Precise acoustic cell manipulation in spherical microfluidic chambers for cell function analysis

• Applicant: Professor Dr. Oliver Hayden
• Subject Area: Biomedical Systems Technology ; Acoustics ; Microsystems
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562496419

Cancer is the most rapidly growing chronic disease in aging societies. Animal testing is the gold standard in preclinical cancer research. Preclinical animal models of human cancers are indispensable in cancer research, but due to the genetic and epigenetic heterogeneity of human cancers, they are however imperfect and biased. Due to ethics to reduce animal testing, the search for alternative in vitro models become more and more prominent. Most of the widely used models for investigating immunotherapy are based on 2D or mouse models, which have various limitations. Amongst others, 2D culture models fail to mimic natural 3D tissue morphology, and the immune system of mice is very different from humans. This is an inadequate situation considering the increasing importance of immunotherapies as an important pillar for cancer therapy. 2D cell cultures and mouse models are, therefore, not the future for the advancement of personalized medicine. On the other hand, conventional 3D cell cultures can mimic closely tumor microenvironment. However, tumor organoid cultures are established only for a few types of cancers, though still not a well-reproducible and thus standardizable process. Today, emerging technologies, such as microfluidic and lab-on-a-chip technologies, provide 3D cell culture, rapid prototyping, and integration of automatic workflows potentially useful for testing the therapeutic efficacy with patient samples. For therapy decision making a functional understanding of the tumor is very crucial for physician to improve patient outcome. Hence, it is necessary to advance systems, which allow a robust mimic of the cellular micro-environment in vitro with even primary cells from patients. Despite major efforts of the community, broad clinical acceptance of in vitro cell models is still low with mainly niche applications driven by costs, throughput and time-to-results. Acoustofluidics is the ideal candidate, but previously reported results are mainly based on 2D channels of rectangular for cell separation and stochastic cell aggregation. The ‘CellLEGO’ acoustofluidics platform is focused on establishing a label-free 3D modelling system without cell-wall contacts, which allows a continuous perfusion workflow and opens up opportunities for micro-cell-cell interaction studies in 3D, which goes way beyond the state-of-the-art. Our system is independent of cellular migration over days, thus potentially reducing the cell-cell interaction test time by an order of magnitude. To achieve such 3D, wall-contact-free, deterministic, and precise cell trapping, we propose the use of acoustic focusing in microfluidic resonance cavities as a form of functional microscope slide to allow for controlled rotation and microscopic cell inspection at any time constant in perfusion conditions.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Shilpi Pandey