Wearable medical device with stress sensor

Abstract

Disclosed are devices, systems, and methods for ex vivo monitoring of internal mechanical stress associated with physiological phenomena of an internal body structure, such as the heart, lungs and / or gastrointestinal tract, from outside the body of a host. The disclosed devices, systems, and methods include a mechanical stress sensor for monitoring internal physiological phenomena from outside the host's body.

Description

Docket No.: CANA.476PCWEARABLE MEDICAL DEVICE WITH STRESS SENSORCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] All applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference.TECHNICAL FIELD

[0002] This patent document relates generally to health monitoring techniques and devices including devices having a physical stress sensor such as wearable medical devices capable of detecting and distinguishing internal mechanical energy associated with physiological phenomena originating within the host.BACKGROUND

[0003] According to the World Health Organization (WHO), cardiovascular diseases are among the leading causes of death globally, resulting in an estimated 17.9 million lives lost each year. In the United States, heart disease is the leading cause of death, with coronary artery disease (CAD) being the most pernicious class by causing decreased blood flow to the heart that often leads to a heart attack. CAD and other heart valve diseases, like mitral valve prolapse (MVP) and mitral valve regurgitation (MVR), are silent killers because persons typically do not know the existence of their underlying heart problems and therefore are not diagnosed until the person experiences signs or symptoms of a heart attack, heart failure, or an arrhythmia— which may be too late to survive or recover with a reasonable quality of life. Even now, a person must typically have a secondary medical condition, such as diabetes or obesity, or be identified with one or more significant risk factors, such as high blood pressure, high cholesterol, high alcohol use, or smoking, for the physician to initiate a round of testing and remote monitoring of the person's heart. This is because there is not an accessible, uncomplicated, and affordable device or technique to observe and track a person's heart function.

[0004] Presently, examination of heart function to potentially diagnose heart disease is limited to the clinical environment. Typically, a patient would undergo a variety of different tests, including analyte testing from blood samples; imaging such as a chest X-ray, CT-scan, or magnetic resonance imaging (MRI) of the heart; and physiological signal monitoring, such as an electrocardiogram (ECG or EKG), which are electrical signal recordings of the heart thatDocket No.: CANA.476PCcan indicate heart rate and detect irregular heartbeats when monitored remotely (e.g., by a Holter monitor), or an echocardiogram, which is a noninvasive sound signal monitoring technique used to create images of the heart and blood in motion. Moreover, patients are only prescribed such tests after experiencing an acute or emergency medical treatment, such as cardiac arrest, stroke, severe dizziness or unconsciousness, or extreme chest pain.

[0005] To date, there have been some advancements in remote monitoring to begin turning the tide against heart disease. For instance, wearable heart rate monitors are becoming a ubiquitous option for tracking heart rate during exercise or daily activity, monitoring stress and movement levels, tracking sleep habits at night, and in some versions of these wearable devices, testing certain vital signs outside of the clinic, such as ECG to determine singular heart rhythm events, such as a healthy sinus rhythm or risky atrial fibrillation. While these devices are well suited to promote healthier active lifestyles that may contribute to preventing the onset of heart disease or mitigating minor-to-moderate heart disease in the long run, they are ill equipped to identify symptoms or hallmarks of the vast array of heart diseases and incapable of determining any underlying biological or physiological factors at the root of heart disease.

[0006] The challenge for clinicians is to catch heart disease early or manage and monitor diagnosed heart disease post-treatment. Yet, monitoring heart function relies on patient participation and compliance; and existing systems and methods are too time intensive, costly, and under-resourced to be effective.

[0007] There is a need for a new paradigm of health monitoring sensors wearable by a patient user and capable of monitoring mechanical energy associated with physiological phenomena, such as blood flow across a valve of the heart, to characterize overall heart function.SUMMARY

[0008] In brief, in one aspect disclosed are devices, systems, and methods for monitoring of internal mechanical stress (also referred to as physical stress) associated with physiological phenomena of an internal body structure, such as the heart, lungs and / or gastrointestinal tract, measured from outside the host. The disclosed devices, systems, and methods include a wearable or ex vivo physical stress sensor to be worn on the host's body. Herein, the terms "wearable" and "ex vivo" may be used interchangeably. The wearable physical stress sensor may be configured in a device structure that is easily securable to a selected region or portionDocket No.: CANA.476PCof the host's body. The wearable sensor may be used to obtain information about the host and optionally the sole use of the wearable sensor is to obtain that information. Optionally, the wearable device may be physically associated with or connected to a therapeutically effective device. The information may be useful in understanding the medical condition of the host, where the device may, as examples, detect and / or quantify and / or characterize and / or monitor and / or diagnose a health and / or disease state of the host who is wearing the sensor, e.g., wearing a device that includes the sensor.

[0009] The ex vivo physical stress sensor is a component of a wearable medical device for monitoring a mechanical stress originating from with a host, the host being the subject wearing the ex vivo physical stress sensor. In some embodiments, the ex vivo physical stress sensor may be configured in a device structure that is hermetically sealed, biocompatible, and sterile; yet, the ex vivo stress sensor does not necessarily need to be hermetically sealed, biocompatible, and / or sterile when interfaced with the outside of the host's body. In some embodiments, the device containing the ex vivo physical stress sensor, e.g., a wearable medical device for monitoring mechanical stress originating from within a host, includes a housing able to securely attach to a region or location outside of the host's body. The outside skin surface of the host is a region or location outside of the host's body. For example, the device may be secured to the skin on the person's chest or back. The housing is securely attached when it effectively maintains its location while the host moves during normal daily activities, such that, for example, the ex vivo stress sensor portion of the housing maintains significant contact with the outside skin of the host during normal daily activities.

[0010] In some implementations of the disclosed ex vivo physical stress sensor technology, mechanical energy associated with a physiological phenomenon or phenomena, such as mechanical waves, is involuntarily generated by an anatomical structure or structures of the host that emanate internally within the host's body and are detectable, from outside the host's body, by the ex vivo physical stress sensor as an applied mechanical force or moment that transduces the mechanical stress into an electrical signal corresponding to one or more parameters of the mechanical energy, which are analyzed to determine information about the physiological phenomenon or phenomena that occurred in the host.

[0011] For example, the source of the mechanical wave may be associated with movement of tissue within the host. Also, for example, the source of the mechanical wave may be associated with the movement of fluid within the host. Also, for example, the sourceDocket No.: CANA.476PCof the mechanical wave may be associated with the movement of liquid within the host. Also, for example, the source of the mechanical wave may be associated with the movement of gas within the host. In some implementations, the source of the mechanical wave is an organ. In some implementations, the organ can include the heart, lungs, and / or gastrointestinal tract of the patient. In some implementations, the organ can include the small and / or large intestines, stomach, or other gastrointestinal organ of the host. In some implementations, for example, mechanical energy originating within the body are generated by pressure changes, blood and air flow, and the mechanical motion of organs and tissues. Examples of mechanical waves detectable by the ex vivo physical stress sensor of the present technology can be turbulent flow of fluids, such as air flow in / out of the lungs or blood flow in structures of the heart or the vasculature, or the impulses from motion / movement of the heart structures (e.g., valves).

[0012] In some embodiments in accordance with the present technology, the disclosed ex vivo physical stress sensor technology provides a wearable medical device (WMD) which can be used to characterize mechanical waves generated by the host, e.g., the frequency, intensity, duration, number, and / or quality of a mechanical wave. In some embodiments in accordance with the present technology, the disclosed ex vivo physical stress sensor technology provides a method that includes measuring internal mechanical energy as stress, via a transducing element of a wearable sensor positioned outside the host's body, to characterize a physiological phenomenon occurring within the host's body, and using the measured stress data to diagnose and / or detect and / or quantify a health and / or disease state of the host, e.g., the cardiac health of the host including information about the host's heart disease state, and / or the respiratory health of the host. Thus, the disclosed methods may include monitoring mechanical energy from cardiac function, e.g., heart health or disease, for some embodiments, while in the same or other embodiments, the disclosed methods monitoring mechanical energy from pulmonary function, e.g., respiration, for some embodiments.

[0013] In some implementations of the disclosed ex vivo physical stress sensor technology, an inertial measurement unit (IMU), capable of monitoring movement parameters, may be included in the wearable medical device for detecting, monitoring, and / or quantifying heart disease of the host, such as a valvular disease selected from stenosis, incontinence, and myxomatous, where the valvular disease is associated with a valve selectedDocket No.: CANA.476PCfrom tricuspid, pulmonary, pulmonic, mitral and aortic, e.g., the medical condition may be myxomatous mitral valve disease, congestive heart failure, atrial fibrillation; and coronary artery disease, as examples. In some implementations of the disclosed ex vivo physical stress sensor technology, an IMU, capable of monitoring movement parameters, is included in the wearable medical device for detecting, monitoring, and / or quantifying respiratory conditions of the host, including but not limited to pulmonary disease, chronic obstructive pulmonary disease (COPD, a condition involving constriction of the airways and difficulty or discomfort in breathing), sleep apnea, emphysema, pulmonary embolism (PE), and asthma. These are examples of respiratory quality that may be evaluated by way of the devices and methods of the present technology.

[0014] In some aspects a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable medical device includes a housing able to securely attach to a region or location outside of the host's body; and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure. In some embodiments the wearable medical device is configured fora short duration of use comprising a plurality of days or weeks up to four weeks to continuously monitor one or more health parameters of the host, without requiring patient compliance by the host for the wearable medical device to monitor one or more health parameters. In some embodiments, the wearable medical device is configured for a long duration of use comprising a plurality of months or years up to three years to continuously monitor one or more health parameters of the host. In some embodiments, the physical stress sensor of the wearable medical device includes a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

[0015] In some embodiments, a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable device includes a housing ableDocket No.: CANA.476PCto securely attach to a region or location of the host's body; a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing; and at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host, wherein the at least one secondary sensor comprises an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, the electrophysiological sensor comprising an electrocardiogram (ECG) sensor.

[0016] Optionally, in addition to the ECG sensor, the at least one secondary sensor of the device may further comprise an inertial measurement unit (IMU). The IMU may be configured to detect motion of the wearable medical device in multiple degrees of freedom. When the device includes both an ECG and IMU, the device may be configured to concurrently detect at least (i) an internal mechanical energy signal detectable by the physical stress sensor, ii) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detectable by the ECG sensor, and iii) a position, orientation, and / or a movement of the host detectable by the IMU. In addition to detecting, the device may process the detected signals. For example, the device may be configured to process the detected internal mechanical energy signal, the detected electrophysiological energy signal, and the detected position, orientation, and / or a movement of the host to produce biomedical data; and use the biomedical data to determine a health and / or disease state of the host. As another example, the device may be configured to process the detected position, orientation, and / or movement of the host to determine a host state of whether the host is (1) awake and at rest, (2) undergoing activity, or (3) sleeping; process the detected ECG signals to provide at least timing markers of a cardiac cycle of the host; and process the detected internal mechanical energy signals to provide sound signatures associated with heart function. The device may be configured to monitor one or more disease states of the subject's heart suchDocket No.: CANA.476PCas stenosis, regurgitation, and / or myxomatous.

[0017] In some embodiments, a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable device includes a housing able to securely attach to a region or location outside of the host's body. As mentioned elsewhere herein, the outside skin surface of the host is a region or location outside of the host's body. The housing is securely attached when it effectively maintains its location while the host moves during normal daily activities, such that, for example, the stress sensor portion of the housing maintains significant contact with the outside skin of the host during normal daily activities. A physical stress sensor is encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

[0018] In some embodiments, a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable device includes a housing able to securely attach to a region or location outside of the host's body, and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for theDocket No.: CANA.476PCunimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer, the device further comprising at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host on which the wearable medical device is deployed.

[0019] In some embodiments, a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable device includes a housing able to securely attach to a region or location outside of the host's body, and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer, the device further comprising at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host on which the wearable medical device is deployed, wherein the at least one secondary sensor includes an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor.Docket No.: CANA.476PC

[0020] In some embodiments, a wearable medical device for monitoring mechanical stress originating from within a host is disclosed. The wearable device includes a housing able to securely attach to a region or location outside of the host's body, and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer, the device further comprising at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host on which the wearable medical device is deployed, wherein the at least one secondary sensor includes (a) an electrophysiological sensor including an electrocardiogram (ECG) sensor, and (b) an inertial measurement unit (IMU), and wherein the medical device is configured to: simultaneously detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure, from within the host, detectable by the ECG sensor, (b) a position, orientation, and / or a movement of the host detectable by the IMU.

[0021] The above-mentioned and additional features of the present technology and the manner of obtaining them will become apparent, and the disclosed technology may be best understood by reference to the following more detailed description. It is noted that all references disclosed herein are hereby incorporated by reference in their entirety as if eachDocket No.: CANA.476PCwas incorporated individually.

[0022] This Summary has been provided to introduce certain concepts in a simplified form that are further described in detail below in the Detailed Description. Except where otherwise expressly stated, this Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter.

[0023] The details of one or more embodiments are set forth in the description below. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Thus, any of the various embodiments described herein can be combined to provide further embodiments. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications as identified herein to provide yet further embodiments. Other features, objects and advantages will be apparent from the description, the drawings, and the claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Many aspects of the present disclosure can be better understood with reference to the following drawings. The features in the drawings are not necessarily to scale, fully shown, or depicted in the same manner as would be physically constructed. Instead, emphasis is placed on clearly illustrating the principles of the present disclosure. The drawings should not be taken to limit the disclosure to the specific embodiments depicted but are for explanation and understanding only.

[0025] FIG. 1A shows a diagram illustrating an example embodiment of a system for monitoring, analyzing, and reporting events associated with the cardiovascular and / or pulmonary health of a patient with a wearable medical device (WMD) including a physical stress sensor device, in accordance with the present technology.

[0026] FIG. IB shows a block diagram of an example embodiment of a WMD including a physical stress sensor device, in accordance with the present technology.

[0027] FIGS. 2A and 2B show diagrams depicting an example embodiment of a WMD of the present technology having an ex vivo physical stress sensor, in accordance with the present technology.

[0028] FIGS. 2C, 2D and 2E show diagrams depicting an example embodiment of a flexible retainer for some embodiments of a WMD in accordance with the present technology.

[0029] FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3J, and 3K show diagrams depicting exampleDocket No.: CANA.476PCembodiments of a unimorph piezoelectric sensor device, in accordance with the present technology.

[0030] FIGS. 3H and 31 show diagrams depicting example embodiments of an amplifier circuit, in accordance with the present technology, which interfaces with an example embodiment of the unimorph piezoelectric sensor device shown in FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3J, and 3K.

[0031] FIG. 4 shows diagrams depicting example geometries of some example embodiments of a unimorph piezoelectric sensor device, in accordance with the present technology.

[0032] FIG. 5 shows a diagram of an example embodiment of a method for monitoring an anatomic structure of a subject from a wearable medical device, in accordance with the present technology.

[0033] FIG. 6 shows an illustration of the example embodiment of the WMD including an exemplary physical stress sensor and auxiliary electrocardiogram (ECG) sensor, in accordance with the present technology, to continuously measure mechanical energy signals and electrophysiological signals of the cardiovascular system and / or the pulmonary system in human and non-human subjects.

[0034] FIGS. 7A and 7B show exploded diagrams of example embodiments of the WMD shown in FIG. 6.

[0035] FIG. 8 shows a diagram of an example embodiment of a WMD, in accordance with the present technology, which electrically interfaces with a remote power source via a wire or cable.DETAILED DESCRIPTION

[0036] The present technology provides a wearable medical device (WMD) and system for monitoring and collecting data from the WMD worn on-body by a host for assessment of one or more clinical conditions. In some embodiments, the WMD of the present technology may be reversibly secured to the body of the host by the host, e.g., without requiring intervention from a health care provider (HCP). In some embodiments, for example, a WMD includes an ex vivo physical stress sensor that can detect and measure mechanical energy generated within the body of the host. For example, the disclosed devices, systems, and methods can be configured to monitor internal mechanical stress (referred to as physical stress) associated with physiological phenomena of an internal body structure, including butDocket No.: CANA.476PCnot limited to the heart, lungs and / or gastrointestinal tract, from outside of the host. The disclosed devices, systems, and methods provide an ex vivo physical stress sensor, where the physical stress sensor may be positioned on the outside of the host's body and measures physiological-related mechanical stress generated and emanating within the host's body. Herein, the terms "host," "patient," "person", "user", "patient user", "subject" and like terms may be used interchangeably.

[0037] As used herein, mechanical energy can refer to mechanical waves in gases, liquids, and solids, including vibration, sound, ultrasound, and infrasound. The present technology provides WMDs that may detect and measure mechanical waves that travel through the gases, liquids and / or solids that make up the internal anatomy of the host. In some embodiments, the WMD includes one or more auxiliary sensors to detect and measure motion and / or position or orientation of the patient, electrophysiological signals associated with one or more anatomic structures of the host, such as the heart, and / or an analyte or multiple analytes present in an in vivo fluid of the patient, such as interstitial fluid (ISF).

[0038] The mechanical energy detected by a WMD in accordance with the present technology may propagate with a frequency in a range of, for example, 0.1 Hz to 50 kHz, or a portion thereof. As such, the disclosed ex vivo physical stress sensor may be responsive to a variety of physiological phenomena associated with the host's health and / or disease from mechanical energy generated by the host, e.g., the beating of a heart, the flow of blood moving through a blood vessel or organ, or the inhale and exhale of respiration.

[0039] The disclosed wearable medical devices, systems, and methods of the present technology can be implemented for monitoring the state of a patient's cardiovascular and / or pulmonary disease for management of the patient's treatment and care of the disease, which includes heart failure, a valvular disease, a coronary disease, thoracic aortic aneurysm, chronic obstructive pulmonary disease (COPD), sleep apnea, asthma, and / or other acute or chronic disease or conditions. In particular, the disclosed wearable medical devices, systems, and methods of the present technology can be implemented to assist the patient's HCP(s) in the medication management for the patient's disease or condition.

[0040] For example, in some embodiments, an exemplary WMD can monitor cardiovascular function using an ex vivo physical stress sensor of the WMD for continuously detecting abnormal blood flow associated with aortic stenosis (AS) and mitral valve regurgitation (MVR) for valvular disease drug management. Also, as an example, someDocket No.: CANA.476PCembodiments of the exemplary WMD can be implemented to monitor both cardiovascular and pulmonary function using the WMD's ex vivo physical stress sensor for continuously detecting mechanical energy associated with abnormal blood flow, as in AS and / or MVR, and for continuously detecting other mechanical waves generated by heart valve in conjunction with or exclusive from mechanical energy associated with breathing and other pulmonary function, including but not limited to edema in the lungs, asthma, COPD, or other pulmonary conditions, for cardiovascular and pulmonary disease drug management. In such cases, the exemplary WMD can be worn outside the patient's body, e.g., on the patient's chest just left of center from the sternum, which can be secured to the patient's body in a variety of ways discussed later in this disclosure.

[0041] Among the greatest challenges for patients and their HCPs in managing their cardiovascular and / or pulmonary disease conditions is patient compliance. Patients must comply with two facets of their own health care: (1) regularly (e.g., multiple times daily) take their prescribed medications precisely when and how they are prescribed, and (2) regularly (e.g., one or more times daily) measure and record multiple physiological measurements, including blood pressure (BP), body weight (BW), and blood oxygen level (PulseOx). Current heart monitoring systems are a compilation of external sensors, such as the combination of a blood pressure cuff (digital), a body weight scale (digital), and a pulse oximeter (digital), which require discrete and separate measurements of the patient's BP, BW, and PulseOx, respectively. Yet, when patients comply, the system can gauge risk levels for whether the patient is successfully managing his / her heart disease or trending toward DHF. For instance, if a patient is developing a lot of fluid in his / her lungs and the patient's heart rate is increasing, then the patient's BW increases and is measurable by the body weight scale and the patient's heart rate increase and is measurable by the blood pressure cuff— which can collectively indicate the patient may be decompensating and in need of immediate medical attention (e.g., trip to emergency room where an HOP can adjust the concentrations of the ACE inhibitors, Beta blockers, and diuretics for avoiding DHF).

[0042] While studies have shown patients generally can be relied upon to regularly take their medications as prescribed, most patients struggle to keep with the strict protocols to measure and record their BP, BW, and PulseOx. The conventional approach for treating cardiovascular and pulmonary disease is severely flawed because of the reliance on patient compliance. The disclosed wearable medical devices, systems, and methods of the presentDocket No.: CANA.476PCtechnology can be implemented to continuously, passively, and autonomously (i.e., no patient interaction) monitor, from outside the patient's body, a multitude of internal physiological markers associated with cardiovascular and / or pulmonary health and disease, thereby taking patient compliance out of the equation (or at least substantially minimizing patient compliance) for the physiological monitoring component of the patient's treatment and care.

[0043] The disclosed wearable medical devices, systems, and methods of the present technology can continuously, autonomously, and passively monitor one or more clinically useful host properties including heart rate, cardiac valvular function, respiratory rate, respiratory quality, myocardial function, and degree of coronary artery disease, each based on information obtained from the WMD's ex vivo physical stress sensor. The device of the present technology having a physical stress sensor may be configured in conjunction with one or more auxiliary sensors, such as an ultrasonic transducer array, a motion sensor such as an inertial measurement unit (IMU), an electrophysiological sensor such as an ECG sensor, an analyte sensor such as a continuous analyte monitor, or other sensor, as disclosed herein. For example, in some implementations of the WMD using the ex vivo physical stress sensor and an ECG sensor as a temporal qualifier, i.e., a timing marker for events during the cardiac cycle, the WMD can interrogate for particular mechanical energy phenomena to distinguish between healthy and unhealthy markers of cardiac function. For example, in some embodiments of the WMD using the x vivo physical stress sensor and the ultrasonic transducer array, the ultrasonic transducer array can be configured to detect vascular blood flow, vessel wall thickness, and / or vessel diameter, e.g., either at a reference point in the cardiac cycle or as a function of time during the cardiac cycle. For example, vascular refers to both arterial and venous vessels, in non-limiting examples. Such implementation of the WMD the ex vivo physical stress sensor and the ultrasonic transducer array can obtain both static measurements (e.g., any point in the cardiac cycle) and dynamic measurements (e.g., measurements during the cardiac cycle as a function of time).

[0044] The ex vivo physical stress and auxiliary sensors of a WMD of the present technology are out of body and thus not blood-contacting, i.e., the sensors are engineered to detect physiological phenomena, particularly including those associated with blood flow, without being positioned inside blood vessels. For example, despite not being implanted within the patient's body, once an exemplary WMD, e.g., having the ex vivo physical stressDocket No.: CANA.476PCsensor and certain auxiliary sensors (e.g., such as the ECG and IMU), is positioned on the skin at a region or location of the patient's body proximate the patient's heart, such as on the chest of the host, for example, on the chest but left of the sternum, the WMD can monitor multiple disease states for each of the four valves of the heart, e.g., (1) stenosis (narrowing of the valve in a large blood vessel branching off or into the heart, which typically is caused due to calcification); (2) regurgitation (backwards flow of blood through due to a valve defect); and (3) myxomatous, a combination of stenosis and regurgitation (degeneration of the cardiac valves). The continuous, autonomous, and passive ex vivo monitoring capability by the disclosed embodiments of the WMD of the present technology is important for the advancement of cardiovascular healthcare because none of these disease states are easy to observe presently due to the fact that it is the change over time in these disease states that allows for their diagnosis, and conventional diagnostic systems, devices, and techniques are incapable of or severely limited to accurately, reliably, and conveniently track the physiological markers over such time durations to effectively and optimally enable HCPs to make proper diagnoses. In addition, the WMD of the present technology can utilize its IMU sensor(s) to controllably collect and distinguish data at both a resting state and a state of activity which can simulate a stress test, thereby increasing the WMD's capability to assess patient disease conditions. In some implementations, the disclosed embodiments of the WMD of the present technology can be configured with a miniaturized footprint size to be capable of inconspicuously characterizing cardiovascular and / or pulmonary function in multiple states and situations of the patient's condition— without reliance on patient compliance— and without disrupting or intruding on the patient's appearance or lifestyle.

[0045] In some implementations of the WMD of the present technology, for example, the WMD can operate like a continuous and / or real time stethoscope monitor for an HCP that is continuously measuring acoustic phenomena of the patient's heart and patient respiration. The WMD may, for example, measure or monitorthe host's respiration rate. Respiration rate, which is also known as respiratory rate or breathing rate or breathing frequency, refers to the rate at which breathing occurs, and is usually measured in breaths per minute. The WMD may, for example, measure or monitor or otherwise provide data that may be used to characterize the host's respiration quality. Healthy quality breathing is sometimes referred to as unlabored respiration, while gasping and wheezing are examples of labored respiration. Identifying the quality of a host's breathing (respiration quality) may be used to characterizeDocket No.: CANA.476PCa disease state of the host, for example, to identify and characterize one or more of congestive heart failure (CHF), pneumonia, COPD, asthma, etc. These signatures and the graduations of these signatures as a function of disease severity have been characterized with external auscultation. The devices, systems, and methods of the present technology provide improved signal to noise ratio for respiration-related signals, e.g., based on the device architecture of the ex vivo physical stress sensor, despite those signals having to pass through a skin / air interface such as occurs when respiration-related signals are obtained by an external digital stethoscope. The devices, systems, and methods of the present technology may be used to monitor pulmonary conditions, such as asthma or COPD, and may also pick up mitral valve regurgitation and heart failure because the breathing acoustics are changed when there is fluid in the lungs, and MVR and heart failure can cause such fluid accumulation. Thus, the disclosed embodiments of the WMD of the present technology can supplement or replace external digital stethoscopes, which suffer from poor fidelity and reliability (poor compliance) due to over 90% signal loss from transmission of the acoustic signals from the tissues of the body through air to be transduced by the external microphone of the digital stethoscope.

[0046] In some embodiments, for example, a WMD in accordance with the present technology includes a stress-mediated sensor operable to measure mechanical force applied to a transducer element that causes physical stress within the transducer material. In some embodiments, the WMD includes a stress-mediated microelectromechanical sensor (MEMS) device to transduce mechanical waves that apply force on the MEMS device into electrical signals. Some examples of a MEMS stress-mediated sensor can include a piezoelectric stress sensor, and in some embodiments, for example, the piezoelectric stress sensor includes a unimorph piezoelectric sensor device.

[0047] These and other example embodiments are discussed in further detail below. Example Embodiments

[0048] FIG. 1A shows a diagram illustrating an example embodiment of a sensor system 10 for monitoring, analyzing, and reporting events associated with the physical health condition of a user, e.g., the cardiovascular and / or pulmonary health of a user (also referred to as a patient or host) based on a wearable medical device (WMD) 100, including an ex vivo physical stress sensor, in accordance with the present technology. The WMD 100, which includes the ex vivo physical stress sensor, may also include one or more additional sensors,Docket No.: CANA.476PCincluding but not limited to electrophysiological sensor(s), temperature sensor(s), position sensor(s), rate sensor(s), acceleration sensor(s), chemical sensor(s), or biological sensor(s), or other. Therefore, the WMD 100 is also referred to herein as an / the "wearable sensor device 100," "wearable stress sensor device 100," "wearable mechanical stress sensor device 100," "wearable physical stress sensor device 100," or just "sensor device 100;" but it is understood that the WMD 100 may or may not include the one or more additional sensors with the ex vivo physical stress sensor regardless of the particular name referred to in the disclosure.

[0049] The system 10 includes an example embodiment of the wearable stress sensor device 100 that is worn on the outside of the body of the patient and is capable of detecting and distinguishing signals from mechanical energy (e.g., mechanical waves) originating within the host, such as one or more structures of the heart, vasculature, and / or lungs. The wearable stress sensor device 100 includes a sensor unit 110 in communication with an electronics unit 120, which are encased within a housing 101. The system 10 includes a data processing system 150 in communication with the wearable stress sensor device 100. In some embodiments, the system 10 includes an external receiver device 130 operable to receive a wireless transmission carrying data indicative of detected signals acquired from the wearable stress sensor device 100 and to transmit and / or store the data to the data processing system 150. In some embodiments, the wearable stress sensor device 100 and / or the external receiver device 130 is / are in communication with the data processing system 150 via a network 140 of computers in communication with each other and accessible through the Internet (e.g., referred to as the "cloud"), where the data from the wearable stress sensor device 100 and / or the external receiver device 130 can be transferred to the data processing system 150. Similarly, information from the data processing system 150 can be transferred to the external receiver device 130 and / or the wearable stress sensor device 100. For example, the data processing system 150 can manage data compilation(s) into a directional or changing modality to provide a continuous, long-term representation (i.e., far more than a moment representation) informative of the patient's health and disease, and which can also provide a delta change representation (whether on a short-term or long-term temporal scale) to aid in the analysis of the patient's health and disease from a point in time (e.g., any point in time defined as an initial point (To) to a point in future time (Tf)), thereby functionally providing deterioration or improvement of the physical state of the patient from a point of securement of the wearable stress sensor device 100 and treatment and / or behaviorDocket No.: CANA.476PCmodification thereafter by the patient.

[0050] In some implementations, the wearable stress sensor device 100 wirelessly communicates the acquired data (associated with the detected mechanical waves propagating within the body) directly to the external receiver device 130. For example, the wearable stress sensor device 100 can transfer the data to the external receiver device 130 using a low power wireless communication protocol, e.g., such as Bluetooth Low Energy (BLE), Near Field Communication (NFC), low frequency radio frequency (RF) signal in a range of 3 kHz to 1.3 MHz, or other. Example embodiments of the external receiver device 130 include a computing device 130A or a dedicated base station 130B. For example, the computing device 130A can include, but is not limited to, a smartphone, tablet, a home device (e.g., Alexa, Nest, Echo, Google Home, Smart TVs, etc.), a wearable computing device (e.g., smartwatch, smartglasses or headgear, etc.), a laptop or desktop computer, or other. The dedicated base station 130B can include data storage and / or data communication units that facilitate the communication of data from the wearable stress sensor device 100 to the data processing system 150 through a Wi-Fi access or cellular link to the network 140. In some implementations, for example, the external receiver device 130 can be embodied on multiple receiver devices, such as both the computing device 130A (e.g., smartphone, tablet, etc.) and the dedicated base station 130B, as illustrated in the example of FIG. 1A. In some implementations, for example, the external receiver device 130 can (i) process, at least partially, the received data for display on a display screen of the external receiver device 130 and / or for transfer of the received data to an external computer or computing system, such as the data processing system 150. In some embodiments, for example, the system 10 optionally includes a software application ("app") that is resident on the external receiver device 130 to control various data processing, storage, and communication functionalities for management of the received data.

[0051] In the example of the system 10 illustrated in FIG. 1A, the data processing system 150 can include one or more server computer devices 152, one or more client computer devices 154, and / or one or more databases 156, in data communication with each other. In implementations, for example, the computer device(s) 152, 154 and the database(s) 156 are in communication with each other and / or in communication with the other devices of the system 10 via the network 140. In some implementations, for example, the data processing system 150 can remotely monitor data associated with the patient user obtained by theDocket No.: CANA.476PCwearable stress sensor device 100 and / or remotely operate aspects of the system 10, e.g., such as modify sensing parameters or protocols of the wearable stress sensor device 100, data display or processing features of the app on the receiver device 130, or other.

[0052] In some embodiments, for example, the system 10 optionally includes a remote computing device 160 operated by a remote user to remotely monitor data associated with the patient user obtained by the wearable stress sensor device 100 that is transferred to the data processing system 150. For example, the remote computer 160 can include a personal computer such as a desktop or laptop computer, a mobile computing device such as a smartphone, tablet, smartwatch, etc., or other computing device. In some implementations, for example, the remote computing device 160 is configured to only receive data that is curated (e.g., selected, pre-processed, and / or formatted) by the data processing system 150. In some implementations, for example, the remote computing device 160 is configured to remotely operate one or more aspects (e.g., functionalities) of the system 10. For example, the remote computing device 160 can implement a remote user software application (remote user app) that is configured to provide the remote user with such display, storage, and / or management features. The remote user, for example, can include a health care provider (HCP), such as a physician, nurse, family member of the patient user, or other caregiver, or a medical insurance payer, or other type of stakeholder entity or individual with respect to the patient user's health.

[0053] FIG. IB shows a block diagram of the wearable stress sensor device 100, depicting an example embodiment of the sensor unit 110 and the electronics unit 120. While the stress sensor device 100 is described in the context of a wearable sensor device in FIG. IB, it is understood that the example embodiment of the wearable stress sensor device 100 shown in FIG. IB may also be implemented in an implantable or in vivo medical devices, such as in examples described later in this disclosure. The sensor unit 110 includes at least one physical stress sensor 111 to detect stress caused from internal mechanical energy associated with physiological phenomena of an internal body structure from within the host that is received by the at least one physical stress sensor 111, which is positioned outside of the host's body.

[0054] One or both of the sensor unit 110 and the electronics unit 120 are housed, fully or at least partially, in and / or coupled via a casing or housing 101 that is securable to the outside of the host's body (e.g., such as to skin at a particular region or location of the host's body). In one embodiment, when a device as disclosed herein is being used primarily toDocket No.: CANA.476PCobtain information about cardiac function, the casing or housing may be configured to secure the wearable device to skin that is close to the heart, e.g., the front of the host, e.g., near but to the left of the sternum. When heart auscultation for the aortic area is desired, the device may be located near but to the right of the sternum, at the second IC (intercostal) space. When heart auscultation for the tricuspid area is desired, the device may be located near but to the left of the sternum at the fourth IC space. When heart auscultation of the mitral area is desired, the device may be located near but to the left of the sternum at the fifth IC space, on the midclavicular line. When heart auscultation of the pulmonic area is desired, the device may be placed left of the sternum, at the second IC space. However, when a device as disclosed herein is being used primarily to obtain information about pulmonary function, the casing or housing may be configured to secure the wearable to skin that is close to the lungs, e.g., the back or posterior of the host (between the scapula and the vertebrae), or perhaps the side of the host over the ribs. For instance, in the region of C7-T3, which is close to the upper lobes the lungs. The region of T3-T10 may be preferred when assessing the lower lobes of lung function. The casing or housing may be configured to allow the stress sensor to lay flat against the host's skin at the selected region of the host's body. Regardless of whether the device is placed on the front chest (e.g., near the sternum) or on the back (e.g., between the shoulder blades) of the host, the stress sensor will sense sounds created by both cardiac and pulmonary function. The devices as disclosed herein may detect sounds due to both cardiac and pulmonary function, but the sound signatures may be processed differently in order to focus on one or the other of the pulmonary or cardiac functions. Heart rate is typically two to three times faster than respiratory rate, so that the corresponding cardiac sounds occur more frequently than respiratory sounds and may be distinguished from one another on that basis. Differences in sound signature frequency (wavelength) may also be used to distinguish between pulmonary and cardiac functions.

[0055] In some embodiments, for example, the physical stress sensor 111 includes a transducer element 112 coupled to a casing structure 113. The transducer element 112 is able to receive a mechanical wave that emanates from a source (e.g., tissue, organ, bodily fluid, or other) within the host's body such that the transducer element converts energy of the received mechanical wave to electrical energy, thereby producing an electrical signal corresponding to the mechanical wave. In some embodiments, for example, the transducer element 112 includes a piezoelectric material, including but not limited to lead zirconateDocket No.: CANA.476PCtitanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF) aluminum nitride (AIN), scandium aluminum nitride (ScAIN), barium titanate (BaTiOs), lead titanate (PbTiCh), potassium niobate (KNbCh), lithium niobate (LiNbCh), lithium tantalate (LiTaCh), and / or sodium tungstate (Na2WO4). In example embodiments where the transducer element 112 includes PZT, the PZT can be PZT-5A, PZT-5H, or PZT-5K. In implementations of the physical stress sensor 111, for example, the casing structure 113 provides a firm, inflexible material and is configured to secure and / or position the transducer element 112 in the physical stress sensor 111 to receive a mechanical wave for transduction to the electrical signal indicative of an in vivo mechanical energy signal within the body. In some embodiments, for example, the casing structure 113 of the physical stress sensor may be a hermetically sealed containment structure, which can include a metal, plastic, composite, or other material. The physical stress sensor 111 is configured in electrical communication with the electronics unit 120 via electrical interconnection(s) 117.

[0056] In some embodiments, the sensor unit 110 may include an inertial measurement unit (IMU) 115 to monitor motion (in multiple degrees of freedom) and / or determine an orientation of the wearable stress sensor device 100. The IMU 115 is configured in electrical communication with the electronics unit 120 via the electrical interconnection(s) 117. In some embodiments of the sensor unit 110, for example, the IMU 115 can include an accelerometer and / or a rotational rate sensor (e.g., gyroscope) to monitor patient motion and / or position. In some embodiments of the sensor unit 110, for example, the IMU 115 can include a magnetometer. In example embodiments including the IMU 115, the IMU 115 is in communication with a data processing unit 121 of the electronics unit 120.

[0057] In some embodiments of the wearable stress sensor device 100, for example, the sensor unit 110 may optionally include one or more secondary sensor(s) 119, also referred to herein as auxiliary sensor(s). For instance, in some implementations, the secondary sensor(s) 119 may include an analyte sensor to measure a parameter (e.g., concentration) of an analyte in the region proximate the location (e.g., surrounding tissue) where the wearable stress sensor device 100 is deployed from outside the host, such as at or proximate the heart, lungs and / or gastrointestinal tract. In some examples, the optional secondary analyte sensor can include, but is not limited to, a glucose sensor, such as a continuous glucose monitor (CGM). Some examples of a CGM that can be employed in the wearable stress sensor device 100 asDocket No.: CANA.476PCan example embodiment of the secondary sensor(s) 119 include those described in U.S. Patent No. 10,827,954 B2, U.S. Patent No. 10,980,452 B2, U.S. Patent Publication No. 2017 / 0128009A1, U.S. Patent No. 10,092,207 Bl, and U.S. Patent Publication No. 2023 / 0012662A1, which are incorporated by reference as part of this disclosure for all purposes. Example CGM devices embodied as an example secondary sensor(s) 119 can include microneedle-based glucose sensors and / or canula-type glucose sensors. In some embodiments of the WMD 100 including a CGM and / or other analyte sensor, the CGM and / or other analyte sensor can be external to the housing 101 and tethered to the electronics unit 120 of the WMD 100 via wire, cable, or other connection that allows for data communication and power between the electronics unit 120 and the optional the CGM and / or other analyte sensor. In such embodiments, for example, the CGM and / or other analyte sensor can be wearable by the host around the host's abdomen region while the housing 101 having the physical stress sensor 111 of the WMD 100 is positioned in a region proximate to the host's heart and lungs.

[0058] Additionally or alternatively to a secondary analyte sensor, the secondary sensor(s) 119 may optionally include a pulse oximeter to measure the oxygen level in the host's blood, e.g., indicative of the saturation of oxygen carried by the host's blood cells. In some implementations, the optional pulse oximeter can be used to measure the host's heart rate via the host's pulse. In some embodiments of the WMD 100 including a pulse oximeter, the WMD 100 can include at least one optical sensor that it emits a probe light at and through the skin of the user and receives a reflected light that is reflected from a blood vessel to be detected by a light detector of the optical sensor, which is transduced as data that the electronics unit 120 can process to estimate oxygen saturation of the hemoglobin in the blood vessel. Some examples of the optional secondary pulse oximeterof the WMD 100 can include a pulse oximeter and / or optical sensor disclosed U.S. Patent Publication No. 2024 / 0130648A1, which is incorporated by reference as part of this disclosure for all purposes. In such embodiments, the implantable contingent having the pulse oximeter can be integrated with the housing 101 of the WMD 100 or can be an external sensor contingent that is tethered to the housing 101, e.g., in electrical communication with the electronics unit 120 for data communication and / or power. In example implementations of the WMD 100, the physical stress sensor 111 can monitor physical stress signals associated with the host's respiratory function, e.g., respiration rate and quality indicating whether the host gasps orDocket No.: CANA.476PCwheezes, optionally in compilation with the pulse oximeter monitoring the blood oxygen level, thereby providing a comprehensive characterization of the host's respiration function in terms of how the host is breathing and how effective the breathing is able to absorb oxygen.

[0059] Additionally or alternatively to a secondary analyte sensor and / or secondary pulse oximeter, the secondary sensor(s) 119 may optionally include a pH sensor to measure the pH level in the region proximate the location where the wearable stress sensor device 100 is deployed. In some embodiments of the WMD 100 including a pH sensor, the WMD 100 can include an implantable contingent that inserts into the host's skin to detect the pH level in the region of interest within the host's body. In such embodiments, the implantable contingent having the pH sensor can be integrated with the housing 101 of the WMD 100 or can be an external sensor contingent that is tethered to the housing 101, e.g., in electrical communication with the electronics unit 120 for data communication and / or power.

[0060] Additionally or alternatively to a secondary analyte sensor, secondary pulse oximeter, and / or secondary pH sensor, the secondary sensor(s) 119 may optionally include a temperature sensor to measure the temperature in the region proximate the location where the wearable stress sensor device 100 is deployed. This temperature may be referred to as the host's core (or internal) body temperature, as opposed to a host's surface (or peripheral) temperature. A surface temperature is measured at a host's surface, e.g., a skin temperature, or a temperature measured underthe host's tongue, or a temperature measured in the host's ear canal. A surface temperature can fluctuate based on external environmental conditions. A core body temperature refers to temperature within the body and / or internal organs of the host, such as the heart, liver, brain or internal bodily fluid such as blood. In some embodiments of the WMD 100 including a temperature sensor, the WMD 100 can include an implantable contingent that inserts into the host's skin to the region of interest to detect the core body temperature of the host. In such embodiments, the implantable contingent having the core body temperature sensor can be integrated with the housing 101 of the WMD 100 or can be an external sensor contingent that is tethered to the housing 101, e.g., in electrical communication with the electronics unit 120 for data communication and / or power. In some embodiments, the WMD 100 can include a surface temperature sensor that is configured to measure the skin surface temperature of the host, e.g., which can be positioned proximate to the physical stress sensor 111 on the housing 101 of the WMD 100. In some embodiments, the WMD 100 can include both the example implantable contingent having an exemplary coreDocket No.: CANA.476PCbody temperature sensor and the example surface temperature sensor.

[0061] Additionally or alternatively to a secondary analyte sensor, secondary pulse oximeter, secondary pH sensor, and / or a secondary temperature sensor, the optional one or more secondary sensor(s) 119 may include an ECG sensor that includes two electrodes separated by a space that creates an electrical potential, e.g., positioned at or toward opposing ends of the housing 101, where the two electrodes are operable to measure an electrical signal (e.g., spike) that is indicative of the electrophysiological signals of the cardiac muscle tissue for controlling the patient's heartbeat, where the spikes give rise to the ECG signal of the patient. For example, a device 100 of the present technology including both a physical stress sensor and an ECG as a secondary sensor 119, may be worn on the body of the host and utilized to estimate the pulmonary arterial pressure (PAP) of the host. The physical stress sensor is responsive to, i.e., can detect, mechanical waves generated by the heart as it proceeds through the aortic (A2) and the pulmonary (P2) components of the second heart sound (S2). Simultaneously collected ECG data may be used to identify the S2 region of the data obtained from the stress sensor. That detection of A2 and P2 allows for the data from the device to be used to determine the A2-P2 splitting interval (SI), i.e., the time interval between the A2 and the P2, which is recognized to be a useful parameter for estimating the PAP. See, e.g., Wu J., Durand L-G, and Pibarot, P. Heart 2002, vol. 88, pp. 76-80.

[0062] Additionally or alternatively to a secondary analyte sensor, secondary pulse oximeter, secondary pH sensor, secondary temperature sensor, and / or a secondary ECG sensor, the optional one or more secondary sensor(s) 119 may include an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter. In some embodiments, the optional ultrasound sensor can be configured at a region of the wearable stress sensor device 100 and span or project an array of acoustic transducer elements outward of the housing 101 to make contact with skin of the patient when wearing the WMD 100. In some example embodiments, the optional ultrasound sensor can include an acoustic interface pad (e.g., hydrogel) to provide acoustic impedance matching between the surface of the skin and the acoustic transducers. In implementations of the optional ultrasound sensor, the ultrasound sensor may operate in combination with another sensor, for example, in compilation with the example ECG sensor to provide one or more temporal reference point(s) in a cardiac cycle of the host to detect the one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter as a function of timeDocket No.: CANA.476PCduring the cardiac cycle, which is processed in compilation with the detected internal mechanical energy monitored by the physical stress sensor 111.

[0063] In such cases, for example, the optional one or more secondary sensor(s) 119 comprising, for example, one or more of the analyte sensor, the pulse oximeter, the pH sensor, the temperature sensor, and / or the ECG sensor can be used to obtain data indicative of clinically-relevant conditions about both the anatomic structure (e.g., heart, lungs and / or gastrointestinal tract) and conditions of the in vivo environment of the heart, lungs and / or gastrointestinal tract, such as a potential infection or inflammatory response to the implantation of implantable features (e.g., such as a pH sensor contingent or core body temperature sensor contingent) of the wearable stress sensor device 100. In some embodiments, for example, the optional one or more secondary sensor(s) 119 can be attached to the housing 101 of the wearable stress sensor device 100, e.g., via weld, chemical adhesion, clip, clamp, or other attachment means. In some embodiments, for example, the optional one or more secondary sensor(s) 119 can be integrated as part of the structure of the housing 101 of the wearable stress sensor device 100. In some embodiments, for example, the optional one or more secondary sensor(s) 119 can be external to the housing 101 and tethered to the electronics unit 120 of the WMD 100 via wire, cable, or other connection that allows for data communication and power between the electronics unit 120 and the optional one or more secondary sensor(s) 119.

[0064] In some embodiments of the wearable stress sensor device 100, the housing 101 can itself be a hermetically sealed containment structure, e.g., comprising a metal, plastic, composite, or other material. In some embodiments, for example, the housing 101 includes a titanium (Ti) container that houses the one or more sensors of the sensor unit 110 and / or electronic components of the electronics unit 120, e.g., which may include but is not limited to any of sensor(s), a telemetry system, a microprocessor, memory, and / or a battery. For example, the housing 101 is configured to shield components of the electronics unit 120 from fluids or substances when the wearable stress sensor device 100 is deployed on the patient's body, e.g., such as sweat, blood, or water from washing, swimming, or other types of fluid exposures. As depicted in the diagram of FIG. IB, the housing 101 can include a containment structure that fully covers the electronics unit 120 and at least partially covers at least one or some or all of the components of the sensor unit 110; whereas in some embodiments, the containment structure of the housing 101 can fully cover at least one or some or all of theDocket No.: CANA.476PCcomponents of the sensor unit 110.

[0065] The electronics unit 120 of the wearable stress sensor device 100 includes a data processing unit 121, an optional signal conditioning unit 123, a power supply 129, a wireless communications unit 127, and an electrical interface 125, which can include electrically conductive contact sites (e.g., pads, pins, or other contact configuration) that electrically interface with the electrical interconnection(s) 117 of the sensor unit 110. The electronics unit 120 is configured to receive and at least partially process electrical signals acquired from the physical stress sensor 111 of the sensor unit 110 (and signals acquired from optional IMU 115 or optional secondary sensor(s) 119). For example, in some embodiments, the electrical signals are received at the corresponding contact sites of the electrical interface 125 and provided to the data processing unit 121 (or, optionally, first to the signal conditioning unit 123 to improve the quality of the acquired electrical signals from the sensor unit 110 prior to providing to the data processing unit 121). In such implementations, the output of the data processing unit 121 can include raw or processed data associated with the detected data from the sensor unit 110, to be wirelessly transmitted to an external device by the wireless communications unit 127. In example embodiments of the electronics unit 120, the power supply 129 can include a battery (e.g., primary or rechargeable), fuel cell or other power source to supply power to the components of the electronics unit 120 and / or the sensor unit 110. In some implementations, for example, the power supply 129 includes an ultra-low power system (e.g., operating in the micro amp or nano amp range).

[0066] In some implementations, the data processing unit 121 is configured to at least partially process the conditioned electrical signals to (i) produce data, e.g., in an analog or a digital form, and / or (ii) control functionality of the electronics unit 120 and / orthe sensor unit 110. For example, the data processing unit 121 can be configured to manage data acquisition on data channels associated with the physical stress sensor 111 and (optional) IMU 115 and / or (optional) secondary sensor(s) 119 of the sensor unit 110.

[0067] In some implementations, for example, the data processing unit 121 can be configured to control and manage the power consumption by at least one of the sensors of the sensor unit 110. For example, in embodiments of the wearable stress sensor device 100 including an example secondary sensor 119, e.g., such as an accelerometer (e.g., low power accelerometer), rate sensor, IMU, or other sensor operable to detect movement, the data processing unit 121 can be configured to process the data from the motion sensing secondaryDocket No.: CANA.476PCsensor 119 to determine an activity state or rest state of the patient, and based on the determined activity state or rest state of the patient, the data processing unit 121 can manage power allocation from the power supply 129 to the one or more sensor(s) of the sensing unit 110 and / or to the components of the electronics unit 120. As an illustrative example, in some embodiments, for example, the data processing unit 121 processes the data signal from an exemplary motion sensing secondary sensor 119 (e.g., low power accelerometer) to determine the activity state or rest state of the patient and generates an power control signal that controls allocation of electrical power from the power supply 129 to the physical stress sensor 111 to perform sensing for a certain period or periods of time when the patient is in the activity state and when the patient is in the resting state. In this manner, an appropriate amount of sensing activity is carried out by the physical stress sensor 111. Also, in some implementations, for example, the power control signal may power up some or all of the sensors on the device 100 at the same time or in a cascading times, whether intermittently or continuously, and / or for the same or differing time periods, e.g., such as power supplied for sensing functionality for 1-2 seconds or any appropriate time cadence based on the desired sensing application.

[0068] In some embodiments, for example, the wireless communications unit 127 includes a wireless transmitter, receiver, and / or transceiver device, e.g., including an antenna, which is capable of communicating with an external device to communicate raw, partially-processed, or fully-processed data from the signal conditioning unit 123 (and / or the data processing unit 121, discussed below). For example, the wireless communications unit 127 can be configured to manage the communication protocol for transmission or reception via the antenna. Examples of antenna can include, but are not limited to, a whip antenna, a loop antenna, or a conformal antenna. For example, an antenna system can be attached to the housing 101 (e.g., Ti containment structure) to enable bi-directional communication for data transfer and device management between the wearable stress sensor device 100 and one or more remote devices, e.g., various embodiments of the external receiver device 130 (see FIG. 1A), such as a base station or phone-based interface system or other computing device. An example transceiver unit can include a BLE chipset to communicate with a BLE-enabled device, e.g., a smartphone, tablet, or other external computing device. Additionally or alternatively, in some embodiments, for example, the wireless communications unit 127 is configured as a scaffolding around the electronics unit 120, e.g., such as coupled to orDocket No.: CANA.476PCintegrated with the housing 101, that is structured to provide wireless communication means for the wearable stress sensor device 100.

[0069] In some optional embodiments, for example, the optional signal conditioning unit 123 can include a circuit including one or more filters and / or one or more amplifiers to augment the raw electrical signals detected by the physical stress sensor 111 of the sensor unit 110 (e.g., transducer element 112) to increase a signal-to-noise ratio (SNR) of the electrical signals, thereby producing data containing the signal-processed electrical signals. In some optional embodiments, the optional signal conditioning unit 123 can include drive circuitry to produce operating electrical signals that generate electrical potentials and / or currents at the sensors, e.g., including but not limited to example embodiments of the optional secondary sensor(s) 119, such as analyte sensor electrode contingent(s) and / or temperature sensor contingent for operating an electrochemical sensing technique and / or electrophysiological or kinetic sensing technique to be performed at electrode(s) in some implementations of the optional secondary sensor(s) 119 of the sensor unit 110.

[0070] In some embodiments of the data processing unit 121, for example, the data processing unit 121 can include a processor 121A to process data and a memory 121B in communication with the processor 121A to store and / or buffer data. In various embodiments, for example, the processor 121A can include one or multiple processors, and the memory 121B can include one or multiple memory units. For example, the processor 121A can include a central processing unit (CPU), a microcontroller unit (MCU), a graphics processing unit (GPU), or other type of processor. For example, the memory 121B can include and store processor-executable code, which when executed by the processor, configures the data processing unit 121 to perform various operations, e.g., such as receiving information, commands, and / or data, processing information and data, and transmitting or providing information / data to another device. To support various functions of the data processing unit 121, the memory 121B can store information and data, such as instructions, software, values, images, and other data processed or referenced by the processor 121A. For example, various types of random access memory (RAM) devices, read only memory (ROM) devices, flash memory devices, and other suitable storage media can be used to implement storage functions of the memory 121B. In some embodiments, the data processing unit 121 includes an input / output (I / O) unit 121Cto interface the processor 121A and / or memory 121B to other modules, units or devices. In some embodiments, the processor 121A, the memory 121B,Docket No.: CANA.476PCand / or the I / O unit 121C is in communication with the wireless communications unit 127, e.g., such as a transmitter (Tx) or a transmitter / receiver (Tx / Rx) unit. For example, in such embodiments, the I / O unit 121C can interface the processor 121A and memory 121B with the wireless communications unit 127, e.g., to utilize various types of wireless interfaces compatible with typical data communication standards, which can be used in communications of the data processing unit 121 with otherdevices. The data communication standards include, but are not limited to, Bluetooth, Bluetooth Low Energy (BLE), Zigbee, Medical Implant Communication Service (MICS), industrial, scientific, and medical (ISM) band, IEEE 802.11, Wireless Local Area Network (WLAN), Wireless Personal Area Network (WPAN), Wireless Wide Area Network (WWAN), WiMAX, IEEE 802.16 (Worldwide Interoperability for Microwave Access (WiMAX)), 3G / 4G / LTE / 5G / 6G cellular communication methods, and parallel interfaces. In some implementations, the data processing unit 121 can interface with other devices using a wired connection via the I / O unit 121C, e.g., such as prior to or during securement to the patient user's body to be in data communication and / or power connection with another medical device attached to or implanted in the patient user's body. The data processing unit 121 can also interface, e.g., via wireless communication, with other external interfaces, sources of data storage, and / or visual or audio display devices, etc. to retrieve and transfer data and information that can be processed by the processor 121A, stored in the memory 121B, or exhibited on an output unit of the external receiver device 130 (see FIG. 1A, e.g., smartphone, tablet, etc.) or other external device to the wearable stress sensor device 100. In some embodiments, for example, the electronics unit 120 can include a global positioning system (GPS) to determine a location of the patient user of the wearable stress sensor device 100.WMD with Stress-Mediated Sensor

[0071] An exemplary stress-mediated sensor in accordance with the present technology is configured to measure stress— not displacement— to provide in vivo sensing of mechanical energy (mechanical waves) that emanate from within the body, e.g., from anatomical structures of the cardiovascular system and / or pulmonary system, such as the heart and lungs, and propagate in a local region including to the body's periphery where the exemplary stress-mediated sensor is positioned on the outside (e.g., skin). The disclosed stress-mediated sensor is operable to detect an in vivo mechanical signal by measuring, from outside the body, an applied force or moment upon the electromechanical transducer component ofDocket No.: CANA.476PCthe sensorto convert the received mechanical energy (mechanical stress signal) into electrical energy (electrical signal), which is addressable and processible to decipher the physiological phenomenon associated with the detected mechanical signal and to determine clinically relevant information about the patient's health and / or disease. In some embodiments of the stress-mediated sensor, the transducer component includes a piezoelectric material and electrically-conductive non-piezoelectric material(s) configured in a piezoelectric sensing unit.

[0072] Some example embodiments of a wearable medical device having the exemplary stress-mediated sensor can include a short-term WMD configuration that a clinician secures to the patient's body to be worn fora matter of days to a few or more weeks (e.g., four weeks) to continuously monitor one or more health parameters of the patient, e.g., without requiring patient compliance during the monitoring. An example short-term WMD could be configured for re-use after each patient, where data is stored on the device and only accessible to the device manufacturer to provide to the clinician after a patient's use (e.g., thereby not requiring wireless communication capabilities for some embodiments of the short-term WMD). Yet some embodiments of the short-term WMD can include a wireless communication unit to transmit the patient data acquired by the sensor(s) of the short-term WMD to a remote device, such as the patient's smartphone via Bluetooth, WiFi, cellular, or other wireless communication technique. For a CHF patient, the short-term WMD with a wireless communication capability worn by a patient for three to four weeks allows the clinician to adjust doses of the prescribed medicines for the patient's CHF condition. An example use case of an exemplary short-term WMD is when a patient exits an intensive care unit (ICU) of a hospital after undergoing cardiac decompensation (e.g., with NYHA class III CHF (New York Heart Association class III congestive heart failure).

[0073] In some example implementations of the exemplary short-term WMD, the cardiologist team would provide the exemplary short-term WMD to the patient by activating the device and applying it to the chest (e.g., holding it in place with an adhesive dressing) for securement to the patient's body at the area or location of interest, e.g., above the heart. The patient would be able to go home, and the exemplary short-term WMD records data for the desired time period (e.g., days to few weeks). After expiration of the time period, the patient would return the exemplary short-term WMD to the manufacturer of the WMD (e.g., via mail by a stamped self-addressed packaging that could be provided when the patient receives the device). In this manner, for example, the WMD device manufacturer would (1)Docket No.: CANA.476PCupload the patient data recorded by the device during the patient monitoring, (2) provide the data to the HCP (and / or process the data and provided analyzed data to the HCP), (3) inspect and clean the short-term WMD for next use, (4) recondition the WMD as needed and recertify the WMD, e.g., including clearing the memory, (ii) calibrating the sensors, and / or charging the re-chargeable battery, and (5) return the certified short-term WMD to the HCP for its next use.

[0074] In other example implementations of the exemplary short-term WMD, the cardiologist team would provide the exemplary short-term WMD to the patient while under direct or indirect care, such as in a hospital or clinic (e.g., including in the ICU), where the cardiologist team would activate the device and apply and attach it to the chest (e.g., holding it place with an adhesive dressing) for securement to the patient's body at the area or location of interest, e.g., above the heart. While the patient is in the hospital or clinic, the exemplary short-term WMD would be in communication (e.g., wired or wireless communication) with the health monitoring system of the hospital, such that the WMD could monitor the patient's internal physical stress signals for measuring and / or characterizing physiological phenomena of one or more anatomic structures of interest, such as the patient's heart and / or lungs, while the patient is concurrently being monitored by other health monitoring devices in the hospital setting, e.g., including but not limited to an electrocardiogram monitor, a pulse oximeter, blood pressure device, etc. In some example embodiments, the data from the exemplary short-term WMD can be accessed by connecting a dongle from the hospital's health monitoring system to a data port on the exemplary short-term WMD; whereas, additionally or alternatively, in some embodiments, the exemplary short-term WMD can wirelessly communicate (e.g., through Bluetooth Low Energy (BLE)) the acquired physical stress signal data (e.g., raw and / or signal processed) to the hospital's health monitoring system received at a wireless receiver (e.g., base station). In this manner, for example, the exemplary shortterm WMD can provide real time or pseudo-real time monitoring of the internal physiological phenomena of the patient's heart and / or lungs and / or gastrointestinal tract while the hospital monitoring system is monitoring other patient health parameters (e.g., 'vitals', like blood pressure, blood oxygen levels, heart rate, and electrocardiogram signals, etc.). Example hospital systems that the exemplary short-term WMD can communicate with include, but are not limited to, GE Healthcare CARESCAPE™ ONE monitor system, Philips Capsule Medical Device Information Platform (MDIP) clinical surveillance system, and Siemens MindrayDocket No.: CANA.476PCpatient monitors.

[0075] Some example embodiments of a wearable medical device having the exemplary stress-mediated sensor can include a long-term WMD configuration that either the patient or a clinician secures to the patient's body to be worn for a matter of months or years to continuously monitor one or more health parameters of the patient, e.g., requiring little to no patient compliance during the monitoring. An example long-term WMD could be configured for real time or intermittent secure data transfer to the cloud (e.g., data processing system 150), to enable the clinician to view the patient's data or analysis of the patient's data during the continuous monitoring of the patient's one or more health parameters. An example use case of an exemplary long-term WMD is when a patient would receive the WMD along with a re-charging station and an external data receiver (e.g., external receiver device 130), such as when exiting the clinic or by mail. For instance, a clinician could directly secure the device to the patient's body or provide instructions (e.g., directly or indirectly, via written on online information) for the patient to secure the device to his / her body, e.g., using a dressings kit (e.g., Tegaderm medical tape) to adhere the device to their chest. For instance, the dressing can be of a flexible, stretchable, bendable, and / or waterproof material to be accommodating for daily living (e.g., movement, bathing, etc.). During the long-term use, the data is collected and uploaded to cloud, via the external data receiver, e.g., on a daily basis or other time frame. In some instances, the patient may have to remove the exemplary longterm WMD weekly or monthly for re-charging and re-apply the long-term WMD to the body with a new dressing, e.g., depending on the battery's storage capacity, which affects the size of the device. This example of a long-term WMD requires some patient compliance to care, charge, and re-apply the device; yet, this example of a long-term WMD still provides a level of autonomy for the patient during daily activities while requiring no intervention by the patient while worn to obtain the important health data from the patient. Notably, for some embodiments, the long-term WMD could be configured without a wireless communication unit (and thereby not require the external data receiver) such that the long-term WMD collects the health parameter data and provides it to the clinician or manufacturer only when the WMD is available to the clinician or manufacturer (e.g., on return of the device or clinical check-ins by the patient with his / her clinician).

[0076] In some embodiments of a short-term WMD or a long-term WMD in accordance with the present technology, the WMD is configured in a housing (e.g., that can beDocket No.: CANA.476PChermetically sealed) that has a curved skin-interfacing side to be form-fitting to a particular area or region where the WMD is intended to be deployed, e.g., such as the chest area above a human subject's heart. In some embodiments of a short-term WMD or a long-term WMD in accordance with the present technology, the WMD is configured in a housing of low-cost materials, such as plastic or low-cost metals, like aluminum. In some embodiments of the long-term WMD, the WMD is configured in a housing (e.g., that may be hermetically sealed) that has a small form factor to allow to be integrated into clothing article, such as a shirt, band, wrap or other, where the patient can wear the clothing article 24 / 7 on their body such that the clothing article positions the WMD in the intended position on the patient's body, and where the patient is able to wash the clothing article as needed to accommodate the long-term use of the WMD.

[0077] FIGS. 2A and 2B show diagrams depicting an exemplary WMD of the present technology, labeled 200, having a stress-mediated sensor. FIG. 2A shows multiple views of the exterior of the WMD 200 depicting an exemplary body structure; and FIG. 2B shows an exploded view of the WMD 200 depicting an example configuration of the components of the WMD 200.

[0078] FIG. 2A shows a perspective view illustrating an exemplary body of the WMD 200, showing a main body 241 of the WMD 200 encased in a flexible retainer 245 and in electrical communication (e.g., wired) with an external electrode assembly 294 of the WMD 200 via an interconnect assembly 297 of the WMD 200. The main body 241 includes a housing 201 that seals (e.g., may hermetically-seal) within the WMD 200 a sensor unit (including stress-mediated sensor 211, illustrated in broken lines) and an electronics unit 220 (illustrated in another set of broken lines) that is in communication with the stress-mediated sensor 211. The perspective view diagram of FIG. 2A also shows an example embodiment of a wireless communications unit 227 of the electronics unit 220 (illustrated in another set of broken lines), e.g., which can be embodied as a wire antenna, that is disposed in a distal chamber 201C of the housing 201, e.g., to facilitate wireless communication transmission(s) and / or reception(s) between the WMD 200 and an external device (e.g., the external receiver device 130).

[0079] Also shown in FIG. 2A are a top view, a bottom view, and a side view of the WMD 200, depicting the main body 241 of the WMD 200, the external electrode assembly 294, and the interconnect assembly 297, which collectively illustrates an example of some of theDocket No.: CANA.476PCfeatures and the shape, size and dimensions of an example embodiment of the WMD 200. For example, the bottom view illustrates an example position where an example biocompatible interface layer of the stress-mediated sensor 211 and an ECG electrode 291 of the WMD 200 are positioned with respect to the main body 241. In some embodiments, for example, the interface layer of the stress-mediated sensor 211 includes titanium (Ti), e.g., which may optionally be coated with a dielectric material (e.g., parylene), and the outer surface of the ECG electrode 291 includes titanium nitride (TiN), e.g., a TiN coating. Also depicted in the bottom view is the bottom surface of the main body 241 and external electrode assembly 294, which can include an adhesive layer 299, e.g., able to attach to skin of a user and thereby secure the WMD 200 to the outer body of the user. In some example embodiments, the adhesive layer 299 may include, but is not limited to, Tegaderm™, DuPont™ Liveo™ Soft Skin tape, Flexcon® Omni-Wave™ tape, or other adhesive material. It is understood that the main body 241 of the WMD 200 can be configured to have a range of sizes and shapes to accommodate the stress-mediated sensor 211 and the electronics unit 220 contained therein, which are beyond the particular sizes, dimensions, and shapes shown in FIG. 2A for the example WMD 200. In the non-limiting example shown in FIG. 2A, the end-to-end length (L241) of the housing 201 (shown in the top view) is configured to be 51.6 mm, the end-to-end width (W241) of the housing 201 is configured to be 14.72 mm, and the end-to-end height (H241) of the housing 201 is configured to be 6.78mm. Other non-limiting example shapes for the WMD 200 and for various portions of the housing 201 are contemplated, including rectangular, square, triangular, elliptical, circular, cylindrical, conical, or others or combinations thereof or of others.

[0080] FIG. 2B shows an exploded view of an example embodiment of the WMD 200, featuring components of the stress-mediated sensor 211 and the electronics unit 220 that are contained within the housing 201 (e.g., hermetically-sealed in some embodiments), which includes a first chamber enclosed by a housing top 201T and a housing bottom 201B and an adjacent second chamber (i.e., distal chamber 201C) enclosed by housing end 201E. In some embodiments, the housing 201 is coated by a dielectric layer to protect the WMD 200 (e.g., parylene). In some embodiments, the housing bottom 201B or at least a portion of the housing bottom 201B is coated by the dielectric layer. In some embodiments of the WMD 200, for example, the stress-mediated sensor 211 includes transducer assembly 212 that is coupled to an electronics interface structure 213 (e.g., electrical interconnect board), whichDocket No.: CANA.476PCis configured to interface the transducer assembly 212 to a data and / or signal processing unit 220PCB of the electronics unit 220. For example, in some embodiments of the stress-mediated sensor 211, the transducer assembly 212 includes a piezoelectric material and at least one electrically-conductive non-piezoelectric material (e.g., transducer electrode) coupled to the piezoelectric material to receive the transduced electrical signals generated upon applied stress to the stress-mediated sensor 211 that is received by the piezoelectric material. In some embodiments, like that shown in FIG. 2B, for example, the transducer electrode is positioned on an interior-facing side of the piezoelectric material and electrically coupled with the electronics interface structure 213 to be in electrical communication with the data and / or signal processing unit 220PCB. In some embodiments, for example, electrical interface components 225 can be configured in contact with or as part of the electronics interface structure 213, e.g., to bridge electrical connections between the data and / or signal processing unit 220PCB and various electronic components or sensors of the WMD 200. In some embodiments, for example, the transducer assembly 212 includes a non-piezoelectric material (shown in FIG. 2B as 212B) that is positioned on an exterior-facing side of the piezoelectric material and to be disposed at the housing opening 2010 (i.e., opening through a side of the housing bottom 201B), which can be hermetically-sealed when assembled for some embodiments of the WMD 200. In some embodiments, for example, the exemplary non-piezoelectric material 212B can be biocompatible and configured to have a Young's modulus close to (e.g., within 2X - 3X of) or substantially matching (e.g., within 20% of) that of the piezoelectric material.

[0081] In some embodiments of the WMD 200, for example, the data and / or signal processing unit 220PCB can be embodied by any of the exemplary embodiments of the data processing unit 121 and / or the optional signal conditioning unit 123, respectively, disclosed herein. In the example shown in FIG. 2B, the data and / or signal processing unit 220PCB includes a processor coupled to a memory which receives digital signal data from a signal processing circuit, all mounted on a printed circuit board (PCB). In some example embodiments, for example, the signal processing circuit includes a differential amplifier and / or charge amplifier to amplify the electrical signals received from the stress-mediated sensor 211 (e.g., from the at least one electrically-conductive non-piezoelectric material), and / or an analog-to-digital (A / D) converter to digitize the electrical signals. In some example embodiments, for example, the signal processing circuit includes filter circuit(s) to removeDocket No.: CANA.476PCsignal outside frequency range(s) of non-interest, which can include low-pass, bandpass, and / or high-pass filters, e.g., to improve signal-to-noise ratio of the detected mechanical energy signal of interest. The exemplary data and / or signal processing unit 220PCB can be programmable for some embodiments. In some embodiments, for example, the data and / or signal processing unit 220PCB can be secured and / or positioned within the main chamber of the housing 201 by the electronics interface structure 213 and / or an (optional) internal housing frame (not shown), which may also be used to secure and / or position one or more components of the stress-mediated sensor 211 for some example embodiments. In some embodiments, for example, the housing 201 can include an insulative material 226 (e.g., polyimide layer, such as Kapton®) to shield the data and / or signal processing unit 220PCB from other components of the WMD 200, such as the housing top 201T.

[0082] In some embodiments of the WMD 200, for example, the electronics unit 220 includes a power supply 229 electrically connected, via components (e.g., wires or other connectors of the electronics interface structure 213), to the data and / or signal processing unit 220PCB and other components of the electronic unit 220 (or other unit of the WMD 200, such as some embodiments of the stress-mediated sensor 211, when electrical power is needed to be supplied to such units). The power supply 229 can be embodied by any of the exemplary embodiments of the power supply 129 disclosed herein. For example, the power supply 229 can include a battery (e.g., primary or rechargeable), fuel cell, or other power source to supply power to the components of the electronics unit 220 (and, optionally, the stress-mediated sensor 211). In some example embodiments, for example, the power supply 229 can include an electrical receiving port (not shown) to receive a wire that can supply the WMD 200 from a remote power source, e.g., an external power supply (e.g., an electronic device with a battery or a power adapter to plug into a wall power source).

[0083] In some embodiments of the WMD 200, for example, the wireless communications unit 227 of the electronics unit 220 is electrically connected, via components (e.g., wires or other connectors of the electronics interface structure 213, to the data and / or signal processing unit 220PCB and other components of the electronic unit 220 (or other unit of the WMD 200, such as some embodiments of the stress-mediated sensor 211, e.g., for transmitting raw electrical signals transduced by the sensor). The wireless communications unit 227 can include a wireless transmitter, receiver, and / or transceiver device, e.g., antenna as shown in FIG. 2B, which is capable of communicating with an external device toDocket No.: CANA.476PCcommunicate raw, partially-processed, or fully-processed data from the data and / or signal processing unit 220PCB. For example, the wireless communications unit 227 can be configured to manage the communication protocol for transmission or reception via the antenna. The wireless communications unit 227 can be embodied by any of the exemplary embodiments of the wireless communications unit 127 disclosed herein. Examples of the antenna can include, but are not limited to, a whip antenna, a loop antenna, a chip antenna, a planar inverted F antenna (PIFA), a bipolar antenna, and / or a conformal antenna. In some embodiments of the WMD 200, like that shown in FIG. 2B for example, the wireless communications unit 227 can be contained in the housing end 201E (e.g., enclosed between a separable top portion and bottom portion of the housing end 201E securable (closed) by pins 201EP, which can hermetically-seal the housing end 201E with respect to the outside environment).

[0084] In some embodiments of the WMD 200, for example, the external electrode assembly 294 includes an electrode 294E coupled to a cap or casing 294C that is connected to the outer shell or casing of the interconnect assembly 297. The electrode 294E is in electrical connection with a wire spanning through the interconnect assembly 297, which is electrically connected to the data and / or signal processing unit 220PCB and / or other components of the electronic unit 220 (e.g., such as the wireless communications unit 227 or other unit of the WMD 200). The electrode 294E can serve as a reference electrode for an electrophysiological measurement in compilation with the ECG electrode 291 (not shown in FIG. 2B). For example, the electrode 294E can be positioned a particular distance or distance range from the electrode 291 so that the separation between them is sufficient to obtain an ECG measurement from skin-surface electrodes. In some embodiments, the separation distance between reference electrode 294E and ECG electrode 291 can be between 5 cm to 20 cm; whereas, in some embodiments where both electrodes are configured within the housing 201 (and without the external electrode assembly 294 and the interconnect assembly 297, such as the exemplary WMD 700A discussed later), the separation distance can be in a range of 1 cm to 5 cm, where the electronics unit includes signal processing circuit for small signal analysis. In some embodiments, for example, the external electrode 294 can include an adhesive band 294B that is coupled to the electrode 294E and that has the adhesive layer 299 configured on the skin-facing side of the adhesive band 294B.

[0085] In some embodiments of the WMD 200, for example, the main body 241 of theDocket No.: CANA.476PCWMD 200 is encased around its sides by the flexible retainer 245. The flexible retainer 245 can be made of a silicone rubber, polydimethylsiloxane (PDMS), or other solid, flexible / bendable and / or stretchable polymer material. The flexible retainer 245 is configured to hold the main body 241 in place while securely and safely attaching to the skin of the patient using the WMD 200.

[0086] FIG. 2C shows a diagram depicting a perspective view of an example embodiment of the flexible retainer 245 in isolation. The flexible retainer 245 includes a main open chamber 245H, within which the main body 241 of the WMD 200 is encased. The adhesive layer 299 (not shown in FIG. 2C) can be attached to a bottom surface 245BT of the flexible retainer 245. In some embodiments, the flexible retainer 245 can include one or more ribs 245R that wrap around the interior wall 245W to form the main open chamber 245H. The one or more ribs 245R can be configured to flex inwardly when the main body 241 is inserted into the main open chamber 245H; and when the one or more ribs 245R includes a plurality of ribs, then multiple pressure points or regions can be applied on the housing 201 of the main body 241 to hold the main body 241 securely within the flexible retainer 245. In some embodiments of the flexible retainer 245, like that shown in FIG. 2C for example, the one or more ribs 245R can include a top rib 245RT that projects into and / or above the main open chamber 245H such that, when the main body 241 of the WMD 200 is inserted into the flexible retainer 245, the top rib 245RT overhangs on an outer-peripheral portion of the top surface of the housing 201.

[0087] In some embodiments, the flexible retainer 245 includes a plurality of pores 245P that pass through the bottom surface 245BT to a top surface 245TT of the flexible retainer 245. The plurality of pores 245P can be organized in multiple concentric rows (e.g., such as two or three rows, like that shown in FIG. 2C) that wrap around the flexible retainer 245. For example, the plurality of pores 245P can help enable the flexibility of the flexible retainer 245 when secured to the skin of the user so that the overall WMD 200 can be comfortable and convenient to wear during daily activities and sleep for the user. In some embodiments where the adhesive layer 299 includes at least some openings that align with the plurality of pores 245P, the plurality of pores 245P can allow air flow and fluid flow (e.g., perspiration) between the skin and the outside environment of the user, e.g., providing breathability for the skin.

[0088] FIG. 2D shows diagrams depicting a top view and bottom view of the flexible retainer 245 in isolation.Docket No.: CANA.476PC

[0089] FIG. 2E shows a diagram depicting a rear side view of the flexible retainer 245 in isolation, with a zoomed cut-away diagram illustrating an outside row pore 245P1. As illustrated in the cut-away diagram, for example, the outside row pore 245P1 is structured to have additional curvature on the top portion of the pore wall creating a dip, which can create an air gap between the adhesive 299 (not shown) and clothing that would cover the upper, outer walls of the flexible retainer 245 when a user is wearing the WMD 200.Unimorph Piezoelectric Sensor

[0090] In some embodiments, for example, the exemplary stress-mediated sensor includes a unimorph structure for sensing stress, also referred to as physical stress or mechanical stress, which causes a pressure differential on a detecting region of the unimorph stress sensor of the disclosed technology that is measurable to characterize a physical phenomenon (e.g., including but not limited to sound) occurring at a volume of interest for sensing. Example embodiments of a unimorph stress-mediated sensor includes a piezoelectric material coupled to a biocompatible, non-piezoelectric material to absorb stress applied on the sensor and coupled to an electrically conductive material, providing a piezoelectric sensing unit that generates a measurable electrical signal proportionate to the applied stress (force or moment) on the unimorph structure, and which is electrically addressable by a receiving circuit (e.g., for signal processing and / or data processing). Such a stress-mediated unimorph-structured piezoelectric sensor (also referred to herein as a "unimorph piezoelectric sensor") is substantially less sensitive (e.g., insensitive) to any potential non-physiological, external forces applied on the sensor due to (i) the stress sensing modality that does not require displacement of the transducing component and (ii) the material selection of the tissue-facing outer (non-piezoelectric) material component to address impedance matching between the skin and sensor (e.g., to minimize attenuation and noise for detecting the internal mechanical energy from outside the body). For example, the exemplary unimorph stress-mediated sensor is able to detect internal stress signals from outside the body with minimal signal attenuation of 30 dB or less compared to if the exemplary unimorph stress-mediated sensor were implanted within the subject's body. The disclosed wearable medical devices including an exemplary unimorph stress-mediated sensor are engineered with a structural configuration that enables the stress detection components (assembly) to operate at high sensitivity and resolution (i.e., high signal-to-noise) to detect internal mechanical energy within a living subject's body from outside the subject's body,Docket No.: CANA.476PCwhile also shielding the stress detection assembly from damage by external environment factors, and thus protecting the integrity of the sensor device to allow for long-term, continuous operation ex vivo. The housing of the exemplary unimorph stress-mediated sensor may be configured to hermetically seal the stress detection assembly, which protects the stress sensor from damage and protects its stable and highly sensitive physical stress sensing capability.

[0091] Example embodiments of the unimorph piezoelectric sensor in accordance with the present technology are configured to have a rigid unimorph piezoelectric structure that includes a rigid piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode. The biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and the electrode is operable to receive the electrical signal operable to transduced by the piezoelectric transducer. Some embodiments of the physical stress sensor 111 include a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, where the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and where the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer. In some embodiments, the biocompatible stress absorption material can include an electrically conductive material and serve a second electrode; whereas in other embodiments the biocompatible stress absorption material can include an electrically insulative material, such that the rigid unimorph piezoelectric structure includes a second electrode coupled between the piezoelectric transducer and the biocompatible stress absorption material.

[0092] While in operation to detect and measure host-generated internal mechanical energy signals (e.g., pressure waves that propagate within the host's body), the physical stress sensor of an exemplary WMD of the present technology (e.g., exemplary unimorph stress-mediated sensor) transduces a pressure differential upon the sensor portion caused by the internal mechanical energy signal and undergoes little or no displacement on a macroscopic or microscopic scale. If minute displacement does occur, the extent of displacement is of a sub-nanometer magnitude (less than 1 nm), or low nanometer magnitude (e.g., less thanDocket No.: CANA.476PC10 nm). The stress sensor of the present technology is not intended to measure displacement but is instead measuring the pressure differential between the inside and outside of the physical stress sensor (e.g., with respect to WMD housing, where that pressure differential creates a stress inside the housing that is detectable and measurable by the piezoelectric transducer layer that directly or indirectly contacts the inside wall of the housing).

[0093] Thus, the exemplary unimorph stress-mediated sensor is able to successfully operate to pick up in vivo mechanical energy based on a sensing modality (i.e., force or moment (pressure) differential) that is different than a conventional displacement- or bending-type (movement-based) piezoelectric sensor, which lack the sensitivity to detect the minute movements (e.g., sub-nanometer, angstrom and / or sub-angstrom level(s)) induced upon the piezoelectric material. Furthermore, the unimorph piezoelectric sensor is capable of exhibiting substantially lower noise and substantially higher mechanical signal resolution for improved sensitivity to dynamic range, e.g., as compared to a displacement-mediated sensor. In some embodiments, for example, the stress-mediated sensor includes a charge amplifier circuit to condition the electrical signal generated by the piezoelectric material in various embodiments of the stress-mediated sensor, including but not limited to the unimorph piezoelectric sensor.

[0094] In some embodiments of the unimorph piezoelectric structure, the device structure includes an active piezoelectric material (e.g., piezoelectric film) capable of imparting or detecting a stress and a stable, non-piezoelectric material (e.g., metal substrate) disposed on a side of the active piezoelectric material; which, after a load is applied on the unimorph piezoelectric structure (e.g., on the metal substrate), it causes a moment (stress) that propagates to the active piezoelectric film, thereby generating an electrical signal corresponding to the applied stress that is detectable as a mechanical force sensor, i.e., capable to detect mechanical energy signals (mechanical waves). In some embodiments of the physical stress sensor 111, the piezoelectric material of the exemplary unimorph piezoelectric sensor can include, but is not limited to, PZT (e.g., PZT-5A, PZT-5H, or PZT-5K), PLZT, quartz, ZnO, AIN, ScAIN, BaTiO3, PbTiO3, KNbO3, LiNbO3, LiTaO3, and / or Na2WO4. In some embodiments of the physical stress sensor 111, the non-piezoelectric material of the exemplary unimorph piezoelectric sensor can include, but is not limited to, titanium (Ti), a biocompatible stainless-steel, cobalt-chromium, nitinol, or high-purity ceramic (e.g., alumina AbO3). For instance, the unimorph stress-mediated sensor includes a rigid structure thatDocket No.: CANA.476PCprovides stability to piezoelectric-detection assembly, allowing detection of pressure differential. The rigid structure of the unimorph piezoelectric sensor will not deflect when exposed to mechanical energy. The rigid structure of the unimorph piezoelectric sensor is in contrast with a flexible piezoelectric sensor designed to deflect upon incidence of mechanical energy, which, over time, deflection causes the sensor structure to physically degrade. And, at some point, the sensor structure of a flexible piezoelectric sensor may break due to the amount of deflections undergone by the sensor structure (e.g., including range or extent of deflections and large occurrences or frequency of deflections). The rigid structure of the disclosed unimorph piezoelectric sensor is configured to not break under internal mechanical energy throughout the lifetime of the patient, as well as can withstand unintended external forces, and thereby provide safety for the patient throughout the use of the WMD having the unimorph piezoelectric sensor. In implementations, for example, the unimorph piezoelectric sensor receives an internal mechanical energy signal, i.e., the stress, that emanates from within the host from an internal body structure and transduces the received internal mechanical energy signal (the stress) to an electrical signal indicative of a physiological function by the internal body structure. This detection of the stress by the unimorph piezoelectric sensor is imparted at least by the rigid unimorph piezoelectric structure of the unimorph piezoelectric sensor, which does not deflect greater than 10 nm when exposed to the internal mechanical energy signal. As discussed herein, some embodiments of the rigid unimorph piezoelectric structure comprises a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, where the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and where the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

[0095] In example embodiments of the wearable stress sensor device 100, the unimorph piezoelectric sensor can be configured with the piezoelectric material and non-piezoelectric material selected and engineered for the unimorph piezoelectric sensor to be sufficiently sensitive to receive and transduce low amplitude mechanical signals of a large frequency range, i.e., having large dynamic range. For example, the unimorph piezoelectric sensor is capable of measuring and resolving sound levels as low as 20 dB SPL (decibel sound pressure level), e.g., barely above threshold of human hearing, and as high as 110 dB SPL (e.g.,Docket No.: CANA.476PCapproaching human pain threshold).

[0096] FIGS. 3A-3C, 3J, and 3K show diagrams depicting example embodiments of a unimorph piezoelectric sensor device 311, labeled 311A, 311B, 311C, 311J, and 311K, in FIGS. 3A-3C, 3J, and 3K, respectively, in accordance with the present technology. FIG. 3A shows a cross-sectional view and a top view (below the cross-sectional view) of an example embodiment of the unimorph piezoelectric sensor device having at least one electrode electrically-interfaced with and of a smaller diameter than a piezoelectric transducer material coupled to a biocompatible, electrically-conductive, non-piezoelectric material. FIG. 3B shows a cross-sectional view and a top view (below the cross-sectional view) of an example embodiment of the unimorph piezoelectric sensor device having at least one electrode electrically-interfaced with and of a smaller diameter than a piezoelectric transducer material coupled to a biocompatible, non-electrically-conductive, non-piezoelectric material with an intermediary electrically-conductive material layer therebetween. FIG. 3C shows an example embodiment of the unimorph piezoelectric sensor device having at least two electrodes electrically-interfaced with a piezoelectric transducer material. FIG. 3J shows a cross-sectional view and a top view (below the cross-sectional view) of an example embodiment of the unimorph piezoelectric sensor device having at least one electrode electrically-interfaced with and of substantially the same diameter as a piezoelectric transducer material coupled to a biocompatible, electrically-conductive, non-piezoelectric material. FIG. 3K shows a cross-sectional view and a top view (below the cross-sectional view) of an example embodiment of the unimorph piezoelectric sensor device having at least one electrode electrically-interfaced with and of substantially the same diameter as a piezoelectric transducer material coupled to a biocompatible, non-electrically-conductive, non-piezoelectric material with an intermediary electrically-conductive material layer therebetween.

[0097] As shown in FIG. 3A, the unimorph piezoelectric sensor device 311A of an example WMD 100 includes a piezoelectric material 312 (also referred to as "piezoelectric layer 312") disposed between and coupled to a first layer 313 and a second layer 315. The first layer 313 includes a biocompatible, electrically conductive, non-piezoelectric material. In some embodiments, the biocompatible, electrically conductive, non-piezoelectric material of the first layer 313 has a Young's modulus close within to (e.g., within 2X - 3X of) or substantially the same as (e.g., within 20% of) the Young's modulus of the piezoelectric material 312. In implementations of the unimorph piezoelectric sensor device 311A, the first layer 313 isDocket No.: CANA.476PCconfigured to be a sensing layer that receives the mechanical wave emanated from within the patient's body and that propagates to the interface of the unimorph piezoelectric sensor device 311A secured to the patient's skin, such that an applied force on the first layer 313 is transferred through the first layer 313 and into the piezoelectric material 312, which acts to transduce the mechanical energy (stress) into electrical energy. In some embodiments of the unimorph piezoelectric sensor device 311A, the first layer 313 is positioned at a location of the WMD, where the first layer 313 is tightly coupled to a WMD housing wall 319, e.g., which can be made of the same material as the first layer 313 that, for example, can be used to hermetically seal the other components of the unimorph piezoelectric sensor device 311A within the enclosure, for some embodiments of the WMD. Yet, in some embodiments, the first layer 313 is positioned in the unimorph piezoelectric sensor device 311A to be at an aperture of the WMD housing wall 319 (not shown), where the WMD housing wall 319 is tightly coupled to a portion (e.g., outer region) of the first layer 313, e.g., which can hermetically seal the other components of the unimorph piezoelectric sensor device 311A within the enclosure.

[0098] The second layer 315 includes a non-piezoelectric, electrically conductive material. In implementations of the unimorph piezoelectric sensor device 311A, the second layer 315 provides at least one electrically-addressable electrode to receive the electrical signal generated from the piezoelectric material 312; and the electrically conductive material of the first layer 313 provides an electrically-addressable electrode for the piezoelectric sensing unit. Moreover, for some embodiments of the unimorph piezoelectric sensor device 311A, because the material of the first layer 313 is biocompatible, the housing of the WMD (e.g., WMD housing wall(s) 319) can be configured as the first layer 313, thereby allowing the piezoelectric material 312 (and second layer 315) to be manufactured directly on a region of the housing structure of the WMD.

[0099] In some embodiments of the unimorph piezoelectric sensor device 311A, for example, the piezoelectric material 312 includes PZT (e.g., PZT-5A, PZT-5H, or PZT-5K), the first layer 313 includes titanium, and the second layer 315 includes at least one of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy thereof. In such example embodiments where the first layer 313 is electrically conductive, biocompatible, and mechanically matched (e.g., close Young's modulus) to the piezoelectric material 312, such as Titanium is with PZT-5A, for example, theDocket No.: CANA.476PCfirst layer 313 can be coupled to the electronics unit 220, as is the non-piezoelectric, electrically conductive material of the second layer 315, so that both sides of the piezoelectric material 312 can connect to an amplifier circuit (not shown) to amplify the transduced electrical signal, i.e., the captured charge generated by the piezoelectric material 312 in response to the applied stress. The unimorph piezoelectric sensor device 311A can be configured to have a variety of material configurations for the first layer 313, the piezoelectric layer 312, and the second layer 315, including but not limited to the following examples. For example, the piezoelectric material of the piezoelectric layer 312 can include, but is not limited to, PZT (e.g., PZT-5A, PZT-5H, or PZT-5K), PLZT, quartz, ZnO, AIN, ScAIN, BaTiO3, PbTiO3, KNbO3, LiNbO3, LiTaO3, and / or Na2WO4. The biocompatible material of the first layer 313 can include, but is not limited to, titanium (Ti), a biocompatible stainless-steel, cobalt-chromium, nitinol, or high-purity ceramic (e.g., alumina AbO3). The electrically conductive material of the second layer 315 can include, but is not limited to, titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy thereof. The unimorph piezoelectric sensor device 311A can be configured to have a variety of size configurations for the first layer 313, the piezoelectric layer 312, and the second layer 315, including but not limited to the following examples. For example, the first layer 313 can be configured to have a thickness in a range of 150 pm to 250 pm, and the piezoelectric layer 312 can be configured to have a thickness in a range of 150 pm to 250 pm. In some examples, the thickness of the first layer 313 and the piezoelectric layer 312 are configured to be the same thickness. For example, the second layer 315 can be configured to have a thickness in a range of 100 nm to 20 pm. In some examples, the second layer 315 can be configured to be thinner than 100 nm (e.g., up to 50% thinner than 100 nm, i.e., 50 nm). In some examples, the second layer 315 can be configured to be thicker (e.g., up to lOx or more than 20 pm, i.e., 200 pm or 250 pm). The thickness of the second layer 315 is preferably thinner (e.g., submicron thickness) to minimize the flexural rigidity and ultimate sensitivity on the piezoelectric layer 312.

[0100] In some embodiments of the unimorph piezoelectric sensor device 311A, the amplifier circuit can be configured as a charge amplifier (or other type of amplifier) which conditions, processes, and passes the transduced stress signal (i.e., electrical signal) for higher-order electronic functions by the WMD, e.g., such as data processing, data storage, wireless transmission, or other. The amplifier circuit that is part of or integrated with exampleDocket No.: CANA.476PCembodiments of the unimorph piezoelectric sensor device 311A can be included as part of the sensor unit 110, as part of the electronics unit 120 (e.g., part of the optional signal conditioning unit 123), or as part of both the sensor unit 110 and the electronics unit 120 for various embodiments of the unimorph piezoelectric sensor device 311A in accordance with the WMD 100. Example embodiments of an amplifier circuit that can be electrically interfaced to the unimorph piezoelectric sensor device 311A, or to other embodiments of a mechanical stress sensor for example embodiments of the wearable sensor device 100, is shown later in FIGS. 3H-3I.

[0101] Further, for example, in some example embodiments of a unimorph piezoelectric sensor device of the disclosed technology, the first layer 313 can be configured of a material that is biocompatible but not electrically conductive, where, in such embodiments, an intermediary electrically conductive layer is included for the unimorph piezoelectric sensor device, i.e., coupled to the piezoelectric material 312 and the first layer 313.

[0102] FIG. 3B shows an example embodiment of the unimorph piezoelectric sensor device 311B that includes the piezoelectric material 312 disposed between (i) a first layer 313B comprising a biocompatible, non-electrically conductive, non-piezoelectric material and (ii) the electrically-conductive, non-piezoelectric second layer 315, where the piezoelectric material 312 is coupled to the second layer 315 and an intermediary layer 316 comprising an electrically conductive, non-piezoelectric material. Also shown in the example of FIG. 3B, in some embodiments of the unimorph piezoelectric sensor device 311B, the first layer 313B is positioned at a location of the WMD and tightly coupled to the WMD housing wall 319, e.g., which can be made of the same material as the first layer 313B that, for example, can be used to hermetically seal the other components of the unimorph piezoelectric sensor device 311B within the enclosure, for some embodiments of the WMD. Yet, in some embodiments, the first layer 313B is positioned in the unimorph piezoelectric sensor device 311B to be at an aperture of the WMD housing wall 319 (not shown), where the WMD housing wall 319 is tightly coupled to a portion (e.g., outer region) of the first layer 313B, e.g., which can hermetically seal the other components of the unimorph piezoelectric sensor device 311B within the enclosure. Like the first layer 313 of FIG. 3A, the first layer 313B of FIG. 3B includes a biocompatible, non-piezoelectric material, but is non-conductive. In some embodiments of the first layer 313B of the unimorph piezoelectric sensor device 311B, for example, the biocompatible, non-electrically conductive, non-piezoelectric material of the first layer 313BDocket No.: CANA.476PCcan be selected to have a Young's modulus close to (e.g., within 0.5X - 3X of) the Young's modulus of the piezoelectric material 312. In implementations of the unimorph piezoelectric sensor device 311B, the at least one electrode of the second layer 315 and the electrically conductive material of the intermediary layer 316 and electrically interfaced with the piezoelectric material 312 and an amplifier circuit (e.g., of the electronics unit 220) to receive the transduced electrical signal generated from the piezoelectric material 312 for signal processing at the amplifier.

[0103] In some embodiments of the unimorph piezoelectric sensor device 311B, for example, the piezoelectric material includes PZT (e.g., PZT-5A, PZT-5H, or PZT-5K), the first layer 313B includes a high purity ceramic (e.g., alumina), and the second layer 315 and / or the intermediary layer 316 includes at least one of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy thereof. In some example embodiments, the first layer 313 includes an electrically insulative, biocompatible material such as Alumina, which can be mechanically matched (e.g., close Young's modulus and / or optimized thickness) to the piezoelectric material 312 of the unimorph piezoelectric sensor device 311B. The intermediary layer 316 and the first layer 315 are coupled to the electronics unit 220, so that both sides of the piezoelectric material 312 can connect to an amplifier circuit (not shown) to amplify the transduced electrical signal, i.e., the captured charge generated by the piezoelectric material 312 in response to the applied stress. The unimorph piezoelectric sensor device 311B can be configured to have a variety of size configurations for the first layer 313B, the piezoelectric layer 312, the intermediary layer 316, and the second layer 315, including but not limited to the following examples. For example, the first layer 313B (e.g., alumina) can be configured to have a thickness in a range of 150 pm to 250 pm, and the piezoelectric layer 312 can be configured to have a thickness in a range of 150 pm to 250 pm. In some examples, the thickness of the first layer 313B and the piezoelectric layer 312 are configured to be the same thickness. For example, the second layer 315 can be configured to have a thickness in a range of 100 nm to 20 pm. In some examples, the second layer 315 can be configured to be thinner (e.g., up to 50% thinner) than 100 nm. In some examples, the second layer 315 can be configured to be thicker (e.g., up to lOx than 20 pm). Similarly, for example, the intermediary layer 316 can be configured to have a thickness in a range of 100 nm to 20 pm. In some examples, the intermediary layer 316 can be configured to be thinner than 100 nm (e.g., up to 50% thinner than 100 nm, i.e., 50 nm).Docket No.: CANA.476PCIn some examples, the intermediary layer 316 can be configured to be thicker (e.g., up to lOx or more than 20 pm, i.e., 200 pm or 250 pm). The thicknesses of the second layer 315 and the intermediary layer 316 are preferably thinner (e.g., sub-micron thickness) to minimize the flexural rigidity and ultimate sensitivity on the piezoelectric layer 312.

[0104] The unimorph piezoelectric sensor device 311A and 311B can be configured in a variety of shapes and geometries of the WMD within which it is employed. For example, the unimorph piezoelectric sensor device 311A and 311B can be configured with a cylindrical geometry and a circular-shaped sensor profile. The lower diagrams of FIGS. 3A and 3B (i.e., top views) show a top side of the device 311A and 311B, respectively, that is contained within the housing of the WMD, where the at least one electrically-addressable electrode 315 is centrally positioned on the piezoelectric material 312. For example, in the top side view of the device 311A and 311B in the diagrams of FIGS. 3A and 3B, respectively, the electrode 315 has a radius b, and the piezoelectric material 312 has a radius a, where a > b. In such embodiments where the radius of the piezoelectric material 312 is greater than radius of the electrode 315 (i.e., a > b), this design can provide immunity from noise sources, e.g., environmental noise sources such as temperature, stray RF signals, etc. Whereas in some embodiments of the unimorph piezoelectric sensor device 311, like the unimorph piezoelectric sensor device 311J and 311K shown in FIGS. 3J and 3K, respectively, for example, the radius b of the electrode 315 can be configured to be the same length as the radius a of the piezoelectric material 312, e.g., where radius a = b. In such embodiments where the radius of the piezoelectric material 312 and the electrode 315 are matched (i.e., a = b), the overall noise floor for a given amount of electronic power consumption can be lower and the unimorph piezoelectric sensor device 311A and 311B may be easier and / or cheaper to manufacture (e.g., no masking process). Notably, the lower diagrams of FIGS. 3A, 3B, 3J, and 3K (top views) show stress vectors orr a nd oee, i.e., radial stress vector and / or tangential stress vectors, that radiate from center or tangentially, respectively. The stress vectors add linearly to produce a net polarization (charge) in the piezoelectric material 312.

[0105] FIG. 3C shows a top view of an example embodiment of the unimorph piezoelectric sensor device 311C, which is in accordance with either of the unimorph piezoelectric sensor device 311A or the unimorph piezoelectric sensor device 311B, or other example embodiments such as the unimorph piezoelectric sensor device 311D, 311E, 311F, and 311G (shown later). The unimorph piezoelectric sensor device 311C includes aDocket No.: CANA.476PCcircular / cylind rical shape / geometry having two electrode structures of the second layer 315: center electrode 315C and annular electrode 315A that is positioned around and separated from the center electrode 315C by a gap c. The gap c provides an electrical discontinuity between the two electrode structures 315C and 315A to create a voltage differential (potential) across the two electrodes, such that when a mechanical wave is incident (i.e., applied force or moment) on the first layer 313 or 313B (i.e., body-interfacing layer in an exemplary WMD), the compressive stress caused by the applied force or moment propagates through the piezoelectric material 312, which generates electric fields due to dipoles in the material structure causing different electrical potentials at the two electrode structures, resulting an addressable electrical signal across the center electrode 315C and the annular electrode 315A for the WMD.

[0106] The circular electrode, cylindrical shape of the example unimorph piezoelectric device 311C shown in FIG. 3C possesses many advantages, including (but not limited to) the capability to provide an even distribution of stress in the materials of the unimorph piezoelectric device 311C, so that there are no "hotspots" which can nucleate fracture / crack propagation; as well as reliability and safety for the unimorph piezoelectric device 311, e.g., where the example unimorph piezoelectric device 311C can be part of a hermetic enclosure, where the circular / cylindrical configuration of the example unimorph piezoelectric device 311C mitigates against potential degradation issues, such as corners that create stress risers and / or nucleation sites for cracks.

[0107] FIG. 3D and 3E show diagrams depicting example embodiments of the unimorph piezoelectric sensor device 311A, labeled as device 311D and 311E, respectively. As shown in FIG. 3D, the unimorph piezoelectric sensor device 311D includes a dielectric layer 318 configured on the outside of the WMD housing wall 319. For example, the dielectric layer 318 configured on the outside of the WMD housing wall 319 can provide a physical and electrical barrier layer to protect the WMD from corrosion, moisture, contaminants, or others and electrically shield the components of the WMD from the patient's body, and vice versa. In some embodiments, for example, the dielectric layer 318 can comprise or be parylene or other biocompatible dielectric material that is chemically inert, configurable as a thin film, and conformable to titanium or other material of the first layer 313 and / or WMD housing wall 319. For example, parylene is a biocompatible dielectric material that can provide a low surface tension and low insertion friction for the dielectric layer 318; and parylene is aDocket No.: CANA.476PCmaterial that is relatively inexpensive and readily manufacturable for medical devices. In some example embodiments, the dielectric layer 318 may comprise parylene, alumina (AI2O3), sapphire (a crystal form of alumina), a urethane, or a silicone, or a combination of any two or more thereof.

[0108] As shown in FIG. 3E, the unimorph piezoelectric sensor device 311E includes the dielectric layer 318 configured on the inside of the WMD to encompass the piezoelectric sensing components including the first layer 313, the piezoelectric layer 312, and the second layer 315. In the example shown in FIG. 3E, the first layer 313 is positioned in the unimorph piezoelectric sensor device 311E to be at an aperture 319x of the WMD housing wall 319, where the WMD housing wall 319 is tightly coupled to a portion (e.g., sidewall outer region) of the first layer 313, e.g., which can hermetically seal the piezoelectric sensing components within the enclosure, and where the dielectric layer 318 encompasses the interiorly-exposed surfaces of the first layer 313, the piezoelectric layer 312, and the second layer 315 to restrict their exposure. In some embodiments of the unimorph piezoelectric sensor device (not shown), the WMD does not include the aperture 319x and instead the first layer 313 is tightly coupled to the WMD housing wall 319 (like for the unimorph piezoelectric sensor device 311D), but where the dielectric layer 318 is configured on both (i) the outside of the WMD housing wall 319 (like for the unimorph piezoelectric sensor device 311D) and (ii) the inside of the WMD to encompass the piezoelectric sensing components including the first layer 313, the piezoelectric layer 312, and the second layer 315 (like for the unimorph piezoelectric sensor device 311E).

[0109] FIG. 3F and 3G show diagrams depicting example embodiments of the unimorph piezoelectric sensor device 311B, labeled as device 311F and 311G, respectively. As shown in FIG. 3F, the unimorph piezoelectric sensor device 311F includes the dielectric layer 318 configured on the outside of the WMD housing wall 319, in manner like that for the unimorph piezoelectric sensor device 311D of FIG. 3D. And, as shown in FIG. 3G, the unimorph piezoelectric sensor device 311G includes the dielectric layer 318 configured on the inside of the WMD to encompass the piezoelectric sensing components including the first layer 313B, the intermediary layer 316, the piezoelectric layer 312, and the second layer 315, in manner like that for the unimorph piezoelectric sensor device 311E of FIG. 3E. In some embodiments of the unimorph piezoelectric sensor device (not shown), the WMD does not include the aperture 319x and instead the first layer 313B is tightly coupled to the WMD housing wall 319Docket No.: CANA.476PC(like for the unimorph piezoelectric sensor device 311D or 311F), but where the dielectric layer 318 is configured on both (i) the outside of the WMD housing wall 319 (like for the unimorph piezoelectric sensor device 311D or 311F) and (ii) the inside of the WMD to encompass the piezoelectric sensing components including the first layer 313B, the intermediary layer 316, the piezoelectric layer 312, and the second layer 315 (like for the unimorph piezoelectric sensor device 311E or 311G). While not shown, it is understood that the unimorph piezoelectric sensor device 311D or 311F and the unimorph piezoelectric sensor device 311E and 311G can be configured where the piezoelectric layer 312 and the second layer 315 have the same diameter, like the unimorph piezoelectric sensor device 311J and the unimorph piezoelectric sensor device 311K, respectively, shown later in FIGS. 3J and 3K, respectively.

[0110] FIGS. 3H and 31 show diagrams depicting example embodiments of an amplifier circuit, in accordance with the present technology, which can be electrically interfaced with an example embodiment of the unimorph piezoelectric sensor device in accordance with the present technology. In some embodiments, the signal conditioning unit 123 of the sensor unit 110 and / or the electronics unit 120 of the stress sensor device 110 (shown in FIG. IB) may be embodied by the example embodiments of the amplifier circuit shown in FIGS. 3H and 31.

[0111] FIG. 3H shows a block diagram of an amplifier circuit 380 that is electrically interfaced to an example unimorph piezoelectric sensor device, such as the unimorph piezoelectric sensor device 311A, 311B, 311C, 311D, 311E, 311F, 311G, 311J, and 311K shown in FIGS. 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3J, and 3K, respectively. The amplifier circuit 380 is configured to amplify the electrical signal provided by the unimorph piezoelectric sensor device for circuit frequency band(s) of the detected physical stress signal (transduced by the unimorph piezoelectric sensor device as the electrical signal output). The amplifier circuit 380 includes an input that is electrically connected to the second layer 315 (e.g., each of the at least one electrically-addressable electrode(s)). Notably, the first layer 313 (for example embodiments like unimorph piezoelectric sensor device 311A and the like) or the intermediary layer 316 (for example embodiments like in unimorph piezoelectric sensor device 311B and the like) can be electrically connected to ground of the amplifier circuit 380 or an independent electrical ground. In some embodiments (not shown), for example, the first layer 313 (for example embodiments like unimorph piezoelectric sensor device 311A andDocket No.: CANA.476PCthe like) or the intermediary layer 316 (for example embodiments like in unimorph piezoelectric sensor device 311B and the like) can be electrically connected to the input of the amplifier circuit 380, and the second layer 315 (e.g., each of the at least one electrically-addressable electrode(s)) can be connected to the ground of the amplifier circuit 380 or an independent electrical ground. The output of the amplifier circuit 380 can be electrically connected to a data processing unit and / or wireless signal communication unit of the WMD 100 to further process the amplified signal, e.g., digitize, data-process, and / or transmit the amplified signal. The amplifier circuit 380 can be configured with one or more operational amplifier (op-amp) circuit components in electrical connection with other circuit components (e.g., resistors, capacitors, inductors, etc.) to create a desired frequency band filter that removes undesired signal components of the transduced electrical signal from the detected physical stress signal. The desired frequency range can be based on the expected frequency of the physical phenomena to be detected by the unimorph piezoelectric stress sensor. For example, in some embodiments, the amplifier circuit 380 can be configured to have a bandpass filter to amplify a pass band signal in a range of 1 Hz to 2 kHz; whereas in some embodiments, the amplifier circuit 380 can be configured to have bandpass filter to amplify a pass band signal in a range of 1 Hz to 5 kHz; whereas in some embodiments, the amplifier circuit 380 can be configured to have a bandpass filter to amplify a pass band signal in a range of 1 Hz to 10 kHz; whereas in some embodiments, the amplifier circuit 380 can be configured to have a bandpass filter to amplify a pass band signal in a range of 10 Hz to 1 kHz; whereas in some embodiments, the amplifier circuit 380 can be configured to have a bandpass filter to amplify a pass band signal in a range of 10 Hz to 10 kHz; whereas in some embodiments, the amplifier circuit 380 can be configured to have a bandpass filter to amplify a pass band signal in a range of 10 Hz to 100 kHz. In some embodiments, the amplifier circuit 380 can be configured to have a ba nd pass filter to amplify a pass band signal in a range of 1 Hz to 100 kHz.

[0112] FIG. 31 shows a circuit diagram of an example embodiment of the amplifier circuit 380, which is configured as a differential amplifier and / or charge amplifier circuit 380'. The exemplary charge amplifier circuit 380' can include at least one of a low noise amplifier (LNA) 381, a variable gain amplifier (VGA) 383, a band-pass filter (BPF) 385, a notch filter (NF) 387, and an analog-to-digital converter (ADC) 389.

[0113] In some example embodiments of the charge amplifier circuit 380', the LNA 381 is configured to receive the output of the physical stress sensor 111 (e.g., such as embodimentsDocket No.: CANA.476PCof the unimorph piezoelectric stress sensor 311A, 311B, 311C, 311D, 311E, 311F, 311G, 311J, 311K, etc.) as the input to the charge amplifier circuit 380', e.g., the raw analog electrical signal transduced by the physical stress sensor 111. In such embodiments, the LNA 381 is electrically coupled to the VGA 383, which is electrically coupled to the BPF 385, which is electrically coupled to the NF 387, which is electrically coupled to the ADC 389. It is understood that in other embodiments, one or more the amplifier and filter units (e.g., LNA 381, VGA 383, BPF 385, and NF 387) can be configured in a different electrical connection arrangement. Yet, in some embodiments, the charge amplifier circuit 380' includes the LNA 381, the ADC 389, the VGA 383, and optionally one or more of the BPF 385, and / or the NF 387. For example, in some embodiments, the LNA 381 in electrical connection with the output of the physical stress sensor 111, and optionally one of the VGA 383 and / or the optional BPF 385, and / or the optional NF 387 is coupled to the output of the LNA 381 (in any sequence of the VGA 383, the optional BPF 385, and / or the optional NF 387), from which the output of the VGA 383 and / or the optional BPF 385 and / or the optional NF 387 is electrically connected to the input of the ADC 389.

[0114] The exemplary charge amplifier circuit 380' shown in FIG. 31 can be implemented in the following way. For example, the physical stress sensor 111 produces a transduced electrical signal (output) in response to applied mechanical stress on the physical stress sensor 111 of the WMD 100, e.g., mechanical stress signal emanating from an in vivo anatomic structure or region of the body for a physiological phenomenon that propagates to the region where the WMD 100 is positioned outside of the body (ex vivo) and interfaced with the subject's skin to receive the mechanical stress. The produced electrical signal is received at the LNA 381, which amplifies the electrical signal from stress sensor and is the first stage of the signal conditioning process. In some embodiments, for example, depending on specifications or constraints of the implementation of the physical stress sensor 111, the LNA may be configured as a voltage amplifier with voltage input and amplified voltage output, or may be a charge amplifier with a charge input and voltage output. The low-noise amplified electrical output signal from the LNA 381 is received at the VGA 383. For example, it can be beneficial to have a variable gain amplifier in the signal conditioning process, e.g., particularly one where the gain may be programmable by the user or the gain may be varied automatically, for instance, to keep the output level in a desired range. The variable-gain amplified electrical output signal of the VGA 383 is received at the BPF 385. For example, inDocket No.: CANA.476PCsome implementations, the BPF 385 provides an audio / acoustic amplifier to the charge circuit amplifier 380' and is configured to band-pass filter its input signal to only allow frequency components within a certain range to pass (e.g., which can be pre-determined) and to block (or at least substantially attenuate) frequency components outside that band. In some examples, the frequency bands to which the BPF 385 will allow can include one or more ranges among, but not limited to, a range of 1 Hz to 10 kHz; a range of 1 Hz to 5 kHz; a range of 10 Hz to 1 kHz; a range of 10 Hz to 10 kHz; a range of 10 Hz to 100 kHz, or a range of 1 Hz to 100 kHz. In some embodiments, the charge amplifier circuit 380' includes the NF 387 to block certain frequency components within the band-passed signal that is the output of the BPF 385. For example, in some implementations, the NF 387 can be configured to block frequencies at substantially 60 Hz and / or at substantially 50 Hz, which may be noise artifacts in some environment(s) of the body of the subject hosting the WMD 100. The output of the BPF 385 (or optional NF 387) is received at the ADC 389, which converts an analog signal (e.g., the electrical signal representative of the detected mechanical stress signal (e.g., audio / acoustic signal)) to a digital electrical signal. In various embodiments, the Nyquist sampling frequency can be set at a frequency of at least 2x the largest frequency of the passed frequency band to ensure full signal preservation in the digitization of the output electrical signal. Examples of the digital sampling frequency can include 200 kHz, 500 kHz, 1 MHz, 2 MHz, 5 MHz, or higher. Whereas, in some examples, the digital sampling frequency can include 2 kHz, 20 kHz, 50 kHz, or higher. In some implementations, for example, preferred data conversion rates of the ADC are typically in the range 1,000-10,000 samples per second, which are suitable for heart and respiratory sound and physical phenomena monitoring, e.g., providing a data resolution between 8-24 bits with preference for 16 bits. The digitized signal output of the exemplary charge amplifier circuit 380' can be transferred to a data processing unit (e.g., microcontroller) of the electronics unit 120 of the WMD 100, e.g., for storage in memory, subsequent data processing (e.g., based on algorithms programmed in the data processing unit), and / or transmission from the WMD 100 to an external device.

[0115] FIG. 4 shows diagrams depicting example geometries of example embodiments of the unimorph piezoelectric sensor device of FIG. 3A, labeled as 411 in FIG. 4. The unimorph piezoelectric sensor device 411 includes at least two electrode structures of the second layer 315, shown in the top diagram of FIG. 4 as first electrode 315X and second electrode 315Y, which are separated from the each other by a gap, and are coupled to the piezoelectricDocket No.: CANA.476PCmaterial 312 that is coupled to the first layer 313 (e.g., positioned in the WMD housing 319 to be exposed through an (optional) aperture). As depicted in lower diagrams 411A, 411B, and 411C of FIG. 4, the at least two electrodes of the unimorph piezoelectric sensor device 411 can be configured in a variety of geometries and configurations, including but not limited to rectangular, elliptical, and triangular, and can include three or more electrodes.Exemplary Methods and Data

[0116] In some embodiments in accordance with the present technology, there are provided methods for ex vivo monitoring of internal mechanical energy, including acoustic energy such as sound, associated with physiological phenomena originating from an anatomic structure within a host. In some embodiments, for example, the methods include monitoring one or more aspects of a body tissue, e.g., body anatomy, physiology, metabolism, and / or function, via a wearable device having a physical stress sensor, including a physical stress sensor as disclosed herein. Monitoring may include, for example monitoring, detecting, measuring, identifying, and / orcharacterizing one or more of the aspects of a body tissue. The physical stress sensor, optionally with one or more auxiliary sensors, may be incorporated into a wearable device as disclosed herein, such as a mechanical stress sensor device, a piezoelectric sensor device, a unimorph piezoelectric sensor device. The method may include obtaining an internal mechanical energy signal via the wearable physical stress sensor. The method may include processing, via a data processing device, the internal mechanical energy signal, such as measuring the intensity of the internal mechanical energy signal, to produce biomedical data. The method may include using the biomedical data to characterize a status of the host, e.g., to detect a health and / or disease state of the host, to diagnose a health and / or disease state of the host, and / or to quantify a health and / or disease state of the host. Methods in accordance with the present technology, for ex vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure within a host, may be described below or elsewhere herein.

[0117] In some embodiments, there are provided methods for ex vivo monitoring of internal mechanical energy associated with physiological phenomena originating from a heart within a host. The host may be a human. The host may be a non-human mammal, such as a dog, pig or a horse, where optionally the mammal is at least 30 pounds in weight. The method may include obtaining an internal mechanical energy signal from the heart of the host via the wearable physical stress sensor. For example, the device having a wearable physical stressDocket No.: CANA.476PCsensor may monitor internal mechanical energy associated with activity of the heart, such as a series of heart beats, i.e., the beating of the heart, from the device worn outside the host's body. The present technology may thus provide a measure of the host's heart rate, which refers to the number of times the heart beats within a certain time period, usually a minute. The measure of the host's heart rate may allow the clinician to know whether the host's heart rate is within the normal range, or whether the heart rate is faster or slower than normal. The present technology may also provide a measure of the regularity of the host's heart beats, e.g., whether the host has regular or irregular heartbeats. The mechanical energy signal may be processed, via a data processing device, to provide biomedical data.

[0118] In some embodiments, a method for monitoring a host's cardiac function can include the following. An example embodiment of a wearable medical device (WMD) having, at least, an electrocardiogram sensor and a physical stress sensor in accordance with the present technology is secured to the body of the subject, e.g., in the vicinity of the subject's chest proximate to the subject's heart. The WMD acquires electrophysiological data from the electrocardiogram sensor that can depict cardiac cycle events including the systole and diastole events, i.e., diastole represents ventricular filling, and systole represents ventricular contraction / ejection. The initial electrophysiological data can be processed as baseline data, where certain points in the data can determine certain physiological functions, e.g., such as a first point designated SI that identifies the biological event of mitral / tricuspid valve closure and a second point designated S2 that identifies the biological event of aortic / pulmonic valve closure. After obtaining the baseline data, the method can include monitoring the host for potential mitral regurgitation (MR), also known as mitral valve regurgitation (MVR) or mitral insufficiency. MR is a common heart valve disorder in mammals including humans. When MR is present, blood leaks backwards through the mitral valve when the heart contracts. This reduces the amount of blood that is pumped out to the body. When MR occurs in the host being monitored by the method using the WMD, additional mechanical energy signals are obtained by the physical stress sensor of the WMD over a monitoring period of time. The new mechanical energy signals will not be in the baseline environment. These new mechanical energy signals are attributed to the mechanical energy that emanates from the beating heart due to the MR problem, including the blood regurgitation that is occurring by virtue of the malfunctioning of the mitral valve. It is noted that the WMD in this example method may also be used to monitor more than just cardiac function, including but notDocket No.: CANA.476PClimited to respiratory function, gastrointestinal function, among others.

[0119] FIG. 5 shows a diagram of an example embodiment of a method for monitoring an anatomic structure, such as a blood vessel or multiple blood vessels, the heart, an airway or multiple airways, and / or the lung(s) of a subject, from a wearable medical device, in accordance with the present technology, including but not limited to WMD 100, 200, 600, 700A, 700B, or other embodiments disclosed herein. The method 500 includes a process 510 to receive, at a physical stress sensor of a WMD worn outside a subject's body, an internal mechanical energy signal that emanates within the subject's body from the anatomic structure of interest. The method 500 includes a process 520 to convert, by the physical stress sensor, the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the anatomic structure of interest. In various example implementations, the anatomic structure of interest includes a heart of the subject, a lung or lungs of the subject, or both the heart and the lung or lungs of the subject. In various example implementations, the method 500 detects an acoustic signal (e.g., sound) generated from an event or events associated with the anatomic structure of interest that is measured by the physical stress sensor.

[0120] In some embodiments of the method 500, the method 500 may include (optionally) a process 580 to determine a health and / or disease state of the subject. For example, the method can be implemented to detect a fluid turbulence within or proximate of the anatomic structure. In some examples, the fluid turbulence includes at least one of a breathing turbulence or blood flow turbulence as blood travels through the heart or a blood vessel of the subject. For example, the method can be implemented to detect a tissue contact of the anatomic structure from the detectable mechanical energy that emanates from that physiological event (tissue contact). In some examples, the tissue contact includes closing of a heart valve or at least two heart valves closing. For example, the method 500 can be implemented to detect a blood flow through a lesion caused by a restenosis of a blood vessel. In various implementations of the method 500, for example, the process 580 to determine the health and / or disease state of the subject can include data-processing the electrical signal indicative of the physiological function for the subject into an individual data set; and comparing the individual data set of the subject with a standard reference data set of a population of subjects (e.g., standard clinical study data) to identify the health and / or disease state, e.g., by correlating the individual data set or at least a portion of the individual data setDocket No.: CANA.476PCwith the standard reference data set or at least a portion of the standard reference data set associated with one or more classification(s) of a health state or a disease state.

[0121] In some embodiments of the method 500, the method 500 may include (optionally), implemented prior to the process 510, a process to provide the WMD that comprises the physical stress sensor to a region within the subject's body, wherein the WMD is positioned on the outside of the subject's body proximate to the anatomic structure of interest in the subject's body. In some implementations, for example, the WMD is positioned to be coupled to the subject's skin at a region outside the body that is within 10 cm or 5 cm or less of the anatomic structure of interest. In some examples, the process 510 can include attaching the WMD to the outer epidermis layer of the skin above the pectoralis major muscle near the subject's heart by adhering the WMD to the skin. Example techniques to adhere the WMD to the skin can include using an adhesive dressing that attaches to the housing of the WMD and to the skin. For example, the rigid structural design of the physical stress sensor (e.g., example embodiment of the unimorph piezoelectric sensor 311) and the WMD overall allows for the WMD to be safely secured at various locations of the subject's body because the structural rigidity of the physical stress sensorand WMD ensure safety to the subject from potential, unintended damage (e.g., ability to withstand external or internal forces and preserve structural integrity) while effectively carrying out its intended sensing monitoring functions.WMD with Stress-Mediated Sensor and ECG

[0122] FIG. 6 shows an illustration of the example embodiment of the WMD 100, labeled WMD 600 in the drawing, to measure mechanical energy signals and electrophysiological signals (i.e., ECG) of the cardiovascular system (e.g., the heart and major arteries and veins) and / or the pulmonary system (e.g., the lungs and airways) in human and non-human living subjects. In some implementations, for example, the WMD 600 is configured to continuously measure mechanical energy signals and electrophysiological signals (i.e., ECG) of the cardiovascular system and / or the pulmonary system in human and non-human living subjects; whereas, in some implementations, for example, the WMD 600 is configured to periodically or intermittently measure mechanical energy signals and electrophysiological signals (i.e., ECG) of the cardiovascular system and / or the pulmonary system in human and non-human living subjects. In some implementations of the WMD 600, for example, the WMD 600 can be secured on the skin in the chest area of the subject (placeable near theDocket No.: CANA.476PCsubject's heart with the physical stress sensor facing medially), e.g., which enables the attachment of the WMD 600 to be in a non-hospital clinic, such as the primary care physician clinic of the subject, or in some cases, to be secured to the subject by the subject him / herself. For instance, the WMD 600 can be placed near the subject's heart (on the skin), in which the WMD 600 is oriented during placement to have the exemplary physical stress sensor 111 facing toward the subject's heart. The sensor unit and electronics unit of the WMD 600 can be hermetically-sealed within a housing of the WMD 600. In various examples of the WMD 600, the entirety or at least a portion of the hermetically sealed WMD 600 can be coated in a dielectric material, e.g., parylene, in a manner discussed above with respect to the exemplary unimorph piezoelectric stress sensors. Example embodiments of the WMD 600 are shown in FIGS. 2A and 2B.

[0123] FIG. 7A shows an exploded view of an example embodiment of the WMD, labeled WMD 700A in FIG. 7A, featuring components of an example embodiment of the physical stress sensor 111 (e.g., unimorph piezoelectric stress sensor 311A, 311B, 311C, 311D, 311E, 311F, 311G, 311J, 311K, etc.) and an example embodiment of the electronics unit 120, which can be hermetically-sealed within a housing 701. In some embodiments, for example, the housing 701 of the WMD 700A includes a chamber enclosed by a housing top 701T and a housing bottom 701B. In some embodiments of the WMD 700A, for example, a physical stress sensor assembly 712 of the example physical stress sensor 111 is configured at a housing opening 7010 of the housing bottom 701B to position the physical stress sensor assembly 712 at a location of the WMD 700A able to receive mechanical energy indicative of the anatomy of interest where the WMD 700A is secured to the body of the subject. For example, in some embodiments of the example physical stress sensor 111, the physical stress sensor assembly 712 includes a piezoelectric material and at least one electrically-conductive non-piezoelectric, biocompatible material coupled to the piezoelectric material to receive the transduced electrical signals generated upon applied stress to the example physical stress sensor 111 that is received by the piezoelectric material. In some embodiments, for example, the at least one electrically-conductive non-piezoelectric, biocompatible material is positioned on an interior-facing side of the piezoelectric material and configured at the housing opening 7010 of the housing bottom 701B. In some embodiments, for example, the WMD 700A includes an internal housing frame 701F to at least partially encase the physical stress sensor assembly 712 to position and orient the physical stress sensor assembly 712 inDocket No.: CANA.476PCthe housing 701.

[0124] The WMD 700A includes an example embodiment of the electronics unit 120. In some embodiments, the example electronics unit 120 of the WMD 700A includes a data and / or signal processing unit 720PCB, which can be embodied by any of the exemplary embodiments of the data processing unit 121 and / or the optional signal conditioning unit 123, respectively, disclosed herein. In the example shown in FIG. 13A, the data and / or signal processing unit 720PCB includes a processor coupled to a memory which receives digital signal data from a signal processing circuit, all mounted on a printed circuit board (PCB). In some example embodiments, for example, the signal processing circuit includes a differential amplifier and / or charge amplifier (like that shown in FIG. 31, for example) to amplify the electrical signals received from the example physical stress sensor 111 (e.g., a unimorph piezoelectric stress sensor, such as from the at least one electrically-conductive nonpiezoelectric material) via the electrical interface component(s) 725 that connect the example physical stress sensor 111 to the example electronics unit 120). In some example embodiments, for example, the data and / or signal processing unit 720PCB includes an analog-to-digital (A / D) converter to digitize the electrical signals. In some example embodiments, for example, the signal processing circuit includes filter circuit(s) to remove signal outside frequency range(s) of non-interest, which can include low-pass, bandpass, and / or high-pass filters, e.g., to improve signal-to-noise ratio of the detected mechanical energy signal of interest. The exemplary data and / or signal processing unit 720PCB can be programmable for some embodiments. In some embodiments, for example, the data and / or signal processing unit 720PCB can be secured and / or positioned within a chamber of the housing bottom 701B by the example internal housing frame 701F.

[0125] In some embodiments, for example, the WMD 700A may optionally include an inertial measurement unit (IMU) to monitor motion (in multiple degrees of freedom) and / or determine an orientation of the WMD 700A (and thereby of the example embodiment of the physical stress sensor 111 in the WMD 700A). The IMU is configured in electrical communication with the electronics unit 120 via the electrical interconnection(s), e.g., in communication with the exemplary embodiments of the data processing unit 121 and / or the optional signal conditioning unit 123. In some embodiments, the IMU (not shown) can be configured on the printed circuit board of the data and / or signal processing unit 720PCB. In some embodiments, for example, the IMU can include an accelerometer and / or a rotationalDocket No.: CANA.476PCrate sensor (e.g., gyroscope) to monitor patient motion and / or position. In some embodiments, for example, the IMU can include a magnetometer.

[0126] In some embodiments, for example, the WMD 700A may optionally include a temperature sensor to measure the temperature (e.g., surface temperature) in the region proximate the location where the WMD 700A is deployed or a core body temperature sensor via an implantable contingent of the WMD 700A, which can monitor changes in core body temperature, such as between the subject's resting state, active state (e.g., exercise), and sleeping state. In some embodiments of the WMD 700A includingthe core body temperature sensor, the implantable contingent (not shown) can be configured to span through an opening (not shown) of the housing bottom 701B, such as a canula that inserts through the subject's skin to a region of interest to detect the core body temperature of the subject. In some embodiments, the WMD 700A can include a surface temperature sensorthat is configured at an opening (not shown) of the housing bottom 701B to measure the skin surface temperature of the host when the WMD 700A is secured to the host's body.

[0127] In some embodiments, for example, the WMD 700A may optionally include a separate step counter sensor (e.g., comprising at least one accelerometer and / or one or more rotational rate sensors) that is separate from an exemplary (optional) IMU of the WMD 700A. Yet, in some embodiments, the WMD 700A can utilize the (optional) IMU to track steps or otherwise serve as a step counter of the subject.

[0128] In some embodiments, for example, the WMD 700A may optionally include an analyte sensor to measure a parameter (e.g., concentration) of an analyte in the region proximate the location (e.g., surrounding tissue) where the WMD 700A is deployed on the body the subject. For example, in such embodiments of the WMD 700A including the analyte sensor, the analyte sensor can include an implantable contingent (e.g., such as an array of microneedles or a canula (not shown) spanning through an opening (not shown) of the housing bottom 701B) that penetrates into a subcutaneous space beneath the skin where the WMD 700A is mounted to detect one or more analyte concentration(s) in interstitial fluid in the location where the analyte sensor is deployed.

[0129] In some embodiments, for example, the WMD 700A may optionally include a pH sensor to measure the pH level in the region proximate the location where the WMD 700A is deployed. In such embodiments of the WMD 700A including the pH sensor, the pH sensor can include an implantable contingent (not shown) that inserts into the subject's skin to theDocket No.: CANA.476PCregion of interest to detect a pH level of an interstitial fluid of the subject.

[0130] The electronics unit 120 of the WMD 700A includes a power supply 729 electrically connected, via components (e.g., wires or other connectors) of the electrical interface 725, to the data and / or signal processing unit 720PCB and other components of the electronic unit 120 (or other unit(s) of the WMD 700A, such as some embodiments of the physical stress sensor 111, when electrical power is needed to be supplied to such units). The power supply 729 can be embodied by any of the exemplary embodiments of the power supply 729 disclosed herein. For example, the power supply 729 can include a battery (e.g., primary or rechargeable), fuel cell, or other power source to supply power to the components of the electronics unit 120 (and, optionally, the physical stress sensor 111). In some example embodiments, for example, the power supply 729 can be an electrical receiving port to receive a wire that can supply the WMD 700A from a remote power source, e.g., such as a wire connectable to a wall socket power source (e.g., 110V or 220V AC source) or a wire connectable to another wearable device power supply (e.g., connecting to a battery worn by the user with the wire connecting the battery to another device worn by the subject). In some embodiments, the power supply 729 may include an AC / DC converter to convert AC power to DC power.

[0131] FIG. 8 shows a diagram of an example embodiment of an example embodiment of the WMD 600 with a wire or cable 893 (e.g., having biocompatible and electrically shielding cover) to be in wired communication with a remote power source (not shown) via terminal 892 of the wire or cable 893.

[0132] Referring back to FIG. 7A, in some embodiments of the WMD 700A, for example, the example electronics unit 120 includes a wireless communications unit that includes an antenna 727A, which is electrically connected, via components (e.g., wires or other connectors) of the electrical interface 725, to the data and / or signal processing unit 720PCB and other components of the wireless communications unit of the electronic unit 120 (or other unit of the WMD 700A, such as some embodiments of the physical stress sensor assembly 712, e.g., for transmitting raw electrical signals transduced by the sensor). The wireless communication unit of the WMD 700A can include a wireless transmitter, receiver, and / or transceiver device, e.g., which can include antenna 727 , which is capable of communicating with an external device to communicate raw, partially-processed, or fully-processed data from the data and / or signal processing unit 720PCB. For example, the wirelessDocket No.: CANA.476PCcommunications unit can be configured to manage the communication protocol for transmission or reception via the antenna 727A. The wireless communication unit can be embodied by any of the exemplary embodiments of the wireless communications unit 127 disclosed herein. Examples of the antenna 727A can include, but are not limited to, a whip antenna, a loop antenna, a chip antenna, a planar inverted F antenna (PIFA), a bipolar antenna, and / or a conformal antenna.

[0133] The WMD 700A includes a plurality of ECG sensor assemblies, with a first ECG sensor assembly 719 configured on a first end of the housing 701 and a second ECG sensor assembly 719 configured on a second end of the housing 701, which is separated from the first ECG sensor assembly 719 by a distance of at least the length of the housing bottom 701. Each ECG sensor assembly 719 includes an end case having an end case housing top 793T and an end case housing bottom 793B that are joinable together and which position an ECG electrode 791 with respect to the end case. For instance, in some embodiments, the ECG electrode 791 is configured on a side of the WMD 700A that is the same side as the housing opening 7010 where the physical stress sensor assembly 712 is positioned. In the example shown in FIG. 7A, for each ECG sensor assembly 719, the ECG electrode 791 is configured to couple with an outward -fa ci ng portion of the end case housing bottom 793B such that it (i) exposes at least a portion of the surface of the ECG electrode 791 to the outer environment of the WMD 700A and (ii) is electrically connected, via components (e.g., wires or other connectors) of the electrical interface 725, to be in electrical communication with the data and / or signal processing unit 720PCB.

[0134] In some embodiments, for example, like that shown in FIG. 7A, the end case housing top 793T and the end case housing bottom 793B are both joined together and connected to the end portions of the housing bottom 701B via connection pins 795, e.g., which connection pins are able to be retained in protrusion channels 796 rigidly connected to the outer wall of the housing bottom 701B. In some embodiments of the ECG sensor assembly 719, like that shown in FIG. 7A, the antenna 727A can be housed, at least partially, in a region within the ECG sensor assembly 719, e.g., such as a cavity between the end case housing top 793T and the end case housing bottom 793B. For example, the WMD 700A may be configured such that only one of the plurality of ECG sensor assemblies includes the antenna 727A in one of the end cases; whereas in other examples, the WMD 700A may include two antennas 727A each housed in the end case structures of the respective ECGDocket No.: CANA.476PCsensor assembly 719 for the plurality of ECG sensor assemblies.

[0135] The example ECG sensor assembly 719 is operable to measure an electrical signal (e.g., spike) corresponding to the electrophysiological signals of the cardiac muscle tissue for controlling the patient's heartbeat, where the spikes give rise to the ECG signal of the host. For example, the WMD 700A, having both an example embodiment of the physical stress sensor 111 and an example embodiment of an ECG sensor (e.g., the ECG sensor assembly 719), the WMD 700A is capable of estimating the pulmonary arterial pressure (PAP) of the host when deployed on the host's body near the host's heart (e.g., in a subcutaneous region of the host's chest area). For instance, the physical stress sensor of the WMD 700A is responsive to, i.e., can detect, mechanical waves generated by the host's heart as it proceeds through the aortic (A2) and the pulmonary (P2) components of the second heart sound (S2); and, simultaneously (e.g., concurrently over a short time period of a fraction of a second), the ECG sensor collects ECG data that is used to identify the S2 region of the data obtained from the stress sensor. That detection of A2 and P2 allows for the data from the device to be used to determine the A2-P2 splitting interval (SI), i.e., the time interval between the A2 and the P2, which is recognized to be a useful parameter for estimating the PAP.

[0136] In the example WMD 700A, the ECG sensor assembly 719 includes two ECG electrodes 791 configured at opposing ends of the WMD housing (e.g., housing bottom 701B). Yet, it is understood that the ECG sensor assembly 791 can be configured with a single ECG electrode 791, as shown and discussed in another embodiment of the WMD shown in FIG. 7B (i.e., WMD 700B).

[0137] FIG. 7B shows an exploded view of another example embodiment of the WMD, labeled WMD 700B in FIG. 7B. The WMD 700B is configured similarly (e.g., includes the same or similar features) to the WMD 700A, but with only one ECG sensor assembly 719 configured on one end of the WMD 700B, e.g., the end closest to the housing opening 7010.

[0138] The disclosed devices, systems, and methods for ex vivo monitoring of internal mechanical energy can be advantageous over conventional devices, systems, and techniques, e.g., including but not limited to the continuous and multi-situational data (e.g., data from the patient at rest, at activity (e.g., exercise), and during sleep); the elimination of patient participation or compliance in the ex vivo monitoring process; by the access to otherwise difficult or impossible signal data to acquire, and by improved the signal detection parameters themselves, such as signal resolution, signal-to-noise quality, etc.Docket No.: CANA.476PC

[0139] Thus, the present technology provides methodology for ex vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure within a host, comprising: measuring, via a wearable medical device of the present technology, an internal mechanical energy signal; processing, via a data processing device, the measured internal mechanical energy signal to produce biomedical data; and using the biomedical data to diagnose and / or detect and / or quantify a health and / or disease state of the host, where the physiological phenomena is beating and the anatomic structure is the heart, which may also be referred to as periodic systole and diastole, the host is a mammal, and the health state of the host is mitral regurgitation (MR).

[0140] In some embodiments there are provided methods for ex vivo monitoring of internal mechanical energy associated with physiological phenomena originating from a lung within a host, where the physiological phenomena may be expansion and contraction of the lung volume, e.g., breathing, and the host is a mammal.

[0141] For example, in conventional phonocardiography, a physician will target stethoscope placement based on the organ of interest, such as the chest for heart auscultation and the back for lungs auscultation to obtain the best, discernable audio signal to listen to the patient's heartbeat and breathing, respectively. Yet, with the WMD in accordance with the present technology, both the heart and the lungs acoustic data can be captured and analyzed from a single device deployment location without the need for a clinician to take the measurement.

[0142] In some implementations, for example, an example embodiment of the WMD 100 that is secured on the body near the subject's heart can isolate the subject's respiratory acoustic signature, e.g., from raw data acquired by the example physical stress sensor 111 of the WMD that is filtered by an example embodiment of the signal conditioning unit 123 (e.g., charge amplifier 380') for higher frequency data, e.g., in the 256-512 Hz band. For example, the exemplary filter(s) of the signal conditioning unit 123 (e.g., charge amplifier 380') can remove signal from most of the cardiac signature, while maintaining the respiratory signature, even with the wearable device placed on the chest. For example, in some implementations, the raw data can be filtered for both the cardiac signature and the respiratory signature in parallel, allowing for simultaneous monitoring from a single wearable device.

[0143] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising detecting anDocket No.: CANA.476PCinternal mechanical energy signal associated with a physiological phenomenon of an internal body structure from outside of the patient's body, wherein the detecting is accomplished by a wearable medical device that comprises a physical stress sensor. In some embodiments, the method may also include processing the detected internal mechanical energy signal to produce biomedical data; and using the biomedical data to determine (e.g., diagnose and / or quantify) a health and / or disease state of the patient.

[0144] For example, the internal mechanical energy signal may be an internal mechanical pressure wave, as non-limiting examples. The physiological phenomenon may be a movement, e.g., a movement of a fluid or of an organ, as non-limiting examples. The internal body structure may include a heart, a blood vessel, a lung or lungs, and / or a region of a gastrointestinal system, as non-limiting examples. The physical stress sensor may be detecting a fluid turbulence (as the internal mechanical energy signal) within an internal body structure, e.g., breathing turbulence or blood flow turbulence as blood travels through the heart ora blood vessel, as non-limiting examples. The physical stress sensor may be detecting tissue contact, e.g., a heart valve or valves closing, such as two or more heart valve structure contacting each other as the valves close. For example, the physical stress sensor may be detecting blood flow through a lesion caused, for example, by restenosis (restenosis is a recurrence of stenosis, which is a narrowing of a blood vessel that leads to restricted blood flow).

[0145] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting a first internal mechanical energy signal and a second internal mechanical energy signal associated with a first physiological phenomenon and a second physiological phenomenon, respectively, of a first internal body structure and a second internal body structure, respectively, from outside of the patient's body, wherein the detecting is accomplished by a single wearable medical device that comprises a physical stress sensor.

[0146] For example, the first internal mechanical energy signal may be an internal mechanical pressure wave generated by the heart or fluid flow within the heart or at least one proximate blood vessel, and the second internal mechanical energy signal may be an internal mechanical pressure wave generated by the lung or lungs or fluid inhaled by, within, or expelled by the lung or lungs, as non-limiting examples. The first physiological phenomenon may be a movement of blood in the heart or heart valves opening or closing, asDocket No.: CANA.476PCnon-limiting examples. The second physiological phenomenon may be a movement of air into, within, or out of the lung or lungs, as non-limiting examples. The first internal body structure may include a heart and / or a blood vessel, and the second internal body structure may include a lung or lungs, as non-limiting examples. The physical stress sensor may be detecting a fluid turbulence (as the internal mechanical energy signal) within an internal body structure, e.g., breathing turbulence or blood flow turbulence as blood travels through the heart or a blood vessel, as non-limiting examples. The physical stress sensor may be detecting tissue contact, e.g., a heart valve or valves closing, such as two or more heart valve structure contacting each other as the valves close. For example, the physical stress sensor may be detecting blood flow through a lesion caused, for example, by restenosis (restenosis is a recurrence of stenosis, which is a narrowing of a blood vessel that leads to restricted blood flow).

[0147] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting an internal mechanical energy signal and an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, wherein the detecting is accomplished by a single wearable medical device that comprises a physical stress sensor and an electrophysiological sensor (e.g., electrocardiogram (ECG) sensor).

[0148] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting (i) an internal mechanical energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, and (ii) a position, orientation, and / or a movement of the patient, wherein the detecting is accomplished by a single wearable medical device that comprises a physical stress sensor and an inertial measurement unit (IMU) (e.g., the IMU comprising at least one of an accelerometer, a rotational rate sensor, or a magnetometer).

[0149] For example, the position, orientation, and / or movement of the patient detected by the IMU is used to determine whether the patient is (1) at rest (i.e., awake and stationary and / or exhibiting low activity), (2) undergoing activity (e.g., exercise or substantial movement or activity), or (3) is sleeping (e.g., laying down in a horizontal or substantially reclined position).Docket No.: CANA.476PC

[0150] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting (i) an internal mechanical energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, and (ii) a core body temperature of the patient, wherein the detecting is accomplished by a single wearable medical device that comprises a physical stress sensor and a temperature sensor, respectively.

[0151] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting (i) an internal mechanical energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, (ii) a position, orientation, and / or a movement of the patient, and (iii) a core body temperature of the patient, wherein the detecting is accomplished by a single wearable medical device that comprises a physical stress sensor, an inertial measurement unit (IMU) (e.g., the IMU comprising at least one of an accelerometer, a rotational rate sensor, or a magnetometer), and a temperature sensor, respectively.

[0152] In some example embodiments in accordance with the present technology, a method for assessing a clinical condition of a patient, the method comprising simultaneously detecting (i) an internal mechanical energy signal and (ii) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, (iii) a position, orientation, and / or a movement of the patient, and (iv) a core body temperature of the patient, wherein the detecting is accomplished by a wearable medical device that comprises (i) a physical stress sensor and (ii) an electrophysiological sensor (e.g., electrocardiogram (ECG) sensor), (iii) an inertial measurement unit (IMU) (e.g., the IMU comprising at least one of an accelerometer, a rotational rate sensor, or a magnetometer), and (iv) a temperature sensor, respectively. In some embodiments, the method may also include processing the detected internal mechanical energy signal and at least one of the detected electrophysiological energy (e.g., ECG), core body temperature, and / or position, orientation, and / or a movement of the patient to produce biomedical data; and using the biomedical data to determine (e.g., diagnose and / or quantify) a health and / or disease state of the patient.

[0153] For example, in some implementations of the method, the clinical conditionDocket No.: CANA.476PCincludes mitral valve regurgitation (MVR), which is a disease state of the patient that can be determined by implementation of the method. MVR or other disease state of the patient can be determined by a compilation of the detected internal mechanical energy with at least one of the detected electrophysiological energy (e.g., ECG), core body temperature, and / or position, orientation, and / or a movement of the patient. For example, the position, orientation, and / or movement of the patient detected by the IMU can be used to determine whether the patient is (1) at rest (i.e., awake and stationary and / or exhibiting low activity), (2) undergoing activity (e.g., exercise or substantial movement or activity), or (3) is sleeping (e.g., laying down in a horizontal or substantially reclined position).

[0154] In some example embodiments in accordance with the present technology, a method for monitoring an anatomic structure from a wearable medical device includes: deploying the wearable medical device on a region or location of the subject's body proximate to an anatomic structure of interest (e.g., heart and / or lungs), where the wearable medical device comprises a physical stress sensor; receiving, at the physical stress sensor, an internal mechanical energy signal that emanates within the subject's body from the anatomic structure of interest, which is received at the physical stress sensor of the wearable medical device from outside the subject's body; and converting, by the physical stress sensor, the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure.

[0155] In some embodiments, the wearable medical device is positioned to be coupled to subject's body at the region or location within 50 mm or less, or 100 mm or less, or 200 mm or less, or 500 mm or less of the anatomic structure of interest. For example, in some implementations, the anatomic structure of interest is the heart, a lung or the lungs, or both the heart and the lung(s) of the subject. In some embodiments, the wearable medical device further comprises an electrophysiological sensor (e.g., electrocardiogram (ECG) sensor), and the method further includes simultaneously detecting (i) the internal mechanical energy signal and (ii) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure, from outside of the patient's body, e.g., by receiving, at the electrophysiological sensor, the electrophysiological energy signal that emanates within the subject's body from the anatomic structure of interest, and converting, by the electrophysiological energy signal, the electrophysiological energy signal to a second electrical signal indicative of an electrophysiological function by the internal body structure.Docket No.: CANA.476PCIn some embodiments, the wearable medical device further comprises an inertial measurement unit (IMU), and the method further includes simultaneously detecting (i) the internal mechanical energy signal and (ii) a position, orientation, and / or a movement of the subject, e.g., by transducing, at the IMU, the position, orientation, and / or movement by the subject to a third electrical signal indicative of physical function of the subject and thereby associated with the internal body structure. For example, the position, orientation, and / or movement of the patient detected by the IMU can be used to determine whether the patient is (1) at rest (i.e., awake and stationary and / or exhibiting low activity), (2) undergoing activity (e.g., exercise or substantial movement or activity), or (3) is sleeping (e.g., laying down in a horizontal or substantially reclined position). In some embodiments, the wearable medical device further comprises a temperature sensor, and the method further includes simultaneously detecting (i) the internal mechanical energy signal and (iv) a core body temperature of the subject, e.g., by transducing, at the temperature sensor, a temperature measurement of the subject to a fourth electrical signal indicative of core body temperature of the subject within a region proximate where the wearable medical device is deployed. In some embodiments, the wearable medical device comprises each of the physical stress sensor, the electrophysiological sensor, the IMU, and the temperature sensor, and the method includes the detecting as described above.

[0156] In some embodiments, the wearable medical device may be used in a method for assessing a clinical condition of a patient having a beating heart, where the clinical condition is pulmonary arterial pressure (PAP), the method comprising: (a) detecting ECG data generated by the beating heart while simultaneously (b) detecting mechanical pressure wave data generated by the beating heart, (i) the detecting ECG data and the detecting mechanical pressure wave data occurring simultaneously while the heart proceeds through an aortic (A2) and a pulmonary (P2) component of a second heart sound (S2) of a heartbeat, (ii) wherein the mechanical pressure wave and the ECG data are obtained simultaneously by a single wearable medical device comprising a physical stress sensor and an electrophysiological (e.g., ECG) sensor; (c) optionally, analyzing the ECG data to identify a time point when the beating heart is in an S2 region of the heartbeat; (d) optionally, analyzing the ECG data to identify a time point when A2 and a time point when P2 are taking place in an S2 region; (e) optionally, determining a A2-P2 splitting interval (SI), where SI is a time interval between the time point of A2 and the time point of P2 of a heartbeat, where the time interval is normalized to theDocket No.: CANA.476PCheart rate; (f) optionally, calculating a pulmonary arterial pressure (PAP) based on the determined SI.Performance Systems for Subjects (e.q., humans or animals)

[0157] "Sensor" refers to a device that can be utilized to do one or more of detect, measure and / or monitor one or more different aspects of a body (anatomy, physiology, metabolism, and / or function / mechanics). Representative examples of sensors suitable for use within the sensor devices include, for example, fluid pressure sensors, fluid volume sensors, contact sensors, position sensors, pulse pressure sensors, blood volume sensors, blood flow sensors, acoustic sensors (including ultrasound), chemistry sensors (e.g., for blood and / or other fluids), metabolic sensors (e.g., for blood and / or other fluids), accelerometers, gyroscopes, mechanical stress sensors and temperature sensors. Within certain embodiments the sensor can be a wireless sensor, or, within other embodiments, a sensor connected to a wireless microprocessor.

[0158] " Biomarker," as used herein, refers to an objective indication of a medical state or physical condition, which can be measured accurately and reproducibly, and used to monitor and treat progression of the medical state or physical condition. Biomarkers individually or collectively include physiological measurements, anatomical measurements, metabolic measurements (e.g., glucose and / or oxygen), and functional / mechanical measurements, such as may be provided by the above-described sensors. Biomarkers also include quantifiable aspects or characteristics of the aforementioned measurements. For example, biomarkers include kinematic parameters, such as cadence, stride length, walking speed, tibia range of motion, knee range of motion, step count and distance traveled, that may be derived from kinematic data. Examples of kinematic data that can be monitored, analyzed, and reported by the system 10 of FIG. 1A are disclosed in WO 2023 / 278775A1 (which is incorporated by reference herein). Examples of metabolic measurements for metabolic functions such as glucose and / or oxygen can be found in U.S. Patent Nos. 11,013,440, 11,000,216, 11,000,213, 10,980,452, 10,973,443, 10,966,644, 10,959,654, 10,952,653, 10,945,649, 10,945,647, 10,881,341, 10,874,338, 10,827,954, 10,820,842, 10,702,215, 10,702,193, and 10,993,642, all of which are incorporated by reference in their entirety.

[0159] In an example application of the system 10, the system 10 monitors for a digestive disorder, e.g., colic, based on sound / motion / stress information and temperature information provided by an example embodiment of the WMD 100 having the physical stress sensor 111Docket No.: CANA.476PCand an example embodiment of the secondary sensor(s) 119 as a temperature sensor. To this end, the external receiver device 130 of the system 10 is configured to establish normal / baseline digestive sound / motion / stress and normal / baseline temperatures for the digestive system of the subject based on sound / motion / stress information and temperature information provided by the WMD 100. The external receiver device 130 of the system 10 is also configured to monitor the sound / motion / stress information and temperature information over time for a deviation from the baselines that is indicative of a digestive disorder, e.g., colic, and to provide an alert if a digestive disorder is detected or a measure indicative of the digestive disorder. For example, the amount of deviation from the baselines may provide a measure of the severity of the digestive disorder. One or more computing devices of the data processing system 150 of the system 10 can also be configured to monitor the sound / motion / stress information and temperature information overtime.

[0160] In another example configuration, the system 10 includes an example embodiment of the WMD 100 that is configured to be associated with the cardiac system of the subject. This WMD 100 is primarily configured to collect ECG data corresponding to the functionality of the heart of the subject. To this end, the WMD 100 can include an ECG sensor such as disclosed above with reference to FIG. IB. The WMD 100 may also include a physical stress sensor and a temperature sensor.

[0161] In another example configuration, the system 10 includes an example embodiment of the WMD 100 that is configured to monitor cardiac performance based on one or more of ECG information, sound / motion / stress information (if a physical stress sensor is present), and temperature information (if a temperature sensor is present). To this end, the external receiver 130 device 130 of the system 10 is configured to establish normal / baseline ECG information, sound / motion / stress information and temperature information of the subject based on ECG information, sound / motion / stress information and temperature information provided by the WMD 100 while the subject is at rest. The external receiver 130 device 130 of the system 10 is configured to monitor ECG information, heart rate information (derived from ECG information), respiration (derived from stress information), and temperature information based on sound / motion / stress information and temperature information provided by the WMD 100 while the subject is exercising and while the subject is recovering after exercise, and is configured to provide a representation based on the information. Examples of representations include an alert of cardiac arrythmia, a measure ofDocket No.: CANA.476PCheart rate, and an ECG waveform. One or more computing devices of the data processing system 150 of the system 10 can also be configured to monitor the ECG information, sound / motion / stress information and temperature information overtime.

[0162] This example configuration of the system 10 may also include one or more kinematic sensors (e.g., IMU, accelerometer, rate sensor, etc.) that provides kinematic information. In this case, the external receiver device 130 of the system 10 is also configured to monitor kinematics information (e.g., gait, cadence, step count) during exercise and during recovery after exercise for comparison against normal / baseline kinematic information. One or more computing devices of the data processing system 150 of the system 10 can also be configured to monitor the kinematic information over time.Examples

[0163] The following are some exemplary, i.e., non-limiting, embodiments of the present technology.

[0164] In some embodiments in accordance with the present technology (example Al), a wearable medical device for monitoring mechanical stress originating from within a host includes a housing able to securely attach to a region or location outside of the host's body; and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure.

[0165] Example A2 includes the device of example Al or any of examples A1-A65, wherein the wearable medical device is configured for a short duration of use comprising a plurality of days or weeks up to four weeks to continuously monitor one or more health parameters of the host, without requiring patient compliance by the host for the wearable medical device to monitor one or more health parameters.

[0166] Example A3 includes the device of example A2 or any of examples A1-A65, wherein the wearable medical device is able to be configured for re-use after the host for another patient.

[0167] Example A4 includes the device of example A3 or any of examples A1-A65, wherein the wearable medical device is configured to store data associated with the one or more health parameters, and wherein the stored data on the wearable medical device is onlyDocket No.: CANA.476PCaccessible to a manufacturer of the wearable medical device to provide to a clinician of the host after use.

[0168] Example A5 includes the device of example A3 or any of examples A1-A65, wherein the wearable medical device is configured to store data associated with the one or more health parameters, and wherein the wearable medical device is in wired communication or wireless communication with a health monitoring system in a hospital.

[0169] Example A6 includes the device of example Al or any of examples A1-A65, wherein the wearable medical device is configured for a long duration of use comprising a plurality of months or years up to three years to continuously monitor one or more health parameters of the host.

[0170] Example A7 includes the device of example A6 or any of examples A1-A65, wherein the wearable medical device is configured to transmit data associated with the one or more health parameters to an external receiver device that is in communication with a data processing server via a network of computers.

[0171] Example A8 includes the device of example A7 or any of examples A1-A65, wherein the data is transmittable in real time or intermittently to be received at the data processing server to provide access to a clinician of the host to view the data or an analysis of the data during the use of the wearable medical device by the host.

[0172] Example A9 includes the device of example Al or any of examples A1-A65, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

[0173] Example A10 includes the device of example A9 or any of examples A1-A65, wherein the housing includes a hermetically sealed housing.

[0174] Example All includes the device of example A9 or any of examples A1-A65, wherein the rigid unimorph piezoelectric structure includes a thickness in a range of 300 pm to 750 pm.

[0175] Example A12 includes the device of example All or any of examples A1-A65,Docket No.: CANA.476PCwherein the piezoelectric transducer includes a thickness in a range of 150 pm to 250 pm, the biocompatible stress absorption material includes a thickness in a range of 150 pm to 250 pm, and the electrode includes a thickness in a range of 100 nm to 250 pm.

[0176] Example A13 includes the device of example All or any of examples A1-A65, wherein the piezoelectric transducer includes lead zirconate titanate (PZT), the biocompatible stress absorption material includes titanium, and the electrode includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or combination thereof.

[0177] Example A14 includes the device of example A13 or any of examples A1-A65, wherein the biocompatible stress absorption material constitutes a portion of the housing.

[0178] Example A15 includes the device of example A9 or any of examples A1-A65, wherein the rigid unimorph piezoelectric structure is configured to transduce an applied stress from the received internal mechanical energy to a measurable electrical signal proportionate to the applied stress without undergoing displacement greater than 10 nm.

[0179] Example A16 includes the device of example A9 or any of examples A1-A65, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer; a first layer coupled to a first side of the piezoelectric material layer and configured in the housing to face outward of the wearable medical device, the first layer comprising a biocompatible, electrically conductive, non-piezoelectric material having a Young's modulus within 2X - 3X of a Young's modulus of the piezoelectric material layer; and a second layer coupled to a second side of the piezoelectric material layer opposite the first side, the second layer comprising an electrically conductive, non-piezoelectric material, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically conductive, non-piezoelectric material is transferred through the first layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the first layer and the second layer are electrically addressable to detect the electrical signal by an electrical circuit.

[0180] Example A17 includes the device of example A16 or any of examples A1-A65, wherein the piezoelectric material layer includes one or more of lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF) aluminum nitride (AIN), scandium aluminum nitride (ScAIN),Docket No.: CANA.476PCbarium titanate (BaTiCh), lead titanate (PbTiCh), potassium niobate (KNbCh), lithium niobate (LiNbOs), lithium tantalate (LiTaCh), and / or sodium tungstate (Na2WO4).

[0181] Example A18 includes the device of example A16 or any of examples A1-A65, wherein the biocompatible, electrically conductive, non-piezoelectric material of the first layer includes one or more of titanium, a biocompatible stainless-steel, a cobalt-chromium alloy, nitinol, or a combination thereof.

[0182] Example A19 includes the device of example A16 or any of examples A1-A65, wherein the electrically conductive, non-piezoelectric material of the second layer includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, orother conductive material, including an alloy or other combination thereof.

[0183] Example A20 includes the device of example A16 or any of examples A1-A65, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.

[0184] Example A21 includes the device of example A16 or any of examples A1-A65, wherein the second layer of the unimorph piezoelectric sensor is configured as two electrode structures, comprising: a center electrode; and an annular electrode that is positioned around and separated from the center electrode by a gap.

[0185] Example A22 includes the device of example A9 or any of examples A1-A65, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer; a first layer configured in the housing to face outward of the wearable medical device, the first layer comprising a biocompatible, electrically insulative, non-piezoelectric material; a second layer coupled to a first side of the piezoelectric material, the second layer comprising an electrically conductive, non-piezoelectric material; and a third layer coupled to a second side of the piezoelectric material layer opposite the first side and coupled to a side of the first layer, the third layer comprising an electrically conductive, non-piezoelectric material, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically insulative, non-piezoelectric material is transferred through the first layer and through the third layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the secondDocket No.: CANA.476PClayer and the third layer are electrically addressable to detect the electrical signal by an electrical circuit.

[0186] Example A23 includes the device of example A22 or any of examples A1-A65, wherein the piezoelectric material layer includes one or more of lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF) aluminum nitride (AIN), scandium aluminum nitride (ScAIN), barium titanate (BaTiOs), lead titanate (PbTiCh), potassium niobate (KNbCh), lithium niobate (LiNbOs), lithium tantalate (LiTaCh), and / or sodium tungstate (Na2WO4).

[0187] Example A24 includes the device of example A22 or any of examples A1-A65, wherein the biocompatible, electrically insulative, non-piezoelectric material of the first layer includes a high-purity ceramic.

[0188] Example A25 includes the device of example A24 or any of examples A1-A65, wherein the high-purity ceramic includes alumina (AI2O3).

[0189] Example A26 includes the device of example A22 or any of examples A1-A65, wherein the electrically conductive, non-piezoelectric material of the second layerand / orthe third layer includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy or other combination thereof.

[0190] Example A27 includes the device of example A22 or any of examples A1-A65, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.

[0191] Example A28 includes the device of example A22 or any of examples A1-A65, wherein the second layer of the unimorph piezoelectric sensor is configured as two electrode structures, comprising: a center electrode; and an annular electrode that is positioned around and separated from the center electrode by a gap.

[0192] Example A29 includes the device of example A9 or any of examples A1-A65, wherein the unimorph piezoelectric sensor is configured to have a cylindrical shape.

[0193] Example A30 includes the device of example A9 or any of examples A1-A65, wherein the unimorph piezoelectric sensor is configured to have a rectangular, elliptical, triangular, or other polygonal shape.

[0194] Example A31 includes the device of example A9 or any of examples A1-A65, further comprising a dielectric material layer surrounding an outside of the housing.Docket No.: CANA.476PC

[0195] Example A32 includes the device of example A31 or any of examples A1-A65, wherein the dielectric material layer includes at least one of parylene, sapphire, a urethane, a silicone, or an AI2O3 material.

[0196] Example A33 includes the device of example Al or any of examples A1-A65, wherein the housing includes titanium (Ti).

[0197] Example A34 includes the device of example Al or any of examples A1-A65, wherein the internal mechanical energy signal includes a transmission of mechanical energy that propagates in an in vivo medium including one or more of a gas, liquid, or solid.

[0198] Example A35 includes the device of example A34 or any of examples A1-A65, wherein the transmission of mechanical energy includes sound energy associated with one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host, and wherein the physical stress sensor is operable to detect the sound energy at a distance of at least 0.1 cm from a source of the sound energy and from outside the body with a signal attenuation of 30 dB or less.

[0199] Example A36 includes the device of example A35 or any of examples A1-A65, wherein the unimorph piezoelectric sensor is configured to detect the transmission of mechanical energy in a frequency range of 10 Hz to 1,000 Hz indicative of one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host. The unimorph piezoelectric sensor may be referred to as the physical stress sensor for consistency with the language of the referenced Examples, e.g., Example A35.

[0200] Example A37 includes the device of example Al or any of examples A1-A65, comprising: an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing.

[0201] Example A38 includes the device of example A37 or any of examples A1-A65, wherein the electronics unit comprises a power supply.

[0202] Example A39 includes the device of example A37 or any of examples A1-A65, wherein the electronics unit comprises a signal processing unit and a wireless communications unit configured to process electrical signals associated with the detected internal mechanical energy signal as data and wirelessly transmit the data to an external processor. Reference to the detected internal mechanical energy signal may be changed to the internal mechanical energy signal for consistency with the identified Examples.

[0203] Example A40 includes the device of example A39 or any of examples A1-A65,Docket No.: CANA.476PCwherein the signal processing unit includes a signal conditioning circuit configured to process the electrical signals associated with the received internal mechanical energy signal by one or more of amplifying the electrical signals, filtering the electrical signals, or converting the electrical signals from analog to digital.

[0204] Example A41 includes the device of example A39, A40, or any of examples A1-A65, wherein the electronics unit comprises a data processing unit in communication with the signal conditioning circuit, the data processing unit comprising a processor and a memory and configured to process the amplified, filtered, or converted electrical signals as biomedical data.

[0205] Example A42 includes the device of example A37 or any of examples A1-A65, wherein the electronics unit comprises a printed circuit board (PCB) having a substrate and electrical interconnections disposed on the substrate, wherein the electrical interconnections are coupled to a plurality of electrical interconnection wires that span from the physical stress sensor.

[0206] Example A43 includes the device of example A37 or any of examples A1-A65, comprising: at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with or in combination with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host.

[0207] Example A44 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes an inertial measurement unit (IMU) configured to detect motion of the wearable medical device in multiple degrees of freedom.

[0208] Example A45 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor.

[0209] Example A46 includes the device of example A45 or any of examples A1-A65, wherein the ECG sensor includes a first electrode positioned at a first location of the housing to contact skin of the host at the region or location outside of the host's body to acquire electrophysiological signals generated by the host's heart, and a second electrode positioned at a second location to acquire reference electrophysiological signals to produceDocket No.: CANA.476PCelectrocardiogram data of the host's cardiac cycle.

[0210] Example A47 includes the device of example A46 or any of examples A1-A65, wherein the second location of the second electrode is positioned at a location of the housing separated from the first location of the housing.

[0211] Example A48 includes the device of example A46 or any of examples A1-A65, wherein the second electrode is configured as an external electrode assembly comprising the second electrode, a skin attachment band, and a cap or casing that is connected to an interconnect assembly comprising a wire that electrically connects with an electronics component within the housing.

[0212] Example A49 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time.

[0213] Example A50 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes an analyte sensor configured to detect an analyte of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

[0214] Example A51 includes the device of example A50 or any of examples A1-A65, wherein the analyte sensor is configured as a continuous glucose monitor (CGM) that includes an implantable contingent comprising a canula having one or more electrodes to insert within subcutaneous tissue of the host to detect a glucose level in interstitial fluid.

[0215] Example A52 includes the device of example A50 or any of examples A1-A65, wherein the analyte sensor is configured as a continuous glucose monitor (CGM) that includes an array of microneedles having electrodes to penetrate through an epidermis layer to a dermis layer of the host's skin to detect a glucose level in interstitial fluid.

[0216] Example A53 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes a pulse oximeter configured to detect a blood oxygen level of the host.

[0217] Example A54 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes a pH sensor configured to include an implantable contingent to insert within the host's body to detect a pH level of a biological fluid of the host in an area inside the host's body proximate to the region or location outsideDocket No.: CANA.476PCof the host's body where the wearable medical device is deployed.

[0218] Example A55 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes a temperature sensor configured at a skinfacing surface of the housing to detect skin surface temperature or configured to include an implantable contingent to insert within the host's body to detect temperature of a tissue structure or an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

[0219] Example A56 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

[0220] Example A57 includes the device of example A43 or any of examples A1-A65, wherein the at least one secondary sensor includes (a) an electrophysiological sensor including an electrocardiogram (ECG) sensor, (b) an inertial measurement unit (IMU), and (c) a pulse oximeter, and wherein the wearable medical device is configured to: concurrently detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detectable by the ECG sensor, (b) a position, orientation, and / or a movement of the host detectable by the IMU, and (c) a blood oxygen level of the host detectable by the pulse oximeter.

[0221] Example A58 includes the device of example A57 or any of examples A1-A65, wherein the wearable medical device is configured to: process the detected internal mechanical energy signal, the detected electrophysiological energy signal, the detected position, orientation, and / or a movement of the host, and the detected blood oxygen level of the host to produce biomedical data; and use the biomedical data to determine a health and / or disease state of the host.

[0222] Example A59 includes the device of example A57 or any of examples A1-A65, wherein position, orientation, and / or movement of the host detected by the IMU is used to determine whether the host is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

[0223] Example A60 includes the device of example Al or any of examples A1-A65, comprising: a flexible retainer comprising an electrically insulative, flexible material having anDocket No.: CANA.476PCouter wall that surrounds a main chamber within which the housing is encased; and an adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the outside of the host's body.

[0224] Example A61 includes the device of example A60 or any of examples A1-A65, wherein the flexible retainer includes one or more ribs that wrap around an interior wall of the main and that flex inwardly when the housing is inserted into the main chamber so as to apply pressure and / or friction between the one or more ribs and an external wall of the housing to hold the housing securely within the flexible retainer.

[0225] Example A62 includes the device of example A61 or any of examples A1-A65, wherein the one or more ribs includes a top rib that projects into and / or above the main chamber such that, when the housing is inserted into the flexible retainer, the top rib overhangs on an outer-peripheral portion of a top wall of the housing.

[0226] Example A63 includes the device of example A60 or any of examples A1-A65, wherein the flexible retainer includes a plurality of pores that pass through the bottom surface to a top surface of the flexible retainer.

[0227] Example A64 includes the device of example A63 or any of examples A1-A65, wherein the plurality of pores is organized in a plurality of concentric rows that wrap around the flexible retainer.

[0228] Example A65 includes the device of example A63 or any of examples A1-A65, wherein at least some of the plurality of pores are structured to include an increased curvature on a top portion of a pore wall, with respect to curvature of other pores of the plurality of pores, to provide an air gap between the adhesive layer and the host's clothing that would cover the flexible retainer when the wearable medical device is worn by the host.

[0229] In some embodiments in accordance with the present technology (example A66), a system for in vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure includes: the wearable medical device of any of examples A1-A65, A85-A87, and A90-A126; and a data processing system, comprising a processor and a memory, in data communication with the wearable medical device and configured to receive the data from the wearable medical device and process the received data to determine an internal mechanical energy signal parameter associated with a physiological function of the anatomic structure.Docket No.: CANA.476PC

[0230] In some embodiments in accordance with the present technology (example A67), a method for monitoring an anatomic structure from a wearable medical device includes: receiving, at a physical stress sensor of a wearable medical device attachable to skin of a subject, an internal mechanical energy signal that emanates within the subject's body from an anatomic structure of interest; and converting, by the physical stress sensor, the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the anatomic structure of interest.

[0231] Example A68 includes the method of example A67 or any of examples A67-A84, wherein the anatomic structure of interest includes a heart of the subject, a lung or lungs of the subject, or both the heart and the lung or lungs of the subject.

[0232] Example A69 includes the method of example A67 or any of examples A67-A84, wherein the wearable medical device is positioned on the skin of the subject at a region or location of the subject's body proximate to the anatomic structure of interest within 5 cm or less of the anatomic structure.

[0233] Example A70 includes the method of example A67 or any of examples A67-A84, wherein the physical stress sensor detects, from a location outside of the subject's body, transmission ofthe internal mechanical energy that propagates in an in vivo medium including one or more of a gas, liquid, or solid in a frequency range of 10 Hz to 1,000 Hz.

[0234] Example A71 includes the method of example A67 or any of examples A67-A84, comprising continuously or intermittently monitoring the anatomic structure from the wearable medical device for a short duration of use lasting a plurality of days or weeks up to four weeks to measure one or more health parameters ofthe host (subject), without requiring patient compliance by the host (subject) for the wearable medical device to measure one or more health parameters.

[0235] Example A72 includes the method of example A71 or any of examples A67-A84, comprising storing data associated with the one or more health parameters on a memory of an electronics unit of the wearable medical device, wherein the stored data on the wearable medical device is only accessible to a manufacturer ofthe wearable medical device to provide to a clinician of the host (subject) after use.

[0236] Example A73 includes the method of example A71 or any of examples A67-A84, further comprising configuring the wearable medical device for re-use by another patient and completion of the monitoring by the host (subject).Docket No.: CANA.476PC

[0237] Example A74 includes the method of example A71 or any of examples A67-A84, transmitting, via wired communication or wireless communication, data associated with the one or more health parameters to a health monitoring system in a hospital.

[0238] Example A75 includes the method of example A67 or any of examples A67-A84, comprising continuously or intermittently monitoring the anatomic structure from the wearable medical device for a long duration of use lasting a plurality of months or years up to three years to measure one or more health parameters of the host (subject), without requiring patient compliance by the host (subject) for the wearable medical device to measure one or more health parameters.

[0239] Example A76 includes the method of example A75 or any of examples A67-A84, further comprising transmitting data associated with the one or more health parameters to an external receiver device that is in communication with a data processing server via a network of computers, wherein the data is transmittable in real time or intermittently to be received at the data processing server to provide access to a clinician of the host (subject) to view the data or an analysis of the data during the monitoring of the anatomic structure of the host (subject) by the wearable medical.

[0240] Example A77 includes the method of example A67 or any of examples A67-A84, wherein the wearable medical device further comprises an electrophysiological sensor, the method further comprising concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor and (ii) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detected by the electrophysiological sensor, from outside the subject's body.

[0241] Example A78 includes the method of example A77 or any of examples A67-A84, wherein the anatomic structure of interest includes a heart of the subject, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor, and wherein the concurrently detecting comprises: receiving, at the ECG sensor, electrocardiogram (ECG) signals that are associated with a cardiac cycle of a heart of the subject, and converting, by the ECG sensor, the ECG signals to a set of second electrical signals indicative of cardiac function of the heart.

[0242] Example A79 includes the method of example A78 or any of examples A67-A84, wherein the wearable medical device further comprises an inertial measurement unit (IMU),Docket No.: CANA.476PCand the method further comprising concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor, (ii) the ECG signals associated with the cardiac cycle of the heart detected by the ECG sensor, and (iii) a position, orientation, and / or a movement of the subject detected by the IMU.

[0243] Example A80 includes the method of example A79 or any of examples A67-A84, wherein the position, orientation, and / or movement of the subject detected by the IMU is used to determine a state of the subject indicative of whether the subject is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

[0244] Example A81 includes the method of example A80 or any of examples A67-A84, further comprising processing the ECG signals as timing markers of the cardiac cycle of the host (subject) in compilation with, i.e., and combining the resulting information with information resulting from, processing the state of the subject and processing the internal mechanical energy signal to interrogate for particular sound signatures associated with heart valve function to distinguish between healthy and unhealthy markers of the cardiac function of the heart.

[0245] Example A82 includes the method of example A81 or any of examples A67-A84, wherein the wearable medical device is configured to monitor one or more disease states of the subject's heart including (i) stenosis, (ii) regurgitation , or (iii) myxomatous.

[0246] Example A83 includes the method of example A80 or any of examples A67-A84, wherein the wearable medical device further comprises a pulse oximeter, the method further comprising: concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor, (ii) the ECG signals associated with the cardiac cycle of the heart detected by the ECG sensor, and (iii) a position, orientation, and / or a movement of the subject detected by the IMU, and (iv) a blood oxygen level of the subject detected by the pulse oximeter.

[0247] Example A84 includes the method of any of examples A67-A83, wherein the wearable medical device is the wearable medical device of any of examples A1-A65, A85-A87, and A90-A126.

[0248] In some embodiments in accordance with the present technology (example A85), a wearable medical device for monitoring mechanical stress originating from within a host includes a housing able to securely attach to a region or location outside of the host's body;Docket No.: CANA.476PCand a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the wearable medical device is configured to monitor the internal mechanical energy signal without acoustic data acquired from an ultrasound sensor or acoustic microphone device.

[0249] Example A86 includes the device of example A85, wherein the wearable medical device is the wearable medical device of any of examples A1-A55 and A57-A65.

[0250] In some embodiments in accordance with the present technology (example A87), a wearable medical device for monitoring mechanical stress originating from within a host consists of: a housing able to securely attach to a region or location outside of the host's body; a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing; at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with, i.e., which information is compiled with, an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host; a flexible retainer comprising an electrically insulative, flexible material having an outer wall that surrounds a main chamber within which the housing is encased; and an adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the outside of the host's body.

[0251] Example A88 includes the device of example A87, wherein the wearable medical device includes at least one feature from any of examples A1-A36, A38-A42, A44-A59, and A61-A65.

[0252] In some embodiments in accordance with the present technology (example A89), a method for assessing a clinical condition of a patient, where the clinical condition is pulmonary arterial pressure (PAP) includes (a) detecting electrocardiogram (ECG) dataDocket No.: CANA.476PCgenerated by a beating heart of the patient wearing a wearable medical device securely attach to a region or location outside of the patient's body while concurrently (b) detecting mechanical pressure wave data generated by the beating heart, (i) the detecting ECG data and the detecting mechanical pressure wave data occurring concurrently while the beating heart proceeds through an aortic (A2) and a pulmonary (P2) component of a second heart sound (S2) of a heartbeat, (ii) wherein the mechanical pressure wave and the ECG data are obtained concurrently by the wearable medical device comprising a physical stress sensor and an electrophysiological sensor comprising an ECG sensor; (c) optionally, analyzing the ECG data to identify a time point when the beating heart is in an S2 region of the heartbeat; (d) optionally, analyzing the ECG data to identify a time point when A2 and a time point when P2 are taking place in an S2 region; (e) optionally, determining a A2-P2 splitting interval (SI), where SI is a time interval between the time point of A2 and the time point of P2 of a heartbeat, where the time interval is normalized to the heart rate; (f) optionally, calculating a pulmonary arterial pressure (PAP) based on the determined SI.

[0253] In some embodiments in accordance with the present technology (Example A90), a wearable medical device for monitoring mechanical stress originating from within a host, includes: a housing able to securely attach to a region or location of the host's body; a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing; and at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host, wherein the at least one secondary sensor comprises an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, the electrophysiological sensor comprising an electrocardiogram (ECG) sensor.

[0254] Example A91 includes the device of example A90, or any of examples A90-A112, wherein the ECG sensor includes a first electrode positioned at a first location of the housingDocket No.: CANA.476PCto contact skin of the host at the region or location outside of the host's body to acquire electrophysiological signals generated by the host's heart, and a second electrode positioned at a second location to acquire reference electrophysiological signals to produce electrocardiogram data of the host's cardiac cycle.

[0255] Example A92 includes the device of Example A91, or any of examples A90-A112, wherein a separation distance between the first electrode of the ECG sensor and the second electrode of the ECG sensor is between 1 cm to 20 cm.

[0256] Example A93 includes the device of Example A92, or any of examples A90-A112, wherein the device includes: an external electrode assembly comprising the second electrode; and an interconnect assembly comprising an outer shell or casing that encompasses a wire spanning through the interconnect assembly between the electronics unit contained in the housing and the second electrode of the external electrode assembly.

[0257] Example A94 includes the device of Example A93, or any of examples A90-A112, wherein the external electrode assembly further comprises a cap or a casing that is in connection with the outer shell or casing of the interconnect assembly.

[0258] Example A95 includes the device of Example A93, or any of examples A90-A112, wherein the external electrode assembly further comprises an adhesive band that is coupled to the second electrode, wherein the adhesive band includes an opening to expose at least a portion of the second electrode through the opening, and an adhesive layer configured on a skin-facing side of the adhesive band with respect to the host.

[0259] Example A96 includes the device of Example A92, or any of examples A90-A112, wherein the second electrode of the ECG sensor is at least partially contained in the housing, and wherein the separation distance between the first electrode of the ECG sensor and the second electrode of the ECG sensor is between 1 cm to 5 cm.

[0260] Example A97 includes the device of Example A90, or any of examples A90-A112, including: a flexible retainer comprising an electrically insulative, flexible material having an outer wall that surrounds a main chamber within which the housing is encased; and an adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the skin of the host's body.

[0261] Example A98 includes the device of Example A97, or any of examples A90-A112, wherein the flexible retainer includes one or more ribs that wrap around an interior wall of the main and that flex inwardly when the housing is inserted into the main chamber so as toDocket No.: CANA.476PCapply pressure and / or friction between the one or more ribs and an external wall of the housing to hold the housing securely within the flexible retainer.

[0262] Example A99 includes the device of Example A98, or any of examples A90-A112, wherein the one or more ribs includes a top rib that projects into and / or above the main chamber such that, when the housing is inserted into the flexible retainer, the top rib overhangs on an outer-peripheral portion of a top wall of the housing.

[0263] Example A100 includes the device of Example A97, or any of examples A90-A112, wherein the flexible retainer includes a plurality of pores that pass through the bottom surface to a top surface of the flexible retainer.

[0264] Example A101 includes the device of Example A100, or any of examples A90-A112, wherein the plurality of pores is organized in a plurality of concentric rows that wrap around the flexible retainer.

[0265] Example A102 includes the device of Example A100, or any of examples A90-A112, wherein at least some of the plurality of pores are structured to include an increased curvature on a top portion of a pore wall, with respect to curvature of other pores of the plurality of pores, to provide an air gap between the adhesive layer and the host's clothing that would cover the flexible retainer when the wearable medical device is worn by the host.

[0266] Example A103 includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further comprises an inertial measurement unit (IMU) configured to detect motion of the wearable medical device in multiple degrees of freedom.

[0267] Example A104 includes the device of Example A103, or any of examples A90-A112, wherein the wearable medical device is configured to concurrently detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detectable by the ECG sensor, and (b) a position, orientation, and / or a movement of the host detectable by the IMU.

[0268] Example A105 includes the device of Example A104, or any of examples A90-A112, wherein the wearable medical device is configured to process the detected internal mechanical energy signal, the detected electrophysiological energy signal, and the detected position, orientation, and / or a movement of the host to produce biomedical data; and use the biomedical data to determine a health and / or disease state of the host.Docket No.: CANA.476PC

[0269] Example A106 includes the device of Example A105, or any of examples A90-A112, wherein the wearable medical device is configured to process the detected position, orientation, and / or movement of the host to determine a host state of whether the host is (1) awake and at rest, (2) undergoing activity, or (3) sleeping; process the detected ECG signals to provide at least timing markers of a cardiac cycle of the host; and process the detected internal mechanical energy signals to provide sound signatures associated with heart function.

[0270] Example A107 includes the device of Example A106, or any of examples A90-A112, wherein the wearable medical device is configured to monitor one or more disease states of the host's heart, where examples are stenosis, regurgitation, and myxomatous.

[0271] Example A108 includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further includes an analyte sensor configured to detect an analyte of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

[0272] Example A109 includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further includes a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time.

[0273] Example A110 includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further includes a pH sensor configured to include an implantable contingent to insert within the host's body to detect a pH level of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

[0274] Example Alli includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further includes a temperature sensor configured at a skin-facing surface of the housing to detect skin surface temperature or configured to include an implantable contingent to insert within the host's body to detect temperature of a tissue structure or an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

[0275] Example A112 includes the device of Example A90, or any of examples A90-A112, wherein the at least one secondary sensor further includes an ultrasound sensor configuredDocket No.: CANA.476PCto detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

[0276] In some embodiments in accordance with the present technology (Example A113), a wearable medical device for monitoring mechanical stress originating from within a host, includes: a housing able to securely attach to a region or location outside of the host's body; and a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

[0277] Example A114 includes the device of Example A113, or any of Examples A113-A127, wherein the rigid unimorph piezoelectric structure includes a thickness in a range of 300 pm to 750 pm.

[0278] Example A115 includes the device of Example A114, or any of Examples A113-A127, wherein the piezoelectric transducer includes lead zirconate titanate (PZT), the biocompatible stress absorption material includes titanium, and the electrode includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or combination thereof.

[0279] Example 116 includes the device of Example A113, or any of Examples A113-A127, wherein the biocompatible stress absorption material constitutes a portion of the housing.

[0280] Example 117 includes the device of Example A113, or any of Examples A113-A127, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer operable as the piezoelectric transducer; a first layer coupled to a first side of the piezoelectric material layer and configured in the housing to face outward of the medical device, the first layerDocket No.: CANA.476PCcomprising a biocompatible, electrically conductive, non-piezoelectric material having a Young's modulus within 2x-3x of a Young's modulus of the piezoelectric material layer, wherein the first layer is operable as the biocompatible stress absorption material; and a second layer coupled to a second side of the piezoelectric material layer opposite the first side, the second layer comprising an electrically conductive, non-piezoelectric material, wherein the second layer is operable as the electrode, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically conductive, non-piezoelectric material is transferred through the first layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the first layer and the second layer are electrically addressable to detect the electrical signal by an electrical circuit.

[0281] Example A118 includes the device of Example A117, or any of Examples A113-A127, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.

[0282] Example A119 includes the device of Example A113, or any of Examples A113-A127, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer operable as the piezoelectric transducer; a first layer configured in the housing to face outward of the medical device, the first layer comprising a biocompatible, electrically insulative, non-piezoelectric material, wherein first layer is operable as the biocompatible stress absorption material; a second layer coupled to a first side of the piezoelectric material, the second layer comprising an electrically conductive, non-piezoelectric material, wherein second layer is operable as the electrode; and a third layer coupled to a second side of the piezoelectric material layer opposite the first side and coupled to a side of the first layer, the third layer comprising an electrically conductive, non-piezoelectric material, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically insulative, non-piezoelectric material is transferred through the first layer and through the third layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signalDocket No.: CANA.476PCindicative of the physiological function by the internal body structure, wherein the second layer and the third layer are electrically addressable to detect the electrical signal by an electrical circuit.

[0283] Example A120 includes the device of Example A113, or any of Examples A113-A127, wherein the housing includes titanium (Ti).

[0284] Example A121 includes the device of Example A113, or any of Examples A113-A127, wherein the internal mechanical energy signal includes a transmission of mechanical energy that i) propagates in an in vivo medium including one or more of a gas, liquid, or solid, and ii) propagates through skin, wherein: the transmission of mechanical energy includes sound energy associated with one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host, and wherein the physical stress sensor is operable to detect the sound energy at a distance of at least 0.5 cm from a source of the sound energy, and / or the unimorph piezoelectric sensor is configured to detect the transmission of mechanical energy in a frequency range of 10 Hz to 1,000 Hz indicative of one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host.

[0285] Examples A122 includes the device of Example A113, or any of Examples A113-A127, comprising: an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is in a casing, wherein the electronics unit comprises: a power supply, and a signal processing unit and a wireless communications unit configured to process electrical signals associated with the internal mechanical energy signal as data and wirelessly transmit the data to an external processor.

[0286] Example A123 includes the device of Example A122, or any of Examples A113-A127, comprising at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host on which the wearable medical device is deployed.

[0287] Example A124 includes the device of Example A123, or any of Examples A113-A127, comprising at least one secondary sensor including one or more of the following: an inertial measurement unit (IMU) configured to detect motion of the medical device inDocket No.: CANA.476PCmultiple degrees of freedom, an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor, a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time, or an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

[0288] Example A125 includes the device of Example A123, or any of Examples A113-A127, comprising at least one secondary sensor including (a) an electrophysiological sensor including an electrocardiogram (ECG) sensor, and (b) an inertial measurement unit (IMU), and wherein the medical device is configured to: simultaneously detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure, from within the host, detectable by the ECG sensor, (b) a position, orientation, and / or a movement of the host detectable by the IMU.

[0289] Example A126 includes the device of Example A125, or any of Examples A113-A127, wherein the medical device is configured to: process the detected internal mechanical energy signal, the detected electrophysiological energy signal, and the detected position, orientation, and / or a movement of the host, to produce processed data; and wherein position, orientation, and / or movement of the host detected by the IMU is used to determine whether the host is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

[0290] Example A127 includes the device of Example A113, or any of Examples AA system for in vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure, comprising: the wearable medical device of claim 113; and a data processing system, comprising a processor and a memory, in data communication with the wearable medical device and configured to receive the data from the wearable medical device and process the received data to determine an internal mechanical energy signal parameter associated with a physiological function of the anatomic structure.

[0291] Example A128 includes the device of Example A90, wherein the wearable medical device includes at least one feature from any of Examples A1-A36, A38-A42, A44-A59, andDocket No.: CANA.476PCA61-A65.

[0292] Example A129 includesthe method of Example A89, wherein the wearable medical device includes at least one feature from any of Examples A1-A36, A38-A42, A44-A59, A61-A65, and A90-A126.Conclusion

[0293] Implementations of the subject matter and the functional operations described in this patent document can be implemented in various systems, digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Implementations of the subject matter described in this specification can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible and non-transitory computer readable medium for execution by, or to control the operation of, data processing apparatus. The computer readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of matter effecting a machine-readable propagated signal, or a combination of one or more of them. The term "data processing unit" or "data processing apparatus" encompasses all apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, or multiple processors or computers. The apparatus can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them.

[0294] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). A computer program can be deployed to be executed on oneDocket No.: CANA.476PCcomputer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0295] The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0296] Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor will receive instructions and data from a read only memory or a random access memory or both. The essential elements of a computer are a processor for performing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. However, a computer need not have such devices. Computer readable media suitable for storing computer program instructions and data include all forms of nonvolatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0297] The present technology may be understood more readily by reference to the following detailed description of preferred embodiments of the invention and the Examples included herein. In reading this detailed description, and unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms "a," "an," and "the" may include plural referents unless context clearly indicates otherwise. Similarly, the word "or" may include "and / or" unless the context clearly indicates otherwise. The term "comprises" means "includes." The abbreviation, "e.g." is derived from the Latin exempli gratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "e.g." is synonymous with the term "for example."

[0298] While this patent document contains many specifics, these should not beDocket No.: CANA.476PCconstrued as limitations on the scope of any invention or of what may be claimed, but rather as descriptions of features that may be specific to particular embodiments of particular inventions. Certain features that are described in this patent document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.

[0299] Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Moreover, the separation of various system components in the embodiments described in this patent document should not be understood as requiring such separation in all embodiments.

[0300] Only a few implementations and examples are described, and other implementations, enhancements, and variations can be made based on what is described and illustrated in this patent document.

Claims

Docket No.: CANA.476PCCLAIMSWhat is claimed is:

1. A wearable medical device for monitoring mechanical stress originating from within a host, comprising:a housing able to securely attach to a region or location outside of the host's body; anda physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure.

2. The device of claim 1, wherein the wearable medical device is configured for a short duration of use comprising a plurality of days or weeks up to four weeks to continuously monitor one or more health parameters of the host, without requiring patient compliance by the host for the wearable medical device to monitor one or more health parameters.

3. The device of claim 2, wherein the wearable medical device is able to be configured for reuse after the host for another patient.

4. The device of claim 3, wherein the wearable medical device is configured to store data associated with the one or more health parameters, and wherein the stored data on the wearable medical device is only accessible to a manufacturer of the wearable medical device to provide to a clinician of the host after use.

5. The device of claim 3, wherein the wearable medical device is configured to store data associated with the one or more health parameters, and wherein the wearable medical device is in wired communication or wireless communication with a health monitoring system in a hospital.

6. The device of claim 1, wherein the wearable medical device is configured for a long duration of use comprising a plurality of months or years up to three years to continuously monitor one or more health parameters of the host.

7. The device of claim 6, wherein the wearable medical device is configured to transmit data associated with the one or more health parameters to an external receiver device that is in communication with a data processing server via a network of computers.Docket No.: CANA.476PC8. The device of claim 7, wherein the data is transmittable in real time or intermittently to be received at the data processing server to provide access to a clinician of the host to view the data or an analysis of the data during the use of the wearable medical device by the host.

9. The device of claim 1, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

10. The device of claim 9, wherein the housing includes a hermetically sealed housing.

11. The device of claim 9, wherein the rigid unimorph piezoelectric structure includes a thickness in a range of 300 pm to 750 pm.

12. The device of claim 11, wherein the piezoelectric transducer includes a thickness in a range of 150 pm to 250 pm, the biocompatible stress absorption material includes a thickness in a range of 150 pm to 250 pm, and the electrode includes a thickness in a range of 100 nm to 250 pm.

13. The device of claim 11, wherein the piezoelectric transducer includes lead zirconate titanate (PZT), the biocompatible stress absorption material includes titanium, and the electrode includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or combination thereof.

14. The device of claim 13, wherein the biocompatible stress absorption material constitutes a portion of the housing.

15. The device of claim 9, wherein the rigid unimorph piezoelectric structure is configured to transduce an applied stress from the received internal mechanical energy to a measurable electrical signal proportionate to the applied stress without undergoing displacement greater than 10 nm.

16. The device of claim 9, wherein the unimorph piezoelectric sensor comprises:a piezoelectric material layer;a first layer coupled to a first side of the piezoelectric material layer and configured in the housing to face outward of the wearable medical device, the first layer comprising aDocket No.: CANA.476PCbiocompatible, electrically conductive, non-piezoelectric material having a Young's modulus within 2X - 3X of a Young's modulus of the piezoelectric material layer; anda second layer coupled to a second side of the piezoelectric material layer opposite the first side, the second layer comprising an electrically conductive, non-piezoelectric material,wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically conductive, non-piezoelectric material is transferred through the first layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure,wherein the first layer and the second layer are electrically addressable to detect the electrical signal by an electrical circuit.

17. The device of claim 16, wherein the piezoelectric material layer includes one or more of lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF) aluminum nitride (AIN), scandium aluminum nitride (ScAIN), barium titanate (BaTiCh), lead titanate (PbTiCh), potassium niobate (KNbCh), lithium niobate (LiNbCh), lithium tantalate (LiTaCh), and / or sodium tungstate (Na2WO4).

18. The device of claim 16, wherein the biocompatible, electrically conductive, nonpiezoelectric material of the first layer includes one or more of titanium, a biocompatible stainless-steel, a cobalt-chromium alloy, nitinol, or a combination thereof.

19. The device of claim 16, wherein the electrically conductive, non-piezoelectric material of the second layer includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy or other combination thereof.

20. The device of claim 16, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.Docket No.: CANA.476PC21. The device of claim 16, wherein the second layer of the unimorph piezoelectric sensor is configured as two electrode structures, comprising:a center electrode; andan annular electrode that is positioned around and separated from the center electrode by a gap.

22. The device of claim 9, wherein the unimorph piezoelectric sensor comprises:a piezoelectric material layer;a first layer configured in the housing to face outward of the wearable medical device, the first layer comprising a biocompatible, electrically insulative, non-piezoelectric material;a second layer coupled to a first side of the piezoelectric material, the second layer comprising an electrically conductive, non-piezoelectric material; anda third layer coupled to a second side of the piezoelectric material layer opposite the first side and coupled to a side of the first layer, the third layer comprising an electrically conductive, non-piezoelectric material,wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically insulative, nonpiezoelectric material is transferred through the first layer and through the third layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the second layer and the third layer are electrically addressable to detect the electrical signal by an electrical circuit.

23. The device of claim 22, wherein the piezoelectric material layer includes one or more of lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF) aluminum nitride (AIN), scandium aluminum nitride (ScAIN), barium titanate (BaTiCh), lead titanate (PbTiCh), potassium niobate (KNbCh), lithium niobate (LiNbCh), lithium tantalate (LiTaCh), and / or sodium tungstate (Na2WO4).

24. The device of claim 22, wherein the biocompatible, electrically insulative, nonpiezoelectric material of the first layer includes a high-purity ceramic.

25. The device of claim 24, wherein the high-purity ceramic includes alumina (AI2O3).Docket No.: CANA.476PC26. The device of claim 22, wherein the electrically conductive, non-piezoelectric material of the second layer and / or the third layer includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or other conductive material, including an alloy or other combination thereof.

27. The device of claim 22, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.

28. The device of claim 22, wherein the second layer of the unimorph piezoelectric sensor is configured as two electrode structures, comprising:a center electrode; andan annular electrode that is positioned around and separated from the center electrode by a gap.

29. The device of claim 9, wherein the unimorph piezoelectric sensor is configured to have a cylindrical shape.

30. The device of claim 9, wherein the unimorph piezoelectric sensor is configured to have a rectangular, elliptical, triangular, or other polygonal shape.

31. The device of claim 9, further comprising a dielectric material layer surrounding an outside of the housing.

32. The device of claim 31, wherein the dielectric material layer includes at least one of parylene, sapphire, a urethane, a silicone, or an AI2O3 material.

33. The device of claim 1, wherein the housing includes titanium (Ti).

34. The device of claim 1, wherein the internal mechanical energy signal includes a transmission of mechanical energy that propagates in an in vivo medium including one or more of a gas, liquid, or solid.

35. The device of claim 34, wherein the transmission of mechanical energy includes sound energy associated with one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host, and wherein the physical stress sensor is operable to detect the sound energy at a distance of at least 0.1 cm from a source of the sound energy and from outside the body with a signal attenuation of 30 dB or less.

36. The device of claim 35, wherein the unimorph piezoelectric sensor is configured to detect the transmission of mechanical energy in a frequency range of 10 Hz to 1,000 Hz indicativeDocket No.: CANA.476PCof one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host.

37. The device of claim 1, comprising:an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing.

38. The device of claim 37, wherein the electronics unit comprises a power supply.

39. The device of claim 37, wherein the electronics unit comprises a signal processing unit and a wireless communications unit configured to process electrical signals associated with the detected internal mechanical energy signal as data and wirelessly transmit the data to an external processor.

40. The device of claim 39, wherein the signal processing unit includes a signal conditioning circuit configured to process the electrical signals associated with the received internal mechanical energy signal by one or more of amplifying the electrical signals, filtering the electrical signals, or converting the electrical signals from analog to digital.

41. The device of claim 39, wherein the electronics unit comprises a data processing unit in communication with the signal conditioning circuit, the data processing unit comprising a processor and a memory and configured to process the amplified, filtered, or converted electrical signals as biomedical data.

42. The device of claim 37, wherein the electronics unit comprises a printed circuit board (PCB) having a substrate and electrical interconnections disposed on the substrate, wherein the electrical interconnections are coupled to a plurality of electrical interconnection wires that span from the physical stress sensor.

43. The device of claim 37, comprising:at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, ora physical parameter of the host.

44. The device of claim 43, wherein the at least one secondary sensor includes an inertial measurement unit (IMU) configured to detect motion of the wearable medical device in multiple degrees of freedom.Docket No.: CANA.476PC45. The device of claim 43, wherein the at least one secondary sensor includes an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor.

46. The device of claim 45, wherein the ECG sensor includes a first electrode positioned at a first location of the housing to contact skin of the host at the region or location outside of the host's body to acquire electrophysiological signals generated by the host's heart, and a second electrode positioned at a second location to acquire reference electrophysiological signals to produce electrocardiogram data of the host's cardiac cycle.

47. The device of claim 46, wherein the second location of the second electrode is positioned at a location of the housing separated from the first location of the housing.

48. The device of claim 46, wherein the second electrode is configured as an external electrode assembly comprising the second electrode, a skin attachment band, and a cap or casing that is connected to an interconnect assembly comprising a wire that electrically connects with an electronics component within the housing.

49. The device of claim 43, wherein the at least one secondary sensor includes a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time.

50. The device of claim 43, wherein the at least one secondary sensor includes an analyte sensor configured to detect an analyte of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

51. The device of claim 50, wherein the analyte sensor is configured as a continuous glucose monitor (CGM) that includes an implantable contingent comprising a canula having one or more electrodes to insert within subcutaneous tissue of the host to detect a glucose level in interstitial fluid.

52. The device of claim 50, wherein the analyte sensor is configured as a continuous glucose monitor (CGM) that includes an array of microneedles having electrodes to penetrate through an epidermis layer to a dermis layer of the host's skin to detect a glucose level in interstitial fluid.

53. The device of claim 43, wherein the at least one secondary sensor includes a pulse oximeter configured to detect a blood oxygen level of the host.Docket No.: CANA.476PC54. The device of claim 43, wherein the at least one secondary sensor includes a pH sensor configured to include an implantable contingent to insert within the host's body to detect a pH level of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

55. The device of claim 43, wherein the at least one secondary sensor includes a temperature sensor configured at a skin-facing surface of the housing to detect skin surface temperature or configured to include an implantable contingent to insert within the host's body to detect temperature of a tissue structure or an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

56. The device of claim 43, wherein the at least one secondary sensor includes an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

57. The device of claim 43, wherein the at least one secondary sensor includes (a) an electrophysiological sensor including an electrocardiogram (ECG) sensor, (b) an inertial measurement unit (IMU), and (c) a pulse oximeter, and wherein the wearable medical device is configured to:concurrently detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detectable by the ECG sensor, (b) a position, orientation, and / or a movement of the host detectable by the IMU, and (c) a blood oxygen level of the host detectable by the pulse oximeter.

58. The device of claim 57, wherein the wearable medical device is configured to:process the detected internal mechanical energy signal, the detected electrophysiological energy signal, the detected position, orientation, and / or a movement of the host, and the detected blood oxygen level of the host to produce biomedical data; anduse the biomedical data to determine a health and / or disease state of the host.Docket No.: CANA.476PC59. The device of claim 57, wherein position, orientation, and / or movement of the host detected by the IMU is used to determine whether the host is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

60. The device of claim 1, comprising:a flexible retainer comprising an electrically insulative, flexible material having an outer wall that surrounds a main chamber within which the housing is encased; andan adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the outside of the host's body.

61. The device of claim 60, wherein the flexible retainer includes one or more ribs that wrap around an interior wall of the main and that flex inwardly when the housing is inserted into the main chamber so as to apply pressure and / or friction between the one or more ribs and an external wall of the housing to hold the housing securely within the flexible retainer.

62. The device of claim 61, wherein the one or more ribs includes a top rib that projects into and / or above the main chamber such that, when the housing is inserted into the flexible retainer, the top rib overhangs on an outer-peripheral portion of a top wall of the housing.

63. The device of claim 60, wherein the flexible retainer includes a plurality of pores that pass through the bottom surface to a top surface of the flexible retainer.

64. The device of claim 63, wherein the plurality of pores is organized in a plurality of concentric rows that wrap around the flexible retainer.

65. The device of claim 63, wherein at least some of the plurality of pores are structured to include an increased curvature on a top portion of a pore wall, with respect to curvature of other pores of the plurality of pores, to provide an air gap between the adhesive layer and the host's clothing that would cover the flexible retainer when the wearable medical device is worn by the host.

66. A system for in vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure, comprising:the wearable medical device of any of claims 1-65, 85-87 and 90-126; anda data processing system, comprising a processor and a memory, in data communication with the wearable medical device and configured to receive the data from the wearable medical device and process the received data to determine an internalDocket No.: CANA.476PCmechanical energy signal parameter associated with a physiological function of the anatomic structure.

67. A method for monitoring an anatomic structure from a wearable medical device, the method comprising:receiving, at a physical stress sensor of a wearable medical device attachable to skin of a subject, an internal mechanical energy signal that emanates within the subject's body from an anatomic structure of interest; andconverting, by the physical stress sensor, the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the anatomic structure of interest.

68. The method of claim 67, wherein the anatomic structure of interest includes a heart of the subject, a lung or lungs of the subject, or both the heart and the lung or lungs of the subject.

69. The method of claim 67, wherein the wearable medical device is positioned on the skin of the subject at a region or location of the subject's body proximate to the anatomic structure of interest within 5 cm or less of the anatomic structure.

70. The method of claim 67, wherein the physical stress sensor detects, from a location outside of the subject's body, transmission of the internal mechanical energy that propagates in an in vivo medium including one or more of a gas, liquid, or solid in a frequency range of 10 Hz to 1,000 Hz.

71. The method of claim 67, comprising continuously or intermittently monitoring the anatomic structure from the wearable medical device for a short duration of use lasting a plurality of days or weeks up to four weeks to measure one or more health parameters of the host, without requiring patient compliance by the host for the wearable medical device to measure one or more health parameters.

72. The method of claim 71, comprising storing data associated with the one or more health parameters on a memory of an electronics unit of the wearable medical device, wherein the stored data on the wearable medical device is only accessible to a manufacturer of the wearable medical device to provide to a clinician of the host after use.

73. The method of claim 71, further comprising configuring the wearable medical device for re-use by another patient and completion of the monitoring by the host.Docket No.: CANA.476PC74. The method of claim 71, transmitting, via wired communication or wireless communication, data associated with the one or more health parameters to a health monitoring system in a hospital.

75. The method of claim 67, comprising continuously or intermittently monitoring the anatomic structure from the wearable medical device for a long duration of use lasting a plurality of months or years up to three years to measure one or more health parameters of the host, without requiring patient compliance by the host for the wearable medical device to measure one or more health parameters.

76. The method of claim 75, further comprising transmitting data associated with the one or more health parameters to an external receiver device that is in communication with a data processing server via a network of computers, wherein the data is transmittable in real time or intermittently to be received at the data processing server to provide access to a clinician of the host to view the data or an analysis of the data during the monitoring of the anatomic structure of the host by the wearable medical.

77. The method of claim 67, wherein the wearable medical device further comprises an electrophysiological sensor, the method further comprising concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor and (ii) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detected by the electrophysiological sensor, from outside the subject's body.

78. The method of claim 77, wherein the anatomic structure of interest includes a heart of the subject, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor, and wherein the concurrently detecting comprises: receiving, at the ECG sensor, electrocardiogram (ECG) signals that are associated with a cardiac cycle of a heart of the subject, and converting, by the ECG sensor, the ECG signals to a set of second electrical signals indicative of cardiac function of the heart.

79. The method of claim 78, wherein the wearable medical device further comprises an inertial measurement unit (IMU), and the method further comprising concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor, (ii) the ECG signals associated with the cardiac cycle of the heart detected by the ECG sensor, and (iii) a position, orientation, and / or a movement of the subject detected by the IMU.Docket No.: CANA.476PC80. The method of claim 79, wherein the position, orientation, and / or movement of the subject detected by the IMU is used to determine a state of the subject indicative of whether the subject is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

81. The method of claim 80, further comprising processing the ECG signals as timing markers of the cardiac cycle of the host in compilation with processing the state of the subject and processing the internal mechanical energy signal to interrogate for particular sound signatures associated with heart valve function to distinguish between healthy and unhealthy markers of the cardiac function of the heart.

82. The method of claim 81, wherein the wearable medical device is configured to monitor one or more disease states of the subject's heart including (i) stenosis, (ii) regurgitation , or (iii) myxomatous.

83. The method of claim 80, wherein the wearable medical device further comprises a pulse oximeter, the method further comprising: concurrently detecting (i) the internal mechanical energy signal that emanates from the anatomic structure of interest detected by the physical stress sensor, (ii) the ECG signals associated with the cardiac cycle of the heart detected by the ECG sensor, and (iii) a position, orientation, and / or a movement of the subject detected by the IMU, and (iv) a blood oxygen level of the subject detected by the pulse oximeter.

84. The method of any of claims 67-83, wherein the wearable medical device is the wearable medical device of any of claims 1-65, 85-87 and 90-126.

85. A wearable medical device for monitoring mechanical stress originating from within a host, comprising:a housing able to securely attach to a region or location outside of the host's body; anda physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure,wherein the wearable medical device is configured to monitor the internal mechanical energy signal without acoustic data acquired from an ultrasound sensor or acoustic microphone device.Docket No.: CANA.476PC86. The device of claim 85, wherein the wearable medical device is the wearable medical device of any of claims 1-55 and 57-65, 87, 88, and 90-126.

87. A wearable medical device for monitoring mechanical stress originating from within a host, consisting of:a housing able to securely attach to a region or location outside of the host's body; a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure,an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing;at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host;a flexible retainer comprising an electrically insulative, flexible material having an outer wall that surrounds a main chamber within which the housing is encased; andan adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the outside of the host's body.

88. The device of claim 87, wherein the wearable medical device includes at least one feature from any of claims 1-36, 38-42, 44-59, and 61-65.

89. A method for assessing a clinical condition of a patient, where the clinical condition is pulmonary arterial pressure (PAP), the method comprising:(a) detecting electrocardiogram (ECG) data generated by a beating heart of the patient wearing a wearable medical device securely attach to a region or location outside of the patient's body while concurrently (b) detecting mechanical pressure wave data generated by the beating heart,(i) the detecting ECG data and the detecting mechanical pressure wave data occurring concurrently while the beating heart proceeds through an aortic (A2) and a pulmonary (P2) component of a second heart sound (S2) of a heartbeat,Docket No.: CANA.476PC(ii) wherein the mechanical pressure wave and the ECG data are obtained concurrently by the wearable medical device comprising a physical stress sensor and an electrophysiological sensor comprising an ECG sensor;(c) optionally, analyzing the ECG data to identify a time point when the beating heart is in an S2 region of the heartbeat;(d) optionally, analyzing the ECG data to identify a time point when A2 and a time point when P2 are taking place in an S2 region;(e) optionally, determining a A2-P2 splitting interval (SI), where SI is a time interval between the time point of A2 and the time point of P2 of a heartbeat, where the time interval is normalized to the heart rate;(f) optionally, calculating a pulmonary arterial pressure (PAP) based on the determined SI.

90. A wearable medical device for monitoring mechanical stress originating from within a host, comprising:a housing able to securely attach to a region or location of the host's body;a physical stress sensor encased within the housing and configured to receive an internal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure,an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is contained in the housing; andat least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, ora physical parameter of the host,wherein the at least one secondary sensor comprises an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, the electrophysiological sensor comprising an electrocardiogram (ECG) sensor.

91. The device of claim 90, wherein the ECG sensor includes a first electrode positioned at a first location of the housing to contact skin of the host at the region or location outside of the host's body to acquire electrophysiological signals generated by the host's heart, andDocket No.: CANA.476PCa second electrode positioned at a second location to acquire reference electrophysiological signals to produce electrocardiogram data of the host's cardiac cycle.

92. The device of claim 91, wherein a separation distance between the first electrode of the ECG sensor and the second electrode of the ECG sensor is between 1 cm to 20 cm.

93. The device of claim 92, comprising:an external electrode assembly comprising the second electrode; andan interconnect assembly comprising an outer shell or casing that encompasses a wire spanning through the interconnect assembly between the electronics unit contained in the housing and the second electrode of the external electrode assembly.

94. The device of claim 93, wherein the external electrode assembly further comprises a cap or a casing that is in connection with the outer shell or casing of the interconnect assembly.

95. The device of claim 93, wherein the external electrode assembly further comprises an adhesive band that is coupled to the second electrode, wherein the adhesive band includes an opening to expose at least a portion of the second electrode through the opening, and an adhesive layer configured on a skin-facing side of the adhesive band with respect to the host.

96. The device of claim 92, wherein the second electrode of the ECG sensor is at least partially contained in the housing, and wherein the separation distance between the first electrode of the ECG sensor and the second electrode of the ECG sensor is between 1 cm to 5 cm.

97. The device of claim 90, comprising:a flexible retainer comprising an electrically insulative, flexible material having an outer wall that surrounds a main chamber within which the housing is encased; andan adhesive layer attached to a bottom surface of the flexible retainer configured to attach to skin of the host and thereby secure the wearable medical device to the skin of the host's body.

98. The device of claim 97, wherein the flexible retainer includes one or more ribs that wrap around an interior wall of the main and that flex inwardly when the housing is inserted into the main chamber so as to apply pressure and / or friction between the one or more ribs and an external wall of the housing to hold the housing securely within the flexible retainer.Docket No.: CANA.476PC99. The device of claim 98, wherein the one or more ribs includes a top rib that projects into and / or above the main chamber such that, when the housing is inserted into the flexible retainer, the top rib overhangs on an outer-peripheral portion of a top wall of the housing.

100. The device of claim 97, wherein the flexible retainer includes a plurality of pores that pass through the bottom surface to a top surface of the flexible retainer.

101. The device of claim 100, wherein the plurality of pores is organized in a plurality of concentric rows that wrap around the flexible retainer.

102. The device of claim 100, wherein at least some of the plurality of pores are structured to include an increased curvature on a top portion of a pore wall, with respect to curvature of other pores of the plurality of pores, to provide an air gap between the adhesive layer and the host's clothing that would cover the flexible retainer when the wearable medical device is worn by the host.

103. The device of claim 90, wherein the at least one secondary sensor further comprises an inertial measurement unit (IMU) configured to detect motion of the wearable medical device in multiple degrees of freedom.

104. The device of claim 103, wherein the wearable medical device is configured to:concurrently detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal body structure detectable by the ECG sensor, and (b) a position, orientation, and / or a movement of the host detectable by the IMU.

105. The device of claim 104, wherein the wearable medical device is configured to:process the detected internal mechanical energy signal, the detected electrophysiological energy signal, and the detected position, orientation, and / or a movement of the host to produce biomedical data; anduse the biomedical data to determine a health and / or disease state of the host.

106. The device of claim 104, wherein the wearable medical device is configured to:process the detected position, orientation, and / or movement of the host to determine a host state of whether the host is (1) awake and at rest, (2) undergoing activity, or (3) sleeping;process the detected ECG signals to provide at least timing markers of a cardiac cycle of the host; andDocket No.: CANA.476PCprocess the detected internal mechanical energy signals to provide sound signatures associated with heart function.

107. The device of claim 106, wherein the wearable medical device is configured to monitor one or more disease states of the subject's heart including (i) stenosis, (ii) regurgitation, or (iii) myxomatous.

108. The device of claim 90, wherein the at least one secondary sensor further includes an analyte sensor configured to detect an analyte of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

109. The device of claim 90, wherein the at least one secondary sensor further includes a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time.

110. The device of claim 90, wherein the at least one secondary sensor further includes a pH sensor configured to include an implantable contingent to insert within the host's body to detect a pH level of a biological fluid of the host in an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

111. The device of claim 90, wherein the at least one secondary sensor further includes a temperature sensor configured at a skin-facing surface of the housing to detect skin surface temperature or configured to include an implantable contingent to insert within the host's body to detect temperature of a tissue structure or an area inside the host's body proximate to the region or location outside of the host's body where the wearable medical device is deployed.

112. The device of claim 90, wherein the at least one secondary sensor further includes an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

113. A wearable medical device for monitoring mechanical stress originating from within a host, comprising:a housing able to securely attach to a region or location outside of the host's body; anda physical stress sensor encased within the housing and configured to receive anDocket No.: CANA.476PCinternal mechanical energy signal that emanates from within the host from an internal body structure and to transduce the received internal mechanical energy signal to an electrical signal indicative of a physiological function by the internal body structure, wherein the physical stress sensor is a unimorph piezoelectric sensor having a rigid unimorph piezoelectric structure that does not deflect greater than 10 nm when exposed to the internal mechanical energy signal, the rigid unimorph piezoelectric structure comprising a piezoelectric transducer coupled to a biocompatible stress absorption material and to an electrode, wherein the biocompatible stress absorption material is operable to receive the internal mechanical energy signal for the unimorph piezoelectric sensor and transfer the internal mechanical energy signal to the piezoelectric transducer, and wherein the electrode is operable to receive the electrical signal transduced by the piezoelectric transducer.

114. The device of claim 113, wherein the rigid unimorph piezoelectric structure includes a thickness in a range of 300 pm to 750 pm.

115. The device of claim 114, wherein the piezoelectric transducer includes lead zirconate titanate (PZT), the biocompatible stress absorption material includes titanium, and the electrode includes one or more of titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or combination thereof.

116. The device of claim 113, wherein the biocompatible stress absorption material constitutes a portion of the housing.

117. The device of claim 113, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer operable as the piezoelectric transducer; a first layer coupled to a first side of the piezoelectric material layer and configured in the housing to face outward of the medical device, the first layer comprising a biocompatible, electrically conductive, non-piezoelectric material having a Young's modulus within 2x-3x of a Young's modulus of the piezoelectric material layer, wherein the first layer is operable as the biocompatible stress absorption material; and a second layer coupled to a second side of the piezoelectric material layer opposite the first side, the second layer comprising an electrically conductive, non-piezoelectric material, wherein the second layer is operable as the electrode, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically conductive, non-piezoelectric material is transferred through the first layerDocket No.: CANA.476PCand into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the first layer and the second layer are electrically addressable to detect the electrical signal by an electrical circuit.

118. The device of claim 117, wherein the second layer of the unimorph piezoelectric sensor is configured to have a length or a diameter that is equal to the length or the diameter of the piezoelectric material layer of the unimorph piezoelectric sensor.

119. The device of claim 113, wherein the unimorph piezoelectric sensor comprises: a piezoelectric material layer operable as the piezoelectric transducer; a first layer configured in the housing to face outward of the medical device, the first layer comprising a biocompatible, electrically insulative, non-piezoelectric material, wherein first layer is operable as the biocompatible stress absorption material; a second layer coupled to a first side of the piezoelectric material, the second layer comprising an electrically conductive, non-piezoelectric material, wherein second layer is operable as the electrode; and a third layer coupled to a second side of the piezoelectric material layer opposite the first side and coupled to a side of the first layer, the third layer comprising an electrically conductive, non-piezoelectric material, wherein the first layer is configured to receive an applied force caused from the internal mechanical energy signal emanated from the internal body structure within the host, such that stress caused by the applied force on the biocompatible, electrically insulative, non-piezoelectric material is transferred through the first layer and through the third layer and into the piezoelectric material to transduce the stress into electrical energy corresponding to the electrical signal indicative of the physiological function by the internal body structure, wherein the second layer and the third layer are electrically addressable to detect the electrical signal by an electrical circuit.

120. The device of claim 113, wherein the housing includes titanium (Ti).

121. The device of claim 113, wherein the internal mechanical energy signal includes a transmission of mechanical energy that i) propagates in an in vivo medium including one or more of a gas, liquid, or solid, and ii) propagates through skin, wherein: the transmission of mechanical energy includes sound energy associated with one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host, and wherein the physical stress sensor is operable to detect the sound energyDocket No.: CANA.476PCat a distance of at least 0.5 cm from a source of the sound energy, and / or the unimorph piezoelectric sensor is configured to detect the transmission of mechanical energy in a frequency range of 10 Hz to 1,000 Hz indicative of one or both of blood flow in a blood vessel or a heart of the host and an airflow in an airway or a lung of the host.

122. The device of claim 113, comprising: an electronics unit in electrical communication with the physical stress sensor, wherein the electronics unit is in a casing, wherein the electronics unit comprises: a power supply, and a signal processing unit and a wireless communications unit configured to process electrical signals associated with the internal mechanical energy signal as data and wirelessly transmit the data to an external processor.

123. The device of claim 122, comprising: at least one secondary sensor in communication with the electronics unit and operable to measure a secondary measurement in compilation with an internal mechanical energy signal measurement by the physical stress sensor, wherein the secondary measurement includes one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the host on which the wearable medical device is deployed.

124. The device of claim 123, wherein the at least one secondary sensor includes one or more of the following: an inertial measurement unit (IMU) configured to detect motion of the medical device in multiple degrees of freedom, an electrophysiological sensor configured to detect an electrophysiological signal of an anatomic structure of the host, wherein the electrophysiological sensor includes an electrocardiogram (ECG) sensor, a step counter comprising one or more of at least one accelerometer or at least one rotational rate sensor to detect a quantity of steps moved by the host over a period of time, or an ultrasound sensor configured to detect one or more of a vascular blood flow, a vessel wall thickness, and / or a vessel diameter at a reference point in a cardiac cycle of the host or as a function of time during the cardiac cycle.

125. The device of claim 123, wherein the at least one secondary sensor includes (a) an electrophysiological sensor including an electrocardiogram (ECG) sensor, and (b) an inertial measurement unit (IMU), and wherein the medical device is configured to: simultaneously detect (i) the internal mechanical energy signal detectable by the physical stress sensor and (ii) a plurality of secondary signals comprising (a) an electrophysiological energy signal associated with a physiological phenomenon of at least one internal bodyDocket No.: CANA.476PCstructure, from within the host, detectable by the ECG sensor, (b) a position, orientation, and / or a movement of the host detectable by the IMU.

126. The device of claim 125 wherein the medical device is configured to: process the detected internal mechanical energy signal, the detected electrophysiological energy signal, and the detected position, orientation, and / or a movement of the host, to produce processed data; and wherein position, orientation, and / or movement of the host detected by the IMU is used to determine whether the host is (1) awake and at rest, (2) undergoing activity, or (3) is sleeping.

127. A system for in vivo monitoring of internal mechanical energy associated with physiological phenomena originating from an anatomic structure, comprising: the wearable medical device of claim 113; and a data processing system, comprising a processor and a memory, in data communication with the wearable medical device and configured to receive the data from the wearable medical device and process the received data to determine an internal mechanical energy signal parameter associated with a physiological function of the anatomic structure.

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