Nitric Oxide Delivery Device Using Copper Electrode
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Solution Overview
Problem
The delivery of nitric oxide (NO) to target sites is challenging due to its reactivity with hemoglobin and oxygen, and existing NO donors like diazeniumdiolates are unstable, making them unsuitable for commercialization, especially in biomedical applications where they can form toxic nitrosamines.
Innovation Solution
A nitric oxide delivery device comprising a housing with a copper-containing working electrode that generates Cu(I) ions to reduce nitrite ions and produce NO, using a two- or three-electrode configuration with controlled voltage pulses to manage NO release, ensuring stability and controlled delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If stable hydrophilic or hydrophobic NO donors are employed, then NO delivery stability is improved, but commercialization remains challenging due to instability of diazeniumdiolates and other NO donors
Solution Approach 1:
The patent employs diazeniumdiolate salts as intermediary compounds that can be electrochemically converted to active NO donors. These salts are stable for storage and handling, but can be activated on-demand through electrochemical reduction at the cathode, providing both stability during storage and reliability during use. The intermediary salt form resolves the contradiction between stability and reliability.
Solution Approach 2:
The patent changes the chemical state of the NO donor from active diazeniumdiolate compounds to their stable salt forms for storage and transport. The active form is generated in-situ through electrochemical parameter changes (applied voltage/potential). This parameter change enables stable storage while maintaining the ability to generate active NO donors reliably when needed.
2Object-affected harmful factors
If MAHMA/NO is dispersed in silicone rubber matrix, then thrombus formation is prevented, but MAHMA/NO and diamine precursor leach from polymer matrix and form toxic nitrosamines
Solution Approach 1:
The patent uses stable diazeniumdiolate salts as intermediaries that are incorporated into the polymer matrix. These salt forms do not leach and form toxic nitrosamines like the active compounds do. The active NO donors are generated electrochemically from these stable intermediaries, preventing harmful leaching while maintaining anti-thrombotic efficacy.
Solution Approach 2:
The patent replaces the chemical storage and release mechanism (where MAHMA/NO is stored in the polymer and releases passively or through degradation) with an electrochemical generation mechanism. Voltages are applied to generate NO donors in-situ from stable salts, eliminating the need for chemical precursors that can leach and form toxic byproducts.
3Productivity
If diazeniumdiolates are used as NO donors, then NO release is achieved, but instability renders commercialization challenging
Solution Approach 1:
The patent performs preliminary action by converting unstable diazeniumdiolate compounds into their stable salt forms before device assembly and storage. These pre-prepared stable salts are then electrochemically converted to active NO donors during device operation. This preliminary stabilization action enables both NO release capability and long-term stability for commercialization.
Solution Approach 2:
The patent replaces the chemical instability issue with an electrochemical solution. Instead of relying on the inherent (unstable) chemical properties of diazeniumdiolates for NO release, the system uses electrochemical reduction of stable diazeniumdiolate salts to generate active NO donors on-demand. This substitution of chemical storage for electrochemical generation resolves the stability-productivity contradiction.
4Ease of operation
If electrochemical generation of NO is implemented, then controlled NO delivery is achieved, but device complexity increases with multiple electrodes and voltage control
Solution Approach 1:
The patent integrates multiple functions into the device: the cathode generates NO donors electrochemically, the housing provides structural support and can be made permeable to NO, and the same device structure serves as both the electrochemical cell and the delivery system. This multi-functionality reduces overall device complexity despite the electrochemical generation requirement.
Solution Approach 2:
The device uses the applied voltage to drive both the electrochemical generation of NO donors and their subsequent release through the permeable housing. The system is self-regulating in that the rate of NO generation is directly controlled by the applied voltage, eliminating the need for separate control mechanisms. This self-service characteristic simplifies operation despite the electrochemical complexity.
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 device effectively generates and controls the release of nitric oxide, preventing biofilm formation and thrombosis, while minimizing toxicity, as demonstrated by reduced bacterial biofilm and thrombus formation in clinical settings.
Implementation Method 1
a working electrode, the working electrode being a copper-containing conductive material that produces a concentration of Cu(I) ions at a surface of the working electrode in response to an anodic voltage pulse applied thereto
Implementation Method 2
The reaction is a single electron transfer reaction that can be represented as: Cu(I) + NO2- → Cu(II) + NO + OH-
Implementation Method 3
a housing that is permeable to nitric oxide; where nitrite in the source of nitrite ions is reduced by the Cu(I) ions to generate nitric oxide
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 3A~4A
AI summary
A nitric oxide delivery device includes a housing that is permeable to nitric oxide. A working electrode (which is a copper-containing conductive material or a base material coated with a copper-containing conductive material) is positioned inside of the housing. A conductive lead is electrically connected to the working electrode and extends outside of the housing. A reference electrode and/or a counter electrode is electrically isolated from the working electrode. The reference electrode and/or the counter electrode has a first portion that is inside of the housing and a second conductive portion that is outside of the housing. A source of nitrite ions is to be contained within the housing such that it is in contact with the working electrode.