METHOD AND SYSTEM FOR QUANTITATIVE THREE-DIMENSIONAL MEASUREMENT OF DENSITY, ANISOTROPY, AND ORIENTATION WITHOUT LABEL
Researchers at the Chan Zuckerberg Biohub have developed a label-free computational imaging method for measuring optical properties of a specimen.
Biological architecture is intrinsically tensorial. The permittivity tensor (PT) of biological material reports the density, angular anisotropy, symmetry, and 3D orientation of biomolecules. Despite the progress that has been made in optical microscopy and the measurement of optical properties of materials, there exists a need for improved methods and systems for performing quantitative imaging of three-dimensional (3D) density, anisotropy, and orientation (i.e., PT) without the use of labels.
Stage of Research
The inventors have developed a label-free computational imaging method for volumetric measurement of PT with diffraction-limited resolution. Their method and system, uPTI (uniaxial permittivity tensor imaging), provides measurements of complete uniaxial PT, including absorption, phase, principal retardance, 3D orientation, and symmetry in 2D and 3D space. uPTI captures these properties of the specimen by combining oblique illumination with polarization-sensitive detection. Moreover, the inventors developed a vectorial imaging model and corresponding multi-channel deconvolution algorithm to extract spatial distribution of the uPTI components. The inventors validate the accuracy and resolution of uPTI with isotropic polystyrene beads and anisotropic laser-written glass targets. They further demonstrate the value of uPTI in analysis of mouse brain architecture across biological scales.
Applications
- Label-free measurement for comprehensive high-resolution imaging of biological architecture
- Automated acquisition and analysis methods for a complete description of uniaxial PT (i.e., 3D anisotropy, isotropic density, and the material symmetry) in 3D space
Advantages
- Specimens can be biological or inorganic
- System is modular with a simple optical design that can be multiplexed with complementary imaging modalities
- Label-free microscopy enables quantitative imagine of primary cells, non-mode organisms that cannot be labeled genetically, or tissue or biopsy slices
- Method provides reliable measurement of uniaxial component for structures with biaxial permittivity tensors
Stage of Development
Research – in vitro
Publications
Yeh L-H, Ivanov IE, et al. uPTI: uniaxial permittivity tensor imaging of intrinsic density and anisotropy. bioRxiv. 2021. Doi: 10.1101/2020.12.15.422951
PCT Publication No. WO2021242741
Related Web Links
https://www.czbiohub.org/comp-micro/
Keywords
Biomolecules, microscopy, optical imaging, polarization, density, anisotropy
Technology Reference
CZB-151