MHD Tissue Clearing and Labeling for Fast 3D Imaging
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Solution Overview
Problem
Current methods for rendering biological tissues transparent for high-resolution imaging are costly, time-consuming, and often damage endogenous fluorescence, while efficiently labeling large tissue samples with antibodies is impractical due to slow diffusion and potential damage.
Innovation Solution
A magnetohydrodynamic (MHD) system is employed to accelerate the removal of lipids and introduction of fluorescent antibodies into tissue samples, using a combined electrical and magnetic field to induce charged particles to flow perpendicular to both fields, facilitating rapid and efficient clearing and labeling of large tissue samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If chemical clearing strategies are used to render tissues transparent, then tissue transparency is improved, but endogenous fluorescence is quenched and fluorescent imaging becomes untenable
Solution Approach 1:
The invention changes the chemical parameters of the clearing solution by using non-quenching solvents such as fructose, glycerol, or their mixtures with water, replacing traditional quenching agents. This parameter change allows tissue transparency to be achieved while preserving endogenous fluorescence signals for imaging
Solution Approach 2:
The invention uses readily available, inexpensive clearing agents like fructose and glycerol that can be easily prepared and disposed of, replacing complex and expensive commercial clearing solutions. These simple sugar-based solutions achieve effective clearing without fluorescence quenching
2Quantity of substance
If antibody labeling is performed on large tissue samples using diffusion, then labeling is achieved, but the process takes impractically long time
Solution Approach 1:
The invention transforms the static diffusion process into a dynamic flow process by pumping clearing solution through the tissue sample. This dynamic circulation continuously brings fresh antibody-containing solution into contact with the tissue, dramatically accelerating labeling from weeks to days or hours
Solution Approach 2:
The invention implements continuous circulation of the clearing and labeling solution through the tissue sample using a pump system. This continuous flow ensures uninterrupted delivery of antibodies and clearing agents, maintaining constant labeling action without the need for repeated medium changes
3Productivity
If electrophoretic forces or chemical permeability induction are used to accelerate antibody penetration, then labeling speed is improved, but endogenous fluorescence is damaged
Solution Approach 1:
The invention introduces a permeabilizing agent such as saponin or Triton X-100 as an intermediary substance that temporarily increases tissue permeability to allow faster antibody penetration. This intermediary enables accelerated labeling without requiring harsh electrophoretic fields that would damage endogenous fluorescence
Solution Approach 2:
The invention changes the physical-chemical parameters of the tissue by adding mild detergents or saponins to the clearing solution, which temporarily alter membrane permeability. This parameter change allows faster passive diffusion of antibodies into the tissue without applying damaging electrical fields
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 high-resolution 3-dimensional anatomical analysis of intact tissues, achieving transparency and labeling in a fraction of the time required by existing methods, while preserving endogenous proteins and reducing tissue damage, with the added benefits of being cost-effective and adaptable for various tissue types.
Implementation Method 1
A magnetohydrodynamic (MHD) force is employed to accelerate the removal of lipids from and the introduction of fluorescent antibody labels into tissue samples
Implementation Method 2
The electric field and the magnetic field jointly induce charged particles in the sample and/or the electrically conducting solution to flow in a direction perpendicular to both the electric field and the magnetic field
Data Source
AI summary
The invention provides devices and methods for moving charged molecules into and out of tissue samples. This invention is particularly useful for removing endogenous heterogenous particles from tissue samples and for introducing exogenous charged molecules (e.g., antibodies, dyes) into tissue samples.