Integrated Waveguide Flow Cell for Parallel Fluorescence Lifetime Sequencing
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Solution Overview
Problem
Current sequencing methods, particularly real-time single molecule sequencing, face challenges due to system complexity, sub-optimal setups, and slower speeds attributed to stochastic processes and fluidic manipulations, with existing CMOS SPAD arrays experiencing disadvantages in parallelized detection.
Innovation Solution
An integrated detection, flow cell, and photonics (DFP) device is developed, featuring a CMOS substrate with photon time of arrival detector elements, waveguides, optical isolation layers, and functionalization layers for improved photon detection and fluid handling, enabling efficient real-time sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If real-time single molecule sequencing is implemented, then sequencing speed is improved, but system complexity increases due to stochastic processes and fluidic manipulations
Solution Approach 1:
The patent combines multiple functions into a single integrated device: the flow cell structure, waveguide array for light delivery, and detector array for photon detection are merged into one unified system. This integration reduces the number of separate components and interfaces, thereby reducing system complexity while maintaining high sequencing speed through real-time single molecule detection
Solution Approach 2:
The waveguides serve multiple functions: they guide excitation light to the flow cell, collect emitted photons from fluorescent labels, and enable parallel detection of multiple nucleotides simultaneously. This multi-functionality reduces the need for separate optical paths and detection systems, simplifying the overall system architecture while enabling high-speed real-time sequencing
2Productivity
If fluidic manipulations are used for reagent delivery, then sequencing cycles can be completed, but processing time increases
Solution Approach 1:
The flow cell design enables continuous flow of reagents through the channel, allowing nucleotides to be continuously delivered to the single molecules without discrete stopping and starting. This continuous action eliminates dead time between reagent deliveries and maintains constant detection, thereby reducing total processing time while maintaining high sequencing throughput
Solution Approach 2:
Nucleotides are pre-loaded into the flow cell channel before the sequencing reaction begins. The flow cell is filled with nucleotide solution in advance, and the sequencing reaction proceeds by simply initiating the flow or activation, rather than requiring step-by-step reagent addition. This preliminary preparation reduces the time required for reagent delivery during the actual sequencing process
3Measurement precision
If CMOS SPAD arrays are used for photon detection, then detection capability is improved, but parallelized detection performance is sub-optimal
Solution Approach 1:
The detection system is segmented into multiple independent waveguide-detector pairs, with each waveguide optically coupled to its own detector element in the array. This segmentation allows each detector to independently process photons from its associated waveguide, enabling true parallelized detection of multiple nucleotides simultaneously, thereby improving both detection precision and parallel processing performance
Solution Approach 2:
The waveguides act as intermediaries between the flow cell and the detector array. Each waveguide is optically coupled to a specific detector element, creating a dedicated optical path that mediates the transfer of photon information from the single molecules in the flow cell to the detector. This intermediary structure enables efficient parallelized detection by preventing cross-talk between detectors and ensuring that each detector receives photons only from its associated waveguide region
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 DFP device enhances sequencing efficiency by optimizing photon detection and fluid management, facilitating faster and more accurate real-time single molecule sequencing while reducing system complexity.
Implementation Method 1
at least one wave guide formed on the IC photo detection layer as a photonics layer
Implementation Method 2
pixel elements that sense photons during active periods, the substrate and pixel elements forming an IC photon detection layer
Data Source
AI summary
An integrated detection, flow cell and photonics (DFP) device is provided that comprises a substrate having an array of pixel elements that sense photons during active periods. The substrate and pixel elements form an IC photon detection layer. At least one wave guide is formed on the IC photo detection layer as a photonics layer. An optical isolation layer is formed over at least a portion of the wave guide. A collection of photo resist (PR) walls patterned to define at least one flow cell channel that is configured to direct fluid along a fluid flow path. The wave guides align to extend along the fluid flow path. The flow cell channel is configured to receive samples at sample sites that align with the array of pixel elements.