Barcoded NGS Assay for Massively Parallel Pathogen and Host Response Detection
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Solution Overview
Problem
Current COVID-19 diagnostic methods, particularly qPCR-based tests, face challenges in scalability and throughput, leading to bottlenecks in diagnosis and increased occupational hazards for healthcare workers due to slow diagnostic times and limited testing capacity.
Innovation Solution
A method using next-generation sequencing (NGS) with sample-specific barcoded indexes to detect SARS-CoV-2 viral gRNA and host transcriptional responses, involving the assembly of agnostic nucleic acid libraries, selective enrichment of pathogen-derived nucleic acids, and bioinformatic alignment to reference genomes, followed by machine-learning classification for infection status.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If qPCR-based fluorometric tests are used for SARS-CoV-2 detection, then diagnostic sensitivity is maintained, but testing capacity and throughput are limited
Solution Approach 1:
The patent segments the testing process by using individual patient barcodes to divide and track multiple patient samples within a single NGS run. Each patient's sample is tagged with a unique barcode, allowing the system to process many samples in parallel while maintaining individual identification and diagnostic accuracy, thus resolving the contradiction between maintaining sensitivity and increasing throughput.
Solution Approach 2:
The patent transitions from the traditional single-target qPCR dimension to a multi-dimensional NGS approach that simultaneously detects pathogen nucleic acids and host transcriptional responses. This dimensional expansion enables concurrent analysis of multiple targets and patients within a single test run, dramatically increasing testing capacity while preserving diagnostic sensitivity through comprehensive molecular profiling.
2Measurement precision
If single-plex qPCR fluorometry is used, then diagnostic accuracy is ensured, but high throughput clinical diagnostics become inadequate
Solution Approach 1:
The patent implements a universal NGS platform that performs multiple diagnostic functions simultaneously: detecting SARS-CoV-2 viral nucleic acids, identifying host transcriptional responses, and providing patient-specific barcode tracking. This multi-functionality allows a single test system to handle high-volume clinical diagnostics with maintained accuracy, as the same platform can process numerous samples through barcode-based multiplexing.
Solution Approach 2:
The patent merges pathogen detection and host response analysis into a single integrated NGS assay. By combining these previously separate diagnostic objectives into one simultaneous measurement process, the system achieves high throughput without sacrificing accuracy, as both pathogen presence and host physiological state are determined concurrently from the same nucleic acid sequencing data.
3Productivity
If diagnostic testing is delayed, then testing capacity is conserved, but occupational hazard for healthcare workers increases
Solution Approach 1:
The patent employs preliminary barcode assignment and sample tagging during the initial patient sampling phase. This preliminary organization of samples with unique identifiers enables rapid batch processing and immediate diagnostic results generation, eliminating delays that would otherwise expose healthcare workers to prolonged occupational hazards. The pre-established barcode system allows for efficient sample tracking and quick turnaround times.
4Productivity
If multiplexed screening is implemented, then testing throughput increases, but detection complexity increases
Solution Approach 1:
The patent introduces patient-specific barcodes as intermediary elements that simplify the complexity of multiplexed detection. These barcodes serve as mediators between the complex NGS sequencing process and the diagnostic interpretation, enabling systematic organization and tracking of multiple patient samples. The barcode system acts as an intermediary layer that manages detection complexity while maintaining high throughput capability.
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
Enables rapid, scalable, and accurate SARS-CoV-2 testing at a population scale, allowing for simultaneous detection of pathogens and host responses, thereby improving diagnostic capacity and reducing delays in patient management.
Implementation Method 1
nucleic acid sequencing (NGS) with sample-specific barcoded indexes to detect SARS-CoV-2 viral gRNA and host transcriptional responses
Data Source
AI summary
The invention generally relates to detecting the presence of a pathogen in a sample, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and physiological effects on the host with prognostic value, by methods that can simultaneously detect the pathogen and a host's transcriptional response to infection by the pathogen.