Flow Cell Scanning Optics for Parallel Sequencing Detection
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Solution Overview
Problem
Existing sequencing instrumentation is time-consuming and costly due to significant time spent moving stages and scanning multiple times for nucleotide, dye, or color, limiting the benefits of excitation power and reducing acquisition time.
Innovation Solution
Implementing multiple cameras or imaging devices sharing a single excitation source, along with a scanning detector array, to collect emissions simultaneously from different groups of locations on a substrate, and using modulating optics to shape radiation for efficient detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If a single camera and stage positioning system are used for sequencing data acquisition, then the system structure remains simple, but the acquisition time increases significantly due to repeated stage movement and settling
Solution Approach 1:
The imaging system is segmented into multiple independent camera units, each capable of simultaneously capturing data from different spatial locations. This segmentation allows parallel processing of sequencing data acquisition across multiple positions, eliminating the sequential bottleneck of single-camera systems and reducing total acquisition time without requiring complex coordination between imaging components
Solution Approach 2:
The system transitions from a single-point detection approach to a multi-point parallel detection approach by adding the dimension of multiple simultaneous cameras. This dimensional expansion from one camera to multiple cameras enables concurrent imaging at different locations, fundamentally changing the time complexity from sequential to parallel processing
2Productivity
If excitation power is increased to improve signal strength, then the integration time can be reduced, but the benefit is limited when most time is spent moving the stage rather than collecting data
Solution Approach 1:
By segmenting the detection function across multiple cameras, the system can simultaneously image multiple locations without requiring stage movement between each location. This segmentation of the imaging task allows the stage to remain stationary while multiple cameras capture data in parallel, eliminating stage movement time from the productivity calculation
Solution Approach 2:
The useful action of data collection continues simultaneously at multiple locations through the parallel camera system, rather than sequentially moving through locations one by one. This continuous parallel imaging eliminates idle time between measurements and maintains productive action throughout the entire measurement cycle
3Measurement precision
If multiple scans are performed for each nucleotide or dye (four or more scans), then accurate sequence information can be generated, but the time required and operational cost increase significantly
Solution Approach 1:
The segmentation into multiple cameras allows each camera to be dedicated to a specific nucleotide or dye channel, enabling simultaneous acquisition of all sequence information in a single scan. This eliminates the need for repeated sequential scans while maintaining the precision of multi-channel sequencing data
Solution Approach 2:
Each camera in the array serves multiple functions by simultaneously detecting different fluorescent signals corresponding to different nucleotides or dyes. This multi-functionality allows a single imaging cycle to capture information that would traditionally require multiple separate scans, reducing total time while preserving measurement precision
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
Improves throughput by reducing integration time and increasing system speed while maintaining accuracy in sequencing data acquisition.
Implementation Method 1
one or more irradiation sources configured to irradiate the substrate and cause a first reaction, such as a fluorescence emission, to occur at a first group of locations on the substrate
Implementation Method 2
A scanning detector, for example, a detector array, can be included that is positioned with respect to the one or more irradiation sources so as to collect emission from the first group of locations
Data Source
AI summary
A scanning detection system is provided wherein emissions from locations in a flow cell are detected. In some embodiments, the system can comprise an excitation source, a photocleavage source, and modulating optics configured to cause an excitation beam generated by the excitation source to irradiate a first group of the fixed locations and to cause a photocleavage beam generated by the photocleavage source to irradiate a second group of the fixed locations, which is separate and apart from the first group of fixed locations. Methods of detecting sequencing reactions using such a system are also provided.