Transdermal Optogenetic Nerve Stimulation via Viral Vector Density

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Solution Overview

Problem

Peripheral nerves located beneath tissue types such as skin, blood vessels, adipose tissue, and muscle are challenging to target with transdermal optogenetic stimulation due to significant attenuation of visible light, preventing effective activation and inhibition of neural populations.

Innovation Solution

A wearable device employing a high concentration of viral particles to achieve a higher density of ChR2 channels in motor neurons, allowing for transdermal optogenetic control of nerves using selective transdermal light stimulation, which can penetrate deep tissues and activate nerves without the need for invasive implants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If transdermal optogenetic stimulation is applied to peripheral nerves, then non-invasive nerve activation is achieved, but light attenuation by tissue prevents effective stimulation

Engineering Contradiction:
Improvenon-invasive stimulationVSAvoidlight attenuation
Core Design Contradiction:
Ease of operationVSIllumination intensity

Solution Approach 1:

The patent changes the wavelength parameter of light from visible spectrum to near-infrared spectrum, which has better penetration depth through tissues. This parameter change allows light to reach deeper peripheral nerves without significant attenuation, resolving the contradiction between non-invasive access and effective light delivery.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary substance - optogenetic viral vectors (AAV) - that deliver light-sensitive opsin proteins to peripheral nerves. This intermediary enables the nerves to respond to light stimulation, bridging the gap between non-invasive light delivery and effective neural activation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If higher concentration of viral particles is used to increase ChR2 channel density, then optical sensitivity of nerves is improved, but risk of tissue damage and mechanical failure increases

Engineering Contradiction:
Improveoptical sensitivityVSAvoidtissue damage risk
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent optimizes the concentration parameter of viral particles to achieve the minimum effective density of ChR2 channels for optical stimulation. By carefully controlling this parameter, the patent achieves sufficient optical sensitivity while avoiding excessive viral load that could cause tissue damage or mechanical failure.

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 effective motor control and sensation restoration in mammals by increasing the optical sensitivity of nerves, allowing for the treatment of conditions like chronic pain, paralysis, and mood disorders with reduced risk of mechanical failure and tissue heating associated with implantable devices.

Implementation Method 1

The retrograde transfection of AAV6-hSyn-ChR2-YFP, injected intramuscularly, has been shown to result in a repeatable muscle activation in response to direct optical stimulation of the peroneal and tibial nerves

Methodology Applied
Scientific EffectOptogenetic stimulation: Photoelectric Effect

Implementation Method 2

The retrograde transfection of AAV6-hSyn-ChR2-YFP, injected intramuscularly, has been shown to result in a repeatable muscle activation

Methodology Applied
Scientific EffectViral transduction:

Data Source

PatentEP3535024B1Transdermal optogenetic peripheral nerve stimulation
Publication Date: 2024.12.04 MASSACHUSETTS INST OF TECH
  • EP3535024B1 patent drawingFigure 1A~2B
  • EP3535024B1 patent drawingFigure 3A~3B
  • EP3535024B1 patent drawingFigure 4A~4B

AI summary

A nerve in a mammal is optogenetically transduced, wherein the nerve is susceptible to stimulus by selective application of transdermal light, and a light source is applied to dermis of the mammal at or proximate to the optogenetically transduced nerve, to thereby stimulate the nerve. A wearable device for optogenetic motor control and sensation restoration of a mammal includes a wearable support, a power source at the wearable support, a controller at the wearable support and in electrical communication with a power source, and a transdermal light source coupled to the controller.