A three-dimensional model of fluid-structural interactions for quantifying the contractile force for cardiomyocytes on hybrid biopolymer microcantilever

Quantitatively analysis of the contractility of cardiomyocytes is important for understanding the mechanism of heart failure as well as the molecular alterations in diseased heart cells. This paper presents a realistic computational model, which considers the three-dimensional fluid-structural interactions (FSI), to quantify the contractile force of cardiomyocytes on hybrid biopolymer microcantilevers. Prior to this study, only static modeling of the microscale cellular force has been reported. This study modeled the dynamics of cardiomyocytes on microcantilevers in a medium using the FSI. This realistic model was compared with static finite element modeling (FEM) analysis and the Stoney's equation-based analytical solution, and was validated by the deflections of the microcantilevers in the experimental results. Using harmonic response analysis in FSI modeling, the motion of a hybrid biopolymer microcantilever in the medium was identified as a second-order system and the influence of the dynamics of cardiomyocytes could be evaluated quantitatively.     

Microcantilever biosensors

Biosensors are sensors in which biomolecular interactions are used as sensing reactions. Biomolecular interactions, when combined with a microcantilever platform, can produce an extremely powerful biosensing design. The resonance frequency of a microcantilever shifts sensitively due to mass loading from molecular interaction as in the case of any acoustic sensors. In addition, the microcantilevers also undergo bending if the molecular adsorption is confined to a single surface of a microcantilever. This cantilever bending is due to a differential surface stress caused by the forces involved in the adsorption process and is amplified by making the cantilever surfaces chemically different. Lack of specificity, the main disadvantage of the cantilevers, can be overcome by using the extremely selective biochemical reactions such as receptor-ligand, antibody-antigen, or enzyme-substrate reactions. Here we review the microcantilever technology and discuss a number of highly sensitive biochemical sensor applications based on microcantilevers.     

Evaluation of dentinal fluid flow behaviours: a fluid-structure interaction simulation

This study uses the fluid-structure interaction (FSI) method to investigate the fluid flow in dental pulp. First, the FSI method is used for the biomechanical simulation of dental intrapulpal responses during force loading (50, 100 and 150 N) on a tooth. The results are validated by comparison with experimental outcomes. Second, the FSI method is used to investigate an intact tooth subjected to a mechanical stimulus during loading at various loading rates. Force loading (0–100 N) is applied gradually to an intact tooth surface with loading rates of 125, 62.5, 25 and 12.5 N/s, respectively, and the fluid flow changes in the pulp are evaluated. FSI analysis is found to be suitable for examining intrapulpal biomechanics. An external force applied to a tooth with a low loading rate leads to a low fluid flow velocity in the pulp chamber, thus avoiding tooth pain.     

Nanomechanical microcantilever operated in vibration modes with use of RNA aptamer as receptor molecules for label-free detection of HCV helicase

We report the nanomechanical microcantilevers operated in vibration modes (oscillation) with use of RNA aptamers as receptor molecules for label-free detection of hepatitis C virus (HCV) helicase. The nanomechanical detection principle is that the ligand-receptor binding on the microcantilever surface induces the dynamic response change of microcantilevers. We implemented the label-free detection of HCV helicase in the low concentration as much as 100 pg/ml from measuring the dynamic response change of microcantilevers. Moreover, from the recent studies showing that the ligand-receptor binding generates the surface stress on the microcantilever, we estimate the surface stress, on the oscillating microcantilevers, induced by ligand-receptor binding, i.e. binding between HCV helicase and RNA aptamer. In this article, it is suggested that the oscillating microcantilevers with use of RNA aptamers as receptor molecules may enable one to implement the sensitive label-free detection of very small amount of small-scale proteins.     

Numerical simulation of the dynamics of a bileaflet prosthetic heart valve using a fluid-structure interaction approach

The main purpose of this study is to reproduce in silico the dynamics of a bileaflet mechanical heart valve (MHV; St Jude Hemodynamic Plus, 27mm characteristic size) by means of a fully implicit fluid-structure interaction (FSI) method, and experimentally validate the results using an ultrafast cinematographic technique. The computational model was constructed to realistically reproduce the boundary condition (72 beats per minute (bpm), cardiac output 4.5l/min) and the geometry of the experimental setup, including the valve housing and the hinge configuration. The simulation was carried out coupling a commercial computational fluid dynamics (CFD) package based on finite-volume method with user-defined code for solving the structural domain, and exploiting the parallel performance of the whole numerical setup. Outputs are leaflets excursion from opening to closure and the fluid dynamics through the valve. Results put in evidence a favorable comparison between the computed and the experimental data: the model captures the main features of the leaflet motion during the systole. The use of parallel computing drastically limited the computational costs, showing a linear scaling on 16 processors (despite the massive use of user-defined subroutines to manage the FSI process). The favorable agreement obtained between in vitro and in silico results of the leaflet displacements confirms the consistency of the numerical method used, and candidates the application of FSI models to become a major tool to optimize the MHV design and eventually provides useful information to surgeons.     

Fluid–structure interaction analysis of the left coronary artery with variable angulation

The aim of this study is to elucidate the correlation between coronary artery branch angulation, local mechanical and haemodynamic forces at the vicinity of bifurcation. Using a coupled fluid–structure interaction (FSI) modelling approach, five idealized left coronary artery models with various angles ranging from 70° to 110° were developed to investigate the influence of branch angulations. In addition, one CT image-based model was reconstructed to further demonstrate the medical application potential of the proposed FSI coupling method. The results show that the angulation strongly alters its mechanical stress distribution, and the instantaneous wall shear stress distributions are substantially moderated by the arterial wall compliance. As high tensile stress is hypothesized to cause stenosis, the left circumflex side bifurcation shoulder is indicated to induce atherosclerotic changes with a high tendency for wide-angled models.     

Fluid-Structure Interaction Simulation of Prosthetic Aortic Valves: Comparison between Immersed Boundary and Arbitrary Lagrangian-Eulerian Techniques for the Mesh Representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations’ outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results.     

Validation of a fluid-structure interaction model of a heart valve using the dynamic mesh method in fluent

Simulations of coupled problems such as fluid-structure interaction (FSI) are becoming more and more important for engineering purposes. This is particularly true when modeling the aortic valve, where the FSI between the blood and the valve determines the valve movement and the valvular hemodynamics. Nevertheless only a few studies are focusing on the opening and closing behavior during the ejection phase (systole). In this paper, we present the validation of a FSI model using the dynamic mesh method of Fluent for the two-dimensional (2D) simulation of mechanical heart valves during the ejection phase of the cardiac cycle. The FSI model is successfully validated by comparing simulation results to experimental data obtained from in vitro studies using a CCD camera.     

Effect of the fluid-structure interactions on low-density lipoprotein transport within a multi-layered arterial wall

The effects of fluid-structure interactions (FSI) and pulsation on the transport of low-density lipoprotein (LDL) through an arterial wall are analyzed in this work. To this end, a comprehensive multi-layer model for both LDL transport as well as fluid-structure interaction (FSI) is introduced. The constructed model is analyzed and compared with the existing results in the limiting cases. Excellent agreement is found between the presented model and the existing results in the limiting cases. The presented model takes into account the complete multi-layered LDL transport while incorporating the FSI aspects to enable a comprehensive study of the deformation effect on the pertinent parameters of the transport processes within an artery. Since the flow inside an artery is time-dependent, the impact of pulsatile flow is also analyzed with and without FSI. A detailed analysis is presented to illustrate the consequence of different factors on the LDL transport in an artery.     

Systolic fluid–structure interaction model of the congenitally bicuspid aortic valve: assessment of modelling requirements

A transient fluid–structure interaction (FSI) model of a congenitally bicuspid aortic valve has been developed which allows simultaneous calculation of fluid flow and structural deformation. The valve is modelled during the systolic phase (the stage when blood pressure is elevated within the heart to pump blood to the body). The geometry was simplified to represent the bicuspid aortic valve in two dimensions. A congenital bicuspid valve is compared within the aortic root only and within the aortic arch. Symmetric and asymmetric cusps were simulated, along with differences in mechanical properties. A moving arbitrary Lagrange–Euler mesh was used to allow FSI. The FSI model requires blood flow to induce valve opening and induced strains in the region of 10%. It was determined that bicuspid aortic valve simulations required the inclusion of the ascending aorta and aortic arch. The flow patterns developed were sensitive to cusp asymmetry and differences in mechanical properties. Stiffening of the valve amplified peak velocities, and recirculation which developed in the ascending aorta. Model predictions demonstrate the need to take into account the category, including any existing cusp asymmetry, of a congenital bicuspid aortic valve when simulating its fluid flow and mechanics.     

Accuracy vs. computational time: translating aortic simulations to the clinic

State of the art simulations of aortic haemodynamics feature full fluid-structure interaction (FSI) and coupled 0D boundary conditions. Such analyses require not only significant computational resource but also weeks to months of run time, which compromises the effectiveness of their translation to a clinical workflow. This article employs three computational fluid methodologies, of varying levels of complexity with coupled 0D boundary conditions, to simulate the haemodynamics within a patient-specific aorta. The most comprehensive model is a full FSI simulation. The simplest is a rigid walled incompressible fluid simulation while an alternative middle-ground approach employs a compressible fluid, tuned to elicit a response analogous to the compliance of the aortic wall. The results demonstrate that, in the context of certain clinical questions, the simpler analysis methods may capture the important characteristics of the flow field.     

Effect of a lipid pool on stress/strain distributions in stenotic arteries: 3-D fluid-structure interactions (FSI) models

Nonlinear 3-D models with fluid-structure interactions (FSI) based on in vitro experiments are introduced and solved by ADINA to perform flow and stress/strain analysis for stenotic arteries with lipid cores. Navier-Stokes equations are used as the governing equations for the fluid. Hyperelastic Mooney-Rivlin models are used for both the arteries and lipid cores. Our results indicate that critical plaque stress/strain conditions are affected considerably by stenosis severity, eccentricity, lipid pool size, shape and position, plaque cap thickness, axial stretch, pressure, and fluid-structure interactions, and may be used for possible plaque rupture predictions.     

Control mechanism for the upper airway collapse in patients with obstructive sleep apnea syndrome: a finite element study

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent collapses of the upper airway, which lead to repetitive transient hypoxia, arousals and finally sleep fragmentation. Both anatomical and neuromuscular factors may play key roles in the pathophysiology of OSAS. The purpose of this paper was to study the control mechanism of OSAS from the mechanical point of view. A three-dimensional finite element model was developed, which not only reconstructed the realistic anatomical structure of the human upper airway, but also included surrounding structures such as the skull, neck, hyoid, cartilage and soft tissues. The respiration process during the normal and apnea states was simulated with the fluid-structure interaction method (FSI) and the computational fluid dynamics method (CFD). The airflow and deformation of the upper airway obtained from the FSI and the CFD method were compared and the results obtained under large negative pressure during an apnea episode were analyzed. The simulation results show that the FSI method is more feasible and effective than the CFD method. The concave configuration of the upper airway may accelerate the collapse of the upper airway in a positive feedback mechanism, which supplies meaningful information for clinical treatment and further research of OSAS.     

Peptide receptor-based selective dinitrotoluene detection using a microcantilever sensor

We reported that peptide could be utilized as receptor molecule in the gas phase for application in micro/nano sensors by using a specific peptide that recognizes 2,4-dinitrotoluene at room temperature and in an atmospheric environment and measuring changes in the resonant frequency of the peptide immobilized microcantilevers. By using these peptides as receptors on a microcantilever sensor, we were able to experimentally detect 2,4-dinitrotoluene (DNT) vapor at concentrations as low as parts per billion (ppb) in the gas phase. While resonant frequency changes after binding between 2,4-DNT and the specific peptide receptor that was immobilized on microcantilevers were observed, the resonant frequency of DNT nonspecific peptide immobilized microcantilever did not change when exposed to 2,4-DNT vapor. The limit of detection (LOD) was calculated to be 431 ppt of limit of detection is numerically expected by experimental based on an equation that describes the relationship between the noise-equivalent analyte concentration. These results indicate that the peptide receptors hold great promise for use in the development of an artificial olfactory system and electronic nose based on micro/nanotechnology for monitoring various chemical vapors in the gas phase such as explosive mixtures of chemicals and/or volatile organic compounds.     

Fluid–structure interaction simulation of the brain–skull interface for acute subdural haematoma prediction

Traumatic brain injury is a leading cause of disability and mortality. Finite element-based head models are promising tools for enhanced head injury prediction, mitigation and prevention. The reliability of such models depends heavily on adequate representation of the brain–skull interaction. Nevertheless, the brain–skull interface has been largely simplified in previous three-dimensional head models without accounting for the fluid behaviour of the cerebrospinal fluid (CSF) and its mechanical interaction with the brain and skull. In this study, the brain–skull interface in a previously developed head model is modified as a fluid–structure interaction (FSI) approach, in which the CSF is treated on a moving mesh using an arbitrary Lagrangian–Eulerian multi-material formulation and the brain on a deformable mesh using a Lagrangian formulation. The modified model is validated against brain–skull relative displacement and intracranial pressure responses and subsequently imposed to an experimentally determined loading known to cause acute subdural haematoma (ASDH). Compared to the original model, the modified model achieves an improved validation performance in terms of brain–skull relative motion and is able to predict the occurrence of ASDH more accurately, indicating the superiority of the FSI approach for brain–skull interface modelling. The introduction of the FSI approach to represent the fluid behaviour of the CSF and its interaction with the brain and skull is crucial for more accurate head injury predictions.

     

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.     

Effects of wall distensibility in hemodynamic simulations of an arteriovenous fistula

Arteriovenous fistulae are created surgically to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is in part a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. The current study presents fluid–structure interaction (FSI) simulations of a patient-specific model of a mature arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are compared with previously published data of the same model but with rigid walls. Ultrasound-derived wall motion measurements are also used to validate the FSI simulations of the wall motion. Very large time-averaged shear stresses, 10–15 Pa, are calculated at the fistula anastomosis in the FSI simulations, values which are much larger than what is typically thought to be the normal homeostatic shear stress in the peripheral vasculature. Although this result is systematically lower by as much as 50 % compared to the analogous rigid-walled simulations, the inclusion of distensible vessel walls in hemodynamic simulations does not reduce the high anastomotic shear stresses to “normal” values. Therefore, rigid-walled analyses may be acceptable for identifying high shear regions of arteriovenous fistulae.     

Validation of a fluid–structure interaction numerical model for predicting flow transients in arteries

Fluid–structure interaction (FSI) numerical models are now widely used in predicting blood flow transients. This is because of the importance of the interaction between the flowing blood and the deforming arterial wall to blood flow behaviour. Unfortunately, most of these FSI models lack rigorous validation and, thus, cannot guarantee the accuracy of their predictions. This paper presents the comprehensive validation of a two-way coupled FSI numerical model, developed to predict flow transients in compliant conduits such as arteries. The model is validated using analytical solutions and experiments conducted on polyurethane mock artery. Flow parameters such as pressure and axial stress (and precursor) wave speeds, wall deformations and oscillating frequency, fluid velocity and Poisson coupling effects, were used as the basis of this validation. Results show very good comparison between numerical predictions, analytical solutions and experimental data. The agreement between the three approaches is generally over 95%. The model also shows accurate prediction of Poisson coupling effects in unsteady flows through flexible pipes, which up to this stage have only being predicted analytically. Therefore, this numerical model can accurately predict flow transients in compliant vessels such as arteries.     

Detection of heavy metal ions using protein-functionalized microcantilever sensors

Microcantilevers functionalized with metal-binding protein, AgNt84-6, are demonstrated to be sensors for the detection of heavy metal ions like Hg(2+) and Zn(2+). AgNt84-6, a protein that has the ability to bind multiple atoms of Ni(2+), Zn(2+), Co(2+), Cu(2+), Cd(2+) and Hg(2+) was attached to the gold-coated side of silicon nitride cantilevers via linker groups. Upon exposure to 0.1 mM HgCl(2) and 0.1 mM ZnCl(2) solutions, the microcantilevers underwent bending corresponding to an expanding gold side. Exposure to a 0.1 mM solution of MnCl(2) solution did not result in a similar bending indicating a weak or no interaction of Mn(2+) ions with the AgNt84-6 protein. The microcantilever bending data were consistent with data from electrophoresis carried out on SDS-PAGE gels containing metal ions that showed protein interaction with Zn(2+) ions but not with Mn(2+) ions. Thus, we demonstrate that microcantilever bending can be used to discriminate between metal ions that bind and do not bind to AgNt84-6 protein in real time.     

Comparison of a potentiometric and a micromechanical triglyceride biosensor

Sensitive biosensors for detection of triglyceride concentration are important. In this paper we report on two types of silicon based triglyceride sensors: an electrolyte-insulator-semiconductor capacitor (EISCAP) which is a potentiometric device and a polysilicon microcantilever. The detection principle for both sensors is based on the enzymatic hydrolysis of triglyceride though the sensing mechanisms are different: electronic for the EISCAP and mechanical for the microcantilever. The characteristics and performances of the two sensors are critically compared. The EISCAP sensor necessitates the presence of a buffer for stable measurements which limits the sensitivity of the sensor at low concentrations of the bioanalyte to 1mM. The cantilever sensor works without a buffer which improves the lower level of sensitivity to 10 microm. Both sensors are found to give reproducible and reliable results.