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Permittivity tensor imaging: modular label-free imaging of 3D dry mass and 3D orientation at high resolution

Li-Hao Yeh, Ivan E. Ivanov, Talon Chandler, Janie R. Byrum, Bryant B. Chhun, Syuan-Ming Guo, C. B. Foltz, Ezzat Hashemi, Juan A. Pérez-Bermejo, Huijun Wang, Yan‐Hao Yu, Peter G. Kazansky, Bruce R. Conklin, May Han, Shalin B. Mehta

2024Nature Methods15 citationsDOIOpen Access PDF

Abstract

The dry mass and the orientation of biomolecules can be imaged without a label by measuring their permittivity tensor (PT), which describes how biomolecules affect the phase and polarization of light. Three-dimensional (3D) imaging of PT has been challenging. We present a label-free computational microscopy technique, PT imaging (PTI), for the 3D measurement of PT. PTI encodes the invisible PT into images using oblique illumination, polarization-sensitive detection and volumetric sampling. PT is decoded from the data with a vectorial imaging model and a multi-channel inverse algorithm, assuming uniaxial symmetry in each voxel. We demonstrate high-resolution imaging of PT of isotropic beads, anisotropic glass targets, mouse brain tissue, infected cells and histology slides. PTI outperforms previous label-free imaging techniques such as vector tomography, ptychography and light-field imaging in resolving the 3D orientation and symmetry of organelles, cells and tissue. We provide open-source software and modular hardware to enable the adoption of the method.

Topics & Concepts

VoxelAnisotropyMaterials scienceOpticsOrientation (vector space)Polarization (electrochemistry)PhysicsNuclear magnetic resonanceComputer scienceArtificial intelligenceChemistryGeometryMathematicsPhysical chemistryDigital Holography and MicroscopyAdvanced Fluorescence Microscopy TechniquesMicrofluidic and Bio-sensing Technologies
Permittivity tensor imaging: modular label-free imaging of 3D dry mass and 3D orientation at high resolution | Litcius