RET Biomaterial Sensor for In Vivo Protein Detection

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Solution Overview

Problem

Current protein analysis methods for disease diagnosis and monitoring are limited by low accuracy, invasiveness, and the need for large sample sizes, with a lack of real-time, non-invasive techniques for accurately detecting protein levels in vivo.

Innovation Solution

A resonance energy transfer (RET)-based sensor system comprising a donor linked to a target binding moiety and an acceptor molecule, which produces a detectable signal when the target binds, allowing for accurate, real-time, in vivo protein detection through FRET, BRET, or CRET mechanisms, and can be implanted or used in various formats for different environments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional protein analysis methods (IHC, ELISA, flow cytometry) are used, then protein levels can be detected, but the methods are invasive, require large sample sizes, and lack real-time capability

Engineering Contradiction:
Improveprotein detection accuracyVSAvoidinvasiveness of sample collection
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces traditional mechanical/invasive sampling methods with an optical detection system. The FRET-based sensor uses fluorescent donor and acceptor molecules that emit light signals when bound to target proteins, allowing non-invasive detection through optical measurement rather than physical tissue sampling or blood draws.

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

Solution Approach 2:

The patent introduces an intermediary FRET sensor system that mediates between the target protein and the detection device. The sensor comprises a donor fluorophore and acceptor fluorophore that act as intermediaries to translate protein binding events into detectable optical signals, enabling indirect but non-invasive measurement of protein levels.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If traditional protein analysis methods are used, then protein detection is possible, but real-time in vivo detection capability is lacking

Engineering Contradiction:
Improvereal-time detection capabilityVSAvoidsensor system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the detection system into distinct functional modules: a donor fluorophore component, an acceptor fluorophore component, and target binding domains. This segmentation allows each component to be optimized independently and facilitates the construction of complex sensor systems with specific targeting capabilities for different proteins.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a universal FRET sensor platform that can detect multiple different proteins by changing the target binding domains while maintaining the same donor-acceptor fluorophore architecture. This multi-functionality reduces overall system complexity compared to developing separate detection systems for each protein target.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If traditional protein analysis methods are used, then protein levels can be measured, but accuracy and sensitivity are limited

Engineering Contradiction:
Improvedetection accuracy and sensitivityVSAvoidsample size required
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent utilizes parameter changes in the optical domain to enhance detection sensitivity. By measuring changes in fluorescence intensity ratios between donor and acceptor channels, the system can detect minute changes in protein levels with high precision, requiring minimal sample quantities compared to traditional methods.

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

The RET-based sensor system provides non-invasive, real-time detection of protein levels with increased accuracy and sensitivity, enabling effective disease diagnosis, monitoring, and treatment decision-making by measuring protein expression levels in vivo.

Implementation Method 1

a Forster resonance energy transfer (FRET) from the donor fluorophore to the acceptor molecule occurs and a detectable signal is produced

Methodology Applied
Scientific EffectForster resonance energy transfer (FRET):

Implementation Method 2

bioluminescent resonance energy transfer (BRET)

Methodology Applied
Scientific EffectBioluminescent resonance energy transfer (BRET): Bioluminescence

Implementation Method 3

chemiluminescent resonance energy transfer (CRET)

Methodology Applied
Scientific EffectChemiluminescent resonance energy transfer (CRET): Chemiluminescence

Data Source

PatentUS20240085407A1Biomaterial sensor systems
Publication Date: 2024.03.14 THE RGT UNIV OF MICHIGAN
  • US20240085407A1 patent drawing
  • US20240085407A1 patent drawing
  • US20240085407A1 patent drawing

AI summary

Provided herein is a biomaterial comprising a sensor system comprising a donor fluorophore linked to a target binding moiety (TBM) and an acceptor molecule linked to a TBM, wherein, when the TBM linked to the donor fluorophore and the TBM linked to the acceptor molecule binds to a target, a resonance energy transfer (RET; e.g., Forster (or Fluorescence) resonance energy transfer (FRET), bioluminescent resonance energy transfer (BRET), chemiluminescent resonance energy transfer (CRET), or a combination thereof) from the donor fluorophore to the acceptor molecule occurs and a detectable signal is produced. An medical device, e.g., an implant, comprising the presently disclosed biomaterial comprising a sensor system is further provided. Related medical devices and solid supports are furthermore provided herein. Use of the biomaterials and medical devices in methods of determining a level of expression of a gene, an RNA, or a protein, is additionally provided.