Surface-Bound Affinity Ligands for High-Purity Nucleic Acid Separation
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Solution Overview
Problem
Existing chromatography methods struggle to efficiently separate and purify target macromolecules like DNA and RNA from complex biological samples without denaturing the proteins, especially in high-performance applications where regulatory purity levels are required.
Innovation Solution
A method using affinity ligands bound to a solid surface to selectively bind and separate target macromolecules such as DNA and RNA, employing minor groove binders, major groove binders, or intercalating ligands, which are covalently attached to surfaces like beads or membranes, allowing for high-purity isolation and removal of these molecules from samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional chromatography methods are used to separate DNA and RNA from biological samples, then separation is achieved, but protein denaturation occurs and purity levels are insufficient for regulatory standards
Solution Approach 1:
The patent introduces affinity ligands as intermediary molecules that specifically bind to target macromolecules (DNA, RNA, proteins) through selective interactions. These ligands are coupled to solid surfaces to create a mediator system that enables separation based on specific molecular recognition rather than harsh chemical conditions, thereby achieving high purity separation without denaturing proteins
Solution Approach 2:
The patent employs parameter changes by varying the chemical properties of affinity ligands (such as charge, hydrophobicity, and specific binding affinity) to optimize separation conditions. By adjusting parameters like pH, ionic strength, and ligand density on the solid surface, the method achieves regulatory purity levels while maintaining protein integrity through controlled binding and elution conditions
2Manufacturing precision
If high-performance chromatography is used to achieve regulatory purity levels, then separation precision improves, but process complexity and difficulty increase
Solution Approach 1:
The patent extracts the essential separation function from complex multi-step chromatography processes by using solid surface-bound affinity ligands that provide specific binding in a single step. This extraction of the core separation mechanism eliminates the need for multiple sequential chromatography steps, reducing process complexity while maintaining high separation precision for regulatory compliance
Solution Approach 2:
The patent creates a universal platform using solid surfaces functionalized with various affinity ligands that can selectively bind different target macromolecules. This multi-functional approach allows a single system to handle diverse separation needs (DNA, RNA, proteins) with high precision, replacing multiple specialized chromatography methods and simplifying the overall process
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 method achieves high-purity separation of DNA and RNA from biological samples with minimal protein denaturation, meeting regulatory purity standards and providing eluents with less than 0.001% residual target macromolecules.
Implementation Method 1
selecting an affinity ligand that will bind to the target macromolecule; introducing the sample containing the target macromolecule to the coupled surface-affinity ligand and causing the coupled surface-affinity ligand to incubate with the sample for a residence time, wherein the target macromolecule binds to the affinity ligand
Data Source
AI summary
A method of isolating and separating a target macromolecule, such DNA (double stranded or single stranded), RNA (double stranded or single stranded), messenger RNA, or other oligonucleotide or oligonucleoside, from a sample by binding the target macromolecule to an affinity ligand that is bound to a surface is disclosed. The method may be employed in chromatography or any other of the separation sciences.