1,659 research outputs found
Integrating Experimental and Computational Approaches to Optimize 3D Bioprinting of Cancer Cells
A key feature distinguishing 3D bioprinting from other 3D cell culture techniques is its precise control over created structures. This property allows for the high-resolution fabrication of biomimetic structures with controlled structural and mechanical properties such as porosity, permeability, and stiffness. However, for bioprinting to be successful, a comprehensive understanding of cell behavior is essential, yet challenging. This includes the survivability of cells throughout the printing process, their interactions with the printed structures, and their responses to environmental cues after printing. There are numerous variables in bioprinting which influence the cell behavior, so bioprinting quality during and after the procedure. Thus, to achieve desirable results, it is necessary to consider and optimize these influential variables. So far, these optimizations have been accomplished primarily through trial and error and replicating several experiments, a procedure that is not only time-consuming but also costly. This issue motivated the development of computational techniques in the bioprinting process to more precisely predict and elucidate cells’ function within 3D printed structures during and after printing.
During printing, we developed predictive machine learning models to determine the effect of different variables such as cell type, bioink formulation, printing settings parameters, and crosslinking condition on cell viability in extrusion-based bioprinting. To do this, we first created a dataset of these parameters for gelatin and alginate-based bioinks and the corresponding cell viability by integrating data obtained in our laboratory and those derived from the literature. Then, we developed regression and classification neural networks to predict cell viability based on these bioprinting variables. Compared to models that have been developed so far, the performance of our models was superior and showed great prediction results. The study further demonstrated that among the variables investigated in bioprinting, cell type, printing pressure, and crosslinker concentration, respectively, had the most significant impact on the survival of cells.
Additionally, we introduced a new optimization strategy that employs the Bayesian optimization model based on the developed regression neural network to determine the optimal combination of the selected bioprinting parameters for maximizing cell viability and eliminating trial-and-error experiments. In our study, this strategy enabled us to identify the optimal crosslinking parameters, within a specified range, including those not previously explored, resulting in optimum cell viability. Finally, we experimentally validated the optimization model's performance.
After printing, we developed a cellular automata model for the first time to predict and elucidate the post-printing cell behavior within the 3D bioprinted construct. To improve our model, we bioprinted a 3D construct using cell-laden hydrogel and evaluated cellular functions, including viability and proliferation, in 11 days. The results showed that our model successfully simulated the 3D bioprinted structure and captured in-vitro observations. The proposed model is beneficial for demonstrating complex cellular systems, including cellular proliferation, movement, cell interactions with the environment (e.g., extracellular microenvironment and neighboring cells), and cell aggregation within the scaffold. We also demonstrated that this computational model could predict post-printing biological functions for different initial cell numbers in bioink and different bioink formulations with gelatin and alginate without replicating several in-vitro measurements.
Taken all together, this thesis introduces novel bioprinting process design strategies by presenting mathematical and computational frameworks for both during and after bioprinting. We believe such frameworks will substantially impact 3D bioprinting's future application and inspire researchers to further realize how computational methods might be utilized to advance in-vitro 3D bioprinting research
Image-based Decision Support Systems: Technical Concepts, Design Knowledge, and Applications for Sustainability
Unstructured data accounts for 80-90% of all data generated, with image data contributing its largest portion. In recent years, the field of computer vision, fueled by deep learning techniques, has made significant advances in exploiting this data to generate value. However, often computer vision models are not sufficient for value creation. In these cases, image-based decision support systems (IB-DSSs), i.e., decision support systems that rely on images and computer vision, can be used to create value by combining human and artificial intelligence. Despite its potential, there is only little work on IB-DSSs so far.
In this thesis, we develop technical foundations and design knowledge for IBDSSs and demonstrate the possible positive effect of IB-DSSs on environmental sustainability. The theoretical contributions of this work are based on and evaluated in a series of artifacts in practical use cases: First, we use technical experiments to demonstrate the feasibility of innovative approaches to exploit images for IBDSSs.
We show the feasibility of deep-learning-based computer vision and identify future research opportunities based on one of our practical use cases. Building on this, we develop and evaluate a novel approach for combining human and artificial intelligence for value creation from image data. Second, we develop design knowledge that can serve as a blueprint for future IB-DSSs. We perform two design science research studies to formulate generalizable principles for purposeful design — one for IB-DSSs and one for the subclass of image-mining-based decision support systems (IM-DSSs). While IB-DSSs can provide decision support based on single images, IM-DSSs are suitable when large amounts of image data are available and required for decision-making. Third, we demonstrate the viability of applying IBDSSs to enhance environmental sustainability by performing life cycle assessments for two practical use cases — one in which the IB-DSS enables a prolonged product lifetime and one in which the IB-DSS facilitates an improvement of manufacturing processes.
We hope this thesis will contribute to expand the use and effectiveness of imagebased decision support systems in practice and will provide directions for future research
Characterisation and State Estimation of Magnetic Soft Continuum Robots
Minimally invasive surgery has become more popular as it leads to less bleeding, scarring, pain, and shorter recovery time. However, this has come with counter-intuitive devices and steep surgeon learning curves. Magnetically actuated Soft Continuum Robots (SCR) have the potential to replace these devices, providing high dexterity together with the ability to conform to complex environments and safe human interactions without the cognitive burden for the clinician. Despite considerable progress in the past decade in their development, several challenges still plague SCR hindering their full realisation. This thesis aims at improving magnetically actuated SCR by addressing some of these challenges, such as material characterisation and modelling, and sensing feedback and localisation.
Material characterisation for SCR is essential for understanding their behaviour and designing effective modelling and simulation strategies. In this work, the material properties of commonly employed materials in magnetically actuated SCR, such as elastic modulus, hyper-elastic model parameters, and magnetic moment were determined. Additionally, the effect these parameters have on modelling and simulating these devices was investigated.
Due to the nature of magnetic actuation, localisation is of utmost importance to ensure accurate control and delivery of functionality. As such, two localisation strategies for magnetically actuated SCR were developed, one capable of estimating the full 6 degrees of freedom (DOFs) pose without any prior pose information, and another capable of accurately tracking the full 6-DOFs in real-time with positional errors lower than 4~mm. These will contribute to the development of autonomous navigation and closed-loop control of magnetically actuated SCR
Interaction of elastomechanics and fluid dynamics in the human heart : Opportunities and challenges of light coupling strategies
Das menschliche Herz ist das hochkomplexe Herzstück des kardiovaskulären Systems, das permanent, zuverlässig und autonom den Blutfluss im Körper aufrechterhält. In Computermodellen wird die Funktionalität des Herzens nachgebildet, um Simulationsstudien durchzuführen, die tiefere Einblicke in die zugrundeliegenden Phänomene ermöglichen oder die Möglichkeit bieten, relevante Parameter unter vollständig kontrollierten Bedingungen zu variieren. Angesichts der Tatsache, dass Herz-Kreislauf-Erkrankungen die häufigste Todesursache in den Ländern der westlichen Hemisphäre sind, ist ein Beitrag zur frühzeit- igen Diagnose derselben von großer klinischer Bedeutung. In diesem Zusammenhang können computergestützte Strömungssimulationen wertvolle Einblicke in die Blutflussdynamik liefern und bieten somit die Möglichkeit, einen zentralen Bereich der Physik dieses multiphysikalischen Organs zu untersuchen. Da die Verformung der Endokardoberfläche den Blutfluss antreibt, müssen die Effekte der Elastomechanik als Randbedingungen für solche Strömungssimulationen berücksichtigt werden. Um im klinischen Kontext relevant zu sein, muss jedoch ein Mittelweg zwischen dem Rechenaufwand und der erforderlichen Genauigkeit gefunden werden, und die Modelle müssen sowohl robust als auch zuverlässig sein. Daher werden in dieser Arbeit die Möglichkeiten und Herausforderungen leichter und daher weniger komplexer Kopplungsstrategien mit Schwerpunkt auf drei Schlüsselaspekten bewertet:
Erstens wird ein auf dem Immersed Boundary-Ansatz basierender Fluiddynamik-Löser implementiert, da diese Methode mit einer sehr robusten Darstellung von bewegten Netzen besticht. Die grundlegende Funktionalität wurde für verschiedene vereinfachte Geometrien verifiziert und zeigte eine hohe Übereinstimmung mit der jeweiligen analytischen Lösung. Vergleicht man die 3D-Simulation einer realistischen Geometrie des linken Teils des Herzens mit einem körperangepassten Netzbeschreibung, so wurden grundlegende globale Größen korrekt reproduziert. Allerdings zeigten Variationen der Randbedingungen einen großen Einfluss auf die Simulationsergebnisse.
Die Anwendung des Lösers zur Simulation des Einflusses von Pathologien auf die Blutströmungsmuster ergab Ergebnisse in guter Übereinstimmung mit Literaturwerten. Bei Simulationen der Mitralklappeninsuffizienz wurde der rückströmende Anteil mit Hilfe einer Partikelverfolgungsmethode visualisiert. Bei hypertropher Kardiomyopathie wurden die Strömungsmuster im linken Ventrikel mit Hilfe eines passiven Skalartransports bewertet, um die lokale Konzentration des ursprünglichen Blutvolumens zu visualisieren.
Da in den vorgenannten Studien nur ein unidirektionaler Informationsfluss vom elas- tomechanischen Modell zum Strömungslöser berücksichtigt wurde, wird die Rückwirkung des räumlich aufgelösten Druckfeldes aus den Strömungssimulationen auf die Elastomechanik quantifiziert. Es wird ein sequenzieller Kopplungsansatz eingeführt, um fluiddynamische Einflüsse in einer Schlag-für-Schlag-Kopplungsstruktur zu berücksichtigen. Die geringen Abweichungen im mechanischen Solver von 2 mm verschwanden bereits nach einer Iteration, was darauf schließen lässt, dass die Rückwirkungen der Fluiddynamik im gesunden Herzen begrenzt ist.
Zusammenfassend lässt sich sagen, dass insbesondere bei Strömungsdynamiksimula- tionen die Randbedingungen mit Vorsicht gewählt werden müssen, da sie aufgrund ihres großen Einflusses die Anfälligkeit der Modelle erhöhen. Nichtsdestotrotz zeigten verein- fachte Kopplungsstrategien vielversprechende Ergebnisse bei der Reproduktion globaler fluiddynamischer Größen, während die Abhängigkeit zwischen den Lösern reduziert und Rechenaufwand eingespart wird
Beam scanning by liquid-crystal biasing in a modified SIW structure
A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium
Study of neural circuits using multielectrode arrays in movement disorders
Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Rodríguez Allué, Manuel JoséNeurodegenerative movement-related disorders are characterized by a progressive degeneration and loss of neurons, which lead to motor control impairment. Although the precise mechanisms underlying these conditions are still unknown, an increasing number of studies point towards the analysis of neural networks and functional connectivity to unravel novel insights. The main objective of this work is to understand cellular mechanisms related to dysregulated motor control symptoms in movement disorders, such as Chorea-Acanthocytosis (ChAc), by employing multielectrode arrays to analyze the electrical activity of neuronal networks in mouse models. We found no notable differences in cell viability between neurons with and without VPS13A knockdown, that is the only gene known to be implicated in the disease, suggesting that the absence of VPS13A in neurons may be partially compensated by other proteins. The MEA setup used to capture the electrical activity from neuron primary cultures is described in detail, pointing out its specific characteristics. At last, we present the alternative backup approach implemented to overcome the challenges faced during the research process and to explore the advanced algorithms for signal processing and analysis.
In this report, we present a thorough account of the conception and implementation of our research, outlining the multiple limitations that have been encountered all along the course of the project. We provide a detailed analysis on the project’s economical and technical feasibility, as well as a comprehensive overview of the ethical and legal aspects considered during the execution
Is attention all you need in medical image analysis? A review
Medical imaging is a key component in clinical diagnosis, treatment planning
and clinical trial design, accounting for almost 90% of all healthcare data.
CNNs achieved performance gains in medical image analysis (MIA) over the last
years. CNNs can efficiently model local pixel interactions and be trained on
small-scale MI data. The main disadvantage of typical CNN models is that they
ignore global pixel relationships within images, which limits their
generalisation ability to understand out-of-distribution data with different
'global' information. The recent progress of Artificial Intelligence gave rise
to Transformers, which can learn global relationships from data. However, full
Transformer models need to be trained on large-scale data and involve
tremendous computational complexity. Attention and Transformer compartments
(Transf/Attention) which can well maintain properties for modelling global
relationships, have been proposed as lighter alternatives of full Transformers.
Recently, there is an increasing trend to co-pollinate complementary
local-global properties from CNN and Transf/Attention architectures, which led
to a new era of hybrid models. The past years have witnessed substantial growth
in hybrid CNN-Transf/Attention models across diverse MIA problems. In this
systematic review, we survey existing hybrid CNN-Transf/Attention models,
review and unravel key architectural designs, analyse breakthroughs, and
evaluate current and future opportunities as well as challenges. We also
introduced a comprehensive analysis framework on generalisation opportunities
of scientific and clinical impact, based on which new data-driven domain
generalisation and adaptation methods can be stimulated
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