Multiplexed Expansion Pathology Nanoscale Imaging
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Solution Overview
Problem
Current microscopy techniques, such as diffraction-limited microscopy, struggle to provide nanoscale precision for the examination of biomolecules in large-scale samples like human tissues, making it difficult to diagnose diseases effectively.
Innovation Solution
A method is developed to prepare an expanded biological specimen by anchoring biomolecules to a swellable polymer network, allowing for isotropic expansion while retaining spatial orientation, enabling nanoscale imaging without the need for complex hardware.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If super-resolution microscopy methods are used to achieve nanoscale precision, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent applies dimensional transformation by physically expanding the biological sample in three-dimensional space (typically 4-fold expansion), which converts nanoscale structures into sub-micron to micron-scale structures that can be resolved by conventional diffraction-limited microscopy. This spatial expansion maps nanoscale features to a larger dimensional scale accessible to standard microscopes.
Solution Approach 2:
The patent introduces an intermediary expansion medium (swellable hydrogel matrix) that acts as a physical mediator between the fixed biological sample and the imaging system. This hydrogel matrix allows controlled isotropic expansion of the sample, effectively bridging the gap between nanoscale biological structures and the resolution capabilities of conventional microscopes.
2Measurement precision
If electron microscopy methods are used to achieve nanoscale resolution, then measurement precision is improved, but ease of operation deteriorates
Solution Approach 1:
The patent replaces complex mechanical and operational systems (electron microscopy hardware and procedures) with a chemical-biological expansion process combined with conventional optical microscopy. The expansion medium chemically interacts with the sample to achieve physical expansion, eliminating the need for complex electron microscopy instrumentation and specialized operational skills.
3Ease of operation
If conventional diffraction-limited microscopy is used, then ease of operation is maintained, but measurement precision deteriorates
Solution Approach 1:
The patent applies dimensional transformation by physically expanding the biological sample in three-dimensional space (typically 4-fold expansion), which converts nanoscale structures into sub-micron to micron-scale structures that can be resolved by conventional diffraction-limited microscopy. This spatial expansion maps nanoscale features to a larger dimensional scale accessible to standard microscopes.
4Measurement precision
If super-resolution imaging is applied to large-scale samples, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent applies dimensional transformation by physically expanding the biological sample in three-dimensional space (typically 4-fold expansion), which converts nanoscale structures into sub-micron to micron-scale structures that can be resolved by conventional diffraction-limited microscopy. This spatial expansion maps nanoscale features to a larger dimensional scale accessible to standard microscopes.
Solution Approach 2:
The patent introduces an intermediary expansion medium (swellable hydrogel matrix) that acts as a physical mediator between the fixed biological sample and the imaging system. This hydrogel matrix allows controlled isotropic expansion of the sample, effectively bridging the gap between nanoscale biological structures and the resolution capabilities of conventional microscopes.
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 method allows for nanoscale precision in microscopic analysis of clinical samples, including FFPE and fresh frozen tissues, using conventional laboratory equipment, facilitating the diagnosis of diseases with enhanced resolution and molecular identity.
Implementation Method 1
contacting the swellable polymer with a solvent or liquid to cause the swellable polymer to swell
Implementation Method 2
treating the specimen with a bifunctional crosslinker
Implementation Method 3
polymerizing the precursors to form a swellable polymer within the specimen
Data Source
AI summary
The invention provides a method for preparing an expanded biological specimen suitable for microscopic analysis. Expanding the biological sample can be achieved by anchoring biomolecules to a polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described below. 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, biological specimen.