bluuebunny/crossref_metadata_2025 huggingface dataset:
On Structure and Elastic Fields of Random Fiber Networks
Authors: Hatami-Marbini Hamed , Picu Catalin R.
Published: January 2011

Random filamentous networks and their response to the applied load can be considered as a model to study the mechanical properties of biological systems such as cytoskeleton of a cell and connective tissues. A mathematical model for the actual and complex deformation of these networks under stress is developed using a micromechanics approach. We recently studied the effect of various micro-structural parameters such as fiber length, mean segment length and fiber flexibility on the network deformation field at various length scales. The network elasticity is mapped into a two dimensional heterogeneous continuum domain in order to show that the elastic fields of dense fiber networks show long range correlations over a range of scales for which we gave the upper and lower bounds. It is concluded that the deformation of random networks is similar to that of highly heterogeneous continuum domains with stochastic distribution of moduli. We employed the stochastic finite element method to solve boundary value problems defined on the random fiber network domain. Here, we present a brief review of this methodology and report new results on scaling properties of the structure of fiber networks using box-counting method.
Modeling of Drug and Drug-Encapsulated Nanoparticle Transport in Patient-Specific Coronary Artery Walls to Treat Vulnerable Plaques
Authors: Hossain Shaolie , Hossainy Syed , Bazilevs Yuri , Calo Victor M. , Hughes Thomas J. R.
Published: January 2011

The main objective of this work is to develop computational tools to support the design of a catheter-based local drug delivery system that uses nanoparticles as drug carriers in order to treat vulnerable plaques and diffuse atherosclerotic disease.
Influence of Nanoparticle Design on Binding Efficiency
Authors: Liu Yaling , Shah Samar , Hu Walter , Gao Jinming
Published: January 2011

The shape of nanoparticles plays a vital role in their transportation and adhesion in to cardiovascular system. The specific adhesion of nanoparticles to vascular surface has numerous potential applications such targeted drug delivery, biomedical imaging, and cancer treatment. This paper proposes a novel modeling method that provides insights of the dynamic interaction between nanoparticle and vessel wall. The ligand-receptor adhesion kinetics along with brownian dynamics is coupled with hydrodynamics to study the dynamic delivery process. The binding probability of two different shaped nanoparticles is evaluated and compared using Brownian adhesion dynamics model. Nanorod is found to contact and adhere to the wall surface easier than conventional nanosphere under same vascular flow conditions. This research work will explore the shape effect on targeted delivery process and eventually that will help researchers to design micro/nanoparticles for enhanced targeted adhesion to cells of interest.
A Study of Bifurcation Design Used in CD-ELISA Micro-Fluidic Platform
Authors: Lin Samuel I. En
Published: January 2011

Enzyme-linked immunosorbent assays (ELISA), one of the most common immunoassays, is widely used for detection and quantification of chemical and biological molecules and is becoming more and more important in clinical diagnostics, food safety testing, and environmental monitoring. A major challenge in developing the CD-ELISA is to split the flow (e.g., bio-reagents) evenly on the micro-channels. The Coriolis force resultant from CD rotation can disturb the flow in the splitter region and thus cause the failure mode in delivering the solution from each reservoir in a pre-specified manner. In this study, we investigate on the effects of inlet pressure and Coriolis force on the splitting ratio under two splitter structures. The analysis is based on the incompressible Navier-Stokes equation and the simulation results agree well with our experimental work.
Hierarchical Structure Controls Nanomechanical Properties of Vimentin Intermediate Filaments
Authors: Buehler Markus J. , Bertaud Je´re´mie
Published: January 2011

Intermediate filaments (often abbreviated as IFs), in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells (Figure 1). It has been suggested that intermediate filaments are crucial in defining key mechanical functions of cells such as cell migration, cell division and mechanotransduction, and have also been referred to as the “safety belts of cells” reflecting their role in preventing exceedingly large cell stretch [1, 2]. Vimentin is a specific type of this protein filament found in fibroblasts, leukocytes, and blood vessel endothelial cells, representing the most widely distributed type of intermediate filaments. Several diseases have been linked to the structure and density of intermediate filaments. Here we report a systematic study of the effects of intermediate filaments on cell mechanics, specifically focused on changes in the density of filaments. We compare the results with experimental studies in vimentin deficient cells, showing good qualitative agreement.
Divide-and-Conquer Based Adaptive Coarse Grained Simulation of RNA
Authors: Poursina Mohammad , Bhalerao Kishor , Anderson Kurt
Published: January 2011

Molecular modeling has gained increasing importance in recent years for predicting important structural properties of large biomolecular systems such as RNA which play a critical role in various biological processes. Given the complexity of biopolymers and their interactions within living organisms, efficient and adaptive multi-scale modeling approaches are necessary if one is to reasonably perform computational studies of interest. These studies nominally involve multiple important physical phenomena occurring at different spatial and temporal scales. These systems are typically characterized by large number of degrees of freedom O(103) – O(107). The temporal domains range from sub-femto seconds (O(10−16)) associated with the small high frequency oscillations of individual tightly bonded atoms to milliseconds (O(10−3)) or greater for the larger scale conformational motion. The traditional approach for molecular modeling involved fully atomistic models which results in fully decoupled equations of motion. The problems with this approach are well documented in literature.
Gold Nanoparticle Self Assembly on Diblock Copolymers for Application as Biomolecular Sensors
Authors: Adams Sarah M. , Ragan Regina
Published: January 2011

Current efforts in medical diagnostic technology focus toward developing biological sensors with the capacity for detecting trace quantities of specified organic molecules. In this study, metallic nanoparticles were investigated for the development of field-enhanced chemical and biological detection devices with the capacity to achieve single-molecule level detection resulting from surface enhanced Raman scattering (SERS) associated with closely spaced noble metal nanostructures.[1, 2] Localized surface plasmon resonance (LSPR) sensors likewise benefit from the incorporation of ordered metal nanoparticles on surfaces, providing increased shift in minimum of reflectivity with biological binding event (figure 1).[3]
Mechanical and In-Vitro Cell Compatibility Properties of Silk-Elastinlike Protein-Based Biomaterial
Authors: Teng Weibing , Huang Yiding , Cappello Joseph , Wu Xiaoyi
Published: January 2011

A series of genetically engineered recombinant silk-elastinlike proteins (SELPs) have been produced by combining polypeptide sequences derived from native silk of superior mechanical strength and elastin that is extremely durable and resilient. They have displayed a set of outstanding properties such as good biocompatibility and controllable biodegradation rates. In the study, we characterized the mechanical property of genetically engineered, recombinant silk-elastinlike protein copolymer, SELP-47K, under physical and chemical treatments. The biocompatibility of the SELP-47K was also evaluated by cell culture. The ultimate goal of this study is to explore the potential of SELPs for applications in the engineering of load-bearing tissues such as arteries.
A Hybrid Nano-Bioprinting Device for Tissue Engineering
Authors: Buyukhatipoglu Kivilcim , Sun Wei , Morss Clyne Alisa
Published: January 2011

Tissue engineering may require precise patterning of cells and bioactive factors to recreate the complex, 3D architecture of native tissue. These cells and bioactive components may then need to be repositioned during tissue growth in vitro and noninvasively imaged to track tissue development. We developed a new hybrid nano-bioprinting system by combining the initial patterning capabilities of a direct cell writing system with the active patterning capabilities of superparamagnetic nanoparticles. The iron oxide nanoparticles can be conjugated with proteins or loaded inside cells, printed into computer-defined patterns, and then manipulated and imaged within the 3D tissue engineering construct. In this study, iron oxide nanoparticles were bioprinted either in an alginate scaffold or inside endothelial cells. Cell viability, patterning, and imaging were assessed.
Computational Investigation of Dynamic Properties of Actin Networks With Crosslinking Proteins
Authors: Kim Taeyoon , Hwang Wonmuk , Kamm Roger D.
Published: January 2011

Due to the increasing recognition of the role that force plays in biological processes, a new field, mechanobiology, has recently emerged. One aspect of this is the need to gain a physical understanding of the viscoelastic properties of the cytoskeleton. Numerous studies, both in living cells and in reconstituted actin gels, have been conducted, but important questions still remain. Of these an important issue revolves around the role played by actin crosslinking proteins (ACPs), and whether they undergo unfolding or unbinding under stress. This issue is complicated by the fact that single molecule studies show that both events occur within a similar range of forces, on the order of 20–100 pN.
Molecular and Mesoscale Mechanisms of Osteogenesis Imperfecta Disease
Authors: Uzel Sebastien , Buehler Markus J.
Published: January 2011

Collagen is a crucial structural protein material, formed through a hierarchical assembly of tropocollagen molecules, arranged in collagen fibrils that constitute the basis for larger-scale fibrils and fibers. Osteogenesis imperfecta is a genetic disorder in collagen characterized by mechanically weakened tendon, fragile bones, skeletal deformities and in severe cases prenatal death. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. In this study, we report a series of systematic molecular scale based bottom-up computational experiments focused on pure collagenous tissue, carried out using atomistic-level molecular dynamics (MD), adaptive Poison-Boltzmann solver (APBS) calculations, and a mesoscale molecular model of collagen fibrils.
Micro-Porous PLLA Scaffolds for Orthopedic Surgical Fixation Devices
Authors: Zhang Qingwei , Zhang Wei , Yao Donggang , Wootton David M. , Lelkes Peter I. , Zhou Jack G.
Published: January 2011

Anterior cruciate ligament (ACL) reconstructive surgery is a major health concern world-wide because of a large aging population and increased occurrence of sport-related injuries. Tissue engineering is a rapidly growing interdisciplinary field that offers a promising new approach for ACL repair. The aim of this project is to explore novel “smart” surgical fixation devices that not only secure a graft in place without strength failure, but also incorporate and release bioactive materials, intended to promote bone tissue growth. In order to facilitate bioactive reagent release, biopolymeric scaffolds with continuous micro-porous structure were developed. The morphology of the porous structures in the poly-L-lactic acid (PLLA) matrix reflects the differential influence of the concentration of sacrificial material (PS-polystyrene), phase separation levels of the immiscible polymers (PLLA and PS), and melt-blending conditions (Fig. 1) [1]. During removal of the sacrificial material, the chemical solvent might introduce some chemical reactant into the scaffolds. In order to assess the feasibility of using the micro-porous structures for medical applications, 7F2 osteoblasts were cultured on these scaffolds for 7 days. The attachment and proliferation of 7F2 cells on all scaffolds were assessed by fluorescent nuclear staining with Hoechst 33258 and phalloidin. The morphology of 7F2 osteoblasts on solid PLLA and PLLA/HA with 40% porous structure scaffolds till the 7 days pos-seeding was observed under confocal microscopy (Fig. 2A and B). The results showed that removal of the sacrificial material does not influence cell growth and the composites are biocompatible. Besides in vitro cytotoxicity test, in vivo test of all the micro-porous structural scaffolds was performed through rat subcutaneous surgery. Histological analysis (H&E staining) of the porous PLLA/HA with 40% pores retrieved from rat subcutaneous tissue 4 weeks postimplantation show that cells start to grow inside the porous scaffold (Fig. 3A). The morphology of surrounding extracellular matrix (ECM) growing on the scaffolds was observed under SEM. Figure 3B shows soft tissue attached onto PLLA/HA porous scaffold after 1 month post implantation time point, which indicates the good biocompatibility of the scaffolds. Based on these data we predict that these scaffolds will be suitable for inducing and sustaining bone tissue regeneration, and will be feasible for ACL repair.
Multiscale Modeling of Protein Crystals: Application to Tetragonal Lysozyme
Authors: Zamiri Amir Reza , De Suvranu
Published: January 2011

Recently, protein crystals have emerged as promising bionanoporous materials for different applications including highly selective biocatalysis, biosensing, bioseparation, vaccine formulation, and drug delivery. The environmental working conditions require the protein crystals to be both chemically and mechanically stable. The structure, behavior, and mechanical properties of protein crystals play an important role in the performance and life cycle of these materials [1,2]. In this work we introduce a strategy for evaluating the mechanical response of protein crystals with the tetragonal lysozyme crystal as a model.
Hyperthermic Cytotoxicity Induced by Noninvasive Radiofrequency Field Exposure After Delivery of EGFR Family Targeted Gold Nanoparticles
Authors: Glazer Evan S. , Kaluarachchi Warna D. , Curley Steven A.
Published: January 2011

Noninvasive radiofrequency (RF) fields heat metal nanoparticles in a concentration dependent fashion. Gold nanoparticles are especially interesting for biomedical applications because they not only heat well, but they have an established biosafety profile. Antibody-targeted gold nanoparticles have been used to induce hyperthermic cytotoxicity when exposed to RF fields. Two carcinoma cells lines, Panc-1 and Hep3B, were individually treated with 100 nM panitumumab and trastuzumab antibody conjugated 10 nm gold nanoparticles and subsequently exposed to an RF field for a total generator power of ∼100 kJ. Two days later, control cells treated with antibody labeled gold nanoparticles, but not exposed to the RF field, maintained an average viability of 92.1% ± 2.5% for Hep 3B cells and 89.1% ± 2.1% for Panc-1 cells based on flow cytometry. Panc-1 cells treated the same way with subsequent RF field exposure had viability less than 80% (p ∼ 0.001). Hep3B cells showed a similar decrease in viability after trastuzumab-gold treatment (74.5% ± 6.9%), but not panitumumab. This demonstrates a new and developing use of antibodies, specifically, against EGFR family targets.
Multifaceted Nano- and Micropatterned Surfaces for Cell Adhesion Manipulation
Authors: Slater John H. , Miller Jordan S. , Yu Shann S. , West Jennifer L.
Published: January 2011

Surfaces displaying nano- and micropatterned cell adhesive ligands have led to numerous discoveries in cell biology. Soft lithography techniques such as microcontact printing are well suited for creating surfaces displaying micropatterns of one ligand type in a single arrangement but are difficult to implement for the creation of multifaceted surfaces that present multiple ligand types with each ligand confined to their own pattern. To better understand the influence of extracellular matrix (ECM) composition on adhesion site formation and gross cell behavior (motility, proliferation, differentiation, etc.) it would be advantageous to posses the ability to create surfaces displaying multiple patterned ligands with length scales ranging from < 0.25 μm2, the typical size of a focal complex to > 1 μm2, the size of focal adhesions. Higher spatial resolution than what is easily achieved with microcontact printing is also desired. Such surfaces would allow for the simultaneous investigations of adhesion site maturation and composition and how changes in these properties can be implemented to engineer cell behavior via cell-surface interactions.
Cancer Imaging and Thermal Therapy Facilitated by Nanoparticles and Multiphoton Microscopy
Authors: Day Emily S. , Bickford Lissett R. , Drezek Rebekah A. , West Jennifer L.
Published: January 2011

Despite use of currently available technologies, cancer remains one of the leading causes of death worldwide. Gold-based nanoparticles that strongly absorb near-infrared light, such as nanoshells and nanorods, have shown potential as both diagnostic and therapeutic agents for cancer management (1–3). In this work we explored the use of gold-gold sulfide nanoparticles (mean diameter = 37 nm) with peak plasmon resonance at 800 nm for combined imaging and therapy of breast cancer. Upon excitation with a pulsed laser, these particles exhibit two-photon induced luminescence which may be used to image cancer cells. In addition, by increasing the power output of the laser, cancer cells can be thermally ablated as the gold-gold sulfide nanoparticles convert the light energy into heat.
Gas-Phase Production of Multifunctional Composite Nanoparticles by Photoinduced Chemical Vapor Deposition
Authors: Boies Adam , Lei Pingyan , Roberts Jeff , Girshick Steven
Published: January 2011

Nano-scale materials and devices allow for unique interactions that are not possible at larger scales. Magnetic particles below a critical size (∼10 nm) demonstrate distinctive behavior known as superparamagnetism, where particles do not exhibit any net magnetic force outside the presence of an external magnetic field. However, within an alternating magnetic field, as in a magnetic resonance imaging (MRI) machine, superparamagnetic particles give off heat as a result of Brownian and Nee´lian relaxation. Heat produced by the shifting pole orientation can raise the temperature of the tissue sufficient to cause cell death through necrosis or apoptosis [1]. Additionally, combinations of electrically conductive and insulating materials within a single nanoparticle give rise to surface plasmon resonance. The resonance of the plasmon absorption can be tuned based on the relative thicknesses of the two layers. These particles can be used to thermally ablate cancer cells if the resonance is tuned to absorb light from an infrared laser. The penetrating ability of the nanoparticles combined with their capacity to kill cells make them excellent candidates for treatment of conditions such as brain tumors and prostate cancer.
Molecular Delivery Into Live Cells Using Gold Nanoparticle Arrays Fabricated by Polymer Mold Guided Near-Field Photothermal Annealing
Authors: Wu Ting-Hsiang , Xiao Fan , Kalim Sheraz , Teslaa Tara , Teitell Michael A. , Chiou Pei-Yu
Published: January 2011

A massively-parallel molecular delivery system for mammalian cells is demonstrated by pulsed-laser irradiation of a gold nanoparticle array situated below a cell monolayer. This system is capable of high throughput and spatially-targeted delivery into desired areas of a cell culture by designing the laser irradiation pattern. Rapid fabrication of gold nanoparticle arrays over large areas (>1 mm2) is achieved by polymer mold guided near-field photothermal annealing.
Fabrication of Polymeric Nano-Valve Array for Biomedical Applications
Authors: Chang Kuang-Fu , Shih Wen-Pin , Chen Chuin-Shan
Published: January 2011

Electro-active polymer working in aqueous medium has short response time and small power consumption. Polypyrrole is one of such electro-active polymers. Due to its stability, incorruptibility and micromachining compatibility, polypyrrole plays an important role in developing micro/nano-actuators for biological and chemical applications. This paper presents a flexible and reusable polypyrrole nano-valve array for biomedical applications. The nano-valves are formed by depositing polypyrrole on the anodic aluminum oxide (AAO) film by a novel method to ensure the integrity of the AAO film. The valves are actuated through the oxidation and reduction of the polypyrrole. The oxidation state of the polypyrrole makes sodium ions leaving the polypyrrole and hence contracts the polypyrrole. So the gold/polypyrrole bilayer was bended and the valves blocked. Conversely, the valve is opened as the reduction state. By controlling the open/close time with constant voltage, the diffusive quantity of the nano-valves can be easily changed.
Aptamer-Based Lab-on-Chip for Cancer Cell Isolation and Detection
Authors: Wan Yuan , Kim Young-tae , Na Li , Ellington Andrew D. , Iqbal Samir M.
Published: January 2011

The isolation and detection of circulating tumor cells (CTCs), when these are few in number or small in mass, can enable early cancer detection [1]. Currently, most research endeavors to isolate circulating tumor cells rely on antibodies and immunohistochemistry [2,3]. Aptamer are alternative molecules that have affinities and specificities that are comparable to those of antibodies [4,5], but these can be more readily adapted to many applications [6–9], including lab-on-a-chip devices. Here, we report use of a novel epidermal growth factor receptor (EGFR) aptamer biochip to identify and isolate cancer cells that overexpress EGFR. These results provide a solid basis for the development of diagnostic devices that can readily identify and isolate CTCs.
Wireless Point-of-Care Patient Monitoring System Using Zigbee and Wi-Fi Standards
Authors: Oh Sechang , Kwon Hyeokjun , Yoon Hargsoon , Varadan Vijay K.
Published: January 2011

This paper describes a wireless point-of-care patient monitoring system to monitor 3 channels of biopotential signals using a wireless sensor unit, a wireless receiver unit, and a monitoring unit. The wireless sensor unit transmits signals with Zigbee, and the wireless receiver unit which has both Zigbee and Wi-Fi transceivers receives the signals from the sensor unit and transmits the signals to the monitoring unit with Zigbee and Wi-Fi, respectively. By using both Zigbee and Wi-Fi, the wireless sensor system can achieve low power consumption and wide range coverage. The features of the system are presented, as well as biopotential monitoring results.
Silica Nanochannel Surface Effect on Monosaccharide Transport
Authors: Ziemys Arturas , Grattoni Alessandro , Gill Jaskaran , Ferrari Mauro
Published: January 2011

The interface of silica nanochannel of 10 nm was studied by molecular modeling and experimental methods. Molecular Dynamics study on glucose solution revealed that 2–3 nm of interface solution to silica walls has reduced glucose diffusivity. That reduction affects the effective diffusivity of glucose in silica nanochannel. Experimental results show Fickian-like release of glucose through 13 nm nanochannel. Molecular modeling and experimental results suggest that glucose is not sufficiently confined to possess non-Fickian behavior.
Fluorescence Amplification Using Biospecific Nanoparticle Conjugates as Labels in Microfluidic Heterogeneous Immunoassays
Authors: Li Peng , Chen Hong , Anagnostopoulos Constantine , Faghri Mohammad
Published: January 2011

In microfluidic sensing systems, it is challenging to achieve desirable sensitivity for detecting reduced number of analytes in a small volume (pL–nL). Many efforts have been made in order to improve the sensitivity of microfluidic fluorescence detection systems. Some prevalent methods (e.g., optical components integration and analyte enrichment) either increase cost or require extra operational steps. Fluorescence amplification using dye-doped silica nanoparticles has proved to be an inexpensive and efficient approach; however, this technique is still far from perfect. For instance, dye molecules physically entrapped in the silica nanoparticles occasionally leak and can cause false-negative results. In addition, the nonspecific adsorption of nanoparticles has not been resolved.
Studying the Mechanical Sensitivity of Human Colon Cancer Cells Through a Novel Bio-MEMS Force Sensor
Authors: Tang Xin , Cappa Tony , Kuhlenschmidt Theresa B. , Kuhlenschmidt Mark S. , Saif Taher A.
Published: January 2011

Cancer deaths are primarily caused by metastases, not by the parent tumor. During the metastasis, malignant cancer cells detach from the parent tumor, and spread through the patient’s circulatory system to invade new tissues and organs [1]. To study the role played by the mechanical microenvironment on the cancer cell growth and malignancy promotion, we cultured human colon carcinoma (HCT-8) cells in vitro on substrates with varied mechanical stiffness, from the physiologically relevant 1 kPa, 20 kPa to very stiff 3.5 GPa. A novel and versatile micro-electromechanical systems (Bio-MEMS) force sensor [2] is developed to quantify the strength of non-specific adhesion between living cancer cells membrane and probe, an important hallmark of cancer cell malignancy level. Immunoflurescent staining and Confocal microscopy imaging are used to visualize the cellular organelle organization and cooperate to explore the underlying mechanism.
Mechanically Based Simulations of the Dynamics of Growing Cell Clusters
Authors: Romero Ignacio , Arribas Juan J.
Published: January 2011

We outline the basic ingredients of a novel framework for the large scale mechanical simulation of multi-cellular clusters. Standard techniques of nonlinear finite elements are combined with parallel computing and versatile data structures to allow full mechanical resolution in cell-like spheroids which, furthermore, mimic the cell life cycle.
Electrical Impedance Spectroscopy Microsystem as a Tool for Cancer Cell Analysis
Authors: Kim Hyun Soo , Cho Younghak , Frazier A. Bruno , Chen Zhuo G. , Shin Dong Moon , Han Arum
Published: January 2011

Conventional methods for diagnosing and analyzing cancer cells are based on histology, genetic analysis, and protein analysis. Specific genotypes or proteins have been used as biomarkers in identifying cancer cells with specific phenotypes. Despite recent advances in cancer research, quantifying the heterogeneous tumor cell populations has been one of the main challenges in cancer diagnosis and prognosis [1]. The heterogeneous population of cells in the same tissues at different tumor development stages makes analyzing genetic alteration in tumors complicated. Methods conventionally used to study the heterogeneity of cancer cells are based on bulk analysis requiring large number of cells for assay. The resultant measurements are an average from multiple cells. As a result, any single protein or biomarker assay is not capable of determining the cellular heterogeneity of tumor [2]. To overcome such challenges, technologies capable of conducting reliable and high throughput sample analysis with single cell resolution is crucial.
Flow Structures in Three-Dimensional Fish-Like Swimming
Authors: Zhang Xing , Wang Shizhao , He Guowei
Published: January 2011

The swimming of a fish-like body is numerical simulated. The wake structures consist of a series of hairpin-like vortices braided together. The caudal fins generated vorticity interacts constructively with the body-bounded vorticity.
Chemotherapeutic Synergy Enhancement Through Micellar Nanotherapeutics
Authors: Blanco Elvin , Sangai Takafumi , Meric-Bernstam Funda , Ferrari Mauro
Published: January 2011

Current chemotherapeutic regimens involve the administration of a combination of agents with hopes of gaining synergistic cell-killing effects observed in vitro. However, drug synergy is rarely realized clinically given the different pharmacokinetic profiles of the drugs. Recent findings show that a combination of rapamycin and paclitaxel proves highly effective at hindering growth of tumors wherein the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Our objective was to fabricate a micellar nanotherapeutic platform capable of delivering a multitude of agents shown to synergistically affect a specific pathway (PI3K/Akt/mTOR) in breast cancer. We hypothesized that this concomitant delivery strategy will result in increased antitumor efficacy, given the site-specific and controlled delivery of the two agents. Herein, we demonstrate the successful fabrication of a nanotherepeutic strategy for the treatment of breast tumors with aberrant PI3K/Akt/mTOR pathways. Resulting polymer micelles were small in size (∼30 nm) and showed high levels of drug incorporation efficiency of both rapamycin and paclitaxel. Current studies involve the examination of release kinetics and antitumor efficacy in in vitro and in vivo models.
Modeling and Simulations of the Motion of Bio-Inspired Micro Swimming Robots
Authors: Tabak A. F. , Yesilyurt S.
Published: January 2011

Micro swimming robots that mimic the motion of micro organisms can carry out a variety of medical tasks including drug delivery, micro surgery and minimally invasive diagnostic tasks. Micro organisms such as spermatozoa and bacteria use their flagella to propel themselves. The artificial micro swimmer presented in this study is composed of a body that carries a medical payload, and one wave propagating tail attached to it. In this study, forces and torques exerted on the tail structure by the surrounding fluid are computed with the help of corresponding force coefficients. Rigid body dynamics computations are carried out by four-dimensional quaternion configuration to eliminate numerical error accumulation during matrix integrations, and, hence, instantaneous rotation matrix for rigid body rotation is extracted from the quaternion. Propulsive force obtained by waving tail is balanced by the drag force on the micro swimmers’ total wet surface and dynamic behavior of the micro swimmer is obtained as a rigid body motion. The effect of swimmer and waving geometry is parameterized to study the swimming behavior. Simulations carried out to explore the effect of wave length, wave amplitude, driving frequency. Translational and rotational velocities and hydrodynamic power requirements are presented for each individual set of design parameters. Validity of the model is tested by comparing the numerical results and finite element simulation results. Lastly, the model is modified to utilize the mobility matrix coefficients obtained from inertia eliminated finite element simulations governed by time dependent Navier-Stokes equations.
Modeling of Endothelial Cell Adhesion Dynamics Modulated by Molecular Engineering
Authors: Kopacz Adrian M. , Tefft Brandon J. , Liu Shu Q. , Liu Wing K.
Published: January 2011

Vascular thrombosis, intimal hyperplasia, and atherosclerosis are common disorders affecting a very large portion of the human population. A potential reduction in these disorders will elicit a significant impact. It has been shown that endothelial cells play a critical role in protecting blood vessels against the formation of thrombosis and atherosclerosis. Hence, a successful endothelial cell lining of arterial constructs will prevent intimal hyperplasia in reconstructed arteries. However, in practice endothelial cells often detach from reconstructed arteries due to weak adhesion strength, hindering the effectiveness of endothelial cell lining.
Random Sampling Monte-Carlo Approach to Studying Entropic Elasticity Properties of Cell Proteins and Lipids
Authors: Karpov Eduard
Published: January 2011

An efficient numerical Monte-Carlo method is proposed for the estimation of the entropic contribution to the elastic properties of cell protein and lipid chain biomolecules. Specific load-extension curves are obtained numerically for a group of molecules with degenerate potential energy profiles. Spread of the linear elastic regimes and dependence on the molecular weight and geometric parameters of the molecules are discussed.
Coaxial Electrospinning Biopolymer With Living Cells
Authors: Hamid Qudus , Sun Wei
Published: January 2011

Tissue engineering and regenerative medicine aim to produce tissue constructs in vitro which can subsequently be implanted in vivo to repair damaged or diseased tissues in a clinically relevant time scale. Coaxial electrospinning techniques are capable of producing 3D scaffolds with living cells, growth factors, and or time release drugs embedded within nano fibers. The fabrication of such electrospun mats requires a novel coaxial delivery system which provides encapsulation, protection and hydration of living cells. The electrospun fibers will form a mat adaptive to its collector that facilitates cell adhesion, differentiation, and proliferation. The embedded living cells may be employed to perform vital tasks such as secretion of matrix components and growth factors. These electrospun mats would improve viability of tissue engineered constructs, and may be made into biomedical devices. Cold water fish skin gelatin (high polarity natural polymer) is used to encapsulate cells while Poly(ethylene oxide) (PEO) serves as the electrospinning filler in the biosuspension. Glutaraldehyde (GTA) solution is used to preserve the 3D environment and structural integrity of the electrospun mats.
Characterzation and Quality Control for Micro- and Nanochanneled Silicon Membranes
Authors: Gill Jaskaran Singh , Grattoni Alessandro , Ziemys Arturas , Ferrari Mauro
Published: January 2011

The rapid advancement of silicon fabrication techniques has enabled the production of large numbers of precisely designed devices. Such devices are appealing to a wide range of industries and have already seen use in energy conversion [1] and medical applications [2]. Our group’s interest is in the latter; specifically the use of micro- and nanofabricated channels in silicon for the controlled release of drugs.
Switching Between Magnetic or Oxigen Sensory Input for the MC-1 Flagellated Bacteria to be Used for Controlling the Motion of Swarms of Bacterial Microscale Nanorobots
Authors: Martel Sylvain , Mohammadi Mahmood , Mokrani Nisryn
Published: January 2011

Our previous studies have shown that the flagellated nanomotors combined with the nanometer-sized chain of magnetosomes of a single Magnetotactic Bacterium (MTB) can be used as an effective integrated propulsion and steering system for microscale nanorobots. In this case, magnetotaxis has been exploited to control the swimming direction of the flagellated bacteria. This was done by inducing a directional torque on the chain of magnetosomes embedded in each bacterial cell. This approach allowed us to control swarms of flagellated bacteria of type MC-1 to accomplish relatively complex computer coordinated tasks such as micro-assemblies and drug deliveries, to name but only two examples. But the motion of each cell can also be influenced by other sensory means besides magnetotaxis, and includes chemotaxis, phototaxis, and aerotaxis. Here we show examples of MC-1 flagellated bacteria being controlled by magnetotaxis or aerotaxis. It is then demonstrated that these flagellated bacteria can not only provide an effective propulsion and steering system for future bio-nanorobots but also various sensory means capable of influencing their motions and swarm formations.
Finite Element Framework for Mechanics and Dynamics of Supramolecular Protein Assemblies
Authors: Kim Do-Nyun , Sedeh Reza Sharifi , Nguyen Cong Tri , Bathe Mark
Published: January 2011

The conformational dynamics and mechanical properties of supramolecular protein assemblies play a central role in a broad array of cellular functions ranging from migration and division to transcription and translation. The finite element method (FEM) provides a natural framework for the computation of protein normal modes and mechanical response based either on atomic coordinates or electron density maps [1]. Here, we present development of the finite element framework for the computation of actin filament mechanics and solvent damping effects. A new normal modes data bank for structures in the electron microscopy data bank (EMDB [2]) is also presented.
Mechanical Characterization of Biological Tissue: Finite Element Modeling
Authors: Xuan Yue , Tong Wei
Published: January 2011

Indentation, in addition to the traditional tensile testing, has been widely used for evaluating mechanical properties of hard materials such as metals and bone as well as soft materials like polymer and soft tissues. However, it is difficult to measure the contact area and surface deformation in conventional indentation tests of soft tissue which will bring large errors to the evaluation of the material properties. Also the assumption of isotropic property limited the usage of indentation test in characterizing the nonlinear, anisotropic properties of soft tissue thin film. In this project, 2D and 3D finite element analyses has been carried out to predict hyperelastic material response under indentation and punch tests. A novel indentation test system was developed, which made the direct measurement of local deformation and contact area possible. The apparatus consists of a transparent indenter, a digital microscope, and a computer based control and data acquisition system. The proposed testing system and associated finite element analysis are used to characterize the mechanical properties of multiscale (bulk and thin film) biological tissues.
A Micro-Architectural Based Structural Model for Elastomeric Electrospun Scaffolds
Authors: D’Amore Antonio , Stella John A. , Schmidt David E. , Wagner William R. , Sacks Michael S.
Published: January 2011

Interest in electrospun polymeric nano-microfibers for tissue engineering applications has rapidly grown during the last decade. In spite of this technique’s flexibility and ability to form complex fiber assemblies, additional studies are required to elucidate how the fibrous microstructure translates into specific tissue (or meso-scale) level mechanical behavior. Deterministic structural models can quantify how key structures contribute to the mechanical response as a function of bulk deformation across multiple scales, as well as provide a better understanding of cellular mechanical response to local micro-structural deformations. Our ultimate aim is to utilize such models to assist tissue engineering scaffold design. In the current work, we present a novel approach to automatically quantify key micro-architectural descriptors (fiber overlaps, connectivity, orientation, and diameter) from SEM images of electrospun poly (ester urethane) urea (PEUU) to recreate statistically equivalent scaffold mechanical models. An appropriate representative volume element (RVE) size was determined by quantifying the point of stabilization of the architectural descriptors over image areas of increasing size. Material models were then generated specifying: fiber overlap density, fiber orientation, connectivity and fiber diameter. Macro-meso mechanical response was predicted via FEM simulations.
Micro-Mechanical Characterisation of Human Cortical Bone
Authors: Jonvaux Julien , Budyn Elisa , Hoc Thierry
Published: January 2011

We present a numerical model to mechanically characterise real and Monte-Carlo microstructures of human cortical bone. Femoral mid-shaft human bone microstructures are specific to each individual and exhibit unique morphological and mechanical properties. Real microstructures of female bone samples are explicitly reconstructed using a finite element model. Patient-dependent statistically equivalent models are built from natural morphological parameters measured under reflected light microscopy (RLM) and back-scattered electron microscopy (BSEM). The micro mechanical properties are provided by nanoindentations and microextensometry. The morphological and mechanical characteristics are incorporated into the model to mimic bone micro-scale heterogeneity. The overall stiffness of the microstructure is calculated for a distribution of samples. The effects of the variations of local parameters on the global stiffness are studied. The evolution of these parameters indicates various aging signs of bone. These results are validated through comparison to experiments to assess fracture risk.
Ordered Au Nanodisk and Nanohole Arrays: Fabrications and Applications
Authors: Zheng Yue Bing , Shi Jinjie , Juluri Bala Krishna , Huang Tony Jun
Published: January 2011

We have advanced nanosphere lithography for fabricating ordered Au nanodisk and nanohole arrays on glass substrates. Further, we demonstrate the applications of the nanodisks and nanoholes in understanding exciton-plasmon couplings and patterning micro-/nano-particles, respectively.
Added-Mass Effect in Modeling of Cilia-Based Devices for Microfluidic Systems
Authors: Kongthon J. , McKay B. , Iamratanakul D. , Oh K. , Chung J.-H. , Riley J. , Devasia S.
Published: January 2011

This article shows that the added mass due to fluid structure interaction significantly affects the vibrational dynamics of cilia-based devices. Our main contribution is to show that such damping effects cannot explain the substantial reduction in the resonant vibrational frequency of the cilia operating in liquid when compared to the natural frequency of the cilia in air. It is shown that an added-mass approach (that accounts for the inertial loading of the fluid) can explain this reduction in the resonant vibrational frequency when operating the cantilever-type devices in liquids. Additionally, it is shown that the added-mass effect can explain why the cilia-vibration amplitude is not substantially reduced in a liquid by the hydrodynamic drag force. Thus, this article shows the need to model the added-mass effect, both, theoretically and by using experimental results.
Manipulation of Clinical Materials Using AC Electrokinetics
Authors: Sin Mandy L. Y. , Wong Pak Kin
Published: January 2011

AC electrokinetics is a promising approach for sample preparation and reaction enhancement in lab-on-a-chip devices. However, relative little has been done on the electrokinetic manipulation of physiological fluids and buffers with similar properties, such as conductivity. Herein, electrokinetic manipulation of fluids with a wide range of conductivities has been studied as a function of voltage and frequency. AC electrothermal flow is determined to dominate the fluid motion when the applied frequency of the AC potential is above 100 kHz. Interestingly, experimental data deviate from theoretical prediction for fluids with high conductivities (> 1 Sm−1). The deviation can be understood by voltage modulated electrochemical reactions and should be accounted for when manipulating clinical materials with high conductivities. The study will provide useful in sights in designing lab-on-a-chip devices for manipulating clinical samples in the future.
Development of Nanofiber Scaffolds for Engineering an Artificial Salivary Gland
Authors: Larsen Melinda , Jean-Gilles Riffard , Soscia David , Sequeira Sharon , Melfi Michael , Gadre Anand , Castracane James
Published: January 2011

There is currently a significant clinical need for artificial salivary glands as a therapeutic option for patients suffering from xerostomia. To achieve unidirectional fluid secretion, the epithelial acinar cells must establish and maintain polarity by partitioning the plasma membrane into distinct apical and basolateral membrane surfaces to achieve unidirectional fluid secretion. Establishment and maintenance of epithelial acinar cell polarity has been difficult to achieve in vitro, and yet is critical saliva secretion in an engineered salivary gland. Physical properties of the scaffold provided to epithelial cells will likely influence their ability to differentiate and achieve apical-basal polarity. We have engineered nanofiber matrices using the biocompatible polymer, PLGA (poly-L-lactic-co-glycolic acid) having differing topology and organization and documented the structure of these scaffolds using SEM. We evaluated the effects of several factors on epithelial cell attachment, self-organization, and apico-basal polarity on the scaffolds using confocal microscopy to examine expression and organization of apical tight junction proteins, ZO-1 and claudins, and basal markers, such as integrin α6 and the ECM protein fibronectin. The surface of the nanofiber matrix was functionalized with chemically-linked ligands to further optimize apical-basal polarity. These studies will identify an optimal scaffold for future use in an engineered functional salivary gland construct.
Elucidating the Interactions of Nanomaterials With Biological Systems
Authors: Chan Warren C. W.
Published: January 2011

Nanotechnology is a rapidly growing research fields with many applications in biology and medicine. At a heart of nanotechnology research is engineered nanostructures, which possess distinct optical, electronic, and magnetic properties based on their size, shape, and chemical composition. Researchers can now design their surface chemistry with small bi-functional organic molecules or amphiphillic polymers so that they are biocompatible and can be coated with bio-recognition molecules such as antibodies, aptamers, and peptides. Nanoparticles are used as a platform for drug delivery, as a physical trigger for controlling drug release, as a contrast agent for quantifying biological molecules. Thus, the applications of engineered nanostructures are diverse. In this presentation, an overview of the field of nanomedicine is described with an emphasis on results obtained from studying the in vivo interactions of nanostructures as it pertains to their applications in cancer.
Hybrid Systems for Cooling Turbine Inlet Air for Preventing Capacity Loss and Energy Efficiency Reduction of Combustion Turbine Systems
Authors: Punwani Dharam V.
Published: January 2011

Combustion turbines in cogeneration (combined heat & power) and combined-cycle systems are the most energy efficient systems for fossil fuel energy utilization and power generation, respectively. Therefore, for reducing carbon footprint of energy utilization and power generation, it is important to maximize the utilization of these systems. This approach allows minimization of electric energy from less energy efficient systems such as combustion turbines in simple-cycle and steam-turbine systems. When the full potentials of cogeneration and combined-cycle systems have been utilized, simple-cycle combustion systems should be used next because these are, generally, more energy efficient than the steam-turbine based power plants. Unfortunately, during hot weather just when power demand and market value/price of electric energy are high, output capacity of all combustion turbine systems decreases by as much as 30% of the rated capacity (at the ISO temperature of 59F). Hot weather also decreases the energy efficiency of all combustion turbine systems by as much as 5%. Cooling the inlet air to combustion turbines is a well recognized approach for preventing the loss of power output capacity and reduction in energy efficiency of all combustion turbine systems. Several technologies are commercially available for this application. This paper focuses on the use of hybrid cooling systems, which incorporate two or more cooling technologies (instead of a single technology) that are used in sequential processing. The paper discusses the pros and cons of the hybrid systems and includes some examples of the combustion turbine systems that have been successfully using some of the hybrid systems for turbine inlet cooling.