Presented here is the design of the Mechanical Ventilator Milano (MVM), a novel mechanical ventilator designed for rapid mass production in response to the COVID-19 pandemic to address the urgent shortage of intensive therapy ventilators in many countries, and the growing difficulty in procuring these devices through normal supply chains across borders.
This ventilator is an electro-mechanical equivalent of the old and reliable Manley Ventilator, and is able to operate in both pressure-controlled and pressure-supported ventilation modes.
MVM is optimized for the COVID-19 emergency, thanks to the collaboration with medical doctors in the front line. MVM is designed for large-scale production in a short amount of time and at a limited cost, as it relays on off-the-shelf components, readily available worldwide Operation of the MVM requires only a source of compressed oxygen (or compressed medical air) and electrical power. Initial tests of a prototype device with a breathing simulator are also presented. Further tests and developments are underway. At this stage the MVM is not yet a certified medical device but certification is in progress.
The large number of people affected by SARS-CoV-2 has created an urgent demand for ventilators on a global basis, a demand that exceeds the capacity of the existing supply chains, especially in some regions where cross-border supply has been disrupted. This need has motivated the development of the mechanical ventilator (Mechanical Ventilator Milano, MVM) -a reliable, fail-safe, and easy to operate mechanical ventilator that can be produced quickly, at large scale, based on readily-available parts. It was inspired by the Manley ventilator [1] , which was proposed in 1961, based on "the possibility of using the pressure of the gases from the anaesthetic machine as the motive power for a simple apparatus to ventilate the lungs of the patients in the operating theatre" [2] . The MVM is designed with the same principle of simplicity in mind.
The current version of this paper reflects up to date revisions stemming from our testing and from recommendation by medical doctors. However, we foresee possible future updates to this paper, as we proceed with testing and as we assess parts availability which may vary from country to country. We are also proceeding with the required tests for certification of this ventilator, working with regulators in Italy and several other countries.
MVM is designed to work in a pressure-controlled mode, which appears to be the correct operation mode for the COVID-19 patients, for whom a high pressure may damage further the lungs. MVM and can be operated in both independent ventilation (pressure-controlled ventilation, PCV) and patient-assisted control modes (pressure-supported ventilation, PSV).
The system connects directly to a line of pressurized medical oxygen or medical air, and relies on regulation of the flow to deliver medical air, medical oxygen, or a mixture of air and oxygen to the patient at a pressure in the range suitable for treatment. Pressure regulation of the end-expiratory cycle is achieved by discharging the expiratory flow through a valve which sets the desired minimum positive end-expiratory pressure (PEEP). Another adjustable pressure limiting valve is connected to the inspiratory line and ensures that the maximum pressure delivered does not exceed the pre-set value.
Vocabulary and semantics are defined as per ISO 19223:2019 [3] . The system is designed to satisfy compliance with the guidelines defined in the international standard ISO 80601-2-12:2020 [4] . The most significant qualification tests in this respect are discussed in Sec. 6 . Important features of the MVM are: Small Number of Components: as described in Sec. 2. Ease of Procurement: the parts required for the construction of the MVM have been selected based on those that are available in many nations globally. The parts selected are also characterized by their ease of use in large-scale manufacturing and assembly. Simplicity of Construction: assembly of the parts into a complete MVM is achievable based on a small set of clear instructions. The process for loading the software into the controller is simple. The controller software is open source and available for customization by end users. Cost Containment: the total cost of the components is in the hundred e 's. Convenience of Deployment: the device requires only connection to a line of pressurized oxygen and standard AC electrical power (either 110 or 220 V); this makes the MVM readily deployable in medical clinics with centralized oxygen and air supply systems, such as COVID-19 hospitals or COVID-19-care areas in general hospitals. Customizability: the MVM can operate in different ventilation modes: independent (PCV) and patient-assisted (PSV) as described in Sec. 3. Also, the operating parameters can be tuned by the operator with a simple user interface. Reliability: the components in the MVM are commercial and readily available. We note that the reliability of MVM has to be carefully studied based on the specifications of the components. The system is designed to be easy to repair, just by replacing any non-functioning parts. Limited oxygen consumption: the consumption of oxygen with this device will not exceed 6 slpm.
The illustration in Fig. 1 shows the MVM ventilator (components within the light blue box) and a possible setup for the corresponding breathing circuit. The main components are described below: Connection to oxygen and air supply: at the left-hand side, the MVM is connected to a pressurized oxygen/air line; Sintered filters SF-1, SF-2 the sintered filters remove particulate in the inline that can clog the pipes; Gas blender GB-1 The oxygen and air flow are mixed in a medical gas blender. GB-1 is external to the MVM unit. The FiO2 set point is set manually, directly on the GB-1 unit. Differential pressure sensors: Four differential pressure sensors PS-1, PS-2, PS-3, and PS-4 monitor the pressure and flow at different points of the breathing system. Air/Oxygen delivery proportional valve PV-1: The incoming gas flow to the patient is controlled by the proportional valve PV-1 using a process control loop based on the value of PS-1 to ensure that the proper respiratory minute volume is delivered to the patient. PV-1 is a normally close (NC) valve; Adjustable pressure limiting valve PV-3: Mechanical valve that sets the value of the maxi-mum inspiratory pressure in the range 20-80 cm H 2 O; Negative pressure relief valve PV-4: A check valve to avoid any negative pressures during patient assisted ventilation. In that mode, the patient is active and can spontaneously request more air. As long as there is a positive pressure in the respiratory lines this valve remains closed. A bacterial/viral filter may be required just before the valve to prevent contaminated room air entering the upstream part of the system; Oxygen sensor OS-1: An oxygen sensor OS-1 is used to continuously monitor the fraction of inspired oxygen FiO2; Spirometer SP-1: A precision spirometer is connected to the input line to monitor the inspiratory flow rate; Breathing system: The breathing system, connected to the tracheal tube, supports the attachment of two plastic tubes of standard size 22 mm connecting respectively to valves PV-1 and PV-2, and to a smaller plastic tube leading to the differential pressure sensors PS-1, PS-2, PS-3, and PS-4 to monitor pressure and flow. The standard for connection of the breathing system is the 22 mm cone and socket combination defined in the standard [5] ; Condensate trap CT-1: The expiration tube passes through a condensate trap allowing for removal of condensed vapor from the patient's breath; Silicone membrane SM-1: The silicone membrane filters access to the machine of the wet flow; Expiration valve PV-2: This high throughput valve with low pressure-drop controls the expiratory flow. An adequate orifice diameter guarantees the flow corresponding to the expiration of a proper respiratory minute volume at the given PEEP values; the valve is controlled by the three-way solenoid valve PV-6. PEEP valve PV-5: A mechanical valve that controls and defines the positive end-expiratory pressure PEEP in the range 5-20 cm H 2 O. A first technical layout of the MVM controller base assembly box is shown in Fig. 2 .
The control system performs supervision and actuation of the two valves (PV-1 and PV-2) based on the programmed respiratory cycle.
The pressure sensor PS-1measures the pressure at the patient. The control system reads the pressure on PS-1and appropriately adjusts the two valves. This ensures that the pressure is always within the operating range: 20-80 cm H 2 O for the inspiratory phase and 5 cm H 2 O for the expiratory phase.
During the inspiratory phase, PV-2 is closed and PV-1 is open. The setting of PV-1 is adjusted to maintain the pressure within the desired range during the inspiratory period. At the end of the programmed inspiratory period, PV-1 is closed and, after a small pause, PV-2 is opened to allow the discharge of the lung pressure. The expiratory pressure limit PEEP is set by PV-5.
The main controller runs on a (Arduino-compatible) micro-controller board based on a 32 bit micro-controller. These boards have a small form factor and integrate all I/O functions required for this system.
A daughter board interfaces to the controller and provides four opto-coupled switches to operate the electrically-controlled valves. The daughter board is provided with 24 V VDC supply and includes the low voltage regulator to supply the central unit.
The differential pressure gauges are based on a 60 cm H 2 O differential pressure sensor with a resolution better than 0.2 cm H 2 O.
A buzzer and a high luminosity LED are incorporated to signal alarms. The MVM is equipped with an industrial power supply unit capable of at least 50 W and battery backup operated in fail-safe mode. Under normal circumstances, the power supply will feed the controller and keep the battery charged. In case of power failure, the battery will automatically provide the power for ongoing system operation for up to 120 min. The power supply is hosted in a separate enclosure to provide isolation between the oxygen lines and possible spark sources. The backup power supply unit will include two 12 V, 1.2 A h batteries.
In the pressure-controlled ventilation (PCV) configuration, the unit will operate the valves in regular cycles. The operator defines the cycle by setting the inspiratory time, PEEP, and respiratory rate. The operator is also required to set the target inspiratory pressure. The maximum inspiratory pressure threshold is manually set by PV-3 for patient safety. Alarms are set on the basis of the inspiratory pressure, the minute ventilation, and the tidal volume, measured by the system itself. Preliminary ranges of values for control and alarm parameters are listed in Table I .
In pressure-supported ventilation (PSV) mode, the patient triggers the ventilator. Inspiration pressure support is given at a preset constant pressure. The ventilator regulates the pressure during inspiration so that it corresponds to preset values within the operating ranges listed in Table II .
The goals of the MVM electronics are:
• Control the valve system; • Read the pressure and the oxygen sensors;
• Generate hardware (LED, Buzzer) and visual alarms;
• Provide a simple Graphic User Interface (GUI). • Visualize the system parameters on a display. It is composed by a board hosting an ESP32 micro-controller and a Raspberry 4 unit. The parameters are displayed on a 7 touch-screen that allows also a few parameter settings. Fig. 3 shows the block diagram of the electrical connections.
The MVM operations are managed by an electronic system which includes all the components to measure relevant quantities, to drive the solenoid and proportional valves and to interface to the user via a touchscreen. The micro-controller unit is based on a commercial product by Adafruit within the Feather line: these units all share the same form factor and connections pinout while offering different micro-controller and connectivity options. Moreover a set of daughter boards, called Wings, provide extensions (Ethernet, touchscreen displays, LoRa radios, etc.): the wings can be stacked. For the MVM project two feathers are of interest:
• The Huzzah32 unit is based on a 32 bit micro-controller (ESP32) produced by Espressif. Both Feathers can be programmed with Arduino. Between the two units we picked the ESP32based solution given the more widespread use of this micro-controller in the IOT environment. This in turns corresponds to a larger availability of the units.
The control board has been developed at LNGS, according to the design requirements of the Milano team that is testing the proposed solution in the field. The control boards include the following sub-systems:
• The connection to the Feather micro-controller and the voltage regulators. From the main power supply 5 and 3.3 V are obtained via switching buck regulators providing up to 3 A. The 5 V is then forwarded to the raspberry via a USB-C connector. The Feather connectors provide access to all 21 GPIO pins; • Up to 6 differential pressure sensors, model 5525DSO-DB001DS. The sensors are connected via a I2C multiplexer; • Two voltage regulators for the valves: since the operation voltage of the solenoid changed few times during the project, a proper regulation was required. Therefore a 3 A step-down buck regulator can provide any voltage below in the range 3-11 V, while a step-up boost regulator can provide up to 24 V 3 A; • Two ON/OFF opto-coupled valve control; • Two analog controlled valves. The circuit allows both PWM modulation and current control:
• Two button input and high-power two alarm outputs (for buzzer and LED).
• Four I2C ports (2 of which can operated with 5 V equipment) all connected via a multiplexer, 1 SPI port and 1 UART port, 3 analog ports. Up to two I2C are reserved to the gas flow meters (Sensirion SFM3019), and other is reserved to the oxymeter. The oxygen sensor has not yet been identified yet: however several readout options are available.
The control firmware runs on the micro-controller: the firmware implements a state machine whose transitions are defined based on the sensor inputs and on the commands received from the GUI (via the Raspberry unit). The state machine in turn controls the phase of the respiratory Reported values may be unrealistic cycle (inhalation, pause, exhalation) by operating on the valves. The PV-1 valve is controlled via a double feedback system: the first PID loop ensures that the PS-3 sensor always matches the set value (Pin). The second feedback programs the Pin value to maintain the breathing cycle at the required pressure measured at the mask level (sensor PS-2). The firmware also continuously monitors the gas flow meter (PS-1) to decide when to interrupt the inspiration phase. Both manual and the assisted operation modes are available. The Raspberry 4 micro-computer is connected to the micro-controller unit via a micro-usb cable: this allow to reprogram the micro-controller easily via the serial line. The Raspberry unit communicates with the micro-controller with the serial line during normal operations, accessing the sensor parameters and configuring the set-points. A 7 touchscreen is connected to the Raspberry: a proper GUI is under development to interact with the user.
Alarms are issued directly by the ESP32 firmware or by the GUI. The microcontroller unit monitors the behavior of the connected sensors and will generate alarms when a condition happens such that the normal operation cannot be maintained. The possible alarms include:
• Sensor not working properly • Pressure level cannot be reached or goes in overflow • Exhaust line reaches differential pressure equal to zero (PEEP valve not working.) • power cut: the system is running in battery mode
The above alarms will be notified by a high luminosity LED and by a buzzer. A push button is available to silence the alarm. The corresponding alarm code will be displayed in the LCD screen. Furthermore the GUI will monitor the following parameters and will generate alarms in case the parameters will exceed the selected boundaries: • Inspiratory pressure: the pressure applied during the inspiration phase to the patient • Vtidal (tidal volume): Volume of gas provided to the patient in a respiration cycle • MVe (respiratory minute volume): Volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person's lungs per minute • FiO2 (fraction of inspired oxygen): Concentration of oxygen in the gas mixture that the patient inhales
The MVM GUI is a Python3 software, written using the PyQt5 toolkit, that allows steering and monitoring the MVM equipment. Fig. 4 shows two screenshots of it.
Project design principles: • Ease of use and interface simplicity to make it immediate to understand and to give a familiar feeling by the user; • Use of entirely open-source software to let the project be easily spreadable and adaptable to different possible needs of users in other countries and to different approach to medical procedures;
• Agile development techniques to speed up all phases of development (design, code, documentation, testing) and allow contributions from people having different skills; • Portability by default to support possible hardware platform and software environment (Operating System, OS) changes with minimal effort; • Support distributed input devices such as touchscreen, mouse and keyboard.
Involved technologies: • Target computing platform: Raspberry Pi 4 (any memory size), chosen as a trade-off between its computing power over power consumption ratio and its wide availability on the market; • Target operating: Raspbian version 2020-02-13; • Target programming language: Python 3.5; • Target PyQt5: version 5.11.3.
The MVM GUI runs smoothly on the target hardware and software environment.
Tests were performed with a breathing simulator, ALS 5000 of IngMar Medical [6] . In the MVM the airway pressure curve take some time to reach the saturation value due to impedance of the tube connecting the pressure sensors of the MVM to the simulator. The MVM precision spirometer is unidirectional and is therefore able only to measure the inspiratory flow. The measurement of the expiratory flow is measured with a lesser precision by the Venturi spirometer SP-2 and not shown in Fig. 5 .
As an example, let's consider the top two plots of Fig. 5 . On the right-hand side, the Servo 900C ventilator maintains a steady, but convoluted with a clear oscillatory pattern, flow. Both airway and lung pressures experience a linear increase in time.
On the left-hand side, the MVM, operating in a pressure-controlled ventilation (PCV) mode, aims at maintaining a constant pressure, but while simultaneously implementing two crucial precautions. First, the flow is maximised at the beginning of the inspiratory cycle: this is the most appropriate procedure for COVID-19 patients as it allows the immediate reopening of the alveoli, and is strongly recommended by the doctors and nurses in the COVID-19 wards of Lombardy, rather than the constant flow procedure. Second, following the immediate increase in airway and lung pressure in coincidence with the start of the inspiratory cycle, the pressure is raised gently for the last fifteenth percentile of the full pressure differential (pressure differential is the difference between set inspiratory pressure and PEEP) through the end of the inspiratory cycle. The reader will also notice that, during the inspiratory cycle, through the last fifteenth percentile of the full pressure differential, the pressure rises smoothly and without any sort of oscillatory pattern through.
These superior characteristics of the MVM pressure transient during the inspiratory cycle are crucial to avoid barotrauma and to minimise long term fatigue of muscles and alveoli induced by forced mechanical ventilation. This special MVM pressure transient is achieved thanks to its ability to finely tune the airway and lung pressure by controlling the input pressure through a complex yet fail-safe feedback control loop.
In essence, by listening to the precious advice of medical doctors and nurses in the COVID-19 wards of Lombardy, we implemented in the MVM what we believe to be the safest and most beneficial pressure transient for treatment of COVID-19 patients. Our test setup is equivalent to that described in figure 201 .102 of the same documents. The measurement performed with the MVM are those reported in table 201.105. We performed the measurements over 30 cycles in accordance to the prescription of the reference standard [4] The MVM unit does not include an internal oxygen control unit. Instead, the FiO2 level can be independently set by using gas blender GB-1, external to the unit, controlled either manually or directly by the MVM unit. For this reason, the FiO2 level is not varied during the tests as control of its value pertains to the performance of GB-1 as opposed to the performance of the MVM. Therefore, for this round of measurements the output value of the oxygen sensors OS-1 is not reported as the tests are done with air and the measured concentration of oxygen is constant at 21 %.
Tidal volume is displayed both measured by the simulator and for the MVM. The MVM measures the tidal volume by integration of the inspiratory and expiratory flows. For simplicity of rendering of the data, the direct measurement of the expiratory flow is not shown. To best support the understanding of the performance of the MVM, data collected with the MVM's own sensors are shown along with the data collected with the ALS 5000 breathing simulator. Pressure and PEEP are measured according to the requests in the last 50 ms respectively of the inspiratory and expiratory phase. A humidifier was not included in this test as its presence is not expected to affect qualification of the MVM performance.
The recorded waveforms are presented in Fig. 6 to 8. (e) TV=300, C=20, R=20, p=20, r=20, PEEP=5 (b) TV=500, C=20, R=5, p=30, r=20, PEEP=5 (g) TV=50, C=3, R=20, p=25, r=30, PEEP=10 Measured quantities as extracted from the measured waveforms vs set quantities are reported in Fig. 9 . The average values and the maximum errors are calculated by separating them in groups of tidal volumes (V tidal ) as requested in [4] . Linear fits were performed to extract the accuracies on the various parameters. The results show that
• the measured P plateau accuracy is ±(0.3 +(0.3% of the value))cm H 2 O • the measured tidal volume accuracy is ±(27.7 +(4.2% of the value))ml • the measured PEEP accuracy ±(0.1 +(0.3% of the value))cm H 2 O It should be noted that the accuracies extracted from comparison with the simulator are overestimates since they neglect the accuracy of the simulator devices which has certainly a finite value.
Waveforms with pressure-supported ventilation mode are shown in Fig. 10 FIG. 10: Waveforms with pressure support ventilation mode. The green line represents the muscle pressure as exerted by the breathing simulator.
The MVM will also integrate advanced features designed by anaesthesiologists participating to the project who happen to work in the medical wards in Lombardy, the region most severely hit by the COVID-19 epidemics. MVM will enable at the touch of a button the measurements of two vital parameters crucial for the determination of the best course of care for COVID-19 patients.
The first parameter is the Plateau Pressure (PP), the pressure reached inside the alveoli at the end of the inspiratory cycle. PP may be lower than the Set Inspiratory Pressure (SIP) provided by the ventilator. The difference between PP and the PEEP is called Driving Pressure, DP (DP = PP PEEP). The PP is measured through a forced hold at the end of inspiration, activated through the Inspiratory Hold Maneuver (IHM) button through the touch-screen of the GUI. When the IHM is pressed, the MVM will wait for the end of the next inspiration phase, and if the IHM is still pressed, at that moment will hold both the inspiratory and expiratory valves closed till the IHM button is released. An emergency reset button allows to override internal controls and to resume the regular breathing cycle.
The PP is the pressure reached in the airway at the end of the IHM. At the end of IHM, the screen will show a freeze frame of the cycle and will show the number of the measured PP.
The DP should be kept below 14 cm H 2 O, as a pressure value too high may results in long term damage to the lungs. Measurement of PP and DP should be performed early in the start of care of sedated patients, to fine tune the best care regimen, which typically start by setting a Tidal Volume (TV) of 6-8 ml/kg/IBW (Ideal Body Weight). The DP permits to fine tune the TV delivered to the patient, taking note of the portion of the lung under viral attack and permitting doctors to determine the best adjustment of the TV delivered to the patients.
The second parameter is the AutoPEEP, which may be zero for most patients or significantly different from zero for patients that have obstructions in the exhalation channel, as possibly generated by secretions. In this case, the small flow during exhalation may result in an incomplete drain of the alveoli during the expiration phase. An expiratory hold maneuver permits to momentarily close both inspiratory and expiratory valve at the end of the expiration phase, and measure the residual pressure in the alveoli above he PEEP level, the residual value being PEEP + AutoPEEP. This measurement is once again performed by pushing a single button. At the press of the button, the expiratory hold will be performed at the end of the following expiratory phase, and the hold action will be completed at the release of the button. At this instant, the screen will show a freeze frame of the cycle and will show the number of the measured AutoPEEP.
The true value of DP is (PP PEEP AutoPEEP). Measurement of both PP and AutoPEEP is crucial for the determination of DP.
MVM will also carry out at the touch of a button the lung recruitment procedure, i.e., the Recruitment Maneuver (RM), i.e., the emergency procedure required immediately after the end of the intubation. RM consists in the prolonged lung inflation at increased inspiratory set pressure, as necessary to reactivate the alveoli immediately after intubation. Before the start of procedure, the doctor must be able to set the Pressure for the Recruitment Maneuver (PRM, from 25 to 50 cm H 2 O, settable with a ±1 cm pace). The doctor will also have the choice of setting a fixed time for the RM (Time for Recruitment Maneuver, TRM, settable from 5 to 40 seconds, pace of ±1 sec), with a reset button that can stop the procedure and return the breathing cycle to normal, or will have the choice to keep the RM button pressed and terminate the procedure on release of the button.
9. LICENSE AGREEMENT ©2020: this paper describes Open Hardware and is licensed under the CERN-OHL-S v2. You may redistribute and modify this documentation and make products using it under the terms of the CERN-OHL-S v2 [7] . This documentation is distributed without any express or implied warranty, including of merchantability, satisfactory quality or fitness for a particular purpose. Please see CERN-OHL-S v2 [7] for applicable conditions.