NIR-II Imaging Probe for Stem Cell Tracking

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Solution Overview

Problem

Current optical imaging techniques face challenges in precisely and quantitatively tracking stem cells in vivo due to low resolution, radioactive risks, and limited tissue penetration depth, making it difficult to evaluate cell distribution, migration, and engraftment effectively in stem cell therapy.

Innovation Solution

Development of NIR-II optical imaging probes comprising a biocompatible NIR-II dye molecule coupled with an organic protein carrier complex, including a carrier protein and a cell-penetrating peptide, which allows for long-term, real-time tracking of stem cells with high temporospatial resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional optical imaging techniques are used for in vivo cell tracking, then the imaging can be performed with available equipment, but the resolution is low and tissue penetration depth is limited

Engineering Contradiction:
Improveimaging resolutionVSAvoidtissue penetration limitation
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the wavelength parameter of the imaging technique from conventional visible/NIR-I range to NIR-II range (1000-1700 nm). This parameter change enables deeper tissue penetration and improved resolution simultaneously, as NIR-II light experiences less scattering and absorption in biological tissues compared to shorter wavelengths.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite imaging probes consisting of NIR-II fluorescent dyes conjugated to cell-penetrating peptides or antibodies. This composite structure combines the deep-tissue penetration capability of NIR-II light with the specific cell-targeting ability of the peptide-antibody conjugates, achieving both high resolution and deep tissue imaging.

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If magnetic resonance imaging or positron emission tomography is used for cell tracking, then tissue penetration is improved, but the resolution remains low and radioactive risks are introduced

Engineering Contradiction:
Improvetissue penetration depthVSAvoidimaging resolution
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent replaces the mechanical/electromagnetic field-based MRI and PET imaging systems with optical imaging in the NIR-II window. This substitution achieves both deep tissue penetration (comparable to MRI/PET) and high spatial resolution (superior to MRI/PET) without introducing radioactive hazards, as optical imaging uses non-ionizing light.

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

Solution Approach 2:

The patent changes the detection parameter from radiofrequency waves (MRI) or gamma rays (PET) to NIR-II light wavelengths. This parameter change eliminates radioactive risks while maintaining deep tissue penetration capability and achieving superior resolution through the optical properties of NIR-II light in biological tissues.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If current imaging techniques are used for stem cell therapy evaluation, then the therapy can proceed, but precise and quantitative evaluation of cell distribution, migration, and engraftment cannot be achieved

Engineering Contradiction:
Improvetherapeutic evaluation capabilityVSAvoidcell tracking precision
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent introduces NIR-II fluorescent probes as intermediaries that specifically bind to or are internalized by stem cells. These probes act as mediators that enable precise optical detection of stem cells in vivo, allowing quantitative evaluation of cell distribution, migration, and engraftment patterns that were previously impossible with conventional imaging techniques.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the evaluation parameter from qualitative or semi-quantitative assessment to precise quantitative measurement by utilizing the intensity-dependent nature of NIR-II fluorescence signals. The strong fluorescence emission in the NIR-II window enables sensitive detection and quantitative analysis of stem cell behavior, dramatically improving therapeutic evaluation capability.

Inventive Principle:
Principle #35Parameter changes

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

The NIR-II imaging probes enable precise and safe tracking of stem cells in vivo with high sensitivity and specificity, overcoming the limitations of existing methods by providing clear visualization of cell distribution and migration, facilitating better evaluation and therapeutic outcomes in stem cell therapies.

Implementation Method 1

the probe emits detectable NIR-II fluorescence

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11951187B2NIR-II imaging probe and methods of using the NIR-II imaging probe for dynamic in vivo tracking
Publication Date: 2024.04.09 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US11951187B2 patent drawing
  • US11951187B2 patent drawing
  • US11951187B2 patent drawing

AI summary

The disclosure provides NIR-II imaging probes and methods of using the NIR-II imaging probes for dynamic in vivo tracking of cells, such as stem cells, or other substances. NIR-II imaging probes can include a biocompatible NIR-II dye molecule coupled to an organic, biocompatible protein carrier complex, including a carrier protein coupled to a cell-penetrating peptide.