Microfluidic Cartridge for Parallel Antibiotic Susceptibility Testing

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Solution Overview

Problem

Current antibiotic susceptibility testing (AST) methods, both phenotypic and genetic, face challenges such as long processing times, limited ability to test multiple antibiotics simultaneously, and require specialized knowledge and equipment, necessitating a more efficient and automated approach for analyzing phenotypic responses of bacteria to antibiotics.

Innovation Solution

A cartridge for microfluidic chips that includes a chip chamber with multiple cell channels, a sample chamber, and medium reservoirs, allowing for the capture and analysis of cells from a biological sample with preloaded culture medium and agents, enabling fully automated and rapid phenotyping of bacterial responses to various antibiotics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If phenotypic methods (agar plates, disc diffusion) are used for AST, then bacterial growth response can be visually observed, but processing time is long (at least overnight)

Engineering Contradiction:
Improvevisual response observationVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention divides the AST process into multiple parallel microchannels, each containing a population of bacteria exposed to different antibiotic concentrations. This segmentation allows simultaneous monitoring of multiple conditions, reducing overall processing time while maintaining visual observation capability through transparent chip walls and imaging systems.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from traditional 2D agar plate diffusion to 3D microfluidic channels with controlled flow dynamics. This dimensional change enables precise control of antibiotic exposure while maintaining bacterial culture conditions, achieving rapid phenotypic response observation without overnight incubation.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Measurement precision

If traditional phenotypic methods are used, then bacterial susceptibility can be determined, but only a single antibiotic or low number of antibiotics can be tested simultaneously

Engineering Contradiction:
Improvesusceptibility determinationVSAvoidnumber of antibiotics tested
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The microfluidic chip is divided into multiple independent channels or zones, each capable of testing a different antibiotic or concentration. This segmentation allows parallel testing of multiple antibiotics simultaneously, increasing versatility while maintaining accurate susceptibility determination through controlled bacterial exposure in each channel.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microfluidic chip design provides a universal platform that can test multiple antibiotics with different mechanisms of action simultaneously. The system uses a common bacterial inoculation source that distributes cells to multiple channels, each configured for different antibiotic testing, making the device multi-functional and highly adaptable.

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

3Loss of time

If genetic methods (PCR, DNA microarrays) are used, then AST can be performed rapidly, but specialized knowledge and expensive equipment are required

Engineering Contradiction:
Improveprocessing timeVSAvoidequipment and expertise required
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The microfluidic chip enables bacteria to self-express their phenotypic response to antibiotics through natural growth and metabolic processes. This self-service approach eliminates the need for complex genetic analysis equipment or specialized molecular biology expertise, as the bacteria themselves provide the test result through their growth or inhibition patterns that can be observed and imaged.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention replaces complex genetic analysis systems (PCR machines, sequencers, specialized software) with a simpler microfluidic imaging system. The phenotypic response is captured through transparent chip walls using standard microscopy or imaging cameras, substituting complex mechanical and computational systems with a more accessible optical observation approach.

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

4Loss of time

If genetic methods are used, then rapid AST is achieved, but the genotypic profile may not always match the phenotypic resistance profile

Engineering Contradiction:
Improveprocessing timeVSAvoidprofile matching accuracy
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The system uses the bacteria's own phenotypic expression in response to antibiotic exposure as the test result. By observing actual bacterial growth or inhibition in the presence of antibiotics, the method directly measures the phenotypic resistance profile that clinicians need, ensuring reliability and direct clinical relevance without relying on genotypic predictions.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP4234087B1Cartridge and method of analysing a biological sample
Publication Date: 2024.07.03 SYSMEX ASTREGO AB
  • EP4234087B1 patent drawingFigure 1A
  • EP4234087B1 patent drawingFigure 1B
  • EP4234087B1 patent drawingFigure 2A

AI summary

A cartridge (1) comprises a chip chamber (105) configured to house a microfluidic chip (500) comprising a plurality of sets (531) of cell channels (530) configured to capture cells from a biological sample. The cartridge (1) also comprises a sample chamber (140) configured to receive the biological sample and be in fluid connection with the plurality of sets (531) of cell channels (530) and a plurality of medium reservoirs (170). Each medium reservoir (170) of the plurality of medium reservoirs (170) is configured to be in fluid connection with a respective set (531) of cell channels (530) of the plurality of sets (531) of cell channels (530). The cartridge (1) further comprises culture medium source (110, 400) in fluid connection with the plurality of medium reservoirs (170) and configured to supply a culture medium to the plurality of medium reservoirs (170).