TTA-UC Upconversion Nanoparticles for Deep-Tissue Optogenetics

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Solution Overview

Problem

Current methods for manipulating cellular behavior in three-dimensional (3D) environments are limited by the physical limitations of visible light penetration, which prevents deep tissue activation of optogenetic proteins, as high-energy blue light does not penetrate deeply into tissues, while low-energy near-infrared (NIR) light lacks the energy to trigger these proteins.

Innovation Solution

Development of optically active, 3D biomaterials using triplet-triplet annihilation upconversion (TTA-UC) chromophores that convert low-energy NIR or red light into high-energy blue light within hydrogel scaffolds, enabling deep tissue activation of optogenetic proteins with spatiotemporal control.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If high-energy blue light is used to activate optogenetic proteins, then the activation efficiency is improved, but the light penetration depth deteriorates

Engineering Contradiction:

Improveoptogenetic protein activation energyVSAvoidlight penetration depth

Core Design Contradiction:

Use of energy by moving objectVSLength of moving object

Solution Approach 1:

The patent introduces an upconversion nanoparticle as an intermediary substance that absorbs low-energy NIR light and converts it to high-energy blue light through the TTA-UC mechanism. This mediator enables deep tissue penetration by using NIR light while still providing the high-energy blue light needed to activate optogenetic proteins, thus resolving the contradiction between activation energy and penetration depth

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the energy parameter of light by implementing a wavelength conversion process. NIR light (low energy, deep penetration) is converted to blue light (high energy, protein activation) through the upconversion nanoparticles. This parameter transformation allows the system to benefit from both low-energy light penetration and high-energy light activation capabilities

Inventive Principle:

Principle #35Parameter changes

2Length of moving object

If low-energy NIR light is used for deep tissue penetration, then the penetration depth is improved, but the energy to activate optogenetic proteins deteriorates

Engineering Contradiction:

Improvelight penetration depthVSAvoidoptogenetic protein activation energy

Core Design Contradiction:

Length of moving objectVSUse of energy by moving object

Solution Approach 1:

The upconversion nanoparticle serves as a mediator that receives low-energy NIR light and transforms it into high-energy blue light. The nanoparticle's TTA-UC mechanism enables this energy transformation, allowing NIR light to penetrate deep tissues while still providing sufficient energy to activate optogenetic proteins through the converted blue light

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The system implements a parameter change by converting the wavelength and energy of light from NIR (low energy) to blue (high energy) through the upconversion process. This enables the light to maintain deep penetration capability while acquiring the necessary activation energy for optogenetic proteins

Inventive Principle:

Principle #35Parameter changes

3Reliability

If visible light is used to trigger photochemical processes, then the photochemical activation is improved, but the tissue penetration capability deteriorates

Engineering Contradiction:

Improvephotochemical activation reliabilityVSAvoidtissue penetration depth

Core Design Contradiction:

ReliabilityVSLength of moving object

Solution Approach 1:

The upconversion nanoparticle acts as an intermediary that enables photochemical activation by converting penetrating NIR light into the blue light wavelength required for optogenetic protein activation. This mediator ensures reliable photochemical responses while utilizing light that can penetrate deep into tissues

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The system changes the light parameter from NIR wavelength to blue light wavelength through upconversion, enabling the light to both penetrate tissue effectively and trigger the required photochemical processes in optogenetic proteins with high reliability

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

This approach allows for precise and dynamic control of cellular behavior in 3D settings by generating sufficient blue light to activate optogenetic proteins, overcoming the limitations of traditional light penetration and providing unprecedented specificity and precision in cellular manipulation.

Implementation Method 1

triplet-triplet annihilation upconversion (TTA-UC) chromophores that convert low-energy NIR or red light into high-energy blue light

Methodology Applied

Scientific EffectTriplet-triplet annihilation upconversion (TTA-UC):

Data Source

PatentUS20240110150A1Photon upconversion biomaterials, micelle and nanoparticles for three-dimensional (3D) optogenetics

Publication Date: 2024.04.04 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

Exemplary embodiments of the present disclosure provides biomaterials, systems, and methods that utilize upconversion biomaterials to stimulate optogenetic cells in three-dimensional settings. Provided is a biomaterial including chromophores capable of converting low-energy light to high-energy light embedded in biocompatible materials. This technology enables more selective stimulation of optogenetic cells in three-dimensional scaffolds and has the potential to provide critical insights into cell function and disease.