Flow Cell Layout for Multi-Surface Sequencing Imaging
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Solution Overview
Problem
Fluorescence-based genomic testing assays face errors due to dense packing of labeled molecules and low contrast-to-noise ratio, leading to incorrect attribution of fluorescence signals.
Innovation Solution
The development of flow cell devices with axially-displaced fluidic channels and optical systems that allow imaging of multiple surfaces without moving optical compensators, using an objective lens with a field-of-view greater than 1.0 mm² and a numerical aperture less than 0.6, and a processor for correcting optical aberrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple surfaces are imaged using traditional optical systems, then optical compensators must be moved in and out of the optical path, but this increases system complexity and vulnerability to vibration errors
Solution Approach 1:
The flow cell device utilizes axially-displaced surfaces positioned at different depths along the optical axis, allowing the imaging system to capture multiple surfaces simultaneously by focusing at different axial positions. This eliminates the need for mechanical movement of optical compensators while maintaining the capability to image multiple surfaces independently.
Solution Approach 2:
The optical system is designed with a large field-of-view objective lens that can image multiple axially-displaced surfaces within a single field of view, making the system universally capable of imaging any surface within the flow cell without requiring additional optical elements or mechanical adjustments.
2Quantity of substance
If labeled molecules are densely packed on the substrate, then sample capacity increases, but detection accuracy decreases due to low contrast-to-noise ratio
Solution Approach 1:
The system transitions from imaging a single two-dimensional surface to simultaneously imaging multiple surfaces at different axial positions. This three-dimensional approach distributes the detection volume across multiple planes, effectively increasing the total sample capacity while maintaining adequate spacing between molecules on each individual surface to preserve detection accuracy.
Solution Approach 2:
The flow cell is divided into multiple discrete surfaces that are axially displaced from each other. Each surface can be independently imaged and analyzed, allowing the system to process large quantities of samples distributed across multiple surfaces while maintaining the detection precision that would be achievable on a single surface with lower density.
3Productivity
If traditional flow cells with one or dual surfaces are used, then optical systems are simpler, but sequencing throughput is limited
Solution Approach 1:
The flow cell incorporates multiple surfaces displaced along the axial dimension, allowing the imaging system to capture data from multiple surfaces simultaneously within a single field of view. This multiplies the sequencing throughput by the number of surfaces imaged while avoiding the need for complex mechanical systems to switch between surfaces.
Solution Approach 2:
Multiple imaging surfaces are combined within a single flow cell device, and the optical system is designed to image all surfaces simultaneously. This merging of multiple surfaces into one integrated device increases throughput without requiring multiple separate flow cells or complex switching mechanisms.
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 sequencing throughput, reduces errors, and minimizes reagent consumption while maintaining accurate imaging and sequencing efficiency.
Implementation Method 1
an objective lens having a field-of-view (FOV) of greater than 1.0 square millimeters (mm2)
Implementation Method 2
a fluorescence photon signal is generated in one or more spatially-localized positions on the substrate
Implementation Method 3
the optical system exhibits a root-mean-square (RMS) wavefront error of less than 0.09λ, wherein λ is a center wavelength of the excitation energy source
Implementation Method 4
an excitation energy source configured to illuminate one or more surfaces of a flow cell
Data Source
AI summary
Fluorescence imaging systems designs, flow cell devices, and methods of are described herein that enable imaging of three or more axially displaced surfaces without using any optical compensators. The optical systems and flow cell devices herein provides higher throughput analysis for genomics and other imaging applications at a lower cost.