Low Cost Electrochemical Gas Phase Nitric Oxide Generator for Biomedical Applications

ABSTRACTTherapeutic use of gas phase nitric oxideNOhas several important applications in medicineSince its first medical application more thanyears agoinhaled nitric oxideINOhas become a mainstay of intensive care for lung failure patientsAs a pulmonary vasodilatorINO is essential in neonatologylung transplantationand pulmonary hypertensionAs an inhaled antiseptic agentNO has been proposed in the treatment of chronic airway infection that occurs in cystic fibrosissinusitisand tuberculosisFurtherNO added to the sweep gas in extracorporeal circulationECCprevents activation of plateletspreventing thrombosisand white blood cellspreventing systemic inflammatory response syndromeSIRSCurrent methods of creating and monitoring gas phase NO for these applications are expensive and inconvenient owing to the instability of high concentrations of NO within conventional gas cylindersIn this combined Phase I II STTR applicationNOTA Laboratories LLC will collaborate with researchers at the University of MichiganU of Mto further develop a completely new and very low cost electrochemicalE chembased compactportable instrument to generate high purity gas phase NO for clinical applicationsNOGENThe method is based on the E chem reduction of simple nitrite ions to NO gas via an optimized Cu IIligand complex that channels electrons from a working electrode to efficiently reduce NOto NO gIn Phase Iresearchers at U of M and scientists engineers at NOTA will work together to optimize the design of the E chem NOGEN systemin terms of key componentse gusing various metal mesh or foamor metal carbon ink electrodesan optimized gas separator made with highly NO permeable silicone hollow fibersoptimal nitrite and Cu IIcomplex levels in the solution phaseand incorporation of NO NOsensors for feedback tight control of NO productionetcThe accuracy in creating targeted gas phase NO levels with the high purity required for medical applications will also be verified in Phase IIn Phase IIfurther development of a prototype product will continue with full incorporation of all the components into a single compact NOGEN unit that will have replaceable electrode and electrolyte solution modulesIn additionthe new prototype NOGEN system will be tested in animal models of CPB and INO at U of M to demonstrate the clinical potential and safety of this newlow cost systemNOTA intends to first market the NOGEN system for use in preventing platelet activation and SIRS during CPB and then pursue applications of the NOGEN system for treating neonate adult pulmonary hypertensionand further use as a home INO unit to treat chronic lung infections in cystic fibrosis patients NarrativeInhaled nitric oxideINOgas is used routinely to treat pulmonary hypertension in newborns as well as adult patients with lung disordersUse of NO within the oxygenator sweep gas during cardiopulmonary bypassCPBsurgery is known to reduce activation of white cells that can lead to systemic inflammatory response syndromeSIRSas well as decrease platelet activationCurrent medical use of NO requires tanks of NO gas that are very costly and unstableIn this Phase I II STTRNOTA Laboratories LLC will collaborate with researchers at the University of Michigan to further develop a completely newlow cost electrochemical gas phase NO generatorNOGENfor medical applicationsThis application focuses on developing a compact system initially for the CPB marketwhere higher levels of NO may be neededalthough the proposed system can also be readily designed for hospital INO therapy as well as for use at home for patients with cystic fibrosis chronic lung infections