Electrochemical Bacterial Susceptibility Testing via Mediated Electron Transfer

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Solution Overview

Problem

Current antibiotic susceptibility testing methods are slow and inefficient, often taking 2-3 days to complete, which delays the identification of antibiotic-susceptible or resistant bacteria, leading to suboptimal treatment decisions and potential morbidity and mortality due to empirical antibiotic prescriptions.

Innovation Solution

A multiplexed electrochemical drug susceptibility method using a multi-electrode system with an electron transfer mediator in a growth medium to rapidly assess antibiotic susceptibility and resistance by measuring current responses from bacteria exposed to varying antibiotic concentrations, providing a susceptibility index within 90 minutes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional culturing methods (diffusion assays or microdilution assays) are used to test antibiotic susceptibility, then accurate classification of bacterial strains as susceptible or resistant can be achieved, but the testing process takes 2-3 days to complete

Engineering Contradiction:
Improveaccuracy of susceptibility classificationVSAvoidtesting duration
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the traditional mechanical/optical measurement systems (agar plate diffusion, broth culture optical density) with an electrochemical detection system. Bacterial respiration reduces an electron transfer mediator (such as phenazine methosulfate or 2,6-dichlorophenolindophenol), and the reduced mediator is reoxidized at an electrode, generating a measurable current signal that directly reflects bacterial metabolic activity and antibiotic susceptibility within minutes.

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

Solution Approach 2:

The patent introduces an electron transfer mediator as an intermediary substance between bacterial respiration and electrode detection. The mediator shuttles electrons from bacterial respiratory enzymes to the electrode surface, enabling rapid electrochemical detection of bacterial metabolic status without requiring traditional culture growth, thus reducing testing time from days to minutes while maintaining accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If rapid electrochemical methods are used to detect bacterial respiration, then testing time is reduced to minutes, but the ability to systematically classify different strains within the same species as resistant or susceptible when challenged with antibiotics of varying mechanisms of action has been limited

Engineering Contradiction:
Improvetesting durationVSAvoidapplicability to multiple antibiotic mechanisms
Core Design Contradiction:
Loss of timeVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal electrochemical platform that can systematically assess antibiotic susceptibility across multiple antibiotic classes with different mechanisms of action (cell wall synthesis inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors). The electron transfer mediator detects bacterial respiration regardless of the specific antibiotic mechanism, enabling broad applicability while maintaining rapid testing.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 simultaneous classification of antibiotic-susceptible and resistant bacteria strains, reducing the time to determine appropriate antibiotic treatments and limiting the selection of antimicrobial-resistant bacteria, thereby improving treatment outcomes.

Implementation Method 1

Through extracellular electron transfer, electrons are liberated via cellular respiration to the surface of inert electrodes resulting in a measurable flow of electrons i.e., electrical current

Methodology Applied
Scientific EffectExtracellular electron transfer: Conduction (electrical)

Implementation Method 2

electrons are liberated via cellular respiration to the surface of inert electrodes resulting in a measurable flow of electrons

Methodology Applied
Scientific EffectMediated electron transfer: Conduction (electrical)

Data Source

PatentUS20240426776A1Rapid differentiation of antibiotic-susceptible and -resistant bacteria through mediated extracellular electron transfer
Publication Date: 2024.12.26 WASHINGTON STATE UNIVERSITY
  • US20240426776A1 patent drawing
  • US20240426776A1 patent drawing
  • US20240426776A1 patent drawing

AI summary

A mediated extracellular electron transfer as a rapid and direct method to classify antibiotic-susceptible and -resistant bacteria is disclosed herein. Particularly, devices and methodologies to interpret antibiotic susceptibility index of a known bacteria strain or uncharacterized bacteria by treating it with antibiotics of different mechanisms or different concentrations of an antibiotic is provided. In an example methodology, the process includes a number of current control signal responses and a number of inoculated current response signals and thereafter analyzing the inoculated current response signals over a range of concentrations of up to about 24 times a breakpoint of the antibiotic with respect to current control signal responses to provide a susceptibility index assessment indicative of the susceptibility or resistance of the pathogen to the antibiotic.