Patent Publication Number: US-2023149656-A1

Title: Electrodes for Nitric Oxide Generation

Description:
RELATED APPLICATIONS 
     This application is a continuation patent application of U.S. application Ser. No. 17/331,793, filed May 27, 2021, which is a continuation patent application of U.S. application Ser. No. 16/875,687, filed May 15, 2020, which claims the benefit of and priority to U.S. Provisional Application No. 62/959,942 filed Jan. 11, 2020, U.S. Provisional Application No. 62/959,933 filed Jan. 11, 2020, and U.S. Provisional Application No. 62/848,530 filed May 15, 2019. The contents of each of these applications are hereby incorporated herein by reference in their entireties. 
    
    
     FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with government support under Grant No. R44 HL134429 and Grant No. R44 TR001704, awarded by the National Institutes of Health (NIH). The government has certain rights in the invention. 
    
    
     FIELD 
     The present disclosure relates to systems and methods for generating nitric oxide and various electrode designs associated therewith. 
     BACKGROUND 
     Nitric oxide has found to be useful in a number of ways for treatment of disease, particularly cardiac and respiratory ailments. Previous systems for producing NO and delivering the NO gas to a patient have a number of disadvantages. For example, tank-based systems required large tanks of NO gas at a high concentration and pressure. When treatment using this system is paused, NO in the circuit stalls and converts into NO 2 , requiring the user to purge the manual ventilation circuit before resuming manual ventilation. Synthesizing NO from NO 2  or N 2 O 4  requires the handling of toxic chemicals. Prior electric generation systems involve generating plasma in the main flow of air to be delivered to patients or pumped through a delivery tube. 
     SUMMARY 
     The present disclosure is directed to systems, methods and devices for nitric oxide generation for use with various ventilation and/or medical devices and having various electrode designs for generating the nitric oxide (NO). 
     In some embodiments, a nitric oxide (NO) generation system includes at least one pair of electrodes configured to generate a product gas containing NO from a flow of a reactant gas, the at least one pair of electrodes having a first end and second end with a length therebetween such that a plasma produced is carried by the flow of the reactant gas and glides along the length of the at least one pair of electrodes from the first end towards the second end; and a controller configured to regulate the amount of nitric oxide in the product gas produced by the at least one pair of electrodes using one or more parameters as an input to the controller, the one or more parameters including information from a plurality of sensors configured to collect information relating to at least one of the reactant gas, the product gas, and a medical gas into which the product gas flows. 
     The pair of electrodes is formed from a material selected from the group consisting of hafnium, glassy carbon, iridium, rhodium, platinum, graphite, carbon-carbon composite, steel, stainless steel, titanium, copper, nickel, tungsten-silver alloy, tungsten, and alloys thereof. In some embodiments, more than one material is used to form at least one of the electrodes in the at least one pair of electrodes along an edge thereof. 
     In some embodiments, the electrodes in the at least pair of electrodes diverge from one another such that the electrodes move away from each along their length from the first end to the second end. In some embodiments, the diverging electrodes form a gap at the first end in a range of about 0.05 mm to about 10 mm. In some embodiments, the diverging electrodes form a gap at the second end in a range of about 1 mm to about 100 mm. In some embodiments, a distance the plasma glides along the length of the electrodes ranges from 1 mm to 200 mm. 
     In some embodiments, the nitric oxide (NO) generation further comprises a nozzle through which the reactant gas flows to the at least one pair of electrodes. In some embodiments, the nozzle ranges in diameter from about 0.1 to about 15 mm. In some embodiments, a cross-sectional area of the nozzle ranges from 0.03 mm 2  to 707 mm 2 . In some embodiments, a cross-sectional area of the nozzle can be varied by the NO generation system. In some embodiments, the reactant gas flow along the electrode surfaces ranges in velocity from about 1 to about 100 m/second. 
     In some embodiments, a shape of an edge of the electrodes in the at least one electrode pair are configured to increase the length of an arc at a specific rate for a specific flow rate of reactant gas. In some embodiments, a shape of an edge of the electrodes in the at least one electrode pair is configured to increase the length of an arc at a specific rate for a specific reactant gas flow velocity. 
     In some embodiments, a nitric oxide (NO) generation system includes a plasma chamber comprising: at least one pair of electrodes configured to generate a product gas containing NO from a flow of a reactant gas. The at least one pair of electrodes have a first end and a second end and a length therebetween such that a plasma produced is carried by the flow of the reactant gas and glides along the length of the at least one pair of electrodes from the first end towards the second end of the at least one electrode pair. The system also includes at least one nozzle through which the reactant gas flows into the plasma chamber to the at least one pair of electrodes. A controller is configured to regulate the amount of nitric oxide in the product gas by the at least one pair of electrodes using one or more parameters as an input to the controller. The one or more parameters include information from a plurality of sensors configured to collect information relating to at least one of the reactant gas, the product gas, and a medical gas into which the product gas flows. 
     In some embodiments, a shape of an edge of the electrodes in the at least one electrode pair are configured to increase the length of an arc at a specific rate for a specific flow rate of reactant gas. In some embodiments, the at plasma chamber is formed from a material selected from the group consisting of a high temperature polymer, ceramic, metal, coated metal, and composite materials. 
     In some embodiments, the at least one nozzle comprises a first nozzle configured to supply reactant NO gas to the at least one pair of electrodes and a second nozzle configured to cool the plasma chamber. In some embodiments, the at least one nozzle comprises a first nozzle configure to supply reactant gas to the at least one pair of electrodes and a second nozzle configured to vary an interaction between the plasma and the reactant gas. 
     A method of generating nitric oxide includes ionizing a reactant gas inside one or more plasma chambers to generate a plasma for producing a product gas containing nitric oxide using a flow of the reactant gas through the one or more plasma chambers, the plasma chamber including at least one pair of electrodes for generating the product gas and having a first end and a second end and a length therebetween such that a plasma produced is carried by the flow of the reactant gas and glides along the length of the at least one pair of electrodes from the first end towards the second end; and controlling the amount of nitric oxide in the product gas using one or more parameters as input to a control algorithm used by one or more controllers to control the one or more plasma chambers, at least one of the one or more parameters being related to a target concentration of NO in an inspired gas, where the inspired gas is one of the product gas or a combination of the product gas and a medical gas into which the product gas flows. 
     In some embodiments, control outputs of the control algorithm include one or more of reactant gas flow rate, duty cycle, AC waveform, frequency current, voltage, and power. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present disclosure is further described in the detailed description which follows, in reference to the noted plurality of drawings by way of non-limiting examples of exemplary embodiments, in which like reference numerals represent similar parts throughout the several views of the drawings, and wherein: 
         FIG.  1    is an exemplary embodiment of a system for generating an NO-enriched product gas; 
         FIG.  2    is another exemplary embodiment of a system for generating an NO-enriched product gas; 
         FIG.  3    is an exemplary embodiment of an NO generation system; 
         FIG.  4    illustrates an embodiment of a schematic of a controller of an NO generation system; 
         FIG.  5    is an embodiment of a pneumatic circuit; 
         FIG.  6    is another embodiment of a pneumatic circuit; 
         FIG.  7 A  and  FIG.  7 B  are exemplary embodiments of electrodes formed from non-electrically conductive rods; 
         FIG.  8    is an exemplary embodiment of an electrode design having two electrodes oriented parallel to one another; 
         FIG.  9    is an exemplary embodiment of an electrode with a “T” orientation; 
         FIG.  10    is an exemplary embodiment of a monolithic electrode and heat sink design; 
         FIG.  11    is an exemplary embodiment of an electrode design having three electrodes providing two gaps; 
         FIG.  12    is an exemplary embodiment of a circuit having a transformer tuned to raise the voltage to one that will arc across a specific electrode gap size; 
         FIG.  13    is an exemplary embodiment of two electrode pairs with different gap sizes; 
         FIG.  14    is an exemplary embodiment of an electrode with coolant passageways; 
         FIG.  15 A ,  FIG.  15 B ,  FIG.  15 C ,  FIG.  15 D ,  FIG.  15 E ,  FIG.  15 F ,  FIG.  15 G , and  FIG.  15 H  illustrate an embodiment of a removable plasma chamber; 
         FIG.  16 A  and  FIG.  16 B  illustrate embodiments of a plasma chamber that is aligned with a plasma chamber entry point; 
         FIG.  17 A ,  FIG.  17 B , and  FIG.  17 C  illustrate an embodiment of a plasma chamber in the form of a dome; 
         FIG.  18 A ,  FIG.  18 B ,  FIG.  18 C , and  FIG.  18 D  illustrate various embodiments of electrode arrays; 
         FIG.  19 A ,  FIG.  19 B , and  FIG.  19 C  illustrate various views of an embodiment of an electrode design; 
         FIG.  20    depicts an exemplary insulator around an electrode; 
         FIG.  21 A  illustrates an exemplary arc initiated on the upstream edge of the electrodes where electric field strength is high; 
         FIG.  21 B  illustrates the arc of  FIG.  21 A  that has migrated across the surface of the electrode; 
         FIG.  22    illustrates an embodiment of a nitric oxide generation system that can adjust the electrode gap with a stepper motor; 
         FIG.  23    is an exemplary plasma chamber design including a nozzle end, a flare, and a chamber; 
         FIG.  24 A  illustrates an exemplary embodiment of a plasma chamber having surface features within the chamber; 
         FIG.  24 B  illustrates an exemplary embodiment of a plasma chamber having surface features within the chamber; 
         FIG.  25    is an exemplary plasma chamber having an electrode within a non-conductive tube with a clearance; 
         FIG.  26 A  illustrates an exemplary embodiment of an electrode insulator having grooves to shield a portion of a plasma chamber wall from sputtered electrode materials; 
         FIG.  26 B  illustrates an exemplary embodiment of an electrode insulator having ridges to shield a portion of a plasma chamber wall from sputtered electrode materials; 
         FIG.  27    illustrates an exemplary embodiment of an electrode recessed within an insulator; 
         FIG.  28    illustrates an embodiment of a gliding arc electrode design constructed from bent rods; 
         FIG.  29 A  illustrates an embodiment of a gliding arc electrode design constructed from straight rods; 
         FIG.  29 B  illustrates an embodiment of a gliding arc electrode design constructed from straight rods; 
         FIG.  30    is an exemplary embodiment of two gliding arc electrodes cut into sheet metal; 
         FIG.  31    is an exemplary gliding arc electrode pair design that is machined from a single piece of material; 
         FIG.  32 A ,  FIG.  32 B  and  FIG.  32 C  depict embodiments of gliding arc electrodes constructed from more than one material; 
         FIG.  33    illustrates an exemplary gliding arc electrode surface profile; 
         FIG.  34    illustrates an exemplary embodiment of a gliding arc plasma source; 
         FIG.  35    illustrates an exemplary cross-sectional view of a gliding arc plasma source; 
         FIG.  36    illustrates an exemplary cross-sectional view (from the inlet) of a gliding arc plasma reactor; 
         FIG.  37    illustrates an exemplary cross-sectional view of the gliding arc plasma reactor; 
         FIG.  38    illustrates an exemplary graph showing NO and NO 2  concentration and NO/NO 2  ratio versus power; 
         FIG.  39    is an exploded view of a gliding arc electrode chamber; 
         FIG.  40    is an exemplary view of a plasma chamber design that minimizes tolerance stack-up between the nozzle and electrodes; 
         FIG.  41 A  and  FIG.  41 B  are an exemplary embodiment of a plasma torch electrode configuration; 
         FIG.  42    is an exemplary embodiment of a plasma torch design with an increasing gap along the direction of reactant gas flow; 
         FIG.  43    is a cross-sectional view of an exemplary embodiment of a plasma torch design with helical outer conductive path; 
         FIG.  44 A  and  FIG.  44 B  illustrate an embodiment of a combination of a gliding arc and an opposed electrode; 
         FIG.  45 A  and  FIG.  45 B  illustrate an embodiment of an electrode ring cartridge; 
         FIG.  46 A ,  FIG.  46 B ,  FIG.  46 C ,  FIG.  46 D ,  FIG.  46 E , and  FIG.  46 F  illustrate an embodiment of an electrode cartridge; and 
         FIG.  47 A ,  FIG.  47 B ,  FIG.  47 C , and  FIG.  47 D  illustrate examples of pneumatic connections that can be used between the HEPA filter and ventilator cartridge and/or NO generator. 
     
    
    
     While the above-identified drawings set forth presently disclosed embodiments, other embodiments are also contemplated, as noted in the discussion. This disclosure presents illustrative embodiments by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of the presently disclosed embodiments. 
     DETAILED DESCRIPTION 
     The following description provides exemplary embodiments only, and is not intended to limit the scope, applicability, or configuration of the disclosure. Rather, the following description of the exemplary embodiments will provide those skilled in the art with an enabling description for implementing one or more exemplary embodiments. It will be understood that various changes may be made in the function and arrangement of elements without departing from the spirit and scope of the presently disclosed embodiments. 
     Specific details are given in the following description to provide a thorough understanding of the embodiments. However, it will be understood by one of ordinary skill in the art that the embodiments may be practiced without these specific details. For example, systems, processes, and other elements in the presently disclosed embodiments may be shown as components in block diagram form in order not to obscure the embodiments in unnecessary detail. In other instances, well-known processes, structures, and techniques may be shown without unnecessary detail in order to avoid obscuring the embodiments. 
     Also, it is noted that individual embodiments may be described as a process which is depicted as a flowchart, a flow diagram, a data flow diagram, a structure diagram, or a block diagram. Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be re-arranged. A process may be terminated when its operations are completed, but could have additional steps not discussed or included in a figure. Furthermore, not all operations in any particularly described process may occur in all embodiments. A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc. When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function. 
     Subject matter will now be described more fully with reference to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific example aspects and embodiments of the present disclosure. Subject matter may, however, be embodied in a variety of different forms and, therefore, covered or claimed subject matter is intended to be construed as not being limited to any example embodiments set forth herein; example embodiments are provided merely to be illustrative. The following detailed description is, therefore, not intended to be taken in a limiting sense. 
     In general, terminology may be understood at least in part from usage in context. For example, terms, such as “and”, “or”, or “and/or,” as used herein may include a variety of meanings that may depend at least in part upon the context in which such terms are used. Typically, “or” if used to associate a list, such as A, B, or C, is intended to mean A, B, and C, here used in the inclusive sense, as well as A, B, or C, here used in the exclusive sense. In addition, the term “one or more” as used herein, depending at least in part upon context, may be used to describe any feature, structure, or characteristic in a singular sense or may be used to describe combinations of features, structures or characteristics in a plural sense. Similarly, terms, such as “a,” “an,” or “the,” again, may be understood to convey a singular usage or to convey a plural usage, depending at least in part upon context. In addition, the term “based on” may be understood as not necessarily intended to convey an exclusive set of factors and may, instead, allow for existence of additional factors not necessarily expressly described, again, depending at least in part on context. 
     The present disclosure relates to systems and methods of nitric oxide (NO) delivery for use in various applications, for example, inside a hospital room, in an emergency room, in a doctor&#39;s office, in a clinic, and outside a hospital setting as a portable or ambulatory device. An NO generation and/or delivery system can take many forms, including but not limited to a device configured to work with an existing medical device that utilizes a product gas, a stand-alone (ambulatory) device, a module that can be integrated with an existing medical device, one or more types of cartridges that can perform various functions of the NO system, and an electronic NO tank. The NO generation system uses a reactant gas, including but not limited to ambient air, to produce a product gas that is enriched with NO. 
     An NO generation device can be used with any device that can utilize NO, including but not limited to a ventilator, an anesthesia device, a defibrillator, a ventricular assist device (VAD), a Continuous Positive Airway Pressure (CPAP) machine, a Bilevel Positive Airway Pressure (BiPAP) machine, a non-invasive positive pressure ventilator (NIPPV), a nasal cannula application, a nebulizer, an extracorporeal membrane oxygenation (ECMO), a bypass system, an automated CPR system, an oxygen delivery system, an oxygen concentrator, an oxygen generation system, and an automated external defibrillator AED, MRI, and a patient monitor. In addition, the destination for nitric oxide produced can be any type of delivery device associated with any medical device, including but not limited to a nasal cannula, a manual ventilation device, a face mask, inhaler, or any other delivery circuit. The NO generation capabilities can be integrated into any of these devices, or the devices can be used with an NO generation device as described herein. 
       FIG.  1    illustrates an exemplary embodiment of an NO generation system  10  that includes components for reactant gas intake  12  and delivery to a plasma chamber  22 . The plasma chamber  22  includes one or more electrodes  24  therein that are configured to produce, with the use of a high voltage circuit (plasma generator)  28 , a product gas  32  containing a desired amount of NO from the reactant gas. The system includes a controller  30  in electrical communication with the plasma generator  28  and the electrode(s)  24  that is configured to control the concentration of NO in the product gas  32  using one or more control parameters relating to conditions within the system and/or conditions relating to a separate device for delivering the product gas to a patient and/or conditions relating to the patient receiving the product gas. In some embodiments, the plasma generator circuit is a high voltage circuit that generates a potential difference across an electrode gap. 
     In some embodiments, plasma is generated with radio frequency energy. In some embodiments, NO generation can be modulated by adjusting one or more of the following parameters: RF Frequency, wave guide spacing, electrode gap, flow, pressure, temperature, etc. as variables in production. In some embodiments, the plasma generator circuit is a radio frequency (RF) power generator delivering RF power to one or more RF electrodes. In some embodiments, the RF power operates around 13.56 MHz with power in the 50-100 W range, however other power ranges can be effective depending on electrode design, production targets and reactant gas conditions. In some embodiments, RF power operates around 2.45 GHz for improved coupling and excitation of N 2  molecules. The controller  30  is also in communication with a user interface  26  that allows a user to interact with the system, view information about the system and NO production, and control parameters related to NO production. 
     In some embodiments, the reactant gas flow makes the plasma arc increase beyond the length of the electrode gap. NO production for a given electrode spacing is maximized by stretching the arc with reactant gas flow. 
     In some embodiments, the NO system pneumatic path includes a pump pushing air through a manifold  36 . The manifold is configured with one or more valves: three-way valves, binary valves, check valves, and/or proportional orifices. The treatment controller  30  controls the flow of the pump, the power in the plasma and the direction of the gas flow post-electrical discharge. By configuring valves, the treatment controller can direct gas to the manual respiration pathway, the ventilator pathway or the gas sensor chamber for direct measurement of NO, NO 2  and O 2  levels in the product gas. In some embodiments, respiratory gas (i.e. the treatment flow) can be directed through a ventilator cartridge that measures the flow of the respiratory gas and can merge the respiratory gas with NO product gas. 
     The output from the NO generation system in the form of the product gas  32  enriched with the NO produced in the plasma chamber  22  can either be directed to a respiratory or other device for delivery to a patient, or can be directed to a plurality of components provided for self-test or calibration of the NO generation system. In some embodiments, the system collects gases to sample in two ways: 1) gases are collected from a patient inspiratory circuit near the patient and pass through a sample line  48 , a filter  50 , and a water trap  52 , or 2) gases are shunted directly from the pneumatic circuit as they exit the plasma chamber  22 . In some embodiments, product gases are shunted with a shunt valve  44  to the gas sensors after being scrubbed but before dilution into a patient airstream. In some embodiments, product gases are collected from an inspiratory air stream near the device and/or within the device post-dilution. Within the gas analysis portion of the device, the product gas passes through one or more sensors to measure one or more of temperature, humidity, concentrations, pressure, and flow rate of various gasses therein. 
       FIG.  2    depicts an embodiment of a NO generation and delivery system  60 . Reactant gas  62  enters the system through a gas filter  64 . A pump  66  is used to propel gas through the system. Whether or not a system includes a pump can depend on the pressure of the reactant gas supply. If reactant gas is pressurized, a pump may not be required. If reactant gas is at atmospheric pressure, a pump or other means to move reactant gas through the system is required. A reservoir  68  after the pump attenuates rapid changes in pressure and/or flow from a pump. Coupled with a flow controller  70 , the reservoir, when pressurized, can enable a system to provide flow rates to the plasma chamber  72  that are greater than the pump  66  flow rate. Electrodes  74  within the plasma chamber  72  are energized by a plasma generation circuit  78  that produces high voltage inputs based on desired treatment conditions received from a treatment controller  80 . A user interface  76  receives desired treatment conditions (dose, treatment mode, etc.) from the user and communicates them to the main control board  105 . The main control board  105  relays to the treatment controller  80  a target dose and monitors measured NO concentrations from the gas analysis sensor pack  104 . The main control board  105  monitors the system for error conditions and can generate alarms, as required. Reactant gas  62  is converted into product gas  82  when it passes through the plasma chamber  72  and is partially converted into nitric oxide and nitrogen dioxide. An altitude compensator  84 , typically consisting of one or more valves (i.e. proportional valves, binary valves, 3-way valves, etc.), is optionally used to provide a back-pressure within the plasma chamber  72  for additional controls in nitric oxide production. Product gases pass through a manifold  86 , as needed, to reach a filter-scavenger-filter  88  assembly that removes nitrogen dioxide from the product gas. From the filter-scavenger-filter  88 , product gas is introduced to a patient treatment flow directly, or indirectly through a vent cartridge  90 . In some embodiments, the vent cartridge  90  includes a flow sensor  92  that measures the treatment flow  93 . The treatment flow measurements from the flow sensor  92  serve as an input into the reactant gas flow controller  70  via the treatment controller  80 . After product gas  82  is introduced to the treatment flow, it passes through inspiratory tubing. Near the patient, a fitting  96  is used to pull a fraction of inspired gas from the inspiratory flow, through a sample line  98 , filter  100 , water trap  102  and Nafion tubing to prepare the gas sample and convey it to gas sensors  104 . Sample gas exits the gas analysis sensor pack  104  to ambient air. In some embodiments, the system  60  can optionally direct gas through a shunt valve  94  and shunt gas path  95  directly to the gas sensor pack and out of the system. In some embodiments involving the shunt valve  94 , the manifold  86  includes a valve (not shown) to block flow to the filter-scavenger-filter when the shunt valve  94  is open. 
     Another exemplary embodiment of an NO generation system is shown in  FIG.  3   , which includes a carrying handle  110 , an interface  112 , a high voltage cage  114 , a control board  116 , one or more cooling fans  118 , and a water trap PCB  120 . The system also includes a gas sensor pack  122 , a lower manifold  124 , an air pump  126 , a high voltage PCB  128 , an upper manifold  130 , a proportional valve  132 , a DC power entry  134 , a high voltage (HV) transformer  136 , an AC power entry  138 , a reservoir  140 , and a flow director valve  142 . 
       FIG.  4    depicts a schematic showing all the components of an embodiment of an NO device  150 , including a control board  152 , a power management circuit  154 , one or more electrode assemblies  156 , and a peripherals interface  158 . A plasma chamber can be part of the reusable controller or removable and disposable. 
       FIG.  5    and  FIG.  6    depict embodiments of NO generation and delivery systems with redundant NO generators.  FIG.  5    depicts an exemplary pneumatic design  160  for an NO generation and delivery system. In the upper left of the diagram, sample gases  162  originating in the treatment circuit (lower right of  FIG.  5    labeled ‘A’) enter the system through a hydrophilic filter  164  and travel through a water trap  166 . In some embodiments, this filter  164  is disposable so that the user can replace it as needed when it clogs. An additional filter  168  after the water trap  166  protects the gas analysis sensors from contaminants. In some embodiments, the additional filter  168  is hydrophobic to prevent liquid contents from the water trap from entering the gas sensor assembly. Sample gases then flow through a pump  170  and then through a fixed orifice  172  that limits the gas flow rate through the sensors and diminishes pulsatility in the sample gas flow. Some gas sensors, for example electrochemical sensors, are sensitive to the amount of water content within a sample gas and can require the gas to have approximately 50% relative humidity. Gas flows through Nafion tubing  174  to add humidity to the sample from the atmosphere in the event that sample gases are very dry as can be the case when calibration gases are used. Conversely, if the gas sample to too humid, Nafion tubing  174  can remove humidity from the gas sample, driving the sample gas humidity towards ambient levels. Next, the sample gas flows through one or more gas analysis sensors. Sensor  176  measures NO 2 , sensor  178  measures NO, sensor  180  measures O 2 . A differential pressure sensor shown on the left side of the sensor manifold block is used to measure the flow rate through the gas sensor manifold  182 . This flow rate can be used to ensure that the sample pump is functioning and that the sample line, disc filter, and water trap are not clogged and/or kinked. An absolute pressure sensor near the end (bottom) of the sensor manifold is used to measure atmospheric pressure. Gases exit the sensor manifold and flow through a T-fitting, where one leg is connected to atmospheric pressure and the other leg is connected to an external port in the device. The second leg is connected to atmosphere to prevent hospital vacuum from affecting the flow rate through the gas sensor manifold and potentially affecting patient treatment. The external port can be connected to hospital vacuum or just vented to atmosphere. 
     Moving to the right in  FIG.  5   , at the top of the diagram there is an inlet  184  to receive reactant gas into the system. In some embodiments, this is a 22 mm medical air connection. Incoming reactant gas flows through a filter  186  to remove particulate then bifurcates into two parallel NO generation paths. Each path consists of a pump  188   a ,  188   b , a reservoir  190   a ,  190   b , a reservoir pressure sensor  192   a ,  192   b , a proportional flow valve  194   a ,  194   b , a fixed orifice, a plasma chamber pressure sensor  196   a ,  196   b , and a plasma chamber  198   a ,  198   b . After the plasma chamber  198   a ,  198   b , each flow path has a flow director  200   a ,  200   b  that can direct gases to either the gas sensor manifold  182  or towards the patient inspiratory air. These side paths to the gas sensor manifold  182  enable a system to evaluate the gas produced and/or redirect gases within the plasma chamber away from the patient. After the gas analysis side paths, one of the gas paths utilizes a flow director  202  to select whether product gases will flow to a ventilator circuit (B in the figure) or to a manual bag outlet (C in the figure). Gases then flow through one of three parallel scrubber passages in a disposable cartridge  204 . The scrubber passages consist of a filter, scrubber material, a second filter and a one-way valve. The one-way valve ensures that pressures and materials outside of the system do not enter the cartridge and controller. 
     In the lower right corner of  FIG.  5   , a treatment setup is depicted. In a ventilator circuit  206 , inspiratory gases exit the ventilator and enter a ventilator cartridge  208 . The gases flow through two flow sensors  210 ,  212 . In some embodiments, the flow sensors measure pressure, humidity and temperature in addition to flow. NO-containing product gas is merged with the inspiratory flow after the flow sensors. Inspiratory flow continues through a HEPA filter  214 , a humidifier  216  and on to a “T” fitting  218 , where sample gases are pulled, then on to the patient. 
     Also shown in the lower right corner of  FIG.  5    is a manual bagging circuit  220 . Inspiratory gases are sourced from a blender/wall outlet/cylinder  222  and enter the ventilator cartridge  208 . Flow is measured within the ventilator cartridge  208  prior to adding NO-containing gas. Gases flow through an optional humidifier  224  and on to a “T” fitting  226  where sample gases are pulled and then on to the patient. 
       FIG.  6    illustrates a similar system to the embodiment of the system shown in  FIG.  5   . As explained above,  FIG.  5    depicts how the filter-scrubber-filter assemblies can be grouped into a cartridge  204 , and  FIG.  5    also depicts how gas sensors ( 176 ,  178 ,  180 ), Nafion tubing  174 , a manifold, and pressure/flow sensors can be grouped into a gas sensor assembly  182 . In  FIG.  6   , a gas sensor assembly  232  includes a pump  234  and a flow sensor  236 .  FIG.  5    depicts how vent flow sensors  210 ,  212 , a bag flow sensor  223 , pressure sensors, and NO injectors can be grouped into the vent cartridge  208 . 
     A HEPA filter  214  connects to the ventilator cartridge  208  to keep the ventilator cartridge clean. In some embodiments, the HEPA filter utilizes a standard, 22 mm pneumatic connection for ease of replacement and optional use. In some embodiments, the HEPA filter connects to the ventilator cartridge with a connection to ensure that the system cannot be used without it. The connection prevents uses from connecting an inspiratory limb to a NO generator with standard 10 mm, 15 mm, and 22 mm male and female tubing fittings.  FIG.  47 A ,  FIG.  47 B ,  FIG.  47 C  and  FIG.  47 D  depict examples of pneumatic connections that can be used between the HEPA filter and ventilator cartridge and/or NO generator.  FIG.  47 A  is an O-ring seal between HEPA and controller. As the HEPA is inserted, the O-ring is compressed within a bore within the controller. In some embodiments, a retention feature (not shown) is engaged that prevents the HEPA filter from pulling out without a use-step of releasing the retention feature. In some embodiments, the interface between HEPA filter and vent cartridge is comprised of a tapered tubing connection similar to standard connections but with a different diameter that prevents engagement of standard tubing sizes.  FIG.  47 B  shows another embodiment where the HEPA filter includes a magnet. When the HEPA filter is engaged, the magnet actuates a Reed switch within the NO generator that informs the NO generator that the HEPA filter is present. 
       FIG.  47 C  depicts an embodiment where the HEPA filter includes a conductive surface that closes a circuit within the NO generator when the HEPA filter is fully inserted.  FIG.  47 D  depicts an embodiment where the HEPA filter has a reflective feature that closes an optical circuit when the HEPA filter is fully inserted. In some embodiments, the HEPA filter is engages the ventilator cartridge or NO generation device with threads. 
       FIG.  5    and  FIG.  6    further differ in pneumatic design post-plasma chamber. In  FIG.  5   , in both NO generation channels, a first flow-director ( 200   a ,  200   b ) directs product gases to either the gas sensor pack  182  or the gas scrubber cartridge  204 . In the secondary channel, a second flow director directs product gases to either a vent circuit (path B) or a bag circuit (path C). In  FIG.  6   , the pneumatic pathway differs in that a first flow director selects between vent circuit and the sensors while a second flow director selects between shunting to the sensors and bag circuit. The pneumatic design in  FIG.  6    has an advantage over the flow design of  FIG.  5    due to having equal flow restriction in both channels between the plasma chamber and the vent flow injector. This relates to minimizing the flow path length and having the flow restriction of the two paths be substantially identical so that they can have similar if not identical calibration settings and NO production. 
     In some embodiments, a scrubber cartridge can be used for demonstration purposes. The demo device can be identified by RFID, memory device, 2-d bar code, mechanical interface, optical interface, lower flow restriction, or other means by a controller to enable a demonstration mode for training purposes. In some embodiments, the demonstration scrubber cartridge is non-functional for clinical purposes. 
     Electrode Design 
     The orientation of electrodes can vary with respect to the reactant gas flow. In some embodiments, the electrode gap is orthogonal with the reactant gas flow. Typically, the reactant gas flow is directed towards or through the gap. This allows for stretching of the arc, which facilitates higher NO productions for a given input power than would otherwise be possible for a specified gap. Larger gaps are more power efficient (production per watt), so stretching the arc achieves efficiencies of larger gaps. Larger gaps also require higher voltages to initiate the plasma, so a stretched arc requires less voltage for the same production. In some embodiments, the electrode gap is parallel, or axial, to the reactant gas flow. Axial orientation can be less sensitive to reactant gas velocity changes. The gap can be increased for larger production levels or higher efficiencies. 
     In some embodiments, an electrode can be comprised of a non-electrically conductive rod with beads (short tubes) slid onto its length, as shown in  FIG.  7 A  and  FIG.  7 B . A non-conductive bead  302  (i.e. an insulator bead) is located in the middle of the central rod  300  with conductive beads on either side. High voltage is applied to beads located at each end of the rod with electrical arcing taking place across the center bead location. Springs  304   a ,  304   b  on one or both sides of the assembly complete the electrical connections and ensure that the electrode gap remains consistent by pressing the stack of beads towards the non-conductive bead in the center. This design offers consistent gap length and long electrode life because it accommodates for electrode wear. This design can also decouple reactant gas flow from NO production by eliminating arc bending described above. The orientation of this electrode with respect to the flow of reactant gas can have an effect on electrode life, the product gas and reactor production. This electrode is best suited to reactant gas flow that is parallel to the electrode long axis (as shown in  FIG.  7 B ), where the plasma will wear the electrodes evenly, whereas orthogonal flow (as shown in  FIG.  7 A ) will generally wear the electrodes on the down-stream side of the electrodes, meaning the springs will not be able to maintain the intended gap length set by the non-conductive bead. 
     In some embodiments, two electrodes can be oriented parallel to each other, such as electrodes  310 ,  312  shown in  FIG.  8   , providing increased surface area for prolonged longevity. This design has the benefit of electrodes entering from opposite ends of the plasma chamber to keep high voltage lines far apart to minimize internal and external creepage distances around the chamber. Ridges inside and outside the chamber can further increase creepage distances. Larger overlap between the electrodes can improve electrode longevity by providing more material for arcing. This design has shown two discrete arcing locations from the end of one electrode to the side of the other, and vice-versa. When alternating current is applied, the electrodes break down from point to line fairly evenly between the two electrodes This design provides further benefit by establishing the electrode gap by the hole locations in the chamber, rather than sliding electrodes along their long axis. In some embodiments, the rods are not parallel so that a gliding arc design is created. Electrodes can be circular in cross section or have a non-circular cross section. Non-circular cross sections can provide sharp edges and features to intensify the electric field in that area to reduce break-down voltage. The electric field can be high between the electrodes.  FIG.  8    shows air flow parallel to the electrodes  310 ,  312 . This can be beneficial because gas can be more focused towards both arcing locations. A further benefit is that one electrode is upstream of the plasma, decreasing the potential for sputtered electrode materials establishing a conductive path between the two electrodes. In some embodiments, a parallel electrode design utilizes different materials at tip and shaft. In some embodiments, tungsten is the cathode and a noble metal or alloy, such as iridium, rhodium or palladium is the anode. This solution provides the high temperature resistance of tungsten but protects the tungsten from the highly oxidizing environment of the anode. Palladium is more resistant to oxidation, so it serves as the anode. In some embodiments, air flow is orthogonal to the plane of the electrodes and directed towards the region defined by the electrode gap and overlap region. Nozzle size and electrode overlap can impact NO production efficiency significantly. 
     In some embodiments, the orientation of electrodes is asymmetrical to generate an asymmetrical electrical field. This can lower DC breakdown voltage. In some embodiments, this can be achieved with electrodes oriented like a “T” for a point-plane relationship, such as electrodes  320 ,  322  shown in  FIG.  9   . A similar approach can be achieved with two electrode rods where by the end of one electrode arcs to the side of the other electrode, which could be referred to as “point to line.” 
     In some embodiments, as shown in  FIG.  10   , a monolithic electrode  330  and heat sink design is used in a plasma chamber  334  to maintain electrode temperature at an optimal level. A monolithic electrode can be made out of an economical base metal and plated with a desired electrode material. The monolithic electrode  330  can have cooling lines running through it, or can have cooling fins  332  to act as a heat sink. A monolithic electrode can be beneficial because the geometric features required to facilitate the plasma are not generally the features which facilitate heat removal, mechanical mounting, electrical connection, or pneumatic sealing. Because of the different features required for different requirements of the design, the electrode is typically more than one parts which must be joined together. The joining methods create failure modes, such as leak points or electrical shorts, as well as adding manufacturing complexities and costs. By having a single monolithic electrode, all required features can be combined into one part, thereby reducing complexity and increased reliability. 
     In some embodiments, the relationship between gas flow rate or velocity and electrode diameter and electrode length is controlled to maintain electrode temperature at optimal level. For example, the bulk of the electrode could be buried within a manifold thus relying on conduction to remove heat, or some amount of surface area could be intentionally in the gas flow path to remove heat from convection. The amount of surface area is controlled by the diameter and length. 
     In some embodiments, a pair of electrodes is provided where one electrode is a different material from the other electrode. 
     In some embodiments, a pair of electrodes is provided where the AC waveform is rectified to create a dedicated anode and dedicated cathode. 
     In some embodiments, a pair of electrodes is provided where a dedicated cathode, which is no longer subject to mass erosion via ion-bombardment is to be considered a permanent (or longer-lasting) part of the device and may be made from a noble metal, which is less susceptible to erosion via oxidization or vaporization of the base metal or its oxide species, while the dedicated anode which may be made from an economical electrode material, such as copper, tungsten, or steel which will not be in use long enough to experience mass erosion from ion-bombardment, but can be replaced before it erodes substantially from vaporization or oxidation. 
     In some embodiments, a pair of electrodes is provided where one electrode is tied to chassis or earth ground inside the device. This electrode can be at low voltage and therefore safely incorporated into a disposable cartridge which would otherwise require excessive creepage and clearance distances. 
     In some embodiments, an electrode is provided with an additive metal to form an alloy intended to lower the work function and improve the arc initiation or arc stability. 
     In some embodiments, one or more electrodes can be constructed from a metal that forms an oxide that has a substantially lower melting temperature than the base metal, such that a non-conductive oxide layer never builds up over the electrode surface. This improves arc starting stability as the non-conductive oxide layer. 
     In some embodiments, there are three electrodes  340 ,  342 ,  344  providing two gaps, as shown in  FIG.  11   . In some embodiments, there is a short gap A and a long gap B as shown in  FIG.  11   . The short gap can be used for low NO production levels and can provide electrons to assist in breaking down the long gap. The long gap can be used for higher range NO production. Using short and long gap for different NO production ranges drastically improves the total dynamic range of an NO Production system, while also drastically improving resolution within that range. In some embodiments, arcing is initiated at the short gap prior to changing the high voltage circuit to pass through the long gap. In some embodiments, the short gap sustains a plasma during device operation to shorten the breakdown of the large gap by providing constant source of electrons in the vicinity of the electrodes, much like a pilot light for a natural gas water heater maintains a flame. The dimensions of the short and long gaps can vary. In some embodiments, the short gap is roughly 0.1-0.5 mm while the large gap can be 1.5-6 mm depending on the desired dynamic range or resolution. In some pulsed NO generation embodiments, the short gap is energized before the large gap for each NO generation pulse. This can improve the reliability of breaking down the large gap. A double pole, single throw switch as shown in  FIG.  11    can be used for DC applications. For AC applications, the switch would be a double pole, double throw unit. 
     In some embodiments, a capacitor is loaded with energy between electrical discharges and delivers its energy to an electrode gap at a time selected by the NO generation controller. The circuit  350  shown in  FIG.  12    is a DC powered circuit with a transformer (Trans) tuned to raise the voltage from the battery voltage to a voltage that will arc across a specific gap size. R 1  sets the bias voltage and limits the current to the base of the transistor (BJT 1 ) thus enabling current to flow through BJT 1 . The microprocessor provides timing for the charging and enabling of the capacitor (C 1 ). The microprocessor provides a switching circuit (TS 1 ) to turn off and on the voltage/current to the transformer (which in-turn generates a high enough voltage to discharge across the electrode. In conjunction with this timing the microprocessor can coordinate the switching circuit TS 2  to charge and discharge C 1  allowing for the additional current into the primary circuit (when the discharge gap is generating plasma). As a person skilled in the art would know, C 1  is tuned to the impedance of the circuit to maintain the proper time constants. 
     In some embodiments, multiple pairs of electrodes are located within a common plasma chamber. A first pair of electrodes  360  has a short gap for generating low amounts of NO. A second pair of electrodes  362  has a longer gap for generating high amounts of NO, as shown in  FIG.  13   . In some embodiments, the short gap electrode is energized first to generate electrons  364  (or an ion cloud) to facilitate break down of the longer gap electrodes. In some embodiments, a short gap generates electrical discharges at different frequency than a large gap. In some embodiments, two electrode pairs are used with the same gap by different electrode materials to provide different amounts of NO production from each electrode pair. In some embodiments, a channel of a NO generation device can include two or more flow controllers, each with a plasma chamber and specific electrode gap. 
     In some embodiments, a NO generation device contains multiple plasma chambers that can be selected one at a time for NO generation. In some embodiments, the chambers are oriented like a revolver where each chamber can be indexed into the flow path of the reactant gas. 
     In some embodiments, electrodes have coolant passageways within them, as shown in  FIG.  14   . Coolant passageways  372  pass through electrodes  370  to keep them cool and prolong electrode life. In some embodiments, reactant gas passes through the electrodes prior to being stored in the reservoir to minimize humidity condensation. In some embodiments, gliding arc electrodes include tubes with coolant flow within them. Coolant can be gas or liquid. In some embodiments, a non-electrically conductive coolant is pumped from a reservoir through one or more electrodes and back to the coolant reservoir. 
     In some embodiments, the NO generation system can include features that can be configured to cool the electrodes and/or plasma chamber. For example, reactant gases can be used to cool the electrodes and/or plasma chamber. In some embodiments, a plasma chamber can be removable for servicing. Removable plasma chambers can be made from high temperature materials, such as metals, glass, ceramic, composite and high temperature polymers. In some embodiments, the plasma chamber can be made from a thermally conductive material, such as aluminum. Seals between a removable plasma chamber and a manifold can be made with O-rings, lip-seals, gaskets, elastomeric materials, compression fittings, barb fittings, and the like. Space between the O-rings can collect NO 2  over time. In some embodiments, gas travels from the manifold to an O-ring groove and travels circumferentially around the plasma chamber prior to entry into the plasma chamber. A similar approach can be done for product gases exiting the plasma chamber. This approach can allow gases passing circumferentially around the plasma chamber to cool the plasma chamber and no dead-end cavities where NO 2  can stagnate. FIG.  15 A,  FIG.  15 B ,  FIG.  15 C ,  FIG.  15 D ,  FIG.  15 E ,  FIG.  15 F ,  FIG.  15 G  and  FIG.  5 H  illustrate an embodiment of a removable plasma chamber. 
       FIG.  15 A  and  FIG.  15 B  depict an electrode  382  mounted to a plasma chamber  380 . Circumferential grooves around the plasma chamber are used for O-ring seals and for routing reactant and product gas as shown. A high voltage connection is at one end of the assembly. High voltage current conducts through an insulator to a center electrode within the plasma chamber. The plasma chamber is grounded and electrically connected to the ground electrode. 
       FIG.  15 C ,  FIG.  15 D ,  FIG.  15 E ,  FIG.  15 F , and  FIG.  15 G  depict cross-sectional views of a high voltage electrode assembly. The electrode  382  seals to the plasma chamber with an O-ring and is held in place with a retaining plate. The orientation of the ground electrode with respect to air flow is selected so that the electrode does not interfere with gas flow through the electrode gap while remaining upstream of the plasma. This prevents deposition of conductive materials from electrode degradation or carbon formation between the two electrodes, thereby creating a short circuit. In some embodiments, a staggered inlet and outlet facilitate one blind mate connection. In some embodiments, features that can contribute to air exchange in order to minimize a stagnant bolus of nitrogen dioxide include air circling the plasma chamber before entry and after exit ensures complete exchange, and staggered inlet and outlet within the plasma chamber. In some embodiments, the electrode can be “clocked” so the “ground wire” is upstream of any iridium oxide deposited on the ceramic which could create a creepage path. 
       FIG.  15 H  shows an exploded view of an electrode and plasma chamber assembly. A plasma chamber component includes a cavity (directed away from the viewer) and has circumferential grooves for O-ring seals and gas pathways. In some embodiments, the plasma chamber is constructed from aluminum. A set-screw  384  is used to lock the electrode  382  in place and provide a reliable electrical connection between the electrode and the plasma chamber. A plasma manifold  386  provides reactant gas to the plasma chamber and directs product gases away from the plasma chamber. In some embodiments, the manifold is constructed from PEEK polymer. A clamp  388  and screws  390  provide compressive force to hold the electrode  382  to the plasma chamber  380  and maintain a pneumatic seal provided by the O-ring  392 . The electrode consists of a center electrode housed within a ceramic insulator and secondary J-shaped electrode. A retaining nut  394  threads onto the top of the electrode and is used to jam against the threaded adaptor component  396  to provide a specific length to the assembly. The entire assembly (minus the manifold) can be removably inserted into the plasma manifold for replacement, as needed. 
     Conductive heat transfer between the electrode and chamber can be enhanced by material selection. Ceramic plasma chambers conduct heat better than polymeric chambers, resulting in lower electrode temperatures. Cooling fins on the inside or outside of the plasma chamber can aid in convective heat transfer into the internal or external gas flow, respectively. Certain ceramics can provide substantially better heat conductive over commodity ceramics such as alumina or quartz. These specialty ceramics include but are not limited to beryllium oxide, aluminum nitride, and boron nitride. 
     In some embodiments, there are one or more partially- or fully circumferential grooves around a plasma chamber. Grooves can be used for O-ring seals to prevent cross-communication of reactant gas and product gas that would decrease flow through the plasma chamber. In some embodiments, the reactant gas inlet is aligned with the electrode gap to aid in directing reactant gas flow through the plasma. In some embodiments, the complexity of the manifold that houses the plasma chamber does not support alignment of the reactant gas port in the manifold with the reactant gas inlet in the plasma chamber. In some embodiments, this is addressed by having a first groove that can receive reactant gas from a surrounding manifold, and a second groove that delivers the reactant gas to the plasma chamber with both grooves in fluid communication by use of slots between the first and second groove to enable cross flow. In some embodiments, the width of a single groove is made wider, rather than having two grooves that are connected by a slot. The second groove can be located in a position so that an entry portal into the plasma chamber is located such that reactant gas is directed towards an electrode gap for maximizing NO production 
     In some embodiments, spiral grooves on the exterior of a removable plasma chamber can pneumatically connect the reactant gas galley from the plasma manifold to the reactant gas entry point with the plasma chamber. In some embodiments, reactant gas flows from the plasma manifold galley to the chamber entry point. In some embodiments, the plasma chamber galley is aligned with the chamber entry point. Alignment of the chamber entry point to the electrode gap is another variable. In some embodiments, a reactant gas flow  400  enters into a plasma chamber through a reactant gas entry point  402  that is aligned directly with the electrode gap to maximize reactant gas/plasma interaction, as shown in  FIG.  16 A . 
     Electrodes in the form of a single-sided electrode pair, for example a J-shaped ground electrode, can generate a low-pressure zone  414  between the ground electrode and the center electrode.  FIG.  16 B  illustrates a reactant gas flow  410  that can enter through the wall of the chamber through a reactant gas entry point  412 , directed at the J-shaped electrode. The flow divides around the J-shaped electrode, creating a region of low pressure downstream of the J-shaped electrode. As materials sputter from the electrodes, this low-pressure zone can promote deposition of electrode materials which can lead to electrical creepage and ultimately reduced NO production. In some embodiments, the electrode ground electrode is rotated with respect to the reactant gas flow to be upstream but out of the reactant gas flow. For example, the ground electrode can be rotated 60% along its axis. This approach can prevent electrically conductive deposits between the center electrode and ground electrode while also enabling more consistent flow the plasma chamber across a range of flow rates. 
     In some embodiments, the plasma chamber can be in the form of a dome  420 , as shown in  FIG.  17 A ,  FIG.  17 B , and  FIG.  17 C . This approach is an example of one or more of the electrodes being part of the chamber wall. It provides a large surface area of electrode which prolongs electrode life. 
     In some embodiments, an array of center electrodes arc to an array of outer electrodes. This approach provides redundancy and a way to shift heating so that no one electrode pair gets too hot. In some embodiments, pairs of electrodes are energized at a time, one inner and one outer. In some embodiments, all center electrodes are energized and outer electrodes are connected to close the circuit one at a time. Various embodiments of electrode arrays can be seen in  FIG.  18 A ,  FIG.  18 B ,  FIG.  18 C , and  FIG.  18 D .  FIG.  18 A  depicts four electrode pairs  430 ,  432 ,  434 ,  436  where the inner four electrodes are at one polarity and the outer four electrodes are at the opposite polarity.  FIG.  18 C  depicts a way of flowing gas through the electrodes shown in  FIG.  18 A .  FIG.  18 B  shows four electrode pairs  440 ,  442 ,  444 ,  446  where the upper electrodes are at one polarity and the bottom electrodes are at the opposite polarity.  FIG.  18 D  shows how air flow can be directed over all four electrode pairs. Electrode pairs can be energized as pairs. Alternatively, all upper electrodes could be energized, but only one bottom electrode is electrically connected so that arcing only occurs between one pair of electrodes. 
     Plasma Electrodes 
     In some embodiments, the electrodes and plasma chamber of an NO generator are integrated into a single assembly. The one or more electrodes can be made from a single material, such as Iridium, or a composite. In some embodiments, a composite electrode is made from a titanium or tungsten substrate welded to an iridium tip. This approach offers the benefit of lower cost metal while still being weldable to iridium due to having a similar melting point. Electrodes are fixed into electrically conductive pucks that serve to transfer heat, anchor the electrodes in position at a specified electrode gap, and provide an electrical interface to a power supply. Pucks connect to a plasma chamber with sealed connections. In some embodiments, the seal between puck and plasma chamber employs an O-ring to seal in NO-containing gases. The plasma chamber can be made from ceramic, glass, high-melting point polymer, or a composite. In some embodiments, the plasma chamber is made from a polymer material with ceramic inserts in the region of the plasma chamber to prevent polymer melting. Reactant gas flow through the plasma chamber is directed towards the electrode gap for increased NO production and to direct any sputtered electrode materials away from the electrodes. In some embodiments, pneumatic fittings on either end of the plasma chamber consist of 90-degree angles so that the pneumatic openings are parallel with high voltage electrical connectors to enable connection of the plasma chamber and electrodes to an NO generator in a single motion.  FIG.  19 A ,  FIG.  19 B , and  FIG.  19 C  illustrate an embodiment of an electrode design including a plasma manifold  450 , and air inlet  452 , an air outlet  454 , a pneumatic connection  456 , and a plasma generation chamber  460  with controlled airflow for producing plasma  462 .  FIG.  19 B  shows a close-up view of an individual composite electrode  458  with a head that is larger in diameter and different material than the substrate shaft. In the embodiment shown, reactant gas flow is directed through a 4 mm nozzle to a 2.5 mm electrode gap. The nozzle terminates as it reaches the plasma chamber  460  and the internal diameter increase to 9 mm. This increase in diameter provides clearance between the electrode and plasma chamber and increases the surface distance/area between electrodes to prevent electrical creepage.  FIG.  19 C  illustrates an embodiment of an opposing electrode assembly  464 . 
     The relationship between nozzle size, electrode gap and spacing between nozzle and electrode gap have significant effects on plasma-gas interaction and resulting NO production. In some embodiments, a 1 mm nozzle is directed at a 0.5 mm gap. In this embodiment, high gas-plasma interaction results in a high level of NO conversion within the reactant gas. In some embodiments, a 2 mm nozzle is directed at a 0.5 mm gap. In this embodiment, less gas-plasma interaction results in low NO production levels, which can be advantageous in low NO doses. In some embodiments, a nozzle has variable size so that NO production can be optimized for a given treatment. In some embodiments, the orientation of the nozzle with respect to the electrode gap can be varied to adjust NO production. This can be accomplished by re-orienting a single nozzle or changing from a first nozzle to a second nozzle. In some embodiments, a first nozzle is aimed directly at an electrode gap and a second nozzle is parallel to a first nozzle but offset so that reactant gas passing through it is not directed towards the electrode gap. A system can choose between nozzles in a binary fashion or titrate between the two by means of a flow diverter or one or more proportional or digital valves. 
     In some embodiments, two or more independent pairs of electrodes are located within a single plasma chamber. This can provide electrode redundancy without added volume. In some embodiments, the two or more independent pairs of electrodes are configured like cross hairs in a gun site. 
     In some embodiments, a gas discharge tube is located in parallel with the electrode gap within the circuit. This provides protection to the system from excess voltage in the event of electrode failure. Electrical current, heat or optical emissions from the gas discharge tube can be used by the system to detect electrode failure. 
     The NO generation characteristics of sharp-edged solid electrodes can vary over their service life due to erosion of the sharp edges. In some embodiments, the electrode is constructed from a tube to ensure that there is always a relatively sharp edge at the end as it wears, ensuring consistent performance across its service life. This embodiment is also beneficial because it provides sharp edges provide high electric field strength. 
     Sharp edges on an electrode become rounded over time due to preferential arcing, resulting in a decreased electric field over the electrode surfaces. This decreased electric field at a given voltage can make arc formation take more time or fail to happen at all. In an NO generation device, longer or variable arc formation times can affect the stability of NO production and dose accuracy over time. In some embodiments, electrode edges are rounded during manufacturing to have a similar shape to a worn electrode. When this is done, higher voltage and longer duration are required to achieve breakdown within the gap, but those voltages and durations are more predictable over a longer period of time. 
     One way to increase the electric field in the proximity of the electrode gap is to concentrate electric field between the electrode and an insulator. In some embodiments, the electrode and plasma chamber are designed to increase electric field in the vicinity of the electrode when voltage is applied. In some electric field concentrator embodiments, the junction between electrode, reactant gas, and electrode insulator have one or more of the following parameters tuned to increase electric field strength in the vicinity of the electrodes: geometry, relative permittivity (i.e. dielectric constant), and other insulator material properties (susceptibility, polarizability, melting temperature). Increasing electric field strength can intentionally exceed the critical displacement (electric flux density) of the reactant gas, which will result in either partial discharge or corona, thereby generating free electrons that facilitate initiating a full discharge between the electrodes. This effect can be considered to be effectively a starter discharge that facilitates the generation of a larger arc. In some embodiments, the E-field concentrator is integral to the plasma chamber. A field concentrator can be made of a material with appropriate relative permittivity, such as ceramic, glass or polymer. In some embodiments, the field concentrator is made from alumina. 
       FIG.  20    depicts an exemplary insulator around an electrode with “h,” the height of the insulator with respect to the end of the electrode and “α,” the angle between insulator and electrode. In some embodiments, “h” is between 0.1 and 0.5 mm and “α” is between 15 and 60 degrees to ensure that the electric field is concentrated while minimizing the impact to reactant gas flow. In some embodiments, a large angle α is used so that the angle remains in a functional range in the presence of carbon deposits. In some embodiments, a radial gap between the insulator and the electrode can create a local concentration of electric field. 
     The materials that form the insulator can vary. In some embodiments, electrode insulator materials have high chemical stability, high melting temperature and appropriate relative permittivity. In some embodiments, titanium dioxide is used to shape the electric field in the vicinity of an electrode gap. This material can be used as it is biocompatible and benign if it enters the patient airstream. 
     Electrical discharge for a given gap occurs at lower voltages when free electrons are available. Lower voltages are beneficial to an NO generation system because they decrease the potential for electrical discharge elsewhere in the system. In some embodiments, a specific class of materials release electrons more readily due to a low work function of the oxide layer. In some embodiments, pure yttrium oxide is used as a source of Schottky/Thermionic Emissions source. In some embodiments, yttrium partially stabilized zirconia can be used as a source of Schottky/Thermionic Emissions source. In some embodiments, barium titanate can be used as a very high relative permittivity (greater than 70 C/m2) and possibly Schottky/Thermionic Emission source. 
     In some embodiments, an insulator  470  surrounds an electrode with a sloped end near the electrode gap, as shown in  FIG.  21 A  and  FIG.  21 B . The tallest portion of the slope is located upstream in the reactant gas flow. The electric field is concentrated between the insulator and electrode at the upstream side, facilitating the breakdown of the gap in the presence of high voltage. The reactant gas flow directs the arc across the top of the electrode to the downstream edge as the arc is sustained. The insulator does not interfere with the arc on the downstream side because it is further from the electrode gap at that location. This approach enables the plasma to generate NO without interacting with the insulator material and potentially contaminating the plasma. In some embodiments, the insulator material is a ceramic. As shown in  FIG.  21 A , an arc initiates on the upstream edge where electric field strength is high due to proximity of the ceramic and electrode. As shown in  FIG.  21 B , the arc has migrated across the surface of the electrode and clings to the downstream edge of the electrodes. As shown, the arc has elongated due to the flow of reactant gas through the chamber. 
     Materials 
     Electrode performance is influenced by a variety of material properties, including but not limited to work function, melt temperature of the base material, and melt temperature of oxide layers (as applicable). NO generation electrodes can be made partially or wholly from graphite (carbon), carbon-carbon composite, glassy/vitreous carbon, iridium, tungsten, tungsten-silver alloy, hafnium, titanium, tantalum, barium, strontium, yttrium, lanthanum, and cerium. Copper, stainless steel, and electrically conductive ceramics (indium tin oxide (ITO), lanthanum-doped strontium titanate (SLT), yttrium-doped strontium titanate (SYT) can also serve as electrode materials. A substrate electrode can be plated with an ideal electrode material. For example, a titanium electrode can be plated with a noble metal such as Iridium. Alloys of more than one material can be used to leverage benefits of each constituent material. Biocompatibility of an electrode should also be considered due to the potential of electrode particles entering the inspiratory airstream. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                 Overall Work 
                 Base melt 
                 Oxide melt 
               
               
                 Material 
                 Function 
                 temperature 
                 temperature 
               
               
                   
               
             
            
               
                 Titanium 
                 Good 
                 1941 K 
                 2116 K 
               
               
                 Hafnium 
                 Good 
                 2506 K 
                 3031 K 
               
               
                 Tantalum 
                 Good 
                 3290 K 
                 2145 K 
               
               
                 Glassy Carbon 
                 Good 
                 3925 K 
               
               
                 Stainless Steel 440c 
                 Good 
                 1756 K 
               
               
                 Tungsten 
                 Good 
                 3695 K 
                 1746 K 
               
               
                 Iridium 
                 Poor 
                 2719 K 
                 1370 K 
               
               
                 Barium 
                 Excellent 
                 N/A* 
                 2196 K 
               
               
                 Strontium 
                 Excellent 
                 N/A* 
                 2804 K 
               
               
                 Yttrium 
                 Excellent 
                 N/A* 
                 2698 K 
               
               
                 Lanthanum 
                 Excellent 
                 N/A* 
                 2588 K 
               
               
                 Cerium 
                 Excellent 
                 N/A* 
                 2670 K 
               
               
                   
               
               
                 *N/A because metal does not exist as base metal in the presence of oxygen. 
               
            
           
         
       
     
     In some embodiments, the electrode surfaces comprise a material with low work function, i.e. more readily releasing electrons. In some embodiments, an electrode substrate is coated with an oxide layer consisting of one or more of the following materials: alkaline oxide, barium oxide, strontium oxide, calcium oxide, aluminum oxide, or thorium oxide. In some embodiments, an electrode is coated with a boride-containing material, such as lanthanum hexaboride or cerium hexaboride to achieve a low work function. In some embodiments, the electrode contains an electron-emissive layer of thorium, zirconium dioxide, lanthanum oxide, yttrium(III) oxide, cerium(IV) oxide, and alloys thereof in the outer surface. In some embodiments, carbide materials provide a low work function on an electrode, such as zirconium carbide, tungsten carbide, hafnium carbide, and tantalum carbide. In some embodiments, the electrode material is selected from the group including: scandium, yttrium, gadolinium, lanthanides, samarium, hafnium, zirconium, and titanium). Tungsten, tantalum, molybdenum, and rhenium can also be used, owing to their high boiling point. In some embodiments, electrodes are made from a single-crystal manufacturing process. Single crystal materials can be beneficial because they do not have grain boundaries which are a common site for initiation of oxidation. By reducing the formation of oxides, which typically have a much lower melting temperature than their parent metal, the electrode erosion and NO production changes that result can be slowed. 
     Electrode Gap Adjustment 
     In some embodiments, a nitric oxide generation system can adjust the electrode gap with a stepper motor, as shown in  FIG.  22   . The system can zero itself by running the electrodes together until they contact, then the stepper motor is operated to separate the electrodes by a known amount. This enables a system to accommodate for electrode wear. As shown in  FIG.  22   , a first electrode  480  can be fixed in position and a second electrode  482  can be movable such that a variable gap  484  exists between them. It will be understood that either or both electrodes can be movable to vary the size of the gap therebetween. In some embodiments, the electrode gap is varied to adjust the amount of NO produced and/or the NO/NO 2  ratio. Electrode gap adjustment can be made before NO generation and/or during NO generation. In some embodiments, the relationship between gap size and NO production at various input powers and flow rates is thoroughly characterized, enabling a controller to adjust the gap to achieve desired NO production levels during therapy. 
     It is possible for the system to vary the electrode gap to vary NO production and make up for worn electrodes. In some embodiments, a brush can make contact with the electrode. The electrode is mounted in a non-electrically conductive shaft that can be translated (or rotated) away from another electrode. Motion of the electrodes can be manual or by motor. In some embodiments, the electrodes are moved towards each other to establish zero gap and then moved apart a known amount. For example, possible ranges for the electrode gap are from 0.1 mm for low productions, up to 5 mm for high productions. This would establish a known zero-point, enabling the device to compensate for an offset change the latest calibration due to electrode wear. The movable electrode length could be designed so that several millimeters of electrode wear may be anticipated and accommodated over the service life of the device. In this manner, a substantially longer-life electrode can be created. 
     In some embodiments, an electrode assembly is disposable, lasting hours to days. This enables a lower cost material to be used, such as copper, titanium. 
     In some embodiments, electrodes are mounted in materials that have a coefficient of thermal expansion to minimize stress in components during thermal cycling. For example, for iridium and titanium electrodes, alumina has similar coefficient of thermal expansion. 
     Plasma Chamber Design 
     An NO generator plasma chamber has many requirements. The chamber must be gas-tight, preventing the loss of reactant and product gases. The chamber must locate electrodes in a consistent manner. The chamber must direct reactant gas towards the electrodes in a predictable manner. The chamber must prevent electrical shorting between electrodes other than within the electrode gap. This last requirement can present a challenge to designers when electrical creepage is considered. Electrical creepage is the phenomenon whereby electricity travels along the surface of a material. The distance in which electricity will creep depends on many factors, including but not limited to the distance between conductors, material type, material cleanliness, and voltage applied. In an NO generator, electrical creepage between electrodes would prevent electrical breakdown within the electrode gap and plasma formation. Thus, it is important to prevent electrical creepage within the plasma chamber. In some embodiments, undulations in the wall of the plasma chamber increase creepage distance. 
     As electrodes wear, there is a potential for electrically conductive electrode material to sputter onto the internal surfaces of a plasma chamber, changing the conductivity of plasma chamber walls and decreasing the voltage required to cause electrical creepage. One benefit to using undulations within the plasma chamber walls is that valleys are less likely to be coated with conductive deposits such as iridium-oxide or carbon. 
     In some embodiments, a plasma chamber is insulated to maintain a high temperature, thereby increasing the NO to NO 2  ratio. In some embodiments, the reactant gas is actively heated prior to the plasma chamber and/or within the plasma chamber. 
     Plasma chambers can be made from a variety of materials. In some embodiments, ceramic is used for its electrical resistance and thermal conductivity (for example, alumina nitride with a k=140-180 W/mK). In some embodiments, a high temperature polymer is used for its lower cost to ceramic, electrical resistance, chemical resistance, and light weight. Examples of a suitable polymer are PEEK, Ultem, PVDF, FEP, and PTFE. 
     Polymer materials can be susceptible to melting due to plasma temperatures. In some embodiments, the plasma chamber includes ceramic inserts to insulate chamber material from high temperature electrodes and/or plasma. 
     In some embodiments, a plasma chamber recycles heat from the product gas exiting the chamber to the inlet gas stream for the purpose of increasing NO:NO 2  ratios. 
     In some embodiments, a plasma chamber recycles heat from the exhaust gas to the inlet gas stream for the purpose of cooling the outlet gas stream to a manageable temperature for downstream seals, valves, scrubber materials or sensors. 
     In some embodiments, a plasma chamber is provided that removes heat from the exhaust gas so as to “quench” the NO and prevent formation of NO 2 . This can be accomplished by passing outlet gas through geometry which facilitates heat exchange to another air flow (for example, flowing over fins, or splitting flow over many smaller diameter tubes). 
     A plasma chamber can incorporate a heat exchanger to actively transport thermal energy from one manifold element to another. In some embodiments, a heat exchanger cools the outlet gas stream and moves the heat into the inlet gas stream. In some embodiments, a heat exchanger can cool electrodes and heat an inlet gas stream. In some embodiments, a heat exchanger can heat electrodes and cool an outlet gas stream. In some embodiments, the heat exchanger can be a Peltier device. In some embodiments, the head exchanger uses compression and expansion of a coolant gas. In some embodiments, the heat exchanger involves the pumping of a liquid. In some embodiments, heat transfer between components relies on thermal contact and conduction through thermally conductive materials (for example, aluminum or copper). In some embodiments, copper electrodes are plated with iridium in the region of arcing. This provides excellent electrical thermal conduction of copper and high melting temperature and electrically conductive oxides of iridium. 
     In some embodiments, a plasma chamber can use reactant gas flow velocity to create an elongated beam of plasma as a means of controlling of NO production. 
     In some embodiments, a plasma chamber design can include a nozzle end  490 , a flare  492 , electrodes  496 , and a chamber  494 , as shown in  FIG.  23   . The nozzle diameter is centered with the electrode gap and sized to produce a desired reactant gas velocity at the electrodes for a specific volumetric/mass flow rate. The flare increases the diameter of the chamber, thereby increasing the electrical creepage distance from one electrode to another. 
     Creepage distance within the plasma chamber can be increased further by adding surface features, such as ridges, valleys or splines within the chamber, as shown in  FIG.  24 A  and  FIG.  24 B  (which includes a plurality of splines  500  inside the chamber). Because the junction between electrode, air, and insulator typically results in a locally intense electric field, arcs often appear to run along the surface of an insulator—so adding features to increase that length makes the distance function more like an equivalently sized gap, not aided by the increased electrode. 
     Creepage distance within the plasma chamber can be increased further by locating the electrodes  510  within a non-conductive tube  512  with a clearance, as shown in  FIG.  25   . This can prevent sputtered electrode materials from shorting the path between electrodes because materials cannot sputter down into the tubes. 
     Creepage distance can be increased by shielding a portion of the plasma chamber wall from sputtered electrode materials, as shown in  FIG.  26 A  and  FIG.  26 B . In some embodiments, surface features  520 ,  522 , such as grooves or ridges, in an electrode insulator provide creepage distance in addition to protection from sputtered materials. 
     In some embodiments, an electrode  530  can be recessed within an insulator  532  to shield the chamber from sputtered electrode materials, as shown in  FIG.  27   . This feature can also provide enhancement of the electric field at the electrode/insulator interface to decrease the voltage required to initiate plasma in the electrode gap. 
     Gliding Arc 
     In some embodiments, a gliding arc design can be used. A gliding arc electrode design can include two or more electrodes with elongated surfaces. The surface can be parallel or diverging with respect to the direction of reactant gas flow. This type of design offers benefits in electrode longevity because plasma is carried by the flow along the surfaces of the electrodes, thereby distributing electrode wear over a greater surface area, decreasing the electrode surface temperatures and erosion. Gliding arc electrodes have a range of electrode gap and can provide a small gap to improve the reliability of initial electrode breakdown. This offers benefits in lower voltage being required to initiate the arc. Gliding arc also offers the potential to decrease the back pressure associated with flowing gas through plasma since the arc can travel with the air flow. The duration of an individual arc can be limited by the voltage applied to the electrodes, the duty cycle, and/or the gas flow rate. In some applications, it is possible to extinguish an arc before it reaches the far end of the electrode where the arc elongates and NO production is less precise. A gliding arc design can be used in the field of NO generation because 1) arcing occurs over large surfaces of the electrodes, decreasing temperatures and decreasing electrode wear, 2) The initial gap can be very short to initiate the arc with low voltage, thereby decreasing the potential for arcing elsewhere in the system, 3) NO production can be very high due to the large gap that can occur with long duty cycles, 4) NO production can be continuous (duty cycle=100%), and 5) NO production can be very low with fine resolution, owing to the small gap. 
     In some embodiments, a gliding arc design includes electrodes constructed from monolithic blocks with edges that diverge. As arcs travel along the length of the electrode edges, the velocity of the arc slows due to the increasing cross-sectional area. This can produce more NO as the arcs spend more time at long lengths. In some embodiments, the length required for gliding arc electrodes is determined by the reactant gas flow rate through the plasma chamber, maximum voltage available and the maximum duty cycle. The length and surface profile of the gliding arc can be tuned to a particular flow rate and duty cycle/period, so as to clear all electrons &amp; ions from the chamber during the “off-time” of the plasma. A desired NO output curve can create by setting the electrode&#39;s angle of divergence. If a single angle represents a linear equation, then a polynomial, exponential, power, log or any other type of function, including a combination of functions, can be utilized to create a desired NO output curve. 
     The electrodes of a gliding arc design can be constructed from bent rods or straight rods. One benefit of straight rods is ease of insertion into the plasma chamber. When rods (such as rods  542 ,  544  shown in  FIG.  28   ) are inserted from opposite ends of a plasma chamber  540 ,  550 ,  560 , as shown in  FIG.  28   ,  FIG.  29 A , and  FIG.  29 B , there is significant creepage distance between electrodes. In some embodiments, straight electrode rods can be rotated about their long axis periodically to align a new surface with the electrode gap, thereby prolonging the useful life of a particular electrode. Curved arrows in the  FIG.  29 B  depict this rotation. 
     The electrodes of a gliding arc can be constructed from sheet metal where the edge of the sheet metal serves as the arcing surface. This edge can be rounded, as needed, to make electrode performance more consistent over time. It will be understood that the edges of the gliding arc electrodes can be, but do not need to be, straight. In some embodiments, sheet metal is cut to contain two, opposed gliding arc electrodes  570 ,  572  held at a correct gap  576  by one or more metal tabs  574 , as shown in  FIG.  30   . After installation of the electrodes into the plasma chamber, the one or more metal tabs can be broken off the assembly, leaving the two gliding arc electrodes electrically independent. In some embodiments, a pair of electrodes is machined from a single plate of material to ensure that chamfering of the edges is the same for each electrode. The final machining step is to separate the electrodes so they can be independently mounted to the plasma chamber.  FIG.  31    depicts an embodiment of an electrode design made from sheet material. The upper edges of the electrodes  580 ,  582  are chamfered to present a sharper edge to the electrode gap. An area  584  is removed as a final machining step to separate the two electrodes. 
     A gliding arc electrode plasma chamber can operate at a full range of duty cycles. In some embodiments, a gliding arc plasma chamber can be designed to operate at a low duty cycle due to the small electrode gap that can exist between the gliding arc electrode pair. This can allow for lower amounts of NO to be generated. In some embodiments, a gliding arc plasma chamber is designed to operate at high duty cycles (for example, 50 to 100%). This can allow for a longer electrode life due to distributed wear along the length of the electrodes. It also provides continuous NO production when 100% duty cycle is utilized. 
     The initial gap and angle between gliding arc electrodes are a critical design features of a gliding arc design for nitric oxide generation. Smaller gaps enable lower production levels due to the shorter length arcs and decreased gas/plasms interaction. In some embodiments, the small gap is 0.5 mm in length, however lengths up to 2.5 mm have been utilized. In some embodiments, the angle between electrodes is 30 degrees. In some embodiments, angles of 20 to 40 degrees have been utilized. In some embodiments, angles of 0 to 75 degrees can be used. Arcs travel along the length of the gliding arc electrode due to gas flow. Larger angles between electrodes result in more rapid elongation of the arc and higher production levels for a given electrical discharge duration. It follows that the interaction between electrode angle and gas flow rate is important in specifying a gliding arc electrode design for a specific range of NO production. When gas flow is low, an arc may not glide at all. If the electrode gap increases to rapidly (steep angle), the gas flow could extinguish the arc before the end of the high voltage pulse. In the event of premature extinguishing of the arc, an arc will reform at the small gap and continue generating NO until the end of the high voltage pulse, albeit at a smaller gap and correspondingly lower production levels. This can create a discontinuity in NO production which is typically avoided. In some embodiments, a NO generation system can detect premature extinguishing of the arc and truncate the duration of the arc to protect against applying high levels of current to the small gap. In some embodiments, a NO generation system can detect premature extinguishing of an arc and reset current modulation within the arc for an appropriate level of the small gap. In some embodiments, a NO generation system can detect premature extinguishing of an arc and restarting of the arc at the small gap and prolongs the duration of the arc so that the NO production for that electrical discharge remains on target. 
     In some embodiments, an NO generation system can detect premature extinguishing of the plasma during a discharge by detecting discontinuities in either the plasma voltage, plasma power or both. In some embodiments, premature extinguishing of the plasma arc can be detected as a discontinuity in the plasma light output using an optical sensor. In some embodiments, the optical sensor is directed towards the small gap region of a gliding arc electrode. In some embodiments, the optical sensor can view the electrode gap through a optically transparent window, such as a quartz window. 
     Electrical field strength is higher in the small gap region of a gliding arc electrode. For a fixed current in the plasma, this contributes to higher energy density in the small gap than other locations along the length of the gliding arc electrode. High energy density is associated with increased temperature and sputtering of electrode materials, which corresponds with higher levels of electrode erosion in the small gap region of a gliding arc electrode. Because the voltage is set by the gap, modulation of power density must be accomplished by modulation of the plasma current. In some embodiments, current applied to the plasma is modulated within an electric discharge event to minimize energy density within the electrode gap. This approach offers two significant benefits: 1) Electrode erosion is lessened and 2) lower NO production levels can be achieved. 
     The orientation of the gliding arc electrode can have an effect on gas production. For example, gliding arc electrodes can produce additional gas that can travel further when oriented vertically. In some embodiments, a system can use an orientation sensor to compensate for differences in NO production based on the orientation of the system. 
     In some embodiments, an NO generation system can truncate the duration of an electrical discharge in the event that the arc extinguishes prematurely. 
     In some embodiments, a gliding arc electrode is constructed from more than one material. In some embodiments, a high melting temperature/high cost electrode material is used in the small gap region and a lower cost material is utilized in the large gap region.  FIG.  32 A  depicts an embodiment including electrodes  590 ,  592  having two electrode materials located in series.  FIG.  32 B  depicts an embodiment where only one side of the gliding arc electrode pair  594 ,  596  is a composite. This can be used in DC current systems where further cost reduction can be achieved by only using high melting point/high cost material at the cathode.  FIG.  32 C  depicts an embodiment in which gliding arc electrode pair  598 ,  600  is plated/coated/shielded by a higher melting point material in the short gap region. 
     In some embodiments, multiple electrode pairs are stacked within a plasma chamber. The NO generation controller can selectively energize one or more electrode pairs at a time. In some embodiments, the system exhausts one electrode pair prior to using the next and so-on. Each electrode pair may have a dedicated nozzle, or they can share a common nozzle. In designs with multiple nozzles, the system can flow through reactant gas through all nozzles at the same time, or a subset of the nozzles at one time. In some embodiments, only the nozzle(s) associated with active electrodes flows reactant gas at a time. In some embodiments, a nozzle that is not associated with the active electrode is utilized to reduce NO production due to decreased plasma/reactant gas interaction. 
     With every electrical discharge, NO is formed. Making copious amounts of NO is a function of gap, gas/plasma interaction and energy density and is straight-forward. Making low levels of NO is a challenge, however, because there are practical limits to how short an electrical discharge duration and gap length can be. Lower levels of NO generation can be achieved by 1) decreased gap, 2) decreased gas/plasma interaction, and 3) decreased energy/current within the gap. 
     In some embodiments, a nozzle size and orientation with respect to the electrodes (location and angle) is selected to achieve the desired range of NO production. In some embodiments, the degree of gas/plasma interaction is modulated as a way to vary NO production and achieve low levels of NO production. This can be done by varying one or more of the nozzle diameter, nozzle location, nozzle quantity and nozzle orientation. In some embodiments, a plasma chamber has two nozzles. A first nozzle is directed towards the electrode gap for high efficiency in generating NO within the reactant gas. A second nozzle does not flow reactant gas directly towards the electrode gap so that a lower portion of the gas interacts with the plasma. A NO generation system varies the proportion of flow going through each nozzle to modulate the level of NO production to low levels. 
     In some embodiments, electrodes are located in a low-pressure zone within a plasma chamber or in an eddy of the reactant gas flow to reduce the plasma-reactant gas interaction and produce less NO. 
     In some embodiments, a gliding arc electrode surface profile can create a constant arc length growth rate, facilitating stable control of arc length as a function of pulsation duration, as shown in  FIG.  33   . This can be accomplished by maintaining a relatively constant dL/dx across all range of duty cycles, where X is the horizontal direction in  FIG.  33    and L is the arc length (not the gap) as depicted in  FIG.  33   . 
     In a gliding arc configuration, as the arc travels across the electrode surface, it will bend/stretch as a function of the velocity and input power. Because NO production is a function of effective arc length, it is possible that NO production does not change linearly or predictably as pulsation duration changes. To compensate for this, the profile of the electrode may be tuned to a chamber dimensions and flow rates to ensure linear, controllable NO production as a function of pulsation duration. The chamber dimensions, flow rate, and pulsation duration (proxy for input power) can be balanced by considering the gliding arc NO production as an integrator—knowing that at some point in the direction of flow, the surface profile has a gap, which along with a given velocity and input power creates an effective arc length, creates a certain level of NO production. By quantifying the relationship of all of these variables, it is possible to create a surface profile with a linear NO production response for a change in pulsation duration. 
     In some embodiments of the gliding arc electrode, the chamber dimensions, flow rate, and pulsation parameters are balanced such that the resulting velocity moves the plasma arc the desired distance for a given pulsation duration. 
     In some embodiments, a gliding arc design incorporates electrodes with wires sufficiently thin that they do not alter the reactant gas velocity in the region of the electrodes. This approach in concert with a constant cross-section plasma chamber can promote constant gas flow through the plasma chamber to facilitate modeling and NO production control. 
     In some embodiments, a gliding arc design includes electrodes that have sufficiently thin wires so that any mass erosion will electrically isolate the shortest gap area of the electrode, resulting in a detectable failure (input current will be substantially higher). 
     In some embodiments, a gliding arc design can be used for continuous plasma generation (for example, not pulsed, 100% duty cycle). In some embodiments, a system of continuous plasma generation varies one or more of duty cycle of an AC waveform, AC voltage, AC current and AC power to vary NO production. When an AC voltage peak is limited, the length of the arc may be controlled, thereby controlling production of NO. 
     In some embodiments, a gliding arc electrode is used to generate NO generation with DC voltage. In some embodiments, the material for each electrode may be selected for their suitability for cathode and anode applications. 
     In some embodiments, the output of a gliding arc electrode may vary with respect to its orientation with respect to gravity. This effect is more noticeable at slow reactant gas flow rates where the effects of hot air rising contribute a larger component to plasma gas motion. In some embodiments, a NO generation system uses its orientation sensor to compensate for differences in NO production related to the device orientation with respect to gravity. In some embodiments, the orientation sensor is a 3-axis accelerometer. 
     In some embodiments, a gliding arc plasma reactor is presented which produces a desirable amount of nitric oxide for treatment of hypoxic respiratory diseases. The amount of NO can be controlled by the flow and electrical parameters of the plasma source. The feed gas is ambient air which mainly includes oxygen and nitrogen. 
     Gliding arc plasma is a periodic plasma, generated between two diverging electrodes, including a powered electrode  610  and a ground electrode  612  as shown in  FIG.  34    which illustrates an exemplary embodiment of a gliding arc plasma source. The reactant, or working, gas flows from the gas inlet  614  to the outlet  616 . By applying high voltage to the electrodes, an initial arc  618  is initiated in the narrowest gap and glides between electrodes by the gas flow, toward the downstream of the reactor. As the arc glides between diverging electrodes, its length increases (shown as gliding arc  620 ) which causes enhancement of voltage and power consumption. The arc extinguishes at downstream, when the power supply cannot provide the required voltage to sustain the arc. The arc will be reignited in narrowest gap and a new arc movement cycle will be started. 
     In a gliding arc plasma source, the arc carries the gas toward the downstream till the arc extinguishes and a new cycle will be generated. Therefore, in this case the gas residence time in plasma volume is more than the one in conventional arc discharge configuration which can result in more NO production. In addition, as the arc length grows between electrodes, the power deposited inside the plasma increases which can result in higher electron temperature inside the plasma and consequently higher NO production. The gliding arc can also be used due to the convective heat loss of the plasma as the gas pushes the gas along the electrodes. The lower gas temperature in plasma in fixed electron temperature (fixed power deposited) causes the reduction of NO 2  production while the NO production can remain at the high value. It is because the high temperature plasma gas can favor the reaction of NO and O 2  or O to generate NO 2 . 
     The main problem of conventional arc discharge plasmas (free burning opposed electrode arc) to generate the NO, is electrode erosion. In conventional arc discharge, plasma is always attached to the electrode on a tiny surface called electrode spot. The high heat flux from plasma to the electrode spots can cause electrode wear. In gliding arc plasma, the electrode spots move along the surface of the diverging electrodes which reduces electrodes erosion, significantly. 
     In gliding arc technology, voltage can either continuously or partially be applied to the electrodes. Power deposited in plasma can be adjusted by varying the voltage and duty cycle. The voltage and duty cycle flexibility in this system can provide a wide range of power deposited inside the plasma from 5 to 50 W, which leads to 2-8000 ppm.lpm of NO production. Increasing the power can increase the overall plasma volume in one period of gliding operation, meaning that in higher power, gas has more time to be placed inside the plasma. Therefore, a wide range of power operation results in a wide range of NO production. 
       FIG.  35    illustrates an exemplary cross-sectional view of a gliding arc source. It includes two diverging hollow electrodes  630 ,  632 , a gas inlet  634 , a gas outlet  636 , a nozzle  638  and a reactor body  640 . The electrodes are placed between two quartz plates  642 , i.e. electrodes are sandwiched between quartz plates. The benefit of this design is that all the gas inlet is forced to path between the electrodes and placed inside the plasma arc, instead of circumventing the arc. It enhances the efficiency of the process.  FIG.  35    illustrates an exemplary cross-sectional view of a gliding arc plasma reactor. Gas flows from right to left. 
       FIG.  36    illustrates an exemplary cross-sectional view (from inlet) of a gliding arc plasma reactor that includes electrodes  650 ,  652 , an air inlet  654 , quartz plates  656 ,  658 , and a nozzle  660 .  FIG.  36    illustrates a schematic diagram of an exemplary embodiment of an NO generating system. In some embodiments, the air flow is directed to the plasma reactor by a flow controller in the range of 0.05 to 6 slpm. The air flow glides the arc between the electrodes and the treated air which would be air enhanced nitric oxide would be obtained from the outlet. Quartz plates on one or more side of the plasma chamber enable visualization of the plasma and optical means of plasma detection and analysis. In some embodiments, light emitted from the plasma chamber is used to monitor and assess plasma performance. In some embodiments, the outlet of the plasma reactor is connected to a diluted airline controlled by an additional flow controller to keep the NO concentration of the gas below the highest capacity of the NO analyzer. In some embodiments, the concentration of the NO out of the plasma is the concentration of NO measured by analyzer times the dilution ratio. In some embodiments, the internal shape of the plasma chamber is designed to have a constant cross-section along the length of the chamber. This maintains a constant velocity of gas through the plasma chamber, facilitating modeling of the chamber performance and promoting event wear on the electrode surfaces. 
       FIG.  37    illustrates a cross-sectional view of the gliding arc plasma reactor  670 . 
     NO and NO 2  production are modulated by varying one or more of the power supply frequency (20-70 kHz), primary circuit voltage, second circuit voltage (i.e., across the plasma) (5-8 kV), duty cycle and plasma flow rate (0.05-6 slpm). In some embodiments, NO generation can be modulated by varying the impedance of the secondary circuit using a rheostat, or equivalent component, to vary the voltage across the plasma. 
       FIG.  38    illustrates an exemplary graph showing NO and NO 2  concentration and NO/NO 2  ratio versus power for various air flow rates (2 slpm air flow rate  680 , 3.3 slpm air flow rate  682 , and 0.1 slpm air flow rate  684 ). With increasing duty cycle, NO and NO 2  concentration increases as can be seen in  FIG.  38   . Enhancement of the power can make more high energy electrons to dissociate the nitrogen and oxygen molecules (thanks to the vibrational excitation of molecules due to the electrons impact) and increase the possibility of NO/NO 2  production. In addition, power enhancement enlarges the arc discharge gliding distance between the electrodes which can provide more residence time for the gas molecules to exist inside the plasma and increase the possibility of NO production. 
     Furthermore, the results in  FIG.  38    indicate that the gliding arc can provide a large range of NO production from 2 to 8000 ppmlpm which is very desirable for treatment of hypoxic respiratory diseases. Respiratory applications often have variable flow rates to the patient, requiring NO production to vary as well. In some embodiments, NO production is linearly proportional to ventilator flow rates. These results demonstrate that a gliding arc design can produce a wide range of NO concentrations and production levels when regulated by the amount of power delivered to the plasma. 
       FIG.  39    depicts an embodiment of a modular gliding arc design constructed of a plasma chamber  690  with a cavity, triangular gliding arc electrodes, removable nozzle, a seal and a lid. The plasma chamber can be fabricated from high temperature polymers (PEEK), ceramic, or metal. In the event that a conductive material is used, such as metal, additional electrical isolation features are necessary to prevent shorting between electrodes. In this design, the tolerance stack-up between nozzle, chamber and electrode can significantly impact nozzle to gap alignment, thereby affecting NO production efficiency. 
       FIG.  40    depicts an embodiment to an approach to fabricating a plasma chamber to minimize tolerance stack-up between a nozzle and an electrode gap. The chamber is split along a plane orthogonal to the direction of gas flow. The upstream half of the plasma chamber includes features to locate the electrodes  700 ,  702  and the nozzle  704 . 
     Plasma Torch 
     In some embodiments, a plasma torch electrode configuration as shown in  FIG.  41 A  and  FIG.  41 B  are utilized within an NO generation system. This approach offers a large electrode surface for electrode longevity, long creepage distance between electrodes with low probability of sputtering of Ir-oxide shorting the electrode, and passage of all reactant gas through the plasma zone. In one embodiment shown in  FIG.  41 A , reactant gas travels parallel to the center electrode  710 . In some embodiments shown in  FIG.  41 B , reactant gas is introduced to the plasma chamber tangentially, creating a vortex flow within the chamber. A vortex/helical flow pattern increases reactant gas-plasma interaction. In both embodiments, a cylindrical center electrode  710 ,  720  is located within a tubular nozzle electrode  712 ,  722 . Arcing occurs between electrodes, where the gap is minimum. When a reactant gas flow  714  is parallel to the electrodes, as in  FIG.  41 A , only a portion of the reactant gas passes through the electrical discharge. When gas flows in a vortex  724 , as in  FIG.  41 B , gas flow can carry the arc discharge in a helical path, increasing the plasma-gas interaction and NO production in a given amount of reactant gas flow. 
     Diverging Electrode Plasma Torch 
     In some embodiments of an NO generator, the shape of the center electrode and nozzle electrode is such that the gap increases along the direction of reactant gas flow, as shown in  FIG.  42   . This design offers similar features to a plasma torch design with the addition of larger gaps for increased production and the traveling of arcs along the electrode surfaces to prolong electrode life and reduce electrode temperature. Gas-plasma interaction is greater in a diverging electrode plasma torch than in a gliding arc design, thereby increasing NO production efficiency. 
     A plasma torch design  730 , as shown in  FIG.  42    can present a complex phenomenon to model due to plasma and reactant gas flow traveling in three dimensions. In some embodiments, a nozzle contains a helical electrode  732  within it. Reactant gas flow is directed to travel parallel to the helix, thereby generating a predictable and consistent gas and plasma interaction.  FIG.  43    depicts a cross-sectional view of a plasma torch design  740  with helical nozzle electrode. The helical electrode is shown as double lines along the wall of the chamber. In some embodiments, the electrode helix is continuous from the smallest gap region to a point beyond where the plasma can travel. Plasma travel is limited by parameters including, but not limited to voltage duty cycle, gas velocity, gap, electrode cleanliness, and voltage magnitude. 
     Gliding Opposed Electrode 
     A combination of electrode concepts as shown in  FIG.  44 A  and  FIG.  44 B  can combine relative advantages of each electrode.  FIG.  44 A  (a new electrode) and  FIG.  44 B  (an older electrode) depict a combination of a gliding arc and an opposed electrode. The gliding arc portion of the electrode is upstream, so any arc initiated will move with the velocity downstream to where the slope becomes flat, eventually hanging at that location as long as the pulse is held. When the arc is gliding, the air velocity does not stretch the arc, but when the arc reaches the end of the electrodes, it will stretch, resulting in a plasma beam longer than the electrode gap at that point. 
     This combination system can yield greater efficiencies associated with larger plasma beam lengths, while only requiring minimal voltage to initiate associated with small gaps. In a NO generation system designed to run on batteries, or an NO system where set-point resolution requirements are less-demanding, such an electrode can be used. 
     Additionally, this electrode configuration can be used when NO production is controlled via current modulation, while the plasma beam is left on (i.e. not pulsed). This may further enhance the efficiency, as well as result in less NO 2  production associated with long-duration pulses and large gaps. 
     The straight section of the electrode may be intentionally low mass to promote erosion in a controlled manner. 
     Ring Cartridge 
     An electrode pair can be constructed from a rod and concentration ring, as shown in  FIG.  45 A  and  FIG.  45 B . In some embodiments, the rod may have a cut edge aligned with the ring ( FIG.  45 A ) so as to facilitate arcing with the concentrated field of the cut edge. In some embodiments, the rod ends may be substantially far away from the ring electrode; this will impose a higher starter voltage, but will not erode as fast. 
     Electrode Cartridge 
     An electrode may be designed as a cartridge, such that a metal cylinder can contain electrode geometry ( FIG.  46 A ,  FIG.  46 B ,  FIG.  46 C ,  FIG.  46 D ,  FIG.  46 E , and  FIG.  46 F ), including either an opposed electrode ( FIG.  46 B ), a gliding arc ( FIG.  46 D ), or some combination thereof ( FIG.  46 E ). The metal cylinder can be high voltage, but in some embodiments can tie the cylinder electrode to circuit or earth ground. Grounding the cylinder can allow for the creation of an EMI cage and facilitating management of creepage and clearance distances. Additional benefits of the cartridge pertain to thermal management—manifolds and housings supporting most electrode concepts are inherently large or heavy, owing to use of dense ceramics and large creepage distances. A metal cylinder as the manifold is intrinsically heat resistant with generally similar temperatures to ceramics, but without the difficult manufacturing processes. 
     In some embodiments, the grounded electrode is a unibody construction with the metal cylinder to facilitate conductive heat transfer to reduce electrode erosion. This can be accomplished through an extrusion, welding a feature, or a casting. 
     An insulative body containing one electrode is inserted into the metal cylinder. The insulative body may have ridges to create adequate creepage &amp; clearance distances within the cartridge. The insulative body must contain holes or create them upon insertion to the cylinder to allow air to pass through the cartridge. 
     In some embodiments, both electrodes are packaged within the cylinder to create one electrode cartridge ( FIG.  46 A ). In some embodiments that would lean towards a consumable cartridge, the insulative body can be part of the permanent device ( FIG.  46 C ,  FIG.  46 D , FIG.  46 E, and  FIG.  46 F ). In those consumable embodiments, the permanent electrode may be a corrosion resistant metal or alloy, while the other consumable electrode may be a more commodity metal which is not subjected to corrosion because of its replacement schedule. In some consumable embodiments, both electrodes and insulative body would be in the cartridge and therefore replaceable. Accordingly, both electrodes would be a more commodity metal. Additionally, a cylindrical electrode cartridge that inserts in a single direction, creating blind pneumatic and electrical connections inside of a controller, is well suited to being replaced by someone less skilled than a technician, such as a respiratory therapist or an end-user of an ambulatory device. 
     In some embodiments, a consumable cartridge may also contain a NO 2  scrubbing media immediately after the electrode pair ( FIG.  46 B ). 
     Clinical Applications 
     Various therapies can be used with an NO generation device. In some embodiments, an NO generation and delivery device can be combined with a humidifier. 
     In some embodiments, an NO generation and delivery device is in the form of an ET tube. In some embodiments, the ET tube generates NO continuously with NO-containing gas entering and exiting the patient. In some embodiments, the system only generates NO as inspiratory gas enters the patient. The system can use a flow sensor to measure inspired gas and generate plasma accordingly. In some embodiments, the device pulses plasma constantly at an adjustable frequency and or duty cycle. The user can increase plasma activity to vary the dose 
     In some clinical applications in home and/or in hospital, it can be advantageous to inhale NO for short intervals, periodically. In some embodiments, a patient inhales NO concentrations in excess of 80 ppm for several minutes, multiple times a day to treat or prevent pulmonary infection. In some embodiments, the range of inhaled NO concentration to prevent infection can be 100 to 300 ppm. NO delivery means for periodic dosing include but are not limited to an inhaler, an ambulatory device, a ventilator, an oxygen concentrator, and a NO tank. Treatments at high NO concentration can be based on elapsed time or clinical parameters, such as methemoglobin level. In some embodiments, a NO delivery system measures and/or receives methemoglobin readings and terminates a treatment when methemoglobin levels reach a threshold. In some embodiments, a NO delivery system can resume NO delivery when methemoglobin levels fall below a threshold. 
     In some clinical applications, a patient inhales NO on an as-needed basis. For example, after a short walk, ascending a flight of stairs, when their SpO 2  is low, when 02 needs are high. In some embodiments, a NO delivery device permits the patient to select a dose within a pre-determined range. In some embodiments, a NO delivery device limits the amount of NO a patient can inhale over a period of time. 
     There are also a variety of clinical applications of inhaled NO in a hospital/clinical setting. Clinical applications include but are not limited to respiratory failure of prematurity, bronchopulmonary dysplasia (infants), serious lung infection, respiratory failure in the intensive care unit (PCU) or pediatric intensive care unit (PICU), heart surgery, acute iNO testing in pulmonary hypertension (PH) or chronic pulmonary hypertension (e.g. PAH), cardiac surgery in the USA, acute respiratory distress syndrome, cardiopulmonary resuscitation, cardiopulmonary bypass prevention of renal injury, acute stroke and traumatic brain injury, and acute ST-Elevation myocardial infarction (STEMI). 
     In some embodiments, a clinical application can include the prevention and/or treatment of ventilator associated pneumonia. NO is an anti-infective agent currently being explored in cystic fibrosis (CF) for mycobacterial infections and bacterial infections, e.g pseudomonas. It can be used with prolonged ventilated patients to reduce ventilator associated pneumonia. 
     In some embodiments, a clinical application can include periodically dosing a patient with NO to prevent ventilator associated pneumonia. In some embodiments, a ventilator that generates NO periodically doses a patient to prevent ventilator associated pneumonia. 
     In some embodiments, a clinical application can include Acute Right Heart Failure (diverse etiology) including pulmonary embolism. In this application, NO decreasing the pulmonary resistance, thereby offloading the right heart. 
     In some embodiments, a clinical application can include Administration with hemoglobin oxygen carriers and stored blood. Hemoglobin-based oxygen carriers (HBOCs) or hemoglobin based oxygen carrying solutions (HBOCs) can cause scavenging of NO and systemic and pulmonary vasoconstriction inhibited by iNO. Hemolyzed blood scavenges NO leading to systemic and pulmonary vasoconstriction. 
     There are also a variety of clinical applications of inhaled NO in an ambulatory setting, including the following:
         WHO Group 1 PAH—Potential to subtype e.g. idiopathic, familial etc., pediatric PAH, and PAH during pregnancy (avoids toxicity from PAH drugs)   WHO group 2 PAH—Selected well-controlled patients with left heart failure (risk of pulmonary edema, and LVAD recipients with right heart disease (RHD) and pulmonary hypertension (PH) (Orphan)   WHO group 3 PH—PH-ILD or subtype ILD e.g. IPF, CT-related ILD, cHP, etc., PH-COPD, and Combined pulmonary fibrosis emphysema (CPFE)   WHO group 4 Chronic Thromboembolic PH (CTEPH)—Improve right heart disease (RHD)   Sarcoidosis   Right heart dysfunction, diverse etiology—Afterload reduction even in absence of pulmonary hypertension (PH), and Etiologies include ischemic heart disease, valvular disease etc.   Infectious diseases, such as cystic fibrosis e.g. pseudomonas, B. Cepacia, NTM, Multiple Drug-resistant tuberculosis, Non-tuberculous mycobacterial infection (NTM), and Bronchiectasis   Bridge to lung and/or heart transplant—Addresses pulmonary hypertension (PH), oxygenation, RVD etc   Post lung and.or heart transplant—Reduces pulmonary vascular resistance and contributes to the prevention of bacterial infections   High altitude medicine—To address mountain sickness, High altitude pulmonary edema (HAPE), and reduce hypoxic pulmonary vasoconstriction   Military field applications, such as inhalation injury, cardiopulmonary resuscitation/shock, and High-altitude sickness including during flight   Cardiopulmonary Resuscitation—reverses acute PH due to pulmonary vasoconstriction increasing cardiac output (compressions)   With stored blood or hemoglobin oxygen carriers to prevent complications   During cardiopulmonary bypass to prevent complications   With ECMO to reduce the use of heparin       

     All publications, patent applications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. Reference is made to U.S. application Ser. No. 15/907,241, filed Feb. 27, 2018, U.S. application Ser. No. 16/388,464, filed Apr. 18, 2019, U.S. application Ser. No. 16/697,498, filed Nov. 27, 2019, U.S. application Ser. No. 15/907,258, filed on Feb. 27, 2018, U.S. application Ser. No. 16/363,505, filed Mar. 25, 2019 and U.S. application Ser. No. 16/724,233, filed Dec. 21, 2019 which are hereby incorporated by reference in their entireties.