Hybridization Device Mixing Beads Bubble Formation

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Solution Overview

Problem

Current methods for manufacturing high-density microarrays face challenges in efficiently hybridizing target oligonucleotides with complementary probes, particularly in ensuring effective mixing and reducing bubble formation during the hybridization process, which can affect the accuracy and sensitivity of nucleic acid assays.

Innovation Solution

A method and system utilizing mixing beads to agitate and mix the target solution while hybridizing it with complementary probes on an array, where the beads are either magnetically agitated or contained within a permeable barrier to prevent direct contact with the array surface, enhancing hybridization efficiency and reducing bubble issues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If mixing beads are agitated to mix the target solution during hybridization, then hybridization efficiency is improved, but bubbles may form and affect assay accuracy

Engineering Contradiction:
Improvehybridization efficiencyVSAvoidbubble formation
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a permeable barrier as an intermediary component that separates the mixing beads from the array surface. This barrier allows small molecules and target oligonucleotides to pass through while containing the mixing beads, enabling effective mixing without direct bead-array contact that would cause bubble formation and assay interference

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The hybridization chamber is segmented into distinct zones: a bead-containing region for mixing and a bead-free region for array placement. This spatial segmentation allows mixing beads to be agitated vigorously for efficient hybridization while maintaining a bubble-free zone where the array remains undisturbed for accurate detection

Inventive Principle:
Principle #1Segmentation

2Stability of the object's composition

If mixing beads are used to agitate the solution, then mixing thoroughness is improved, but direct contact with the array surface may occur causing damage

Engineering Contradiction:
Improvesolution mixing thoroughnessVSAvoidarray surface integrity
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

A permeable barrier serves as a protective intermediary between mixing beads and the array surface. This barrier physically separates the two components, allowing the beads to be agitated for thorough mixing while preventing direct contact that would damage the delicate array surface

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The permeable barrier is implemented as a flexible thin film or membrane that allows molecular passage while providing mechanical protection. This thin film structure enables solution mixing through the barrier while protecting the array surface from mechanical damage by the mixing beads

Inventive Principle:
Principle #30Flexible shells and thin films

3Productivity

If hybridization time is reduced to increase productivity, then throughput is improved, but hybridization completeness may be compromised

Engineering Contradiction:
Improvehybridization throughputVSAvoidhybridization completeness
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The mixing beads are agitated through mechanical vibration or shaking during hybridization. This mechanical agitation enhances the kinetics of target oligonucleotide-probe interactions, ensuring complete hybridization even at reduced time points and thereby maintaining high throughput without sacrificing hybridization completeness

Inventive Principle:
Principle #18Mechanical vibration

Solution Approach 2:

The system transitions from static hybridization to dynamic mixing by introducing agitated mixing beads. This dynamic approach accelerates hybridization kinetics, allowing shorter incubation times while achieving the same level of hybridization completeness, thus improving overall productivity

Inventive Principle:
Principle #15Dynamics

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 increases hybridization efficiency, reduces hybridization time, and enhances assay sensitivity by ensuring thorough mixing, while minimizing the impact of bubbles on the array, allowing for lower target concentrations and reduced amplification requirements.

Implementation Method 1

The mixing beads may be magnetic and agitated to mix the target solution. In one embodiment, a magnetic field is applied to agitate the mixing beads in the target solution.

Methodology Applied
Scientific EffectMagnetic agitation: Magnetic Field

Implementation Method 2

In another embodiment, an optional permeable barrier is provided. The permeable barrier contains the beads in a sub chamber of the container, preventing the mixing beads from directly contacting the array surface.

Methodology Applied
Scientific EffectPermeable barrier containment: Semipermeable Membrane

Data Source

PatentUS8445201B2Hybridization device, methods, and system using mixing beads
Publication Date: 2013.05.21 AFFYMETRIX INC
  • US8445201B2 patent drawing
  • US8445201B2 patent drawing
  • US8445201B2 patent drawing

AI summary

A method, device and system for hybridizing a target oligonucleotide to at least one array comprising a plurality of mixing beads are provided. A target solution is mixed by agitating the mixing beads while the target oligonucleotides are hybridizing to the complementary probes on the array. In another embodiment, a permeable barrier contains the mixing beads, thereby preventing them from contacting the array surface.