U.S. patent application number 16/933666 was filed with the patent office on 2020-11-05 for synthesis of nitric oxide gas for inhalation.
The applicant listed for this patent is The General Hospital Corporation. Invention is credited to Paul Hardin, Matthew Hickcox, Binglan Yu, Warren M. Zapol.
Application Number | 20200345966 16/933666 |
Document ID | / |
Family ID | 1000004969846 |
Filed Date | 2020-11-05 |
View All Diagrams
United States Patent
Application |
20200345966 |
Kind Code |
A1 |
Zapol; Warren M. ; et
al. |
November 5, 2020 |
SYNTHESIS OF NITRIC OXIDE GAS FOR INHALATION
Abstract
In some additional aspects, an apparatus for generating nitric
oxide (NO) can include one or more pairs of electrodes configured
to initiate a series of electric arcs to synthesize a reactant gas
into a product gas comprising NO, a sensor configured to measure a
flow of a gas in a respiratory system into which the product gas is
provided, a controller in communication with the one or more pairs
of electrodes and the sensor. The controller is configured to
adjust at least one of a pulse width, pulse period, pulse count per
pulse group, pulse groups per second, energy generated by the one
or more pairs of electrodes, arc frequency, arc current, and a
voltage supplied to the one or more pairs of electrodes based on
the measured flow to control a concentration of nitric oxide in the
product gas.
Inventors: |
Zapol; Warren M.;
(Cambridge, MA) ; Yu; Binglan; (Lexington, MA)
; Hardin; Paul; (Lowell, MA) ; Hickcox;
Matthew; (Groton, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The General Hospital Corporation |
Boston |
MA |
US |
|
|
Family ID: |
1000004969846 |
Appl. No.: |
16/933666 |
Filed: |
July 20, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14777084 |
Sep 15, 2015 |
10773047 |
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PCT/US2014/027986 |
Mar 14, 2014 |
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16933666 |
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61789161 |
Mar 15, 2013 |
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61792473 |
Mar 15, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2205/3303 20130101;
A61M 16/0057 20130101; A61M 2205/3592 20130101; A61M 2205/3334
20130101; A61M 2202/0208 20130101; A61M 2205/3569 20130101; A61M
16/0072 20130101; A61M 16/0003 20140204; A61M 2205/3584 20130101;
A61M 2205/33 20130101; A61M 2016/1025 20130101; A61M 16/0465
20130101; A61M 2205/3606 20130101; A61M 2205/366 20130101; B01D
2251/304 20130101; A61M 2205/50 20130101; B01D 2251/306 20130101;
A61M 16/20 20130101; B01D 2251/404 20130101; A61M 16/101 20140204;
A61M 2202/0275 20130101; A61M 16/209 20140204; A61M 2205/3561
20130101; A61M 15/02 20130101; A61M 2205/04 20130101; A61M
2016/1035 20130101; B01D 53/56 20130101; A61M 2205/3553 20130101;
A61M 16/108 20140204; A61M 16/06 20130101; A61M 2202/0216 20130101;
A61M 16/12 20130101; A61M 16/202 20140204; A61M 16/10 20130101;
C01B 21/203 20130101; A61M 2016/0033 20130101; A61M 2230/40
20130101; A61M 2016/0021 20130101; A61M 2210/1032 20130101; A61M
16/0063 20140204; A61M 16/107 20140204; A61M 2205/7545
20130101 |
International
Class: |
A61M 16/12 20060101
A61M016/12; A61M 16/00 20060101 A61M016/00; A61M 16/10 20060101
A61M016/10; C01B 21/20 20060101 C01B021/20; A61M 15/02 20060101
A61M015/02; B01D 53/56 20060101 B01D053/56; A61M 16/04 20060101
A61M016/04; A61M 16/06 20060101 A61M016/06; A61M 16/20 20060101
A61M016/20 |
Claims
1. An apparatus for generating nitric oxide (NO) comprising: one or
more pairs of electrodes configured to initiate a series of
electric arcs to synthesize a reactant gas into a product gas
comprising NO; a sensor configured to measure a flow of a gas in a
respiratory system into which the product gas is provided; and a
controller in communication with the one or more pairs of
electrodes and the sensor, the controller being configured to
adjust at least one of a pulse width, pulse period, pulse count per
pulse group, pulse groups per second, energy generated by the one
or more pairs of electrodes, arc frequency, arc current, and a
voltage supplied to the one or more pairs of electrodes based on
the measured flow to control a concentration of nitric oxide in the
product gas to treat at least one of pulmonary fibrosis, infection,
malaria, myocardial infarction, stroke, pulmonary hypertension,
persistent pulmonary hypertension in newborns, hypoxia as a result
of explosive decompression of an aircraft or spacecraft, and high
altitude pulmonary edema.
2. The apparatus of claim 1, wherein the controller adjusts the at
least one of a pulse width, pulse period, pulse count per pulse
group, pulse groups per second, energy generated by the one or more
pairs of electrodes, arc frequency, arc current, and a voltage to
minimize a concentration of NO2 in the product gas.
3. The apparatus of claim 1, wherein the controller controls the
nitric oxide concentration of the product gas with the flow rate of
the reactant gas.
4. The apparatus of claim 1, wherein the NO generator is configured
to produce gas for respiration with a concentration of NO between
0.5 ppm and 500 ppm.
5. The apparatus of claim 1, wherein the flow of gas into which the
product gas is provided flows into an inspiratory limb associated
with the ventilator.
6. The apparatus of claim 1, wherein a timing of the synthesis of
the product gas is configured to be synchronized with the
inspiratory pressurization or gas flow in the respiratory
system.
7. The apparatus of claim 1, wherein the one or more pairs of
electrodes include a noble metal.
8. The apparatus of claim 1, wherein the one or more pairs of
electrodes include iridium.
9. An apparatus for generating nitric oxide (NO) comprising: one or
more pairs of electrodes configured to initiate a series of
electric arcs to synthesize a reactant gas into a product gas
comprising NO; a sensor configured to measure a condition
associated with at least one of the reactant gas, the product gas,
and a gas in a respiratory system into which the product gas is
provided; and a controller in communication with the one or more
pairs of electrodes and the sensor, the controller being configured
to adjust at least one of a pulse width, pulse period, pulse count
per pulse group, pulse groups per second, energy generated by the
one or more pairs of electrodes, arc frequency, arc current, and a
voltage supplied to the one or more pairs of electrodes based on
the measurement from the sensor to control a concentration of
nitric oxide in the product gas to treat at least one of pulmonary
fibrosis, infection, malaria, myocardial infarction, stroke,
pulmonary hypertension, persistent pulmonary hypertension in
newborns, hypoxia as a result of explosive decompression of an
aircraft or spacecraft, and high altitude pulmonary edema.
10. The apparatus of claim 9, wherein the NO generator is
configured to produce gas for respiration with a concentration of
NO between 0.5 ppm and 500 ppm.
11. The apparatus of claim 9, wherein the flow of gas into which
the product gas is provided flows into an inspiratory limb
associated with the ventilator.
12. The apparatus of claim 9, wherein the one or more pairs of
electrodes include a noble metal.
13. The apparatus of claim 9, wherein the one or more pairs of
electrodes include iridium.
14. A method for generating nitric oxide (NO), the method
comprising: providing a reactant gas containing nitrogen and oxygen
to one or more pairs of electrodes, initiating a series of electric
arcs in the one or more pairs of electrodes to synthesize the
reactant gas to a product gas containing nitric oxide; measuring a
flow of a gas in a respiratory system into which the product gas is
provided; and adjusting one or more conditions associated with the
one or more electrodes based on the measured flow of gas in the
respiratory system to control a concentration of nitric oxide in
the product gas to treat at least one of pulmonary fibrosis,
infection, malaria, myocardial infarction, stroke, pulmonary
hypertension, persistent pulmonary hypertension in newborns,
hypoxia as a result of explosive decompression of an aircraft or
spacecraft, and high altitude pulmonary edema.
15. The method of claim 14, wherein 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,
energy generated by the one or more pairs of electrodes, arc
frequency, arc current, and a voltage supplied to the one or more
pairs of electrodes based on the measured flow to control the
series of electrical arcs to control a concentration of nitric
oxide in the product gas.
Description
CLAIM OF PRIORITY
[0001] This application claims the benefit of U.S. Patent
Application Ser. No. 61/789,161 and U.S. Patent Application Ser.
No. 61/792,473, filed on Mar. 15, 2013, the entire contents of
which are hereby incorporated by reference.
TECHNICAL FIELD
[0002] This invention is related to synthesis of nitric oxide gas
for inhalation.
BACKGROUND
[0003] 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.
[0004] 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.
[0005] U.S. Pat. No. 5,396,882 to Zapol, which is incorporated by
reference herein, describes electric generation of nitric oxide
(NO) from air at ambient pressure for medical purposes. As
described in U.S. Pat. No. 5,396,882, an air input port of the
system is used for continuously introducing air into the region of
the electric arc.
SUMMARY
[0006] 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.
[0007] Embodiments can include one or more of the following.
[0008] 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.
[0009] 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.
[0010] The pulse width of initial pulses in one of the pulse groups
can be wider than other pulses in the pulse group.
[0011] The series of electric arcs can generate a reduced level of
nitrogen dioxide.
[0012] The series of electric arcs can generate a reduced level of
ozone.
[0013] The reduced level of nitrogen dioxide can be further reduced
by a scavenger including one or more of KaOH, CaOH, CaCO3, and
NaOH.
[0014] The reduced level of nitrogen dioxide can have a
concentration that is less than 20%, 10%, 6%, or 5% of a
concentration of the generated nitric oxide.
[0015] The series of electric arcs can be generated by electrodes
including a noble metal.
[0016] The series of electric arcs can be generated by electrodes
including iridium.
[0017] The series of electric arcs can be generated by electrodes
including nickel.
[0018] 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.
[0019] Embodiments can include one or more of the following.
[0020] 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.
[0021] The volume and timing of an inspiration can be received from
a ventilator.
[0022] A pulse train can initiate the series of electric arcs, and
the pulse train can include pulse groups having pulses with
different pulse widths.
[0023] The pulse width of initial pulses in one of the pulse groups
can be wider than other pulses in the pulse group.
[0024] The series of electric arcs can generate a reduced level of
nitrogen dioxide.
[0025] The series of electric arcs can generate a reduced level of
ozone.
[0026] The series of electric arcs can be initiated when the
chamber has a pressure greater than 1 ATA or less than 1 ATA.
[0027] 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.
[0028] The reduced level of nitrogen dioxide can have a
concentration that is less than 20%, 10%, 6%, or 5% of a
concentration of the generated nitric oxide.
[0029] The electrodes can include a noble metal.
[0030] The electrodes can include iridium.
[0031] The electrodes can include nickel.
[0032] 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.
[0033] Embodiments can include one or more of the following.
[0034] 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.
[0035] The volume and timing of an inspiration can be received from
a ventilator.
[0036] A pulse train can initiate the series of electric arcs, and
the pulse train can include pulse groups having pulses with
different pulse widths.
[0037] The pulse width of initial pulses in one of the pulse groups
can be wider than other pulses in the pulse group.
[0038] The series of electric arcs can generate a reduced level of
nitrogen dioxide.
[0039] The series of electric arcs can generate a reduced level of
ozone.
[0040] The series of electric arcs can be initiated when the
chamber has a pressure greater than 1 ATA or less than 1 ATA.
[0041] 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.
[0042] The reduced level of nitrogen dioxide can have a
concentration that is less than 20%, 10%, 6%, or 5% of a
concentration of the generated nitric oxide.
[0043] The electrodes can include a noble metal.
[0044] The electrodes can include iridium.
[0045] The electrodes can include nickel.
[0046] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, objects, and advantages of the invention will be
apparent from the description and drawings, and from the
claims.
DESCRIPTION OF DRAWINGS
[0047] FIG. 1 is a block diagram of a respiratory system for
producing NO.
[0048] FIG. 2 is an example of an NO generator.
[0049] FIG. 3 is an example of an NO generator.
[0050] FIG. 4 depicts a device for concentrating oxygen.
[0051] FIG. 5 depicts a device for cooling a gas.
[0052] FIG. 6 is an example of an NO generator.
[0053] FIG. 7 is an example of an NO generator.
[0054] FIG. 8 is an example of an NO generator.
[0055] FIG. 9A is a photograph showing an example of a respiratory
system for producing NO.
[0056] FIG. 9B is a photograph of an NO generator.
[0057] FIG. 10 depicts a representation of a pulse train and a
pulse group.
[0058] FIG. 11A shows average current and voltage as a function of
sparks per second.
[0059] FIG. 11B shows average power as a function of sparks per
second.
[0060] FIGS. 12A-B show tracings of voltage and current during two
sparks of a 1 spark/second discharge.
[0061] FIG. 13 shows NO and NO.sub.2 concentrations using various
electrode materials.
[0062] FIG. 14 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations.
[0063] FIG. 15 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations.
[0064] FIG. 16 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations.
[0065] FIG. 17 shows ozone levels at various oxygen
concentrations.
[0066] FIG. 18 shows ozone levels at various oxygen
concentrations.
[0067] FIG. 19 shows ozone levels at various oxygen
concentrations.
[0068] FIG. 20 shows ozone levels at various oxygen
concentrations.
[0069] FIG. 21 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations.
[0070] FIG. 22 shows a test setup for measuring NO and NO.sub.2
levels in a hypobaric chamber at various atmospheric pressures.
[0071] FIG. 23 shows NO and NO.sub.2 levels at various atmospheric
pressures.
[0072] FIG. 24 is a flowchart.
[0073] FIG. 25 illustrates an example of a computing device and a
mobile computing device that can be used to implement the
operations and techniques described herein.
[0074] Like reference symbols in the various drawings indicate like
elements.
DETAILED DESCRIPTION
[0075] Synthesis of NO for inhalation is achieved by electrically
sparking a reactant gas including N.sub.2 and O.sub.2 (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 1 ATA (atmosphere absolute), and
"hyperbaric" to a pressure greater than 1 ATA. The product gas can
include a medically acceptable level of NO.sub.2 (e.g., usually
less than 5 ppm, and sometimes less than 1-2 ppm). The product gas
may be inhaled either with or without reducing the concentration of
NO.sub.2 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 0.5 ppm
to 500 ppm and a concentration of NO.sub.2 of less than 1% of the
NO concentration, or even lower (e.g., less than 1%) after using a
scavenger.
[0076] FIG. 1 shows an example of a respiratory system 100 for
producing NO. A reactant gas (e.g., air, or a 10-90% oxygen mixture
in nitrogen) enters an NO generator 102, and a product gas
(including NO) exits the NO generator 102. The NO generator 102
includes electrodes 106 and a controller 110. If the reactant gas
is a gas other than air, the NO generator 102 can include an oxygen
level sensor 112. NO production is proportional to oxygen and
nitrogen concentration and maximal at about 50% oxygen at
atmospheric pressure (1 ATA). The oxygen level sensor 112 can be an
electrode configured to detect a concentration of oxygen in the
reactant gas, as described in more detail below. The electrodes 106
generate sparks in the presence of the reactant gas to produce NO
104, as described herein.
[0077] FIG. 2 shows an example of an NO generator 200. NO generator
200 includes chamber 202 having inlet valve 204 and outlet valve
206. In some cases, filter 208 is coupled to NO generator 200, such
that a gaseous mixture including N.sub.2 and O.sub.2 entering
chamber through inlet valve 204 is filtered to remove particulate
matter (e.g., dust) or water vapor. Chamber 202 includes electrodes
210. Electrodes 210 are separated by a gap, and one of the
electrodes is coupled to voltage source 212. Voltage source 212 is
suitable to create a spark or corona discharge capable of forming
NO from N.sub.2 and O.sub.2 between electrodes 210. Examples of
voltage source 212 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 1 to 25
kV (e.g., a power of 1 to 100 watts), or a voltage of 1 to 10 kV or
1 to 5 kV.
[0078] When NO generator 200 is used for hypobaric or hyperbaric
synthesis of NO, chamber 202 may be a cavity in a positive
displacement pump. As shown in FIG. 2, chamber 202 may be a cavity
in a piston pump and has a variable volume defined by the position
of piston 214 in barrel 216. Piston 214 is coupled to actuator 218.
In one example, actuator 218 includes an eccentric mechanism driven
by a rod or shaft. Actuator 218 is driven by prime mover 120 in a
reciprocating manner. Prime mover 220 may be, for example, a motor
or engine (e.g., an electric or gasoline or diesel powered engine)
arranged to translate piston 214 with respect to barrel 216 by way
of actuator 218. Seal 222 inhibits the flow of air into or out of
chamber 202 between piston 214 and barrel 216. Thus, when both
inlet valve 204 and outlet valve 206 are closed, translation of
piston 214 away from electrodes 210 by actuator 218 increases the
volume of chamber 202, thereby reducing the pressure in chamber 202
to a pressure below atmospheric pressure and reducing a
concentration of gases (e.g., N.sub.2 and O.sub.2) in a reactant
gas present in the chamber. Conversely, translation of piston 214
toward the electrodes 210 by actuator 218 decreases the volume of
chamber 202, thereby increasing the pressure in chamber 202 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 202 can have an effect on the production of
NO. For example, when the chamber 202 has a relatively high
pressure (e.g., 2 ATA), NO production is increased.
[0079] Inlet valve 204 may be exposed to the environment such that,
with the inlet valve open, ambient air (or other reactant gas
containing N.sub.2 and O.sub.2) enters chamber 202. With air in
chamber 202, inlet valve is closed and piston 214 translates away
from electrodes 210, thereby increasing the volume of chamber 202
and decreasing the pressure inside chamber 202 to a pressure below
atmospheric pressure. As the volume of chamber 202 increases, the
concentration of O.sub.2 in the chamber falls below the
concentration of O.sub.2 in air at atmospheric pressure (e.g.,
falls below 21 vol %). Actuator 218 may be controlled to increase a
volume of chamber 202 by a factor of 2, 3, 4, etc., thereby
reducing a pressure in chamber 202 to a fraction (e.g., 1/2, 1/3,
1/4, etc.) of atmospheric pressure. While the pressure in chamber
202 is below atmospheric pressure, voltage source 212 initiates
sparks or corona discharges across electrodes 210, thereby
electrically generating NO. Following the sparks or corona
discharges, actuator 218 continues its reciprocating cycle, and
outlet valve 206 is opened to release the product gas containing
the electrically generated NO. Thus, inlet valve 204 and outlet
valve 206 operate out of phase with each other, such that outlet
valve 206 is closed when inlet valve 104 is open, and inlet valve
204 is closed when outlet valve 206 is open.
[0080] Conversely, with air in chamber 202, inlet valve is closed
and piston 214 translates toward the electrodes 210, thereby
decreasing the volume of chamber 202 and increasing the pressure
inside chamber 202 to a pressure above atmospheric pressure. As the
volume of chamber 202 decreases, the pressure (concentration) of
O.sub.2 in the chamber rises above the pressure (concentration) of
O.sub.2 in air at atmospheric pressure (e.g., rises above 21 vol
%). Actuator 218 may be controlled to decrease a volume of chamber
202 to a fraction of 1/2, 1/3, 1/4, etc., thereby increasing a
pressure in chamber 202 to 2, 3, 4, etc. times atmospheric
pressure. While the pressure in chamber 202 is above atmospheric
pressure, voltage source 212 initiates sparks or corona discharges
across electrodes 210, thereby electrically generating NO.
[0081] In some examples, electrodes in an NO generator (e.g.,
electrodes 210) can be duplicated for safety purposes to provide a
spare. The electrodes 210 can be doubled or tripled for increased
power and NO production with large tidal volumes. Referring briefly
to FIG. 13, the electrodes 210 can contain iridium, tungsten,
stainless steel, or nickel, to name a few. In some examples,
electrodes 210 that contain a noble metal (e.g., iridium) produce
the smallest ratio of NO.sub.2/NO.
[0082] FIG. 3 shows an example of an NO generator 300. NO generator
300 includes components of NO generator 200, as described with
respect to FIG. 2, with source 302 coupled to inlet valve 204 and
arranged to provide a reactant gas to chamber 202. In some
instances, source 302 is an apparatus arranged to provide a
reactant gas with a concentration of O.sub.2 less than 21 vol % or
less than 20 vol %. In some instances, source 302 is an apparatus
arranged to provide a reactant gas with a concentration of O.sub.2
more than 21 vol % but not more than 90 vol %. For example, source
302 may include a cylinder of N.sub.2 or an inert gas (e.g., argon
or helium) and a mechanism to mix the N.sub.2 or inert gas with air
or an enriched oxygen containing source at a selected ratio to
achieve a desired concentration of O.sub.2, N.sub.2, and/or other
components in the reactant gas provided to chamber 202. 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 202
at a pressure of 1 ATA (atmosphere absolute) or above (e.g.,
slightly above, to 3 ATA) to avoid admixture of the reactant gas
with air. Before entering chamber 202, reactant gas from source 302
may pass through an equilibrium bag 304, held slightly above
atmospheric pressure. Blow-off valve 306 may be present to allow
the pressure of the reactant gas to be maintained close to
atmospheric pressure.
[0083] In some instances, source 302 includes an oxygen
concentrator, oxygen generator, or oxygen cylinder. FIG. 4 depicts
an oxygen concentrator 400, in which pressurized air enters oxygen
concentrator 400 through inlet 402 and passes through molecular
sieve 404, yielding oxygen-enriched gas (e.g., having at least 30
vol % or 50 vol % O.sub.2). The exhaust gas, which has an O.sub.2
concentration less than that of ambient air and a N.sub.2
concentration greater than that of ambient air, exits oxygen
concentrator 400 through valve 406, and is provided to the inlet
valve 204.
[0084] In some instances, source 302 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 0.degree. K) is provided to chamber 202 through valve
204, and the spark or corona discharge occurs in a cooled reactant
gas having a temperature less than room temperature. Source 302 may
operate to cool air by refrigeration or heat exchange methods
generally known in the art. FIG. 5 depicts one example of a cooling
device 500, in which air or another reactant gas (e.g., a mixture
of air and N.sub.2 or an inert gas, such as argon, helium, or the
like) flows through coil 502 and is cooled by coolant 504, which
enters chamber 506 through inlet 508 and exits the chamber through
outlet 510. Coil 502 may be a heat-conductive tubing such as, for
example, copper tubing. Coolant 504 may be, for example, liquid
N.sub.2 or a cycling refrigerant (e.g., chlorofluorocarbon or
hydrochlorofluorocarbon).
[0085] In certain instances, one or more implementations of source
302 as described above with respect to FIG. 3 are combined to form
a gaseous mixture. For example, source 302 may include a cylinder
of N.sub.2 or an inert gas (e.g., argon or helium) and a mechanism
to mix the N.sub.2 or inert gas with air at a selected ratio to
achieve a desired concentration of O.sub.2 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 202. 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 204, and the
like).
[0086] In other embodiments, as shown in FIG. 6, an NO generator
600 includes constant volume chamber 602. In some cases, inlet
valve 204 is exposed to the environment such that, with the inlet
valve open, ambient air enters chamber 602 (e.g., through filter
208). Inlet valve 204 and outlet valve 206 may be synchronized such
that a gaseous mixture flows into chamber 602 through inlet valve
204, and the inlet valve is closed before the sparks or corona
discharges are initiated. Outlet valve 206 is typically closed
while inlet valve 204 is open, and may open prior to, during, or
after initiation of the sparks or corona discharges. In certain
cases, constant volume chamber 602 is coupled to source 302, and
reactant gas is provided to chamber 602 by source 302. Filter 208
may be positioned between source 302 and chamber 602 (e.g., between
source 302 and equilibrium bag 304, as illustrated, or between
blow-off valve 306 and inlet valve 204, as shown in FIG. 3). The
exhaust of an oxygen concentrator may be used to provide a reactant
gas having a decreased O.sub.2 content to chamber 602. NO generator
600 may be operated in an environment having an ambient pressure
less than 1 ATA (e.g., at high altitude). Alternatively, constant
volume 602 chamber is coupled to pump 604 through valve 606. Pump
604 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 602, thereby decreasing the concentration of O.sub.2 and
N.sub.2 in the reactant gas in chamber 602. Similarly, pump 604 can
be arranged to increase the gas pressure in chamber 602, thereby
increasing the concentration of O.sub.2 and N.sub.2 in the reactant
gas in chamber 602 to achieve higher levels of NO generation.
[0087] FIG. 7 shows an example of an NO generator 700. NO generator
700 includes components of NO generator 500, as described with
respect to FIG. 6, with source 302, as described with respect to
FIG. 3, coupled to inlet valve 204 and arranged to provide a
reactant gas to chamber 602. As noted with respect to FIG. 6, NO
may be selectively synthesized in chamber 602 at ambient pressure,
at a reduced pressure, or at an increased pressure achieved with
pump 604.
[0088] The product gas that exits chamber 202 or 602 through outlet
valve 206 of NO generator 200, 300, 600, and 700 includes the
electrically generated NO, and may include low levels of NO.sub.2
and O.sub.3. 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 endrotracheal 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.sub.2 and O.sub.3) by contacting the product
gas with a scavenger (e.g., scavenger 226). In some examples, the
scavenger 226 includes one or more of KaOH, CaOH, CaCO.sub.3, and
NaOH.
[0089] Referring to FIG. 2, the scavenger 226 can be placed in a
cartridge 228 to process produced gas exiting the outlet valve 206.
The cartridge 228, the scavenger 226, or both may be replaceable
due to the limited absorption capabilities of the scavenger
material. The scavenger 226 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 80 ppm NO
in the product gas, a scavenger 226 having a volume of 100 ml can
reduce the concentration of NO.sub.2 to about 0 ppm.
[0090] In certain cases, including implementations of NO generator
300 and 700 in which exhaust gas from an oxygen concentrator is
used for hypobaric synthesis of NO, the product gas that exits
chamber 202 or 602 through outlet valve 206 may be combined with
O.sub.2-enriched air from the oxygen concentrator or pure O.sub.2
from a source to form a gaseous mixture including a medically
effective level of NO in O.sub.2-enriched air, with low levels of
NO.sub.2. One or more methods of treating the product gas can be
combined in any order such that, for example, NO.sub.2 is removed
from a product gas that exits chamber 202 or 602 through outlet
valve 206 to yield a gaseous mixture, and this gaseous mixture is
then combined with O.sub.2-enriched air from an oxygen
concentrator, or a product gas that exits chamber 202 or 602
through outlet valve 206 is combined with O.sub.2-enriched air from
an oxygen concentrator to form a gaseous mixture, and NO.sub.2 is
then removed from the gaseous mixture. The final mixture can be
again subjected to scavenging to remove NO.sub.2.
[0091] 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.
[0092] FIG. 8 depicts a respiratory system 800 for electric
synthesis of NO in which product gas from output valve 206 of NO
generator 802 is provided to monitor 804. The monitor 804 can
collect information related to one or more conditions associated
with the respiratory system. NO generator 802 may be any NO
generator described herein. Monitor 804 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.sub.2, O.sub.3, O.sub.2, or any combination
thereof. In some cases, monitor 804 provides feedback to NO
generator 802 or source 302 to adjust production of NO, decrease
production of NO.sub.2 or O.sub.3, 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.sub.2, an inert gas, air, or O.sub.2) into the chamber (e.g.,
chamber 202 or 602), 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 804 can include a gas flow
sensor for measuring the flow rate of the gas entering the
chamber.
[0093] As described herein, an NO generator produces gas for
respiration with a concentration of NO between 0.5 ppm and 500 ppm
(e.g., at least 0.5 ppm and up to 1 ppm, 5 ppm, 10 ppm, 20 ppm, 40
ppm, 80 ppm, or 500 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.
[0094] 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.sub.2 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.sub.2 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.
[0095] FIG. 9A shows an example of a respiratory system 900 for
producing NO. In some embodiments, NO is produced electrically
under ambient conditions, or hypobaric or hyperbaric conditions.
The respiratory system 900 includes power supply 902 and chamber
904. Various components (e.g., an oscilloscope) can make electrical
measurements of the respiratory system 900. In some embodiments,
power supply 902 is a battery, and the respiratory system 900 is
portable and wearable. FIG. 9B shows an example of an NO generator
916 of respiratory system 900. Reactant gas is provided to chamber
904 through inlet 908, and product gas exits chamber 904 via outlet
910. Power supply 902 is coupled to electrodes 906 in chamber 904
to generate sparks therebetween. Power supply 902 may be
operatively coupled to pulse generator 912. Sparks across
electrodes 906 form NO in chamber 904 as described herein. For an
NO generator such as NO generator 916, a 1 kV to 10 kV spark across
electrodes 906 for 10-30 milliseconds that has microampere current,
requiring less than 20 W or less than 10 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 0.1 W to 1 W).
[0096] Systems for producing NO described herein, including
respiratory system 900 and others, may also include a controller
914. The controller 914 coordinates triggering of a voltage source
to deliver a series of electrical pulses to the electrodes (e.g.
electrodes 806), 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 914 can be coupled to the pulse generator 912 and at
least a portion of the NO generator 916 (e.g., the electrodes 906)
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.sub.2, O.sub.3).
[0097] The controller 914 can be configured to receive information
from one or more sensors in the respiratory system 900. The
controller 914 can use the information received from the sensors to
determine one or more control parameters for the respiratory system
900. For example, readings from the oxygen level sensor 112 can be
used by the controller 914 to determine the one or more control
parameters. The respiratory system 900 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 914 can determine control parameters based on one or
more of: i) information received from a monitor (e.g., monitor 804
of FIG. 8 for assessing the concentration of components in the
product gas or ventilator, such as the NO and NO.sub.2
concentration; ii) concentration of components in the reactant gas
(e.g., oxygen concentration); iii) operating parameters of the NO
generator 900; iv) pressure in the chamber 202 (e.g., especially
for embodiments where the NO generator 200, 300 includes a piston
214 for adjusting pressure in the chamber 202); 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.
[0098] The NO generator 900 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 900 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.
[0099] Adult humans normally breathe from 10-20 times per minute,
each breath having a duration of 3-6 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 500 ml. In
children, each breath typically has less volume, but breathing
occurs at a higher rate. Thus, in the average adult, about 10-20
breaths per minute with 1 second inspirations allow intervals for
spark generation of about 10 seconds per minute.
[0100] The expected volume of an inspiration can be calculated
using previous tidal volume measurements. For example, the
controller 914 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 914 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 914 can obtain an expected tidal
volume value from the ventilator.
[0101] Implementations of controller 914 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 914
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.
[0102] Controller 914 can include clients and servers and/or master
and slave controllers. A client and server are generally remote
from each other and typically interact through a communication
network. The relationship of client and server arises by virtue of
computer programs running on the respective computers and having a
client-server relationship to each other. In some aspects,
controller 914 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 914 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.
[0103] FIG. 10 shows a representation of a pulse train 1000 that is
triggered by the controller 914. The controller 914 can determine
one or more control parameters to create a pulse train. FIG. 10
also shows zoomed in view of one of the pulse groups 1002 of the
pulse train 1000. Electrical pulses are delivered to the electrodes
(e.g., electrodes 906), and the electrodes 906 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 914, and can be optimized to produce the needed amount
of NO while producing minimal NO.sub.2 and O.sub.3. In some
examples, the controller 914 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 1000 initiates the series of electric arcs.
[0104] Variables B and N control the overall energy that is created
by the electrodes 906. 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.sub.2, and O.sub.3 that is created. The values for B and N also
influence how much heat is produced by the electrodes 806. Larger
values of either B or N create more NO and cause the electrodes 906
to produce more heat.
[0105] 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.
[0106] 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 906 producing more energy. When the
electrodes 906 create a spark, plasma is established. The
temperature of the plasma is proportional to the amount of energy
produced by the electrodes 906. In some examples, for plasma to be
produced, the reactant gas has both nitrogen and oxygen
content.
[0107] B is typically in the range of 5-80 pulse groups per second,
N is typically in the range of 1-50 sparks per pulse group, P is
typically in the range of 10-800 microseconds, and H is typically
in the range of 5-600 microseconds.
[0108] The chemical reactions that cause NO and NO.sub.2 to be
produced are a function of plasma temperature. That is, higher
plasma temperatures result in more NO and NO.sub.2 being produced.
However, the relative proportions of the produced NO and NO.sub.2
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.sub.2 being
produced, the relatively high plasma temperature may not be ideal
for producing the desired proportions of NO and NO.sub.2. The
material of the electrodes 906 can play a major role in determining
the amount of energy needed to generate a particular spark, thus
affecting the ratio of NO.sub.2/NO produced. In some examples,
tungsten electrodes produce a relatively high ratio of NO.sub.2/NO,
nickel electrodes produced a lower ratio of NO.sub.2/NO, and
iridium electrodes produce an even lower ratio of NO.sub.2/NO, as
shown in FIG. 13.
[0109] 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 914 receives information from the
tidal volume sensor mentioned above to determine control parameters
for maintaining an appropriate inspired NO concentration.
[0110] The controller 914 may be configured to communicate with the
NO generator wirelessly (e.g., via Bluetooth). The controller 914
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 914 or to
aid the controller 914 in performing functions.
[0111] In some examples, the controller 914 can disable certain
components of the NO generator during, before or after a series of
sparks is generated. In some examples, the controller 914 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.
[0112] Results achieved with an NO generator (e.g., NO generator
916) are described with respect to FIGS. 11 through 13.
[0113] FIG. 11A is an average current and voltage chart 1100 that
shows the average current and voltage vs. sparks/second for NO
generator 916. FIG. 11B is an average power chart 1102 that shows
the average power vs. sparks/second for NO generator 916. Average
current and power peak between 0.5 and 2 sparks/second, and average
voltage dips over the same range. FIG. 12A shows oscilloscope
traces 1200 for voltage (upper trace) and current (lower trace)
during 2 sparks of a 1 spark/second discharge. FIG. 12B shows
oscilloscope traces 1202 for voltage (upper trace) and current
(lower trace) traces for a 1 spark/second discharge with a spark
duration (single spark) of 27 msec.
[0114] FIG. 13 shows NO and NO.sub.2 concentrations from an NO
generator (e.g., NO generator 916 of FIG. 9B) using various
electrode materials. The test conditions included the use of a
1/4'' rod, an electrode gap of 2.0 mm, constant air flow at 5
L/min, and a FiO.sub.2 of 0.21. For the tungsten electrode, B=40
pulse groups per second, N=30 sparks per pulse group, P=100
microseconds, and H=20 microseconds. For the nickel electrodes,
B=35 pulse groups per second, N=40 sparks per pulse group, H=180
microseconds, and P=70 microseconds. For the iridium electrodes,
B=35 pulse groups per second, N=40 sparks per pulse group, H=180
microseconds, and P=80 microseconds.
[0115] FIG. 14 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations from the NO generator using mini
spark plug (Micro Viper Z3 with 6 mm HEX and 10-40 THRD, Rimfire,
Benton City, Wash.) that is continuously sparking.
[0116] FIG. 15 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations from the NO generator using
iridium spark plug (ACDelco 41-101, Waltham, Mass.) that are
continuously sparking.
[0117] FIG. 16 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations from the NO generator using
iridium spark plug with intermittent sparking.
[0118] Ozone (O.sub.3) 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.sub.2) and O.sub.2 or reacts with N.sub.2 to
produce NO and O.sub.2. In some examples, ozone levels are greater
with continuous sparking than with intermittent sparking, and also
increase with increasing O.sub.2 concentrations.
[0119] FIG. 17 shows O.sub.3 levels at various O.sub.2
concentrations using mini spark plug and iridium spark plug with
continuous sparking. In this example, B=60 pulse groups per second,
N=50 sparks per pulse group, P=140 microseconds, H=40 microseconds,
and air flow rate is 5 L/min.
[0120] FIG. 18 shows O.sub.3 levels at various O.sub.2
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=60 pulse groups per second, N=50 sparks per pulse group, P=140
microseconds, H=40 microseconds, and air flow rate is 5 L/min.
[0121] FIG. 19 shows O.sub.3 levels at various O.sub.2
concentrations using mini spark plug and iridium spark plug with
continuous sparking. In this example, B=35 pulse groups per second,
N=25 sparks per pulse group, P=240 microseconds, H=100
microseconds, and air flow rate is 5 L/min.
[0122] FIG. 20 shows O.sub.3 levels at various O.sub.2
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=35 pulse groups per second, N=25 sparks per pulse group, P=240
microseconds, H=100 microseconds, and air flow rate is 5 L/min.
[0123] FIG. 21 shows NO and NO.sub.2 concentrations at various
reactant gas oxygen concentrations using an oxygen concentrator. In
this example, B=5 pulse groups per second, N=25 sparks per pulse
group, P=200 microseconds, H=60 microseconds, and air flow rate is
5 L/min.
[0124] FIG. 22 shows a test setup for measuring NO and NO.sub.2
levels in a hypobaric chamber 2200 at various atmospheric
pressures. The results of the test are shown in FIG. 23. To create
a negative pressure (e.g., 1/2 ATA, 1/3 ATA) inside the hypobaric
chamber 2200, inlet and outlet valves were closed and a piston
translated away from the spark plug. The spark plug was then fired
for 30 seconds. In this example, B=100 pulse groups per second,
N=10 sparks per pulse group, P=140 microseconds, and H=10
microseconds. The piston was then translated toward the spark plug
to bring the pressure in the hypobaric chamber 2200 back to 1 ATA.
The outlet valve was opened, and gas samples were collected in a 3
L respiratory bag by further translating the piston toward the
spark plug. The collected gas samples were analyzed with Sievers
NOA i280 immediately after collection.
[0125] Referring to FIG. 24, a flowchart 2400 represents an
arrangement of operations of the controller (e.g., controller 914,
shown in FIG. 9A). 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.
[0126] Operations include collecting 2402 information related to
one or more conditions of a respiratory system associated with a
patient. For example, one or more sensors of the monitor 804 of
FIG. 8 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 2404 one or more control parameters based on the
collected information. For example, the controller 914 of FIG. 9A
can determine one or more control parameters. The control
parameters may create a pulse train. Operations also include
initiating 2406 a series of electric arcs external to the patient
to generate nitric oxide based on the determined control
parameters. For example, the electrodes 906 of FIG. 9B 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.sub.2
generated by the series of electric arcs (e.g., amounts of NO and
NO.sub.2 previously generated).
[0127] FIG. 25 shows an example of example computer device 2500 and
example mobile computer device 2550, 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
914 of FIG. 9A) may be executed by the computer device 2500 and/or
the mobile computer device 2550. Computing device 2500 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 2550 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.
[0128] Computing device 2500 includes processor 2502, memory 2504,
storage device 2506, high-speed interface 2508 connecting to memory
2504 and high-speed expansion ports 2510, and low speed interface
2512 connecting to low speed bus 2514 and storage device 2506. Each
of components 2502, 2504, 2506, 2508, 2510, and 2512, are
interconnected using various busses, and can be mounted on a common
motherboard or in other manners as appropriate. Processor 2502 can
process instructions for execution within computing device 2500,
including instructions stored in memory 2504 or on storage device
2506 to display graphical data for a GUI on an external
input/output device, including, e.g., display 2516 coupled to high
speed interface 2508. 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 2500 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).
[0129] Memory 2504 stores data within computing device 2500. In one
implementation, memory 2504 is a volatile memory unit or units. In
another implementation, memory 2504 is a non-volatile memory unit
or units. Memory 2504 also can be another form of computer-readable
medium, including, e.g., a magnetic or optical disk.
[0130] Storage device 2506 is capable of providing mass storage for
computing device 2500. In one implementation, storage device 2506
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 2504, storage device 2506, memory on processor 2502, and the
like.
[0131] High-speed controller 2508 manages bandwidth-intensive
operations for computing device 2500, while low speed controller
2512 manages lower bandwidth-intensive operations. Such allocation
of functions is an example only. In one implementation, high-speed
controller 2508 is coupled to memory 2504, display 2516 (e.g.,
through a graphics processor or accelerator), and to high-speed
expansion ports 2510, which can accept various expansion cards (not
shown). In the implementation, low-speed controller 2512 is coupled
to storage device 2506 and low-speed expansion port 2514. The
low-speed expansion port, which can include various communication
ports (e.g., USB, Bluetooth.RTM., 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.
[0132] Computing device 2500 can be implemented in a number of
different forms, as shown in the figure. For example, it can be
implemented as standard server 2520, or multiple times in a group
of such servers. It also can be implemented as part of rack server
system 2524. In addition or as an alternative, it can be
implemented in a personal computer including, e.g., laptop computer
2522. In some examples, components from computing device 2500 can
be combined with other components in a mobile device (not shown),
including, e.g., device 2550. Each of such devices can contain one
or more of computing device 2500, 2550, and an entire system can be
made up of multiple computing devices 2500, 2550 communicating with
each other.
[0133] Computing device 2550 includes processor 2552, memory 2564,
an input/output device including, e.g., display 2554, communication
interface 2566, and transceiver 2568, among other components.
Device 2550 also can be provided with a storage device, including,
e.g., a microdrive or other device, to provide additional storage.
Each of components 2550, 2552, 2564, 2554, 2566, and 2568, are
interconnected using various buses, and several of the components
can be mounted on a common motherboard or in other manners as
appropriate.
[0134] Processor 2552 can execute instructions within computing
device 2550, including instructions stored in memory 2564. 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 2550, including, e.g., control of user interfaces,
applications run by device 2550, and wireless communication by
device 2550.
[0135] Processor 2552 can communicate with a user through control
interface 2558 and display interface 2556 coupled to display 2554.
Display 2554 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
2556 can comprise appropriate circuitry for driving display 2554 to
present graphical and other data to a user. Control interface 2558
can receive commands from a user and convert them for submission to
processor 2552. In addition, external interface 2562 can
communicate with processor 2542, so as to enable near area
communication of device 2550 with other devices. External interface
2562 can provide, for example, for wired communication in some
implementations, or for wireless communication in other
implementations, and multiple interfaces also can be used.
[0136] Memory 2564 stores data within computing device 2550. Memory
2564 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 2574 also can be provided
and connected to device 2550 through expansion interface 2572,
which can include, for example, a SIMM (Single In Line Memory
Module) card interface. Such expansion memory 2574 can provide
extra storage space for device 2550, or also can store applications
or other data for device 2550. Specifically, expansion memory 2574
can include instructions to carry out or supplement the processes
described above, and can include secure data also. Thus, for
example, expansion memory 2574 can be provided as a security module
for device 2550, and can be programmed with instructions that
permit secure use of device 2550. 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.
[0137] 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 2564, expansion memory 2574, and/or memory
on processor 2552, which can be received, for example, over
transceiver 2568 or external interface 2562.
[0138] Device 2550 can communicate wirelessly through communication
interface 2566, which can include digital signal processing
circuitry where necessary. Communication interface 2566 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 2568. In
addition, short-range communication can occur, including, e.g.,
using a Bluetooth.RTM., WiFi, or other such transceiver (not
shown). In addition, GPS (Global Positioning System) receiver
module 2570 can provide additional navigation- and location-related
wireless data to device 2550, which can be used as appropriate by
applications running on device 2550. Sensors and modules such as
cameras, microphones, compasses, accelerators (for orientation
sensing), etc. maybe included in the device.
[0139] Device 2550 also can communicate audibly using audio codec
2560, which can receive spoken data from a user and convert it to
usable digital data. Audio codec 2560 can likewise generate audible
sound for a user, including, e.g., through a speaker, e.g., in a
handset of device 2550. 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 2550.
[0140] Computing device 2550 can be implemented in a number of
different forms, as shown in the figure. For example, it can be
implemented as cellular telephone 2580. It also can be implemented
as part of smartphone 2582, personal digital assistant, or other
similar mobile device.
[0141] Various implementations of the systems and techniques
described here can be realized in digital electronic circuitry,
integrated circuitry, specially designed ASICs (application
specific integrated circuits), computer hardware, firmware,
software, and/or combinations thereof. 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.
[0142] These computer programs (also known as programs, software,
software applications or code) include machine instructions for a
programmable processor, and can be implemented in a high-level
procedural and/or object-oriented programming language, and/or in
assembly/machine language. 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.
[0143] 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.
[0144] 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.
[0145] The computing system can include clients and servers. A
client and server are generally remote from each other and
typically interact through a communication network. The
relationship of client and server arises by virtue of computer
programs running on the respective computers and having a
client-server relationship to each other.
[0146] In some implementations, the engines described herein can be
separated, combined or incorporated into a single or combined
engine. The engines depicted in the figures are not intended to
limit the systems described here to the software architectures
shown in the figures.
* * * * *