Nanoarray Wells and Interstitial Regions for Sequencing
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Solution Overview
Problem
Current microarray technologies face challenges in miniaturization for next-generation sequencing, particularly in submicron domains, leading to increased reagent consumption and reduced data acquisition rates due to non-specific binding issues and particle trapping in interstitial spaces.
Innovation Solution
A nanoarray design featuring a solid support with wells and interstitial regions, where particles with bioconjugate reactive moieties and oligonucleotide moieties are used, reducing non-specific binding through polymer coatings and optimized particle loading, allowing for efficient hybridization and amplification of target polynucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If miniaturization is pursued to increase amplicon density, then sequencing throughput and data acquisition rate improve, but non-specific binding increases and particle trapping in interstitial spaces occurs
Solution Approach 1:
The patent applies local quality by creating distinct regions with different properties: wells with specific geometry (e.g., conical or cylindrical shapes with optimized depth-to-diameter ratios) that promote particle retention, and interstitial regions with modified surface properties (e.g., different polymer coatings or topography) that reduce non-specific binding. This spatial differentiation allows high-density particle placement while maintaining binding specificity.
Solution Approach 2:
The patent introduces intermediary elements such as polymer coatings (e.g., PEG-based polymers) on particle surfaces and well walls that act as mediators to reduce non-specific binding interactions. These coatings create a steric barrier that prevents unwanted adhesion while allowing specific hybridization events to occur, thus maintaining reliability at high densities.
2Loss of substance
If feature dimensions are reduced to submicron domains, then reagent consumption decreases, but particle trapping in interstitial spaces increases
Solution Approach 1:
The patent segments the surface into discrete wells with controlled dimensions and spacing. By optimizing well geometry (e.g., tapered walls, specific depth) and interstitial region characteristics, particles are guided into individual wells during loading, preventing them from becoming trapped in interstitial spaces. The segmentation creates defined capture zones that facilitate efficient particle loading even at submicron scales.
Solution Approach 2:
The patent employs parameter changes by varying well dimensions (depth, diameter, aspect ratio), interstitial region width, and surface energy characteristics to optimize particle loading. By adjusting these parameters, the system achieves efficient particle confinement in submicron wells while minimizing trapping in interstitial regions, thereby reducing reagent consumption without compromising ease of operation.
3Productivity
If amplicon density is increased, then sequencing data acquisition rate improves, but non-specific binding increases
Solution Approach 1:
The patent applies local quality by implementing spatially varying surface properties: wells are designed with specific geometries and coated with materials that promote particle retention, while interstitial regions have contrasting surface properties (e.g., hydrophilic vs. hydrophobic, charged vs. neutral) that actively repel particles and reduce non-specific binding. This local differentiation enables high amplicon density while suppressing harmful non-specific interactions.
Solution Approach 2:
The patent introduces intermediary polymer coatings (e.g., polyethylene glycol, carboxymethyl cellulose) on well walls and particle surfaces that act as steric barriers. These intermediaries prevent non-specific binding by creating a physical and chemical barrier that blocks unwanted interactions, while allowing specific hybridization to proceed. This enables high-density amplicon arrays to maintain low non-specific binding levels.
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 nanoarray design enhances the density and efficiency of nucleic acid sequencing by minimizing non-specific binding, improving reagent utilization, and maintaining high data acquisition rates, thereby overcoming the limitations of miniaturization in submicron domains.
Implementation Method 1
amplifying includes extension of the oligonucleotide moiety hybridized to the target polynucleotide
Implementation Method 2
each oligonucleotide moiety including a bioconjugate reactive moiety that reacts and forms a bioconjugate linker that covalently links the oligonucleotide moiety to the particle
Data Source
AI summary
Disclosed herein, inter alia, are nanoarrays and methods of use thereof.