Integrated Sequencing Read Head With Parallel Microfluorometer Imaging
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Solution Overview
Problem
Current nucleic acid sequencing technologies are costly and time-consuming, hindering the transition of genomic research findings into clinical applications, and there is a need for more affordable and rapid sequencing methods to support large genetic correlation studies and individual patient treatment.
Innovation Solution
A detection apparatus with integrated microfluorometers for wide-field image detection and a fluidics cartridge for nucleic acid sequencing, enabling high-resolution imaging and modular fluidic processing to reduce costs and increase throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional sequencing techniques are used, then sequencing accuracy is maintained, but throughput is slow and cost is high
Solution Approach 1:
The system divides the sequencing task into parallel processing units by using multiple microfluorometers (e.g., 4, 9, or 16 detectors) that simultaneously image different regions of the flow cell. Each microfluorometer captures images of a specific area, and the data are combined to achieve complete genome sequencing, thereby increasing throughput without sacrificing accuracy
Solution Approach 2:
The patent transitions from sequential single-point detection to simultaneous wide-field planar imaging. By using wide-field objectives with large fields of view (e.g., 2.4mm diameter), the system captures thousands of clusters across the entire flow cell surface at once, adding a spatial dimension to the detection process and dramatically improving productivity
2Productivity
If conventional sequencing techniques are used, then sequencing accuracy is maintained, but cost is high
Solution Approach 1:
The system uses a single wide-field objective lens to perform multiple functions: excitation light delivery, fluorescence collection, and wide-area imaging. The objective serves as both the illumination path and detection path, eliminating the need for separate laser delivery optics and simplifying the overall system architecture while maintaining high throughput
Solution Approach 2:
The patent combines the excitation source, objective lens, and detector into an integrated microfluorometer unit. The beam splitter merges the excitation light path and emission light path, allowing both functions to occur simultaneously through the same optical components, thereby reducing device complexity while achieving parallel processing
3Productivity
If multiple detection channels are used to increase throughput, then imaging speed is improved, but optical alignment difficulty increases
Solution Approach 1:
The system merges the excitation and emission optical paths into a single wide-field objective. By using a beam splitter to combine these paths, the system achieves simultaneous illumination and detection through the same objective, ensuring automatic alignment between excitation and detection channels and eliminating complex multi-objective alignment requirements
Solution Approach 2:
The patent uses identical microfluorometer units (each with matching objectives and detectors) to create multiple detection channels. This modular copying approach ensures that all channels have the same optical characteristics and alignment requirements, simplifying the calibration and alignment process compared to using different or custom-configured detection systems
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
The apparatus facilitates rapid and cost-effective nucleic acid sequencing by allowing high-resolution imaging and efficient fluidic processing, reducing the time and expense required for genetic correlation studies and clinical applications.
Implementation Method 1
each of the microfluorometers includes an objective
Implementation Method 2
acquire a plurality of wide-field images of a first portion of the surface using a plurality of microfluorometers
Data Source
AI summary
A detection apparatus having a read head including a plurality of microfluorometers positioned to simultaneously acquire a plurality of the wide-field images in a common plane; and (b) a translation stage configured to move the read head along a substrate that is in the common plane. The substrate can be a flow cell that is included in a cartridge, the cartridge also including a housing for (i) a sample reservoir, (ii) a fluidic line between the sample reservoir and the flow cell; (iii) several reagent reservoirs in fluid communication with the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the flow cell; and (v) at least one pressure source configured to move liquids from the reservoirs to the flow cell. The detection apparatus and cartridge can be used together or independent of each other.