Ultrafast light-sheet optical tweezers for in situ parallelized biomechanical characterization of cells and soft tissues

Abstract

Quantitative characterization of the mechanical properties of cells and tissues is essential for understanding disease progression and tissue regeneration. Optical tweezers (OT) enable the direct application of biologically relevant forces; however, OT has been limited to single axial indentations of cells, thereby restricting throughput. Furthermore, the use of quadrant photodiodes is insufficient for assessing the large displacements required for biomechanical characterization of tissues. We present light-sheet optical tweezers as a force transducer (LOFT), an approach that improves the throughput by at least 3x through simultaneous multiparticle trapping and parallelized characterization under sub-nN forces. LOFT is achieved by uniquely integrating light-sheet illumination for extended trapping, femtosecond-pulsed lasers to augment the optical gradient force, and videography-based particle tracking for observation of force transduction. The platform is validated through single-cell indentation experiments. We then apply LOFT to myocardial tissue, revealing significant biomechanical differences between healthy and infarcted regions; the interpretation of which is further supported by quantitative multiphoton imaging using the same optical source and platform. This work represents the first demonstration of OT for the mechanical testing of intact soft tissues, and establishes LOFT as a versatile, multifunctional platform for high-throughput, minimally invasive, mechanical characterization of complex biological systems in situ.