Lanthanide Nanoparticle Upconversion for Deep Brain Optogenetics

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Solution Overview

Problem

Current optogenetic methods require invasive procedures to deliver light to neurons, as visible light struggles to penetrate deep into brain tissue, necessitating the insertion of light sources that can cause tissue damage.

Innovation Solution

The use of lanthanide-doped nanoparticles that upconvert infrared or near-infrared electromagnetic radiation into visible light, allowing for non-invasive activation of light-responsive opsin proteins on neural cells, eliminating the need for direct light source placement and minimizing tissue damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If visible light is used to activate opsins in deep brain regions, then neural control precision is improved, but light penetration capability deteriorates

Engineering Contradiction:
Improveneural control precisionVSAvoidlight penetration capability
Core Design Contradiction:
Measurement precisionVSIllumination intensity

Solution Approach 1:

The patent changes the wavelength parameter of light from visible spectrum to infrared spectrum. Infrared light has better penetration capability through biological tissue while the upconversion nanoparticles convert it back to visible light for opsin activation, thus resolving the contradiction between penetration capability and control precision

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces upconversion nanoparticles as an intermediary substance. These nanoparticles absorb infrared light and convert it to visible light through upconversion, serving as a mediator that enables deep tissue penetration while maintaining the ability to activate opsins with precise spatial control

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If fiber optic light sources are inserted into the brain to deliver light, then light delivery effectiveness is improved, but tissue damage increases

Engineering Contradiction:
Improvelight delivery effectivenessVSAvoidtissue damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses upconversion nanoparticles as an intermediary that can be delivered systemically or locally without requiring invasive fiber optic insertion. The nanoparticles convert infrared light to visible light in situ, eliminating the need for physical light source implantation and associated tissue damage

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical fiber optic light delivery system with a nanoparticle-based optical conversion system. Instead of physically inserting light sources into the brain, the system uses administrable nanoparticles that perform optical conversion chemically/physically, thereby eliminating mechanical tissue disruption

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

3Illumination intensity

If infrared light is used for deep tissue penetration, then light penetration capability is improved, but direct opsin activation capability deteriorates

Engineering Contradiction:
Improvelight penetration capabilityVSAvoidopsin activation capability
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent introduces upconversion nanoparticles as an intermediary that absorbs infrared light (which penetrates deep tissue) and converts it to visible light (which activates opsins). This two-step process maintains both deep penetration capability and reliable opsin activation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs parameter transformation by changing the wavelength of light from infrared to visible spectrum through the upconversion process. This parameter change enables the system to benefit from both the deep penetration of infrared light and the high opsin activation efficiency of visible light

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

Enables the non-invasive and efficient delivery of light to neurons deep within the brain, reducing tissue damage and allowing for precise control of neural membrane polarization without the need for invasive light source implantation.

Implementation Method 1

nanoparticles capable of upshifting electromagnetic radiation from wavelengths associated with the infrared (IR) or near infrared (NIR) spectrum into wavelengths associated with visible light

Methodology Applied
Scientific EffectUpconversion: Photoluminescence

Data Source

PatentUS10252076B2Upconversion of light for use in optogenetic methods
Publication Date: 2019.04.09 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US10252076B2 patent drawing
  • US10252076B2 patent drawing

AI summary

Provided herein are compositions comprising lanthanide-doped nanoparticles which upconvert electromagnetic radiation from infrared or near infrared wavelengths into the visible light spectrum. Also provided herein are methods activating light-responsive opsin proteins expressed on plasma membranes of neurons and selectively altering the membrane polarization state of the neurons using the light delivered by the lanthanide-doped nanoparticles.