NIR Fluorescent Probe RTMI for Lysosomal ROS Imaging

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Solution Overview

Problem

Current fluorescent sensors for detecting reactive oxygen species (ROS) in living systems suffer from poor sensitivity, limited reactivity, poor photostability, and inability to image basal ROS levels at subcellular resolution, particularly in the near-infrared (NIR) region, which is essential for deep tissue penetration and reduced photo damage.

Innovation Solution

Development of a Near Infrared Reactive Oxygen Species (NIR ROS) Sensor compound (RTMI) with a controlled fluorescence on-off switching mechanism, synthesized from IR780 and resorcinol, which reacts with ROS to emit strong fluorescence at 705 nm, allowing for subcellular resolution imaging of ROS in live cells, particularly in lysosomes, with improved reactivity and photo stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current fluorescent sensors are used to detect ROS in living systems, then detection capability is provided, but sensitivity is poor and subcellular resolution imaging is not achieved

Engineering Contradiction:
Improvedetection sensitivityVSAvoidbasal ROS levels
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs parameter changes by utilizing near-infrared (NIR) fluorescence emission (700-900 nm) instead of traditional visible light wavelengths. This parameter change in the electromagnetic spectrum enables deeper tissue penetration, reduced background autofluorescence, and improved detection sensitivity for basal ROS levels in living systems without requiring high ROS concentrations

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite fluorescent sensor molecules that combine ROS-reactive moieties with NIR fluorophore structures. These composite materials integrate the ROS detection capability with enhanced optical properties, achieving both specific ROS reactivity and superior NIR fluorescence emission for high-sensitivity imaging

Inventive Principle:
Principle #40Composite materials

2Reliability

If traditional fluorescent sensors are used, then ROS detection is possible, but photostability is poor leading to photo damage

Engineering Contradiction:
Improvephoto stabilityVSAvoidphoto damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent shifts the operational wavelength parameter to the near-infrared region (700-900 nm), which has lower photon energy compared to visible light. This parameter change reduces photodamage to biological samples while maintaining detection capability, thereby improving photostability and reliability for long-term imaging experiments

Inventive Principle:
Principle #35Parameter changes

3Illumination intensity

If visible light fluorescence is used for imaging, then detection is achieved, but deep tissue penetration is limited and background interference occurs

Engineering Contradiction:
Improvefluorescence signalVSAvoidbackground interference
Core Design Contradiction:
Illumination intensityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the fluorescence emission parameter from visible light (400-700 nm) to near-infrared light (700-900 nm). This parameter change exploits the optical window in biological tissues where absorption and scattering are minimized, enabling deep tissue penetration and significantly reducing background autofluorescence interference while maintaining strong fluorescence signals

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If conventional ROS sensors are used, then general ROS detection is possible, but subcellular resolution imaging is not achieved

Engineering Contradiction:
Improvespatial resolutionVSAvoidsubcellular region
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent utilizes the superior optical properties of near-infrared fluorescence (reduced scattering, increased penetration depth) to enhance the effective resolution for subcellular imaging. The NIR parameter enables clearer visualization of subcellular structures and ROS localization with spatial resolution that exceeds the capabilities of traditional visible light fluorescence microscopy

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

RTMI effectively detects a broad range of ROS, including hydroxyl radicals, superoxide, and peroxynitrite, providing superior spatial resolution and retention within cells, while avoiding interference from cellular pigments, thus enabling effective imaging of ROS in live cells with reduced photo damage.

Implementation Method 1

a new near infrared (NIR) reactive oxygen species (ROS) sensor designed with controlled fluorescence on-off switching mechanism

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

reacts with ROS to emit strong fluorescence at 705 nm

Methodology Applied
Scientific EffectChemiluminescence: Chemiluminescence

Data Source

PatentUS11422091B2Turn-on near infrared fluorescent probes for imaging lysosomal ROS in live cells at subcellular resolution
Publication Date: 2022.08.23 UNIV OF MASSACHUSETTS
  • US11422091B2 patent drawing
  • US11422091B2 patent drawing
  • US11422091B2 patent drawing

AI summary

This invention is in the field of fluorescence imaging and relates to a new near infrared (NIR) reactive oxygen species (ROS) sensor designed with controlled fluorescence on-off switching mechanism.