Aldehyde Crosslinking Blood Composition for Hemolysis and Vesicle Control
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Solution Overview
Problem
Existing blood collection tubes fail to simultaneously stabilize both circulating RNA and DNA, leading to dilution of target transcripts and contamination from red blood cell-specific transcripts, while also causing hemolysis and release of extracellular vesicles, which compromises the integrity of blood samples for downstream diagnostic analysis.
Innovation Solution
A composition comprising aldehydes, anticoagulants, chelating agents, and polysaccharides, with a pH of 4 to 6, that stabilizes erythrocytes and white blood cells, preventing hemolysis and release of nucleic acids and extracellular vesicles, maintaining sample integrity for up to 6 days across a broad temperature range.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If complete lysis of blood sample is used for RNA stabilization, then RNA is stabilized, but red blood cell-specific transcripts are released overwhelming the target mRNA pool
Solution Approach 1:
Instead of lysing cells to stabilize RNA (conventional approach), the patent uses formaldehyde to crosslink and stabilize cells in their intact state, preventing the release of contaminating red blood cell transcripts while maintaining RNA stability for downstream analysis
Solution Approach 2:
The patent changes the chemical parameters by using formaldehyde crosslinking instead of mechanical or enzymatic lysis, fundamentally altering how RNA is stabilized—from a lysis-based approach to an intact cell preservation approach—thereby eliminating the problem of red blood cell transcript contamination
2Duration of action of stationary object
If blood storage time is extended for transport, then diagnostic testing flexibility is improved, but cellular and nucleic acid degradation increases
Solution Approach 1:
The patent applies formaldehyde crosslinking immediately at the point of collection to prevent subsequent degradation. This preliminary stabilization action locks nucleic acids and cellular structures in place before transport, enabling extended storage times without loss of integrity
Solution Approach 2:
The patent converts the typically harmful effect of formaldehyde (cellular fixation) into a benefit by using it to prevent nucleic acid degradation during storage. The crosslinking that would normally be seen as interfering with downstream applications is instead used to stabilize the sample against the harmful effects of time-dependent degradation during transport
3Reliability
If anticoagulant formulations are used to prevent coagulation, then blood coagulation is prevented, but erythrocyte mean cell volume increases leading to hemolysis
Solution Approach 1:
The patent introduces a new intermediary substance (formaldehyde) that mediates between the conflicting requirements of coagulation prevention and cell integrity maintenance. The formaldehyde crosslinking stabilizes cells against the osmotic stress caused by anticoagulants, preventing hemolysis while allowing coagulation prevention to occur
4Reliability
If multiple commercial stabilization options are used for DNA or RNA, then specific nucleic acid is stabilized, but both DNA and RNA cannot be stabilized simultaneously
Solution Approach 1:
The patent creates a universal stabilization solution using formaldehyde crosslinking that simultaneously stabilizes both DNA and RNA in intact cells. This single approach replaces the need for separate DNA-specific and RNA-specific stabilization systems, providing multi-functionality for liquid biopsy applications requiring both nucleic acid types
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 effectively maintains baseline levels of extracellular vesicles and nucleic acids, enabling accurate downstream analysis of cfRNA, cfDNA, and other cellular components, facilitating immunophenotyping and multiple component testing in blood samples.
Implementation Method 1
The composition may include one or more formaldehyde donors... one or more components capable of releasing an aldehyde
Implementation Method 2
The composition may include one or more anticoagulants or chelating agents... citrate-based anticoagulant
Implementation Method 3
maintains erythrocyte mean cell volume (MCV)... maintains red blood cell structural integrity
Data Source
AI summary
A composition and method of use thereof wherein the composition comprises one or more components capable of releasing an aldehyde, one or more anticoagulants or chelating agents, and one or more polysaccharides. The composition has a pH of from about 4 to about 6.