Optical Stimulation of Target Cells Using Photosensitive Proteins

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Solution Overview

Problem

Electrode-based brain stimulation techniques face challenges due to the distributed nature of neurons, making it difficult to selectively stimulate specific neuron types, and they often suffer from mechanical instability and encapsulation issues, leading to unintended stimulation of additional cells.

Innovation Solution

The use of photosensitive bio-molecular structures and light-activated proteins, such as halorhodopsin and channelrhodopsin, to optically stimulate target cells by controlling ion flow across cell membranes in response to light, allowing for precise modulation of neuronal activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrode-based stimulation is used to activate neurons, then electrical current can be delivered to target cells, but mechanical stability is inadequate leading to lead migration and encapsulation

Engineering Contradiction:
Improveelectrode stabilityVSAvoidlong-term electrode functionality
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent replaces the mechanical electrode system with an optical system. Light-sensitive proteins (opsins) are introduced into target neurons, and light delivery devices (optical fibers, LEDs) are used instead of electrical electrodes. This substitution eliminates mechanical contact issues such as lead migration and encapsulation, as light can be delivered through flexible optical fibers that do not require direct electrical contact with tissue.

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

2Measurement precision

If electrodes are used for brain stimulation, then neurons can be activated, but selectivity is poor due to the distributed nature of neurons and physical proximity requirements

Engineering Contradiction:
Improvecellular stimulation precisionVSAvoidunintended neuron stimulation
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making only specific target neurons light-sensitive through selective expression of opsins. This genetic targeting allows precise spatial selectivity - only neurons expressing the light-sensitive protein will respond to light stimulation, while neighboring neurons remain unaffected. This resolves the selectivity problem of electrode stimulation by creating functionally distinct responsive vs. non-responsive cells in close proximity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent introduces light-sensitive proteins (opsins) as an intermediary between the light delivery system and the neuron's electrical activity. These proteins act as molecular mediators that convert optical energy into electrical signals (ion flow) specifically within target cells. This intermediary enables selective activation without the need for direct electrical contact, solving the specificity problem of electrode-based stimulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Power

If electrical current is increased to compensate for electrode encapsulation, then power delivery to target cells improves, but unintended stimulation of additional cells increases

Engineering Contradiction:
Improveelectrical power deliveryVSAvoidspread of electrical current
Core Design Contradiction:
PowerVSObject-affected harmful factors

Solution Approach 1:

The patent replaces electrical current delivery with optical energy delivery. Light can be delivered with high spatial precision through optical fibers or localized light sources, and only the light-sensitive target neurons will respond. This eliminates the problem of current spread that occurs when increasing electrical power to overcome encapsulation resistance, as light energy does not diffuse in the same manner as electrical current through tissue.

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

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 enables selective and precise stimulation of target cells, reducing unintended activation and improving long-term efficacy by using light to control neuronal firing and hyperpolarization, potentially offering a more precise therapeutic option for various medical conditions.

Implementation Method 1

The use of photosensitive bio-molecular structures and light-activated proteins, such as halorhodopsin and channelrhodopsin, to optically stimulate target cells by controlling ion flow across cell membranes in response to light

Methodology Applied
Scientific EffectPhotoactivation of ion channels: Photoelectric Effect

Data Source

PatentUS10052497B2System for optical stimulation of target cells
Publication Date: 2018.08.21 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US10052497B2 patent drawing
  • US10052497B2 patent drawing
  • US10052497B2 patent drawing

AI summary

Stimulation of target cells using light, e.g., in vivo, is implemented using a variety of methods and devices. In one example, embodiments involve methods for stimulating target cells using a photosensitive protein that allows the target cells to be stimulated in response to light. In another specific example embodiment, target cells are stimulated using an implantable arrangement. The arrangement includes an electrical light-generation means for generating light and a biological portion. The biological portion has a photosensitive bio-molecular arrangement that responds to the generated light by stimulating target cells in vivo. Other aspects and embodiments are directed to systems and methods for screening chemicals based screening chemicals to identify their effects on cell membrane ion channels and pumps, and to systems and methods for controlling an action potential of neuron (e.g., in in vivo and in vitro environments).