Nebuliser systems

Abstract

In various embodiments, the present invention provides a system for identifying and / or classifying a liquid to be nebulised. The system comprises a nebuliser comprising a reservoir for receipt of a liquid to be nebulised, an ultrasonic transmitter, and an ultrasonic receiver. The ultrasonic transmitter is configured to emit an emitted acoustic signal for interrogation of liquid within the reservoir. The ultrasonic receiver is configured to receive an acoustic response signal arising from propagation of the emitted acoustic signal through the liquid within the reservoir. The system comprises a signal processing module configured to perform one or more signal processing functions on the acoustic response signal and output a processed acoustic response signal. The system comprises a data processing module, configured to receive the processed acoustic response signal, analyse the processed acoustic response signal to thereby determine at least one time domain parameter of the acoustic response signal, compare the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids, and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison. Also provided are methods of identifying and / or classifying a liquid to be nebulised, and a software application comprising instructions which, when executed by a processor of a device, cause the processor to execute the steps of a computer-implemented such method.

Description

[0001] 008855074

[0002] 1

[0003] Nebuliser systems

[0004] This application claims priority from GB2416466.7 filed 8 November 2024, the contents and elements of which are herein incorporated by reference for all purposes.

[0005] Field of the Invention

[0006] The present invention relates to nebuliser systems. In particular, although not exclusively, it relates to systems for identifying and / or classifying a liquid to be nebulised by a nebuliser, and nebulisers for use in such systems.

[0007] Background

[0008] Patient compliance to prescribed therapies with medication intake is crucial for successful healthcare outcomes. However, studies indicate that a large fraction (-50%) of patients with persistent illnesses do not follow prescribed medication regimens [1], Self-management of medication intake requires patient readiness which is heavily influenced by social and economic factors.

[0009] Technological advancement may not be able to stimulate medication intake when needed but may enable direct confirmation of medication intake, including timing and dosage. This can then trigger clinicians to make informed decisions about therapy amendments.

[0010] Several smart devices make use of electronics features that recognise when a drug container has been opened or, when labelled with barcodes or tags (RFID, NFC), are scanned by a smartphone or drug delivery device. For instance, a popular device for inhalation therapy that features a tag-based approach is the l-neb AAD mesh nebuliser - in this device, the patient is required to insert a drug specific disc tag into the nebuliser which then activates the device and monitors use associated with the tag. However, this strategy assumes that the patient fills the medication cup with the correct drug, without mistakenly or intentionally inhaling a different one.

[0011] Many known concepts which claim to monitor medication intake and / or patient compliance primarily provide information about patient behaviour rather than direct confirmation of medication intake.

[0012] The present inventors have realised that there is a desire for new devices and / or systems which allow more accurate determination of medication intake by a patient.

[0013] The present invention has been devised in light of the above considerations.

[0014] Summary of the Invention

[0015] The present inventors have realised that it is possible to use the acoustic properties of a liquid to be nebulised in order to determine or predict an identity or classification of the liquid to be nebulised. In 008855074

[0016] 2 particular, the present inventors have realised that commercial inhalation drug formulations each have unique compositions which influence their respective acoustic properties, such as compressibility. By appropriate analysis of the acoustic properties of a liquid to be nebulised, the identity or classification of the liquid to be nebulised can accordingly be determined or predicted, to a high degree of accuracy.

[0017] Accordingly, in a first aspect, the present invention provides a system for identifying and / or classifying a liquid to be nebulised, the system comprising: a nebuliser comprising a reservoir for receipt of a liquid to be nebulised, an ultrasonic transmitter, and an ultrasonic receiver, wherein the ultrasonic transmitter is configured to emit an emitted acoustic signal for interrogation of liquid within the reservoir, and wherein the ultrasonic receiver is configured to receive an acoustic response signal arising from propagation of the emitted acoustic signal through the liquid within the reservoir; a signal processing module, configured to perform one or more signal processing functions on the acoustic response signal and output a processed acoustic response signal; and a data processing module, configured to receive the processed acoustic response signal, analyse the processed acoustic response signal to thereby determine at least one time domain parameter of the acoustic response signal, compare the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids, and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison.

[0018] In a second aspect, the present invention provides a method of identifying and / or classifying a liquid to be nebulised, the method comprising performing the steps of: generating an emitted acoustic signal for interrogation of the liquid; receiving an acoustic response signal arising from propagation of the emitted acoustic signal through the liquid; performing one or more signal processing functions on the acoustic response signal and outputting a processed acoustic response signal to a data processing module; determining at least one time domain parameter of the acoustic response signal; comparing the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids; and performing a determination or predicting of an identity or classification of the liquid to be nebulised on the basis of the comparison.

[0019] The step of comparing the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids include comparing the determined at least one time domain parameter of the processed acoustic response signal against a database of liquids and / or classes of liquids with known corresponding time domain parameters. 008855074

[0020] 3

[0021] The emited acoustic signal may comprise a pulsed acoustic wave. The acoustic response signal may accordingly comprise pulse echoes arising from propagation of the pulsed acoustic wave through the liquid within the reservoir.

[0022] In such arrangements, the at least one time domain parameter of the acoustic response signal includes at least one of a phase velocity or an attenuation coefficient of the acoustic response signal. The data processing module may be configured to determine both a phase velocity and an atenuation coefficient of the acoustic response signal, for example using techniques as disclosed in references [2] and [3] indicated below, the contents of which are herein incorporated by reference.

[0023] Where both the phase velocity and an attenuation coefficient of the acoustic response signal are determined, the data processing module may be configured to compare the determined phase velocity and attenuation coefficient of the acoustic response signal in a 2D feature space against known phase velocities and attenuation coefficients of one or more known liquids and / or classes of liquids (e.g. by comparison with a database containing the known velocities and atenuation coefficients of the known liquids or classes of liquids), and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison in the 2D feature space.

[0024] The comparison of the determined phase velocity and attenuation coefficient of the acoustic response signal may be performed by ploting the respective features on first and second axes of the 2D feature space - e.g. plotting the determined phase velocity on a first axis within the 2D feature space against the determined attenuation coefficient on a second axis within the 2D feature space, and noting a location of the resulting data point within the 2D feature space. This location of the data point within the 2D features space may then be compared against a database of liquids and / or classes of liquids with known phase velocities and attenuation coefficients to thereby allow the data processing unit to determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison in the 2D feature space.

[0025] It has been found that the use of pulse-echo acoustic analysis, and in particular, analysis of the location of the determined phase velocity and attenuation coefficient of the pulse-echo signals within a 2D feature space, offers a particularly convenient method of determining or predicting an identity or classification of the liquid to be nebulised, to a high degree of accuracy.

[0026] The present inventors have found that it is possible to identify and / or classify a wide variety of liquids to be nebulised in this way. The determined or predicted identification and / or classification of the liquid to be nebulised may be stored by the device, and / or output to a user of the device, and / or transmitted to a remote device (e.g. communicated to a device accessible by a healthcare professional).

[0027] The liquid to be nebulised may comprise:

[0028] - a suspension formulation (a formulation wherein the active component comprises nanoparticles and / or microparticles) a small molecule formulation (a formulation wherein the active component comprises small molecules with a size on the order of 1 nm) 008855074

[0029] 4 a biological formulation (a formulation wherein the active component comprises a substance made from living organisms or their products including e.g. proteins, DNA and / or RNA), or

[0030] - a surfactant formation.

[0031] The data processing module may be configured to classify the liquid to be nebulised into one or more of the above types of formulation, based on the determined at least one time domain parameter of the processed acoustic response signal, e.g. based on the determined phase velocity and / or the attenuation coefficient of the acoustic response signal. The classification may be performed based on a determined or predicted identification of the liquid to be nebulised, or may alternatively be based on a more general determination that the liquid to be nebulised falls within one of these classes without making a specific identification of the identity of the liquid to be nebulised.

[0032] The liquid to be nebulised may comprise a formulation having a therapeutic purpose. The data processing module may be configured to classify the liquid to be nebulised into one or more different classes corresponding to different therapeutic purposes, based on the determined at least one time domain parameter of the processed acoustic response signal, e.g. based on the determined phase velocity and / or the attenuation coefficient of the acoustic response signal. The classification may be performed based on a determined or predicted identification of the liquid to be nebulised, or may alternatively be based on a more general determination that the liquid to be nebulised falls within one of a particular class corresponding to a defined therapeutic purpose, without making a specific identification of the identity of the liquid to be nebulised.

[0033] As one example, a first therapeutic purpose may include treatment of asthma and / or chronic obstructive pulmonary disease (COPD). Formulations having a therapeutic purpose of treatment of asthma and / or chronic obstructive pulmonary disease (COPD) may be more broadly referred to as respiratory formulations. The system may be configured to determine if liquid to be nebulised comprises a formulation having a therapeutic purpose including treatment of asthma and / or chronic obstructive pulmonary disease (COPD), based on the determined at least one time domain parameter of the processed acoustic response signal, e.g. based on the determined phase velocity and / or the attenuation coefficient of the acoustic response signal. The class of respiratory formulations may comprise e.g. budesonide, salbutamol and / or saline. It will be appreciated that in practice, the class of respiratory formulations may include many further possible formulations, however it may be of most interest for the system to be able to identify and / or classify formulations that comprise budesonide, salbutamol and / or saline, given the prevalence of use of such formulations in nebuliser-based treatments.

[0034] As a second example, a second therapeutic purpose may include treatment of bacterial infection. Formulations having a therapeutic purpose of treatment of bacterial infection may be more broadly referred to as antibiotic formulations. The system may be configured to determine if liquid to be nebulised comprises a formulation having a therapeutic purpose including treatment of bacterial infection, based on the determined at least one time domain parameter of the processed acoustic response signal, e.g. based on the determined phase velocity and / or the attenuation coefficient of the acoustic response signal. The class of antibiotic formulations may comprise e.g. tobramycin, amikacin and / or colomycin. It will be 008855074

[0035] 5 appreciated that in practice, the class of antibiotic formulations may include many further possible formulations, however it may be of most interest for the system to be able to identify and / or classify formulations that comprise tobramycin, amikacin and / or colomycin, given the prevalence of use of such formulations in nebuliser-based treatments.

[0036] The present inventors have identified that it would be particularly advantageous to provide a system which can reliably differentiate at least between respiratory formulations and antibiotic formulations - for example, on the basis of the identification of the liquid to be nebulised as a specific formulation that is determined to fall within one of these classes, or alternatively, by making more general determination that the liquid to be nebulised falls within one of these classes without making a specific identification of the identity of the liquid to be nebulised. By providing a system which is capable of differentiating between at least these classes of formulas, the system may be able to prevent a user unintentionally inhaling a nebulised formulation having a therapeutic purpose that is not the intended formulation (e.g. by providing an indication / warning / alert to a user when the liquid to be nebulised is determined not to be an intended liquid to be nebulised.

[0037] Accordingly, the system may be configured to compare the determined or predicted identity or classification of the liquid to be nebulised against a stored indication of an intended identity or classification of the liquid to be nebulised (e.g. an indication stored in a memory moule of the system), and trigger an alert to a user where the determined or predicted identity or classification of the liquid to be nebulised does not match the intended identity or classification.

[0038] The term “intended identity or classification of the liquid to be nebulised” is used herein to define the identity or classification of the liquid to be nebulised as defined in e.g. a health-care plan of the user or prescribed by a health-care provider. The stored indication of an intended identity or classification of the liquid to be nebulised may be pre-programmed into the system. Alternatively, the stored indication of an intended identity or classification of the liquid to be nebulised may be manually input by a user of the system. Alternatively, the stored indication of an intended identity or classification of the liquid to be nebulised may be remotely transmitted to the system e.g. from a remote device controlled and / or accessible by a healthcare professional.

[0039] In some arrangements, the ultrasonic transmitter and the ultrasonic receiver may comprise separate components. However, in preferred arrangements, the ultrasonic transmitter and the ultrasonic receiver may form part of a single component, said single component being an ultrasonic transducer configured to perform the functions of the ultrasonic transmitter and the ultrasonic receiver. Use of a single ultrasonic transducer for both emitting and receiving acoustic signals allows for simplification of the structure of the system compared with arrangements employing a separate transmitter and receiver.

[0040] The nebuliser may further comprise a temperature sensor configured to measure the temperature of liquid within the reservoir. The temperature sensor many be disposed within the reservoir itself, or may be disposed outside of the reservoir but arranged to measure the temperature of liquid within the reservoir. It will be appreciated by those skilled in this field that the acoustic properties of the liquid to be nebulised may vary based on the temperature of the liquid to be nebulised. Accordingly, the system may 008855074

[0041] 6 be configured to correct the comparison of the determined at least one time domain parameter of the acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids based on the measured temperature of liquid within the reservoir. This correction may be performed e.g. by the data processing module of the system.

[0042] Where the comparison is made by comparison with a database, the database of liquids and / or classes of liquids with known corresponding time domain parameters may include information about a correspondence between the known corresponding time domain parameters and temperature. Alternatively or additionally, the database of liquids and / or classes of liquids with known corresponding time domain parameters may include different values for the known corresponding time domain parameters of the liquids and / or classes of liquids at different temperatures, such that a comparison can be made by using the measured temperature to select an appropriate value for the known corresponding time domain parameter of the liquids and / or classes of liquids from the database against which to compare the determined time domain parameter(s) of the acoustic response signal.

[0043] As noted above, the system includes a signal processing module configured to perform one or more signal processing functions on the acoustic response signal and output a processed acoustic response signal. The signal processing module may comprise one or more of: a filter, an amplifier, and / or a digitiser. Where the signal processing module comprises a filter, this may comprise e.g. a bandpass filter. Where the signal processing module comprises an amplifier, this may comprise e.g. a low noise amplifier. Where the signal processing module comprises a digitiser, this may comprise an analog-to-digital converter (ADC) suitable for converting an analogue acoustic signal to a digital acoustic signal, and may preferably comprise a high-speed analog-to-digital converter (ADC) (e.g. >10 megasamples per second MSPS). In some arrangements, such signal processing functions may be provided by a dedicated chip (e.g. a Tl AFEXX chip).

[0044] As noted above, the system includes a data processing module, configured to receive the processed acoustic response signal, analyse the processed acoustic response signal to thereby determine at least one time domain parameter of the acoustic response signal, compare the determined at least one time domain parameter of the processed acoustic response signal against a database of liquids and / or classes of liquids with known corresponding time domain parameters, and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison. The data processing module may comprise a field programmable gate array (FPGA) or a microcontroller unit.

[0045] It is contemplated that various functions of the system could be performed either locally or remotely. Accordingly, in some arrangements, the signal processing module and / or the data processing module are provided locally as part of the nebuliser. In some arrangements, the signal processing module and / or the data processing module are provided remotely of the nebuliser. In some arrangements, the signal processing module is provided locally as part of the nebuliser, and data processing module is provided remotely of the nebuliser. 008855074

[0046] 7

[0047] Where one or both of the signal processing module and / or the data processing module are provided remotely of the nebuliser, they may be provided on a remote computer terminal, e.g. on a personal mobile computer, or on a remote computer.

[0048] Where one or both of the signal processing module and / or the data processing module are provided remotely of the nebuliser, the nebuliser may be configured to wireless transmit signals to the respective remote module(s). For example, where the signal processing module is provided locally as part of the nebuliser, and the data processing module is remotely of the nebuliser, the signal processing module may be configured to convey the processed acoustic response signal to the data processing module wirelessly.

[0049] It is contemplated that even where data processing is performed locally (e.g. where the signal processing module and / or the data processing module are provided locally as part of the nebuliser), there may be some advantages where information about the known corresponding time domain parameter of one or more known liquids and / or classes of liquids (e.g. the database of liquids and / or classes of liquids with known corresponding time domain parameters) is held remotely: in particular, where the information / database is held remotely, it may be more simple to update the information / database as compared to arrangements in which the information / database is stored locally e.g. in memory of the nebuliser. Accordingly, the information / database may be stored on a remote server, and the system may be configured to remotely correspond with the remote server in order to query the database or otherwise obtain information remotely, in order to perform the comparison of time domain parameter(s) as previously discussed.

[0050] It is considered that the present invention may find application for a wide range of different types of nebulising system. In this regard, the precise mode of function of the nebuliser is not limited: the nebuliser may comprise a mesh-based nebulising unit, a jet nebulising unit, or an ultrasonic nebulising unit, and the nebuliser may comprise a fluid flow path for conveying a substance to be nebulised from the reservoir to the nebulising unit for nebulisation.

[0051] The reservoir may comprise e.g. a tank or other suitable storage space for storing the liquid to be nebulised. The reservoir may be refillable.

[0052] The nebuliser may comprise a controller module. Where the signal processing module and / or the data processing module are provided locally as part of the nebuliser, they may form part of the controller module - in other words, the controller module may comprise the signal processing module and / or the data processing module.

[0053] The nebuliser may comprise a memory module for storing data.

[0054] The nebuliser may comprise a power module (e.g. a battery) for powering one or more operations of the nebuliser. The power module may be arranged to be in electrical communication with the controller module and / or the memory module, e.g. by means of electrical circuitry.

[0055] The system may comprise a notifier for providing an indication I warning I alert to a user (e.g. when the liquid to be nebulised is determined not to be an intended liquid to be nebulised, although it is 008855074

[0056] 8 contemplated that the notifier may be more generally configured to alert the user in response to detection of a fault condition within the nebuliser). The notifier may comprise a light, a display screen configured to display information to the user, and / or a speaker. In some arrangements the notifier may be provided locally on the nebuliser. In other arrangements, the notifier may be provided remotely, e.g. on a remote device such a personal mobile computer with which the nebuliser is configured to remotely connect.

[0057] Whilst it is of primary interest for the present invention that the system is able to determine or predict an identity or classification of the liquid to be nebulised, the system may be further configured to determine or monitor one or more parameters related to use of the system.

[0058] In some arrangements, the system may be configured to monitor and / or track breathing patterns of a user. Systems that monitor and / or track breathing patterns can verify that the medication is being inhaled correctly. When coupled with formulation identification, this feature can confirm that the patient is not only using the correct medication but also using the device properly for efficient dose delivery.

[0059] In some arrangements, the system may be configured to monitor and / or track times at which the system is used. Systems that monitor and / or track times at which the system is used can verify that the medication is being inhaled according to an intended dosing schedule.

[0060] In some arrangements, the system may comprise means for biometric authentication of a user - in other words, means for detecting one or more biological characteristics of the user to verify the identity of a user. For example, the system may comprise a biometric identification module e.g. a fingerprint scanner, or a camera configured for facial and / or iris recognition. Providing means for biometric authentication of a user may help ensure that not only is the correct medication being used, but also to ensure that the correct medication is administered to the correct user: this dual verification system can significantly reduce the risk of medication misuse or abuse.

[0061] By combining the ability for the system to determine or predict an identity or classification of the liquid to be nebulised with additional features such as biometric authentication and / or monitoring of breathing patterns and usage times, reliable data on dose administration and / or prescription management can be obtained by the system.

[0062] The system may be configured to transmit information relating to the system to an external healthcare provider. For example, real-time data on breathing patterns and medication intake can be transmitted to an external healthcare provider, allowing them to monitor adherence (e.g. with a health-care plan of the user or with a prescribed dosing schedule). T ransmitting information relating to the system to an external healthcare provider can prompt timely interventions if irregularities are detected. For example, if a patient frequently uses their nebuliser incorrectly, healthcare providers can tailor their interventions, such as providing additional training or adjusting the medication regimen. This data-driven approach can facilitate personalised treatment plans, potentially improving patient outcomes and reducing healthcare costs associated with non-adherence. 008855074

[0063] 9

[0064] The method of the second aspect may be a computer-implemented method. Accordingly, in a third aspect, the present invention provides a computer-implemented method of identifying and / or classifying a liquid to be nebulised, the method comprising the method of the second aspect.

[0065] In a fourth aspect, the present invention provides a software application comprising instructions which, when executed by a processor of a device, cause the processor to execute the steps of the computer- implemented method according to the third aspect.

[0066] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0067] Summary of the Figures

[0068] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0069] Figure 1 is a schematic illustration of an experimental setup for identifying and / or classifying a liquid to be nebulised according to the present invention.

[0070] Figure 2 is a graph showing an example time domain signal as obtained via the experimental setup shown in Figure 1, the signal having been digitized with an oscilloscope and having undergone signal processing.

[0071] Figure 3 is a (partially exploded) model of a nebuliser according to the present invention, in which an acoustic transducer is coupled to the reservoir of the nebuliser.

[0072] Figure 4 shows (a) measured attenuations and phase velocities for budesonide, salbutamol, saline, tobramycin, amikacin, and colomycin formulations (n=5) at 25°C; (b) the influence of temperature on measured attenuations and phase velocities for tobramycin, amikacin, and colomycin formulations (antibiotic drug formulations); and (c) the influence of temperature on measured attenuations and phase velocities for budesonide, salbutamol, saline formulations (common drug formulations).

[0073] Figure 5 shows a process flow diagram for one event logging concept in a system according to the present invention.

[0074] Detailed Description of the Invention

[0075] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0076] In order to assess feasibility of providing a system for identifying and / or classifying a liquid to be nebulised as described above, the following experimental work was completed:

[0077] Experimental method 008855074

[0078] 10

[0079] 0.9% saline, salbutamol (5 mg / ml, Ventolin-GSK), budesonide (0.25 mg / ml, Pulmicort-AstraZeneca), colomycin (0.5 Million ILJ / ml, TEVA ), tobramycin (40 mg / ml, Flynn Pharma), amikacin (50 mg / ml, Vianex) were used as sample formulation.

[0080] In the following discussion, saline, salbutamol and budesonide are referred to as ‘common drugs’, while colomycin, amikacin and tobramycin are referred as ‘antibiotics’.

[0081] Briefly, the ultrasonic transducer (V129-RM, Evident, Tokyo, Japan) with 3.175 mm (0.125 inch) element diameter and centre frequency of 10 MHz was used as the signal transmitter and receiver.

[0082] As illustrated in Figure 1, the transducer was attached to the reservoir and driven by a waveform generator with 1-cycle sinusoidal signal. The resulting echo signal was amplified by 20 dB using an amplifier before being digitized with an oscilloscope. The oscilloscope operated at sampling frequency of 2 GS / s, with 50 000 sample points, and 128 signals were averaged to enhance the signal-to-noise ratio (SNR). To further illustrate how such an arrangement could be achieved in practice in a nebulising system, Figure 3 shows a (partially exploded) model of a nebuliser 100 having a main body 110 and a mouthpiece 120. An acoustic transducer 130 is arranged such that in use, it is coupled to the reservoir 140 of the nebuliser (although in this picture, it is shown separately, for improved clarity).

[0083] Subsequently, the digitized signal underwent signal & data processing, adapted from the theoretical framework outlined in references [2] and [3], It provided the access of phase velocities and attenuation coefficients from the signal, which served as the identification markers. Figure 2 shows a graph showing an example time domain signal as obtained via the experimental setup shown in Figure 1 .

[0084] T o investigate the influence of temperature on the ability to identify formulations, a Peltier was used to adjust the temperatures 10 °C steps between 15 to 35 °C. Five measurements were performed for each formulation at each temperature. The measurements were conducted by following a sequence: first, the formulation was poured into a dry medication cup, followed by the measurement. The reservoir was then emptied and dried before the next filling and subsequent measurement.

[0085] Results

[0086] Processing of the reflected ultrasonic pulses enabled the determination of signal attenuation and phase velocity for each formulation. These measurements were used as input features, representing each formulation as a point in a 2D feature space together with the temperature influence, as shown in Figure 4.

[0087] From Figure 4, it can be seen that antibiotic drug formulations are distinctly separated from common drug formulations in the feature space in the analysed case.

[0088] Phase velocities and attenuation were found to be higher for the antibiotics, whereas the common drugs (i.e. saline, budesonide and salbutamol) clustered closely together due to smaller differences in phase velocities and attenuations (see inset in Figure 4 (a)). 008855074

[0089] 11

[0090] Increasing the temperature of the formulations from 15 °C to 35 °C resulted in reduced signal attenuation and increased phase velocities. Despite these changes, the separation between antibiotics and common drugs in the feature space remained consistent. The same pattern was observed for common drugs.

[0091] The results of this work highlight the potential for using an ultrasonic pulse-echo technique to identify medication formulations in a smart nebuliser. The distinct separation of antibiotics as well as common drug formulations in the 2D feature space, based on simple ultrasonic measurements, demonstrates the feasibility of this approach for real-time formulation identification at different conditions, e.g. even at different temperatures.

[0092] Figure 5 shows a process flow diagram for one possible event logging concept in a system according to the present invention, in which features such as biometric authentication and breath actuation monitoring are also implemented. The process flow diagram in this possible event logging concept includes the following events, in sequence (although it will be appreciated that in some embodiments, the system may be configured not to log one or more of the below listed events):

[0093] Nebuliser Powered

[0094] Biometric Authentication

[0095] Pre-Use-check (inc. assembly check)

[0096] Medication loading and identification check

[0097] Breath Actuation Monitoring

[0098] Medication Nebulisation (during which flow rate and inhalation duration are monitored)

[0099] Dose confirmation (during which any stop of nebulisation is noted, and the dose delivery is recorded)

[0100] Post-use verification (inc. logging of completion of a nebulising session by a user)

[0101] Data storage / T ransmission (in which data is shared with a healthcare provider)

[0102] As shown in Fig. 5, the system is configured to log events that occur during use, and is further configured to take action in response to detection of one or more fault conditions on occurrence of a log failure, including, but not limited to, occasions of detection of an incorrect biometric authentication (prompting user re-authentication), detection of incorrect assembly of the device (prompting alert to trigger user correction to correct the assembly), detection of an incorrect medication filled into the device (prompting alert to user), detection of no inhalation (prompting alert to a user to inhale), detection of an incorrect inhalation pattern of a user (prompting alert to a user to adjust their inhalation pattern), detection of a dose delivery issue (prompting alert to a user), detection that a nebulising session is incomplete (prompting alert to a user).

[0103] It is considered that the combination of a system which allows identification and / or classification of a liquid to be nebulised, coupled with the integration of biometric authentication and breathing monitoring, as shown in this process flow diagram, would allow for effective adherence monitoring of patients. The 008855074

[0104] 12 proposed approach has the potential to fulfil real-time, data-driven healthcare, improve patient safety and treatment efficacy, and reduce costs associated with medication non-adherence.

[0105] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0106] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0107] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0108] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0109] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0110] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.

[0111] References

[0112] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein.

[0113] [1] World Health Organization: Adherence to Long-Term Therapies: Evidence for Action. Sabate D.G., editor. World Health Organization; Geneva, Switzerland: 2003. 008855074

[0114] 13

[0115] [2] Zhang G, Li X, Zhang S, Kundu T: Investigation of frequency-dependent attenuation coefficients for multiple solids using a reliable pulse-echo ultrasonic measurement technique, Measurement 2021 ; 177: pp 109270. [3] Jeong H, Hsu D K: Experimental analysis of porosity-induced ultrasonic attenuation and velocity change in carbon composites, Ultrasonics 1995; 33(3): pp 195-203.

Claims

00885507414Claims:1 . A system for identifying and / or classifying a liquid to be nebulised, the system comprising: a nebuliser comprising a reservoir for receipt of a liquid to be nebulised, an ultrasonic transmitter, and an ultrasonic receiver, wherein the ultrasonic transmitter is configured to emit an emitted acoustic signal for interrogation of liquid within the reservoir, and wherein the ultrasonic receiver is configured to receive an acoustic response signal arising from propagation of the emitted acoustic signal through the liquid within the reservoir; a signal processing module, configured to perform one or more signal processing functions on the acoustic response signal and output a processed acoustic response signal; and a data processing module, configured to receive the processed acoustic response signal, analyse the processed acoustic response signal to thereby determine at least one time domain parameter of the acoustic response signal, compare the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids, and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison.

2. The system according to claim 1 wherein the emitted acoustic signal comprises a pulsed acoustic wave, the acoustic response signal comprises pulse echoes arising from propagation of the pulsed acoustic wave through the liquid within the reservoir, and wherein the at least one time domain parameter of the acoustic response signal includes: a phase velocity or an attenuation coefficient of the acoustic response signal.

3. The system according to claim 2 wherein the data processing module is configured to determine both a phase velocity and an attenuation coefficient of the acoustic response signal, compare the determined phase velocity and attenuation coefficient of the acoustic response signal in a 2D feature space against known phase velocities and attenuation coefficients of one or more known liquids and / or classes of liquids, and determine or predict an identity or classification of the liquid to be nebulised on the basis of the comparison in the 2D feature space.

4. The system according to any one of the preceding claims, wherein the ultrasonic transmitter and the ultrasonic receiver are a single component, said single component being an ultrasonic transducer configured to perform the functions of the ultrasonic transmitter and the ultrasonic receiver.

5. The system according to any one of the preceding claims, wherein the nebuliser further comprises a temperature sensor configured to measure the temperature of liquid within the reservoir, and wherein the comparison of the determined at least one time domain parameter of the acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids is corrected based on the measured temperature of liquid within the reservoir008855074156. The system according to any one of the preceding claims, wherein the signal processing module comprises one or more of: a filter, an amplifier, and / or a digitiser.

7. The system according to any one of the preceding claims, wherein the data processing module comprises a field programmable gate array (FPGA) or a microcontroller unit.

8. The system according to any one of the preceding claims, wherein the signal processing module and / or the data processing module are provided locally as part of the nebuliser.

9. The system according to any one of the preceding claims, wherein the signal processing module and / or the data processing module are provided remotely of the nebuliser.

10. The system according to claim 8 or claim 9, wherein the signal processing module is provided locally as part of the nebuliser, and wherein data processing module is remotely of the nebuliser.

11. The system according to claim 10 wherein the signal processing module is configured to convey the processed acoustic response signal to the data processing module wirelessly.

12. The system according to any one of the preceding claims, wherein the system is configured to compare the determined or predicted identity or classification of the liquid to be nebulised against a stored indication of an intended identity or classification of the liquid to be nebulised, and trigger an alert to a user where the determined or predicted identity or classification of the liquid to be nebulised does not match the intended identity or classification.

13. The system according to any one of the preceding claims, wherein the liquid to be nebulised comprises formulation having a therapeutic purpose, and wherein the processing module is configured to classify the liquid into one or more different classes corresponding to different therapeutic purposes.

14. The system according to claim 13, wherein the one or more different classes comprise a class of respiratory formulations and a class of antibiotic formulations.

15. The system according to claim 14, wherein the class of antibiotic formulations include tobramycin, amikacin and / or colomycin.

16. The system according to claim 14 or claim 15, wherein the class of respiratory formulations include budesonide, salbutamol and / or saline.

17. The system according to any one of the preceding claims, wherein the nebuliser comprises one of: a mesh-based nebulising unit, a jet nebuliser unit, or an ultrasonic nebuliser unit.0088550741618. The system according to any one of the preceding claims, wherein the system comprises means for biometric authentication of a user.

19. The system according to any one of the preceding claims, wherein the system is configured to monitor and / or track one or more of: (i) breathing patterns of a user, and / or (ii) times at which the system is used.

20. The system according to any one of the preceding claims, wherein the system is configured to transmit information relating to the system to an external healthcare provider.

21. A method of identifying and / or classifying a liquid to be nebulised, the method comprising performing the steps of: generating an emitted acoustic signal for interrogation of the liquid; receiving an acoustic response signal arising from propagation of the emitted acoustic signal through the liquid; performing one or more signal processing functions on the acoustic response signal and outputting a processed acoustic response signal to a data processing module; determining at least one time domain parameter of the acoustic response signal; comparing the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids and / or classes of liquids; and performing a determination or predicting of an identity or classification of the liquid to be nebulised on the basis of the comparison.

22. The method of claim 21, further comprising the steps of: measuring the temperature of the liquid to be nebulised, conveying signals corresponding to the temperature to the data processing module, and correcting the comparison of the determined at least one time domain parameter of the processed acoustic response signal against the known corresponding time domain parameter of one or more known liquids and / or classes of liquids, on the basis of the conveyed temperature signals.

23. The method of claim 21 or claim 22, where the step of comparing the determined at least one time domain parameter of the processed acoustic response signal against a known corresponding time domain parameter of one or more known liquids includes comparing the determined at least one time domain parameter of the processed acoustic response signal against a database of liquids and / or classes of liquids with known corresponding time domain parameters.

24. A computer-implemented method of identifying and / or classifying a liquid to be nebulised, the method comprising the method of any one of claims 21 to 23.0088550741725. A software application comprising instructions which, when executed by a processor of a device, cause the processor to execute the steps of the computer-implemented method according to claim 24.

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