread use of networks of sensors that are used to monitor key data center environmental variables such as temperature, relative humidity, air flow rate, pressure, and energy consumption. Such data is then used to visualize and analyze data center problem areas (e.g., hotspots), which is then followed by control/management actions designed to alleviate such problem areas. The authors have been researching the operational benefits of a network of sensors tied in to a software package that uses the data to visualize, analyze, and control/manage the data center cooling system and IT Equipment for maximum operational efficiency. The research is being conducted in a corporate production data center that is networked in to the authors’ company’s global network of data centers. Results will be presented that highlight the operational benefits that are realizable through real-time monitoring and visualization.
Effects of TSV (Through Silicon Via) Interposer/Chip on the Thermal Performances of 3D IC Packaging
Authors: Lau John H. , Tang Gong Yue , Hoe Germaine Yen Yi , Zhang Xiao Wu , Chai Tai Chong , Damaruganath Pinjala , Vaidyanathan Kripesh
Published: January 2011

Thermal performances of 3D SiP (system-in-package) with TSV (through silicon via) interposer/chip are investigated based on heat-transfer CFD (computational fluid dynamic) analyses. Emphases are placed on the determination of (1) the equivalent thermal conductivity of interposers/chips with various copper-filled, aluminum-filled, and polymer w/o filler filled TSV diameters, pitches, and aspect ratios, and (2) the junction temperature and thermal resistance of 3D SiP with various TSV parameters. Useful design charts and guidelines are provided for engineering practice convenient.
Characterization of Die Stress Distributions in Area Array Flip Chip Packaging
Authors: Roberts Jordan , Rahim M. Kaysar , Suhling Jeffrey C. , Jaeger Richard C. , Lall Pradeep , Zhang Ron
Published: January 2011

On-chip piezoresistive stress sensors represent a unique approach for characterizing stresses in silicon die embedded within complicated packaging architectures. In this work, we have used test chips containing such sensors to measure the stresses induced in microprocessor die after various steps of the assembly process, as well as to continuously characterize the in-situ die surface stress during thermal cycling and power cycling. The utilized (111) silicon sensor rosettes were able to measure the complete three-dimensional stress state (all 6 stress components) at each sensor site being monitored by the data acquisition hardware. The test chips had dimensions of 20 × 20 mm, and 3600 lead free solder interconnects (full area array) were used to connect the chips to high CTE ceramic chip carriers. Before packaging, the sensor resistances were measured by directly probing the test chip wafers. The chips were then diced, reflowed to the ceramic substrate, and then underfilled and cured. Finally, a metallic lid was attached to complete the ceramic LGA package. After every packaging step (solder reflow, underfill dispense and cure, lid attachment and adhesive cure), the sensor resistances were re-measured, so that the die stresses induced by each assembly operation could be characterized. The build-up of the die stresses was found to be monotonically increasing, and the relative severity of each assembly step was judged and compared. Such an approach also allows for various material sets (solders, underfills, TIM materials, lid metals, and lid adhesives) to be analyzed and rated for their contribution to the die stress level. After first level packaging of the chips on the ceramic chip carriers, initial experiments have been performed to analyze the effects of thermal cycling and power cycling on the die stresses. Thermal cycling of selected parts was performed from 0 to 100 C (40 minute cycle, 10 minute ramps and dwells). Power cycling of selected parts was performed by exciting the on-chip heaters on the test chips with power levels typical of microprocessor die. During the thermal/power cycling, sensor resistances at critical locations on the die device surface (e.g. die center and die corners) were recorded continuously. From the resistance data, the stresses at each site were calculated and plotted versus time. The experimental observations show some cycle-to-cycle evolution in the stress magnitudes due to material aging effects, stress relaxation and creep phenomena, and development of interfacial damage. The observed stress variations as a function of temperature cycling duration are currently being correlated with the delaminations occurring at the interfaces between the die and underfill and the die and lid adhesive. In addition, finite element models of the packages are being developed and correlated with the data.
Scaling Analysis of Performance Trade-Offs in Electronics Cooling
Authors: Green Craig E. , Fedorov Andrei G. , Joshi Yogendra K.
Published: January 2011

Using the governing equations for internal fluid flow and heat transfer, scaling laws are developed to predict how the selection of a liquid or gas coolant and geometry affects the pumping power and volume requirements of heat sinks in electronics cooling applications. One of the principal outcomes of the presented scaling analysis is derivation, based on first principles, of new figure-of-merit parameters that can be used to evaluate cooling performance and guide efforts on development of new cooling fluids. The new figures-of-merits are critically compared to existing performance metrics and experimental data from the literature to emphasize the relevance and accuracy of developed scaling laws.
Predicting Crack Growth and Fatigue Lives of QFN Solder Joints Using a Multiscale Fracture Model
Authors: Chan Dennis , Bhate Dhruv , Subbarayan Ganesh , Zhao Jeff , Edwards Darvin
Published: January 2011

The hierarchal fracture process model is a theory derived from continuum thermodynamics and information theory. This single parameter model provides a non-empirical approach able to predict crack growth for solder interconnects regardless of package or solder interconnect geometry. The model relates inelastic dissipations to the probability of failure at a given material point. The hierarchal fracture process model is used to predict crack growth and fatigue lives in a package with atypical solder interconnect geometry: a quad-flat-no-lead (QFN) package. The fracture model uses the material parameter calibrated for Sn3.8wt%0.7wt%Cu solder in a previous study of wafer-level CSP packages. Finite element models of these packages are created in ABAQUS with the solder interconnects given full creep and plastic properties. The results obtained from the hierarchal fracture process model are validated against the experimentally obtained fatigue lives and cross-sectional images of the crack path.
Co-Generation: Grid Independent Power and Cooling for a Data Center
Authors: Schmidt Roger , Iyengar Madhusudan , Steffes James , Lund Vijay
Published: January 2011

This paper presents an overview of the application of co-generation technology to data centers. Data center powers are increasing at an ever increasing rate and the power and cooling supply to these data centers are putting pressure on businesses to evaluate the issues related to the delivery of power and cooling. These evaluations stem from three key concerns in providing power to IT equipment in data centers — total cost of power delivery, reliability of power delivery, and finally the availability of power. This paper will present the key features of the cogeneration technology and where it might make business sense to consider its application.
System Level Thermal Design Challenges in Validation Platforms
Authors: Mohammed Rahima K. , Sahan Ridvan A. , Pang Ying-Feng
Published: January 2011

Unprecedented growth in the semiconductor industry has been enabled by decreasing transistor feature size. As silicon technology continues to scale per Moore’s law, multi-core and many-core are the new trends of the semiconductor industry. While bus speeds, features and functionalities are increasing, shrinking system volume, compact component placements on the board and system noise reduction are the trends. These silicon and system trends make the thermal design challenging. Validation platforms are used to validate processors/chipsets to ensure world-class quality and reliable Intel products. These platforms are usually open chassis to allow ease of accessibility. In this paper, we present an innovative methodology of active air cooling coupled with mechanical retention designs at the component level. Component level thermal testing data are correlated with computational fluid dynamics (CFD) simulations to provide guidance for system simulations. Well-validated and correlated active heatsink thermal model can be used in the system level thermal simulations for studying the mutual pre-heating effect among the components around the heatsink and other thermally critical components. System level thermal design incorporating the effects of memory cooling, voltage regulator module cooling, graphics card preheating, air blockages effect due to probing cables are presented. In addition, system level acoustic measurements methodology is shown. Finally, fan control methodologies to control the noise below safety guidelines while enhancing the validation customer’s experience are presented.
Investigation of Transfer Mold Process Effects on Semiconductor Package Warpage
Authors: Brand Jason M. , Yim Myung J. , Kumar Ravi
Published: January 2011

In recent years, Package on Package (PoP) is increasingly used for high density package solutions. Generally the top package is a stacked memory packaging system connected to a bottom logic packaging system via solder joint: this is representative of PoP configurations. To guarantee the assembly yield and reliability of the solder joint between the top package and bottom package, mechanical compliance between these two packages is crucial during package stacking. Henceforth package warpage needs to be understood and controlled to meet the assembly yield targets. The complexity of the package configuration increases by thinner package thickness, higher number of stacking dies and large package size. Controlling the warpage within the target requirement is very challenging, especially when the material behaviors of substrate, die, molding compound and die attach film are different and also changing as a function of temperature. Certainly, the material properties of key components in top PoP package plays a crucial role in warpage performance. Among various material properties, the chemical cure shrinkage, coefficient of thermal expansion and storage modulus for the molding compounds are determining factors on the temperature dependant warpage control of top PoP package. Warpage variation still exists within parts processed at the same time mainly due to slight material property variation. In this paper, the cause of the warpage variation is investigated. The main cause was found to be filler migration effect in narrow gaps with in the stacked die package during the mold process, which resulted in different filler concentration and distribution, and finally different local molding compound material property among the package unit location in the substrate strip. The findings indicate that mold pressure is not a major modulator of warpage, while filler distribution can dramatically alter the warpage behavior. FEA model results and warpage data are presented to validate the filler migration phenomena and warpage behavior impact. The findings and results provide some clues and design/process guideline for warpage control in Top PoP package, which influence the PoP assembly yield and reliability.
Predicting Thermal Stresses Induced by Conjugate Heat Transfer
Authors: Sabry Mohamed-Nabil
Published: January 2011

Thermal stresses developed in electronic systems mainly depend, not only on average temperature values, but rather on wall temperature profiles. These profiles are difficult to predict unless one uses detailed finite element or finite difference modeling and simulation techniques. This type of analysis is only suitable at final design phases were geometrical details are available or being finalized. It is not suitable at early design phases to get a rapid estimate of wall thermal gradients to orient design appropriately. Standard approaches involving correlations for the heat transfer coefficient fail to predict temperature profiles for many reasons. In fact, these correlations depend on temperature profile as an input. In most engineering applications, walls are neither infinitely conducting nor of negligible conductivity to justify the usage of either uniform temperature or uniform heat flux assumptions. Correlations addressing conjugate heat transfer would not be able to solve the problem, unless a large number of them were available covering all possible combinations of fluid and wall conditions. Besides, the case of multiple heat sources, quite common in modern systems, can never be correctly handled by such an approach. The flexible profile technology was proposed earlier to model heat transfer in either solids (conduction) or fluids (forced convection. The model depends on domain (fluid or solid) geometry and physical properties, regardless of the particular set of applied boundary conditions, including that of multiple heat sources. Combining a fluid flexible profile model with a solid one, will allow predicting wall temperature profiles, with an adjustable level of precision, depending on the number of degrees of freedom retained. It will be applied in this paper to predict thermally induced stresses in some simple test cases as a demonstrator of the potentials behind this approach.
Nanocidals for Osteomyelitis Management
Authors: Haik Yousef , Qadri Shahnaz
Published: January 2011

In this article we present the value of nanoparticles alloys made out of Ag:Cu as nanocidals for possible treatment of infected bone cells.
Non-Cd Based Quantum Dots for Molecular Imaging
Authors: Gao Jinhao , Chen Kai , Xie Renguo , Peng Xiaogang , Chen Xiaoyuan
Published: January 2011

Compared with the organic dyes and fluorescent proteins, quantum dots (QDs) show many unique optical properties, such as narrow and tunable emission spectra, superior photostability, high quantum yields, and the capacity of simultaneous excitation of multiple fluorescence colors. The QDs emitting at above 700 nm in the NIR region minimize the problems of indigenous fluorescence of tissues and meet the requirements of in vivo biological imaging applications. However, most of QDs containing cadmium showed potential cytotoxicity under extreme conditions limiting their further applications and clinical translations.
Protein Molecules as Natural Nano Bio Devices: Mobility Analysis
Authors: Shahbazi Zahra , Ilies¸ Horea T. , Kazerounian Kazem
Published: January 2011

Proteins are nature’s nano-robots in the form of functional molecular components of living cells. The function of these natural nano-robots often requires conformational transitions between two or more native conformations that are made possible by the intrinsic mobility of the proteins. Understanding these transitions is essential to the understanding of how proteins function, as well as to the ability to design and manipulate protein-based nano-mechanical systems [1]. Modeling protein molecules as kinematic chains provides the foundation for developing powerful approaches to the design, manipulation and fabrication of peptide based molecules and devices. Nevertheless, these models possess a high number of degrees of freedom (DOF) with considerable computational implications. On the other hand, real protein molecules appear to exhibits a much lower mobility during the folding process than what is suggested by existing kinematic models. The key contributor to the lower mobility of real proteins is the formation of Hydrogen bonds during the folding process.
Sensory Biofuel Cell for Self-Sustained Glucose Sensing in Healthcare Applications for Diabetes Patients
Authors: Rai Pratyush , Xie Jining , Varadan Vijay K. , Ho Thang , Hestekins Jamie A.
Published: January 2011

In biosensor design, sensor for blood-glucose-level detection is one of the elementary concepts. Many research groups have reported opto-electro-mechanical and biomimetic techniques for glucose sensing based on nanomaterials. (1) However, the popular commercialized techniques involve drawing blood samples and in-vitro processing. An implantable sensor requires energy source for operation with wire in-out provision for acquiring power and sending signals. Needless to say, the limitation for such a glucose sensor is alimentary rather than elementary. The problem requires innovative design to develop sustainable ensemble of bio-energy harvesting, sensing and telemetry components. The study, reported in this article, is directed towards developing a sensor-fuel cell technology with the potential of miniaturization for implants. The device design is a combination of nano-engineered composites and flexible thin film processing to achieve high density packaging. Of which, the end goal is simultaneous generation-transmission of sensory signals and production of energy.
Quantifying the Nanomechanical Properties of Bacillus Anthracis and Implications for Spore Killing
Authors: Camesano Terri A. , Pinzo´n-Arango Paola A. , Nagarajan Ramanathan
Published: January 2011

Atomic force microscopy (AFM) was used to study the changes in the nanomechanical properties of the surface of Bacillus anthracis spores during germination. The Hertz model of continuum mechanics of contact was used to evaluate the Young’s or tensile elastic modulus of the spores before and after germination by applying the model to load-indentation curves obtained during force cycles. The highest elastic modulus was obtained with dormant spores, with average elasticity values of 197 ± 81 MPa. Fully vegetative spores had the lowest elasticity values. The elasticity decreased when spores were incubated with either L-alanine or inosine, and the decrease was greatest when both of these germinants were used in combination. We also found that as the spore elasticity values increasd, the indentation depth of the AFM probe into the surface increased, with vegetative B. anthracis cells having elasticity depths of up to 246.2 nm. We have shown that spore nanomechanical properties change during germination, and depend on the type of germinant that is used. Weakening of the spore cell wall may help explain why germinating cells are much more susceptible to anti-sporal agents. The study of elasticity of spores may be a valuable tool in the development of antibiotics or anti-sporal treatments.
Pumping Characteristics of the Lymphatic System
Authors: Moore James E.
Published: January 2011

The lymphatic system is crucial for maintaining fluid and protein balance, and for immune function. It also plays an important role in the spread of cancer. Lymphedema can form when parts of the system are not functioning, such as in patients who have undergone lymph node resection as part of cancer therapy. Lymphedema is a painful, debilitating condition for which there is no cure. This research is aimed at constructing multi-scale models of lymphatic pumping function, incorporating information from the cellular to the whole organ level. Lymphatic endothelial and smooth muscle cell mechanotransduction events are incorporated into a single lymphangion pumping unit. The performance of this pumping unit is shown to exhibit behaviors observed in experiments with rat mesentery.
Nanomechanochemical Delivery of Nanoparticles for Nanomechanics Inside Living Cells
Authors: Yum Kyungsuk , Na Sungsoo , Xiang Yang , Wang Ning , Yu Min-Feng
Published: January 2011

Studying biological processes and mechanics in living cells is challenging but highly rewarding. Recent advances in experimental techniques have provided numerous ways to investigate cellular processes and mechanics of living cells. However, most of existing techniques for biomechanics are limited to experiments outside or on the membrane of cells, due to the difficulties in physically accessing the interior of living cells. On the other hand, nanomaterials, such as fluorescent quantum dots (QDs) and magnetic nanoparticles, have shown great promise to overcome such limitations due to their small sizes and excellent functionalities, including bright and stable fluorescence and remote manipulability. However, except a few systems, the use of nanoparticles has been limited to the study of biological studies on cell membranes or related to endocytosis, because of the difficulty of delivering dispersed and single nanoparticles into living cells. Various strategies have been explored, but delivered nanoparticles are often trapped in the endocytic pathway or form aggregates in the cytoplasm, limiting their further use. Here we show a nanoscale direct delivery method, named nanomechanochemical delivery, where we manipulate a nanotube-based nanoneedle, carrying “cargo” (QDs in this study), to mechanically penetrate the cell membrane, access specific areas inside cells, and release the cargo [1]. We selectively delivered well-dispersed QDs into either the cytoplasm or the nucleus of living cells. We quantified the dynamics of the delivered QDs by single-molecule tracking and demonstrated the applicability of the QDs as a nanoscale probe for studying nanomechanics inside living cells (by using the biomicrorhology method), revealing the biomechanical heterogeneity of the cellular environment. This method may allow new strategies for studying biological processes and mechanics in living cells with spatial and temporal precision, potentially at the single-molecule level.
Development of Neural Probe With Wireless Power Feed
Authors: Choi Sang H. , Song Kyo D. , Park Yeonjoon , Lee Uhn
Published: January 2011

New medical device technology is essential for diagnosing, monitoring, and curing wide spectrum of diseases, anomalies and inflictions. For neural applications, no matter whether non-intrusive or not, currently available devices are generally limited to either a curing or a probing function. In this paper we review the technology requirements for new neural probe and cure device technology. Recent advances in micro and nano-scale devices engineering and wireless power technology offer a great potential to revolutionize many health care systems. The integration of wireless power technology into smart microsensor and probe systems greatly simplifies the healthcare devices and systems and also offers additional device functions for even complex jobs. The wireless power feed technology eliminates the pains and irritations associated with implanted power devices and wires. Neural electronics interfaces (NEI) can be coupled and integrated with the wireless power receiver (WPR). The implantable probe-pin devices (PPD) that include the NEI and WPR allow real-time measurement and control/feedback possible for remedial process of neural anomaly from normal functions. Such a system like a PPD should have an embedded expert system that performs semi-autonomous functions through a routine of sensing, judging, and controlling the neural anomaly.
Inkjet Printing of High-Density Bacterial Arrays for Biosensor Applications
Authors: Cho Myoung-Ock , Yoon Sunghee , Kim Jung Kyung
Published: January 2011

Inkjet printing technique has been developed and applied in many areas. This rapid and simple technique can dispense small amount of selected material at intended location accurately. Due to these advantages, it has been applied to the field of biology such as tissue engineering and microbiology lately. We developed patterning methods based on inkjet printing technique employing bacteria, and generated two-dimensional bacterial cell array on the agar media using a commercially available thermal inkjet printer reformed partially. In this study, we aimed to apply the inkjet-printed bacterial cell array to biosensor. We measured the maximum resolution, accuracy and reproducibility of the bacterial array printed at 600 dpi. In addition, we were able to print three kinds of bacterial strains simultaneously using color cartridges which also enabling synchronous printing of both bacterial solution and known chemical. We applied this technique for studying the growth response of individual bacteria to different levels of stiffness, and the chemotactic response of bacterial colonies.
Tuberculosis Diagnostics Using a Nanotip Sensor
Authors: Yeo Woon-Hong , Chung Jae-Hyun , Lee Kyong-Hoon
Published: January 2011

Tuberculosis (TB) is one of the most widely spread diseases. In 2006, 9.2 million new TB cases were reported with 1.7 million victims [1]. To diagnose TB, Mycobacterium tuberculosis (MTB) is identified in clinical samples. The challenge of TB diagnostics is high-performance screening conducted by nontrained personnel. Currently, nucleic acid testing with target-amplification strategy such as polymerase chain reaction (PCR) is available for detection of TB. However, this entails cumbersome procedures run by skilled operators with expensive instrumentation and reagents. To overcome these challenges, this paper presents a nanotip sensor to diagnose TB rapidly without target-amplification. The proposed methodology uses a nanostructured tip as a biosensor to detect target analytes. The novelty of this approach is in the superior concentration and detection mechanisms of nucleic acids on the terminal end of a nanotip using an alternating current (AC) electric field, specific chemical binding, and capillary action. Confirmatory identification of MTB is achieved by detecting MTB strains on a nanostructured tip through DNA hybridization. In this paper, the working principle is presented with the demonstration of amplification-free detection of MTB genomic DNA using the nanotip sensor. The performance of the tip sensor is characterized.
Multiscale Modeling of Cortical Bone
Authors: Hamed Elham , Lee Yikhan , Jasiuk Iwona M.
Published: January 2011

Bone is an important multifunctional biological tissue with remarkable mechanical properties: high strength and stiffness, high fracture toughness, and light weight. These superior properties are due, in part, to the hierarchical structure of bone ranging from molecular to macroscopic levels, Fig. 1. Nevertheless, it is not clearly understood how the microstructure and mechanical properties of various hierarchies at different length scales affect the overall behavior of bone. Such understanding is essential in orthopedics for designing implant materials and fabricating synthetic bone substitutes and also for assessing the effect of bone diseases and their medications on bone’s properties. It can, moreover, serve as a guide in design of advanced synthetic bio-inspired materials for a wide range of engineering applications.
Modeling DNA Translocation Kinetics in Nanopores With Selectivity
Authors: Ramachandran Abhijit , Guo Qingjiang , Iqbal Samir , Liu Yaling
Published: January 2011

The development in nanotechnology has made fabrication of solid-state nanopores with 20nm diameter possible. These nanopores have found a variety of applications, with the foremost one being sensing of the biological molecules. To achieve molecular sensing, a major requirement of these solid state nanopores is molecular selectivity. This paper focuses on modeling the DNA translocation in functionalized nanopore with application on gene sequencing.
Modeling Targeted Drug Delivery in a Vascular Network
Authors: Liu Yaling , Nguyen Kytai , Mariyappa Manohara , Shah Samar , Tan Jifu
Published: January 2011

Nanomedicine dosages are selected in part based on the competing goals of maximizing death of malignant cells while minimizing damage to healthy cells. Determination of proper nanomedicine dosage and concentration is difficult to due the lack of understanding of nanoparticle targeted delivery process in complex vascular environment. This paper presents a continuum model of the transportation and targeted deposition of nanoparticles in a vascular network, which is an essential component of a multi-scale targeted delivery predictive tool being developed.
Ink-Jet as a Manufacturing Method for Drug Delivery, Tissue Engineering, and Medical Device Applications
Authors: Antohe Bogdan V. , Wallace David B.
Published: January 2011

Recent drug delivery applications have stressed the need for precise dosage in the context of complex delivery vehicles. Ink-jet technology incorporates data-driven, non-contact techniques that enable precise, picoliter volumes of material to be deposited with high speed and accuracy at target sites (even onto non-planer surfaces) and thus has emerged as a front runner for drug delivery applications. Being data-driven, ink-jet dispensing is highly flexible and can be readily automated into manufacturing lines. Moreover, the ability to precisely target the delivery location reduces waste, an important factor when the active biological materials to be deposited are high value / high cost. Some of the applications that have made use of ink-jet methods for dosage and distribution of biologically active agents are: loading of active agents onto drug eluting stents (DES); generation of drug loaded microspheres; fabrication of polymeric nerve conduits loaded with nerve growth factor; and coating of the active components onto patches for transdermal delivery.
Nanoscale Analysis of the Effect of Pathogenic Mutations on Polycystin-1
Authors: Ma Liang , Xu Meixiang , Oberhauser Andres F.
Published: January 2011

The activity of proteins and their complexes often involves the conversion of chemical energy (stored or supplied) into mechanical work through conformational changes. Mechanical forces are also crucial for the regulation of the structure and function of cells and tissues. Thus, the shape of eukaryotic cells is the result of cycles of mechano-sensing, mechano-transduction, and mechano-response. Recently developed single-molecule atomic force microscopy (AFM) techniques can be used to manipulate single molecules, both in real time and under physiological conditions, and are ideally suited to directly quantify the forces involved in both intra- and intermolecular protein interactions. In combination with molecular biology and computer simulations, these techniques have been applied to characterize the unfolding and refolding reactions in a variety of proteins, such as titin (an elastic mechano-sensing protein found in muscle) and polycystin-1 (PC1, a mechanosensor found in the kidney).
Hierarchical Structure Controls Nanomechanical Properties of Vimentin Intermediate Filaments
Authors: Buehler Markus J. , Qin Zhao
Published: January 2011

Intermediate filaments (IFs), in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, playing a vital role in mechanotransduction and in providing mechanical stability to cells (Figure 1) [1]. Despite the importance of IF mechanics for cell biology and cell mechanics, the structural basis for their mechanical properties remains unknown. Specifically, our understanding of fundamental filament properties, such as the basis for their great extensibility, stiffening properties, and their exceptional mechanical resilience remains limited. This has prevented us from answering fundamental structure-function relationship questions related to the biomechanical role of intermediate filaments, which is crucial to link structure and function in the protein material’s biological context.
Structure of Water Hydration Around Collagen
Authors: Ravikumar Krishnakumar M. , Hwang Wonmuk
Published: January 2011

We investigate the hydration structure of collagen using molecular dynamics simulations. The water density maximum, and orientation near the surface of collagen and their specificity to the proximal collagen sequence are clearly visible in our analysis. These results provide insights into the effect of hydration in collagen self-assembly, and more generally, the anomalous behavior of water near protein surfaces.
Enhanced Generation of Reactive Oxygen Species Using Gold Nanoparticles Conjugated With Protoporphyrin IX
Authors: Khaing Oo Maung Kyaw , Gomez Maria , Wang Hongjun , Du Henry
Published: January 2011

Reactive oxygen species (ROS) is a vital trigger for photodynamic therapy (PDT) of cancer. We report the production of elevated ROS using gold nanoparticles (GNP) (20–100 nm in diameter) conjugated with Protophorphyrin IX (PpIX). The amount of ROS formation increases with the size of the GNP due to enhanced electromagnetic field resulting from localized surface plasmonic resonance.
Investigation of RBC Remodeling With a Multiscale Model
Authors: Zhu Qiang , Peng Zhangli , Asaro Robert J.
Published: January 2011

Erythrocyte (red blood cell, or RBC) possesses one of the simplest and best characterized molecular architectures among all cells. It contains cytosol enclosed inside a composite membrane consisting of a fluidic lipid bilayer reinforced by a single layer of protein skeleton pinned to it. In its normal state, this system demonstrates tremendous structural stability, manifested in its ability to sustain large dynamic deformations during circulation. On the other hand, it has been illustrated in experiments that triggered by mechanical loads structural remodeling may occur. A canonical example of this remodeling is vesiculation, referring to the partial separation of the lipid bilayer from the protein skeleton and the formation of vesicles that contain lipids only.
Controllable Growth of Gradient Structures for Biomedical Applications
Authors: Zhang Wei , Yao Donggang , Zhou Jack G.
Published: January 2011

Co-continuous phase structures of immiscible polymers can be developed under appropriate melt-blending conditions. Because of the presence of interfacial tension, such co-continuous structures start to coarsen when heated to a temperature higher than the melting/softening temperature of both phases. In this article, a systemic study of controllable growth of gradient porous structures utilizing variable coarsening rates in either a gradient temperature field or a gradient shear field is presented. Based on experimental results, the gradient of shear viscosity is identified as the mechanism for generating variable coarsening rates inside a co-continuous blend. By controllable variation of the shear viscosity distribution in a blend, a spatially varied and controllable gradient in phase structure is created. After dissolution of one of the two phases, the desired porous structure of the remaining polymer is obtained. A poly (lactic acid) (PLA)/polystyrene (PS) 50/50 wt% blend was used as a model system. By designing proper thermal and/or dynamic boundary conditions and introducing different thermal/shear rate gradients during annealing, several gradient porous structures of PLA were created.
Templated Assembly by Selective Removal for Size-Selective Sorting of Biological Materials
Authors: Agarwal Gunjan , Livermore Carol
Published: January 2011

This work presents the size-selective sorting of single biological cells using the assembly process known as Templated Assembly by Selective Removal (TASR). We have demonstrated experimentally, for the first time, the selective self assembly and sorting of single SF9 cells (a clonal isolate, derived from Spodoptera frugiperda (Fall Armyworm) IPLB-Sf21-AE cells) into patterned hemispherical sites on rigid assembly templates using TASR. TASR-based size-selective assembly of biological systems represents a potentially valuable tool, with potential for implementation in several biological applications, such as cell sorting for medical research or diagnostics, or isolation of single cells for the study of biological or mechanical behavior.
Electrospun Recombinant Protein Polymer Nanofibers as a Biomaterial
Authors: Qiu Weiguo , Huang Yiding , Cappello Joseph , Wu Xiaoyi
Published: January 2011

Micro/nanometer protein fibers are fundamental building blocks of extra-/intracellular matrices, providing structural support, stability and protection to cells, tissue and organism [1]. Fabricating performance protein micro/nanofibers has been extensively pursued for a variety of biomedical application. In this study, silk-elastinlike protein (SELP) polymer will be electrospun into nanofibers as a biomaterial.
Development of Microfluidic Chips to Study the Effects of Shear Stress on Cell Functions
Authors: Wang Jianbin , Heo Jinseok , Hua Susan Z.
Published: January 2011

Fluid shear stress has profound effect on many cell functions, including proliferation, migration, transport, and gene expression. Cellular systems such as endothelial cells in heart artery and epithelial cells in kidney tubule are constantly subject to fluid flow. We have developed a series of microfluidic chips that generate a wide range and modes of shear stresses within a perfusion chamber, enabling us to culture cells on chip and examine the effects of shear stress on cell growth and cell functions.
Self Thermal Elimination of Nanomechanics-Based Biosensor Using a Single Free-Standing Piezoresistive Microcantilever
Authors: Ku Yu-Fu , Yen Yi-Kuang , Lin Ping-Yen , Huang Long-Sun
Published: January 2011

A compact piezoresistive microcantilever platform integrated by MEMS technique provides a convenient and reliable approach for biochemical detection. In contrast to the conventional double free-standing piezoresistive cantilever beams of heterogeneous sensing surfaces, a single free-standing piezoresistive microcantilever sensor was first proposed with the elimination of interference of chemical effect. The single beam piezoresistive sensor which is temperature-sensitive was well controlled within ±0.2°C by introducing the novel method of self elimination of thermal effect. This new approach maintains device compactness with no additional use of bulky temperature-controlled apparatus, and significantly reduces noises of temperature coefficient of resistance (TCR) and bimorph effect. The C-reactive protein (CRP) detection of the microcantilever biosensor with self elimination of thermal effect was verified with the concentration of 100 μg/mL in a room-temperature environment.
Magnetic Resonance Imaging of Magnetic Particles for Targeted Drug Delivery
Authors: Dahmen Christian , Wortmann Tim , Fatikow Sergej
Published: January 2011

Recently there have been initial investigations towards magnetic resonance imaging (MRI) guided actuation and control of untethered devices inside the human cardiovascular system. This form of therapy has the potential to revolutionize today’s treatment of cancer and other diseases by providing an accuracy of targeted drug application far beyond conventional approaches. Additionally it is based on standard MRI hardware and does not require any special or tailored hardware. In this article, we present recent work that is focused on visual feedback for the position control of untethered magnetic devices in the MRI. For reliable recognition and tracking, a thorough understanding of the impact of magnetic material on the process of MRI image acquisition is required. A simulation of the image formation process has been implemented. Additionally, initial experimental results of MRI artifact imaging are presented.
Growth Responses of Swarming and Gliding Bacteria on Substrates With Different Levels of Stiffness
Authors: Park Eun-Jung , Cho Myoung-Ock , Kim Jung Kyung
Published: January 2011

We conducted experiments to decipher the interplays among bacterial motility, surface stiffness of culture medium, and growth of colony when bacteria grow on semi-solid substrate. We observed the growth kinetics of two kinds of bacteria, swarming Escherichia coli (E.coli) and gliding Myxococcus Xanthus (M.xanthus), grown on semi-solid agar substrates with different stiffness. The colony of M.xanthus moved by traction force on the surface shows a tendency to grow larger on soft substrate. The colony of E.coli using flagella shows a similar tendency in the early phase but later grows smaller on substrate with lower stiffness. We found that the growth of bacterial colony is affected by the mechanical properties of the substrate and the type of bacterial motility as well.
Swimming Microorganisms in Complex Media
Authors: Fu Henry C. , Shenoy Vivek , Powers Thomas , Wolgemuth Charles W.
Published: January 2011

Microogranisms such as sperm and E. coli swim in a low-Reynolds number environment. In the zero-Reynolds-number Stokes limit, their kinematics are completely controlled by viscous forces and inertia is unimportant. This swimming environment is quite different from our usual (high Reynolds number) intuition about swimming. For example, due to the kinematic reversibility of Stokes flow, motions that look the same going forward and backward in time, such as the linear motion of an oar-like appendage, do not lead to net translation. Thus microorganisms in Newtonian fluids use swimming motions with a clear time-direction, such as the traveling waves or rotating corkscrew shapes of eukaryotic and bacterial flagella, respectively. While there has been much investigation of microorganism swimming in Newtonian fluids such as water, much less attention has been paid to swimming in complex materials, such as non-Newtonian, viscoelastic fluids and gels. However, in many cases microorganisms do in fact swim through such complex materials in their natural biological environments. For example, mammalian sperm swim through viscoelastic cervical mucus in the female reproductive tract, while H. pylori swim through the gastric mucus lining the inside of the stomach. In this talk I discuss two ways in which swimming through complex media differs from swimming in Newtonian fluids. First, the forces exerted by a viscoelastic medium are different from those exerted by a Newtonian fluid. I address how this affects swimming shapes and speeds of flexible swimmers such as sperm. Second, I discuss swimming through solids such as gels, where compressibility and heterogeneity become important.
Rho-GTPase Regulation by GEFs, GAPs and GDIs in Cell Migration
Authors: Diego Xavier , On˜ate Eugenio , Liu Wing Kam
Published: January 2011

The family of small RhoGTPases plays a crucial role in the spatial and temporal coordination cell migration. GEFs, GAPs and GDIs are the enzymes that regulate their activity, although the mechanism is poorly understood. Regulation models proposed to date have focused on GEFs as the main modulators of RhoGTPase activity, leaving a passive role to GAPs and GDIs. In this work we show that this assumption leads to models with properties that may be inconsistent with observations, more precisely, appearance of Turing instabilities and reduced sensitivity to secondary stimuli. The mathematical basis of this behavior is established, and a general class of interaction schemes that bypass it by including GAP and GDI regulation, which is supported by experimental evidence, is proposed.
The Contribution of Proteoglycans on the Mechanical Properties of the Corneal Stroma
Authors: Hatami-Marbini Hamed , Pinsky Peter M.
Published: January 2011

This paper studies the electrostatic contribution to the elasticity of corneal stroma using the Poisson-Boltzmann (PB) equation. Corneal stroma is a transparent connective tissue consisting of regularly organized collagen fibrils and proteoglycans (PGs) within an aqueous matrix. The cornea proteoglycan decorin is crucial for the regulation of collagen fibril diameters and their spacings. Decorin is the simplest small leucine-rich PG and is made up of a core protein and a glycosaminoglycan (GAG) side chain. Under physiological pH conditions, GAG molecules are completely ionized and become negatively charged. Their repulsive electrostatic interaction, mediated by free ions inside the bath, controls collagen interfibril spacings and contributes to corneal stiffness. In order to quantify the electrostatic contribution of GAGs to the elastic properties of the cornea, we define a unit cell in which GAGs are represented as cylindrical rods with a fixed charge density. The unit cell is deformed affinely and the electrical potential and free ion distribution inside the unit cell are obtained from the solution of the nonlinear PB equation. Having the potential and charge distribution, the changes in electrostatic free energy due to the deformation gives the electrostatic elastic moduli.
DNA Damage by Nanoparticles
Authors: Prevenslik Thomas
Published: January 2011

Nanoparticles (NPs) have provided significant technological advancements including bactericidal agents in food processing, and treatment of cancer tumors. However, there is a darkside. Over the past decade, experiments [1,2] have shown NPs to be a health risk by inducing DNA damage that can lead to cancer.