Multiplexed Optical Sequencing Chips With Integrated Waveguide Layout
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Solution Overview
Problem
Existing nucleic acid sequencing technologies face challenges in increasing multiplexing capability while reducing instrument size and cost, due to design constraints and high complexity of optical systems.
Innovation Solution
The development of optical analytical systems comprising multiplexed optical chips with integrated optical waveguides, input optical couplers, detectors, and optical sources, which simplify the optical pathways and reduce the need for complex components like mirrors and prisms, allowing for higher multiplexing and efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional optical systems with complex optical trains are used, then light can be directed, focused, filtered, split, and detected, but the system becomes complex, costly, and requires significant space
Solution Approach 1:
The patent integrates multiple optical functions (direction, focusing, filtering, splitting, detection) into a single integrated optical circuit chip. This merging eliminates the need for separate mirrors, lenses, and optical elements, thereby reducing system complexity while maintaining full optical manipulation capability.
Solution Approach 2:
The patent replaces mechanical optical components (mirrors, lenses, prisms) with integrated optical circuit structures fabricated on a chip. This substitution transitions from discrete mechanical optical elements to a unified planar optical system, significantly reducing complexity and space requirements.
2Productivity
If the scale of sequencing arrays is increased beyond current size, then multiplexing capability improves, but design rule constraints related to wafer field stitching, number of dies per wafer, and chip yield concerns prevent further scaling
Solution Approach 1:
The patent divides the large-scale sequencing array into multiple smaller unit cells that can be independently fabricated on standard wafers. These segmented unit cells are then stitched together to form the complete large-scale array, bypassing wafer field stitching constraints and enabling higher multiplexing capability.
Solution Approach 2:
The patent implements a hierarchical structure where multiple unit cells (smaller functional modules) are nested within a larger sequencing array. This nested architecture allows the system to achieve large-scale multiplexing while maintaining compatibility with standard fabrication processes and wafer sizes.
3Productivity
If the multiplex is increased by decreasing the size of individual unit cell, then sequencing capacity improves, but crosstalk between unit cells and fabrication limitations prevent further miniaturization
Solution Approach 1:
The patent applies different structural characteristics to different regions of the optical circuit chip. Specifically, isolation structures are strategically positioned between unit cells to prevent crosstalk, while the internal structure of each unit cell is optimized for high-density sequencing. This local differentiation enables miniaturization without sacrificing reliability.
Solution Approach 2:
The patent introduces isolation structures as intermediary elements between adjacent unit cells. These intermediaries act as barriers that prevent optical and electrical crosstalk while allowing the unit cells to be densely packed, thereby enabling higher multiplexing without compromising signal integrity.
4Productivity
If laser irradiance is increased to service a larger sequencing area on a single microchip, then sequencing throughput improves, but aggregate laser cost and overall instrument size increase
Solution Approach 1:
The patent divides the sequencing array into multiple unit cells that can be serviced by multiple lower-power laser sources distributed across the chip. This segmentation allows each laser to illuminate a smaller area with adequate power, avoiding the need for a single high-power laser and reducing aggregate laser cost and instrument size.
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 the multiplexing capability of nucleic acid sequencing, reduces instrument size and cost, and improves signal detection by minimizing optical losses and cross-talk, thereby increasing throughput and accuracy.
Implementation Method 1
at least one optical waveguide in optical connection with the plurality of reaction regions
Implementation Method 2
an input optical coupler in optical connection with the at least one optical waveguide
Implementation Method 3
an optical detector in optical connection with the plurality of reaction regions
Implementation Method 4
an optical source; and a plurality of optical delivery devices in optical connection with the optical source
Data Source
AI summary
Provided herein are highly multiplexed optical analytical systems for improved nucleic acid sequencing. The systems include a plurality of highly multiplexed optical chips, at least one optical source, and a plurality of optical delivery devices for illuminating an array of nanoscale rection regions on each of the optical chips. In use, the reaction regions contain fluorescent nucleic acid sequencing reagents and are arranged to report nucleic acid sequence information to optical detectors associated with the multiplexed optical chips in real time. The systems enable a massive increase in the scale of nucleic acid sequencing reactions capable of being performed within a single instrument without a corresponding increase in size, complexity, or cost of the instrument.