High-Throughput Pathogen Sequencing for Rapid Variant Surveillance
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Solution Overview
Problem
Existing PCR-based methods lack the power, responsiveness, and scalability to efficiently detect and track new variants of pathogens, particularly in large population centers, posing a challenge during pandemic-scale crises.
Innovation Solution
A high-throughput nucleic acid sequencing and analysis system utilizing a one-step RT-PCR protocol with optimized parameters, including primer modifications and temperature gradients, to rapidly determine pathogen genomes and variants, enabling efficient and scalable biosurveillance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional PCR-based methods are used for pathogen detection, then diagnostic accuracy is maintained, but the system lacks scalability and responsiveness to pandemic-scale crises
Solution Approach 1:
The system divides the testing infrastructure into modular components: sample collection units, nucleic acid extraction modules, RT-PCR amplification systems, and sequencing platforms. This segmentation allows independent optimization and scaling of each component, enabling the overall system to achieve both high throughput and adaptability to new pathogen variants
Solution Approach 2:
The patent transitions from traditional endpoint PCR detection to real-time quantitative PCR with cycle threshold (Ct) value measurement, adding a dimensional aspect of quantitative analysis. This enables not only detection but also characterization of viral load and variant identification, simultaneously improving throughput capacity and adaptability to new variants
2Productivity
If existing PCR infrastructure is scaled up, then testing capacity increases, but the system remains insufficient for tracking new variants in large populations
Solution Approach 1:
The system performs preliminary RT-PCR amplification and Ct value determination on all samples in a high-throughput manner before proceeding to sequencing analysis. This preliminary action filters samples and prepares them in advance, allowing the sequencing step to focus resources on variant detection with high precision while maintaining overall high testing capacity
Solution Approach 2:
The patent uses RT-PCR to generate multiple copies of the viral genome from limited input RNA, creating amplified cDNA templates. This copying process enables subsequent sequencing reactions to achieve high measurement precision for variant detection while the initial RT-PCR step maintains high productivity through parallel processing of many samples
3Speed
If rapid pathogen identification is implemented at ports of entry, then spread prevention is improved, but the complexity of the system increases
Solution Approach 1:
The patent combines multiple functions into integrated systems: sample processing and nucleic acid extraction are merged with RT-PCR amplification, which is then merged with sequencing library preparation. This consolidation reduces the number of separate devices and operations needed, achieving rapid identification at ports of entry while managing system complexity through integration rather than proliferation of separate components
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 system allows for rapid identification and characterization of pathogen variants within populations, enhancing the speed and accuracy of genomic surveillance, enabling timely public health responses and mitigation strategies.
Implementation Method 1
performing a RT-PCR protocol on RNA from a biological sample to generate a plurality of cDNA molecules
Data Source
AI summary
Provided herein are methods and systems for high throughput sequencing of nucleic acids for the surveillance of pathogens in a population and efficient identification of new pathogen variants of concern.