Portable Fluorimeter for Rapid Beta-Lactamase Detection

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Solution Overview

Problem

Current methods for diagnosing antibiotic-resistant bacteria in neonates are inefficient, particularly in resource-limited settings, due to the need for laboratory-based MIC testing that is slow and not readily available, leading to delayed treatment and poor clinical outcomes.

Innovation Solution

A portable wide field fluorimeter system that performs fluorometric assays using a microfluidic device and a detection reagent with a fluorescent probe to detect beta-lactamase enzymes in patient samples, providing results within 20 minutes, suitable for point-of-care settings.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If laboratory culture and MIC testing are used to identify antibiotic resistance, then measurement precision is improved, but loss of time worsens (1-3 days required)

Engineering Contradiction:
Improveantibiotic resistance identification accuracyVSAvoidtesting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the mechanical/cultural laboratory testing system with a fluorometric detection system that uses fluorescent probes to detect beta-lactamase enzyme activity. This substitution enables rapid detection within 20 minutes while maintaining accuracy by measuring enzyme presence that indicates antibiotic resistance, eliminating the need for prolonged culture and MIC testing.

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

Solution Approach 2:

The patent changes the detection parameter from measuring bacterial growth inhibition (MIC) to measuring beta-lactamase enzyme activity through fluorescence intensity. This parameter change allows direct detection of resistance mechanism presence, providing rapid results without requiring the time-consuming process of observing bacterial growth patterns over days.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If comprehensive gene sequence analysis is used to identify beta-lactamase types, then measurement precision is improved, but device complexity and cost worsen

Engineering Contradiction:
Improvebeta-lactamase type identification accuracyVSAvoidtesting system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex molecular biology equipment required for PCR and gene sequence analysis with a simple fluorimeter system. The detection uses fluorescent probes that directly bind to beta-lactamase enzymes, allowing type identification through fluorescence patterns without requiring sophisticated genetic analysis instrumentation.

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

Solution Approach 2:

The patent changes the detection approach from analyzing genetic sequences to detecting enzyme activity and characteristics. By measuring fluorescence intensity, spectral properties, and kinetic parameters of beta-lactamase enzyme action on fluorescent substrates, the system can identify enzyme types without the complexity of comprehensive gene sequencing.

Inventive Principle:
Principle #35Parameter changes

3Speed

If broad-spectrum antibiotics are administered empirically, then treatment speed is improved, but harmful factors worsen (antibiotic resistance spread)

Engineering Contradiction:
Improvetreatment initiation speedVSAvoidantibiotic resistance spread
Core Design Contradiction:
SpeedVSObject-generated harmful factors

Solution Approach 1:

The patent implements a feedback mechanism where rapid fluorometric detection of beta-lactamase enzyme activity provides immediate information about antibiotic resistance status. This feedback allows clinicians to adjust treatment decisions within 20 minutes, prescribing targeted antibiotics based on actual resistance detection rather than continuing broad-spectrum empiric therapy, thus preventing resistance spread while maintaining treatment speed.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent performs preliminary detection of beta-lactamase presence and characteristics before finalizing treatment decisions. By quickly identifying the specific type of beta-lactamase enzyme through fluorometric analysis, the system enables preliminary guidance of antibiotic selection, preventing inappropriate broad-spectrum antibiotic use from the outset while maintaining rapid treatment initiation.

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

Enables rapid and cost-effective detection of antibiotic resistance directly from patient samples, facilitating timely treatment and improving clinical outcomes by reducing the spread of antibiotic-resistant bacteria.

Implementation Method 1

an optical assembly to collect and process a fluorescent signal associated with the fluorometric assay

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11635379B2Portable wide field fluorimeter systems
Publication Date: 2023.04.25 THE GENERAL HOSPITAL CORP
  • US11635379B2 patent drawing
  • US11635379B2 patent drawing
  • US11635379B2 patent drawing

AI summary

The present disclosure features portable wide field fluorimeter systems, e.g., in the form of low-cost mobile platforms, and methods to perform fluorometric assays to detect a change in fluorescence intensity in liquid samples, e.g., caused by the presence of a target analyte, e.g., a protein, e.g., an enzyme (e.g., β-lactamase) expressed by a target pathogen in a liquid sample in a point-of-care setting. In some implementations, a portable system for detecting a change in fluorescence intensity in a liquid sample includes a microfluidic device, an optical assembly including an emission filter and one or more lenses, and an analyzer device that collects and processes a fluorescent signal for the detection of a target analyte produced by the target pathogen present in the liquid sample.