Live-Cell Computed Tomography for Isotropic 3D Imaging

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Solution Overview

Problem

Current 3D imaging technologies for live cells and tissues in suspension often compromise biological dynamics due to the need for immobilization, which alters cellular organization and signaling pathways, and lack true isotropic resolution necessary for accurate disease detection and biological studies.

Innovation Solution

A Live-Cell Computed Tomography (LCCT) system that rotates live or fixed cells and tissues in suspension within a biocompatible gel in a capillary imaging chamber, using a rotating electric field to maintain natural dynamics while acquiring 3D images with isotropic spatial resolution through a combination of optical trains and computer algorithms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cells are immobilized during imaging, then image stability is improved, but biological dynamics are compromised

Engineering Contradiction:
Improveimage stabilityVSAvoidbiological dynamics compromise
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces mechanical immobilization with optical trapping using optical tweezers. The optical field generates gradient forces that hold cells in position without physical contact, eliminating mechanical stress and damage while maintaining image stability during 3D imaging acquisition

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces a biocompatible gel medium as an intermediary between the cell and the imaging system. The gel provides a natural-like suspension environment that maintains cell viability and biological dynamics while allowing stable positioning and imaging, replacing direct mechanical immobilization

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If anisotropic resolution is used, then imaging speed is improved, but measurement precision deteriorates

Engineering Contradiction:
Improveimaging speedVSAvoidspatial resolution isotropy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent employs dynamic scanning strategies where the focal plane rapidly moves through the cell volume while the cell is held stationary by optical tweezers. This dynamic acquisition approach collects data from multiple angles and depths, enabling isotropic 3D reconstruction with uniform resolution in all spatial directions while maintaining efficient imaging speed

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent transitions from 2D planar imaging to 3D volumetric imaging by scanning the focal plane through the entire cell depth and combining multiple angular projections. This dimensional expansion enables isotropic resolution where pixel sizes are equal in all three spatial dimensions (x, y, z), providing accurate spherical cell morphology measurement without compromising imaging efficiency

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables the synthesis of high-resolution, distortion-free 3D images of cells and tissues, providing quantitative biosignatures for disease diagnosis and biological studies without compromising cellular function or structure.

Implementation Method 1

generating a rotating electric field; inducing an electric dipole moment in the object by the rotating electric field; and rotating the object at a speed by the rotating electric field

Methodology Applied
Scientific EffectElectric dipole moment induction: Electrostatic Induction

Data Source

PatentUS11315292B2Live-cell computed tomography
Publication Date: 2022.04.26 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US11315292B2 patent drawing
  • US11315292B2 patent drawing
  • US11315292B2 patent drawing

AI summary

Systems and methods of using the same for functional fluorescence imaging of live cells in suspension with isotropic three dimensional (3D) diffraction-limited spatial resolution are disclosed. The method-live cell computed tomography (LCCT)-in-volves the acquisition of a series of two dimensional (2D) pseudo-projection images from different perspectives of the cell that rotates around an axis that is perpendicular to the optical axis of the imaging system. The volumetric image of the cell is then tomographically reconstructed.