CTC Detection via FISH Genomic Probes
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting circulating tumor cells (CTCs) in lung cancer are not sensitive enough, particularly in low cell counts, and lack the ability to quantify chromosomal abnormalities, which are crucial for early detection and monitoring of cancer progression.
Innovation Solution
A method involving the selection of CTCs based on nuclear area and circularity, followed by hybridization with labeled nucleic acid probes for specific chromosomal regions (3p22.1, 10q22.3, chromosome 10 centromeric, and chromosome 3 centromeric) and evaluation through fluorescence in situ hybridization (FISH) to detect genetic abnormalities, combined with immunohistochemistry for surfactant proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional CTC detection methods are used, then the detection process is simple, but the sensitivity is insufficient particularly in low cell counts
Solution Approach 1:
The detection process is divided into distinct sequential steps: (1) nuclear area and circularity assessment to identify candidate cells, (2) FISH hybridization with labeled probes for specific chromosomal regions, (3) signal evaluation to detect genetic abnormalities, and (4) CTC detection based on hybridization patterns. This segmentation allows each step to be optimized independently, improving overall detection sensitivity while maintaining manageable complexity through standardized protocols.
Solution Approach 2:
Labeled nucleic acid probes serve as intermediaries between the CTCs and the detection system. The probes hybridize to specific chromosomal regions (3p22.1, 10q22.3, centromeric regions) and produce detectable signals that amplify the presence of CTCs, enabling sensitive detection even at low cell counts without requiring direct visualization of the rare cells themselves.
2Measurement precision
If chromosomal abnormalities are quantified using conventional methods, then the analysis is straightforward, but the ability to quantify chromosomal abnormalities is lacking
Solution Approach 1:
The mechanical/cytogenetic analysis of chromosomal abnormalities is replaced with a molecular biology approach using FISH. Instead of physically analyzing chromosome structures, the method uses labeled nucleic acid probes that hybridize to specific chromosomal regions, allowing quantitative detection of chromosomal abnormalities through fluorescent signal analysis. This substitution enables precise quantification of abnormalities such as gains or losses of specific chromosomes or chromosomal regions.
Solution Approach 2:
The method employs fluorescently labeled nucleic acid probes that produce detectable color/fluorescence changes when hybridized to target chromosomal regions. Different probes are labeled with distinct fluorescent markers, allowing simultaneous detection of multiple chromosomal abnormalities. The intensity and distribution of fluorescent signals provide quantitative information about the extent and type of chromosomal abnormalities present in CTCs.
3Reliability
If early detection methods are used, then the diagnosis timing is early, but the accuracy and reliability are insufficient
Solution Approach 1:
The method changes the detection parameters from conventional CTC counting to multi-parameter analysis including nuclear area, circularity, and FISH signal patterns. By analyzing multiple parameters simultaneously (morphological features combined with chromosomal abnormality detection), the system achieves higher diagnostic accuracy and reliability for early detection, reducing false positives and enabling more confident early diagnosis.
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 the sensitive detection and quantification of CTCs, enabling early diagnosis, monitoring treatment response, and staging of lung cancer, with improved sensitivity and accuracy compared to existing methods.
Implementation Method 1
hybridizing the selected cells with labeled nucleic acid probes for 3p22.1, 10q22.3, chromosome 10 centromeric (cep10) and chromosome 3 centromeric (cep3); evaluating the signal pattern for the selected cells by detecting fluorescence in situ hybridization from cells
Data Source
AI summary
The present disclosure comprises a method of detecting circular tumor cells and methods of detecting, evaluating, or staging cancer in a patient, as well as a method of monitoring treatment of cancer in a patient using the claimed method. In other embodiments, the method provides for directed to a method of determining the level of circulating tumor cells (CTCs) in a sample having blood cells from a patient by contacting a sample having blood cells from a patient.