Kidney Tissue Expansion for Nanoscale Imaging
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Solution Overview
Problem
Current microscopy techniques, such as electron microscopy and super-resolution optical microscopies, are expensive, complex, and not readily accessible in clinical settings, making it difficult to observe the small, nanoscale changes in kidney podocyte foot processes, which are crucial for diagnosing proteinuric kidney diseases like minimal change disease.
Innovation Solution
The expansion pathology method (ExPath) physically expands kidney tissue samples by anchoring biomolecules to a polymer network and swelling it, allowing for nanoscale imaging with conventional optical microscopes without the need for specialized hardware, enabling the visualization of podocyte foot processes and other nanoscale structures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If electron microscopy or super-resolution optical microscopies are used to image podocyte foot processes, then imaging resolution is improved, but device complexity and cost increase
Solution Approach 1:
The patent changes the physical state of the tissue sample by expanding it 4-10 fold through hydrogel integration, which physically separates structures and allows conventional optical microscopes to resolve nanoscale features that were previously only visible with electron microscopy or super-resolution techniques
Solution Approach 2:
The patent creates an expanded copy of the tissue architecture within a hydrogel matrix, preserving the spatial relationships of cellular structures while enlarging them to be visible with conventional optical microscopy, thereby avoiding the need for complex electron microscopy equipment
2Measurement precision
If electron microscopy or super-resolution optical microscopies are used to image podocyte foot processes, then imaging resolution is improved, but cost increases
Solution Approach 1:
The patent uses conventional optical microscopes that are already widely available in clinical settings, replacing the need for expensive electron microscopes or super-resolution equipment, thereby significantly reducing the cost of achieving nanoscale imaging capability
Solution Approach 2:
By changing the scale parameter through physical expansion of the tissue sample, the patent makes nanoscale structures visible to conventional microscopes, eliminating the need for expensive specialized imaging equipment
3Device complexity
If conventional optical microscopy is used to image podocyte foot processes, then device complexity is reduced, but measurement precision deteriorates
Solution Approach 1:
The patent physically expands the tissue sample 4-10 fold by integrating it with a hydrogel matrix, which enlarges subcellular structures to a scale that can be resolved by conventional optical microscopes, thereby achieving nanoscale imaging capability without increasing device complexity
Solution Approach 2:
The patent adds a physical expansion dimension to the imaging problem, using hydrogel swelling to magnify the tissue architecture in three dimensions, which allows conventional microscopes to resolve features that would otherwise require super-resolution techniques
4Ease of operation
If conventional optical microscopy is used to image podocyte foot processes, then ease of operation is improved, but measurement precision deteriorates
Solution Approach 1:
The patent uses physical expansion of the tissue sample through hydrogel integration to enlarge nanoscale structures, making them visible with conventional optical microscopes that are easy to operate, thereby combining ease of use with improved measurement precision
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
ExPath provides high-resolution imaging of kidney tissue samples, improving the diagnosis of kidney diseases by enabling the visualization of nanoscale changes that were previously unresolvable with conventional microscopes, facilitating accurate identification of pathological alterations and enhancing computational diagnosis in early breast lesions.
Implementation Method 1
contacting the swellable polymer with a solvent or liquid to cause the swellable polymer to swell
Data Source
AI summary
The invention provides a method for preparing an expanded renal (kidney) tissue sample suitable for microscopic analysis. Expanding the kidney sample can be achieved by binding, e.g., anchoring, key biomolecules to a polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described herein. As the biomolecules are anchored to the polymer network, isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, kidney sample.