1,720,966 research outputs found
DEVELOPMENT OF MEASUREMENT METHODOLOGIES IN METROLOGY FOR CELL BIOLOGY AND REGENERATIVE MEDICINE
Get PDFAim of this thesis is the development of measurement methodologies in metrology for cell biology and regenerative medicine. Regenerative medicine is a novel branch of medicine based on the use of autologous stem cells and biocompatible medical devices to regenerate and repair damaged tissues of patients, i.e. by using three-dimensional scaffolds to implant stem cells into the tissue to be regenerated. Stakeholders of metrology for regenerative medicine are: health care providers who require safe, reliable and cost effective treatments, supported by evidence and approved by regulators; regulators who require standard materials and traceable data demonstrating the safety and efficacy of new products and treatments; medical products companies who require advanced and traceable techniques to develop new products and need methods to measure processes, such as cell growth on scaffolds, to ensure quality and efficiency of the medical products implanted into the patients. Consequently, regenerative medicine has the important requisite of a real time monitoring and not invasiveness neither destructiveness processes to measure the cell-scaffold interactions, in order to preserve the samples from any contamination or modification. Thus non-invasive measurement methodologies need to be developed for analysing the 3D cell culture on scaffolds and, in order to evaluate the uncertainty, highly reproducible measurement procedures are strongly required to minimize the type A uncertainties and to define the type B uncertainties. The non-invasive and non-destructive measurement of cell-scaffold interactions (i.e. stem cell proliferation and differentiation on scaffolds) is one of the most effective methodology to answer the need of testing the efficacy of the design, production/manufacturing, development and performances of stem cell-scaffold products. To satisfy the requirements and the needs for metrology in regenerative medicine, for this thesis it has been chosen to develop a measurement methodology for cellular activity (proliferation and differentiation) on 3D Biocoral® scaffolds and to conduce a metrological study to evaluate the uncertainty of the methodology. This thesis has been developed in the Bioscience group of the Italian National Metrological Institute (Istituto Nazionale di Ricerca Metrologica - INRIM). The main important contributes of this thesis to the metrology in biosciences have been: • to lay the foundations for a metrological approach to cell biology and particularly to regenerative medicine research and applications; • to address the filling of the lack of traceability in the metrology for cell biology metabolic methodologies used to evaluate cellular activities in living sample with non-invasive procedures. The main results and originalities achieved during this PhD work are: • a metabolic assay, the resazurin/resorufin assay, for the first time, has been metrologically characterized and the uncertainty of the measurement has been evaluated; • the resazurin/resorufin assay has been for the first time tailored for a 3D cell culture on Biocoral® scaffolds and the uncertainty of the measurement has been evaluated; • it was demonstrated that Biocoral® induces osteodifferentiation of stem cells and for the first time it was demonstrated on human mesenchymal stem cells; • it was demonstrated, for the first time, that the resazurin/resorufin metabolic assay can be a methodology to detect not only the proliferation but also the differentiation of stem cells on Biocoral® scaffolds; A description of the METREGEN regional project, which this thesis is part of, will follow in the introduction. The chapter 1 will give an overview on regenerative medicine field and its application with scaffolds, particularly referring to the Biocoral® scaffold. The resazurin/resorufin methodology will be deeply described in chapter 2 with a uncertainty budget evaluation and discussion. Chapter 3 will present in details a series of experiments made to establish and characterize a hMSCs in vitro 2D culture, establish a hMSCs in vitro 3D culture on Biocoral, tailor the resazurin/resorufin assay for 3D cell culture on Biocoral and evaluate the hMSCs osteodifferentiation induced by Biocoral scaffolds. All the results have been analysed with a metrological approach to evaluate the uncertainty. Finally, the conclusion will give a recapitulation and some interesting perspective of employment for the resazurin/resorufin methodology to final users, such as the cell factorie
Orthogonal-Array based Design Methodology for Complex, Coupled Space Systems
Get PDFThe process of designing a complex system, formed by many elements and sub-elements interacting between each other, is usually completed at a system level and in the preliminary phases in two major steps: design-space exploration and optimization. In a classical approach, especially in a company environment, the two steps are usually performed together, by experts of the field inferring on major phenomena, making assumptions and doing some trial-and-error runs on the available mathematical models. To support designers and decision makers during the design phases of this kind of complex systems, and to enable early discovery of emergent behaviours arising from interactions between the various elements being designed, the authors implemented a parametric methodology for the design-space exploration and optimization. The parametric technique is based on the utilization of a particular type of matrix design of experiments, the orthogonal arrays. Through successive design iterations with orthogonal arrays, the optimal solution is reached with a reduced effort if compared to more computationally-intense techniques, providing sensitivity and robustness information. The paper describes the design methodology in detail providing an application example that is the design of a human mission to support a lunar base
GENERAL METHODOLOGY FOR DEMONSTRATION MISSION DESIGN
No full textFuture human exploration programs point towards new and more challenging objectives. The exploration of Moon and Mars requires new technologies that shall be developed to have them available in the future. These technologies shall complete demonstration missions in space environment in order to be considered flight qualified. The paper deals with the description of the methodology for the design of the demonstration missions. First the technologies to be tested are selected and for them the TRL is assessed according to the European standards. Then, all the activities necessary to increase the TRL, including analysis, experiments, breadboard/prototype development and tests are identified and planned. The demonstration mission design activity starts after the performance requirements for the technologies are defined. Then, the set of possible mission scenario options is defined and the trade-off activity is performed to choose the most cost-effective solution. The trade-offs are performed considering mass, cost, design complexity and risk level indexes. Finally, the detailed description of the demonstration mission(s) is provided through a complete set of requirement
Applied design methodology for lunar rover elastic wheel
No full textIn recent years an increasing interest in the Moon surface operations has been experienced. In the future robotic and manned missions of Moon surface exploration will be fundamental in order to lay the groundwork for more ambitious space exploration programs. Surface mobility systems will be the key elements to ensure an efficient and safe Moon exploration. Future lunar rovers are likely to be heavier and able to travel longer distances than the previously developed Moon rover systems. The Lunar Roving Vehicle (LRV) is the only manned rover, which has so far been launched and used on the Moon surface. Its mobility system included flexible wheels that cannot be scaled to the heavier and longer range vehicles. Thus the previously developed wheels are likely not to be suitable for the new larger vehicles. Taking all these considerations into account, on the basis of the system requirements and assumptions, several wheel concepts have been discussed and evaluated through a trade-off analysis. Semi-empirical equations have been utilized to predict the wheel geometrical characteristics, as well as to estimate the motion resistances and the ability of the system to generate thrust. A numerical model has also been implemented, in order to define more into the details the whole wheel design, in terms of wheel geometry and physical properties. As a result of the trade-off analysis, the ellipse wheel concept has shown the best behavior in terms of stiffness, mass budget and dynamic performance. The results presented in the paper have been obtained in cooperation with Thales Alenia Space-Italy and Sicme motori, in the framework of a regional program called STEP
SET, A SCENARIO EVALUATOR TOOL FOR SUPPORTING SPACE-EXPLORATION MISSION-ARCHITECTURE DESIGN
Get PDFThe design of space-exploration missions begins with a mission statement that defines the ultimate goals of the mission itself. The mission-architecture defines, instead, how the mission will work in practice, and encompasses all the elements that will take part in it. It includes such issues as the synergies of manned and robotic resources, mission control, and the mission timeline. The mission-architecture design activity is an iterative process in general aimed at the maximization of the cost effectiveness (or value) of the mission and minimization of costs. This is performed by successive comparisons and evaluation of the alternative generated mission architectures. The Scenario Evaluator Tool (SET) is conceived to support the engineering team in the framework of the space mission design process. In particular, SET is a simulation software tool that allows building mission architectures with a significant reduction of development time and computational effort. The software allows the characterization, the comparison, and optimization of exploration scenarios and building blocks through a user friendly graphical interface. Each mission-architecture is characterized and evaluated on the basis of the mass budget of the building blocks, cost index and exploration capabilities. SET is general enough to allow the design of several space exploration scenarios for Gap-analysis studies (flexibility). Further, it allows the users to introduce new model libraries (expandability). This paper describes the main features and the potentialities of the simulation software. To show the working principle of SET, a hypothetical human space-exploration mission scenario has been developed and implemented. The results has been accomplished in the framework of STEPS (Systems and Technologies for the ExPloration of Space), which is a research project co-financed by Piedmont Region (Italy), firms and universities of the Piedmont Aerospace District
Rational and affordable concepts of Landing Gear for small reentry vehicle demonstrators
Get PDFThe paper proposes an innovative solution for landing gear of small space vehicles, in particular of technological demonstrators of reentry space vehicles. After explaining why small space vehicles can benefit from landing gears, the work investigates a solution, which avoids the use of fluidic systems and minimizes constraints on the whole vehicle, thus limiting cost raising and making the installation of the landing gear easier on vehicles that originally did not envisage landing gears
A methodology for system-of-systems design in support of the engineering team
Get PDFSpace missions have experienced a trend of increasing complexity in the last decades, resulting in the design of very complex systems formed by many elements and sub-elements working together to meet the requirements. In a classical approach, especially in a company environment, the two steps of design-space exploration and optimization are usually performed by experts inferring on major phenomena, making assumptions and doing some trial-and-error runs on the available mathematical models. This is done especially in the very early design phases where most of the costs are locked-in. With the objective of supporting the engineering team and the decision-makers during the design of complex systems, the authors developed a modelling framework for a particular category of complex, coupled space systems called System-of-Systems. Once modelled, the System-of-Systems is solved using a computationally cheap parametric methodology, named the mixed-hypercube approach, based on the utilization of a particular type of fractional factorial design-of-experiments, and analysis of the results via global sensitivity analysis and response surfaces. As an applicative example, a system-of-systems of a hypothetical human space exploration scenario for the support of a manned lunar base is presented. The results demonstrate that using the mixed-hypercube to sample the design space, an optimal solution is reached with a limited computational effort, providing support to the engineering team and decision makers thanks to sensitivity and robustness informa- tion. The analysis of the system-of-systems model that was implemented shows that the logistic support of a human outpost on the Moon for 15 years is still feasible with currently available launcher classes. The results presented in this paper have been obtained in cooperation with Thales Alenia Space—Italy, in the framework of a regional programme called STEP
Experimental assessment of not pneumatic wheel for lunar rover technological demonstrator
No full text- …
