Integrated Microfluidic Device for Nucleic Acid Detection

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Solution Overview

Problem

Current analyte analysis methods require complex and expensive systems for sample preparation and analysis, which are not suitable for point-of-care applications, and there is a need for integrated devices that can simplify and cost-effectively perform analyte detection, especially for clinical use.

Innovation Solution

An integrated digital microfluidic and analyte detection device that includes a sample preparation module and an analyte detection module, utilizing electrodes and an array of wells for amplifying and detecting nucleic acids, with a method that involves amplifying target nucleic acid, incorporating a tag, capturing and labeling the product, and spatially segregating capture objects to detect the presence of nucleic acids in a fluid sample.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If manual or complicated robotic sample preparation is used, then sample preparation can be performed, but the process becomes complex and expensive

Engineering Contradiction:
Improvesample preparation simplicityVSAvoidsample preparation system complexity
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent combines sample preparation and analyte detection functions into a single integrated microfluidic device. The device integrates sample lysis, nucleic acid extraction, amplification, and detection capabilities within one chip, eliminating the need for separate manual or robotic preparation steps and complex external instrumentation.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device performs multiple functions including sample lysis, nucleic acid extraction, amplification, and detection within a single platform. This multi-functional integration simplifies the overall system by replacing multiple specialized devices with one universal device that handles the entire analytical workflow.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If expensive and complicated systems are used for transporting and analyzing prepared samples, then accurate analyte detection is achieved, but the cost and system complexity increase

Engineering Contradiction:
Improveanalyte detection accuracyVSAvoidanalysis system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The device merges sample preparation and analyte detection into a single integrated platform. The microfluidic chip contains all necessary components for nucleic acid extraction, amplification, and detection, eliminating the need for separate transport systems and external analytical instruments, thereby reducing complexity while maintaining detection accuracy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses magnetic beads as an intermediary for nucleic acid capture and enrichment within the microfluidic device. These beads facilitate efficient nucleic acid isolation and transfer to the detection zone, enabling accurate detection without requiring complex sample preparation equipment or multiple processing steps.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If more amplification cycles are performed, then detection sensitivity for low concentration nucleic acids is improved, but the analysis time increases

Engineering Contradiction:
Improvenucleic acid detection sensitivityVSAvoidamplification time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent employs isothermal amplification methods that operate at constant temperature rather than requiring thermal cycling. This approach achieves high amplification efficiency and detection sensitivity for low-concentration nucleic acids while significantly reducing the total analysis time compared to conventional PCR methods that require multiple heating and cooling cycles.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The device replaces thermal cycling mechanisms with isothermal amplification chemistry. By using enzymatic reactions that proceed at constant temperature, the system eliminates the time-consuming thermal cycles while maintaining amplification efficiency, thereby reducing analysis time without sacrificing detection sensitivity.

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

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 efficient and cost-effective detection of low concentrations of nucleic acids with reduced amplification cycles and time, facilitating point-of-care applications by integrating sample preparation and analysis in a single device.

Implementation Method 1

capturing the amplification product on a plurality of capture objects comprising a binding member that specifically binds to the tag

Methodology Applied
Scientific EffectMolecular recognition: Adsorption

Implementation Method 2

detecting the presence of the detectably labeled complex in the plurality of wells

Methodology Applied
Scientific EffectOptical detection: Fluorescence

Data Source

PatentEP3512862B1Devices and methods for sample analysis
Publication Date: 2024.05.01 ABBOTT LAB INC
  • EP3512862B1 patent drawingFigure 1A~1B
  • EP3512862B1 patent drawingFigure 2A~2B
  • EP3512862B1 patent drawingFigure 3A~3B

AI summary

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells. The detection modules disclosed here can be used for detecting analytes of interest which analytes may have been enriched by amplification, isolation, or other techniques.