Muscle Nanosensor for Minimally Invasive Mitochondrial Testing

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Solution Overview

Problem

Current methods for measuring muscle tissue oxygen levels in vivo are invasive, costly, and lack real-time capabilities, hindering effective monitoring and treatment of mitochondrial myopathy and other disorders.

Innovation Solution

Development of an implantable oxygen nanosensor comprising a working electrode, reference electrode, counter electrode, and O2-permeable membrane, which can be implanted in muscle tissue to measure O2 levels non-invasively and provide real-time data on mitochondrial function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If open biopsy is used to obtain muscle for ex vivo spectrophotometric-based electron transport chain enzyme activity assays, then precise definition of mitochondrial function is achieved, but invasiveness and cost increase, prohibiting routine use

Engineering Contradiction:
Improvemitochondrial function measurement precisionVSAvoidinvasiveness and operational complexity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces the mechanical/open biopsy system with an optical/nanosensor-based system. The nanosensor uses optical detection methods to measure mitochondrial function parameters (such as oxygen consumption, pH, calcium) directly in vivo, eliminating the need for surgical biopsy and ex vivo analysis while maintaining measurement precision.

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

Solution Approach 2:

The patent introduces nanosensors as intermediary devices that can be minimally invasively inserted into muscle tissue to directly measure mitochondrial function parameters. These nanosensors act as mediators between the measurement system and the biological tissue, enabling real-time monitoring without requiring open biopsy or complex ex vivo processing.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If open biopsy is performed, then mitochondrial function can be measured, but real-time monitoring is not possible and results are not accessible in real-time

Engineering Contradiction:
Improvemitochondrial function measurementVSAvoidreal-time data availability
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent implements continuous real-time monitoring of mitochondrial function parameters using implantable nanosensors. The system continuously measures parameters such as oxygen consumption, pH, and calcium levels in vivo, providing uninterrupted data streams that enable real-time assessment of mitochondrial function and its changes over time or in response to interventions.

Inventive Principle:
Principle #20Continuity of useful action

3Measurement precision

If muscle biopsy is performed, then OXPHOS capacity can be assessed, but general anesthesia is often poorly tolerated and biopsies are performed typically only once in a patient's lifetime

Engineering Contradiction:
ImproveOXPHOS capacity measurementVSAvoidanesthesia tolerance and procedural risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent employs disposable or biodegradable nanosensors that can be minimally invasively inserted and removed or allowed to degrade naturally. These nanosensors eliminate the need for repeated general anesthesia by enabling multiple measurements over time through simple insertion procedures that do not require anesthesia, thereby removing the harmful factor of anesthesia tolerance issues.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Measurement precision

If conventional measurement methods are used, then mitochondrial function can be assessed, but the methods are invasive and costly, prohibiting use in routine screening and disease monitoring

Engineering Contradiction:
Improvemitochondrial function assessmentVSAvoidcost and procedural complexity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent changes the measurement parameters and methods by using nanoscale sensors that detect mitochondrial function parameters (oxygen, pH, calcium, etc.) through optical or electrochemical means. This paradigm shift from macroscopic biopsy-based measurement to nanoscale in vivo sensing dramatically reduces procedural complexity and cost while maintaining measurement precision, enabling routine screening and monitoring applications.

Inventive Principle:
Principle #35Parameter changes

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 minimally-invasive, repeated, and quantitative assessments of mitochondrial function, allowing for improved diagnosis, monitoring, and therapeutic interventions in mitochondrial diseases and other conditions affecting muscle oxygen levels.

Implementation Method 1

an O2-permeable membrane bounding at least one portion of the inner electrolyte cell

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

an O2 sensor comprising: (i) a working electrode; (ii) a reference electrode; (iii) a counter electrode; (iv) an inner electrolyte cell

Methodology Applied
Scientific EffectElectrochemical reaction: Electrochemiluminescence

Data Source

PatentUS20250268495A1Muscle nanosensor for minimally-invasive tissue measurement of mitochondrial functions
Publication Date: 2025.08.28 THE CHILDRENS HOSPITAL OF PHILADELPHIA
  • US20250268495A1 patent drawing
  • US20250268495A1 patent drawing
  • US20250268495A1 patent drawing

AI summary

The present disclosure provides methods, nanosensor devices, and uses for in vivo tissue measurement of mitochondrial physiology, including tissue oxygen and other readouts, such as in mitochondrial myopathy, disease, diagnosis, biomarker assessment, and monitoring of interventions and therapies.