Fluid-Immersion Optical Scanning for High-Throughput Sequencing
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Solution Overview
Problem
Conventional imaging systems for biochemical experiments, such as step-and-repeat and TDI imagers, struggle to achieve high throughput and resolution required for large-scale nucleic acid sequencing, leading to increased costs due to the need for higher reagent consumption.
Innovation Solution
An optical imaging system that replaces the air gap between the objective and substrate with a fluid medium of higher refractive index, such as water or oil, and employs an actuator to maintain contact with the droplet or immerse the objective in fluid, while optimizing surface chemistries to manage friction and turbulence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional step-and-repeat or TDI imaging systems are used, then imaging throughput is limited, but system complexity and cost remain manageable
Solution Approach 1:
The patent replaces conventional mechanical imaging systems (step-and-repeat or TDI imagers) with an optical scanning system that uses a scanning objective to rapidly scan the substrate. This substitution enables higher imaging throughput by using optical scanning mechanisms instead of mechanical sensor arrays, achieving up to 100x improvement in throughput while maintaining manageable system complexity through refined optical design.
Solution Approach 2:
The patent changes the refractive index parameter by introducing a fluid medium (such as water or oil) between the scanning objective and the substrate. This parameter change improves imaging resolution and enables higher throughput scanning by reducing optical aberrations and improving light collection efficiency, thereby resolving the contradiction between throughput and system complexity.
2Measurement precision
If higher magnification is used to resolve individual samples, then spatial resolution improves, but field of view decreases
Solution Approach 1:
The patent applies segmentation by dividing the imaging process into multiple scanned regions. The scanning objective systematically moves across different fields of view on the substrate, capturing images of individual samples with high magnification in each region. This segmented approach allows the system to achieve high spatial resolution for each sample while ultimately covering a large total field of view through coordinated scanning of multiple regions.
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 imaging resolution, allowing for increased density of samples on the substrate, reducing reagent consumption and costs, and enables rapid scanning without compromising image quality.
Implementation Method 1
replaces the air gap between the objective and substrate with a fluid medium of higher refractive index
Implementation Method 2
employs an actuator to maintain contact with the droplet or immerse the objective in fluid, while optimizing surface chemistries to manage friction
Data Source
AI summary
Embodiments of the disclosure include methods and systems for nucleic acid sequencing that may include an objective coupled to an actuator, wherein the actuator is configured to move the objective over a surface of a substrate. In some embodiments, a droplet may be disposed on the surface of the substrate, and the droplet may be moved along with the objective. The distal end of the objective may include a material that provides a higher friction against the droplet than a material of the surface of the substrate. In some embodiments, the distal end of the objective may be immersed in a fluid as it is moved over the surface of the substrate. The substrate may include vertical walls within a region to retain the fluid.