Substrate With Selective Active Regions For Single Molecule Sequencing

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Solution Overview

Problem

Current methods for analyzing individual molecules or low concentrations of molecules lack selectivity in reaction component localization, leading to interference from other reaction components and background noise in analytical operations, particularly in nucleic acid sequencing.

Innovation Solution

The development of substrates with selectively active regions, utilizing nanostructures and optical analysis structures to provide enhanced optical access and control over chemical groups, allowing for the precise localization and activation of molecules within optical confinements like zero mode waveguides, using techniques such as photoactivation and deactivation to create trapping forces and immobilize molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If molecules are analyzed in solution without localization, then analysis can be performed on individual molecules, but interference from other reaction components and background noise increases

Engineering Contradiction:
Improveanalysis accuracyVSAvoidinterference and background noise
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The substrate surface is divided into discrete reaction sites or regions, each capable of containing individual molecules or small numbers of molecules. This segmentation isolates reaction components spatially, preventing interference from other molecules while enabling individual molecule analysis through optical confinement techniques.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the substrate are provided with specific functional properties to create localized reaction environments. Optical confinement structures are selectively positioned at reaction sites to trap and concentrate light, enhancing signal detection while maintaining spatial isolation from background interference.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If optical confinement techniques are used to monitor single molecule reactions, then selectivity is improved, but device complexity increases

Engineering Contradiction:
Improvereaction component selectivityVSAvoidoptical confinement structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The optical confinement structures are integrated directly into the substrate architecture, merging the optical monitoring function with the reaction platform. This combination eliminates the need for separate optical apparatus while maintaining single-molecule detection capability, thereby reducing overall device complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The substrate structures themselves provide the optical confinement properties needed for single-molecule detection. The geometric features of the reaction sites naturally trap and concentrate light, eliminating the need for external optical components and simplifying the overall system design.

Inventive Principle:
Principle #25Self-service

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 enables the selective immobilization of molecules within desired regions, reducing interference and background noise, allowing for accurate analysis of individual molecules by enhancing the spatial control and isolation of reaction sites, particularly in single molecule sequencing applications.

Implementation Method 1

Surface functional groups are then provided that are capable of being activated or deactivated by a first electromagnetic radiation, which is directed at the substrate whereby the optical analysis structure directs the electromagnetic radiation to selectively activate or deactivate the surface functional groups

Methodology Applied
Scientific EffectPhotoactivation: Photopolymerisation

Implementation Method 2

The substrate comprises an optical analysis structure disposed thereon, the optical analysis structure providing enhanced optical access to selected regions of the substrate

Methodology Applied
Scientific EffectElectromagnetic radiation direction: Waveguide (optics)

Data Source

PatentUS11186871B2Articles having localized molecules disposed thereon and methods of producing same
Publication Date: 2021.11.30 PACIFIC BIOSCIENCES OF CALIFORNIA INC
  • US11186871B2 patent drawing
  • US11186871B2 patent drawing
  • US11186871B2 patent drawing

AI summary

Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.