Fluorescent Nanotube Conjugates for EV Detection

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Solution Overview

Problem

The detection and quantification of extracellular vesicles (EVs) are hindered by their small size and low refractive index, leading to challenges in accurate counting and phenotyping due to weak fluorescence signals from the limited number of fluorophores, which impedes their use as diagnostic biomarkers and therapeutics.

Innovation Solution

A compound comprising a nanomaterial carrier, such as boron nitride nanotubes or carbon nanotubes, linked with a fluorescent entity and a biomolecule configured to connect to EVs, enhancing light scattering and fluorescence detection signals for improved EV detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If conventional fluorophores are used to stain EVs, then the EVs can be detected by fluorescent imaging, but the fluorescence signal is too weak due to the small number of fluorophores on each EV

Engineering Contradiction:

Improvefluorescence signal intensityVSAvoidnumber of fluorophores per EV

Core Design Contradiction:

Illumination intensityVSQuantity of substance

Solution Approach 1:

The patent uses composite fluorescent nanoparticles consisting of a fluorescent core (such as quantum dots or fluorescent polymers) combined with targeting ligands (such as antibodies or peptides) on the surface. This composite structure provides both strong fluorescence signal and specific binding to EV surface markers, resolving the contradiction between signal intensity and binding capacity.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The fluorescent nanoparticles are designed to perform multiple functions simultaneously: they provide strong fluorescence signal for detection, enable specific binding to EVs through surface ligands, and can also serve as platforms for multiplexed detection of multiple EV markers. This multi-functionality allows a single probe to address multiple detection requirements.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If high-resolution imaging flow cytometry is used to detect EVs, then phenotyping can be performed by fluorescent signals, but accurate quantification is hindered by small size and low refractive index causing weak light scattering

Engineering Contradiction:

ImproveEV quantification accuracyVSAvoidlight scattering detection difficulty

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent modifies the optical parameters of the detection system by using fluorescent nanoparticles with high quantum yield and appropriate size (50-200 nm) to enhance light scattering properties. The nanoparticles' optical parameters are optimized to improve both fluorescence signal and light scattering, enabling accurate EV quantification despite their small size and low refractive index.

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If more fluorophores are added to each EV to enhance fluorescence signal, then phenotyping sensitivity improves, but the small size of EVs limits the number of fluorophores that can be accommodated

Engineering Contradiction:

Improvephenotyping sensitivityVSAvoidEV volume

Core Design Contradiction:

Measurement precisionVSVolume of moving object

Solution Approach 1:

The patent replaces traditional small-molecule fluorophores with fluorescent nanoparticles that have significantly higher brightness per particle. This substitution allows achieving the same or better phenotyping sensitivity with fewer particles, accommodating the limited volume of small EVs while maintaining high detection sensitivity.

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

The described solution significantly enhances the detection and quantification of EVs through increased light scattering and fluorescence signals, overcoming the limitations of existing methods and facilitating their validation as diagnostic biomarkers and therapeutics.

Implementation Method 1

enhancing light scattering and fluorescence detection signals for improved EV detection

Methodology Applied

Scientific EffectLight scattering: Scattering

Implementation Method 2

fluorescent entity connected to a second end of the first linker... detecting at least one of light scattering and fluorescence of the marked EV

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS20220291207A1High-brightness fluorophores for quantification and phenotyping of extracellular vesicles

Publication Date: 2022.09.15 MICHIGAN TECHNOLOGICAL UNIVERSITY

AI summary

A compound includes a nanomaterial carrier, a first linker having a first end connected to the nanomaterial carrier, a second linker having a second end connected to the nanomaterial carrier, a fluorescent entity connected to a second end of the first linker, and a biomolecule connected to a second end of the second linker. The biomolecule is configured to connect to a cluster of differentiation (CD) of an extracellular vesicle (EV). A method is also disclosed.