IP Library Granted Patent US 10,166,352
Granted Patent B2
US 10,166,352 · App. 15/256,053 · Granted Jan 1, 2019

Systems and methods for compensating long term sensitivity drift of electrochemical gas sensors exposed to nitric oxide

Inventors: Craig R. Tolmie (Stoughton, WI); Jeff Milsap (Cambridge, WI); Jaron M. Acker (Madison, WI)
Assignee: Mallinckrodt Hospital Products IP Limited
A61M16/0051A61M16/0003A61M16/024A61M16/085A61M16/1005A61M16/12A61M16/201G01N27/4163G01N33/0006G01N33/0008G01N33/0037A61M16/16A61M2016/102A61M2016/1035A61M2202/0275A61M2205/18A61M2205/27A61M2205/33A61M2205/502A61M2205/52A61M2205/581A61M2205/583A61M2205/70A61M2205/702Y02A50/245
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Quick Facts
Patent No.
US 10,166,352
App. No.
15/256,053
Granted
Jan 1, 2019
Kind
B2
Abstract

Described are systems and methods for compensating long term sensitivity drift of catalytic type electrochemical gas sensors used in systems for delivering therapeutic nitric oxide (NO) gas to a patient by compensating for drift that may be specific to the sensors atypical use in systems for delivering therapeutic nitric oxide gas to a patient. The long term sensitivity drift of catalytic type electrochemical gas sensors may be addressed using calibration schedules, which can factor in the absolute change in set dose of NO being delivered to the patient that can drive one or more baseline calibrations. The calibration schedules can be used to reduce the amount of times the sensor goes offline.

Claims (51)

1. A method for compensating nitric oxide sensor drift affiliated with therapeutic gas delivery, comprising:

delivering, via a flow control valve affiliated with a therapeutic gas delivery system, a predetermined dosage of therapeutic gas comprising nitric oxide to a breathing circuit for delivery to a patient;

detecting, via a system controller affiliated with the therapeutic gas delivery system, if an alarm is active or has been active within a predetermined timeframe at a time a nitric oxide sensor calibration is to be executed according to an identified sensor calibration schedule stored in a system controller memory, wherein the nitric oxide sensor calibration is postponed if the active alarm is detected or has been detected within the predetermined timeframe, and the nitric oxide sensor calibration is executed when the active alarm is not detected or has not been detected within the predetermined timeframe, wherein the nitric oxide sensor calibration schedule is modified based upon a change in the predetermined dosage of nitric oxide being delivered to the patient, and wherein the change in the predetermined dosage is an increase in the predetermined dosage, the nitric oxide sensor calibration occurs with a greater frequency;

continuously monitoring, via the nitric oxide sensor affiliated with the therapeutic gas delivery system, a signal indicative of a concentration of nitric oxide in the breathing circuit; and

determining a compensated response to the signal indicative of the nitric oxide concentration in the breathing circuit after the nitric oxide sensor calibration occurs.

2. The method of claim 1 , further comprising:

retrieving a baseline calibration value, the baseline calibration value corresponding to a known output concentration of therapeutic gas at a specified output current; and

retrieving a slope associated with the baseline calibration value, the slope corresponding to a correlation between measured output current at specific output concentrations;

the method further comprising utilizing the previous value of the slope to determine a set of correlated values between voltages and nitric oxide.

3. The method of claim 2 , wherein determining a compensated response further comprises:

storing, in memory affiliated with the therapeutic gas delivery system, expected signals from the nitric oxide sensor correlated to nitric oxide concentrations in the breathing circuit;

determining, via the system controller affiliated with the therapeutic gas delivery system, signal drift between (i) a signal received from the nitric oxide sensor during the nitric oxide calibration indicative of zero concentration nitric oxide and (ii) an expected signal, stored in memory affiliated with the therapeutic gas delivery system, from the nitric oxide sensor when exposed to zero concentration nitric oxide; and

offsetting the expected signals from the nitric oxide sensor correlated to nitric oxide concentrations in the breathing circuit by the determined signal drift of the nitric oxide sensor.

4. The method of claim 3 , further comprising postponing the execution of the nitric oxide sensor calibration by a predetermined time period if (i) the presence of interfering gas is detected and/or (ii) if a user is interacting with or has interacted with the therapeutic gas delivery system within a predetermined timeframe at the time the nitric oxide sensor calibration is intended to be executed.

5. The method of claim 2 , wherein the calibration includes:

interrupting the continuous monitoring of the signal indicative of nitric oxide concentration according to the identified sensor calibration schedule;

exposing the nitric oxide sensor to a gas having a zero concentration of nitric oxide for a period of time sufficient to detect the output signal indicative of the zero concentration; and

determining the response by the nitric oxide sensor to the gas having a zero concentration of nitric oxide.

6. The method of claim 5 , wherein the identified sensor calibration schedule comprises a set of signals representing intended intervals between interruptions of the continuous monitoring of the signal indicative of nitric oxide concentration.

7. The method of claim 6 , wherein the intended intervals are larger for a smaller change in the setting in the system controller.

8. The method of claim 5 , further comprising:

storing the signal, received from the nitric oxide sensor during the nitric oxide calibration indicative of zero concentration of nitric oxide, in the system controller memory affiliated with the therapeutic gas delivery system.

9. The method of claim 8 , further comprising:

accessing a slope of a previous calibration line stored in the memory affiliated with the therapeutic gas delivery system, and generating a new calibration line using the stored signal received from the nitric oxide sensor during the nitric oxide calibration indicative of zero concentration nitric oxide and the slope of a previous calibration line.

10. The method of claim 5 , further comprising postponing the execution of the nitric oxide sensor calibration by a predetermined time period if (i) the presence of interfering gas is detected and/or (ii) if a user is interacting with or has interacted with the therapeutic gas delivery system within a predetermined timeframe at the time the nitric oxide sensor calibration is intended to be executed.

11. The method of claim 5 , further comprising:

communicating to a user when (i) monitoring the concentration of nitric oxide in the breathing circuit with the nitric oxide sensor is interrupted and/or (ii) performing the nitric oxide sensor calibration.

12. The method of claim 5 wherein the nitric oxide sensor is a first nitric oxide sensor, further comprising:

monitoring the concentration of nitric oxide in the breathing circuit with a second nitric oxide sensor when monitoring the concentration of nitric oxide in the breathing circuit with the first nitric oxide sensor is interrupted, whereby communication of the nitric oxide concentration to a user during calibration is enabled.

13. The method of claim 12 , further comprising

exposing the second nitric oxide sensor to the gas having a zero concentration of nitric oxide for the period of time sufficient to de-saturate and/or detect the output signal indicative of the zero concentration after exposing the first nitric oxide sensor to the gas having a zero concentration of nitric oxide for the period of time sufficient to de-saturate and/or detect the output value indicative of the zero concentration; and

comparing the signal from the second nitric oxide sensor to the signal of the first nitric oxide sensor to determine the difference in drift between the first nitric oxide sensor and the second nitric oxide sensor.

14. The method of claim 1 , further comprising:

identifying the type of nitric oxide sensor continuously monitoring the signal indicative of the concentration of nitric oxide in the breathing circuit;

storing the type of nitric oxide sensor in the memory affiliated with the therapeutic gas delivery system; and

utilizing the type of nitric oxide sensor in identifying the sensor calibration schedule.

15. The method of claim 14 , wherein the nitric oxide sensor is a three terminal electrochemical nitric oxide gas sensor or a four terminal electrochemical nitric oxide gas sensor.

16. The method of claim 15 , further comprising:

exposing the nitric oxide sensor to ambient air when interrupting the continuous monitoring of the signal indicative of the concentration of nitric oxide in the breathing circuit while a sample line from an inspiratory side of the patient breathing circuit is connected to the therapeutic gas delivery system.

17. The method of claim 15 , which further comprises switching a valve in fluid communication with the patient breathing circuit to expose the nitric oxide sensor to ambient air when interrupting the continuous monitoring of the signal indicative of the concentration of nitric oxide in the breathing circuit while a sample line from an inspiratory side of the patient breathing circuit is connected to the therapeutic gas delivery system.

18. The method of claim 17 , which further comprises verifying the valve has switched to expose the nitric oxide sensor to ambient air.

19. A method for compensating for output drift of an electrochemical gas sensor exposed to nitric oxide during therapeutic gas delivery, comprising:

delivering, via a flow control valve, a predetermined dosage of therapeutic gas comprising nitric oxide to a breathing circuit for delivery to a patient in need thereof;

detecting, via the system controller, if an alarm is active or has been active within a predetermined timeframe at the time the calibration is to be executed according to an identified sensor calibration schedule stored in a system controller memory, wherein the calibration is postponed when the active alarm is detected or has been detected within the predetermined timeframe;

detecting, via the system controller, if a user is interacting with or has interacted with the therapeutic gas delivery system within a predetermined timeframe at the time the calibration is to be executed, wherein the calibration is postponed when the user is interacting with or has interacted with the therapeutic gas delivery system within the predetermined timeframe; and

executing, via the system controller, the calibration (i) when the active alarm is not detected or has not been detected within the predetermined timeframe, and (ii) when the user is not interacting or has not interacted with the therapeutic gas delivery system within the predetermined timeframe, wherein the calibration schedule is modified based upon a change in the predetermined dosage of nitric oxide being delivered to the patient, and wherein the change in the predetermined dosage is an increase in the predetermined dosage, the nitric oxide sensor calibration occurs with a greater frequency.

20. A method for compensating for output drift of an electrochemical gas sensor exposed to nitric oxide in a controlled environment, compromising:

delivering, via a flow control valve, a predetermined dosage of therapeutic gas comprising nitric oxide to a breathing circuit for delivery to a patient in need thereof;

detecting, via the system controller, if an alarm is active or has been active within a predetermined timeframe at the time the calibration is to be executed according to an identified sensor calibration schedule stored in a system controller memory, wherein the calibration is postponed when the active alarm is detected or has been detected within the predetermined timeframe, wherein the calibration schedule is modified based upon a change in the predetermined dosage of nitric oxide being delivered to the patient, and wherein the change in the predetermined dosage is an increase in the predetermined dosage, the nitric oxide sensor calibration occurs with a greater frequency;

executing, via the system controller, the calibration when the active alarm is not detected or has not been detected within the predetermined timeframe; and

displaying, via a display, a message to a user, when executing the calibration, indicating that the calibration is in effect and/or recording in an electronic medical record (EMR) the occurrence of calibration, whereby the user is informed of the system's activity.

Assignments (21)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2026
From: MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY
To: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED COMPANY
Reel/Frame 075393/0361 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 73375 FRAME 395. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 075021/0263 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF US PATENT 10828415 AND REMOVE IT FROM THE LISTING PREVIOUSLY RECORDED ON REEL 72331 FRAME 1. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Mar 6, 2026
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 075021/0204 →
SECURITY INTEREST Recorded Oct 28, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: GOLDMAN SACHS BANK USA, AS ADMINISTRATIVE AGENT
Reel/Frame 073375/0395 →
RELEASE OF SECURITY INTEREST Recorded Aug 14, 2025
From: ACQUIOM AGENCY SERVICES LLC
To: SPECGX LLC; MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; OCERA THERAPEUTICS LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC
Reel/Frame 072324/0740 →
SECURITY INTEREST Recorded Aug 1, 2025
From: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 072331/0001 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 043601, FRAME 0025 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS LLC (F/K/A MALLINCKRODT US HOLDINGS INC.); MALLINCKRODT CARRIBEAN, INC.; MALLINCKRODT US POOL LLC; MNK 2011 LLC (F/K/A MALLINCKRODT INC.); LUDLOW LLC (F/K/A LUDLOW CORPORATION); CNS THERAPEUTICS, INC.; MALLINCKRODT ENTERPRISES HOLDINGS LLC (F/K/A MALLINCKRODT ENTERPRISES HOLDINGS, INC.); MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS LLC (F/K/A MALLINCKRODT BRAND PHARMACEUTICALS, INC.); MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC.; MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC (F/K/A VTESSE INC.); MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING D.A.C.); INFACARE PHARMACEUTICAL CORPORATION; ST SHARED SERVICES LLC; THERAKOS, INC.; IKARIA THERAPEUTICS LLC; INO THERAPEUTICS LLC
Reel/Frame 065610/0233 →
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 060434, FRAME 0536 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; VTESSE LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; SUCAMPO PHARMA AMERICAS LLC
Reel/Frame 065601/0347 →
SECURITY INTEREST Recorded Nov 15, 2023
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; OCERA THERAPEUTICS LLC; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC
To: ACQUIOM AGENCY SERVICES LLC
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RELEASE OF SECURITY INTERESTS IN PATENTS AT REEL 060389/FRAME 0913 Recorded Nov 15, 2023
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); MALLINCKRODT LLC; MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY; SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
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NOTICE OF GRANT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Jun 22, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY
To: DEUTSCHE BANK AG NEW YORK BRANCH
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RELEASE OF SECURITY INTEREST Recorded Jun 17, 2022
From: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
To: OCERA THERAPEUTICS, INC.; MALLINCKRODT LLC; MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY); SPECGX LLC; STRATATECH CORPORATION; VTESSE LLC (F/K/A VTESSE INC.)
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SECURITY INTEREST Recorded Jun 17, 2022
From: MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; SPECGX LLC; OCERA THERAPEUTICS, INC.; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC; MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
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SECURITY INTEREST Recorded Dec 10, 2019
From: MALLINCKRODT ARD IP LIMITED; MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED; SPECGX LLC; OCERA THERAPEUTICS, INC.; MALLINCKRODT PHARMA IP TRADING DESIGNATED ACTIVITY COMPANY; STRATATECH CORPORATION; VTESSE INC.; MALLINCKRODT LLC
To: WILMINGTON SAVINGS FUND SOCIETY, FSB, AS SECOND LIEN COLLATERAL AGENT
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NOTICE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Aug 18, 2017
From: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 043601/0025 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: TOLMIE, CRAIG R.; MILSAP, JEFF; ACKER, JARON M.
To: INO THERAPEUTICS LLC
Reel/Frame 040200/0857 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: MALLINCKRODT PHARMA IP TRADING DAC
To: MALLINCKRODT IP
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: MALLINCKRODT CRITICAL CARE FINANCE INC.
To: MALLINCKRODT PHARMA IP TRADING DAC
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ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: THERAKOS, INC.
To: MALLINCKRODT CRITICAL CARE FINANCE INC.
Reel/Frame 040201/0139 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: INO THERAPEUTICS LLC
To: THERAKOS, INC.
Reel/Frame 040201/0045 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2016
From: MALLINCKRODT IP
To: MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED
Reel/Frame 040201/0843 →
Continuity (4)
Continuation 15010999 · Jan 29, 2016
Continuation 14626409 · Feb 19, 2015
Provisional Application 61941725 · Feb 19, 2014
Related Publication 20160367775A1 · Dec 22, 2016