Patent Description:
Nitric oxide (NO) is a crucial mediator of many biological systems, and is known to mediate the control of systemic and pulmonary artery blood pressure, help the immune system kill invading parasites that enter cells, inhibit the division of cancer cells, transmit signals between brain cells, and contribute to the death of brain cells that can debilitate people with strokes or heart attacks. Nitric oxide also mediates the relaxation of smooth muscle present, for example, in the walls of blood vessels, bronchi, the gastrointestinal tract, and urogenital tract. Administration of nitric oxide gas to the lung by inhalation has been shown to produce localized smooth muscle relaxation to treat pulmonary hypertension, pneumonia, hypoxemic respiratory failure of the newborn, etc. without producing systemic side effects.

Inhaled nitric oxide is a potent local pulmonary vasodilator that improves the matching of ventilation with perfusion, thereby increasing the injured lungs oxygen transport efficiency, and raises the arterial oxygen tension. Breathing nitric oxide combines a rapid onset of action occurring within seconds with the absence of systemic vasodilation. Once inhaled, NO diffuses through the pulmonary vasculature into the bloodstream, where it is rapidly inactivated by combination with hemoglobin. Therefore, the vasodilatory effects of inhaled nitric oxide are limited to the pulmonary vasculature. The ability of nitric oxide to dilate pulmonary vessels selectively provides therapeutic advantages in the treatment of acute and chronic pulmonary hypertension. Inhaled NO has also been used to prevent ischemia reperfusion injury after PCI in adults with heart attacks. Inhaled NO can produce systemic anti-inflammatory and anti-platelet effects by increasing the levels of circulating NO biometabolites and other mechanisms.

<CIT> describes electric generation of nitric oxide (NO) from air at ambient pressure for medical purposes. As described in <CIT>, an air input port of the system is used for continuously introducing air into the region of the electric arc.

<CIT> describes a method and an apparatus for plasma-chemical production of nitrogen monoxide, which is used to produce inhalation gas enriched with nitrogen monoxide for medical purposes. The nitrogen-monoxide production is achieved through the use of a dielectric barrier discharge created in a process gas containing nitrogen and oxygen.

The invention is defined in the independent claim. In some aspects, a method includes collecting information related to one or more conditions of a respiratory system associated with a patient. The method also includes determining one or more control parameters based on the collected information. The method also includes initiating a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters.

Embodiments can include one or more of the following.

The conditions associated with the respiratory system can include one or more of the oxygen concentration of a reactant gas, a flow rate of the reactant gas, a volume and timing of an inspiration, the oxygen concentration of a product gas, the nitric oxide concentration of the product gas, the nitrogen dioxide concentration of the product gas, the ozone concentration of the product gas, the nitric oxide concentration of an inhaled gas, and the nitrogen dioxide concentration of the inhaled gas.

The volume and timing of an inspiration can be received from a ventilator.

A pulse train can initiate the series of electric arcs, and the pulse train can include pulse groups having pulses with different pulse widths.

The pulse width of initial pulses in one of the pulse groups can be wider than other pulses in the pulse group.

The series of electric arcs can generate a reduced level of nitrogen dioxide.

The series of electric arcs can generate a reduced level of ozone.

The reduced level of nitrogen dioxide can be further reduced by a scavenger including one or more of KaOH, CaOH, CaCO<NUM>, and NaOH.

The reduced level of nitrogen dioxide can have a concentration that is less than <NUM>%, <NUM>%, <NUM>%, or <NUM>% of a concentration of the generated nitric oxide.

The series of electric arcs can be generated by electrodes including a noble metal.

The series of electric arcs can be generated by electrodes including iridium.

The series of electric arcs can be generated by electrodes including nickel.

In some additional aspects, an apparatus includes a chamber having an inlet valve for receiving a reactant gas and an outlet valve for delivering a product gas. The apparatus also includes a sensor for collecting information related to one or more conditions of a respiratory system associated with a patient. The apparatus also includes a controller for determining one or more control parameters based on the collected information. One or more pairs of electrodes are included in the apparatus and positioned inside the chamber for initiating a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters.

The conditions associated with the respiratory system can include one or more of the oxygen concentration of the reactant gas, a flow rate of the reactant gas, a volume and timing of an inspiration, the oxygen concentration of the product gas, the nitric oxide concentration of the product gas, the nitrogen dioxide concentration of the product gas, the ozone concentration of the product gas, the nitric oxide concentration of an inhaled gas, the nitrogen dioxide concentration of the inhaled gas, and the pressure in the chamber.

The series of electric arcs can be initiated when the chamber has a pressure greater than 1ATA or less than <NUM> ATA.

The apparatus can also include a scavenger for further reducing the reduced level of nitrogen dioxide, and the scavenger can include one or more of KaOH, CaOH, CaCO3, and NaOH.

The electrodes can include a noble metal.

In some additional aspects, an apparatus includes a chamber having an inlet valve for receiving a reactant gas and an outlet valve for delivering a product gas. The apparatus also includes a piston positioned inside the chamber and configured to move along a length of the chamber for adjusting pressure in the chamber. The apparatus also includes a sensor for collecting information related to one or more conditions of a respiratory system associated with a patient. The apparatus includes a controller for determining one or more control parameters based on the collected information. One or more pairs of electrodes are included and positioned inside the chamber for initiating a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters.

The series of electric arcs can be initiated when the chamber has a pressure greater than <NUM> ATA or less than <NUM> ATA.

Synthesis of NO for inhalation is achieved by electrically sparking a reactant gas including N<NUM> and O<NUM> (e.g., air), thereby forming a product gas including the electrically synthesized NO. The synthesis may be achieved under hypobaric or hyperbaric conditions. As used herein, "hypobaric" generally refers to a pressure less than <NUM> ATA (atmosphere absolute), and "hyperbaric" to a pressure greater than <NUM> ATA. The product gas can include a medically acceptable level of NO<NUM> (e.g., usually less than <NUM> ppm, and sometimes less than <NUM>-<NUM> ppm). The product gas may be inhaled either with or without reducing the concentration of NO<NUM> in the product gas. Apparatuses described herein for synthesis of nitric oxide can be portable, light-weight, self-powered, and can be used to provide product gas for therapeutic use, with a concentration of NO in the range of <NUM> ppm to <NUM> ppm and a concentration of NO<NUM> of less than <NUM>% of the NO concentration, or even lower (e.g., less than <NUM>%) after using a scavenger.

<FIG> shows an example of a respiratory system <NUM> for producing NO. A reactant gas (e.g., air, or a <NUM>-<NUM>% oxygen mixture in nitrogen) enters an NO generator <NUM>, and a product gas (including NO) exits the NO generator <NUM>. The NO generator <NUM> includes electrodes <NUM> and a controller <NUM>. If the reactant gas is a gas other than air, the NO generator <NUM> can include an oxygen level sensor <NUM>. NO production is proportional to oxygen and nitrogen concentration and maximal at about <NUM>% oxygen at atmospheric pressure (<NUM> ATA). The oxygen level sensor <NUM> can be an electrode configured to detect a concentration of oxygen in the reactant gas, as described in more detail below. The electrodes <NUM> generate sparks in the presence of the reactant gas to produce NO <NUM>, as described herein.

<FIG> shows an example of an NO generator <NUM>. NO generator <NUM> includes chamber <NUM> having inlet valve <NUM> and outlet valve <NUM>. In some cases, filter <NUM> is coupled to NO generator <NUM>, such that a gaseous mixture including N<NUM> and O<NUM> entering chamber through inlet valve <NUM> is filtered to remove particulate matter (e.g., dust) or water vapor. Chamber <NUM> includes electrodes <NUM>. Electrodes <NUM> are separated by a gap, and one of the electrodes is coupled to voltage source <NUM>. Voltage source <NUM> is suitable to create a spark or corona discharge capable of forming NO from N<NUM> and O<NUM> between electrodes <NUM>. Examples of voltage source <NUM> include, but are not limited to, a piezoelectric crystal, a battery (e.g., a motorcycle battery), a solar cell, a wind generator, or other source suitable to produce a current on the order of nanoamperes or milliamperes and a voltage of <NUM> to <NUM> kV (e.g., a power of <NUM> to <NUM> watts), or a voltage of <NUM> to <NUM> kV or <NUM> to <NUM> kV.

When NO generator <NUM> is used for hypobaric or hyperbaric synthesis of NO, chamber <NUM> may be a cavity in a positive displacement pump. As shown in <FIG>, chamber <NUM> may be a cavity in a piston pump and has a variable volume defined by the position of piston <NUM> in barrel <NUM>. Piston <NUM> is coupled to actuator <NUM>. In one example, actuator <NUM> includes an eccentric mechanism driven by a rod or shaft. Actuator <NUM> is driven by prime mover <NUM> in a reciprocating manner. Prime mover <NUM> may be, for example, a motor or engine (e.g., an electric or gasoline or diesel powered engine) arranged to translate piston <NUM> with respect to barrel <NUM> by way of actuator <NUM>. Seal <NUM> inhibits the flow of air into or out of chamber <NUM> between piston <NUM> and barrel <NUM>. Thus, when both inlet valve <NUM> and outlet valve <NUM> are closed, translation of piston <NUM> away from electrodes <NUM> by actuator <NUM> increases the volume of chamber <NUM>, thereby reducing the pressure in chamber <NUM> to a pressure below atmospheric pressure and reducing a concentration of gases (e.g., N<NUM> and O<NUM>) in a reactant gas present in the chamber. Conversely, translation of piston <NUM> toward the electrodes <NUM> by actuator <NUM> decreases the volume of chamber <NUM>, thereby increasing the pressure in chamber <NUM> to a pressure above atmospheric pressure and increasing the pressure and concentration of gases in a reactant gas present in the chamber. Because NO production is proportional to oxygen concentration, the pressure of the chamber <NUM> can have an effect on the production of NO. For example, when the chamber <NUM> has a relatively high pressure (e.g., <NUM> ATA), NO production is increased.

Inlet valve <NUM> may be exposed to the environment such that, with the inlet valve open, ambient air (or other reactant gas containing N<NUM> and O<NUM>) enters chamber <NUM>. With air in chamber <NUM>, inlet valve is closed and piston <NUM> translates away from electrodes <NUM>, thereby increasing the volume of chamber <NUM> and decreasing the pressure inside chamber <NUM> to a pressure below atmospheric pressure. As the volume of chamber <NUM> increases, the concentration of O<NUM> in the chamber falls below the concentration of O<NUM> in air at atmospheric pressure (e.g., falls below <NUM> vol%). Actuator <NUM> may be controlled to increase a volume of chamber <NUM> by a factor of <NUM>, <NUM>, <NUM>, etc., thereby reducing a pressure in chamber <NUM> to a fraction (e.g., <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, etc.) of atmospheric pressure. While the pressure in chamber <NUM> is below atmospheric pressure, voltage source <NUM> initiates sparks or corona discharges across electrodes <NUM>, thereby electrically generating NO. Following the sparks or corona discharges, actuator <NUM> continues its reciprocating cycle, and outlet valve <NUM> is opened to release the product gas containing the electrically generated NO. Thus, inlet valve <NUM> and outlet valve <NUM> operate out of phase with each other, such that outlet valve <NUM> is closed when inlet valve <NUM> is open, and inlet valve <NUM> is closed when outlet valve <NUM> is open.

Conversely, with air in chamber <NUM>, inlet valve is closed and piston <NUM> translates toward the electrodes <NUM>, thereby decreasing the volume of chamber <NUM> and increasing the pressure inside chamber <NUM> to a pressure above atmospheric pressure. As the volume of chamber <NUM> decreases, the pressure (concentration) of O<NUM> in the chamber rises above the pressure (concentration) of O<NUM> in air at atmospheric pressure (e.g., rises above <NUM> vol%). Actuator <NUM> may be controlled to decrease a volume of chamber <NUM> to a fraction of <NUM>/<NUM>, <NUM>/<NUM>, <NUM>/<NUM>, etc., thereby increasing a pressure in chamber <NUM> to <NUM>, <NUM>, <NUM>, etc. times atmospheric pressure. While the pressure in chamber <NUM> is above atmospheric pressure, voltage source <NUM> initiates sparks or corona discharges across electrodes <NUM>, thereby electrically generating NO.

In some examples, electrodes in an NO generator (e.g., electrodes <NUM>) can be duplicated for safety purposes to provide a spare. The electrodes <NUM> can be doubled or tripled for increased power and NO production with large tidal volumes. Referring briefly to <FIG>, the electrodes <NUM> can contain iridium, tungsten, stainless steel, or nickel, to name a few. In some examples, electrodes <NUM> that contain a noble metal (e.g., iridium) produce the smallest ratio of NO<NUM>/NO.

<FIG> shows an example of an NO generator <NUM>. NO generator <NUM> includes components of NO generator <NUM>, as described with respect to <FIG>, with source <NUM> coupled to inlet valve <NUM> and arranged to provide a reactant gas to chamber <NUM>. In some instances, source <NUM> is an apparatus arranged to provide a reactant gas with a concentration of O<NUM> less than <NUM> vol% or less than <NUM> vol%. In some instances, source <NUM> is an apparatus arranged to provide a reactant gas with a concentration of O<NUM> more than <NUM> vol% but not more than <NUM> vol%. For example, source <NUM> may include a cylinder of N<NUM> or an inert gas (e.g., argon or helium) and a mechanism to mix the N<NUM> or inert gas with air or an enriched oxygen containing source at a selected ratio to achieve a desired concentration of O<NUM>, N<NUM>, and/or other components in the reactant gas provided to chamber <NUM>. In some examples, an oxygen cylinder, an oxygen concentration, or an oxygen generator is used to raise the concentration of oxygen in the reactant gas. The reactant gas is typically provided to chamber <NUM> at a pressure of <NUM> ATA (atmosphere absolute) or above (e.g., slightly above, to <NUM> ATA) to avoid admixture of the reactant gas with air. Before entering chamber <NUM>, reactant gas from source <NUM> may pass through an equilibrium bag <NUM>, held slightly above atmospheric pressure. Blow-off valve <NUM> may be present to allow the pressure of the reactant gas to be maintained close to atmospheric pressure.

In some instances, source <NUM> includes an oxygen concentrator, oxygen generator, or oxygen cylinder. <FIG> depicts an oxygen concentrator <NUM>, in which pressurized air enters oxygen concentrator <NUM> through inlet <NUM> and passes through molecular sieve <NUM>, yielding oxygen-enriched gas (e.g., having at least <NUM> vol% or <NUM> vol% O<NUM>). The exhaust gas, which has an O<NUM> concentration less than that of ambient air and a N<NUM> concentration greater than that of ambient air, exits oxygen concentrator <NUM> through valve <NUM>, and is provided to the inlet valve <NUM>.

In some instances, source <NUM> includes an apparatus for cooling air (e.g., a copper tube heat exchanger), such that air at a temperature less than room temperature (e.g., a temperature approaching <NUM>°K) is provided to chamber <NUM> through valve <NUM>, and the spark or corona discharge occurs in a cooled reactant gas having a temperature less than room temperature. Source <NUM> may operate to cool air by refrigeration or heat exchange methods generally known in the art. <FIG> depicts one example of a cooling device <NUM>, in which air or another reactant gas (e.g., a mixture of air and N<NUM> or an inert gas, such as argon, helium, or the like) flows through coil <NUM> and is cooled by coolant <NUM>, which enters chamber <NUM> through inlet <NUM> and exits the chamber through outlet <NUM>. Coil <NUM> may be a heat-conductive tubing such as, for example, copper tubing. Coolant <NUM> may be, for example, liquid N<NUM> or a cycling refrigerant (e.g., chlorofluorocarbon or hydrochlorofluorocarbon).

In certain instances, one or more implementations of source <NUM> as described above with respect to <FIG> are combined to form a gaseous mixture. For example, source <NUM> may include a cylinder of N<NUM> or an inert gas (e.g., argon or helium) and a mechanism to mix the N<NUM> or inert gas with air at a selected ratio to achieve a desired concentration of O<NUM> as measured, for example, with a sensor including an electrode, as well as an apparatus to cool the reactant gas before the reactant gas is provided to chamber <NUM>. An apparatus to cool the reactant gas may cool the reactant gas at more than one location (e.g., at the regulator or cylinder head of a gas cylinder, at valve <NUM>, and the like).

In other embodiments, as shown in <FIG>, an NO generator <NUM> includes constant volume chamber <NUM>. In some cases, inlet valve <NUM> is exposed to the environment such that, with the inlet valve open, ambient air enters chamber <NUM> (e.g., through filter <NUM>). Inlet valve <NUM> and outlet valve <NUM> may be synchronized such that a gaseous mixture flows into chamber <NUM> through inlet valve <NUM>, and the inlet valve is closed before the sparks or corona discharges are initiated. Outlet valve <NUM> is typically closed while inlet valve <NUM> is open, and may open prior to, during, or after initiation of the sparks or corona discharges. In certain cases, constant volume chamber <NUM> is coupled to source <NUM>, and reactant gas is provided to chamber <NUM> by source <NUM>. Filter <NUM> may be positioned between source <NUM> and chamber <NUM> (e.g., between source <NUM> and equilibrium bag <NUM>, as illustrated, or between blow-off valve <NUM> and inlet valve <NUM>, as shown in <FIG>). The exhaust of an oxygen concentrator may be used to provide a reactant gas having a decreased O<NUM> content to chamber <NUM>. NO generator <NUM> may be operated in an environment having an ambient pressure less than <NUM> ATA (e.g., at high altitude). Alternatively, constant volume <NUM> chamber is coupled to pump <NUM> through valve <NUM>. Pump <NUM> may be, for example, a positive displacement pump such as a lobe pump or a vane pump, arranged to decrease the gas pressure in chamber <NUM>, thereby decreasing the concentration of O<NUM> and N<NUM> in the reactant gas in chamber <NUM>. Similarly, pump <NUM> can be arranged to increase the gas pressure in chamber <NUM>, thereby increasing the concentration of O<NUM> and N<NUM> in the reactant gas in chamber <NUM> to achieve higher levels of NO generation.

<FIG> shows an example of an NO generator <NUM>. NO generator <NUM> includes components of NO generator <NUM>, as described with respect to <FIG>, with source <NUM>, as described with respect to <FIG>, coupled to inlet valve <NUM> and arranged to provide a reactant gas to chamber <NUM>. As noted with respect to <FIG>, NO may be selectively synthesized in chamber <NUM> at ambient pressure, at a reduced pressure, or at an increased pressure achieved with pump <NUM>.

The product gas that exits chamber <NUM> or <NUM> through outlet valve <NUM> of NO generator <NUM>, <NUM>, <NUM>, and <NUM> includes the electrically generated NO, and may include low levels of NO<NUM> and O<NUM>. In some cases, the product or effluent gas can be gauged to a piston to raise the pressure of the produced gas for injection into a ventilator, or coupled to an endotracheal tube for continuous injection or injection coupled with inspiration and proportional to airway flow. The product gas can be stored briefly at atmospheric pressure (e.g., stored for seconds before direct inhalation by a patient through a mask, before injection into an airstream for ventilation, or before use thereof to drive a ventilator). The product gas can be admixed in ventilator gases. In certain cases, the product gas may be treated to reduce a concentration of one or more components in the gas. In one example, the product gas is combined with ambient or pressurized air or oxygen to yield a lower effective concentration of NO. In some examples, the product gas is treated to remove one or more unwanted by-products (e.g., NO<NUM> and O<NUM>) by contacting the product gas with a scavenger (e.g., scavenger <NUM>). In some examples, the scavenger <NUM> includes one or more of KaOH, CaOH, CaCO<NUM>, and NaOH.

Referring to <FIG>, the scavenger <NUM> can be placed in a cartridge <NUM> to process produced gas exiting the outlet valve <NUM>. The cartridge <NUM>, the scavenger <NUM>, or both may be replaceable due to the limited absorption capabilities of the scavenger material. The scavenger <NUM> can indicate its extent of absorption (i.e., how close the scavenger is to maximum absorption) by changing color. In some examples, at a concentration of 80ppm NO in the product gas, a scavenger <NUM> having a volume of <NUM> can reduce the concentration of NO<NUM> to about 0ppm.

In certain cases, including implementations of NO generator <NUM> and <NUM> in which exhaust gas from an oxygen concentrator is used for hypobaric synthesis of NO, the product gas that exits chamber <NUM> or <NUM> through outlet valve <NUM> may be combined with O<NUM>-enriched air from the oxygen concentrator or pure O<NUM> from a source to form a gaseous mixture including a medically effective level of NO in O<NUM>-enriched air, with low levels of NO<NUM>. One or more methods of treating the product gas can be combined in any order such that, for example, NO<NUM> is removed from a product gas that exits chamber <NUM> or <NUM> through outlet valve <NUM> to yield a gaseous mixture, and this gaseous mixture is then combined with O<NUM>-enriched air from an oxygen concentrator, or a product gas that exits chamber <NUM> or <NUM> through outlet valve <NUM> is combined with O<NUM>-enriched air from an oxygen concentrator to form a gaseous mixture, and NO<NUM> is then removed from the gaseous mixture. The final mixture can be again subjected to scavenging to remove NO<NUM>.

In some instances, the concentration of one or more components in the product gas can be adjusted by varying the flow of gas through the inlet valve, varying the spark or discharge frequency, varying the voltage or current supplied to the electrodes, as described in more detail below, or adding multiple series of sparking electrodes.

<FIG> depicts a respiratory system <NUM> for electric synthesis of NO in which product gas from output valve <NUM> of NO generator <NUM> is provided to monitor <NUM>. The monitor <NUM> can collect information related to one or more conditions associated with the respiratory system. NO generator <NUM> may be any NO generator described herein. Monitor <NUM> may include one or more sensors for assessing a concentration of one or more components in the product gas. In some examples, the sensors use electrodes, chemiluminescent, or UV absorption means to measure the concentration of NO, NO<NUM>, O<NUM>, O<NUM>, or any combination thereof. In some cases, monitor <NUM> provides feedback to NO generator <NUM> or source <NUM> to adjust production of NO, decrease production of NO<NUM> or O<NUM>, etc. For instance, an assessed concentration of NO is used to adjust the flow or concentration of reactant gas or a gas to be mixed with the reactant gas (e.g., N<NUM>, an inert gas, air, or O<NUM>) into the chamber (e.g., chamber <NUM> or <NUM>), the electrode size, spacing, or temperature, the spark frequency, or voltage, peak current, or limiting current of an NO generator. In one example, if an assessed concentration of NO is higher than desired, the flow of gas into the chamber can be increased accordingly, thereby reducing the concentration of NO in the product gas. In some examples, a gas pump causes the gas to flow into the chamber. The monitor <NUM> can include a gas flow sensor for measuring the flow rate of the gas entering the chamber.

As described herein, an NO generator produces gas for respiration with a concentration of NO between <NUM> ppm and <NUM> ppm (e.g., at least <NUM> ppm and up to <NUM> ppm, <NUM> ppm, <NUM> ppm, <NUM> ppm, <NUM> ppm, <NUM> ppm, or <NUM> ppm). The produced gas may be diluted before inhalation. The gas can be used to oxidize hemoglobin ex vivo (e.g., in a stored blood transfusion) or inhaled by adults, children, or newborns to therapeutically treat respiratory disorders by selective pulmonary vasodilation, including pulmonary fibrosis, infection, malaria, myocardial infarction, stroke, pulmonary hypertension, persistent pulmonary hypertension newborns, and other conditions in which breathing NO to oxidize hemoglobin or to deliver NO metabolites into the circulation is valuable. In some cases, the NO generator can be used to supply gas for breathing to humans experiencing pulmonary hypertension and hypoxia as a result of explosive decompression of an aircraft or spacecraft, to treat high altitude pulmonary edema, and/or to treat any medical condition at high altitude by sparking or corona discharge of air in a hypobaric environment, with advantages including rapid, hypobaric synthesis of a breathable therapeutic gas including NO in the absence of gas cylinders.

In some embodiments, for example when an NO generator is used to provide input to a ventilator, the operation of the NO generator (e.g., the timing and frequency of the spark or corona discharge, the opening and closing of the inlet valve and the outlet valve, and the like) is synchronized with the inspiratory pressurization or gas flow in the airway (e.g., as measured by a hot wire anemometer or pneumotachograph), such that the necessary quantity of NO supplemented gas for respiration is produced and injected when needed. This coordinated production of NO for medical uses provides the additional advantage that NO is breathed as it is produced in an oxygen containing gas mixture, allowing less time for NO to oxidize to NO<NUM> before inhalation. When NO is produced, it only lasts for a short period time. After the short period of time, it begins to oxidize into NO<NUM> which, when dissolved in water, forms nitric acid and nitrate salts. If NO is produced long before a user is ready to inhale it, the NO can be oxidized into these toxic products at the time of inspiration. The nitric acid and nitrate salts can damage components of the NO generator as well as the lungs. In combination with spontaneous ventilation, inhalation can be tracked by the EMG of the diaphragm, or a thoracic or abdominal impedance belt, or various airway flow sensors, or taken directly from the ventilator software triggering program, and the electrically generated NO can be injected in the respiratory gas at the onset of inspiration via the nose or trachea with a tube or mask.

<FIG> shows an example of a respiratory system <NUM> for producing NO. In some embodiments, NO is produced electrically under ambient conditions, or hypobaric or hyperbaric conditions. The respiratory system <NUM> includes power supply <NUM> and chamber <NUM>. Various components (e.g., an oscilloscope) can make electrical measurements of the respiratory system <NUM>. In some embodiments, power supply <NUM> is a battery, and the respiratory system <NUM> is portable and wearable. <FIG> shows an example of an NO generator <NUM> of respiratory system <NUM>. Reactant gas is provided to chamber <NUM> through inlet <NUM>, and product gas exits chamber <NUM> via outlet <NUM>. Power supply <NUM> is coupled to electrodes <NUM> in chamber <NUM> to generate sparks therebetween. Power supply <NUM> may be operatively coupled to pulse generator <NUM>. Sparks across electrodes <NUM> form NO in chamber <NUM> as described herein. For an NO generator such as NO generator <NUM>, a <NUM> kV to <NUM> kV spark across electrodes <NUM> for <NUM>-<NUM> milliseconds that has microampere current, requiring less than <NUM> W or less than <NUM> W, based on averaging over the length of the duration of the pulse. Averaging the power consumption over a longer time (e.g., a second) would yield a lower average power consumption (e.g., an order of magnitude or two lower, or about <NUM> W to <NUM> W).

Systems for producing NO described herein, including respiratory system <NUM> and others, may also include a controller <NUM>. The controller <NUM> coordinates triggering of a voltage source to deliver a series of electrical pulses to the electrodes (e.g. electrodes <NUM>), thereby generating NO. The electrodes may be composed of or plated with a material that is capable of optimally producing NO with minimal unwanted toxic by-products. In some examples, the electrodes include a noble metal such as iridium. The controller <NUM> can be coupled to the pulse generator <NUM> and at least a portion of the NO generator <NUM> (e.g., the electrodes <NUM>) and can control parameters such as spark frequency, spark duration, and the like to generate the needed amount of NO and minimum amount of unwanted toxic by-products (e.g., NO<NUM>, O<NUM>).

The controller <NUM> can be configured to receive information from one or more sensors in the respiratory system <NUM>. The controller <NUM> can use the information received from the sensors to determine one or more control parameters for the respiratory system <NUM>. For example, readings from the oxygen level sensor <NUM> can be used by the controller <NUM> to determine the one or more control parameters. The respiratory system <NUM> can include a tidal volume or respiratory gas flow sensor (e.g., a thermistor, a hot wire anemometer) for measuring the volume, timing, and oxygen concentration of inspired gas. The controller may receive information from the ventilator related to ventilatory time of inspiration or inspired oxygen concentrations. In some examples, the controller <NUM> can determine control parameters based on one or more of: i) information received from a monitor (e.g., monitor <NUM> of <FIG> for assessing the concentration of components in the product gas or ventilator, such as the NO and NO<NUM> concentration; ii) concentration of components in the reactant gas (e.g., oxygen concentration); iii) operating parameters of the NO generator <NUM>; iv) pressure in the chamber <NUM> (e.g., especially for embodiments where the NO generator <NUM>, <NUM> includes a piston <NUM> for adjusting pressure in the chamber <NUM>); v) flow rate of the reactant gas; vi) actual or expected volume of an inspiration, and vii) whether the produced NO will be diluted with other respiratory gases (e.g., oxygen), to name a few.

The NO generator <NUM> can provide all or a portion of the product gas at the extremely high breathing frequency of a High Frequency Oscillatory Ventilator (HFOV). The NO generator <NUM> can provide all or a portion of the product gas to a positive pressure ventilator, an anesthesia machine, a continuous positive airway pressure apparatus, or a manual resuscitator, to name a few.

Adult humans normally breathe from <NUM>-<NUM> times per minute, each breath having a duration of <NUM>-<NUM> seconds. Typically, about one half to one third of the breath's duration is inspiration. On average, each breath has a tidal volume of about <NUM>. In children, each breath typically has less volume, but breathing occurs at a higher rate. Thus, in the average adult, about <NUM>-<NUM> breaths per minute with <NUM> second inspirations allow intervals for spark generation of about <NUM> seconds per minute.

The expected volume of an inspiration can be calculated using previous tidal volume measurements. For example, the controller <NUM> may determine that the expected tidal volume of a subsequent inspiration is going to be the same as the tidal volume measurement for the most recent inspiration. The controller <NUM> can also average the tidal volumes of several prior inspirations to determine the expected tidal volume of a subsequent inspiration. In some examples, the controller <NUM> can obtain an expected tidal volume value from the ventilator.

Implementations of controller <NUM> can include digital electronic circuitry, or computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or combinations of one or more of them. An optical or electrical sensor can be incorporated into the device to observe and report the occurrence of the spark(s), and give an alarm if the sparks are not occurring. For example, controller <NUM> can be a microprocessor based controller (or control system) as well as an electro-mechanical based controller (or control system). Instructions and/or logic in the controller can be implemented as one or more computer programs, i.e., one or more modules of computer program instructions, encoded on computer storage medium for execution by, or to control the operation of, data processing apparatus. Alternatively or in addition, the program instructions can be encoded on an artificially generated propagated non-transitory signal, e.g., a machine-generated electrical, optical, or electromagnetic signal that is generated to encode information for transmission to suitable receiver apparatus for execution by a data processing apparatus.

Controller <NUM> can include clients and servers and/or master and slave controllers. In some aspects, controller <NUM> represents a main controller (e.g., master) communicably coupled through communication elements (e.g., wired or wireless) with each of the components of an NO generator. Controller <NUM> may be configured to adjust parameters related to duration and frequency of the spark based at least in part on the composition of the product gas produced in the chamber.

<FIG> shows a representation of a pulse train <NUM> that is triggered by the controller <NUM>. The controller <NUM> can determine one or more control parameters to create a pulse train. <FIG> also shows zoomed in view of one of the pulse groups <NUM> of the pulse train <NUM>. Electrical pulses are delivered to the electrodes (e.g., electrodes <NUM>), and the electrodes <NUM> generate a series of sparks (sometimes referred to as electric arcs). The timing of the pulses (and of the resulting sparks) is controlled by the controller <NUM>, and can be optimized to produce the needed amount of NO while producing minimal NO<NUM> and O<NUM>. In some examples, the controller <NUM> causes a greater amount of NO to be produced if the NO will subsequently be diluted with other respiratory gases (e.g., oxygen). Multiple sparks make up a pulse group, and multiple pulse groups make up the pulse train. Thus, the pulse train <NUM> initiates the series of electric arcs.

Variables B and N control the overall energy that is created by the electrodes <NUM>. Variable N sets the number of sparks per pulse group, and variable B sets the number of pulse groups per second. The values for B and N influence the amount of NO, NO<NUM>, and O<NUM> that is created. The values for B and N also influence how much heat is produced by the electrodes <NUM>. Larger values of either B or N create more NO and cause the electrodes 906to produce more heat.

Variables E, F, H, and P control the timing of the sparks produced in each pulse group. Variable H is the high time of a pulse (e.g., the amount of time the voltage source is activated for each electrical pulse). The high time is sometimes referred to as the pulse width. High time and pulse width can be visually represented in a graph of a voltage of a pulse over a period of time. The high time and the pulse width are measured from the time the voltage of the pulse exceeds a voltage threshold until the time the voltage of the pulse falls below the voltage threshold, and are generally in the order of microseconds. The longer the voltage source is activated for a particular electric pulse, the larger the visual representation of the width of the particular electric pulse.

P is the amount of time between pulses. Thus, P minus H represents a period of time when no pulses occur (e.g., the voltage source is not active). Larger values of H and smaller values of P result in the electrodes <NUM> producing more energy. When the electrodes <NUM> create a spark, plasma is established. The temperature of the plasma is proportional to the amount of energy produced by the electrodes <NUM>. In some examples, for plasma to be produced, the reactant gas has both nitrogen and oxygen content.

B is typically in the range of <NUM>-<NUM> pulse groups per second, N is typically in the range of <NUM>-<NUM> sparks per pulse group, P is typically in the range of <NUM>-<NUM> microseconds, and H is typically in the range of <NUM>-<NUM> microseconds.

The chemical reactions that cause NO and NO<NUM> to be produced are a function of plasma temperature. That is, higher plasma temperatures result in more NO and NO<NUM> being produced. However, the relative proportions of the produced NO and NO<NUM> vary across different plasma temperatures. In some examples, the sparks generated by the first two pulses in a pulse group establish the plasma. The first two sparks can have a high time that is longer than the sparks produced by the rest of the pulses in the pulse group. The amount of time that the first two pulses are extended is represented by variables E and F, respectively. Sparks generated by pulses beyond the first two pulses require less energy to maintain the plasma, so the high time of subsequent pulses (represented by variable H) can be shorter to prevent the plasma temperature from getting too high. For instance, while a relatively high plasma temperature may result in more NO and NO<NUM> being produced, the relatively high plasma temperature may not be ideal for producing the desired proportions of NO and NO<NUM>. The material of the electrodes <NUM> can play a major role in determining the amount of energy needed to generate a particular spark, thus affecting the ratio of NO<NUM>/NO produced. In some examples, tungsten electrodes produce a relatively high ratio of NO<NUM>/NO, nickel electrodes produced a lower ratio of NO<NUM>/NO, and iridium electrodes produce an even lower ratio of NO<NUM>/NO, as shown in <FIG>.

Each spark that is generated creates a particular amount of NO. The NO is diluted in the volume of gas that is produced. To ensure the concentration of NO in the inspired gas is at the expected level, the controller <NUM> receives information from the tidal volume sensor mentioned above to determine control parameters for maintaining an appropriate inspired NO concentration.

The controller <NUM> may be configured to communicate with the NO generator wirelessly (e.g., via Bluetooth). The controller <NUM> can also be configured to communicate with external devices (e.g., a computer, tablet, smart phone, or the like). The external devices can then be used to perform functions of the controller <NUM> or to aid the controller <NUM> in performing functions.

In some examples, the controller <NUM> can disable certain components of the NO generator during, before or after a series of sparks is generated. In some examples, the controller <NUM> can also include features to: i) detect and cease unintended sparks; ii) confirm that a series of sparks is safe before triggering the series of sparks; iii) verify that timing values are checked against back-up copies of timing values after every series of sparks is generated to detect timing variable corruption; and iv) determine whether back-up copies of timing variables are corrupt.

Results achieved with an NO generator (e.g., NO generator <NUM>) are described with respect to <FIG>.

<FIG> is an average current and voltage chart <NUM> that shows the average current and voltage vs. sparks/second for NO generator <NUM>. <FIG> is an average power chart <NUM> that shows the average power vs. sparks/second for NO generator <NUM>. Average current and power peak between <NUM> and <NUM> sparks/second, and average voltage dips over the same range. <FIG> shows oscilloscope traces <NUM> for voltage (upper trace) and current (lower trace) during <NUM> sparks of a <NUM> spark/second discharge. <FIG> shows oscilloscope traces <NUM> for voltage (upper trace) and current (lower trace) traces for a <NUM> spark/second discharge with a spark duration (single spark) of <NUM> msec.

<FIG> shows NO and NO<NUM> concentrations from an NO generator (e.g., NO generator <NUM> of <FIG>) using various electrode materials. The test conditions included the use of a ¼" rod, an electrode gap of <NUM>, constant air flow at <NUM>/min, and a FiO<NUM> of <NUM>. For the tungsten electrode, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, P=<NUM> microseconds, and H=<NUM> microseconds. For the nickel electrodes, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, H=<NUM> microseconds, and P=<NUM> microseconds. For the iridium electrodes, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, H=<NUM> microseconds, and P=<NUM> microseconds.

<FIG> shows NO and NO<NUM> concentrations at various reactant gas oxygen concentrations from the NO generator using mini spark plug (Micro Viper Z3 with <NUM> HEX and <NUM>-<NUM> THRD, Rimfire, Benton City, WA) that is continuously sparking.

<FIG> shows NO and NO<NUM> concentrations at various reactant gas oxygen concentrations from the NO generator using iridium spark plug (ACDelco <NUM>-<NUM>, Waltham, MA) that are continuously sparking.

<FIG> shows NO and NO<NUM> concentrations at various reactant gas oxygen concentrations from the NO generator using iridium spark plug with intermittent sparking.

Ozone (O<NUM>) is a powerful oxidant that has many industrial and consumer applications related to oxidation. However, its high oxidizing potential causes damage to mucus membranes and respiratory tissues in animals. This makes ozone a potent respiratory hazard and pollutant near ground level. Ozone is formed from atmospheric electrical discharges, and reacts with NO to form nitric dioxide (NO<NUM>) and O<NUM> or reacts with N<NUM> to produce NO and O<NUM>. In some examples, ozone levels are greater with continuous sparking than with intermittent sparking, and also increase with increasing O<NUM> concentrations.

<FIG> shows O<NUM> levels at various O<NUM> concentrations using mini spark plug and iridium spark plug with continuous sparking. In this example, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, P=<NUM> microseconds, H=<NUM> microseconds, and air flow rate is <NUM>/min.

<FIG> shows O<NUM> levels at various O<NUM> concentrations using mini spark plug and iridium spark plug with intermittent sparking triggered on each breath commencing with inspiration, or shortly before inspiration began. In this example, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, P=<NUM> microseconds, H=<NUM> microseconds, and air flow rate is <NUM>/min.

<FIG> shows NO and NO<NUM> concentrations at various reactant gas oxygen concentrations using an oxygen concentrator. In this example, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, P=<NUM> microseconds, H=<NUM> microseconds, and air flow rate is <NUM>/min.

<FIG> shows a test setup for measuring NO and NO<NUM> levels in a hypobaric chamber <NUM> at various atmospheric pressures. The results of the test are shown in <FIG>. To create a negative pressure (e.g., ½ ATA, <NUM>/<NUM> ATA) inside the hypobaric chamber <NUM>, inlet and outlet valves were closed and a piston translated away from the spark plug. The spark plug was then fired for <NUM> seconds. In this example, B=<NUM> pulse groups per second, N=<NUM> sparks per pulse group, P=<NUM> microseconds, and H=<NUM> microseconds. The piston was then translated toward the spark plug to bring the pressure in the hypobaric chamber <NUM> back to <NUM> ATA. The outlet valve was opened, and gas samples were collected in a <NUM> respiratory bag by further translating the piston toward the spark plug. The collected gas samples were analyzed with Sievers NOA i280 immediately after collection.

Referring to <FIG>, a flowchart <NUM> represents an arrangement of operations of the controller (e.g., controller <NUM>, shown in <FIG>). Typically, the operations are executed by a processor present in the controller. However, the operations may also be executed by multiple processors present in the controller. While typically executed by a single controller, in some arrangements, operation execution may be distributed among two or more controllers.

Operations include collecting <NUM> information related to one or more conditions of a respiratory system associated with a patient. For example, one or more sensors of the monitor <NUM> of <FIG> can collect information related to one or more conditions of the respiratory system. In some examples, other sensors in the respiratory system collect information related to one or more conditions of the respiratory system. The conditions associated with the respiratory system include one or more of the oxygen concentration of an input gas (e.g., reactant gas), an input flow rate of the reactant gas, a gas volume and frequency of an inspiration, the pressure in a chamber of the respiratory system, and the oxygen concentration of a product gas before and after admixture in the respiratory system. Operations also include determining <NUM> one or more control parameters based on the collected information. For example, the controller <NUM> of <FIG> can determine one or more control parameters. The control parameters may create a pulse train. Operations also include initiating <NUM> a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters. For example, the electrodes <NUM> of <FIG> can initiate a series of electric arcs external to the patient to generate nitric oxide based on the determined control parameters. The control parameters may control the timings of the series of electric arcs. In some examples, the conditions associated with the respiratory system also include the amounts of NO and NO<NUM> generated by the series of electric arcs (e.g., amounts of NO and NO<NUM> previously generated).

<FIG> shows an example of example computer device <NUM> and example mobile computer device <NUM>, which can be used to implement the operations and techniques described herein. For example, a portion or all of the operations of a controller (e.g., controller <NUM> of <FIG>) may be executed by the computer device <NUM> and/or the mobile computer device <NUM>. Computing device <NUM> is intended to represent various forms of digital computers, including, e.g., laptops, desktops, workstations, personal digital assistants, servers, blade servers, mainframes, and other appropriate computers. Computing device <NUM> is intended to represent various forms of mobile devices, including, e.g., personal digital assistants, tablet computing devices, cellular telephones, smartphones, and other similar computing devices. The components shown here, their connections and relationships, and their functions, are meant to be examples only, and are not meant to limit implementations of the techniques described and/or claimed in this document.

Computing device <NUM> includes processor <NUM>, memory <NUM>, storage device <NUM>, high-speed interface <NUM> connecting to memory <NUM> and high-speed expansion ports <NUM>, and low speed interface <NUM> connecting to low speed bus <NUM> and storage device <NUM>. Each of components <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>, are interconnected using various busses, and can be mounted on a common motherboard or in other manners as appropriate. Processor <NUM> can process instructions for execution within computing device <NUM>, including instructions stored in memory <NUM> or on storage device <NUM> to display graphical data for a GUI on an external input/output device, including, e.g., display <NUM> coupled to high speed interface <NUM>. In other implementations, multiple processors and/or multiple buses can be used, as appropriate, along with multiple memories and types of memory. Also, multiple computing devices <NUM> can be connected, with each device providing portions of the necessary operations (e.g., as a server bank, a group of blade servers, or a multi-processor system).

Memory <NUM> stores data within computing device <NUM>. In one implementation, memory <NUM> is a volatile memory unit or units. In another implementation, memory <NUM> is a non-volatile memory unit or units. Memory <NUM> also can be another form of computer-readable medium, including, e.g., a magnetic or optical disk.

Storage device <NUM> is capable of providing mass storage for computing device <NUM>. In one implementation, storage device <NUM> can be or contain a computer-readable medium, including, e.g., a floppy disk device, a hard disk device, an optical disk device, or a tape device, a flash memory or other similar solid state memory device, or an array of devices, including devices in a storage area network or other configurations. A computer program product can be tangibly embodied in a data carrier. The computer program product also can contain instructions that, when executed, perform one or more methods, including, e.g., those described above. The data carrier is a computer- or machine-readable medium, including, e.g., memory <NUM>, storage device <NUM>, memory on processor <NUM>, and the like.

High-speed controller <NUM> manages bandwidth-intensive operations for computing device <NUM>, while low speed controller <NUM> manages lower bandwidth-intensive operations. Such allocation of functions is an example only. In one implementation, high-speed controller <NUM> is coupled to memory <NUM>, display <NUM> (e.g., through a graphics processor or accelerator), and to high-speed expansion ports <NUM>, which can accept various expansion cards (not shown). The low-speed expansion port, which can include various communication ports (e.g., USB, Bluetooth®, Ethernet, wireless Ethernet), can be coupled to one or more input/output devices, including, e.g., a keyboard, a pointing device, a scanner, or a networking device including, e.g., a switch or router, e.g., through a network adapter.

Computing device <NUM> can be implemented in a number of different forms, as shown in the figure. For example, it can be implemented as standard server <NUM>, or multiple times in a group of such servers. It also can be implemented as part of rack server system <NUM>. In addition or as an alternative, it can be implemented in a personal computer including, e.g., laptop computer <NUM>. In some examples, components from computing device <NUM> can be combined with other components in a mobile device (not shown), including, e.g., device <NUM>. Each of such devices can contain one or more of computing device <NUM>, <NUM>, and an entire system can be made up of multiple computing devices <NUM>, <NUM> communicating with each other.

Computing device <NUM> includes processor <NUM>, memory <NUM>, an input/output device including, e.g., display <NUM>, communication interface <NUM>, and transceiver <NUM>, among other components. Device <NUM> also can be provided with a storage device, including, e.g., a microdrive or other device, to provide additional storage. Each of components <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>, are interconnected using various buses, and several of the components can be mounted on a common motherboard or in other manners as appropriate.

Processor <NUM> can execute instructions within computing device <NUM>, including instructions stored in memory <NUM>. The processor can be implemented as a chipset of chips that include separate and multiple analog and digital processors. The processor can provide, for example, for coordination of the other components of device <NUM>, including, e.g., control of user interfaces, applications run by device <NUM>, and wireless communication by device <NUM>.

Processor <NUM> can communicate with a user through control interface <NUM> and display interface <NUM> coupled to display <NUM>. Display <NUM> can be, for example, a TFT LCD (Thin-Film-Transistor Liquid Crystal Display) or an OLED (Organic Light Emitting Diode) display, or other appropriate display technology. Display interface <NUM> can comprise appropriate circuitry for driving display <NUM> to present graphical and other data to a user. Control interface <NUM> can receive commands from a user and convert them for submission to processor <NUM>. In addition, external interface <NUM> can communicate with processor <NUM>, so as to enable near area communication of device <NUM> with other devices. External interface <NUM> can provide, for example, for wired communication in some implementations, or for wireless communication in other implementations, and multiple interfaces also can be used.

Memory <NUM> stores data within computing device <NUM>. Memory <NUM> can be implemented as one or more of a computer-readable medium or media, a volatile memory unit or units, or a non-volatile memory unit or units. Expansion memory <NUM> also can be provided and connected to device <NUM> through expansion interface <NUM>, which can include, for example, a SIMM (Single In Line Memory Module) card interface. Such expansion memory <NUM> can provide extra storage space for device <NUM>, or also can store applications or other data for device <NUM>. Specifically, expansion memory <NUM> can include instructions to carry out or supplement the processes described above, and can include secure data also. Thus, for example, expansion memory <NUM> can be provided as a security module for device <NUM>, and can be programmed with instructions that permit secure use of device <NUM>. In addition, secure applications can be provided through the SIMM cards, along with additional data, including, e.g., placing identifying data on the SIMM card in a non-hackable manner.

The memory can include, for example, flash memory and/or NVRAM memory, as discussed below. In one implementation, a computer program product is tangibly embodied in a data carrier. The computer program product contains instructions that, when executed, perform one or more methods, including, e.g., those described above. The data carrier is a computer- or machine-readable medium, including, e.g., memory <NUM>, expansion memory <NUM>, and/or memory on processor <NUM>, which can be received, for example, over transceiver <NUM> or external interface <NUM>.

Device <NUM> can communicate wirelessly through communication interface <NUM>, which can include digital signal processing circuitry where necessary. Communication interface <NUM> can provide for communications under various modes or protocols, including, e.g., GSM voice calls, SMS, EMS, or MMS messaging, CDMA, TDMA, PDC, WCDMA, CDMA2000, or GPRS, among others. Such communication can occur, for example, through radio-frequency transceiver <NUM>. In addition, short-range communication can occur, including, e.g., using a Bluetooth®, WiFi, or other such transceiver (not shown). In addition, GPS (Global Positioning System) receiver module <NUM> can provide additional navigation- and location-related wireless data to device <NUM>, which can be used as appropriate by applications running on device <NUM>. Sensors and modules such as cameras, microphones, compasses, accelerators (for orientation sensing), etc. maybe included in the device.

Device <NUM> also can communicate audibly using audio codec <NUM>, which can receive spoken data from a user and convert it to usable digital data. Audio codec <NUM> can likewise generate audible sound for a user, including, e.g., through a speaker, e.g., in a handset of device <NUM>. Such sound can include sound from voice telephone calls, can include recorded sound (e.g., voice messages, music files, and the like) and also can include sound generated by applications operating on device <NUM>.

Computing device <NUM> can be implemented in a number of different forms, as shown in the figure. For example, it can be implemented as cellular telephone <NUM>. It also can be implemented as part of smartphone <NUM>, personal digital assistant, or other similar mobile device.

These various implementations can include implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which can be special or general purpose, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device.

As used herein, the terms machine-readable medium and computer-readable medium refer to a computer program product, apparatus and/or device (e.g., magnetic discs, optical disks, memory, Programmable Logic Devices (PLDs)) used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions.

To provide for interaction with a user, the systems and techniques described here can be implemented on a computer having a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying data to the user and a keyboard and a pointing device (e.g., a mouse or a trackball) by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; for example, feedback provided to the user can be a form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user can be received in a form, including acoustic, speech, or tactile input.

The systems and techniques described here can be implemented in a computing system that includes a back end component (e.g., as a data server), or that includes a middleware component (e.g., an application server), or that includes a front end component (e.g., a client computer having a user interface or a Web browser through which a user can interact with an implementation of the systems and techniques described here), or a combination of such back end, middleware, or front end components. The components of the system can be interconnected by a form or medium of digital data communication (e.g., a communication network). Examples of communication networks include a local area network (LAN), a wide area network (WAN), and the Internet.

Claim 1:
An apparatus (<NUM>) comprising:
an inlet configured to receive a reactant gas containing nitrogen and oxygen;
an outlet configured to provide a product gas for inhalation containing nitric oxide, wherein the product gas is formed by a synthesis of the reactant gas;
a reaction chamber (<NUM>) arranged between the inlet and the outlet; one or more pairs of electrodes (<NUM>) within the reaction chamber and configured to initiate electric arcs to synthesize the reactant gas to the product gas;
a sensor configured to measure a flow of a gas into which the product gas is provided through the outlet; and
a controller (<NUM>) in communication with the one or more pairs of electrodes and the sensor, the controller being configured to adjust one or more conditions within the reaction chamber to control a concentration of nitric oxide in the product gas;
characterized in that
the one or more conditions within the reaction chamber include at least one of a pulse width, pulse period, pulse count per pulse group, pulse groups per second, and arc frequency.