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As cells and tissues are highly dependent on their specific microenvironment, in-vitro models need to incorporate this 3D structure to yield reliable results in biomedical research. Cancer cell spheroids and organoids have become valuable tools in oncology and development studies as they are more representative of in-vivo tissues than the traditional 2D cell culture models and have the potential to improve throughput in drug-screening compared to animal-models and also to go towards personalized medicine. Platforms for both assembly and non-invasive long-term monitoring of such models and also for layered bio-engineered tissues are of great interest. We have developed a sono-optical microfluidic device with 3D acoustic trapping and optical tweezers for non-contact manipulation and imaging of biological samples in liquid suspension. 3D acoustic trapping is achieved with two orthogonal side-transducers and an optically transparent top-transducer that enables optical access for imaging and tweezers to the sample volume. We have demonstrated trapping of biological samples and cancer cell spheroids of several 100µm in size. With acoustics alone or combined with optical tweezers, we can trap samples, change their location and orientation or induce sustained rotation of them, without the sample being in contact with confining structures or embedded in gels. With 3D independent control of the transducers we can adjust the relative strength of the acoustic radiation and viscous torques which will determine whether transient reorientation or continuous rotation of a given sample takes place, and along with numerical simulations and experimental insight we can optimize our strategy to achieve a desired manipulation, within limitations depending on sample size and shape asymmetry. Our technique offers access to optical tomographic information, by rotation of samples around one chosen axis or two axes, and mechanical probing or it can be used for 3D patterning of cells and cell structures in gel precursors for tissue-engineering.
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