Tangential Flow Membrane Device for Pathogen Isolation

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Solution Overview

Problem

Current methods for isolating and concentrating pathogens from biological samples, such as blood cultures, are labor-intensive and time-consuming, often requiring subculturing steps that delay identification and antimicrobial susceptibility testing, which is critical for patients with severe sepsis.

Innovation Solution

The use of tangential flow membrane devices with multiple stages and recirculating flow paths to selectively isolate and concentrate pathogens by size exclusion, allowing for rapid separation and purification without the need for subculturing, using membranes with specific pore sizes and controlled trans-membrane pressures to retain or pass through target constituents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If centrifugation and wash methods are used to isolate pathogens, then separation is achieved, but the process becomes labor-intensive and subject to user variability

Engineering Contradiction:
Improveseparation consistencyVSAvoidlabor intensity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces manual centrifugation and wash procedures with an automated membrane-based filtration system that uses controlled pressure differentials to achieve pathogen separation, eliminating user variability and reducing labor intensity while maintaining reliable separation

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

Solution Approach 2:

The invention employs porous membranes with specific pore sizes to selectively retain or pass through target pathogens based on their physical characteristics, providing consistent separation without manual intervention

Inventive Principle:
Principle #31Porous materials

2Reliability

If standard subculturing methods are used to isolate pathogens from blood cultures, then pathogen separation is achieved, but the time to results is delayed by approximately 18-24 hours

Engineering Contradiction:
Improvepathogen isolation accuracyVSAvoidtime to results
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent directly extracts and concentrates pathogens from positive blood cultures using membrane filtration, bypassing the time-consuming subculturing step entirely while maintaining accurate pathogen isolation through selective membrane retention

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention skips the intermediate subculturing step by implementing a direct filtration and concentration process that rapidly isolates pathogens from blood cultures, reducing the time to results by 18-24 hours

Inventive Principle:
Principle #21Skipping (Rushing through)

3Reliability

If filtration methods are used to separate pathogens, then separation is achieved, but the component of interest is lost to interactions with the filter surface

Engineering Contradiction:
Improveseparation efficiencyVSAvoidpathogen loss
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent uses controlled pressure differentials applied across the membrane to facilitate pathogen separation, allowing pathogens to be retained or passed through based on pore size without excessive contact time that would cause surface interactions and loss

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The invention optimizes filtration parameters including pressure differential, flow rate, and membrane pore size to achieve effective pathogen separation while minimizing pathogen loss to filter surface interactions

Inventive Principle:
Principle #35Parameter changes

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

This approach significantly reduces the time to results for pathogen identification and antimicrobial susceptibility testing, improving patient outcomes by enabling rapid isolation and concentration of pathogens directly from biological samples, potentially cutting the processing time by 18 hours or more.

Implementation Method 1

the membrane having a characteristic to selectively permit one or more constituents of the biological sample to pass through the membrane from the first side to the second side while retaining other constituents of the biological sample at the first side

Methodology Applied
Scientific EffectSize exclusion: Filter (physical)

Implementation Method 2

a tangential flow of the biological sample along a first surface of the membrane at the first side from the inlet to the outlet

Methodology Applied
Scientific EffectTangential flow: Flow Separation

Implementation Method 3

a trans-membrane passing of the one or more constituents of the biological sample from the first side to the second side

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Data Source

PatentEP3914388B1Methods and apparatus to selectively extract constituents from biological samples
Publication Date: 2024.07.03 BECTON DICKINSON & CO
  • EP3914388B1 patent drawingFigure 1
  • EP3914388B1 patent drawingFigure 2~3
  • EP3914388B1 patent drawingFigure 4~5

AI summary

Methods and apparatus provide filtration for concentrating analytes, such as bacteria or exosomes, of a biological sample, such as blood or urine. The technology may employ membrane devices that implement one or more tangential flow filtration processes such as in stages. An example membrane device may typically include a membrane having sides and ends. The membrane may selectively permit constituent(s) of the sample to pass through while retaining other constituents at one side. An input chamber of the device may include an inlet near one end and an outlet near the other end, and that may permit a tangential flow of the sample along the first side surface, and a trans-membrane passing of constituent(s). An output chamber of the device may be configured at the second side surface to receive the passing constituents. Such devices may be provided in a kit to facilitate targeting of a desired biological analyte concentration.