Implantable fluid flow and acoustic sensor

Abstract

Disclosed are devices, systems, and methods for in vivo monitoring of biological fluid flow within anatomical structures, such as blood flow through a heart valve (e.g., mitral, tricuspid, and / or aortic valve) or heart chamber. The disclosed devices, systems, and methods can continuously measure and evaluate blood flow before and after the entrance of a heart valve for compilation with other monitored data that can be used to determine cardiac function or dysfunction and / or to measure or predict secondary factors.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS All applications for which a claim of foreign or domestic priority is identified in the Application Data Sheet filed with this application are hereby incorporated by reference.

[0002] The present disclosure relates to sensors deployable within the body of a patient-user for monitoring fluid flow and biological functions in vivo. [Background technology]

[0003] According to the World Health Organization (WHO), cardiovascular disease is one of the leading causes of death worldwide, killing an estimated 17.9 million people each year. In the United States, heart disease is the leading cause of death, with coronary artery disease (CAD) being the most damaging class by causing reduced blood flow to the heart, often leading to heart attacks. CAD and other heart valve diseases, such as mitral valve prolapse (MVP) and mitral valve regurgitation (MVR), are silent killers because the existence of the underlying cardiac problem is typically unknown and therefore not diagnosed until the person experiences signs or symptoms of a heart attack, heart failure, or arrhythmia, which may be too late to survive or recover with a reasonable quality of life. Yet, currently, physicians 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, before initiating rounds of cardiac testing and remote monitoring. This is due to a lack of accessible, complex, and affordable equipment or technology for observing and tracking a person's cardiac function.

[0004] Currently, testing of cardiac function to potentially diagnose heart disease is limited to clinical settings. Patients typically undergo a variety of tests, including analyte testing from blood samples; imaging such as chest X-rays, CT scans, or cardiac magnetic resonance imaging (MRI); physiological signal monitoring, such as electrocardiograms (ECGs or EKGs), which are recordings of the heart's electrical signals that indicate heart rate and can detect irregular heartbeats when monitored remotely (e.g., by a Holter monitor); and echocardiograms, a noninvasive acoustic (sound) signal monitoring technique used to generate images of the heart and blood in motion. Furthermore, patients are prescribed such tests only after experiencing acute or emergency medical treatment, such as cardiac arrest, stroke, severe dizziness or loss of consciousness, or extreme chest pain.

[0005] To date, there have been several advances in remote monitoring to turn the tide against heart disease. For example, wearable heart rate monitors track heart rate during exercise or daily activities, monitor stress and movement levels, track nighttime sleep habits, and some versions of these wearable devices have become ubiquitous options for testing specific vital signs outside of the clinic, such as ECGs, to determine single heart rhythm events, such as healthy sinus rhythm or at-risk atrial fibrillation. While these devices are well suited to promoting a healthier, more active lifestyle that may contribute to preventing the onset of heart disease or reducing mild to moderate heart disease over the long term, they have the ability to identify a wide range of heart disease symptoms or characteristics and are unable to determine any underlying biological or physiological factors at the root of heart disease.

[0006] A challenge for clinicians is to catch cardiac disease early or manage and monitor diagnosed cardiac disease after treatment. However, monitoring cardiac function relies on patient participation and compliance, and existing systems and methods are too time-consuming, expensive, and resource-starved to be effective.

[0007] There is a need for a new paradigm of sensors that can be deployed on a patient-user's body and monitor the dynamic in vivo flow of biological fluids, such as blood flow across the valves of the heart, to characterize overall cardiac function. Summary of the Invention

[0008] Briefly, devices, systems, and methods are disclosed for in vivo monitoring of both biological fluid flow in anatomical structures, such as blood flow through cardiac chambers or vessels that carry blood into or out of the heart, and acoustic signals related to physiological phenomena in internal body structures, such as the heart and / or lungs, all from within a host. The disclosed devices, systems, and methods include an in vivo fluid flow sensor and an in vivo acoustic sensor, which may be configured as part of a single device structure or separate device structures implanted in the host's body.

[0009] In some embodiments according to the present invention, the implantable medical device includes an in-vivo fluid flow sensor and an in-vivo acoustic sensor. For example, in some implementations, the in-vivo fluid flow sensor is configured to transmit an ultrasonic signal to propagate through an anatomical structure and detect the ultrasonic signal that propagates through the anatomical structure and is indicative of fluid flow of a biological fluid within the anatomical structure, and the in-vivo acoustic sensor is configured to detect an acoustic signal emanating from an internal body structure. For example, in some embodiments, the in-vivo fluid flow sensor comprises a linkage assembly having a first arm configured to attach to a first portion of the anatomical structure and a second arm configured to attach to a second portion of the anatomical structure opposite the first portion, an ultrasonic sensor assembly including a plurality of ultrasonic transducer elements coupled to the linkage assembly, and the in-vivo acoustic sensor comprises a hermetically sealed housing and a transducer element configured to receive the acoustic signal emanating from the internal body structure such that the transducer element converts energy of the received acoustic signal into an electrical signal indicative of a physiological function by the internal body structure.

[0010] In some embodiments according to the present invention, an implantable medical device for in vivo monitoring of an anatomical structure from within a host body comprises: (i) an in vivo fluid flow sensor; a linkage assembly comprising a first arm configured to attach to a first portion of the anatomical structure and a second arm configured to attach to a second portion of the anatomical structure opposite the first portion; and a connecting device coupled to each of the first arm and the second arm; and an ultrasonic sensor assembly including a plurality of ultrasonic transducer elements coupled to the linkage assembly, the plurality of ultrasonic transducer elements comprising: a first ultrasonic transducer element configured to transmit an ultrasonic signal to propagate through the anatomical structure, and second and third ultrasonic transducer elements configured to propagate through the anatomical structure and receive ultrasonic signals indicative of a fluid flow parameter of a biological fluid within the anatomical structure. 10. The electronic device of claim 1, further comprising: (ii) an in-vivo acoustic sensor; and a transducer element configured to receive acoustic signals emanating from a source within the body of the host, the transducer element comprising a hermetically sealed housing, the transducer element configured to convert energy of the received acoustic signals into electrical signals indicative of a physiological function of the source within the body of the host; and (iii) an electronic unit at least partially contained in the connection device of the in-vivo fluid flow sensor and / or at least partially contained in the hermetically sealed housing of the in-vivo fluid flow sensor, the electronic unit in electrical communication with the plurality of ultrasonic transducer elements of the ultrasonic sensor assembly and in electrical communication with the transducer elements of the in-vivo acoustic sensor, the electronic unit configured to process the received ultrasonic signals and electrical signals associated with the received acoustic signals as data and to wirelessly transmit the data to an external processor.

[0011] In some embodiments according to the present invention, the system comprises: a system for in vivo monitoring of fluid flow in an anatomical structure, the system comprising an implantable medical device including an in vivo fluid flow sensor and an in vivo acoustic sensor; and a data processing system, the system comprising a processor and memory, in data communication with the implantable medical device, receiving the data from the implantable medical device, and processing the received data to determine fluid flow parameters associated with biological fluid within the anatomical structure and / or acoustic signal parameters associated with physiological functions of internal body structures, as described in claim 1.

[0012] The above and additional features of the present invention, and the manner of obtaining them, will become apparent and the present invention will be best understood by reference to the following more detailed description, in which: All references disclosed herein are incorporated by reference in their entirety as if each were incorporated individually.

[0013] This Summary is provided to introduce certain concepts in a simplified form that are described in more detail below in the Detailed Description. Unless expressly stated otherwise, 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.

[0014] Details of one or more embodiments are set forth in the description below. Features illustrated or described in connection with one exemplary embodiment may be combined with 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, as necessary, to employ concepts from the various patents, applications, and publications identified herein to provide further embodiments. Other features, objects, and advantages will be apparent from the description, drawings, and claims.

[0015] Many aspects of the present disclosure can be better understood with reference to the following drawings. Features in the drawings are not necessarily shown to scale, fully illustrated, or depicted in the same manner as they are physically constructed. Emphasis instead is placed upon clearly illustrating the principles of the present disclosure. The drawings should not be taken to limit the disclosure to the particular embodiments illustrated, but are for purposes of explanation and understanding only. [Brief explanation of the drawings]

[0016] [Figure 1A] 1 illustrates an exemplary embodiment of a system for in vivo monitoring of biological fluid flow and acoustic signals from within a patient with an implantable medical device (IMD) according to the present invention, and shows diagrams for monitoring, analyzing, and reporting events related to a user's cardiovascular and / or pulmonary health according to the present invention. [Figure 1B] 1B shows a block diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1A, in accordance with the present invention. [Figure 1C] 1B shows a block diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1A, in accordance with the present invention. [Figure 2A] 1C shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 2B] 1C shows a diagram illustrating another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B including a second set of ultrasonic sensor assemblies according to the present invention. [Figure 2C] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 2D] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 3] 2B shows a diagram of an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 2A attached to a patient-user's heart, in accordance with the present invention. [Figure 4A] 1 shows a diagram illustrating an insertion site for implanting an in vivo fluid flow sensor device according to the present invention. [Figure 4B]1A-1C show diagrams illustrating exemplary configurations of exemplary embodiments of an in-vivo fluid flow sensor device according to the present invention for the process of implantation near a target anatomical structure and the process of placement for fixation to the target anatomical structure. [Figure 5A] 1A-1C show diagrams illustrating exemplary embodiments of single-sided acoustic transducer configurations for in-vivo fluid flow sensor devices in accordance with the present invention. [Figure 5B] 10A-10C show diagrams illustrating another exemplary arrangement of a one-sided acoustic transducer configuration on an array for an in-vivo fluid flow sensor device according to the present invention. [Figure 5C] 10A-10C show diagrams illustrating another exemplary embodiment of a one-sided acoustic transducer configuration with a reflector for an in-vivo fluid flow sensor device according to the present invention. [Figure 5D] 1A-1C show diagrams illustrating exemplary embodiments of double-sided acoustic transducer configurations for in-vivo fluid flow sensor devices in accordance with the present invention. [Figure 6A] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 6B] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 6C] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 6D] 6B and 6C show enlarged views illustrating an exemplary embodiment of the electronics unit and housing of the in-vivo fluid flow sensor device of FIGS. 6A, 6B, and 6C. [Figure 7A] 1C shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 7B] 1C shows a diagram of an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 7C] 1C shows a diagram of an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 8] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 9]1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J ... [Figure 10A] 1C shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B attached to a patient-user's heart in an exemplary implantation of the device. [Figure 10B] 1C shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B attached to a patient-user's heart in an exemplary implantation of the device. [Figure 11A] 1D shows a diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C shown in a portion of an exemplary IMD of the present invention. [Figure 11B] FIG. 11B shows a cross-sectional view of an enlarged portion of the view of FIG. 11A, with the membrane of the in-vivo acoustic sensor in a relaxed state. [Figure 11C] 11A shows a cross-sectional view showing an enlarged portion of the image of FIG. 11A with the membrane of the in-vivo acoustic sensor in a deflected state. [Figure 12A] 1D shows a diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C configured as an in-vivo microphone in an exemplary IMD of the present invention, including strain gauges and / or piezoelectric elements. [Figure 12B] 1D shows a diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C configured as an in-vivo microphone in an exemplary IMD of the present invention, including strain gauges and / or piezoelectric elements. [Figure 13A] 1D shows a diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C configured as an in-vivo microphone in an exemplary IMD of the present invention, including a sensor having a capacitive electrode sensor and / or an electrode condenser element. [Figure 13B] 1D shows a diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C configured as an in-vivo microphone in an exemplary IMD of the present invention, including a sensor having a capacitive electrode sensor and / or an electrode condenser element. [Figure 14A]1D shows a top view of an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C in an IMD, illustrating an exemplary form factor configuration of the IMD including a battery, electronics package, and antenna. [Figure 14B] 14B illustrates a side view of the exemplary IMD of FIG. 14A. [Figure 15A] 1D shows a top view of an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C in an IMD, illustrating an exemplary form factor configuration of the IMD including a battery, an electronics package with a deflection membrane, and an antenna. [Figure 15B] 15B illustrates a side view of the exemplary IMD of FIG. 15A. [Figure 16A] 1D shows a top view of an exemplary embodiment of the in-vivo acoustic sensor device of FIG. 1C in an IMD, illustrating an exemplary form factor configuration of the IMD including a battery, electronics package, and antenna, with the accelerometer housed within the wired components. [Figure 16B] 16B shows a side view of the exemplary IMD of FIG. 16A, but omitting the wired components. [Figure 17] 14A and 14B and / or 15A and 15B show block diagrams illustrating exemplary IMDs of the present invention, including the internal components of the IMDs corresponding to FIGS. 14A and 14B and / or 15A and 15B. [Figure 18] FIG. 16B shows a block diagram illustrating an exemplary IMD of the present invention having wired components, including an in-vivo acoustic sensor device with a high-fidelity (HF) accelerometer, and including the internal components of the IMD corresponding to FIGS. 16A and 16B. [Figure 19] FIG. 1 shows a block diagram illustrating an exemplary IMD of the present invention having a microphone included in an in-vivo acoustic sensor device. [Figure 20A] 1 shows a diagram illustrating an exemplary embodiment of an IMD of the present invention having a stress-mediated acoustic sensor according to the present invention hermetically sealed with an electronic unit in a housing. [Figure 20B] 1 shows a diagram illustrating an exemplary embodiment of an IMD of the present invention having a stress-mediated acoustic sensor according to the present invention hermetically sealed with an electronic unit in a housing. [Figure 21A]1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 21B] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 21C] 1C shows a diagram of another exemplary embodiment of the in-vivo fluid flow sensor device of FIG. 1B, in accordance with the present invention. [Figure 22] 1A-1C show diagrams illustrating exemplary geometries of several exemplary embodiments of monomorphic piezoelectric sensor devices according to the present invention; [Figure 23] 1 illustrates an exemplary embodiment of an implantable medical device according to the present invention, showing a diagram integrating an exemplary embodiment of an in-vivo fluid flow sensor device and an exemplary embodiment of an in-vivo acoustic sensor device according to the present invention; [Figure 24A] 1 shows a diagram illustrating an exemplary embodiment of an implantable medical device according to the present invention interconnecting an exemplary embodiment of an in-vivo fluid flow sensor device and an exemplary embodiment of an in-vivo acoustic sensor device according to the present invention. [Figure 24B] 1 shows a diagram illustrating an exemplary embodiment of an implantable medical device according to the present invention interconnecting an exemplary embodiment of an in-vivo fluid flow sensor device and an exemplary embodiment of an in-vivo acoustic sensor device according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention provides a system for monitoring and collecting data from one or more implantable medical devices implanted into a living subject for assessment of one or more health and / or disease states. The living subject may also be referred to herein as a recipient, a patient, or simply a subject, which may include a human or a non-human animal. The IMD(s) of the present invention may be surgically implanted and removed from the recipient.

[0018] In some embodiments, for example, the IMD includes an in-vivo fluid flow sensor including an ultrasound transducer array mountable outside an anatomical structure, such as a cardiac chamber or blood vessel entering or exiting the heart or regions of the lungs or other organs, capable of measuring fluid flow through the anatomical structure. In some embodiments, for example, the IMD includes an in-vivo acoustic sensor capable of detecting and measuring acoustic signals generated by the host. IMDs including in-vivo fluid flow sensors may also include in-vivo acoustic sensors that may be configured as part of a single device structure (e.g., a shared housing) or may be configured as part of separate device structures that may be electrically connected to share electronic components, including, for example, but not limited to, a power source, a wireless communication unit, a data processing unit, or other electronic resources and functions.

[0019] As used herein, acoustic signals refer to mechanical waves in gases, liquids, and solids, including vibration, sound, ultrasound, and infrared. Thus, in-vivo fluid flow sensors and in-vivo acoustic sensors can detect and measure mechanical waves traveling through gases, liquids, and / or solids that make up the host's internal anatomical structures. Acoustic signals originating from the body are generated by pressure changes, blood and air flows, and mechanical movements of organs and tissues. Examples of acoustic signals detectable by the in-vivo acoustic sensors of the present invention can be fluid turbulence, such as airflow in the lungs, or blood flow in the heart or vascular structures, or impulses from the movement / movement of cardiac structures (e.g., valves).

[0020] In some embodiments, an IMD including an in-vivo fluid flow sensor and / or an in-vivo acoustic sensor may include one or more auxiliary sensors for detecting and measuring patient movement and / or position or orientation, electrophysiological signals associated with one or more anatomical structures of the host, such as the heart, and sensors for detecting blood flow velocity and vessel diameter in the patient's in-vivo fluid, and / or an analyte or analytes. Exemplary embodiments including one or more auxiliary sensors with an in-vivo fluid flow sensor and / or an in-vivo acoustic sensor are discussed in detail below.

[0021] The term sound is generally used to refer to audible mechanical waves (e.g., sound waves) that can be detected by the human ear (i.e., heard or audible by the human ear). IMDs of the present invention can detect and measure such sound waves, but IMDs can detect and measure mechanical waves that are not heard by the human ear. As used herein, and unless the context indicates otherwise, the terms "sound wave" and "sound wave" and "acoustic wave" and "mechanical wave" can be used interchangeably without limiting the meaning of these terms to audible mechanical waves that can be heard by the human ear, i.e., mechanical waves in the frequency range of 20 Hz to 20 kHz.

[0022] Disclosed are devices, systems, and methods for in vivo monitoring of blood flow through a heart valve (e.g., mitral, tricuspid, and / or aortic valve), or through a heart chamber, e.g., the atrium or ventricle, or the flow of biological fluids in an anatomical structure, such as a major blood vessel into or out of the heart, e.g., the aorta, vena cava, or pulmonary veins or arteries. The disclosed devices, systems, and methods can continuously measure and assess blood flow forward and backward in regions of the heart (e.g., the inlet or outlet of a heart valve), compiled with other monitored data that can be used to determine cardiac function or dysfunction (e.g., mitral valve regulation (MVR), etc.) and / or to measure or predict secondary factors (e.g., heart rate (HR), cardiac output (CO), or features of congestive heart failure (CHF), etc.).

[0023] Implementation of the disclosed technology is envisioned to shift the paradigm from different acute or emergency medical procedures to remote and continuous monitoring and management for long-term diagnostic and predictive care. For example, acute management of treatment sites in the heart currently remains undetectable after treatment (e.g., implantation of stents, implants (mitroplasty, mitral valve, percutaneous mitral valve, etc.)). However, when a patient experiences severe functional problems that cause them to return to a medical professional, this is often in an emergency situation. An in-vivo fluid flow sensor device of the disclosed in-vivo fluid flow sensor platform can be implanted directly around the heart (and in a manner independent of any existing biomedical devices implanted in the heart) to detect blood flow within the heart that indicates potential differences, including, for example, cardiac output, stroke volume, total peripheral resistance, and / or the onset of restenosis.

[0024] For example, in some implementations, the disclosed in-vivo fluid flow sensor device can measure fluid flow through the atria into the ventricles of the heart, for example, to determine blood flow at the mitral valve in the left or right tricuspid valve, thereby determining the fluid flow rate through the valve volume, known as the "valve flow volume," by measuring "Q," i.e., flow rate (volume of blood / time) or the amount of pressure difference between the ends of the flow path divided by resistance), which can be used to characterize natural fluid backflow, potential leaks through the valve, and interrupted backflow. When placed in proximity to a heart valve, for example, once in place and properly calibrated, the disclosed in-vivo fluid flow sensor device can detect where valve malfunction (e.g., leaks) is occurring. The disclosed in vivo fluid flow sensor platform (i.e., device, system, and / or technique) can also detect the diameter, or predicted area and / or volume, of a heart chamber, and changes over time relative to a baseline measurement, which may indicate potential adverse effects on cardiac function / performance relative to that baseline and / or deterioration after treatment (e.g., which may lead to heart disease such as congestive heart failure (CHF), a chronic condition in which the heart is unable to pump blood and is often attributed to weak or stiff cardiac tissue). For example, detection of blood flow and regurgitation across a heart valve can be used to correlate with cardiac function / performance and the effects of heart failure, as defined by CHF.

[0025] Also, for example, data obtained by embodiments of the disclosed fluid flow sensor technology can be used in compilations containing information to enable or optimize the administration of pharmaceutical prescriptions (e.g., dosage) for optimal patient care. For example, data obtained by embodiments of the disclosed fluid flow sensor technology can be used to assess valvular function and deterioration, and can be used in valvular or vascular treatments (e.g., compilation with EKG data). As an illustrative example, the disclosed in-vivo fluid flow sensor platform can position an in-vivo fluid flow sensor device over a vena cava and apply an ultrasound signal to obtain information (e.g., vessel dimensions (thickness) and velocity of blood flow through the vena cava) that can be used to determine pulmonary wedge pressure, thereby monitoring the effectiveness of specific pharmaceutical dosages in treating patients with various forms of cardiac disease. Additionally, for patients with cardiac disease who take a cocktail of drugs to manage their cardiac condition (e.g., diuretics for fluid volume, ACE inhibitors for peripheral resistance, and beta-blockers for contractility), blood pressure and flow through the vena cava can indicate whether the patient is adequately adhering to the drug regimen or whether the regimen is not optimal or effective, such as due to the body developing tolerance to the drugs over time.

[0026] The disclosed in-vivo fluid flow sensor platform provides the ability to acquire acoustic signal measurements of fluid flow directly through anatomical structures (without other anatomical structures in the acoustic signal path) and provide the acquired acoustic signal measurements to a remote device (e.g., a remote in-vivo device in communication with the in-vivo fluid flow sensor device, and / or a remote device outside the body in communication with the in-vivo fluid flow sensor device and / or the remote in-vivo device), and also has low power requirements and a relatively small physical footprint (i.e., for long periods of time (e.g., 10 years or more)).

[0027] Although the disclosed embodiments of the in-vivo sensor are described herein primarily in terms of monitoring blood flow across cardiac structures (such as heart valves) within a patient's body to facilitate understanding of the concepts underlying the present invention, it is understood that the disclosed embodiments according to the present invention can also include monitoring the dynamic flow of other biological fluids and other systems, including, but not limited to, fluid flow within the gastrointestinal system, kidneys, etc.

[0028] In some embodiments, a sensor device for in vivo monitoring of fluid flow within an anatomical structure, for example, while coupled to an anatomical structure such as an atrium, a ventricle, a chamber, or a great vessel, comprises: a linkage assembly including a first arm configured to be attached to a first portion of the anatomical structure and a second arm configured to be attached to a second portion of the anatomical structure opposite the first portion; a connection device coupled to each of the first and second arms; an ultrasonic sensor assembly including a plurality of acoustic transducer elements coupled to the linkage assembly, wherein the plurality of acoustic transducer elements include a first acoustic transducer element configured to transmit an acoustic signal to propagate through the anatomical structure, and second and third acoustic transducer elements configured to propagate through the anatomical structure and receive acoustic signals indicative of fluid flow parameters of a biological fluid within the anatomical structure; and an electronics unit contained within the connection device and in electrical communication with the plurality of acoustic transducer elements of the ultrasonic sensor assembly, wherein the electronics unit is configured to process electrical signals associated with the received acoustic signals as data and transmit the data wirelessly to an external processor.

[0029] In some embodiments, the device may comprise a sensor device for in vivo monitoring of fluid flow within an anatomical structure, for example, while coupled to the anatomical structure, including a first ultrasound assembly including a first set of one or more acoustic transducer elements in a major blood vessel of the heart, such as for monitoring blood flow within the atria, ventricles, and valves therebetween, a second ultrasound assembly including a second set of one or more acoustic transducer elements, a first linkage coupled to the first ultrasound assembly, a second linkage coupled to the second ultrasound assembly, and an electronics unit in electrical communication with the first ultrasound assembly and the second ultrasound assembly, and a spring connection device coupled to each of the first and second linkages, the spring connection device being configured to process electrical signals associated with the returned acoustic signals as data and to wirelessly transmit the data to an external processor, the spring connection device being operable to position the first ultrasonic assembly at a first location on the anatomical structure and the second ultrasonic assembly at a second location on the anatomical structure to form a plane across the first and second locations of the anatomical structure, and to transmit and receive acoustic signals from the first set of one or more acoustic transducer elements and the second set of one or more acoustic transducer elements indicative of fluid flow parameters of the biological fluid within the anatomical structure.

[0030] Some implementations of the disclosed devices, systems, and methods include in vivo monitoring of a patient's cardiovascular and / or pulmonary disease status to manage the patient's treatment and care for diseases including heart failure, valvular disease, coronary artery disease, thoracic vena cava inflammation, chronic obstructive pulmonary disease (COPD), sleep apnea, asthma, and / or other acute or chronic diseases or conditions. In particular, the disclosed implantable medical devices, systems, and methods of the present invention can be implemented to assist a patient's healthcare professional (HCP) in managing medications for the patient's disease or condition.

[0031] By way of example, some embodiments of the exemplary IMD may be implemented to acoustically monitor cardiovascular function using the IMD's high-fidelity implantable acoustic sensor to continuously detect abnormal blood flow associated with molar stenosis (AS) and mitral valve regurgitation (MVR) for valvular drug management. Also by way of example, some embodiments of the exemplary IMD may be implemented to acoustically monitor both cardiovascular and pulmonary function using the IMD's high-fidelity acoustic sensor to continuously detect abnormal blood flow associated with AS, MVR, other cardiac valve sounds, including pulmonary edema, in conjunction with or exclusively from pulmonary sounds related to breathing, asthma, sleep apnea, COPD, or other pulmonary conditions for cardiovascular and pulmonary drug management.

[0032] For example, the disclosed implantable medical devices, systems, and methods, including the in-vivo fluid flow sensor and in-vivo acoustic sensor of the present invention, can simultaneously provide a patient's HCP with clinical data related to the contractility, resistance, and / or volume of blood pumped by the patient's heart, allowing the HCP to make immediate decisions to influence medications for managing cardiovascular diseases or conditions. For example, an IMD including an in-vivo fluid flow sensor can continuously measure cardiac output, compiled with continuous measurements of mechanical (acoustic) waves associated with stenosis or regurgitation by the in-vivo fluid flow sensor, which together provide a complete, continuous assessment of the patient's cardiovascular health to characterize cardiac function / dysfunction, and the effectiveness of the patient's treatment regimen, including compliance therewith.

[0033] Currently, many forms of heart disease are treated with a variety of medications, including: (i) angiotensin-converting enzyme (ACE) inhibitors, which lower blood pressure by relaxing veins and arteries by preventing the production of an enzyme necessary for the production of angiotensin II; (ii) beta-adrenergic blocking agents (beta-blockers), which block the effects of the hormone epinephrine, causing the heart to beat more slowly and with less force, potentially widening veins and arteries to improve blood flow; and (iii) diuretics, which reduce the amount of fluid flowing through veins and arteries, thereby lowering blood pressure and reducing fluid accumulation in the body, for example, by promoting kidney function to remove saltwater in the urine. These medications are administered, particularly to patients with stage 3 or 4 heart disease, to prevent the patient from decompensating, i.e., when structural or functional changes in the patient's heart prevent the heart from pumping and / or accommodating blood within physiological pressure levels, thereby causing life-threatening cardiac limitations and requiring immediate therapeutic intervention (e.g., emergency room). Some DHF symptoms include the patient's inability to breathe, low pulse oximetry, high heart rate, or others that may precede organ system failure.

[0034] One of the greatest challenges for patients and their HCPs in managing cardiovascular and / or pulmonary disease states is patient compliance. Patients must adhere to two aspects of their medical care: (1) regularly (e.g., multiple times daily) taking prescribed medications exactly when and how prescribed, and (2) regularly (e.g., at least once daily) measuring and recording multiple physiological measurements, including blood pressure (BP), body weight (BW), and blood oxygen level (PulseOx). Current cardiac monitoring systems are compilations of external sensors, such as blood pressure cuffs (digital), weight scales (digital), and pulse oximeters (digital), each requiring separate and distinct measurements of the patient's BP, BW, and PulseOx. However, when patients comply, the system can determine their risk level—whether they are successfully managing their cardiac disease or predisposing to DHF. For example, if a patient develops a large amount of fluid in the lungs and their heart rate increases, then the patient's BW will increase, measurable by weight scale, and the patient's heart rate will increase, measurable by blood pressure cuff, which may collectively indicate that the patient is decompensating and may require immediate medical care (e.g., transport to an emergency room where the HCP can adjust the concentration of ACE inhibitors, beta blockers, and diuretics to avoid DHF).

[0035] While studies have shown that patients are generally reliable in taking their medications regularly as prescribed, most patients struggle to maintain strict protocols for measuring and recording their BP, BW, and PulseOx. Traditional approaches to treating cardiovascular and pulmonary diseases are significantly flawed because they rely on patient compliance. The disclosed implantable medical devices, systems, and methods of the present invention can be implemented to continuously, passively, and autonomously (i.e., without patient interaction) monitor multiple physiological markers associated with cardiovascular and / or pulmonary health and disease from within a patient's body, thereby eliminating patient compliance from the equation for the physiological monitoring component of patient treatment and care.

[0036] The disclosed implantable medical devices, systems, and methods of the present invention continuously, autonomously, and passively monitor heart rate, fluid flow and accumulation in tissues or organs, patient movement and activity, electrophysiological signals such as an electrocardiogram (ECG or EKG), and other physiological measurements based on in vivo acoustic and / or fluid flow sensor(s) in an IMD, and can be configured in conjunction with one or more auxiliary sensors, including motion sensors or inertial measurement units, and electrophysiological sensors, as otherwise disclosed herein. For example, in some implementations of IMDs that use acoustic and ECG sensors as temporal qualifiers, i.e., timing markers of events in the cardiac cycle, the IMD can study specific sounds to distinguish between healthy and unhealthy markers of cardiac function.

[0037] The in vivo acoustic, fluid flow, and auxiliary sensors of the IMDs of the present invention are not blood-contacting, i.e., the sensors are not positioned within blood vessels and are operated to detect physiological phenomena, including those specifically associated with blood flow. For example, if an IMD containing the in vivo fluid flow sensor, the in vivo acoustic sensor, and certain auxiliary sensors (e.g., ECG and IMU) are implanted near a patient's heart, the IMD can monitor 12 pathologies for each of the heart's four valves, including (1) stenosis (narrowing of a valve in a large blood vessel branching off from or into the heart, typically caused by vasculitis), (2) regurgitation (backflow of blood due to a valve defect), and (3) myxomatous, a combination of stenosis and regurgitation (degeneration of a heart valve). The continuous, autonomous, passive in vivo monitoring capabilities of the disclosed embodiments of the IMDs of the present invention are important for the advancement of cardiovascular medicine, as none of these disease states are currently easily observed, as are changes over time in these disease states that allow for diagnosis. Conventional diagnostic systems, devices, and techniques conveniently track physiological markers over such periods to accurately ensure HCPs can effectively and optimally make an appropriate diagnosis. Furthermore, the IMD of the present invention can utilize its IMU sensor(s) to controllably collect data during both resting and active states to simulate stress testing, thereby increasing the IMD's ability to assess a patient's disease state. In such implementations, disclosed embodiments of the IMD of the present invention can unobtrusively characterize cardiovascular and / or pulmonary function across multiple states and contexts of a patient's condition without relying on patient compliance.

[0038] In some implementations of the IMD of the present invention, for example, an IMD including an in-vivo acoustic sensor can act like an internal stethoscope for a HCP, continuously measuring a patient's respiration. Not only can it be used to monitor pulmonary conditions such as asthma or COPD, but respiratory acoustics change when there is fluid in the lungs, and MVR and heart failure can cause such fluid accumulation. Thus, the disclosed embodiments of the in-vivo acoustic sensor of the present invention can complement or replace external digital stethoscopes, which suffer from poor fidelity and reliability (poor compliance) due to over 90% signal loss from the transmission of acoustic signals from body tissues through the air transduced by the digital stethoscope's external microphone. In some embodiments, the in-vivo acoustic sensor of the present invention can sense acoustic signals having frequencies of 1 Hz, or 2 Hz, or 10 Hz, up to about 20,000 Hz, or up to about 18,000 Hz, or up to about 16,000 Hz, or up to about 14,000 Hz, or up to about 12,000 Hz, or up to about 10,000 Hz. For example, various embodiments of an exemplary IMD including an in-vivo acoustic sensor may be configured to detect acoustic signals within a frequency range of 0.1 Hz to 20 kHz or within a frequency range of 0.1 Hz to 20 kHz, where the particular range may be defined based on the particular embodiment of the acoustic sensor.

[0039] In some embodiments of an IMD including an in-vivo acoustic sensor according to the present invention, for example, the in-vivo acoustic sensor includes a displacement-mediated acoustic sensor for measuring structural changes caused by mechanical waves on a transducer material. In some embodiments, for example, the in-vivo acoustic sensor includes a microphone. In some embodiments, for example, the in-vivo acoustic sensor may include an accelerometer. In some embodiments, for example, the in-vivo acoustic sensor may include a diaphragm that contacts and vibrates or otherwise extends in response to acoustic waves, where the extension is measured over time to provide a temporal measurement of the sound. In some embodiments, for example, the in-vivo acoustic sensor includes a strain gauge operable to detect strain and / or deformation of a material by measuring resistivity. In some embodiments, for example, the in-vivo acoustic sensor includes a piezoelectric sensor operable to measure changes by converting pressure, acceleration, temperature, strain, or force into electrical charge.

[0040] In some embodiments of an IMD including an in-vivo acoustic sensor according to the present invention, for example, the in-vivo acoustic sensor includes a stress-mediated acoustic sensor operable to measure stress applied to a transducer material. In some embodiments, the acoustic sensor includes a stress-mediated microelectromechanical sensor (MEMS) device for transducing mechanical waves applying a force to the MEMS device into an electrical signal. Some examples of MEMS stress-mediated acoustic sensors can include piezoelectric stress sensors, and in some embodiments, the piezoelectric stress sensor includes a monolithic piezoelectric sensor device.

[0041] These and other embodiments are discussed in more detail in the examples that follow.

[0042] Illustrative Embodiments 1A shows a diagram illustrating an exemplary embodiment of a system 10 for in-vivo monitoring of patient-user fluid flow in accordance with the present invention. System 10 includes an implantable medical device (IMD) 100 that may be implanted within a patient-user and includes one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y, and a data processing system 150 in communication with the one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y. In some embodiments, system 10 includes a receiver device 130 operable to receive wireless transmissions carrying data indicative of detected signals obtained from one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y, and to transmit and / or store the data to data processing system 150. In some embodiments, implantable medical devices 100 and / or receiver devices 130 communicate with each other and with a data processing system 150 via a network of computers 140 accessible via the Internet (e.g., referred to as the cloud), and data from one or more implantable medical devices 100 and / or receiver devices 130 may be transferred to the data processing system 150. Similarly, information from the data processing system 150 may be transferred to the receiver device 130 and / or one or more implantable medical devices 100. For example, the data processing system 150 may manage data compilation(s) across directional or changing modalities to provide continuous, longitudinal representations (i.e., rather than one-time representations) of patient health and disease information, as well as time points (e.g., from any time point defined as an initial point (T0) to a future time point (T F ) thereby functionally providing treatment for deterioration or improvement of the physical condition from the point of implantation and one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y of the implantable medical device 100.

[0043] In an exemplary embodiment, implantable medical device 100 includes a sensor unit 110 and an electronic unit 120, one or both of which are contained within and / or coupled via a housing or casing 101. The sensor unit 110 and electronic unit 120 of implantable medical device 100 may be configured as a single unit for each of one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y of implantable medical device 100, or may be configured as multiple separate, or partially shared and partially separated, units for one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y of implantable medical device 100. In some examples, housing or casing 101 is configured to protect components of electronic unit 120 from body fluids or substances when implantable medical device 100 is deployed inside a patient-user.

[0044] 1A includes a first implantable device, i.e., at least one in-vivo fluid flow sensor device 100X, deployed in a first portion of a patient's body, such as the chest, head, torso, appendages, or other region, and a second implantable device, i.e., at least one in-vivo acoustic sensor device 100Y, deployed in a second portion of the patient's body. One or both of the first and / or second in-vivo fluid flow sensor devices 100Y and / or 100X may be directly coupled to an organ or tissue within the patient's body at the first portion and / or second portion, respectively. In some implementations, for example, the first in-vivo fluid flow sensor device 100Y may be coupled to an implant device deployed in or near a first portion of a patient-user's body, such as an implant in the heart, lungs, skull, neck, intestines, and digestive track, limbs, or extremities. Similarly, for example, the second device of either or both of the in vivo fluid flow sensor device 100X and / or the in vivo acoustic sensor device 100Y may be positioned at or near a third portion of the patient's body, or at or near one of the first or second portions in which the in vivo fluid flow sensor device 100X and the in vivo acoustic sensor device 10100Y are respectively positioned.

[0045] In some embodiments of the implantable medical device 100, for example, one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y can be configured as part of a single device structure (e.g., a shared housing), while in some embodiments, one or more in-vivo fluid flow sensor devices 100X and / or one or more in-vivo acoustic sensor devices 100Y can be configured as part of separate device structures. In such embodiments having separate device structures, the one or more in-vivo fluid flow sensor devices 100X and / or the one or more in-vivo acoustic sensor devices 100Y can be electrically connected to each other, and in some embodiments, the separate in-vivo fluid flow sensor device(s) 100X and the in-vivo acoustic sensor device(s) 100Y can be configured to share electronic components, including, for example, a power source, a wireless communication unit, a data processing unit, and other electronic resources and functionality.

[0046] In some exemplary embodiments, such as those described below in connection with FIG. 1B , a sensor unit 110 includes at least one of a first ultrasonic sensor assembly and a second ultrasonic sensor assembly, each including one or more acoustic transducer elements, configured to be positioned over and in contact with an anatomical structure, such as the heart, and an electronics unit 120 (e.g., housed within a casing 101, wherein one or both of the first and second ultrasonic sensor assemblies transmit and receive acoustic signals over a region of interest in the anatomical structure, and the electronics unit 120 monitors and stores data associated with the monitored acoustic signals. 1B and other figures.

[0047] 1A , in some implementations, one or more implantable medical devices 100 (e.g., in-vivo fluid flow sensor device 100X and / or in-vivo fluid flow sensor device 100Y) wirelessly communicate acquired data directly to receiver device 130. For example, implantable medical device 100 may transfer data to receiver device 130 using a low-power wireless communication protocol, such as Bluetooth Low Energy (BLE), near-field communication (NFC), low-frequency radio frequency (RF) signals in the range of 3 kHz to 1.3 MHz, or others. Exemplary embodiments of receiver device 130 include computing device 130A or dedicated base station 130B. For example, computing device 130A may include, but is not limited to, a smartphone, a tablet, a home device (e.g., Alexa, Nest, Echo, Google Home, smart TV, etc.), a wearable computing device (e.g., smartwatch, smart glasses, or headgear, etc.), a laptop or desktop computer, or others. The dedicated base station 130B may include a data storage and / or data communication unit to facilitate communication of data from the implantable medical device 100 to the data processing system 150 via Wi-Fi access or a cellular link to the network 140. In some implementations, for example, the receiver device 130 may be embodied on multiple receiver devices, such as both a computing device 130A (e.g., a smartphone, a tablet, etc.) and a dedicated base station 130B, as shown in the example of FIG. 1. In some implementations, for example, the receiver device 130 may at least partially process the received data for display on a display screen of the 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) resident on the receiver device 130 to control various data processing, storage, and communication functions for management of the received data.

[0048] 1A , data processing system 150 may include one or more server computing devices 152, one or more client computing devices 154, and / or one or more databases 156 in data communication with each other. In implementations, for example, computing devices 152, 154, and database 156 communicate with each other and / or with other devices in system 10 via network 140. In some implementations, for example, data processing system 150 can remotely monitor patient-user related data acquired by implantable medical device 100 and / or remotely control aspects of system 10, such as modifying sensing parameters or protocols of one or more in-vivo fluid flow sensor devices 100X, data display or processing features of an app on receiver device 130, or others.

[0049] In some embodiments, for example, system 10 optionally includes a remote computing device 160 operated by a remote user to remotely monitor data related to the patient-user acquired by implantable medical device 100 that is forwarded to data processing system 150. For example, remote computer 160 may include a personal computer, such as a desktop or laptop computer, a mobile computing device, such as a smartphone, tablet, smartwatch, or other computing device. In some implementations, for example, remote computing device 160 is configured to receive only data curated (e.g., selected, pre-processed, and / or formatted) by data processing system 150. In some implementations, for example, remote computing device 160 is configured to remotely operate one or more aspects (e.g., functions) of system 10. For example, remote computing device 160 may implement a remote user software application (remote user app) configured to provide such display, storage, and / or management capabilities to the remote user. Remote users may include, for example, healthcare providers (HCPs), such as doctors, nurses, family members or other caregivers of the patient user, or health insurance payers or other types of stakeholder entities or individuals with respect to the patient user's health.

[0050] FIG. 1B shows a block diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor 100X shown in FIG. 1A, which is shown in FIG. 1B as in-vivo fluid flow sensor 100X. In the example of FIG. 1B, in-vivo fluid flow sensor 100X includes an exemplary embodiment of sensor unit 110 (shown as sensor unit 110X) and an exemplary embodiment of electronic unit 120 (shown as electronic unit 120X). Sensor unit 110X of in-vivo fluid flow sensor 110X includes at least one ultrasonic assembly in electrical communication with electronic unit 120 via electrical interconnect 117X, which is shown in FIG. 1B as having first ultrasonic sensor assembly 111 and optional second ultrasonic sensor assembly 112, each in electrical communication with electronic unit 120 via electrical interconnect 117X. The first ultrasonic sensor assembly 111 includes one or more acoustic transducer elements 113 (also referred to herein as “transducer 113” or “one or more transducers 113”), and the optional second ultrasonic sensor assembly 112 includes one or more acoustic transducer elements 114 (also referred to herein as “transducer 114” or “one or more transducers 114”). The one or more transducers 113 of the first ultrasonic sensor assembly 111 include transducer element 113a and optionally include an additional transducer element, represented as transducer element 113b in FIG. 1B . Similarly, the one or more transducers 114 of the second ultrasonic sensor assembly 112 include transducer element 114a and optionally include an additional transducer element, represented as transducer element 114b in FIG. 1B . For example, embodiments having multiple acoustic transducer elements may be configured as an array of transducers in each ultrasonic sensor assembly. The electrical interconnect 117X is configured to couple each of the one or more acoustic transducer elements 113 of the first ultrasonic sensor assembly 111 and the one or more acoustic transducer elements 114 of the optional second ultrasonic sensor assembly 112 to an electrical interface of the electronic unit 120X.In various implementations of the exemplary embodiment of in-vivo fluid flow sensor 100X, first ultrasonic sensor assembly 111 and optional second ultrasonic sensor assembly 112 may transmit and receive acoustic signals at one or more frequencies within a frequency range of 2 MHz to 20 MHz. In various embodiments, for example, first ultrasonic sensor assembly 111 and optional second ultrasonic sensor assembly 112 may each include a frame, casing, or housing structure (not shown) for structurally supporting one or more acoustic transducer elements 113 and one or more acoustic transducer elements 114, respectively, and positioning them in fixed positions relative to one another.

[0051] In some embodiments, for example, a transducer element or an element of the one or more acoustic transducer elements 113 and the one or more acoustic transducer elements 114 comprises a piezoelectric transducer operable to transmit an acoustic signal based on an electrical input signal, receive an acoustic signal, and generate an electrical output signal. For example, the piezoelectric transducer may comprise a solid-state piezoelectric ultrasonic transducer or a piezoelectric micromachined ultrasonic transducer (PMUT), such as a MEMS-based piezoelectric ultrasonic transducer for acoustic imaging of the environment. In some embodiments, for example, a transducer element or an element of the one or more acoustic transducer elements 113 and the one or more acoustic transducer elements 114 comprises a ferroelectric hafnium oxide transducer.

[0052] In-vivo fluid flow sensor device 100X includes a linkage assembly 103B that couples first ultrasonic sensor assembly 111 to electronics unit 120X (and, in embodiments including second ultrasonic sensor assembly 112, couples second ultrasonic sensor assembly 112 to electronics unit 120X). In some embodiments, linkage assembly 103B may include a pair of linkages configured to (1) secure (e.g., attach and anchor) in-vivo fluid flow sensor device 100X to a target in-vivo organ or tissue, and (2) carry respective electrical interconnects 117X (connected to transducers 113 and / or 114) from first ultrasonic sensor assembly 111 and / or optional second ultrasonic sensor assembly 112 to electronics unit 120X. In some embodiments, for example, the linkage pair of linkage assembly 103B includes a spring connection device, as discussed later in connection with FIG. 2A, while in some embodiments, for example, the linkage pair of linkage assembly 103B includes a flexible band, with or without a spring, as discussed later in this patent document.

[0053] In some embodiments of the in vivo fluid flow sensor device 100X, for example, the sensor unit 110X may optionally include one or more secondary sensors 119X. For example, in some implementations, the secondary sensor 119X may include an analyte sensor for measuring an analyte parameter (e.g., concentration) in a region adjacent to the anatomical structure in which the in vivo fluid flow sensor device 100X is deployed. In some examples, the optional secondary analyte sensor may include, but is not limited to, a glucose sensor. In addition to or alternatively to the secondary analyte sensor, the secondary sensor 119X may include a pH sensor for measuring a pH level in a region adjacent to the anatomical structure. In addition to or alternatively to the secondary analyte sensor and / or the secondary pH sensor, the secondary sensor 119X may include a temperature sensor for measuring a temperature in a region adjacent to the anatomical structure. In such cases, any one or more secondary sensors 119X, including, for example, an analyte sensor, a pH sensor, and / or a temperature sensor, may be used to obtain data indicative of clinically relevant conditions related to the anatomical structures and / or conditions of the in vivo environment in which the in vivo fluid flow sensor device 100X is deployed, such as a potential infection or inflammatory response to implantation of the in vivo fluid flow sensor device 100X. In some embodiments, for example, the optional one or more secondary sensors 119X may be attached to the casing 101 of the in vivo fluid flow sensor device 100X, e.g., via welding, chemical bonding, clips, clamps, or other attachment means. In some embodiments, for example, the optional one or more secondary sensors 119X may be attached to one or both of the first ultrasonic sensor assembly 111 and / or the (optional) second ultrasonic sensor assembly 112, e.g., via attachment to a frame or casing structure.

[0054] In some embodiments, for example, the optional one or more secondary sensors 119X of the in-vivo fluid flow sensor device 100X may include an inertial measurement unit (IMU) configured to monitor movement of the in-vivo fluid flow sensor device 100X in multiple degrees of freedom. In some embodiments, for example, the optional one or more secondary sensors 119X of the in-vivo fluid flow sensor device 100X may include an accelerometer in communication with the data processing unit 121 of the electronic unit 120X. In some embodiments, for example, the optional one or more secondary sensors 119X of the in-vivo fluid flow sensor device 100X may include a velocity sensor in communication with the data processing unit 121 of the electronic unit 120X. In some embodiments, for example, the optional one or more secondary sensors 119X of the in-vivo fluid flow sensor device 100X may include a magnetometer in communication with the data processing unit 121 of the electronic unit 120X. In such an implementation, for example, the in-vivo fluid flow sensor device 100X is operable to measure heart rate compiled with fluid flow through the heart (e.g., across the mitral valve or tricuspid valve) when the in-vivo fluid flow sensor device 100X is deployed outside the heart, e.g., within the pericardium.

[0055] 1B , electronic unit 120X of in-vivo fluid flow sensor device 100X includes a data processing unit 121, an optional signal conditioning unit 123, a power source 129, a wireless communication unit 127, and an electrical interface 125, which may include conductive contact locations (e.g., pads, pins, or other contact configurations) that electrically couple with electrical interconnects 117X of sensor unit 110X. Electronic unit 120X is configured to receive and at least partially process electrical signals obtained from one or more acoustic transducers 113 of first ultrasonic sensor assembly 111 and one or more acoustic transducers 114 of second ultrasonic sensor assembly 112 of sensor unit 110X. For example, in some embodiments, the electrical signals are received at corresponding contact locations of electrical interface 125 and provided to data processing unit 121 (or, optionally, first provided to signal conditioning unit 123 to improve the quality of the electrical signals obtained from sensor unit 110X before providing them to data processing unit 121). In such implementations, the output of data processing unit 121 may include raw or processed data associated with the wirelessly transmitted detected data from sensor unit 110X that is wirelessly transmitted to an external device by wireless communication unit 127. In an exemplary embodiment of electronic unit 120X, power source 129 may include a battery (e.g., primary or rechargeable), a fuel cell, or other power source for powering components of electronic unit 120X and / or sensor unit 110X. In some implementations, for example, power source 129 includes an ultra-low power system (e.g., operating in the microampere range).

[0056] In some optional embodiments, for example, signal conditioning unit 123 may include circuitry including one or more filters and / or one or more amplifiers to enhance the raw electrical signals detected by ultrasonic sensor assemblies 111, 112 of sensor unit 110X to increase the signal-to-noise ratio (SNR) of the electrical signals, thereby generating data including signal-processed electrical signals. In some optional embodiments, signal conditioning unit 123 may include drive circuitry to generate operating electrical signals that generate electrical potentials and / or currents at electrode assemblies and / or temperature sensor assemblies of the analyte sensors of sensor unit 110X for operating electrochemical and / or electrophysical or dynamic sensing methods to be performed at the electrodes in an optional secondary sensor 119X implementation of sensor unit 110X.

[0057] In some embodiments, for example, wireless communication unit 127 includes a wireless transmitter, receiver, and / or transceiver device including an antenna capable of communicating with an external device to communicate raw, partially processed, or fully processed data from signal conditioning unit 123 (and / or data processing unit 121, discussed below). For example, wireless communication unit 127 may be configured to manage a communication protocol for transmission or reception via the antenna. Examples of antennas may include, but are not limited to, a whip antenna, a loop antenna, or a conformal antenna. An exemplary transceiver unit may include a BLE chipset for communicating with a BLE-enabled device, e.g., a smartphone, a tablet, or other external computing device, such as receiver device 130. Additionally or alternatively, in some embodiments, for example, wireless communication unit 127 is configured as a scaffold around electronic unit 120X, e.g., coupled to or integrated with casing 101, which is structured to provide wireless communication means for in-vivo fluid flow sensor device 100X.

[0058] In some embodiments, electronics unit 120X includes a data processing unit 121 that at least partially processes the conditioned electrical signals to (i) generate data, for example, in analog or digital form, and / or (ii) control the functionality of electronics unit 120X and / or sensor unit 110X. For example, data processing unit 121 may be configured to manage data acquisition on data channels associated with one or more acoustic transducers 113 and one or more acoustic transducers 114 of sensor unit 110X.

[0059] In some embodiments of data processing unit 121, for example, data processing unit 121 may include a processor 121AY for processing data and a memory 121BY in communication with processor 121AY for storing and / or buffering data. In various embodiments, for example, processor 121AY may include one or more processors, and memory 121BY may include one or more memory units. For example, processor 121AY may include a central processing unit (CPU), a microcontroller unit (MCU), a graphics processing unit (GPU), or other type of processor. For example, memory 121BY may include and store processor-executable code that, when executed by the processor, configures data processing unit 121 to perform various operations, 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 data processing unit 121, memory 121BY may store information and data, such as instructions, software, values, images, and other data processed or referenced by processor 121AY. For example, various types of random access memory (RAM) devices, read only memory (ROM) devices, flash memory devices, and other suitable storage media may be used to implement the storage functionality of memory 121BY. In some embodiments, data processing unit 121 includes an input / output (I / O) unit 121C for interfacing processor 121AY and / or memory 121BY to other modules, units, or devices associated with external devices, such as, for example, receiver device 130, data processing system 150, remote computing device 160, and / or other external devices. In some embodiments, processor 121AY, memory 121BY, and / or I / O unit 121C communicate with a wireless communication unit 127, such as, for example, a transmitter (Tx) or a transmitter / receiver (Tx / Rx) unit.For example, in such an embodiment, I / O unit 121C interfaces processor 121AY and memory 121BY with wireless communication unit 127, e.g., to utilize various types of wireless interfaces compatible with typical data communication standards that may be used for communication between data processing unit 121 and other devices. Data communication standards include, but are not limited to, Bluetooth, Bluetooth Low Energy (BLE), Zigbee, IEEE 802.11, wireless local area network (WLAN), wireless personal area network (WPAN), wireless wide area network (WWAN), WiMAX, IEEE 802.16 (Worldwide Microwave Access Interoperability (WiMAX)), 3G / 4G / LTE / 5G / 6G cellular communication methods, and parallel interfaces. In some implementations, data processing unit 121 may interface with other devices using a wired connection via I / O unit 121C, e.g., prior to implantation within a patient-user. The data processing unit 121 may also interface with other external interfaces, data storage sources, and / or visual or audio display devices, etc., to obtain and transfer data and information that may be processed by the processor 121AY, stored in memory 121BY, or presented on an output unit of the receiver device 130 (e.g., a smartphone, tablet, etc.) or other external device to the in-vivo fluid flow sensor device 100X.

[0060] In an implementation of in-vivo fluid flow sensor device 100X, first ultrasonic sensor assembly 111 (and optional second ultrasonic sensor assembly 112) are controlled by data processing unit 121 to transmit and receive acoustic signals. For example, in some implementations, in-vivo fluid flow sensor device 100X is configured to measure the Doppler shift of an acoustic probe signal across an anatomical structure. For example, the travel time of the acoustic signal indicates the estimated distance traveled, and the frequency shift of the received acoustic signal is proportional to the velocity of the fluid flowing along the acoustic path. The data processing unit 121 is configured to provide a set of electrical control signals to the one or more transducers 113 and / or the one or more transducers 114 to stimulate transmission of the acoustic probe signal across a region of interest, such as the mitral valve of the heart, so that opposing sets of transducers of the one or more transducers 113 and / or the one or more transducers 114 receive the fluid flow shift acoustic probe signal, and based on the time of flight of the acoustic probe signal and the known fixed positions of the one or more transducers 113 and the one or more transducers 114, the data processing unit 121 processes the electrical signals transduced from the one or more transducers 113 and / or the one or more transducers 114 associated with the received acoustic probe signal to determine fluid flow, for example, forward flow or possible backward flow of blood across the mitral valve of the heart.

[0061] FIG. 1C is a block diagram illustrating an exemplary embodiment of the in-vivo acoustic sensor 100Y shown in FIG. 1A. In the example of FIG. 1C, the in-vivo acoustic sensor 100Y includes an exemplary embodiment of a sensor unit 110 (denoted as sensor unit 100Y) and an exemplary embodiment of an electronics unit 120 (denoted as electronics unit 120Y). The sensor unit 110Y includes at least one acoustic sensor 111Y for detecting acoustic signals originating within the host. One or both of the sensor unit 110Y and the electronics unit 120Y are housed within, or at least partially coupled to, a casing or housing 101Y that is deployable and biocompatible within the host's body. In some embodiments, for example, the acoustic sensor 111Y includes a transducer element 112Y coupled to a casing structure 113Y. The transducer element 112Y can receive mechanical waves emanating from a source (e.g., tissue, organ, or other) within the host's body such that the transducer element converts the energy of the received mechanical waves into electrical energy, thereby generating an electrical signal corresponding to the mechanical waves. In some embodiments, for example, the transducer element 112Y comprises a piezoelectric material, including, but not limited to, lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF), aluminum nitride (AlN), scandium aluminum nitride (ScAlN), barium titanate (BaTiO), lead titanate (PbTiO), potassium niobate (KNbO), lithium niobate (LiNbO), lithium tantalate (LiTaO), and / or sodium tungstate (NaWO). In an exemplary embodiment in which the transducer element 112Y comprises PZT, the PZT may be PZT-5A, PZT-5H, or PZT-5K. In an implementation of the acoustic sensor 111Y, for example, the casing structure 113Y provides a rigid, inflexible material and is configured to secure and / or position the transducer element 112Y within the acoustic sensor 111Y to receive mechanical waves for transduction into electrical signals indicative of in vivo acoustic signals within the body.In some embodiments, for example, the acoustic sensor casing structure 113Y is an airtight encapsulation structure that may include metal, plastic, composite, or other materials. The acoustic sensor 111Y is configured to electrically connect with the electronic unit 120Y via the electrical interconnect 117Y.

[0062] In some embodiments, the sensor unit 110Y may include an inertial measurement unit (IMU) 115Y for monitoring motion (in multiple degrees of freedom) and / or determining orientation of the in-vivo acoustic sensor 100Y. The IMU 115Y is configured to electrically communicate with the electronic unit 120Y via an electrical interconnect 117Y. In some embodiments of the sensor unit 110Y, for example, the IMU 115Y may include an accelerometer and / or a rotation rate sensor (e.g., a gyroscope) for monitoring patient movement and / or position. In some embodiments of the sensor unit 110Y, for example, the IMU 115Y may include a magnetometer. In an exemplary embodiment including the IMU 115Y, the IMU 115Y communicates with a data processing unit of the electronic unit 120Y.

[0063] In some embodiments of the in vivo fluid flow sensor device 100Y, for example, the sensor unit 110Y may optionally include one or more secondary sensors 119Y. For example, in some implementations, the secondary sensor(s) 119Y may include an analyte sensor for measuring an analyte parameter (e.g., concentration) in a region adjacent to a location (e.g., surrounding tissue) where the in vivo acoustic sensor 100Y is deployed within the host, at or adjacent to the heart and / or lungs. In some examples, the optional secondary analyte sensor may include, but is not limited to, a glucose sensor. In addition to or alternatively to the secondary analyte sensor, the secondary sensor 119Y may include a pH sensor for measuring a pH level in a region adjacent to the anatomical structure. In addition to or alternatively to the secondary analyte sensor and / or secondary pH sensor, the secondary sensor 119Y may include a temperature sensor for measuring a temperature in a region adjacent to the anatomical structure. In such cases, optional one or more secondary sensors 119Y, including, for example, an analyte sensor, a pH sensor, and / or a temperature sensor, can be used to obtain data indicative of clinically relevant conditions related to the anatomical structures and / or conditions of the in vivo environment in which the in vivo fluid flow sensor device 100Y is deployed, such as a potential infection or inflammatory response to implantation of the in vivo fluid flow sensor device 100Y. In some embodiments, for example, the optional one or more secondary sensors 119Y may include an ECG sensor including two electrodes separated by a space that generate an electrical potential, e.g., positioned at or toward opposite ends of the housing 101Y, where the two electrodes generate an electrical signal (e.g., a spike) indicative of an electrophysiological signal of myocardial tissue for controlling the patient's heartbeat, where the spike gives rise to the patient's ECG signal. In some embodiments, for example, optional one or more secondary sensor(s) 119Y may be attached to the housing 101Y of the in vivo acoustic sensor device 100Y via, for example, welding, chemical bonding, clips, clamps, or other attachment means.

[0064] In some embodiments of the in-vivo acoustic sensor device 100Y, the housing 101Y itself can be an airtight containment structure, including, for example, metal, plastic, composite, or other material. In some embodiments, for example, the housing 101Y includes a titanium (Ti) enclosure that houses one or more sensors of the sensor unit 110Y and / or electronic components of the electronic unit 120Y, which may include, but are not limited to, any of, for example, a sensor, a telemetry system, a microprocessor, a memory, and / or a battery. For example, the housing 101Y is configured to protect the components of the electronic unit 120Y from bodily fluids or substances when the acoustic sensor device 100Y is deployed inside a patient-user. As shown in FIG. 1C , the housing 101Y can include an enclosure structure that completely encases the electronic unit 120Y and completely encases at least one, some, or all of the components of the sensor unit 110Y; however, in some embodiments, the enclosure structure of the housing 101Y can completely encase at least one, some, or all of the components of the sensor unit 110Y.

[0065] The electronic unit 120Y of the in-vivo acoustic sensor device 100Y includes a data processing unit 121Y, an optional signal conditioning unit 123Y, a power source 129Y, a wireless communication unit 127Y, and an electrical interface 125Y, which may include conductive contacts (e.g., pads, pins, or other contact configurations) that electrically interface with the electrical interconnects 117Y of the sensor unit 110Y. In some embodiments of the in-vivo acoustic sensor device 100Y, for example, the electronic unit 120Y may be the same as or include some of the same components as the electronic unit 120X of the in-vivo fluid flow sensor device 100X. The electronic unit 120Y is configured to receive and at least partially process electrical signals obtained from the acoustic sensor 111Y of the sensor unit 110Y (and signals obtained from the optional IMU 115Y or optional secondary sensor(s) 119Y). For example, in some embodiments, the electrical signals are received at corresponding contact sites of the electrical interface 125 and provided to the data processing unit 121 (or, optionally, first provided to a signal conditioning unit 123Y to improve the quality of the electrical signals obtained from the sensor unit 110Y before providing them to the data processing unit 121). In such implementations, the output of the data processing unit 121 may include raw or processed data associated with the wirelessly transmitted detected data from the sensor unit 110Y that is wirelessly transmitted to an external device by the wireless communication unit 127. In an exemplary embodiment of the electronic unit 120X, the power source 129 may include a battery (e.g., primary or rechargeable), a fuel cell, or other power source for powering components of the electronic unit 120Y and / or the sensor unit 110Y. In some implementations, for example, the power source 129Y includes an ultra-low power system (e.g., operating in the microampere range).

[0066] In some embodiments, electronics unit 120Y includes a data processing unit 121Y that at least partially processes the conditioned electrical signals to (i) generate data, for example, in analog or digital form, and / or (ii) control the functionality of electronics unit 120Y and / or sensor unit 110Y. For example, data processing unit 121Y may be configured to manage data acquisition on data channels associated with acoustic sensor 111Y and (optional) IMU 115Y and / or (optional) secondary sensor(s) 119Y of sensor unit 110Y.

[0067] In some embodiments, for example, the wireless communication unit 127 includes a wireless transmitter, receiver, and / or transceiver device including an antenna capable of communicating with an external device to communicate raw, partially processed, or fully processed data from the signal conditioning unit 123Y (and / or the data processing unit 121, discussed below). For example, the wireless communication unit 127 may be configured to manage a communication protocol for transmission or reception via the antenna. Examples of antennas may include, but are not limited to, a whip antenna, a loop antenna, or a conformal antenna. For example, an antenna system may be attached to the housing 101Y (e.g., a Ti containment structure) to enable bidirectional communication for data transfer and device management between the in-vivo acoustic sensor device 100Y and one or more remote devices, e.g., various embodiments of the external remote device 130, such as a base station or a telephone-based interface system. An exemplary transceiver unit may include a BLE chipset for communicating with BLE-enabled devices, e.g., smartphones, tablets, or other external computing devices, such as the receiver device 130. Additionally or alternatively, in some embodiments, for example, wireless communication unit 127Y is configured as a scaffold around electronic unit 120Y and is structured to provide wireless communication means for in-vivo acoustic sensor device 100Y, such as being coupled to or integrated into housing 101Y.

[0068] In some optional embodiments, for example, the signal conditioning unit 123Y may include circuitry including one or more filters and / or one or more amplifiers to enhance the raw electrical signals detected by the ultrasonic sensor assemblies 111, 112 of the sensor unit 110Y to increase the signal-to-noise ratio (SNR) of the electrical signals, thereby generating data including signal-processed electrical signals. In some optional embodiments, the signal conditioning unit 123Y may include drive circuitry to generate operating electrical signals that generate electrical potentials and / or currents at the electrode assemblies and / or temperature sensor assemblies of the analyte sensors of the sensor unit 110Y for operating electrochemical and / or electrophysical or dynamic sensing methods to be performed at the electrodes in the implementation of the optional secondary sensor 119Y of the sensor unit 110Y.

[0069] In some embodiments of the data processing unit 121Y, for example, the data processing unit 121Y may include a processor 121AY for processing data and a memory 121BY in communication with the processor 121AY for storing and / or buffering data. In various embodiments, for example, the processor 121AY may include one or more processors, and the memory 121BY may include one or more memory units. For example, the processor 121AY may include a central processing unit (CPU), a microcontroller unit (MCU), a graphics processing unit (GPU), or other types of processors. For example, the memory 121BY may include and store processor-executable code that, when executed by the processor, configures the data processing unit 121Y to perform various operations, 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 121Y, the memory 121BY may store information and data, such as instructions, software, values, images, and other data processed or referenced by the processor 121AY. 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 the storage functionality of memory 121BY. In some embodiments, data processing unit 121Y includes an input / output (I / O) unit 121C for interfacing processor 121AY and / or memory 121BY to other modules, units, or devices associated with external devices, such as, for example, receiver device 130, data processing system 150, remote computing device 160, and / or other external devices. In some embodiments, processor 121AY, memory 121BY, and / or I / O unit 121C communicate with a wireless communication unit 127, such as, for example, a transmitter (Tx) or a transmitter / receiver (Tx / Rx) unit.For example, in such an embodiment, I / O unit 121C may interface processor 121AY and memory 121BY with wireless communication unit 127 to utilize various types of wireless interfaces compatible with typical data communication standards that may be used, for example, for communication between data processing unit 121Y and other devices, including, but not limited to, Bluetooth, Bluetooth Low Energy (BLE), Zigbee, IEEE 802.11, Wireless Local Area Network (WLAN), Wireless Personal Area Network (WPAN), Wireless Wide Area Network (WWAN), WiMAX, IEEE 802.16 (Worldwide Microwave Access Interoperability (WiMAX)), 3G / 4G / LTE / 5G / 6G cellular communication methods, and parallel interfaces. In some implementations, the data processing unit 121Y may interface with other devices using a wired connection via the I / O unit 121CY, for example, to provide data communication and / or power connection with another implanted device inside the patient-user's body or a wearable device worn or attached outside the patient-user's body prior to or during implantation within the patient-user. The data processing unit 121Y may also interface with other external interfaces, data storage sources, and / or visual or audio display devices, etc., to obtain and transfer data and information that may be processed by the processor 121AY, stored in the memory 121BY, or presented on an output unit of the receiver device 130 (e.g., a smartphone, tablet, etc.) or other external device to the in-vivo acoustic sensor device 100Y. In some embodiments, for example, the electronics unit 120Y may include a global positioning system (GPS) for determining the patient-user's location of the in-vivo acoustic sensor 100Y.

[0070] Various exemplary embodiments of the in-vivo fluid flow sensor device 100X, as well as systems and methods involving the in-vivo fluid flow sensor device 100X, are described below in relation to Figures 2A-10B, and various exemplary embodiments of the in-vivo acoustic sensor device 100Y, as well as systems and methods involving the in-vivo acoustic sensor device 100Y, are described below in relation to Figures 11A-22.

[0071] In-vivo fluid flow sensor 2A shows a diagram illustrating an exemplary embodiment of in-vivo fluid flow sensor device 100X of FIG. 1B, shown in FIG. 2A as in-vivo fluid flow sensor device 200. In-vivo fluid flow sensor device 200 includes a sensor unit (e.g., coupled to or partially housed within a linkage, such as an arm of linkage assembly 203) comprising an ultrasonic sensor assembly 211 and an ultrasonic sensor assembly 212 in electrical communication with electronics unit 220 via electrical interconnect 217. Ultrasonic sensor assembly 211 includes a plurality of acoustic transducer elements 213, i.e., three acoustic transducer elements 213a, 213b, and 213c in this example, and ultrasonic sensor assembly 212 includes a plurality of acoustic transducer elements 214, i.e., three acoustic transducer elements 213a, 213b, and 213c in this example. This embodiment is not limited to three acoustic transducer elements for each ultrasonic sensor assembly and may include fewer or more configurations than shown in the diagram of Figure 2A, including, for example, but not limited to, one or more acoustic transducer elements for each of ultrasonic sensor assemblies 211 and 212. Ultrasonic sensor assembly 211 and ultrasonic sensor assembly 212 include a frame, casing, or housing structure (not shown) for securing acoustic transducer element 213 and acoustic transducer element 214, respectively, to arms of linkage assembly 203 and positioning them in fixed positions relative to each other.

[0072] The electronics unit 220 of the in-vivo fluid flow sensor device 200 is configured to be encased by spring connectors 235 that couple to each linkage of the linkage assembly 203. The spring connectors 235 provide sufficient travel for the arms of the linkage assembly 203 to couple the ultrasonic sensor assemblies 211 and 212 to their intended placement locations, for example, across the proximal and distal sides of the left or right atrium of the heart, sufficient to secure the in-vivo fluid flow sensor device 200 to the anatomical structure (e.g., the heart) without interfering with the normal function of the anatomical structure of the intended use of the in-vivo fluid flow sensor device 200. For example, the spring connection device 235 may include a spring that provides a compressive force to the linkage sets of the linkage assembly 203 to transmit sufficient force to facilitate and / or maintain fixation of the in vivo fluid flow sensor device 200 to the target portion of the heart (e.g., the left and right atria), while also allowing the device 200 to be stable in its position while withstanding continuous movement (duty cycles) of the anatomical structure to which it is attached (e.g., heartbeats) without suffering damage for millions to billions of cycles, thus providing the in vivo fluid flow sensor device 200 with a significant lifespan (e.g., 50-60 million heartbeats per year) during decades of use. Additionally, the linkage sets of the linkage assembly 203 may be adjusted in all three planes (xy, xz, yz) to allow for initial proper alignment of the ultrasonic sensor assemblies 211, 212.

[0073] In some embodiments, for example, in vivo fluid flow sensor device 200 can be secured to the anatomical structure by a network of prongs, screws, barbs, sutures, adhesive (e.g., a bio-inert adhesive), or gripping mechanisms (not shown) disposed through the frame or casing of ultrasonic sensor assembly 211 and ultrasonic sensor assembly 212. In some embodiments of in vivo fluid flow sensor device 200 (not shown in FIG. 2A ), the frame, casing, or housing structure can include one or more openings on each linkage of linkage assembly 203 that can allow for secondary attachment of device 200 to the target anatomical structure, e.g., openings having anchor sites for applying sutures connecting the linkages of linkage assembly 203 to the anatomical structure (e.g., the atrial wall of the heart). In some embodiments, linkage assembly 203 can include a material that provides sufficient flexibility and rigidity to allow in vivo fluid flow sensor device 200 to be deployed on the anatomical structure without such deleterious interference. For example, in some embodiments, linkage assembly 203 may include nitinol, platinum, MP35N, or other materials or combinations thereof. In some embodiments, linkage assembly 203 provides a catch to lock onto the heart, e.g., not allow further movement of the linkage.

[0074] FIG. 2B shows a diagram illustrating another exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, designated in FIG. 2B as in-vivo fluid flow sensor device 200B. In-vivo fluid flow sensor device 200B includes a sensor unit comprising two or more sets of ultrasonic sensor assemblies 250 (depicted in FIG. 2B as sets 250A and 250B) in electrical communication with an electronics unit 220 (e.g., coupled to or partially housed within sets of linkage assemblies 203A and 203B, respectively) via electrical interconnect 217. Each set of ultrasonic sensor assemblies 251 and 252 includes an ultrasonic sensor assembly 211 and an ultrasonic sensor assembly 212, each comprising a plurality of acoustic transducer elements 213 and a plurality of acoustic transducer elements 214, respectively, such that multiple planes of acoustic signal propagation are measured in a region of interest of an anatomical structure (e.g., the mitral valve of the heart). In this embodiment, electronic unit 220 is partially encased by spring connection devices 235B corresponding to a set of ultrasonic sensor assemblies 250B, and by two or more sets of spring connection devices 235A represented by ultrasonic sensor assemblies 250A.

[0075] 2C shows a diagram illustrating another exemplary embodiment of in-vivo fluid flow sensor apparatus 100X of FIG. 1B, designated in FIG. 2C as in-vivo fluid flow sensor apparatus 200C. In-vivo fluid flow sensor apparatus 200C may be configured similarly to in-vivo fluid flow sensor apparatus 200 (described above in FIG. 2A), e.g., sensor units including ultrasonic sensor assemblies 211 and 212 in electrical communication with electronics unit 220 via electrical interconnect 217 (e.g., coupled to or partially contained within linkages of linkage assembly 203). 2C , however, electronics unit 220 of in-vivo fluid flow sensor device 200C is configured to be encased by flex connection device 235C, which includes a first link 236 that can pivotally move relative to a second link 237, and / or vice versa, providing device 200C with sufficient flexibility to both remain stable in its position while withstanding continuous movement (load cycles) of the anatomical structure to which it is attached (e.g., heartbeat) without suffering damage for millions to billions of cycles. In some embodiments, flex connection device 235 includes a spring. In some embodiments, first link 236 can move within a cavity in second link 237, and / or vice versa.

[0076] Flex connection device 235C also couples sensor unit 220 to each linkage of linkage assembly 203C, shown in FIG. 2C as linkage 203C. Also in FIG. 2C, linkage assembly 203C includes a linear arm portion proximal to flex connection device 235C and a curved arm portion distal to flex connection device 235C and proximal to ultrasonic sensor assembly 211 and ultrasonic sensor assembly 212. In this manner, for example, in vivo fluid flow sensor device 200C's structure can be mounted to a curved geometry for an anatomical structure, such as the left or right atrium of the heart, and can provide sufficient compressive force for mounting with appropriate flexion to mitigate duty cycle. In some embodiments, for example, one or both of linkages 203C can be used to mount an additional power source (e.g., one or more batteries), which can be electrically connected to electronics unit and ultrasonic sensor assemblies 211 and / or 212 (optional).

[0077] Additionally, ultrasonic sensor assembly 211 and ultrasonic sensor assembly 212 include a frame, casing, or housing structure 219 for securing acoustic transducer element 213 and acoustic transducer element 214, respectively, to the linkage of linkage assembly 203C and positioning them in fixed positions relative to each other. Although not shown in FIG. 2C , frame, casing, or housing structure 219 may include one or more openings to allow for secondary attachment means of device 200 to the target anatomical structure, for example, openings having anchor sites for applying sutures to secure ultrasonic sensor assembly 211 and ultrasonic sensor assembly 212 at the ends of the arms of linkage assembly 203C to the anatomical structure (e.g., the wall of the atrium of the heart). In some embodiments, similar to the example shown in FIG. 2C, the distal ends of the arms or linkages of the linkage assembly 203C of the in vivo fluid flow sensor device 200C are angled or curved inward, which can help, for example, to facilitate attachment to the anatomical structure and conformation during placement, as well as aid in delivery of the device 200C, for example, via a catheter.

[0078] Although not shown in FIG. 2C, the sensor unit of the in-vivo fluid flow sensor device 200C may include a set of two or more ultrasonic sensor assemblies 250 (such as the configuration of ultrasonic sensor assemblies 250A and 250B as shown in FIG. 2B) which are in electrical communication with the electronic unit 220C via electrical interconnects 217 (e.g., each coupled to or partially contained within a respective arm of the linkage assembly 203C).

[0079] FIG. 2D shows a diagram illustrating another exemplary embodiment of in-vivo fluid flow sensor device 100X of FIG. 1B, designated in FIG. 2D as in-vivo fluid flow sensor device 200D. In-vivo fluid flow sensor device 200D can be configured similarly to in-vivo fluid flow sensor device 200 (described above in FIG. 2A) and / or in-vivo fluid flow sensor device 200C (described above in FIG. 2C), for example, in which the sensor units include ultrasonic sensor assemblies (i.e., ultrasonic sensor assembly 211D and ultrasonic sensor assembly 212D) in electrical communication with electronic unit 220 via electrical interconnects (not shown in FIG. 2D). Electronic unit 220 is housed within connection device 235. The acoustic transducer elements of ultrasonic sensor assemblies 211D and 212D are each coupled to a linkage of linkage assembly 203D, positioning them in fixed positions relative to each other. In some embodiments, for example, the connection device 235D includes a hermetically sealed package body capable of carrying and supporting a power source, a data processing unit, and a wireless communication unit (e.g., having an antenna for transmission), allowing, for example, power transfer to implement a charging system for power management for functional performance. For example, mechanical force for closure by the linkage can be provided by a spring coil, a bias spring, or other compression method to connect the ultrasonic sensor assemblies 211D and 212D for placement around an anatomical structure. Still referring to FIG. 2D , the linkage assembly 203D of the in vivo fluid flow sensor device 200D is configured to include an anchor support 233D on each linkage of the linkage assembly 203D. The anchor support 233D may be made of a metallic or polymeric material and is an item that may be positioned on the linkage between the connection device 235D and the distal portion of the linkage 239D, supporting the ultrasonic sensor assemblies 211D and 212D. In an exemplary implementation of device 200D, for example, anchor support 233D passes through opening 218, allowing the linkage to be sutured or connected onto an anatomical structure (e.g., a tissue or organ or vessel) by a material capable of binding anchor support 233D to the anatomical structure's 233D wall, such as suture silk, polymer thread, or a metal suture needle.

[0080] FIG. 3 illustrates an exemplary embodiment of the in-vivo fluid flow sensor device 200 attached to a patient-user's heart in an exemplary implementation of the device 200. While FIG. 3 illustrates the exemplary in-vivo fluid flow sensor device 200, it is understood that other embodiments of the in-vivo fluid flow sensor device 100X may be attached to a patient-user's heart to assess blood flow at a target region of the heart. In this example, the in-vivo fluid flow sensor device 200 is configured to assess blood flow across the mitral valve by positioning a first ultrasonic sensor assembly 211 proximal to the outer surface of the left atrium (LA) of the heart and a second ultrasonic sensor assembly 212 distal to the outer surface of the LA, e.g., to assess mitral regurgitation (MR). For example, the in-vivo fluid flow sensor device 200 may be secured to the LA by clamping the first and second ultrasonic sensor assemblies 211, 212 onto the LA, which creates a plane perpendicular to the mitral valve for propagating acoustic signals. 3, the arms of the in vivo fluid flow sensor device 200 (e.g., the linkages of the linkage assembly 203 of the device 200) can extend around an organ, such as the LA of the heart, with a particular spring constant that can support various orientations to optimize functional alignment with the target anatomical structure. Furthermore, optimal functional alignment can be maintained by the spring constant or degree of flexion of the connection device, which can be positioned and secured to the target anatomical structure individually or (optionally) in conjunction with one or more secondary attachment mechanisms, such as with sutures (secured at suture ports), adhesives, or anchor structures (secured at anchor ports), and placement relative to the intended region of the organ / tissue can be optimized for consistent measurements (e.g., by initial monitoring to establish calibration, followed by comparison with constant monitoring and comparison from a baseline). Also, in some implementations, for example, multiple in vivo fluid flow sensor devices 200 may be deployed in different locations of the same anatomical structure, such as the LA of the heart (as shown in FIG. 3), and in major blood vessels of the heart, such as a vein or pulmonary artery or vein (not shown in FIG. 3).

[0081] FIG. 4A shows a diagram illustrating an insertion site for implanting various embodiments of an in vivo fluid flow sensor device 100X, such as the in vivo fluid flow sensor device 200 shown in FIG. 3. In some implementations, for example, the in vivo fluid flow sensor device 200 (or other embodiments of the in vivo fluid flow sensor device 100X) may be implanted and positioned on the heart via apical pericardial puncture and delivery of the device within the pericardial sac, as shown in FIG. 3. The exemplary in vivo fluid flow sensor device 200 may be attached to a mechanism for loading, transporting, and delivering it to the thoracic cavity, or for placement on the surface of the heart (e.g., across the left or right atrium) within the pericardium to monitor fluid flow (e.g., forward and reverse flow) and other cardiac functions. For example, an apical pericardial implantation procedure may include attaching the exemplary in vivo fluid flow sensor device 200 (or other embodiments of the in vivo fluid flow sensor device 100X) in a first configuration to a catheter that is inserted into one of insertion sites 402, 404, 406, 408, or 410, or another implantation site not shown in FIG. 4A , after which the exemplary in vivo fluid flow sensor device 100X may change to a second configuration to secure the opposing ultrasound sensor assembly over a target region of the heart, e.g., over the left atrium in the normal plane of the mitral valve. In some implementations, for example, the catheter may be used to communicate with the exemplary in vivo fluid flow sensor device 100X or to recharge a power source (e.g., power source 129) in an embodiment of the device 100, as needed. In some implementations, an embodiment of the in vivo fluid flow sensor device 100X may be implanted and positioned on the heart outside the pericardial sac.

[0082] In some implementations, for example, the in-vivo fluid flow sensor device 100X can be inserted in a first stage (first configuration) into a patient-user device by a physician-user, such as a thoracic surgeon, through the patient-user's chest cavity via a main sternotomy or thoracotomy procedure. After insertion, the in-vivo fluid flow sensor device 100X can undergo a second stage (second configuration) for placement around the heart, for example, in the transition region between the atrium and ventricle on the left side or in the same position on the right side. The in-vivo fluid flow sensor device 100X can be secured to the anatomical site where it is located by the surgeon, for example, based on the compression and bending characteristics of the connecting device and / or arms (of the linkage assembly 103B), and / or can be secured in place with, for example, sutures or metal anchors performed by the physician-user.

[0083] FIG. 4B shows a diagram illustrating an exemplary configuration of an exemplary embodiment of an in vivo fluid flow sensor device according to the present invention for implantation near a target anatomical structure and positioning for anchoring to the target anatomical structure. FIG. 400A shows another exemplary embodiment of the in vivo fluid flow sensor device 100X of FIG. 1B, shown in FIG. 4B as in vivo fluid flow sensor device 400, with arms of linkage assembly 403 extending outward from connection device 435 and in a first configuration for insertion or implantation, such as implemented by a catheter. For example, in some implementations, the in vivo fluid flow sensor device 400 can be inserted into a patient's body (e.g., through a port through a rib, such as the insertion site shown in FIG. 4A) to access a region where the target anatomical structure is located, e.g., the heart. Prior to the insertion process, the patient can be prepared by undergoing an imaging session (e.g., a CT scan of the target region) that can be used to assist with insertion.

[0084] FIG. 400B shows in vivo fluid flow sensor device 400 in a second configuration with the arms of linkage assembly 403 extending inward toward a centerline through connecting device 435, for example, for a deployment process for attachment to anatomical structure 490. In vivo fluid flow sensor device 400 may be configured similarly to in vivo fluid flow sensor device 200 (described above in FIG. 2A), for example, in which the sensor unit includes ultrasonic sensor assembly 411 and ultrasonic sensor assembly 412 in electrical communication with electronics unit 420 via an electrical interconnect (not shown). For example, during or after attachment of the in-vivo fluid flow sensor device 400 to the anatomical structure 490, the ultrasonic sensor assemblies 411 and 412 on the distal portion of the linkage 403 can be oriented (e.g., via contact placement and / or transmission and reception of acoustic signals for calibration measurements) such that line of sight of the acoustic transducers of the ultrasonic sensor assemblies 411 and 412 can be established with the intended measurement site (e.g., by the insertion tool before the insertion tool is withdrawn). Also, for example, prior to withdrawal of the insertion tool, the in-vivo fluid flow sensor device 400 can be tested for wireless data communication with a remote device (e.g., remote computing device 130A and / or remote base station 130b). In some implementations, the in-vivo fluid flow sensor device 400 can be further secured using, for example, sutures or other securement techniques (e.g., adhesive or other).

[0085] In some exemplary embodiments of the ultrasonic sensor assembly for various embodiments of the in vivo fluid flow sensor device 100X of FIG. 1B, the transducer array is designed to spatially configure a single transmitter with at least two receivers interleaving and alternating receivers and transmitters so that one or more fields of ultrasonic energy move around a heart chamber (e.g., atrium or ventricle) to detect, for example, Q-wave flow patterns or disruptions in the flow pattern. By detecting Q-wave flow patterns or disruptions in the flow pattern, this data can be interrogated and mapped to regurgitation of blood flowing through and back through the heart chamber valves, indicating wall / chamber dysfunction (e.g., which may be related to electrical signal disruption of the heartbeat and / or static blood clotting). Additionally, mechanical analysis of changes in cardiac chamber diameter can be calibrated for and detected for changes in use by exemplary ultrasonic sensor assemblies 511 and / or 112 and therefore can be a tool for predicting cardiac structural changes indicative of dysfunction in the removal of cellular analytes such as water, electrolytes, and / or cellular waste products that may result in CHF in a patient, for example, due to water absorption by cardiac cells, which may result in saturation or supersaturation.

[0086] 5A shows a diagram illustrating an exemplary implementation of the in-vivo fluid flow sensor device 100X of FIG. 1B, shown as an in-vivo fluid flow sensor device 500 attached to an anatomical structure 590 (e.g., an atrium or ventricle of the heart or a blood vessel feeding or draining blood from the heart), illustrating an exemplary embodiment of an acoustic transducer configuration in accordance with the present invention. The exemplary in-vivo fluid flow sensor device 500 includes an embodiment of an electronics unit 120X coupled to a linkage assembly 103B having two opposing arms, at their distal ends being a first ultrasonic sensor assembly 511 disposed on the first arm and a second ultrasonic sensor assembly 512 disposed on the second arm. The first ultrasonic sensor assembly 511 includes at least one ultrasonic transmitter (Tx) transducer 513a, and the second ultrasonic sensor assembly 512 includes at least two ultrasonic receiver (Rx) transducers 514b and 514c. 5A graphically depicts a single Tx transducer 513a on one arm of the exemplary linkage assembly 103B and two Rx transducers 514b and 514c on opposing arms of the exemplary linkage assembly 103B, in some exemplary embodiments, additional Tx transducer elements or additional Tx transducer elements can be included on the first ultrasonic sensor assembly 511, and in some exemplary embodiments, additional Rx transducer elements or additional Rx transducer elements can be included on the second ultrasonic sensor assembly 512. Also, for example, in some embodiments, the first ultrasonic sensor assembly 511 can include two or more Rx transducer elements (e.g., at least two Rx transducers 514b and 514c), and in some embodiments, the second ultrasonic sensor assembly 512 can include one or more Tx transducer elements (e.g., at least one Tx transducer 513a).

[0087] In the embodiment shown in FIG. 5A, the in vivo fluid flow sensor device 500 provides a single-sided acoustic detection system, with one or more Tx transducers 513a on one side (i.e., acoustic signals (e.g., pulses, waveforms, etc.)) and at least two Rx transducers 514b and 514c on either (i) the opposite side (i.e., the other arm of the linkage assembly as Tx transducer 513a of device 500) receiving an acoustic signal corresponding to the transmitted acoustic signal after propagation through the fluid in the anatomical structure 590 and being subjected to reflection, refraction, or other propagation changes due to fluid flow, or (ii) the same side (i.e., the same arm of the linkage assembly as Tx transducer 513a of device 500) receiving an acoustic signal corresponding to the transmitted acoustic signal after propagation through the fluid in the anatomical structure 590 and being subjected to reflection, refraction, or other propagation changes due to fluid flow, and being reflected back by a reflector structure (not shown in FIG. 5A, but described below).

[0088] In some exemplary embodiments, as shown in FIG. 5A , the acoustic transducers on the first and second ultrasonic sensor assemblies 511 and 512 are configured such that the Tx transducer 513a is positioned on / around another portion (e.g., an opposite portion) of the anatomy 590 from the Rx transducers 514b, 514c, and the center (C Tx ) is the center-to-center distance (d) between the Rx transducers 514b and 514c, i.e., (Cd Rx ) of the Tx converter 513a. Tx and the Rx converters 514b and 514c Rx The spatial alignment of the Tx transducers 513a, C is configured to minimize interference of acoustic energy during operation of the ultrasonic sensor assembly. Tx is the midpoint of the length (l), which defines the length of the side of the Tx transducer 513a in that dimension along the x-axis, for example, as shown by the example coordinate map 598 of FIG. 5A. In the vertical dimension, for example, along the z-axis, the center of the Tx transducer 513a, C TxThe center of the Rx converters 514b, 514c, i.e., (Cd Rx 5 shows that the center-to-center distance (d) between the Rx transducers 514b, 514c is based on the relative lengths of the sides of the Rx transducers 514b, 514c in that dimension, for example, along the x-axis, as shown by exemplary coordinate map 598. In particular, the fluid flow direction is in the direction of the x-axis of coordinate map 598, which corresponds to the ultrasound sensor assemblies shown in inserts 599T and 599R, as well as in the direction of coordinate map 597, which corresponds to the view of device 500 secured to anatomical structure 590.

[0089] As shown in insert box 599T, in some exemplary embodiments, Tx transducer 513a may be coupled to a backing or base 513, which may be attached to an inner surface of an arm of linkage assembly 103B. For example, base 513 may provide thermal synchronization for management of heat generation by the acoustic transducer. Similarly, insert box 599R shows an exemplary embodiment of Rx transmitters 514b, 514c coupled to a backing or base 514, which may be attached to an inner surface of an arm of linkage assembly 103B. For example, in some embodiments, one or more of Rx transmitters 514b, 514c may be disposed on a single base 514 or on individual bases 514, in various combinations. Similarly, for example, base 514s may provide thermal synchronization for management of heat generation by the acoustic transducer.

[0090] In some embodiments, for example, the Tx transducer 513a may be 4 mm 2 or 4πmm 2 It is understood that the width, length, or diameter (or any size dimension) of the Tx transducer 513a may be greater than or less than 2 mm, for example, the size dimension (e.g., width, length, diameter, etc.) of the Tx transducer 513a may be between 1 mm and 4 mm. In some embodiments, for example, each of the Rx transducers 514b, 514c may be configured to have a 4 mm diameter for receiving acoustic signals. 2or 4πmm 2 The Rx transducers 514b, 514c are configured to have a transducer area of ​​1 mm (e.g., 2 mm diameter). It is understood that the width, length, or diameter (or any size dimension) of the Rx transducers 514b, 514c may be greater than or less than 2 mm, for example, the size dimension (e.g., width, length, diameter, etc.) of the Rx transducers 514b, 514c may be between 1 mm and 4 mm.

[0091] In some embodiments, for example, the Tx transducer 513a and the Rx transducers 514b, 514c are positioned to be positioned in-plane (0 degrees) for site line and wave detection, such that the Rx transducers 514b, 514c detect and respond to acoustic signals from the Tx transducer 513a propagating through the anatomy 590 and effected by fluid flow (e.g., blood flow in the heart or blood vessels leading to or leading from the heart). Also, in some embodiments, for example, the Tx transducer 513a and the Rx transducers 514b, 514c are positioned to be positioned (e.g., rotated) out-of-plane for site line and wave detection, up to 90 degrees relative to each other. Similarly, in some embodiments, for example, the Tx transducer 513a and / or the Rx transducers 514b, 514c can be tilted out-of-plane for site line and wave detection, up to 20 degrees relative to each other.

[0092] In some implementations, for example, the substrate 513s of the Tx transducer 513a has a width (W Tx ) and 10mm length (L Tx ) and, for example, in some implementations, the base 514 of the Rx transducers 514b, 514c may be configured to have a width (W Rx ) and 10mm length (L Rx )

[0093] 5B shows a diagram illustrating an example arrangement of acoustic transducers on an ultrasonic sensor assembly 511B for an exemplary embodiment of in vivo fluid flow sensor device 100X, such as for one or both of first ultrasonic sensor assembly 511B and second ultrasonic sensor assembly 512 of in vivo fluid flow sensor device 500 shown in FIG. 5A. Ultrasonic sensor assembly 511B includes multiple acoustic transducer elements 563, in this example, two acoustic transducer elements 563a and 563b, and multiple acoustic transducer elements 564, in this example, three acoustic transducer receiver elements 564d, 564e, and 564f. This embodiment is not limited to two acoustic transducer transmitter elements and three acoustic transducer receiver elements for ultrasonic sensor assembly 511B and may include fewer or more configurations than shown in the diagram of FIG. 5B. In this example, the transmitter elements 563a, 563b are arranged in a row along a single direction, and the receiver elements 564d, 564e, 564f are arranged along different rows above and below the transmitter row, positioned at a distance (d1) relative to the centers of the transmitter and receiver elements. The configuration of the transmitter elements 563a, 563b and receiver elements 564d, 564e, 564f is based on line-of-sight transmission and reception (LOSTR) for operation of acoustic transducers within an array. In the exemplary embodiment shown in FIG. 5B, for a single transmitter element corresponding to at least two receiver transducers (e.g., transmitter element 563a corresponding to receiver elements 564d, 564e), the center of the Tx1 transducer 563a is aligned with the center of the Rx transducers 564d, 564e, i.e., (Cd Rx1 ) and C of Tx converter 563a. Tx1 and Cd between Rx converters 564d and 564e Rx1 The spatial alignment of the transducers is configured to minimize interference of acoustic energy during operation of that transmitter-receiver group of the ultrasonic sensor assembly 511B. Similarly, for example, the center (C Tx2 ) is connected to the Rx converters 564e and 564f, i.e., (Cd Rx2 ) center-to-center distance (d), resulting in C Tx2 and Cd between Rx converters 564e and 564f Rx2The spatial alignment of the ultrasonic sensor assembly 511B with the transmitter-receiver group is configured to minimize interference of acoustic energy during operation of that transmitter-receiver group of the ultrasonic sensor assembly 511B.

[0094] In particular, for example, some exemplary embodiments of ultrasonic sensor assembly 511B may configure the transmitter and receiver arrays to vary with combinations of transmitter and receiver elements integrated together in the same array. For example, in some implementations, Tx transducer 563a may be configured to transmit one or more acoustic signals that propagate through anatomy 590 and are receivable by Rx transducers 564d and 564e, and simultaneously or subsequently, transducer 564e may be configured to transmit one or more acoustic signals that propagate through anatomy 590 and are receivable by transducers 563a and 563b.

[0095] In some embodiments, for example, transmitter elements 56a, 56b may be 2.25 mm 2 or 2.25πmm 2 and receiver elements 564d, 564e, 564f can be configured to have a transducer area of ​​2.25 mm for receiving acoustic signals (e.g., 1.5 mm diameter). 2 or 2.25πmm 2 The array can be configured to have a transducer area of ​​1.5 mm (e.g., 1.5 mm diameter), or 2.25 mm (1.5 mm × 1.5 mm) for reception of the transmitted signal from opposing side arrays on opposing arms of the linkage assembly. 2The ultrasonic sensor assembly 511B may be configured to have a transducer area of ​​1.5 mm (e.g., 1.5 mm diameter). It is understood that the width, length, or diameter (or any size dimension) of the transmitter and / or receiver transducer elements 563a, 563b and / or 564d, 564e, 564f may be greater than or less than 1.5 mm. In some embodiments of the ultrasonic sensor assembly 511B, the distance (d1) between the transmitter and receiver arrays, i.e., the distance between centerlines, may be substantially 5 mm, for example, to achieve optimal LOSTR (e.g., as a minimum distance to minimize interference). For this exemplary configuration of the ultrasonic sensor assembly 511B, the distance separation (d1) is optimized to ensure no cross-reflections, which may resemble ghost signals or signal jamming that can produce false readings. The carrier for the transmitter and receiver may act as a coupler for electronic communication to a processing unit and power source. In some embodiments, for example, one or more of transmitter elements 563a and 563b can be rotated up to 90 degrees from the same plane relative to at least two corresponding receiver elements 564d, 564e, and 564f, or vice versa.

[0096] Ultrasonic sensor assembly 511B optionally includes a backing or base 563 that can be used to attach ultrasonic sensor assembly 511B to an arm of a linkage assembly of device 500. For example, base 563 can provide a thermal synchronization for managing heat generation by acoustic transducers (e.g., acoustic transducers 563a, 563b, 564d, 564e, 564f). In some embodiments, for example, base 563 has a first side length ( S1 1) (perpendicular to the row of transmitters and receivers), and a second side length (l S2 ) (parallel to the rows of transmitters and receivers).

[0097] In some implementations, for example, the ultrasonic sensor assembly 511B may be used in an exemplary single-sided acoustic detection system of the in-vivo fluid flow sensor device 100X, where at least two Rx transducers corresponding to one or more Tx transducers are configured to transmit acoustic signals (e.g., pulses, waveforms, etc.) across the anatomical structure on one side (i.e., arm of the linkage assembly) such that at least two Rx transducers corresponding to the Tx transducers are configured to receive acoustic signals on the opposite side (i.e., other arm of the linkage assembly) that correspond to the transmitted acoustic signals after propagation through the fluid in the anatomical structure, subject to reflection, refraction, or other propagation changes due to fluid flow. However, in some implementations, for example, the ultrasonic sensor assembly 511B may be used in an exemplary dual-sided acoustic detection system of the in vivo fluid flow sensor device 100X, where a first set of one or more Tx transducers is configured on one side (i.e., arm of a linkage assembly) of at least two corresponding first set of receiver elements across the anatomy to operate (e.g., transmit and receive) simultaneously from a second set of at least two corresponding receiver elements across the anatomy on the opposing arm. An example of a dual-sided acoustic detection system is described below in FIG. 5D.

[0098] 5C shows a diagram illustrating an exemplary implementation of in-vivo fluid flow sensor device 100X of FIG. 1B, shown as in-vivo fluid flow sensor device 500C attached to an anatomical structure 590 (e.g., an atrium or ventricle of the heart or a blood vessel feeding into or out of the heart) illustrating an exemplary embodiment of an acoustic transducer configuration in accordance with the present invention. Exemplary in-vivo fluid flow sensor device 500C includes an embodiment of electronics unit 120X coupled to an embodiment of linkage assembly 103B having two opposing arms, where the distal end of one of arms 503C1 is an ultrasonic sensor assembly 511C and the distal end of the opposing arm 503C2 is a reflector 516. In some embodiments, for example, reflector 516 may be configured as a specular reflector having a substantially flat surface, a substantially smooth surface, and a boundary / area sized greater than the acoustic signal wavelength. However, in some embodiments, for example, reflector 516 may be configured as a non-specular reflector having an uneven surface, a rough or irregular surface texture, and / or boundaries / regions smaller in size than the acoustic signal wavelength. Also, in some embodiments, reflector 516 may be configured with specular and non-specular reflector portions. In various embodiments, for example, reflector 516 may be configured in a shape and size that conforms to the contours of an anatomical site (e.g., an organ or blood vessel) coupled with a focal length reflection for optimal energy response. Exemplary materials for reflector 516 may include, but are not limited to, Mylar (e.g., on a substrate), precious metals (e.g., vacuum-deposited precious metals) such as silver, platinum, gold, palladium, or standard metals (e.g., polished to wavelength) such as silver, titanium, nitinol, or stainless steel, or combinations thereof.

[0099] The ultrasonic sensor assembly 511C includes at least one ultrasonic transmitter (Tx) transducer 513a and at least two ultrasonic receiver (Rx) transducers 514b and 514c. In this configuration, the in-vivo fluid flow sensor device 500 provides a one-sided acoustic detection system, where one or more Tx transducers 513a are configured in an array with at least two Rx transducers 514b, 514c on one side of the device 500C (i.e., an arm of a linkage assembly) to transmit an acoustic signal (e.g., a pulse, waveform, etc.) that propagates across the anatomical structure 590, is affected by fluid flow through the anatomical structure 590, is reflected from a reflector 516 on the opposite side of the device 500C (i.e., the other arm of the linkage assembly), and is received as an acoustic signal corresponding to the transmitted acoustic signal.

[0100] In some exemplary embodiments, these acoustic transducers on the ultrasonic sensor assembly 511C may be configured with exemplary sizes, spacing, materials, and structures as described for exemplary acoustic transducers for the first and second ultrasonic sensor assemblies 511 and 512 in connection with Figures 5A and 5B, respectively.

[0101] An exemplary implementation of the in-vivo fluid flow sensor device 500 was performed in a laboratory benchtop device designed to simulate blood flow through a chamber or tube similar to an anatomical structure 590, testing the characteristics of the received acoustic signal. Table 1 describes the frequency and sensitivity functions of an exemplary single-sided acoustic detection system, i.e., at least one transmitter configured on opposing arms of a linkage assembly, relative to at least two receivers, as exemplified by an exemplary embodiment of the in-vivo fluid flow sensor device 500 incorporating, for example, ultrasonic sensor assemblies 511, 512 shown in FIG. 5A, 511B shown in FIG. 5B, and / or 511C shown in FIG. 5C. [Table 1]

[0102] Table 1 shows the relationship between flow sensitivity (ΔΦ / Δt) and exemplary frequencies (e.g., 3 MHz, 6 MHz, and 9 MHz) and the distance (mm) between the transmitting and receiving acoustic transducers for a single-sided transducer configuration. ΔΦ, the unit of sensitivity, is (degrees / [l / min]), and Δt, the period or duration of function, is (ps / [l / min]).

[0103] 5D shows a diagram illustrating an exemplary implementation of the in-vivo fluid flow sensor device 100X of FIG. 1B, shown as in-vivo fluid flow sensor device 500D attached to an anatomical structure 590 (e.g., an atrium or ventricle of the heart or a blood vessel feeding or draining blood from the heart), illustrating an exemplary embodiment of an acoustic transducer configuration in accordance with the present invention. The exemplary in-vivo fluid flow sensor device 500D includes an embodiment of an electronics unit 120X coupled to a linkage assembly 103B having two opposing arms, the distal ends of which are a first ultrasonic sensor assembly 511D disposed on the first arm and a second ultrasonic sensor assembly 512D disposed on the second arm. The first ultrasonic sensor assembly 511D, shown in insert 595, includes at least one ultrasonic transmitter (Tx) transducer 523a, and the second ultrasonic sensor assembly 512D, shown in insert 596, includes at least two ultrasonic receiver (Rx) transducers 534b and 534c corresponding to the Tx transducer 523a. In the exemplary embodiment shown in FIG. 5D, the second ultrasonic sensor assembly 512D also includes at least one ultrasonic transmitter (Tx) transducer 533a, and the first ultrasonic sensor assembly 511D also includes at least two ultrasonic receiver (Rx) transducers 524b and 524c corresponding to the Tx transducer 533a.

[0104] In the embodiment shown in FIG. 5D , in vivo fluid flow sensor device 500D provides a double-sided acoustic detection system for in vivo fluid flow sensor device 100X, where a first set of one or more Tx transducers (e.g., Tx transducer 523a) are configured on one side (i.e., arm of a linkage assembly) across the anatomical structure 590 to operate (e.g., transmit and receive) simultaneously with a second set of one or more Tx transducers on the opposing arm from a second set of at least two corresponding receiver elements (e.g., Rx transducers 524b, 524c) on the opposing arm, and from a first set of at least two corresponding receiver elements (e.g., Rx transducers 534b, 534c) from the first set of Rx transducers across the anatomical structure 590.

[0105] In some exemplary embodiments, these acoustic transducers on the first ultrasonic sensor assembly 511D and / or the second ultrasonic sensor assembly 512D may be configured with exemplary sizes, spacing, materials, and structures as described for exemplary acoustic transducers for the first and second ultrasonic sensor assemblies 511 and 512 in connection with Figures 5A and 5B, respectively.

[0106] An exemplary implementation of the in-vivo fluid flow sensor device 500D was performed in a laboratory benchtop device designed to simulate blood flow through a chamber or tube similar to the anatomical structure 590, testing the characteristics of the received acoustic signal. Table 2 describes the frequency and sensitivity functions of an exemplary dual-sided acoustic detection system, as exemplified by the exemplary embodiment of the in-vivo fluid flow sensor device 500D incorporating the ultrasonic sensor assemblies 511D, 512D shown in FIG. 5D . [Table 2]

[0107] Table 2 shows flow sensitivity (ΔΦ / Δt) and exemplary frequencies (e.g., 3 MHz, 6 MHz, and 9 MHz), as well as the distance (mm) between transmitting and receiving acoustic transducers for a double-sided transducer configuration, i.e., a first set of at least one transducer element on opposing arms across the anatomy from a first set of at least two corresponding receiver elements operating simultaneously (e.g., transmitting and receiving) with a second set of at least one transducer element on opposing arms across the anatomy from a second set of at least two corresponding receiver elements. ΔΦ, the unit of sensitivity, is (degrees / [l / min]), and Δt, the period or duration of function, is (ps / [l / min]).

[0108] The exemplary data in Table 2 shows a damping effect using two opposing transmitters (e.g., Tx transducer 523a of the first ultrasonic sensor assembly 511D and Tx transducer 533a of the second ultrasonic sensor assembly 512D configured to simultaneously transmit acoustic signals in opposing directions), which is approximately half the flow sensitivity compared to the exemplary data in Table 1, which is based on a unilateral transmitter-transducer arrangement of the ultrasonic sensor assembly transmitting toward a reflector with at least two receiver transducers on the same side as the transmitter transducer, or with at least two receiver transducers on the opposite side of the anatomical structure from the transmitter transducer.

[0109] In some exemplary implementations of various embodiments of the in-vivo fluid flow sensor device 100X, the device can be operated to transmit and receive acoustic signals (e.g., ultrasound signals) in Doppler mode. In contrast to typical ultrasound techniques for interrogating stationary objects, Doppler ultrasound can be used to characterize fluid flow characteristics. For example, if a target of interest (such as blood cells in blood flowing through an anatomical structure) is moving relative to the ultrasound signal, more vibrations per unit time are encountered than a stationary equivalent, such that the frequency of the reflected wave increases; if the target of interest is moving away from the ultrasound signal, the frequency of the reflected signal decreases. The Doppler effect can be used to measure the velocity of blood flow through an anatomical structure.

[0110] An exemplary embodiment of the in-vivo fluid flow sensor device 100X may be positioned at an angle (θ) relative to the direction of blood flow in the anatomy 590, such that the frequency shift measured by the Doppler mode is (f R -f T )=2v f T cos(θ) / c, where f T is the frequency of the transmitted acoustic signal, and f R is the frequency of the received acoustic signal, c is the velocity of an acoustic signal of a given wavelength propagating in the medium, and v is the velocity of the acoustic signal traveling towards the acoustic transducer receiving the signal.

[0111] For example, the in-vivo fluid flow sensor device 100X can use Doppler techniques in conjunction with blood mass flow calculations through an anatomical structure, such that the body mass flow in a confidence interval equates to the density (of known blood) and diameter change (used to calculate area), which allows for the determination of velocity. From the velocity and diameter, the device 100X can then determine the Q of the fluid flow. Additionally, the in-vivo fluid flow sensor device 100X can measure the planar dimensions of a target anatomical structure based on determinable changes in fluid flow relative to a baseline measurement, for example, because increased fluid volume typically causes the walls of the anatomical structure (e.g., major blood vessels) to dilate, i.e., increase in wall diameter.

[0112] In some exemplary embodiments of various embodiments of the in-vivo fluid flow sensor device 100X, the device may be operated to transmit and receive acoustic signals (e.g., ultrasound signals) to create ultrasound images of a target anatomical structure, for example, using A-mode, B-mode, and / or C-mode ultrasound data acquisition techniques. In some examples, embodiments of the in-vivo fluid flow sensor device 100X may be used in A-mode ultrasound acquisition to obtain a one-dimensional representation from the transmitted and received acoustic signal waves in the direction the ultrasound transducer assembly is oriented, e.g., one axis representing depth and a perpendicular axis representing amplitude. In some examples, embodiments of the in-vivo fluid flow sensor device 100X may be used in B-mode, also referred to as 2D mode, to obtain a two-dimensional representation from the transmitted and received acoustic signal waves, for example, based on the angle at which the ultrasound transducer assembly is positioned relative to the anatomical structure. In some examples, embodiments of the in-vivo fluid flow sensor device 100X may be used in C-mode to obtain both depth range from A-mode and 2D information from B-mode.

[0113] FIG. 6A shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, designated in FIG. 6A as in-vivo fluid flow sensor device 600A. The in-vivo fluid flow sensor device 600A includes a sensor unit comprising at least one ultrasonic sensor assembly 611 in electrical communication with an electronic unit 620 via an electrical interconnect (not shown), which is configured on a surface of the clip band 603 or within the body of material. The electronic unit 620 is housed within a connecting device 635 that connects the arms of the clip band 603. The ultrasonic sensor assembly 611 includes a plurality of acoustic transducer elements 613, for example, five acoustic transducer elements 613a, 613b, 613c, 613d, and 613e, in this example, positioned on the inward-facing sides of the arms of the clip band 603. This embodiment is not limited to five acoustic transducer elements for each ultrasonic sensor assembly and may include fewer or more configurations than shown in the diagram of FIG. 6A , including, for example, but not limited to, one or more acoustic transducer elements for ultrasonic sensor assembly 611. The other arm of clip band 603 may include an embodiment of reflector 516 (shown in FIG. 6A as reflector 616) configured to reflect acoustic signals transmitted by ultrasonic sensor assembly 611 propagating across the anatomical structure, affected by fluid flow through the anatomical structure, reflected from reflector 616, and received as a returned acoustic signal by ultrasonic sensor assembly 611 (corresponding to the transmitted acoustic signal). In some embodiments, reflector 616 may be attached to a backing or substrate 616, which may be attached to an inner surface of the arm of clip band 603.

[0114] The clip band 603 is configured to secure the acoustic transducer element 613 and the reflector 616, positioning them in a fixed position relative to one another. In some embodiments, for example, the clip band 603 may be composed of a composite material having a durometer parameter of the polymer component (e.g., 20A-95A) and a reinforcement material (e.g., made of a shape-setting material such as Nitinol), which allows the clip band 603 to be pre-shaped and / or pre-trained (allowing the clip band 603 to be set in a first shape / configuration for delivery / implantation, and then be able to assume a second shape / configuration for deployment / operation). Some non-limiting examples of composite materials for the clip band 603 can include Nitinol, gold, platinum, platinum / iridium, etc., encased in a polymer such as silicone, polyethylene, polyimide, polyamide, or hybrid polyimide-polyamide, or other polymeric material.

[0115] In some embodiments of the in vivo fluid flow sensor device 600A, the clip band 603 may include one or more openings 600A18 on at least one or both arms of the clip band 603 that allow for secondary attachment of the device 600A to a target anatomical structure. For example, the opening 618 shown in the example of FIG. 6A includes a portion of the clip band 603 between two gaps that are openings 618, which provide anchoring sites for applying sutures (e.g., stitch threads, wires, etc.) that affix the arms of the clip band 603 to the anatomical structure (e.g., the wall of the atrium of the heart).

[0116] Figure 6B shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 600A of Figure 6A, designated in Figure 6B as in-vivo fluid flow sensor device 600B. The in-vivo fluid flow sensor device 600B includes a sensor unit including an ultrasonic sensor assembly 611 and a second ultrasonic sensor assembly 612, both in electrical communication with an electronics unit 620 via an electrical interconnect (not shown), configured on the surface of the clip band 603 or within the body of material. The electronics unit 620 is housed within a connecting device 635 that connects the arms of the clip band 603. The ultrasonic sensor assembly 612 includes multiple acoustic transducer elements 614 positioned on an arm of the clip band 603 opposite the arm on which the ultrasonic sensor assembly 611 is located. In the example shown in FIG. 6B , the plurality of acoustic transducer elements includes five acoustic transducer elements 614a, 614b, 614c, 614d, and 614e, which are positioned on the inner surface of the arms of the clip band 603 in a specific configuration relative to each other and relative to the acoustic transducer elements 613 of the ultrasonic sensor assembly 611 on the opposing arm of the clip band 603. This embodiment is not limited to five acoustic transducer elements for each ultrasonic sensor assembly and may include fewer or more configurations than shown in the illustration of FIG. 6B , including, for example, but not limited to, one or more acoustic transducer elements for the ultrasonic sensor assembly 611. The clip band 603 is configured to secure the acoustic transducer elements 613 and 614 and position them in a fixed position relative to each other. In some embodiments, the clip band 603 of the in vivo fluid flow sensor device 600B may include one or more openings 618 on at least one or both of the arms of the clip band 603 to allow for secondary attachment of the device 600B to a target anatomical structure. For example, the opening 618 shown in the embodiment of FIG. 6B includes a portion of the clip band 603 between the two gaps that make up the opening 618, which provides an anchor site for applying a suture (e.g., stitch thread, wire, etc.) that attaches the arms of the clip band 603 to an anatomical structure (e.g., the wall of the atrium of the heart).

[0117] Figure 6C shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 600A of Figure 6A and / or the in-vivo fluid flow sensor device 600B of Figure 6B, shown in Figure 6C as in-vivo fluid flow sensor device 600C. The in-vivo fluid flow sensor device 600C includes a sensor unit including an ultrasonic sensor assembly 611 and / or a second ultrasonic sensor assembly 612, both in electrical communication with an electronics unit 620 via an electrical interconnect (not shown), which is configured on a surface of the clip band 603 or within the body of material. The electronics unit 620 is housed within a connecting device 635 that connects the arms of the clip band 603. In vivo fluid flow sensor device 600C includes an inner curved region 634 at the distal end of each arm of clip band 603, e.g., which helps to facilitate attachment and conformation to the anatomy during deployment as well as aid in delivery of device 600C, e.g., via a catheter. One or more openings 618 may be located on inner curved region 634 and / or on at least one or both of the arms of clip band 603 proximate inner curved region 634, e.g., to allow for secondary attachment of device 600B to the target anatomy. In some embodiments, connection device 635 may be attached to clip band 603 (not shown) outside of the arms, which may be preferred for in vivo applications where device 600C is deployed on a blood vessel (e.g., vena cava or pulmonary artery or vein, etc.).

[0118] The exemplary embodiments of FIGS. 6A - 6C of the in vivo fluid flow sensor devices 600A, 600B, and 600C each include a soft arm configuration of a clip band 603 for flexibility and conformity to the intended placement site. The arms of the clip band 603 can facilitate and maintain electronic transmission to an electronic unit 620 housed within a connection device 635 through an interconnect (not shown). The clip band 603 can enhance the contact between the devices 600A, 600B, 600C and the anatomical structure such that ultrasonic measurements can be detected. The arms of the clip band 603 can include a flexible, non - conductive, biocompatible substrate material embedded on or within it that is a flexible circuit and carrier for an ultrasonic sensor assembly 611 and / or a second ultrasonic sensor assembly 612. In this way, the clip band 603 can withstand mechanical forces during the placement of the device for connection to the intended position and during long - term operation (e.g., hundreds of cycles such as a heartbeat). In some embodiments, the arms of the linkage assembly 603 can use a braided metal sheet or a polymer sheet, which is then woven with trace lines for electrical connection.

[0119] FIG. 6D shows an enlarged view of an exemplary embodiment of an electronic unit housed in a connection device 635 of the in vivo fluid flow sensor devices 600A, 600B, and 600C of FIGS. 6A - 6C. In some embodiments, for example, the connection device 635 includes a base housing 631 and a removably attachable cap 633 that is fixed (e.g., hermetically sealed) to the base housing 631 to protect internal components (e.g., the electronic unit 620) from the external environment (e.g., biological fluids and / or biological substituents). In some (optional) embodiments, for example, the connection device includes an intermediate housing 632 that houses the electronic unit 620, and, for example, the intermediate housing 632 can be manufactured separately and in a number of physical structures (e.g., shapes and sizes) to enable modularity with various embodiments of the connection device 635 in any embodiment of the in vivo fluid flow sensor device 100X.

[0120] In some embodiments, the base housing 631, the intermediate housing 632, and / or the cap 633 may be connected via a hermetic sealing material (e.g., a non-permeable material, such as a metal or metal film (thin film) and / or a woven fabric or polymer, a urethane such as Parylene, or a Teflon (registered trademark) material) coated to ensure a non-permeable interface between any of the base housing 631, the intermediate housing 632, and / or the cap 633, preventing fluids such as water or blood from entering the connection device 635 into the electronic unit 620.

[0121] Electronics unit 620 includes a printed circuit board (PCB) 622 that facilitates a data processing unit, a wireless communication unit, and a power unit. For example, in some embodiments, PCB 622 includes an embodiment of data processing unit 121 to at least partially process the conditioned electrical signals to (i) generate data, e.g., in analog or digital form, and / or (ii) control the functionality of electronics unit 120X and / or ultrasonic sensor assemblies 611 and / or 612. For example, data processing unit 121 may be configured to manage data acquisition on data channels associated with one or more acoustic transducers and ultrasonic sensor assemblies 611 and / or 612. Also, for example, in some embodiments, PCB 622 includes a power cell, which may be, for example, a supercapacitor or miniature Hermitian battery, that can be recharged by inductance and / or function in conjunction with a hybrid supercapacitor battery, such that recharge and run time are balanced to be efficient relative to the required monitoring power and communication drain.

[0122] In some embodiments, the wireless communication unit of the electronic unit 620 may be, for example, a 0.000001 in. 2 ~0.008 in 2The antenna may include platinum, 90 / 10 platinum-iridium, gold, or pure platinum wire, with a cross-sectional size of 1000 .mu.m. .001 ...

[0123] In some embodiments, the wireless communication unit of the electronic unit 620 includes a Bluetooth, galvanic, or radio integrated in antenna communication system. In some implementations, the electronic signals transduced by the ultrasound sensor assemblies 611 and / or 612 may be transmitted as a communication data package to a remote device outside the patient's body, for example, through the thoracic cavity to a receiving scanner, receiver transmitter, receiving card (e.g., similar to an EKG port contact), or base station equivalent.

[0124] 7A shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, shown in FIG. 7A as in-vivo fluid flow sensor device 700. The in-vivo fluid flow sensor device 700 includes a sensor unit including a first ultrasonic sensor assembly 711 and a second ultrasonic sensor assembly 612, both in electrical communication with an electronics unit 720 via an electrical interconnect 717 configured on a surface or within a body of material of an exemplary embodiment of a clip band 603 (shown in FIG. 7A as clip band 703). The electronics unit 720 is housed within a connecting device 735 that connects the arms of the clip band 703.

[0125] Connection device 735 may include features of exemplary embodiments of connection device 235, 235C, and / or 635, such as springs, interconnecting links, housing structures (e.g., bases, caps, etc.), and other features described in connection with other connection device embodiments disclosed herein. With reference to FIG. 7A , connection device 735 includes a power and / or data port 751 operable to interface (e.g., electrically and / or data communicate) with an electronics unit 720 housed within connection device 735. For example, electronics unit 720 of in-vivo fluid flow sensor device 700 may include a rechargeable power source or an intermediate power source that may be tethered via power and / or data port 751 to a separate power source and / or data processing unit remote from device 700. In some exemplary embodiments, the remote power source and / or data processing unit may be an in-vivo device located within the patient's body but in an area that is easily accessible for replacing batteries or communicating wirelessly. For example, the remote in-vivo device may communicate wired and provide power to the electronics unit 720 of the in-vivo fluid flow sensor device 700 via a cable, wire, cord, etc. (e.g., coated with an insulating, bio-inert material) through the power and / or data port 751. As an illustrative example, the in-vivo fluid flow sensor device 700 may be deployed in an enclosed space, such as inside or around the pericardium located in the atrium or ventricle, or around the superior or inferior vena cava or pulmonary artery, and tethered to a larger in-vivo power supply device located in a cavity far from the deployment site of the device 700, e.g., one centimeter away, or several centimeters away, or tens of centimeters away, such as the pleural or intraperitoneal cavity, with greater flexibility, size, and / or positioning to facilitate larger power sources and / or electronic components and allow replacement of such components. In some embodiments, the remote power source may be located outside the patient's body, with a power and / or data cable passing from the power and / or data port 751 of the device 700 to the remote power source outside the patient's body.

[0126] In some exemplary implementations, the in-vivo fluid flow sensor platform including device 700 may include any one or more secondary sensors 119 located within a remote in-vivo device in wired communication with sensor unit 720 via cables, wires, cords, etc. connected via power and / or data port 751. For example, in some implementations, the exemplary secondary sensor 119 may include an IMU to determine the patient-user's motion (e.g., whether they are resting (e.g., sleeping, sitting, etc.) or moving (e.g., walking, running, etc.). Additionally, the exemplary secondary sensor 119 as part of the in-vivo fluid flow sensor platform may, in some embodiments, include an acoustic sensor (e.g., inhalation and exhalation respiration rate, turbulent airflow, etc.) for monitoring respiration by the patient-user (respiratory parameters) that are monitored by the in-vivo fluid flow sensor device 700. Still further, the exemplary secondary sensor 119 as part of the in-vivo fluid flow sensor platform may, in some embodiments, include an EKG monitor (e.g., an external wearable cardiac monitor or an in-vivo insertable cardiac monitor) for measuring the patient's electrocardiogram that is monitored by the in-vivo fluid flow sensor device 700. In this manner, for example, the in-vivo fluid flow sensor device 700 may measure blood flow through the target cardiac anatomy simultaneously (time-synchronized) with sensed information of the patient's motion state, respiratory state, and / or heart rate.

[0127] In some exemplary embodiments, a remote in-vivo device (in wired communication with the in-vivo fluid flow sensor device 700) of the in-vivo fluid flow sensor platform may include a secondary transmitting device (e.g., a wireless communication unit) for power control and optimal continuous data management, which may be communicated to, for example, the remote device 130 (e.g., the base station 130B and / or the mobile communication device 130A). For example, data transmission by the exemplary secondary transmitting device (deployed remotely from the device 700) may wirelessly transmit data collected by the device 700 every minute, every second, etc., due to reduced power consumption constraints and challenges by the remote secondary transmitting device relative to the device 700. In some embodiments, for example, the secondary transmitting device of the remote in-vivo device may include a transmitter, receiver, and / or transceiver and have an antenna using a low-power wireless communication protocol, e.g., Bluetooth Low Energy (BLE), Near Field Communication (NFC), low-frequency radio frequency (RF) signals in the range of 3 kHz to 1.3 MHz, or others.

[0128] 7A , a first ultrasonic sensor assembly 711 includes a plurality of acoustic transducer elements 713 positioned on an arm of the clip band 703 opposite the arm on which the second ultrasonic sensor assembly 712 is disposed. In the example shown in FIG. 7A , the plurality of acoustic transducer elements 713 of the first ultrasonic assembly 711 includes five acoustic transducer elements 713a, 713b, 713c, 713d, 713e, which are positioned on the medial side of the arm of the clip band 703 in a particular configuration relative to each other and relative to the acoustic transducer elements 714 of the second ultrasonic sensor assembly 712 on the opposing arm of the clip band 703. It is understood that this embodiment is not limited to five acoustic transducer elements for the first ultrasonic sensor assembly 711 and may include fewer or more configurations than shown in the diagram of FIG. 7A , including, for example, but not limited to, one or more acoustic transducer elements for the first ultrasonic sensor assembly 711. The second ultrasonic sensor assembly 712 includes a plurality of acoustic transducer elements 714 positioned on the arm of the clip band 703 opposite the arm on which the first ultrasonic sensor assembly 711 is located. In the example shown in Figure 7A, the plurality of acoustic transducer elements includes five acoustic transducer elements 714a, 714b, 714c, 714d, 714e, which are positioned in a particular configuration on the inward-facing side of the arm of the clip band 703 relative to each other and relative to the acoustic transducer elements 713 of the first ultrasonic sensor assembly 711 on the opposing arm of the clip band 703. It will be understood that this embodiment is not limited to five acoustic transducer elements for each ultrasonic sensor assembly and may include fewer or more configurations than those shown in the diagram of Figure 7A, including, for example, but not limited to, one or more acoustic transducer elements for the second ultrasonic sensor assembly 712.

[0129] Clip band 703 is configured to secure acoustic transducer element 713 and acoustic transducer element 714, positioning them in a fixed position relative to one another. In some embodiments, clip band 703 of in vivo fluid flow sensor device 700B can include one or more openings 718 on at least one or both arms of clip band 703 that allow for secondary attachment of device 700B to a target anatomical structure. For example, opening 718 shown in the example of FIG. 7A includes a portion of clip band 703 between two gaps that are openings 718, which provide anchoring sites for applying sutures (e.g., stitch thread, wire, etc.) that affix the arms of clip band 703 to an anatomical structure (e.g., the wall of an atrium of the heart).

[0130] In some embodiments of the in vivo fluid flow sensor device 700, similar to the example shown in FIG. 7A, the device 700 includes an inner curved region 734 at the distal end of each arm of the clip band 703, e.g., which not only helps to facilitate attachment and conformation to the anatomy during deployment, but can also aid in delivery of the device 700, e.g., via a catheter. One or more openings 718 may be located on the inner curved region 734 and / or on at least one or both of the arms of the clip band 703 adjacent the inner curved region 734, e.g., to allow for a secondary means of attachment of the device 700 to the target anatomy.

[0131] 7B and 7C show diagrams illustrating another exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, designated in FIGS. 7B and 7C as in-vivo fluid flow sensor device 700B. In-vivo fluid flow sensor device 700B may be configured similarly to in-vivo fluid flow sensor device 700 (previously shown in FIG. 7A), for example, the sensor unit includes an ultrasonic sensor assembly 712 in electrical communication with an electronics unit 720 via an electrical interconnect 717 (e.g., coupled to or partially housed within an arm of clip band 703), and a connection device 735 including a power and / or data port 751 in electrical communication with electronics unit 720 and a remote device. 7B and 7C, the in-vivo fluid flow sensor device 700B includes an acoustic transducer pad 771 to protect the acoustic transducers 713 and / or 714 and to improve acoustic signal transmission and reception (e.g., improve acoustic impedance matching) between the transducers and the biological tissue of the anatomical structure to which the device 700 is attached. FIG. 7B shows the in-vivo fluid flow sensor device 700B in an exploded view in which the acoustic transducer pad 771 is detached from the ultrasonic sensor assembly 711, and FIG. 7C shows the in-vivo fluid flow sensor device 700B in a rotated view (with respect to FIG. 7B) in which the acoustic transducer pad 771 is coupled to an arm of the clip band 703 and / or to multiple acoustic transducer elements 713 of the ultrasonic sensor assembly 711 positioned on (at least one) of the arms of the clip band 703. Although not shown in FIGS. 7B and 7C, a second acoustic transducer pad 771 may be coupled to an opposing arm of the clip band 703 and / or to at least one of the plurality of acoustic transducer elements 714 of the ultrasonic sensor assembly 712 .

[0132] In various embodiments, the acoustic transducer pad 771 may comprise a hydrogel, which may be packaged in a gelatinous or fluid form, with a casing including a polymeric material having a hardness of up to 40 A durometer (e.g., silicone, polyethylene, or other). In an exemplary implementation of the in vivo fluid flow sensor device 700 using the acoustic transducer pad 771, the acoustic transducer pad 771 may further provide contouring and cushioning to cardiac tissue, e.g., the outer tissue of the walls of the atria or ventricles, as well as the endothelial tissue of major blood vessels, such as the vena cava or pulmonary arteries or veins, when the in vivo fluid flow sensor device 700 is deployed within the pericardium. For example, the acoustic transducer pad 771 may account for contouring variations with anatomical structures with which the device 700 directly interacts. Additionally, for example, the acoustic transducer pad 771 may be operable to support signal separation from noise and provide noise polarization for optimal sensing capabilities. The acoustic transducer pads 771 can reduce the risk of damage from edge abrasiveness, for example, by absorbing mechanical forces potentially occurring on the acoustic transducer elements during deployment and operation (e.g., cyclical movement of the anatomy), which can result in acute harm or long-term wear and tear, particularly while not affecting acoustic signal transmission between the anatomy and the acoustic transducer elements. Similarly, the acoustic transducer pads 771 can reduce the risk of tissue abrasion to the anatomy to maintain contact viability between the device and biological tissue.

[0133] 8 shows a diagram illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, shown in FIG. 8 as in-vivo fluid flow sensor device 800. In-vivo fluid flow sensor device 800 may be configured similarly to in-vivo fluid flow sensor device 700 (previously shown in FIG. 7A) and / or in-vivo fluid flow sensor device 700B (previously shown in FIGS. 7B and 7C and having at least one acoustic transducer pad 771), for example, the sensor unit includes an ultrasonic sensor assembly (shown in FIG. 8 as ultrasonic sensor assembly 712) in electrical communication with electronics unit 720 via electrical interconnect 717 (e.g., coupled to or partially housed within an arm of clip band 703), and connection device 735 includes power and / or data port 751 in electrical communication with electronics unit 720 and a remote device. 8, the in-vivo fluid flow sensor device 800 includes an embodiment of a reflector 516 (shown in FIG. 8 as reflector 816) configured to reflect acoustic signals transmitted by the ultrasonic sensor assembly 712 propagating through the anatomical structure, affected by fluid flow through the anatomical structure, reflected from the reflector 716, and received as returned acoustic signals by the ultrasonic sensor assembly 712 (corresponding to the transmitted acoustic signals). In some embodiments, the reflector 816 may be attached to a backing or substrate (not shown), which may be attached to arms that facilitate the ultrasonic sensor assembly 712 to the inner surface of the opposing arms of the clip band 703.

[0134] 9 shows a diagram of an exemplary embodiment of a remote in-vivo device 990 operable to communicate by wire with the exemplary embodiment of in-vivo fluid flow sensor device 100X of FIG. 1B, which is in-vivo fluid flow sensor device 700, 700B, and / or 700D shown in FIGS. 7, 7B-7C, and / or 7D, respectively. The remote in-vivo device 990 includes a casing or housing 991 within which a power source 998 and a data processing and / or wireless communication unit 997 are housed.

[0135] Examples of the power source 998 may include a battery, a fuel cell, or other power source. In some embodiments, for example, the power source 998 may be configured to be a replaceable and / or rechargeable battery. For example, in implementations where the remote in-vivo device 990 is located within a patient's body in an area or region that is relatively easy and safe for a clinician to access, such as the pleural cavity or abdominal region, the power source 998 may be recharged. In this manner, electrical energy stored in the power source 998 may be used to provide power within the electronics unit 120X, which may have a relatively lower charge storage capacity than the power source 998. Transmission of electrical energy may be provided from the remote in-vivo device 990 to the exemplary in-vivo fluid flow sensor device 700, 700B, 700D via a cable, wire, or cord 993 that interfaces with the power and / or data port 751 of the exemplary in-vivo fluid flow sensor device 700, 700B, 700D via an interface termination 992. In some embodiments of the remote in-vivo device 990, for example, the cable, wire, or cord 993 may be detachable from the housing or casing 991 of the in-vivo device 990 at a receiving port 999. In the exemplary illustration of FIG. 7E , the interface end 992 of the cable, wire, or cord 993 is shown having at least one protruding structure that can be used to create a locking system with the power and / or data port 751 to secure fixation (e.g., exemplary in-vivo fluid flow sensor devices 700, 700B, 800).

[0136] Examples of the data processing and / or wireless communication unit 997 may include a transmitter, receiver, and / or transceiver having an antenna using a low-power wireless communication protocol, such as Bluetooth Low Energy (BLE), near field communication (NFC), low-frequency radio frequency (RF) signals, etc., in data communication with one or more processors coupled to a memory. In this manner, the data processing unit of the electronics unit 720 may manage data processing functions using less on-board power and offload more processing-intensive data processing tasks to one or more processors and memory of the data processing and / or wireless communication unit 997. Additionally, the data processing and / or wireless communication unit 997 may function to at least partially control certain device functions of the exemplary in-vivo fluid flow sensor devices 700, 700B, 700D.

[0137] 10A and 10B show diagrams illustrating an exemplary embodiment of the in-vivo fluid flow sensor device 100X of FIG. 1B, shown in FIGS. 10A and 10B as in-vivo fluid flow sensor devices 1000A and 1000B, respectively, which are attached to a patient-user's heart in an exemplary implementation of the device. In this example, the in-vivo fluid flow sensor devices 1000A and 1000B are configured to assess blood flow across the mitral valve by positioning ultrasound sensor assemblies on opposing sides of the outer surface of the atrium of the heart around the mitral valve, for example, to assess MR. As shown in Figures 10A and 10B, the arms of in vivo fluid flow sensor devices 1000A and 1000B (e.g., the arms of an exemplary embodiment of linkage assembly 103 of device 100X as clip bands 603 and / or 703) can extend around an organ, such as the atrium of the heart, with sufficient flexibility to support a variety of orientations to optimize functional alignment with the target anatomical structure.

[0138] Additionally, optimal functional alignment can be maintained by the arms (e.g., degree of flexion) of the linkage assembly, and the in vivo fluid flow sensor devices 1000A, 1000B can be positioned and secured to the target anatomical structure individually or (optionally) compiled with one or more secondary attachment mechanisms, for example, secured with sutures (secured at suture ports), adhesives, or anchor structures (secured at anchor ports), and placement relative to the intended region of the organ / tissue can be optimized for consistent measurements (e.g., by initial monitoring to establish calibration, followed by comparison with constant monitoring and comparison from a baseline). Also, in some implementations, for example, multiple in vivo fluid flow sensor devices 1000A, 1000B can be deployed at different locations in the same anatomical structure.

[0139] The exemplary embodiment of in vivo fluid flow sensor device 1000A includes a connection device disposed on the inside of the clip band linkage assembly (e.g., proximate to the anatomical structure to which device 1000A is attached). Yet, the exemplary embodiment of in vivo fluid flow sensor device 1000B includes a connection device disposed on the outside of the clip band linkage assembly (e.g., distal from the anatomical structure to which device 1000B is attached). It is understood that the configuration of the connection device can be on the inside or outside of the linkage assembly for various embodiments of in vivo fluid flow sensor device 100X, including any embodiment of linkage assembly 103.

[0140] Displacement-mediated in-vivo acoustic sensor device In some embodiments of the in-vivo acoustic sensor device 100Y, for example, the acoustic sensor 111Y includes a displacement-mediated acoustic sensor, which may include an internal microphone-based acoustic sensor, referred to herein as a microphone acoustic sensor, or simply a microphone.

[0141] FIG. 11A shows a diagram illustrating an exemplary acoustic sensor in a portion of an exemplary embodiment of an implantable medical device 100 of the present invention, shown as IMD 1100A in FIG. 11A. As shown in FIG. 11A, IMD 1100A includes a housing 1102 and a membrane 1104, which together create a sealed enclosure for an exemplary embodiment of in-vivo acoustic sensor 100Y. In some embodiments, for example, membrane 1104 is a deflectable membrane, e.g., capable of elastic deformation to change configuration between a relaxed state and a flexed state (e.g., contracted and / or expanded). In such embodiments, the acoustic sensor may be configured to operate as a microphone, i.e., a device that converts sound (mechanical waves) into an electrical signal, which may be processed (e.g., amplified). In some embodiments, for example, the membrane 1104 comprises titanium (Ti) or other strong, impermeable, biocompatible, and relatively inflexible metals, such as surgical-grade stainless steel (e.g., MP35N) or cobalt-chromium alloy or nitinol, or high-purity aluminum oxide, which are strong, impermeable, biocompatible, and flexible for transmitting pressure differences. In some embodiments, the housing 1102 and the membrane 1104 are formed from the same material, but the membrane 1104 has properties, such as thickness or elasticity, that enable it to achieve a desired response to pressure variations while maintaining airtightness. In some embodiments, the housing 1102 and the membrane 1104 are made from different materials but are firmly joined together to form a sealed enclosure. In some embodiments, for example, the membrane 1104 can be configured in a circular shape so that acoustic signals (e.g., mechanical waves) radiating from an in vivo anatomical structure, such as a portion of the heart or lung, are detectable by the relationship between the pressure difference (q) and the bending stiffness (D) of the membrane 1104 according to equation (1):

number

number

number

[0142] Also shown in the diagram of FIG. 11A, 1106 denotes a gas, liquid, or solid, including tissue within a host, that can transmit pressure fluctuations. The external medium 1106 is in direct contact with the outer surface of the sealed enclosure, particularly the outer surface of the membrane 1104. Also shown in FIG. 11A, 1108 denotes an internal medium of the housing 1102, e.g., a gas, liquid, gel, or other medium within the sealed enclosure of the exemplary embodiment of the in-vivo acoustic sensor 100Y for the exemplary IMD 1100A, through which the internal medium 1108 can transmit pressure fluctuations, such as acoustic signals. The internal medium 1108 is in direct contact with the inner surfaces of the sealed enclosure from the housing 1102 and membrane 1104, particularly the inner surface of the membrane 1104.

[0143] FIG. 11B shows a cross-sectional view illustrating an enlarged view of a portion 1107 of an exemplary embodiment of the in-vivo acoustic sensor 100Y of the exemplary IMD 1100A, identified as portion 1107B in FIG. 11B, with the membrane of the acoustic sensor in a relaxed state. In FIG. 11B, as shown in cross-section, a housing 1102 is present and shown on each end of the membrane 1104. In FIG. 11B, an external medium 1106 is present outside the housing 1102 and contacts the exterior surface of the membrane 1104, and a separate internal medium 1108 is present inside the housing 1102 and contacts the interior surface of the membrane 1104. In FIG. 1B, the membrane 1104 is shown moving in a substantially linear manner between the portion of the housing 1102 and either side of the membrane 1104, indicating that the membrane 1104 is in a relaxed state due to equilibrium or balance of pressures within the media 1106 and 1108.

[0144] FIG. 11C shows a cross-sectional view, identified as portion 1107E of FIG. 11C, illustrating an enlarged portion of the image of FIG. 11A, similar to FIG. 11B, but with the membrane 1104 of the acoustic sensor in a deflected state. FIG. 11C illustrates the effect of a pressure difference between the inner surface of the sealed enclosure and the outer surface of the sealed enclosure. In particular, the external pressure (Po) in the external medium 1106 acting on the IMD is greater than the internal pressure (Pi) in the internal medium 108 of the IMD. Thus, the membrane 1104 is deflected into the sealed enclosure occupied by the internal medium 1108 by an amount that can be defined by the distance between point 1112a, where the membrane 1104 is in a relaxed state, and point 1112b, where the membrane 1104 is in a deflected state. For example, a pressure difference across a plate, such as the membrane 1104, acts as a uniform load, deforming the plate and resulting in stress distribution(s) proportional to the pressure difference.

[0145] There are multiple ways in which a deflectable membrane of an acoustic sensor (e.g., a microphone) converts its deflection into an electrical signal that can be measured in terms of the presence and / or degree of deflection, e.g., optionally as a function of time, see Figure 11C. Exemplary ways in which the deflection can be converted into an electrical signal include the amino acid sequences of Figures 12A, 12B, 13A, and 13B.

[0146] 12A and 12B show diagrams illustrating an exemplary displacement-mediated acoustic sensor configured as an in-vivo microphone for some exemplary embodiments of the in-vivo acoustic sensor 100Y of the IMD 100 according to the present invention, where the exemplary acoustic sensor includes a strain gauge and / or a piezoelectric element. FIG. 12A shows a cross-sectional view of an exemplary acoustic sensor (e.g., microphone) in a portion of an exemplary IMD 1250 of the present invention, including a sensor 1114 that may include one or both of a strain gauge and a piezoelectric element configured in the membrane 1104 of the exemplary acoustic sensor (e.g., microphone) in a relaxed state. FIG. 12B shows a cross-sectional view of an exemplary acoustic sensor (e.g., microphone) in a portion of the exemplary IMD 1250, similar to FIG. 12A, including a sensor 1114 (including one or both of a strain gauge and a piezoelectric element), but with the membrane 1104 of the exemplary acoustic sensor (e.g., microphone) in a deflected state.

[0147] 12A and 12B illustrate an exemplary embodiment of sensor 1114, i.e., how one or more strain gauges and / or one or more piezoelectric elements may be mounted on membrane 1104 such that deflection of membrane 1104 imparts strain to strain gauge(s) 1114 and / or piezoelectric element(s) 1114. The pressure difference between the inner surface (Pi) and outer surface (Po) of the sealed enclosure of IMD 1250 causes membrane 1104 to deflect by an amount identified as the distance between points 1112a and 1112b in response to a pressure difference between the inner and outer surfaces of the sealed enclosure, resulting in a bending moment (strain) of the exemplary strain gauge(s) 1114 and / or piezoelectric element(s) 1114. Thus, sensor 1114 may be used to detect and measure the degree of deflection and, therefore, the pressure difference between the inside and outside of membrane 1104.

[0148] In an exemplary implementation of the sensor 1114 including a strain gauge of the exemplary IMD 1250, for example, the resistance of the strain gauge 1114 changes in response to strain applied by deflecting the membrane 1104. This resistance may be proportionally converted to an electrical signal using well-known techniques, such as a Wheatstone bridge. Alternatively, detection of static pressure changes (e.g., air pressure, blood pressure, etc.) may also be achieved by utilizing strain gauges and known techniques. In some embodiments, the present invention uses strain gauges as components of a microphone to form an acoustic sensor, and in particular, acoustic sensors as components of an IMD.

[0149] In an exemplary implementation of the sensor 1114 including a piezoelectric element for the exemplary IMD 1250, for example, the piezoelectric element(s) 114 are mounted on the inner surface of the membrane 1104 such that the piezoelectric element(s) generate an electric charge in response to a strain imparted by the deflection membrane 1104. This charge may be converted proportionally to an electrical signal using well-known techniques, for example, a charge amplifier. In some embodiments, the present invention utilizes a piezoelectric element as a component of a microphone to form an acoustic sensor, particularly an acoustic sensor as a component of an IMD.

[0150] 13A and 13B show diagrams illustrating an exemplary acoustic sensor configured as an in-vivo microphone for several exemplary embodiments of an in-vivo acoustic sensor 100Y for an IMD 100 according to the present invention, including a sensor having a capacitive electrode sensor or an electronic condenser element. FIG. 13A shows a cross-sectional view of an exemplary acoustic sensor (e.g., membrane 1104) in a portion of an exemplary IMD 1350 of the present invention, including a sensor 1116 that may include one or both of a capacitive electrode sensor and / or a sensor having an electrode condenser element, with the microphone membrane 1104 in a relaxed state. FIG. 13B shows a cross-sectional view of an exemplary acoustic sensor (e.g., microphone 1104) in a portion of an exemplary IMD 1350, including a sensor 1116 (including one or both of a capacitive electrode sensor and / or a sensor having an electrode condenser element) similar to FIG. 13A , but with the microphone membrane 1104 in an extended or deflected state.

[0151] In some exemplary embodiments, as shown in the diagrams of FIG. 13A or 13B, either a capacitance electrode 1116 or an electronic condenser element 1116 is mounted on the membrane 1104, such that deflection of the membrane 1104 changes the separation between the sensor 1116 (e.g., either the capacitance electrode or the electronic condenser element) and the fixed electrode 1118. The membrane 1104 deflects by an amount described by the distance between points 1112a and 1112b in response to a pressure difference between the inner and outer surfaces of the sealed enclosure (Pi) and (Po). The deflection of the membrane 1104 also changes the spacing between the sensor 1116 (either the capacitance electrode or the electronic condenser element) and the fixed electrode 1118, causing a change in the charge on the fixed electrode 1118. The resulting change in charge on the fixed electrode 1118 is detected and amplified by either a charge amplifier or a voltage amplifier.

[0152] In an exemplary implementation of electrode 1116 for exemplary IMD 1350, for example, an electrode condenser element (at 1116) is mounted on the interior surface of membrane 1104. Electrode condenser element 116 on a deflecting surface (such as the interior surface of membrane 1104) can generate a charge signal on a nearby electrode 1118. This charge signal may be proportionally converted to an electrical signal using well-known techniques, for example, using a charge or voltage amplifier. In some embodiments, the present invention utilizes an electronic condenser element as a component of a microphone to form an acoustic sensor, particularly an acoustic sensor as a component of an IMD.

[0153] In an exemplary implementation of the electrode 1116 comprising a capacitive element for the exemplary IMD 1350, for example, a simple capacitive electrode (at 1116) is mounted on the interior surface of the membrane 1104. Applying a constant voltage bias on a conductive moving surface (such as the interior surface of the membrane 1104) can generate a charge signal on a nearby electrode 1118 that can be extracted as an electrical signal. This charge signal may be proportionally converted to an electrical signal using well-known techniques, for example, using a charge or voltage amplifier. In some embodiments, the present invention utilizes a capacitive electrode as a component of a microphone to form an acoustic sensor, particularly an acoustic sensor as a component of an IMD.

[0154] For example, an exemplary IMD having a microphone-type displacement-mediated acoustic sensor may be suitable for use for at least a relatively short period of time (e.g., several months to a year). Over time, biofilm may build up on the diaphragm, thereby altering the diaphragm's response to acoustic waves over time. However, in some embodiments of an IMD having a microphone as a displacement-mediated acoustic sensor, the IMD may include components that prevent or mitigate such biofouling, including, but not limited to, protective and non-inhibitory membranes, coatings (e.g., chemical or biological) or elution mechanisms, allowing the IMD to manage the surrounding environment with minimal or no biological response, enabling both short-term and long-term functioning times, which may include intestinal fluids, muscle regrowth, scar tissue, or capillary in-growth (e.g., by including a microporous membrane in the IMD with an eluting coating for an anticoagulant for capillary growth and / or a nonporous membrane itself, or carrying a drug-eluting compound). However, in some embodiments of IMDs for long-term acoustic detection and measurement, displacement-mediated acoustic sensors that do not have sensing elements in direct contact with tissue within the host may be utilized in the IMDs of the present invention. One such acoustic sensor, for example, the accelerometer discussed next, may be encased within a housing and thus protected from direct contact with host tissue and host fluids, reducing its sensitivity to biofilm deposits.

[0155] In some embodiments of a displacement-mediated acoustic sensor for in-vivo acoustic sensor 100Y, for example, acoustic sensor 111Y includes an accelerometer, which may be referred to herein as an acoustic accelerometer. In some embodiments, the acoustic accelerometer is capable of high-fidelity (HF) acceleration sensing. For example, when performing high-fidelity acceleration sensing, the acoustic accelerometer may be configured to measure mechanical waves within the body and resolve accelerations as small as 100 μg, or 10 μg, or 1 μg. In some embodiments, the acoustic accelerometer senses acceleration frequencies of up to at least 5000 Hz, or up to at least 4000 Hz, or up to at least 3000 Hz, or up to at least 2000 Hz, or up to at least 1000 Hz, or up to about 900 Hz, or up to about 800 Hz, or up to about 700 Hz, or up to about 600 Hz, or up to about 500 Hz.

[0156] An acoustic accelerometer may be sensitive to acceleration frequencies of interest because the accelerometer can be designed to be limited to frequencies of interest, i.e., sensitive only in the frequency range of interest for the acoustic accelerometer. Alternatively, or additionally, the accelerometer may be sensitive at frequencies of interest for the acoustic accelerometer as well as frequencies that are not of interest for the acoustic accelerometer, in which case the IMD may include firmware that limits the accelerometer to sensing at the frequencies of interest rather than frequencies that are not of interest for performance as an acoustic accelerometer. In this way, for example, the accelerometer does not consume power and other IMD resources because it senses at frequencies that are not relevant for monitoring acoustic signals.

[0157] In some embodiments, the acoustic accelerometer operates at a high-frequency sampled data rate. When operating at a high-frequency sampled data rate, the accelerometer samples acceleration data at up to 20,000 samples / second, or up to 18,000 samples / second, or up to 16,000 samples / second, or up to 14,000 samples / second, or up to 12,000 samples / second, or up to 10,000 samples / second, or up to 8,000 samples / second, or up to 6,000 samples / second, or up to 4,000 samples / second, or up to 2,000 samples / second, or up to 1,800 samples / second, or up to 1,600 samples / second, or up to 1,400 samples / second, or up to 1,200 samples / second, or up to 1,000 samples / second, or up to 800 samples per second. In some embodiments, the accelerometer operates at a data sampling rate of 1,400 to 14,000 samples / second. In some embodiments, the displacement-mediated acoustic sensor is configured such that the accelerometer operates at a high frequency sampled data rate.

[0158] In some embodiments, the acoustic accelerometer of the displacement-mediated acoustic sensor operates at low noise. When operating at low noise levels, the accelerometer input reference noise level, referred to as spectral noise density, is less than 500 μg / rtHz, or less than 400 μg / rtHz, or less than 300 μg / rtHz, or less than 200 μg / rtHz, or less than 100 μg / rtHz, or less than 75 μg / rtHz, or less than 50 μg / rtHz, or less than 25 μg / rtHz, or less than 10 μg / rtHz, or less than 5 μg / rtHz, or less than 1 μg / rtHz, or less than 0.8 μg / rtHz, or less than 0.5 μg / rtHz, or less than 0.1 μg / rtHz. In some embodiments, the accelerometer operates at an input reference noise level between 200 μg / rtHz and 0.5 μg / rtHz.

[0159] In some embodiments, the acoustic accelerometer of the displacement-mediated acoustic sensor operates with high precision. When operating with high precision, the accelerometer has an accuracy of less than 50 micrograms, or less than 40 micrograms, or less than 30 micrograms, or less than 20 micrograms, or less than 10 micrograms, or less than 5 micrograms, or less than 1 microgram, or less than 0.5 micrograms, or less than 0.1 micrograms, or less than 0.05 micrograms, or less than 0.01 micrograms. In some embodiments, the accelerometer operates with an accuracy of between 10 micrograms and 1 microgram.

[0160] In some embodiments, the acoustic accelerometer is a single-axis accelerometer. In some embodiments, the acoustic accelerometer is a multi-axis accelerometer. In some embodiments, the multi-axis accelerometer is a dual-axis accelerometer. In some embodiments, the multi-axis accelerometer is a tri-axis accelerometer. Multi-axis (dual-axis or tri-axis) is preferred for multi-directional acoustic detection, where sensing effectiveness is independent of placement within the host anatomy, or at least adapts to changes in anatomical placement.

[0161] In some embodiments, the acoustic accelerometer operates at 16-24 bits, hi some embodiments, the acoustic accelerometer operates at a resolution of 0.01-0.1 milli-g.

[0162] In some embodiments, the acoustic accelerometer is rigidly attached to the housing 101Y of the displacement-mediated acoustic sensor. In some embodiments, the housing is rigid, e.g., does not compress when contacted by an acoustic signal. Rather than compressing, the housing moves within the host in response to contact with the acoustic signal, and because the acoustic accelerometer is rigidly attached either directly or indirectly to the inside of the housing, the acoustic accelerometer experiences the same movement as the housing when the housing is affected by the acoustic signal.

[0163] As mentioned elsewhere in this specification, acoustic waves (or sound) are pressure waves that propagate through various materials, including gases, fluids, or solids. As a result of the pressure waves, sound in air creates vibratory motion of air molecules, such that their velocity is proportional to the pressure wave amplitude. If the molecular velocity is 'v', then v = p / Z, where 'p' is the sound pressure and 'Z' is the acoustic impedance of the material through which the sound propagates. The acoustic impedance Z' is different for different materials. This relationship between acoustic pressure waves and particle / molecular velocity is the basis for sensing acoustic pressure as particle acceleration. For a pressure wave at frequency 'f', the molecules are vibrating at this frequency with velocity v = p / Z as described above, and the molecular acceleration 'a' is a = 2 * pi * f * v = 2 * pi * f * p / Z. Therefore, molecular acceleration is proportional to the sound intensity or pressure wave amplitude (p) and frequency (f).

[0164] When an exemplary IMD having a suitable accelerometer according to the present invention is placed within a material through which acoustic pressure waves propagate, under certain conditions, the accelerometer will see or experience the same acceleration as surrounding tissue molecules. In some embodiments, the conditions for the accelerometer to "move" tissue in response to propagating acoustic pressure waves include (i) the IMD mass density being similar to or lighter than the surrounding material, and (ii) the physical dimensions (size) of the accelerometer in the direction of acoustic pressure wave propagation being similar to or smaller than the wavelength of the pressure wave. Thus, in addition to considering the accelerometer performance requirements discussed above (i.e., sensed frequency range, sampled date rate, noise, accuracy), the physical behavior of acoustic waves propagating in a medium can also impose size and mass density limitations on exemplary displacement-mediated acoustic sensors of IMDs containing acoustic accelerometers.

[0165] Example of auxiliary sensor for in vivo acoustic sensor device In addition to one or more acoustic sensors, the IMD 100 may optionally include one or more auxiliary sensors. The auxiliary sensors can detect and optionally measure non-acoustic signals or characteristics of the host. In some embodiments, the auxiliary sensors provide data that is complementary to data acquired by the acoustic sensors. In other words, the data obtained from the auxiliary sensors is evaluated in combination with an evaluation of the data obtained from the acoustic sensors to provide greater insight into the physical state of the host and the conditions under which the acoustic data was collected. In some embodiments, the acoustic sensors and the auxiliary sensors operate simultaneously, such that data is acquired by the acoustic sensors simultaneously, i.e., during an overlapping period, and data is acquired by the auxiliary sensors. For example, during a single 10-second period, both the acoustic sensors and the auxiliary sensors acquire data. In another example, data sensed by the auxiliary sensors prompts the IMD to activate the acoustic sensors, whereby the acoustic sensors acquire measurements and, optionally, the auxiliary sensors continue to acquire data.

[0166] In some embodiments, for example, in-vivo acoustic sensor device 100Y optionally includes a sensor that measures an electrocardiogram (ECG or EKG) of the host to obtain data that can be evaluated, for example, to provide a galvanic-based EKG of the host. An exemplary ECG sensor that enables generation of an EKG can view the electrical conductivity of the heart. For example, in-vivo acoustic sensor device 100Y may include two electrodes on opposite ends of in-vivo acoustic sensor device 100Y, the ends of these two electrodes separated by a space that generates electrical potentials that generate spikes as the heart beats, and these spikes give rise to the EKG.

[0167] When considering the performance of a host's heart, the heart has a heart rate, or the rate at which the heart beats, which is periodic. These periods can be tracked to the point where the heart valves open and close. If an HCP is interested in understanding the health of the host's valvular tissue, viewing cardiac function in relation to an EKG can be very useful. The EKG can be used to identify threshold events at which the acoustic sensor should begin acoustic monitoring, i.e., data collection. The EKG can identify, for example, when the mitral valve is functioning, which may be a threshold event. The EKG also identifies the periodicity of the heartbeat, allowing the IMD to estimate the periodicity of mitral valve function with high accuracy. Using this information, the in-vivo acoustic sensor device 100Y may respond by collecting data only during the opening and closing of the mitral valve, which may be approximately 100-200 milliseconds. If the host's heart is beating at, for example, 60 beats per minute, the IMD can be configured to activate the acoustic sensor only during the heartbeat periods when the mitral valve is opening and closing, and not collect data at other times that may not be of primary interest. In this way, IMD power is conserved and data of primary interest (e.g., reflecting mitral valve function, e.g., mitral valve progression) is exclusively collected. Alternatively, the in-vivo acoustic sensor device 100Y may continuously collect data for a longer period, e.g., 10 seconds, at a sample rate of 5,000 Hz, and from this large amount of data, acoustic signals from mitral valve function may be extracted. This latter approach utilizes more power and requires more information to be stored in memory.

[0168] In some embodiments, the EKG of the in-vivo acoustic sensor device 100Y is used to identify threshold events that trigger the collection of acoustic data by the in-vivo acoustic sensor device 100Y. By combining EKG information with acoustic information, higher fidelity data can be obtained. The present invention allows for assessment of cardiac performance by acoustic characteristics at time points during the EKG, in other words, by both EKG and acoustic characteristics for a particular time point or family of time points. In some embodiments, the acoustic data is synchronized with the EKG data when the in-vivo acoustic sensor device 100Y includes both an acoustic sensor and an EKG monitor.

[0169] In some embodiments, for example, in-vivo acoustic sensor device 100Y optionally includes a motion sensor. As used herein, a motion sensor can detect and / or measure the movement and orientation of the host relative to Earth's gravity. As used herein, a motion sensor can detect and / or measure the position and / or movement of the host relative to Earth. For example, the motion sensor can detect whether the host is standing, lying down, walking, jogging, running, climbing stairs, playing, riding a bike, etc., and optionally obtain measurements describing the motion, such as, for example, the speed at which the host is running or whether the host is climbing stairs or descending stairs. Accelerometers, such as a three-axis accelerometer, an inclinometer, and an inertial measurement unit (IMU), are each exemplary motion sensors for this purpose.

[0170] The motion sensor can be used to verify or ensure that acoustic data is collected during a particular activity or activity level. For example, the motion sensor may obtain measurements consistent with the host walking, at which point the acoustic sensor of the IMD is activated to obtain acoustic data. For example, when the motion sensor detects that the host is walking, jogging, or running, such as occurs during a stress test when the host moves on a treadmill, the acoustic sensor can begin measuring. For example, the acoustic sensor can listen for sounds coming from a beating heart, which provides information about how the heart is functioning during walking, jogging, or running. In this manner, the acoustic data can be correlated with host position or host movement data. In some embodiments, the acoustic data is synchronized with position and / or movement data when the in-vivo acoustic sensor device 100Y includes both an acoustic sensor and a motion sensor.

[0171] Therefore, a motion sensor may be used to verify or ensure that acoustic data is collected during a particular activity or activity level. Accelerometers, inclinometers, inertial measurement units (IMUs), or preferably, triaxial accelerometers are all embodiments of motion sensors for this purpose. To assess a patient's position and / or movement, the accelerometer of an IMU may generally be configured as a low-fidelity accelerometer, as opposed to a high-fidelity accelerometer that may be used to detect and measure internal (in-vivo) acoustic signals, such as, for example, the acoustic accelerometers described herein.

[0172] The one or more sensors may include a fluid pressure sensor, a fluid volume sensor, a pulse pressure sensor, a blood volume sensor, a blood flow sensor, a chemical sensor (e.g., for blood and / or other fluids), a metabolic sensor (e.g., for blood and / or other fluids).

[0173] Electronic Unit 120Y Exemplary embodiments of the in-vivo acoustic sensor device 100Y may include electronic components in addition to the membrane forming the acoustic sensor, e.g., an acoustic accelerometer, and / or a microphone, and one or more auxiliary sensor(s). The following are some exemplary electronic components of the electronic unit 120Y, which may be optional for some embodiments of the in-vivo acoustic sensor device 100Y:

[0174] In some embodiments, the electronic unit 120Y may include a power supply configured to generate a controlled supply signal in the range of approximately 1 to 24 volts (V), for example, to power the power-consuming components of the IMD. The power supply may include one or more of a battery, a primary cell, or a galvanic cell, which is designed to be used once and then discarded without being electrically recharged, or a rechargeable power device (e.g., a rechargeable battery or a supercapacitor), which may be recharged, for example, inductively.

[0175] The power source may be any suitable battery, such as a lithium carbon monofluoride (LiCFx) battery or other storage cell configured to store energy for powering the components of the electronic assembly for the expected lifetime of the IMD (e.g., 2-25 years or more). Optionally, the power source may be a rechargeable power device, such as a lithium ion battery or a supercapacitor. In this case, the power source includes additional components for charging the power source by an external recharging unit. These additional components may include a power coil configured to generate a voltage and current in response to a near magnetic field generated by the external recharging unit.

[0176] Alternatively, the power source may include an energy harvester configured to convert environmental stimuli into energy for charging a rechargeable power device. For example, the harvester may convert one or more of body heat from the subject in which the IMD is implanted, kinetic energy generated by the subject's movement, changes in pressure (e.g., air pressure or pressure within the subject, such as the subject's blood pressure), energy generated by electrochemical reactions within the subject's body, energy generated by radio frequency (RF) fields, and light into a current or voltage for charging a battery or energy for charging a supercapacitor.

[0177] In some embodiments, the electronics unit 120Y includes a processor, such as a microcontroller. An exemplary microcontroller can be any suitable microcontroller or microprocessor and is configured to control the configuration and operation of one or more other electronic components. For example, the microcontroller may be configured to control one or more sensors of the implanted IMD to sense associated measurement data and store the measurement data generated by the one or more sensors in memory. The microcontroller may also be configured to generate messages for communication via one or more types of communication interfaces. For example, in the case of RF telemetry communication, the microcontroller generates messages including the stored data as a payload, packetizes the messages, and provides the message packets to an RF transceiver for transmission to a base station. The microcontroller may also be configured to execute commands received from a base station via a communication interface, e.g., an antenna, a filter, and an RF transceiver. For example, the controller 1032 may be configured to receive configuration data from a base station and provide the configuration data to components of the electronics assembly 1010 to which the base station directs the configuration data. When the base station directs the configuration data to the controller 1032, the control circuitry is configured to configure itself in response to the configuration data.

[0178] In some embodiments, electronic unit 120Y includes memory. Exemplary memory may include volatile memory and non-volatile memory. For example, the volatile memory may be configured to store an operating system and one or more applications executed by the microcontroller. The non-volatile memory may be configured to store configuration information for the IMD, store data written by the microcontroller, and provide data in response to read commands from the microcontroller.

[0179] In some embodiments, the electronics unit 120Y may include an antenna with associated telemetry circuitry, which may also be referred to as a communications interface. These components are configured to enable the implanted IMD to transmit and receive wireless data between the implanted device and an external device. The antenna and telemetry circuitry may operate using a medical implant communications service (e.g., 400-405 MHz) or using Bluetooth (e.g., 2400-2500 MHz). In some embodiments, the antenna is a housed antenna, i.e., an antenna that is completely housed within the housing 101Y of the in-vivo acoustic sensor device 100Y.

[0180] In some embodiments, electronics unit 120Y may include a communication interface that facilitates communication between in-vivo acoustic sensor device 100Y of IMD 100 and another device or device of in-vivo fluid flow sensor device 100X. For example, the other device may be an external device, e.g., a base station, located outside or remote from the patient receiving the IMD, or an internal device located within the patient receiving the IMD. Exemplary modes of intra-body communication include (i) RF telemetry communication, (ii) tissue conductive communication, e.g., galvanic coupled communication, and / or (iii) data-over-sound communication, e.g., ultrasound or acoustic communication.

[0181] The communications interface includes communications circuitry generally, but not necessarily, associated with the in-vivo acoustic sensor device 120Y100Y. The communications circuitry may include any hardware, firmware, software, or any combination thereof suitable for enabling one or more intra-body communication modes. To this end, the communications circuitry may include, for example, voltage regulators, current generators, oscillators, or circuits for generating signals, resistors, capacitors, inductors, and other filtering circuits for processing received signals, as well as circuits for modulating and / or demodulating signals in accordance with a communications protocol.

[0182] Depending on the communication mode, the communication circuitry may also include transistors or other switching circuitry for selectively coupling transmitted signals to or receiving signals from a desired transceiver, such as an antenna (which may be used for electromagnetic communication, e.g., RF telemetry communication), an electrode (which may be used for tissue conductive communication), or an acoustic transducer (which may be used for voice-to-voice data communication). Under control of the microcontroller, the communication circuitry may receive downlink communication signals from an external device or another implanted device and may transmit uplink communication signals. Additionally, the communication circuitry may communicate with external devices and networked computing devices via a computer network, such as the CareLink® network. Further details regarding each of the data-over-sound communication modes of RF telemetry communication, tissue conductive communication, and intra-body communication follow.

[0183] The RF telemetry mode of intra-body communication is enabled by an RF communication interface including an antenna and RF telemetry circuitry, e.g., an RF transceiver and a filter. The RF transceiver 1026 can be a transceiver configured to enable the controller 1032 (and optionally the fuse 1014) to communicate with a base station (not shown in FIG. 8 ) configured for use with the intelligent implant. For example, the RF transceiver 1026 can be any suitable type of transceiver (e.g., Bluetooth, Bluetooth Low Energy (BTLE), and WiFi), can be configured to operate according to any suitable protocol (e.g., MICS, ISM, Bluetooth, Bluetooth Low Energy (BTLE), and WiFi), and can be configured to operate in a frequency band within the range of 1 MHz to 5.4 GHz, or any other suitable range. In some embodiments, the filter 1028 can be any suitable bandpass filter, such as a surface acoustic wave (SAW) filter or a bulk acoustic wave (BAW) filter. The antenna 1030 may be any antenna suitable for the frequency band in which the RF transceiver 1026 generates signals for transmission by the antenna and in which the base station (not shown in FIG. 8 or FIG. 9) generates signals for reception by the antenna.

[0184] The tissue conductive communication (TCC) intrabody communication mode may include a TCC interface including a TCC circuit and a pair of electrodes. The TCC interface allows the microcontroller to communicate with another device that has the same TCC interface as the implanted IMD. The other device may be an implanted medical device or a base station configured for use with the implanted IMD. The TCC may be configured to rely on the ionic content of the patient's body tissue in which the IMD is implanted, and is therefore often referred to as galvanic communication. The ionic content of the body tissue provides an electrical communication medium for transmitting and receiving information to and from the implanted IMD. To communicate in transmit mode, the TCC circuit applies a voltage across the electrodes, causing a current between the electrodes and a corresponding electrical signal to propagate through the host's body tissue. The propagated current may be detected by the receiving device by measuring the voltage generated between the two electrodes. To communicate in receive mode, the TCC circuit measures the voltage across the electrodes.

[0185] The data-over-sound mode of intrabody communication may include a data-over-sound communication interface including data-over-sound circuitry and at least one acoustic transducer. The data-over-sound communication interface allows the exemplary processor (e.g., a microcontroller) to communicate with another device that has the same data-over-sound communication interface as the implanted IMD. The other device may be another implanted medical device or a base station configured for use with the exemplary embodiment of the IMD 100.

[0186] In some embodiments, for example, the electronic components of electronic unit 120Y may include a fuse. The fuse may be any suitable fuse (e.g., permanent) or circuit breaker (e.g., resettable) configured to prevent the power source or current flowing from the power source from injuring the patient and / or damaging one or more electronic components of in vivo acoustic sensor device 100Y. For example, the fuse may be configured to prevent the power source from generating enough heat to burn the patient, damage the electronic components, or damage structural components of in vivo acoustic sensor device 100Y.

[0187] In some embodiments, for example, the electronic components of electronic unit 120Y may include a clock associated with the power management unit. Referring to FIGS. 8 and 9 , clock and power management circuit 1020 may be configured to generate clock signals for one or more of the other components of electronics assembly 1010 and to generate periodic commands or other signals (e.g., interrupt requests) in response to controller 1032 causing one or more components of the implantable circuit to enter or exit a sleep mode or other low-power mode. Clock and power management circuit 1020 may also be configured to regulate voltage from battery 1012 and provide a regulated power supply voltage to some or all of the other components of electronics assembly 1010. For example, in some embodiments, the electronic components of electronic unit 120Y may include a real-time clock (RTC).

[0188] In some embodiments, for example, the in vivo fluid flow device 100X and / or the in vivo acoustic sensor device 100Y of the IMD 100 include a hermetic seal. The hermetic seal can provide a barrier between the IMD's electronic components, such as one or more sensors or memory, and the tissue sounding the implanted IMD. The hermetic seal protects the internal electronics from degradation by bodily fluids and the host from harmful effects that may occur if the IMD's electronics come into contact with the host's tissue or fluids.

[0189] The housing 101Y that houses the in-vivo acoustic sensor device 100Y has a mass density. In some embodiments, the mass density of the in-vivo acoustic sensor device 100Y is comparable to the mass density of the tissue into which the in-vivo acoustic sensor device 100Y is implanted. In embodiments, the mass density of the in-vivo acoustic sensor device 100Y is within 1%, or within 2%, or within 3%, or within 4%, or within 5%, or within 6%, or within 7%, or within 8%, or within 9%, or within 10% of the mass density of the tissue into which the in-vivo acoustic sensor device 100Y is implanted. In some embodiments, the mass density of the in-vivo acoustic sensor device 100Y is less than the mass density of the surrounding tissue, i.e., the tissue into which the in-vivo acoustic sensor device 100Y is implanted. In an embodiment, the mass density of the in vivo acoustic sensor device 100Y is 99% to <100% of the mass density of the surrounding tissue, or 98% to <100% of the mass density of the surrounding tissue, or 97% to <100% of the mass density of the surrounding tissue, or 96% to <100% of the mass density of the surrounding tissue, or 95% to <100% of the mass density of the surrounding tissue, or 94% to <100% of the mass density of the surrounding tissue, or 93% to <100% of the mass density of the surrounding tissue, or 92% to <100% of the mass density of the surrounding tissue, or 91% to <100% of the mass density of the surrounding tissue, or 90% to <100% of the mass density of the surrounding tissue.

[0190] Most living tissues have a density of 1g / cc or 1000kg / m 3 In an embodiment, the housing 101Y that houses the in-vivo acoustic sensor device 100Y according to the present invention has a mass density similar to that of water of 1000 kg / m 3 Less than or 950 kg / m 3 Less than or 900 kg / m 3 Less than or 850 kg / m 3 Less than or 800 kg / m 3 Less than or 750 kg / m 3 or have a mass density less than any of these recited values, e.g., 1000 kg / m 3 ~950kg / m 3 has a mass density of

[0191] In some embodiments, the acoustic sensor 111Y of the in vivo acoustic sensor device 100Y is located within a housing 101Y that provides and maintains isolation between the in vivo acoustic sensor device 100Y and the host tissue into which the in vivo acoustic sensor device 100Y is implanted. The housing 101Y may be formed from a biocompatible material, which term includes one or more biocompatible materials. A biocompatible material does not cause harm to the host in physical contact with the material or to degradation products of the material formed when the material contacts the host in vivo. For example, the material itself or its in vivo biodegradation products (if present) do not exhibit harmful cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, or immunogenicity to the host. Exemplary biocompatible materials are biocompatible metals and metal alloys, such as titanium. Exemplary biocompatible materials are biocompatible polymers, such as plastics such as polyetheretherketone (PEEK). The housing may be formed from a mixture of biocompatible materials; for example, both metal and plastic may be used to form the housing 101Y.

[0192] In some embodiments, the in-vivo acoustic sensor device 100Y includes a first housing structure containing a sensor, e.g., the acoustic sensor 111Y, and few or no other components, which may be referred to herein as wired components, and a second housing structure containing the other components of the in-vivo acoustic sensor device 100Y. Because the housing of the wired components encloses only very few components, e.g., one or more sensors, such as the acoustic sensor 111Y, the wired components can be prepared to have a particularly low mass density. As mentioned elsewhere herein, it can be advantageous for the acoustic sensor to be contained within a housing having a mass density lower than that of the surrounding tissue. By attaching only one or more sensors to the housing, the resulting tethered components can be made to have a particularly low mass density. In some embodiments, the tethered components are physically connected to a base component of the in-vivo acoustic sensor device 100Y, e.g., the second housing structure. In such embodiments, for example, a base component of in-vivo acoustic sensor device 100Y contains most of the electronic components of electronic unit 120Y, and one or more of, for example, an antenna, telemetry circuitry, memory configured to store sensor data, a power source, auxiliary sensor(s), etc. may be located within the housing of the base component of in-vivo acoustic sensor device 100Y. In some embodiments, the mass density of the base component is greater than the mass density of the tethered components.

[0193] In some embodiments, sensor(s) whose performance is not affected by the mass density of the component on which they are located may be located on a base component of in-vivo acoustic sensor device 100Y. For example, the performance of a motion sensor is not affected by the mass density of the component to which the motion sensor is physically affixed. Thus, the motion sensor may be located on a base component of in-vivo acoustic sensor device 100Y.

[0194] The base component may be physically connected to the wired component by leads running between the base component and the wired component. The tethered component may be said to be tethered to the base component via the leads. The leads may allow sensor data acquired by the sensor(s) located in the wired component to be transferred to the base component of the in-vivo acoustic sensor device 100Y, e.g., to memory located in the base component. Additionally, the leads may allow power stored in the base component to be transferred to the wired component and available to activate and / or power the sensor(s) of the wired component. In some embodiments, the leads are flexible. In some embodiments, the leads are biocompatible. By way of analogy, the wired component secured to the flexible leads resembles a fly fishing rod, with the base component resembles the rod and the reel to which the fly (similar to the wired component) is secured by the fish line (similar to the leads).

[0195] In some embodiments, the in-vivo acoustic sensor device 100Y includes a base component and a wired component with leads running between them. In some embodiments, the in-vivo acoustic sensor device 100Y includes a base component and two wired components. In some embodiments, the in-vivo acoustic sensor device 100Y includes a base component, two wired components, and two leads, with leads running between the base component and each of the two wired components. In some embodiments, the in-vivo acoustic sensor device 100Y includes a single base component and multiple wired components. In some embodiments, the in-vivo acoustic sensor device 100Y includes a single base component, multiple tethered components, and one or more leads that allow data from the tethered components to be communicated to the base component. In some embodiments, in-vivo acoustic sensor device 100Y includes a single base component, multiple tethered components, at least one of which is directly physically associated with an accelerometer that functions as an acoustic sensor, and one or more leads that allow data from the tethered components to be communicated to the base component. In effect, the tethered component(s) decouple the mass of the overall in-vivo acoustic sensor device 100Y, so that, for example, the acoustic sensors of in-vivo acoustic sensor device 100Y may be physically associated with a relatively small mass (represented as the tethered components).

[0196] In some embodiments, the in-vivo acoustic sensor device 100Y includes a wired component including an accelerometer configured to function as an acoustic sensor, the accelerometer completely enclosed by a housing. Additionally, the in-vivo acoustic sensor device 100Y includes a base component and leads running between the base component and the tethered component. For example, the base component may include a housing enclosing one or more electrical components selected from a power source, an antenna, telemetry circuitry, and a memory for storing sensor data. Optionally, the base component may also include an auxiliary sensor disclosed herein, such as one auxiliary sensor, two auxiliary sensors, or three or more auxiliary sensors. For example, in some embodiments, the base component may include a motion sensor. As another example, in some embodiments, the base component may include an ECG sensor. As yet another example, in some embodiments, the base component may include an ultrasonic sensor assembly including one or more ultrasonic transducer elements. As yet another example, in some embodiments, the base component may include one or more auxiliary sensors, including one or more of a temperature sensor, an analyte sensor, or a pressure sensor.

[0197] FIG. 14A illustrates the implantable structure of an exemplary embodiment of an in vivo acoustic sensor device 100Y, labeled IMD 1450, showing a top view illustrating the location of internal components, specifically, battery 1121, electronics package 1122, and antenna 1124. There are no tethered components in IMD 1450. Each of the elements of IMD 1450 is contained within a single housing, shown in the view of FIG. 14A as having dimensions of 8 mm (width) by 28 mm (length), where these are exemplary sizes only. In some embodiments, for example, the length of IMD 1450 may be about 25 mm to about 35 mm, e.g., about 25 mm, or about 26 mm, or about 27 mm, or about 28 mm, or about 29 mm, or about 30 mm. In some embodiments, the width of IMD 1450 may be about 6 mm to about 10 mm, e.g., about 6 mm, or about 7 mm, or about 8 mm, or about 9 mm, or about 10 mm. In particular, the housing may be made from more than one material. For example, the housing surrounding the antenna 1124 may be made from a radio transparent material such as PEEK to form a radome for the antenna, while the housing surrounding the battery 1121 and electronics package 1122 may be made from a metal or plastic, including PEEK.

[0198] 14B shows a side view of the example IMD 1450 of FIG. 14A. The side view of the IMD 1450 shows an example size of 20 mm for the combined length of the battery 1121 and electronics package 1122, and an example height of 4 mm for the IMD 1450. In some embodiments, for example, the height of the IMD 1450 can be about 3 mm to about 5 mm, e.g., about 3 mm, or about 4 mm, or about 5 mm.

[0199] 15A shows an implantable structure of an exemplary embodiment of an in-vivo acoustic sensor device 100Y, labeled IMD 1550, showing a top view illustrating the location of the internal components, particularly the battery 1121, the electronics package 1122 with membrane 1126, and the antenna 1124. The features discussed in FIG. 14A can be applied to the IMD 1550 of FIG. 15A for various embodiments.

[0200] Figure 15B shows a side view of the example IMD 1550 of Figure 15A. The features discussed in Figure 14B may be applied to the IMD 1550 of Figure 15B, for various embodiments.

[0201] 16A shows an implantable structure of an exemplary embodiment of in-vivo acoustic sensor device 100Y, labeled IMD 1650, showing a top view illustrating the location of the internal components, specifically the battery 1121, electronics package 1122, and antenna 1124, with the accelerometer contained within a wired component 1626 connected to the main component by leads 1128. The features discussed in FIG. 14A can be applied to IMD 1650 of FIG. 16A for various embodiments.

[0202] Figure 16B shows a side view of the example IMD 1650 of Figure 16A, but omits the tethered component 1626 and associated leads 1128. The features discussed in Figure 14B may be applied to the IMD 1650 of Figure 16B, for various embodiments.

[0203] FIG. 17 shows a block diagram illustrating an IMD 1700, including an exemplary embodiment of an in-vivo acoustic sensor device 100Y, including a representation of its optional internal components. In the IMD 1700 of FIG. 17, the exemplary acoustic sensor is an accelerometer, shown as a high-fidelity (HF) accelerometer. Optional components of the IMD 1700 are also shown in FIG. 17 and may include a main hermetic casing, a low-fidelity (LF) accelerometer serving as a secondary sensor, or more specifically, a motion sensor. Optional components of the IMD 1700 shown in FIG. 17 may include memory for storing sensor-derived data, a microcontroller, an RF wireless transceiver as a component of a telemetry assembly, a battery as an exemplary power source, a power management circuit, and a real-time clock. In some embodiments, for example, the IMD 1700 may include an RF antenna connected to the main hermetic casing by a hermetic feedthrough. The RF antenna may be enclosed within the hermetic casing, as shown in FIG. 17, or may be enclosed within a non-hermetic antenna header. The example IMD 1700 may include other components discussed in connection with other embodiments of the IMD disclosed herein.

[0204] In some embodiments of the IMD 1700, for example, if all components of the IMD 1700 are contained within a single housing, which may be a composite housing (e.g., a metal that surrounds and protects the electronic components, and a polymer that surrounds and protects the antenna, etc.), the IMD 1700 may be referred to as having a cartridge design.

[0205] FIG. 18 shows a block diagram illustrating an exemplary IMD, including an exemplary embodiment of an in-vivo acoustic sensor device 100Y, labeled 1800, with tethered components and including a representation of its internal components. In the IMD 1800 of FIG. 18, the exemplary acoustic sensor is an accelerometer, depicted as a high-fidelity (HF) accelerometer (also referred to as a vibration sensor) capable of measuring and resolving accelerations on the order of 100 μg, 10 μg, or 1 μg, located within the wired components of the IMD 1800 and contained within a secondary hermetic casing along with power / I / O circuitry. The tethered component is an exemplary lead, coupled to the main component by a hermetic feedthrough, which may be biocompatible. In the main component, optional components of the IMD 1800 are shown in FIG. 18 and may include the main hermetic casing, power / I / O, a low-fidelity (LF) accelerometer functioning as an auxiliary sensor, or more specifically, a motion sensor. Optional components of the IMD 1800 shown in FIG. 18 may include memory for storing sensor-derived data, a microcontroller, an RF wireless transceiver as a component of the telemetry assembly, a battery as an exemplary power source, power management circuitry, and a real-time clock. In some embodiments, for example, the IMD 1800 may include an RF antenna connected to the main hermetic casing by a hermetic feedthrough. The RF antenna may be enclosed within the hermetic casing or, as shown in FIG. 18, may be enclosed within a non-hermetic antenna header. The exemplary IMD 1800 may include other components discussed in connection with other embodiments of the IMDs disclosed herein.

[0206] FIG. 19 shows a block diagram illustrating an exemplary IMD, including an exemplary embodiment of an in-vivo acoustic sensor device 100Y, labeled 1900, having a microphone as the acoustic sensor. Optional components of the IMD 1900 are also shown in FIG. 19 and may include a main hermetic casing, a low-fidelity (LF) accelerometer serving as a secondary sensor, and more specifically, a motion sensor. Optional components of the IMD 1900 shown in FIG. 19 may include memory for storing sensor-derived data, a microcontroller for processing the data, an RF wireless transceiver as a component of the telemetry assembly, a battery as an exemplary power source, a power management circuit, and a real-time clock. In some embodiments, for example, the IMD 1900 may include an RF antenna connected to the main hermetic casing by a hermetic feedthrough. The RF antenna may be enclosed within the hermetic casing, as shown in FIG. 19, or may be enclosed within a non-hermetic antenna header. The exemplary IMD 1900 may include other components discussed in connection with other embodiments of the IMDs disclosed herein.

[0207] In some embodiments, the housing of an IMD of the present invention includes fixation aids that facilitate holding the IMD in a specific location within the host. For example, the housing of either or both of the main and wired components can include rings that allow for the use of sutures to secure the components to the host's tissue. The rings can be secured, for example, by welding to the outside of the housing, and sutures can be threaded through the rings and through the host's tissue to secure the housing, and therefore the IMD, to the host at a selected location.

[0208] Some embodiments of the present invention include manufacturing an IMD as described herein, performing quality control on the IMD, packaging the IMD for shipping or storage, providing instructions for use of the IMD making the IMD available to a surgeon, identifying a host having a medical condition requiring monitoring, implanting the IMD into the host, assisting the surgeon in implanting the IMD into the host, operating a robot to assist the surgeon in implanting the IMD into the host, transmitting a wireless signal to the implanted IMD, thereby activating the implanted IMD, sensing an acoustic signal generated by the host using the acoustic sensor of the implanted IMD, and optionally, the acoustic signal being generated by one or more of the host's heart and controlling the host's blood flow in response to the host's respiration, the sensed acoustic signal, or an induction thereof. the host's physical condition in a memory located within the IMD to provide stored data, optionally wherein the stored data is stored in the memory for at least 1 hour, or at least 6 hours, or at least 12 hours, or at least 18 hours, or at least 24 hours, or at least 48 hours; transmitting the stored data from the implanted IMD to a receiving device located outside the host; providing received data that is stored in a memory of the receiving device; analyzing the received data to generate health information that is information regarding the host's physical condition; providing the medical information to a healthcare provider (HCP); and evaluating the medical information as a component of developing a medical plan for the host.

[0209] In some embodiments of the in vivo acoustic sensor device 100Y, the present invention provides methods that include measuring internal sounds with a medical implant and using those sounds to diagnose and / or detect and / or quantify a physical condition of the host, such as the host's cardiac health and / or respiratory health. In some embodiments, the measurements are made in an acoustic spectral range beginning at about 1 Hz, or 2 Hz, or 5 Hz, or 10 Hz, or 50 Hz, or 100 Hz, or 200 Hz, or 500 Hz. In some embodiments, the measurements are made in an acoustic spectral range extending up to about 10,000 Hz, or up to about 8,000 Hz, or up to about 6,000 Hz, or up to about 4,000 Hz, or up to about 2,000 Hz, or up to about 1,000 Hz. In embodiments, the measurements are made in an acoustic spectral range extending from 1 Hz to 2,000 Hz, or from 10 Hz to 10,000 Hz, or from 50 Hz to 2,000 Hz.

[0210] Exemplary embodiments of an IMD 100 according to the present invention can be partially or completely placed (implanted) within a host. When only partially implanted within a host, in some embodiments, the IMD may include a tethered component that is completely implanted within the host, and optionally, the base component of the IMD may be located outside the host, or partially within the host and partially outside the host. In some embodiments, the IMD may include a base component and a wired component, and the entire IMD is implanted within the host.

[0211] In some exemplary embodiments of the IMD 100, the in-vivo acoustic sensor device 100Y and / or the in-vivo fluid flow sensor device 100X can be used to acoustically monitor and quantify a medical condition of a host. For example, the IMD 100 can monitor and quantify cardiac conditions, including valvular diseases such as stenosis (narrowing), incontinence (leakage), and myxoma, for either the tricuspid, pulmonary, pulmonary, mitral, or vena cava valves. Myxoma is particularly problematic for the mitral valve and is currently the most common form of valvular heart disease. The pathological symptoms of myxomatous mitral valve disease vary depending on the thickness of the valve, the degree of leaflet progression, and the presence or absence of chisel leaves. Each of these different diseases for each heart valve produces a unique acoustic signature that can be detected with the IMD of the present invention. Other cardiac conditions that may be acoustically detected and assessed using the IMD 100 include congestive heart failure, arteriolar fibrosis, coronary artery disease, and other adverse cardiac-related medical conditions.

[0212] The IMD 100 may also, or alternatively, monitor and quantify respiratory conditions such as pulmonary diseases, chronic obstructive pulmonary disease (COPD, a condition involving narrowing of the airways and difficulty or discomfort in breathing), emphysema, pulmonary embolism (PE), and asthma.

[0213] The IMD 100 is intended to be implanted into a host. For example, it may be implanted into the host's coelom, into the host's peritoneal cavity, into the host's dorsal cavity, into the host's thoracic cavity, into the host's upper peritoneal cavity, into the host's lower peritoneal cavity, into the host's upper dorsal cavity, into the host's lower dorsal cavity, into the host's pleural cavity, into the host's pericardial cavity, into the host's abdominopelvic cavity, into the host's peritoneal cavity, into the host's pelvis, into the host's spinal cavity, or into the host's lower torso adipose tissue. The IMD 100 may be implanted into and secured to the host's heart, for example, across the cardiac septum between the two ventricles, or within or secured to the left ventricular appendage, i.e., the left atrium. Once implanted, it may operate to collect daily information reflecting the host's health. For example, it may collect daily cardiovascular and / or respiratory acoustic signatures of a host when implanted, for example, in the host's lower torso adipose tissue.

[0214] The present invention also provides a method for removing an implanted IMD described herein from a host. The IMD may be removed for any of a variety of reasons, such as when the host no longer needs the IMD to monitor a medical condition, to create a procedure for a different implanted device, or to provide recharging for a battery. The method includes selecting a host having an implanted IMD as described herein, performing surgery on the host to provide access to the implanted IMD, and then removing the implanted IMD from the host through the access created by the surgery.

[0215] In some embodiments, the in-vivo acoustic sensor device 100Y includes both an acoustic sensor and a motion sensor, and the in-vivo acoustic sensor device 100Y is configured to obtain acoustic information when the motion sensor detects a threshold event. For example, if the motion sensor detects that the host has begun walking, the IMD is configured to activate the acoustic sensor and begin measurement if walking is a threshold event. In some embodiments, the in-vivo acoustic sensor device 100Y waits to acquire acoustic data after the motion sensor detects threshold movement. In some embodiments, the acoustic data is acquired for 5 to 30 seconds. The threshold movement may be walking. The threshold movement may also be stationary. Thus, the in-vivo acoustic sensor device 100Y operates to acquire acoustic data under controlled conditions when the in-vivo acoustic sensor device 100Y detects a specific movement or non-movement of the host and then begins collecting acoustic data affected by that specific threshold activity performed by the host. For example, when the host moves, this stresses the host's body, and the cardiovascular system must respond by increasing output. Under these conditions, sounds produced by the cardiovascular system may reflect health concerns that would not otherwise be apparent from acoustic signals acquired when the recipient is at rest. This is the reason for stress testing, in which the subject is asked to run on a treadmill while an HCP listens to the host's heart.

[0216] Information collected from an exemplary embodiment of the IMD 100 implanted in a recipient may be used to inform clinical decision-making. For example, the information may characterize the effectiveness of ongoing treatment and potentially prompt the HCP to consider and implement alternative treatments. The information may characterize disease progression, which, when reviewed by the HCP, may prompt the HCP to modify, e.g., escalate, the treatment protocol. In addition to providing valuable information to the HCP, information from the implanted IMD may reduce the need for emergency room visits by recipients due to early detection of congestive heart failure and potential non-adherence to medication. In practice, exemplary embodiments of the IMD 100 enable an HCP with a remote stethoscope for daily remote monitoring of a patient's medical condition, e.g., the patient's cardiovascular health.

[0217] Stress-mediated in vivo acoustic sensor device In some embodiments of the in-vivo acoustic sensor device 100Y, for example, the acoustic sensor 111Y includes a stress-mediated acoustic sensor. Exemplary stress-mediated acoustic sensors according to the present invention are configured to measure stress rather than displacement to provide in-vivo sensing of acoustic energy (mechanical waves) emanating from within the body, e.g., from anatomical structures of the cardiovascular and / or pulmonary systems, such as the heart and lungs. The disclosed stress-mediated acoustic sensors are operable to detect in-vivo acoustic signals by measuring mechanical forces applied to an electromechanical transducer component of the sensor and converting the received mechanical energy (acoustic signal) into electrical energy (electrical signal), which is addressable and processable to decipher physiological phenomena associated with the detected acoustic signal and determine clinically relevant information regarding the patient's health and / or disease. In some embodiments of the stress-mediated acoustic sensor, the transducer component includes a piezoelectric material and a conductive non-piezoelectric material(s) configured within a piezoelectric sensing unit.

[0218] 20A and 20B show diagrams illustrating an exemplary IMD of the present invention, labeled 2000, having a stress-mediated acoustic sensor. FIG. 20A shows multiple views of the exterior of IMD 2000 showing an exemplary body structure, and FIG. 20B shows an exploded view of IMD 2000 showing an example configuration of the components of IMD 2000.

[0219] 20A shows a perspective view illustrating an exemplary body of an IMD 2000, showing a housing 2001 that hermetically seals within a sensor unit of the IMD 2000, the housing 2001 including a stress-mediated acoustic sensor 2011 (illustrated in dashed lines) and an electronics unit 2020 (illustrated in dashed lines) in communication with the stress-mediated acoustic sensor 2011. The perspective view of FIG. 20A also shows an exemplary embodiment of a wireless communication unit 2027 embodied as a wire antenna disposed within a distal chamber 2001C of the housing 2001, for example, to facilitate wireless communication transmission(s) and / or reception(s) between the IMD 2000 and an external device (e.g., external remote device 130).

[0220] FIG. 20A illustrates top, bottom, and side views of an exemplary body of an IMD 2000, showing one example of the shape, size, and dimensions of an exemplary embodiment of a housing 2001 of the IMD 2000. It is understood that the IMD 2000 may be configured to have a variety of sizes and shapes to accommodate the stress-mediated acoustic sensor 2011 and electronic unit 2020 contained therein, beyond the specific size, dimensions, and shape shown in FIG. 20A for the exemplary IMD 2000. In the non-limiting example shown in FIG. 20A , the end-to-end length of the housing 2001 is configured to be 51.6 mm, the end-to-end width of the housing 2001 is configured to be 14.72 mm, and the end-to-end height of the housing 2001 is configured to be 6.78 mm. Other non-limiting exemplary shapes for the various portions of the IMD 2000 and housing 2001 are contemplated, including rectangular, square, triangular, oval, circular, cylindrical, conical, or the like, or combinations thereof.

[0221] 20B shows an exploded view of an example embodiment of an IMD 2000 featuring components of a stress-mediated acoustic sensor 2011 and an electronics unit 22001E hermetically sealed within a housing 2001, the components including a first chamber surrounded by a housing top 2001T and a housing bottom 2001B, and an adjacent second chamber (i.e., distal chamber 2001C) surrounded by a housing end 2001E. In some embodiments of the IMD 2000, for example, the stress-mediated acoustic sensor 2011 includes a transducer assembly 2012 coupled to a casing structure 2013 configured to secure the transducer assembly 2012. For example, in some embodiments of the stress-mediated acoustic sensor 2011, the transducer assembly 2012 includes a piezoelectric material and at least one electrically conductive non-piezoelectric material coupled to the piezoelectric material to receive a transduced electrical signal generated in response to a stress applied to the stress-mediated acoustic sensor 2011 that is received by the piezoelectric material. In some embodiments, for example, at least one electrically conductive non-piezoelectric material is positioned on the interior-facing side of the piezoelectric material and coupled to electrical interface component(s) 2025. In some embodiments, for example, the electrical interface component(s) may be configured within or on casing structure 2013. In some embodiments, for example, casing structure 2013 or a portion thereof may include at least a portion of at least one electrically conductive non-piezoelectric material for receiving and transmitting generated electrical signals. In some embodiments, for example, the transducer assembly 2012 is positioned on the exterior-facing side of the piezoelectric material and is hermetically sealed when assembled with the housing opening 20B (i.e., opens through a side of housing bottom 2001B), and the non-piezoelectric material has a Young's modulus that is within 2X to 3X or substantially matches (e.g., within 20%) the Young's modulus.

[0222] In some embodiments of IMD 2000, for example, electronics unit 2020 includes a data and / or signal processing unit 2020 PCB, which may each be embodied by any of the exemplary embodiments of data processing unit 121Y and / or optional signal conditioning unit 123Y disclosed herein. In the example shown in FIG. 20B , data and / or signal processing unit 2020 PCB includes a processor coupled to memory that receives digital signal data from signal processing circuitry, all mounted on a printed circuit board (PCB). In some exemplary embodiments, for example, signal processing circuitry includes a differential amplifier and / or a charge amplifier for amplifying electrical signals received from the stress-mediated acoustic sensor 2011 (e.g., from the at least one electrically conductive non-piezoelectric material via the electrical interface component(s) 2025 connecting the stress-mediated acoustic sensor 2011 to the electronic unit 2020), and / or an analog-to-digital (A / D) converter for digitizing electrical signals. In some exemplary embodiments, for example, signal processing circuitry includes filter circuit(s) for removing signals outside of frequency ranges of non-interest, which may be used, for example, to filter signals received from the at least one electrically conductive non-piezoelectric material via the electrical interface component(s) 2025 connecting the stress-mediated acoustic sensor 2011 to the electronic unit 2020. It may include low-pass, band-pass, and / or high-pass filters to improve the signal-to-noise ratio of the emitted acoustic signal of interest. The exemplary data and / or signal processing unit 2020 PCB may be programmable in some embodiments. In some embodiments, for example, the data and / or signal processing unit 2020 PCB may be secured and / or positioned within the first chamber of the housing 2001 by an (optional) internal housing frame 2001F, which may also be used to secure and / or position one or more components of the stress-mediated acoustic sensor 2011 for some exemplary embodiments.

[0223] In some embodiments of the IMD 2000, for example, the electronics unit 2020 includes a power source 2029 electrically connected to the data and / or signal processing unit 2020 PCB and other components of the electronics unit 2020 (or other units of the IMD 2000, such as some embodiments of the stress-mediated acoustic sensor 2011, when such units need to be powered) via components (e.g., wires or other connectors) of the electrical interface 2025. The power source 2029 may be embodied by any of the exemplary embodiments of the power source 129 disclosed herein. For example, the power source 2029 may include a battery (e.g., a primary or rechargeable battery), a fuel cell, or other power source for powering the components of the electronics unit 2020 (and, if necessary, the stress-mediated acoustic sensor 2011). In some exemplary embodiments, for example, power source 2029 may be an electrical receiving port for accepting wires capable of supplying IMD2000 from a remote power source, such as an implantable (in vivo) power source (e.g., a battery associated with one or more other implanted medical device(s)) and / or a wearable (in vitro) power source (e.g., a battery worn by a user with wires connecting the battery to another in vivo device implanted in the patient's body).

[0224] In some embodiments of the IMD 2000, for example, the electronics unit 2020 includes a wireless communication unit 2027 electrically connected to the data and / or signal processing unit 2020 PCB and other components of the electronics unit 2020 (or other units of the IMD 2000, such as some embodiments of the stress-mediated acoustic sensor 2011 for transmitting raw electrical signals transmitted by the acoustic sensor) via components (e.g., wires or other connectors) of the electrical interface 2025. The wireless communication unit 2027 may include a wireless transmitter, receiver, and / or transceiver device, such as an antenna 2027A as shown in FIG. 20B, capable of communicating with an external device to communicate raw data, partially processed data, or fully processed data from the data and / or signal processing unit 2020 PCB. For example, the wireless communication unit 2027 may be configured to manage a communication protocol for transmitting or receiving via the antenna. The wireless communication unit 2027 may be embodied by any of the exemplary embodiments of the wireless communication unit 127Y disclosed herein. Examples of antenna 2027A may 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.

[0225] Single-type piezoelectric sensor In some embodiments of the in-vivo acoustic sensor 100Y, for example, the exemplary stress-mediated acoustic sensor includes a monomorphic structure for sensing stress, including a piezoelectric material biocompatiblely coupled to a non-piezoelectric material that is electrically conductive and has a Young's modulus similar to that of the piezoelectric material, and a piezoelectric sensing unit that generates a measurable electrical signal proportional to a stress (force or moment) applied to the monomorphic structure, and receiving circuitry (e.g., for signal processing and / or data processing). Such stress-mediated monomorphic structure piezoelectric acoustic sensors (also referred to herein as monomorphic piezoelectric sensors) benefit from (i) a stress-sensing modality that does not require displacement of a transduction component, and (ii) material selection of the tissue-facing outer (non-piezoelectric) component to minimize granulation tissue formation (e.g., from an immune response to implantation of an IMD). Furthermore, monomorphic piezoelectric sensors can exhibit substantially lower noise and substantially higher acoustic resolution for improved sensitivity over a dynamic range compared to displacement-mediated acoustic sensors, such as, for example, battery microphones or condenser microphones. In some embodiments, for example, the stress-mediated acoustic sensor includes a charge amplifier circuit for conditioning the electrical signal generated by the piezoelectric material in various embodiments of the stress-mediated acoustic sensor, including but not limited to, a monolithic piezoelectric sensor.

[0226] In some embodiments of a monolithic piezoelectric structure, the device structure includes an active piezoelectric material (e.g., a piezoelectric film) capable of applying or detecting stress and stability, a non-piezoelectric material (e.g., a metal substrate disposed on a side of the active piezoelectric material), and a lab load applied to the monolithic piezoelectric structure (e.g., on the metal substrate), causing a bending moment (stress) that propagates through the active piezoelectric film, thereby generating an electrical signal corresponding to the applied stress that can be detected as a mechanical force sensor, i.e., an acoustic signal (mechanical wave). In some embodiments of the acoustic sensor 111Y, the piezoelectric material of an exemplary monolithic piezoelectric sensor can include, but is not limited to, PZT (e.g., PZTPZT-5A, PZT-5H, or PZT-5K), PLZT, quartz, ZnO, AlN, ScAlN, BaTiO, PbTiO, KNbO, LiNbO, LiTaO, and / or NaWO. In some embodiments of the acoustic sensor 111Y, the non-piezoelectric material of the exemplary monomorphic piezoelectric sensor may include, but is not limited to, titanium (Ti), biocompatible stainless steel, cobalt chrome, nitinol, or high-purity ceramic (e.g., alumina Al2O3).

[0227] In the exemplary embodiment of the IMD 100 of FIGS. 20A and 20B , for example, a monomorphic piezoelectric sensor may be incorporated into a biocompatible, hermetically sealed housing structure for longevity and safety when implanted in a patient, while the non-piezoelectric component (e.g., Ti) is positioned on (or forms) the device housing and is exposed to the external environment (tissue-facing). The piezoelectric component (e.g., PZT material) is not exposed to the external environment of the IMD 100 but is instead contained within the hermetically sealed interior of the IMD. In such an embodiment, for example, the piezoelectric and non-piezoelectric materials are selected and engineered such that the monomorphic piezoelectric sensor is sensitive enough to receive and transmit low-amplitude acoustic signals over a large frequency range, i.e., with a large dynamic range. For example, the monomorphic piezoelectric sensor can measure and resolve sound levels as low as 20 dB SPL (e.g., barely above the human hearing threshold) and 110 dB SPL (e.g., approaching the human pain threshold).

[0228] 21A-21C show diagrams illustrating exemplary embodiments of a single-type piezoelectric sensor device according to the present invention, labeled 2111A, 2111B, and 2111C, respectively. FIG. 21A illustrates an exemplary embodiment of a single-type piezoelectric sensor device having at least one electrode electrically connected to a piezoelectric transducer material bonded to a biocompatible, electrically conductive, non-piezoelectric material. FIG. 21B illustrates an exemplary embodiment of a single-type piezoelectric sensor device having at least one electrode electrically connected to a piezoelectric transducer material bonded to a biocompatible, electrically non-conductive, non-piezoelectric material. FIG. 21C illustrates an exemplary embodiment of a single-type piezoelectric sensor device having at least two electrodes electrically connected to a piezoelectric transducer material.

[0229] As shown in FIG. 21A, the single piezoelectric sensor device 2111A includes a piezoelectric material 2112 disposed between and coupled to a first layer 2113 and a second layer 2115. The first layer 2113 includes a biocompatible, conductive, non-piezoelectric material and has a Young's modulus that is substantially the same as (e.g., within 2×-3×) or within 20% of (e.g., within 20%) that of the piezoelectric material. In implementations of the single piezoelectric sensor device 2111A, the first layer 2113 is configured to be a sensing layer that receives mechanical waves emanating from within the patient's body such that forces applied to the first layer 2113 are transmitted through and into the piezoelectric material 2112, which serves to transfer mechanical energy (stress) to electrical energy. The first layer 2113 is positioned within the single piezoelectric sensor device 2111A and positioned in the opening of the IMD, and the first layer 2113 is closely coupled to the IMD housing wall to hermetically seal other components of the single piezoelectric sensor device 2111A within the enclosure. The second layer 2115 includes a non-piezoelectric, electrically conductive material. In implementations of the single piezoelectric sensor device 2111A, the second layer 2115 provides at least one electrically addressable electrode for receiving an electrical signal generated from the piezoelectric material 2112, and the electrically conductive material of the first layer 2113 provides an electrically addressable electrode for the piezoelectric sensing unit. Furthermore, in some embodiments of the single piezoelectric sensor device 2111A, because the material of the first layer 2113 is biocompatible, the housing of the IMD (e.g., housing wall(s)) can be configured as the first layer 2113, thereby allowing the piezoelectric material 2112 (and second layer 2115) to be fabricated on areas of the IMD housing structure.

[0230] In some embodiments of the single-type piezoelectric sensor device 2111A, for example, the piezoelectric material includes PZT (e.g., PZTPZT-5A, PZT-5H, or PZT-5K), the first layer 2113 includes titanium, and the second layer 2115 includes at least one of other conductive materials including titanium, gold, platinum, silver, copper, nickel, aluminum, palladium, or alloys thereof. In such exemplary embodiments, the first layer 2113 is electrically conductive, biocompatible, mechanically matched (e.g., Young's modulus) to the piezoelectric material 2112, e.g., titanium PZT-5A, and the first layer 2113 can be coupled to an electronic unit 2020, as in the non-piezoelectric system, including the conductive material of the second layer 2115, and both sides of the piezoelectric material 2112 can be connected to an amplifier circuit to amplify the transduced electrical signal, i.e., the trapped charge generated by the piezoelectric material 2112 in response to the applied stress. The amplifier circuit can be configured as a charge amplifier (or other type of amplifier) ​​to condition, process, and pass the acoustic / stress signal for higher electronic functions by IMD, such as data processing, data storage, wireless transmission, or others.

[0231] Also, in some exemplary embodiments of the type 1 piezoelectric sensor device of the disclosed technology, the first layer 2113 may be composed of a material that is biocompatible but not conductive, and in such embodiments, an intermediate conductive layer is included in the type 1 piezoelectric sensor device, i.e., is bonded to the piezoelectric material 2112 and the first layer 2113.

[0232] 21B illustrates an exemplary embodiment of a single piezoelectric sensor device 2111B, comprising: (i) a piezoelectric material 2112 disposed between a first layer 2113B of a biocompatible, non-electrically conductive, non-piezoelectric material; and (ii) a conductive, non-piezoelectric second layer 2115, wherein the piezoelectric material 2112 is coupled to an intermediate layer 2116 comprising the second layer 2115 and the conductive, non-piezoelectric material. Also shown in the example of FIG. 1B, the first layer 2113B is positioned within the single piezoelectric sensor device 2111B and in the opening of the IMD housing, such that the first layer 2113B is intimately coupled to the IMD housing wall to hermetically seal the other components of the single piezoelectric sensor device 2111A within the enclosure. Similar to first layer 2113 of Figure 21A, Figure 2113B21B includes a biocompatible non-piezoelectric material having a Young's modulus that is close to (e.g., within 2X to 3X of) or substantially the same as (e.g., within 20% of) the Young's modulus of piezoelectric material 2112. In a monomorphic piezoelectric sensor device 2111B implementation, at least one electrode of second layer 2115 and conductive material of intermediate layer 2116 electrically interface with piezoelectric material 2112 and amplifier circuitry (e.g., of electronic unit 2020) to receive a transduced electrical signal generated from piezoelectric material 2112 for signal processing in the amplifier.

[0233] The single piezoelectric sensor devices 2111A and 2111B can be configured in a variety of shapes and geometries or the IMD in which they are used. In the example shown in Figures 21A and 21B, the single piezoelectric sensor devices 2111A and 2111B are configured with cylindrical and circular sensor profiles, and at least one electrically addressable electrode 2115 has piezoelectric material 2112 (e.g., the electrode 2115 has a radius b and the piezoelectric material 2112 has a radius a), as illustrated by the bottom view showing the top side of the devices 2111A and 2111B contained within the housing of an IMD. The bottom views of Figures 21A and 21B show stress vectors radiating from the center or tangent, respectively. σrr and σθθ, i.e., the radial and / or tangential stress vectors. The stress vectors add linearly to produce a net polarization (charge) in the piezoelectric material 2112.

[0234] 21C shows an exemplary embodiment of a monolithic piezoelectric sensor device 2111C including a circular / cylindrical / geometry measurement having two electrode structures, a central electrode 2115C and an annular electrode 2115A, separated from the central electrode 2115C by a gap c. The gap c provides an electrical discontinuity between the two electrode structures 2115C and 2115A, creating a voltage difference (potential) across the two electrodes, and when a mechanical wave is incident (i.e., first layer 2113 (i.e., tissue interface layer 2113 at an IMD), the compressive stress caused by the applied force or moment propagates through the piezoelectric material 2112, and dipoles within the material structure create an electric field by inducing different potentials across the two electrode structures, resulting in an addressable electrical signal across the central electrode 2115C and the annular electrode 2115A relative to the IMD.

[0235] The circular electrode, cylindrical shape of the exemplary monomorphic piezoelectric device 2111C shown in FIG. 21C has many advantages, including (but not limited to) the ability to provide uniform stress distribution in the material of the monomorphic piezoelectric device 2111C, as well as the reliability and safety of the device 2111 so that there are no hot spots that can nucleate fracture / crack propagation, particularly since the exemplary monomorphic piezoelectric device 2111C is part of a sealed enclosure for an implantable device, the circular / cylindrical configuration of the exemplary monomorphic piezoelectric device 2111C reduces potential degradation issues, such as stress risers and / or corners that create crack nucleation sites.

[0236] 22 shows a diagram illustrating an example geometry of an example embodiment of the single piezoelectric sensor device of FIG. 21A, designated as numeral 2211 in FIG. 22. The single piezoelectric sensor device 2211 includes at least two electrode structures of a second layer 2115, shown in the top view of FIG. 22 as a first electrode 2115X and a second electrode 2115Y, separated from each other by a gap and coupled to a piezoelectric material 2112 (e.g., positioned within the housing of the IMD so as to be exposed through an opening) that is coupled to the first layer 2113. As shown in 1211A, 1211B, and 1211C in FIG. 12, the at least two electrodes of the single piezoelectric sensor device 1211 may be configured in various shapes and configurations, including, but not limited to, rectangular, oval, and triangular, and may include three or more electrodes.

[0237] Integrated / interconnected in-vivo fluid flow sensor and in-vivo acoustic sensor 23 shows a diagram illustrating an exemplary embodiment of implantable medical device 100, labeled as IMD2300, illustrating an integrated device including an exemplary embodiment of in-vivo fluid flow sensor device 100X (in this exemplary embodiment, as in-vivo fluid flow sensor device 700B) and an exemplary embodiment of in-vivo acoustic sensor device 100Y (i.e., in this exemplary embodiment, as in-vivo acoustic sensor device 2000). In this example, in-vivo acoustic sensor device 2000 is coupled to clip band 703 of in-vivo fluid flow sensor device 700B such that electronic unit 2020 of device 2000 is in electrical and / or data communication with electronic unit 720 of device 700B. For example, in some embodiments of IMD 2300, the power source for IMD 2300 may be configured in only one of electronic unit 2020 or electronic unit 720, or similarly, the data processing unit for IMD 2300 may be configured in only one of electronic unit 2020 or electronic unit 720, and / or other components of electronic unit 2020 and electronic unit 720 may be shared and / or integrated. Also, for example, in-vivo acoustic sensor device 2000 may be in data communication with in-vivo fluid flow sensor device 700B, enabling data communication between electronic unit 2020 of device 2000 and electronic unit 720 of device 700B, which may be used for synchronized data collection and processing protocols of IMD 2300.

[0238] 24A is a diagram illustrating an exemplary embodiment of an implantable medical device 100, labeled as IMD 2400A, illustrating electrically and communicatively interconnected devices including an exemplary embodiment of an in-vivo fluid flow sensor device 100X (in this exemplary embodiment, as in-vivo fluid flow sensor device 700B) and an exemplary embodiment of an in-vivo fluid flow sensor device 100X (i.e., in this exemplary embodiment, as in-vivo acoustic sensor device 2000). In this example, in-vivo acoustic sensor device 2000 is electrically and / or communicatively connected to clip band 703 of in-vivo fluid flow sensor device 700B via a cable, wire, or cord (e.g., cable, wire, or cord 993 of a remote in-vivo device 990, etc.). In some embodiments of IMD 2400A, for example, electronics unit 2020 of device 2000 may be in electrical and / or data communication with electronics unit 720 of device 700B, thereby allowing various components of the respective electronic units to be shared and / or integrated. In this example, the in-vivo acoustic sensor device 2000 is in data communication (wired) with the in-vivo fluid flow sensor device 700B, allowing data communication between the electronics unit 2020 of device 2000 and the electronics unit 720 of device 700B, which can be used for the synchronized data collection and processing protocol of IMD2400A.

[0239] 24B is a diagram showing an exemplary embodiment of implantable medical device 100, labeled as IMD2400B, illustrating a wireless communication capable interconnection device including an exemplary embodiment of in-vivo fluid flow sensor device 100X (in this exemplary embodiment, as in-vivo fluid flow sensor device 700B) and an exemplary embodiment of in-vivo fluid flow sensor device 100X (i.e., in this exemplary embodiment, as in-vivo acoustic sensor device 2000). In this example, in-vivo acoustic sensor device 2000 wirelessly communicates with in-vivo fluid flow sensor device 700B, enabling data communication between electronics unit 2020 of device 2000 and electronics unit 720 of device 700B, which can be used for synchronous data collection and processing protocols of IMD2400B.

[0240] Example In some embodiments (Example A1) according to the present invention, a sensor device for in vivo monitoring of fluid flow within an anatomical structure comprises: a first ultrasonic assembly including a first set of one or more acoustic transducer elements in a major blood vessel of the heart; a second ultrasonic assembly including a second set of one or more acoustic transducer elements; a first linkage coupled to the first ultrasonic assembly; a second linkage coupled to the second ultrasonic assembly; and an electronic unit in electrical communication with the first ultrasonic assembly and the second ultrasonic assembly, wherein the electronic unit is configured to process electrical signals associated with returned acoustic signals as data and wirelessly transmit the data to an external processor; and a spring connection device coupled to each of the first and second linkages, positioning the first ultrasonic assembly at a first position on the anatomical structure and positioning the second ultrasonic assembly at a second position on the anatomical structure to form a plane across the first and second positions of the anatomical structure, and operable to transmit and receive acoustic signals from the first set of one or more acoustic transducer elements and the second set of one or more acoustic transducer elements indicative of fluid flow parameters of a biological fluid within the anatomical structure.

[0241] Example A2 includes the sensor device according to any one of Examples A1 to A4, where the anatomical structure is a heart.

[0242] Example A3 includes a sensor device described in any of Examples A1 to A4, wherein the first position and the second position are positioned over the left atrium of the heart and the plane through which the acoustic signals are transmitted and received intersects at the mitral valve of the heart.

[0243] Example A4 includes the sensor device of any of Examples A1 to A3, wherein the first position and the second position are positioned over the right atrium of the heart and the plane through which the acoustic signals are transmitted and received intersects at the tricuspid valve of the heart.

[0244] In some embodiments (Example B1) according to the present invention, a sensor device for in vivo monitoring of fluid flow within an anatomical structure comprises: a linkage assembly having a first arm configured to be attached to a first portion of the anatomical structure and a second arm configured to be attached to a second portion of the anatomical structure opposite the first portion; a connection device coupled to each of the first arm and the second arm; an ultrasonic sensor assembly including a plurality of acoustic transducer elements coupled to the linkage assembly, wherein the plurality of acoustic transducer elements include a first acoustic transducer element configured to transmit an acoustic signal to propagate through the anatomical structure, and a second acoustic transducer element and a third acoustic transducer element configured to propagate through the anatomical structure and receive an acoustic signal indicative of a fluid flow parameter of a biological fluid within the anatomical structure; and an electronic unit housed within the connection device and in electrical communication with the plurality of acoustic transducer elements of the ultrasonic sensor assembly, wherein the electronic unit is configured to process an electrical signal associated with the received acoustic signal as data and wirelessly transmit the data to an external processor.

[0245] Example B2 includes the sensor device of any of Examples B1 to B50, and the ultrasonic sensor assembly includes a first ultrasonic sensor assembly disposed on a first arm of the linkage assembly and a second ultrasonic sensor assembly disposed on a second arm of the linkage assembly.

[0246] Example B3 includes the sensor device of example B2 or any of Examples B1-B50, wherein the first ultrasonic sensor assembly includes a first acoustic transducer element positioned on a distal region of the first arm and configured to transmit acoustic signals to interface with a first portion of the anatomy; the second ultrasonic sensor assembly includes second and third acoustic transducer elements positioned on a distal region of the second arm and configured to receive the acoustic signals to interface with a second portion of the anatomy; and Tx ) is located between the center distance (d) of the second acoustic transducer element and the third acoustic transducer element, and the second center point (CdRx ) and align.

[0247] Example B4 includes the sensor device of example B2 or any of Examples B1-B50, wherein the first ultrasonic sensor assembly includes a first acoustic transducer element positioned on a distal region of the first arm and configured to transmit acoustic signals to interface with a first portion of the anatomical structure; the second ultrasonic sensor assembly includes second and third acoustic transducer elements positioned on the distal region of the second arm and configured to receive acoustic signals to interface with the second portion of the anatomical structure; the first ultrasonic sensor assembly further includes fourth and fifth acoustic transducer elements positioned on the distal region of the second arm and interface with the second portion of the anatomical structure and configured to receive a first set of acoustic signals associated with transmission of the acoustic signals by the first acoustic transducer elements; the second ultrasonic sensor assembly includes a sixth acoustic transducer element positioned on the distal region of the first arm and interface with the first portion of the anatomical structure and configured to transmit second acoustic signals associated with the acoustic signals received at the second and third acoustic transducer elements; Tx1 ) is a first distance (d Rx1 1) and the second center point (Cd Rx1 ) and a third center point (C Tx2 ) is the second distance (d Rx2 2) and the fourth center point (Cd Rx2 ) and align.

[0248] Example B5 includes the sensor device of any of Examples B1 to B50, wherein the plurality of acoustic transducer elements of the ultrasonic sensor assembly are disposed on a first arm of the linkage assembly, and the sensor device further includes a reflector disposed on a second arm of the linkage assembly.

[0249] Example B6 includes the sensor device of any of Examples B1 to B50, wherein at least one of the first acoustic transducer element, the second acoustic transducer element, or the third acoustic transducer element is configured to have a size dimension of 1 mm to 4 mm.

[0250] Example B7 includes the sensor device of any of Examples B1 to B50, wherein the ultrasonic sensor assembly further includes a base connected to an inward-facing surface of at least one of the first arm or the second arm of the linkage assembly and coupling at least one of the plurality of acoustic transducer elements.

[0251] Example B8 includes the sensor device of example B7 or any of examples B1-B50, wherein the substrate is configured to provide thermal synchronization for management of heat generation by the at least one acoustic transducer element.

[0252] Example B9 includes the sensor device of any of Examples B1-B50, wherein at least one of the plurality of acoustic transducer elements includes a piezoelectric micromachined ultrasonic transducer (PMUT).

[0253] Example B10 includes the sensor device of any of Examples B1-B50, wherein the sensor device further includes acoustic transducer pads coupled to at least some of the acoustic transducer elements of the ultrasonic sensor assembly and configured to provide contouring and cushioning against an anatomical structure.

[0254] Example B11 includes the sensor device of Example B10 or any of Examples B1-B50, wherein the acoustic transducer pad includes a hydrogel.

[0255] Example B12 includes the sensor device of any of Examples B1-B50, wherein the linkage assembly is operable to flexibly secure the sensor device to the anatomical structure so as to withstand continuous movement of the anatomical structure to which it is attached while remaining stable in its position relative to the anatomical structure.

[0256] Example B13 includes the sensor device of example B12 or any of examples B1-B50, wherein the linkage assembly includes a clip band operable to provide a compressive force by each of the first and second arms of the clip band to facilitate securing the sensor device to the first and second portions of the anatomical structure, and to absorb forces exerted by the anatomical structure on the first and second arms of the clip band due to continuous movement of the anatomical structure.

[0257] Example B14 includes the sensor device of Example B13 or any of Examples B1-B50, wherein the clip band includes a composite material having a flexible polymer component and a shape stabilizer component that is pre-formed and capable of undergoing a shape change.

[0258] Example B15 includes the sensor device of example B14 or any of examples B1-B50, wherein the shape stabilizer component of the composite includes one or more of nitinol, gold, platinum, or iridium, encased in a polymer component of the composite including one or more of silicone, polyethylene, polyimide, polyamide, or mixtures thereof.

[0259] Example B16 includes the sensor device of any of Examples B1-B50, wherein the connection device is operable to mechanically resiliently secure the linkage assembly to the anatomical structure such that the sensor device is stable in its position relative to the anatomical structure while withstanding continuous movement of the anatomical structure to which it is attached.

[0260] Example B17 includes the sensor device of example B16 or any of examples B1-B50, wherein the connection device includes a spring operable to provide a compressive force to each of the first and second arms of the linkage assembly to facilitate securing the sensor device to the first and second portions of the anatomical structure and to absorb forces exerted by the anatomical structure on the first and second arms of the linkage assembly due to continuous movement of the anatomical structure.

[0261] Example B18 includes the sensor device of any of Examples B1 to B50, wherein the electronic unit includes a power source and a wireless communication unit including a wireless transmitter or a wireless transceiver.

[0262] Example B19 includes the sensor device of example B18 or any of examples B1 to B50, and the power source includes at least one of a battery or a fuel cell.

[0263] Example B20 includes the sensor device of any of Examples B18 or B1-B50, wherein the electronics unit comprises a signal conditioning unit in communication with the plurality of acoustic transducer elements of the ultrasonic sensor assembly via one or more electrical interface components, the signal conditioning unit comprising electrical circuitry configured to process an electrical signal associated with the received acoustic signal by one or more of amplifying the electrical signal, filtering the electrical signal, or converting the electrical signal from analog to digital.

[0264] Example B21 includes the sensor device of Example B20 or any of Examples B1-B50, wherein the electronic unit comprises a data processing unit in communication with the signal conditioning unit, the data processing unit comprising a processor and memory and configured to process the amplified, filtered, or converted electrical signal as data representative of a fluid flow parameter of the biological fluid.

[0265] Example B22 includes the sensor device of Example B18 or any of Examples B1 to B50, wherein the electronic unit includes a data processing unit in communication with the wireless communication unit, and the data processing unit includes a processor and memory and is configured to process the electrical signal as data representing a fluid flow parameter of the biological fluid.

[0266] Example B23 includes the sensor device of Example B18 or any of Examples B1 to B50, wherein the electronic unit comprises a printed circuit board (PCB) having a substrate and electrical interconnects disposed on the substrate, and the electrical interconnects are coupled to a plurality of electrical interconnect wires extending between the plurality of acoustic transducer elements of the ultrasonic sensor assembly and the PCB of the electronic unit.

[0267] Example B24 includes the sensor device of example B23 or any of examples B1 to B50, wherein the electronic unit comprises a casing that contains the electronic unit to protect the electronic unit from exposure to bodily fluids when the sensor device is inserted and deployed in vivo.

[0268] Example B25 includes the sensor device of example B24 or any of examples B1-B50, wherein the casing includes one or both of flat sides or curved sides to provide a form factor of the sensor device, including at least one of a rectangular, cylindrical, conical, elliptical, pyramidal, trapezoidal, or non-uniform shape.

[0269] Example B26 includes the sensor device of example B24 or any of examples B1-B50, and includes: the casing is coupled to the linkage assembly on an inward facing surface of the linkage assembly that faces toward the anatomical structure; or the casing is coupled to the linkage assembly on an outward facing surface of the linkage assembly that faces away from the anatomical structure.

[0270] Example B27 includes the sensor device of example B24 or any of examples B1-B50, wherein the PCB of the electronic unit is sealed within the casing with an impermeable material covering the PCB and providing an electrical shield from the bodily fluids.

[0271] Example B28 includes the sensor device of example B27 or any of examples B1-B50, wherein the non-permeable material includes at least one of a parylene, a urethane, or a Teflon material.

[0272] Example B29 includes the sensor device of any of Examples B1 to B50, and further includes a secondary sensor coupled to at least one of the linkage assembly or the connection device and in communication with the electronic unit, the secondary sensor operable to measure one or more biological parameters, physiological parameters, electrophysiological parameters, or physical parameters of a body in which the sensor device is deployed.

[0273] Example B30 includes the sensor device of example B29 or any of examples B1-B50, wherein the secondary sensor includes an analyte sensor configured to detect an analyte of a biological fluid or bodily fluid in an area proximate to an anatomical structure in which the sensor device is deployed.

[0274] Example B31 includes the sensor device of example B29 or any of examples B1-B50, wherein the secondary sensor includes a pH sensor configured to detect the pH level of a biological fluid within the anatomical structure in which the sensor device is deployed, or within an area adjacent to the anatomical structure.

[0275] Example B32 includes the sensor device of example B29 or any of examples B1-B50, wherein the secondary sensor includes a temperature sensor configured to detect the temperature of a biological fluid within the anatomical structure in which the sensor device is deployed or within an area proximate to the anatomical structure.

[0276] Example B33 includes the sensor device of example B29 or any of examples B1-B50, wherein the secondary sensor includes an inertial measurement unit (IMU) configured to detect movement of the sensor device in multiple degrees of freedom.

[0277] Example B34 includes the sensor device of any of Examples B1-B50, further including a secondary attachment component including one or more of a suture, prongs, screws, barbs, adhesive, or gripping mechanism disposed on at least a portion of the linkage assembly and configured to secure the ultrasonic sensor assembly to an anatomical structure via the linkage assembly.

[0278] Example B35 includes the sensor device of any of Examples B1-B50, wherein the linkage assembly has the ability to change shape from a first shape configuration and expand to a second shape configuration such that the first arm and the second arm of the linkage assembly are insertable into a patient's body outward from a centerline through at least one of the linkage assembly or the connecting device, and the first arm and the second arm of the linkage assembly extend inward toward the centerline through at least one of the linkage assembly or the connecting device such that the sensor device is attachable to an anatomical structure for operation.

[0279] Example B36 includes the sensor device of any of Examples B1-B50, and includes a second linkage assembly having a third arm configured to be attached to a third portion of the anatomical structure and a fourth arm configured to be attached to a fourth portion of the anatomical structure opposite the third portion, a connecting device coupled to each of the third arm and the fourth arm, and an ultrasonic sensor assembly coupled to the second linkage assembly and including an additional set of multiple acoustic transducer elements configured to transmit second acoustic signals that propagate through the anatomical structure across the third and fourth portions and receive a second set of acoustic signals that propagate through the anatomical structure across the third and fourth portions and are indicative of a second fluid flow parameter of the biological fluid within the anatomical structure.

[0280] Example B37 includes the sensor device of any of Examples B1-B50, wherein the connection device includes a port in electrical communication with an electronic unit housed within the connection device and operable to electrically couple to a remote power source housed within the remote device via at least one of a cable, wire, or cord, and the remote device is located at another location distinct from and at a distance from the anatomical structure.

[0281] Example B38 includes the sensor device of example B37 or any of examples B1-B50, wherein the port is housed within the connection device and is operable to interface the electronic unit to a data processing unit located in the remote device via at least one of a cable, wire, or cord, and to output data from the electronic unit of the sensor device through the port to the data processing unit of the remote device via at least one of the cable, wire, or cord.

[0282] Example B39 includes the sensor device of example B38 or any of examples B1-B50, wherein the sensor device is configured to wirelessly transmit data to an external processor via a secondary transmitting device that includes a wireless transmitter or transceiver.

[0283] Example B40 includes the sensor device of example 37 or any of examples B1-B50, wherein the other location where the remote device is located is at least 2 cm from the anatomical structure.

[0284] Example B41 includes the sensor device of example 37 or any of examples B1-B50, and the other location includes the pleural cavity, the intraperitoneal cavity, the subcutaneous space, or an extracorporeal location.

[0285] Example B42 includes the sensor device of any of Examples B1-B50, wherein an external processor capable of receiving data wirelessly transmitted by the electronic unit of the sensor device is located outside the patient-user's body where the sensor device is implantable and deployable in an anatomical structure.

[0286] Example B43 includes the sensor device of any of Examples B1-B50, wherein the fluid flow parameters of the biological fluid in the anatomical structure include at least one of a flow rate or an amount of pressure difference between ends of a flow path in the anatomical structure.

[0287] Example B44 includes the sensor device of example B43 or any of examples B1-B50, wherein the device is operable to detect a size dimension of an anatomical structure or a predicted area or volume of an anatomical structure based on a baseline measurement of flow rate and a change in flow rate over time.

[0288] Example B45 includes the sensor device of any of Examples B1 to B50, wherein the anatomical structure is a heart and the biological fluid is blood.

[0289] Example B46 includes the sensor device of example B45 or any of examples B1-B50, wherein the sensor device is deployable within at least one layer of the pericardium of the heart, or the sensor device is deployable on an outer layer of the pericardium of the heart.

[0290] Example B47 includes the sensor device of Example B45 or any of Examples B1-B50, wherein the first arm and the second arm of the linkage assembly are positioned on opposite portions of the left atrium of the heart, and the received acoustic signal is indicative of blood flow at the mitral valve of the heart.

[0291] Example B48 includes the sensor device of Example B45 or any of Examples B1-B50, wherein the first arm and the second arm of the linkage assembly are positioned on opposite portions of the right atrium of the heart, and the received acoustic signal indicates blood flow at the tricuspid valve of the heart.

[0292] Example B49 includes the sensor device of Example B45 or any of Examples B1-B50, wherein the first arm and the second arm of the linkage assembly are positioned over the superior vena cava or the inferior vena cava adjacent to the heart, and the received acoustic signal indicates blood flow in the superior vena cava or the inferior vena cava.

[0293] Example B50 includes the sensor device of Example B45 or any of Examples B1 to B49, wherein the first arm and the second arm of the linkage assembly are positioned on a pulmonary artery or pulmonary vein adjacent to the heart, and the received acoustic signal indicates blood flow in the pulmonary artery or pulmonary vein.

[0294] In some embodiments (Example B51) according to the present invention, a sensor device for in vivo monitoring of blood flow in a heart or blood vessel leading to or from a heart within a patient's body includes a linkage assembly including a first arm configured to be attached to a first portion of the heart or blood vessel and a second arm configured to be attached to a second portion of the heart or blood vessel, a connecting device coupled to each of the first arm and the second arm, and an ultrasonic sensor assembly including a plurality of acoustic transducer elements coupled to the linkage assembly, the first acoustic transducer element configured to transmit an acoustic signal for propagation through the heart or blood vessel, and the plurality of acoustic transducer elements configured to transmit an acoustic signal for propagation through the heart or blood vessel and for measuring a fluid flow parameter of the blood flowing within the heart or blood vessel. and an electronic unit housed within the connecting device and in electrical communication with the plurality of acoustic transducer elements of the ultrasonic sensor assembly, wherein the electronic unit is configured to process the electrical signals associated with the received acoustic signals as data and wirelessly transmit the data to an external processor. The linkage assembly includes a clip band operable to provide a compressive force by each of the first and second arms of the clip band to facilitate securing the sensor device to the first and second portions of the heart or blood vessel, and to absorb forces exerted on the first and second arms of the clip band due to heartbeat or changes in size of the heart or blood vessel.

[0295] Example B52 includes the sensor device of any of Examples B51-B60, wherein the clip band includes a composite material having a flexible polymer component and a shape stabilizer component that is pre-formed and capable of undergoing a shape change.

[0296] Example B53 includes the sensor device of example B52 or any of examples B51-B60, wherein the shape stabilizer component of the composite includes one or more of nitinol, gold, platinum, or iridium, and is encased in a polymer component of the composite including one or more of silicone, polyethylene, polyimide, polyamide, or mixtures thereof.

[0297] Example B54 includes the sensor device of any of Examples B51 to B60, wherein the ultrasonic sensor assembly includes a first ultrasonic sensor assembly disposed on a first arm of the clip band and a second ultrasonic sensor assembly disposed on a second arm of the clip band, wherein the plurality of acoustic transducer elements of the ultrasonic sensor assembly are disposed on the first arm of the clip band, and the sensor device further includes a reflector disposed on the second arm of the clip band.

[0298] Example B55 includes the sensor device of any of Examples B51-B60, wherein the sensor device further includes an acoustic transducer pad coupled to at least some of the acoustic transducer elements of the ultrasonic sensor assembly and including a hydrogel configured to provide contouring and cushioning to the heart or blood vessel.

[0299] Example B56 includes the sensor device of any of Examples B51-B60, wherein the sensor device is deployable within at least one layer of the pericardium of the heart, or the sensor device is deployable on an outer layer of the pericardium of the heart.

[0300] Example B57 includes the sensor device of any of Examples B51 to B60, wherein the first arm and the second arm of the clip band are positioned on opposite portions of the left atrium of the heart, and the received acoustic signal is indicative of blood flow at the mitral valve of the heart.

[0301] Example B58 includes the sensor device of any of Examples B51 to B60, wherein the first arm and the second arm of the clip band are positioned on opposite portions of the right atrium of the heart, and the received acoustic signal is indicative of blood flow at the tricuspid valve of the heart.

[0302] Example B59 includes the sensor device of any of Examples B51 to B60, wherein the first arm and the second arm of the clip band are positioned on the superior vena cava or the inferior vena cava adjacent to the heart, and the received acoustic signal indicates blood flow in the superior vena cava or the inferior vena cava.

[0303] Example B60 includes the sensor device of any of Examples B51 to B59, wherein the first arm and the second arm of the clip band are positioned over a pulmonary artery or pulmonary vein adjacent to the heart, and the received acoustic signal indicates blood flow in the pulmonary artery or pulmonary vein.

[0304] In some embodiments (Example B61) according to the present invention, a system for in vivo monitoring of fluid flow within an anatomical structure includes an in vivo sensor device operable to be deployed on a patient-user's body and attached to the anatomical structure, and a data processing system in data communication with the in vivo sensor device. The in-vivo sensor device comprises: a linkage assembly including a first arm configured to be attached to a first portion of the anatomical structure and a second arm configured to be attached to a second portion of the anatomical structure opposite the first portion; a connection device coupled to each of the first and second arms; an ultrasonic sensor assembly including a plurality of acoustic transducer elements coupled to the linkage assembly, the plurality of acoustic transducer elements including a first acoustic transducer element configured to transmit an acoustic signal to propagate through the anatomical structure, a second acoustic transducer element configured to receive an acoustic signal that propagates through the anatomical structure and is indicative of a fluid flow parameter of a biological fluid within the anatomical structure, and a third acoustic transducer element; and an electronics unit housed within the connection device and in electrical communication with the plurality of acoustic transducer elements of the ultrasonic sensor assembly, the electronics unit configured to process electrical signals associated with the received acoustic signals as data and wirelessly transmit the data to an external processor. The data processing system includes a processor and a memory and is configured to receive data from the in-vivo sensor device and process the received data to determine a fluid flow parameter associated with the biological fluid within the anatomical structure.

[0305] Example B62 includes the sensor device of any of Examples B61-B72, wherein the in-vivo sensor device includes one or more features associated with the sensor device recited in any of Examples B1-B50 and / or Examples B51-B60.

[0306] Example B63 includes a sensor device of any of Examples B61 to B72, and is equipped with a remote in-vivo intermediate device having a power source, a wireless communication unit including at least one of a transmitter or a transceiver, and a data processing unit including a data processor and a data memory, wherein the remote in-vivo intermediate device is in wireless or wired communication with the in-vivo sensor device and is located in another location in the body that is different from the anatomical structure and at a distance from the anatomical structure.

[0307] Example B64 includes the sensor device of Example B63 or any of Examples B61 to B72, wherein the in-vivo sensor device is in wired communication with a remote in-vivo intermediate device via at least one of a cable, wire, or cord that is coupled to a port of a connection device of the in-vivo sensor device that electrically communicates with the electronic unit of the in-vivo sensor device, and the remote in-vivo intermediate device is operable to supply electrical energy stored in the power source to the electronic unit of the in-vivo sensor device.

[0308] Example B65 includes the sensor device of example B63 or any of examples B61 to B72, wherein the remote in-vivo intermediate device is operable to interface the electronic unit of the in-vivo sensor device to a data processing unit located within the remote in-vivo intermediate device to process data and determine fluid flow parameters associated with biological fluid within the anatomical structure.

[0309] Example B66 includes the sensor device of example B63 or any of examples B61 to B72, wherein the remote in-vivo intermediate device is operable to interface the electronic unit of the in-vivo sensor device to a wireless communication unit disposed within the remote in-vivo intermediate device to wirelessly transmit data directly or indirectly to a data processing system.

[0310] Example B67 includes the sensor device of example B63 or any of examples B61-B72, wherein the other location where the remote device is located is at least 2 cm from the anatomical structure.

[0311] Example B68 includes the sensor device of example B63 or any of examples B61-B72, and the other location includes the pleural cavity, the intraperitoneal cavity, the subcutaneous space, or an extracorporeal location.

[0312] Example B69 includes a sensor device of any of Examples B61 to B72, and a data processing system includes a server computer having a processor and memory, and one or more databases in data communication with the server computer, and the data processing system is configured to remotely monitor data associated with the patient-user acquired by the sensor device.

[0313] Example B70 includes the sensor device of any of Examples B61 to B72, and further includes a receiver device including a processor and memory operable to (i) receive wirelessly transmitted carrier data indicative of an electrical signal acquired from the sensor device, and (ii) transmit the data to a data processing system.

[0314] Example B71 includes the sensor device of example B64 or any of examples B61 to B72, and the receiver device is configured to store data in a memory of the receiver device, and / or the receiver devices communicate with each other and with a data processing system via a network of computers accessible via the Internet.

[0315] Example B72 further includes a remote client computing device including a sensor device of any of Examples B61 to B71, and including a data processor and a data memory configured to communicate data with the data processing system and receive processed data that is selected, filtered, and / or formatted by the data processing system.

[0316] In some embodiments (Example B73) according to the present invention, a sensor device for monitoring cardiac function in vivo includes a linkage assembly having a first arm configured to be attached to a first external portion of the heart and an optional second arm that may be configured to be attached to a second external portion of the heart, a housing coupled to the linkage assembly, a sensor assembly coupled to the first arm and configured to detect a functional parameter of the heart, and an electronic unit disposed within the housing and in electrical communication with the sensor assembly, wherein the electronic unit is configured to process an electrical signal associated with the detected functional parameter as data and wirelessly transmit the data to an external processor.

[0317] Example B74 includes the sensor device of any of examples B73-B76, wherein the sensor device is deployable within at least one layer of the pericardium of the heart, or the sensor device is deployable on an outer layer of the pericardium of the heart.

[0318] Example B75 includes the sensor device of any of examples B73-B76, wherein the sensor assembly includes at least one of an accelerometer, a gyroscope, a magnetometer, an acoustic transducer, a temperature sensor, an analyte sensor, or a pH sensor.

[0319] Example B76 includes the sensor device of any of Examples B73-B76, wherein the sensor device includes one or more features associated with the sensor device recited in any of Examples B1-B50 and / or Examples B51-B60.

[0320] In some embodiments according to the present invention (Example C1), the implantable medical device (IMD) includes an acoustic sensor.

[0321] Example C2 includes the IMD of example C1 or any of examples C1-C25, where the IMD includes an electronic component and a housing that encapsulates the electronic component.

[0322] Example C3 includes the IMD of example C1 or any of examples C1-C25, where the housing provides a hermetic seal around the electronic component.

[0323] Example C4 includes the IMD of Example C1 or any of Examples C1-C25, where the housing is formed from a material that is biocompatible and optionally includes an organic polymer.

[0324] Example C5 includes the IMD of example C2 or any of examples C1-C25, where the acoustic sensor is a microphone.

[0325] Example C6 includes the IMD of example C5 or any of examples C1-C25, wherein the microphone comprises a flexible membrane that undergoes deflection in response to acoustic waves contacting an outer surface of the flexible membrane, the membrane being a component of the housing, and the microphone further comprises an electronic component responsive to the deflection.

[0326] Example C7 includes the IMD of example C6 or any of examples C1-C25, where the deflection-responsive electronic component includes a strain gauge.

[0327] Example C8 includes the IMD of example C6 or any of examples C1-C25, where the deflection-responsive electronic component includes a piezoelectric element.

[0328] Example C9 includes the IMD of any of Examples C6 or C1-C25, wherein the deflection-responsive electronic component includes a fixed-position electrode that does not change position relative to the flexible membrane when the flexible membrane is deflected in response to acoustic waves contacting the outer surface of the flexible membrane.

[0329] Example C10 includes the IMD of example C6 or any of examples C1-C25, wherein the deflection-responsive electronic component includes an electronic condenser element.

[0330] Example C11 includes the IMD of example C6 or any of examples C1-C25, wherein the deflection-responsive electronic component includes a capacitive electrode.

[0331] Example C12 includes the IMD of example C6 or any of examples C1-C25, in which the deflection-responsive electronic component is affixed to the inner surface of the flexible membrane.

[0332] Example C13 includes the IMD of example C2 or any of examples C1-C25, where the acoustic sensor is an accelerometer referred to as an acoustic accelerometer.

[0333] Example C14 includes the IMD of example C13 or any of examples C1-C25, where ...

Claims

1. 1. An implantable medical device comprising: an in-vivo fluid flow sensor; an in-vivo acoustic sensor; and

2. 10. The device of claim 1, wherein the in-vivo fluid flow sensor is configured to transmit an ultrasonic signal to propagate through an anatomical structure and detect the ultrasonic signal that has propagated through the anatomical structure indicative of fluid flow of a biological fluid within the anatomical structure.

3. the in-vivo fluid flow sensor comprising: a linkage assembly comprising a first arm configured to attach to a first portion of the anatomical structure and a second arm configured to attach to a second portion of the anatomical structure opposite the first portion; an ultrasonic sensor assembly including a plurality of ultrasonic transducer elements coupled to the linkage assembly;

4. 4. The device of claim 3, wherein the plurality of ultrasonic transducer elements comprises a first ultrasonic transducer element configured to transmit the ultrasonic signal to propagate through the anatomical structure, and a second ultrasonic transducer element and a third ultrasonic transducer element configured to receive the ultrasonic signal indicative of a fluid flow parameter of the biological fluid within the anatomical structure that has propagated through the anatomical structure.

5. The device of claim 1 , wherein the in-vivo acoustic sensor is configured to detect acoustic signals emanating from an internal body structure.

6. the in-vivo acoustic sensor a sealed housing; 6. The device of claim 5, further comprising: a transducer element configured to receive acoustic signals emanating from the internal body structure so as to convert energy of the received acoustic signals into electrical signals indicative of a physiological function by the internal body structure.

7. The apparatus of claim 1 , wherein the in-vivo acoustic sensor comprises a displacement-mediated acoustic sensor for measuring changes in the structure of a transducer element caused by an acoustic signal on the transducer element.

8. The device of claim 7 , wherein the in-vivo acoustic sensor comprises a microphone.

9. The device of claim 7 , wherein the in-vivo acoustic sensor comprises an accelerometer.

10. The apparatus of claim 7 , wherein the in-vivo acoustic sensor comprises a strain gauge.

11. The device of claim 7 , wherein the in-vivo acoustic sensor comprises a pressure sensor.

12. The apparatus of claim 1 , wherein the in-vivo acoustic sensor comprises a stress-mediated acoustic sensor operable to measure stress caused by an acoustic signal applied onto a transducer element.

13. The device of claim 12 , wherein the in-vivo acoustic sensor comprises a monolithic piezoelectric sensor device.

14. The device of claim 1 , wherein the acoustic signal comprises a transmission of mechanical energy propagating in an in vivo medium comprising one or more of a gas, a liquid, or a solid.

15. 10. The apparatus of claim 1, comprising: an in-vivo fluid flow sensor; and an electronics unit in electrical communication with the in-vivo acoustic sensor, the electronics unit being within a hermetically sealed casing.

16. 16. The apparatus of claim 15, wherein the electronic unit comprises a signal processing unit and a wireless communication unit configured to process electrical signals associated with the detected ultrasonic signals and / or the detected acoustic signals as data and to transmit the data wirelessly to an external processor.

17. 16. The device of claim 15, wherein the electronic unit comprises a power source.

18. 16. The apparatus of claim 15, wherein the signal processing unit comprises signal conditioning circuitry configured to process the electrical signal associated with the received ultrasound signal by one or more of amplifying the electrical signal, filtering the electrical signal, or converting the electrical signal from analog to digital.

19. 20. The device of claim 18, wherein the electronics unit comprises a data processing unit in communication with the signal conditioning circuitry, the data processing unit comprising a processor and a memory and configured to process the amplified, filtered or converted electrical signals as biomedical data.

20. 16. The device of claim 15, wherein the electronic unit comprises a printed circuit board (PCB) having a base and electrical interconnects disposed on the base, the electrical interconnects being coupled to a plurality of electrical interconnect wires extending between sensors of the in-vivo fluid flow sensor and the in-vivo acoustic sensor.

21. 1. An implantable medical device for in vivo monitoring of an anatomical structure from within the body of a host, comprising: an in-vivo fluid flow sensor, the in-vivo fluid flow sensor comprising: a linkage assembly including a first arm configured to attach to a first portion of the anatomical structure and a second arm configured to attach to a second portion of the anatomical structure opposite the first portion; a connection device coupled to each of the first arm and the second arm; an ultrasonic sensor assembly comprising a plurality of ultrasonic transducer elements coupled to the linkage assembly, the plurality of ultrasonic transducer elements including a first ultrasonic transducer element configured to transmit an ultrasonic signal to propagate through the anatomical structure, and a second ultrasonic transducer element and a third ultrasonic transducer element configured to receive ultrasonic signals propagated through the anatomical structure indicative of a fluid flow parameter of a biological fluid within the anatomical structure; The medical device further comprises an in-vivo acoustic sensor, the in-vivo acoustic sensor comprising: a sealed housing; a transducer element configured to receive acoustic signals emanating from a source within the host's body so as to convert energy of the received acoustic signals into electrical signals indicative of a physiological function of the source within the host's body; The medical device further includes an electronic unit at least partially contained in the connection device of the in-vivo fluid flow sensor and / or at least partially contained in the sealed housing of the in-vivo fluid flow sensor, the electronic unit being in electrical communication with the plurality of ultrasonic transducer elements of the ultrasonic sensor assembly and in electrical communication with the transducer elements of the in-vivo acoustic sensor, the electronic unit being configured to process the received ultrasonic signals and electrical signals associated with the received acoustic signals as data and to wirelessly transmit the data to an external processor.

22. The apparatus of claim 21 , wherein the in-vivo acoustic sensor comprises a stress-mediated acoustic sensor.

23. 23. The device of claim 22, wherein the transducer element comprises a piezoelectric material.

24. The piezoelectric material may be lead zirconate titanate (PZT), lead lanthanum zirconate titanate (PLZT), zinc oxide (ZnO), quartz, polyvinylidene fluoride or polyvinylidene difluoride (PVDF), aluminum nitride (AlN), scandium aluminum nitride (ScAlN), barium titanate (BaTiO 3 ), lead titanate (PbTiO 3 ), potassium niobate (KNbO 3 ), lithium niobate (LiNbO 3 ), lithium tantalate (LiTaO 3 ), and / or sodium tungstate (Na 2 WO 4 24. The apparatus of claim 23, comprising one or more of:

25. The stress-mediated acoustic sensor comprises a monomorphic piezoelectric sensor, the monomorphic piezoelectric sensor comprising: a biocompatible, electrically conductive, non-piezoelectric material coupled to a first side of the piezoelectric material and configured to face outwardly of the in-vivo acoustic sensor within the sealed housing, the biocompatible, electrically conductive, non-piezoelectric material having a Young's modulus that is between two and three times that of the piezoelectric material; an electrically conductive non-piezoelectric material coupled to a second side of the piezoelectric material opposite the first side; 24. The device of claim 23, wherein the biocompatible, electrically conductive, non-piezoelectric material is configured to receive an applied force resulting from the acoustic signal emitted from the source within the host's body, such that stress caused by the applied force on the biocompatible, electrically conductive, non-piezoelectric material is transmitted through and into the piezoelectric material to convert the stress into electrical energy corresponding to the electrical signal captured in the conductive, non-piezoelectric material.

26. 26. The device of claim 25, wherein the biocompatible, electrically conductive, non-piezoelectric material comprises one or more of titanium (Ti), biocompatible stainless steel, cobalt chromium alloy, nitinol, or combinations thereof.

27. The stress-mediated acoustic sensor comprises a monomorphic piezoelectric sensor, the monomorphic piezoelectric sensor comprising: a biocompatible, electrically insulating, non-piezoelectric material configured within the sealed housing and facing outwardly of the in-vivo acoustic sensor, the biocompatible, electrically insulating, non-piezoelectric material having a Young's modulus that is between two and three times that of the piezoelectric material; a first electrically conductive non-piezoelectric material coupled to a first side of the piezoelectric material; an electrically conductive non-piezoelectric material coupled to a second side of the piezoelectric material opposite the first side; 24. The device of claim 23, wherein the biocompatible, electrically insulating, non-piezoelectric material is configured to receive an applied force resulting from the acoustic signal emitted from the source within the host's body, such that stress caused by the applied force on the biocompatible, electrically insulating, non-piezoelectric material is transmitted through and into the piezoelectric material to convert the stress into electrical energy corresponding to the electrical signal captured in the first and second electrically conductive, non-piezoelectric materials.

28. 28. The device of claim 27, wherein the biocompatible, electrically insulating, non-piezoelectric material comprises a high purity ceramic.

29. 23. The apparatus of claim 22, wherein the stress-mediated acoustic sensor does not involve displacement of the transducer element.

30. 22. The device of claim 21, wherein the in-vivo acoustic sensor further comprises a casing structure providing a rigid, inflexible material and configured to secure and / or position the transducer element within the sealed housing.

31. 31. The device of claim 30, wherein the casing structure is part of the sealed housing.

32. 32. The apparatus of claim 30 or claim 31, wherein the casing structure comprises titanium (Ti).

33. The apparatus of claim 21 , wherein the in-vivo acoustic sensor comprises a displacement-mediated acoustic sensor.

34. 34. The device of claim 33, wherein the transducer element comprises a microphone.

35. 35. The apparatus of claim 34, wherein the microphone includes a membrane that undergoes deflection in response to acoustic waves contacting an outer surface of the membrane, the membrane being coupled to or a component of the sealed housing, and the microphone further including an electronic component responsive to the deflection.

36. 36. The device of claim 35, wherein the electronic component responsive to the deflection comprises at least one of a strain gauge, a piezoelectric element, a capacitor element, a capacitance electrode, or a fixed position electrode that does not change position relative to the membrane when the membrane is deflected in response to the acoustic waves contacting the outer surface of the flexible membrane.

37. 34. The apparatus of claim 33, wherein the transducer element comprises an accelerometer.

38. 22. The apparatus of claim 21, wherein the ultrasonic sensor assembly includes a first ultrasonic sensor assembly disposed on the first arm of the linkage assembly and a second ultrasonic sensor assembly disposed on the second arm of the linkage assembly.

39. The first ultrasonic sensor assembly includes the first ultrasonic transducer element positioned on a distal region of the first arm and configured to transmit the ultrasonic signal and interface with the first portion of the anatomical structure, the second ultrasonic sensor assembly includes the second and third ultrasonic transducer elements positioned on a distal region of the second arm and configured to receive the ultrasonic signal and interface with the second portion of the anatomical structure, and a first center point (C Tx ) is located between the center distance (d) of the second ultrasonic transducer element and the third ultrasonic transducer element, and a second center point (Cd Rx 39. The device of claim 38, wherein the

40. The first ultrasonic sensor assembly includes the first ultrasonic transducer element positioned on a distal region of the first arm and configured to transmit the ultrasonic signals to interface with the first portion of the anatomical structure, the second ultrasonic sensor assembly includes the second and third ultrasonic transducer elements positioned on the distal region of the second arm and configured to receive the ultrasonic signals to interface with the second portion of the anatomical structure, the first ultrasonic sensor assembly further includes fourth and fifth ultrasonic transducer elements positioned on the distal region of the second arm and configured to interface with the second portion of the anatomical structure and receive a first set of ultrasonic signals associated with transmission of the ultrasonic signals by the first ultrasonic transducer elements, the second ultrasonic sensor assembly includes a sixth ultrasonic transducer element positioned on the distal region of the first arm and interface with the first portion of the anatomical structure and configured to transmit second ultrasonic signals associated with the ultrasonic signals received at the second and third ultrasonic transducer elements, and a first center point (C Tx1 ) is located between a first distance (d1) separating the centers of the fourth ultrasonic transducer element and the fifth ultrasonic transducer element, and a second center point (Cd Rx1 ) and a third center point (C Tx2 ) is located between a second distance (d2) separating the centers of the second ultrasonic transducer element and the third ultrasonic transducer element, and a fourth center point (Cd Rx2 39. The device of claim 38, wherein the

41. 22. The apparatus of claim 21, wherein the plurality of ultrasonic transducer elements of the ultrasonic sensor assembly are disposed on the first arm of the linkage assembly, and the in-vivo fluid flow sensor further comprises a reflector disposed on the second arm of the linkage assembly.

42. 22. The device of claim 21, wherein at least one of the first ultrasonic transducer element, the second ultrasonic transducer element, or the third ultrasonic transducer element is configured to have a size dimension between 1 mm and 4 mm.

43. 22. The apparatus of claim 21 , wherein the ultrasonic sensor assembly further comprises a base connected to an inward-facing surface of at least one of the first arm or the second arm of the linkage assembly and coupling at least one of the plurality of ultrasonic transducer elements.

44. 44. The apparatus of claim 43, wherein the substrate is configured to provide thermal synchronization for management of heat generation by the at least one ultrasonic transducer element.

45. 22. The apparatus of claim 21, wherein at least one of the plurality of ultrasonic transducer elements comprises a piezoelectric micromachined ultrasonic transducer (PMUT).

46. 22. The device of claim 21, wherein the in-vivo fluid flow sensor further comprises an ultrasound transducer pad coupled to at least some of the ultrasound transducer elements of the ultrasound sensor assembly and configured to provide contouring and cushioning to the anatomical structure.

47. 47. The device of claim 46, wherein the ultrasound transducer pad comprises a hydrogel.

48. 22. The device of claim 21, wherein the linkage assembly is operable to flexibly secure the in-vivo fluid flow sensor to the anatomical structure so as to withstand continuous movement of the anatomical structure to which it is attached while remaining stable in its position relative to the anatomical structure.

49. 49. The device of claim 48, wherein the linkage assembly includes a clip band operable to provide a compressive force by each of the first arm and the second arm to facilitate fixation of the in-vivo fluid flow sensor to the first and second portions of the anatomical structure and to absorb forces exerted by the anatomical structure on the first and second arms of the clip band due to the continuous movement of the anatomical structure.

50. 50. The device of claim 49, wherein the clip band comprises a composite material having a flexible polymer component and a shape stabilizer component that is pre-formed and capable of undergoing a shape change.

51. 51. The device of claim 50, wherein the shape stabilizer component of the composite material comprises one or more of nitinol, gold, platinum, or iridium, which is encased in the polymer component of the composite material comprising one or more of silicone, polyethylene, polyimide, polyamide, or mixtures thereof.

52. 52. The device of claim 51, wherein the connection device is operable to mechanically resiliently secure the linkage assembly to the anatomical structure such that the in-vivo fluid flow sensor is stable in its position relative to the anatomical structure while withstanding continuous movement of the anatomical structure to which it is attached.

53. 53. The device of claim 52, wherein the connection device comprises a spring operable to provide a compressive force to each of the first and second arms of the linkage assembly to facilitate fixation of the in-vivo fluid flow sensor to the first and second portions of the anatomical structure and to absorb forces exerted by the anatomical structure on the first and second arms of the linkage assembly due to the continuous movement of the anatomical structure.

54. 22. The device of claim 21, wherein the electronic unit comprises a power source and a wireless communication unit including a radio transmitter or transceiver.

55. 55. The apparatus of claim 54, wherein the power source comprises at least one of a battery or a fuel cell.

56. 55. The apparatus of claim 54, wherein the electronics unit comprises a signal conditioning unit in communication with the plurality of ultrasonic transducer elements of the ultrasonic sensor assembly via one or more electrical interface components, the signal conditioning unit comprising electrical circuitry configured to process the electrical signals associated with the received ultrasonic signals by one or more of amplifying the electrical signals, filtering the electrical signals, or converting the electrical signals from analog to digital.

57. 57. The apparatus of claim 56, wherein the electronics unit comprises a data processing unit in communication with the signal conditioning unit, the data processing unit comprising a processor and memory and configured to process the amplified, filtered or converted electrical signals as data representative of the fluid flow parameters of the biological fluid.

58. 55. The device of claim 54, wherein the electronics unit comprises a data processing unit in communication with the wireless communication unit, the data processing unit comprising a processor and memory and configured to process the electrical signals as data representative of the fluid flow parameters of the biological fluid.

59. 55. The apparatus of claim 54, wherein the electronic unit comprises a printed circuit board (PCB) having a base and electrical interconnects disposed on the base, the electrical interconnects coupled to a plurality of electrical interconnect wires extending between the plurality of ultrasonic transducer elements of the ultrasonic sensor assembly and the PCB of the electronic unit.

60. 55. The device of claim 54, wherein the electronic unit comprises a casing that encloses the electronic unit to protect it from exposure to bodily fluids when the implantable medical device is inserted and deployed in vivo.

61. 61. The device of claim 60, wherein the casing includes one or both of flat or curved sides to provide a form factor for the implantable medical device, including at least one of rectangular, cylindrical, conical, elliptical, pyramidal, trapezoidal, or non-uniform shapes.

62. 61. The device of claim 60, wherein the casing is coupled to the linkage assembly on an inwardly facing surface of the linkage assembly that faces toward the anatomical structure, or the casing is coupled to the linkage assembly on an outwardly facing surface of the linkage assembly that faces away from the anatomical structure.

63. 61. The device of claim 60, wherein the electronics unit PCB is sealed within the casing by a non-permeable material that covers the PCB and provides an electrical shield from the bodily fluids.

64. 64. The apparatus of claim 63, wherein the non-permeable material comprises at least one of a parylene, a urethane, or a Teflon material.

65. 22. The device of claim 21, further comprising a secondary sensor coupled to at least one of the in-vivo fluid flow sensor or the in-vivo acoustic sensor and in communication with the electronic unit, the secondary sensor operable to measure one or more of a biological parameter, a physiological parameter, an electrophysiological parameter, or a physical parameter of the body in which the device is deployed.

66. 66. The device of claim 65, wherein the secondary sensor comprises an analyte sensor configured to detect an analyte in the biological fluid in the anatomical structure or in a bodily fluid in an area where the implantable medical device is deployed.

67. 66. The apparatus of claim 65, wherein the secondary sensor comprises a pH sensor configured to detect a pH level of the biological fluid in the anatomical structure or a bodily fluid in a region in which the implantable medical device is deployed.

68. 66. The apparatus of claim 65, wherein the secondary sensor comprises a temperature sensor configured to detect the temperature of the biological fluid in the anatomical structure or the bodily fluid in the region in which the implantable medical device is deployed.

69. 66. The apparatus of claim 65, wherein the secondary sensor comprises an inertial measurement unit (IMU) configured to detect movement of the implantable medical device in multiple degrees of freedom.

70. 22. The device of claim 21, further comprising a secondary attachment component comprising one or more of a suture, prongs, screws, barbs, adhesive, or gripping mechanism disposed on at least a portion of the linkage assembly and configured to secure the ultrasound sensor assembly to the anatomical structure via the linkage assembly.

71. 22. The device of claim 21, wherein the linkage assembly is capable of changing shape from a first shape configuration and expanding to a second shape configuration such that the first and second arms of the linkage assembly are insertable into a patient's body outward from a centerline through at least one of the linkage assembly or the connection device, and the first and second arms of the linkage assembly extend inward toward the centerline through at least one of the linkage assembly or the connection device such that the linkage assembly is attachable to the anatomical structure for operation of the in vivo fluid flow sensor.

72. a second linkage assembly including a third arm configured to attach to a third portion of the anatomical structure and a fourth arm configured to attach to a fourth portion of the anatomical structure opposite the third portion; the connecting device is coupled to each of the third arm and the fourth arm; 22. The device of claim 21, wherein the ultrasonic sensor assembly includes an additional set of the plurality of ultrasonic transducer elements coupled to the second linkage assembly, the additional set of the plurality of ultrasonic transducer elements configured to transmit second ultrasonic signals to propagate through the anatomical structure across the third portion and the fourth portion and to receive second set of ultrasonic signals indicative of a second fluid flow parameter of the biological fluid within the anatomical structure that has propagated through the anatomical structure across the third portion and the fourth portion.

73. 22. The device of claim 21, wherein the connection device includes a port in electrical communication with the electronics unit housed within the connection device and operable to electrically couple via at least one of a cable, wire, or cord to a remote power source housed within a remote device, the remote device being located at another location distinct from and at a distance from the anatomical structure.

74. 74. The device of claim 73, wherein the port is contained within the connection device and interfaces the electronics unit to a data processing unit located in the remote device via the at least one of the cables, wires, or cords, and is in data communication with the electronics unit operable to output the data from the electronics unit of the sensor device through the port to the data processing unit of the remote device via the at least one of the cables, wires, or cords.

75. 75. The apparatus of claim 74, wherein the implantable medical device is configured to wirelessly transmit the data to the external processor by a secondary transmitting device comprising a wireless transmitter or transceiver.

76. 74. The device of claim 73, wherein the other location at which the remote device is located is at least 2 cm from the anatomical structure.

77. 74. The device of claim 73, wherein the other location comprises the pleural cavity, the intraperitoneal cavity, the subcutaneous space, or an extracorporeal location.

78. 22. The device of claim 21, wherein the external processor capable of receiving the data wirelessly transmitted by the electronic unit of the sensor device is located outside the body of a patient-user in which the sensor device is implantable and deployable in the anatomical structure.

79. 22. The apparatus of claim 21, wherein the fluid flow parameters of the biological fluid in the anatomical structure include at least one of a flow rate or an amount of pressure difference between ends of a flow path in the anatomical structure.

80. 80. The device of claim 79, wherein the device is operable to detect a size dimension of the anatomical structure or a predicted area or volume of the anatomical structure based on a baseline measurement of the flow rate and a change in the flow rate over time.

81. 22. The device of claim 21, wherein the anatomical structure is the heart and the biological fluid is blood.

82. 82. The apparatus of claim 81, wherein the in-vivo fluid flow sensor is deployable within at least one layer of the pericardium of the heart or a sensor device is deployable on an outer layer of the pericardium of the heart.

83. 82. The device of claim 81, wherein the first arm and the second arm of the linkage assembly are positioned on opposite portions of the left atrium of the heart, and the received ultrasound signal is indicative of blood flow at the mitral valve of the heart.

84. 82. The device of claim 81, wherein the first arm and the second arm of the linkage assembly are positioned on opposite portions of the right atrium of the heart and the received ultrasound signals are indicative of blood flow at the tricuspid valve of the heart.

85. 82. The device of claim 81, wherein the first arm and the second arm of the linkage assembly are positioned over the superior vena cava or the inferior vena cava proximate the heart, and the received ultrasound signals are indicative of blood flow in the superior vena cava or the inferior vena cava.

86. 82. The device of claim 81, wherein the first arm and the second arm of the linkage assembly are positioned over a pulmonary artery or pulmonary vein proximate the heart, and the received ultrasound signals are indicative of blood flow in the pulmonary artery or pulmonary vein.

87. 1. A system for in vivo monitoring of fluid flow in an anatomical structure, comprising: An implantable medical device according to claim 1 or 21; a data processing system in data communication with the implantable medical device, the data processing system comprising a processor and a memory; The data processing system is configured to receive data from the implantable medical device and process the received data to determine fluid flow parameters associated with biological fluids within the anatomical structure and / or acoustic signal parameters associated with physiological functions of internal body structures.

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