Ambient Blood Stabilization Formulation for Nucleic Acids
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Solution Overview
Problem
Current methods for stabilizing nucleic acid molecules and polypeptides in blood samples at ambient temperatures often result in denatured conformations and cell lysis, leading to contamination and limited storage duration, which restricts the availability of whole blood supplies, especially in areas lacking refrigeration facilities.
Innovation Solution
Formulations comprising a pH buffer, non-reducing sugars, water-soluble polymers, cationic or zwitterionic compounds, and phosphatase inhibitors are used to maintain nucleic acid molecules and polypeptides in their native, non-denatured conformation, preventing cell lysis and contamination, allowing for stable storage at ambient temperatures for extended periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current stabilization formulations are used at ambient temperatures, then nucleic acid molecules and polypeptides are preserved from degradation, but they are maintained in a denatured conformation and blood cells undergo lysis
Solution Approach 1:
The invention changes the chemical parameters of the stabilization formulation by replacing formaldehyde-releasing agents with a new composition comprising a pH buffer (maintaining pH 6.0-8.0), a non-reducing sugar (such as sucrose or trehalose), and specific inhibitors. This parameter change allows the formulation to stabilize nucleic acids and polypeptides while preserving their native conformation and preventing cell lysis.
Solution Approach 2:
The invention introduces intermediary substances that mediate between the stabilizing function and the preservation of native structure. The pH buffer maintains optimal pH conditions, the non-reducing sugar provides structural support and prevents denaturation, and the specific inhibitors block degradation pathways without causing cell lysis or conformational changes.
2Stability of the object's composition
If cold refrigeration storage is used for whole blood, then cells remain intact and viable, but storage facilities requiring constant electrical power and refrigeration equipment are needed
Solution Approach 1:
The invention extracts the cooling function from the storage system by removing the need for refrigeration equipment and electrical power. Instead of using cold temperatures to prevent degradation, the formulation achieves stabilization through chemical means, allowing whole blood to be stored at ambient temperatures without compromising cell integrity.
Solution Approach 2:
The invention replaces expensive, complex refrigeration infrastructure with a simple, inexpensive chemical formulation that can be added to blood collection tubes. This disposable formulation approach eliminates the need for costly cold storage facilities, making blood banking accessible in resource-limited settings.
3Duration of action of stationary object
If formaldehyde-releasing agents are used to stabilize cell-free nucleic acids, then nucleic acids are stabilized for up to 7 days, but cells are fixed and become less permeable leading to contamination
Solution Approach 1:
The invention converts the harmful effect of cell fixation into a beneficial outcome. Instead of using formaldehyde that fixes cells and causes lysis, the new formulation uses a pH buffer and non-reducing sugar that stabilize nucleic acids while keeping cells intact and permeable, thus preventing contamination while achieving similar or extended stability duration.
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 proposed formulations ensure that at least 80% of polypeptides and nucleic acid molecules remain in a native, non-denatured state for several days to weeks, facilitating diagnostic and therapeutic applications without the need for refrigeration.
Implementation Method 1
a pH buffer
Implementation Method 2
non-reducing sugars
Implementation Method 3
water-soluble polymers
Implementation Method 4
cationic or zwitterionic compounds
Implementation Method 5
phosphatase inhibitors
Data Source
AI summary
Provided herein are formulations for the stabilization of one or more polypeptide or nucleic acid molecule in a native, non-denatured state at ambient temperatures. Also provided are compositions, articles of manufacture, kits and methods for substantially stable storage of one or more polypeptide or nucleic acid molecule in a native, non-denatured, and/or functionally active conformation substantially free on intracellular polypeptides and nucleic acids at ambient temperatures are provided. Also provided are formulations for the stabilization of one or more exosome at ambient temperatures, and compositions, articles of manufacture, kits and methods of use.