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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Multiscale Modelling of Proximal Femur Growth : Importance of Geometry and Influence of Load

Yadav, Priti January 2017 (has links)
Longitudinal growth of long bone occurs at growth plates by a process called endochondral ossification. Endochondral ossification is affected by both biological and mechanical factors. This thesis focuses on the mechanical modulation of femoral bone growth occurring at the proximal growth plate, using mechanobiological theories reported in the literature. Finite element analysis was used to simulate bone growth. The first study analyzed the effect of subject-specific growth plate geometry over simplified growth plate geometry in numerical prediction of bone growth tendency. Subject-specific femur finite element model was constructed from magnetic resonance images of one able- bodied child. Gait kinematics and kinetics were acquired from motion analysis and analyzed further in musculoskeletal modelling to determine muscle and joint contact forces. These were used to determine loading on the femur in finite element analysis. The growth rate was computed based on a mechanobiological theory proposed by Carter and Wong, and a growth model in the principal stress direction was introduced. Our findings support the use of subject- specific geometry and of the principal stress growth direction in prediction of bone growth. The second study aimed to illustrate how different muscle groups’ activation during gait affects proximal femoral growth tendency in able-bodied children. Subject-specific femur models were used. Gait kinematics and kinetics were acquired for 3 able-bodied children, and muscle and joint contact forces were determined, similar to the first study. The contribution of different muscle groups to hip contact force was also determined. Finite element analysis was performed to compute the specific growth rate and growth direction due to individual muscle groups. The simulated growth model indicated that gait loading tends to reduce neck shaft angle and femoral anteversion during growth. The muscle groups that contributes most and least to growth rate were hip abductors and hip adductors, respectively. All muscle groups’ activation tended to reduce the neck shaft and femoral anteversion angles, except hip extensors and adductors which showed a tendency to increase the femoral anteversion. The third study’s aim was to understand the influence of different physical activities on proximal femoral growth tendency. Hip contact force orientation was varied to represent reported forces from a number of physical activities. The findings of this study showed that all studied physical activities tend to reduce the neck shaft angle and anteversion, which corresponds to the femur’s natural course during normal growth. The aim of the fourth study was to study the hypothesis that loading in the absence of physical activity, i.e. static loading, can have an adverse effect on bone growth. A subject-specific model was used and growth plate was modeled as a poroelastic material in finite element analysis. Prendergast’s indicators for bone growth was used to analyse the bone growth behavior. The results showed that tendency of bone growth rate decreases over a long duration of static loading. The study also showed that static sitting is less detrimental than static standing for predicted cartilage-to-bone differentiation likelihood, due to the lower magnitude of hip contact force. The prediction of growth using finite element analysis on experimental gait data and person- specific femur geometry, based on mechanobiological theories of bone growth, offers a biomechanical foundation for better understanding and prediction of bone growth-related deformity problems in growing children. It can ultimately help in treatment planning or physical activity guidelines in children at risk at developing a femur or hip deformity. / <p>QC 20170616</p>
22

Finite Element and Neuroimaging Techniques toImprove Decision-Making in Clinical Neuroscience

Li, Xiaogai January 2012 (has links)
Our brain, perhaps the most sophisticated and mysterious part of the human body, to some extent, determines who we are. However, it’s a vulnerable organ. When subjected to an impact, such as a traffic accident or sport, it may lead to traumatic brain injury (TBI) which can have devastating effects for those who suffer the injury. Despite lots of efforts have been put into primary injury prevention, the number of TBIs is still on an unacceptable high level in a global perspective. Brain edema is a major neurological complication of moderate and severe TBI, which consists of an abnormal accumulation of fluid within the brain parenchyma. Clinically, local and minor edema may be treated conservatively only by observation, where the treatment of choice usually follows evidence-based practice. In the first study, the gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue. Thus, the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a Finite Element (FE) model. The model revealed that water content (WC) increment at the edema zone remained nearly identical for both supine and prone positions. However, the interstitial fluid pressure (IFP) inside the edema zone decreased around 15% by having the head in a prone position compared with a supine position. The decrease of IFP inside the edema zone by changing patient position from supine to prone has the potential to alleviate the damage to axonal fibers of the central nervous system. These observations suggest that considering the patient’s head position during intensive care and at rehabilitation should be of importance to the treatment of edematous regions in TBI patients. In TBI patients with diffuse brain edema, for most severe cases with refractory intracranial hypertension, decompressive craniotomy (DC) is performed as an ultimate therapy. However, a complete consensus on its effectiveness has not been achieved due to the high levels of severe disability and persistent vegetative state found in the patients treated with DC. DC allows expansion of the swollen brain outside the skull, thereby having the potential in reducing the Intracranial Pressure (ICP). However, the treatment causes stretching of the axons and may contribute to the unfavorable outcome of the patients. The second study aimed at quantifying the stretching and WC in the brain tissue due to the neurosurgical intervention to provide more insight into the effects upon such a treatment. A nonlinear registration method was used to quantify the strain. Our analysis showed a substantial increase of the strain level in the brain tissue close to the treated side of DC compared to before the treatment. Also, the WC was related to specific gravity (SG), which in turn was related to the Hounsfield unit (HU) value in the Computerized Tomography (CT) images by a photoelectric correction according to the chemical composition of the brain tissue. The overall WC of brain tissue presented a significant increase after the treatment compared to the condition seen before the treatment. It is suggested that a quantitative model, which characterizes the stretching and WC of the brain tissue both before as well as after DC, may clarify some of the potential problems with such a treatment. Diffusion Weighted (DW) Imaging technology provides a noninvasive way to extract axonal fiber tracts in the brain. The aim of the third study, as an extension to the second study was to assess and quantify the axonal deformation (i.e. stretching and shearing)at both the pre- and post-craniotomy periods in order to provide more insight into the mechanical effects on the axonal fibers due to DC. Subarachnoid injection of artificial cerebrospinal fluid (CSF) into the CSF system is widely used in neurological practice to gain information on CSF dynamics. Mathematical models are important for a better understanding of the underlying mechanisms. Despite the critical importance of the parameters for accurate modeling, there is a substantial variation in the poroelastic constants used in the literature due to the difficulties in determining material properties of brain tissue. In the fourth study, we developed a Finite Element (FE) model including the whole brain-CSF-skull system to study the CSF dynamics during constant-rate infusion. We investigated the capacity of the current model to predict the steady state of the mean ICP. For transient analysis, rather than accurately fit the infusion curve to the experimental data, we placed more emphasis on studying the influences of each of the poroelastic parameters due to the aforementioned inconsistency in the poroelastic constants for brain tissue. It was found that the value of the specific storage term S_epsilon is the dominant factor that influences the infusion curve, and the drained Young’s modulus E was identified as the dominant parameter second to S_epsilon. Based on the simulated infusion curves from the FE model, Artificial Neural Network (ANN) was used to find an optimized parameter set that best fit the experimental curve. The infusion curves from both the FE simulations and using ANN confirmed the limitation of linear poroelasticity in modeling the transient constant-rate infusion. To summarize, the work done in this thesis is to introduce FE Modeling and imaging technologiesincluding CT, DW imaging, and image registration method as a complementarytechnique for clinical diagnosis and treatment of TBI patients. Hopefully, the result mayto some extent improve the understanding of these clinical problems and improve theirmedical treatments. / QC 20120201
23

Coupled flow and geomechanics modeling for fractured poroelastic reservoirs

Singh, Gurpreet, 1984- 16 February 2015 (has links)
Tight gas and shale oil play an important role in energy security and in meeting an increasing energy demand. Hydraulic fracturing is a widely used technology for recovering these resources. The design and evaluation of hydraulic fracture operation is critical for efficient production from tight gas and shale plays. The efficiency of fracturing jobs depends on the interaction between hydraulic (induced) and naturally occurring discrete fractures. In this work, a coupled reservoir-fracture flow model is described which accounts for varying reservoir geometries and complexities including non-planar fractures. Different flow models such as Darcy flow and Reynold's lubrication equation for fractures and reservoir, respectively are utilized to capture flow physics accurately. Furthermore, the geomechanics effects have been included by considering a multiphase Biot's model. An accurate modeling of solid deformations necessitates a better estimation of fluid pressure inside the fracture. The fractures and reservoir are modeled explicitly allowing accurate representation of contrasting physical descriptions associated with each of the two. The approach presented here is in contrast with existing averaging approaches such as dual and discrete-dual porosity models where the effects of fractures are averaged out. A fracture connected to an injection well shows significant width variations as compared to natural fractures where these changes are negligible. The capillary pressure contrast between the fracture and the reservoir is accounted for by utilizing different capillary pressure curves for the two features. Additionally, a quantitative assessment of hydraulic fracturing jobs relies upon accurate predictions of fracture growth during slick water injection for single and multistage fracturing scenarios. It is also important to consistently model the underlying physical processes from hydraulic fracturing to long-term production. A recently introduced thermodynamically consistent phase-field approach for pressurized fractures in porous medium is utilized which captures several characteristic features of crack propagation such as joining, branching and non-planar propagation in heterogeneous porous media. The phase-field approach captures both the fracture-width evolution and the fracture-length propagation. In this work, the phase-field fracture propagation model is briefly discussed followed by a technique for coupling this to a fractured poroelastic reservoir simulator. We also present a general compositional formulation using multipoint flux mixed finite element (MFMFE) method on general hexahedral grids with a future prospect of treating energized fractures. The mixed finite element framework allows for local mass conservation, accurate flux approximation and a more general treatment of boundary conditions. The multipoint flux inherent in MFMFE scheme allows the usage of a full permeability tensor. An accurate treatment of diffusive/dispersive fluxes owing to additional velocity degrees of freedom is also presented. The applications areas of interest include gas flooding, CO₂ sequestration, contaminant removal and groundwater remediation. / text
24

Efficient finite element approach for structural-acoustic applicationns including 3D modelling of sound absorbing porous materials

Rumpler, Romain 13 March 2012 (has links) (PDF)
In the context of interior noise reduction, the present work aims at proposing Finite Element (FE) solution strategies for interior structural-acoustic applications including 3D modelling of homogeneous and isotropic poroelastic materials, under timeharmonic excitations, and in the low frequency range. A model based on the Biot-Allard theory is used for the poroelastic materials, which is known to be very costly in terms of computational resources. Reduced models offer the possibility to enhance the resolution of such complex problems. However, their applicability to porous materials remained to be demonstrated.First, this thesis presents FE resolutions of poro-elasto-acoustic coupled problems using modal-based approaches both for the acoustic and porous domains. The original modal approach proposed for porous media, together with a dedicated mode selection and truncation procedure, are validated on 1D to 3D applications.In a second part, modal-reduced models are combined with a Padé approximants reconstruction scheme in order to further improve the efficiency.A concluding chapter presents a comparison and a combination of the proposed methods on a 3D academic application, showing promising performances. Conclusions are then drawn to provide indications for future research and tests to be conducted in order to further enhance the methodologies proposed in this thesis.
25

Analysis and control of elastic waves in phononic structures of poroelastic inclusions in a fluid / Analyse et contrôle des ondes élastiques dans une structure phononique constituée d’inclusions poroélastiques dans un fluide.

Alevizaki, Athina 28 September 2018 (has links)
Dans le présent document de thèse, une extension de la méthode de calcul de la diffusion multiple stratifiée est développée en y incluant des structures phononiques à base de diffuseurs sphériques poroélastiques saturés immergés dans un fluide, en combinant la théorie de Biot avec le formalisme de diffusion multiple. La méthode est alors appliquée à une étude théorique, bien au-delà de l’approximation à grandes longueurs d’onde d’un milieu effectif, de la réponse acoustique d’un milieu granulaire à double porosité saturé, formé d’un réseau cristallin compact de sphères poreuses rigides ou molles. On montre que la variation de la taille des pores et/ou celle de la porosité dans une gamme allant du millimètre au micromètre pour le diamètre des sphères altère d’une façon significative les spectres de transmission, réflexion, et d’absorption d’une couche plane d’épaisseur finie de ces matériaux. Les spectres présentés sont analysés par référence aux modes acoustiques de sphères poreuses isolées d’une part, puis par rapport aux diagrammes de dispersion des cristaux infinis correspondants. Une interprétation cohérente de la physique sous-jacente est donnée. Ces résultats mettent en évidence l’occurrence de nouveaux modes, localisés dans la sphère, provenant des ondes longitudinales lentes propres aux milieux poroélastiques. Ces modes induisent quelques caractéristiques remarquables dans le comportement acoustique de ces matériaux à double porosité, comme des bandes d’absorption non-dispersive larges ou étroites en fréquence et/ou des bandes d’arrêt directionnel. Les propriétés acoustiques de ces structures phononiques à l’échelle sub-micrométrique, i.e. en régime hypersonique (GHz), peuvent être évaluées expérimentalement par diffusion Brillouin. Dans ce document, une approche théorique élasto-optique rigoureuse, basée sur les fonctions de Green, est proposée afin de décrire la diffusion inélastique de la lumière due aux variations spatiotemporelles de l’indice de réfraction du matériau induites par des phonons. Dans ce cadre des expressions analytiques de l’intensité d’un faisceau de lumière diffusé par une particule sphérique dans le vide sont dérivées, permettant ainsi d’améliorer la précision et rapidité des calculs précédents. Les grandes lignes de ce développement théorique jettent les bases pour une description rigoureuse de cet effet dans le cas de cristaux phononiques composés de particules sphériques colloïdales. / In the present thesis, an extension of the layer multiple scattering computational methodology to phononic structures of fluid-saturated poroelastic spherical bodies, combining Biot's theory with multiple scattering techniques, is developed. The method is applied to the theoretical study, beyond the long wavelength effective-medium approximation, of the acoustic response of double-porosity liquid-saturated granular materials consisting of close-packed hard or soft porous spheres. It is shown that variations of the pore size and/or the porosity within the millimeter and submillimeter-sized spherical grains signicantly alters the transmission, reflection, and absorption spectra of finite slabs of these materials. The calculated spectra are analyzed by reference to the acoustic modes of the constituent porous spherical grains as well as to relevant dispersion diagrams of correspondingly infinite crystals, and a consistent interpretation of the underlying physics is presented. Our results provide evidence for the occurrence of novel, unprecedented modes, localized in the sphere, which arise from slow longitudinal waves that are peculiar to poroelastic media. These modes induce some remarkable features in the acoustic behavior of these double-porosity materials under study, such as broad or narrow dispersionless absorption bands and/or directional transmission gaps. The acoustic properties of phononic (sub)micro structures, in the hypersonic (GHz) regime, can be probed, in general, by Brillouin light scattering experiments. In the present thesis we undertake a rigorous full elasto-optic theoretical approach to inelastic light scattering due to phonon induced spatiotemporal variations of the refractive index of a medium, based on Green's functions, and derive analytical expressions for the intensities of the scattered light beams by single spherical particles in vacuum, thus improving the computational efficiency and accuracy of previous calculations. The above framework provides, also, the basis for a rigorous description of the effect for phononic crystals of colloidal spherical particles.
26

On multilayered system dynamics and waves in anisotropic poroelastic media

Parra Martinez, Juan Pablo January 2016 (has links)
The mechanical and acoustic anisotropy of media is a governing factor in the behaviour of multilayered systems including such media. The understanding of the mechanisms conditioning the dynamic behaviour of multilayered systems is of paramount importance. In particular, the intrinsic anisotropy of poroelastic media presents a potential for the optimal design of systems for multifunctional performances. Indeed, these multilayered systems are bound by stiffness, thermal and acoustic performance constraints in simultaneously. A plane wave method is presented to study the influence of material orientation in the dynamic behaviour of multilayered systems composed of anisotropic poroelastic media. The method is applied to a system composed of an anisotropic open-celled melamine foam core in between two metal sheets. This particular multilayered configuration allows to shed light on phenomena intrinsic to layers composed of anisotropic poroelastic materials, such as the frequency shift of the fundamental resonance of the panel, or the compression-shear coupling effects taking place in the poroelastic core layers. The latter phenomena is of particular importance, as it is evidenced on the unconventional polarisation of waves in anisotropic poroelastic media. Finally, the method is adapted to the optimisation of multilayered systems for acoustic performance. the design variables are consequently the core material orientations with respect to the global coordinate system. The solutions to the optimisation problem are analysed in terms of dynamic behaviour, thus allowing to correlate acoustic performance of the overall structure, and the response of each individual layer. / <p>QC 20161110</p>
27

Efficient Finite Element Approach for Structural-Acoustic Applications including 3D modelling of Sound Absorbing Porous Materials

Rumpler, Romain January 2012 (has links)
In the context of interior noise reduction, the present work aims at proposing Finite Element (FE) solution strategies for interior structural-acoustic applications including 3D modelling of homogeneous and isotropic poroelastic materials, under timeharmonic excitations, and in the low frequency range. A model based on the Biot-Allard theory is used for the poroelastic materials, which is known to be very costly in terms of computational resources. Reduced models offer the possibility to enhance the resolution of such complex problems. However, their applicability to porous materials remained to be demonstrated.First, this thesis presents FE resolutions of poro-elasto-acoustic coupled problems using modal-based approaches both for the acoustic and porous domains. The original modal approach proposed for porous media, together with a dedicated mode selection and truncation procedure, are validated on 1D to 3D applications.In a second part, modal-reduced models are combined with a Padé approximants reconstruction scheme in order to further improve the efficiency.A concluding chapter presents a comparison and a combination of the proposed methods on a 3D academic application, showing promising performances. Conclusions are then drawn to provide indications for future research and tests to be conducted in order to further enhance the methodologies proposed in this thesis. / Dans le contexte de lutte contre les nuisances sonores, cette thèse porte sur le développement de méthodes de résolution efficaces par éléments finis, pour des problèmes de vibroacoustique interne avec interfaces dissipatives, dans le domaine des basses fréquences. L’étude se limite à l’utilisation de solutions passives telles que l’intégration de matériaux poreux homogènes et isotropes, modélisés par une approche fondée sur la théorie de Biot-Allard. Ces modèles étant coûteux en terme de résolution, un des objectifs de cette thèse est de proposer une approche modale pour la réduction du problème poroélastique, bien que l’adéquation d’une telle approche avec le comportement dynamique des matériaux poreux soit à démontrer.Dans un premier temps, la résolution de problèmes couplés élasto-poro-acoustiques par sous-structuration dynamique des domaines acoustiques et poreux est établie. L’approche modale originale proposée pour les milieux poroélastiques, ainsi qu’une procédure de sélection des modes significatifs, sont validées sur des exemples 1D à 3D.Une deuxième partie présente une méthode combinant l’utilisation des modèles réduits précédemment établis avec une procédure d’approximation de solution par approximants de Padé. Il est montré qu’une telle combinaison offre la possibilité d’accroître les performances de la résolution (allocation mémoire et ressources en temps de calcul).Un chapitre dédié aux applications permet d’évaluer et comparer les approches sur un problème académique 3D, mettant en valeur leurs performances encourageantes. Afin d’améliorer les méthodes établies dans cette thèse, des perspectives à ces travaux de recherche sont apportées en conclusion. / <p>QC 20120224</p> / FP6 Marie-Curie Smart Structures / FP7 Marie-Curie Mid-Frequency
28

Efficient finite element approach for structural-acoustic applicationns including 3D modelling of sound absorbing porous materials / Modélisation de problèmes de vibro-acoustique interne avec traitement poroélastique : approche efficace par la méthode des éléments finis

Rumpler, Romain 13 March 2012 (has links)
Dans le contexte de lutte contre les nuisances sonores, cette thèse porte sur le développement de méthodes de résolution efficaces par éléments finis, pour des problèmes de vibroacoustique interne avec interfaces dissipatives, dans le domaine des basses fréquences. L’étude se limite à l’utilisation de solutions passives telles que l’intégration de matériaux poreux homogènes et isotropes, modélisés par une approche fondée sur la théorie de Biot-Allard. Ces modèles étant coûteux en terme de résolution, un des objectifs de cette thèse est de proposer une approche modale pour la réduction du problème poroélastique, bien que l’adéquation d’une telle approche avec le comportement dynamique des matériaux poreux soit à démontrer. Dans un premier temps, la résolution de problèmes couplés élasto-poro-acoustiques par sous-structuration dynamique des domaines acoustiques et poreux est établie. L’approche modale originale proposée pour les milieux poroélastiques, ainsi qu’une procédure de sélection des modes significatifs, sont validées sur des exemples 1D à 3D. Une deuxième partie présente une méthode combinant l’utilisation des modèles réduits précédemment établis avec une procédure d’approximation de solution par approximants de Padé. Il est montré qu’une telle combinaison offre la possibilité d’accroître les performances de la résolution (allocation mémoire et ressources en temps de calcul). Un chapitre dédié aux applications permet d’évaluer et comparer les approches sur un problème académique 3D, mettant en valeur leurs performances encourageantes. Afin d’améliorer les méthodes établies dans cette thèse, des perspectives à ces travaux de recherche sont apportées en conclusion. / In the context of interior noise reduction, the present work aims at proposing Finite Element (FE) solution strategies for interior structural-acoustic applications including 3D modelling of homogeneous and isotropic poroelastic materials, under timeharmonic excitations, and in the low frequency range. A model based on the Biot-Allard theory is used for the poroelastic materials, which is known to be very costly in terms of computational resources. Reduced models offer the possibility to enhance the resolution of such complex problems. However, their applicability to porous materials remained to be demonstrated.First, this thesis presents FE resolutions of poro-elasto-acoustic coupled problems using modal-based approaches both for the acoustic and porous domains. The original modal approach proposed for porous media, together with a dedicated mode selection and truncation procedure, are validated on 1D to 3D applications.In a second part, modal-reduced models are combined with a Padé approximants reconstruction scheme in order to further improve the efficiency.A concluding chapter presents a comparison and a combination of the proposed methods on a 3D academic application, showing promising performances. Conclusions are then drawn to provide indications for future research and tests to be conducted in order to further enhance the methodologies proposed in this thesis.
29

Transport and lymphatic uptake of monoclonal antibodies after subcutaneous injection

Ehsan Rahimi (11892065) 02 August 2023 (has links)
<p>The subcutaneous injection has emerged as a common approach for self-administration of biotherapeutics due to the patient comfort and cost-effectiveness. However, the available knowledge about transport and absorption of these agents after subcutaneous injection is limited. Here we aim to find drug distribution in the tissue and lymphatic uptake after subcutaneous (SC) injection. In the first part of the study, a mathematical framework to study the subcutaneous drug delivery from injection to lymphatic uptake is presented. A three-dimensional poroelastic model is exploited to find the biomechanical response of the tissue by taking into account tissue deformation during the injection. The results show that including tissue deformability noticeably changes tissue poromechanical response due to the significant dependence of interstitial pressure on tissue deformation. Moreover, the importance of the amount of lymph fluid at the injection site and injection rate on the drug uptake to lymphatic capillaries is highlighted. Finally, the variability of lymphatic uptake due to uncertainty in parameters, including tissue poromechanical and lymphatic absorption parameters, is evaluated. It is found that interstitial pressure due to injection is the major contributing factor in short-term lymphatic absorption, while the amount of lymph fluid at the site of injection determines the long-term absorption of the drug. Finally, it is shown that the lymphatic uptake results are consistent with experimental data available in the literature.</p><p>In the second part, drug transport and distribution in different tissue layers are studied. A single-layer model of the tissue as a base study was first explored. During injection, the difference between the permeability of the solvent and solute results in a higher drug concentration proportional to the inverse of the permeability ratio. Then the effects of layered tissue properties with primary layers, including epidermis, dermis, subcutaneous, and muscle layers, on tissue biomechanical response to injection and drug transport are studied. The drug distributes mainly in the SQ layer due to its lower elastic moduli. Finally, the effect of secondary tissue elements like the deep fascia layer and the network of septa fibers inside the SQ tissue is investigated. The Voronoi algorithm is exploited to create random geometry of the septa network. It is shown how drug molecules accumulate around these tissue components as observed in experimental SC injection. Next, the effect of injection rate on drug concentration is studied. Higher injection rates slightly increase the drug concentration around septa fibers. Finally, it is demonstrated that the concentration-dependent viscosity increases the concentration of biotherapeutics in the direction of septa fibers.</p><p>In the third part of this thesis, a poro-hyperelastic model of the tissue is exploited to find the biomechanical response of the tissue together with a transport model based on an advection-diffusion equation in large-deformation poro-hyperelastic Media. The process of mAbs transport to the lymphatic system is explored. This process has two major parts. First, the initial phase, where mAbs are dispersed in the tissue as a result of momentum exerted by injection. This stage last for only a few minutes after the injection. Then there is the second stage, which can take tens of hours, and as a result, monoclonal antibodies (mAbs) molecules are transported from the subcutaneous layer towards initial lymphatics in the dermis to enter the lymphatic system. In third chapter, both stages are studied. The process of plume formation, interstitial pressure, and velocity development is explored. Then the effect of the injection device, injection site, and sensitivity of long-term lymphatic uptake due to variability in permeability, diffusivity, viscosity, and binding of mAbs are investigated. Then the results are used to find an equivalent lymphatic uptake coefficient that is widely used in pharmacokinetic (PK) models to study the absorption of mAbs. We show that the injection rate is the least, and the injection site is the most important parameter in the uptake of mAbs. Injection depth and mAbs dose also significantly alter lymphatic absorption. Finally, the computational model is validated against experimental studies available in the literature.</p>

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