Blood-Based Diagnostic System for Circulating Nucleic Acid Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current tissue-based genomic tests for cancer, particularly in non-small cell lung cancer, face challenges such as sampling bias, contamination, degradation, and poor reproducibility due to the need for tissue biopsies, which are not feasible for all patients and do not account for tumor heterogeneity, leading to inadequate molecular testing.
Innovation Solution
A blood-based diagnostic test system that stabilizes and processes whole blood samples to isolate and detect circulating nucleic acids, including DNA and mRNA, using specialized collection tubes, prioritized shipment, and digital PCR for reproducible detection of clinically actionable variants, enabling rapid reporting of results within 72 hours.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If tissue-based genomic tests are used for cancer diagnosis, then molecular testing can be performed, but sampling bias and tumor heterogeneity lead to inadequate representation of the full tumor landscape
Solution Approach 1:
The patent extracts circulating nucleic acids from the bloodstream to perform genomic testing, bypassing the need for tissue biopsy. This extraction approach captures tumor-derived genetic material that circulates systemically, thereby representing the full tumor heterogeneity without the sampling bias inherent in tissue-based methods.
Solution Approach 2:
The patent employs a multi-functional blood collection tube system that simultaneously performs anticoagulation, nucleic acid stabilization, and preservation of circulating cell-free DNA and RNA. This universal approach enables comprehensive molecular profiling from a single blood sample, capturing both genomic and transcriptomic information across the entire tumor burden.
2Measurement precision
If tissue biopsies are performed for genomic testing, then molecular information can be obtained, but the procedure is not feasible for all patients and does not reflect metastatic sites
Solution Approach 1:
The patent uses circulating nucleic acids as an intermediary to obtain molecular information without direct tissue contact. These nucleic acids serve as mediators that carry tumor genetic information from primary and metastatic sites through the bloodstream, enabling testing in patients who cannot undergo tissue biopsy while still reflecting the full tumor landscape.
Solution Approach 2:
The patent leverages the body's own circulatory system to deliver tumor-derived nucleic acids to the bloodstream, where they can be accessed non-invasively. This self-service approach allows the tumor to effectively present its own genetic material for analysis without requiring external intervention such as biopsy procedures.
3Measurement precision
If tissue samples are used for nucleic acid extraction, then genomic testing can be performed, but fixation time and varied fixatives contribute to degradation and crosslinking of nucleic acids
Solution Approach 1:
The patent incorporates preliminary stabilization actions directly into the blood collection tube before sample acquisition. The tubes contain specialized reagents that immediately stabilize nucleic acids upon blood collection, preventing degradation and crosslinking before any processing occurs. This preliminary protection ensures high-quality nucleic acid recovery without the fixation-related problems of tissue samples.
Solution Approach 2:
The patent fundamentally changes the sample type parameter from fixed tissue to liquid blood, and alters the preservation parameter from chemical fixation to enzymatic inhibition and stabilization reagents. These parameter changes eliminate the degradation and crosslinking issues associated with tissue fixation while maintaining nucleic acid integrity for reproducible genomic testing.
4Productivity
If conventional PCR methods are used for nucleic acid detection, then amplification can be performed, but contamination by normal or non-rearranged tumor regions reduces test specificity
Solution Approach 1:
The patent extracts circulating nucleic acids from plasma, separating them from cellular components that contain normal or non-rearranged tumor DNA. This extraction from the liquid phase eliminates contamination from adjacent normal tissues or non-rearranged tumor regions that would be present in disaggregated tissue samples, thereby improving variant detection specificity while maintaining amplification productivity.
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 system allows for the rapid, reproducible, and sensitive detection of nucleic acid variants and fusion transcripts in whole blood, overcoming the limitations of tissue-based tests by providing actionable molecular information for cancer diagnosis and treatment planning.
Implementation Method 1
reverse transcription of said RNA into complementary DNA by a reverse transcriptase enzyme, such as SuperScript RT IV
Implementation Method 2
amplifying said isolated nucleic acid of step (c) or a complementary DNA generated from said nucleic acid of step (c)
Data Source
Figure 1A~2L
Figure 3A~4
Figure 5A~6B
AI summary
The present disclosure relates to a rapid diagnostic test system that includes the prospective collection of whole blood, preservation of circulating nucleic acids at ambient temperature, and the reproducible detection of nucleic acids including DNA and mRNA (including fusion transcripts and differentially expressed transcripts) by different genomic methodologies.