CTC Size Distribution Analysis for Metastasis Detection

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Solution Overview

Problem

Current methods for assessing prostate cancer, particularly for detecting visceral metastasis, lack effective biomarkers, and existing circulating tumor cell (CTC) assays are not sensitive enough to predict the onset or presence of aggressive forms of the disease.

Innovation Solution

A method involving the isolation and analysis of circulating tumor cells using a nanostructured surface device with a microfluidic chaotic mixer, followed by measuring and comparing cell and nucleus size distributions to assign a metastatic stage of prostate cancer, utilizing a computer-based system for accurate assessment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional CTC assays are used to detect circulating tumor cells, then CTC detection is achieved, but the sensitivity is insufficient to predict aggressive disease forms and visceral metastasis

Engineering Contradiction:
ImproveCTC detection sensitivityVSAvoidprediction accuracy for visceral metastasis
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent segments CTCs into distinct subpopulations based on nuclear size (large, medium, small, and very small nuclear CTCs). This segmentation allows for more precise characterization of aggressive disease forms, as very small nuclear CTCs specifically correlate with visceral metastasis, thereby improving both detection sensitivity and prediction accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by focusing measurement on specific nuclear size ranges rather than treating all CTCs uniformly. By measuring and analyzing the distribution of nuclear sizes, the method identifies specific subpopulations (particularly very small nuclear CTCs) that have higher predictive value for visceral metastasis, enhancing the reliability of disease progression prediction

Inventive Principle:
Principle #3Local quality

2Measurement precision

If additional morphological analysis is incorporated into CTC assays, then detection accuracy for aggressive disease forms improves, but assay complexity increases

Engineering Contradiction:
Improvedetection accuracy for aggressive diseaseVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex manual morphological analysis with automated image analysis technology. Digital imaging and computer-based measurement systems automatically quantify nuclear size and classify CTCs into subpopulations, maintaining high detection accuracy while significantly reducing assay complexity and enabling high-throughput processing

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from general CTC presence to specific nuclear size distribution. By measuring nuclear diameter or area and comparing against established thresholds, the assay efficiently identifies aggressive disease forms without requiring complex multi-parameter analysis, thus improving accuracy while keeping the assay relatively simple

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS10823736B2Method of assessing disease condition of cancer
Publication Date: 2020.11.03 RGT UNIV OF CALIFORNIA
  • US10823736B2 patent drawing
  • US10823736B2 patent drawing
  • US10823736B2 patent drawing

AI summary

A method, system and computer-readable medium for assessing a disease condition of a cancer of a subject, including: receiving a blood sample from the subject; isolating a plurality of circulating tumor cells (CTCs) from the blood sample; measuring at least one of cell or cell nucleus sizes of each of the plurality of CTCs; determining a measured CTC size distribution of the plurality of CTCs based on the measuring; comparing the measured CTC size distribution to a reference CTC size distribution using a computer; and assigning the disease condition of the cancer of the subject based on the comparing.