Folic Acid Functionalized Copper Sulfide Nanoparticles for Ovarian Cancer Detection

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Solution Overview

Problem

Current methods for detecting ovarian circulating tumor cells (CTCs) lack sensitivity and specificity, particularly due to the rarity of ovarian CTCs and down-regulation of EpCAM surface antigens, making it difficult to accurately identify these cells in peripheral blood.

Innovation Solution

A photoacoustic flow cytometry system using folic acid functionalized copper sulfide nanoparticles (FA-CuS NPs) that are specifically taken up by ovarian cancer cells, allowing for the detection of ovarian CTCs through photoacoustic signals generated by laser illumination and detected with an acoustic sensor.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional enrichment methods using EpCAM are used to detect ovarian CTCs, then the detection process is simplified, but the sensitivity is insufficient due to down-regulation of EpCAM and rarity of ovarian CTCs

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the detection parameter from EpCAM surface antigen to folate receptor alpha (FRα) surface antigen. Ovarian CTCs overexpress FRα while maintaining other epithelial markers, providing a reliable target for detection. This parameter change enables sensitive detection of ovarian CTCs that have down-regulated EpCAM during EMT.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces folate-conjugated nanoparticles as intermediaries that specifically bind to FRα on ovarian CTC surfaces. These nanoparticles serve as mediators between the detection system and the rare ovarian CTCs, enabling sensitive detection through their unique optical properties and targeted binding to FRα-overexpressing cells.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If flow cytometry is used to detect rare ovarian CTCs, then the detection speed is improved, but the ability to detect cells at physiologically relevant concentrations is insufficient

Engineering Contradiction:
Improvedetection speedVSAvoiddetection accuracy at low concentration
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

Folate-conjugated nanoparticles act as amplifying intermediaries that bind to FRα on rare ovarian CTCs. Each nanoparticle carries multiple folate molecules and generates strong optical signals, enabling detection of cells at physiologically relevant concentrations (1-10 cells/mL) with high speed and accuracy through flow cytometry.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses composite nanoparticle structures combining folate conjugates with materials exhibiting unique optical properties (such as gold nanoparticles or quantum dots). These composite materials provide both specific binding to FRα and strong detection signals, enabling sensitive and rapid detection of rare ovarian CTCs in clinical samples.

Inventive Principle:
Principle #40Composite materials

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

The system enables non-invasive, high-intensity photoacoustic signal detection of ovarian CTCs at physiologically relevant concentrations, improving the sensitivity and specificity of ovarian cancer diagnosis and potentially detecting early stages of metastasis.

Implementation Method 1

illuminating the test sample with laser light, and detecting the presence of the ovarian circulating tumor cell in the subject when a photoacoustic signal generated by the nanoparticle is detected with an acoustic sensor

Methodology Applied
Scientific EffectPhotoacoustic effect: Photoacoustic Effect

Data Source

PatentUS20230400412A1Folic acid functionalized copper sulfide nanoparticles for the detection of ovarian cancer cells in flow
Publication Date: 2023.12.14 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US20230400412A1 patent drawing
  • US20230400412A1 patent drawing
  • US20230400412A1 patent drawing

AI summary

The disclosure provides a system, compositions, and methods for detecting ovarian cancer cells by photoacoustic flow cytometry.