Process development for improved Car-t production utilizing an automated single use perfusion stirred-tank bioreactor

Ex vivo genetically-modified cellular immunotherapies, such as chimeric antigen receptor T-cells (CAR-T), have generated significant clinical and commercial outcomes due to their unparalleled response rates against refractory/relapsed blood cancers. However, the development and manufacture of these advanced therapies face a number of translational bottlenecks that must be addressed to ensure long-term commercial viability. The cost and variability associated with these personalized advanced therapies presents a critical manufacturing and translational challenge. Due to the nature of cell therapies, single-use technologies are typically used for their production. This work demonstrates the importance of determining critical manufacturing process parameters using single-use technologies and incorporating automation into the process. The work builds off of previous proof of concept work completed in the group for the production of CAR-T cells in automated, stirred tank, single-use ambr250® bioreactors. These follow-on experiments utilize concepts of quality by design and design of experiments (DoE) to systematically determine the impact of process parameters on CAR-T production. Please click Additional Files below to see the full abstract

FEM with web-spline-basis : analysis and numericss of suitable weight functions

Die Diplomarbeit beschäftigt sich mit Eigenschaften wie Glattheit und Ableitung einer mittels eines singulären Integralterms definierten Gewichtsfunktion und ihrer Verwendbarkeit für die web-Methode (weighted extended B-Splines, siehe auch www.web-spline.de). Abschließend wird die Matlab-Implementierung der Gewichtsfunktion für beliebige, mit Bezierkurven berandete Gebiete beschrieben

Contents

Modelling and analysis in two and three dimension

Angewandte Analysis und Numerische Simulation

Asymptotic models for piezoelectric stack actuators with thin metal inclusion