Publications (122)167.22 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Abstract Better understanding of airway wall shear stress/strain rate is very important in order to prevent inflammation in patients undergoing mechanical ventilation due to respiratory problems in intensive-care medicine. The objective of this study was to investigate the role of mechanical ventilation waveforms on airway wall shear/strain rate using computational fluid dynamics analysis. Six different waveforms were considered to investigate the airway wall shear stress (WSS) from fluid dynamics analysis for the airway geometry of two-to-three generations. The simulation results showed that Original with Sine Inhale Waveform (OSIW) produced the highest WSS value and the Near True Sine Waveform produced the lowest WSS value. Also, the Original with Sine Inhale Waveform and the Short Sine Inhale with Long Sine Exhale Waveform (SSILSEW) produced a higher shear strain rate in comparison to the Original Waveform (OW). These results, combined with optimization, suggest that it is possible to develop a set of mechanical ventilation waveform strategies to avoid inflammation in the lung.
- [Show abstract] [Hide abstract] ABSTRACT: There is an increasing need to develop implantable drug delivery devices for effective therapeutic management of chronic ocular diseases such as age-related macular degeneration (AMD). In this work, we designed four different micro-channel configurations for an implantable device and elucidate drug diffusion characteristics using both simulation and experimental measurements. Our simulation and experimental results show that three micro-channel configurations are capable of sustaining drug release and can be incorporated into an implantable device to exert long-term drug release required for therapeutic management of AMD.
- [Show abstract] [Hide abstract] ABSTRACT: Ocular drug delivery is a complex and challenging process and understanding the transport characteristics of drug-loaded particles is very important for designing safe and effective ocular drug delivery devices. In this paper, we investigated the effect of the microchannel configuration of the microdevice, the size of drug-loaded nanoparticles (NPs), and the pressure gradient of fluid flow in determining the maximum number of NPs within a certain outlet region and transportation time of drug particles. We employed a hybrid computational approach that combines the lattice Boltzmann model for fluids with the Brownian dynamics model for NPs transport. This hybrid approach allows to capture the interactions among the fluids, NPs, and barriers of microchannels. Our results showed that increasing the pressure gradient of fluid flow in a specific type of microchannel configuration (tournament configuration) effectively decreased the maximum number of NPs within a certain outlet region as well as transportation time of the drug loaded NPs. These results have important implications for the design of ocular drug delivery devices. These findings may be particularly helpful in developing design and transport optimization guidelines related to creating novel microchannel configurations for ocular drug delivery devices.
- [Show abstract] [Hide abstract] ABSTRACT: This paper presents an implantable device concept with applications for treating ocular diseases such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa. The design of a biodegradable drug delivery device concept consisting of a polydimethylsiloxane (PDMS) shell with a fluid reservoir and micro/nano-fluidic tubes that allow the drug to be stored and delivered at a specified rate is discussed. Computational fluid dynamics simulations were conducted through various tube configurations in order to obtain the drug diffusion characteristics. The results from the simulation studies revealed information related to drug transport under varying design parameters. The design simulations were conducted with a desired rate. Based on results from several simulations, an optimization study was conducted to achieve the required dosage for about 2 years. The results obtained from the optimization study shows that the device concept can be extended for different drugs to treat ocular diseases.
- [Show abstract] [Hide abstract] ABSTRACT: Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
- [Show abstract] [Hide abstract] ABSTRACT: Better understanding of alveolar mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. The objective of this study was to investigate the alveolar mechanics for two different alveolar sac models, one based on actual geometry and the other an idealized spherical geometry using coupled fluid-solid computational analysis. Both the models were analyzed through coupled fluid-solid analysis to estimate the parameters such as pressures/velocities and displacements/stresses under mechanical ventilation conditions. The results obtained from the fluid analysis indicate that both the alveolar geometries give similar results for pressures and velocities. However, the results obtained from coupled fluid-solid analysis indicate that the actual alveolar geometry results in smaller displacements in comparison to a spherical alveolar model. This trend is also true for stress/strain between the two models. The results presented indicate that alveolar geometry greatly affects the pressure/velocities as well as displacements and stresses/strains.
- [Show abstract] [Hide abstract] ABSTRACT: Better understanding of the acute/chronic inflammation in airways is very important in to order avoid lung injuries for patients undergoing mechanical ventilation. Inflammation is a complex and dynamic process triggered by many mechanisms within the lung and involves multiple scales starting from organ level to cellular level. In this study, a multiscale modeling framework is being developed to address the cellular inflammation due to mechanical ventilation at the organ level. The developed multiscale modeling framework is illustrated through a case study to investigate inflammatory responses at the alveolar sac during mechanical ventilation. The simulation results showed that high tidal volume (1400 cc) during mechanical ventilation can cause tissue injury due to high concentration of activated immune cells. These results can be further extended to investigate the effects of mechanical ventilation parameters.
- [Show abstract] [Hide abstract] ABSTRACT: Airway disease such as tumours and asthma lead to lung injuries. Therefore, a better understanding of airway mechanics parameters is very important to avoid lung injuries in patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine as well as pulmonary medicine. The objective of this study was to investigate the role of airway diseases such as asthma and tumours on airway mechanics parameters using coupled fluid-solid computational analysis. The results obtained indicate that both tumours and asthma greatly affect the airway mechanics parameters (airflow velocity increased by about 15% and the strains increased by about 40%). Strain results of this study highlight significant changes in levels of airway parameters, which may translate into higher health risk associated with airway tumours and the asthmatic airways. These results combined with optimization suggest that it is possible to develop mechanical ventilation protocols to avoid lung injuries in patients.
- [Show abstract] [Hide abstract] ABSTRACT: Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS) which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.
Conference Paper: An Implantable Device Design Concept for Ocular Drug Delivery[Show abstract] [Hide abstract] ABSTRACT: New drugs for curing eye diseases have been developing for a decade and are very unique for each eye diseases such as glaucoma, cataracts, and age-related macular degeneration (AMD). It is estimated that 1.6 million adults in the US over the age of 50 and above suffer from age-related macular degeneration and about 200,000 cases are diagnosed annually. Worldwide, about 500,000 cases are diagnosed annually . Drugs currently utilized for AMD are delivered via repeated intravitreal injections of the drug into the eye. Risks of repeated intravitreal injections can include intraocular infections (endophthalmitis), intraocular hemorrhage, and retinal detachment. Also, reducing the frequency of dosing will clearly benefit the patient by reducing the need for risky intravitreal injections and improving the pharmacokinetics of the drug in the eye. The eye disease of posterior segment (Dry and Wet) has limits to deliver the drug to retina region using typical eye drop. The drug injection using a needle with syringe can deliver but it barely provide right amount of doses, or over doses that may cause more severe problem such as swelling, fatigue, and damaging photoreceptor molecules. Furthermore, most drugs run away in a month so that repeated injection is necessary. Developing an implantable drug delivery device will help reduce the costs and risks associated with frequent injections and facilitate delivering the drug in a controlled manner and in the required amounts, and improve therapeutic efficacy and safety of drugs. This study focuses on the design, simulation and development of the implantable ocular drug delivery device.
- [Show abstract] [Hide abstract] ABSTRACT: Inflammation has been recognized as a major integral component for most of the acute and chronic diseases. Inflammation can be initiated within the body as an innate process or by external factors such as infections and trauma. Inflammation is a complex and dynamic process, and involves nonlinearity and stochasticity. Without the inflammation, the harmful stimuli cannot be removed and the healing process cannot occur. However, an over-expression or under-expression of inflammatory responses can lead to severe consequences, such as Multiple Organ Dysfunction Syndrome (MODS), which is characterized by sequential organ failure. Acute lung injury (ALI) is typically one of the first manifestation of MODS. It can be triggered by external stimuli such as pathogens or from inflammatory mediators produced from various other processes ranging from other damaged organs or to blood transfusions to even the biomechanical forces of mechanical ventilation itself.
- [Show abstract] [Hide abstract] ABSTRACT: Better understanding of the acute/chronic inflammation in airways is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Local lung inflammation is triggered by many mechanisms within the lung, including pathogens. In this study, a cellular automata based model (CA) for pulmonary inflammation that incorporates biophysical processes during inflammatory responses was developed. The developed CA results in three possible outcomes related to homeostasis (healing), persistent infection, and resolved infection with high inflammation (inflamed state). The results from the model are validated qualitatively against other existing computational models. A sensitivity analysis was conducted on the model parameters and the outcomes were assessed. Overall, the model results showed possible outcomes that have been seen in clinical practice and animal models. The present model can be extended to include inflammation resulting from damage tissue and eventually to model inflammation resulting from acute lung injury and multiple organ dysfunction syndromes in critical illness and injury.
- [Show abstract] [Hide abstract] ABSTRACT: The nuclear pore complex (NPC) controls the transport of all cellular material between the cytoplasm and the nucleus that occurs naturally in biological cells of many organisms including yeast, vertebrate and others. In order to understand NPC's global motion dynamics during transport, we investigated the structural morphology changes through a computational vibrational analysis using a coarse-grained representation of the NPC. Results of various NPC global motion characteristics specifically, the cytoplasmic unit, spoke complex and nuclear basket are obtained and discussed. The present results of spoke complex octagonal structure motions were compared with experimental observations and the existing literature in order to validate the present computational model. The cytoplasmic unit and nuclear basket structural frequencies and motions also reveal their role in NPC transport. The present approach can be extended along with multi-scale mechanics to further understand the transport mechanisms of NPC.
- [Show abstract] [Hide abstract] ABSTRACT: Better understanding of airway mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine, as well as pulmonary medicine. Mechanical ventilation depends on several parameters, all of which affect the patient outcome. As there are no systematic numerical investigations of the role of mechanical ventilation parameters on airway mechanics, the objective of this study was to investigate the role of mechanical ventilation parameters on airway mechanics using coupled fluid-solid computational analysis. For the airway geometry of 3 to 5 generations considered, the simulation results showed that airflow velocity increased with increasing airflow rate. Airway pressure increased with increasing airflow rate, tidal volume and positive end-expiratory pressure (PEEP). Airway displacement and airway strains increased with increasing airflow rate, tidal volume and PEEP form mechanical ventilation. Among various waveforms considered, sine waveform provided the highest airflow velocity and airway pressure while descending waveform provided the lowest airway pressure, airway displacement and airway strains. These results combined with optimization suggest that it is possible to obtain a set of mechanical ventilation strategies to avoid lung injuries in patients.
- [Show abstract] [Hide abstract] ABSTRACT: Molecular motors are nature's nano-devices and the essential agents of movement that are an integral part of many living organisms. The supramolecular motor, called Nuclear Pore Complex (NPC), controls the transport of all cellular material between the cytoplasm and the nucleus that occurs naturally in biological cells of many organisms. In order to understand the design characteristics of the NPC, we developed a microdevice for drug/fluidic transport mimicking the coarse-grained representation of the NPC geometry through computational fluid dynamic analysis and optimization. Specifically, the role of the central plug in active fluidic/particle transport and passive transport (without central plug) was investigated. Results of flow rate, pressure and velocity profiles obtained from the models indicate that the central plug plays a major role in transport through this biomolecular machine. The results of this investigation show that fluidic transport and flow passages are important factors in designing NPC based nano- and micro-devices for drug delivery.
- [Show abstract] [Hide abstract] ABSTRACT: Corrosion is one of the most damaging mechanisms in aluminum alloys commonly used in aerospace engineering structures. Cracks usually initiate from the pits/defects, and currently, there are no measurement probes that can estimate the stress environment around corrosion pits. In this article, a systematic study is conducted to investigate the evolution of corrosion-damage-induced stresses in aluminum alloy 2024-T3 as a function of time. Corrosion experiments were conducted on a metal sample under controlled electrochemical conditions and the surfaces were imaged using AFM techniques. A computational procedure was developed to investigate the stresses resulting from corrosion damage/pits using the AFM image, CAD, and finite element analysis. Analysis was also carried out on corroded specimens under bending and tension loadings in order to see how the loading affects the induced stresses. The results indicated that the stress distribution and levels on the corroded surface varied due to irregularities and randomness in the metal sample. The results also indicated that the stress initially increases and reaches a plateau with increasing corrosion time and may be responsible for failure (crack initiation) of the metals. KeywordsAFM–aluminum alloys–finite element analysis–pit-induced corrosion–stresses
- [Show abstract] [Hide abstract] ABSTRACT: Better understanding of the stress/strain environment in airway tissues is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Airway tissue strains responsible for stressing the lung's fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. A computational model that incorporates the heterogeneity of the airways was developed to study the effects of airway tissue material properties on strain distributions within each layer of the airway wall. The geometry and boundary conditions of the tissue strain analysis were obtained from the organ-level analysis model. Two sets of airway tissue properties (heterogeneous and homogeneous) were considered in order to estimate the strain levels induced within the tissue. The simulation results showed that the homogeneous model overestimated the maximum strain in the mucosa layer and underestimated the maximum strain in the smooth muscle and cartilage layers. The results of strain levels obtained from the tissue analysis are very important because these strains at the cellular-level can create inflammatory responses, thus damaging the airway tissues.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study is to demonstrate particle separation through a novel mechanism termed as "time series alternate flow" using a microdevice as it is a real challenge to separate particles with a narrow size range (i.e., 1-10 μm or smaller), especially achieving particles separation through the hydrodynamic method without the help from additional flow or force fields. High fidelity computational fluid dynamics with particle trajectory approach was employed for simulations. Particle separation of different sizes in the range 2-10 μm size was achieved by operating the microdevice at various actuating frequencies. The results obtained indicated that the proposed mechanism is feasible for particle separation of multiple sizes. Our novel mechanism proposed potentially represents a viable microtechnological approach for particle separation in many drug delivery applications.
- [Show abstract] [Hide abstract] ABSTRACT: Micropumps with varying nozzle-diffuser geometry and actuations are being explored for many drug delivery applications. Power consumption and reliability become very critical in the realization of these micropumps. In this study, the performance of a micropump consisting of three nozzle/diffuser elements designed and fabricated from PDMS material and actuated on top by a reciprocal motor was evaluated. The performance characteristics related to the flow rate obtained from testing demonstrated the efficiency of the micropump. The results obtained illustrate the relationship between actuation frequency and fluid flow through the micropump. The effects of fluid viscosity and actuator location were also investigated and the results are presented and discussed.
Virginia Commonwealth University
Ричмонд, Virginia, United States
- Department of Mechanical and Nuclear Engineering
Indiana University-Purdue University Indianapolis
Indianapolis, Indiana, United States
- • Department of Mechanical Engineering
- • Department of Cellular and Integrative Physiology
West Lafayette, Indiana, United States
- School of Aeronautics and Astronautics