Catheter Fluorescence Mitochondrial Function Assessment

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Solution Overview

Problem

Current methods for assessing mitochondrial function in living subjects are limited in their ability to detect early-stage myocardial injury and infarct size following ischemic events, which hinders timely intervention and effective treatment of coronary diseases.

Innovation Solution

A catheter-based device that uses fluorescence signals from intrinsic mitochondrial fluorophores like NADH and flavoprotein to assess mitochondrial function non-invasively, correlating the redox ratio with metabolic states and mitochondrial dysfunction, allowing for early detection of myocardial injury and infarct size.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If molecular methods (e.g., MMP expression, radiolabeled Annexin A5) are used to detect atherosclerotic plaques or programmed cell death, then detection capability is provided, but early-stage detection of coronary events is not enabled and clinical efficacy is limited

Engineering Contradiction:
Improvedetection capabilityVSAvoidearly-stage detection timing
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes the detection parameter from molecular markers (MMP expression, Annexin A5) to optical parameters (fluorescence signals from intrinsic mitochondrial fluorophores). This parameter change enables earlier detection by directly measuring mitochondrial function, which changes before molecular marker expression becomes detectable, thus resolving the timing limitation of conventional molecular methods

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces complex molecular detection systems with a simplified optical measurement system. By using fluorescence spectroscopy to detect intrinsic mitochondrial fluorophores (NADH, flavoproteins), the system substitutes complex molecular assays with direct optical measurement, enabling earlier and more reliable detection of mitochondrial dysfunction that precedes molecular changes

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

2Loss of time

If infarct size is quantified early after reperfusion therapy, then timely intervention is enabled, but the parameter is difficult to quantify

Engineering Contradiction:
Improvetiming of infarct size quantificationVSAvoidinfarct size quantification accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent introduces fluorescence signals from intrinsic mitochondrial fluorophores as an intermediary marker to indirectly quantify infarct size. Instead of directly measuring infarct size (which is difficult early after reperfusion), the system measures fluorescence changes that correlate with mitochondrial dysfunction and infarct development, providing both early timing capability and accurate quantification through the intermediary optical signal

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates an optical copy of mitochondrial function through fluorescence emission. The fluorescence signals from NADH and flavoproteins serve as an optical replica of mitochondrial metabolic state, which correlates with infarct size. This optical copying enables non-invasive, early, and accurate quantification without requiring direct tissue sampling or complex imaging

Inventive Principle:
Principle #26Copying

3Measurement precision

If invasive procedures are used to assess mitochondrial function, then accurate measurement is achieved, but patient risk and procedure complexity increase

Engineering Contradiction:
Improvemitochondrial function assessment accuracyVSAvoidinvasiveness of procedure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs self-service by measuring intrinsic fluorescent signals that are naturally present in mitochondria without requiring external contrast agents, dyes, or invasive tissue sampling. The mitochondrial fluorophores (NADH, flavoproteins) serve themselves as the measurement target, eliminating the need for invasive procedures while maintaining measurement accuracy through direct optical detection of native mitochondrial components

Inventive Principle:
Principle #25Self-service

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

Enables accurate and early assessment of myocardial injury and infarct size, potentially predicting acute cardiac events and guiding therapeutic interventions, while minimizing invasive procedures.

Implementation Method 1

a light guide for radiating light onto a target within the subject and for receiving a fluorescence signal from the target

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8473036B2In vivo measurement of mitochondrial function
Publication Date: 2013.06.25 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US8473036B2 patent drawing
  • US8473036B2 patent drawing
  • US8473036B2 patent drawing

AI summary

Disclosed herein are devices for assessing mitochondrial function in a living subject comprising a catheter comprising a sheath defining a lumen, a distal end, and a proximal end comprising a light guide for radiating light onto a target within the subject and for receiving a fluorescence signal from the target; a light source, wherein the catheter is adapted for transmitting light from the light source to the light guide; and, a detector for receiving the fluorescence signal from the light guide and for correlating the fluorescence signal to the mitochondrial function of the target. Also disclosed are methods for assessing mitochondrial function in a living subject comprising placing a catheter proximate to a site of interest within the subject; using the catheter to acquire fluorescence signals from cells at the site of interest; and, correlating the fluorescence signals to the mitochondrial function of the cells.