Nanoparticle-PCR Microorganism Detection via Circular Dichroism

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Solution Overview

Problem

Current methods for diagnosing intravascular device-related infections, such as blood cultures, are inefficient due to low sensitivity, lack of specificity, and long turnaround times, leading to delayed and inappropriate antibiotic treatment, which can result in antibiotic resistance, side effects, and under-treatment of patients.

Innovation Solution

A method using PCR with nanoparticle-attached primers to generate metal-coated amplification products, detected via circular dichroism, allowing for rapid and sensitive detection of microorganisms in unpurified biological samples, including whole blood, with the ability to perform multiplex detection and determine antibiotic susceptibility in under 3 hours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If blood cultures are used to detect pathogens, then detection capability is provided, but sensitivity is low and turnaround time is long (24-72 hours)

Engineering Contradiction:

Improvedetection sensitivityVSAvoidturnaround time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the traditional mechanical/cultural detection system with a molecular biology-based PCR system. Instead of relying on bacterial growth and visual inspection in culture media, the method uses nucleic acid amplification to detect pathogen DNA directly in blood samples, achieving both high sensitivity and rapid results within hours rather than days

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from bacterial biomass (measured by culture growth) to nucleic acid concentration (measured by PCR amplification). This parameter change enables detection at much lower pathogen loads and dramatically reduces the time required for diagnosis, as nucleic acids can be amplified and detected before bacterial cultures become visible

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If blood cultures are used for pathogen detection, then detection is performed, but specificity is poor due to routine contamination with normal skin flora

Engineering Contradiction:

Improvedetection specificityVSAvoidfalse positive contamination

Core Design Contradiction:

Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and targets specific pathogen-specific nucleic acid sequences using primer pairs designed to bind only to particular pathogen genomes. By extracting only the relevant pathogen DNA sequences and ignoring background bacterial DNA, the method eliminates false positives from normal skin flora while maintaining high specificity for the target pathogen

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by using pathogen-specific primer sequences that are uniquely tailored to detect specific pathogens. Each primer pair is designed with specific nucleotide sequences that match only the target pathogen's genome, creating a localized detection mechanism that distinguishes between different pathogens and eliminates cross-contamination from normal flora

Inventive Principle:

Principle #3Local quality

3Productivity

If empiric broad-spectrum antibiotics are administered pending culture results, then patient treatment is initiated, but antibiotic resistance and side effects increase

Engineering Contradiction:

Improvetreatment speedVSAvoidantibiotic resistance

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent enables preliminary identification of the specific pathogen and its antibiotic susceptibility profile before initiating antibiotic therapy. By performing rapid PCR-based detection and susceptibility testing, the system allows clinicians to select targeted antibiotics based on actual pathogen identification rather than guessing, thereby reducing unnecessary broad-spectrum antibiotic use and preventing resistance development

Inventive Principle:

Principle #10Preliminary action

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

This approach significantly enhances the sensitivity and speed of microorganism detection, reducing morbidity and mortality by enabling early diagnosis and targeted antibiotic therapy, while minimizing the risk of antibiotic resistance and side effects.

Implementation Method 1

performing nucleic acid amplification (e.g., PCR) on a biological sample to generate a plurality of amplification products

Methodology Applied

Scientific EffectPCR amplification:

Implementation Method 2

depositing a metal shell on the nanoparticles incorporated in the amplification products to generate amplification products comprising metal coated nanoparticles

Methodology Applied

Scientific EffectMetal shell deposition: Deposition (physical)

Implementation Method 3

detecting the amplification products comprising metal coated nanoparticles using circular dichroism (CD)

Methodology Applied

Scientific EffectCircular dichroism:

Data Source

PatentUS11313001B2Compositions and methods for detection of microorganisms

Publication Date: 2022.04.26 THE RGT UNIV OF MICHIGAN

AI summary

Provided herein are compositions, systems, and methods for detecting microorganisms. In particular, provided herein are compositions, systems, and methods for rapid, multiplex detection of microorganism in unpurified biological samples.