Hybrid Microfluidic Biosensors for Rapid Pathogen Detection

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Solution Overview

Problem

Current pathogen detection methods are costly, complex, and require cumbersome procedures such as DNA extraction and amplification, making them inefficient for rapid and sensitive detection of infectious pathogens.

Innovation Solution

A polymer/paper hybrid microfluidic system that integrates aptamer-functionalized graphene oxide biosensors, allowing for direct pathogen detection without DNA treatment, using a simple and rapid 'turn-on' mechanism based on fluorescence quenching and recovery, enabling multiplexed detection of various pathogens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If DNA-based methods (PCR, DNA microarrays, DNA sequencing) are used for pathogen detection, then detection specificity is improved, but procedural complexity and cost increase due to requirements for cell lysis, DNA extraction, amplification and purification

Engineering Contradiction:
Improvedetection specificityVSAvoidprocedural complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the complex DNA extraction, amplification and purification steps from the detection workflow. By using whole-cell lysates directly as the target for aptamer binding, the method removes these cumbersome intermediate procedures while maintaining detection capability through the use of cell-associated or secreted markers that can be detected directly from crude lysates

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention segments the detection process into a simplified two-step workflow: (1) direct aptamer binding to pathogen markers in crude cell lysates, and (2) signal amplification through rolling circle amplification of captured aptamer-pathogen complexes. This segmentation eliminates the need for traditional DNA extraction and amplification steps while maintaining high specificity

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If DNA-based methods are used for pathogen detection, then detection sensitivity is improved, but detection time increases due to multiple processing steps

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

Solution Approach 1:

The invention performs preliminary action by pre-conjugating aptamers to graphene oxide nanoparticles before sample introduction. This pre-preparation of the detection probe allows for immediate binding to pathogen markers upon sample addition, eliminating the need for time-consuming DNA extraction and amplification steps that traditionally preceded detection

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention replaces the mechanical and chemical processes of cell lysis, DNA extraction, and amplification with a direct biochemical binding approach. Aptamers on graphene oxide nanoparticles directly bind to pathogen markers in crude lysates, and rolling circle amplification provides signal enhancement without requiring traditional PCR thermal cycling

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

3Reliability

If antibodies are used for direct pathogen detection, then detection capability is improved, but cost increases and stability decreases due to denaturation

Engineering Contradiction:
Improvedetection capabilityVSAvoidantibody stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention uses aptamers as disposable, stable alternatives to antibodies. Aptamers are synthetic oligonucleotides that are chemically stable, resistant to denaturation, and can be mass-produced at low cost. They maintain their binding capability across a wide range of conditions without the fragility associated with protein-based antibodies

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention changes the fundamental parameter of the binding agent from protein-based (antibodies) to nucleic acid-based (aptamers). This parameter change confers superior stability to the binding agent, as nucleic acids are resistant to denaturation by heat, pH changes, and chemical agents that would inactivate antibodies

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If PDMS or glass microfluidic systems are used, then device functionality is improved, but manufacturing complexity increases due to surface treatment and aptamer/probe immobilization requirements

Engineering Contradiction:
Improvedevice functionalityVSAvoidsurface treatment complexity
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The invention introduces graphene oxide as an intermediary carrier that simplifies the manufacturing process. Instead of directly immobilizing aptamers on complex PDMS or glass surfaces requiring sophisticated surface treatment, the aptamers are conjugated to graphene oxide nanoparticles, which then serve as the functional element in the microfluidic device. This intermediary approach eliminates the need for complex surface modification protocols

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The system provides a low-cost, sensitive, and rapid pathogen detection method that eliminates the need for complex surface modifications and DNA treatment, enabling fast and accurate identification of multiple pathogens in a single step, suitable for resource-limited settings.

Implementation Method 1

The probe or aptamer can be complexed with graphene, graphene oxide (GO), and/or other carbon nanoparticles to form a biosensor

Methodology Applied
Scientific EffectFluorescence quenching: Fluorescence

Data Source

PatentUS10620200B2Methods and compositions for hybrid microfluidic devices integrated with nano-biosensors
Publication Date: 2020.04.14 BOARD OF RGT THE UNIV OF TEXAS SYST
  • US10620200B2 patent drawing
  • US10620200B2 patent drawing
  • US10620200B2 patent drawing

AI summary

Certain embodiments are directed to paper/polymer hybrid microfluidic devices integrated with nano-biosensors for pathogen detection and infectious disease diagnosis.