3D Microarrays for Direct Nucleic Acid Detection

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Solution Overview

Problem

Current methods for detecting nucleic acids and determining methylation in promoter regions are limited by low sensitivity, require pre-concentration, and are often complex, costly, and time-consuming, making them unsuitable for on-site testing and accurate detection beyond certain sensitivity limits.

Innovation Solution

Development of three-dimensional microarrays with functionalized surface structures that allow for the direct detection of nucleic acids and methylation status without pre-concentration, using sensory agents and signal entities to provide a detectable response, enabling high sensitivity and selectivity in detecting target compounds and quantifying nucleic acid sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional detection methods are used, then detection capability is achieved, but sensitivity is insufficient and pre-concentration is required

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

Solution Approach 1:

The patent transitions from traditional two-dimensional surface detection to three-dimensional microarray structures with protruding elements. This dimensional change increases the effective surface area for nucleic acid binding by orders of magnitude, enabling direct detection without pre-concentration while maintaining high sensitivity. The three-dimensional architecture allows multiple binding sites to be accessible simultaneously, resolving the contradiction between sensitivity and method complexity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The microarray structures incorporate porous or surface-modified regions that enhance nucleic acid binding capacity. The functionalized surfaces within the three-dimensional structure provide extensive binding sites for nucleic acids, allowing direct detection at low concentrations without requiring pre-concentration steps, thus improving sensitivity while simplifying the overall method.

Inventive Principle:
Principle #31Porous materials

2Measurement precision

If PCR amplification is used, then detection sensitivity is improved, but time consumption and cost increase

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

Solution Approach 1:

The patent extracts and eliminates the need for PCR amplification step from the detection workflow. By incorporating high-capacity binding sites directly into the three-dimensional microarray structure, the system can detect nucleic acids at their native concentrations without requiring prior amplification. This extraction of the amplification step reduces testing time and cost while maintaining detection sensitivity through the enhanced surface area and functionalization of the microarray.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The microarray structure provides self-service detection capability through its inherent high surface area and functionalized binding sites. The three-dimensional architecture automatically offers extensive binding opportunities for nucleic acids without requiring external amplification processes. This self-service approach enables direct detection, eliminating the need for time-consuming PCR steps while maintaining sensitivity through the structure's intrinsic properties.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If conventional sensing technology is used, then detection is possible, but sensitivity limits accurate detection beyond certain concentrations

Engineering Contradiction:
Improvedetection accuracyVSAvoidtarget analyte concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs three-dimensional microarray structures with protruding elements that extend into the sample environment. This dimensional extension increases the effective binding surface area by orders of magnitude compared to conventional two-dimensional surfaces. The enhanced surface area provides numerous binding sites that can detect nucleic acids at much lower concentrations, pushing the detection limit to the single-molecule level and enabling accurate detection across a broader concentration range.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The microarray incorporates porous or high-surface-area materials that dramatically increase binding capacity. These porous structures provide extensive internal surface area for nucleic acid binding, enabling detection at extremely low concentrations without requiring high analyte quantities. This material strategy resolves the contradiction by providing high detection accuracy while requiring minimal target analyte concentration.

Inventive Principle:
Principle #31Porous materials

4Measurement precision

If large sensing instrumentation is used, then detection capability is achieved, but portability is lost

Engineering Contradiction:
Improvedetection capabilityVSAvoidinstrument size
Core Design Contradiction:
Measurement precisionVSWeight of moving object

Solution Approach 1:

The patent employs three-dimensional microarray structures that pack an enormous surface area into a compact footprint. By utilizing vertical dimensionality with protruding elements, the system achieves high detection capability within a small physical volume. This dimensional packing allows the microarray to provide laboratory-grade detection sensitivity in a portable form factor, eliminating the need for large instrumentation while maintaining detection capability.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The use of porous or high-surface-area materials enables extreme surface area density within a compact structure. These materials provide extensive binding sites in a space-efficient manner, allowing the microarray to achieve high detection capability without requiring large instrumentation. The porous architecture maximizes the use of available volume, enabling portable deployment while maintaining laboratory-grade detection performance.

Inventive Principle:
Principle #31Porous materials

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 microarrays enable accurate and sensitive detection of nucleic acids and methylation status, reducing the need for amplification techniques like PCR, allowing for on-site testing and providing a cost-effective, rapid method for analyzing nucleic acid sequences and methylation patterns.

Implementation Method 1

the subsequent methodology used to analyse the sample depends on the quantity of nucleic acid in the sample and the detail required in the analysis

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

the surface areas on which reactions or binding under study can occur

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

the detectable sensor response is selected from colour, fluorescence, magnetic or light blocking

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 4

the detectable sensor response is capable of being read by digital counting, weight measurements, fluorescence, optical, and/or electrical means

Methodology Applied
Scientific EffectAbsorption Spectroscopy: Absorption Spectroscopy

Implementation Method 5

DNA methylation is the covalent addition of a methyl group to the 5-carbon of Cytosine in a CpG dinucleotide

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 6

the surface areas on which reactions or binding under study can occur and the correspondingly low surface area availability

Methodology Applied
Scientific EffectSurface area effect:

Data Source

PatentEP2558859B1Three dimensionsal microarrays
Publication Date: 2017.09.27 DIGITAL SENSING
  • EP2558859B1 patent drawingFigure 1(A)~1(D)
  • EP2558859B1 patent drawingFigure 2(A)~2(C)
  • EP2558859B1 patent drawingFigure 3(A)~4

AI summary

Disclosed is a method of producing a two dimensional microarray using a three dimensional or structured microarray. The invention involves forming defined functionalized areas by layering an inert material over the surface structures of the three dimensional microarray. Sufficient of the inert material and of the top of the surface structures are then removed to expose defined areas of the surface structures within the inert material.