Nucleic Acid-Functionalized Nanoparticles for Rapid Staph Detection

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Solution Overview

Problem

Current clinical methods for detecting staphylococcus infections are slow, taking 2-3 days, which delays prognosis and allows infections to progress, necessitating a rapid, sensitive, and cost-effective point-of-care diagnostic platform.

Innovation Solution

Development of functionalized nanoparticles with a nanoparticle core and a coating of nucleic acid moieties, including a single-stranded sequence of 50 or less nucleotides with a nuclease cleavage site, that aggregate upon nuclease treatment, enabling rapid detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current clinical methods are used for detecting staphylococcus, then detection can be performed with existing technology, but the detection process takes 2-3 days which delays prognosis and allows infection to progress

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes the physical-chemical parameters of the detection system by using gold nanoparticles functionalized with specific nucleic acid sequences that undergo aggregation upon nuclease cleavage. This aggregation causes a measurable color change from red to purple/blue, enabling rapid visual detection within minutes rather than days, thus resolving the contradiction between detection sensitivity and detection time

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces complex mechanical/chemical laboratory processing systems with a simplified biosensing system based on nanoparticle aggregation and colorimetric detection. The nuclease-cleaved nucleic acid triggers nanoparticle aggregation that produces a visible color change, eliminating the need for lengthy culture methods and complex instrumentation while maintaining detection sensitivity

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

2Loss of time

If rapid detection is implemented, then detection time is reduced, but the diagnostic platform must be highly sensitive and specific to avoid false results

Engineering Contradiction:
Improvedetection timeVSAvoiddetection sensitivity
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent applies local quality by functionalizing only specific portions of the nucleic acid coating on gold nanoparticles with nuclease cleavage sites. The 5'-terminal region contains the cleavage site while other regions maintain binding specificity, allowing the nanoparticle to respond locally to nuclease presence through aggregation while maintaining overall detection specificity, thus achieving rapid detection without sacrificing sensitivity

Inventive Principle:
Principle #3Local quality

3Productivity

If a point-of-care diagnostic platform is created, then detection becomes rapid and accessible, but the platform must remain simple and cost-effective to implement

Engineering Contradiction:
Improvedetection speedVSAvoidplatform complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent implements self-service through the autonomous aggregation behavior of functionalized gold nanoparticles upon nuclease cleavage. The system requires no external power source, complex instrumentation, or sophisticated sample preparation - the nanoparticle-nuclease interaction automatically produces a visible color change, enabling simple, rapid, cost-effective point-of-care detection that maintains high productivity while minimizing device complexity

Inventive Principle:
Principle #25Self-service

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 solution allows for rapid and sensitive detection of staphylococcus infections, potentially preventing the progression to chronic diseases by providing a quick diagnostic platform.

Implementation Method 1

the single-stranded nucleic acid sequence includes a nuclease cleavage site

Methodology Applied
Scientific EffectNuclease cleavage: Enzyme

Implementation Method 2

The plurality of cleaved nanoparticles are allowed to bind to each other, thereby forming a nanoparticle aggregate

Methodology Applied
Scientific EffectNanoparticle aggregation: Coagulation

Data Source

PatentUS11549941B2Nucleic acid-functionalized nanoparticles
Publication Date: 2023.01.10 CITY OF HOPE
  • US11549941B2 patent drawing
  • US11549941B2 patent drawing
  • US11549941B2 patent drawing

AI summary

Provided herein are functionalized nanoparticle compositions and methods of using the same. The functionalized nanoparticles provided include a nuclease cleavage site and are, inter alia, useful for the formation of nanoparticle aggregates and detection of nuclease activity through nanoparticle aggregate formation.