Cartridge Microscopy for Extracellular Bacteria Detection
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Solution Overview
Problem
Conventional methods for detecting extracellular bacteria in aspirated samples are prone to contamination and require skilled personnel, leading to inaccurate infection diagnosis due to the difficulty in distinguishing between contamination and true infection, especially when cells are flattened on a glass slide.
Innovation Solution
A method involving a cartridge-based, slide-free process where a liquid biological sample is diluted with a sterilized diluent, imaged using a microscopy system, and analyzed to detect extracellular bacteria above a configurable threshold, maintaining cell morphology and reducing contamination risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional glass slide preparation is used, then intracellular bacteria can be visualized, but the process is time-consuming and requires trained personnel
Solution Approach 1:
The system performs automated preliminary actions by capturing images of the biological sample and automatically analyzing them for bacteria detection. The processor pre-processes the images and compares them against trained models before final interpretation, eliminating the need for manual slide preparation and initial assessment by trained personnel.
Solution Approach 2:
The patent replaces the manual mechanical process of slide preparation, staining, and microscopic evaluation with an automated imaging system. The system uses captured images and computational algorithms to substitute the mechanical and skill-based processes previously performed by trained personnel preparing and examining glass slides.
2Reliability
If extracellular bacteria are detected in FNA samples, then contamination cannot be distinguished from true infection, but intracellular bacteria detection is more reliable
Solution Approach 1:
The system employs feedback mechanisms by comparing detected bacterial features against pre-trained models and criteria established from known infected and non-infected samples. The processor continuously refines its analysis by comparing new detections against accumulated data, providing feedback that improves the distinction between contamination and true infection over time.
Solution Approach 2:
The patent changes the detection parameter from simply identifying extracellular bacteria to analyzing intracellular bacteria within preserved cell structures. By shifting the detection focus to intracellular locations and using image analysis parameters that identify bacteria within cellular boundaries, the system achieves more reliable infection diagnosis while managing complexity through automated processing.
3Difficulty of detecting and measuring
If cells are flattened on glass slides for visualization, then bacteria become more visible, but cell morphology is distorted from natural state
Solution Approach 1:
The system creates accurate optical copies of the biological sample in its natural state. By capturing images of cells suspended in liquid within the cartridge without physical contact or flattening, the system produces visual replicas that preserve three-dimensional morphology while maintaining bacteria visibility through high-resolution imaging and image processing techniques.
Solution Approach 2:
The patent transitions from two-dimensional glass slide visualization to three-dimensional imaging within the cartridge. By maintaining cells in their natural three-dimensional suspended state and using imaging capabilities that capture depth and spatial relationships, the system preserves cell morphology while enabling bacteria detection through enhanced dimensional visualization rather than flattening.
4Ease of manufacture
If slide-free cartridge process is used, then cell damage is reduced and preparation is simpler, but intracellular bacteria are harder to visualize
Solution Approach 1:
The system replaces manual microscopic evaluation with automated image analysis. The processor uses captured images from the cartridge to automatically detect and identify intracellular bacteria, substituting the need for manual visualization and interpretation. This maintains the simplicity of the slide-free cartridge process while overcoming the visualization challenge through computational analysis.
Solution Approach 2:
The patent introduces an intermediary image analysis system between the cartridge sample and the final diagnosis. The captured images serve as an intermediary that preserves the simple cartridge preparation while enabling detailed intracellular bacteria detection through computational processing, acting as a bridge between the simplified physical preparation and the complex detection requirement.
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 accurate and sensitive detection of extracellular bacteria, allowing earlier infection detection and reducing the need for skilled personnel, by maintaining cell morphology and minimizing artifactual contamination.
Implementation Method 1
imaging the sample mixture with a microscopy system
Data Source
AI summary
Disclosed herein are methods and systems for evaluating an aspirated fluid for the presence of extracellular bacteria. The method generally includes receiving a sample cartridge comprising a sample mixture, the sample mixture comprising a liquid biological sample from a subject and a sterilized diluent, in an interior volume of the sample cartridge; imaging the sample mixture with a microscopy system; determining whether bacteria present within the sample mixture is above a configurable threshold; and in response to determining that the bacteria within the sample mixture is above the configurable threshold, determining that the liquid biological sample has extracellular bacteria.