Semiconductor Biosensor Base Calling From Mixed Cluster Pixel Signals
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Solution Overview
Problem
Conventional solid-state imaging systems for DNA sequencing are limited by pixel density, leading to low throughput and high costs due to the need for large optical systems and expensive equipment, which restricts the ability to detect millions of nucleic acid sites accurately and efficiently.
Innovation Solution
A device and method for base calling that utilizes a biosensor with an array of sensors to generate pixel signals from multiple clusters per sensor, allowing for the classification of nucleotide bases using a signal processor that combines signals from multiple clusters, thereby increasing throughput without the need for extensive optical assemblies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional solid-state imaging systems are used for DNA sequencing, then detection capability is provided, but throughput is limited due to pixel density constraints
Solution Approach 1:
Multiple clusters are merged into a single pixel area, allowing a single sensor to detect signals from multiple clusters simultaneously. The signal processor combines these signals to identify multiple nucleotide bases, thereby increasing throughput without sacrificing detection accuracy
Solution Approach 2:
Each sensor is made multi-functional by enabling it to detect and process signals from multiple clusters rather than just one. This universal detection capability allows the same sensor array to handle higher sequencing loads without requiring proportional increases in sensor count
2Productivity
If pixel density is increased to improve throughput, then more clusters can be detected, but device complexity and cost increase due to larger optical systems
Solution Approach 1:
The system transitions from a one-to-one mapping (one cluster per pixel) to a many-to-one mapping (multiple clusters per pixel). This dimensional change in the detection relationship allows throughput to scale without proportionally increasing the sensor array size or optical system complexity
Solution Approach 2:
The patent creates a computational model that replicates the detection capability across multiple clusters within each pixel. The signal processor uses algorithms that copy and combine signal processing operations to identify multiple bases from combined cluster signals, effectively multiplying detection capacity without physical hardware expansion
3Measurement precision
If one cluster per sensor is used, then detection accuracy is maintained, but throughput is restricted and costs are high
Solution Approach 1:
The signal processor implements feedback mechanisms where signals from multiple clusters are iteratively processed and combined. The system uses feedback loops to refine base calling accuracy by comparing combined signals against expected patterns, ensuring accurate identification of multiple nucleotide bases simultaneously
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 throughput of DNA sequencing by enabling the detection of multiple clusters per sensor, reducing the need for expensive optical systems and increasing accuracy, while maintaining cost-effectiveness.
Implementation Method 1
a solid-state imager (e.g., charged-coupled device (CCD) or a complementary metal-oxide-semiconductor (CMOS) sensor) that does not require a large optical assembly to detect the fluorescent emissions
Data Source
AI summary
A device for base calling is provided. The device includes a receptacle configured to hold a biosensor having a sample surface holding a plurality of clusters during a sequence of sampling events, an array of sensors sensing information from clusters disposed in corresponding pixel areas of the sample surface during the sampling events and generate sequences of pixel signals and a communication port configured to output the sequences of pixel signals. The device also includes a signal processor coupled to the communication port and configured to receive and process at least one pixel signal in the sequences of pixel signals that mixes light gathered from at least two clusters in a corresponding pixel area, and to base call each of the at least two clusters using the at least one pixel signal.