Asymmetric Nanowell Flowcells for Reduced-Dimensionality SIM Imaging

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Solution Overview

Problem

Conventional structured illumination microscopy (SIM) techniques require a large number of images and dimensions to achieve high resolution, which is inefficient and incompatible with line scanning techniques, limiting their application in nucleic acid sequencing and imaging.

Innovation Solution

The use of asymmetrically or square patterned flowcells with optical diffraction gratings that are phase shifted and oriented to capture fewer images, leveraging line scanning techniques like time delay integration (TDI) to achieve high resolution imaging by reducing the number of angles and phases needed, thereby simplifying the imaging process and reducing computational requirements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional SIM techniques are used to achieve high resolution imaging, then imaging resolution is improved, but the number of images and dimensions required increases significantly

Engineering Contradiction:
Improveimaging resolutionVSAvoidnumber of images
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and removes redundant imaging dimensions from conventional SIM by using asymmetric flow cell patterns that inherently provide spatial encoding in one dimension, eliminating the need for multiple angular acquisitions and reducing the total number of images required while maintaining high resolution

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent transitions from conventional 2D symmetric patterns to asymmetric patterns that utilize the third dimension (flow direction) for spatial encoding, allowing high resolution imaging with fewer images by leveraging the flow dimension for positional information

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Measurement precision

If conventional SIM techniques are used to achieve high resolution imaging, then imaging resolution is improved, but device complexity and computational requirements increase

Engineering Contradiction:
Improveimaging resolutionVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The asymmetric flow cell pattern serves multiple functions simultaneously: it provides spatial encoding, defines the imaging geometry, and enables resolution enhancement without requiring external modulation devices, making the system self-sufficient and reducing overall complexity

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The asymmetric flow cell pattern performs multiple functions including spatial encoding, resolution enhancement, and flow direction indication, eliminating the need for separate components and reducing device complexity while maintaining high resolution capability

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If conventional SIM techniques are used to achieve high resolution imaging, then imaging resolution is improved, but processing power and storage needs increase

Engineering Contradiction:
Improveimaging resolutionVSAvoidprocessing power
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The asymmetric flow cell pattern pre-encodes spatial information in the flow direction before imaging, so that during image processing, less computational effort is needed to reconstruct high resolution images, reducing processing power requirements while maintaining resolution

Inventive Principle:
Principle #10Preliminary action

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 reduces the number of images and dimensions required for high resolution imaging, making it more efficient and compatible with line scanning techniques, thereby enhancing the resolution and reducing processing power and storage needs in nucleic acid sequencing and imaging applications.

Implementation Method 1

a linearly polarized light beam is directed through an optical diffraction grating that diffracts the beam into two or more separate orders that may be projected on the imaged sample as a sinusoidal interference fringe pattern

Methodology Applied
Scientific EffectDiffraction: Diffraction

Implementation Method 2

a linearly polarized light beam is directed through an optical diffraction grating that diffracts the beam into two or more separate orders that may be projected on the imaged sample as a sinusoidal interference fringe pattern

Methodology Applied
Scientific EffectInterference: Interference

Data Source

PatentUS11933728B2Reduced dimensionality structured illumination microscopy with patterned arrays of nanowells
Publication Date: 2024.03.19 ILLUMINA CAMBRIDGE LTD
  • US11933728B2 patent drawing
  • US11933728B2 patent drawing
  • US11933728B2 patent drawing

AI summary

Techniques are described for reducing the number of angles needed in structured illumination imaging of biological samples through the use of patterned flowcells, where nanowells of the patterned flowcells are arranged in, e.g., a square array, or an asymmetrical array. Accordingly, the number of images needed to resolve details of the biological samples is reduced. Techniques are also described for combining structured illumination imaging with line scanning using the patterned flowcells.