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Acoustic manipulation for cell and spheroid cellomics

Time: Fri 2021-06-11 10.00

Location: Via zoom, (English)

Subject area: Physics, Biological and Biomedical Physics

Doctoral student: Karl Olofsson , Biomedicinsk fysik och röntgenfysik, Science for Life Laboratory, SciLifeLab

Opponent: Professor Maria Tenje, Uppsala universitet

Supervisor: Professor Martin Viklund,

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Ultrasonic standing wave (USW) particle manipulation has during the last two decades matured into a valuable tool to combine with microfluidics. Acoustophoresis, migration through sound, is the result of the acoustic radiation force acting on particles suspended in an acoustic field. The acoustic radiation force magnitude is proportional to the acoustic energy density, frequency and particle size. The acoustic radiation force has successfully been implemented in particle washing, size-based separation, mechanical phenotype-based cell separation and trapping applications. The force magnitude and direction also depend on the difference between the mechanical properties of the fluid and particle. In the first part of this thesis, we show that the mechanical properties of dead cells are a function of the surrounding fluid which was used to acoustically separate dead and viable cells in a density modulated medium.The non-invasive and biocompatible acoustic radiation force has also been used in trapping applications tailored towards tissue modelling and engineering. One of the explored models is the multicellular tumor spheroid (MTCS) which is a spherical aggregate of tumor cells. The MCTS models a solid tumor and is increasingly used to replace regular 2D cell culture techniques in cancer research and drug screening pipelines. The majority of this thesis will be dedicated to the formation and culture of scaffold-free MCTSs using the acoustic radiation force in silicon and glass microwells. We have developed two multiwell microplate designs where either a 100 MCTSs in a single compartment or 576 MCTSs divided into 16 compartments can be formed in parallel using USWs. By using a sequential cell seeding method it is possible to control the MCTS structural architecture and create core-shell MCTSs. The glass bottom in the microwells in combination with efficient clearing protocols also enabled whole MCTS imaging which was utilized to characterize the cell cycle and the volumetric parameters of the nuclei within the MCTSs using image analysis. Finally, we used the 16 chamber multiwell microplate to investigate the drug response in MCTSs from 4 different cell lines simultaneously and evaluate the NK cell cytotoxic response towards MCTSs in presence of different treatments.