Image Sensor Nanowell Segmentation for Paired-End Sequencing
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Solution Overview
Problem
Current image sensor structures for sequencing polynucleotide strands are time-consuming due to serial synthesis of forward and reverse strands, and suffer from increased probability of polyclonality and crosstalk with larger nanowells and closely spaced clusters.
Innovation Solution
The image sensor structure enables simultaneous paired-end sequencing by incorporating an array of light detectors, light guides, and nanowells with distinct primer sets in adjacent well regions, allowing for simultaneous sequencing of forward and reverse strands while reducing polyclonality and crosstalk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If serial synthesis of forward and reverse strands is used, then the sequencing process can be completed, but the sequencing time is very long
Solution Approach 1:
The nanowell is divided into two separate well regions: a first well region for forward strand synthesis and a second well region for reverse strand synthesis. This spatial segmentation allows both strands to be synthesized simultaneously in parallel, reducing total sequencing time from serial to parallel processing.
Solution Approach 2:
The invention transitions from temporal sequencing (one strand after another) to spatial sequencing (both strands simultaneously in different regions). By adding the spatial dimension of parallel well regions, the system achieves concurrent synthesis of forward and reverse strands, significantly improving productivity.
2Quantity of substance
If larger nanowells are used to accommodate larger clusters, then more polynucleotide strands can be sequenced, but the probability of polyclonality increases
Solution Approach 1:
Each well region is further divided into multiple sub-regions (e.g., first sub-region and second sub-region within each well region). This segmentation allows the large nanowell to be functionally partitioned into smaller effective synthesis zones, reducing the probability that multiple different polynucleotide strands will simultaneously seed and amplify within the same region, thereby reducing polyclonality.
3Productivity
If clusters are placed closer together to increase density, then more clusters can be sequenced, but the probability of crosstalk increases
Solution Approach 1:
The nanowell is segmented into distinct first and second well regions separated by a partition structure. This physical separation creates optical barriers that prevent light emitted from one cluster region from reaching detectors in adjacent regions, thereby eliminating crosstalk even when clusters are densely packed.
Solution Approach 2:
The partition structure acts as an intermediary barrier between the first and second well regions. This physical intermediary blocks the propagation of light signals between adjacent clusters, preventing crosstalk while allowing the clusters to be positioned close together for high density.
4Productivity
If multiple primer sets are placed in adjacent well regions for simultaneous sequencing, then sequencing throughput increases, but the complexity of the device structure increases
Solution Approach 1:
Both the first and second well regions utilize the same basic primer set structure (forward and reverse primers) and the same sequencing chemistry. This universality allows the system to achieve simultaneous sequencing of both strands using standardized components, reducing the actual complexity increase despite the added functionality.
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 significantly accelerates the sequencing process, reduces the likelihood of polyclonality, and minimizes crosstalk, thereby enhancing the efficiency and accuracy of polynucleotide strand sequencing.
Implementation Method 1
The light guides direct the emissive light photons to light detectors disposed within the image sensor structure and associated with the light guides
Implementation Method 2
The labeled strands may then emit photons of an emissive light, indicative of the order of nucleotide bases in the strand
Data Source
AI summary
An image sensor structure includes an image layer having an array of light detectors disposed therein. A device stack is disposed over the image layer. An array of light guides is disposed in the device stack. Each light guide is associated with a light detector. An array of nanowells is disposed over the device stack. Each nanowell is associated with a first light guide of the array of light guides. A first primer set is disposed throughout a first well region of each nanowell. A second primer set is disposed throughout a second well region of each nanowell. The second well region is adjacent the first well region. The first and second primer sets are operable to attach a forward strand cluster of forward polynucleotide strands in the first well region and a reverse strand cluster of reverse polynucleotide strands in the second well region.