Core-Shell Polymer Structures for High-Resolution Nucleic Acid Sequencing
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Solution Overview
Problem
Sequencing-by-synthesis methods face limitations in achieving high resolution due to diffraction limits and the need for high numerical aperture microscope objectives, which restrict the field of view and imaging density, making it challenging to meet the demands of high imaging rates in DNA sequencing.
Innovation Solution
The use of core-shell polymer structures, where cores are surrounded by a shell polymer, with attached core polynucleotide primers and target nucleic acids, allows for amplification and sequencing of target polynucleotides, enabling detection of amplicon clusters in multiple two-dimensional planes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high numerical aperture microscope objectives are used to achieve high resolution, then optical resolution is improved, but the field of view is limited
Solution Approach 1:
The patent transitions from two-dimensional imaging to three-dimensional imaging by incorporating z-axis information through focal plane stacking. Multiple images at different focal planes are captured and processed to create a three-dimensional representation of the sample, allowing high resolution without sacrificing field of view. This dimensional expansion enables the system to achieve both high resolution (through focused imaging) and large field of view (through volumetric coverage).
Solution Approach 2:
The patent divides the imaging process into multiple discrete focal planes, capturing images at different depths separately. Each focal plane can be optimized for resolution, while the collection of all planes provides comprehensive coverage. This segmentation allows the system to maintain high resolution at each plane while expanding the overall field of view through the aggregation of multiple planes.
2Productivity
If high imaging rates are utilized for DNA sequencing, then productivity is improved, but the complexity of maintaining resolution increases
Solution Approach 1:
The patent implements continuous imaging through automated focal plane scanning and real-time image processing. The system continuously captures images at multiple focal planes and processes them to maintain resolution without interrupting the sequencing process. This continuous operation enables high imaging rates while automatically maintaining resolution through persistent focus management and rapid data processing.
Solution Approach 2:
The patent employs automated image processing algorithms that self-adjust focus and optimize resolution parameters without manual intervention. The system automatically processes multiple focal planes, identifies the optimal focus positions, and reconstructs high-resolution images through computational methods. This self-service approach maintains resolution at high imaging rates by eliminating manual focus adjustment and using algorithmic optimization.
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 enhances optical resolution and imaging capabilities, allowing for efficient sequencing of nucleic acids by overcoming diffraction limits and improving the information content in each image.
Implementation Method 1
The maximum resolving power of imaging systems is limited by factors such as diffraction
Implementation Method 2
one or more core polynucleotide primer(s) is attached to the core polymer within the core and a target nucleic acid is hybridized to the core primer
Implementation Method 3
amplifying the target polynucleotide to produce an amplicon
Data Source
AI summary
Provided herein are methods and compositions for improved sequencing techniques using, for example, polymeric particles and/or three-dimensional structures.