Plasmonic Imaging Tracking Antibiotic Susceptibility

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Solution Overview

Problem

Current antibiotic susceptibility testing (AST) methods are time-consuming, limited to cultivable bacteria, and unable to effectively handle non-cultivable and slow-growing microorganisms, leading to delayed antibiotic administration in acute cases like sepsis, which increases morbidity and mortality.

Innovation Solution

A plasmonic imaging and tracking system that measures the binding kinetics and treatment effects of antibiotics on bacteria in a culture-free environment, allowing for rapid detection of antibiotic-resistant strains and generation of antibiotic susceptibility profiles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional culturing techniques (disk-diffusion, broth-dilution) are used for AST, then measurement precision is improved, but loss of time increases significantly (up to two days required)

Engineering Contradiction:

ImproveAST accuracyVSAvoidtime required for AST

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces conventional mechanical culturing techniques with a micro-cantilever based sensing system. The micro-cantilever detects bacterial metabolic activity through nanomotion measurements, eliminating the need for traditional culturing while providing rapid AST results within hours rather than days.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from visual inspection of bacterial growth (turbidity, colony formation) to detection of bacterial-induced nanomotion of micro-cantilevers. This parameter change enables detection of metabolic activity at much earlier stages, dramatically reducing the time required for AST while maintaining precision.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If conventional culturing techniques are used, then cultivable strains can be tested, but non-cultivable and slow-growing microorganisms cannot be assessed

Engineering Contradiction:

Improverange of bacteria types testableVSAvoidAST reliability for non-cultivable bacteria

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The micro-cantilever based system provides universal detection capability for all bacteria types including non-cultivable and slow-growing species. The system detects metabolic activity through nanomotion, a universal characteristic of living bacteria, rather than relying on culturing-specific parameters, thereby achieving both versatility and reliability across diverse bacterial populations.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If magnetic beads or optical imaging are used to measure cell growth, then some time savings are achieved, but the techniques remain time-consuming and semi-quantitative requiring high bacterial density

Engineering Contradiction:

ImproveAST speedVSAvoidquantification accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent replaces optical imaging and magnetic bead methods with micro-cantilever based nanomotion detection. This mechanical sensing approach provides quantitative measurements of bacterial metabolic activity at much lower cell densities, eliminating the semi-quantitative nature and high-density requirements of previous methods while maintaining rapid assessment capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Difficulty of detecting and measuring

If AFM cantilevers are used as metabolic sensors, then detection capability is improved, but the ability to differentiate strains and obtain strain-specific susceptibility results is lost

Engineering Contradiction:

Improvemetabolic detection sensitivityVSAvoidstrain-specific differentiation capability

Core Design Contradiction:

Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The patent segments the detection process by individually monitoring nanomotion signals from multiple micro-cantilevers, each interacting with specific bacterial cells. This segmentation enables differentiation of strain-specific responses and susceptibility patterns, overcoming the limitation of bulk measurement while maintaining high detection sensitivity.

Inventive Principle:

Principle #1Segmentation

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 automated AST, applicable to both cultivable and non-cultivable bacteria, providing kinetic and MIC measurements in a single step, and capable of characterizing AST in mixed microbial populations, significantly reducing the time required for susceptibility reports.

Implementation Method 1

A plasmonic imaging and tracking system that measures the binding kinetics and treatment effects of antibiotics on bacteria

Methodology Applied

Scientific EffectPlasmonic imaging:

Data Source

PatentUS10782292B2Antibiotic susceptibility testing via plasmonic imaging and tracking

Publication Date: 2020.09.22 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

AI summary

A rapid antibiotic susceptibility test (AST) based on the detection and quantification of the movement of single bacterial cells with a plasmonic imaging and tracking (PIT) technology. The PIT-based AST detects changes in the metabolic activity of the bacterial cells long before cell replication, and allows rapid AST for both cultivable and non-cultivable strains. PIT tracks 3D movement with sub-nanometer resolution and millisecond temporal resolution. PIT also allows simultaneous measurement of the binding kinetic constants of antibiotics and bacterial metabolic state after the introduction of antibiotics.