Single-Analyte Array Surface Passivation for Orthogonal Binding

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Solution Overview

Problem

Orthogonal binding phenomena interfere with the detection of array features at single-molecule resolution in single-molecule arrays, caused by unintended or unexpected binding of assay components to non-intended locations, leading to false positives or negatives.

Innovation Solution

A composition and method for forming arrays with spatially separated sites on a solid support, incorporating interstitial regions and passivating molecules to inhibit binding, and strategically placing defects to minimize orthogonal binding, using sequential chemical strategies and surface layers to enhance resistance to unwanted binding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If passivating molecules are added to interstitial regions to inhibit orthogonal binding, then binding specificity is improved, but array surface coverage and assay agent accessibility are worsened

Engineering Contradiction:
Improvebinding specificityVSAvoidarray surface coverage
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies local quality by creating distinct functional zones: interstitial regions are passivated with molecules having specific chemical properties to prevent orthogonal binding, while defect regions maintain different chemical characteristics to permit intentional assay agent binding. This spatial differentiation of molecular properties enables simultaneous inhibition of unwanted binding and preservation of desired binding functionality.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent introduces passivating molecules as intermediary substances that mediate between the solid support and assay agents. These passivating molecules selectively interact with assay agents to prevent non-specific binding in interstitial regions, while the presence of defects in this passivated layer creates localized areas where assay agents can still bind intentionally to defects rather than to the passivating molecules themselves.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If defects are introduced into passivated interstitial regions to enable assay agent binding, then orthogonal binding is reduced, but manufacturing precision is worsened

Engineering Contradiction:
Improveorthogonal binding resistanceVSAvoiddefect distribution control
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent converts the harmful effect of manufacturing imperfections into a beneficial feature by intentionally creating and utilizing defects in the passivated interstitial regions. These defects, which would normally be considered manufacturing errors, are instead engineered to serve as controlled binding sites for assay agents, transforming a source of variability into a functional advantage that reduces orthogonal binding.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent employs parameter changes by controlling the chemical and physical properties of the passivating molecules and the characteristics of the defects they form. By adjusting parameters such as molecular size, charge, hydrophobicity, and defect density, the system optimizes the balance between preventing orthogonal binding and maintaining sufficient assay agent binding sites, thereby managing manufacturing precision requirements.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If multiple passivating molecules with different chemical structures are used in random distributions, then inhibition of orthogonal binding is improved, but system complexity is worsened

Engineering Contradiction:
Improveorthogonal binding inhibitionVSAvoidmolecular composition complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent utilizes composite materials by combining multiple types of passivating molecules with different chemical structures within the interstitial regions. This composite approach creates a heterogeneous molecular environment that provides broad-spectrum inhibition of orthogonal binding through diverse chemical interactions, while the random distribution pattern simplifies the overall system architecture compared to highly ordered multi-component systems.

Inventive Principle:
Principle #40Composite 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 proposed methods and compositions significantly reduce orthogonal binding, improving the accuracy and reliability of single-molecule detection by minimizing false signals and enhancing the resolution of single-analyte assays.

Implementation Method 1

a first plurality of molecules, in which the first plurality of molecules is coupled to the one or more interstitial regions, and in which each molecule of the first plurality of molecules comprises a moiety that is configured to inhibit binding of an assay agent

Methodology Applied
Scientific EffectSurface passivation: Adsorption

Implementation Method 2

a plurality of defects occurring in a random spatial distribution on the one or more interstitial regions, and in which each defect of the plurality of defects comprises a moiety that is configured to bind the assay agent

Methodology Applied
Scientific EffectDefect-mediated binding: Adsorption

Data Source

PatentUS20250222450A1Preparation of array surfaces for single-analyte processes
Publication Date: 2025.07.10 NAUTILUS SUBSIDIARY INC
  • US20250222450A1 patent drawing
  • US20250222450A1 patent drawing
  • US20250222450A1 patent drawing

AI summary

Compositions and methods are provided for forming single-analyte arrays with enhanced characteristics for inhibiting orthogonal binding of molecules to the array. Arrays are modified to contain covalently incorporated passivating moieties at array addresses where orthogonal binding may occur. The compositions and methods may facilitate detection of an increased quantity of array features at single-analyte resolution.