Fluid Manipulation by Bio-Mimetic Cilia

This paper describes the fabrication and actuation of bio-mimetic cilia for fluid manipulation. High aspect ratio cilia made of polydimethylsiloxane (PDMS) were successfully assembled in a microfluidic device by our novel fabrication method. This method was to release the PDMS cilia from a Si mold and assemble the cilia in a device. All the process was performed under water in order to avoid the stiction and pairing of the PDMS cilia. The underwater assembly method enabled a high aspect ratio PDMS structure assembly in a fluidic device. The PDMS cilia were actuated in air and water by lead-zirconate-titanate (PZT) microstage. In the fabricated device, the maximum displacement of the cilia was observed at 120Hz in air and at 50Hz in de-ionized (DI) water with our experimental condition. The actuated cilia in a solution produced convective and propulsive fluid flow near the cilia structure. The developed device can be used for precise handling of small volume sample (e.g., 1 μL).

The Effects of Tibiofemoral Angle and Body Weight on the Stress Field in the Knee Joint

Osteoarthritis (OA) is a degenerative disease of articular cartilage that may lead to pain, limited mobility and joint deformation. It has been reported that abnormal stresses and irregular stress distribution may lead to the initiation and progression of OA. Body weight and the frontal plane tibiofemoral angle are two biomechanical factors which could lead to abnormal stresses and irregular stress distribution at the knee. The tibiofemoral angle is defined as the angle made by the intersection of the mechanical axis of the tibia with the mechanical axis of the femur in the frontal plane. In this study, reflective markers were placed on the subjects’ lower extremity bony landmarks and tracked using motion analysis. Motion analysis data and force platform data were collected together during single-leg stance, double-leg stance and walking gait from three healthy subjects with no history of osteoarthritis (OA), one with normal tibiofemoral angle (7.67°), one with varus (bow-legged) angle (0.20°) and one with valgus (knocked-knee) angle (10.34°). The resultant moment and forces in the knee were derived from the data of the motion analysis and force platform experiments using inverse dynamics. The results showed that Subject 1 (0.20° valgus) had a varus moment of 0.38 N-m/kg, during single-leg stance, a varus moment of 0.036 N-m/kg during static double-leg stance and a maximum varus moment of 0.49 N-m/kg during the stance phase of the gait cycle. Subject 2 (7.67° valgus tibiofemoral angle) had a varus moment of 0.31 N-m/kg, during single-leg stance, a valgus moment of 0.046 N-m/kg during static double-leg stance and a maximum varus moment of 0.37 N-m/kg during the stance phase of the gait cycle. Subject 3 (10.34° valgus tibiofemoral angle) had a varus moment of 0.30 N-m/kg, during single-leg stance, a valgus moment of 0.040 N-m/kg during static double-leg stance and a maximum varus moment of 0.34 N-m/kg during the stance phase of the gait cycle. In general, the results show that the varus moment at the knee joint increased with varus knee alignment in static single-leg stance and gait. The results of the motion analysis were used to obtain the knee joint contact stress by finite element analysis (FEA). Three-dimensional (3-D) knee models were constructed with sagittal view MRI of the knee. The knee model included the bony geometry of the knee, the femoral and tibial articular cartilage, the lateral and medial menisci and the cruciate and the collateral ligaments. In initial FEA simulations, bones were modeled as rigid, articular cartilage was modeled as isotropic elastic, menisci were modeled as transversely isotopic elastic, and the ligaments were modeled as 1-D nonlinear springs. The material properties of the different knee components were taken from previously published literature of validated FEA models. The results showed that applying the axial load and varus moment determined from the motion analysis to the FEA model Subject 1 had a Von Mises stress of 1.71 MPa at the tibial cartilage while Subjects 2 and 3 both had Von Mises stresses of approximately 1.191 MPa. The results show that individuals with varus alignment at the knee will be exposed to greater stress at the medial compartment of the articular cartilage of the tibia due to the increased varus moment that occurs during single leg support.

An Analysis of Laminated Piezoelectric Infinite Plate for Broadband Biomedical Ultrasound Transducer Design

This work investigates the use of frequency spectrum analysis of waveguide propagation in multi-layered anisotropic piezoelectric transducers. A semi-analytical finite-element analysis (SAFE) is used to model the transducer as a piezoelectric infinite plate. Dispersion curves, group velocities and displacement frequency spectra can be obtained for any multilayered piezoelectric plate. Stress-free boundary conditions were assumed for all analyses. Results for open and closed circuit boundary conditions were analyzed. Zero-Group-Velocity (ZGV) frequencies of high-order waveguide modes were observed to provide multi-resonant displacement frequency spectrum. Comparison of numerical and experimental results shows a good agreement between peak and off-peak values of the displacement spectrum. Results showed that optimization of layered structure may provide an efficient means for generating multi-thickness (ZGV) waveguide modes, thus increasing the bandwidth of harmonic ultrasound transducers for contrast imaging.

Prediction of Biomechanical Properties of Bone Implant Scaffolds

This work is concerned with the 3D finite element modeling of porous implants in which the pore characteristics and distribution are taken into account. The analysis is conducted for scaffolds composed of various biocompatible materials such as Hydroxyapatite, PMMA, PEEK, Ti-6Al-4V, Silicon Nitride, Zirconia and Alumina. Furthermore, the potential of bone growth within the scaffolds is investigated using principal strain histograms of loaded scaffolds. The results show that the histogram of the principal strain resembles a top hat distribution while the porosity (void fraction) decreases. For a specific porosity, the principal strain distribution falls within the desired region (for optimal bone growth) by selecting materials with some particular Poisson’s ratio, although stress-shielding possibility rises due to an increase in the apparent stiffness of the scaffold. The increase in the apparent stiffness is a result of high Young modulus of the above-mentioned materials. The model will provide a platform for designers to adjust internal architecture features (e.g., the porosity level, shape/size/orientation of pores and the material properties) based on the host bone data prior to the scaffold fabrication.

Finite Element Modeling of Brain Tissue Retraction for Neurosurgical Simulation

The simulation capability for intraoperative brain tissue deformation by the surgical procedures using computational Finite Element analysis is demonstrated in this paper. Our research group has been developing the patient-specific three-dimensional Finite Element brain deformation model consisting of precise anatomical structures, i.e., brain parenchyma with both gyri and sulci on the surface, falx cerebri, and tentorium, in order to evaluate brain shift during navigation surgery without additional acquisition of intraoperative imaging. In this study, both gray and white matters of the brain tissues were modeled as homogeneous nonlinear hyper-viscoelastic material. The falx cerebri with tentorium was modeled as linear elastic material which is much stiffer than the brain tissue. The skull was modeled as a rigid body. In the numerical simulation, the computation of the intraoperative cerebellum tissue deformation due to retraction by spatula for posterior fossa surgery was conducted by ABAQUS/Explicit. The illustrative results successfully demonstrate the interaction between brain tissue and spatula.

Post Healing Structural Response of an Internal Fixation System for a Mid-Shaft Radius Fracture

Inexpensive models of the radius with and without an internal fixation system for a mid-shaft fracture are developed and analyzed using the Finite Element Method (FEM). FE models are based on geometry obtained from simple yet effective manufacturing methods. Median trabecular and cortical bone mechanical properties for a healthy adult male are used in the FEM model. These models are used to quantify the changes in bone stresses that occur when internal fixation devices are retained after the fracture has healed. The linear static responses to tensile and torsional loads with and without bone plates are examined. The static response trends obtained agree reasonably well with current literature where more expensive modeling techniques were used. A fatigue analysis is also performed based on the FE static results coupled with S-N curves for the plate and bone material in order to predict the combined mechanical response of the bone plate system over time. Recommendations are suggested which may be used as additional guidelines to consider for bone plate system selection and determination of hardware removal.

Dynamics of Single Cavitation Bubble Oscillation Inside an Elastic Tube

Understanding the dynamics of bubble oscillation in tissue-constrained media such as within blood vessels is important for many current and potential therapeutic ultrasound applications. Cavitation is a primary mechanism responsible for vessel rupture and tissue injury in shock wave lithotripsy [1]. In sonoporation cavitation can be used to increase permeability of biological membranes. Particularly, ultrasound contrast agents are widely used for imaging of blood vessels and for enhancement of ultrasound-mediated gene delivery [2]. Modeling of non-linear oscillations of bubbles in acrylic capillaries in a high-intensity focused ultrasound field revealed a clear dependence of bubble displacement and fragmentation on tube diameter [3]. However, the effect of elastic boundary on bubble dynamics may differ significantly from that of a rigid boundary [4, 5]. In this study, experimental investigation of the dynamics of bubble oscillation in an elastic tube was performed and preliminary results from tubes of different inner diameters are presented.

A Real-Time Continuous Flow Polymerase Chain Reactor for DNA Expression Quantification

Real-time quantitative Polymerase Chain Reaction (PCR) is an extremely sensitive and reliable method for quantifying gene expression, allowing subtle shifts in gene expression to be easily monitored. Currently, stationary real-time PCR is readily achieved using fluorescent labels which increase in fluorescence as the DNA is exponentially amplified. Quantitative PCR is used in a myriad of applications. However currently most commercial real-time PCR devices are batch process stationary well based systems, limiting their throughput. Continuous flow microfluidic PCR devices have allowed for advancement in terms of improved PCR throughput and reduced reagent usage. As part of an overall total analysis system a device integrating all the functional steps of continuous flow realtime quantitative PCR has been designed and fabricated. Initially the PCR reaction mixture is segmented into nano-litre PCR reactors which are then thermally cycled on a two temperature fifty cycle flow-through PCR device, which allows laser induced fluorescent imaging of the nanoreactors. Previous studies into continuous flow PCR have demonstrated endpoint fluorescent measurements, however this research allows PCR nanoreactors to be fluorescently monitored after every PCR thermal cycle. Fluorescent optical monitoring is achieved through laser excitation of the nanoreactors while a Charged Coupled Device (CCD) camera is used to record the fluorescent emissions from the nanoreactors. Intensity analysis of the recorded images is then preformed using MATLAB to accurately determine the fluorescence intensity level, thereby allowing real-time quantitative amplification curves to be generated. This has major advantages over existing continuous flow PCR devices which use endpoint fluorescence and capillary electrophoresis, as the amplification curves allow far more information to be gleaned and allow the initial DNA template concentration to be accurately determined.

FE Modeling of the Three-Layer Human Carotid Artery Under Impact Loadings

Blunt traumatic rupture of the carotid artery is a rare but life threatening injury. The histology of the artery is key to understanding the aetiology of this injury. The carotid artery is composed of three layers known as the tunica intima, media, and adventitia, with distinct biomechanical properties. In order to examine the behaviour of the carotid artery under external load we have developed a three layer finite element model of this vessel. A rubber-like material model from LS-DYNA was selected for the FE model. The Arbitrary-Lagrangian Eulerian (ALE) approach was adopted to simulate the interaction between the fluid (blood) and the structure (carotid). To verify the FE model, the impact bending tests are simulated using this FE model. Simulation results agree with tests results well. Furthermore, the mechanical behaviour of carotid artery tissues under impact loading were revealed by the simulations. The results provide a basis for a more in-depth investigation of the carotid artery in vehicle crashes. In addition, it provides a basis for further work on aortic tissue finite element modeling.

Mapping of Regional Cancerous Tissue Mechanical Property Changes Using Harmonic Motion Imaging

Mechanical changes in breast tissues as a result of cancer are usually detected through palpation by the physician and/or self examination. However, physicians are unable to palpate most masses under 1 cm in diameter and microscopic diseases. The goal of our study is to introduce the application of the Harmonic Motion Imaging (HMI), an acoustic radiation force technique, for reliable sensitive tumor detection and real-time monitoring of tumor ablation. Here, we applied the HMI technique using a single-element Focused Ultrasound (FUS) transducer. Due to the highly localized and harmonic nature of the response, the motion characteristics can be directly linked to the regional tissue modulus. In this experiment, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) probe, was used. The FUS beam was further modulated by a low AM continuous wave at 25 Hz. A pulser/receiver was used to drive the pulse-echo transducer at a Pulse Repetition Frequency (PRF) of 5.4 kHz. The radio-frequency (RF) signals were acquired using a standard pulse echo technique. The intensity amplitudes of the FUS beam at the focus (Ispta) were 231 W/cm2 for tumor detection and 1086 W/cm2 for FUS ablation. An analog bandpass filter was used to remove the spectrum of the FUS beam prior to displacement estimation. The resulting axial tissue displacement (i.e., HMI displacement) was estimated using an RF-based speckle tracking technique based on 1D cross-correlation. For tumor mapping, a harmonic radiation force was applied using a 2D raster-scan technique. The 3D HMI image was obtained by combining multiple 2D planes at different depths. The 2D and 3D HMI images in ex vivo breast tissues could detect a benign tumor (2×5×5mm3) surrounded by normal tissue, and a malignant tumor (8×7×5mm3) embedded in glandular and fat tissues. For FUS therapy, temperature measurements and RF signals were acquired during thermal ablation. HMI images during FUS ablation showed lower displacements, indicating thus tissue hardening due to lesion formation at temperatures higher than 50°C. A finite-element model (FEM) simulation was also used to analyze the findings of the experimental results. In conclusion, this technique demonstrates feasibility of the HMI technique for tumor detection and characterization, as well as real-time monitoring of tissue ablation based on the associated tissue elasticity changes.