Cartridge with Micro-Pore Capture for Nucleic Acid Detection
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Solution Overview
Problem
Current diagnostic technologies face challenges in detecting early cancer, distinguishing disease-specific nucleic acid markers from normal tissue markers, and accurately quantifying low-abundance mutations and methylation changes in blood samples, due to high error rates and inefficiencies in sequencing and amplification methods.
Innovation Solution
A system comprising a cartridge with primary and secondary reaction chambers and product capture subunits with hydrophilic micro-pores, where nucleic acid molecules are purified, amplified, and detected using real-time PCR or sequencing, allowing for simultaneous identification and enumeration of multiple DNA mutational and methylation changes at the single-molecule level.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional sequencing and amplification methods are used, then the diagnostic process can be performed, but high error rates and PCR dropout occur, reducing detection accuracy
Solution Approach 1:
The patent divides the diagnostic process into multiple sequential reaction chambers, each performing a specific function (amplification, sequencing, detection). This segmentation allows each step to be optimized independently, reducing cumulative errors and improving overall detection accuracy while maintaining reliability.
Solution Approach 2:
The patent introduces intermediary steps between amplification and sequencing, including purification chambers and control reactions. These intermediaries remove contaminants and verify reaction success, reducing error propagation and improving both measurement precision and reliability.
2Measurement precision
If multiple markers are examined to improve disease detection, then diagnostic accuracy improves, but test cost and complexity increase
Solution Approach 1:
The patent designs a universal reaction chamber system where the same physical infrastructure can perform multiple different reactions (amplification, sequencing, detection) by simply changing the reagents. This allows examination of multiple markers without proportionally increasing device complexity, as the system is optimized for multi-functionality.
Solution Approach 2:
The patent enables examination of multiple markers by changing reaction parameters (temperature, pH, enzyme types) rather than requiring separate physical systems for each marker. This approach maintains diagnostic accuracy while controlling test complexity through parameter optimization rather than structural multiplication.
3Measurement precision
If sensitive detection of low-abundance mutations is performed, then early cancer detection improves, but false signals from normal nucleic acids increase
Solution Approach 1:
The patent extracts and removes normal nucleic acids through selective amplification and purification steps before sequencing. By taking out the background signal from normal cells, the system can detect low-abundance mutations without interference, improving sensitivity while reducing false positives.
Solution Approach 2:
The patent incorporates control reactions and validation steps that provide feedback on signal authenticity. These feedback mechanisms distinguish true mutation signals from false signals by comparing against control samples and verifying signal characteristics, enabling sensitive detection while maintaining specificity.
4Measurement precision
If targeted gene sequencing is performed to improve detection of rare events, then sensitivity improves, but sequencing depth and time requirements increase
Solution Approach 1:
The patent performs preliminary amplification and enrichment of target genes before sequencing in dedicated reaction chambers. This preliminary action concentrates the rare events of interest, allowing shallower sequencing depth to achieve the same sensitivity, thereby reducing total sequencing time while maintaining detection capability.
Solution Approach 2:
The patent uses periodic sampling and monitoring during the sequencing process to detect rare events early. By performing sequential reads and analyzing results in real-time, the system can stop sequencing once sufficient sensitivity is achieved, reducing overall sequencing time while maintaining detection of rare mutations.
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 accurate and sensitive detection of cancer markers and viral or bacterial loads, facilitating early cancer detection, monitoring treatment efficacy, and identifying infectious diseases, while reducing PCR dropout and error rates, thereby improving diagnostic accuracy and efficiency.
Implementation Method 1
a product capture housing enclosing a solid support with a plurality of separate columns of a plurality of product capture subunits with each separate product capture subunit comprising an array of a plurality of individual hydrophilic micro-pores or micro-wells separated by hydrophobic surfaces
Data Source
AI summary
The present invention relates to methods, devices, instruments, processes, and systems for the highly specific, targeted molecular analysis of regions of human genomes and transcriptomes from the blood, i.e. from cell free circulating DNA, exosomes, microRNA, lncRNA, circulating tumor cells, or total blood cells. The technology enables highly sensitive identification and enumeration of mutation, expression, copy number, translocation, alternative splicing, and methylation changes using spatial multiplexing and combined nuclease, ligation, polymerase, and sequencing reactions. Such technology may be used for non-invasive early detection of cancer, non-invasive cancer prognosis, and monitoring both treatment efficacy and disease recurrence of cancer.