Flow Cell Optical Layout for Multi-Surface Sequencing Accuracy
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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
Flow cell devices with axially-displaced fluidic channels and optical systems that allow imaging of multiple surfaces without moving optical compensators, enabling homogenous illumination and reduced reagent consumption, with simultaneous sequencing of morphological, RNA, and protein targets.
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 susceptibility to vibration errors
Solution Approach 1:
The optical system is divided into distinct modules: a fixed objective lens for imaging, a separate illumination system with multiple light sources, and a detection system. This segmentation allows each component to be optimized independently while maintaining the ability to image multiple surfaces without moving compensators, thus reducing overall system complexity while preserving versatility.
Solution Approach 2:
A beam splitter or dichroic mirror is introduced as an intermediary element that allows the illumination light to be directed onto the sample while simultaneously allowing the emitted fluorescence signal to pass through to the detector. This intermediary enables multiple surfaces to be imaged without requiring physical movement of optical compensators, reducing system complexity while maintaining adaptability.
2Productivity
If labeled molecules are densely packed on substrate to increase throughput, then sequencing throughput increases, but detection errors increase due to low contrast-to-noise ratio
Solution Approach 1:
The system transitions from imaging a single 2D surface to simultaneously imaging multiple surfaces stacked in the axial dimension. By utilizing flow cells with multiple surfaces separated by transparent spacing, the system increases the effective number of samples being sequenced without increasing the density of molecules on any single surface, thereby maintaining detection accuracy while improving overall throughput.
Solution Approach 2:
The optical system is designed to universally image multiple surfaces simultaneously using a single objective lens and detection system. This multi-functional capability allows the system to process samples from multiple surfaces in parallel, increasing throughput without requiring higher molecule density on individual surfaces, thus preserving measurement precision.
3Device complexity
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 system adds the axial dimension by utilizing flow cells with multiple surfaces stacked vertically. A single objective lens is positioned to image through the transparent flow cell structure, capturing fluorescence signals from multiple surfaces simultaneously. This dimensional expansion increases sequencing throughput without significantly increasing optical system complexity, as the same objective and detection components are used for all surfaces.
Solution Approach 2:
Multiple imaging tasks (imaging of multiple surfaces) are merged into a single simultaneous operation using one objective lens and one detection system. The illumination system is configured to illuminate all surfaces simultaneously, and the detection system captures signals from all surfaces at the same time, thereby increasing throughput while maintaining optical system simplicity.
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
Improved sequencing throughput and accuracy with reduced errors and hands-on time, allowing for simultaneous imaging and sequencing of multiple targets with enhanced image quality and reduced reagent use.
Implementation Method 1
a light source configured to illuminate the cell or the tissue, thereby generating a plurality of signals corresponding to the plurality of analytes
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.