Gold Nanoparticles for Noninvasive Kidney Functional Imaging

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Solution Overview

Problem

Current noninvasive fluorescence imaging techniques for kidney function are limited due to rapid accumulation and long retention of conventional organic fluorophores in background tissues, leading to low contrast and short detection time windows, making it difficult to accurately assess kidney function, especially in unilateral renal disease.

Innovation Solution

The use of NIR-emitting glutathione-coated gold nanoparticles (GS-AuNPs) that exhibit deep tissue penetration and desired in vivo behaviors, providing high-contrast noninvasive kidney functional imaging with a 50-fold contrast enhancement and a 1000-fold longer detection time window compared to conventional organic fluorophores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If conventional organic fluorophores are used for noninvasive fluorescence imaging, then the imaging can be performed with simple administration, but the fluorophores accumulate rapidly in background tissues causing low contrast and short detection time windows

Engineering Contradiction:
Improveease of administrationVSAvoidimaging contrast
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the fundamental parameter of the fluorophore material from conventional organic dyes to inorganic nanoparticles (quantum dots, upconversion nanoparticles, luminescent nanoparticles). This material parameter change enables deep tissue penetration, rapid renal clearance, and high imaging contrast while maintaining ease of intravenous administration. The inorganic nature of these nanoparticles provides unique optical properties that resolve the contradiction between simple administration and high imaging contrast.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite nanoparticle structures combining inorganic cores (semiconductor quantum dots, metal oxide upconversion nanoparticles) with functional coatings (ligands, polymers, antibodies). These composite structures integrate rapid renal clearance properties with targeted kidney imaging capabilities, achieving both high contrast imaging and ease of administration through intravenous injection.

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If conventional organic fluorophores are used, then the administration procedure is simple, but the detection time window is short due to rapid accumulation in background tissues

Engineering Contradiction:
Improveadministration simplicityVSAvoiddetection time window
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent changes the material parameter from organic fluorophores to inorganic nanoparticles with specific size and surface properties. These nanoparticles exhibit rapid renal clearance (half-life < 24 hours) while maintaining stability in circulation, creating an extended detection time window that allows longitudinal studies of kidney function without the rapid background accumulation that limits conventional organic dyes.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes short-lived inorganic nanoparticles that are rapidly cleared by the kidneys, making them ideal for single-use diagnostic imaging. Their transient presence in the body (rapid clearance) provides a limited but sufficient detection window for imaging studies, after which they are eliminated, allowing repeated imaging studies with new administrations without long-term accumulation concerns.

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

3Measurement precision

If radiological imaging techniques are used for kidney function evaluation, then accurate kidney function assessment is achieved, but the cost is high and radiation exposure occurs

Engineering Contradiction:
Improvekidney function assessment accuracyVSAvoidradiation exposure
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent substitutes radiological imaging (ionizing radiation-based) with fluorescence imaging using inorganic nanoparticles. This replacement eliminates radiation exposure while maintaining accurate kidney function assessment through the unique optical properties of nanoparticles that enable high-contrast imaging of kidney accumulation and clearance dynamics.

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

Solution Approach 2:

The patent introduces inorganic fluorescent nanoparticles as intermediary contrast agents that mediate between the imaging system and kidney function. These nanoparticles accumulate in the kidneys and provide fluorescent signals that report kidney function, replacing the need for direct radiological measurement while eliminating radiation exposure.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Illumination intensity

If in vivo NIR fluorescence imaging is used, then visualization of biological processes is achieved at high spatial and temporal resolution, but extremely low contrast in noninvasive kidney images limits its effectiveness

Engineering Contradiction:
Improvespatial and temporal resolutionVSAvoidimaging contrast
Core Design Contradiction:
Illumination intensityVSMeasurement precision

Solution Approach 1:

The patent employs composite nanoparticle structures with inorganic fluorescent cores and functional surface coatings. The inorganic core provides intense and stable fluorescent signals with deep tissue penetration, while the surface coating enables renal clearance and reduces background accumulation. This composite structure resolves the low contrast problem while maintaining high spatial and temporal resolution for visualizing kidney biological processes.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent changes the fluorophore material parameter from organic dyes to inorganic nanoparticles, which provide significantly higher fluorescent intensity and stability. This parameter change increases the signal-to-background ratio, enabling high-contrast noninvasive imaging of kidney function at high spatial and temporal resolution.

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

GS-AuNPs enable effective noninvasive imaging of kidney function, allowing for the identification of impaired kidneys and differentiation of dysfunction stages, consistent with histological evaluations, and provide comparable results to invasive imaging, overcoming the limitations of conventional organic dyes.

Implementation Method 1

illuminating the kidney with a near infrared excitation wavelength such that the nanoparticles in the kidney fluoresce

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10300151B2Methods and systems for noninvasive fluorescence-based functional imaging of kidneys
Publication Date: 2019.05.28 BOARD OF RGT THE UNIV OF TEXAS SYST
  • US10300151B2 patent drawing
  • US10300151B2 patent drawing
  • US10300151B2 patent drawing

AI summary

Methods and systems for evaluating renal function of a live subject. The method includes intravenously administering nanoparticles of a noble metal to the kidney of the live subject, followed by illuminating the kidney with a near infrared excitation wavelength such that the nanoparticles in the kidney fluoresce, and finally detecting presence or absence of nanoparticle fluorescence in the kidney. Detecting presence or absence of nanoparticle fluorescence includes obtaining at least one image of the kidney through the subject's skin.