Arterial blockage detector

Abstract

The present invention relates to a device for detecting an arterial blockage, the device comprising a flexible substrate configured to conform to the skin of a patient; a plurality of microphones arranged on the flexible substrate for sensing acoustic vibrations relating to an arterial blockage; and a plurality of accelerometers arranged on the flexible substrate for sensing movement at the surface of the skin of the patient. A system for detecting an arterial blockage is also disclosed.

Description

[0001] ARTERIAL BLOCKAGE DETECTOR

[0002] FIELD

[0003] The present disclosure relates to a device and a system for detecting an arterial blockage.

[0004] BACKGROUND

[0005] Existing diagnostic methods for diagnosing coronary artery disease (CAD) include electrocardiogram (ECG), cardiac or nuclear stress tests, echocardiography, coronary calcium scanning, magnetic resonance imaging or x-ray computed tomographic angiography and, the most widely used method, x- ray angiography. Except for ECG, these methods require skilled operators and expensive equipment, and are therefore unsuitable for large scale deployment. More recently, transthoracic Doppler echocardiography of the coronary arteries has also been used. Although this technique is entirely non- invasive, its applicability is limited by patients’ acoustic windows and spatial resolution (small vessels). Furthermore, coronary arteries other than the left anterior descending branch are extremely difficult or impossible to evaluate by this method due to their more posterior position in the mediastinum.

[0006] US20090177107A1 and US2006 / 245597A describe electronic stethoscope systems that automatically detect coronary artery disease in patients. The systems use an electronic stethoscope to record acoustic data from the fourth left intercostal space of a patient. A processing technique is then applied in order to filter the data and produce Fast Fourier Transform (FFT) data of magnitude versus frequency.

[0007] US2011 / 137310A describes a tissue ablation probe comprising an elongated shaft, at least one electrode tine carried by the elongated shaft, at least one tine exit from which the electrode tine(s) can be deployed from the elongated shaft and retracted within the elongated shaft, and a sheath covering the electrode tine exit(s).

[0008] US2014 / 171812A describes non-invasive medical devices, systems and methods for the detection of coronary artery disease.

[0009] US2014 / 243616A describes systems, methods and apparatuses which use acoustic data in the detection of coronary artery disease.

[0010] WO2016 / 033521 describes a handheld coronary artery disease (CAD) detection device.

[0011] US5638823A describes a system and method for non-invasively detecting coronary artery disease, utilising a vasodilator drug to increase the signal-to-noise ratio of an acoustic signal that represents diastolic heart sounds of a patient. US20080013747A1 describes an electronic stethoscope including a microphone, an accelerometer to detect stethoscope movement, a processor coupled to the microphone and the accelerometer, and a speaker coupled to the processor to reproduce a biological sound.

[0012] EP0980672A1 describes a diagnostic system for coronary artery disease comprising a detector of vibration signal of subject using pulsed laser beam, which is placed apart from the subject, and a detector of vibration signal of environmental noise.

[0013] US9775520B2 describes a system including one or more sensors to detect activities of a mobile object, and a processor coupled to the sensor and the wireless transceiver to classify sequences of motions into groups of similar postures each represented by a model and to apply the models to identify an activity of the object.

[0014] US10055549B2 describes a method and apparatus for wireless, remote, physiological monitoring in the evaluation of health and disease state specifically with respect to cardiac and pulmonary pathologies, including heart failure and sleep apnea.

[0015] A novel approach to diagnosing coronary artery disease: acoustic detection of coronary turbulence, Thomas, J.L., Winther, S., Wilson, R.F. et al., The International Journal of Cardiovascular Imaging (2017) 33: 129-126, describes acoustic detection systems for detecting coronary turbulence.

[0016] Likelihood reclassification by an acoustic-based score in suspected coronary artery disease, Rasmussen, L.D. et al., Heart 109, 1223-1230 (2023), describes investigating the diagnostic performance of an acoustic-based CAD score.

[0017] The present disclosure seeks to alleviate, at least to a certain degree, the problems and / or address at least to a certain extent, the difficulties associated with the prior art, by providing means to detect arterial blockages, for example in an artery that is at least partially blocked, non-invasively by identifying acoustic signatures generated by disturbed downstream blood flow.

[0018] SUMMARY

[0019] According to a first aspect of the disclosure, there is provided a device for detecting an arterial blockage, the device comprising: a flexible substrate configured to conform to the skin of a patient; a plurality of microphones arranged on the flexible substrate for sensing acoustic vibrations relating to an arterial blockage; and a plurality of accelerometers arranged on the flexible substrate for sensing movement at the surface of the skin of the patient.

[0020] Advantageously, the device provides for an entirely non-invasive and less time consuming means for detecting arterial blockages. Such a device is thus not only suitable for outpatient screening and in primary care settings, but also can be used to pre-screen symptomatic patients attending a specialist cardiology unit and identify patients with no CAD, so that these patients will therefore not need to undergo further costly, and to some extent, potentially risky, investigations.

[0021] In particular, the combined advantage of sensing acoustic vibrations and movement at the surface of the skin of the patient by the combination of a microphone and an accelerometer is that sensing both acoustics and movements, including shearing movements detected by said accelerometer, can provide a sufficient level of information to not only identify the presence of a stenosis, but also to localise the position, size and / or shape of the stenosis. Also, whetherthe stenosis is symmetrical or non-symmetrical can also be determined.

[0022] Additionally, the sensed data from the microphones and accelerometers can be complementary. For example, the accelerometers can reveal gross movements of the patient which could also give rise to microphone artefacts, thus identifying them as artefacts and advantageously allowing them to be ignored, which could be particularly useful for longer term measurements where patient movement is more likely. Furthermore, the use of a plurality of microphones and a plurality of accelerometers provides that simultaneous measurements can be taken using different sensors in fixed positions, which makes the exploitation of multiple measurement sites more reliable, compared with taking measurements at different locations at time intervals using the same sensors.

[0023] Optionally, the device comprises a plurality of pairs of sensors, each of the pairs of sensors comprising one of said plurality of microphones and one of said plurality of accelerometers arranged adjacent to one another.

[0024] Advantageously, the combination of a microphone and an accelerometer in each pair provides that the presence, size, shape, and / or symmetry of a stenosis can be determined. Furthermore, providing a plurality of pairs of sensors advantageously provides for increased location accuracy in stenosis detection.

[0025] Optionally, the plurality of pairs of sensors are arranged to form an array of pairs of sensors.

[0026] Advantageously, this provides that simultaneous measurements can be taken using different sensors in fixed positions, which makes the exploitation of multiple measurement sites more reliable, compared with taking measurements at different locations at time intervals using the same sensors. Furthermore, this advantageously provides for increased location accuracy in stenosis detection. For example, the arrangement of the sensors in an array of closely paired microphones and accelerometers maximises the chances of locating a stenosis in a coronary artery whose position is not known. In contrast, the investigation of a large artery whose position and path are less uncertain, would work with fewer sensors and a rectangular array of closely paired microphones and accelerometers would not be required. Optionally, the plurality of pairs of sensors comprise 8 pairs of sensors arranged in a 2x4 array, or 16 pairs of sensors arranged in a 4x4 array.

[0027] Optionally, in each of the pairs of sensors, the respective microphone and accelerometer are arranged to be spaced apart from one another, for example by approximately 5mm.

[0028] Optionally, in each of the pairs of sensors, the respective microphone and accelerometer are arranged to abut one another.

[0029] Optionally, the pairs of sensors are spaced apart from one another by between about 5mm to about 40mm, for example by about 30mm.

[0030] Optionally, the flexible substrate is configured to form flexible arms, where the flexible arms can be straight or bent. The flexible arms are protruding members that extend from the side of the flexible substrate, in a straight, bent or branched manner.

[0031] Optionally, each of the pairs of sensors is located on a flexible arm of the flexible substrate.

[0032] Optionally, the plurality of pairs of sensors comprise 8 pairs of sensors arranged on 8 flexible arms of the substrate in a 2x4 array.

[0033] Advantageously, having the sensor pairs mounted on flexible arms allows the sensor pairs to follow small skin movements with less resistance as well as to let the flexible substrate conform more closely and easily to the curvature of the skin of the patient.

[0034] Optionally, the device further comprises a transmitter unit comprising a wireless transmitter configured to communicate with a receiver module, and a power supply configured to power the plurality of microphones, the plurality of accelerometers, and the transmitter.

[0035] Advantageously, this can provide that the device can communicate with a receiver, such as a receiver connected to a data processing unit such as a nearby laptop computer running standard data capture and logging software, but that the device itself can be reusable.

[0036] Optionally, the power supply comprises a battery, for example a miniature lithium ion battery.

[0037] Optionally, the transmitter comprises a Zigbee transmitter, or a Bluetooth transmitter.

[0038] Optionally, the transmitter unit is arranged proximate a side of the flexible substrate. Optionally, the transmitter unit further comprises an analog front-end architecture for detecting, amplifying and pre-processing signals from the microphones and accelerometers before converting said signals into digital form, the analog front-end architecture configured to provide a bandwidth of between about 0.5Hz to 500Hz and comprising: a first stage configured as a differential pre-amplification stage with high pass characteristics; a second stage comprising an active, first order high pass filter; and a third stage comprising a second order low pass filter.

[0039] Advantageously, the analog front-end architecture provides low-noise electronics to detect, amplify and pre-process the acoustic signals in the analog domain, before converting them into digital form, since the sounds due to coronary stenosis are typically weak.

[0040] Optionally, the differential pre-amplification first stage comprises an amplification of x100, and comprises a low-noise instrumentation amplifier and a high-precision operational amplifier.

[0041] Optionally, the second stage is configured to enhance the DC offset rejection capabilities of the analog front-end architecture and to introduce an additional gain of x10.

[0042] Advantageously, this can better exploit the full-scale voltage range of a subsequent analog digital converter block.

[0043] Optionally, the second order low pass filter of the third stage is configured to define the passband of the analog front-end architecture and serve as an anti-alias filter.

[0044] Optionally, each of the microphones and accelerometers comprises an analog output, and each of the analog outputs is connected to the analog front-end architecture of the transmitter unit.

[0045] Optionally, the microphones and accelerometers are connected to the analog front-end architecture by one or more wires.

[0046] Optionally, the transmitter unit further comprises an analog to digital converter configured to digitise the analog signals originating from an output of the analog front-end architecture.

[0047] Optionally, a field programmable gate array is provided to control the communication between the analog to digital converter and the transmitter.

[0048] Optionally, each of the plurality of accelerometers is configured to sense movement in a direction perpendicular to the surface of the skin of a patient and / or in a direction parallel to the surface of the skin of a patient. Advantageously, data obtained by sensing movement in a direction parallel to the surface of the skin of a patient, i.e. sensing shear acceleration, can be used with models for predicting shear waves generated by a stenosis in order to identify an arterial blockage.

[0049] Optionally, each of the plurality of accelerometers is a 1 axis accelerometer.

[0050] Optionally, each of the plurality of accelerometers is a 2 axis accelerometer.

[0051] Optionally, each of the plurality of accelerometers is a 3 axis accelerometer.

[0052] Optionally, the device comprises eight accelerometers which are each configured to sense movement in at least one direction.

[0053] Optionally, the device comprises four accelerometers which are each configured to sense movement in at least two directions.

[0054] Optionally, each of the plurality of accelerometers is an ADXL335 accelerometer.

[0055] Optionally, each of the plurality of accelerometers has a sensitivity rating of between about 270mV / g to about 330mV / g, for example about 300mV / g.

[0056] Advantageously, using accelerometers with such a sensitivity can provide for improved detection of the movements due to coronary stenosis, which are typically weak.

[0057] Optionally, each of the plurality of microphones has a sensitivity rating of between about -41dBV / Pa to about -35dBV / Pa, for example about -38dBV / Pa.

[0058] Advantageously, using microphones with such a sensitivity can provide for improved detection of the sounds due to coronary stenosis, which are typically weak.

[0059] Optionally, each of the plurality of microphones has a signal to noise ratio of between about 50dB to about 70dB, for example about 63dB.

[0060] Optionally, the device further comprises an additional microphone configured to sense acoustic vibrations relating to ambient noise, to minimise external acoustic interference.

[0061] Advantageously, the signal from the additional microphone can be used to determine external acoustic interference, by subtracting said signal from the signals obtained from the other microphones, thus providing for improved detection of acoustic vibrations relating to an arterial blockage. Since, stenosis sounds occur during diastole when flow in the coronary arteries is maximal and the heart valves are inactive, optionally, the device can be configured to extract repetitive aspects of the signal by the process of autocorrelation, where repetitive aspects of the signal can be identified and enhanced. Furthermore, the signal can optionally be broken into separate time segments and the autocorrelation applied to those segments which contain the stenotic signal.

[0062] Advantageously, the autocorrelation process provides a way to extract the weak signal of stenosis- associated sounds, for example coronary stenosis, from its stronger neighbours, for example respiratory sounds.

[0063] Optionally, the plurality of microphones and the plurality of accelerometers are bonded, for example soldered, to the flexible substrate.

[0064] Advantageously, this can provide that the device has improved conformity to the skin of a patient, to provide for improved contact of the sensors with the skin and hence improved sensing as well as the freedom to follow the weak acoustic movements associated with disturbed flow in the smaller and more deeply embedded coronary arteries. This can also provide that at least a portion of the device, for example the flexible substrate and the sensors arranged thereon, are reusable. This provides for a device with improved wearability and usability.

[0065] Optionally, the device further comprises an adhesive layer configured to removably attach the device to the skin of a patient, and the plurality of microphones and the plurality of accelerometers are arranged between the flexible substrate and the adhesive layer.

[0066] Advantageously, this can provide that the device has improved contact and conformity with the skin of a patient, to provide for improved contact of the sensors with the skin and hence improved sensing, and this can also provide that at least a portion of the device, for example the flexible substrate and the sensors arranged thereon, are reusable, whilst another portion of the device, for example the adhesive layer, is disposable, such that the device can be reused again with the same patient and / or different patients. This provides for a device with improved wearability and usability.

[0067] Optionally, the adhesive layer is configured to be disposable.

[0068] Optionally, the adhesive layer comprises an adhesive arranged on a film.

[0069] Optionally, the adhesive layer comprises double sided tape.

[0070] Optionally, the adhesive layer has a thickness of between about 0.1 mm to about 0.4mm, for example about 0.25mm. Advantageously, this can minimise acoustic losses.

[0071] Optionally, the flexible substrate has a thickness of between about 0.5mm to about 3mm, for example about 1 ,5mm.

[0072] Advantageously, this can minimise acoustic losses.

[0073] Optionally, the flexible substrate comprises a flexible non-conductive material, for example, a polymer or an elastomer.

[0074] Optionally, the flexible substrate comprises a polyimide film.

[0075] Optionally, the flexible substrate comprises a printed circuit board and a flexible core, and the flexible core comprises a polymer or an elastomer, for example a polyimide film.

[0076] According to a second aspect of the disclosure, there is provided a system for detecting an arterial blockage, the system comprising a device according to the first aspect of the disclosure, and a receiver module configured to communicate with the transmitter, to receive acoustic and movement sensing data therefrom.

[0077] Optionally, the system further comprises a computer, for example a laptop computer, configured to communicate with the receiver module

[0078] Optionally, the computer is configured to run data capture and logging software, for example, Nl Labview, AD Instruments Labchart or MathWorks MATLAB.

[0079] BRIEF DESCRIPTION OF THE DRAWINGS

[0080] The present disclosure may be carried out in various ways and embodiments of the disclosure will now be described by way of example with reference to the accompanying drawings, in which:

[0081] Figure 1 shows a cross-sectional view of a stenosed coronary artery;

[0082] Figure 2 shows a device for detecting an arterial blockage arranged on a patient’s chest over a coronary artery;

[0083] Figure 3 shows the device of Figure 2;

[0084] Figure 4 shows a side view of the device of Figure 2;

[0085] Figure 5 shows a receiver module;

[0086] Figure 6 shows a system for detecting an arterial blockage in a wired setting;

[0087] Figure 7 shows a system for detecting an arterial blockage in a wireless setting;

[0088] Figure 8 shows a system for detecting an arterial blockage in a wireless setting; Figure 9 shows an analog front-end architecture;

[0089] Figure 10 shows a plot illustrating the effect of position and flow rate on acoustic energy due to disturbed stenotic flow;

[0090] Figure 11 shows a plot illustrating the effect on microphone signal and accelerometer signal of increasing distance from a stenosis;

[0091] Figure 12 shows a plot illustrating positional information on microphones;

[0092] Figure 13 shows (a) a bottom view and (b) a top view of an alternative configuration of the flexible substrate of the device, wherein the flexible substrate is configured to form flexible arms;

[0093] Figure 14 shows a device for detecting an arterial blockage comprising the alternative configuration of the flexible substrate; and

[0094] Figure 15 shows a system for detecting an arterial blockage comprising the alternative configuration of the flexible substrate in a wireless setting.

[0095] DETAILED DESCRIPTION

[0096] Figure 1 shows a cross-sectional view of a stenosed coronary artery 1 . A stenosis 2 accumulated on the inner lining 3 of the artery 1 causes a narrowing in the artery 1 , resulting in an obstruction to the flow of blood inside the artery 1 . As such, the flow of blood is generally laminar upstream of the stenosis 2 in a first region 4a, and the flow of blood is then narrowed in a more downstream second region 4b in the vicinity of the stenosis 2. Downstream of the stenosis 2, in a third region 4c, the flow of blood is relatively disturbed and hence possibly turbulent, compared with in the generally laminar first region 4a. This results in shear and pressure waves 5 (see Figure 2) in the artery 1 , and emanating therefrom.

[0097] Figure 2 shows a device 6 for detecting an arterial blockage, for example a stenosis in a stenosed coronary artery 1 , applied to the chest 12 of a patient 13. The device 6 comprises a flexible substrate 11 on which a plurality of microphones 7a, 7b, 7c, 7d and a plurality of accelerometers 8a, 8b, 8c, 8d are arranged. The plurality of microphones 7a, 7b, 7c, 7d may hereinafter be collectively referred to as microphones 7, and similarly the plurality of accelerometers 8a, 8b, 8c, 8d may hereinafter be collectively referred to as accelerometers 8. The plurality of microphones 7a, 7b, 7c, 7d are configured to sense acoustic vibrations relating to an arterial blockage, i.e. in the example shown, to sense acoustic vibrations relating to the waves 5 caused by the stenosis 2. Similarly, the plurality of accelerometers 8a, 8b, 8c, 8d are configured to sense movement at the surface of the skin of the patient 13, said movement also relating to the waves 5 caused by the stenosis, and / or gross movement of the patient. The flexible substrate 11 is configured to conform to the skin 18 of a patient, for example, to their chest.

[0098] The plurality of microphones 7a, 7b, 7c, 7d and the plurality of accelerometers 8a, 8b, 8c, 8d are arranged in pairs to form a plurality of pairs of sensors 9a, 9b, 9c, 9d. In each pair 9a, 9b, 9c, 9d, a respective one of the plurality of microphones 7a, 7b, 7c, 7d is arranged adjacent to a respective one of the plurality of accelerometers 8a, 8b, 8c, 8d. That is, a first sensor pair 9a comprises a first microphone 7a arranged adjacent a first accelerometer 8a, a second sensor pair 9b comprises a second microphone 7b arranged adjacent a second accelerometer 8b, a third sensor pair 9c comprises a third microphone 7c arranged adjacent a third accelerometer 8c, and a fourth sensor pair 9d comprises a fourth microphone 7d arranged adjacent a fourth accelerometer 8d. While in the examples illustrated herein, each of the sensor pairs 9 comprises a microphone 7 and an accelerometer 8, it is alternatively envisaged that each of the sensor pairs 9 may alternatively comprise two sensors of any other suitable type, for example, two sensors selected from the group of microphones, accelerometers, ultrasonic, optical, electrical or impedance sensors. It is also envisaged that the microphones 7 and the accelerometers 8 need not necessarily be arranged in pairs, and that they may be arranged on the flexible substrate 11 in any other suitable layout or formation.

[0099] The pairs 9a, 9b, 9c, 9d are arranged to form an array of sensors. In each of the sensor pairs 9a, 9b, 9c, 9d, the respective microphones 7a, 7b, 7c, 7d and accelerometers 8a, 8b, 8c, 8d are arranged to be spaced apart from one another, for example by approximately 5mm. However, it is alternatively envisaged that the respective microphone 7a, 7b, 7c, 7d and accelerometer 8a, 8b, 8c, 8d may be arranged to abut one another. The sensor pairs 9a, 9b, 9c, 9d are spaced apart from one another by between about 5mm to about 40mm, for example by about 30mm.

[0100] In the example shown in Figure 2, four sensor pairs 9a, 9b, 9c, 9d are arranged in a 2x2 array to form an array of four sensors. However, it is also envisaged that the device 6 may comprise any other number of microphones 7a, 7b, 7c, 7d, accelerometers 8a, 8b, 8c, 8d, and / or pairs of sensors 9a, 9b, 9c, 9d, and that these may be arranged in any suitable configuration. For example, they may be arranged to form an array of any other size, for example a 2x4 array of eight sensor pairs or a 4x4 array of 16 sensor pairs. For example, Figure 3 shows an alternative embodiment of the device 6 in which there are eight sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, comprising eight microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and eight accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h respectively. The eight sensor pairs 9a, 9b, 9c, 9d are arranged in a 2x4 array. Figure 8 shows another embodiment of the device 6 in which there are sixteen sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, 9i, 9j, 9k, 9I, 9m, 9n, 9o, 9p arranged in a 4x4 array. Further details of the device 6 shall now be described with reference to the exemplary embodiment shown in Figure 3, although it is to be understood that said other details also apply to the other exemplary embodiments shown in Figures 1 , 2 and 8.

[0101] Advantageously, the device 6 can provide for an entirely non-invasive and less time consuming means for detecting arterial blockages. Such a device 6 is thus not only suitable for outpatient screening and in primary care settings, but also can be used to pre-screen symptomatic patients attending a specialist cardiology unit and identify patients with no CAD, so that these patients will therefore not need to undergo further costly investigations.

[0102] In particular, the combined advantage of sensing acoustic vibrations and movement at the surface of the skin of the patient by the combination of microphones 7 and accelerometers 8 is that sensing both acoustics and movements can provide a sufficient level of information to not only identify the presence of a stenosis, but also to localise the position, size and / or shape of the stenosis. Also, whether the stenosis is symmetrical or non-symmetrical can also be determined.

[0103] Additionally, the sensed data from the microphones 7 and accelerometers 8 can be complementary. For example, the accelerometers 8 can reveal gross movements of the patient which could also give rise to microphone 7 artefacts, thus identifying them as artefacts and advantageously allowing them to be ignored, which could be particularly useful for longer term measurements where patient movement is more likely. Furthermore, the use of a plurality of microphones 7 and a plurality of accelerometers 8 as a plurality of sensor pairs 9 provides that simultaneous measurements can be taken using different sensors 7, 8 in fixed positions, which makes the exploitation of multiple measurement sites more reliable, compared with taking measurements at different locations at time intervals using the same sensors. Furthermore, this advantageously provides for increased location accuracy in stenosis detection.

[0104] The accelerometers 8 are configured to sense movement in a direction perpendicular and / or parallel to the skin of a patient. Advantageously, data obtained by sensing movement in a direction parallel to the surface of the skin of a patient, i.e. sensing shear acceleration, can be used with models for predicting shear waves generated by a stenosis in order to identify an arterial blockage. In order to sense movement in at least one of a direction perpendicular or parallel to the patient’s skin, each of the accelerometers 8 may be a 1 axis accelerometer. However, it is also envisaged that each of the accelerometers may advantageously be a 2 axis or 3 axis accelerometer. As such, the accelerometers 8 may each be configured to sense movement in at least one direction, or more preferably, in at least two directions. As an example, each of the accelerometers may be an ADXL335 accelerometer.

[0105] In order to sufficiently detect the acoustic vibrations and movement at the surface of the skin of the patient due to coronary stenosis, which are typically relatively weak, the microphones 7 and accelerometers 8 are required to have an appropriate sensitivity. For example, each of the accelerometers 8 may have a sensitivity rating of between about 270mV / g to about 330mV / g, for example about 300mV / g. Each of the plurality of microphones 7 may have a sensitivity rating of between about -41dBV / Pa to about -35dBV / Pa, for example about -38dBV / Pa. Advantageously, this can provide for improved detection of the movements and sounds due to coronary stenosis. Each of the microphones may have a signal to noise ratio of between about 50dB to about 70dB, for example about 63dB.

[0106] Optionally, as shown in Figure 3, the device 6 further comprises an additional microphone 19 configured to sense acoustic vibrations relating to ambient noise, to minimise external acoustic interference. Advantageously, the signal obtained from the additional microphone 19 can be used to determine external acoustic interference, by subtracting said signal from the signals obtained from the other microphones, thus providing for improved detection of acoustic vibrations relating to an arterial blockage. With further reference to Figure 3, the flexible substrate 11 is a patch comprising a printed circuit board (PCB) 14 and a flexible core 15. The flexible core 15 comprises a flexible non-conductive material such as a polymer or an elastomer, for example a polyimide film. The microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and the accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h are bonded, for example soldered, onto the flexible substrate 11 , to form a reusable portion of the device 6. Advantageously, this provides that the device 6 has improved conformity to the skin of a patient, to provide for improved contact of the sensors with the skin and hence improved sensing, thus increasing wearability and usability. The flexible substrate 1 1 may have a thickness of between about 0.5mm to about 3mm, for example about 1 ,5mm, which can advantageously minimise acoustic losses.

[0107] As shown in Figure 4, the device 6 further comprises an adhesive layer 17 configured to removably attach the device 6 to the skin 18 of a patient 13. The sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h and hence the microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and the accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h are arranged between the flexible substrate 11 and the adhesive layer 17. That is, the flexible substrate 1 1 is arranged further away from the skin than the adhesive layer 17. The adhesive layer 17 is configured to be removable and disposable, such that a new adhesive layer 17 may be applied, so that the device 6 may be reused again with the same patient 13 and / or with a different patient 13. The adhesive layer 17 may, for example, comprise an adhesive arranged on a film, and / or may comprise a double sided tape. The adhesive layer 17 may have a thickness of between about 0.1 mm to about 0.4mm, for example about 0.25mm, which can advantageously minimise acoustic losses.

[0108] Referring back to Figure 2, the device 6 further comprises a transmitter unit 10 arranged proximate a side of the flexible substrate 11 . The transmitter unit 10 comprises a transmitter, for example a Zigbee transmitter or a Bluetooth transmitter, configured to communicate with a receiver module 20 (see Figure 5), and a power supply configured to power the microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h, the accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h and the transmitter. For example, the power supply may comprise a miniature lithium ion battery. Optionally, the transmitter unit 10 may comprise a USB port or other port for charging the battery, and / or an analog to digital converter configured to digitise the analog signals originating from an output of the analog front-end architecture. A field programmable gate array may be provided to control the communication between the analog to digital converter and the transmitter. The transmitter unit 10 may be configured to be reusable.

[0109] Arranged on a side of the flexible substrate 11 are one or more analog output connectors 16 (see Figure 3), for connecting the transmitter unit 10 to the flexible substrate, so that the transmitter unit 10 can receive data from the microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and the accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h. As shown in Figures 9 and 10, one or more cables 21 , for example jumper cables, connect the analog outputs 16 of the flexible substrate 1 1 to analog inputs 23 of the transmitter unit 10.

[0110] The transmitter of the transmitter unit 10 is configured to communicate with the receiver module 20, an example of which is shown in Figure 5, to transmit data recorded by the microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and the accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h to the receiver module 20. It is envisaged that the transmitter may be configured to communicate with the receiver module 20 via a wired or wireless connection between the transmitter unit 10 and the receiver module 20. In the example shown in Figure 6, the transmitter unit 10 is connected to the receiver module 20 via one or more cables 22, for example an HDMI cable, to form a wired connection, and the receiver module 20 communicates with a nearby (for example about 5 metres from the patient) laptop computer 26 via serial communication. In the example shown in Figure 7, the transmitter unit 10 comprises an antenna 24 for communicating with the receiver module 20 via a wireless connection 25, and the receiver module 20 communicates with a nearby (for example about 5 metres from the patient) laptop computer 26 via serial communication. The data may be analysed and processed on the laptop computer, which may for example be running standard data capture and logging software, for example; Nl Labview, AD Instruments Labchart or MathWorks MATLAB. Another example of a system with a wireless connection is similarly shown in Figure 8.

[0111] Since the sounds due to coronary stenosis are weak, sensitive microphones and accelerometers are required. Thus, low noise electronics are required in order to successfully detect, amplify and pre- process the acoustic signals in the analog domain before converting them into digital form. Thus, to meet the requirements for acoustic data acquisition, the transmitter unit 10 further comprises an analog front-end architecture 27, an example of which is shown in Figure 9. The analog front-end architecture 27 has a bandwidth of between about 0.5Hz to 500 Hz and comprises a first stage 28, a second stage 29, and a third stage 30.

[0112] The first stage 28 is a differential pre-amplification (x100) stage with high-pass characteristics, designed using a low-noise instrumentation amplifier and a high-precision operational amplifier. The second stage 29 is an active, first order high-pass filter that enhances the DC offset rejection capabilities of the analog front-end architecture 27 and introduces an additional gain (x10) in order to better exploit the full-scale voltage range of the subsequent analog-digital-converter block (±2.5V). The third stage 30 is a passive, second order low-pass filter that defines the passband of the analog front-end architecture 27 and also serves as an anti-alias filter for the analog-digital-converter block that follows in the signal chain.

[0113] Figure 10 shows a representative area under a FFT (Fast Fourier Transform) plot, showing the effect of position and flow rate on acoustic energy due to disturbed stenotic flow. The results shown in Figure 10 were obtained by a frequency domain analysis of the received signal at the skin surface, directly above and at two positions downstream of a stenosis. Data set 31 shows data from a received signal measured directly above the stenosis. Data set 32 shows data from a received signal measured 1 ,5cm downstream of the stenosis. Data set 33 shows data from a received signal measured 3cm downstream of the stenosis. The data shows that in the frequency range of 390-400Hz, the energy of the signal (with respect to the no flow condition) increases with increasing distance from the stenosis up to 3cm and that at frequencies above 100Hz there is an increase in energy with increasing flow rate. Thus, these results clearly show the presence of disturbed flow associated with a stenosis, and demonstrate that the device 6 is able to detect this.

[0114] Similarly, Figure 11 also shows data sets 31 , 32 and 33 taken from received signals measured directly above a stenosis, 1 ,5cm downstream of a stenosis, and 3cm downstream of a stenosis respectively. As shown, the microphone signal obtained from microphones 7 generally increases with increasing distance from the stenosis, while a contrasting pattern is shown in the signals obtained from accelerometers 8.

[0115] Figure 12 shows further, more detailed positional information obtained in experimental data for the microphones 7. At frequencies below 200Hz, signals measured downstream of the stenosis were found to be weaker than those measured at the stenosis, whereas at frequencies above 200Hz, signals measured downstream of the stenosis were found to be stronger than those measured at the stenosis. Thus, a positional signature can be determined through acoustic measurement at multiple locations on the patient, i.e. at multiple locations relative to the position of the stenosis, through the use of the plurality of microphones 7, so that the position of the stenosis can be determined.

[0116] During use of the device 6, measurements may, for example, be taken for between 30 and 60 seconds for each sensor type, thus for around a maximum of 2 minutes in total in maximum (for example, up to 60 seconds for the microphones and up to 60 seconds for the accelerometers). Each sensor type may be configured to capture between around 10 to 20 heartbeats, and thus take measurements for a minimum of about 20-30 seconds. It is envisaged that the device 6 may be worn and used for any appropriate amount of time ranging from about a few hours up to a few days, for continuous monitoring of a patient. Advantageously, this could be very useful for monitoring the effect of treatment, particularly in the short term.

[0117] Figure 13 shows an alternative configuration for the flexible substrate 11 that can also be used as part of a device 6 for detecting an arterial blockage, for example a stenosis in a stenosed coronary artery 1 , wherein the flexible substrate 11 is configured to form flexible arms 34. Figure 13(a) shows a view of the bottom, i.e. skin side, of the flexible substrate 11 wherein a plurality of microphone ports 35a, 35b, 35c, 35d, 35e, 35f, 35g, 35h are arranged, while Figure 13 (b) shows a view of the top of the flexible substrate 11. The flexible substrate 11 is a patch comprising a printed circuit board (PCB) 14, and optionally a flexible core 15, on which a plurality of microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and a plurality of accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h are arranged. The plurality of microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h may hereinafter be collectively referred to as microphones 7, and similarly the plurality of accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h may hereinafter be collectively referred to as accelerometers 8. The flexible core 15 can comprise a flexible non-conductive material such as a polymer or an elastomer, for example a polyimide film. Optionally, an adhesive layer can be used, as discussed in relation to Figure 4, above. The microphones 7 and the accelerometers 8 are bonded, for example soldered, onto the flexible substrate 11 , to form a reusable portion of the device 6. Advantageously, this provides that the device 6 has improved conformity to the skin of a patient, to provide for improved contact of the sensors with the skin and hence improved sensing, thus increasing wearability and usability. The flexible substrate 11 may have a thickness of between about 0.5mm to about 3mm, for example about 1 ,5mm, which can advantageously minimise acoustic losses.

[0118] Arranged on a side of the flexible substrate 11 are one or more analog output connectors 16, for connecting the transmitter unit 10 to the flexible substrate 11 , so that the transmitter unit 10 can receive data from the microphones 7 and the accelerometers 8.

[0119] The plurality of microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and the plurality of accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h can be arranged in pairs to form a plurality of pairs of sensors 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, which may hereinafter be collectively referred to as sensor pairs 9. In each pair 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, a respective one of the plurality of microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h can be arranged adjacent to a respective one of the plurality of accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h. That is, a first sensor pair 9a comprises a first microphone 7a arranged adjacent a first accelerometer 8a, a second sensor pair 9b comprises a second microphone 7b arranged adjacent a second accelerometer 8b, a third sensor pair 9c comprises a third microphone 7c arranged adjacent a third accelerometer 8c, and a fourth sensor pair 9d comprises a fourth microphone 7d arranged adjacent a fourth accelerometer 8d, a fifth sensor pair 9e comprises a fifth microphone 7e arranged adjacent a fifth accelerometer 8e, a sixth sensor pair 9f comprises a sixth microphone 7f arranged adjacent a sixth accelerometer 8f, a seventh sensor pair 9g comprises a seventh microphone 7g arranged adjacent a seventh accelerometer 8g, and an eighth sensor pair 9h comprises an eighth microphone 7h arranged adjacent a eighth accelerometer 8h. While in the examples illustrated herein, each of the sensor pairs 9 comprises a microphone 7 and an accelerometer 8, it is alternatively envisaged that each of the sensor pairs 9 may alternatively comprise two sensors of any other suitable type, for example, two sensors selected from the group of microphones, accelerometers, ultrasonic, optical, electrical or impedance sensors. It is also envisaged that the microphones 7 and the accelerometers 8 need not necessarily be arranged in pairs, and that they may be arranged on the flexible substrate 11 in any other suitable layout or formation.

[0120] In the example shown in Figure 13, the flexible substrate is configured to form flexible arms 34, wherein each sensor pair 9 is located on a separate flexible arm. That is, the first sensor pair 9a is located on a first flexible arm 34a, the second sensor pair 9b is located on a second flexible arm 34b, the third sensor pair 9c is located on a third flexible arm 34c, the fourth sensor pair 9d is located on a fourth flexible arm 34d, the fifth sensor pair 9e is located on a fifth flexible arm 34e, the sixth sensor pair 9f is located on a sixth flexible arm 34f, the seventh flexible pair 9g is located on a seventh flexible arm 34g, and the eighth sensor pair 9h is located on an eighth flexible arm 34h. The flexible arms 34 are configured so that the sensor pairs 9 are arranged to form an array of sensors. Optionally, the flexible arms can be straight or bent. In each of the sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h the respective microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h are arranged to be spaced apart from one another, for example by approximately 5mm. However, it is alternatively envisaged that the respective microphone 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h and accelerometer 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h may be arranged to abut one another. The sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h can be spaced apart from one another by between about 5mm to about 40mm, for example by about 30mm.

[0121] In the example shown in Figure 13, eight sensor pairs 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h are arranged on eight flexible arms so that they form a 2x4 array of eight sensors. However, it is also envisaged that the device 6 may comprise any other number of flexible arms, microphones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h accelerometers 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h and / or pairs of sensors 9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, and that these and the flexible arms 34 on which they are located may be arranged in any suitable configuration. For example, they may be arranged to form a 4x4 array of 16 sensor pairs.

[0122] Optionally, as shown in Figure 13, the device 6 further comprises an additional microphone 19 configured to sense acoustic vibrations relating to ambient noise, to minimise external acoustic interference. Advantageously, the signal obtained from the additional microphone 19 can be used to determine external acoustic interference, by subtracting said signal from the signals obtained from the other microphones, thus providing for improved detection of acoustic vibrations relating to an arterial blockage.

[0123] Advantageously, having the sensor pairs 9 mounted on flexible arms 34 allows the sensor pairs 9 to follow small skin movements with less resistance as well as to let the flexible substrate 11 conform more closely and easily to the curvature of the skin of the patient 13.

[0124] Figures 14 and 15 show a device 6 for detecting an arterial blockage, for example a stenosis in a stenosed coronary artery 1 , wherein the flexible substrate 11 is configured to form flexible arms 34. The device 6 further comprises a transmitter unit 10 arranged proximate a side of the flexible substrate 11 . The transmitter unit 10 comprises a transmitter, for example a Zigbee transmitter or a Bluetooth transmitter, configured to communicate with a receiver module 20, and a power supply configured to power the microphones 7, the accelerometers 8 and the transmitter. For example, the power supply may comprise a miniature lithium ion battery. Optionally, the transmitter unit 10 may comprise a USB port or other port for charging the battery, and / or an analog to digital converter configured to digitise the analog signals originating from an output of the analog front-end architecture. A field programmable gate array may be provided to control the communication between the analog to digital converter and the transmitter. The transmitter unit 10 may be configured to be reusable. Arranged on a side of the flexible substrate 11 are one or more analog output connectors 16, for connecting the transmitter unit 10 to the flexible substrate, so that the transmitter unit 10 can receive data from the microphones 7 and the accelerometers 8. One or more cables 21 , for example jumper cables, connect the analog outputs 16 of the flexible substrate 11 to analog inputs 23 (see Figure 15) of the transmitter unit 10.

[0125] The transmitter of the transmitter unit 10 is configured to communicate with the receiver module 20, to transmit data recorded by the microphones 7 and the accelerometers 8 to the receiver module 20. It is envisaged that the transmitter may be configured to communicate with the receiver module 20 via a wired connection, for example an HDMI cable, or wireless connection between the transmitter unit 10 and the receiver module 20. In the example shown in Figure 15, the transmitter unit 10 comprises an antenna 24 for communicating with the receiver module 20 via a wireless connection 25, and the receiver module 20 communicates with a nearby (for example about 5 metres from the patient) laptop computer 26 via serial communication. The data may be analysed and processed on the laptop computer, which may for example be running standard data capture and logging software, for example, Nl Labview, AD Instruments Labchart or MathWorks MATLAB.

[0126] Various modifications may be made to the described embodiment(s) without departing from the scope of the invention as defined by the accompanying claims.

[0127] CLAUSES

[0128] Clause 1 A device for detecting an arterial blockage, the device comprising: a flexible substrate configured to conform to the skin of a patient; a plurality of microphones arranged on the flexible substrate for sensing acoustic vibrations relating to an arterial blockage; and a plurality of accelerometers arranged on the flexible substrate for sensing movement at the surface of the skin of the patient.

[0129] Clause 2 A device according to clause 1 , wherein the device comprises a plurality of pairs of sensors, each of the pairs of sensors comprising one of said plurality of microphones and one of said plurality of accelerometers arranged adjacent to one another.

[0130] Clause 3 A device according to clause 2, wherein the plurality of pairs of sensors are arranged to form an array of pairs of sensors.

[0131] Clause 4 A device according to clause 3, wherein the plurality of pairs of sensors comprise 8 pairs of sensors arranged in a 2x4 array, or 16 pairs of sensors arranged in a 4x4 array.

[0132] Clause 5 A device according to any of clauses 2 to 4, wherein in each of the pairs of sensors, the respective microphone and accelerometer are arranged to be spaced apart from one another, for example by approximately 5mm.

[0133] Clause 6 A device according to any of clauses 2 to 4, wherein in each of the pairs of sensors, the respective microphone and accelerometer are arranged to abut one another.

[0134] Clause 7 A device according to any of clauses 2 to 6, wherein the pairs of sensors are spaced apart from one another by between about 5mm to about 40mm, for example by about 30mm.

[0135] Clause 8 A device according to any preceding clause, wherein the device further comprises a transmitter unit comprising a transmitter configured to communicate with a receiver module, and a power supply configured to power the plurality of microphones, the plurality of accelerometers, and the transmitter.

[0136] Clause 9 A device according to clause 8, wherein the transmitter unit is arranged on a side of the flexible substrate.

[0137] Clause 10 A device according to clause 8 or clause 9, wherein the transmitter unit further comprises an analog front-end architecture for detecting, amplifying and pre-processing signals from the microphones and accelerometers before converting said signals into digital form, the analog front-end architecture configured to provide a bandwidth of between about 0.5Hz to 500Hz and comprising: a first stage configured as a differential pre-amplification stage with high pass characteristics; a second stage comprising an active, first order high pass filter; and a third stage comprising a second order low pass filter.

[0138] Clause 11 A device according to clause 10, wherein the differential pre-amplification first stage comprises an amplification of x100, and comprises a low-noise instrumentation amplifier and a high-precision operational amplifier.

[0139] Clause 12 A device according to clause 10 or clause 11 , wherein the second stage is configured to enhance the DC offset rejection capabilities of the analog front-end architecture and to introduce an additional gain of x10.

[0140] Clause 13 A device according to any of clauses 10 to 12, wherein the second order low pass filter of the third stage is configured to define the passband of the analog front-end architecture and serve as an anti-alias filter.

[0141] Clause 14 A device according to any preceding clause, wherein each of the plurality of accelerometers is configured to sense movement in a direction perpendicular to the surface of the skin of a patient and / or in a direction parallel to the surface of the skin of a patient.

[0142] Clause 15 A device according to any preceding clause, wherein each of the plurality of accelerometers is a 3 axis accelerometer.

[0143] Clause 16 A device according to any preceding clause, wherein each of the plurality of accelerometers has a sensitivity rating of between about 270mV / g to about 330mV / g, for example about 300mV / g.

[0144] Clause 17 A device according to any preceding clause, wherein each of the plurality of microphones has a sensitivity rating of between about -41dBV / Pa to about -35dBV / Pa, for example about -38dBV / Pa.

[0145] Clause 18 A device according to any preceding clause, wherein each of the plurality of microphones has a signal to noise ratio of between about 50dB to about 70dB, for example about 63dB.

[0146] Clause 19 A device according to any preceding clause, wherein the device further comprises an additional microphone configured to sense acoustic vibrations relating to ambient noise, to minimise external acoustic interference.

[0147] Clause 20 A device according to any preceding clause, wherein the plurality of microphones and the plurality of accelerometers are bonded, for example soldered, to the flexible substrate. Clause 21 A device according to any preceding clause, wherein the device further comprises an adhesive layer configured to removably attach the device to the skin of a patient, wherein the plurality of microphones and the plurality of accelerometers are arranged between the flexible substrate and the adhesive layer.

[0148] Clause 22 A device according to clause 21 , wherein the adhesive layer has a thickness of between about 0.1 mm to about 0.4mm, for example about 0.25mm.

[0149] Clause 23 A device according to any preceding clause, wherein the flexible substrate has a thickness of between about 0.5mm to about 3mm, for example about 1 ,5mm.

[0150] Clause 24 A device according to any preceding clause, wherein the flexible substrate comprises a printed circuit board and a flexible core, wherein the flexible core comprises a polymer or an elastomer, for example a polyimide film.

[0151] Clause 25 A system for detecting an arterial blockage, the system comprising a device according to any of clauses 8 to 13, and a receiver module configured to communicate with the transmitter, to receive acoustic and movement sensing data therefrom.

Claims

CLAIMS1 . A device for detecting an arterial blockage, the device comprising: a flexible substrate configured to conform to the skin of a patient; a plurality of microphones arranged on the flexible substrate for sensing acoustic vibrations relating to an arterial blockage; and a plurality of accelerometers arranged on the flexible substrate for sensing movement at the surface of the skin of the patient.

2. A device as claimed in claim 1 , wherein the device comprises a plurality of pairs of sensors, each of the pairs of sensors comprising one of said plurality of microphones and one of said plurality of accelerometers arranged adjacent to one another.

3. A device as claimed in claim 2, wherein the plurality of pairs of sensors are arranged to form an array of pairs of sensors.

4. A device as claimed in claim 3, wherein the plurality of pairs of sensors comprise 8 pairs of sensors arranged in a 2x4 array, or 16 pairs of sensors arranged in a 4x4 array.

5. A device as claimed in any of claims 2 to 4, wherein in each of the pairs of sensors, the respective microphone and accelerometer are arranged to be spaced apart from one another, for example by approximately 5mm.

6. A device as claimed in any of claims 2 to 4, wherein in each of the pairs of sensors, the respective microphone and accelerometer are arranged to abut one another.

7. A device as claimed in any of claims 2 to 6, wherein the pairs of sensors are spaced apart from one another by between about 5mm to about 40mm, for example by about 30mm.

8. A device as claimed in any of claims 2 to 7, wherein the flexible substrate is configured to form flexible arms.

9. A device as claimed in claim 8, wherein each of the pairs of sensors is located on a flexible arm of the flexible substrate.

10. A device as claimed in claim 9, wherein the plurality of pairs of sensors comprise 8 pairs of sensors arranged on 8 flexible arms of the substrate in a 2x4 array.11 . A device as claimed in any of the preceding claims, wherein the device further comprises a transmitter unit comprising a transmitter configured to communicate with a receiver module, anda power supply configured to power the plurality of microphones, the plurality of accelerometers, and the transmitter.

12. A device as claimed in claim 11 , wherein the transmitter unit is arranged on a side of the flexible substrate.

13. A device as claimed in claim 11 or claim 12, wherein the transmitter unit further comprises an analog front-end architecture for detecting, amplifying and pre-processing signals from the microphones and accelerometers before converting said signals into digital form, the analog front-end architecture configured to provide a bandwidth of between about 0.5Hz to 500Hz and comprising: a first stage configured as a differential pre-amplification stage with high pass characteristics; a second stage comprising an active, first order high pass filter; and a third stage comprising a second order low pass filter.

14. A device as claimed in claim 13, wherein the differential pre-amplification first stage comprises an amplification of x100, and comprises a low-noise instrumentation amplifier and a high- precision operational amplifier.

15. A device as claimed in claim 13 or claim 14, wherein the second stage is configured to enhance the DC offset rejection capabilities of the analog front-end architecture and to introduce an additional gain of x10.

16. A device as claimed in any of claims 13 to 15, wherein the second order low pass filter of the third stage is configured to define the passband of the analog front-end architecture and serve as an anti-alias filter.

17. A device as claimed in any of the preceding claims, wherein each of the plurality of accelerometers is configured to sense movement in a direction perpendicular to the surface of the skin of a patient and / or in a direction parallel to the surface of the skin of a patient.

18. A device as claimed in any of the preceding claims, wherein each of the plurality of accelerometers is a 3 axis accelerometer.

19. A device as claimed in any of the preceding claims, wherein each of the plurality of accelerometers has a sensitivity rating of between about 270mV / g to about 330mV / g, for example about 300mV / g.

20. A device as claimed in any of the preceding claims, wherein each of the plurality of microphones has a sensitivity rating of between about -41 dBV / Pa to about -35dBV / Pa, for example about - 38dBV / Pa.21 . A device as claimed in any of the preceding claims, wherein each of the plurality of microphones has a signal to noise ratio of between about 50dB to about 70dB, for example about 63dB.

22. A device as claimed in any of the preceding claims, wherein the device further comprises an additional microphone configured to sense acoustic vibrations relating to ambient noise, to minimise external acoustic interference.

23. A device as claimed in any of the preceding claims, wherein the plurality of microphones and the plurality of accelerometers are bonded, for example soldered, to the flexible substrate.

24. A device as claimed in any of the preceding claims, wherein the device further comprises an adhesive layer configured to removably attach the device to the skin of a patient, wherein the plurality of microphones and the plurality of accelerometers are arranged between the flexible substrate and the adhesive layer.

25. A device as claimed in claim 24, wherein the adhesive layer has a thickness of between about 0.1 mm to about 0.4mm, for example about 0.25mm.

26. A device as claimed in any of the preceding claims, wherein the flexible substrate has a thickness of between about 0.5mm to about 3mm, for example about 1 ,5mm.

27. A device as claimed in any of the preceding claims, wherein the flexible substrate comprises a printed circuit board and a flexible core, wherein the flexible core comprises a polymer or an elastomer, for example a polyimide film.

28. A system for detecting an arterial blockage, the system comprising a device as claimed in any of claims 11 to 16, and a receiver module configured to communicate with the transmitter, to receive acoustic and movement sensing data therefrom.

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