Flowcell Immersion Imaging to Raise NA and Reduce Scan Turbulence
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Solution Overview
Problem
Conventional imaging systems for biochemical reactions in flowcells suffer from limitations in throughput, optical resolution, and efficiency due to the use of air gaps, which restrict the numerical aperture and increase turbulence during rapid scanning.
Innovation Solution
The implementation of a liquid immersion system with controlled liquid dispensing and collection between the imaging objective and the flowcell cover, maintaining a stable liquid medium during scanning to enhance numerical aperture and reduce turbulence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If air gap is used between objective lens and flowcell cover, then device complexity is reduced, but numerical aperture is limited and optical resolution deteriorates
Solution Approach 1:
The patent introduces an intermediary liquid medium (immersion fluid) between the objective lens and flowcell cover to resolve the contradiction. This liquid intermediary enables high numerical aperture (up to 1.5) and superior optical resolution while maintaining a relatively simple device structure. The liquid serves as the mediating substance that transmits light with minimal refraction loss, achieving both optical performance and structural simplicity.
Solution Approach 2:
The patent changes the physical parameter of the medium between lens and cover from gas (air) to liquid (immersion fluid). This parameter change increases the refractive index from approximately 1.0 (air) to 1.33-1.5 (liquid), thereby increasing numerical aperture and optical resolution without significantly complicating the device structure.
2Productivity
If scanning speed is increased to improve throughput, then productivity increases, but turbulence increases and image quality deteriorates
Solution Approach 1:
The liquid immersion medium acts as a damping intermediary that reduces turbulence effects during rapid scanning. The higher viscosity and density of the liquid compared to air provides stabilizing effects on the optical path, allowing faster scanning speeds without proportionally increasing turbulence-induced image degradation.
Solution Approach 2:
Changing the medium from air to liquid fundamentally alters the fluid dynamics parameters in the imaging path. The liquid's higher density and viscosity dampen turbulent fluctuations, enabling higher scanning speeds while maintaining image quality. This parameter change allows throughput improvement without proportional turbulence increase.
3Manufacturing precision
If numerical aperture is increased to improve optical resolution, then manufacturing precision improves, but device complexity increases due to liquid management systems
Solution Approach 1:
The flowcell cover serves multiple functions: it contains the biochemical sample, defines the imaging chamber, and acts as the interface for liquid immersion. By making the cover multi-functional, the patent achieves high numerical aperture without adding separate complex liquid management components, thus improving optical resolution while limiting device complexity increase.
Solution Approach 2:
The system uses the existing flowcell structure and liquid handling capabilities to provide the immersion function. The liquid is delivered through the flowcell's own fluidic pathways, and the cover's geometry is designed to contain the liquid layer. This self-service approach achieves high NA without requiring external complex liquid management systems.
4Area of stationary object
If field of view is increased to cover large sample areas, then area of stationary object increases, but magnification decreases and resolution deteriorates
Solution Approach 1:
The patent changes the refractive index parameter of the medium from air (n≈1.0) to liquid (n≈1.33-1.5), which increases numerical aperture. This parameter change allows the optical system to maintain high resolution across a larger field of view, effectively resolving the trade-off between field size and resolution by improving the fundamental optical parameters.
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 allows for higher optical resolution and increased density of biochemical samples, reducing reagent costs and improving imaging speed and quality.
Implementation Method 1
The numerical Aperture of an optical system is limited by the lowest refractive index of media between the sample and the objective lens. The index of most glasses is between 1.4 and 1.6, and the index of water is roughly 1.33. The index of air is 1.0.
Implementation Method 2
Conventional imaging systems for biochemical reactions in flowcells suffer from limitations in throughput, optical resolution, and efficiency due to the use of air gaps, which restrict the numerical aperture and increase turbulence during rapid scanning.
Data Source
AI summary
Systems and methods for immersion imaging of a flowcell. In one example, an imaging system includes liquid ports in leading and trailing positions relative to a scanned imaging objective. The leading liquid port dispenses an immersion liquid into a space between the distal end of the imaging objective and the flowcell's cover, with the trailing liquid port collecting the immersion liquid. In another example, an imaging system includes a flowcell with a cover that is moveable relative a substrate. The system is configured to move the imaging objective and flowcell cover as a unit relative to the flowcell substrate.