Optical Clearing Compositions Using Kramers-Kronig Index Matching
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Solution Overview
Problem
Existing optical tissue clearing methods are not biocompatible and cannot be used in live organisms due to the use of toxic substances and the removal of vital molecules, limiting their effectiveness in reducing refractive index mismatch and scattering in biological tissues.
Innovation Solution
The use of absorbing substances that absorb light at specific wavelengths to modulate the refractive index of biological tissues, leveraging the Kramers-Kronig relation to increase the refractive index of the aqueous phase, thereby reducing scattering and increasing transmission, as demonstrated by the use of tartrazine as a safe and soluble pigment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing optical tissue clearing methods use toxic substances and remove lipids to reduce refractive index mismatch, then light scattering is reduced and imaging depth is improved, but biocompatibility is lost and live organism imaging becomes impossible
Solution Approach 1:
The patent converts the harmful effect of light absorption into a beneficial one by using absorbing substances to modulate refractive index through the Kramers-Kronig relation. The absorption at one wavelength induces refractive index changes at neighboring wavelengths, reducing scattering without requiring toxic clearing agents or lipid removal, thereby enabling biocompatible optical clearing in live organisms
Solution Approach 2:
The patent changes the physical parameter of refractive index by introducing absorbing substances that modify the optical properties of the aqueous phase. By tuning the absorption characteristics of these substances, the refractive index of the aqueous phase is modulated to match that of lipid-based components, reducing optical contrast and scattering while maintaining tissue viability
2Loss of energy
If water and lipids are removed from tissues to reduce scattering, then optical transparency is improved, but vital molecules are lost and live organism imaging is precluded
Solution Approach 1:
The patent introduces absorbing substances as intermediaries that mediate the optical properties of the tissue. These substances are introduced into the aqueous phase and modulate its refractive index to match that of lipid-based components, thereby reducing scattering without requiring the removal of water or lipids. This intermediary approach preserves the native tissue composition while achieving optical clearing
3Measurement precision
If high-RI chemicals are used to replace water and reduce refractive index differences, then optical contrast is reduced and scattering is minimized, but toxic substances are introduced that cannot be used in live tissues
Solution Approach 1:
The patent converts the harmful effect of light absorption into a beneficial one by using absorbing substances to modulate refractive index through the Kramers-Kronig relation. The absorption at one wavelength induces refractive index changes at neighboring wavelengths, reducing scattering without requiring toxic clearing agents or lipid removal, thereby enabling biocompatible optical clearing in live organisms
Solution Approach 2:
The patent changes the physical parameter of refractive index by introducing absorbing substances that modify the optical properties of the aqueous phase. By tuning the absorption characteristics of these substances, the refractive index of the aqueous phase is modulated to match that of lipid-based components, reducing optical contrast and scattering while maintaining tissue viability
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 clear visualization of deep tissues in live organisms by increasing transmission and reducing scattering, allowing for non-invasive imaging of muscles, bones, and nerves without the use of toxic chemicals.
Implementation Method 1
an absorbing substance that absorbs light at specific wavelengths
Implementation Method 2
allowing the refractive index of the medium at neighboring wavelengths to be modulated accordingly
Implementation Method 3
reduction of the refractive index mismatch between separate phases with distinct refractive indices, thus mitigating scattering
Implementation Method 4
significantly increasing the refractive index at desired wavelengths
Data Source
AI summary
In one aspect, the disclosure relates to compositions and use thereof including an absorbing substance that absorbs light at specific wavelengths, thus allowing the refractive index of the medium at neighboring wavelengths to be modulated accordingly. This modulation allows reduction of the refractive index mismatch between separate phases with distinct refractive indices, thus mitigating scattering. The compositions are soluble in water and have high absorptivity, thus significantly increasing the refractive index at desired wavelengths. In one aspect, these materials have been proved safe in oral administration. In another aspect, provided herein is a protocol that enables diffusion of these substances into the aqueous phase of biological tissues, including in living organisms, thereby achieving increased transmission in muscles and allowing clear visualization of deep bones, vessels, and nerves that are otherwise invisible in the body.