AFM Stiffness Mapping for Tumor Malignancy Classification
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Solution Overview
Problem
Current methods for assessing cancer progression in tumors are limited by their inability to accurately measure the mechanical properties of cancer cells and tissues, particularly in the context of hypoxia, and often focus on peripheral regions rather than the entire tumor, neglecting structural and mechanical heterogeneity.
Innovation Solution
A method using atomic force microscopy (AFM) to measure the stiffness distribution of tumor biopsy samples with high spatial resolution, distinguishing between normal, benign, and malignant tissues by analyzing the elasticity of tissue samples from core to periphery and correlating with hypoxia-induced softening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If stiffness is measured at one specific site only, then the measurement is simple and quick, but it does not appropriately reflect the structural heterogeneity of a cell
Solution Approach 1:
The patent divides the tumor tissue into multiple measurement sites (periphery and core regions) and performs stiffness measurements at each site. This segmentation allows the system to capture the mechanical heterogeneity of the tumor by measuring multiple locations rather than a single point, thereby resolving the contradiction between measurement speed and representation of heterogeneity.
Solution Approach 2:
The patent applies different measurement approaches to different regions of the tumor tissue. The periphery region is measured using one method while the core region is measured using another method, allowing each region to be characterized according to its specific local properties. This local quality approach enables accurate representation of structural heterogeneity while maintaining efficient measurement throughput.
2Area of stationary object
If unconfined compression is used to measure the whole mammary gland, then the entire tissue can be assessed, but only the peripheral region is accessible for testing while the bulk of the underlying cancer is not accessible
Solution Approach 1:
The patent segments the tumor assessment into two distinct regions: the peripheral region and the core region. By measuring both regions separately using appropriate methods for each, the system achieves comprehensive tissue coverage while overcoming the accessibility limitation. The peripheral region can be accessed through standard compression methods, while the core region is accessed through targeted measurement techniques.
Solution Approach 2:
The patent introduces an intermediary approach to access the tumor core region. By using a specialized measurement system that can penetrate or access the core area, the system overcomes the physical barrier created by the peripheral tissue and blood vessels, enabling measurement of the previously inaccessible bulk cancer tissue.
3Ease of operation
If mechanical properties are measured in isolated cancer cells, then the cells can be studied in a controlled environment, but the absence of the native tissue environment influences the mechanical behavior
Solution Approach 1:
The patent changes the measurement parameters and conditions to better reflect the native tissue environment. By adjusting factors such as measurement depth, force application methods, and environmental conditions, the system maintains the controlled environment benefits while obtaining mechanical behavior data that accurately represents the cells in their native context.
Solution Approach 2:
The patent introduces the native tissue environment as an intermediary factor in the measurement process. By incorporating elements of the original tissue context into the measurement system, the system preserves the mechanical behavior accuracy while maintaining sufficient control over the measurement process.
4Quantity of substance
If stiffness data is obtained from individual cells in culture and from tissues in situ, then comprehensive data is collected, but the inconsistency of stiffness data emphasizes the importance of considering microenvironmental factors
Solution Approach 1:
The patent changes the measurement parameters to account for microenvironmental factors such as extracellular matrix composition, tissue architecture, and physiological conditions. By adjusting these parameters, the system achieves consistent stiffness data across different measurement contexts while maintaining comprehensive data collection from both cultured cells and in situ tissues.
Solution Approach 2:
The patent incorporates feedback mechanisms that compare stiffness measurements from different sources (cells in culture vs. tissues in situ) and adjust the measurement protocol accordingly. This feedback approach identifies and corrects inconsistencies caused by microenvironmental differences, ensuring precise and reliable stiffness data while maintaining comprehensive data volume.
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 allows for accurate classification of tumor samples based on stiffness distributions, providing a reliable marker for malignant transformation and tumor progression by capturing the heterogeneity of tumor tissues and the impact of hypoxia on mechanical properties.
Implementation Method 1
Atomic force microscopy (AFM) has been used to probe the mechanical properties of isolated cancer cells
Implementation Method 2
Cell elasticity and deformability have been recognized as a marker for the phenotypic consequences of alterations in cytoarchitecture and adhesion
Implementation Method 3
Stiffness or elasticity in the sense of the invention means the resistance of a tissue sample or tissue to deformation by an applied force
Implementation Method 4
cancer detection has been achieved by unconfined compression of the whole mammary gland
Data Source
Figure 1a~1d
Figure 2a~2b
Figure 3a~3c
AI summary
The present invention relates to a method for classifying a tissue biopsy sample obtained from a tumour, comprising determining a plurality of stiffness values for said sample by measuring a plurality of points on the sample with a spatial resolution of at least 100 µm and assigning the sample to a probability of malignancy. A sample showing a unimodal stiffness distribution is assigned to a high probability of being non-malignant, and a sample showing an at least bimodal stiffness distribution is assigned to a high probability of being malignant, wherein said stiffness distribution is characterized by a first peak exhibiting an at least two fold higher stiffness value than a second peak. The present invention further relates to a system for classifying a tumour tissue biopsy sample.