CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. provisional application No. 62/991 ,997 filed on March 19, 2020 incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] Respiratory failure leading to the need for respiratory support is a very serious problem that may yield a lower functional lung volume and decreases the ability of the patient to successfully perform gas transfer with the alveoli in the lungs, thus limiting the intake of oxygen and the exhalation of carbon dioxide. Mechanical ventilators are designed to treat a wide range of respiratory issues, including pneumonia, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and more. A mechanical ventilator is a machine that takes over the work of breathing when a person is not able to breathe sufficiently on their own. Mechanical ventilation can be noninvasive in cases of a milder degree of respiratory insufficiency, or invasive requiring endotracheal intubation. Endotracheal intubation is a procedure by which an endotracheal tube (ETT) is inserted through the mouth into the trachea.

[0003] Modern mechanical ventilators utilize variable flow valves and orifices. These devices are cost prohibitive, difficult to produce, difficult to service, and l require significant training to operate. They are not appropriate for low-resource settings or as a broad public or global health tool.

[0004] Thus, there is a need in the art for an improved mechanical ventilator system that can better address these obstacles.

SUMMARY OF THE INVENTION

[0005] In one embodiment, a ventilation system includes an inspiratory flow breathing circuit having multiple flow paths arranged in parallel, each of the flow paths having a valve and a fixed orifice of a different size, an expiratory flow breathing circuit having an expiratory valve, and a controller configured to receive a target tidal volume value and a target respiratory rate value, calculate an l:E ratio for each possible inspiratory flow path in the inspiratory flow breathing circuit, select a calculated l:E ratio that is closest to a target l:E ratio, and open one or more of the plurality of valves based on the inspiratory flow path that most closely matches the selected I: E ratio. In one embodiment, the controller is configured to operate the ventilation system in one of four states selected from the group consisting of inspiratory flow breathing circuit open, inspiratory flow breathing circuit closed, expiratory flow breathing circuit open, and expiratory flow breathing circuit closed. In one embodiment, a time or pressure trigger initiates a change in state from inspiratory flow breathing circuit open to inspiratory flow breathing circuit closed. In one embodiment, a time trigger initiates a change in state from inspiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, an inspiratory hold trigger initiates a change in state from inspiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, a time trigger initiates a change in state from expiratory flow breathing circuit open to expiratory flow breathing circuit closed. In one embodiment, a pressure trigger initiates a change in state from expiratory flow breathing circuit open to expiratory flow breathing circuit closed. In one embodiment, the pressure trigger is activated by dropping below a PEEP threshold pressure. In one embodiment, a pressure trigger initiates a change in state from expiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, the pressure trigger is activated by raising above a PEEP threshold pressure. In one embodiment, a time trigger initiates a change in state from expiratory flow breathing circuit closed to inspiratory flow breathing circuit open. In one embodiment, a patient initiated breath trigger initiates a change in state from expiratory flow breathing circuit closed to inspiratory flow breathing circuit open. In one embodiment, the patient initiated breath trigger is activated by exceeding a pressure or flow threshold. In one embodiment, a first pressure sensor is configured upstream of the plurality of valves and a second pressure sensor is configured downstream of the plurality of valves. In one embodiment, a pressure regulator is configured upstream of the first pressure sensor. In one embodiment, a flow meter is configured upstream or downstream of the expiratory valve. In one embodiment, the system includes a positive-end expiratory pressure (PEEP) control system configured to initiate transitions between the states of expiratory flow breathing circuit open and expiratory flow breathing circuit closed for controlling a descent towards a desired set point. In one embodiment, the PEEP control system comprises a machine learning algorithm that is trained to minimize the number of valve cycles which are required to achieve a given PEEP setpoint. In one embodiment, the PEEP control system receives input from at least one sensor. [0006] In one embodiment, a method for providing flow control in a ventilator having multiple of flow paths arranged in parallel, each of the flow paths having a valve and a fixed orifice of a different size, the method including the steps of receiving a target tidal volume value and a target respiratory rate value, calculating an l:E ratio for each possible inspiratory flow path in the inspiratory flow breathing circuit, selecting a calculated l:E ratio that is closest to a target l:E ratio, and sending an instruction to open one or more of the plurality of valves based on the inspiratory flow path which matches the selected l:E ratio. In one embodiment, limiting flow control to one of four states selected from the group consisting of inspiratory flow breathing circuit open, inspiratory flow breathing circuit closed, expiratory flow breathing circuit open, and expiratory flow breathing circuit closed. In one embodiment, a time trigger initiates a change in state from inspiratory flow breathing circuit open to inspiratory flow breathing circuit closed. In one embodiment, a time trigger initiates a change in state from inspiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, an inspiratory hold trigger initiates a change in state from inspiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, a time trigger initiates a change in state from expiratory flow breathing circuit open to expiratory flow breathing circuit closed. In one embodiment, a pressure trigger initiates a change in state from expiratory flow breathing circuit open to expiratory flow breathing circuit closed. In one embodiment, the pressure trigger is activated by dropping below a PEEP threshold pressure. In one embodiment, a pressure trigger initiates a change in state from expiratory flow breathing circuit closed to expiratory flow breathing circuit open. In one embodiment, the pressure trigger is activated by raising above a PEEP threshold pressure. In one embodiment, a time trigger initiates a change in state from expiratory flow breathing circuit closed to inspiratory flow breathing circuit open. In one embodiment, a patient initiated breath trigger initiates a change in state from expiratory flow breathing circuit closed to inspiratory flow breathing circuit open.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The foregoing purposes and features, as well as other purposes and features, will become apparent with reference to the description and accompanying figures below, which are included to provide an understanding of the invention and constitute a part of the specification, in which like numerals represent like elements, and in which:

[0008] Fig. 1 is a diagram of a flow control system according to one embodiment.

[0009] Fig. 2 is a finite state machine (FSM) for the ventilator in assist- controlled/volume-controlled (AC/VC) mode according to one embodiment.

[0010] Fig. 3 is a flow chart of a method for selecting an optimal flow path according to one embodiment.

[0011] Fig. 4 is a functional block diagram of a ventilator when in assist- controlled/volume-controlled (AC/VC) mode according to one embodiment.

[0012] Fig. 5 is a diagram of a ventilator system according to one embodiment.

[0013] Fig. 6 is a table of eight test cases according to an experimental example.

[0014] Fig. 7 is a diagram of a ventilator test setup according to an experimental example.

[0015] Fig. 8 is a table of test results according to an experimental example. [0016] Figs. 9A-9H are graphs of test results according to an experimental example. DETAILED DESCRIPTION OF THE INVENTION

[0017] It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a more clear comprehension of the present invention, while eliminating, for the purpose of clarity, many other elements found in systems and methods for mechanical ventilation. Those of ordinary skill in the art may recognize that other elements and/or steps are desirable and/or required in implementing the present invention. However, because such elements and steps are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements and steps is not provided herein. The disclosure herein is directed to all such variations and modifications to such elements and methods known to those skilled in the art.

[0018] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.

[0019] As used herein, each of the following terms has the meaning associated with it in this section.

[0020] The articles “a” and “an” are used herein to refer to one or to more than one (/.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. [0021] “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, and ±0.1% from the specified value, as such variations are appropriate.

[0022] Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Where appropriate, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1 , 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.

[0023] Referring now in detail to the drawings, in which like reference numerals indicate like parts or elements throughout the several views, in various embodiments, presented herein is mechanical ventilation system and method.

[0024] Embodiments of the invention include a mechanical ventilator implemented with a fixed number of orifice plates to generate constant flow paths. These orifice plates meter the mass flow rate of gas from the ventilator to the lungs of a patient. The inspiratory phase of the ventilation cycle allows for a controller to select the desired flow path based on parameters chosen by the user, including tidal volume and respiratory rate. Certain embodiments use advanced learning algorithms to combine multiple flow paths and alter the duty cycle of the control valves to cover a wider range of the parameter space outlined by the tidal volume and respiratory rate variables. The mechanical ventilator may be operated in a number of different standard modes of operation, similar to traditional ventilator devices. These include, but are not limited to, volume-controlled (VC) ventilation, pressure-controlled (PC) ventilation, pressure support (PS) ventilation, assist- controlled (AC) modes such as assist-controlled/volume-controlled (AC/VC), and more.

[0025] With reference now to Fig. 1 , a diagram of a flow control system 100 according to one embodiment is shown. This system 100 can connect to a pressurized gas source such as hospital oxygen supply 102, provided for example from gas cylinders or from wall pressure in a medical environment. Box 1 shows an oxygen blender which mixes air 104 and oxygen 102 to achieve the desired fraction of inspired oxygen (Fi02) level (in certain embodiments ranging between 21 % and 100% oxygen). Box 2 shows the inspiratory module (or inspiratory flow breathing circuit) which controls the flow of gas to the patient during inspiration. Box 3 shows the patient circuit which includes items such as filters, heaters, and humidifiers, to prepare the gas to enter and exit the patient’s body 110. Box 4 shows the expiratory module (or expiratory flow breathing circuit) which controls the flow of gas from the patient during expiration.

[0026] The inspiratory flow breathing circuit (Box 2) has a pressure regulator R-1 implemented to set the upstream pressure in the system 100 and a pressure gauge PG-1 downstream of the pressure regulator R-1 monitors this upstream pressure. A filter F-1 is placed downstream of the pressure regulator R-1 to remove debris from the patient’s breath. In this embodiment a three-valve control valve arrangement is shown having a first valve V-1 , second valve V-2 and third valve V-3 configured in parallel. Each of these valves serves as an orifice plate each having a different fixed diameter, thus providing a unique flow rate of gas given known flow parameters.

The valves can be controlled independently, generating multiple permutations of available flow paths. As the number of valves in the inspiratory flow breathing circuit increases, the total number of permutations of flow paths may also increase. Downstream of the parallel multi-valve arrangement is a pressure relief valve RV-1 which acts as a safety valve to prevent overpressure of gas to the patient, followed by a pair of redundant pressure transducers PT-1 , PT-2 for monitoring pressure levels and triggering an alarm or safety feature, or as a way to control the pressure target for certain ventilatory modes.

[0027] As will be appreciated by those having ordinary skill in the art, different geometries and flow-restrictive structural elements can be implemented to create various permutations of flow paths having different cross-sectional areas. For example, the conduit upstream or downstream of the valve can change diameter for purposes of restricting flow in a particular pathway. Also, while the cross-sectional area will typically be circular, other cross-sectional geometries can be utilized. Regarding parallel arrangements of multi-sized orifices, a basic parallel arrangement can be implemented or branching arrangements of multi-sized orifices can be implemented to create the various permutations of flow paths desired.

[0028] With reference to the patient circuit (Box 3), HEPA filters F-2, F-3 can be implemented for patient safety. A heater and moisture element is utilized just upstream of delivery to the patient 110 to heat and humidify the gas prior to patient delivery. Downstream of the patient circuit is the expiration flow breathing circuit (Box 4). A single expiratory valve V-4 is shown followed downstream by a flow meter FM-1 to measure the amount of gas expired by the patient. A check valve CV- 1 or orifice of known size is placed at the end of the circuit to control the flow rate of gas leaving the patient, preventing the gas from leaving the patient at an unknown rate. It will be apparent to those having ordinary skill in the art that structural components including but not limited to valves, filters, regulators and sensors can in many instances be placed upstream or downstream of locations shown in the instant embodiment, and in certain instances can be eliminated, duplicated or replaced with a different component without altering the advantages of the invention, of which Fig.

1 is merely one of many embodiments possible provided as an example.

[0029] With reference now to Fig. 2, a finite state machine (FSM) for the ventilator in assist-controlled/volume-controlled (AC/VC) mode is shown according to one embodiment. This FSM shows the possible transitions between the four states of the mechanical ventilator, which are Inspiratory Flow breathing circuit Open, Inspiratory Flow breathing circuit Closed, Expiratory Flow breathing circuit Open, and Expiratory Flow breathing circuit Closed. The transitions between states will vary depending on the mode of the device. It is only possible for the device to be in one state at a time and the only allowable transitions between states are shown in arrows, with a description provided of what allows the transition to occur. It is possible for the device to transition between State 1 and State 2 based on a time trigger. It is not possible for the device to transition directly between State 1 and State 3. State 4 is the only state which has multiple possible transitions. When in State 4, the device can transition to either State 1 or State 3. [0030] The embodiment of Fig. 2 depicts the allowable states and possible transitions when the device is in volume-controlled/assist-controlled (VC/AC) mode. In this mode, a set volume of gas is delivered to the patient each breath cycle. The volume is set by the user. The rate at which breaths are delivered, known as the respiratory rate or the breathing rate, is set by the user (for example as breaths-per- minute). However, it is also possible for the patient to trigger their own breath if they exert effort which is detected by the ventilator on either a flow or pressure sensor. In State 1 , the inspiratory flow breathing circuit is open and gas is flowing into the patient’s lungs. This will occur for a set amount of time, after which the device will transition to State 2. In State 2, the inspiratory flow breathing circuit is closed. The device will transition to State 3 either based on a time trigger or an inspiratory hold trigger. If the user engages an inspiratory hold (e.g. 1 second), then the transition between Stage 2 will be delayed for the duration of the inspiratory hold. The transition between State 3 and State 4 will occur after either a set amount of time or based on a pressure trigger, if the pressure drops below a setpoint of positive end- expiratory pressure (PEEP). The device will transition between State 4 and either State 1 or State 3 based on either time, patient initiated breath trigger, or a pressure trigger. The time trigger will determine if the expiratory phase has ended, based on the respiratory rate and control software. The pressure trigger will determine if the airway pressure has dropped below the PEEP setpoint pressure. If either of these conditions are met, the expiratory valve will close. If the expiratory valve closes due to a time trigger, that will also allow the FSM to transition from State 4 to State 1 and begin another inspiratory phase. The expiratory valve can re-open if the pressure increases above PEEP pressure, for instance caused by patient effort during expiration, as long as the time trigger has not yet been met. This allows the patient to have some control over the expiration and expiration is more flexible across a wider range of patient physiologies.

[0031] A method for controlling the positive-end expiratory pressure (PEEP) of the system can be implemented. The PEEP control system will allow for the FSM to transition back from State 4 to State 3 and vice versa in a way that allows for a controlled descent towards the desired set point. The algorithm for control of PEEP may be implemented with a machine learning algorithm that is trained in order to minimize the number of valve cycles which are required to achieve a given PEEP setpoint while maintaining a high level of comfort for the patient. The method can be used to provide predictive care outcomes and personalized medicine for individual patients based on the sensor data collected by the device. The method can be trained in the following, non-inclusive, ways: supervised machine learning, where the data from the device is compared to traditional lung performance test results and other clinical tests; and unsupervised machine learning, where time-based data from the device is used to develop a model based on how future lung performance is impacted by past lung performance.

[0032] With reference now to Fig. 3, a flow chart showing a method 300 for selecting the optimal flow path (i.e. determining the valves which are on or off) is shown according to one embodiment. Based on user setpoints for Target Tidal Volume and Target Respiratory Rate, the system can iterate through all possible combinations of flow paths based on a combination of the number of orifice plates. For each possible flow path, the device will calculate the inspiratory to expiratory (l:E) ratio for that flow path. The device will finally select the optimal flow path based on whichever flow path has the closest l:E ratio to the target l:E ratio, set by the user, or using an advanced algorithm to select the optimal I : E ratio which may involve patient pathophysiology and measured parameters such as end-tidal carbon dioxide or pressure. Inputs to this function are set by the user, and include the tidal volume (breath delivered to the patient each cycle), the respiratory rate (breathing rate), and the target l:E ratio (target inspiratory to expiratory ratio).

[0033] More specifically, a Target Tidal Volume 302 is entered and the system uses this value to calculate the required inspiratory time for each possible flow path 304. The Target Respiratory Rate 306 is entered (e.g. as breaths-per-minute) and the system calculates a cycle time 308. The calculated inspiratory time for each possible flow path 304 and the cycle time 308 are then used to calculate an expiratory time for each possible flow path, based on the cycle time 310. From there, the l:E ratio for each possible flow path can be calculated 312. The l:E ratio that is closest to the target l:E is selected 314 and the target inspiratory time, target expiratory time and target inspiratory flow paths are set 316.

[0034] Now showing one example, an implementation with two valves/orifices in the inspiratory flow breathing circuit yields three possible flow paths (1 , 2, 1+2). On startup, each flow path would be calibrated and a flow rate would be calculated. Table 1 shows some of the calculations which would be performed by the system controller (e.g. implemented by software), assuming a target l:E ratio of 1 :2.

Table 1 - Example calculations for flow paths

[0035] Based on this, the system would select Flow Path 2 where the l:E ratio error is the smallest of all of the different flow paths. As would be apparent to those having ordinary skill in the art, it is possible to use an alternative implementation of selection of flow paths where the absolute value of the l:E ratio error is not the determining factor in the flow path.

[0036] With reference now to Fig. 4, a functional block diagram 400 for the ventilator is shown when it is in assist-controlled/volume-controlled (AC/VC) mode according to one embodiment. There are a variety of inputs to the FBD, including the current state of the device, from the finite state machine (FSM), the sensor readings, system clock, the optimal flow path, and more. This algorithm, implemented in software, will allow the device to control which valves are open and which valves are closed at all points of operation based on the FSM and other inputs. The top two rows show the various inputs to the flow breathing circuit which determine when to open or close specific valve flow breathing circuits. There are five columns shown, each with a decision diamond on top. From left to right, these are for FSM=4, FSM=1 , FSM=2, FSM=3, and FSM=4. Each of these columns represents one transition on the FSM. The reason two columns exist for where FSM=4 is because State 4 is the only state with two allowable transitions out of it.

[0037] Starting from column 2, FSM=1 , one can see how the time trigger functions. After the first decision diamond is passed, identifying us in State 1 , the second decision diamond reads: CURRENT_TIME > LASTJDPENJNSP + INSP_TIME

[0038] This indicates that the software will wait until the inspiratory time (INSP_TIME) has gone by as it does not return a value of true until the current time is greater than the last time the inspiratory valve was opened (LASTJDPENJNSP) plus the inspiratory time. This is how a time trigger is programmed in a functional block diagram and allows for it to be transitioned into software run by the system.

The other columns represent additional decision diamonds which can be implemented in software run by the system.

[0039] With reference now to Fig. 5, a ventilator system 500 diagram is shown according to one embodiment. A controller 502 is configured to receive input for selecting a mode 504 and setpoints 506, and further receives sensor 508 input including pressure data and flow rate date. Pressure and flow rate data can trigger an alarm 512 if thresholds are exceeded as described in the embodiments above. The controller 502 is configured to send output commands to the ventilator system for setting the finite states described in reference to Fig. 2. Manual setpoints 510 such as F1O2 and and Max PIP setpoints can be set directly at the ventilator 516. As described above in Fig. 1 , the ventilator 516 is in flow communication with a supply gas 514 upstream and the exhaust gas 518 is expelled downstream.

[0040] Ventilators may draw intermediate-pressure gas such as oxygen, often supplied at 50 psiG, from the hospital pipeline, and have backup high-pressure cylinders to switch to in the event of pipeline failure. In one embodiment, the system assumes that a hospital pipeline is present to provide air and oxygen to the proposed mechanical ventilator system and will use 50 psiG as the supply pressure to this system. It is possible to include a pressure regulator near the hospital pipeline connection to ensure constant pressure is fed to the ventilator system and improve reliability. A backup can be employed to use either a compressed gas cylinder or an air compressor to provide adequate pressure if a hospital pipeline is not available.

[0041] Embodiments of the system allows for control of a number of critical clinical parameters, including tidal volume, respiratory rate, ventilatory mode, positive-end expiratory pressure (PEEP), fraction of inspired oxygen (FiC^), and more. Unlike a traditional ventilator, the system does not allow the user to independently control the inspiratory time of the ventilatory cycle. Instead, the system will calculate the optimal inspiratory time based on the various combinations of flow paths that are available in the device. The system will attempt to achieve an inspiratory to expiratory (l:E) ratio as close to the target l:E ratio as possible given the various orifice plates.

[0042] In certain embodiments utilizing a controller (e.g. controller 502), processor or computing device for controlling system functions, software executing instructions may be stored on a non-transitory computer-readable medium, wherein the software performs some or all of the steps of the methods described herein. Aspects of the embodiments may relate to algorithms executed in computer software. Though certain embodiments may be described as written in particular programming languages, or executed on particular operating systems or computing platforms, it is understood that the system and method of the present invention is not limited to any particular computing language, platform, or combination thereof. Software executing the algorithms described herein may be written in any programming language known in the art, compiled or interpreted, including but not limited to C, C++, C#, Objective-C, Java, JavaScript, MATLAB, Python, PHP, Perl, Ruby, or Visual Basic. It is further understood that elements of the present invention may be executed on any acceptable computing platform, including but not limited to a server, a cloud instance, a workstation, a thin client, a mobile device, an embedded microcontroller, a television, or any other suitable computing device known in the art.

[0043] Parts of this invention are described as software running on a computing device. Though software described herein may be disclosed as operating on one particular computing device (e.g. a dedicated server or a workstation), it is understood in the art that software is intrinsically portable and that most software running on a dedicated server may also be run, for the purposes of the present invention, on any of a wide range of devices including desktop or mobile devices, laptops, tablets, smartphones, watches, wearable electronics or other wireless digital/cellular phones, televisions, cloud instances, embedded microcontrollers, thin client devices, or any other suitable computing device known in the art.

[0044] Similarly, certain embodiments may rely on signals communicating over a variety of wireless or wired computer networks. For the purposes of this disclosure, the words “network”, “networked”, and “networking” are understood to encompass wired Ethernet, fiber optic connections, wireless connections including any of the various 802.11 standards, cellular WAN infrastructures such as 3G, 4G/LTE, or 5G networks, Bluetooth®, Bluetooth® Low Energy (BLE) or Zigbee® communication links, or any other method by which one electronic device is capable of communicating with another. In some embodiments, elements of the networked portion of the invention may be implemented over a Virtual Private Network (VPN). EXPERIMENTAL EXAMPLES

[0045] The invention is now described with reference to the following Examples. These Examples are provided for the purpose of illustration only and the invention should in no way be construed as being limited to these Examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[0046] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.

[0047] The following experimental setup was implemented:

[0048] TEST MATRIX

[0049] An extensive test matrix of over 100 different test cases was performed to validate the performance and design of the ventilator. These test cases cover a variety of device parameters such as the delivered tidal volumes, inspiratory times, respiratory rates, and positive end-expiratory pressure (PEEP) values.

[0050] These test cases also changed patient physiological parameters, such as the lung compliance and airway resistance. [0051] Each test case was run for at least 30 cycles in order to collect averages and standard deviations of important parameters such as delivered tidal volume, inspiratory time, expiratory time, inspiratory to expiratory ratio, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP).

[0052] With reference to Fig. 6, a subset of eight test cases that were adapted from ISO 80601-2-80:2018, Table 201.104 is presented. Based on the theory of operation for the ventilator, the inspiratory time is not independently adjustable by the operator, which leads to a deviation between the below table and the original table from ISO 80601-2-80:2018.

[0053] The ventilator allows for independent control of the delivered tidal volume and the respiratory rate. Based on these setpoints, the device uses the software to calculate the optimal inspiratory time. The device will select an inspiratory time that results in an l:E ratio as close to 1 :2 as achievable based on the clinical parameters. Additional parameters, such as PEEP and Fi02, are independently adjustable by a clinician.

[0054] Eight Test Cases from ISO 80601-2-80:2018, Table 201.104 were also performed using the a 510(k) cleared ventilator (referred to herein as the Predicate ventilator). This device allows for a direct comparison between the test results on the ventilator and the Predicate ventilator for better understanding of device performance and to aid in interpreting the results presented in this report.

[0055] TEST SETUP

[0056] The test setup (Fig. 7) involved connecting the ventilator Unit Under Test (UUT) to wall supply of gas and then connecting the UUT to an ASL 5000 Breathing Simulator from ImgMar Medical. The figure below shows the test setup. Internal to the ASL 5000 Breathing Simulator are a variety of sensors which enable us to validate the UUT performance. The test lung has internal sensors which are able to measure pressure, flow rate, and totalized volume. The data collection rate of the test lung is 512 Hz.

[0057] The ASL 5000 was calibrated in a calibration lab is accredited to ISO/I ES 17025:2017. The ASL 5000 meets or exceeds the requirements for test lungs used for volume testing as specified in the following standards:

[0058] ISO 80601-2-12:2011 (Critical Care Ventilators)

[0059] ISO 80601-2-13:2011 (Anesthetic Workstations)

[0060] ISO 10651-6:2004 (Home Care Ventilatory Support Devices)

[0061 ] ISO 10651-3: 1997 (Emergency and T ransport Ventilators)

[0062] It is important to note that the ventilator circuit tubing used in this test setup, identified as item 4 in Fig. 7 has its own compliance. When patient pathophysiology changes, such as increasing airway resistance or decreasing lung compliance, a given volume of gas will be effectively trapped in the ventilator circuit tubing and will not reach the ASL 5000 breathing simulator. When this occurs, the trapped volume in the ventilator circuit will not be included in the measured delivered tidal volume by the ASL 5000 breathing simulator. This may result in an apparent discrepancy of delivered tidal volume, as measured by the ASL 5000.

[0063] Qualitatively, the parameters that control the amount of gas trapped in the ventilator circuit are the absolute system pressure and the gas flow rate. At higher system pressures, the ventilator circuit tubing will expand more, due to its compliance, and allow for a larger volume of trapped gas. At higher gas flow rates, the differential pressure between the lung simulator and ventilator circuit tubing will be greater due to the airway resistance. Thus, a higher gas flow rate will result in even higher airway pressures, which then results in more trapped volume in the ventilator circuit tubing.

[0064] The Predicate ventilator was used as a baseline device to understand the volume of gas that is trapped in the ventilator circuit tubing for each of the Test Cases. Presented is a series of test results for the ventilator, the Predicate ventilator, and compare the results between them. When the Predicate ventilator was used, the test setup, including ventilator circuit tubing, was identical to what was used to test the ventilator. This allows for a one-to-one comparison of the test results.

[0065] TEST RESULTS

[0066] The Test Cases discussed in Section 3 were analyzed and present data that allow for a more complete characterization of device performance than is afforded by a comparison of output specifications. All cases delivered repeatable volumes, with less than a 0.42% error and extreme repeatability in the inspiratory and expiratory times, showing negligible error on the respiratory rate. The error associated with any value is determined based on the mean and standard deviation of the delivered value over at least 30 cycles for a given Test Case.

[0067] The in Fig. 8 shows key results from this test. The mean and standard deviation values are presented for the delivered tidal volume. All other values presented are the mean values from the multiple cycles performed for each Test

Case. [0068] The mean and standard deviation values for delivered tidal volume show extreme repeatability and consistency of the delivered therapy by the ventilator. For each Test Case, a standard deviation of less than 0.42% of the mean value is observed.

[0069] The plots in Figs. 9A-9H show the waveforms plotting volume vs. time, pressure vs. time, and flow vs. time for a representative set of breathing cycles for each of the selected Test Cases. The displayed pressures are airway pressure, taken from a pressure sensor on the breathing simulator, and alveolar pressure, taken from a pressure sensor inside the breathing simulator lung chamber. The measured value of PEEP can be determined from the alveolar pressure sensor in the final samples before the start of an inspiratory phase.

[0070] DISCUSSION

[0071] Over 100 Test Cases were conducted from an extensive Test Matrix to understand and quantify the performance of the ventilator. A subset of the Test Cases is presented here, adapted from ISO 80601-2-80:2018, Table 201.104. From all testing, extreme consistency and quality of performance is observed, which matches that of currently approved devices that are found in critical care and clinical use in the United States, such as the Predicate ventilator.

[0072] The eight Test Cases presented in detail cover a range of patient physiologies, including lung compliance and airway resistance values. These also demonstrate the ventilator’s ability to provide a wide range of tidal volumes at different respiratory rates. The device possesses an astounding level of repeatability and accuracy over the Test Cases, which occurred over many hours over multiple days of testing. [0073] There are two important areas that deserve additional discussion to properly understand the performance of the ventilator. The first is an apparent discrepancy in the delivered tidal volume from the device. The second is pressure oscillations that occur during the expiratory phase. With the support of data presented in this report, it is demonstrated that these phenomena are present in the Predicate ventilator, which is a 510(k) cleared device for critical care use in the United States.

[0074] The ventilator circuit tubing used in the test setup caused an apparent discrepancy in delivered tidal volume. Specifically, at high absolute pressure and high flow rates, the volume of the ventilator circuit tubing expands. This expansion, which is caused by the high compliance of the circuit, leads to an increased dead volume, or trapped volume, of air within the test setup. Because this gas is trapped, it does not enter the ASL 5000 breathing simulator and thus is not measured as delivered tidal volume during the test. This results in an apparent discrepancy of up to 25% in some Test Cases.

[0075] Multiple tests were performed to demonstrate that the apparent volume discrepancy is nothing more than an artifact of the test setup. First, the length of tubing that was used to connect the ventilator to the ASL 5000 breathing simulator was varied. As the length of tubing was increased, the discrepancy increased. This indicates that the amount of trapped gas, due to the compliance of the ventilator circuit tubing, increased. This supports the hypothesis that the discrepancy is an artifact of the test setup.

[0076] Additionally, a predicate device was tested on the identical test setup, with identical tubing. The same series of Test Cases were run on a Predicate ventilator system version 7.0, software version 7.00.04. The predicate device experienced nearly identical apparent volume discrepancies. However, the flow breathing circuit also displays the delivered and expired volumes on its monitor.

Over a wide range of physiologic parameters, the ASL 5000 indicated tidal volumes that aligned with the previous data collected on the ventilator. The volumes displayed on the Predicate ventilator monitor remained at or near the target setpoint, indicating the apparent volume discrepancy is not a true discrepancy. The Predicate ventilator continued to deliver and expire the same target volume of gas regardless of the test data.

[0077] Qualitatively, the parameters that control the amount of gas trapped in the ventilator circuit are the absolute system pressure and the gas flow rate. At higher system pressures, the ventilator circuit tubing will expand more and allow for a larger volume of trapped gas. At higher gas flow rates, the differential pressure between the lungs and ventilator circuit will be greater due to the airway resistance. Thus, a higher gas flow rate will result in even higher airway pressures, which then result in more trapped volume in the ventilator circuit tubing.

[0078] Based on the results presented in this report, confidence exists that there is no significant deviation of the delivered volume across the Test Cases.

Confidence also lies in the ability of the ventilator to provide a wide range of volumes to a patient and to do so with the consistency and accuracy of other critical care devices that have received 510(k) clearance and are on the market in the United States today.

[0079] The second area of note is the cycling of the expiratory valve during the expiratory phase of device operation under certain circumstances. Due to the implementation of how the device maintains PEEP, which is discussed in the Section 2 and controlled by a Finite State Machine (FSM), the expiratory valve may cycle multiple times to achieve a PEEP setpoint based on measured airway pressure. The important clinical parameter, alveolar pressure, is measured in the ASL 5000 breathing simulator. This measured value shows no large jumps and it is determined that this device is viable for clinical use in an emergency scenario where no other method of providing ventilatory support is available.

[0080] This cycling of the expiratory valve may, in certain situations, result in pressure oscillations. However, no pressure oscillations were noted in the waveforms from the ventilator presented in this revised report for the Test Cases adapted from ISO 80601-2-80:2018, Table 201.104. However, the Predicate ventilator does experience pressure oscillations during expiration. This is indicative that the logic and software in the Predicate ventilator use a similar process to the ventilator. Based on this, and the results presented in this report, there is no increased risk to a patient due to the potential for pressure oscillations during expiration.

[0081] All cases tested on the ventilator delivered highly repeatable volumes, and the eight Test Cases that were presented all had a standard deviation of less than a 0.42% of the delivered volume mean. The error of the device is defined to be one standard deviation from the mean and based on this one-sigma error, the delivered volume has an error of about 0.18% over the range of cases studied. The device was able to consistently maintain a set PEEP at the end of the expiration phase. More impressive is ventilator’s extreme repeatability of the inspiratory and expiratory times, showing negligible error on the respiratory rate. [0082] Based on the data presented, a high level of confidence is established in the ability of this device to assist health care workers in emergency settings and the simplicity and low-cost design made it ideal for scenarios where constrained resources limit access to medical equipment.

[0083] The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention.