Density-Driven Solvent Layering for Bead Sealing in Microarrays

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Solution Overview

Problem

Current methods for detecting low-concentration target molecules, such as disease markers, require extensive time and effort to prepare large numbers of small liquid droplet arrays for efficient bead sealing, making it difficult to apply to cases requiring millions of arrays.

Innovation Solution

A method involving the use of a first solvent with a substance and a second solvent of greater specific gravity, optionally containing surfactants like TWEEN 20 or Triton X-100, to efficiently seal beads, nucleic acid, protein, virus, cells, or lipid membrane complexes into an array by layer substitution, allowing for high-density storage and detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional centrifugal force methods are used to seal beads into arrays, then bead sealing can be achieved, but it requires extensive time and effort to prepare large numbers of arrays and uses strong centrifugal force

Engineering Contradiction:
Improvebead sealing efficiencyVSAvoidarray preparation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The invention changes the physical parameters of the sealing process by using a sealing solution with specific density (greater than the aqueous solution) and introducing surfactants to reduce surface tension. This allows beads to be sealed into arrays through density-driven separation rather than strong centrifugal force, dramatically reducing preparation time and enabling efficient sealing of millions of arrays

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces a sealing solution as an intermediary substance between the bead-containing aqueous solution and the array. This sealing solution, with its specific density and surfactant properties, acts as a mediator that enables gentle, efficient bead sealing without requiring strong external centrifugal force

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If the number of arrays is increased to detect very low concentration target molecules, then detection sensitivity improves, but the time and effort required for array preparation increases significantly

Engineering Contradiction:
Improvedetection sensitivityVSAvoidarray preparation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

By changing the density parameter of the sealing solution and using surfactants to modify surface properties, the invention enables rapid bead sealing that scales efficiently. This allows preparation of millions of arrays for high-sensitivity detection without the time penalty that would normally accompany increased array numbers

Inventive Principle:
Principle #35Parameter changes

3Productivity

If strong centrifugal force is applied to seal beads into arrays, then bead sealing efficiency improves, but the complexity and requirements of the equipment increase

Engineering Contradiction:
Improvebead sealing efficiencyVSAvoidcentrifugal force equipment complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention replaces the strong mechanical centrifugal force system with a gentler density-driven separation mechanism. By using a sealing solution with specifically controlled density and surfactant properties, bead sealing is achieved through natural density stratification rather than strong mechanical centrifugal fields, simplifying equipment requirements

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

Solution Approach 2:

The invention changes the physical parameters of the sealing process by using a sealing solution with specific density (greater than the aqueous solution) and introducing surfactants to reduce surface tension. This allows beads to be sealed into arrays through density-driven separation rather than strong centrifugal force, dramatically reducing preparation time and enabling efficient sealing of millions of arrays

Inventive Principle:
Principle #35Parameter changes

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 the efficient sealing of a large number of substances into arrays, enhancing the sensitivity of target molecule detection, particularly for low-concentration molecules like those found in 10 aM concentrations.

Implementation Method 1

introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent

Methodology Applied
Scientific EffectDensity gradient: Density Gradient

Implementation Method 2

a step of introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent

Methodology Applied
Scientific EffectGravitation: Gravitation

Implementation Method 3

at least one of the first solvent and the second solvent contains a surfactant

Methodology Applied
Scientific EffectSurfactant: Surfactant

Data Source

PatentEP3168624B1Substance sealing method and target molecule detecting method
Publication Date: 2020.08.26 THE JAPAN SCI & TECH AGENCY
  • EP3168624B1 patent drawingFigure 1A~1H
  • EP3168624B1 patent drawingFigure 2

AI summary

As a technique for efficiently sealing many substances, such as beads, nucleic acid, protein, virus, cells, and lipid membrane complex, into an array, the present invention provides a method for sealing a substance, including: (i) a step of introducing a first solvent containing a substance on a substrate on which a plurality of receptacles capable of storing the substance are formed separated from each other by a side wall; and (ii) a step of introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent, the step (ii) being carried out after the step (i).