Nanohistology Sample Embedding for AFM Cross-Section Imaging
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Solution Overview
Problem
Conventional atomic force microscopy (AFM) sample preparation methods limit the ability to access and image the interior structures of biological samples, preventing automated and parallel processing, which is necessary for high-throughput nanohistology applications.
Innovation Solution
A method involving combining a biological material with a monomer-containing material, polymerizing it, and removing the polymer to embed the biological sample, preserving its structure for cross-sectional imaging using AFM, which can be automated and integrated with machine learning for high-throughput analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Difficulty of detecting and measuring
If conventional AFM sample preparation methodology is used, then the surface of biological materials can be imaged with nanoscale resolution, but the ability to access interior structures of sample cross-section is limited
Solution Approach 1:
A polymerizable monomer-containing material is introduced as an intermediary substance that penetrates into the biological sample, allowing access to interior structures while maintaining surface integrity for AFM imaging. The monomer acts as a mediator that can be polymerized to create a removable embedding matrix.
Solution Approach 2:
The patent utilizes polymerization as a parameter change mechanism, transforming the monomer-containing material into a polymeric embedding matrix through chemical reaction. This parameter change enables the material to transition from a penetrable liquid/state to a structural embedding state, facilitating interior structure access while preserving surface morphology.
2Productivity
If conventional AFM sample preparation is used, then nanoscale surface imaging is achieved, but automated and parallel processing is not enabled
Solution Approach 1:
The monomer-containing material serves multiple functions: it acts as a penetration medium, an embedding matrix, and a structural support for the biological sample. This multi-functionality enables a single standardized protocol to handle various sample types, facilitating automated and parallel processing for high-throughput nanohistology applications.
3Difficulty of detecting and measuring
If the biological sample is embedded in polymeric material for cross-sectional imaging, then interior structures become accessible, but the surface shape and outline may be compromised
Solution Approach 1:
The patent applies local quality by ensuring the polymeric material is removed selectively from the surface region while maintaining embedding of interior structures. The monomer-containing material is designed to polymerize throughout the sample but can be locally removed from the surface, creating a duality where the surface retains its original morphology while the interior remains embedded for cross-sectional analysis.
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
Enables automated, high-throughput, and three-dimensional imaging of biological samples with nanoscale resolution, retaining the shape and outline of the biological material, suitable for diagnostic applications.
Implementation Method 1
treating the combination with an agent that polymerizes monomers of the monomer-containing material to provide a polymeric material
Data Source
AI summary
Atomic force microscopy (AFM) can be used to image biological samples with low nanomolar resolution. Compared to other imaging modalities with nanoscale resolution, AFM does not require the use of complex, costly instrumentation or toxic heavy metals to image samples. The ability of AFM to access interior structures of a sample cross-section in nanohistology applications in a controlled and automated manner is limited with conventional AFM sample preparation methodology. The present disclosure provides methods and compositions for preparing a sample for nanohistology. The methods and compositions disclosed herein can prepare a sample for nanohistology that preserve the structure of biological molecules in a sample, allowing for serial cross-sectional imaging of the sample.