Microfluidic Device for Microorganism Detection via Lysis and Nucleic Acid Separation

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Solution Overview

Problem

Current techniques fail to provide a simple, specific, and sensitive method for detecting microorganisms, lacking in terms of specificity, sensitivity, and operational simplicity.

Innovation Solution

A microfluidic device with a lysis section for dissolving microorganisms and a separation section for isolating nucleic acids, using bacteriolytic agents and separation means like molecular size or centrifugation, followed by complex formation and detection using CRISPR-dCas9 or protein markers, and electrochemical or optical detection through nanopores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If PCR is used for microorganism detection, then detection sensitivity and specificity are improved, but device complexity and operational complexity increase

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

Solution Approach 1:

The detection system is divided into distinct functional modules: a lysis section for microorganism lysis, a separation section for nucleic acid isolation, and a detection section for signal generation. This segmentation allows each module to perform its specific function with optimized components, reducing overall system complexity while maintaining high detection sensitivity through specialized processing in each section.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces intermediate processing steps between sample input and final detection: lysis agents break down microorganism cells to release nucleic acids, and separation means isolate the nucleic acids from other cellular components. These intermediary steps simplify the detection process by preparing the sample in a standardized format that the detection section can process directly, avoiding the need for complex PCR amplification while maintaining sensitivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If immunological detection method is used, then operation simplicity is improved, but detection sensitivity deteriorates

Engineering Contradiction:
Improveoperational simplicityVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention replaces the mechanical/chemical immunological binding process with a nucleic acid-based detection system. Instead of using antibodies that require complex incubation and washing steps, the system uses nucleic acid extraction followed by direct detection methods, eliminating the need for immunological reagents and simplifying the operational protocol while achieving comparable or superior sensitivity.

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

Solution Approach 2:

The detection approach shifts from detecting protein antigens (immunological method) to detecting nucleic acid biomarkers. This parameter change allows for simpler sample preparation since nucleic acids are more stable and easier to extract from lysed cells than to maintain antibody-antigen complexes, while the specific nucleic acid sequences provide high detection sensitivity through sequence-specific recognition.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If ATP assay method is used, then operational simplicity is improved, but detection specificity deteriorates

Engineering Contradiction:
Improveoperational simplicityVSAvoiddetection specificity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention applies local quality by using specific nucleic acid sequences as biomarkers for different microorganism types. Instead of a general metabolic activity measurement (ATP), the system targets specific genetic sequences that are unique to pathogenic microorganisms, allowing the same simple operational platform to achieve high specificity through sequence-specific detection probes or primers in the detection section.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The lysis and separation sections provide universal processing for all microorganism samples, handling diverse microbial types through standardized nucleic acid extraction. The detection section then provides specific identification by targeting specific nucleic acid sequences. This universal-s specific architecture maintains operational simplicity across different sample types while achieving high detection specificity for various pathogenic microorganisms.

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

Enables specific and sensitive detection of microorganisms, suitable for various fields including food safety, with improved operational simplicity and sensitivity.

Implementation Method 1

a lysis section for dissolving microorganisms and a separation section for separating out a nucleic acid from a lysate of microorganisms formed in the lysis section

Methodology Applied
Scientific EffectLysis: Decomposition (biological)

Implementation Method 2

the separation section includes a separation means capable of separating out a nucleic acid contained in the lysate from other substances

Methodology Applied
Scientific EffectMolecular size separation: Filter (physical)

Implementation Method 3

a separation means using a molecular size, a separation means using centrifugation, or a separation means using hydraulic filtration

Methodology Applied
Scientific EffectCentrifugation: Centrifugal Separation

Implementation Method 4

a complex forming section for forming a protein-nucleic acid complex from the nucleic acid separated in the separation section

Methodology Applied
Scientific EffectComplex formation: Chemical Bonding

Implementation Method 5

a detection section including a means for detecting the complex communicating with the complex forming section

Methodology Applied
Scientific EffectElectrochemical detection: Electrochemiluminescence

Implementation Method 6

a detection section including a means for detecting the complex communicating with the complex forming section

Methodology Applied
Scientific EffectOptical detection: Fluorescence

Implementation Method 7

a detection section detects the complex using a nanopore

Methodology Applied
Scientific EffectNanopore detection: Nanopore

Data Source

PatentEP4524228A1Method and device for detecting microorganisms
Publication Date: 2025.03.19 KIKKOMAN CORP
  • EP4524228A1 patent drawingFigure 1(a)~1(b)
  • EP4524228A1 patent drawingFigure 2(a)~2(d)
  • EP4524228A1 patent drawingFigure 3

AI summary

A microfluidic device 1 according to the present invention for detecting microorganisms in a sample includes a lysis section 2 for dissolving microorganisms in the sample; and a separation section 3 for separating out a nucleic acid from a lysate of microorganisms formed in the lysis section 2 communicating with the lysis section 2, in which the lysis section 2 includes a channel for holding a bacteriolytic agent for lysing microorganisms, and the separation section 3 includes a means capable of separating out a nucleic acid contained in the lysate from other substances.