Apheresis Device with Affinity Matrix for cfDNA Removal
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Solution Overview
Problem
Current methods for reducing circulating cell-free DNA (cfDNA) in blood, such as systemic administration of deoxyribonuclease enzymes, have shown limited effectiveness in clinical settings, and there is a need for more effective extracorporeal methods and devices to treat diseases associated with high levels of cfDNA.
Innovation Solution
The development of apheresis devices equipped with affinity matrices capable of capturing nucleosome-bound, exosome-bound, and unbound cfDNA, including dsDNA, ssDNA, and oligonucleotides, using materials like DNA binding proteins, antibodies, and polymers to effectively remove cfDNA from blood during apheresis procedures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If systemic administration of deoxyribonuclease enzymes is used to reduce circulating cfDNA, then cfDNA levels can be reduced, but the treatment shows limited effectiveness in clinical settings
Solution Approach 1:
The invention extracts and removes cfDNA directly from the blood circulation using extracorporeal apheresis devices equipped with affinity matrices. This extraction approach bypasses the limitations of systemic enzyme administration by physically removing cfDNA, nucleosomes, and exosomes from the bloodstream, achieving more reliable reduction of cfDNA levels.
Solution Approach 2:
The invention introduces affinity matrices as intermediaries that specifically bind to cfDNA, nucleosomes, and exosomes. These matrices act as mediators between the blood and the removal system, enabling selective capture and removal of cfDNA-containing structures while leaving other blood components intact.
2Quantity of substance
If affinity matrices are used to capture cfDNA during apheresis, then cfDNA removal effectiveness is improved, but device complexity increases
Solution Approach 1:
The affinity matrices are designed to perform multiple functions simultaneously: capturing cfDNA, binding nucleosomes, and removing exosomes. This multi-functionality reduces the need for multiple separate treatment steps or devices, thereby managing complexity while improving overall cfDNA removal efficiency.
Solution Approach 2:
The invention employs composite affinity matrices that combine multiple binding components with different specificities. These composite materials integrate various DNA-binding proteins, antibodies, or polymers into a single matrix structure, enabling simultaneous capture of different cfDNA forms while simplifying the device architecture.
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
These devices can reduce cfDNA levels by at least 25%, 50%, or 75% per apheresis procedure, effectively capturing and removing substantial amounts of cfDNA, including various forms like nucleosome-bound, exosome-bound, and unbound DNA, thereby alleviating the negative effects associated with elevated cfDNA levels in diseases.
Implementation Method 1
affinity matrices capable of capturing nucleosome-bound, exosome-bound, and unbound cfDNA, including dsDNA, ssDNA, and oligonucleotides, using materials like DNA binding proteins, antibodies, and polymers
Data Source
AI summary
The invention provides apheresis devices and their use for removal of substantially all types of cell free DNA (cfDNA) in patients' blood, including nucleosome-bound cfDNA, exosome-bound cfDNA and unbound cfDNA (including double stranded DNA (dsDNA), single stranded DNA (ssDNA) and oligonucleotides), to limit the negative effects of the circulating cfDNA and to treat various diseases.