Aqueous Two-Phase System Concentration for Lateral Flow Pathogen Detection

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Solution Overview

Problem

Lateral-flow immunoassays face challenges in assay sensitivity and signal intensity, particularly in detecting pathogens at low concentrations, such as bacteria, fungi, and viruses, in biological fluids.

Innovation Solution

The use of an aqueous two-phase system (ATPS) in conjunction with a lateral-flow assay (LFA) or flow-through system, which includes a concentration component and a detection component, to enhance the detection and quantification of pathogens by concentrating the target analytes and utilizing specific antibodies and probes for accurate detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If lateral-flow immunoassay is used for pathogen detection, then the assay can be performed rapidly and simply, but the assay sensitivity and signal intensity are insufficient for detecting pathogens at low concentrations

Engineering Contradiction:

Improveassay speedVSAvoidassay sensitivity

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by performing analyte concentration before the detection step. The aqueous two-phase system concentrates the target analytes from the sample matrix prior to application on the lateral-flow assay strip, ensuring that the detection step receives a pre-concentrated sample with sufficient signal intensity for sensitive detection of low-abundance pathogens

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses an aqueous two-phase system as an intermediary between the sample and the lateral-flow assay. This intermediary system performs the function of concentrating and partially purifying the analyte, bridging the gap between the raw sample and the detection platform to enhance sensitivity without compromising the rapidity of the overall assay

Inventive Principle:

Principle #24Intermediary (Mediator)

2Device complexity

If conventional lateral-flow assay without concentration step is used, then the procedure is simple and rapid, but the detection limit is too high to detect pathogens at low concentrations

Engineering Contradiction:

Improveassay procedure complexityVSAvoiddetection limit

Core Design Contradiction:

Device complexityVSMeasurement precision

Solution Approach 1:

The patent merges the concentration function with the lateral-flow assay by integrating an aqueous two-phase system into the assay protocol. This combination allows the concentration step to be performed in a straightforward manner before sample application, maintaining procedural simplicity while achieving the necessary sensitivity improvement to detect low-concentration pathogens

Inventive Principle:

Principle #5Merging (Combining)

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 enables the detection of pathogens at concentrations as low as 6×10^6 cells/mL, improving assay sensitivity and signal intensity, allowing for rapid and accurate detection of clinically relevant pathogens within 10 minutes.

Implementation Method 1

an aqueous two-phase system (ATPS) comprising a mixed phase solution that separates into a first phase solution and a second phase solution

Methodology Applied

Scientific EffectAqueous two-phase separation: Phase Change

Implementation Method 2

a fluid wherein the analyte is to be detected is applied to one end of a porous membrane layer and flows in lateral direction through the membrane under the action of capillary forces

Methodology Applied

Scientific EffectCapillary action: Capillary Action

Implementation Method 3

a receptor, typically an antibody which is specific for the ligand to be detected, is immobilized on a solid support. A test fluid that may comprise the analyte to be detected is contacted with the solid support and a receptor-analyte pair is formed when the target analyte is present

Methodology Applied

Scientific EffectAntibody-antigen binding: Adsorption

Data Source

PatentUS11885803B2Methods and devices for analyte collection, extraction, concentration, and detection for clinical applications

Publication Date: 2024.01.30 RGT UNIV OF CALIFORNIA

AI summary

In various embodiments devices and methods for the detection and/or quantification of clinically relevant pathogens (e.g., bacteria, fungi, viruses, etc.) are provided. In certain embodiments the device comprises a lateral-flow assay that detects the bacterium at a concentration of less than about 6×106 cells/mL, less than about 3×106 cells/ml, less than about 1×106 CFU/mL, or less than about 50 μg/mL. In certain embodiments the device comprises an aqueous two-phase system (ATPS) comprising a mixed phase solution that separates into a first phase solution and a second phase solution; and a lateral-flow assay (LFA). In certain embodiments the device comprises a flow-through system comprising a concentration component comprising an aqueous two-phase system (ATPS) comprising a mixed phase solution that separates into a first phase solution and a second phase solution; and a detection component disposed beneath said concentration component.