Label-Free Cancer Screening via FLIM Redox Ratio Analysis

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Solution Overview

Problem

Current methods for diagnosing and treating prostate cancer are often ineffective due to late-stage diagnoses and resistance to standard chemotherapies, particularly in the castration-resistant prostate cancer phenotype, where there is a lack of experimental tools to predict therapy response and mitochondrial dysfunction is prevalent.

Innovation Solution

A label-free drug screening and diagnostic method using fluorescence lifetime imaging microscopy (FLIM) to determine the ratio of bound NAD(P)H to bound FAD (FLIRR) in cancer cells and tissues, which indicates cancer treatment efficacy and heterogeneity, combined with artificial intelligence (AI) for data analysis and grading, allowing for early detection and personalized treatment approaches.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard chemotherapies are used for castration-resistant prostate cancer, then treatment is provided, but the treatment is largely ineffective

Engineering Contradiction:

Improvetreatment efficacyVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the parameter being measured from standard intensity-based fluorescence to fluorescence lifetime, which provides a different metabolic readout that is not confounded by drug resistance mechanisms. This allows detection of mitochondrial dysfunction and metabolic changes that occur even when cells are resistant to conventional chemotherapies.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses FLIRR as an intermediary biomarker that reflects mitochondrial metabolic state. Rather than directly measuring drug response, the method measures the intermediary metabolic parameter (FLIRR) that correlates with treatment efficacy and can predict response before clinical outcomes are observed.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If late-stage diagnosis is made, then cancer is detected, but chemotherapeutics is less effective

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddiagnosis timing

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent enables preliminary detection of cancer metabolic changes before morphological changes occur. By measuring FLIRR in biopsy samples, the method can identify cancerous tissue based on mitochondrial metabolic alterations that precede visible structural changes, allowing earlier diagnosis and intervention.

Inventive Principle:

Principle #10Preliminary action

3Ease of manufacture

If label-free methods are used, then simplicity is improved, but measurement precision may be affected

Engineering Contradiction:

Improvemethod simplicityVSAvoiddetection accuracy

Core Design Contradiction:

Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent replaces intensity-based optical measurement with fluorescence lifetime measurement. This substitution eliminates the confounding effects of light scattering and absorption that plague intensity-based methods, providing more precise metabolic information without requiring exogenous labels or dyes.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 method enables early detection of prostate cancer, predicts drug response, and identifies effective treatment compounds by quantifying metabolic changes in cancer cells, potentially shortening drug screening time and improving treatment outcomes by addressing mitochondrial dysfunction.

Implementation Method 1

determining the ratio of bound NAD (P) H to bound FAD (the fluorescence lifetime imaging redox ratio (FLIRR)) via fluorescence lifetime imaging microscopy (FLIM)

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

the FLIM is multiphoton FLIM

Methodology Applied

Scientific EffectMultiphoton excitation:

Implementation Method 3

the calculation uses time correlated single photon counting or fast FLIM frequency domain

Methodology Applied

Scientific EffectTime correlated single photon counting:

Data Source

PatentUS20240353393A1Label free drug and tissue biopsy screening/diagnostic in cancer

Publication Date: 2024.10.24 UNIV OF VIRGINIA PATENT FOUND

AI summary

Provided herein is a drug screening method as well as an automatic screening of biopsy tissue to identify and grade cancer progression without any labeling.