Portable systems for intravascular delivery of gas-enriched solution to patients

Abstract

The present disclosure provides systems and methods for controlling gas-enrichment, e.g., oxygen-enrichment, therapy. A portable device (100) includes a pressurized container (102) and actuator (110) for portable delivery of gas-enrichment therapy.

Description

PORTABLE SYSTEMS FOR INTRAVASCULAR DELIVERY OF GAS-ENRICHED SOLUTION TO PATIENTSCLAIM OF PRIORITY

[0001] This application claims priority under 35 U.S.C. §119(e) to U.S. Patent Application Serial No. 63 / 571,838, filed on March 29, 2024, the entire contents of which are hereby incorporated by reference.TECHNICAL FIELD

[0002] The disclosure relates to systems and methods for the delivery of gas-enriched liquid into a patient.BACKGROUND

[0003] Gas-enriched liquids are desirable in a wide variety of applications. However, at ambient pressure, the relatively low solubility of many gases, such as oxygen or nitrogen, within a liquid, such as water, produces a relatively low concentration of the dissolved gas in the liquid. One method of obtaining an increase in the gas concentration level without significant increase in liquid volume involves a mixing of a gas-enriched liquid, into a liquid of interest. A liquid can be gas-enriched at high pressure.SUMMARY

[0004] This document describes various examples of handheld, portable gas-enrichment systems or devices configured to deliver gas-enriched liquid intravenously to a patient. The portable gas-enrichment system or device for delivering gas-enriched liquid within the vasculature of a patient (hereinafter the portable delivery system) may be handheld and / or configured to connect to a catheter device or cannula to deliver the gas-enriched liquid to the patient. A container (e.g., a canister) may include a gas-enriched liquid, such as an oxygen- enriched liquid). In some implementations, oxygen-enriched liquid or solution may include liquid having a dissolved O2 concentration of 0.1 ml Ch / ml liquid (STP) or greater or 0.1 - 6 ml Ch / ml liquid (STP) or 0.2 - 3 ml Ch / ml liquid (STP) (e.g., without clinically significant gas emboli). In some implementations, oxy gen-enriched liquid or solution may be an aqueous solution that has been saturated to an oxygen concentration greater than 1 ATM (760 mmHg).In some implementations, the container can include a premixed gas-enriched liquid that is configured to be shipped or stored in a premixed state. The container filled with the premixed gas-enriched liquid can be combined with an actuator in the field to deliver the gas-enriched liquid to a patient far from a medical service provider (e.g., a hospital), as described herein. In another example, the gas-enriched liquid can be mixed on-site in the field just prior to delivery to the patient. In this example, gas from a first volume can be released into a second volume including the liquid for enriching the liquid just prior to delivery to the patient.

[0005] When delivered to the patient, the gas-enriched liquid creates gas-enriched blood, e.g., oxygen-enriched blood. The gas-enriched liquid is maintained at or above a target pressure to be sufficient to ensure that the gas-enriched liquid remains pre-mixed, and the gas remains dissolved in the liquid for use in a portable device at a moment’s notice. The portable delivery device or system is configured to deliver the a gas-enriched liquid to a patient at a controlled delivery rate while maintaining the pressure during delivery. For example, the portable delivery device or system may be used to deliver the oxygen-enriched liquid directly to at-risk or ischemic tissue in the patient, e.g., myocardial tissue, increasing oxygen diffusion to the ischemic zone. This may reduce endothelial swelling and microvascular resistance in the microvasculature and restore microvascular flow. In other embodiments, the portable delivery device or system may be used to deliver gas-enriched liquid to the peripheral vasculature in the patient. In other embodiments, the portable delivery device or system may be used to treat a patient who has suffered blood loss or other traumatic arrest, as well as cardiac arrest.

[0006] The systems, devices and methods described herein provide one or more advantages. The portable delivery device or system can be transported to any location, such as to the site of an accident or into a mode of transportation while a patient is being transported to a medical service facility. The portable delivery device or system can be interfaced with different patients because the containers of the gas-enriched liquid are modular with the actuator and delivery conduit of portable delivery device or system. A user can manually deliver gas-enriched liquid, e.g., oxygen-enriched liquid, to a patient in the field without having to precisely control the delivery flow rate and pressure to the patient because the portable delivery device or system is configured to control the pressure and / or the flow rate of the gas-enriched liquid delivered to the patient. The user can therefore ensure that a gas enriched liquid is delivered to a patient in the field while maintaining a sufficient controlled flow rate and / or maintaining the pressure in the container above a threshold pressure and / or maintaining a controlled pressure drop from the container, through theconduit and into the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery. In certain aspects, this can be accomplished mechanically. For example, the volume of the container may be changed as the actuator (e.g., the plunger or piston) is advanced within the container to deliver liquid from the container. When the plunger is advanced and liquid is delivered from the container, the space within the container is reduced, thereby maintaining the pressure in the container above the threshold pressure to ensure the gas remains dissolved in the liquid while in the container. The minimum threshold pressure in the container can be maintained or monitoring by using a pressure sensor located in the container, which may be coupled to a pressure gauge on the container. The pressure sensor and / or gauge may also be used to ensure that no leaks have occurred by providing an alert or visual indication of the pressure or a change in pressure. Through the use of this portable delivery device or system, gas-enrichment therapy, e.g., oxygen-enrichment therapy, can be delivered in the field, remote from m a medical service facility. In some embodiments the gas-enriched liquid may be delivered to the patient with a laminar or approximately laminar flow, which helps prevent significant outgassing during delivery; however the gas-enriched liquid need not be delivered to the patient with a laminar or approximately laminar flow. In some embodiments, the gas-enriched liquid may be premixed and loaded and / or stored in the container in a premixed state. In some embodiments, the gas-enriched liquid may not be premixed, but instead the portable delivery device or system may include multiple chambers for holding the gas and liquid, e.g., plasma, separately. Upon activation of a trigger or other mechanism, the chambers may release their contents to be mixed with one another thereby forming a mixed gas-enriched liquid prior to delivery to the patient.

[0007] In certain aspects, a portable delivery system can include a control system including a controller configured to control delivery of the gas-enriched liquid. The control system can be configured to enable a user to operate the portable device. The controller can be configured to receive data from sensors, such as a pressure sensor or patient sensors placed on or in the patient. The controller can control the actuator to cause delivery of the gas- enriched liquid to the patient based on the data received from sensors. For example, the controller can be coupled to a driveshaft configured to operate the actuator to deliver a bolus of liquid to the patient, and / or open or close valves to control container pressure. In an aspect, the controller can control mixing of the liquid by controlling a valve that releases gas into the container from a separate gas source (a tank or reservoir) e.g., in an aspect where the gas- enriched liquid may not be premixed, but instead is mixed by the device during use, but priorto delivery. The controller can thereby control the pressure and concentration of the gas in the liquid of the container.

[0008] The control system may be connected to sensors via wired connection and / or can include a transceiver for receiving data from sensors via wireless signals or for sending instructions to other devices (e.g., a remote display). In some implementations, the control system includes sensor ports for connecting to sensors, a power supply (e.g., a battery), and a display. In some implementations, the display includes controls, such as controls for operating the actuator, such as to deliver a bolus of gas-enriched liquid to the patient.

[0009] In some aspects, the canister is disposable or is provided including a prepressurized volume filled with premixed gas-enriched liquid. The canister can be packaged and shipped as a modular unit that can interface with a delivery device including the actuator. In an example, a pre-loaded canister is coupled to the actuator when manufactured and shipped to end users. One or more of the advantages described herein can be enabled by one or more of the following embodiments.

[0010] In an aspect, a handheld device configured for delivering a gas-enriched liquid intravascularly to a patient. The handheld device includes a container defining a volume, the volume holding a gas-enriched liquid at or above a threshold pressure sufficient to maintain gas dissolved in the gas-enriched liquid; an actuator coupled to the container, the actuator configured to cause the gas-enriched liquid to be released from the container; a conduit coupled to the container, the conduit configured to facilitate intravascular delivery of the gas- enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery; and a valve coupled to the container, the valve configured to maintain the gas-enriched liquid at or above the threshold pressure within the container during delivery to the patient.

[0011] In some implementations, the device includes a coupling interface configured to couple to a patient delivery device, the coupling interface including the conduit. In some implementations, the patient delivery device is a catheter or cannula.

[0012] In some implementations, the conduit is configured to deliver the gas-enriched liquid in a laminar flow or nearly laminar flow having a Reynolds number of less than 2000.

[0013] In some implementations, a connector couples the conduit to the container, and wherein the connector comprises the valve.

[0014] In some implementations, the gas-enriched liquid is part of a solution in the volume, the solution further comprising plasma.

[0015] In some implementations, the gas-enriched liquid is part of a solution in the volume, the solution further comprising blood.

[0016] In some implementations, the gas-enriched liquid is part of a solution in the volume, the solution further comprising an artificial blood substitute.

[0017] In some implementations, the gas-enriched liquid is part of a solution in the volume, the solution further comprising a medicament.

[0018] In some implementations, the gas-enriched liquid is oxygen-enriched liquid. In some implementations, the oxygen-enriched liquid is oxygen-enriched liquid having a dissolved O2 concentration of 0.1 - 6 ml Ch / ml liquid.

[0019] In some implementations, the conduit comprises a cannula having an outside diameter between 0.020 and 0.200 millimeters (mm).

[0020] In some implementations, the container comprises: an external volume that forms a hard shell; and an internal volume inside of the external volume, the internal volume including a flexible lining. In some implementations, the flexible lining is removable from the hard shell.

[0021] In some implementations, an inner surface of the conduit comprises an antinucleation coating configured to prevent nucleation of the gas-enriched liquid inside the conduit.

[0022] In some implementations, the actuator comprises a piston that, when compressed, forces the gas-enriched liquid from the volume at a controlled flow rate. In some implementations, the piston is coupled to a second actuator, the second actuator configured to compress the piston at the controlled flow rate.

[0023] In some implementations, the control of the pressure drop of the gas-enriched liquid during delivery from the container to the patient includes a controlled flow rate that comprises a rate of gas-enriched liquid delivery from the volume that is within a threshold tolerance from a baseline delivery rate. In some implementations, the baseline delivery rate is 2 to 3 cubic centimeters per minute or 1 to 20 ml / sec.

[0024] In some implementations, the conduit comprises an aperture geometry that causes laminar flow or nearly laminar flow of the gas-enriched liquid, the laminar flow or nearly laminar flow being within a threshold distance of an end of the conduit when the gas- enriched liquid is being delivered intravascularly to the patient. In some implementations, laminar or nearly laminar flow comprises fluid flow with a Reynolds number under 1500.

[0025] In some implementations, the actuator comprises a pump configured to deliver the gas-enriched liquid from the volume at a controlled flow rate. In some implementations, thepump comprises a mechanical actuator. In some implementations, the pump comprises an electronic actuator. In some implementations, the electronic actuator is configured to activate a motor that pumps the gas-enriched liquid from the volume at the controlled flow rate.

[0026] In some implementations, the actuator comprises: a button configured to control the delivery of the gas-enriched liquid; and a valve configured to open when the button is pressed to deliver the gas-enriched liquid at a controlled flow rate and close when the button is released to prevent further delivery of the gas-enriched liquid.

[0027] In some implementations, the actuator is configured to deliver a predefined amount of the gas-enriched liquid at a controlled flow rate within a predetermined flow rate range. In some implementations, the predetermined flow rate range is 2-3 cubic centimeters per minute of the gas-enriched liquid.

[0028] In some implementations, the actuator comprises a purge control configured to flush remaining gas-enriched liquid from the actuator.

[0029] In some implementations, the device includes a cannula and a coupling device configured to couple the cannula to the container, wherein the actuator is configured to deliver the gas-enriched liquid through the cannula to the patient. In some implementations, the actuator is fixed to the container by a coupling device. In some implementations, an interior of the cannula is coated in a layer of anti -nucleation material. In some implementations, the anti -nucleation material comprises heparin. In some implementations, a diameter of the cannula is between 0.02 millimeters and 0.200 millimeters. In some implementations, the actuator is removable from the container. In some implementations, the device includes a modular delivery device, the container being configured to receive a different instance of the modular delivery device to replace a removed modular delivery device. In some implementations, the different instance of the modular delivery device is sterile.

[0030] In some implementations, the control of the pressure drop of the gas-enriched liquid during delivery from the container to the patient includes a controlled flow rate that is a constant flow rate for a predefined time period.

[0031] In some implementations, the container is pressurized to least 100 pounds per square inch, and wherein the conduit delivers the gas-enriched liquid at a pressure between 1- 5 atmospheres.

[0032] In some implementations, the device includes a heating element configured to maintain a temperature of the gas-enriched liquid within a predefined range.

[0033] In some implementations, the device includes a cooling element configured to maintain a temperature of the gas-enriched liquid within a predefined range.

[0034] In some implementations, the device includes a hermetic seal configured to seal the volume of the container, wherein the actuator is configured to break the hermetic seal when the actuator is actuated.

[0035] In some implementations, the volume is sterile.

[0036] In some implementations, the device includes a flow sensor configured to measure a flow rate from the conduit.

[0037] In some implementations, the device includes a pressure sensor configured to measure the pressure in the volume.

[0038] In some implementations, the conduit is configured to couple to an intravascular line that is inserted into a vasculature of the patient.

[0039] In some implementations, the device includes a pump configured for pressurizing the volume to the pressure.

[0040] In some implementations, the conduit comprises an adaptor for receiving a patient delivery device, the adaptor comprising a valve that remains closed when the patient delivery device is not attached to the adaptor, the valve configured to open when the patient delivery device is attached to the adaptor. In some implementations, the valve is configured to interface with the patient delivery device to maintain a sterile path to the patient delivery device. In some implementations, the adaptor comprises a Luer adaptor. In some implementations, the adaptor comprises a needleless adaptor.

[0041] In some implementations, the device includes a temperature sensor configured to measure a temperature of the gas-enriched in the container.

[0042] In some implementations, the device includes one or more sensors configured to detect a leak in the volume. In some implementations, the one or more sensors comprises an oxygen concentration detector. In some implementations, the one or more sensors comprises a mechanical pop-up device configured to remain in popped up configuration when no leak has occurred and to transition to a non-popped up configuration when a leak has occurred.

[0043] In some implementations, the actuator comprises a mechanical spring configured to compress the volume to maintain the pressure.

[0044] In some implementations, the actuator comprises a pneumatic piston configured to compress the volume to maintain the pressure.

[0045] In some implementations, the actuator comprises a trigger for actuation of delivery of the gas-enriched liquid at a controlled flow rate.

[0046] In some implementations, the actuator is configured to interface with an external actuation device, the external actuation device comprising a seating for the container and a trigger configured to actuate the actuator for delivery of the gas-enriched liquid at a controlled flow rate.

[0047] In some implementations, the conduit is configured to control the pressure drop of liquid such that liquid is delivered with a flow profile having a Reynolds number within a range of 500 - 10,000.

[0048] In some implementations, the container and actuator are configured to maintains the gas-enriched liquid solution at a target pressure.

[0049] In some implementations, the conduit has an internal diameter and length that are configured to control the pressure drop of the gas-enriched liquid during delivery. In some implementations, controlling the pressure drop of the gas-enriched liquid during delivery comprises maintaining flow from the conduit of the gas-enriched liquid between a Reynolds number of 500 and 15,000.

[0050] In some implementations, the valve is positioned at a connection to the cannula from the conduit.

[0051] In some implementations, the valve comprises a check valve configured to sets a release pressure to control a flow rate and the pressure drop of the gas-enriched liquid during delivery.

[0052] In some implementations, the valve comprises a manually activated valve.

[0053] In some implementations, the valve opens responsive to pressure exceeding a threshold pressure in the container.

[0054] In some implementations, the actuator comprises a pneumatic cylinder in the container that is driven by pressure in the cylinder.

[0055] In some implementations, the container is configured to maintain a pressure enabling laminar flow in a removable cannula.

[0056] In some implementations, the gas is premixed with liquid to form the gas-enriched liquid, and wherein the volume is configured to hold the premixed gas-enriched liquid without outgassing for a minimum period of time that enables storage or shipping of the premixed gas-enriched liquid.

[0057] In an aspect, a system is configured to deliver gas-enriched liquid intravascularly to a patient. The system includes a portable device that is preloaded with a gas-enriched liquid, the portable device comprising: a container defining a volume, the volume holding a gas-enriched liquid at or above a threshold pressure such that gas remains dissolved in thegas-enriched liquid; an actuator coupled to the container, wherein the actuator is configured to cause the gas-enriched liquid to be released from the container; a conduit coupled to the container, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery; a valve coupled to the container, the valve configured to maintain the gas-enriched liquid at or above the threshold pressure within the container during delivery to the patient; and a controller in communication with the actuator, the controller configured to control the actuator to cause intravascular delivery of the gas-enriched liquid to the patient.

[0058] In some implementations, the system includes an external actuation device, the external actuation device comprising a seating for the portable device and a trigger configured to actuate the actuator for delivery of the gas-enriched liquid at the flow rate.

[0059] In some implementations, the system includes a flow sensor configured to measure flow of the gas-enriched liquid from the conduit, the sensor being in communication with the controller, wherein the flow sensor provides a signal to the controller, the signal representing the flow of the gas-enriched liquid, and wherein the controller controls the flow rate based on the signal from the flow sensor.

[0060] In some implementations, the system includes a pressure sensor configured to measure a pressure of the gas-enriched liquid in the volume, the sensor being in communication with the controller. The pressure sensor provides a signal to the controller, the signal representing the pressure of the gas-enriched liquid in the volume, and the controller is configured to maintain the pressure in the volume to be above a threshold pressure based on the signal from the pressure sensor.

[0061] In some implementations, the system includes a sensor configured to measure a value of a patient parameter, the sensor being in communication with the controller, wherein the controller is configured to control, based on the value of the patient parameter, the actuator to deliver the gas-enriched liquid intravascularly to the patient through the conduit.

[0062] In some implementations, the patient parameter comprises a cardiac function of the patient. In some implementations, the patient parameter comprises a blood pressure of the patient. In some implementations, the patient parameter comprises a spontaneous respiration of the patient. In some implementations, the patient parameter comprises a volume of the gas- enriched liquid delivered to the patient. In some implementations, the patient parameter comprises an euvolemia of the patient. In some implementations, the patient parametercomprises a temperature of the patient. In some implementations, the system includes a heating or cooling element in communication with the controller, wherein the controller is configured to heat or cool the gas-enriched liquid by controlling the heating or cooling element.

[0063] In some implementations, the system includes a display in communication with the controller, wherein the display is configured to display one or more values representing a state or operation of the portable device. In some implementations, the display is configured to display a visual representation of one or more of: a delivery flow rate, a total volume of the gas-enriched liquid remaining in the portable device, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery of the portable device, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas-enriched liquid in the volume, a cardiac function of the patient, or a combination thereof.

[0064] In some implementations, the controller is configured to: receive feedback representing a delivery flow rate, a total volume of the gas-enriched liquid remaining in the portable device, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery of the portable device, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas-enriched liquid in the volume, a cardiac function of the patient, or a combination thereof; and control the actuator to deliver the gas-enriched liquid intravascularly to the patient.

[0065] In some implementations, controlling the actuator comprises actuating a portion of the actuator to increase or slow the delivery flow rate of the gas-enriched liquid responsive to receiving the feedback.

[0066] In some implementations, the controller controls a flow rate to ensure a laminar flow or nearly laminar flow of gas-enriched liquid at a point of delivery into the patient from the conduit.

[0067] In some implementations, the laminar flow or nearly laminar flow includes fluid flow having turbulence below a threshold.

[0068] In some implementations, the controller controls a flow rate to ensure that the gas- enriched liquid is free of bubbles or has bubbles below a threshold amount at a point of delivery into the patient from the conduit.

[0069] In some implementations, the system includes a catheter configured to couple to the conduit, the catheter configured to deliver the gas-enriched liquid at the flow rate.

[0070] In some implementations, the system includes a cannula configured to couple to the conduit, the cannula configured to deliver the gas-enriched liquid at the flow rate.

[0071] In some implementations, the gas-enriched liquid is oxygen-enriched liquid.

[0072] In some implementations, the oxygen-enriched liquid is oxygen-enriched liquid having a dissolved O2 concentration of 0.1 - 6 ml Ch / ml liquid.

[0073] In an aspect, a device is configured to deliver a gas-enriched liquid intravascularly to a patient. The device includes a container defining a volume, the volume holding a gas- enriched liquid at or above a threshold pressure such that gas remains dissolved in the gas- enriched liquid; an actuator coupled to the container, the actuator configured to cause the gas- enriched liquid to be released from the container; and a conduit, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient, the conduit configured to control the pressure drop of the gas-enriched liquid to deliver the gas-enriched liquid with a flow profile having a Reynolds number within a range of 500 - 10,000.

[0074] In some implementations, the conduit comprises a variable cross section. In some implementations, the conduit comprises a constant cross section.

[0075] In an aspect, a device is configured for delivering a gas-enriched liquid intravascularly to a patient. The handheld device includes a gas reservoir including gas for dissolving in a liquid to generate a gas-enriched liquid; a container defining a volume, the volume holding the liquid at or above a threshold pressure sufficient to maintain gas dissolved in the gas-enriched liquid; a first valve coupled to the gas reservoir, the first valve configured to release the gas into the container for dissolving in a liquid to generate a gas- enriched liquid; a second valve coupled to the container, the second valve configured to maintain the gas-enriched liquid at or above the threshold pressure within the container; and a controller in communication with the first valve and the second valve, the controller configured to cause the first valve to release the gas from the gas reservoir to mix with the liquid for generating a gas-enriched liquid that is maintained at or above the threshold pressure and the second valve to release the gas-enriched liquid from the container to a conduit; the conduit being coupled to the container, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery.

[0076] In some implementations, the device includes a pressure sensor configured to measure a pressure value within the container, the controller configured to release the gasfrom the gas reservoir to mix with the liquid for generating a gas-enriched liquid based on a pressure value measured by the pressure sensor.

[0077] In some implementations, the device includes a pressure sensor configured to measure a pressure value within the conduit, the controller configured to release the gas from the gas reservoir to mix with the liquid for generating a gas-enriched liquid based on the pressure value measured by the pressure sensor.

[0078] In some implementations, either the first valve includes a pinch valve, the second valve includes a pinch valve, or both the first and second valves comprise respective pinch valves.

[0079] In some implementations, the device includes a user interface, wherein the controller is configured to receive a command through the user interface to control the first valve, the second valve, or both the first and second valves.

[0080] In some implementations, the controller is configured to cause the first valve is configured to release the gas into the container for dissolving in a liquid to generate the gas- enriched liquid in response to a signal to deliver the gas-enriched liquid.

[0081] In a general aspect, there is provided a computer program to operate the controller. The computer program may be stored in a memory or on a non-transitory processor-readable medium. The computer program is configured to cause one or more processors to perform one or more of the operations described with reference to any preceding aspect.

[0082] In a general aspect, the operations performed by a system described herein can be performed as a process by a system, device, or a plurality of devices.

[0083] In general, an implementation described with respect to one aspect may be provided in combination with another aspect. The details of one or more embodiments are set forth in the accompanying drawings and the description. Other features and advantages will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0084] FIG. 1 illustrates a side view of an example portable device configured to deliver gas-enriched liquid to a patient.

[0085] FIG. 2 illustrates a perspective view of an example portable device configured to deliver gas-enriched liquid to a patient.

[0086] FIG. 3 illustrates a side view of a container for the portable device of FIG. 1 or FIG. 2.

[0087] FIG. 4 illustrates a perspective view of an example portable device configured to deliver gas-enriched liquid to a patient.

[0088] FIG. 5 illustrates a side view of an example portable device configured to deliver gas-enriched liquid to a patient.

[0089] FIGS. 6A-6B show an example of a device configured to deliver gas-enriched liquid to a patient.

[0090] FIG. 7 illustrates an example of a system including a portable device configured to deliver gas-enriched liquid to a femoral artery of a patient.

[0091] FIG. 8 illustrates an example of a system including a portable device configured to deliver gas-enriched liquid to a radial artery of a patient.

[0092] FIG. 9 is a flow diagram of an example process for controlling delivery of oxygen-enriched blood to a patient.

[0093] FIG. 10 shows an example computer system.

[0094] The drawings primarily are for illustrative purposes and are not intended to limit the scope of the inventive subject matter described herein. The drawings are not necessarily to scale; in some instances, various aspects of the inventive subject matter disclosed herein may be shown exaggerated or enlarged in the drawings to facilitate an understanding of different features. In the drawings, like reference characters generally refer to like features (e.g., functionally similar and / or structurally similar elements).DETAILED DESCRIPTION

[0095] The following disclosure describes systems, devices, and methods related to, and example embodiments of, gas enrichment therapy or oxygen or gas therapy systems, methods and components. The systems and devices permit gas-enrichment therapy, e.g., oxygen therapy, to be provided to patients using a portable (e.g.,), battery-operated device. Oxygen therapy refers to minimally invasive procedures for enriching oxygen content of blood through catheter-facilitated infusion of oxygen-enriched fluid, such as oxygen-enriched liquid (e.g., saline or blood), directly into a patient’s blood vessel.

[0096] The portable delivery systems and devices described herein are each configured to deliver the gas-enriched liquid to a target region or localized region in the patient, thereby increasing oxygen in the blood of the patient and diffusion of oxygen into tissue, which maytreat ischemic (oxygen-deprived) tissue. These procedures may be used for treating a patient who has suffered blood loss or other traumatic arrest, as well as cardiac arrest. For example, in a case of a cardiac emergency, an ambulance or other caregiver may arrive at the patient between 10-15 minutes after being called. The medical service provider can immediately begin treating the cardiac arrest with the oxygen-enriched fluid. The patient can therefore be treated during his or her return to a hospital, saving 10-15 minutes of time and reducing treatment delay in such situations. For example, for some conditions, such as cardiac arrest, a delay in treating the patient of a few minutes can have significant health consequences. The reduction of time to deliver oxygen therapy can mitigate patient damage.

[0097] The portable delivery systems and devices described herein enable controlled delivery of gas-enriched liquid to a patient in the field where conventional oxygen therapy equipment is not available. For example, a patient being treated for an arrest, either cardiac or traumatic, for instance at the scene of a vehicular accident or cardiac arrest, gun shooting, or other acute resuscitative care. These patients undergoing such acute resuscitative care are in urgent need of stabilizing in the field and may benefit from oxy gen-enriched liquid. Portable delivery devices and systems described herein can enable the delivery of oxygen-enriched liquid in the field, such as at the scene of an accident or cardiac arrest. The portable delivery devices and systems enable the delivery of oxygen-enriched liquid during transportation (e.g., in an ambulance) to a hospital or other medical service facility.

[0098] The portable delivery systems and devices described herein are configured to deliver the gas-enriched liquid, e.g., oxygen-enriched liquid, at a controlled rate while at the same time maintaining the gas-enriched liquid at a pressure that sufficiently ensures gas supersaturation, or in the case of oxy gen-enriched liquid, oxygen supersaturation, within the portable delivery system or device while transport and delivery of the gas-enriched liquid occurs. Specifically, the gas-enriched liquid may be kept within a threshold pressure range (e.g., 100-150 PSI) that does not over deliver liquid to the patient or reach a pressure level that may be unsafe for the patient, but that is sufficient to ensure that significant outgassing or clinically significant undissolved gas bubble formation within the gas-enriched liquid does not occur and the concentration of gas is maintained above a threshold within the gas- enriched liquid. The gas-enriched liquid is kept at or above the threshold pressure prior to use of the portable delivery system or device. The portable delivery system or device maintains the gas-enriched liquid at or above the threshold pressure so that therapy, e.g., the delivery of oxygen-enriched liquid, can be performed by the portable delivery system on demand.,

[0099] The portable delivery systems and devices described herein are further configured to maintain the pressure of the gas-enriched liquid in the container volume at or within a pressure range (e.g., 100 to 150 PSI) during delivery of the gas-enriched liquid to the patient. The conduit of the portable delivery system or device is sized and configured such that it controls a pressure drop of the gas-enriched liquid that occurs when the gas-enriched liquid is released from the container, through the conduit and into the patient. For example, if a patient delivery device (e.g., a cannula) is attached to the portable delivery system, a pressure drop can occur as the gas-enriched liquid exists the container and fills the conduit of the portable delivery system or device.

[0100] The portable delivery systems and devices described herein may also be configured to maintain a pressure of the gas-enriched liquid within the container by reducing a volume of the container storing the gas-enriched liquid or by some other mechanism during delivery. Specifically, as subsequently described, a geometry of a delivery conduit controls a pressure drop to keep the gas dissolved in solution until the solution is in the patient vasculature. A valve is configured to release the solution into the conduit when a pressure in the container exceeds a threshold pressure. An actuator, such as a piston or plunger, reduces a volume of the container to force solution through the valve into the conduit at or near the desired pressure. The portable delivery systems and devices are configured for a controlled flow rate and / or a controlled pressure drop from the container, through the conduit and into the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery. The volume of the container may be changed as the plunger is advanced within the container to deliver fluid from the container. When the plunger is advanced, the space within the container is reduced, thereby maintaining the pressure in the container above the threshold. A pressure sensor located in the container, which is coupled to a pressure gauge on the container, may be used to monitor the pressure in the cannister, detect any leaks and make the user aware of a change in pressure above or below the threshold.

[0101] The portable delivery systems and devices described herein may be configured to control a flow rate of the gas-enriched liquid as it is delivered to the patient. When the portable delivery system or device is actuated to release the gas-enriched liquid for delivery into the patient, a flow of the gas-enriched liquid may be controlled so that the patient does not receive too much gas-enriched liquid at a given time. In certain embodiments, the flow rate may be maintained to cause a laminar or near laminar flow from the conduit of the portable delivery system or device to the vasculature of the patient. In certain embodiments, the flow rate may be maintained to cause a smooth flow from the conduit of the portabledelivery system or device to the vasculature of the patient, which may not be laminar. The portable delivery system or device may control the flow rate and / or pressure to help sufficiently ensure that outgassing or bubble formation at the delivery site is below a threshold level. In addition to controlling the flow rate, the portable delivery system or device may be configured to maintain the pressure of the liquid within the container until the gas- enriched liquid is delivered to the patient. Maintaining the gas-enriched liquid at or above the threshold pressure is sufficient to ensure that a desired gas or oxygen level is maintained within the gas-enriched liquid to cause the desired treatment effect on the patient when the gas-enriched liquid is delivered to the vasculature of the patient.

[0102] The portable delivery systems and devices described herein are configured to maintain the pressure of the gas-enriched liquid in the container volume, control the pressure drop of the gas-enriched liquid as it travels from the container through the conduit and / or control the flow rate of gas-enriched liquid delivery to patients in the field or other location remote from a medical facility. A specific conduit geometry (e.g., length and inner diameter) may be utilized to achieve a pressure drop from the threshold pressure to zero as the gas is delivered to the patient while maintaining oxygen dissolved in the solution without significant outgassing. For example, the conduit geometry may have an inner diameter of 3-5 mm, and length of 20-40 cm to maintain oxygen in the solution without significant outgassing. A pressure drop of 100-150 PSI to 0 PSI (e.g., patient vasculature pressure) may occur from the container through the conduit to the patient

[0103] FIG. 1 illustrates a side view of an example portable delivery device 100 configured to deliver gas-enriched liquid, e.g., premixed gas-enriched liquid, to a patient. Specifically, the portable delivery device 100 is configured to deliver the gas-enriched liquid into a vasculature of the patient. The delivery of the gas-enriched liquid, e.g., oxygen- enriched liquid, increases the oxygen level in the blood and allows for sufficient diffusion of oxygen into the tissue. The portable delivery device 100 can be a handheld system. A user can transport the portable delivery device 100 to the location in the field at which a patient is to receive the gas-enriched liquid.

[0104] The portable delivery device 100 includes a container 102 that may be coupled to a conduit 104 by a connector 106. The container 102 defines a volume that stores a premixed gas-enriched liquid for delivery from the container to the patient. The volume is configured to hold the premixed gas-enriched liquid, which has been preloaded into the container, at or above a threshold pressure such that gas remains dissolved in the gas-enriched liquid. Generally, a physical construction of the container 102 is configured to maintain a pressuresufficiently above a minimum pressure value. In some embodiments, the device 100 can include a pressure sensor 107 that is configured to measure an internal pressure the container 107. The pressure sensor 107 can provide a mechanism for monitoring whether a minimum pressure threshold is maintained. In an aspect, the pressure sensor 107 can be integrated with the container 102 and include a built-in gauge. In an aspect, the pressure sensor 107 can include a separate, disposable pressure gauge. The pressure sensor 107 can be mounted on the container near a conduit 104 or at any location to measure the internal pressure of the container 102. In an aspect a user can connect a patient delivery device 108 to the conduit 104 of the container 102 and check the container 102 pressure by referencing a gauge or other display before use. In an aspect, the pressure sensor 107 is built into the patient delivery device, which includes a canula or catheter inserted in a patient.

[0105] An actuator 110 is coupled to the container 102. The actuator 110 is configured to cause the gas-enriched liquid to be released from the container 102 during delivery from the container to the patient, as subsequently described. The actuator 110, container 102, conduit 104, and connector 106 are coupled together in the device 100 to enable the portable delivery device 100 to maintain the gas-enriched liquid at a target pressure and deliver the gas- enriched liquid at a controlled pressure drop and / or at a controlled flow rate to prevent significant outgassing and minimizes nucleation. For example, the device 100 may be configured to minimize gas that is not dissolved in liquid while delivering the gas-enriched liquid to the patient. For example, 1.0 ml or more of undissolved gas or outgassing of dissolved oxygen from the gas-enriched liquid in a patient’s vasculature may be considered a clinically significant amount of undissolved gas or outgassing. In certain implementations, the device lOOmay deliver gas-enriched liquid (e.g., oxygen-enriched) with no more than 0.99 ml of undissolved gas, e.g., about 0.000 to 0.99 ml of undissolved gas forming in the vasculature. In certain implementations, the device 100 may deliver gas-enriched (e.g., oxygen-enriched) liquid with less than.01 ml of undissolved gas, e.g., about 0.001 to 0.009 ml of undissolved gas forming in the vasculature. In certain implementations, the device 100 may provide an approximately laminar flow of the gas-enriched liquid to the patient, but the flow does not have to be laminar to prevent significant outgassing.

[0106] The container 102 can be formed from various materials and in various configurations that enable the container to maintain the premixed gas-enriched liquid at or above a threshold pressure. Specifically, the container 102 enables the gas-enriched liquid to remain saturated with a high concentration of oxygen, interfaces with the actuator 110 for causing delivery of the gas-enriched liquid from the interior of the container, is coupled to avalve or other mechanism to enable a flow rate from the container that minimizes nucleation, and is coupled to a conduit that enables delivery of the gas-enriched liquid from the container to the conduit and to the vasculature of the patient. The conduit is configured to control a pressure drop of the premixed gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the premixed gas-enriched liquid without significant outgassing during delivery. The conduit may prevent the pressure dop from exceeding a predefined threshold drop in pressure. The conduit may also prevent leaks, and / or prevent the liquid from becoming contaminated.

[0107] To control a pressure drop, the device 100 uses a geometry of the actuator 110 and the container 102 in addition to a geometry of the conduit 104 such that a minimum pressure is maintained within the container and a threshold pressure drop is not exceeded in the conduit. The actuator 110 is configured to move within the container 102 to force the oxygen- enriched liquid from the container 102 by reducing a volume of the container. The oxygen- enriched liquid is maintained above the threshold pressure as delivered because a valve 204 (described in further detail in relation to FIG. 2), is configured to open only when the internal pressure of the container exceeds a threshold pressure that is above the minimum pressure. The oxygen-enriched liquid is forced from the container 102 into the conduit 104 at a pressure above the threshold. The conduit 104 includes a diameter and length that controls the pressure drop, as subsequently described.

[0108] The container 102 includes an external volume that forms a hard shell. The external shell is configured to resist compression that may alter the pressure of the gas- enriched liquid within the volume. In some implementations, the actuation 110 of the delivery of the gas-enriched liquid from the container 102 is based on increasing an internal pressure of the gas-enriched liquid above a threshold pressure (e.g., causing a valve to open). In this case, the wall of the container 102 prevents inadvertent compression of the internal volume of the container that may trigger delivery of the gas-enriched liquid from the container (e.g., through the valve).

[0109] The container 102 is pressurized for storing the premixed gas-enriched liquid. In some implementations, the container 102 is pressurized to at least 100 pounds per square inch (PSI), and the conduit may deliver the gas-enriched liquid at a pressure between 10 and 75 PSI (e.g., about 1-5 atmospheres). This value may be controlled by the valve 204, subsequently described, and the geometry of the conduit 104, subsequently described. Depending on the composition of the gas-enriched liquid, the container 102 can be pressurized to other pressure ranges. Generally, the container maintains the pressure within athreshold of a target pressure. For example, the pressure can be calibrated based on the amount of the gas-enriched liquid stored in the container, the amount of gas, such as oxygen, added to the gas-enriched liquid, and the pressure required to deliver the gas-enriched liquid from the container to the conduit 104 (e.g., the crack pressure required to open a valve). The container 102 can be configured to hold the premixed gas-enriched liquid at a target pressure at or above a minimum pressure for ensuring the premixed gas-enriched liquid does not separate and the oxygen remains dissolved in the liquid. In some implementations, the container 102 can be configured to maintain the pressure at a target pressure that is a threshold amount over the minimum pressure, such as 1%, 2%, 5%, 10%, or any such threshold amount. The container can be configured to deliver the gas-enriched liquid to the conduit 104 and to a patient when the pressure increases more than a threshold amount over the target pressure, which may be required to open or move a valve, such as an increase of 1%, 2%, 5%, 10%, or any such threshold amount.

[0110] The gas-enriched liquid within the container can be configured to have one or more compositions. Generally, for a given composition of oxygen-enriched liquid, the oxygen-enriched liquid may include dissolved oxygen (e.g., in saline) held at 50-150 PSI within the container. In some implementations, the oxy gen-enriched liquid may be an oxygen-enriched liquid having a dissolved O2 concentration of 0.1 - 6 ml Ch / ml liquid.

[0111] The gas-enriched liquid within the container 102 can include one or more solutions in which the gas is dissolved. For example, a premixed oxygen-enriched liquid may form a solution in the container 102 that includes one or more different kinds of liquids. The solution can include blood. The solution can include an artificial blood substitute. The solution can include plasma. The solution can include saline. In some implementations, solution can include isotonic solutions and / or various electrolytes. In an example, an oxygen- enriched solution includes saline and oxygen at a pressure of 50-150 PSI. In some implementations, the oxygen-enriched liquid can include blood or a blood substitute. In some implementations, the oxygen-enriched liquid can include plasma.

[0112] The concentrations of oxygen within the example solutions can vary depending on the application for the portable delivery device 100. In some implementations, oxygen- enriched liquid or solution, e.g., supersaturated oxygen liquid or solution, may include liquid having a dissolved O2 concentration of 0.1 ml Ch / ml liquid (STP) or greater or 0.1 - 6 ml Ch / ml liquid (STP) or 0.2 - 3 ml Ch / ml liquid (STP) (e.g., without clinically significant gas emboli). When such oxygen-enriched liquid or solution is mixed with blood, the resulting blood may be referred to as oxygen-enriched blood. In certain implementations, the portabledelivery device 100 may deliver an infusion of oxygen-enriched blood having an elevated pO2 in a target range of 400 mmHg or greater or 600-1500 mmHg or 760-1200 mmHg or around 1000 mmHg.

[0113] In one example, oxygen-enriched blood may have a pO2 of 760-1500 mmHg.

[0114] In another example, the portable delivery device 100 may deliver an infusion of supersaturated oxy gen-enriched blood having a pCh level of 80 mmHg or greater or 80-760 mmHg. The container 102 can be sized based on a particular use case. The container can be formed to one of several different sizes depending on a type of the liquid in the solution for maintaining the liquid at a predetermined pressure. For example, in certain embodiments the container 102 can be 0.2 to 0.7 liters (L) in size. In some implementations, the container 102 is one or more other sizes, such as 0.25L, IL, 2L, 1 quart, 1 gallon, or any other desired volume.

[0115] The volume in the container 102 is sterile. The container 102 may be sterilized prior to adding the gas-enriched liquid to the container. The gas-enriched liquid is also sterile. The container 102 can be sterilized through one or more mechanisms, such as irradiation of the container with ultraviolet light.

[0116] The container 102 can be formed from one or more materials that enable the container to maintain the gas-enriched liquid at the target pressure. In some implementations, the container 102 is formed from a plastic, such as a thermoplastic. In some implementations, the container 102 is formed from one of the following processes including injection molding, extrusion blow molding, injection blow molding, stretch blow molding, compression molding, reheat blow molding, co-extrusion blow molding, or a similar method. In some implementations, the container 102 includes a metal material. For example, the walls of the container 102 can be rigid under pressure and can be formed from a material such as steel, aluminum, or a similar metal or alloy. In some implementations, the container 102 is formed from a combination of different materials such as metal and plastic. For example, a portion of the container 102 wall can be formed from plastic that is configured to crack at a particular pressure sufficient to allow delivery of the gas-enriched liquid. In some implementations, container 102 can have a portion that is configured to flex in response to the actuator 110 applying pressure to that portion of the container. The actuator 110 can cause the pressure inside the container 102 to rise and cause delivery of the gas-enriched liquid to the conduit 104 when the pressure exceeds the crack pressure or maximum pressure for delivery of the gas-enriched liquid. Specifically, the container 102 can include a base portion (not shown) that is configured to slide inside a cylindrical wall of the container 102. When the actuator110 (e.g., a piston) pushes on the base portion, the actuator 110 causes the base portion to slide within the tube of the container and increases a pressure inside the volume of the container 102. The increased pressure can force the gas-enriched liquid from the container and through the conduit 104 for delivery to the patient. In some implementations, the container 102 wall forms part of the actuator 110. Different examples of actuators 110 and how they interface with the container 102 are subsequently described in further detail.

[0117] In certain embodiments, the container 102 can be coupled to a control system including one or more sensors. The one or more sensors can be on the container 102 wall or inside the volume of the container. Various types and / or combinations of sensors may be utilized. For example, the one or more sensors can include one or more sensors temperature sensor configured to measure a temperature of the gas-enriched in the container 102. The one or more sensors can include one or more sensors pressure sensors configured to measure a pressure inside the volume of the container 102. The one or more sensors can include one or more sensors configured to detect a leak in the volume of the container 102 or conduit 104. The one or more sensors can include an oxygen saturation, concentration or partial pressure detector within the volume of the container 102 or conduit 104. The one or more sensors can include a mechanical pop-up device configured to remain in popped up or extended configuration when no leak has occurred and to transition to a non-popped up or nonextended configuration when a leak has occurred. The one or more sensors can include a flow sensor placed at the exit of the container 102 inside the connector 106 or near the conduit 104 to measure a flow of the gas-enriched liquid from the container into the conduit 104. In some implementations, a pressure transducer 109 can be placed on a wall of the container 102. The pressure sensor 109 can be attached to a gauge for a mechanical readout of the pressure to allow a user to detect leaks or a change in pressure. In some implementations, the pressure sensor 109 is in communication with a controller (described in further detail below) to show a pressure inside the container 102 on a display. In some implementations, a flow sensor 111 can be placed in the conduit 104 of the device 100. For example, the flow sensor 111 can be in-line with the conduit 104 and include a pinwheel sensor to measure how much liquid has moved through the conduit. A magnet and Hall effect sensor can measure a count of rotations of the pinwheel, measuring flow in the conduit 104.

[0118] Other sensors can be included or used when the portable delivery device 100 is delivering the gas-enriched liquid to the patient. For example, the one or more sensors can measure one or more values related to the concentration of oxygen or the flow of the oxygen-enriched liquid into the patient during delivery. These sensors are subsequently described in relation to the patient delivery device 108.

[0119] The container 102 can include a hermetic seal configured to seal the volume of the container. As subsequently described, the actuator 110 can be configured to break the hermetic seal when the actuator is actuated. The seal can be part of the connector 106 or the container. In some implementations, the seal includes a valve that can open as the pressure inside the container 102 increases (e.g., responsive to actuation) and close once the pressure returns to the target pressure or below a pressure threshold (e.g., a baseline storage pressure for the gas-enriched liquid). In some implementations, the seal, once broken, allows continuous flow of the gas-enriched liquid through the conduit 104 to the patient while maintaining the pressure inside the container 102 above the minimum pressure. The seal can be configured to break or open in a manner that controls the flow rate of the gas-enriched liquid through the conduit 104 to maintain the minimum pressure in the container 102 and to make sure the gas-enriched liquid does not flow too quickly or too slowly into the patient. For example, the seal can include a variable aperture size that is responsive to flow rate or other flow control mechanism.

[0120] As previously described, the actuator 110 is coupled to the container 102. The actuator 110 is configured to cause the gas-enriched liquid to be released from the container 102 during delivery from the container to the patient. The actuator 110 is coupled to the container 102 to enable the actuator to force the gas-enriched liquid from the container into the conduit 104. As subsequently described, the gas-enriched liquid is maintained above a threshold pressure within the container 102, but the gas-enriched liquid can also be delivered from the container 102 to the conduit 104 while maintaining the pressure within the container 102. The actuator 110 and / or a valve or other flow control mechanism is configured to control delivery of the gas-enriched liquid from the container 102 while maintaining the pressure.

[0121] The actuator 110 can be coupled to the container 102 and be a part of the container. In some implementations, the actuator 110 is fixed to the container 102 by a coupling device. In some implementations, the actuator 110 is removable from the container 102.

[0122] The actuator can be one of a variety of configurations, including a plunger, a piston, external or internal actuators, and so forth as now described. In some implementations, the actuator 110 is configured to interface with an external actuation device 112. In the example shown in FIG. 1, a leaf spring 118 is configured to couple externalactuation device 112 to the container 102. The external actuation device 112 includes a seating for the container 102 and an actuator trigger 116 configured to actuate the actuator 110 for delivery of the gas-enriched liquid at the controlled flow rate. The container 102 can be removed from the external actuation device 112. In some implementations, the external actuation device 112 is configured to interface with the actuator 110 that is coupled to the container 102. For example, the external actuation device 112 can compress a piston head that is part of the container 102 and that slides within the container to force the gas-enriched liquid from the volume of the container and into the conduit 104. In some implementations, the actuator 110 is part of the external actuation device 112. The actuator 110 is inserted or coupled to the container 102 but is not part of the container. For example, the container 102 can include a flexible bladder or bag within a rigid container wall. A piston attached to the external actuation device 112 is aligned with a tube formed by the rigid container wall. The piston actuator 110 compresses the bag within the container and forces the gas-enriched liquid from the bag and into the conduit 104 through the connector 106. In this example, the connector 106 can be configured to connect the bag to the rigid wall. As subsequently described, the internal bag (also called a liner) could be removable from the rigid container wall for replacement after use, such that the bag internal volume is sterilized, but the container wall need not be. Other such configurations of the external actuation device 112 and the container 102 are possible such that the container 102 is removable from the external actuation device.

[0123] The external actuation device 112 can be reusable, and the container 102 can be swapped with another instance of the container once the gas-enriched liquid has been delivered from the container to the conduit 104 and / or patient. For example, one or more instances of the container 102 can be swapped into the external actuation device 112 to deliver greater quantities of the gas-enriched liquid to a particular patient (or several patients). Each instance of the container 102 can be sterile and interfaced with the external actuation device 112. In some implementations, each instance of the container 102 is preconnected to the conduit 104. In some implementations, each instance of the container 102 can be connected to a fresh conduit 104 (e.g., for a new patient) or to the existing conduit, such as to deliver more gas-enriched liquid to a previous or current patient).

[0124] A user can grasp an actuator handle 114 and compress the actuator trigger 116 to push the actuator 110 (e.g., a piston head or other mechanism) into the container 102 to force the gas-enriched liquid from the volume into the conduit. In some implementations, the connector 106 or conduit 104 are sized or include a valve or other gas-enriched liquid releasemechanism that enables the gas-enriched liquid to exit the volume of the container 102 at a maximum flow rate that is safe for the patient and that is sufficient to ensure that a pressure inside the container 102 remains above the minimum pressure for maintaining the premixed gas-enriched liquid at a predefined concentration while preventing significant outgassing. For example, if the user compresses the trigger 116 at a maximum force, the trigger may cause the actuator 110 to compress the volume of the container 102 at a controlled rate.

[0125] The actuator 110 can include other devices or mechanisms for causing delivery of the gas-enriched liquid at a controlled flow rate. As previously described, the flow rate is controlled by the actuator 110 that controls / maintains a pressure in the container 102 above a minimum pressure. A valve 204 (subsequently described) opens responsive to the internal pressure of the container 102 exceeding a pressure threshold to open the valve. A diameter of the conduit 104 and length of the conduit are sized to control a pressure drop by being a flow rate limiter. The flow sensor 111 can measure the flow rate.

[0126] For example the actuator 110 can include a button configured to control the delivery of the gas-enriched liquid from the container 102. The actuator 110 can be connected to a valve or other gas-enriched liquid release mechanism configured to open when the button is pressed to deliver the gas-enriched liquid and close when the button is released to prevent further delivery of the gas-enriched liquid. In some implementations, a valve can be configured to open for a predetermined amount of time responsive to actuation of the actuator 110.

[0127] In some implementations, the gas-enriched liquid may be delivered at a controlled flow rate as described above. The actuator 110 may be configured to deliver a predefined amount of the gas-enriched liquid at the controlled flow rate within a threshold precision. For example, the threshold precision can be an amount of the gas-enriched liquid. The amount can be between 0-500 cubic centimeters (CCs) of the gas-enriched liquid. In some implementations, the flow rate is generally between 0-5 cubic centimeters per second (cm3 / s). In some implementations, the flow rate is controlled based on the geometry of the connector 106 or based on the geometry of the conduit 104, as subsequently described. In some implementations, the controlled flow rate comprises a rate of gas-enriched delivery from the volume that is within a threshold tolerance from a baseline delivery rate. In some implementations, the baseline delivery rate is 0-20 milliliters per second.

[0128] The actuator 110 can include a purge control device. The purge control device is configured to flush any gas-enriched liquid from the delivery device 100 that may still be present once delivery of the gas-enriched liquid has been completed. For example, theactuator 110, valve 204, or conduit 104 may have liquid in it. The purge control device is configured to clear the device of any liquid before a new container 102is placed into the device 100. In some implementations, the purge control is sufficient to ensure that the actuator 110 and / or conduit 104 are substantially clear of gas-enriched liquid to enable a new container 102 to be swapped to couple to the actuator 110 for the portable delivery device 100.

[0129] The actuator 110 includes a mechanical device configured to physically force the gas-enriched liquid from the container 102, or from a portion of the container, into the conduit 104. In some implementations, the actuator 104 includes a mechanical spring configured to compress the volume to maintain a minimum mixture pressure for oxygen supersaturated liquid. In some implementations, the actuator 110 includes a pneumatic piston configured to compress the volume to maintain a minimum mixture pressure for oxygen supersaturated liquid.

[0130] The actuator 110 can include a movement device for moving the mechanical device (e.g., a piston) to force the gas-enriched liquid from the container 102 into the conduit 104 at the controlled flow rate while maintaining the target minimum pressure. For example, the movement device can include a linear gear (e.g., a worm gear), a spring, a lever, a screw, a motor, a pump, and so forth. In some implementations, the actuator includes a clamp configured to hold a linear actuator rod in place when the rod is exerting force on the gas- enriched fluid in the container 102. For example, a user can compress a piston attached to the rod (e.g., through the trigger 116). When the user releases the trigger 116, a clamp can retain the rod and piston at the advanced position until a clamp release is activated. The trigger 116 can be sized to enable the user to exert a force over a minimum threshold force to enable the gas-enriched liquid to flow from the container 102 at a desired flow rate. The trigger 116 acts as a lever to allow an increased force on the container 102 while less torque is applied to the trigger 116 than would otherwise be needed with a smaller trigger 116.

[0131] A conduit 104 is coupled to the container 102. The conduit configured to facilitate intravascular delivery of the gas-enriched liquid to the patient. The conduit 104 is configured to control a pressure drop of the gas-enriched liquid during delivery from the container 102 to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery.

[0132] The conduit 104 may be connected to the container 102 by a connector 106. The connector 106 includes an interface for connecting the container 102 to the conduit 104 and for preventing a pressure drop in the container 102 during delivery of the gas-enriched liquidto the patient. The interface can include a valve or other gas-enriched liquid releasing mechanism. The valve is configured to maintain the premixed gas-enriched liquid at or above the threshold pressure within the container during delivery to the patient. For example, the valve can be configured to allow the gas-enriched liquid to flow from the container 102 into the conduit 104 at a particular flow rate and responsive to actuation of the actuator 110.When the actuator 110 is actuated, a pressure in the container 102 can increase. The increased pressure enables the gas-enriched liquid in the container to force open the valve and flow through the valve and into the conduit 104 for delivery to the patient.

[0133] The conduit 104 is configured to carry the gas-enriched liquid from the container 102 (via the connector 106 in some implementations) to the patient. In some implementations, the conduit connects to a patient delivery device 108, such as a catheter or cannula, which is inserted into the patient for connecting the conduit 104 to the vasculature of the patient. In some implementations, the conduit 104 can be directly inserted into the patient to deliver gas-enriched liquid to the patient without the use of a patient delivery device.

[0134] The conduit 104 has a diameter and length that controls pressure drop and flow rate, which together enable controlled delivery of the gas-enriched liquid from the container 102 to the patient. The controlled delivery of the gas-enriched liquid enables the gas-enriched liquid to be delivered at or near a target flow rate while maintaining a controlled pressure drop from the container to the conduit and through the conduit to the patient.

[0135] The conduit 104 has an inner diameter that is sized to meter gas-enriched liquid out of the container 102 at a controlled rate and controlled pressure drop. The controlled rate is sufficient to ensure a smooth, controlled pressure drop through the conduit In some implementations, the actuator 110 (or other device) can actuate to raise the pressure of the container 102 back above a minimum pressure if the pressure decreases. In some implementations, the pressure in the container 102 can drop as the container empties out the gas-enriched liquid, such as when there is not enough liquid remaining to exceed a maximum flow rate in the conduit 104. In some implementations, the inner diameter of the conduit 104 can be compatible with a cannula of between 14-22 French (Fr). The conduit 104 inner diameter is sized such that it does not impede flow and does not cause discharge suddenly while maintaining a controlled pressure drop through the conduit. Generally, the inner diameter of the conduit 104 is between 1-3 millimeters (mm).

[0136] The conduit 104 inner diameter can depend on the length of the conduit. For example, a longer conduit may have a smaller inner diameter to enable the controlled pressure drop. The conduit 104 length can be short in scenarios in which the connector (e.g.,including the valve or other exit aperture from the container 102) is placed at the patient. For example, the portable delivery device 100 can be placed in near contact with the patient, such as directly inserted into the patient or directly inserted into a cannula that is inserted into the patient, and the conduit 104 length can be short (e.g., a few millimeters to several centimeters). In some implementations, the portable delivery device 100 is placed some distance from the patient, and the conduit 104 is longer (e.g., greater than 20 cm). In some implementations, the conduit is 1 to 20cm in length. In some implementations, the conduit is 20 to 100 cm in length. In a specific example, for a container having a 100 PSI minimum (target) pressure, the inner diameter of the conduit can be 14 French (4.67 mm), and the conduit can be about 20 cm in length, thereby allowing the conduit to control the pressure drop from the container through the conduit without significant outgassing.

[0137] In certain implementations, a minimum pressure of the cannister for maintaining oxygen dissolved in liquid inside the cannister can be about 100 PSI. In some implementations, the minimum pressure is set between 50-100 PSI. A maximum pressure can be set in a range of 100 to 150 PSI. A range for a pressure drop (e.g., a change in pressure) from the container 102 to the conduit 104 and through the conduit into the patient that would keep oxygen dissolved in solution without significant outgassing can be as follows. A linear pressure dop from 100 PSI to about 0 PSI, the patient pressure, occurs from the container 102 to the end of conduit 104 through patient. Due to kinetics, by providing a quick and smooth delivery, which is a result of conduit 104 geometry as described herein, the oxygen-enriched liquid remains metastable as there is not enough time for oxygen to outgas from the solution. Once in the patient, the oxygen-enriched liquid mixes with blood, thereby reducing the concentration and reducing potential for outgassing, which is a function of concentration.

[0138] In certain implementations, a specific conduit geometry (e.g., length and inner diameter) achieves a pressure drop from the threshold pressure to zero as the gas is delivered to the patient while maintaining oxygen dissolved in the solution without significant outgassing. The conduit 104 geometry can be a conduit that could have an inner diameter of 3-5 mm, and length of 20-40 cm to maintain oxygen in the solution without significant outgassing. A pressure drop of 100 PSI to 0 PSI (patient vasculature pressure) occurs from the container 102 through the conduit 104 to the patient.

[0139] In certain implementations, the inner diameter of the conduit 104 is between 1-3 millimeters (mm). In a specific example, for a container having a 100 PSI minimum (target) pressure, the inner diameter of the conduit can be 1-3 mm, and the conduit can be about 20- 40 cm in length, thereby allowing the conduit to control the pressure drop from the containerthrough the conduit to the patient without significant outgassing. These dimensions may provide a Reynolds flow number of about 20,000-40,000. In certain implementations, a in a 100 PSI container 102, with a conduit having a 1 mm inner diameter, the flow rate is lee per minute with a Reynolds number of 20,000. The PSI drop through this cannula may is 100 to about 0, the patient intravascular pressure. This geometry keeps oxygen dissolved in the solution without significant outgassing, as previously described.

[0140] In certain implementations, a sufficient size, length, and pressure associated with the conduit may be selected to ensure a flow rate that provides a nearly laminar flow through the conduit and from the end of the conduit 104 or associated catheter or cannula. In certain implementations, the flow of the gas-enriched liquid can have a Reynolds number of less than 1500. In certain implementations, the flow of the gas-enriched liquid can have a Reynolds number of less than 2000. In some implementations, the Reynolds number can be above 1500 or 2000 (e.g., 10,000 Reynolds number) to ensure a sufficiently uniform flow, though the flow may not necessarily be laminar. A smaller Reynolds number can enable a smooth pressure profile for the container 102 and for delivery of the gas-enriched liquid at the patient. In some implementations, the flow rate is controlled between a Reynolds number of 500 - 10,000, which may provide a smooth and / or uniform flow. Because laminar flow is a function of flow rate and diameter, an example for a container 102 can be as follows. At a pressure of 100 PSI, a container 102 can deliver 100 cubic centimeters per minute (cc / min) at 2,000 Reynolds (which is a laminar flow) when the conduit 104 is 10 meters long and has a 1 mm inner diameter.

[0141] The conduit 104 may be configured to couple to an intravascular line that is inserted into a vasculature of the patient. In some implementations, the conduit 104 is directly inserted into the patient. For example, the conduit 104 can include a cannula that is formed as part of the conduit. The cannula enables delivery of the gas-enriched liquid into the vasculature of the patient. In some implementations, the conduit 104 is configured to be inserted into a port or other patient delivery device 108 that is inserted into the patient. In some implementations, the conduit 104 includes a coupling interface configured to couple to a patient delivery device 108. The coupling interface includes the conduit 104. In some implementations, the conduit 104 comprises a cannula having an outside diameter between 0.020 and 0.200 millimeters (mm). In some implementations, the conduit 104 comprises a cannula that is about 1 meter long and has an inner diameter that is about 0.100”. This cannula may introduce up to 1 liter of blood substitute in one minute. If the viscosity of the blood substitute is much less than blood, the cannula may be longer and have a smaller innerdiameter (or the delivery rate may be lower). In certain implementations, the cannula may include one or more apertures to facilitate speedy delivery.

[0142] The conduit 104 may include a coating that allows the gas-enriched liquid to flow cleanly (e.g., without turbulence or in a manner that reduces turbulence or below a threshold turbulence) within the conduit, even at small diameters. For example, the conduit 104 can include an anti-nucleation coating configured to prevent or reduce nucleation of the gas- enriched liquid inside the conduit. The anti -nucleation coating thus may prevent bubbles from forming in the gas-enriched liquid that is delivered to the patient.

[0143] The conduit 104 can be connected to the container 104 through a connector 106 with an aperture geometry that causes laminar flow or smooth but not laminar flow of the gas-enriched liquid. The flow may be maintained within a threshold distance of an end of the conduit when the gas-enriched liquid is being delivered intravascularly to the patient. In certain implementations, a laminar or nearly laminar flow may comprise fluid flow with a Reynolds number under 1500.

[0144] The conduit 104 can be connected to a patient delivery device 108. The patient delivery device 108 may be configured to couple to the conduit and can form an interface for delivering the gas-enriched liquid to the patient. For example, the patient delivery device 108 can be a cannula, a needle, or other device for intravascular delivery of the gas-enriched liquid to the patient. In some implementations, patient delivery device 108 is part of the conduit 104. In some implementations, the patient delivery device 108 can be coupled to the conduit 104 or otherwise interfaced with the conduit 104, as subsequently described in further detail. The patient delivery device 108 is configured to maintain the controlled pressure drop of the gas-enriched liquid without significant outgassing as it travels to the patient.

[0145] The patient delivery device 108 can include a cannula and a coupling device or connector 106 configured to couple the cannula to the container via the conduit 104. The actuator 110 is configured to deliver the gas-enriched liquid through the cannula to the patient. In some implementations, the patient delivery device 108 includes a catheter that is inserted into the patient. Similarly to the conduit 104, an interior of the cannula or catheter can be coated in a layer of anti -nucleation material to reduce or prevent bubble formation in the gas-enriched liquid. In some implementations, the anti -nucleation material comprises heparin. In some implementations, a diameter of the cannula is between 0.02 millimeters and 0.200 millimeters.

[0146] The patient delivery device 108 can be disconnected from the conduit 104 or connector 106 so that the portable delivery device 100 can be connected to another instanceof the patient delivery device 108. For example, the patient delivery device 108 can be a modular delivery device. The container 102 may be configured to receive a different instance of the modular delivery device to replace a removed modular delivery device. Each instance of the patient delivery device 108 that is attached to the conduit 104 and / or container 102 via the connector 106 can be sterilized.

[0147] The patient delivery device 108 can be inserted into the patient prior to connection to the conduit 104 of the portable delivery device 100. For example, the patient delivery device 108 can be inserted into a radial artery, a clavicle artery, a femoral artery, and so forth. When the container 102 is coupled to the actuator 110 and ready for delivery of the gas- enriched liquid, an end of the conduit 104 can be put into (and coupled to) the patient delivery device 108 to deliver the gas-enriched liquid to the patient.

[0148] FIG. 2 illustrates a perspective view of the example portable delivery device 100 configured to deliver gas-enriched liquid, e.g., premixed gas-enriched liquid, to a patient. A coupling interface 106 of the portable delivery device 100 may be configured to couple the patient delivery device 108 to the container 102. The connector 106 (e.g., a coupling interface) includes a valve 204 that can enable or restrict the gas-enriched liquid from entering the conduit 104 and / or the patient delivery device 108.

[0149] In some implementations, the conduit 104 includes the connector for receiving a patient delivery device. The connector 106 includes the valve 204. The valve 204 remains closed when the patient delivery device 108 is not attached to the adaptor. The valve 204 opens when the patient delivery device 108 is attached to the adaptor. In some implementations, the valve 204 is configured to interface with the patient delivery device 108 to maintain a sterile path to and through the patient delivery device to the patient’s vasculature.

[0150] The patient delivery device 108 can include a needle 206 that is configured to pierce or crack the valve 204 to open the valve when the patient delivery device is coupled to the connector 106. The needle 206 enters through the valve 204 into the container 102. The needle 206 includes a conduit through which the gas-enriched liquid flows into the patient.

[0151] The patient delivery device 108 can include a conduit interface 128 that can couple the patient delivery device to the connector 106. The patient delivery device 108 is removable and replaceable with respect to the container 102. For example, when the container 102 is empty, a new instance of the container can be attached to the patient delivery device 108. In another example, when the container 102 is to be interfaced with another patient, the container can be detached from the patient delivery device 108 and attached toanother instance of the patient delivery device for insertion into a different patient. In some implementations, the conduit interface 128 (e.g., adaptor) can include a tapped surface, such as a screw. The patient delivery device 108 can have the conduit 104 extend from the needle 206 or can include a cannula or catheter that is inserted directly into the patient's vasculature. In some implementations, the conduit interface 128 or adaptor comprises a Luer fitting.

[0152] In some implementations, the conduit interface 128 may include a needleless adaptor. For example, the needle 206 can be excluded and the valve 204 can be opened or closed based on an internal pressure of the container 102, as previously described. For example, when a pressure inside the container exceeds a maximum threshold, the valve 204 can open and allow the gas-enriched liquid to flow into the patient delivery device 108 and into the conduit 104 to the patient.

[0153] The valve 204 may include a hermetic seal or other mechanism to prevent the gas- enriched liquid from existing the container 102 or reducing in pressure. In some implementations, the valve includes a foil or layer that is pierced by the needle 206 or opening the valve permanently once the patient delivery device 108 is attached. In some implementations, the valve 206 includes a malleable material that allows the needle 206 to pass through for transporting the gas-enriched liquid from the container 102 to the patient delivery device 108 and the conduit 104. The pressure in the container 102 on the malleable material may be configured to cause the valve 204 to close when the needle 206 is not inserted.

[0154] In some implementations, the valve 204 can include a check valve that seals the container 102 until a pressure inside the container exceeds in maximum pressure. The crack pressure of the check valve can be slightly higher than the target pressure drop at which the gas-enriched liquid is controlled and maintained within the container 102 such that the check valve only opens when pressure is exerted by the actuator that increases the internal pressure of the container. In this way, the only way the container 102 depressurizes is when there is discharge of the gas-enriched liquid into the conduit 104.

[0155] The valve 204 can include one or more other configurations. For example, the valve 204 can be manually opened when no conduit 104 or patient delivery device 108 is attached to the container 102. In some implementations, the valve 204 is connected to a conduit 104 that extends from the connector 106 regardless of whether a patient delivery device 108 is present. In this configuration, the valve 204 can be manually opened, such as by rotating a cuff around the valve to open the aperture of the valve or by some other mechanical control. The manual operation of the valve 204 can enable a user to release gas-enrichedliquid from the pressurized container 102 and control the pressure drop in the container. In this configuration, another device, such as the actuator 110, may automatically cause the pressure to be maintained within the container when the valve 204 is opened. In another example, control of the valve 204 is linked to the actuator 110 such that actuation of the actuator opens and closes the valve and also maintains the internal target pressure of the container. In another example, a pump may be connected to a pressure sensor inside the container 102. When the valve 204 is opened by the user, the drop in pressure is detected by a controller (described in further detail below) connected to the pump and the pressure sensor, and the pump is automatically activated to increase the internal pressure of the container back to the target pressure.

[0156] FIG. 3 illustrates a side view of a container 300 for the portable device of FIG. 1 or FIG. 2. In some implementations, the container 300 may be similar to or identical to the container 102 previously described. Pressurized gas is present within the volume 302 of the container 300. The pressure may be maintained by an actuator that comprises a device, such as a piston head 308 that pushes into the volume 302. The pressure may be maintained at a known pressure or force internally in the container 300 or control the pressure drop of the liquid.

[0157] The container 300 can include an actuator interface 310 that couples to an external actuator such as actuator 110. In an example, the actuator interface 310 includes a screw or other coupling interface that mechanically couples the actuator to the replaceable container 102. for example, the piston head 308 can be present within the container 300 whether or not the actuator 110 is attached to the actuator interface 310. In another example, the piston head 308 may be part of the external actuator and is not present within the container 300 until the actuator 110 is coupled to the actuator interface 310.

[0158] The container 102 can include an internal volume 302 inside of the external volume, the internal volume including a flexible liner 306. The container can include a rigid container wall 304, as described previously. The flexible liner 306 can include a bladder or bag that conforms to the rigid container wall 304 that forms the container 300. When the piston had 308 advances within the rigid container wall 304, the bladder or flexible liner 306 may be compressed to reduce the size of the volume 302, increasing the pressure within the volume 302. in some implementations, the increased pressure in the volume 302 can cause the valve, such as valve 204 previously described, to open and allow delivery of the gas- enriched liquid into the conduit 104 while controlling the pressure drop in the container and the conduit. In some implementations, the flexible lining is removable from the hard shell.The flexible lining can be prepared with the gas enriched liquid at a predetermined pressure that maintains the gas-enriched mixture at a supersaturation. In some implementations, the rigid container wall 304 is attached to the actuator 110 and only the flexible lining 306 is replaced to enable delivery of additional gas enriched liquid to the patient. In some implementations, the high pressure flexible lining 306 filled with the gas-enriched liquid conforms to the shape of the rigid container wall 304 and piston head 308 as the piston head advances into the rigid container wall. In some implementations, the rigid container wall 304 and flexible lining 306 are part of the disposable modular container 102.

[0159] FIG. 4 illustrates a perspective view of an example portable delivery device 400 configured to deliver gas-enriched liquid, e.g., premixed gas-enriched liquid, to a patient. The portable delivery device 400 may include a container 402 in which a piston head 404 advances towards the conduit for 414. In some implementations, an actuator coupling 408 may couple the actuator 416 to the container 402.

[0160] The piston head 404 can be a part of the container 402 rather than part of the actuator 416. In some implementations, the piston head 404 is part of the actuator 416 and is not included in the container 402 until the actuator 416 is coupled to the container. In an example, the container 402 is pressurized with the piston head 404 forming a seal with seal 406 as one of the walls of the container 402. A valve may be present within conduit 414 near the tip of the container 402. The conduit 414 can be inserted into a cannula or directly into the patient with a needle (not shown). In some implementations, the actuator comprises the piston head 404 that, when compressed, forces the gas-enriched liquid from the volume at the controlled flow rate.

[0161] The actuator 416 includes an actuator coupling 408, an actuator body 410, a knob 412, and a pressure source 420. In the configuration shown in FIG. 4, the actuator 416 is configured to receive air from the source 412. The actuator body 410 can include a pump that provides air behind the piston head 404 in the container 402 to advance the piston head further into the container and cause delivery of the gas enriched liquid to the patient through the conduit 414. Prior to connection of the actuator 416 by the actuator coupling 408, the piston head 404 rests in the container 402 at an opposite end of the container from the conduit 414. When the actuator 416 is coupled via the actuator coupling 408, the actuator can provide an air pressure behind the piston head 404 that exceeds the pressure in the container 402 to advance the piston head further into the container towards the conduit 414.

[0162] The actuator coupling 408 can include a threaded screw or other mechanical coupling interface. In an example, the actuator coupling includes a seal or other mechanismto prevent air from escaping from behind the piston head 404 so that the target pressure is maintained within the container 402 as gas enriched liquid is delivered from the container through the conduit 414.

[0163] In some implementations, the actuator body 410 can include a pump that is configured to provide a pressure behind the piston head 404. The pump can be controlled by one or more mechanical devices, such as a knob 412 that controls a pressure level of the pump to apply behind the piston head 404 and therefore control the delivery of the gas- enriched liquid to the conduit 414 from the container 402.

[0164] In some implementations, the pump comprises a mechanical actuator, such as the knob 412. In some implementations, the pump comprises an electronic actuator, such as data port connected to a controller, which can be connected to one or more sensors, such as pressure sensors. The controller can be configured to receive data from sensors, such as a pressure sensor or patient sensors placed on or in the patient. The controller can control the actuator to cause delivery of the gas-enriched liquid to the patient based on the data received from sensors. For example, the controller can be coupled to a driveshaft configured to operate the actuator to deliver a bolus of liquid to the patient, open or close valves to control container pressure. In an aspect, the controller can control mixing of the liquid by controlling a valve that releases gas into the container from a separate gas source (a tank or reservoir). The controller can thereby control the pressure and concentration of the gas in the liquid of the container. Examples of a controller and control systems are described in further detail below with respect to FIGS. 6A-6B and FIG. 8. For example, the electronic actuator can be configured to activate a motor that pumps the gas-enriched liquid from the volume at a controlled flow rate. In some implementations, the piston head 414 is coupled to a second actuator that is configured to compress the piston to cause the controlled flow rate into the conduit 414.

[0165] FIG. 5 illustrates a side view of an example portable delivery device 500 configured to deliver gas-enriched liquid, e.g., premixed gas-enriched liquid, to a patient, the portable delivery device 500 can be similar to the portable delivery device 400 previously discussed. In the example of the portable delivery device 500, the actuator 506 may be a mechanical actuator that does not include a pump, but rather includes a knob 512 connected to a spring 502. The spring 502 may be configured to push the piston head 404 into the volume 402 towards the conduit 414.

[0166] The actuator 506 may be coupled to the container 402 in a manner similar to that previously described. For example, the actuator 506 can be screwed onto a threaded screw ofthe container 402. In some implementations, the threaded screw of the coupling interface 508 does not necessarily need to be sealed because a spring 502 maintains a pressure behind the piston head 404.

[0167] A knob 512 may be turned either clockwise or counterclockwise to advance a piston body 510 within the container 402 and therefore advance the piston head 404. The actuator 506 of the portable delivery device 500 may include a the piston body 510. The piston body 510 can be a part of the actuator 506 that may be removable from the container 502. In some implementations, the piston body 510 interfaces with a spring 502. The spring pushes the piston head 404. A spring constant k of the spring 502 can be tuned so that a desired target pressure is maintained within the container 402 as the piston head 404 advances within the container and as the piston body pushes on the back of the spring 502. In some implementations, the piston body 510 and spring 502 configuration enables a fine tuning of the pressure within the container 402. The actuator 506 configuration does not necessarily require a fine-tuned mechanical actuator 506 to advance the piston body 510 to a specific location within the container 402 to maintain the desired pressure.

[0168] FIG. 6A shows an automated device 800 for delivery of gas-enriched liquid. In some implementations, the device 800 can be portable and / or handheld. In this implementation, a compressed gas (e.g., oxygen) is contained in a gas cannister reservoir 802 stored separately from the saline or other liquid solution contained in an internal reservoir 828. A controller 814 with concomitant battery 820, display 820, and other power, support and control elements are housed along with a screw drive motor 816 that is attached to a screw drive shaft 818. When rotated, the screw drive shaft 818 moves a piston up and down in the internal reservoir 828 cavity, similar to actuator 506 described previously. The gas cannister 828 has a seal (such as a foil seal) that is punctured by a puncture tooth 804, allowing gas to flow to a first pinch valve 806. In some implementations, pressure regulators or flow control valves can be used to control flow of the liquid. When opened, the first pinch valve 806 allows for a controlled flow of the compressed gas to flow through the gas supply tubing 824 into the internal reservoir 828 where the gas is mixed with and dissolved in a liquid to generate a gas-enriched liquid. In some examples, compressed gas and physiologic fluids such as plasma, blood, saline are pre-mixed so as to transport the solution in its gas- enriched or super-saturated state for rapid deployment in the pre-hospital environment.

[0169] A second pinch valve 808 controls release of the gas-enriched liquid from the reservoir 828. When the second pinch valve 808 is closed, and the first pinch valve 806 isopen, the gas solution is injected into the internal reservoir so at to inject more of the gas into the liquid.

[0170] Referring to FIG. 6A, in some examples, the controller 814 measures the pressure both proximally and distally at the two pinch valves 806, 808. A first distal pressure sensor 810 is placed on a side of the first pinch valve 806 opposite a first proximal pressure sensor 812. The first proximal pressure sensor 812 measures a pressure from the container 802 near the first pinch valve 806. The first distal pressure sensor 810 measures pressure in the reservoir 828 near the first pinch valve 806. By comparing measurements of first distal pressure sensor 810 to measurements of first proximal pressure sensor 812, the controller 814 can estimate how much gas is left in the container 802 and provide some warning to the user if the gas supply is about to run out.

[0171] A second distal pressure sensor 830 is placed on a side of the second pinch valve 808 opposite a second proximal pressure sensor 834. The second proximal pressure sensor 834 measures a pressure from the container 802 near the second pinch valve 808. The second distal pressure sensor 830 measures a pressure in the conduit 832 near the second pinch valve 808. By comparing measurements of the second distal pressure sensor 830 to the second proximal pressure sensor 834, the controller 814 can estimate how much gas-enriched liquid is left in the reservoir 828 and provide some warning to the user if the liquid supply is about to run out.

[0172] The first pinch valve 806 controls the rate of pressurization in the reservoir 828 allowing the pressure in the reservoir to reach the minimum pressure threshold (e.g.,_100_PSI or a range of 100 PSI to 150 PSI) for the gas to dissolve in the liquid and remain dissolved in the liquid. Once the predetermined pressurization profile has been achieved at the first proximal pressure sensor 812 and the first distal pressure sensor 810, such that the gas is dissolved in the liquid, the controller 814 instructs the user to insert the patient conduit 832 into the patient’s blood vessel. Instructions can include one or more of audio, speech, text, or graphical instructions. When the user confirms proper placement of the conduit 832 in the patient’s blood vessel, the controller 814 opens the second pinch valve 808 for a controlled bolus of the gas-enriched liquid e.g., approximately 1 cubic centimeter. The controller then prompts the user whether the bolus was successfully achieved.

[0173] When the user indicates via the user interface that the bolus was successfully delivered, the controller opens and / or closes the second pinch valve 808 and adjusts flow rate via such means as pulse width modulation of the second pinch valve 808.

[0174] An example arrangement of the second pinch valve 808 and second proximal pressure sensor 834 and distal pressure sensors 830 is shown in FIG. 6B. This arrangement is used to measure relative pressures on either side of the pinch valve 808 (or pinch valve 806) to control mixing of the gas with the liquid (by first pinch valve 806) and delivery of the liquid to the patient (by second pinch valve 808). In certain examples, the pinch valves include a type of valve that directly pinches tubing made of a soft material such as silicone in order to open and close it. The only wetted material may be the tubing. Therefore, a cleanliness of the flow path can be maintained, and cross-contamination avoided, through exchanging tubing after use. It is also possible to use this valve with slurry which is fluid containing small particles. In some examples, there may be a release valve 836 on the reservoir 828 such as a pinch valve which opens abruptly should the controller detect any unsafe condition. For instance, if the pressure is too high at the conduit at the distal pressure sensor 810 pressure reading, a release valve can vent excess gas from the reservoir 828. An example of any of the pinch valves 806, 808 can include a Miniature Valve, provided by Takasago Electric, Inc. of Westborough, MA.

[0175] FIG. 7 illustrates an example of a portable delivery system 600 including a portable device 602 configured to deliver gas-enriched liquid, e.g., premixed gas-enriched liquid, to a femoral artery of a patient 610. The system 600 may be configured to deliver gas- enriched liquid intravascularly to a patient. The system 600 can include a portable device 602 that is preloaded with the gas-enriched liquid. In some implementations, the portable device 602 includes a container defining a volume. The volume can hold the premixed gas-enriched liquid at or above a threshold pressure such that gas remains dissolved in the gas-enriched liquid. The portable device 602 can include an actuator coupled to the container. The actuator can be configured to cause the gas-enriched liquid to be released from the container at a controlled flow rate while maintaining the gas-enriched liquid at or above the threshold pressure in the volume or controlling a pressure drop as the gas-enriched liquid that is delivered. The portable device 602 may be coupled to a conduit configured to allow for intravascular delivery of the gas-enriched liquid to the patient. In some implementations, a controller (e.g., controller 722 described in relation to FIG. 8) is in communication with the actuator. In some implementations, the controller may be configured to control the actuator to cause intravascular delivery of the gas-enriched liquid to the patient at the controlled flow rate.

[0176] In the system 600, the portable device 602 can include the portable delivery device 100 described previously. In an example, the portable device 602 can include one ofthe containers and actuators and a conduit. The conduit is configured to couple to the container and deliver the gas enriched liquid to the intravascular patient delivery device 606, e.g., cannula or catheter, which has been inserted into a patient’s vasculature. In some implementations, the patient delivery device 606 includes a conduit 608, such as a cannula or catheter, which is inserted into a patient. In another embodiment, a separate conduit 611 may be connected to the portable device 602, where the conduit is configured to connect to a port 604 of cannula or catheter that is inserted into a vasculature of the patient 610.

[0177] The port 604 can include a catheter or cannula that is insertable into the patient 610 near a femoral artery. In some implementations, the conduit 608 connects the patient delivery device 606 and thus the portable device 602 to the port 604 for direct injection of the gas enriched liquid into the femoral artery of the patient 610. While the example portable delivery device 602 shown is similar to the portable delivery device 100 described in relation to FIG. 1, any of the portable delivery systems described herein can be used as a part of system 600. Also, like the embodiment shown in FIG. 1, in certain implementations, the conduit of the portable delivery device 602 can be directly inserted into the patient to deliver gas-enriched liquid to the patient without the use of a patient delivery device.

[0178] FIG. 8 illustrates an example of a system 700 including a portable device 705 (e.g., a handheld portable device) configured to deliver gas-enriched liquid to the vasculature of a patient, e.g., a radial artery of a patient. In some implementations, the delivery system 700 and portable device 705 can include a portable delivery device like the portable delivery device described in relation to FIG. 1 for delivering premixed gas-enriched liquid. In some implementations, the delivery device 700 and portable device 705 may include a portable delivery system like the portable delivery device 800 described in relation to FIG. 6A, where the gas and liquid or held in separate containers and mixed prior to delivery to the patient. In some implementations, the portable delivery device 705 may include a canister 702 and a removable actuator 706. The canister 702 may be a full canister that can be used to replace an empty canister 704 such that each of the canisters are modular. In the example shown in system 700, the conduit 714 includes a needle 710 configured to pierce a membrane or valve of the full canister 702 to begin delivery of the gas enriched liquid from the canister 702 to the conduit 714. In some implementations, the needle 710 may include a valve such that delivery of the gas enriched liquid only occurs when the removable actuator 706 causes delivery of the gas enriched liquid from the canister 702. In some implementations, the canister may be preloaded with premixed gas-enriched liquid. In some implementations, thecanister includes separate liquid or gas (or both) that are mixed in the field when preparing to deliver the gas-enriched liquid to the patient.

[0179] The actuator 706 may be removable from the full canister 702 and the empty canister 704. In this example, the actuator 706 may be controlled by a controller 722 of a control system 723 and connected to the controller via wire or wireless connection. The actuator 706 can be removable from the canister but can also be unplugged or detached from the controller 722. In some implementations, the controller 722 is also portable and part of the portable device 705.

[0180] The control system 723 can be configured to enable a user to operate the portable device 705. For example, the control system 723 can include a controller 722 configured to receive data from sensors, such as pressure sensor 709 or sensors 713. The controller 722 can control an actuator 706 to cause delivery of the oxygen-enriched liquid to the patient based on the data received from sensors. For example, the controller 722 can be coupled to a driveshaft 734 configured to operate the actuator 706. When additional liquid is to be delivered, the controller 722 can cause the driveshaft to move a piston or plunger of the actuator 706, cause valves to open or close on the container 702 and control the pressure inside the container and delivery of the oxygen-enriched liquid to the patient through conduit 714. A driver 732, such as a motor, can be used to enable the controller 722 to move the driveshaft 734.

[0181] The control system 723 can include a transceiver for receiving data from sensors via wireless signals 717 or for sending instructions to other devices (e.g., a remote display). In some implementations, the control system 723 includes sensor ports 726 for connecting to sensors via a wired connection, a power supply 728 (e.g., a battery), and a display 730. In some implementations, the display includes controls, such as control 736, for operating the actuator 706, such as to deliver a bolus of gas-enriched liquid to the patient.

[0182] The controller 722 can be configured to receive data from the one or more sensors described herein. In some implementations, the controller 722 is part of a remote system. The one or more sensors (e.g., pressure sensor 709) of the portable device 705 or sensor package 713 are configured to send data to the controller 722 via wireless 717 or wired communication, such as for controlling delivery of the gas-enriched liquid to the patient. The controller 722 can control the actuator 706 in response to measuring one or more values from the one or more sensors, such as a pressure, concentration level of the gas, flow rate, or other value for controlling delivery of the gas-enriched liquid to the patient. When the controller 722 is coupled to the actuator 706, the portable device 705 can include a power supply 728configured to power the controller and the one or more sensors in communication with the controller for portable operation.

[0183] The controller 722 can be configured to be in communication with one or more sensors 713 or other elements of the portable delivery system 700, such as pressure sensors 709 and actuators 706. The controller 722 can be configured to receive data from the one or more sensors and control one or more elements of the portable delivery system 700. For example, the controller 722 can be configured to control operation of the actuator 706 based on pressure data, flow rate data, and so forth. In some implementations, the controller 722 can control the actuator in response to instructions received from a user. The instructions can be received through a user interface. The user interface 730 can be part of the portable device 705. In some implementations, the user can input instructions through a user interface on a remote device. For example, the user can provide instructions through an application hosted on a remote device that is configured to communicate with electronics coupled to the portable delivery system 700 either wirelessly (e.g., over a mobile network) or through a wired connection (e.g., using a device that plugs into a port of the portable delivery system 700).

[0184] The controller 722 can be configured to control one or more active elements coupled to the portable delivery system in response to readings from one or more sensors. For example, the portable delivery system 700 can include a heating element. In another example, the portable delivery system 700 can include a cooling element. The heating element and / or the cooling element are each configured to maintain a temperature of the gas-enriched liquid within a predefined range. The temperature sensors can be configured to periodically measure the temperature of the gas-enriched liquid (e.g., every few seconds, minutes, hours, etc.). When the temperature of the gas-enriched liquid deviates beyond a threshold amount from a target temperature (e.g., more than 1 degree Celsius), the controller 722 can be configured to heat or cool the gas-enriched liquid.

[0185] In some implementations, the controller 722 can control operation of the actuator to cause delivery of the gas enriched liquid to the conduit 714 at a controlled rate and also maintain pressure in the full canister 702 at or above a target or minimum pressure. The actuation device 706 can be an external actuation device. In some implementations, the external actuation device includes a seating for the cannisters, 702, 704.

[0186] The conduit 714 can be coupled to the modular canisters 702, 704, and be inserted into the port 716 via a conduit interface 718. The port 716 can be similar to the port 604 described in relation to FIG. 7. For example, the port 716 can be inserted into a radial or clavicle artery of the patient 720 to deliver the gas enriched liquid to the vasculature in the rearm of the patient (or at one or more other locations), in the example shown in system 700, the portable device 705 operates similar to an intravenous drip system, except that the pressure of the canister 702 is maintained above a minimum pressure and a flow rate of gas enriched liquid within the conduit 714 is maintained at a controlled flow rate.

[0187] The system 700 can include a flow sensor 711 configured to measure flow of the gas-enriched liquid from the conduit. The flow sensor can provide a signal to the controller 722. The signal represents the flow of the gas-enriched liquid. The controller 722 controls the flow rate based on the signal from the flow sensor.

[0188] The system 700 can include a pressure sensor 709 configured to measure a pressure of the gas-enriched liquid in the canister 702. The pressure sensor may provide a signal to the controller 722, The signal represents the pressure of the gas-enriched liquid in the canister 702. The controller 722 is configured to maintain the pressure in the canister 702, e.g., by actuating the actuator and / or opening / closing a valve, to be above a threshold pressure based on the signal from the pressure sensor.

[0189] The system 700 can include a sensor package 713 configured to measure a value of a patient parameter. In some implementations, the sensor is placed inside or on the patient. In some implementations, the sensor is coupled to the cannula or catheter in the vasculature of the patient. The sensor is in communication with the controller 722. The controller 722 is configured to control, based on the value of the patient parameter, the actuator 706 to deliver the gas-enriched liquid intravascularly to the patient through the conduit 714 at the flow rate. The patient parameter can include a cardiac function of the patient. In some implementations, the patient parameter includes a blood pressure of the patient. In some implementations, the patient parameter includes a spontaneous respiration of the patient. In some implementations, the patient parameter includes a volume of gas-enriched liquid delivered to the patient. In some implementations, the patient parameter includes an euvolemia of the patient. In some implementations, the patient parameter includes a temperature of the patient.

[0190] The system 700 can include a heating or cooling element in communication with the controller 722. The controller 722 is configured to heat or cool the gas-enriched liquid by controlling the heating or cooling element. In some implementations, the heating or cooling element may be controlled based on a signal of a temperature sensor in the patient that measures a patient temperature. In some implementations, the heating or cooling element is present within or on the cannister 702, 704.

[0191] The system 700 can include a display in communication with the controller 722. The display can be configured to display one or more values representing a state or operationof the portable device 705. In some implementations, the display may be on the controller or attached to the portable device 705. In some implementations, the display is on a remote device in communication with the controller 722, as described previously.

[0192] The display may be configured to display a visual representation of one or more of operational aspects of the system 700. For example, the display 730 can display data representing a delivery flow rate, a total volume of gas-enriched liquid remaining in the portable device, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery 728 of the portable device 705, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas- enriched liquid in the volume, a cardiac function of the patient, or a combination of these data. The controller 722 may be configured to receive feedback representing a delivery flow rate, a total volume of gas-enriched liquid remaining in the portable device 705, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery of the portable device 705, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas-enriched liquid in the volume, a cardiac function of the patient, or a combination of these data and control the actuator 706 to deliver the gas-enriched liquid intravascularly to the patient at the flow rate through the conduit 714.

[0193] The one or more sensors of the sensor package 713 can be connected to the controller 722 using wired or wireless signals 717 to control actuation of delivery of the oxygen-enriched gas to the patient. In some implementations, the sensor package 713 includes a communication port 715 that plugs into the controller 722 when the package is attached to the patient.

[0194] Examples of patient parameter sensors can include the following:

[0195] One example of a sensor for measuring a partial pressure (pO?) of oxygen or oxygen saturation SO2 in the patient’s blood may be a pulse oximeter. A pulse oximeter may be used for estimating arterial pO2 or SO2. Pulse oximetry estimates the percentage of oxygen bound to hemoglobin in the blood. A pulse oximeter uses light-emitting diodes and a lightsensitive sensor to measure the absorption of red and infrared light. In another example, a sensor for measuring partial pressure of oxygen comprises an electrode such as a Clark electrode for measuring pCh. A Clark electrode includes an electrode that measures ambient oxygen concentration in a liquid using a catalytic platinum surface according to the net reaction 02 + 4 e- + 4 H+ —> 2 H2O. The various sensors may be coupled to a controller of the system via a cable or other wired connection or via a wireless connection.

[0196] A processor of the controller can receive the signals from these sensors, which signals correspond to the measured values of pCh. The processor can compare the measured pO2 to a target range of blood pCh, e.g., 760-1500 mmHg (about 100 kPa to 200 kPa). The target range may be calculated based on a blood flow rate of 50-150 ml / min, saline flow rate of 2-5 ml / min and dissolved O2 concentration in saline of 0.2 - 3 ml Ch / ml saline (STP). The controller can adjust the saline flow rate and / or dissolved O2 concentration in saline based on the measured pCh in blood to achieve an arterial blood pCh within the target range. The processor may generate an alert, e.g., through a user interface, audible alarm and / or visual alarm that indicates the level of pCh. The measured pCh indicates the effectiveness of the oxygen-enriched therapy, letting the caregiver know if the pCh in blood is within the target range for optimizing the delivery of oxygen to the patient’s ischemic tissue. In certain implementations, the processor may control the delivery of oxygen-enriched therapy by modifying one or more of the above referenced saline or oxygen parameters based on the signals received from the sensors.

[0197] Another example of a sensor is an O2 fluorescence probe. The fluorescence probe may be coupled to a controller of the system via a cable or other wired or wireless connection. A light source of the O2 fluorescence probe is illuminated. A fiber optic cable can be used to provide light to the light source in certain implementations, where the fiber optic cable is connected to the controller of the system. The fluorescence of a sensor molecule of the O2 fluorescence probe is measured. The sensor molecule can include fluorophore. A signal is received by the processor from the O2 fluorescence probe based on the fluorescence measurement. Fluorescence is measured by measuring the lifetime or decay of the fluorescence intensity signal from the illuminated sensor molecule (e.g., fluorophore) on the fluorescence probe. The decay of this signal is caused by the quenching effect of oxygen molecules in the blood or in tissue on the fluorescence intensity signal of the sensor molecule. The processor can determine the oxygen concentration, SO2 or pCh in blood or tissue based on the quenching effect of oxygen on the florescence intensity signal of the florescence probe. Changes in the amount of time that is required for the signal to decay due to oxygen quenching are indicative of the local oxygen concentration, SO2 or pCh in blood or tissue. The processor can generate an alert, e.g., through a user interface, audible alarm and / or visual alarm, based on the determined oxygen concentration, SO2 or pCh in blood or tissue. The alert may indicate the effectiveness of the oxygen-enriched therapy. The determined oxygen concentration, SO2 or pO2 indicates the effectiveness of the oxy gen-enriched therapy, letting the caregiver know if the oxygen concentration, SO2 or pCh in blood is within a predefined target range (e.g., theexpected range for a healthy individual) for optimizing the delivery of oxygen to the patient. In certain implementations, the processor may control the delivery of oxygen-enriched therapy by modifying one or more of the saline or oxygen parameters, e.g., saline flow rate or dissolved 02 concentration in saline, based on the determined oxygen concentration, SO2 or pO2 values.

[0198] Another example of a sensor may be a temperature sensor located on or in the catheter. For example, a thermistor may be utilized to measure the blood temperature of the patient. In some implementations, the processor can receive signals from the thermistor, which signals correspond to the measured values of the blood temperature. The processor may generate an alert, e.g., through a user interface, audible alarm and / or visual alarm that indicates the blood temperature, which may alert the caregiver of a hypothermic or hyperthermic, e.g., febrile, state of the patient.

[0199] An example sensor for measuring an arterial pressure of the patient’s blood would be a pressure sensor positioned in or coupled to the communicating lumen. The communicating lumen may be used for direct measurement of arterial pressure. The communicating lumen may be connected to a fluid-filled system, which is connected to an electronic pressure transducer. A change in detected blood pressure may be indicative of improved perfusion and / or restored flow in ischemic tissue as a result of the oxygen-enriched therapy. The therapy may result in improved heart function. In certain implementations, the processor may control the delivery of oxygen-enriched therapy based on the arterial pressure feedback.

[0200] An example sensor used to determine a blood flow rate includes a temperature sensor, e.g., a thermistor, thermocouple, or thermal anemometer. A temperature sensor may be located on a catheter tip, capillary tip or in the communication lumen. The temperature sensor may be heated, such that the sensor temperature is raised. As blood flows past the temperature sensor, the degree to which the temperature sensor cools down is indicative of the flow rate past the temperature sensor. The determined blood flow rate may be fed back to the system and may be indicative of the efficacy of the oxygen-enriched therapy, which results in improved perfusion and / or restored flow in ischemic tissue. In certain implementations, the processor may control the delivery of supersaturated oxygen therapy based on the blood flow rate feedback.

[0201] In some implementations, if the sensor includes a pressure sensor, the sensor may detect a pressure differential between ambient pressure and arterial pressure or an absolute value of arterial pressure. The pressure sensor may be placed anywhere in the communicating lumen but does not necessarily have to be positioned in the communicating lumen and can be located outside of the lumen. One example of a pressure sensor is a strain gauge. In a catheterhaving multiple communicating lumens, a pressure sensor may be located in a first communicating lumen providing an uninterrupted pressure signal while blood sampling may be performed via a second communicating lumen simultaneously. In another example, two pressure sensors can be used, with one located in a first communicating lumen and one located in a second communicating lumen to provide redundancy of pressure readings.

[0202] Controlling the actuator 706 can include actuating a portion of the actuator to increase or slow the delivery flow rate of the gas-enriched liquid responsive to receiving the feedback. In certain implementations, the flow rate may be controlled by the controller 722 to be sufficient to ensure a laminar flow or nearly laminar flow of the gas-enriched liquid at a point of delivery into the patient from the conduit. The laminar flow or nearly laminar flow includes fluid flow having turbulence below a threshold, such as previously described. The flow rate is controlled by the controller 722 to be sufficient to ensure that the gas-enriched liquid is free of bubbles or has bubbles below a threshold amount at a point of delivery into the patient from the conduit. However, the flow of the liquid does not need to be laminar in order to ensure that the liquid is free of bubbles or has bubbles below a threshold amount.

[0203] In some implementations, the system 700 includes a catheter configured to couple to the conduit 714. The catheter may be configured to deliver the gas-enriched liquid at a flow rate. In some implementations, a cannula is configured to couple to the conduit 714. The cannula may be configured to deliver the gas-enriched liquid at the flow rate while controlling the pressure drop such that the gas remains dissolved in the gas-enriched liquid.

[0204] In some implementations, the gas-enriched liquid is oxygen-enriched liquid. The oxygen-enriched liquid is oxygen-enriched liquid having a dissolved 02 concentration of 0.1 - 6 ml O2 / ml liquid.

[0205] FIG. 9 is a flow diagram of an example process 900 for controlling delivery of gas-enriched liquid, e.g., oxygen-enriched liquid to a patient based. In an example, the process 900 can be used to deliver gas-enriched liquid by one or more of the devices or systems described herein, such as in relation to FIG. 1 - FIG. 8. The process 900 includes coupling (902) a container (e.g., container 102) defining a volume, the volume holding a gas- enriched liquid at or above a threshold pressure such that gas remains dissolved in the gas- enriched liquid, e.g., premixed gas-enriched liquid, to an actuator. In some implementations, the container and actuator are coupled prior to controlling delivery. The process 900 includes actuating (904) the actuator (e.g., actuator 110) to push the gas-enriched liquid from the container into the conduit, the actuator configured to raise the pressure inside the container by applying a force to the gas-enriched liquid, which results in opening of the valve whichallows the liquid into the conduit. The process 900 includes controlling (906), by a conduit (e.g., conduit 104) and the actuator, a pressure drop of the gas-enriched liquid during delivery from the container to the patient via the conduit, without significant outgassing the liquid moving through the conduit to the patient. The process 900 includes maintaining (908) the gas-enriched liquid at or above the threshold pressure within the container during delivery to the patient. The process 900 includes optionally measuring (910) a flow rate of the liquid to ensure that the rate is controlled to deliver a therapeutic amount of liquid to the patient.

[0206] Some implementations described in this specification (e.g., the processor of the delivery system or device, etc.) can be implemented as one or more groups or modules of digital electronic circuitry, computer software, firmware, or hardware, or in combinations of one or more of them. Although different modules can be used, each module need not be distinct, and multiple modules can be implemented on the same digital electronic circuitry, computer software, firmware, or hardware, or combination thereof.

[0207] Some implementations described in this specification can be implemented as one or more computer programs, i.e., one or more modules of computer program instructions, encoded on computer storage medium for execution by, or to control the operation of, data processing apparatus. A computer storage medium can be, or can be included in, a computer- readable storage device, a computer-readable storage substrate, a random or serial access memory array or device, or a combination of one or more of them. Moreover, while a computer storage medium is not a propagated signal, a computer storage medium can be a source or destination of computer program instructions encoded in an artificially generated propagated signal. The computer storage medium can also be, or be included in, one or more separate physical components or media (e.g., multiple CDs, disks, or other storage devices).

[0208] The term “data processing apparatus” encompasses all kinds of apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, a system on a chip, or multiple ones, or combinations, of the foregoing. The apparatus can include special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit). The apparatus can also include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, a cross-platform runtime environment, a virtual machine, or a combination of one or more of them. The apparatus and execution environment can realize various different computing model infrastructures, such as web services, distributed computing, and grid computing infrastructures.

[0209] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, declarative or procedural languages. A computer program may, but need not, correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program can be deployed for execution on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0210] Some of the processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform actions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0211] Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and processors of any kind of digital computer. Generally, a processor will receive instructions and data from a read only memory or a random-access memory or both. A computer includes a processor for performing actions in accordance with instructions and one or more memory devices for storing instructions and data. A computer may also include or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. However, a computer need not have such devices. Devices suitable for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example semiconductor memory devices (e.g., EPROM, EEPROM, flash memory devices, and others), magnetic disks (e.g., internal hard disks, removable disks, and others), magneto optical disks, and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0212] To provide for interaction with a user, operations can be implemented on a computer having a display device (e.g., a monitor, or another type of display device) for displaying information to the user and a keyboard and a pointing device (e.g., a mouse, a trackball, a tablet, a touch sensitive screen, or another type of pointing device) by which theuser can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; for example, feedback provided to the user can be any form of sensory feedback, e.g., visual feedback, auditory feedback, or tactile feedback; and input from the user can be received in any form, including acoustic, speech, or tactile input. In addition, a computer can interact with a user by sending documents to and receiving documents from a device that is used by the user; for example, by sending web pages to a web browser on a user’s client device in response to requests received from the web browser.

[0213] A computer system may include a single computing device, or multiple computers that operate in proximity or generally remote from each other and typically interact through a communication network. Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), an inter-network (e.g., the Internet), a network comprising a satellite link, and peer-to-peer networks (e.g., ad hoc peer-to-peer networks). A relationship of client and server may arise by virtue of computer programs running on the respective computers and having a client-server relationship to each other.

[0214] FIG. 10 shows an example computer system 1000 that includes a processor 1000, a memory 1020, a storage device 1030 and an input / output device 1040. Each of the components 1000, 1020, 1030 and 1040 can be interconnected, for example, by a system bus 1050. The processor lOOOis capable of processing instructions for execution within the system 1000. In some implementations, the processor lOOOis a single-threaded processor, a multi -threaded processor, or another type of processor. The processor 1000 is capable of processing instructions stored in the memory 1020 or on the storage device 1030. The memory 1020 and the storage device 1030 can store information within the system 1000.

[0215] The input / output device 1040 provides input / output operations for the system 1000. In some implementations, the input / output device 1040 can include one or more of a network interface device, e.g., an Ethernet card, a serial communication device, e.g., an RS- 232 port, and / or a wireless interface device, e.g., an 802.11 card, a 3G wireless modem, a 4G wireless modem, a 5G wireless modem, etc. In some implementations, the input / output device can include driver devices configured to receive input data and send output data to other input / output devices, e.g., keyboard, printer and display devices 1060. In some implementations, mobile computing devices, mobile communication devices, and other devices can be used.

[0216] While this specification contains many details, these should not be construed as limitations on the scope of what may be claimed, but rather as descriptions of features specific to particular examples. Certain features that are described in this specification in thecontext of separate implementations can also be combined. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple embodiments separately or in any suitable sub-combination.

[0217] Substantial variations may be made in accordance with specific requirements. For example, customized hardware might also be used, and / or particular elements might be implemented in hardware, software (including portable software, such as applets, etc.), or both. Further, connection to other computing devices such as network input / output devices may be employed.

[0218] Information and signals may be represented using any of a variety of different technologies and techniques. For example, data, instructions, commands, information, signals, and symbols that may be referenced throughout the above description may be represented by voltages, currents, electromagnetic waves, magnetic fields or particles, optical fields or particles, or any combination thereof.

[0219] The methods, systems, and devices discussed above are examples. Various alternative configurations may omit, substitute, or add various procedures or components as appropriate. Configurations may be described as a process which is depicted as a flow diagram or block diagram. Although each may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be rearranged. A process may have additional stages not included in the figure. Specific details are given in the description to provide a thorough understanding of example configurations (including implementations). However, configurations may be practiced without these specific details. For example, well-known circuits, processes, algorithms, structures, and techniques have been shown without unnecessary detail in order to avoid obscuring the configurations. This description provides example configurations only, and does not limit the scope, applicability, or configurations of the claims. Rather, the preceding description of the configurations will provide those skilled in the art with an enabling description for implementing described techniques. Various changes may be made in the function and arrangement of elements without departing from the scope of the disclosure.

[0220] Also, configurations may be described as a process which is depicted as a flow diagram or block diagram. Although each may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be rearranged. A process may have additional stages or functions not included in the figure. Furthermore, examples of the methods may be implemented byhardware, software, firmware, middleware, microcode, hardware description languages, or any combination thereof. When implemented in software, firmware, middleware, or microcode, the program code or code segments to perform the tasks may be stored in a non- transitory processor-readable medium such as a storage medium. Processors may perform the described tasks.

[0221] Components, functional or otherwise, shown in the figures and / or discussed herein as being connected or communicating with each other are communicatively coupled. That is, they may be directly or indirectly connected to enable communication between them.

[0222] As used herein, including in the claims, “and” as used in a list of items prefaced by “at least one of’ or “one or more of’ indicates a disjunctive list such that, for example, a list of “at least one of A, B, and C” means A or B or C or AB or AC or BC or ABC (i.e., A and B and C), or combinations with more than one feature (e.g., AA, AAB, ABBC, etc.). As used herein, including in the claims, unless otherwise stated, a statement that a function or operation is “based on” an item or condition means that the function or operation is based on the stated item or condition and may be based on one or more items and / or conditions in addition to the stated item or condition.

[0223] Having described several example configurations, various modifications, alternative constructions, and equivalents may be used without departing from the disclosure. For example, the above elements may be components of a larger system, wherein other rules may take precedence over or otherwise modify the application systems and methods described herein. Also, a number of operations may be undertaken before, during, or after the above elements are considered. Also, technology evolves and, thus, many of the elements are examples and do not bound the scope of the disclosure or claims. Accordingly, the above description does not bound the scope of the claims.

[0224] The claims should not be read as limited to the described order or elements unless stated to that effect. It should be understood that various changes in form and detail may be made by one of ordinary skill in the art without departing from the spirit and scope of the appended claims. All implementations that come within the scope of the following claims and equivalents thereto are claimed.

Claims

WHAT IS CLAIMED IS:

1. A handheld device configured for delivering a gas-enriched liquid intravascularly to a patient, the handheld device comprising: a container defining a volume, the volume holding a gas-enriched liquid at or above a threshold pressure sufficient to maintain gas dissolved in the gas-enriched liquid; an actuator coupled to the container, the actuator configured to cause the gas-enriched liquid to be released from the container; a conduit coupled to the container, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery; and a valve coupled to the container, the valve configured to maintain the gas-enriched liquid at or above the threshold pressure within the container during delivery to the patient.

2. The handheld device of claim 1, further comprising a coupling interface configured to couple to a patient delivery device, the coupling interface including the conduit.

3. The handheld device of claim 2, wherein the patient delivery device is a catheter or cannula.

4. The handheld device of claim 1, wherein the conduit is configured to deliver the gas-enriched liquid in a laminar flow or nearly laminar flow having a Reynolds number of less than 2000.

5. The handheld device of claim 1, wherein a connector couples the conduit to the container, and wherein the connector comprises the valve.

6. The handheld device of claim 1, wherein the gas-enriched liquid is part of a solution in the volume, the solution further comprising plasma.

7. The handheld device of claim 1, wherein the gas-enriched liquid is part of a solution in the volume, the solution further comprising blood.

8. The handheld device of claim 1, wherein the gas-enriched liquid is part of a solution in the volume, the solution further comprising an artificial blood substitute.

9. The handheld device of claim 1, wherein the gas-enriched liquid is part of a solution in the volume, the solution further comprising a medicament.

10. The handheld device of claim 1, wherein the gas-enriched liquid is oxygen- enriched liquid.

11. The handheld device of claim 10, wherein the oxygen-enriched liquid is oxygen-enriched liquid having a dissolved 02 concentration of 0.1 - 6 ml O2 / ml liquid.

12. The handheld device of claim 1, wherein the conduit comprises a cannula having an outside diameter between 0.020 and 0.200 millimeters (mm).

13. The handheld device of claim 1, wherein the container comprises: an external volume that forms a hard shell; and an internal volume inside of the external volume, the internal volume including a flexible lining.

14. The handheld device of claim 13, wherein the flexible lining is removable from the hard shell.

15. The handheld device of claim 1, wherein an inner surface of the conduit comprises an anti -nucleation coating configured to prevent nucleation of the gas-enriched liquid inside the conduit.

16. The handheld device of claim 1, wherein the actuator comprises a piston that, when compressed, forces the gas-enriched liquid from the volume at a controlled flow rate.

17. The handheld device of claim 16, wherein the piston is coupled to a second actuator, the second actuator configured to compress the piston at the controlled flow rate.

18. The handheld device of claim 1, wherein the control of the pressure drop of the gas-enriched liquid during delivery from the container to the patient includes a controlledflow rate that comprises a rate of gas-enriched liquid delivery from the volume that is within a threshold tolerance from a baseline delivery rate.

19. The handheld device of claim 18, wherein the baseline delivery rate is 2 to 3 cubic centimeters per minute or 1 to 20 ml / sec.

20. The handheld device of claim 1, wherein the conduit comprises an aperture geometry that causes laminar flow or nearly laminar flow of the gas-enriched liquid, the laminar flow or nearly laminar flow being within a threshold distance of an end of the conduit when the gas-enriched liquid is being delivered intravascularly to the patient.

21. The handheld device of claim 20, wherein laminar or nearly laminar flow comprises fluid flow with a Reynolds number under 1500.

22. The handheld device of claim 1, wherein the actuator comprises a pump configured to deliver the gas-enriched liquid from the volume at a controlled flow rate.

23. The handheld device of claim 22, wherein the pump comprises a mechanical actuator.

24. The handheld device of claim 22, wherein the pump comprises an electronic actuator.

25. The handheld device of claim 24, wherein the electronic actuator is configured to activate a motor that pumps the gas-enriched liquid from the volume at the controlled flow rate.

26. The handheld device of claim 1, wherein the actuator comprises: a button configured to control the delivery of the gas-enriched liquid; and a valve configured to open when the button is pressed to deliver the gas-enriched liquid at a controlled flow rate and close when the button is released to prevent further delivery of the gas-enriched liquid.

27. The handheld device of claim 1, wherein the actuator is configured to deliver a predefined amount of the gas-enriched liquid at a controlled flow rate within a predetermined flow rate range.

28. The handheld device of claim 27, wherein the predetermined flow rate range is2-3 cubic centimeters per minute of the gas-enriched liquid.

29. The handheld device of claim 1, wherein the actuator comprises a purge control configured to flush remaining gas-enriched liquid from the actuator.

30. The handheld device of claim 1, further comprising a cannula and a coupling device configured to couple the cannula to the container, wherein the actuator is configured to deliver the gas-enriched liquid through the cannula to the patient.

31. The handheld device of claim 30, wherein the actuator is fixed to the container by a coupling device.

32. The handheld device of claim 30, wherein an interior of the cannula is coated in a layer of anti -nucleation material.

33. The handheld device of claim 32, wherein the anti -nucleation material comprises heparin.

34. The handheld device of claim 30, wherein a diameter of the cannula is between 0.02 millimeters and 0.200 millimeters.

35. The handheld device of claim 1, wherein the actuator is removable from the container.

36. The handheld device of claim 35, further comprising a modular delivery device, the container being configured to receive a different instance of the modular delivery device to replace a removed modular delivery device.

37. The handheld device of claim 36, wherein the different instance of the modular delivery device is sterile.

38. The handheld device of claim 1, wherein the control of the pressure drop of the gas-enriched liquid during delivery from the container to the patient includes a controlled flow rate that is a constant flow rate for a predefined time period.

39. The handheld device of claim 1, wherein the container is pressurized to least100 pounds per square inch, and wherein the conduit delivers the gas-enriched liquid at a pressure between 1-5 atmospheres.

40. The handheld device of claim 1, further comprising a heating element configured to maintain a temperature of the gas-enriched liquid within a predefined range.

41. The handheld device of claim 1, further comprising a cooling element configured to maintain a temperature of the gas-enriched liquid within a predefined range.

42. The handheld device of claim 1, further comprising a hermetic seal configured to seal the volume of the container, wherein the actuator is configured to break the hermetic seal when the actuator is actuated.

43. The handheld device of claim 1, wherein the volume is sterile.

44. The handheld device of claim 1, further comprising a flow sensor configured to measure a flow rate from the conduit.

45. The handheld device of claim 1, further comprising a pressure sensor configured to measure the pressure in the volume.

46. The handheld device of claim 1, wherein the conduit is configured to couple to an intravascular line that is inserted into a vasculature of the patient.

47. The handheld device of claim 1, further comprising a pump configured for pressurizing the volume to the pressure.

48. The handheld device of claim 1, wherein the conduit comprises an adaptor for receiving a patient delivery device, the adaptor comprising a valve that remains closed when the patient delivery device is not attached to the adaptor, the valve configured to open when the patient delivery device is attached to the adaptor.

49. The handheld device of claim 48, wherein the valve is configured to interface with the patient delivery device to maintain a sterile path to the patient delivery device.

50. The handheld device of claim 48, wherein the adaptor comprises a Luer adaptor.

51. The handheld device of claim 48, wherein the adaptor comprises a needleless adaptor.

52. The handheld device of claim 1, further comprising a temperature sensor configured to measure a temperature of the gas-enriched in the container.

53. The handheld device of claim 1, further comprising one or more sensors configured to detect a leak in the volume.

54. The handheld device of claim 53, wherein the one or more sensors comprises an oxygen concentration detector.

55. The handheld device of claim 53, wherein the one or more sensors comprises a mechanical pop-up device configured to remain in popped up configuration when no leak has occurred and to transition to a non-popped up configuration when a leak has occurred.

56. The handheld device of claim 1, wherein the actuator comprises a mechanical spring configured to compress the volume to maintain the pressure.

57. The handheld device of claim 1, wherein the actuator comprises a pneumatic piston configured to compress the volume to maintain the pressure.

58. The handheld device of claim 1, wherein the actuator comprises a trigger for actuation of delivery of the gas-enriched liquid at a controlled flow rate.

59. The handheld device of claim 1, wherein the actuator is configured to interface with an external actuation device, the external actuation device comprising a seating for the container and a trigger configured to actuate the actuator for delivery of the gas-enriched liquid at a controlled flow rate.

60. The handheld device of claim 1, wherein the conduit is configured to control the pressure drop of liquid such that liquid is delivered with a flow profile having a Reynolds number within a range of 500 - 10,000.

61. The handheld device of claim 1, wherein the container and actuator are configured to maintains the gas-enriched liquid at a target pressure.

62. The handheld device of claim 1, wherein the conduit has an internal diameter and length that are configured to control the pressure drop of the gas-enriched liquid during delivery.

63. The handheld device of claim 62, wherein controlling the pressure drop of the gas-enriched liquid during delivery comprises maintaining flow from the conduit of the gas- enriched liquid between a Reynolds number of 500 and 15,000.

64. The handheld device of claim 1, wherein the valve is positioned at a connection to a cannula from the conduit.

65. The handheld device of claim 1, wherein the valve comprises a check valve configured to sets a release pressure to control a flow rate and the pressure drop of the gas- enriched liquid during delivery.

66. The handheld device of claim 1, wherein the valve comprises a manually activated valve.

67. The handheld device of claim 1, wherein the valve opens responsive to pressure exceeding a threshold pressure in the container.

68. The handheld device of claim 1, wherein the actuator comprises a pneumatic cylinder in the container that is driven by pressure in the cylinder.

69. The handheld device of claim 1, wherein the container is configured to maintain a pressure enabling laminar flow in a removable cannula.

70. The handheld device of claim 1, wherein the gas is premixed with liquid to form the gas-enriched liquid, and wherein the volume is configured to hold the premixed gas- enriched liquid without outgassing for a minimum period of time that enables storage or shipping of the premixed gas-enriched liquid.

71. A system configured to deliver gas-enriched liquid intravascularly to a patient, the system comprising: a portable device that is preloaded with a gas-enriched liquid, the portable device comprising: a container defining a volume, the volume holding a gas-enriched liquid at or above a threshold pressure such that gas remains dissolved in the gas-enriched liquid; an actuator coupled to the container, wherein the actuator is configured to cause the gas-enriched liquid to be released from the container; a conduit coupled to the container, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery; and a valve coupled to the container, the valve configured to maintain the gas- enriched liquid at or above the threshold pressure within the container during delivery to the patient; and a controller in communication with the actuator, the controller configured to control the actuator to cause intravascular delivery of the gas-enriched liquid to the patient.

72. The system of claim 71, further comprising: an external actuation device, the external actuation device comprising a seating for the portable device and a trigger configured to actuate the actuator for delivery of the gas- enriched liquid.

73. The system of claim 71, further comprising: a flow sensor configured to measure flow of the gas-enriched liquid from the conduit, the sensor being in communication with the controller, wherein the flow sensor provides a signal to the controller, the signal representing the flow of the gas-enriched liquid, and wherein the controller controls a flow rate of delivery based on the signal from the flow sensor.

74. The system of claim 71, further comprising: a pressure sensor configured to measure a pressure of the gas-enriched liquid in thevolume, the sensor being in communication with the controller, wherein the pressure sensor provides a signal to the controller, the signal representing the pressure of the gas-enriched liquid in the volume, and wherein the controller is configured to maintain the pressure in the volume to be above a threshold pressure based on the signal from the pressure sensor.

75. The system of claim 71, further comprising: a sensor configured to measure a value of a patient parameter, the sensor being in communication with the controller, wherein the controller is configured to control, based on the value of the patient parameter, the actuator to deliver the gas-enriched liquid intravascularly to the patient through the conduit.

76. The system of claim 75, wherein the patient parameter comprises a cardiac function of the patient.

77. The system of claim 75, wherein the patient parameter comprises a blood pressure of the patient.

78. The system of claim 75, wherein the patient parameter comprises a spontaneous respiration of the patient.

79. The system of claim 75, wherein the patient parameter comprises a volume of the gas-enriched liquid delivered to the patient.

80. The system of claim 75, wherein the patient parameter comprises an euvolemia of the patient.

81. The system of claim 75, wherein the patient parameter comprises a temperature of the patient.

82. The system of claim 71, further comprising: a heating or cooling element in communication with the controller, wherein the controller is configured to heat or cool the gas-enriched liquid by controlling the heating or cooling element.

83. The system of claim 71, further comprising: a display in communication with the controller, wherein the display is configured to display one or more values representing a state or operation of the portable device.

84. The system of claim 83, wherein the display is configured to display a visual representation of one or more of: a delivery flow rate, a total volume of the gas-enriched liquid remaining in the portable device, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery of the portable device, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas-enriched liquid in the volume, a cardiac function of the patient, or a combination thereof.

85. The system of claim 71, wherein the controller is configured to: receive feedback representing a delivery flow rate, a total volume of the gas-enriched liquid remaining in the portable device, volume of the gas-enriched liquid that is delivered to the patient, a power level for a battery of the portable device, a blood pressure of the patient, a body temperature of the patient, a temperature of the gas-enriched liquid, a pressure of the gas-enriched liquid in the volume, a cardiac function of the patient, or a combination thereof; and control the actuator to deliver the gas-enriched liquid intravascularly to the patient.

86. The system of claim 85, wherein controlling the actuator comprises actuating a portion of the actuator to increase or slow the delivery flow rate of the gas-enriched liquid responsive to receiving the feedback.

87. The system of claim 71, wherein the controller controls a flow rate to ensure a laminar flow or nearly laminar flow of gas-enriched liquid at a point of delivery into the patient from the conduit.

88. The system of claim 87, wherein the laminar flow or nearly laminar flow includes fluid flow having turbulence below a threshold.

89. The system of claim 71, wherein the controller controls a flow rate to ensure that the gas-enriched liquid is free of bubbles or has bubbles below a threshold amount at a point of delivery into the patient from the conduit.

90. The system of claim 71, further comprising: a catheter configured to couple to the conduit, the catheter configured to deliver the gas-enriched liquid at a flow rate.

91. The system of claim 71, further comprising: a cannula configured to couple to the conduit, the cannula configured to deliver the gas-enriched liquid at a flow rate.

92. The system of claim 71, wherein the gas-enriched liquid is oxy gen-enriched liquid.

93. The system of claim 92, wherein the oxy gen-enriched liquid is oxygen- enriched liquid having a dissolved O2 concentration of 0.1 - 6 ml Ch / ml liquid.

94. The system of claim 71, wherein the system is handheld.

95. A handheld device configured to deliver a gas-enriched liquid intravascularly to a patient, the handheld device comprising: a container defining a volume, the volume holding a gas-enriched liquid at or above a threshold pressure such that gas remains dissolved in the gas-enriched liquid; an actuator coupled to the container, the actuator configured to cause the gas-enriched liquid to be released from the container; and a conduit, the conduit configured to facilitate intravascular delivery of the gas- enriched liquid to a patient, the conduit configured to control the pressure drop of the gas- enriched liquid to deliver the gas-enriched liquid with a flow profile having a Reynolds number within a range of 500 - 10,000.

96. The handheld device of claim 95, wherein the conduit comprises a variable cross section.

97. The handheld device of claim 95, wherein the conduit comprises a constant cross section.

98. A device configured for delivering a gas-enriched liquid intravascularly to a patient, the device comprising: a gas reservoir including gas for dissolving in a liquid to generate a gas-enriched liquid; a container defining a volume, the volume holding the liquid at or above a threshold pressure sufficient to maintain gas dissolved in the gas-enriched liquid; a first valve coupled to the gas reservoir, the first valve configured to release the gas into the container for dissolving in a liquid to generate a gas-enriched liquid; a second valve coupled to the container, the second valve configured to maintain the gas-enriched liquid at or above the threshold pressure within the container; and a controller in communication with the first valve and the second valve, the controller configured to cause the first valve to release the gas from the gas reservoir to mix with the liquid for generating a gas-enriched liquid that is maintained at or above the threshold pressure and the second valve to release the gas-enriched liquid from the container to a conduit; the conduit being coupled to the container, the conduit configured to facilitate intravascular delivery of the gas-enriched liquid to a patient wherein the conduit is configured to control a pressure drop of the gas-enriched liquid during delivery from the container to the patient such that the gas remains dissolved in the gas-enriched liquid without significant outgassing during delivery.

99. The device of claim 98, further comprising a pressure sensor configured to measure a pressure value within the container, the controller configured to release the gas from the gas reservoir to mix with the liquid for generating a gas-enriched liquid based on a pressure value measured by the pressure sensor.

100. The device of claim 98, further comprising a pressure sensor configured to measure a pressure value within the conduit, the controller configured to release the gas from the gas reservoir to mix with the liquid for generating a gas-enriched liquid based on the pressure value measured by the pressure sensor.

101. The device of claim 98, wherein either the first valve includes a pinch valve, the second valve includes a pinch valve, or both the first and second valves comprise respective pinch valves.

102. The device of claim 98, further comprising a user interface, wherein the controller is configured to receive a command through the user interface to control the first valve, the second valve, or both the first and second valves.

103. The device of claim 98, wherein the controller is configured to cause the first valve to release the gas into the container for dissolving in a liquid to generate the gas- enriched liquid in response to a signal to deliver the gas-enriched liquid.

104. The device of claim 98, wherein the device is handheld.

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