Spike-In Oligo Validation for Patient-Specific Assays
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Solution Overview
Problem
Current methods for validating patient-specific oligos in genomic sequencing are costly and time-consuming, limiting the practical application of personalized medicine, particularly in liquid biopsies for cancer monitoring, due to the need for repeated assays to establish analytic performance.
Innovation Solution
A method involving the use of spike-in oligo sequences of known concentrations, cosynthesized with synthesis-control oligos, to validate patient-specific oligos by determining their dose-response characteristics, providing a quality control check for batch synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If repeated assays are performed to establish analytic performance characteristics of patient-specific oligos, then validation reliability is improved, but cost and time requirements increase significantly
Solution Approach 1:
The patent uses control oligos as copies of patient-specific oligos that bind to the same spike-in sequences. These control oligos serve as proxies for validating patient-specific oligos without requiring repeated testing of the actual patient-specific oligos, thereby reducing validation time while maintaining reliability
Solution Approach 2:
Spike-in sequences serve as intermediary elements that enable validation. The spike-in sequences are introduced into patient samples at known concentrations, and control oligos bind to these spikes to provide measurable signals that validate assay performance without directly testing the patient-specific oligos repeatedly
2Reliability
If repeated assays are performed to establish analytic performance characteristics of patient-specific oligos, then validation reliability is improved, but cost increases significantly
Solution Approach 1:
Control oligos are used as cost-effective copies that replicate the binding characteristics of patient-specific oligos. By testing control oligos against known concentrations of spike-in sequences, the patent achieves validation without repeatedly purchasing and testing expensive patient-specific oligos
Solution Approach 2:
Spike-in sequences and control oligos function as disposable validation elements that can be used once and then discarded. This approach eliminates the need for expensive repeated testing of patient-specific oligos while maintaining adequate validation through the single-use spike-in controls
3Measurement precision
If multiple ctDNA targets are evaluated to achieve greater sensitivity in liquid biopsy, then detection sensitivity is improved, but cost becomes prohibitive
Solution Approach 1:
The spike-in sequences serve as universal controls that can be detected by multiple different oligos (control oligos and patient-specific oligos) simultaneously. This allows evaluation of multiple ctDNA targets using the same validation framework, achieving sensitivity improvement without proportionally increasing cost
Data Source
AI summary
The invention provides a method for validating patient-specific oligos using spike-in sequences.