Donor DNA Detection via Multiplexed Digital PCR
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Solution Overview
Problem
Current methods for monitoring transplant rejection in transplant recipients are invasive, costly, and require prior knowledge of donor and recipient genotypes, limiting their accuracy and accessibility.
Innovation Solution
The development of novel methods and systems that use highly multiplexed digital PCR to detect and analyze donor DNA in transplant recipients without prior knowledge of genotypes, employing single nucleotide polymorphisms (SNPs) to determine the level of donor-derived cfDNA and predict rejection probability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional methods are used to monitor transplant rejection, then diagnostic accuracy can be achieved, but the methods are invasive and require prior knowledge of genotypes
Solution Approach 1:
The patent extracts and detects only the donor-derived cfDNA fragments from the recipient's plasma, separating the useful diagnostic signal from the background noise of recipient DNA. This targeted extraction enables non-invasive monitoring without requiring prior genotype knowledge, as the method detects donor-specific sequences directly in the plasma sample.
Solution Approach 2:
The patent uses donor-specific SNPs as intermediary markers to indirectly identify donor DNA presence. By detecting these genetic markers in the plasma, the system can infer donor DNA levels without directly analyzing the complex genomic structure, thereby simplifying the operation while maintaining diagnostic accuracy.
2Measurement precision
If comprehensive genotype analysis is performed, then detection accuracy improves, but the cost and complexity increase
Solution Approach 1:
Instead of analyzing the entire genome, the patent focuses on specific local regions - the donor-derived cfDNA fragments containing SNP markers. This localized analysis approach maintains high detection accuracy for donor DNA while significantly reducing the complexity and cost compared to comprehensive genomic sequencing.
Solution Approach 2:
The patent applies partial action by detecting only the necessary SNP markers within the donor DNA fragments rather than performing complete genotype analysis. This selective detection achieves sufficient accuracy for rejection monitoring while avoiding the excessive complexity and cost of full genomic analysis.
3Reliability
If centralized facilities are used for analysis, then specialized equipment is available, but accessibility and timing are limited
Solution Approach 1:
The patent enables self-service by providing a simplified assay that can be performed in local laboratories without requiring centralized specialized facilities. The method uses readily available reagents and standard PCR equipment, allowing clinics and hospitals to conduct donor DNA detection independently, thereby reducing time to results and improving accessibility.
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
These methods provide a non-invasive, cost-effective, and accurate means to monitor transplant rejection, enabling same-day results and reducing the need for centralized facilities, thus improving patient outcomes and simplifying the detection process.
Implementation Method 1
The development of novel methods and systems that use highly multiplexed digital PCR to detect and analyze donor DNA in transplant recipients
Implementation Method 2
the enriching step (b) comprise a ligation step
Implementation Method 3
the enriching step (b) comprise a hybridization capture step
Data Source
AI summary
Described herein are methods, systems, compositions, and macromolecule complexes, for detecting, analyzing, evaluating, screening for, prognosing, diagnosing, and/or monitoring, of donor DNA in a transplant recipient for possible transplant rejection in the transplant recipient.