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Abstract Organoid and spheroid technology provide valuable insights into developmental biology and oncology. Optical coherence tomography (OCT) is a label-free technique that has emerged as an excellent tool for monitoring the structure and function of these samples. However, mature organoids are often too opaque for OCT. Access to multi-angle views is highly desirable to overcome this limitation, preferably with non-contact sample handling. To fulfil these requirements, we present an ultrasound-induced reorientation method for multi-angle-OCT, which employs a 3D-printed acoustic trap inserted into an OCT imaging system, to levitate and reorient zebrafish larvae and tumor spheroids in a controlled and reproducible manner. A model-based algorithm was developed for the physically consistent fusion of multi-angle data from a priori unknown angles. We demonstrate enhanced penetration depth in the joint 3D-recovery of reflectivity, attenuation, refractive index, and position registration for zebrafish larvae, creating an enabling tool for future applications in volumetric imaging.

In the life sciences, there has been growing awareness that the traditional 2D cell culture model has its limitations in advancing our understanding of the mechanisms that underlie cell behavior, as the behavior and response of cells depend on the 3D microenvironment. Studying models such as suspended cell clusters and organoids is a step toward closing the gap between in vitro and in vivo studies. The fact that sample confinement and contact with surfaces have an impact on cells creates a need for contact-less tools for the inspection of live biological samples. Recently, we developed an acoustofluidic chip to trap and manipulate sub-millimeter-sized biological samples, and here, we demonstrate that this device can be adapted to support high-resolution imaging and illumination scanning for multi-view image acquisition. After coupling acoustic bulk waves into a microfluidic chip, the sample is levitated by an optically transparent transducer in the vertical direction. Two orthogonal side-transducers give additional control over the sample. By tuning the relative strengths of the three transducers and thus inducing an acoustic torque, we can transiently rotate the sample into various orientations for image acquisition. Under different operating conditions, exciting other modes, we can also induce sustained rotation of samples by means of other torque contributions and around axes perpendicular to the imaging axis, which is important to avoid “missing cone” artifacts in the tomographic reconstruction of the sample. We will discuss the modifications to our previously established device that were necessary to comply with the requirements for high-NA imaging and high-NA illumination. We provide a characterization of the performance and show examples of rotation and reorientation of biological samples, such as large pollen grains and cancer spheroids.