Tumor-Informed Digital PCR Profiling for Precise MRD Detection
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Solution Overview
Problem
Existing methods for detecting, analyzing, and monitoring pre-cancerous and cancerous conditions with abnormal cell growth in patients are not optimal, necessitating improved systems and compositions.
Innovation Solution
A novel patient-specific PCR composition comprising primers encoding unique tumor variant sequences, DNA polymerase, RNase H, dNTP mixture, buffer, and magnesium compound, along with detection probes conjugated to fluorophores and quenchers, is used for detecting and monitoring tumor variants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing methods are used for detecting and monitoring pre-cancerous and cancerous conditions, then the detection process is simpler, but the measurement precision and reliability are not optimal
Solution Approach 1:
The detection system is segmented into multiple specialized components: tumor-informed primers for specific variant detection, digital PCR for precise quantification, and fluorophore-conjugated probes for sensitive detection. Each component performs a specific function to collectively achieve high measurement precision without requiring a single complex system
Solution Approach 2:
Fluorophore-conjugated detection probes serve as intermediaries between the tumor DNA targets and the detection system. These probes bind specifically to tumor variant sequences and emit fluorescent signals, enabling precise detection while maintaining system modularity and manageable complexity
2Reliability
If existing detection methods are used, then the system is easier to operate, but the ability to detect minimal residual disease and monitor tumor variants is insufficient
Solution Approach 1:
Tumor-informed primers are designed in advance based on patient-specific tumor genomic profiles obtained from biopsy sequencing. This preliminary customization enables the system to reliably detect specific tumor variants and minimal residual disease with high specificity, while the standardized digital PCR platform maintains operational ease
Solution Approach 2:
The system replaces traditional mechanical or manual detection methods with automated digital PCR technology and fluorescent signal detection. This substitution enhances detection reliability for minimal residual disease while reducing manual intervention requirements, maintaining ease of operation through automation
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 composition enables precise detection and monitoring of tumor variants, facilitating early diagnosis and prognosis of pre-cancerous and cancerous conditions, including Minimal Residual Disease (MRD) in various cancers.
Implementation Method 1
each detection probe encodes a sequence complementary to the prime
Implementation Method 2
each detection probe comprises a fluorophore and optionally a quencher
Data Source
AI summary
Described herein are Methods, systems, compositions, and macromolecule complexes, for detecting, analyzing, evaluating, screening for, prognosing, diagnosing, and/or monitoring, pre-cancerous and cancerous conditions with abnormal cell growth in a patient, including patients having Minimal Residual Disease (MRD).