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 artificial immobilization, lacking true isotropic resolution, which is crucial for accurate disease detection and biological studies.

Innovation Solution

A Live-Cell Computed Tomography (LCCT) system that rotates cells or tissues in suspension while acquiring images from multiple angles, using a rotating electric field or hydrodynamic vortex, to reconstruct three-dimensional images with isotropic spatial resolution, allowing for quantitative biosignatures and disease diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cells are immobilized on substrates for imaging, then image stability is improved, but cellular dynamics and natural organization are compromised

Engineering Contradiction:

Improveimage stabilityVSAvoidcellular dynamics

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent replaces mechanical immobilization (adhesion to substrates) with optical trapping using optical tweezers. This allows cells to remain suspended in their natural liquid environment while being held stable enough for imaging, thus maintaining both image stability and cellular dynamics simultaneously

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces optical tweezers as an intermediary mechanism between the imaging system and the cells. This intermediary enables non-contact holding of cells in suspension, avoiding direct mechanical contact that would compromise cellular organization while still providing sufficient stability for high-quality imaging

Inventive Principle:

Principle #24Intermediary (Mediator)

2Loss of information

If traditional tomography methods are used, then 3D imaging capability is achieved, but isotropic spatial resolution is not obtained

Engineering Contradiction:

Improve3D imaging capabilityVSAvoidisotropic spatial resolution

Core Design Contradiction:

Loss of informationVSMeasurement precision

Solution Approach 1:

The patent acquires images from multiple angular perspectives (adding the angular dimension) and uses iterative reconstruction algorithms to synthesize true 3D volumetric data with isotropic resolution, transforming 2D projection images into 3D structures that preserve spatial information equally in all directions

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent combines multiple imaging modalities (transmitted light, reflected light, and fluorescence imaging) within a single tomography system, integrating their complementary strengths to achieve comprehensive 3D visualization with isotropic spatial resolution that no single modality could achieve alone

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If cells are imaged in suspension without rotation, then cellular dynamics are maintained, but orientation-dependent distortion occurs in images

Engineering Contradiction:

Improvecellular dynamicsVSAvoidimage distortion

Core Design Contradiction:

Adaptability or versatilityVSShape

Solution Approach 1:

The patent makes the imaging system dynamic by rotating the sample stage to acquire images from multiple angular perspectives. This dynamic acquisition approach allows reconstruction of orientation-independent 3D structures, eliminating the distortion that would occur with static single-angle imaging while maintaining cellular dynamics during the imaging process

Inventive Principle:

Principle #15Dynamics

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 distortion-free, orientation-independent 3D imaging with isotropic spatial resolution, providing accurate quantitative data for disease diagnosis and biological studies without compromising cellular dynamics.

Implementation Method 1

inducing an electric dipole moment in the object by the rotating electric field

Methodology Applied

Scientific EffectElectric dipole moment induction: Electrostatic Induction

Implementation Method 2

rotating the object at a speed by the rotating electric field

Methodology Applied

Scientific EffectElectrorotation:

Data Source

PatentUS11327004B2Live-cell computed tomography

Publication Date: 2022.05.10 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

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)-involves 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.