Method for detecting presence of liquid in a diaphragm sprayer

Abstract

The invention provides a diaphragm nebulizer having an aerosol generator comprising a vibrator and a membrane, a reservoir for a liquid to be aerosolized, a channel and an optical sensor for detecting the presence of aerosol in the channel. The device determines from the output signal from the optical sensor whether aerosol is present in the channel in order to detect when the reservoir is empty and stops the vibration of the membrane if it is determined that no aerosol is present. A method of operating the device is also provided.

Description

Technical Field

[0001] This invention relates to a vibrating membrane atomizer, and more particularly to a method for detecting the presence of liquid in contact with the membrane. Background Technology

[0002] Aerosols used in medical inhalation therapy typically contain active ingredients dissolved or suspended in an aerosolizable liquid (usually water). For them to reach deep into the lungs, a uniform distribution of aerosol droplets with a droplet size of approximately 5 micrometers is required.

[0003] A vibrating membrane nebulizer is a device that generates this aerosol. These devices include a vibrator, such as a piezoelectric element, which is excited at ultrasonic frequencies to cause a membrane (sometimes called a mesh or orifice plate) to vibrate. The membrane has numerous pores, typically ranging in diameter from 1 to 10 micrometers. A reservoir supplies the membrane with a liquid pharmaceutical formulation. The vibration of the membrane causes liquid aerosol droplets to form and disperse through the pores.

[0004] Continuing to operate a vibrating membrane nebulizer after the reservoir has been emptied can cause the membrane to rupture or break. Therefore, it is important to be able to reliably detect the presence of liquid in the reservoir and / or in contact with the membrane. When the nebulizer detects that the liquid has been used up, it can automatically shut off the vibrator and / or indicate to the patient that the treatment is over.

[0005] One approach is to simply measure the presence or quantity of liquid in the reservoir. For example, US2006 / 0255174 discloses a sprayer in which the amount of liquid in the reservoir is sensed by a piezoelectric sensor, optical sensor, conductivity sensor, or strain gauge. However, this requires contact between the sensor and the liquid, which can present problems.

[0006] An alternative approach leverages the fact that the vibrational characteristics of a membrane (e.g., resonant frequency, power dissipation, etc.) are often significantly different when the membrane is in contact with a liquid compared to when it is dry. For example, US2006 / 0102172 discloses a sprayer that determines the presence of liquid by comparing detected values ​​of electrical parameters (e.g., current flowing to a piezoelectric element) with stored values. WO2015 / 091356 discloses an aerosol delivery device having a membrane, a vibrator, and a fluid reservoir. This device operates the vibrator at multiple different vibration frequencies, and a sensor measures the electrical parameters of the vibrator at each frequency. The device detects the presence of fluid in contact with the membrane and / or in the fluid reservoir based on the frequency dependence of the electrical parameter values. However, differences between different membranes and / or variations in the membrane over its lifetime can cause these methods to fail to detect that the membrane is dry. If the sprayer does not correctly determine the presence of liquid in the reservoir, it can continue vibrating the membrane after the liquid has been depleted, or it can shut off the vibrator while the liquid is still present.

[0007] Therefore, improved methods are still needed to reliably detect the presence of liquid in a reservoir and / or in contact with a membrane. Summary of the Invention

[0008] The inventors have discovered an improved method for determining when a liquid to be aerosolized is depleted. In particular, they have recognized that light scattering can be used to reliably detect the absence of liquid in contact with a membrane by detecting the absence of aerosol within the nebulizer. Therefore, in a first aspect, the present invention provides an inhalation device comprising:

[0009] • A channel with an air inlet opening and an aerosol outlet opening.

[0010] • An aerosol generator including a vibrator and a membrane.

[0011] • A reservoir for aerosolizing the liquid that is fluidly connected to the membrane.

[0012] • An optical sensor used to detect the presence of aerosols within the channel.

[0013] • A controller configured to (i) provide a driver signal to operate the vibrator, causing the membrane to vibrate and generate aerosols in the channel; (ii) receive an output signal from a sensor; (iii) determine, based on the output signal, whether aerosols are present in the channel; and (iv) if it is determined that no aerosols are present, stop operating the vibrator.

[0014] The aerosol generator may include a support member, a vibrator, and / or a membrane mounted on the support member. The vibrator may be a ring-shaped piezoelectric element. The support member may be a transducer in the form of a hollow tubular portion having flanges at or near a first end to which the piezoelectric element is attached and at or near a second end to which the membrane is mounted. Alternatively, the support member may include a substantially flat toroidal surface or a disk; in particular, the membrane and / or piezoelectric element may be mounted on opposite sides of the support member.

[0015] Optical sensors can operate in the infrared region of the electromagnetic spectrum. An optical sensor may include an emitter and a detector located on opposite sides of the channel, such that the detector detects light from the emitter that passes through the aerosol across the channel.

[0016] The controller can be configured to (i) modulate the amplitude of the driver signal at a frequency from 1 to 100 Hz, (ii) demodulate the output signal at the same frequency, and (iii) determine the presence of aerosols in the channel based on the demodulated output signal. The modulation frequency can range from 2 to 70 Hz, 3 to 55 Hz, or 5 to 40 Hz, for example, approximately 10, 20, or 30 Hz. The controller can be configured to modulate the vibration amplitude of the membrane using a sine wave, sawtooth wave, or square wave.

[0017] The controller can be configured to (i) periodically perform scans to determine the resonant frequency of the aerosol generator and / or membrane, during which the membrane generates aerosols at a decreasing rate; (ii) demodulate the output signal at the scan frequency, such as 2 Hz, which corresponds to the period between scans, such as 0.5 s; and (iii) determine the presence of aerosols in the channel based on the demodulated output signal.

[0018] The controller can be configured to determine the phase difference between the driver signal and the output signal, thereby determining the speed of the aerosol as it passes through the optical sensor.

[0019] The inhalation device may further include a variable flow limiter that restricts the flow rate of air and aerosol to a maximum flow rate of approximately 20 liters / minute or 18 liters / minute, for example, approximately 15 liters / minute. The inhalation device may further include a pressure sensor for measuring pressure in the channel, and a signaling device capable of emitting light of varying intensities, and the controller may be configured to (i) receive a signal representing the measured pressure, and (ii) cause the signaling device to emit light of lower intensities as the measured pressure deviates further from the target pressure.

[0020] The channel can be less than 5 cm between the membrane and the optical sensor. 3 The internal volume, for example, ranges from 0.5 to 3 cm. 3 Or from 1 to 2 cm 3 For example, approximately 1.5cm 3 The channel may be a component that can be removed from the rest of the device, or a part of that component, or include that component.

[0021] In a second aspect, the present invention provides a method of operating an inhalation device according to a first aspect of the present invention, the method comprising:

[0022] a) Provide a driver signal to operate the vibrator, causing the membrane to vibrate and generate aerosols in the channel;

[0023] b) Receive the output signal from the optical sensor;

[0024] c) Determine the presence of aerosols in the channel based on the output signal; and

[0025] d) If it is determined in step c) that there is no aerosol, then stop operating the vibrator.

[0026] The method may further include: in step a), modulating the amplitude of the driver signal at a frequency of 1 to 100 Hz; in step b), demodulating the output signal at the same frequency; and in step c), determining the presence of aerosols in the channel based on the demodulated output signal. The modulation frequency can be from 2 to 60 Hz, 3 to 50 Hz, or 5 to 40 Hz, for example, approximately 10, 20, or 30 Hz. The controller can be configured to modulate the vibration amplitude of the membrane with a sine wave, sawtooth wave, or square wave.

[0027] The method may further include: in step a), performing a periodic scan to determine the resonant frequency of the aerosol generator and / or membrane; in step b), demodulating the output signal at the scan frequency; and in step c), determining whether aerosol is present in the channel based on the demodulated output signal.

[0028] The method may also include determining the phase difference between the driver signal and the output signal if an aerosol is present in the channel, thereby determining the velocity of the aerosol as it passes through the optical sensor. Attached Figure Description

[0029] Figure 1 An enlarged view of the vibrating membrane sprayer is shown.

[0030] Figure 2 It shows the use of Figure 1 The aerosol generator of the sprayer.

[0031] Figure 3A and 3B This is a perspective view of either side of the base unit and nozzle component of the sprayer according to the present invention.

[0032] Figure 4 Figure 3 shows a cross-sectional view of the sprayer in the optical sensor region.

[0033] Figure 5 The main components and relevant areas of the channel of the optical sensor are shown.

[0034] Figure 6 shows the presence of aerosols ( Figure 6A ) and non-existent ( Figure 6B The working principle of the optical aerosol detection system.

[0035] Figure 7 The diagram shows the analog output signal from the detector as a function of time when the reservoir becomes empty.

[0036] Figure 8 This explains the principle of amplitude modulation of the driver signal.

[0037] Figure 9A The diagram illustrates the analog output signal from the detector as a function of time when the memory becomes empty, utilizing a modulated driver signal. Figure 9B Showing the understanding after adjustment Figure 9A The output signal.

[0038] Figure 10 shows a graph similar to Figure 9, but with simulated external noise added to the output signal.

[0039] Figure 11 shows the results before, during, and after a frequency scan, without (… Figure 11A ) and there are ( Figure 11B In the case of additional modulation of the driver signal, the output signal from the detector is a function of time.

[0040] Figure 12 The modulation of the driver signal and the resulting output signal from the detector are shown, along with the phase difference between them. Detailed Implementation

[0041] Aerosol nebulizers that detect the presence of aerosols by measuring the amount of light (or other electromagnetic radiation) scattered by droplets are known. For example, US2006 / 102178 discloses a nebulizer having a nozzle with a translucent wall, a light emitter, and two light receivers, one for transmitting light and the other for scattering light. With proper calibration, the aerosol density in the nozzle can be determined from the output signal of the receivers. The emitter can operate intermittently. The influence of ambient light can be reduced by subtracting the signal obtained when the emitter is off from the signal obtained when the emitter is on. US2006 / 102178 discloses that this method can be used in jet aerosolizers or vibrating membrane aerosolizers. It does not address the issue of determining when the membrane dries.

[0042] WO2013 / 042002 discloses a nebulizer that uses a light source and an optical sensor to determine the aerosol density by measuring the amount of scattered light. The nebulizer also determines the aerosol velocity by measuring the time delay between the aerosol generator turning on and the optical sensor detecting the aerosol. Since the distance from the aerosol generator to the optical sensor is known, the velocity can be calculated. The aerosol generator can be turned on and off in a series of short pulses to adjust the average power, thereby regulating the output rate. The nebulizer can be a jet nebulizer, a pMDI (pumped metered inhaler), or a vibrating membrane nebulizer. WO2013 / 042002 does not address the issue of determining when the membrane dries.

[0043] WO2017 / 192778 discloses a nebulizer with an optical aerosol sensor that measures and detects the presence of droplets within the inhalation channel to confirm that a dose has been delivered. Light emitted from an LED light source is scattered or absorbed by the droplets and detected by a photodetector. Multiple light sources and multiple detectors can be used to determine the shape of the aerosol plume, including its cross-section and length, to estimate the spray mass. However, the nebulizer does not use the detected light signal to determine when the membrane dries. Instead, it monitors changes in the membrane's resonant frequency.

[0044] Previously, it was not recognized that this type of optical sensor could be used to reliably detect the absence of liquid in contact with a membrane by detecting the absence of aerosols within the inhalation channel. In the context of this invention, the term "optical sensor" refers to a sensor that detects light, such as visible or infrared light. Similarly, "optical signal" and the like include both visible and infrared light.

[0045] Figure 1 An enlarged view of the vibrating membrane aerosol sprayer device described in detail in EP2724741 and WO2013 / 098334 is shown. The device comprises three parts: a base unit, a nozzle assembly, and an aerosol head. The base unit 100 has one or more air inlet openings, an air outlet opening 102, a recess 103 for receiving the nozzle assembly 200, and one or more keying members 104. The nozzle assembly 200 has an air inlet opening 201 for attachment to the air outlet 102 of the base unit 100, a lateral opening 202 for receiving an aerosol generator 301, and an aerosol outlet opening 203. A channel 205 extends from the air inlet opening 201 to the aerosol outlet opening. The nozzle 200 can be inserted into the recess 103 of the base unit 100. The aerosol head 300 includes an aerosol generator 301, a filling chamber 302 for a liquid pharmaceutical preparation to be aerosolized (which is in fluid contact with the upper end of the aerosol generator 301), and one or more keying members 303 complementary to the keying member 104 of the base unit 100. A cap 304 closes the filling chamber 302 and prevents contamination or spillage of the liquid during use.

[0046] The base unit 100, nozzle 200, and aerosol head 300 are detachably connected to each other. The device is assembled by inserting the nozzle 200 into a recess 103 in the base unit 100, placing the aerosol head 300 on the nozzle 200, and engaging the keying member 303 of the aerosol head 300 with the complementary member 104 of the base unit 100 by gently applying pressure to the aerosol head and the base unit. The aerosol generator 301 is positioned in the aerosol head 300 such that, when the keying member is engaged, the aerosol generator 301 is inserted into a lateral opening 202 in the nozzle 200. This creates an airtight connection between the aerosol generator 301 and the lateral opening 202 in the nozzle, and between the air outlet opening 102 of the base unit 100 and the air inlet opening 201 of the nozzle 200. The base unit 100, nozzle 200, and aerosol head 300 can be separated by reversing these steps.

[0047] The base unit 100 may have one or more indentations 106 located at or near the recess 103, and the nozzle 200 may have one or more positioning members 204. The indentations of the base unit are complementary to the positioning members 204 of the nozzle 200 (i.e., shaped to receive the positioning members 204). In this case, the indentation is a depression (e.g., a recess, pit, cavity, gap, notch, etc.), its "negative" shape complementary to the "positive" shape of the positioning member (which may be a flange, protrusion, nose, projection, etc.). These indentations and positioning members together serve to correctly position the nozzle within the base unit. The indentations 106 and positioning members 204 may be asymmetrical to ensure that the nozzle 200 can only be inserted into the indentation 106 of the base unit 100 in a specific manner. This ensures that the device is assembled in such a way that the nozzle 200 and the base unit 100 are correctly positioned and oriented relative to each other. The base unit contains a controller, such as a printed circuit board (PCB) that controls the operation of the sprayer.

[0048] Figure 2 An aerosol generator is shown (described in detail in WO2008 / 058941). It includes a vibrator, namely a piezoelectric element 308, a transducer body 306, and a diaphragm 309. The transducer body 306 is made of, for example, stainless steel, titanium, or aluminum, and encloses a cavity 307 containing the liquid to be aerosolized. The interior of the filling chamber 302 is conical, allowing the liquid to flow under gravity into the upstream end 306a of the transducer body 306 and downward into the cavity 307. The filling chamber 302 and the cavity 307 together form a reservoir for the liquid to be aerosolized.

[0049] Membrane 309 is located at the downstream end 306b of transducer body 306. Pores in the membrane can be formed by electroforming or laser drilling, with openings typically ranging from about 1 μm to about 10 μm. When the membrane is not vibrating, pressure balance, the shape of the pores, and the properties of the material used for the membrane prevent liquid from seeping through. However, membrane vibration causes the formation and discharge of aerosol droplets through the pores. The membrane can be made of plastic, silicon, ceramic, or more preferably metal, and can be attached to or within the downstream end 306b of aerosol generator 301 by various methods, such as adhesive bonding, brazing, crimping, or laser welding. Optionally, the membrane at least partially forms a dome in its central region, which causes the ejection and dispersion of newly generated aerosol droplets and thus reduces the risk of droplet coalescence.

[0050] The piezoelectric element 308 is preferably a ring-shaped single-layer or multi-layer ceramic that vibrates the transducer body 306 in a longitudinal mode. A drive circuit generates a driver signal that excites the piezoelectric element, thus causing the membrane 309 to vibrate, typically at a frequency in the range of 50-200 kHz. The frequency of the driver signal can be selected as a fixed offset relative to the resonant frequency of the aerosol generator, for example, 500 Hz below it. The excitation of the piezoelectric element causes a small longitudinal displacement and / or deformation in a direction parallel to the axis of symmetry of the transducer body 306. The transducer body 306 has a region with a relatively large wall thickness near the piezoelectric element 308, which serves as a stress concentration region 306c, and a downstream region with a relatively small wall thickness 306d, which serves as a deformation amplification region. In this configuration, the vibration or deformation of the transducer body 306 caused by the piezoelectric element 308 is amplified. Preferably, the piezoelectric element 308 is located at or near the stress concentration region 306c. The inner diameter of the transducer body 306 in the deformation amplification region 306d can be the same as the inner diameter in the stress concentration region 306c, so that the difference in wall thickness corresponds to different outer diameters. Alternatively, the outer diameter of the transducer body 306 can be constant, while the inner diameter differs at the locations of the two regions.

[0051] When the nebulizer is operated, an aerosol is generated by membrane 309 and released into channel 205, where it mixes with incoming air from air inlet opening 201 (via air inlet opening and air outlet opening 102 of the base unit). The air and aerosol then flow along channel 205 and exit through aerosol outlet opening 203 of the mouthpiece, entering the patient's airway. Thus, channel 205 is an inhalation channel that provides a path for air and aerosol to reach the patient.

[0052] Figure 3A and 3B This is a perspective view of either side of the base unit 100 and the nozzle component 200 of the sprayer according to the present invention. The sprayer is essentially... Figure 1The same as shown, except that the base unit has windows 401, 402 on either side of the recess 103 at the narrowest part of the channel 205, downstream of the aerosol generator. Windows 401, 402 can be shaped as lenses.

[0053] Figure 4 This shows a cross-sectional view of this part of the sprayer looking downstream, towards the aerosol outlet orifice of the nozzle. Figure 5 This is a simplified view showing the key components of the optical sensor. For illustration, the base unit and other parts of the nozzle, except for a portion of channel 205, have been removed. A U-shaped bracket 403 forms the base and sides of the recess 103 in this area. Windows 401 and 402 are mounted in the bracket 403. An emitter 404, such as an infrared (IR) light-emitting diode, is located behind one window 401, while a detector 405, such as a photodiode, is located behind the other window 402. The emitter and detector are mounted on PCBs 406 and 407, respectively. The combination of these components forms the optical sensor. They can be standard electronic components and are selected such that they operate within the same IR wavelength range, such as 940 nm. The windows are made of a material transparent to infrared radiation in this range, such as polycarbonate. The windows can also be made of a material that acts as an IR filter, which is transparent to IR radiation but does not transmit other wavelengths, such as visible light. Channel 205 is also made of a material transparent to infrared radiation, such as polypropylene.

[0054] Alternatively, transmitters and detectors operating in different parts of the electromagnetic spectrum (e.g., visible light) can be used. However, there are many advantages to using infrared light. First, it is strongly absorbed by aerosols, and second, because it is invisible, it does not distract the patient. This is particularly important if, as described in WO2013 / 098334, the nebulizer guides the patient by illuminating the mouthpiece with light whose intensity increases as the inhalation rate approaches its optimal rate.

[0055] Figure 6 is a schematic diagram illustrating the basic operation of the optical aerosol detection system. The output signal from the detector depends on the aerosol density. When aerosol 10 is generated by aerosol generator 301, it is inhaled by the patient along channel 205 into the region between emitter 404 and detector 405 located on the opposite side of the channel. Radiation 20 from emitter 404 is scattered by aerosol 10, so only a portion is received by detector 405, such as... Figure 6A As shown. When the liquid in the reservoir is depleted, no more aerosols are generated, therefore the amount of radiation received by the detector increases ( Figure 6BAlternatively, the detector can be positioned to receive scattered light instead of transmitted light. For example, it could be close to the transmitter to receive light scattered at approximately 180°, or at the top or bottom of the channel to receive light scattered at approximately 90°.

[0056] Figure 7 The diagram shows the analog output signal from the detector (expressed in dimensionless units representing light intensity) as a function of time when the reservoir is emptied. At t=0, a small amount of liquid remains in the reservoir, indicating that the treatment is nearing completion. At this time, aerosols are present in the channel, causing light to scatter from the detector, resulting in a low signal. As the reservoir empties, the amount of aerosols in the channel decreases, and the detector signal increases. The signal fluctuates due to inherent noise from the electronic components (this is evident, for example, between approximately 20 and 40 milliseconds); however, external noise sources (such as fluctuations in ambient light) are not included in this analog data. At approximately t=75 milliseconds, the signal begins to plateau because there is very little aerosol in the channel. After approximately t=150 milliseconds, the detector signal reaches its maximum value; at this point, there is no aerosol in the channel. The threshold (here, 2710) is preset. When the detector signal exceeds the threshold of 30, the controller determines that the reservoir is empty.

[0057] In practice, the detector picks up ambient background IR radiation, such as IR radiation from sunlight or indoor lighting, which adds noise to the signal. Other external noise sources exist, such as aerosol droplets deposited inside the channel near the transmitter and / or detector, or minute changes in the nozzle's orientation relative to the base unit when the patient holds the nozzle. When aerosols are still present in the channel, noise can cause the detector signal to reach a threshold level, thus causing the aerosol generator to shut down prematurely. Furthermore, small differences may exist between different nebulizers; for example, there may be small differences in the orientation of the transmitter and detector when they are soldered to their PCBs; or the optical properties of the channel (especially the window) may change slightly over time, for example, due to repeated heating of the nebulizer between treatments for sterilization. Because the threshold used to determine the presence of aerosols in the channel is preset, it cannot account for these effects. This can also lead to incorrect determination of when the reservoir becomes empty.

[0058] The inventors have determined a method for eliminating or at least substantially reducing these effects, resulting in an increased signal-to-noise ratio and improved sensitivity and reliability of the empty detection method. This is achieved by modulating the amplitude of the driver signal 40, such as... Figure 8As illustrated schematically, modulation 45 is shown as a sine wave, but can be any kind of periodic signal, such as a sawtooth wave or a square wave. The amplitude of the driver signal 40 can be modulated at a relatively low frequency, suitably in the range of 1 to 100 Hz, for example, about 2 to 70 Hz or 3 to 55 Hz, or 5 to 40 Hz, for example, about 10, 20, or 30 Hz. However, the power supply voltage frequency (typically 50 Hz or 60 Hz) should not be used to avoid introducing noise caused by light intensity fluctuations of the power-powered light source at the power supply frequency. Although for illustrative purposes, Figure 8 The driver signal 40 is shown to be approximately 15 times the modulation frequency 45, but in reality, the driver signal frequency is usually more like 10,000 times the modulation frequency.

[0059] Modulation of the driver signal produces a corresponding modulation of the aerosol output rate from the membrane. This, in turn, modulates the aerosol density in the channel, and thus modulates the output signal from the detector. This modulation adds information to the driver signal and is transmitted from the detector to the output signal. This additional information is unaffected by external factors such as ambient infrared radiation, droplet deposition within the channel, production variations, and changes in the optical properties of the mixing channel during the atomizer's lifetime.

[0060] Modulation of the driver signal amplitude does not need to cause a decrease in the aerosol output rate because the root mean square amplitude of the driver signal can be the same as when it is not modulated. In other words, when the amplitude decreases during modulation, the lower aerosol output is balanced by the higher aerosol output when the amplitude increases during modulation.

[0061] Figure 9A It shows the relationship with Figure 7 A similar graph, but the driver signal is modulated at a frequency of 75 Hz. The modulation in the driver signal produces a corresponding modulation in the detector signal. At approximately t = 150 milliseconds, the detector signal reaches a plateau, at which point there is very little aerosol in the channel. After t = 225 milliseconds, the modulation disappears because there is no aerosol residue, i.e., the reservoir is empty. Figure 7 Similarly, by comparing the detector signal with a threshold of 30, it is possible to determine when the reservoir becomes empty.

[0062] The output signal from the detector can be demodulated, for example, through digital signal processing, or through an analog filter (e.g., using electronic components on the detector's PCB). Figure 9B Showing from Figure 9AThe demodulated signal. The y-axis is a dimensionless measure of how closely the output signal corresponds to the modulation as a function of time. When the aerosol is present at a relatively high density, i.e., up to about 150 milliseconds, the demodulated signal is quite high. Then, as the aerosol density decreases, the demodulated signal decreases. After about 225 milliseconds, there is no aerosol, so there is no more modulation in the output signal. At this point, the demodulated signal reaches a constant minimum value. The threshold 30 in the demodulated signal can also be used to determine that the reservoir is empty; in this case, 550 is a suitable value.

[0063] As mentioned above, the simulation data in Figure 9 does not include external influences. By using a threshold, it is possible to directly obtain the results from... Figure 9A The method aims to determine when a reservoir becomes empty. However, in reality, many external noise sources can significantly reduce the signal-to-noise ratio, making this method of determining when a reservoir becomes empty quite difficult or unreliable.

[0064] Figure 10A Similar to Figure 9A However, additional factors include simulated external noise, such as fluctuations in background light intensity (which cause fluctuations in the detector signal) and the effects of aerosol droplet deposition within the channel. As more droplets deposit during treatment, the amount of light scattered by the deposited droplets gradually increases, thus reducing transmitted light. Subsequently, as the deposited droplets coalesce into larger droplets, they cause less scattering, and they may also move downwards to the bottom of the channel under gravity, causing them to no longer be in the path of transmitted light, which could lead to an increase. Therefore, compared with... Figure 9A Different, from Figure 10A It is not obvious whether the storage is empty.

[0065] Figure 10B Showing from Figure 10A The demodulated signal. Since the demodulated signal is unaffected by external noise other than the modulation frequency, this signal is... Figure 9B The signals are similar. The demodulated signal has an improved signal-to-noise ratio, so the point at which the reservoir becomes empty can be determined by applying a threshold value of 550 to 30. Figure 9B As shown. Therefore, modulating the driver signal results in more accurate information about the amount of infrared radiation scattered by the aerosol. This not only increases the sensitivity and reliability of the air detection method, but also facilitates the determination of aerosol density.

[0066] In some vibrating mesh nebulizers, the resonant frequency of the aerosol generator may change during treatment, for example, as the amount of fluid in the reservoir decreases. The frequency of the driver signal can be selected based on or dependent on the resonant frequency of the aerosol generator. Therefore, it may be necessary to measure the resonant frequency at regular intervals throughout the operation of the aerosol generator, such as every 0.5 seconds. Typically, to determine the resonant frequency, a scan is performed by vibrating the diaphragm at a series of different frequencies spanning the range in which resonance occurs. However, because most of these frequencies are not optimal driving frequencies, the aerosol output rate inevitably decreases during the scan, which typically takes about 50 milliseconds. Figure 11A The detector signal is shown over a 0.5-second time interval. The scan occurs from approximately t = 100 to 150 milliseconds, causing the aerosol output rate to drop almost to zero. During this period, the detector signal is significantly higher. Therefore, the scan process used to determine the resonant frequency inherently applies square-wave modulation to the driver signal, in this case, a normal output of 450 milliseconds followed by a low aerosol output of 50 milliseconds. Performing one scan every 0.5 seconds corresponds to a scan frequency of 2 Hz.

[0067] Figure 11B It shows the relationship with Figure 11A A similar graph shows the driver signal also modulated at 37 Hz. The modulation is invisible in the detector signal, which is approximately 100 to 150 milliseconds, because the aerosol output rate is essentially zero during the scan.

[0068] The amplitude modulation described above can be replaced by the inherent modulation from the scan, or in addition to, for example... Figure 11B Beyond the amplitude modulation shown. Of course, the frequency and waveform are determined by the scanning parameters. In particular, the scanning frequency needs to be quite low so as not to reduce the overall aerosol output rate. Therefore, scan modulation has a limited sampling rate, which reduces the information that can be obtained.

[0069] Modulation of the actuator signal can also be used to measure aerosol velocity and volumetric flow rate. By measuring the phase difference between the actuator signal and the detector output signal, the time required for the aerosol to move from the membrane to the optical sensor can be determined. This phase difference can be obtained by cross-correlating the actuator and detector signals. The aerosol velocity is then obtained from the calculated time and the known distance between the membrane and the optical sensor. The flow rate can be calculated from the aerosol velocity and the known channel geometry.

[0070] Figure 12The diagram illustrates sawtooth modulation 50 of the driver signal and the resulting detector signal 60, along with the phase difference between them. The phase difference can be determined using an algorithm that moves the signals relative to each other and calculates the locations where the signals overlap the most. This continuously determines the phase difference from a large number of peaks. Therefore, it is more stable than simply measuring the phase difference between individual peaks in each signal, as the phase difference can vary slightly, for example, if there is any turbulence in the channel.

[0071] The advantage of using phase difference to determine aerosol velocity is that aerosol generation is uninterrupted, and therefore the output rate does not decrease. This contrasts with the method in WO 2013 / 042002, in which the aerosol generator is repeatedly turned on and off to generate a series of short pulses in the driver signal, thereby measuring the time delay between the start of each pulse and the time when the optical signal decreases when the aerosol droplets reach the optical sensor.

[0072] This invention can be used in many vibrating membrane atomizers, such as those described in US9027548, WO2012 / 046220, and WO2015 / 193432. In these types of atomizers, the membrane is mounted directly on the piezoelectric element, or has an annular planar support member on which the membrane and piezoelectric element are mounted (compared to the tubular transducer body described above). However, for various reasons, this invention is particularly advantageous in atomizers of the type described in EP2724741 and WO2013 / 098334.

[0073] First, this type of nebulizer is designed to operate at a constant low flow rate in only one direction. To achieve this, it can have a variable flow restrictor that causes less flow restriction at low negative pressure than at high negative pressure. Therefore, if the patient attempts to inhale too forcefully or too quickly (i.e., the negative pressure is too high), the airflow is restricted, and the flow rate does not increase. The nebulizer can be configured to allow the patient to inhale air and / or aerosol through the mouthpiece at an inspiratory flow rate not exceeding about 20 L / min, for example, about 10 to 20 L / min, or about 12 to 18 L / min, for example, about 15 L / min. Alternatively or additionally, the nebulizer can provide the patient with visual, auditory, or tactile feedback or guidance, enabling the patient to inhale at the desired inspiratory flow rate. In particular, the nebulizer can provide feedback on inhalation effort to the patient by illuminating the mouthpiece with light whose intensity increases as inhalation approaches the optimal rate. These collectively guide the patient to inhale at a constant low flow rate. The nebulizer can be breath-actuated and may have a valve (e.g., just upstream of the air outlet opening of the base unit) that opens and closes at the beginning and end of each inhalation (e.g., after a preset inhalation time), preventing the patient from exhaling into the mouthpiece. This ensures that the flow is only in one direction, toward the aerosol outlet orifice.

[0074] Secondly, the channel has a small internal volume and is shaped to generate a laminar aerosol flow. The internal volume of the channel between the membrane and the optical sensor can be less than 5 cm³. 3 For example, from 0.5 to 3cm 3 Or from 1 to 2 cm 3 For example, approximately 1.5cm 3 In contrast, some vibrating mesh nebulizers have large internal volumes inhalation channels or chambers for collecting aerosols. For example, nebulizers that continuously generate aerosols (opposite to respiratory drive) may require larger volumes to store the aerosols generated during patient exhalation so as not to waste them. A large-volume inhalation channel between the membrane and the optical sensor effectively acts as a low-pass filter for regulating aerosol density. Modulation frequencies (~10 Hz) are too high to pass through the large chamber and are averaged as "continuous" aerosol density. Therefore, modulation is not observed in the detector's output signal. The constant, slow laminar flow of aerosols through the small-volume channel to the optical sensor prevents aerosol buildup. If aerosols did accumulate in the channel, the regulation of aerosol density would not be detected. Furthermore, laminar flow reduces aerosol deposition within the channel, thus reducing noise sources in the optical signal.

[0075] Finally, the channel is part of the nozzle assembly, which is detachable from the rest of the sprayer and can therefore be easily made of a material that is transparent to IR and / or visible radiation.

[0076] For methods that determine the presence of liquid on a membrane by measuring the modulated light signal generated by aerosols in the measuring channel, a combination of slow unidirectional flow and small channels as independent components is ideal.

Claims

1. An inhalation device, comprising: • A channel with an air inlet opening and an aerosol outlet opening. • An aerosol generator including a vibrator and a membrane. • A reservoir for aerosolizing the liquid that is fluidly connected to the membrane. • Optical sensors are used to detect the presence of aerosols within the channel. • Controller, which is configured to (i) provide a driver signal to operate the vibrator, causing the membrane to vibrate and generate aerosol in the channel, and to modulate the amplitude of the driver signal at a frequency from 1 to 100 Hz; (ii) Receive the output signal from the sensor and demodulate the output signal; (iii) Determine whether there is aerosol in the channel based on the demodulated output signal; and (iv) If it is determined that there is no aerosol, stop operating the vibrator.

2. The inhalation device according to claim 1, wherein the optical sensor operates in the infrared region.

3. The inhalation device according to claim 1, wherein the optical sensor comprises an emitter and a detector disposed on opposite sides of the channel.

4. The inhalation device according to any one of claims 1 to 3, wherein the controller is configured to modulate the amplitude of the driver signal at a frequency from 5 to 40 Hz.

5. The inhalation device according to any one of claims 1 to 3, wherein the controller is configured to modulate the amplitude of the driver signal at a frequency of 10 Hz.

6. The inhalation device according to any one of claims 1 to 3, wherein the controller is configured to (i) periodically perform scans to determine the resonant frequency of the aerosol generator and / or the membrane; (ii) demodulate the output signal at a scan frequency corresponding to the period between scans; and (iii) determine the presence of aerosol in the channel based on the demodulated output signal.

7. The inhalation device according to any one of claims 1 to 3, wherein the controller is configured to determine the phase difference between the modulation driver signal and the output signal, thereby determining the velocity of the aerosol.

8. The inhalation device according to any one of claims 1 to 3, further comprising a variable flow limiter that limits the flow rate of air and aerosol to a maximum flow rate of 20 liters per minute.

9. The inhalation device according to any one of claims 1 to 3, further comprising a sensor for measuring pressure in the channel and a signaling device capable of emitting light of different intensities, wherein the controller is configured to (i) receive a signal representing the measured pressure, and (ii) cause the signaling device to emit light of lower intensities the further the measured pressure deviates from a target pressure.

10. The inhalation device according to any one of claims 1 to 3, wherein the channel has a spacing of less than 5 cm between the membrane and the optical sensor. 3 The internal volume.

11. The inhalation device according to any one of claims 1 to 3, wherein the channel is part of a component removable from the remainder of the inhalation device.

12. A method of operating an inhalation device according to any one of claims 1 to 11, the method comprising: a) Provide a driver signal to operate the vibrator, causing the membrane to vibrate and generate aerosols in the channel, and modulate the amplitude of the driver signal at a frequency from 1 to 100 Hz; b) Receive the output signal from the optical sensor and demodulate the output signal at the same frequency; c) Determine the presence of aerosols in the channel based on the demodulated output signal; and d) If it is determined in step c) that there is no aerosol, then stop operating the vibrator.

13. The method of claim 12, wherein the amplitude of the driver signal is modulated at a frequency from 5 to 40 Hz.

14. The method of claim 12, wherein the amplitude of the driver signal is modulated at a frequency of 10 Hz.

15. The method of claim 12, wherein the amplitude of the driver signal is modulated with a sine wave, a sawtooth wave, or a square wave.

16. The method according to any one of claims 12 to 15, further comprising: in step a), periodically performing a scan to determine the resonant frequency of the aerosol generator and / or the membrane; in step b), demodulating the output signal at the scan frequency; and in step c), determining the presence of aerosol in the channel based on the demodulated output signal.

17. The method according to any one of claims 12 to 15, further comprising measuring the phase difference between the modulation driver signal and the output signal to determine the velocity of the aerosol.

Images