IP Library › Granted Patent US 12,383,692
Granted Patent B2
US 12,383,692 · App. 17/963,044 · Granted Aug 12, 2025

Systems and methods for synthesis of nitric oxide

Inventors: Warren Zapol (Cambridge, MA); Binglan Yu (Quincy, MA)
Assignee: The General Hospital Corporation
A61M16/12A61M16/009A61M16/1055A61M16/107C01B21/30C01B21/32A61M2016/0039A61M2016/1025A61M2016/1035A61M2202/0275
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,383,692
App. No.
17/963,044
Granted
Aug 12, 2025
Kind
B2
Abstract

Systems and methods for producing nitric oxide (NO) to be used in medical applications are provided. In some embodiments, systems and methods are provided for a NO generator that is capable of generating a desired concentration of NO to be provided to a respiratory system for inhalation by a patient.

Claims (27)

1. An apparatus for generating nitric oxide comprising:

one or more pairs of electrodes configured to generate a gas comprising nitric oxide from a fluid flowing to the one or more pairs of electrodes;

one or more sensors configured to measure at least one of a pressure, a temperature, and a humidity of the fluid flowing to the one or more pairs of electrodes; and

a controller in communication with the one or more pairs of electrodes and the one or more sensors and configured to supply an electrical signal to the electrodes that controls timing and sparking characteristics of the one or more pairs of electrodes to produce a concentration of nitric oxide generated by the one or more pairs of electrodes, the controller being configured to determine the timing and sparking characteristics based on measurements from the one or more sensors to generate a desired concentration of NO,

wherein the controller is configured to determine the timing and sparking characteristics by controlling a value of one or more of a number of spark groups per second (B), a number of individual sparks per group (N), a time between individual sparks (P), and a pulse duration of each individual wave in the spark group (H) based on the measurements from the one or more sensors,

wherein the controller is configured to calculate the value of the one or more of the B, N, P, and H using a model for generating the desired concentration of NO using the measurements from the one or more sensors.

2. The apparatus of claim 1 , wherein the controller is configured to calculate the value of the one or more of the B, N, P, and H based on at least one of the pressure, the temperature, and the humidity of the fluid flowing to the electrodes using information from the one or more sensors.

3. The apparatus of claim 1 , further comprising an NO sensor configured to measure the concentration of NO in the gas flowing from the one or more electrodes, and wherein the NO sensor provides feedback to the controller such that the controller is configured to alter the values of at least one of B, N, P, and H in response to the concentration of NO measured by the NO sensor deviating from the desired concentration of NO.

4. The apparatus of claim 1 , further comprising an ignition coil in communication with the controller and the one or more electrodes.

5. The apparatus of claim 4 , wherein the controller is configured to instruct the ignition coil to supply stored electrical energy to the one or more electrodes.

6. The apparatus of claim 1 , further comprising an inspiration sensor configured to provide an indication of inspiration.

7. The apparatus of claim 6 , wherein the controller is configured to supply the electrical signal to the one or more electrodes in response to detecting inspiration.

8. The apparatus of claim 1 , wherein the desired concentration of NO is between approximately 5 and 80 parts per million.

9. An apparatus for generating nitric oxide comprising:

one or more pairs of electrodes configured to generate a gas comprising nitric oxide from a fluid flowing to the one or more pairs of electrodes;

one or more sensors configured to measure at least one of a pressure, a temperature, and a humidity of the fluid flowing to the one or more pairs of electrodes; and

a controller in communication with the one or more pairs of electrodes and the one or more sensors and configured to supply an electrical signal to the electrodes that controls timing and sparking characteristics of the one or more pairs of electrodes to produce a concentration of nitric oxide generated by the one or more pairs of electrodes, the controller being configured to control the concentration of nitric oxide generated by the one or more pairs of electrodes by controlling one or more of a number of spark groups per second (B), a number of individual sparks per group (N), a time between individual sparks (P), and a pulse duration of each individual wave in the spark group (H) based on the measurements from the one or more sensors,

wherein the controller is configured to calculate the B, N, P, and H using a model for generating a desired concentration of NO with measurements from the one or more sensors.

10. The apparatus of claim 9 , wherein the controller is configured to calculate B, N, P, and H based on at least one of the pressure, the temperature, and the humidity of the fluid flowing to the electrodes using information from the one or more sensors.

11. The apparatus of claim 9 , wherein the desired concentration of NO is between approximately 5 and 80 parts per million.

12. The apparatus of claim 9 , wherein the one or more sensors includes a pressure sensor arranged upstream of the one or more electrodes to measure ambient pressure.

13. The apparatus of claim 9 , further comprising an NO sensor configured to measure the concentration of NO in the gas flowing from the one or more electrodes.

14. The apparatus of claim 13 , wherein the NO sensor provides feedback to the controller such that the controller is configured to alter the values of at least one of B, N, P, and H in response to the concentration of NO measured by the NO sensor deviating from a desired concentration of NO.

15. The apparatus of claim 9 , further comprising an ignition coil in communication with the controller and the one or more electrodes.

16. The apparatus of claim 15 , wherein the controller is configured to instruct the ignition coil to supply stored electrical energy to the one or more electrodes.

17. The apparatus of claim 9 , further comprising an inspiration sensor configured to provide an indication of inspiration.

18. The apparatus of claim 17 , wherein the controller is configured to supply the electrical signal to the one or more electrodes in response to detecting inspiration.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 11, 2022
From: ZAPOL, WARREN; YU, BINGLAN
To: GENERAL HOSPITAL CORPORATION, THE
Reel/Frame 061374/0215 →
Continuity (4)
Continuation 15520137
Provisional Application 62065825 · Oct 20, 2014
Provisional Application 62077806 · Nov 10, 2014
Related Publication 20230140163A1 · May 4, 2023
References Cited (220)
US 2485481A · Cotton · 1949 [cited by applicant]
US 2525938A · Peck · 1950 [cited by applicant]
US 2684448A · Nilles, Jr. · 1954 [cited by applicant]
US 3047370A · Avtges et al. · 1962 [cited by applicant]
US 3225309A · Phelps · 1965 [cited by applicant]
US 4287040A · Alamaro · 1981 [cited by applicant]
US 4500563A · Ellenberger et al. · 1985 [cited by applicant]
US 4505795A · Alamaro · 1985 [cited by applicant]
US 4680694A · Huynh et al. · 1987 [cited by applicant]
US 4695358A · Mizuno et al. · 1987 [cited by applicant]
US 4705670A · O'Hare · 1987 [cited by applicant]
US 4816229A · Jensen et al. · 1989 [cited by applicant]
US 4877589A · O'Hare · 1989 [cited by applicant]
US 5285372A · Huynh et al. · 1994 [cited by applicant]
US 5378436A · Endoh et al. · 1995 [cited by applicant]
US 5396882A · Zapol · 1995 [cited by applicant]
US 5413097A · Birenheide et al. · 1995 [cited by applicant]
US 5471977A · Olsson et al. · 1995 [cited by applicant]
US 5485827A · Zapol et al. · 1996 [cited by applicant]
US 5546935A · Champeau · 1996 [cited by applicant]
US 5558083A · Bathe et al. · 1996 [cited by applicant]
US 5573733A · Salama · 1996 [cited by applicant]
US 5692495A · Sheu · 1997 [cited by applicant]
US 5732693A · Bathe et al. · 1998 [cited by applicant]
US 5752504A · Bathe · 1998 [cited by applicant]
US 5839433A · Higenbottam · 1998 [cited by applicant]
US 5845633A · Psaros · 1998 [cited by applicant]
US 6000397A · Skog · 1999 [cited by applicant]
US 6089229A · Bathe et al. · 2000 [cited by applicant]
US 6109260A · Bathe · 2000 [cited by applicant]
US 6125846A · Bathe et al. · 2000 [cited by applicant]
US 6164276A · Bathe et al. · 2000 [cited by applicant]
US 6224653B1 · Shvedchikov et al. · 2001 [cited by applicant]
US 6250302B1 · Rantala · 2001 [cited by applicant]
US 6290683B1 · Erez et al. · 2001 [cited by applicant]
US 6296827B1 · Castor et al. · 2001 [cited by applicant]
US 6536429B1 · Pavlov et al. · 2003 [cited by applicant]
US 6581599B1 · Stenzler · 2003 [cited by applicant]
US 6668828B1 · Figley et al. · 2003 [cited by applicant]
US 6758214B2 · Fine et al. · 2004 [cited by applicant]
US 6920876B2 · Miller et al. · 2005 [cited by applicant]
US 6955171B1 · Figley et al. · 2005 [cited by applicant]
US 6955790B2 · Castor et al. · 2005 [cited by applicant]
US 6986351B2 · Figley et al. · 2006 [cited by applicant]
US 7025869B2 · Fine et al. · 2006 [cited by applicant]
US 7040313B2 · Fine et al. · 2006 [cited by applicant]
US 7122018B2 · Stenzler et al. · 2006 [cited by applicant]
US 7220393B2 · Miller et al. · 2007 [cited by applicant]
US 7255105B2 · Figley et al. · 2007 [cited by applicant]
US 7299785B1 · Lee · 2007 [cited by applicant]
US 7312584B2 · Tamita et al. · 2007 [cited by applicant]
US 7335181B2 · Miller et al. · 2008 [cited by applicant]
US 7485324B2 · Miller et al. · 2009 [cited by applicant]
US 7498000B2 · Pekshev et al. · 2009 [cited by applicant]
US 7516742B2 · Stenzler et al. · 2009 [cited by applicant]
US 7520866B2 · Stenzler et al. · 2009 [cited by applicant]
US 7531133B2 · Hole et al. · 2009 [cited by applicant]
US 7560076B2 · Rounbehler et al. · 2009 [cited by applicant]
US 7589473B2 · Suslov · 2009 [cited by applicant]
US 7744812B2 · Witherspoon et al. · 2010 [cited by applicant]
US 7776780B1 · Granite et al. · 2010 [cited by applicant]
US 7861717B1 · Krebs · 2011 [cited by applicant]
US 7955294B2 · Stenzler et al. · 2011 [cited by applicant]
US 8030849B2 · Suslov · 2011 [cited by applicant]
US 8043252B2 · Miller et al. · 2011 [cited by applicant]
US 8079998B2 · Hole et al. · 2011 [cited by applicant]
US 8151791B2 · Arlow et al. · 2012 [cited by applicant]
US 8282966B2 · Baldassarre et al. · 2012 [cited by applicant]
US 8291904B2 · Bathe et al. · 2012 [cited by applicant]
US 8293284B2 · Baldassarre et al. · 2012 [cited by applicant]
US 8344627B1 · Hooke et al. · 2013 [cited by applicant]
US 8431163B2 · Baldassarre et al. · 2013 [cited by applicant]
US 8518457B2 · Miller et al. · 2013 [cited by applicant]
US 8573209B2 · Bathe et al. · 2013 [cited by applicant]
US 8573210B2 · Bathe et al. · 2013 [cited by applicant]
US 8574531B2 · Miller et al. · 2013 [cited by applicant]
US 8717733B2 · Gefter et al. · 2014 [cited by applicant]
US 8776794B2 · Bathe et al. · 2014 [cited by applicant]
US 8776795B2 · Bathe et al. · 2014 [cited by applicant]
US 8790715B2 · Montgomery et al. · 2014 [cited by applicant]
US 8795222B2 · Stenzler et al. · 2014 [cited by applicant]
US 8795741B2 · Baldassarre · 2014 [cited by applicant]
US 8821828B2 · Hilbig et al. · 2014 [cited by applicant]
US 8846112B2 · Baldassarre · 2014 [cited by applicant]
US 9067788B1 · Spielman et al. · 2015 [cited by applicant]
US 9095534B2 · Stenzler et al. · 2015 [cited by applicant]
US 9265911B2 · Bathe et al. · 2016 [cited by applicant]
US 9279794B2 · Tolmie et al. · 2016 [cited by applicant]
US 9295802B2 · Bathe et al. · 2016 [cited by applicant]
US 9408993B2 · Bathe et al. · 2016 [cited by applicant]
US 9573110B2 · Montgomery et al. · 2017 [cited by applicant]
US 9770570B2 · Schnitman et al. · 2017 [cited by applicant]
US 9795756B2 · Flanagan et al. · 2017 [cited by applicant]
US 9982354B2 · Kim · 2018 [cited by applicant]
US 10239038B2 · Zapol et al. · 2019 [cited by applicant]
US 10646682B2 · Zapol et al. · 2020 [cited by applicant]
US 10773047B2 · Zapol et al. · 2020 [cited by applicant]
US 11007503B2 · Zapol et al. · 2021 [cited by applicant]
US 11497878B2 · Zapol et al. · 2022 [cited by applicant]
US 11617850B2 · Zapol et al. · 2023 [cited by applicant]
US 20010031230A1 · Castor et al. · 2001 [cited by applicant]
US 20010037810A1 · Fine · 2001 [cited by examiner]
US 20040019274A1 · Galloway, Jr. et al. · 2004 [cited by applicant]
US 20040028753A1 · Hedenstierna et al. · 2004 [cited by applicant]
US 20040031248A1 · Lindsey · 2004 [cited by applicant]
US 20040181149A1 · Langlotz et al. · 2004 [cited by applicant]
US 20050108813A1 · Plut · 2005 [cited by applicant]
US 20050172971A1 · Kolobow et al. · 2005 [cited by applicant]
US 20050218007A1 · Pekshev et al. · 2005 [cited by applicant]
US 20050263150A1 · Chathampally et al. · 2005 [cited by applicant]
US 20050281465A1 · Marquart et al. · 2005 [cited by applicant]
US 20060025700A1 · Fallik · 2006 [cited by applicant]
US 20060172018A1 · Fine et al. · 2006 [cited by applicant]
US 20060173396A1 · Hatamian et al. · 2006 [cited by applicant]
US 20060276844A1 · Alon et al. · 2006 [cited by applicant]
US 20070151561A1 · Laurila · 2007 [cited by applicant]
US 20070190184A1 · Montgomery et al. · 2007 [cited by applicant]
US 20070265877A1 · Rice et al. · 2007 [cited by applicant]
US 20080017030A1 · Fleck · 2008 [cited by applicant]
US 20080078382A1 · LeMahieu et al. · 2008 [cited by applicant]
US 20080135044A1 · Freitag et al. · 2008 [cited by applicant]
US 20080202509A1 · Dillon et al. · 2008 [cited by applicant]
US 20100108493A1 · Wada et al. · 2010 [cited by applicant]
US 20100122705A1 · Moenning, Jr. · 2010 [cited by applicant]
US 20100189808A1 · Gupta et al. · 2010 [cited by applicant]
US 20100245097A1 · Sung · 2010 [cited by applicant]
US 20100275911A1 · Arlow et al. · 2010 [cited by applicant]
US 20120037160A1 · Sung · 2012 [cited by applicant]
US 20120279500A1 · Singvogel et al. · 2012 [cited by applicant]
US 20120296265A1 · Dobrynin et al. · 2012 [cited by applicant]
US 20130123801A1 · Umasuthan et al. · 2013 [cited by applicant]
US 20130150863A1 · Baumgartner · 2013 [cited by applicant]
US 20140031668A1 · Mobasser et al. · 2014 [cited by applicant]
US 20140158121A1 · Flanagan et al. · 2014 [cited by applicant]
US 20140216452A1 · Miller et al. · 2014 [cited by applicant]
US 20140251787A1 · Montgomery et al. · 2014 [cited by applicant]
US 20140363525A1 · Montgomery et al. · 2014 [cited by applicant]
US 20150000659A1 · Martin · 2015 [cited by applicant]
US 20150004248A1 · Morfill et al. · 2015 [cited by applicant]
US 20150034084A1 · Av-Gay et al. · 2015 [cited by applicant]
US 20150044305A1 · Av-Gay et al. · 2015 [cited by applicant]
US 20150072023A1 · Greenberg et al. · 2015 [cited by applicant]
US 20150090261A1 · Crosbie · 2015 [cited by applicant]
US 20150174158A1 · Av-Gay et al. · 2015 [cited by applicant]
US 20150272988A1 · Av-Gay et al. · 2015 [cited by applicant]
US 20150320953A1 · Acker et al. · 2015 [cited by applicant]
US 20160022731A1 · Av-Gay et al. · 2016 [cited by applicant]
US 20160030699A1 · Zapol et al. · 2016 [cited by applicant]
US 20160038710A1 · Zapol et al. · 2016 [cited by applicant]
US 20160183841A1 · Duindam et al. · 2016 [cited by applicant]
US 20160191887A1 · Casas · 2016 [cited by applicant]
US 20160228670A1 · Av-Gay et al. · 2016 [cited by applicant]
US 20160243328A1 · Tolmie et al. · 2016 [cited by applicant]
US 20160324580A1 · Esterberg · 2016 [cited by applicant]
US 20160367775A1 · Tolmie et al. · 2016 [cited by applicant]
US 20170014571A1 · Deem et al. · 2017 [cited by applicant]
US 20170014591A1 · Tolmie et al. · 2017 [cited by applicant]
US 20170014592A1 · Tolmie et al. · 2017 [cited by applicant]
US 20170021124A1 · Tolmie et al. · 2017 [cited by applicant]
US 20170065631A1 · Av-Gay et al. · 2017 [cited by applicant]
US 20170143758A1 · Greenberg et al. · 2017 [cited by applicant]
US 20170239289A1 · Av-Gay et al. · 2017 [cited by applicant]
US 20180049622A1 · Ryan et al. · 2018 [cited by applicant]
US 20180125883A1 · Av-Gay et al. · 2018 [cited by applicant]
US 20180133246A1 · Av-Gay et al. · 2018 [cited by applicant]
US 20200094011A1 · Zapol et al. · 2020 [cited by applicant]
CN 1099997A · 1995 [cited by applicant]
CN 1730115A · 2006 [cited by applicant]
CN 101828432A · 2010 [cited by applicant]
EP 0621051A2 · 1994 [cited by applicant]
EP 0763500A2 · 1997 [cited by applicant]
EP 1036758A1 · 2000 [cited by applicant]
EP 1854494A1 · 2007 [cited by applicant]
EP 2151554A1 · 2010 [cited by applicant]
GB 2277689A · 1994 [cited by applicant]
JP H04132560A · 1992 [cited by applicant]
JP 2000102616A · 2000 [cited by applicant]
JP 2001517108A · 2001 [cited by applicant]
JP 2004065636A · 2004 [cited by applicant]
JP 2006273677A · 2006 [cited by applicant]
JP 2014179563A · 2014 [cited by applicant]
RU 2199167C1 · 2003 [cited by applicant]
WO 9507610A1 · 1995 [cited by applicant]
WO 2004032719A1 · 2004 [cited by applicant]
WO 2008112143A1 · 2008 [cited by applicant]
WO 2011002606A1 · 2011 [cited by applicant]
WO 2012094008A1 · 2012 [cited by applicant]
WO 2012155213A1 · 2012 [cited by applicant]
WO 2013052548A1 · 2013 [cited by applicant]
WO 2013070712A1 · 2013 [cited by applicant]
WO 2013181179A1 · 2013 [cited by applicant]
WO 2014085719A1 · 2014 [cited by applicant]
WO 2014143842A1 · 2014 [cited by applicant]
WO 2015066278A1 · 2015 [cited by applicant]
WO 2015127085A1 · 2015 [cited by applicant]
WO 2016064863A1 · 2016 [cited by applicant]
WO 2017165888A1 · 2017 [cited by applicant]
Encylopaedia Britannica, Inc., Definition of “Soda Lime”, https://www.britannica.com/science/soda-lime, Nov. 12, 2018, 1 page. [cited by applicant]
Gao et al., Natural Convection at Microelectrodes, Analytical Chemistry, 1995, 67(9):1541-1545. [cited by applicant]
Hanning et al., Fortnightly Review—Pulse Oximetry: A Practical Review, BMJ, 1995, 311:367-370. [cited by applicant]
Heli, Study on the Removal of Byproduct Nitrogen Dioxide from the Mixture of Inhaled Nitric Oxide Produced by Pulsed Arc Discharge, Thesis for Degree of Master of Engineering, Huazhong University of Science & Technology… [cited by applicant]
Hui, Research on the Production of Nitric Oxide by Pulsed Arc Discharge and the Curing of Respiratory Distress Instrument, Dissertation for Degree of Doctor of Philosophy in Engineering, Huazhong University of Science a… [cited by applicant]
Hui et al., The Effect of Flow Distribution on the Concentration of NO Produced by Pulsed Arc Discharge, Plasma Science and Technology, 2007, 9(6):766-769. [cited by applicant]
Intersurgical Complete Respiratory Systems, Carbon Dioxide Absorbents, Information Sheet, Issue 203.13, 8 pages. [cited by applicant]
Keshav, Using Plasmas for High-Speed Flow Control and Combustion Control, Dissertation for Degree of Doctor of Philosophy, The Ohio State University, 2008, 268 pages. [cited by applicant]
Kuo, Air Plasma for Medical Applications, Journal of Biomedical Science and Engineering, 2012, 5:481-495. [cited by applicant]
Li, et al., Production of Medically Useful Nitric Monoxide Using AC Arc Discharge, Nitric Oxide, 2018, 73:89-95. [cited by applicant]
Lorente, Chapter 20, Respiratory Filters and Ventilator-Associated Pneumonia: Composition, Efficacy Tests and Advantages and Disadvantages, In Humidification in the Intensive Care Unit, A.M. Esquinas (ed.), Springer-Ver… [cited by applicant]
Mok, et al., Application of Positive Pulsed Corona Discharge to Removal of SO2 and NOx, Proceedings, ICESP VII, Sep. 20-25, 1998, Kyongju, Korea, 8 pages. [cited by applicant]
Namihira et al., Production of Nitric Monoxide Using Pulsed Discharges for a Medical Application, IEEE Transactions on Plasma Science, 2000, 28(1):109-114. [cited by applicant]
Namihira, et al., Production of Nitric Oxide Using a Pulsed Arc Discharge, IEEE Transactions on Plasma Science, 2002, 30(5):1993-1998. [cited by applicant]
Yu et al., Detection and Removal of Impurities in Nitric Oxide Generated from Air by Pulsed Electrical Discharge, Nitric Oxide, Nov. 30, 2016, 60:16-23. [cited by applicant]
Yu et al., Development of a Portable Mini-Generator to Safely Produce Nitric Oxide for the Treatment of Infants with Pulmonary Hypertension, Nitric Oxide, May 1, 2018, 75:70-76. [cited by applicant]
PCT International Search Report, PCT/US2014/028439, Jul. 24, 2014, 2 pages. [cited by applicant]
PCT International Preliminary Report on Patentability, PCT/US2014/028439, Sep. 15, 2015, 13 pages. [cited by applicant]
PCT International Search Report, PCT/US2014/027986, Jul. 17, 2014, 2 pages. [cited by applicant]
PCT International Preliminary Report on Patentability, PCT/US2014/027986, Sep. 15, 2015, 11 pages. [cited by applicant]
PCT International Search Report and Written Opinion, PCT/US2015/056443, Jan. 6, 2016, 19 pages. [cited by applicant]
PCT International Search Report and Written Opinion, PCT/US2017/024331, Jun. 15, 2017, 21 pages. [cited by applicant]
PCT International Search Report and Written Opinion, PCT/US2021/036269, Nov. 22, 2021, 12 pages. [cited by applicant]