Microfluidic Infection Detection via Dissociation and Sedimentation

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Solution Overview

Problem

Current diagnostic platforms face challenges in accurately detecting targets of interest, such as viral and bacterial infections, due to host-responsive proteins binding to targets, limiting sensitivity and requiring extensive sample preparation and manual handling.

Innovation Solution

The method involves treating the sample with a dissociation agent to release targets from host-responsive proteins, using microfluidic devices that apply sedimentation forces to isolate targets through density media, allowing for sensitive and specific detection of multiple targets simultaneously.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If host-responsive proteins are used to detect targets of interest, then the diagnostic platform can detect infections, but the sensitivity of target detection is limited due to binding between host-responsive proteins and targets

Engineering Contradiction:
Improvesensitivity of target detectionVSAvoidbinding interference from host-responsive proteins
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes host-responsive proteins from the sample through chemical treatment (e.g., acidification, protease digestion) before detection. This eliminates the interfering binding between host proteins and targets, allowing for sensitive detection of viral/bacterial targets without false signals from host antibody-antigen complexes.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If extensive sample preparation is performed to ensure accurate detection, then detection accuracy improves, but the turnaround time and complexity of the diagnostic platform increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidturnaround time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the sample preparation process into automated chemical treatment steps (e.g., acidification, neutralization, protease digestion) that can be performed sequentially in a microfluidic device. This automation reduces manual handling time while maintaining detection accuracy, achieving both precision and speed.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary chemical treatment of the sample (removing host proteins, adjusting pH) before the actual detection step. This pre-preparation is automated and rapid, ensuring that when detection occurs, the sample is already optimized for accurate target identification, reducing overall turnaround time.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If manual handling is used for sample preparation and detection, then flexibility is maintained, but simplicity of use and ease of operation are reduced

Engineering Contradiction:
Improveflexibility in detection methodsVSAvoidsimplicity of use
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent implements self-service automation where the microfluidic device automatically performs sample preparation steps (mixing, incubation, separation) and detection without requiring manual intervention. The system self-regulates flow rates, timing, and reagent delivery, making the platform simple to use while maintaining flexible detection capabilities for various pathogens.

Inventive Principle:
Principle #25Self-service

4Productivity

If automated microfluidic processing is implemented, then simplicity of use and rapid turnaround time improve, but device complexity increases

Engineering Contradiction:
Improverapid turnaround timeVSAvoidcomplexity of microfluidic device
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent designs a universal microfluidic device platform that can detect multiple types of pathogens (viruses, bacteria) using the same automated processing steps. The device integrates sample preparation, separation, and detection functions in a single multi-functional system, achieving rapid turnaround time without proportionally increasing complexity through standardization and reusability.

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

This approach enhances the sensitivity and specificity of target detection, enabling rapid and automated diagnosis of active or latent infections, including those caused by M. tuberculosis and HIV, with minimal sample preparation.

Implementation Method 1

layering the treated mixture on a density medium, where the treated mixture further includes a first population of beads; and subjecting the treated mixture to a sedimentation force such that the first population of beads, or a portion thereof, travels through the density medium

Methodology Applied
Scientific EffectSedimentation: Sedimentation

Implementation Method 2

subjecting the treated mixture to a sedimentation force such that the first population of beads, or a portion thereof, travels through the density medium

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Data Source

PatentUS10786811B1Detection of active and latent infections with microfluidic devices and systems thereof
Publication Date: 2020.09.29 NATIONAL TECHNOLOGY & ENGINEERING SOLUTIONS OF SANDIA LLC
  • US10786811B1 patent drawing
  • US10786811B1 patent drawing
  • US10786811B1 patent drawing

AI summary

The present invention relates to methods of detecting one or more targets of interest in a sample. In one instance, the target can be correlated to an active infection (e.g., by a virus and/or a bacterium). Methods can include treating the sample with a dissociation agent, thereby releasing the target of interest for more accurate detection (e.g., by use of a sedimentation-based centrifugal microfluidic devices). Also described herein are microfluidic devices and systems for use with a dissociation agent.