Nitrogen dioxide storage cassette

Abstract

To provide systems and methods for the storage and delivery of a gas including at least 1% nitric oxide.SOLUTION: A nitric oxide delivery system can include a cassette which is a single-use disposable component. The cassette is used to store liquid N2O4, activate upon operator demand, convert N2O4 to NO2 via a heating element(s) controlled by a console to deliver NO2 at a controlled flow rate, direct concentrated NO2 to a contained pair of conversion cartridges and exhaust NO gas to the console for delivery to a patient.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Claim of Priority) This application claims priority to U.S. Patent Application No. 62 / 066,345, filed Oct. 20, 2014, which is hereby incorporated by reference in its entirety under 35 U.S.C. § 119(e).

[0002] (Technical Field) The present invention relates to systems and methods for the storage and delivery of gases containing at least 1% nitric oxide.

Background Art

[0003] (Background) Some disorders or physiological conditions can be modulated by the inhalation of nitric oxide. The use of low concentrations of inhaled nitric oxide can, but is not limited to, prevent, reverse, or limit the progression of disorders including, but not limited to, acute pulmonary vasoconstriction, trauma, aspiration or inhalation injury, fat embolism in the lung, acidosis, pneumonia, adult respiratory distress syndrome, acute pulmonary edema, acute mountain sickness, acute pulmonary hypertension after cardiac surgery, persistent pulmonary hypertension of the newborn, perinatal asphyxia syndrome, hyaline membrane disease, acute pulmonary thromboembolism, heparin-protamine reaction, sepsis, asthma and status asthmaticus, or hypoxia. Nitric oxide can also be used to treat chronic pulmonary hypertension, bronchopulmonary dysplasia, chronic pulmonary thromboembolism, and idiopathic or primary pulmonary hypertension, or chronic hypoxia.

[0004] Generally, nitric oxide can be delivered to each lung by inhalation or other means. By supplying a therapeutic amount of NO, patients with disorders or physiological conditions that can be modulated by the inhalation of NO ​Can be treated, or supplement or Minimize its necessity. Typically, NO gas can be supplied in the form of a gas diluted with nitrogen gas (N2) and filled in a cylinder. Since NO can be oxidized to nitrogen dioxide (NO2) in the presence of O2, great care must be taken to ensure that even a trace amount of oxygen (O2) does not exist in the tank of NO gas. Unlike NO, NO2 gas at ppm levels is highly toxic when inhaled and can produce nitric acid and nitrous acid in the lungs. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEM

[0005] (Overview) Generally, a cassette for converting nitrogen dioxide to nitric oxide includes a sealed housing and a first cartridge capable of converting nitrogen dioxide gas to nitric oxide within the sealed housing, the first cartridge comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, the porous solid matrix being disposed within the first cartridge such that a space exists between the body of the first cartridge and the porous solid matrix, the porous solid matrix having an open passage parallel to the length of the body of the first cartridge, the first cartridge; and a second cartridge capable of converting nitrogen dioxide gas to nitric oxide, the outlet of the first cartridge being connected to the inlet of the second cartridge, the second cartridge comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, the porous solid matrix being ​​​​​​​​​​​​​It is arranged in the first cartridge such that there is a space between it and the matrix, and the porous solid matrix has an opening passage parallel to the length of the body of the first cartridge. the second cartridge; and an inactivation chamber containing an inactivating substance. It can be provided with.

[0006] In a particular embodiment, this space has a width, which is the distance between the surface of the porous solid matrix and the receptacle, and the width of this space can vary along the length of the receptacle. The inlet is configured to receive a gas flow, and the diverter directs the gas flow into the space between the body and the porous solid matrix, and the gas flow is in fluid communication with the outlet through the porous solid matrix to convert nitrogen dioxide in the gas flow into nitric oxide.

[0007] In other embodiments, the width of this space decreases along a part of the length of the receptacle. .

[0008] In other embodiments, the width of this space increases along a part of the length of the receptacle. .

[0009] In other embodiments, the width of this space increases along a part of the length of the receptacle from the inlet to approximately the midpoint of the receptacle, and the width of this space decreases along a part of the length of the receptacle from approximately the midpoint of the receptacle to the outlet. .

[0010] In other embodiments, the sealed housing further comprises a storage device for N2O4 and NO2.

[0011] In other embodiments, the storage device is included in a shuttle tube, and the tube stabilizes the storage device. .

[0012] In other embodiments, the shuttle tube is arranged such that the inactivation chamber opens into the storage device during transportation.

[0013] In other embodiments, the inactivating substance permanently changes color when the storage device is destroyed.

[0014] In other embodiments, the sealed housing further comprises a restrictor.

[0015] In other embodiments, the restrictor connects the storage device and the first cartridge.

[0016] In other embodiments, the sealed housing further comprises a heater.

[0017] In other embodiments, the heater is wound around the storage device and adjusts the emission amount of nitrogen dioxide gas by changing the temperature of the storage device.

[0018] In other embodiments, the cassette is discarded after being used once.

[0019] In other embodiments, the cassette is further connected to the console, and the console adjusts the heater.

[0020] Generally, a storage device for liquid nitrogen dioxide can comprise a container containing an ampoule, an ampoule containing liquid nitrogen dioxide, which is converted to nitrogen monoxide when the ampoule is broken, a restrictor whose proximal end faces the ampoule and whose distal end provides an outlet for nitrogen monoxide gas, a leak valve connected to the ampoule, and a shuttle tube containing the ampoule.

[0021] ​​​​​​​In certain embodiments, the shuttle tube is connected to the restrictor when the user breaks the ampoule. It is restricted.

[0022] In other embodiments, the storage device is further connected to a heater.

[0023] In other embodiments, the heater is activated when the user breaks the ampoule.

[0024] In other embodiments, the storage device is further connected to the inactivation chamber via a leak valve. It is.

[0025] In other embodiments, the shuttle rotates to connect the ampoule to either the inactivation chamber or the restrictor. Either one.

[0026] In other embodiments, the storage device is further connected to a mixing T fitting.

[0027] In other embodiments, air flows into the mixing T fitting.

[0028] In other embodiments, the volume of the storage device is 0.53 mL or less.

[0029] In other embodiments, the storage device is contained within a sealed housing.

[0030] In other embodiments, the sealed housing is a first cartridge capable of converting nitrogen dioxide gas to nitrogen monoxide within the sealed housing, comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, the porous solid matrix being disposed within the first cartridge such that there is a space between the body of the first cartridge and the porous solid matrix, the porous solid matrix being the body of the first cartridge so that there is a space between the body of the first cartridge and the porous solid matrix, the porous solid matrix being disposed within the first cartridge, the porous solid matrix being the body of the first cartridge of the first cartridge and the porous solid matrix, the porous solid matrix being disposed within the first cartridge such that there is a space between the body of the first The first cartridge having an opening passage parallel to the length of the body, and nitrogen dioxide gas to monoxide A second cartridge capable of converting to nitrogen, the outlet of the first cartridge and The inlet of the second cartridge is connected, and the second cartridge includes an inlet, a diverter, a body, An outlet, and a porous solid matrix containing a reducing agent, the porous solid matrix A space exists between the body of the second cartridge and the porous solid matrix Disposed within the second cartridge such that, the porous solid matrix The second cartridge having an opening passage parallel to the length of the body of the second cartridge; further comprising an inactivation chamber containing an inert substance.

[0031] In other embodiments, this space has a width, which is the distance between the surface of the porous solid matrix and The receptacle, and the width of the space varies along the length of the receptacle The inlet is configured to receive a gas stream, the diverter directs the gas stream into the space between the body and the porous solid Matrix, and the gas stream is in fluid communication with the outlet through the porous solid matrix to convert nitrogen dioxide in the gas stream to nitrogen monoxide.

[0032] In other embodiments, the width of this space decreases along a portion of the length of the receptacle

[0033] In other embodiments, the width of this space increases along a portion of the length of the receptacle

[0034] In other embodiments, the width of this space increases along a portion of the length of the receptacle from the inlet to approximately the midpoint of the receptacle The width of this space decreases from approximately the midpoint of the receptacle It decreases along a part of the length of the receptacle to the outlet.

[0035] Other aspects, embodiments, and features will become apparent from the following description, the drawings, and the claims. will be. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] (Brief description of the drawings)

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Mode for Carrying Out the Invention

[0037] (Detailed Description) When delivering nitric oxide (NO) to a mammal for therapeutic use, it may be important to avoid delivering nitrogen dioxide (NO2) to the mammal. Nitrogen dioxide (NO2) can be produced by the oxidation of nitric oxide (NO) with oxygen ( O2). The production rate of nitrogen dioxide (NO2) can be proportional to the value obtained by multiplying the oxygen ( O2) concentration by the square of the nitric oxide (NO) concentration. The NO delivery system can convert nitrogen dioxide (NO2) to nitric oxide (NO). In addition, nitric oxide can produce nitrogen dioxide at high concentrations.

[0038] Referring to Figure 1, there are existing platforms for delivering nitric oxide. For example , a standard platform that is used can include a gas cylinder 100 containing 800 ppm of NO in nitrogen (N2) (Figure 1). The nitric oxide / nitrogen gas can be released from the gas cylinder 100, and the pressure and flow rate of the gas can be adjusted using the gas flow regulator 105 and / or the valve 110 . When using the gas cylinder platform, the NO emission 115 is determined by the nitrogen dioxide concentration in the gas cylinder 100 and cannot be changed by the user. For example, if the gas cylinder contains 80 ppm of NO2 in air or oxygen, the emission can be 80 ppm of NO2 in air or oxygen. The gas can typically be supplied at a pressure of 2000 psi (13.79 MPa) or higher. Typically, the gas cylinder contains at least 99.9% of N2 。The gas cylinder platform can function well, but it may be large and heavy because it can include heavy aluminum or stainless steel gas pressure cylinders, gas flow regulators, and flow control devices, making it difficult to handle. Examples of commercially available platforms are those manufactured by Ikaria, two of which are INOvent and INOmax DS. Both of these systems use gas cylinders filled with NO diluted with nitrogen (N2), mix the NO with oxygen-enriched air, and supply inhaled NO gas. Both of these systems are designed to cooperate with ventilators in hospital intensive care units and are not suitable for portable or home use. Referring to Figure 2, as another example, the platform can be a stand-alone gas cylinder platform. The gas cylinder platform 200 can include a gas cylinder 205, a gas flow regulator 210, and a GeNO cartridge 215. The exhaust from the gas cylinder can be delivered to the GeNO cartridge, where one of the oxygen atoms in NO2 is removed by a reducing agent, such as ascorbic acid, to produce ultra-high purity NO. The GeNO cartridge is described in more detail below and is also described in U.S. Patent Application Nos. 12 / 500,929, 12 / 541,144, 12 / 619,959, and 12 / 951,811, and U.S. Patent No. 7,560,076, the entire contents of which are incorporated herein by reference. This platform has already been approved by the FDA for use in two clinical trials on human patients.

[0039] Examples of commercially available platforms are those manufactured by Ikaria, two of which are INOvent and INOmax DS. Both of these systems use gas cylinders filled with NO diluted with nitrogen (N2), mix the NO with oxygen-enriched air, and supply inhaled NO gas. Both of these systems are designed to cooperate with ventilators in hospital intensive care units. These platforms are not suitable for portable or home use.

[0040] Referring to Figure 2, as another example, the platform can be a stand-alone gas cylinder platform. The gas cylinder platform 200 can include a gas cylinder 205, a gas flow regulator 210, and a GeNO cartridge 215. The exhaust from the gas cylinder can be delivered to the GeNO cartridge, where one of the oxygen atoms in NO2 is removed by a reducing agent, such as ascorbic acid, to produce ultra-high purity NO. The GeNO cartridge is described in more detail below and is also described in U.S. Patent Application Nos. 12 / 500,929, 12 / 541,144, 12 / 619,959, and 12 / 951,811, and U.S. Patent No. 7,560,076, the entire contents of which are incorporated herein by reference. This platform has already been approved by the FDA for use in two clinical trials on human patients. U.S. Patent Application Nos. 12 / 500, 929, 12 / 541,144, 12 / 619,959, and 12 / 951,811, and U.S. Patent No. 7,560,076 are also described herein, and the entire contents of each are incorporated herein by reference. This platform has already been approved by the FDA for use in two clinical trials on human patients. This platform has already been approved by the FDA for use in two clinical trials on human patients.

[0041] Another variation for delivering NO starts with a NO2 gas concentration of up to 2,000 ppm in air or oxygen and can be diluted to 80 ppm of NO2. This procedure will be more complex as it may require precise mass flow controllers and instrumentation to obtain a stable mixing ratio. As noted above, a disadvantage of the gas cylinder platform is that the platform can be large and heavy. This platform will also be inconvenient for use in long-term therapy as a portable platform. Gas cylinders will also be difficult to handle when used in limited spaces such as intensive care units, hospitals, or homes. In addition, gas cylinders need to be strapped down to prevent them from tipping over and causing physical injury. Also, a tipped cylinder can damage the flow regulator and cause a sudden jet of gas from the opening, causing the heavy cylinder to become a missile that can penetrate walls repeatedly and lead to injury or death. Thus, there is a need for a nitric oxide delivery platform that can be equipped with a small and portable nitric oxide source for use as a portable or home use.

[0042]

[0043] The cassette can be a fully integrated single-use disposable component that stores liquid N2O4, operates in response to the operator's request (by breaking a glass ampule), converts N2O4 to NO2 by a heating element(s) controlled by the console, delivers the NO2 at a controlled flow rate, directs the concentrated NO2 to a pair of included conversion cartridges, and can exhaust NO gas to the console for delivery to the patient.

[0044] ​​​​​​​​​​​​​​Referring to FIGS. 3A to 3D, FIG. 3A is a schematic diagram of a cassette comprising two main cartridges 301, a liquid module 302 including an N2O4 ampoule and a shutter mechanism, and a restrictor column assembly 303. In FIG. 3B, the inactivation chamber 304 connects the two main cartridges. The cover 306 is transparent so that the color change of the neutralizing substance can be seen. The contacts 305 of the heater and the thermistor are at the opposite end of the cover. FIG. 3C shows the base 310 of the cassette with an access port. The access port is covered with a foil seal before use. FIG. 3D shows the layout of the base of the cassette with a purge inlet 312, a purge outlet 313, an air inlet 314, a first main cartridge ridge inlet 315, a second main cartridge inlet 316, and a restrictor "T" 317. Safety features incorporated in the cassette The cassette can provide safety elements for limiting the emission of NO and NO2 gases to the atmosphere and converting the NO and NO2 gases. The liquid module can provide sufficient safety features to limit the exposure of the user or transporter of the device to NO2. The cassette can comprise the following protective elements for protecting the transporter and the user from exposure to NO2 gas: Glass ampoule - Safety number 1 The N2O4 can be stored in a glass vial in liquid form. The maximum volume of N2O4 contained in the glass ampoule can be set to 0.53 ml, which is lower than the EPA limit (established for accidental failure of a NO2 gas cylinder in the case of accidental human exposure - NO2) in the event of a sudden failure.

[0045]

[0046]

[0047] ​​​​​​​​​​​​​ occurs. Environmental exposure to liquid N2O4 is low when the gas is significantly heated to convert to NO2 compared to an immediate release into the room due to a failure of the NO2 gas flow regulator with the contents under high pressure and can diffuse into the room at a slow rate. The glass ampoule can be fixed to the shuttle with a Teflon shrink tube which can provide a number of advantages: (a) stabilizing the glass ampoule during transport and damping vibrations; (b) providing a barrier to contain glass fragments .

[0048] Shuttle Seal - Safety Numbers 2A and 2B and 3A and 3B The glass ampoule can be included within a two - position component that can break the glass and seal back and forth against both ends (discharge or inactivation) of the liquid container - each end having a different function. A double - leak - proof safety seal is attached to both ends of the shuttle. The inactivation seal can control the gas flow into the inactivation chamber of the liquid module. The discharge seal controls the gas flow to the patient. The shuttle is manually positioned to direct the gas flow to the inactivation side or the discharge side. The seal is designed to provide redundancy by combining both a radial seal and a Luer seal that fits the polished exhaust port .

[0049] Inactivation Chamber - Safety Number 4 The shuttle mechanism can be positioned with the inactivation chamber open to the liquid container during transport of the product. If the glass ampoule is broken during transport, all the contents within the liquid container can be directed to a neutralizing substance to inactivate the NO2 gas by a chemical reaction. To this ​​​​​​​​​Furthermore, additional safety means for the cassette are provided. In addition, the inactivating substance can undergo a permanent discoloration which can be visually recognized through the window of the cassette, thereby providing an indication to the user that the cassette should no longer be used as it is no longer functional.

[0050] Slow leak valve - Safety number 5 The product can be transported with the inactivation seal open so as to provide direct communication between the liquid chamber and the inactivating substance. If the glass vial is broken during transportation, NO2 gas can be directed to the inactivating substance for neutralization. The gas flow rate to the inactivation chamber can be adjusted to control the rise in reaction temperature and provide sufficient time for the inactivation reaction to occur. The slow leak valve can provide an additional safety function of reducing the discharge rate of NO2 gas into the environment in case of a sudden failure.

[0051]

[0052] Schrader valve (Figure 4) - Safety numbers 6A and 6B There may be three access ports (and a DC power heater connector) on the base of the cassette: for indoor air pump inflow, NO gas outflow, and purge inflow. All high-concentration NO2 gas piping is included within the cassette to reduce environmental exposure due to leaks.

[0053] Referring to Figure 4, both the air inlet port and the NO gas outlet port can provide a redundant seal independent of the shuttle mechanism of the liquid container in case the outlet seal fails. These seals are actuated when the cassette is inserted into the console and the system is operating with the air pump inlet probe and the NO gas outlet probe inserted into the cassette. ​​​​​​​​​ It can be. The Schrader - type seal is normally closed by a spring load and is mechanically moved when a probe is introduced from the console. When the probe is removed from the cassette, the Schrader seal automatically returns to the closed position. Figure 4 shows the Schrader valve 401, the console access 402, the foil seal 403, and the spring(s) 404. The Schrader - type seal is normally closed by a spring load and is mechanically moved when a probe is introduced from the console. When the probe is removed from the cassette, the Schrader seal automatically returns to the closed position. Figure 4 shows the Schrader valve 401, the console access 402, the foil seal 403, and the spring(s) 404. When the probe is removed from the cassette, the Schrader seal automatically returns to the closed position. Figure 4 shows the Schrader valve 401, the console access 402, the foil seal 403, and the spring(s) 404. When the probe is removed from the cassette, the Schrader seal automatically returns to the closed position. Figure 4 shows the Schrader valve 401, the console access 402, the foil seal 403, and the spring(s) 404.

[0054] Tamper - proof seal - Safety numbers 7 and 8 The base of the cassette can be provided with a foil seal that covers the indoor air pump inlet port and the NO gas outlet port. This seal can be punctured during the operation of the system (insertion of the probe into the cassette) and provides an opening - indicating seal against incorrect opening of the Schrader seal by the user. The base of the cassette can be provided with a foil seal that covers the indoor air pump inlet port and the NO gas outlet port. This seal can be punctured during the operation of the system (insertion of the probe into the cassette) and provides an opening - indicating seal against incorrect opening of the Schrader seal by the user. The base of the cassette can be provided with a foil seal that covers the indoor air pump inlet port and the NO gas outlet port. This seal can be punctured during the operation of the system (insertion of the probe into the cassette) and provides an opening - indicating seal against incorrect opening of the Schrader seal by the user. The base of the cassette can be provided with a foil seal that covers the indoor air pump inlet port and the NO gas outlet port. This seal can be punctured during the operation of the system (insertion of the probe into the cassette) and provides an opening - indicating seal against incorrect opening of the Schrader seal by the user.

[0055] The top of the cassette can be provided with a foil seal or a paper seal to cover the cassette - actuating rotary knob. This rotary knob engages with the console to break the glass vial. The top of the cassette can be provided with a foil seal or a paper seal to cover the cassette - actuating rotary knob. This rotary knob engages with the console to break the glass vial. The top of the cassette can be provided with a foil seal or a paper seal to cover the cassette - actuating rotary knob. This rotary knob engages with the console to break the glass vial.

[0056] Purge substance - Safety number 9 The cassette can contain a purge substance that is used to remove NO gas exiting from the console during the priming of the system to remove air from the console line and the components of the cassette. This purge can be directed to the purge substance of the cassette. The cassette can contain a purge substance that is used to remove NO gas exiting from the console during the priming of the system to remove air from the console line and the components of the cassette. This purge can be directed to the purge substance of the cassette. The cassette can contain a purge substance that is used to remove NO gas exiting from the console during the priming of the system to remove air from the console line and the components of the cassette. This purge can be directed to the purge substance of the cassette.

[0057] Cassette structure - Safety number 10 The liquid module can be air - tight welded aluminum and can withstand an internal pressure of 100 psi (0.69 MPa). All seals of the liquid modules are resistant to N2O4 or high - concentration NO2 gas. The liquid module can be air - tight welded aluminum and can withstand an internal pressure of 100 psi (0.69 MPa). All seals of the liquid modules are resistant to N2O4 or high - concentration NO2 gas. It is compatible with the substrate and can withstand a temperature of 70°C.

[0058] Cassette Packaging - Safety Number 11 The cassette can initially be packaged within a foil pouch as a safety and moisture barrier. Stability tests can be performed to determine the long-term requirements of this pouch.

[0059] Cassette Subassembly and Features The cassette can be designed such that the subassembly is not affected by the position and orientation so as not to limit the alignment within the cassette console and not to limit portability.

[0060] Liquid Module Subassembly The liquid module is a self - contained subassembly that houses N2O4 liquid and related integral safety devices, as well as control devices related to the delivery of NO2 gas. The liquid module is initially configured to maintain communication between the liquid container and the inerting chamber in the event of a failure of the glass vial and the filling of the liquid container with N2O4 / NO2.

[0061] The liquid container can be connected to the cassette distribution manifold of the hermetic assembly. The discharged liquid from the liquid container and the concentrated NO2 gas flow released from the restrictor flow column can be discharged into the inlet of the room air pump and carried to the first main cartridge.

[0062] The liquid module can be arranged in the distribution manifold within the cassette such that the actuating cam aligns to its initial position to receive the console actuating knob.

[0063] ​​​​​​​​​A liquid container can have a DC electric flexible heater wrapped around the column segments of the liquid container and the restrictor. A temperature console can adjust the temperature of the liquid / gas to be in milligrams per deciliter (mg / dl) programmed to be delivered to the patient's line. A temperature console can adjust the temperature of the liquid / gas to be in milligrams per deciliter (mg / dl) programmed to be delivered to the patient's line. A temperature console can adjust the temperature of the liquid / gas to be in milligrams per deciliter (mg / dl) programmed to be delivered to the patient's line. A temperature console can adjust the temperature of the liquid / gas to be in milligrams per deciliter (mg / dl) programmed to be delivered to the patient's line.

[0064] Cartridge Subassembly The main cartridge can provide means for converting NO2 to NO gas by reaction with ascorbic acid pre-treated on the surface of a composite matrix of high density polyethylene and silica gel. The cartridge must be able to convert N2O4 of the contents of one liquid vial to NO gas. The cassette can include two main cartridges. The main cartridges can be obtained from two separate manufacturing lots to provide redundant NO2 conversion in case of a "failure" of the cartridge. The main cartridges can be connected in series in an airtight bridge with a conduit to connect the gas outlet of the first main cartridge to the gas inlet of the second main cartridge. The main cartridge can provide means for converting NO2 to NO gas by reaction with ascorbic acid pre-treated on the surface of a composite matrix of high density polyethylene and silica gel. The cartridge must be able to convert N2O4 of the contents of one liquid vial to NO gas. The cassette can include two main cartridges. The main cartridges can be obtained from two separate manufacturing lots to provide redundant NO2 conversion in case of a "failure" of the cartridge. The main cartridges can be obtained from two separate manufacturing lots to provide redundant NO2 conversion in case of a "failure" of the cartridge. The main cartridges can be connected in series in an airtight bridge with a conduit to connect the gas outlet of the first main cartridge to the gas inlet of the second main cartridge. The main cartridges can be connected in series in an airtight bridge with a conduit to connect the gas outlet of the first main cartridge to the gas inlet of the second main cartridge.

[0065] Cassette Distribution Manifold Subassembly The base of the cassette can include a cassette distribution manifold. This manifold is connected to the column of the restrictor of the liquid module, the gas inlet of the first main cartridge, the gas outlet of the second main cartridge, and the inlet port and NO gas outlet port of the indoor air pump of the console. Additionally, the ports are provided for access to the purge chamber of the console. The base of the cassette can include a cassette distribution manifold. This manifold is connected to the column of the restrictor of the liquid module, the gas inlet of the first main cartridge, the gas outlet of the second main cartridge, and the inlet port and NO gas outlet port of the indoor air pump of the console. This manifold is connected to the column of the restrictor of the liquid module, the gas inlet of the first main cartridge, the gas outlet of the second main cartridge, and the inlet port and NO gas outlet port of the indoor air pump of the console. This manifold is connected to the column of the restrictor of the liquid module, the gas inlet of the first main cartridge, the gas outlet of the second main cartridge, and the inlet port and NO gas outlet port of the indoor air pump of the console. Additionally, the ports are provided for access to the purge chamber of the console.

[0066] The cassette distribution manifold is connected to the gas inlet of the first main cartridge and the gas outlet of the second main cartridge An airtight seal can be provided between the gas outlet of the "ji" and something. The cassette distribution manifold can be provided with two Schrader valves independent of the valves provided in the liquid module. These valves provide an escape port for NO2 gas when the cassette is removed from the console or when a malfunction occurs in the discharge shuttle system. One Schrader seal can be incorporated into the inlet port of the indoor air pump, and one Schrader seal is incorporated into the outlet port of NO gas. Both valves are spring-loaded and normally closed and are opened by the console probe. The cassette distribution manifold can be connected to a console having a probe with a double (robust and long-lasting ) O-ring seal. These seals must be compatible with high-concentration NO gas.

[0067] The base of the cassette can be provided with three ports and a DC electrical connector. Foil seals can be placed at the inlet port of the indoor air pump, the outlet port of NO gas, and the purge port of the system. The foil seal(s) is / are designed to be punctured by the console probe (rather than peeled-off) and should not interfere with the O-ring seal of the probe interface.

[0068] Cassette / Console Interface The cassette can be accessed via a cannula probe with a double O-ring seal at each connection for redundancy to ensure absolutely no leakage at the connection: (1 ) The first connection is for the inlet of the air pump accessed via a Schrader safety valve and for can be; (2) The second connection part can similarly be used for discharging the second main cartridge through a Schrader type safety valve for adjusting and distributing NO gas through a console for injection into a nasal cannula line or a ventilator line. For the adjustment and distribution of NO gas through a console for injection into a nasal cannula line or a ventilator line, it can similarly be used for discharging the second main cartridge through a Schrader type safety valve. It can be used for discharging the second main cartridge through a Schrader type safety valve for adjusting and distributing NO gas through a console for injection into a nasal cannula line or a ventilator line.

[0069] The cassette can be accessed through a cannula-shaped probe with a double O-ring seal at a purge port for accessing the purge substance from the console. The cassette can be accessed through a cannula-shaped probe with a double O-ring seal at a purge port for accessing the purge substance from the console. The cassette can be accessed from the console for electrical connection of 12 or 24 VDC to control a flexible heater used to adjust the flow rate of NO2 gas by a console control system. The cassette can be accessed from the console for electrical connection of 12 or 24 VDC to control a flexible heater used to adjust the flow rate of NO2 gas by a console control system. The connection port must be made such that NO2 and air do not leak to the inside of the console. The connection port must be made such that NO2 and air do not leak to the inside of the console.

[0070] Purge chamber The purge chamber can contain removal substances for the discharge piping of the console system. Potassium permanganate or sodium permanganate containing activated carbon can be used. The purge chamber can contain removal substances for the discharge piping of the console system. Potassium permanganate or sodium permanganate containing activated carbon can be used. The purge chamber can be opened to the atmosphere after the NO gas is neutralized by the medium or induced to a pressure safety valve. The removal substances are used during startup and the purge process to remove any NOx before being discharged to the environment. The purge chamber can be opened to the atmosphere after the NO gas is neutralized by the medium or induced to a pressure safety valve. The removal substances are used during startup and the purge process to remove any NOx before being discharged to the environment. The purge chamber can be opened to the atmosphere after the NO gas is neutralized by the medium or induced to a pressure safety valve. The removal substances are used during startup and the purge process to remove any NOx before being discharged to the environment.

[0071] Cassette housing and assembly The cassette housing can contain the above sub-assemblies in a single container. This assembly should be made inaccessible to the user. This can be equipped with a welding assembly or a "special key" for opening the cassette at the manufacturing site. Regulatory agencies The cassette housing can contain the above sub-assemblies in a single container. This assembly should be made inaccessible to the user. This can be equipped with a welding assembly or a "special key" for opening the cassette at the manufacturing site. Regulatory agencies The cassette housing can contain the above sub-assemblies in a single container. This assembly should be made inaccessible to the user. This can be equipped with a welding assembly or a "special key" for opening the cassette at the manufacturing site. Regulatory agencies Appropriate markings approved by the relevant authorities shall be included on the cassette and associated packaging. The top of the cassette can be provided with a tamper-evident strip that isolates the actuating cam from the user and prevents manual actuation of the liquid module during handling of the cassette. .

[0072] Cartridge The cartridge is a system used to convert NO2 gas generated from a liquid module into inhaled NO gas for delivery to a patient and is controlled by a console. The cartridge is housed within a cassette that connects to the console. To minimize risk, two such cartridges are each sized to be able to convert one full N2O4 fill volume and are each included in the cassette from different manufacturing lots. Referring to FIG. 5A, FIG. 5A is an overall view of a cartridge comprising a cartridge housing 501 and a composite cap 502 fixed to the inlet end of the composite material. Referring to FIG. 5B, FIG. 5B shows a cross-section of FIG. 5A where a cap 503 is fixed to an inlet having an end 504.

[0073] The composite material consists of a porous rigid matrix made from a mixture of silica gel and high-density polyethylene (HDPE). HDPE is a binding material used to form the rigid matrix. A sintering process is utilized to fix this structure. The composite material has the highest possible percentage of silica gel (which can be between 40% and 85%) and can be designed to maintain mechanical integrity. To achieve a uniform composite material, the particle size distribution of the HDPE can be selected to be similar to that of the silica gel. To achieve this, the HDPE particles are sieved using a predetermined mesh size, and the particles passing through the mesh are used in this process. To increase the amount of silica gel in the composite, high melt flow HDPE is utilized. This allows the HDPE to melt together more readily, and thus, although the pressure drop is greater, a matrix is provided that allows for more silica gel. Once the HDPE and silica gel are added together, they are mixed for a certain period of time to allow for sufficient mixing. In the proposed mechanism, ascorbic acid is assumed to bind to silica by a water-mediated bond. Water is necessary to initiate the reaction at a level sufficient to achieve the quantitative conversion of NO2 to NO. Based on tests of the pore sizes of various silicas, a pore size of generally 40 - 80 Å (about 4×10~8×10 cm), which is the size of one to two ascorbic acid molecules, is required for maximum conversion ability. Ascorbic acid appears to be bound to the surface of the silica to activate the silica for conversion. This could be due to the nucleophilicity of the silica mediated by the bound water, which promotes the ability of ascorbic acid to donate a proton to NO2 and initiate a rapid concerted reaction to produce NO. Sodium ascorbate does not convert NO2 to NO, which supports the proposed concerted reaction mechanism. Water also facilitates the ability to migrate to ascorbic acid through the silica-bound NO2 cartridge, and thus, the NO emission increases and the cartridge efficiency improves. This water binds only to the silica and not directly to the ascorbic acid. The active surface of the cartridge

[0074] -7 -7

[0075] ​​​​​​​​​​​​​​​​​ Excessive water in the flow rate of the incoming gas to the cartridge, as confirmed by condensation, can dissolve and wash away ascorbic acid, forming a gas path with little or no conversion ability, and the cartridge becomes unusable immediately. Also, excessive water on an anaerobically sealed cartridge can, over time, cause anaerobic decomposition of ascorbic acid, generating CO2, and the conversion ability of the cartridge decreases. Therefore, work continues to optimize storage by achieving a balance between excessive moisture and excessive dryness, but the stored cartridge should have moisture but be moderately dried to maintain the shelf life.

[0076] Main Cartridge Module The main cartridge can be a specially designed composite material treated with ascorbic acid. The requirement for a single main cartridge can be to be able to convert one full load from a liquid vial. For safety and redundancy, two main cartridges can be used, and these can be from different manufacturing lots respectively.

[0077] Composite Material Assembly The composite material is a porous rigid matrix consisting of a mixture of silica gel and high-density polyethylene (HDPE). The silica gel is intended to provide a surface structure that captures ascorbic acid and moisture to initiate the conversion of NO2 gas to NO gas. HDPE is the binding material used to form the rigid matrix. A sintering process is utilized to fix the structure. The composite material is bonded to upper and lower HDPE end caps for transport / storage. is prepared. The composite material has a silica gel with the highest possible percentage (70% - 85%) and can be designed to maintain mechanical integrity. and can be designed to maintain mechanical integrity.

[0078] Derivatization of ascorbic acid An ascorbic acid solution is prepared using ascorbic acid and purified water. The concentration is determined using the weight - volume (w / v) method. The formed composite material is thoroughly washed with a solution of a predetermined concentration (note the following: once the ascorbic acid solution is prepared, it can be used within 48 hours, and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and washed with a solution of a predetermined concentration (note the following: once the ascorbic acid solution is prepared, it can be used within 48 hours, and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and washed with a solution of a predetermined concentration (note the following: once the ascorbic acid solution is prepared, it can be used within 48 hours, and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. Then, the composite material is dried to a controlled dew point.

[0079] Water plays an essential role in the function of the GeNO cartridge. Past research has shown that the cartridge needs to bind ascorbic acid to the solid surface, and silica is the most efficient, and water is necessary for the cartridge to function. Ascorbic acid must be evenly dispersed on the silica, which is achieved by dissolving the ascorbic acid and applying it to the silica as a solution. Then, the mixture is evenly dried to achieve a uniform dispersion that does not provide a preferred gas path through the coated silica. The silica is of a suitable size for filling and has sufficient separation (about 200 - 500 μm) between the beads to allow sufficient gas flow and still allow the gas to have maximum access to the ascorbic acid bound to the silica. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and the solution can be discarded in an approved manner within 48 hours from production. This prevents most of the ascorbic acid from becoming dehydroxyascorbic acid and being unusable as an oxidizing agent). Then, the composite material is dried to a controlled dew point. and still allow the gas to have maximum access to the ascorbic acid bound to the silica.

[0080] Liquid Module Referring to FIG. 6, the liquid module utilized is a subassembly used to store The ampoule 601 is a glass ampoule containing liquid N2O4. The shuttle 602 transmits linear and rotational forces to the distal end Alternatively, the port at the proximal end may be closed and the ampoule may be broken to release the contents of the ampoule. Pull break impingement feature 603. Flexible heater 604 is connected to the liquid module and restrictor column assembly. The "T" fitting 605 is wrapped around the bri The flow rate is then delivered to the flowing room air 606 through the distal end of the flow regulator 607. The limiter 607 is a small diameter glass tube for the NO2 coming out of the liquid module. The valve 608 is connected to a deactivation chamber to neutralize the NO2 gas. is used in research and development to determine acceptable leak rates in design integration. A cam actuating means 609 for movement of the liquid module may be located at the distal end of the liquid module. .

[0081] Upon activation of the system (breaking of the glass ampoule), the liquid module converts the liquid into a gas. The liquid module may contain NO2 and N2O4 gases that are generated when the container is heated to reduce the amount of CO2 released. The valve diverts gas flow to either the inerting chamber or the patient delivery piping of the console. The NO2 gas produced in the liquid module is converted into NO gas. The fluid module is connected to the console and is delivered to the patient and regulated by the console. The cassette is inserted into the chamber.

[0082] The liquid module can accommodate a sealed vial of N2O4 until the system is activated by the user. The liquid vial may contain a measured amount of liquid N2O4 within a hermetically sealed glass container. The liquid module can provide a safe means of transport for chemicals and chemicals compatible with liquid N2O4 and NO2 gas. The liquid module can close the inerting chamber path, open the system flow path, and provide means for breaking the ampoule in response to user requests. When the cassette is removed from the console, means are provided for opening the inerting chamber path and closing the system flow path. The liquid module can provide means for delivering μg of NO2 under control by temperature regulation of the liquid module and the restrictor assembly (by the control unit of the console) using a flexible heating element wrapped around the ampoule. The liquid module can provide means for delivering concentrated NO2 gas to the supplied room air to dilute the NO2 gas before delivery to the conversion cartridge. Mechanical activation of the liquid module The liquid container can be provided with a shuttle mechanism for regulating the delivery of gas within the system. This container is provided with a shuttle function element, a heating function element, and a flow regulator / restrictor function element. The shuttle function element has a plurality of performance requirements:

[0083] The glass vial can be housed within the shuttle for transport and storage. The shuttle houses fragments of the glass vial passing through the ports at either end of the liquid container.

[0084]

[0085] ​​​​​​​It can be provided with functional elements. The shuttle can have two positions caused by the rotation of the shuttle. The shuttle can seal at either end of the liquid container. In one position, the gas flow can be directed towards the inactivation chamber and blocked with respect to the patient flow path. In the other position, the gas flow is directed towards the patient flow path and blocked with respect to the inactivation chamber. There can be a position where both flow paths are blocked from the gas flow by a single seal at either end of the shuttle, but this position occurs instantaneously within the time during the rotation of the shuttle.

[0086] The system can be operated by rotating the shuttle to engage the functional elements, whereby the glass vial can be broken and the liquid N2O4 can be exposed to the liquid container. The shuttle can be locked at the end of the movement. The system should be configured to close the flow path to the patient and open the inactivation chamber before allowing removal of the cassette. The glass vial should maintain its structural integrity during the transportation and storage of the product.

[0087] The heating functional element has a number of performance requirements: A flexible heater can be wound around the outside of the liquid container for use in increasing or decreasing the gas discharge amount of NO2 gas for delivery to the patient. The temperature is controlled by software within the console. Another flexible heater can be wound around the outside of the flow rate regulator / limiter functional element for use in increasing or decreasing the gas discharge amount of NO2 gas for delivery to the patient. The temperature is controlled by software within the console.

[0088] The flow rate regulator / limiter functional element has a number of performance requirements: The flow regulator / limiter is utilized with a heater to regulate the exhaust gas delivered to the fluid stream of the patient-delivered gas. The liquid module can create an internal pressure more than twice the pressure within the air inlet mixture T-fitting.

[0089] Access to the inactivation chamber The liquid module inactivation chamber is coupled to the liquid container via a controlled leak valve. This valve is intended to regulate the gas flow to the inerting substance to minimize the rise in the heat of chemical reaction that occurs when NO2 gas is neutralized.

[0090] The position of the shuttle transport and shut-off design / configuration can expose the liquid container chamber to the inactivation port and shut off the patient delivery port. In the event of glass breakage during product transport, the device is intended to trap the gas by diverting it to the inactivation chamber to neutralize the dangerous NO2 gas.

[0091] Supply subassembly The supply subassembly of the nitric oxide delivery system can include a cassette module, a cartridge(s), and a liquid module. The system includes a control subassembly, a NO supply subassembly, and a sample sensor subassembly. The control subassembly includes a computer system with a small integrated display, a backup battery, application-specific PCBs (heater control unit, solenoid control unit, switches, battery charger, analog inputs, etc.), and a computer storage device system. The NO supply subassembly includes (1) a heating container, a main cartridge, an inerting substance, a purge agent, a limiter, and a housing (s), and ​ A cassette containing a jig, (2) a flow sensor, a pump, a flow limiter, a remover, a particulate filter An injection flow module including an air damper back pressure regulator and a pump backup solenoid, and (3) a proportional valve, a purge solenoid, a purge flow sensor, a purge back pressure regulator, and An NO source control unit including a Hi-C NO sensor. The sample sensor subassembly includes a sample / calibration solenoid, a permeation dryer, a sample flow module (including a flow meter, a flow limiter, and a pump), an external water trap and a pressure transducer, a sensor subassembly (NO, NO2, and oxygen sensors, and a sensor control PCB), and an NO remover. Referring to FIG. 7, FIG. 7 shows a flow diagram of the supply subassembly. Indoor air can be introduced into a particulate filter and flow into two pumps (FIG. 7, pump (1) and pump (2)). Pump (1) can flow at a maximum of 1 L / min at 5 psi (0.034 MPa) or more, and this flow rate can meet the application examples of all ventilators and some cannulas. Pump (2) can be used to supply dilution air to achieve a higher flow rate of the cannula as needed. In the application example of a ventilator, a flow rate of 0.2 to 1.0 L / min may be required. These pumps typically require a back pressure regulator 1 because a large, i.e., 5-fold, dynamic range cannot be obtained without stalling at a lower flow rate. During the operation of a typical ventilator, the proportional valve, Sol2, sets the discharge flow rate, which is also the flow rate measured by the flow sensor (1). The pump is set to the lowest allowable flow rate, and this flow rate is the desired discharge flow rate. A water trap (external) and a pressure transducer, a sensor subassembly (NO, NO2, and oxygen sensors, and a sensor control PCB), and an NO remover. x including.

[0092] Referring to FIG. 7, FIG. 7 shows a flow diagram of the supply subassembly. Indoor air is introduced into a particulate filter and can flow into two pumps (FIG. 7, pump (1) and pump (2)). Pump (1) can flow at a maximum of 1 L / min at 5 psi (0.034 MPa) or more, and this flow rate can meet the application examples of all ventilators and some cannulas. Pump (2) can be used to supply dilution air to achieve a higher flow rate of the cannula as needed. In the application example of a ventilator, a flow rate of 0.2 to 1.0 L / min may be required. These pumps typically require a back pressure regulator 1 because a large, i.e., 5-fold, dynamic range cannot be obtained without stalling at a lower flow rate. During the operation of a typical ventilator, the proportional valve, Sol2, sets the discharge flow rate, which is also the flow rate measured by the flow sensor (1). The pump is set to the lowest allowable flow rate, and this flow rate is the desired discharge flow rate. These pumps typically require a back pressure regulator 1 because a large, i.e., 5-fold, dynamic range cannot be obtained without stalling at a lower flow rate. During the operation of a typical ventilator, the proportional valve, Sol2, sets the discharge flow rate, which is also the flow rate measured by the flow sensor (1). The pump is set to the lowest allowable flow rate, and this flow rate is the desired discharge flow rate. The pump is set to the lowest allowable flow rate, and this flow rate is the desired discharge flow rate. When exceeded, the excess is automatically discharged indoors through the regulator (1). This is only air and since this is the case, the discharge of this gas is acceptable. The pump (1) is selected to achieve a flow rate of up to 1 L / min in the case of an artificial respirator application, and in the case of a cannula application, sometimes a flow rate as high as 4 L / min may be required, so the pump (2) is added as a "dilution" pump. The pump (1) needs to supply 1 L / min at a pressure exceeding 5 psi (0.034 MPa). Since the pump (2) operates at nominal atmospheric pressure, the pump (2) can very likely be made the same as the pump (1), and thus will be able to achieve 3 L / min at nominal 0 psig (0 MPa). The pump (1) needs to supply 1 L / min at a pressure exceeding 5 psi (0.034 MPa). Since the pump (2) operates at nominal atmospheric pressure, the pump (2) can very likely be made the same as the pump (1), and thus will be able to achieve 3 L / min at nominal 0 psig (0 MPa). The pump (1) needs to supply 1 L / min at a pressure exceeding 5 psi (0.034 MPa). Since the pump (2) operates at nominal atmospheric pressure, the pump (2) can very likely be made the same as the pump (1), and thus will be able to achieve 3 L / min at nominal 0 psig (0 MPa). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2).

[0093] The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2). The accumulator (1) can be used, together with the restrictor, to suppress the pulsation from the diaphragm pump. It is desirable for a stable, non-pulsating flow to pass through the rest of the system. It should be noted that restrictor 1 must have a significantly weaker restriction than restrictor 2. The accumulator 2 and the restrictor 3 can be used to suppress the pulsation from the diaphragm pump (2).

[0094] The flow sensor (4) is used to determine the dilution flow rate from the pump (2) that mixes with the acute output. The total flow rate to the patient is the sum of the flow rates of the flow sensors (1) and (4). Based on the flow rate set point, the software can determine the actual ratio of the flow rate from the pump (1) to the flow rate from the pump (2). This is an optional pressure sensor. This pressure sensor determines whether the back pressure regulator 1 is properly set when Sol1 is open. The flow sensor (4) is used to determine the dilution flow rate from the pump (2) that mixes with the acute output. The total flow rate to the patient is the sum of the flow rates of the flow sensors (1) and (4). Based on the flow rate set point, the software can determine the actual ratio of the flow rate from the pump (1) to the flow rate from the pump (2). This is an optional pressure sensor. This pressure sensor determines whether the back pressure regulator 1 is properly set when Sol1 is open. The flow sensor (4) is used to determine the dilution flow rate from the pump (2) that mixes with the acute output. The total flow rate to the patient is the sum of the flow rates of the flow sensors (1) and (4). Based on the flow rate set point, the software can determine the actual ratio of the flow rate from the pump (1) to the flow rate from the pump (2). This is an optional pressure sensor. This pressure sensor determines whether the back pressure regulator 1 is properly set when Sol1 is open. The flow sensor (4) is used to determine the dilution flow rate from the pump (2) that mixes with the acute output. The total flow rate to the patient is the sum of the flow rates of the flow sensors (1) and (4). Based on the flow rate set point, the software can determine the actual ratio of the flow rate from the pump (1) to the flow rate from the pump (2). This is an optional pressure sensor. This pressure sensor determines whether the back pressure regulator 1 is properly set when Sol1 is open. The flow sensor (4) is used to determine the dilution flow rate from the pump (2) that mixes with the acute output. The total flow rate to the patient is the sum of the flow rates of the flow sensors (1) and (4). Based on the flow rate set point, the software can determine the actual ratio of the flow rate from the pump (1) to the flow rate from the pump (2). This is an optional pressure sensor. This pressure sensor determines whether the back pressure regulator 1 is properly set when Sol1 is open. would be used to verify. Under all conditions, i.e., whether Sol1 is operating or not, the pressure sensor measures the pressure of the pump, and this pressure is an evaluation criterion for the performance of the pump. Since the operating voltage of the pump is known, the discharge flow rate and pressure are used to determine whether there is degradation of the pump and to send an early warning signal for replacing the pump before a failure occurs. Even when not operating, the pressure sensor measures the pressure of the pump, and this pressure is an evaluation criterion for the performance of the pump. Since the operating voltage of the pump is known, the discharge flow rate and pressure are used to determine whether there is degradation of the pump and to send an early warning signal for replacing the pump before a failure occurs. Even when not operating, the pressure sensor measures the pressure of the pump, and this pressure is an evaluation criterion for the performance of the pump. Since the operating voltage of the pump is known, the discharge flow rate and pressure are used to determine whether there is degradation of the pump and to send an early warning signal for replacing the pump before a failure occurs.

[0095] Other exemplary embodiments N2O4 liquid-based systems can be used to deliver inhaled nitric oxide (NO). This delivery system can be used with either a ventilator or a cannula. Since NO2 in liquid form can exist as the N2O4 dimer, liquid N2O4 evaporates as NO2 (gas). Then, NO2 can be converted to NO using at least one conversion cartridge. The amount of NO provided to the patient can be changed by varying the temperature of the N2O4 liquid tank, and thus the vapor pressure above the liquid, by the selection and temperature of the restrictor column, and by the setting if a scrubbed by-pass air flow is used. The NO concentration can be adjusted by a feedback loop from an NO sensor that monitors the NO in the patient's ventilator line or cannula line just prior to the patient. This feedback loop can adjust the flow rate through the impurity removal bypass system if the liquid and restrictor temperatures and the impurity removal bypass system are operating. The console can deliver 1 - 40 ppm concentration at a ventilator flow of 2 - 20 l / min in the case of ventilator applications. N2O4 liquid-based systems can be used to deliver inhaled nitric oxide (NO). This delivery system can be used with either a ventilator or a cannula. Since NO2 in liquid form can exist as the N2O4 dimer, liquid N2O4 evaporates as NO2 (gas). Then, NO2 can be converted to NO using at least one conversion cartridge. The amount of NO provided to the patient can be changed by varying the temperature of the N2O4 liquid tank, and thus the vapor pressure above the liquid, by the selection and temperature of the restrictor column, and by the setting if a scrubbed by-pass air flow is used. The amount of NO provided to the patient can be changed by varying the temperature of the N2O4 liquid tank, and thus the vapor pressure above the liquid, by the selection and temperature of the restrictor column, and by the setting if a scrubbed by-pass air flow is used. The amount of NO provided to the patient can be changed by varying the temperature of the N2O4 liquid tank, and thus the vapor pressure above the liquid, by the selection and temperature of the restrictor column, and by the setting if a scrubbed by-pass air flow is used. The NO concentration can be adjusted by a feedback loop from an NO sensor that monitors the NO in the patient's ventilator line or cannula line just prior to the patient. The NO concentration can be adjusted by a feedback loop from an NO sensor that monitors the NO in the patient's ventilator line or cannula line just prior to the patient. This feedback loop can adjust the flow rate through the impurity removal bypass system if the liquid and restrictor temperatures and the impurity removal bypass system are operating. This feedback loop can adjust the flow rate through the impurity removal bypass system if the liquid and restrictor temperatures and the impurity removal bypass system are operating. The console can deliver 1 - 40 ppm concentration at a ventilator flow of 2 - 20 l / min in the case of ventilator applications. Providing NO in the range of 0 degrees, in the application example of the cannula, at a discharge flow rate of 0.5 to 4 l / min and 10 to 80 ppm Providing NO in the concentration range. A second cartridge for converting NO2 to NO is placed immediately before the patient This second cartridge removes all residual NO2 that may be generated in the delivery gas piping Therefore, the gas of the ventilator or cannula provided to the patient must essentially have a NO2 concentration of 0 Degree.

[0096] Referring to Figure 8, in one embodiment, the system (e.g., GeNOsyl Acute DS) includes (1) The main console, (2) the same fully functional backup console (required in ventilator mode And optional in cannula mode), (3) one cassette per console, and (4) external tubing and accessories. The system can include both the main console And the backup console. System failure can include the inability of both the main console And the backup console to deliver NO at the desired set time Including.

[0097] Referring to Figure 9, this drawing shows an exemplary GeNOsyl Acute DS console with the cassette door open and a three-position operating lever Shown.

[0098] The system can be a hospital nitric oxide ( NO) delivery system that can deliver a controlled dose of inhaled NO to a patient for diagnostic or therapeutic purposes in cooperation with a ventilator system or directly by a nasal cannula

[0099] The delivery system can be used in several configurations. The ventilator configuration is for treatment ​​It can be used with a face mask in conjunction with the respirator used in the cannula. This configuration can be used with nasal cannulas or face masks for both therapeutic and diagnostic applications. The console can be used with a single cassette that can contain liquid N2O4 and a gas analyzer that converts NO2 to NO. It may have a pair of cartridges (main cartridges) that are converted.

[0100] When the console starts up, it heats up liquid N2O4 to produce NO 2(ガス) can be converted to the following: The NO2 is then converted to NO using a cartridge that converts NO2 to NO, and the resulting NO2 is then used in the ventilator system. It can be delivered to the patient in conjunction with a nasal prong or directly via a face mask. The amount of NO delivered to the patient can be controlled by changing the temperature of the N2O4 liquid module. The NO concentration in the patient can be altered by changing the NO concentration in the patient ventilator line or cannula line. The feedback loop from an NO electrochemical sensor can monitor NO in the The output of the NO sensor can be controlled to adjust the temperature of the liquid module. The control circuit compares the NO concentration with the required NO concentration (the NO concentration setpoint selected by the user). This can be done.

[0101] Referring to FIG. 10, this figure shows an exemplary power performance curve. The NO concentration ranges from about 0.1 ppm at a ventilator flow rate of 2 l / min to 20 ppm at a ventilator flow rate of 10 l / min. pm range (nominally up to 40 ppm in extreme conditions, but over the life of the cassette The system is placed after the cartridge, e.g., the second cartridge. It works with an optional humidifier. The second cartridge removes any residual NO2 or NO2 from the line. The NO2 generated by the conversion in can be converted to substantially zero. The second cartridge ridge can be placed in front of the humidifier to prevent condensation from occurring within the cartridge. This can be done.

[0102] GeNOsyl (trademark) Acute DS Cannula System GeNOsyl (trademark) Acute DS can supply only a small part of the inhalation volume of respiration, and the rest is composed of indoor air (entrained air). GeNOsyl (trademark) Acute DS can adjust the concentration of NO in the cannula. One advantage of GeNOsyl (trademark) Acute DS compared with the use of a gas tank is that while only the flow rate can be changed with the use of a gas cylinder, with DS, both the flow rate and the concentration can potentially be changed.

[0103] GeNOsyl (trademark) Acute DS Ventilator System with a Second Cartridge In GeNOsyl (trademark) Acute DS, both the exhaust flow rate and the exhaust concentration can be changed. To avoid affecting the control unit of the ventilator, the exhaust flow rate of GeNOsyl (trademark) Acute DS can typically be limited to about 10% or less of the total flow rate from the ventilator. The NO emission of the console can be adjusted by temperature, and by changing the temperature, the mass of NO supplied per minute can be changed, so it can be the temperature of the container that determines the mass delivered to the patient.

[0104] Cassette When the cassette is inserted into the console and activated, for example, by the destruction of the cassette seal, two parts of the cassette interact to adjust the dose of NO gas delivered to the patient. The cassette can be an independent disposable product that can be inserted into a console (e.g., the GeNOsyl Acute DS console), and can be coupled externally to a second cartridge to form a system, e.g., the Acute DS system. Referring to FIG. 11, the cassette 1101 can include various modules for generating and converting NO gas to be delivered to a patient. The cassette and cartridge can be disposable modules that also provide environmental safety functions and displays to the user. For example, the cassette 1101 can be an independent disposable cassette having an observation window 1102, e.g., an observation window of a discoloring inerting substance, configured to safely discard the cartridge. The cassette can include three separate sub-assembly modules.

[0105] Referring to FIG. 11, the cassette 1101 can include various modules for generating and converting NO gas to be delivered to a patient. The cassette and cartridge can be disposable modules that also provide environmental safety functions and displays to the user. For example, the cassette 1101 can be an independent disposable cassette having an observation window 1102, e.g., an observation window of a discoloring inerting substance, configured to safely discard the cartridge. The cassette can include three separate sub-assembly modules. Liquid module assembly

[0106] Referring to FIG. 12, the cassette assembly can include a liquid module assembly 1203, a cartridge 1202, a cartridge bridge tube 1201, and a base 1204. The liquid module assembly can house an N2O4 holding container and can control its integrity. The holding container (also referred to herein as a liquid container) can include one or more components for breaking a glass seal and heating the N2O4 to activate the liquid, a temperature control for generating and maintaining pressure in the container, and one or more components for directing the gas flow to an inerting chamber or for delivery to a patient. The liquid module assembly can measure NO2 from the holding container into an air stream used to carry NO2 via a gas circuit for conversion to NO.

[0107] Liquid module assembly Referring to FIG. 12, the cassette assembly can include a liquid module assembly 1203, a cartridge 1202, a cartridge bridge tube 1201, and a base 1204. The liquid module assembly can house an N2O4 holding container and can control its integrity. The holding container (also referred to herein as a liquid container) can include one or more components for breaking a glass seal and heating the N2O4 to activate the liquid, a temperature control for generating and maintaining pressure in the container, and one or more components for directing the gas flow to an inerting chamber or for delivery to a patient. The liquid module assembly can measure NO2 from the holding container into an air stream used to carry NO2 via a gas circuit for conversion to NO. (The holding container can include one or more components for breaking a glass seal and heating the N2O4 to activate the liquid, a temperature control for generating and maintaining pressure in the container, and one or more components for directing the gas flow to an inerting chamber or for delivery to a patient.) The liquid module assembly can measure NO2 from the holding container into an air stream used to carry NO2 via a gas circuit for conversion to NO. The holding container (also referred to herein as a liquid container) can include one or more components for breaking a glass seal and heating the N2O4 to activate the liquid, a temperature control for generating and maintaining pressure in the container, and one or more components for directing the gas flow to an inerting chamber or for delivery to a patient. The liquid module assembly can measure NO2 from the holding container into an air stream used to carry NO2 via a gas circuit for conversion to NO. may also include a NO2 flow regulator. In the event of an accident or misuse, to provide additional safety against NO2 exposure to the user To provide additional safety against NO2 exposure to the user, the N2O4 liquid chamber can be encapsulated with an inert substance and there may also be a sealing barrier to contain NO2. The inert substance can initiate a color change display that warns the user that N O2 has been discharged into the inactivation chamber and can do so

[0108] The liquid module assembly can be a sub-assembly used to store and contain liquid N2O4. Upon activation of the system (rupture of the glass ampoule), the liquid module a ssembly can contain the N2O4 and NO2 gas generated when the container can be heated to convert the liquid to gas. The liquid module assembly can have internal mechanisms to divert the NO2 gas flow to an incorporated stand-alone inactivation chamber or direct it to a flow restrictor for release into a cassette circuit that converts the NO2 gas to NO. What can be delivered to and adjusted by the console for the patient is this NO gas generated by the cassette and can be contained within a cassette that is connected to the console and can be contained within a cassette that is connected to the console and can be contained within a cassette that is connected to the console and can be contained within a cassette that is connected to the console and can be contained within a cassette that is connected to the console

[0109] The liquid module assembly can include a temperature control unit that effectively regulates the pressure of the NO2 gas and a restrictor that regulates the release rate of the NO2 and can do so

[0110] The liquid module assembly can be operated such that NO2 gas flows into the main cartridge or the inactivation chamber. The mechanism can prevent the simultaneous opening of both valve seals and can do so and can do so

[0111] Referring to FIG. 13, the liquid container and the restrictor assembly include a glass ampoule 1307 containing N2O4 , a flexible heater, a shuttle 1307, and a metal liquid container 1308 equipped with a seal with a slow leak valve 1309 , a restrictor column 1304, a metal restrictor housing 1303, a flexible heater and a T-fitting 1301 , a ferrule 1302, an optional crush Teflon O-ring 1305, and a heater (not shown) wrapping the restrictor housing and the liquid container may be included.

[0112] Referring to FIG. 14, the components of the cartridge include a main cartridge housing 1401, a composite material inlet cap 1402, a composite material 1403 (silica gel / HDPE), and a composite material outlet cap 144 including.

[0113] Cartridge for converting NO2 to NO The cassette may include two independent cartridges for converting NO2 to NO. Referring to FIG. 15 , each cartridge may include a cartridge outlet 1501, a main cartridge housing 1502, and a cartridge inlet 1503, thereby forming a cartridge assembly and, in addition to the total volume of the liquid supply of N2O4, being able to convert an additional volume exceeding 25%. Two or more cartridges can convert NO2 to NO gas with a safety factor exceeding 150% able. The system can be designed to operate safely and effectively even if one of the two cartridges is missing. Referring to FIG. 16, the cartridge can be attached to a base 1602 . .

[0114] The main cartridge can be included in the cassette to convert NO2 gas to NO gas . The cassette may include one or more main cartridges. If the cassette includes two or more cartridges, the cartridges can be arranged in series to provide a dual conversion redundancy before delivering NO gas to the patient. This conversion can be achieved by the reaction of a reducing agent included in the composite matrix with NO2 gas. The gas passes through a coated composite material within a serpentine path formed by the composite matrix for performing the conversion. When including two or more cartridges, the cartridges can be arranged in series to provide a dual conversion redundancy before delivering NO gas to the patient. This conversion can be achieved by the reaction of a reducing agent included in the composite matrix with NO2 gas. The gas passes through a coated composite material within a serpentine path formed by the composite matrix for performing the conversion.

[0115] The composite material can be a porous rigid matrix including a mixture of silica gel and high-density polyethylene (HDPE). HDPE can be a binding material used to form the rigid matrix. A thermal sintering process can be utilized to ensure the structure. HDPE can be a binding material used to form the rigid matrix. A thermal sintering process can be utilized to ensure the structure.

[0116] Main Cartridge Module The main cartridge can be a composite material treated with ascorbic acid. One main cartridge can convert more than 25% excess volume in addition to the total liquid content of the vial. For safety and redundancy, two main cartridges can be used. One main cartridge can convert more than 25% excess volume in addition to the total liquid content of the vial. For safety and redundancy, two main cartridges can be used.

[0117] Composite Material Assembly The composite material cartridge can be a porous rigid matrix. This porous matrix can include a mixture of silica gel and an HDPE binding material. Silica gel provides a surface structure for capturing a reducing agent, such as ascorbic acid, and moisture for initiating the conversion of NO2 gas to NO gas. The binding material can be used to form the rigid matrix. The composite material can be fixed within a housing for stability during transportation / storage. This porous matrix can include a mixture of silica gel and an HDPE binding material. Silica gel provides a surface structure for capturing a reducing agent, such as ascorbic acid, and moisture for initiating the conversion of NO2 gas to NO gas. The binding material can be used to form the rigid matrix. The composite material can be fixed within a housing for stability during transportation / storage. The composite material has the highest possible percentage of silica gel and can still be designed to maintain mechanical integrity. It can be designed to do so.

[0118] Derivatization of ascorbic acid The formed composite material can be thoroughly washed with a known ascorbic acid solution dissolved in water. (Note: It may be important to exclude oxygen to minimize the conversion of ascorbic acid to dehydroascorbic acid.)

[0119] Water can play an important role in the function of the cartridge. The reducing agent can be evenly dispersed on the porous matrix. This can be achieved, for example, by dissolving the reducing agent and applying it as a solution to the porous matrix. Then, this mixture can be evenly dried to achieve a uniform dispersion, thereby not providing a preferred gas path through the matrix. The porous matrix can be of a size suitable for filling, have sufficient separation between particles to allow sufficient gas flow, and still allow the gas to have maximum access to the reducing agent (e.g., ascorbic acid) bound to the porous matrix.

[0120] Cartridge assembly Upon completion, the processed composite material assembly can be assembled into an external housing, and the composite material assembly is shielded from the environment. The cartridge housing can have extremely low permeability to moisture and oxygen, or can be packaged to minimize the permeability to moisture and oxygen. The cartridge can be packaged with a cassette, but it is important to use a material that provides sufficient durability against moisture and gas. ​ obtained. In one embodiment, the two cartridges in each cassette can be formed from different manufacturing process lots for redundancy safety.

[0121] Cassette housing assembly The cassette housing assembly can be a structural base for attaching other cassette components, including a two - Schrader - valve - type assembly to provide independent gas flow, preferably an external housing containing an inerting substance that discolors (as can be seen by looking at the inerting material), and an unsealing - indicating strip that can cover the inlet and outlet ports of the cassette.

[0122] Referring to FIG. 17, the base manifold of the cassette can include a Schrader - type valve assembly 1701, an air - inlet access port 1702, and an air / NO - outlet access port 1703, and a foil seal 1704 covering a port (not shown). The base of the cassette can provide access to the functions of the following system: · Air - inlet access via the Schrader - type valve assembly · Air / NO - outlet access via the Schrader - type valve assembly · Access to the actuator rod via a small access port (not accessible to the user for actuation) · Access to the purge / remover for the NO - inlet gas · Access to the purge / remover for the NO - outlet gas · Electrical contacts for the heater(s) and temperature sensor(s) (all passive components) that are exposed in the non - operating standby mode · An unsealing - indicating foil seal covering the access ports (except for the electrical contacts) ​​​​​​​​​​· By destroying the unsealing display file seal, the reuse of the cassette is mechanically "locked out". It is.

[0123] Referring to FIGS. 18A and 18B, these drawings show the details of the gas flow of one embodiment of the cassette. FIG. 18A shows the gas flow path indicating the outlet position of the base. FIG. 1 8B shows the outlet position of FIG. 18A. The numbers within the squares in the two drawings represent positions, and the details are as follows: 1. The inlet for the gas flow from the console can be a Schrader valve specially designed by the inventors. The Schrader valve can be closed using a ball and a spring, and can be shown in more detail in FIG. 12. It can be shown in more detail in FIG. 12. It can be shown in more detail in FIG. 12. 2. The incoming air flow can be piped to a T - fitting. 3. The incoming air can pass through the T - fitting. Inside the T - fitting, the air can be mixed with NO2 coming from the liquid container. The flow rate out of the liquid container can be adjusted by the pressure upstream of the container, and this pressure can be adjusted by the temperature of the liquid. The flow rate can be determined by the pressure drop across the restrictor tube. The flow rate can be determined by the pressure drop across the restrictor tube. 4. The air containing NO2 can flow out of the T - fitting. 5. The air / NO2 mixture can exit the T - fitting and head towards the first ascorbic acid cartridge. It can head towards the first ascorbic acid cartridge. 6. The air / NO2 mixture can enter the first ascorbic acid cartridge. This flow can be forced outwards of the cartridge, and this flow can exit from the center of the cartridge. The cartridge itself can have a small taper so that it can be molded without the need for chemicals to remove it from the mold. It can exit from the center of the cartridge. The cartridge itself can have a small taper so that it can be molded without the need for chemicals to remove it from the mold. It can have a small taper so that it can be molded without the need for chemicals to remove it from the mold. Here, the gas emerging from the cartridge at the upper part of the drawing may contain a mixture of air and NO. Then , the gas can enter a second overlapping cartridge. 7. The air / NO mixture can emerge from the second cartridge. 8. The air / NO mixture can enter a second Schrader valve. 9. The air / NO mixture can emerge from the cartridge. The cassette design can be such that NO2 is maintained inside the cassette and never escapes from the cassette.

[0124] Referring to FIG. 19, this drawing shows a cross-section of a Schrader-type valve with a spring-loaded ball 1802 that is normally closed. This ball opens when inserted into the console. The cassette can be a fully integrated single-use disposable and is connected to the console. The cassette can be actuated by an interface lever on the console, which causes the mechanism of the console to engage the cassette, break the glass ampoule, and initiate the delivery of NO to the patient.

[0125] The cassette can provide sufficient design safety features listed below to limit exposure of NO2 to the device, user, patient, or transporter.

[0126] i Glass ampoule The amount of N2O4 included in the cassette can be within the safe EPA / FDA / DOT limits.

[0127] ii Shuttle seal N2O4 can be included in a hermetically sealed glass ampoule, which (when open plus that can enable the entry of the NO2 gas stream into the inactivation chamber or the induction to the patient It can be arranged within the tick shuttle mechanism. All seals can be made double - overlapping. It can be done.

[0128] iii Inactivation chamber The cassette can be transported together with a glass ampoule that is exposed to an inactivating substance capable of inactivating N2O4 / NO2 gas when the glass ampoule is broken during transportation. The inactivating substance can permanently change color when exposed to N2O4. The discoloration with NO2 liquid can be seen through the window of the cassette. This provides an indication to the user that the cassette can no longer function and should probably not be used. This provides an indication to the user that the cassette can no longer function and should probably not be used. This provides an indication to the user that the cassette can no longer function and should probably not be used.

[0129] iv Slow leak valve If the glass ampoule is broken beforehand, the gas flow rate into the inactivation chamber can be adjusted, for example, to control the rise in reaction temperature and provide sufficient time for the inactivation reaction to occur. It can be adjusted.

[0130] v Schrader - type valve sub - assembly and port All high - concentration NO2 gas piping can be included within the cassette, thereby completely eliminating the exposure of NO2 to the environment due to leakage. All high - concentration NO2 gas piping can be included within the cassette, thereby completely eliminating the exposure of NO2 to the environment due to leakage.

[0131] Both the air inlet port and the NO / air gas outlet port can provide a backup seal independent of the shuttle mechanism of the liquid container in case the outlet seal fails. These ports can have Schrader valves that are spring - loaded and automatically close. These ports can have Schrader valves that are spring - loaded and automatically close.

[0132] vi Opening - indication seal(s) The base of the cassette can comprise a foil seal that covers the inlet Schrader valve and the NO gas outlet Schrader valve. These seals can be pierced during operation of the system to provide a visual indication that the cassette has been used and to provide a tamper-evident seal against incorrect opening of the Schrader seal by the user. ... ... ...

[0133] vii Purge / Removal Substances The cassette can also include purge / removal substances that are used to remove low levels of NO gas exiting the console during priming of the system and as a bypass during very low NO delivery concentrations. ... ...

[0134] viii Cassette Structure The cassette housing can withstand an internal pressure that is 50% higher than the internal pressure that can occur during operation. ...

[0135] ix Cassette Shipping Packaging The cassette packaging can provide product integrity during shipping / transport handling and can be a transparent container, such as a thermoformed tray, that allows the user to view discoloration of the inactivation chamber (if the glass ampule is broken during transport). ... ...

[0136] Referring to Figure 20, this drawing shows an exemplary cassette packaging.

[0137] The cassette can comprise two main systems: (a) a liquid module and (b) a conversion cartridge. These two systems can be independent but function in cooperation to convert liquid N2O4 to NO gas within a unitized housing. The cassette is connected to the console... ... ... can be connected to the console, which can provide the electronics, software, and mechanical control necessary to regulate the delivery of the desired NO / air gas dose to the patient, delivered in a low concentration

[0138] range of 1 part per million (ppm). This design can include various safety features that provide environmental protection to the user. These safety features can be the result of the mechanism design, but the purpose of

[0139] these safety features is generally to eliminate the potentially harmful results of an unintended failure that may occur. Referring to FIG. 21, the cassette-based assembly can include a cassette housing 1801, a slow roll valve 1802 (optional design), a liquid container heater 1803, a liquid container 1804, a glass ampoule 1805 containing N2O4, a shuttle

[0140] Liquid Module The cassette can contain liquid N2O4. The liquid N2O4 can be released, purified, and its flow rate adjusted to become a known amount of inhaled nitric oxide (NO).

[0141] Liquid N2O4 can be included in various containers. In one method, the liquid is dispensed into a thin-walled semi-transparent glass ampoule, which can be hermetically sealed, for example, by a high-temperature The diameter is 0.28 inches (about 7.112 mm), the length is 1.25 inches (31.75 mm), and the wall thickness is 0.0025 inches (0.0635 mm). The diameter and wall thickness can be those of an industry-standard glass ampoule and can have other functional elements and dimensions of shapes. The filling amount of N2O4 can be less than 0.52 ml and supplies the amount of NO gas for about one day during normal use.

[0142] The glass ampoule can include several features: (a) The glass ampoule can be transparent, thereby allowing the filling volume to be seen during the process: (b) The glass ampoule can provide an environment that is hermetically sealed from the contents and can be made not to be affected by environmental conditions such as temperature, humidity, etc.: (c) The glass ampoule can provide a breakable container for actuation as required : This design allows the contents of the glass ampoule to be exposed to convert liquid N2O4 to NO2 gas and then provides mechanical and thermal functional elements to regulate the flow rate of the NO2 gas and can be achieved within the liquid module.

[0143] The center of the liquid module can be a liquid container and a limiter housing assembly .

[0144] The liquid container can be cylindrical with end-executing functions. The shape does not have to be a control characteristic but can be for the purpose of providing two different operating modes within the device : (a) delivery of NO2 gas from the liquid container to the patient delivery conduit, or (b) delivery of NO2 gas to the inactivation chamber for neutralization . To achieve this, a shuttle mechanism is provided for the liquid The shuttle can be mounted in the container by a link mechanism from the console control unit. The fluid container can be moved between two end positions that are actuated by a single actuator. One end of the fluid container is for delivery to the patient. The other end may be a port connected to a conduit. Between the two rest positions of the shuttle, the shuttle may be connected to a port leading to a heating chamber. The glass ampoule passes through the impact function element, and when the impact function element is first activated, it presses against the glass ampoule. Destroy (release N2O4).

[0145] The shuttle may be housed in a liquid container, the liquid container being made of metal, e.g., stainless steel. The shuttle can be made from stainless steel or titanium. It safely holds the glass ampule. In its position for transport to the customer, the system can be equipped with functional elements for stabilizing it. The shuttle is designed to ensure that the inerting chamber port is (and is not) closed to gas flow from the liquid container. The patient inflow port can be opened (even to the patient inflow port that is in use). This may be for safety reasons in case the glass ampoules are broken during transportation or handling. All the N2O4 / NO2 released from the broken glass is exposed to a passivating substance which neutralizes it.

[0146] System operation can only occur after the cassette has been placed into the console. Actuation of the stem moves the shuttle to the deactivation chamber open / patient inlet port closed position. From the patient inlet port can be moved to the open / deactivation chamber closed position. This can be done by an actuating rod (controlled within the console) that moves the shuttle. When the glass ampoule comes into contact with the impact function element, the glass ampoule may be destroyed.

[0147] To vaporize the liquid N2O4 to discharge a known amount of NO2 from the container and increase the internal gas pressure, heat can be applied to the liquid container. The pressure can determine the controlled amount of NO2 released through the liquid module. The adjustment of temperature can function as the pressure adjustment of the release rate, for example, in the same way as a gas flow rate regulator does to a gas tank. In this design, a flexible electric resistor heater(s) can be wound around the outside of the metal housing of the liquid container. Other heating methods can also be utilized (rope heater, cartridge heater, or other types of heaters that provide means for adjusting the temperature of the liquid container over the intended period of use). The temperature regulated within the system can be adjusted, for example, between 35 °C and 70 °C to deliver the desired dose of NO to the patient. (a) The components of the shuttle can be cylindrical with linear valves at each end. The shuttle can provide several design features: i. A cradle that can safely accommodate the glass ampoule, stabilize the glass ampoule during transportation, and align the position of the glass ampoule for breakage during the operation of the stem. ii. The shuttle can be provided with a pair of seals at each end to seal the respective ports at each end if necessary. iii. The seals at each end can be of different types. For example, a Luer - like tapered seal coupled to a radial seal. These seals can be for redundancy and can be brought into contact with the respective sheets of these seals in the liquid module assembly. iv. The shuttle has a provision that both end ports are closed when the glass ampoule is broken. ​​​​​​​​​​​​​It may include accounting features. This can be achieved by utilizing the radial seals on both sides of the shuttle. v. The shuttle can incorporate a protective functional element that covers the patient inflow port against the intrusion of glass fragments after activation. vi. The shuttle can be formed, for example, from FEP, PTFE, PFA for chemical compatibility in contact with N2O4. Alternatively, a metal shuttle with flexible seal(s) can be utilized. This can be, for example, stainless steel, titanium, aluminum, and brass, etc. vii. The shuttle can be connected to an actuating rod, and the actuating rod can include a spring load such that the shuttle can move the patient inflow port to the closed position / the inactivation chamber port to the open position. This can be for additional safety. viii. The clearance between the shuttle / liquid container can be minimized to reduce the volume within the liquid container. (b) The components of the liquid container can be cylindrical with linear valve seats at each end. The liquid container can have several design features: i. The liquid container is preferably formed from a metal (such as titanium, stainless steel, aluminum, etc.) and can contain and confine N2O4 and the resulting NO2 gas. ii. The liquid container can be provided with a collision functional element along its inner wall, and the liquid ampoule is broken when the collision functional element passes through (note: this collision functional element can be a relative functional element that can also be provided inside or on the shuttle). iii. The liquid container can be provided with a valve seat that connects the seal of the shuttle to the inactivation chamber. ​​​​​​​​​​​​​iv. The outer surface of the liquid container can be wrapped with a flexible heater (controlled by a console). It is possible to do so. v. The outer surface of the liquid container can likewise be surrounded, for safety reasons, by an inert substance (soda lime) contained in a plastic (polycarbonate, HDPE , ABS, etc.) material. Alternatively, this chamber can be made of metal if there is a possibility of a "take-home" type of problem (e.g., the possibility that a dog might eat this chamber). The inerting chamber can be placed in any part adjacent to the discharge port of the liquid container. . In the case where a "take-home" type of problem (e.g., the possibility that a dog might eat this chamber) is considered, it can be made of metal. The inerting chamber can be placed in any part adjacent to the discharge port of the liquid container. The inerting chamber can be placed in any part adjacent to the discharge port of the liquid container. vi. The liquid container can be equipped with a slow leak valve for releasing NO2 into an inert substance. Alternatively, the slow leak valve can be placed on the shuttle. It is possible to do so. vii. If the liquid container is a separate component, the liquid container can be fixed to the limiter housing. The shuttle seat of the patient inflow port can be included in any of the components. It is possible to do so. The shuttle seat of the patient inflow port can be included in any of the components. (c) The slow leak valve can be a component made of laser drilled elements (ruby, stainless steel, titanium, etc.). The slow leak valve can regulate the release of NO2 gas from the liquid container. This valve may be necessary during the release of NO2 because the inerting chemical reaction produces nitrogen and the reaction is exothermic. If the release is too fast, the plastic surface of the surrounding inert substance can overheat. To ensure that the structural integrity of these surfaces is not impaired, it is possible to measure NO2 so that all the contents converted from N2O4 are released within 10 minutes. It is possible to do so. This valve may be necessary during the release of NO2 because the inerting chemical reaction produces nitrogen and the reaction is exothermic. If the release is too fast, the plastic surface of the surrounding inert substance can overheat. To ensure that the structural integrity of these surfaces is not impaired, it is possible to measure NO2 so that all the contents converted from N2O4 are released within 10 minutes. This valve may be necessary during the release of NO2 because the inerting chemical reaction produces nitrogen and the reaction is exothermic. If the release is too fast, the plastic surface of the surrounding inert substance can overheat. To ensure that the structural integrity of these surfaces is not impaired, it is possible to measure NO2 so that all the contents converted from N2O4 are released within 10 minutes. If the release is too fast, the plastic surface of the surrounding inert substance can overheat. To ensure that the structural integrity of these surfaces is not impaired, it is possible to measure NO2 so that all the contents converted from N2O4 are released within 10 minutes. To ensure that the structural integrity of these surfaces is not impaired, it is possible to measure NO2 so that all the contents converted from N2O4 are released within 10 minutes. It is possible to do so. i. The slow leak valve can have a controlled orifice of about 0.005 - 0.030 inches (about 0.127 - 0.762 mm). It is possible to do so. ii. The diameter with respect to the ID length is functionally related to the regulation of the NO2 release rate. In fact, the greater the diameter of the orifice, the longer the lumen to cause a pressure drop and slow down the NO2 release. Referring to FIG. 22, this drawing shows an exemplary shuttle mechanism. Initial position (transport ): The inactivation side is open, the patient inflow side is closed, and the glass ampule is intact. The position of the neutralization device is on the left side, and the position of the patient using the glass limiter is on the right side.

[0148] Referring to FIG. 23, this drawing shows a shuttle mechanism with both valves closed - the glass ampule is broken, and the brown liquid N2O4 is spilling out of the glass. Referring to FIG. 24, this drawing shows a shuttle mechanism with the patient inflow seal (right side) open and the inactivation seal (left side) closed. Referring to FIG. 25, this drawing shows a shuttle mechanism in the return position (the same as the initial shuttle position) for removing the cassette.

[0149] Referring to FIG. 26, the shuttle mechanism can include a liquid container / inactivation chamber 2601, a slow leak valve 2602 (as an alternative design), an inactivation seal sheet 2603, a shuttle inactivation seal 2604 and a Luer - like seal, a radial seal 2605, a shuttle 2606, a glass ampule 2607 and N2O4,

[0150] and a liquid container 2608. Residence time and temperature of the reaction

[0151] The limiter housing can be an assembly including: a lumen of a controlled orifice Referring to FIG. 26, the shuttle mechanism can include a liquid container / inactivation chamber 2601, a slow leak valve 2602 (as an alternative design), an inactivation seal sheet 2603, a shuttle inactivation seal 2604

[0152] Referring to FIG. 26, the shuttle mechanism can include a liquid container / inactivation chamber 2601, a slow leak valve 2602 (as an alternative design), an inactivation seal sheet 2603, a shuttle inactivation seal 2604 and a Luer - like seal, a radial seal 2605, a shuttle 2606, a glass ampule 2607 and N2O4, and a liquid container 2608. The limiter housing can be an assembly including: a lumen of a controlled orifice

[0153] Residence time and temperature of the reaction The limiter housing can be an assembly including: a lumen of a controlled orifice and length, a sintered filter, a fitting for connecting a controlled orifice column to a limiter housing el rule, a T - connector, and attachment means for hermetically joining the limiter housing to a liquid container attachment means.

[0154] The limiter housing can provide an assembly structure used to regulate the delivery of NO2 gas to an air stream (supplied from the console). The NO2 gas can be mixed with air midway to a conversion cartridge (s). ridge (s). To prevent condensation from occurring and blocking the controlled orifice column, heat can be applied to the limiter housing (controlled by the console) to maintain the gas at a temperature 5 °C to 20 °C higher than the temperature of the liquid container.

[0155] To prevent condensation from occurring and blocking the controlled orifice column, heat can be applied to the limiter housing (controlled by the console) to maintain the gas at a temperature 5 °C to 20 °C higher than the temperature of the liquid container. To prevent condensation from occurring and blocking the controlled orifice column, heat can be applied to the limiter housing (controlled by the console) to maintain the gas at a temperature 5 °C to 20 °C higher than the temperature of the liquid container. ℃ higher than the temperature of the liquid container.

[0156] The limiter housing can comprise several components: (a) The limiter column can be a static flow regulator that releases NO2 gas conditional on the inlet pressure occurring in the liquid container. The pressure drop across the limiter column can be a function of the lumen diameter and the lumen length. The pressure drop across the limiter column can be a function of the lumen diameter and the lumen length. The pressure drop across the limiter column can be a function of the lumen diameter and the lumen length. i. The limiter column can have a lumen diameter of 0.010 μm to 0.030 μm and a length of 1 cm to 4 cm. The limiter column can have a lumen diameter of 0.010 μm to 0.030 μm and a length of 1 cm to 4 cm. ii. The glass column can be coated with a PTFE outer sleeve and extruded to prevent damage during glass handling and for assembly compatibility. The glass column can be coated with a PTFE outer sleeve and extruded to prevent damage during glass handling and for assembly compatibility. iii. The limiter column can be of a type 1 glass (preferred) structure, but other limiter materials such as stainless steel, ruby, etc. can also be utilized. iii. The limiter column can be of a type 1 glass (preferred) structure, but other limiter materials such as stainless steel, ruby, etc. can also be utilized. iv. The limiter column can be a compressible ferrule formed from, for example, FEP, PTFE, or PFA It can be attached to the limiter housing using a luer. The v. column may be a microbore quartz GC column coated with Teflon instead of polyimide, or it may include this. Alternatively, a small orifice having the same pressure drop as the GC column can be used. The advantage of using a relatively long column may be that the inner diameter size can be made large enough to minimize clogging.

[0157] Referring to FIG. 27, an exemplary patient inflow port liquid container / limiter housing assembly is shown. Such an assembly may include a glass ampoule 2701, a liquid container 2702, a Teflon crush washer 2703, a glass shroud 2704, a fluid tank 2705 of the liquid container, a shuttle patient inflow seal, e.g., a radial seal 2706 and a luer seal 2707, a patient inflow seat 2708, a liquid container / limiter housing joining means 2709, a limiter housing 2710, a sintered filter 2711, and a limiter column 2712. (b) The limiter housing may be a preferably metallic component having the following characteristics : i. The limiter housing has a lumen for assembling the limiter column and fixing the ferrule. ii. An alternative limiter housing can incorporate a metal tube structure around the limiter column that can be placed within the limiter housing. iii. The limiter housing can be provided with a flexible heater disposed on the outer cylindrical surface, concentrated in the vicinity of the gas discharge end, to maintain a temperature difference between the liquid container and the discharge of the limiter column. iv. The limiter housing can be formed from metal. Titanium, stainless steel, or Aluminum is a preferred material.

[0158] Referring to FIG. 28, the limiter housing T - fitting assembly may include an inerting substance 2 801, a limiter column 2802, a limiter housing 2803, a ferrule 2804, a set screw 2805, the release of NO2 from the limiter column 2806, a base 2807, a T - fitting 2808, an air inlet 2809, and an air / NO2 outlet 2810. (c) The limiter housing can be provided with a functional element for attaching a limiter filter upstream of the limiter column; vi. The limiter filter can be formed from sintered titanium without using a binder. The limiter filter can also be formed from stainless steel. The limiter filter can also be coated with SiO2 to prevent reaction at its large surface area. vii. The limiter filter can be press - fitted into the limiter housing or an intermediate metal tube.

[0159] Other liquid module components can also be included in the assembly. These can include an inerting / purging chamber, an inerting substance, an inerting chamber cap, a purge / removing substance, a filling cap, and an operating rod assembly.

[0160] Referring to FIG. 29, the liquid module housing and the base housing can include an inerting substance surrounding the liquid container / limiter assembly and the removing substance. Specifically, the liquid module housing and the base housing can include a chamber filling port 2901, an inerting chamber 2902 filled with soda lime, a liquid module housing (chamber) 2903, potassium permanganate It can be provided with a removal (purge) chamber 2904 filled with an acid salt and a cartridge stabilizer 2905. It is possible.

[0161] Referring to FIG. 30, a cross-section of the cassette passing through the inactivation chamber and the purge chamber is shown. This includes a shuttle / actuating rod coupler 3001, a purge chamber 3002, an inactivation chamber 3003, a liquid container 3004, a restrictor housing 3005, and a shuttle actuating rod 3006. It is provided with.

[0162] Referring to FIG. 31, a cassette assembly is shown. This includes a cartridge bridge 3101, a cartridge 3102, a liquid module 3103 (including a liquid container / restrictor assembly, an inactivation chamber, and a purge chamber), and a base 3104. It includes. (a) The inactivation / purge chamber housing can be a polycarbonate structure that houses the inactivating substance / liquid container / restrictor housing assembly, and the purge / removing substance can be a unique compartment. The inactivation / purge chamber housing can have several design features: i. The inactivation chamber can completely enclose and seal the liquid module assembly with an inactivating substance. ii. The inactivation chamber can provide a visual indication of whether the discolored inactivating substance has changed color due to exposure to NO2. iii. The inactivation chamber can be connected to the restrictor housing and be provided with an inactivation chamber cap that allows the passage of heater wires and temperature sensors (one for each heater). This cap can be sealed, resulting in the chamber being hermetically sealed. It can have. i. The inactivation chamber can completely contain and seal the liquid module assembly with an inactivating substance. It can be sealed. ii. The inactivation chamber can provide a visual indication of whether the discolored inactivating substance has changed color due to exposure to NO2. It can provide. iii. The inactivation chamber can be connected to the restrictor housing and be provided with an inactivation chamber cap that allows the passage of heater wires and temperature sensors (one for each heater). This cap can be sealed, resulting in the chamber being hermetically sealed. It can be provided with. This cap can be sealed, as a result, the chamber is hermetically sealed. It is sealed. ​iv. The purge / removal chamber can provide a separate housing structure for the purge / removal substances used for the discharge of the console. It can provide a separate housing structure for the purge / removal substances used for the discharge of the console. (b) The inactivating substance can be a mixture of two substances. One substance can provide effective neutralization of NO2, while the other substance can exhibit a permanent color change when exposed to NO2. It can exhibit a permanent color change when exposed to NO2. i. The main inactivating substance can be soda lime (70 - 90% of the mixture). ii. The permanent color-changing inactivating substance can be a formulation different from soda lime (the remainder of the mixture). It can be a formulation different from soda lime (the remainder of the mixture). (c) The purge / removal substance can be utilized to adjust the NO concentration delivered to the patient. If there is a need to rapidly reduce the discharge rate of the liquid module (i.e., rapidly lower the temperature), excess NO can be delivered to the removal substance to neutralize the NO before discharging it to the environment. This substance can oxidize NO to produce NO2. The support can absorb NO2. The support can absorb NO2. i. The purge / removal substance can be a support, for example, potassium permanganate on a molecular sieve. It can be a support, for example, potassium permanganate on a molecular sieve. ii. A further component of activated carbon, namely soda lime, can also be considered. (d) The actuating rod assembly can provide a patient inflow port that is normally closed by a spring load and can drive the shuttle in one direction to break the glass ampoule and close the inactivation chamber seal / open the patient inflow port seal. It can drive the shuttle in one direction to break the glass ampoule and close the inactivation chamber seal / open the patient inflow port seal. i. The actuating rod assembly can be actuated by a functional element within the console and can be coupled to a lever-actuated handle. ii. The actuating rod can be coupled to the shuttle.

[0163] Conversion Cartridge NO2 gas can be pumped into the liquid module T-type (or "T") fitting and transported at a flow rate of up to 1 L / min using indoor air that can be done. The NO2 / air mixture flows into the inlet of the first main cartridge.

[0164] Referring to FIG. 32, a cross-section of the cassette passing through cartridge 3201 is shown. Inside the cassette for the cartridge, the gas flow is from the outside to the inside.

[0165] The main cartridge can include a reducing agent, for example, ascorbic acid on silica gel, included with the matrix, and the ascorbic acid can react with NO2 to produce NO gas when the fluid stream mixture crosses the cartridge wall.

[0166] The cartridge can comprise several components: a composite material (which can be the matrix), a composite material inlet cap, a composite material outlet cap, a composite material housing, a reducing agent (e.g ascorbic acid coating), an inlet fitting including a tube, and an outlet fitting including a tube .

[0167] Two cartridges can be arranged in series after the restrictor column. The bridge from one subassembly to the next subassembly can utilize, for example, a polyethylene tube and a fitting with a hook .

[0168] Referring to FIG. 33, a cross-section of the cassette is shown. This drawing shows the inactivation chamber 33 01, the liquid container 3302 containing the glass ampoule, the cartridge 3303, and the purge chamber 3304 . ​(a) The main cartridge composite material can be a matrix, for example, a mixture of silica gel and HDPE. obtainable. i. The main composite material can be a mixture of 45% - 85% silica gel with respect to HDPE. ii. The main composite material can be substantially cylindrical, having an outer surface and an inner surface, and gas / air can flow (preferably) from the outside to the inside, but can also flow sufficiently from the inside to the outside. flow. iii. HDPE can be used as a binder to form a rigid composite structure. Alternatively, loosely packed silica gel can also be used. iv. The percentage of reducing agent (e.g., ascorbic acid) applied to the composite material can be 10% - 40 %. (b) The main composite material can be attached to the inlet cap to induce the flow of gas / air through the side wall of the cartridge. attach. i. The inlet cap can be a HDPE component. ii. The design features within the inlet cap can be alignment features to direct the housing inlet port to stabilize the cartridge during transportation or to effectively fix both ends of the composite material. or aligning function for element. (c) The main composite material can be attached to the outlet cap to release NO gas from the inside of the composite material and flow it to the next sub - assembly. attach. i. The outlet cap can be a HDPE component. ii. The outlet cap can be attached to the external cartridge housing port to provide an airtight enclosure for the cartridge. attach. (d) The main cartridge housing can be an external structure around the coated composite material. These housings can provide physical protection to the composite material during the storage of the process, can provide a moisture - proof layer against water absorption during storage, and against penetration during storage. can provide physical protection to the composite material during the storage of the process, can provide a moisture - proof layer against water absorption during storage, and against penetration during storage. against storage. It can provide an oxygen barrier. i. The housing can be formed from HDPE. ii. The composite material may require a specific pressure (up to 5 psi (0.03 4 MPa)) to allow NO2 or NO to pass through the composite material wall. The main cartridge housing can maintain a pressure that allows gas to flow through the cartridge. (e) The tubes and fittings can provide conduits for advancing gas from one sub - assembly to another. Alternative methods and mechanisms for attaching components to other components are well - known in the art and may include ultrasonic welding, spin welding, induction welding, and other means.

[0169] The liquid module can be configured in a substantially radial structure similar to a petcock having two opening positions (one for inactivation and one for patient inflow). This can be cylindrical or spherical, but a double seal can be used to prevent leakage between ports.

[0170] The breaking of the glass ampule can currently be a linear motion. Radial motion can also be utilized. This radial motion can include a cam motion where radial and linear motions occur simultaneously.

[0171] Other embodiments are also within the scope of the following claims. This application provides an invention having the following configuration. (Configuration 1) A cassette for the conversion of nitrogen dioxide to nitric oxide, comprising: A sealed housing, A first cartridge capable of converting nitrogen dioxide gas to nitric oxide within the sealed housing A trigger, comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, wherein the porous solid matrix is disposed within the first cartridge such that there is a space between the body of the first cartridge and the porous solid matrix, and the trigger has an open passageway parallel to the length of the body of the first cartridge, the first cartridge; A second cartridge capable of converting nitrogen dioxide gas to nitric oxide, wherein the outlet of the first cartridge is connected to the inlet of the second cartridge, the second cartridge comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, wherein the porous solid matrix is disposed within the first cartridge such that there is a space between the body of the first cartridge and the porous solid matrix, and the trigger has an open passageway parallel to the length of the body of the first cartridge, the second cartridge; and the cassette comprising an inactivation chamber containing an inerting substance. (Configuration 2) wherein the space has a width, the width being the distance between the surface of the porous solid matrix and the receptacle, and the width of the space can vary along the length of the receptacle, the inlet being configured to receive a gas flow, the diverter being configured to direct the gas flow into the space between the body and the porous solid matrix, and the gas flow being in fluid communication with the outlet through the porous solid matrix for converting nitrogen dioxide in the gas flow to nitric oxide, the cassette according to Configuration 1. (Configuration 3) The cassette according to Configuration 2, wherein the width of the space decreases along a part of the length of the receptacle. Cassette. (Configuration 4) The cassette according to Configuration 2, wherein the width of the space increases along a part of the length of the receptacle. Cassette. (Configuration 5) The width of the space increases along a part of the length of the receptacle from the inlet to approximately the midpoint of the receptacle, and the width of the space decreases along a part of the length of the receptacle from approximately the midpoint of the receptacle to the outlet. The cassette according to Configuration 4. (Configuration 6) The cassette according to Configuration 1, wherein the sealed housing further comprises a storage device for N2O4 and NO2. (Configuration 7) The cassette according to Configuration 6, wherein the storage device is included in a shuttle tube, and the tube stabilizes the storage device. (Configuration 8) The cassette according to Configuration 7, wherein the shuttle tube is arranged such that the inactivation chamber opens to the storage device during transportation. (Configuration 9) The cassette according to Configuration 8, wherein the inactivating substance permanently changes color when the storage device is destroyed. Cassette. (Configuration 10) The cassette according to Configuration 1, wherein the sealed housing further comprises a limiter. (Configuration 11) The cassette according to Configuration 10, wherein the limiter connects the storage device and the first cartridge. Cassette. (Configuration 12) The cassette according to Configuration 1, wherein the sealed housing further comprises a heater. (Configuration 13) The heater is wound around the storage device and changes the temperature of the storage device. The cassette according to Configuration 12, which adjusts the emission amount of nitrogen dioxide gas. (Configuration 14) The cassette according to Configuration 1, which is discarded after being used once. (Configuration 15) The cassette according to Configuration 1, which is further connected to a console and the console adjusts a heater. T. (Configuration 16) A storage device for liquid nitrogen dioxide, A container including an ampoule, An ampoule containing liquid nitrogen dioxide, and when the ampoule is broken, the liquid nitrogen dioxide is converted into nitric oxide, the ampoule; A restrictor, whose proximal end faces the ampoule and whose distal end provides an outlet for nitric oxide gas, the restrictor; A leak valve connected to the ampoule; and The storage device including a shuttle tube containing the ampoule. (Configuration 17) The storage device according to Configuration 16, wherein the shuttle tube is connected to the restrictor when a user breaks the ampoule. The storage device according to Configuration 16. (Configuration 18) The storage device according to Configuration 16, which is further connected to a heater. (Configuration 19) The storage device according to Configuration 17, wherein the heater is activated when a user breaks the ampoule. Device. (Configuration 20) The storage device according to Configuration 16, which is further connected to an inactivation chamber via the leak valve. . (Configuration 21) The storage device according to Configuration 20, wherein the shuttle rotates to connect the ampoule to either the inactivation chamber or the restrictor. The storage device according to Configuration 20. (Configuration 22) The storage device according to Configuration 16, which is further connected to a mixing T fitting. (Configuration 23) The storage device according to Configuration 22, in which air flows into the mixing T fitting. (Configuration 24) The storage device according to Configuration 16, in which the volume of the storage device is 0.53 mL or less. (Configuration 25) The storage device according to Configuration 16, which is included in a sealed housing. (Configuration 26) The sealed housing is a first cartridge capable of converting nitrogen dioxide gas to nitric oxide within the sealed housing, comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, wherein the porous solid matrix is disposed within the first cartridge such that there is a space between the body of the first cartridge and the porous solid matrix, and the porous solid matrix has an open passage parallel to the length of the body of the first cartridge, the first cartridge, a second cartridge capable of converting nitrogen dioxide gas to nitric oxide, wherein the outlet of the first cartridge is connected to the inlet of the second cartridge, the second cartridge comprising an inlet, a diverter, a body, an outlet, and a porous solid matrix containing a reducing agent, wherein the porous solid matrix is disposed within the first cartridge such that there is a space between the body of the first cartridge and the porous solid matrix, and the porous solid matrix has an open passage parallel to the length of the body of the first cartridge, the second cartridge; and the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. the storage device according to Configuration 25, further comprising an inactivation chamber containing an inactivating substance. (Configuration 27) The space has a width, and the width is between the surface of the porous solid matrix and the receptacle. is the distance between, and the width of the space may vary along the length of the receptacle, and the inlet is configured to receive a gas stream, and the diverter guides the gas stream into the space between the body and the porous solid ma trix, and the gas stream is in fluid communication with the outlet through the porous solid matrix for converting nitrogen dioxide in the gas stream to nitrogen monoxide . The cassette according to configuration 26 (Configuration 28) The cassette according to configuration 27, wherein the width of the space decreases along a part of the length of the receptacle (Configuration 29) The cassette according to configuration 27, wherein the width of the space increases along a part of the length of the receptacle (Configuration 30) The width of the space increases along a part of the length of the receptacle from the inlet to approximately the midpoint of the receptacle, and the width of the space decreases along a part of the length of the receptacle from approximately the midpoint of the receptacle to the outlet . The cassette according to configuration 29 ​​​​

Claims

1. a storage device, the storage device comprising a container; The container a shuttle tube containing an ampoule containing liquid nitrogen dioxide that is converted to nitric oxide gas when the ampoule is broken; a restrictor, the proximal end of the restrictor facing the ampoule and the distal end of the restrictor providing an outlet for the nitric oxide gas; and a leak valve connected to the ampoule a pre-storage device including:

2. 2. The storage device of claim 1, wherein the restrictor connects to the shuttle tube when the ampoule is broken.

3. 3. The storage device according to claim 1 or 2, wherein the storage device is connected to a heater.

4. 4. The storage device of claim 3, wherein the heater is activated when the ampoule is ruptured.

5. The storage device according to any one of claims 1 to 4, wherein the storage device is further connected to a deactivation chamber.

6. 6. The storage device of claim 5, wherein the shuttle tube rotates to connect the ampoule to either the deactivation chamber or the restrictor.

7. The storage device according to any one of claims 1 to 6, wherein the volume of the storage device is 0.53 mL or less.

8. The storage device according to any one of claims 1 to 7, wherein the storage device is arranged in a sealed housing.

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