Structured Light Modulation for Super-Resolution Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing high-throughput sequencing instruments face limitations due to the optical diffraction limit, resulting in low sequencing throughput, limited DNA sample density on sequencing chips, and high reagent costs.
Innovation Solution
A super-resolution imaging system that uses structured light generation and modulation, combined with image reconstruction techniques, to achieve higher resolution imaging of biological samples and nucleic acid sequencing chips.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If ordinary wide-field fluorescence microscopy is used for signal collection, then the imaging system is simple and easy to operate, but the resolution is limited by the optical diffraction limit to about 0.61λ/NA, resulting in low sequencing throughput
Solution Approach 1:
The patent employs structured illumination with dynamically adjustable patterns (e.g., sinusoidal, grid patterns) that can be modulated in frequency and phase. The illumination system uses spatial light modulators or acousto-optic modulators to dynamically change the illumination pattern, enabling super-resolution imaging by capturing multiple images at different illumination phases and frequencies, then reconstructing high-resolution images through computational algorithms
Solution Approach 2:
The patent changes the physical parameters of illumination light by modulating its spatial distribution, frequency, and phase. By varying the structured illumination parameters (pattern frequency, orientation, phase shifts) and using multiple excitation wavelengths, the system extracts higher spatial frequency information from the sample, achieving resolution beyond the diffraction limit while maintaining imaging speed for high-throughput sequencing
2Measurement precision
If the spacing of DNA samples on the sequencing chip is increased to meet optical resolution requirements, then the imaging quality is maintained, but the sample density is limited and chip utilization is low
Solution Approach 1:
The structured illumination system dynamically adjusts illumination patterns to selectively excite different spatial frequencies of the sample. By modulating the illumination pattern frequency and phase, the system can resolve features at spacings smaller than the diffraction limit, enabling higher DNA sample density on the sequencing chip while maintaining imaging quality through computational reconstruction
Solution Approach 2:
The patent transitions from direct spatial resolution in the object plane to frequency domain analysis by capturing multiple images under different structured illumination conditions. This dimensional transformation allows the system to extract high-frequency spatial information that would be invisible in conventional wide-field imaging, enabling denser sample packing
3Measurement precision
If the density of DNA samples on the sequencing chip is limited by optical resolution, then the imaging system can resolve individual samples, but reagent utilization is low and reagent cost is high
Solution Approach 1:
By modulating the structured illumination parameters (pattern frequency, phase, orientation) and using multiple excitation wavelengths, the system extracts higher spatial frequency information from the sample. This enables resolution of densely packed DNA samples with fewer physical resources, improving reagent utilization efficiency
Solution Approach 2:
The system creates multiple virtual images of the sample under different structured illumination conditions, then computationally reconstructs a high-resolution image. This virtual copying approach allows the system to achieve high resolution without proportionally increasing physical resource consumption (reagents, chip area)
4Measurement precision
If existing super-resolution imaging technology is used to improve resolution, then the imaging detail is enhanced, but the imaging speed is slow, restricting its application in high-throughput sequencing
Solution Approach 1:
The patent uses periodic structured illumination patterns that can be rapidly switched between different phases and orientations. By employing periodic modulation of the illumination (e.g., using acousto-optic modulators or electro-optic modulators), the system captures multiple images quickly at different illumination phases, enabling super-resolution imaging at speeds compatible with high-throughput sequencing workflows
Solution Approach 2:
The system pre-calculates and stores the relationship between structured illumination parameters and the resulting image frequencies. This preliminary preparation allows for rapid image acquisition and reconstruction without real-time complex computations, significantly speeding up the super-resolution imaging process for high-throughput applications
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 system improves the density of samples on sequencing chips, enhances imaging efficiency, and reduces reagent costs by achieving higher resolution and faster identification of biological features and nucleic acid bases.
Implementation Method 1
the structured light generation and modulation device is configured to modulate the excitation light into structured light to irradiate the biological sample
Implementation Method 2
the diffraction splitting device is configured to split the excitation light into multiple beams to form the structured light
Implementation Method 3
the objective lens is configured to eject the structured light as parallel light to the biological sample and form interference fringes
Implementation Method 4
the polarization control system is configured to adjust a polarization direction of the excitation light
Data Source
AI summary
Disclosed are a super-resolution imaging system (1, 41, 51), a super-resolution imaging method, a biological sample identification system (4, 61) and method, a nucleic acid sequencing imaging system (5) and method, and a nucleic acid identification system (6) and method. The super-resolution imaging system (1, 41, 51) includes an illumination system (A) and an imaging system (B). The illumination system (A) outputs excitation light to irradiate a biological sample to generate excited light, and the imaging system (B) collects and records the excited light to generate an excited light image. The illumination system (A) includes an excitation light source (10, 10a) and a structured light generation and modulation device (11, 11a). The excitation light source (10, 10a) outputs the excitation light, and the structured light generation and modulation device (11, 11a) modulates the excitation light into structured light to irradiate the biological sample to generate the excited light.