Patent Application
20240000322
The present invention relates generally to biosensors, and more particularly to advanced mechano-acoustic sensing systems and applications of the same.
The background description provided herein is for the purpose of generally presenting the context of the invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the invention.
The emergence of wearable technologies capable of multimodal, clinical-grade monitoring of physiological health increases the demand for sensors, systems, and data analytics approaches that enable reliable, continuous operation during natural daily activities. By comparison to traditional devices that loosely couple to the wrist, skin-mounted technologies offer vastly superior measurement capabilities due to their persistent, intimate interfaces to the body. This mode of operation can support a range of clinically standard diagnostic assessments, such as those based on electrocardiography, photoplethysmography, arterial tonometry, and others. A recent set of important capabilities follows from wide-bandwidth measurements of subtle motions and vibrations of the surface of the skin (i.e., mechano-acoustic (MA) responses) that arise from activities of internal organs and accelerations due to global movements of the body. Skin-interfaced devices for such purposes use precision, high-bandwidth accelerometers based on microelectromechanical system technologies in layouts that optimize sensitivity to motions of the surface of the skin across a broad range of frequencies, from nearly zero to several thousand hertz. The resulting data reflect not only bulk motions of the body, as with conventional wearable devices, but also features from a broad range of body sounds, as with digital stethoscopes, but impervious to ambient sounds. Additional information appears in a range of frequencies between these limits. For example, when mounted on the neck or the chest, the recordings enable detailed assessments of cardiac activity from motions of the heart and from pulsatile flow of blood through near-surface arteries, of respiratory cycles from chest wall movements, of respiratory sounds from airflow through the lungs and trachea, of swallowing behaviors from laryngeal motions and actions of the esophagus, of vocalization patterns from vocal fold activation, and of movements and changes in orientation of the core body. Distinct features in the temporal and spectral characteristics of these processes yield insights into physical activity and health status via a rich range of conventional (e.g., heart rate (HR)) and unconventional (e.g., coughing frequency) metrics, in a seamless manner, without privacy concerns that would follow from use of microphones or other recording devices.
Through these mechanisms, a single device in a sealed, waterproof package that requires only mechanical coupling to the skin can produce a powerful breadth of health-related information. An important caveat is that the diverse range of MA signals contribute to a single stream of time series data in a temporally overlapping fashion. Advanced data filtering and analytics approaches can separate and quantify different characteristic events on the basis of unique temporal and spectral features, but they fail to operate reliably in many scenarios of practical interest. Particular challenges arise when different activities with similar spectral content occur simultaneously. These circumstances render digital signal processing approaches ineffective. For example, respiration rate cannot be determined accurately while running. Related types of motion artifacts are fundamental limitations to both consumer wearables mounted on the wrist and clinical-grade wired monitoring systems.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.
This invention in certain aspects discloses a novel approach that overcomes the aforementioned limitations through advanced concepts in system designs and optimized choices in anatomical mounting locations, at the hardware level without the need for complex and often ineffective digital signal processing strategies. The approach in some embodiments exploits a pair of time-synchronized, high-bandwidth accelerometers (inertial measurement units (IMUs)) at opposite ends of a skin-interfaced device that locates one of the IMUs at the suprasternal notch (SN) and the other at the sternal manubrium (SM). Differences in movements of the skin associated with cardiac and respiratory activity between these regions lead to differences in signals captured by these IMUs. By contrast, overall movements of the neck and the core of the body produce nearly identical responses. As a consequence, simple differential measurements cleanly eliminate common mode features, thereby separating signals associated with cardiopulmonary and related processes from those due to body movements. An additional benefit of this architecture is that temperature sensors integrated in these IMUs can be used in a similar differential manner to yield estimates of core body temperature, largely independent of the ambient. Here, careful choices in thermal aspects of the device layout, rather than intrinsic anatomical gradients, produce the necessary differential responses.
In one aspect, the invention relates to an electronic device for measuring physiological parameters of a living subject comprising at least a first IMU and a second IMU, the first IMU and the second IMU are time-synchronized to and spatially and mechanically separated from each other; and a microcontroller unit (MCU) electronically coupled to the first IMU and the second IMU for processing of data streams from the first IMU and the second IMU.
In one embodiment, the first IMU is configured to measure data including a first signal related to a physiological signal of the living subject and a second signal, and the second IMU is configured to measure data including at least the second signal. The first signal measured by the first IMU has a signal strength greater than that the second signal measured by the first IMU.
In one embodiment, the data measured by the first IMU and the second IMU are processed such that subtraction of the second signal measured by the second sensor from the second signal measured by the first sensor results in a stronger first signal that is a signal of interest.
In one embodiment, the second signal is related to at least one of ambient, motion and vibration.
In one embodiment, the data measured by the second IMU includes the first signal and the second signal.
In one embodiment, a signal-to-noise ratio (SNR) of a signal measured by the first IMU and the second IMU together is lower than a first SNR of a signal measured by the first IMU individually, or a second SNR of a signal measured by the second IMU individually.
In one embodiment, both of the first IMU and the second IMU are operably in mechanical communication with the skin of the living subject.
In one embodiment, one of the first IMU and the second IMU is operably in directly mechanical communication with the skin of the living subject for sensing physiological signals of the body, while the other of the first IMU and the second IMU is operably in indirectly mechanical communication with the skin of the living subject.
In one embodiment, the first IMU and the second IMU are operably in directly mechanical communication with the skin of the living subject.
In one embodiment, one of the first IMU and the second IMU is separated from the rest of rigid components of the electronic device.
In one embodiment, the electronic device also comprises at least first and second thermal sensing units, wherein one of the first and second thermal sensing units is thermally isolated from an ambient environment and configured to measure a body temperature of the living subject, and the other of the first and second thermal sensing units is configured to measure the ambient temperature.
In one embodiment, each of the first and second thermal sensing units is embedded in a respective one of the first and second IMUs.
In one embodiment, the electronic device is configured to measure a range of physiological information from activity of a cardiopulmonary system and movements of a core body to a diverse collection of processes across thoracic cavity, esophagus, pharynx, and oral cavity related to respiration, speech, swallowing, wheezing, coughing, and sneezing.
In one embodiment, the electronic device is configured to separate signals associated with the cardiopulmonary system and related processes from those due to body movements.
In one embodiment, the electronic device is configured to spatiotemporally map movements of the skin at this region of the anatomy onto which the electronic device is attached during cardiac and respiratory activities.
In one embodiment, the electronic device is configured to continuously measure temperature, heart rate (HR), respiratory rate (RR), activity level, and body orientation, across a range of vigorous activities and conditions.
In one embodiment, the electronic device is configured to monitor key symptoms of a patient with COVID-19 infection to track progress of recovery and response to therapies in hospital and/or home.
In one embodiment, the electronic device is configured to measure any of respiratory or motion related digital biomarkers associated with coughing, swallowing, and/or specific motion related activities.
In one embodiment, the electronic device is configured to assess coughing when the living subject is moving or immobile, and/or to measure muscle motion, when the living subject is moving.
In one embodiment, the electronic device further comprises a bidirectional wireless communication system electronically coupled to the electronic device and configured to send an output signal from the electronic device to an external device.
In one embodiment, the external device is a mobile device, a computer, or a cloud service.
In one embodiment, the bidirectional wireless communication system is further configured to deliver commands from the external device to the electronic device.
In one embodiment, the bidirectional wireless communication system comprises a controller that utilizes at least one of near field communication (NFC), Wi-Fi/Internet, Bluetooth, Bluetooth low energy (BLE), and cellular communication protocols for wireless communication.
In one embodiment, the electronic device further comprises a customized app with a user interface deployed in the external device to allow a user to configure and operate the electronic device for data collection, data transfer, data storage and analysis, wireless charging, and monitoring of user's conditions.
In one embodiment, the customized app is configured to allow time-synchronized operation of a plurality of the electronic devices simultaneously.
In one embodiment, the electronic device further comprises a power module coupled to the first IMU, the second IMU and the MCU for providing power thereto.
In one embodiment, the power module comprises at least one battery for providing the power. In one embodiment, the battery is a rechargeable battery.
In one embodiment, the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery.
In one embodiment, the power module further comprises a failure prevention element including a short-circuit protection component or a circuit to avoid battery malfunction.
In one embodiment, the second IMU is placed in a manner that it bends and folds over the battery.
In one embodiment, the electronic device further comprises a flexible printed circuit board (fPCB) having flexible and stretchable interconnects electrically connecting to electronic components including the first IMU, the second IMU and the MCU and the power module.
In one embodiment, the electronic device further comprises an elastomeric encapsulation layer at least partially surrounding the electronic components and the flexible and stretchable interconnects to form a tissue-facing surface attached to the living subject and an environment-facing surface, wherein the tissue-facing surface is configured to conform to a skin surface of the living subject.
In one embodiment, the encapsulation layer is formed of a flame retardant material.
In one embodiment, the elastomeric encapsulation layer is a waterproof and biocompatible silicone enclosure.
In one embodiment, the electronic device further comprises a biocompatible hydrogel adhesive for attaching the electronic device on the respective region of the living subject, wherein the biocompatible hydrogel adhesive is adapted such that signals from the living subject are operably conductible to the first IMU and the second IMU.
In one embodiment, the electronic device is flexible and conformable to the skin with a specific geometrical polarity for mounting in an anatomical location of interest of the living subject.
In one embodiment, the electronic device is a wearable, twistable stretchable, and/or bendable.
In another aspect, the invention relates to an electronic device for measuring physiological parameters of a living subject, comprising a sensor network comprising a plurality of sensor units operably deployed on a skin of the living subject, the plurality of sensor units being time-synchronized to and spatially and mechanically separated from each other; and an MCU electronically coupled to the plurality of sensor units for processing of data streams from the plurality of sensor units.
In one embodiment, the plurality of sensor units are configured to measure a same physiological parameter, or different physiological parameters.
In one embodiment, each of the plurality of sensor units comprises at least a first sensor and the second sensor time-synchronized to and spatially and mechanically separated from each other.
In one embodiment, for each sensor unit, the first sensor is configured to measure data including a first signal related to a physiological signal of the living subject and a second signal, and the second sensor is configured to measure data including at least the second signal. The first signal measured by the first sensor has a signal strength greater than that the second signal measured by the first sensor.
In one embodiment, the data measured by the first sensor and the second sensor of said sensor unit are processed such that subtraction of the second signal measured by the second sensor from the second signal measured by the first sensor results in a stronger first signal that is a signal of interest
In one embodiment, the second signal is related to at least one of ambient, motion and vibration.
In one embodiment, each of the first sensor and the second sensor comprises the IMU, a thermal sensor, a pressure sensor, and/or optical sensor.
In one embodiment, each of the first sensor and the second sensor comprises the IMU.
In one embodiment, the electronic device further comprises a plurality of thermal sensing units.
In one embodiment, each thermal sensing units is embedded in a respective IMU.
In one embodiment, the MCU operably receives inputs from synchronized outputs of a plurality of thermal sensor units with at least one thermal sensing unit for the ambient environment and at least one thermal sensing unit in direct thermal communication from the body isolated thermally from the ambient environment with in-sensor thermally isolating materials.
In one embodiment, the electronic device is configured to automatically switch operation modes, the operation modes include at least a first mode when the living subject is at rest, and a second modes when the living subject is in a high motion.
In one embodiment, the electronic device is configured to measure a range of physiological information from activity of a cardiopulmonary system and movements of a core body to a diverse collection of processes across thoracic cavity, esophagus, pharynx, and oral cavity related to respiration, speech, swallowing, wheezing, coughing, and sneezing.
In one embodiment, the electronic device is configured to separate signals associated with the cardiopulmonary system and related processes from those due to body movements.
In one embodiment, the electronic device is configured to spatiotemporally map movements of the skin at this region of the anatomy onto which the electronic device is attached during cardiac and respiratory activities.
In one embodiment, the electronic device is configured to continuously measure temperature, heart rate (HR), respiratory rate (RR), activity level, and body orientation, across a range of vigorous activities and conditions.
In one embodiment, the electronic device is configured to monitor key symptoms of a patient with COVID-19 infection to track progress of recovery and response to therapies in hospital and/or home.
In one embodiment, the electronic device is configured to measure any of respiratory or motion related digital biomarkers associated with coughing, swallowing, and/or specific motion related activities.
In one embodiment, the electronic device is configured to assess coughing when the living subject is moving or immobile, and/or to measure muscle motion, when the living subject is moving.
In one embodiment, the electronic device further comprises a bidirectional wireless communication system electronically coupled to the electronic device and configured to send an output signal from the electronic device to an external device.
In one embodiment, the external device is a mobile device, a computer, or a cloud service.
In one embodiment, the bidirectional wireless communication system is further configured to deliver commands from the external device to the electronic device.
In one embodiment, the bidirectional wireless communication system comprises a controller that utilizes at least one of NFC, Wi-Fi/Internet, Bluetooth, BLE, and cellular communication protocols for wireless communication.
In one embodiment, the electronic device further comprises a customized app with a user interface deployed in the external device to allow a user to configure and operate the electronic device for data collection, data transfer, data storage and analysis, wireless charging, and monitoring of user's conditions.
In one embodiment, the customized app is configured to allow time-synchronized operation of a plurality of the sensor network simultaneously.
In one embodiment, the electronic device further comprises a power module coupled to the sensor network for providing power thereto.
In one embodiment, the power module comprises at least one battery for providing the power. In one embodiment, the battery is a rechargeable battery.
In one embodiment, the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery.
In one embodiment, the power module further comprises a failure prevention element including a short-circuit protection component or a circuit to avoid battery malfunction.
In yet another aspect, the invention relates to an electronic device for measuring physiological parameters of a living subject, comprising a first sensor adapted for detecting a first group of data related to the living subject and a second group of data that is different from the first group of data; and a second sensor for detecting a third group of data that is substantially similar to the second group of data. In operation, the first sensor and the second sensor are time-synchronized to allow the third group of data from the second sensor to be used to substantially cancel out the second group of data from the first sensor.
In one embodiment, the first sensor and the second sensor are spatially and mechanically separated from each other.
In one embodiment, the separation of the first sensor and the second sensor is greater than zero and less than a predetermined distance.
In one embodiment, each of the first sensor and the second sensor comprises an IMU, a thermal sensor, a pressure sensor, or optical sensor.
In one embodiment, the first group of data is physiological signals of the living subject, and the second group of data is ambient signals at the first sensor.
In one embodiment, the third group of data is ambient signals at the second sensor.
In one embodiment, both of the first sensor and second sensor are operably in mechanical communication with the skin of the living subject.
In one embodiment, the first sensor is operably in direct mechanical communication with the skin of the living subject for sensing physiological signals from the body, and the second sensor is operably in indirectly mechanical communication with the skin of the living subject.
In one embodiment, the first sensor and the second sensor are operably in directly mechanical communication with the skin of the living subject for sensing physiological signals from the body to assess pulse transit time.
In one embodiment, the electronic device is flexible and conformable to the skin with a specific geometrical polarity for mounting in an anatomical location of interest of the living subject.
In a further aspect, the invention relates to an electronic device for measuring physiological parameters of a living subject, comprising a first sensor adapted for detecting a first group of data related to the living subject and a second group of data that is different from the first group of data; and a second sensor for detecting a third group of data that is substantially similar to the second group of data, wherein in operation, the first sensor is positioned such that there is a first distance d1 between a center of the first sensor and an area of the living subject where physiological signals of the living subject are measurable; the second sensor is positioned such that there is a second distance d2 between a center of the second sensor and the center of the first sensor, wherein the second distance d2 is greater than zero and less than a predetermined distance.
In one embodiment, the second sensor is positioned over the first sensor.
In one embodiment, the second sensor is positioned away from the first sensor.
In one embodiment, each of the first sensor and the second sensor comprises an IMU, a thermal sensor, or a pressure sensor.
In one embodiment, the first group of data is physiological signals of the living subject, and the second group of data is signals related to ambient, motion and/or vibration at the first sensor.
In one embodiment, the third group of data is signals related to ambient, motion and/or vibration at the second sensor.
In one embodiment, both of the first sensor and second sensor are operably in mechanical communication with the skin of the living subject.
In one embodiment, the first sensor is operably in directly mechanical communication with the skin of the living subject for sensing physiological signals from the body, and the second sensor is operably in indirectly mechanical communication with the skin of the living subject.
In one embodiment, both of the first sensor and the second sensor are operably in directly mechanical communication with the skin of the living subject for sensing physiological signals from the body to assess pulse transit time.
In one embodiment, the electronic device is flexible and conformable to the skin with a specific geometrical polarity for mounting in an anatomical location of interest of the living subject.
These and other aspects of the present invention will become apparent from the following description of the preferred embodiment taken in conjunction with the following drawings, although variations and modifications therein may be affected without departing from the spirit and scope of the novel concepts of the disclosure.
The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.
The invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.
The terms used in this specification generally have their ordinary meanings in the art, within the context of the invention, and in the specific context where each term is used. Certain terms that are used to describe the invention are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the invention. For convenience, certain terms may be highlighted, for example using italics and/or quotation marks. The use of highlighting has no influence on the scope and meaning of a term; the scope and meaning of a term is the same, in the same context, whether or not it is highlighted. It will be appreciated that same thing can be said in more than one way. Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein, nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.
One of ordinary skill in the art will appreciate that starting materials, biological materials, reagents, synthetic methods, purification methods, analytical methods, assay methods, and biological methods other than those specifically exemplified can be employed in the practice of the invention without resort to undue experimentation. All art-known functional equivalents, of any such materials and methods are intended to be included in this invention. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
Whenever a range is given in the specification, for example, a temperature range, a time range, or a composition or concentration range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the invention. It will be understood that any subranges or individual values in a range or subrange that are included in the description herein can be excluded from the claims herein.
It will be understood that, as used in the description herein and throughout the claims that follow, the meaning of “a”, “an”, and “the” includes plural reference unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and equivalents thereof known to those skilled in the art. As well, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, and “having” can be used interchangeably.
It will be understood that when an element is referred to as being “on”, “attached” to, “connected” to, “coupled” with, “contacting”, etc., another element, it can be directly on, attached to, connected to, coupled with or contacting the other element or intervening elements may also be present. In contrast, when an element is referred to as being, for example, “directly on”, “directly attached” to, “directly connected” to, “directly coupled” with or “directly contacting” another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the invention.
Furthermore, relative terms, such as “lower” or “bottom” and “upper” or “top,” may be used herein to describe one element's relationship to another element as illustrated in the figures. It will be understood that relative terms are intended to encompass different orientations of the device in addition to the orientation depicted in the figures. For example, if the device in one of the figures is turned over, elements described as being on the “lower” side of other elements would then be oriented on “upper” sides of the other elements. The exemplary term “lower”, can therefore, encompasses both an orientation of “lower” and “upper,” depending of the particular orientation of the figure. Similarly, if the device in one of the figures is turned over, elements described as “below” or “beneath” other elements would then be oriented “above” the other elements. The exemplary terms “below” or “beneath” can, therefore, encompass both an orientation of above and below.
It will be further understood that the terms “comprises” and/or “comprising”, or “includes” and/or “including”, or “has” and/or “having”, or “carry” and/or “carrying”, or “contain” and/or “containing”, or “involve” and/or “involving”, “characterized by”, and the like are to be open-ended, i.e., to mean including but not limited to. When used in this disclosure, they specify the presence of stated features, regions, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the invention, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
As used in the disclosure, “around”, “about”, “approximately” or “substantially” shall generally mean within 20 percent, preferably within 10 percent, and more preferably within 5 percent of a given value or range. Numerical quantities given herein are approximate, meaning that the term “around”, “about”, “approximately” or “substantially” can be inferred if not expressly stated.
As used in the disclosure, the phrase “at least one of A, B, and C” should be construed to mean a logical (A or B or C), using a non-exclusive logical OR. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.
The term “mechano-acoustic”, as used in the disclosure, refers to any sound, vibration or movement by a user that is detectable by an accelerometer or a gyroscope. Accordingly, accelerometers are preferably high frequency, three-axis accelerometers, capable of detecting a wide range of mechano-acoustic signals. Examples include respiration, swallowing, organ (lung, heart) movement, motion (scratching, exercise, and/or movement), talking, bowel activity, coughing, sneezing, and the like.
As used in the disclosure, the term “bidirectional wireless communication system” refers to onboard components of sensors, wireless controller and other electronic components that provides capability of receiving and sending signals using at least one communication protocol of near field communication (NFC), Wi-Fi/Internet, Bluetooth, Bluetooth low energy (BLE), and Cellular communication protocols for wireless communication. In this manner, an output may be provided to an external device, including a cloud-based device, personal portable device, or a caregiver's computer system. Similarly, a command may be sent to the sensor, such as by an external controller, which may or may not correspond to the external device. Machine learning algorithms may be employed to improve signal analysis and, in turn, command signals sent to the medical sensor, including a stimulator of the medical sensor for providing haptic signal to a user of the medical device useful in a therapy. More generally, these systems may be incorporated into a processor, such as a microprocessor located on-board or physically remote from the electronic device of the medical sensor. An example of the wireless controller is a near field communication (NFC) chip, including NFC chips. NFC is a radio technology enabling bi-directional short range wireless communication between devices. Another example of a wireless controller is a Bluetooth® chip, or a BLE system-on-chip (SoC), which enables devices to communicate via a standard radio frequency instead of through cables, wires or direct user action.
The term “flexibility” or “bendability”, as used in the disclosure, refers to the ability of a material, structure, device or device component to be deformed into a curved or bent shape without undergoing a transformation that introduces significant strain, such as strain characterizing the failure point of a material, structure, device or device component. In an exemplary embodiment, a flexible material, structure, device or device component may be deformed into a curved shape without introducing strain larger than or equal to 5%, for some applications larger than or equal to 1%, and for yet other applications larger than or equal to in strain-sensitive regions. A used herein, some, but not necessarily all, flexible structures are also stretchable. A variety of properties provide flexible structures (e.g., device components) of the invention, including materials properties such as a low modulus, bending stiffness and flexural rigidity; physical dimensions such as small average thickness (e.g., less than 100 microns, optionally less than 10 microns and optionally less than 1 micron) and device geometries such as thin film and open or mesh geometries.
The term “stretchable”, as used in the disclosure, refers to the ability of a material, structure, device or device component to be strained without undergoing fracture. In an exemplary embodiment, a stretchable material, structure, device or device component may undergo strain larger than 0.5% without fracturing, for some applications strain larger than 1% without fracturing and for yet other applications strain larger than 3% without fracturing. As used herein, many stretchable structures are also flexible. Some stretchable structures (e.g., device components) are engineered to be able to undergo compression, elongation and/or twisting so as to be able to deform without fracturing. Stretchable structures include thin film structures comprising stretchable materials, such as elastomers; bent structures capable of elongation, compression and/or twisting motion; and structures having an island-bridge geometry. Stretchable device components include structures having stretchable interconnects, such as stretchable electrical interconnects. As used herein, for embodiments where the devices are mounted directly to the skin, the devices may be characterized as stretchable, including stretchable and flexible so as to achieve good conformal contact with underlying skin, if desired. “Conformable” refers to a device, material or substrate which has a bending stiffness sufficiently low and elasticity sufficiently high to allow the device, material or substrate to adopt a desired contour profile, including a contour profile that may change over time, for example a contour profile allowing for conformal contact with a surface having a pattern of relief or recessed features, or. In certain embodiments, a desired contour profile is that of a tissue in a biological environment, for example skin or the epidermal layer.
The term “elastomer”, as used in the disclosure, refers to a polymeric material which can be stretched or deformed and return to its original shape without substantial permanent deformation. Elastomers commonly undergo substantially elastic deformations. Useful elastomers include those comprising polymers, copolymers, composite materials or mixtures of polymers and copolymers. Elastomeric layer refers to a layer comprising at least one elastomer.
Elastomeric layers may also include dopants and other non-elastomeric materials. Useful elastomers useful include, but are not limited to, thermoplastic elastomers, styrenic materials, olefenic materials, polyolefin, polyurethane thermoplastic elastomers, polyamides, synthetic rubbers, PDMS, polybutadiene, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, polychloroprene and silicones. In some embodiments, an elastomeric stamp comprises an elastomer. Exemplary elastomers include, but are not limited to silicon containing polymers such as polysiloxanes including poly(dimethyl siloxane) (i.e. PDMS and h-PDMS), poly(methyl siloxane), partially alkylated poly(methyl siloxane), poly(alkyl methyl siloxane) and poly(phenyl methyl siloxane), silicon modified elastomers, thermoplastic elastomers, styrenic materials, olefenic materials, polyolefin, polyurethane thermoplastic elastomers, polyamides, synthetic rubbers, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, polychloroprene and silicones. In an embodiment, a flexible polymer is a flexible elastomer.
The term “encapsulate” or “encapsulation”, as used in the disclosure, refers to the orientation of one structure such that it is at least partially, and in some cases completely, surrounded by one or more other structures. “Partially encapsulated” refers to the orientation of one structure such that it is partially surrounded by one or more other structures. “Completely encapsulated” refers to the orientation of one structure such that it is completely surrounded by one or more other structures. The invention includes devices having partially or completely encapsulated electronic devices, device components and/or inorganic semiconductor components.
Embodiments of the invention are illustrated in detail hereinafter with reference to accompanying drawings. The description below is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. The broad teachings of the invention can be implemented in a variety of forms. Therefore, while this invention includes particular examples, the true scope of the invention should not be so limited since other modifications will become apparent upon a study of the drawings, the specification, and the following claims. For purposes of clarity, the same reference numbers will be used in the drawings to identify similar elements. It should be understood that one or more steps within a method may be executed in different order (or concurrently) without altering the principles of the invention.
Soft, flexible, and wearable sensors offer the ability to continuously collect physiological parameters of relevance to human health. These systems offer the future ability to provide continuous biofeedback and even therapeutic benefit via on-board analytics and edge computing as we have previously disclosed. A key limitation of nearly all existing wearable sensors is motion artifact related deterioration of signal quality. This includes a lack of accurate sensing for heart rate, respiratory rate, body position, swallowing, talking, crying, or other respiratory signals in scenarios where the living subject is moving. Furthermore, core body temperature sensing remains a challenge for non-invasive skin mounted sensors. Thus, the ability to offer skin mounted continuous measurements of core body temperature would provide significant clinical utility.
One of the objectives of this invention is to provide a new class of wearable sensors that offers dramatically improved motion-resistant and ambient temperature resistant sensing enabled by novel device mechanics and design, and algorithms to subtract noises. This new class of wearable leverages differential measurement of outputs from sensors where one sensor is measuring physiological signals from the body and related ambient and gross body motion signals, and another sensor is measuring at least the related ambient and gross body motion signals allow for effective elimination of noise, e.g., related ambient and gross body motion signals, during rest and motion.
In certain aspects, the invention relates to an electronic device for measuring physiological parameters of a living subject. As shown in
In certain embodiments, the data measured by the first IMU and the second IMU are processed such that subtraction of the second signal measured by the second sensor from the second signal measured by the first sensor results in a stronger first signal that is a signal of interest.
In certain embodiments, the second signal is related to at least one of ambient, motion and vibration.
In certain embodiments, the data measured by the second IMU includes the first signal and the second signal.
In certain embodiments, a signal-to-noise ratio (SNR) of a signal measured by the first IMU and the second IMU together is lower than a first SNR of a signal measured by the first IMU individually, or a second SNR of a signal measured by the second IMU individually.
In certain embodiments, both of the first IMU and the second IMU are operably in mechanical communication with the skin of the living subject.
In certain embodiments, one of the first IMU and the second IMU is operably in directly mechanical communication with the skin of the living subject for sensing physiological signals of the body, while the other of the first IMU and the second IMU is operably in indirectly mechanical communication with the skin of the living subject.
In certain embodiments, the first IMU and the second IMU are operably in directly mechanical communication with the skin of the living subject.
In certain embodiments, one of the first IMU and the second IMU is separated from the rest of rigid components of the electronic device.
In certain embodiments, the electronic device also comprises at least first and second thermal sensing units, wherein one of the first and second thermal sensing units is thermally isolated from an ambient environment and configured to measure a body temperature of the living subject, and the other of the first and second thermal sensing units is configured to measure the ambient temperature.
In certain embodiments, each of the first and second thermal sensing units is embedded in a respective one of the first and second IMUs.
In certain embodiments, the electronic device is configured to measure a range of physiological information from activity of a cardiopulmonary system and movements of a core body to a diverse collection of processes across thoracic cavity, esophagus, pharynx, and oral cavity related to respiration, speech, swallowing, wheezing, coughing, and sneezing.
In certain embodiments, the electronic device is configured to separate signals associated with the cardiopulmonary system and related processes from those due to body movements.
In certain embodiments, the electronic device is configured to spatiotemporally map movements of the skin at this region of the anatomy onto which the electronic device is attached during cardiac and respiratory activities.
In certain embodiments, the electronic device is configured to continuously measure temperature, heart rate (HR), respiratory rate (RR), activity level, and body orientation, across a range of vigorous activities and conditions.
In certain embodiments, the electronic device is configured to monitor key symptoms of a patient with COVID-19 infection to track progress of recovery and response to therapies in hospital and/or home.
In certain embodiments, the electronic device is configured to measure any of respiratory or motion related digital biomarkers associated with coughing, swallowing, and/or specific motion related activities.
In certain embodiments, the electronic device is configured to assess coughing when the living subject is moving or immobile, and/or to measure muscle motion, when the living subject is moving.
In certain embodiments, the electronic device further comprises a bidirectional wireless communication system electronically coupled to the electronic device and configured to send an output signal from the electronic device to an external device.
In certain embodiments, the external device is a mobile device, a computer, or a cloud service.
In certain embodiments, the bidirectional wireless communication system is further configured to deliver commands from the external device to the electronic device.
In certain embodiments, the bidirectional wireless communication system comprises a controller that utilizes at least one of near field communication (NFC), Wi-Fi/Internet, Bluetooth, Bluetooth low energy (BLE), and cellular communication protocols for wireless communication.
In certain embodiments, the electronic device further comprises a customized app with a user interface deployed in the external device to allow a user to configure and operate the electronic device for data collection, data transfer, data storage and analysis, wireless charging, and monitoring of user's conditions.
In certain embodiments, the customized app is configured to allow time-synchronized operation of a plurality of the electronic devices simultaneously.
In certain embodiments, the electronic device further comprises a power module coupled to the first IMU, the second IMU and the MCU for providing power thereto.
In certain embodiments, the power module comprises at least one battery for providing the power. In certain embodiments, the battery is a rechargeable battery.
In certain embodiments, the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery.
In certain embodiments, the power module further comprises a failure prevention element including a short-circuit protection component or a circuit to avoid battery malfunction.
In certain embodiments, the second IMU is placed in a manner that it bends and folds over the battery.
In certain embodiments, the electronic device further comprises a flexible printed circuit board (fPCB) having flexible and stretchable interconnects electrically connecting to electronic components including the first IMU, the second IMU and the MCU and the power module.
In certain embodiments, the electronic device further comprises an elastomeric encapsulation layer at least partially surrounding the electronic components and the flexible and stretchable interconnects to form a tissue-facing surface attached to the living subject and an environment-facing surface, wherein the tissue-facing surface is configured to conform to a skin surface of the living subject.
In certain embodiments, the encapsulation layer is formed of a flame retardant material.
In certain embodiments, the elastomeric encapsulation layer is a waterproof and biocompatible silicone enclosure.
In certain embodiments, the electronic device further comprises a biocompatible hydrogel adhesive for attaching the electronic device on the respective region of the living subject, wherein the biocompatible hydrogel adhesive is adapted such that signals from the living subject are operably conductible to the first IMU and the second IMU.
In certain embodiments, the electronic device is flexible and conformable to the skin with a specific geometrical polarity for mounting in an anatomical location of interest of the living subject.
In certain embodiments, the electronic device is wearable, tissue mountable or in mechanical communication or direct mechanical communication with the skin of the living subject. As used herein mechanical communication refers to the ability for the sensors to interface directly or indirectly with the skin or other tissue in a conformable, flexible, and direct manner (e.g., there is no air gap) which in some embodiments allows for deeper insights and better sensing with less motion artifact compared to accelerometers strapped to the body (wrists or chest).
In certain embodiments, the electronic device is twistable stretchable, and/or bendable.
Various embodiments of the present technology include a soft, conformal, stretchable class of device configured specifically for mechano-acoustic recording from the skin, capable of being used on nearly any part of the body, in forms that maximize detectable signals and allow for multimodal operation, such as electrophysiological recording, and neurocognitive interaction.
Another aspect of the invention provides an electronic device comprising a sensor network comprising a plurality of sensor units operably deployed on a skin of the living subject, the plurality of sensor units being time-synchronized to and spatially and mechanically separated from each other; and an MCU electronically coupled to the plurality of sensor units for processing of data streams from the plurality of sensor units.
In certain embodiments, the plurality of sensor units are configured to measure a same physiological parameter, or different physiological parameters.
In certain embodiments, each of the plurality of sensor units comprises at least a first sensor and the second sensor time-synchronized to and spatially and mechanically separated from each other.
In certain embodiments, for each sensor unit, the first sensor is configured to measure data including a first signal related to a physiological signal of the living subject and a second signal, and the second sensor is configured to measure data including at least the second signal. The first signal measured by the first sensor has a signal strength greater than that the second signal measured by the first sensor.
In certain embodiments, the data measured by the first sensor and the second sensor of said sensor unit are processed such that subtraction of the second signal measured by the second sensor from the second signal measured by the first sensor results in a stronger first signal that is a signal of interest
In certain embodiments, the second signal is related to at least one of ambient, motion and vibration.
In certain embodiments, each of the first sensor and the second sensor comprises the IMU.
In certain embodiments, the electronic device further comprises a plurality of thermal sensing units.
In certain embodiments, the MCU operably receives inputs from synchronized outputs of a plurality of thermal sensor units with at least one thermal sensing unit for the ambient environment and at least one thermal sensing unit in direct thermal communication from the body isolated thermally from the ambient environment with in-sensor thermally isolating materials.
In certain embodiments, the electronic device is configured to automatically switch operation modes, the operation modes include at least a first mode when the living subject is at rest, and a second modes when the living subject is in a high motion.
Yet another aspect of the invention provides an electronic device 1001 for measuring physiological parameters of a living subject 1000, as shown in
In certain embodiments, the first sensor and the second sensor are spatially and mechanically separated from each other.
In certain embodiments, the separation of the first sensor and the second sensor is greater than zero and less than a predetermined distance.
In certain embodiments, each of the first sensor and the second sensor comprises an IMU, a thermal sensor, and/or a pressure sensor.
In certain embodiments, the first group of data is physiological signals of the living subject, and the second group of data is signals related to ambient, motion and/or vibration at the first sensor.
In certain embodiments, the third group of data is signals related to ambient, motion and/or vibration at the second sensor.
In certain embodiments, both of the first sensor and second sensor are operably in mechanical communication with the skin of the living subject.
In certain embodiments, the first sensor is operably in directly mechanical communication with the skin of the living subject for sensing physiological signals from the body, and the second sensor is operably in indirectly mechanical communication with the skin of the living subject.
In certain embodiments, the first sensor and the second sensor are operably in directly mechanical communication with the skin of the living subject for sensing physiological signals from the body to assess pulse transit time.
In certain embodiments, the electronic device is flexible and conformable to the skin with a specific geometrical polarity for mounting in an anatomical location of interest of the living subject.
A further aspect of the invention provides an electronic device 1001 for measuring physiological parameters of a living subject 1000, as shown in
In one embodiment, the second sensor 1004 is positioned over the first sensor 1002, as shown in
In one embodiment, the second sensor 1004 is positioned away from the first sensor 1002, as shown in
In certain embodiments, measurements of physiological parameters can be derived from mechano-acoustic signals from the human body of heart rate, respiratory rate, body position, swallow count, cry time, talk time, singing, coughing, and differential motion of specific body parts when the sensor is mounted across an anatomical boundary (e.g., trunk motion in relation to the head, hand motion in relation to the wrist, lower leg motion in relation to the knee), and other respiratory signals at rest and during motion.
In certain embodiments, the derivation of these physiological resistant to motion allows for applicability across a wide range of medical specialties and acuity ranging from critical care, general medicine care, ambulatory medicine, rehabilitation, and consumer health particularly in high motion scenarios.
In certain embodiments, the core body sensing is resistant to ambient temperature fluctuations and clothing.
In certain embodiments, the single MCU receives inputs from synchronized outputs of a plurality of IMU sensors where an individual IMU sensor is in differential mechanical communication with the body.
In certain embodiments, the single MCU receives inputs from synchronized outputs of a plurality of thermal sensors with at least one thermal sensor for the ambient environment and at least one thermal sensor in direct thermal communication from the body isolated thermally from the ambient with in-sensor thermally isolating materials.
In certain embodiments, the novel mechanics of the sensor/device allows for twisting, stretching, bending to enable a low profile design and thermal/mechanical isolation of various sensing elements in the device.
In certain embodiments, the novel mechanics of the sensor/device enables a physical separation of rigid components of the device and the sensing element enabling mounting in unique anatomical locations for high data fidelity. Further advantages include the ability to obscure the sensor from sight to reduce patient stigma. This represents an umbilical functionality to allow for discrete sensing in sensitive locations with the body of the sensor is mounted in a location easier to obscure with clothing.
In certain embodiments, thermal isolating materials and layers that allow for improved thermal sensing of core body temperature that is resistant to ambient temperature fluctuations. In certain embodiments, the sensor/device is configured such that the modes of operation in situations of high motion allows for automated switching to motion resistant outputs. For example, the preferred measurement of heart rate may be ECG at rest—however, a patient maybe in a situation where they are actively moving. In this instance, the sensor can start actively interrogating the dual IMUS for heart rate derivation where ECG based heart rate is not dependable.
In certain embodiments, the sensor/device has ability to toggle or activate dual sensing functionality in situations of high motion to improve accuracy but conserve power in settings of rest.
The techniques introduced here can be embodied as special purpose hardware (e.g. circuitry) as programmable circuitry appropriately programmed with software and/or firmware, or as a combination of special-purpose and programmable circuitry. Hence, embodiment may include a machine-readable medium having stored thereon instructions which may be used to program a computer (or other electronic devices) to perform a process. The machine-readable medium may include, but is not limited to, floppy diskettes, optical disks, compact disc read-only memories (CD-ROMs), magneto-optical disks, ROMs, random access memories (RAMs), erasable programmable read-only memories (EPROMs), electrically erasable programmable read-only memories (EEPROMs), magnetic or optical cards, flash memory, or other type of media/machine-readable medium suitable for storing electronic instructions.
These and other aspects of the present invention are further described below. Without intent to limit the scope of the invention, exemplary instruments, apparatus, methods and their related results according to the embodiments of the present invention are given below. Note that titles or subtitles may be used in the examples for convenience of a reader, which in no way should limit the scope of the invention. Moreover, certain theories are proposed and disclosed herein; however, in no way they, whether they are right or wrong, should limit the scope of the invention so long as the invention is practiced according to the invention without regard for any particular theory or scheme of action.
Soft, skin-integrated electronic sensors can provide continuous measurements of diverse physiological parameters, with broad relevance to the future of human health care. Motion artifacts can, however, corrupt the recorded signals, particularly those associated with mechanical signatures of cardiopulmonary processes. Design strategies introduced herein address this limitation through differential operation of a matched, time-synchronized pair of high-bandwidth accelerometers located on parts of the anatomy that exhibit strong spatial gradients in motion characteristics. When mounted at a location that spans the suprasternal notch and the sternal manubrium, these dual-sensing devices allow measurements of heart rate and sounds, respiratory activities, body temperature, body orientation, and activity level, along with swallowing, coughing, talking, and related processes, without sensitivity to ambient conditions during routine daily activities, vigorous exercises, intense manual labor, and even swimming. Deployments on patients with COVID-19 allow clinical-grade ambulatory monitoring of the key symptoms of the disease even during rehabilitation protocols.
Specifically, the exemplary work exploits a pair of time-synchronized, high-bandwidth accelerometers (inertial measurement units (IMUs)) at opposite ends of a skin-interfaced device that locates one of the IMUs at the suprasternal notch (SN) and the other at the sternal manubrium (SM). Differences in movements of the skin associated with cardiac and respiratory activity between these regions lead to differences in signals captured by these IMUs. By contrast, overall movements of the neck and the core of the body produce nearly identical responses. As a consequence, simple differential measurements cleanly eliminate common mode features, thereby separating signals associated with cardiopulmonary and related processes from those due to body movements. An additional benefit of this architecture is that temperature sensors integrated in these IMUs can be used in a similar differential manner to yield estimates of core body temperature, largely independent of the ambient. Here, careful choices in thermal aspects of the device layout, rather than intrinsic anatomical gradients, produce the necessary differential responses.
The following sections present (i) designs of automated devices that incorporate matched pairs of high-bandwidth IMUs with optimized soft mechanics for high measurement sensitivity and accurate time synchronization across the SN and SM; (ii) results of spatiotemporal mapping of movements of the skin at this region of the anatomy during cardiac and respiratory activity; (iii) examples of modeling and design approaches for exploiting these IMUs in dual temperature sensing of core body temperature, with minimal influence of the thermal ambient; (iv) demonstrations of continuous, differential measurements of temperature, HR, and respiratory rate (RR) across a range of vigorous activities and conditions, with benchmarking against the most accurate commercial sensors; and (v) illustrations of the use on patients recovering from COVID-19 infections to track key symptoms of the disease even during intense physical rehabilitation protocols.
The platform exploits a thin, flexible printed circuit board (fPCB) in an open architecture, with an elastomeric encapsulation structure that completely seals the system to physically isolate the electronics from the environment and to facilitate sterilization for reuse. The layouts yield soft mechanical characteristics for comfortable mounting on the skin, even at sensitive regions of the body. A touch-free docking interrogator supports wireless charging and initiates data downloads in an automated fashion to eliminate user burden.
Experimental studies, as shown in
The block diagram in
Full automation of the key operational steps minimizes user burden, of particular importance for use with patients with COVID-19, as described subsequently. The user simply mounts the device during use and places it on the wireless charging platform when removed. The sensor continuously stores data from both accelerometers onto the internal memory module when not on the charging platform; when on this platform, the device charges and simultaneously streams data to a user interface device via Bluetooth protocols. The user interface then passes data to a cloud hub for signal processing to extract various physiological information, including cough count, RR, HR, activity level, body orientation, and calibrated body temperature. The cloud hub is HIPAA (Health Insurance Portability and Accountability Act) compliant, and the interface application uses HTTPS transport layer security (TLS 1.2) with an algorithm for encryption/decryption for the application programming interface and a standard for in-storage encryption (AES-256).
Core Body Temperature Estimation with Dual Temperature Sensing
The simplest consequence of the dual-sensing architecture is in temperature measurements that approximate the temperature of the skin (Tskin), largely unperturbed by the ambient (Tamb), following schemes described previously in other contexts. Here, sensors embedded in IMU1 and IMU2, in a configuration illustrated in
Transient heat transfer analysis associated with three-dimensional (3D) thermal conduction and natural convection quantifies these effects. The boundary conditions include a constant temperature at the bottom surface of the tissue layer (Tcore) and convective coupling to the ambient air at the free surfaces (Tamb). The parameters include the room temperature, Tamb=18° to 24° C., and the convection coefficient, h=5 to 30 W m−2 K−1.
A simple demonstration involves a subject wearing a device in an environment with an ambient temperature of 18.2° C., then moving between areas with temperatures of 21.3° and 19.5° C. every 3 to 8 min, and lastly remaining in place as the ambient temperature rises from 19.5° to 24.2° C. for 7 min. The results for temperatures recorded from IMU1 and IMU2 appear in the top graph in
Dual Sensing from the SN and the SM
Dual temperature sensing relies critically on design choices that yield different levels of sensitivity to temperatures of the body and the ambient for IMU1 and IMU2. For dual MA sensing, differential responses arise mainly from spatial gradients in motions across the mounting location, specifically those from the SN, the location of IMU1 and from the SM, the location of IMU2 (2.5 cm below the IMU1). Spatiotemporal maps of motions of this region of the anatomy determined by 3D particle tracking velocimetry (3D-PTV) provide quantitative insights into differential motions associated with respiratory and cardiac activities at these two locations and adjacent regions. 3D-PTV relies on optical techniques to track the Lagrangian paths of fiducial marks on the skin, in 3D using stereoscopic imaging, in a way that recapitulates the point-measurement modality of the IMUs. Here, 3D-PTV can capture the essence of dual sensing from the SN and SM by recording from four time-synchronized, high-speed cameras, each at a frame rate of 200 frames per second (fps) (
Similar considerations apply to differential dynamics associated with respiration.
As verified by 3D-PTV, cardiac and respiratory activities create motions that have different amplitudes at the SN and the SM. Similar amplitudes result from movements of the core body. By consequence, simple subtraction of MA signals measured at these two locations greatly improves the accuracy and reliability of measurements of respiratory and cardiac activity by eliminating large, common-mode features that result from body motions.
The flow chart in
The flow chart in
Athletic competition, fitness training, manual labor, and related activities create daunting challenges for accurate measurements of RR and HR because of fast, dynamic, and highly variable large-amplitude accelerations of the body. The dual-sensor platform offers powerful capabilities in these and other contexts.
Examples during Vigorous Activities in Manual Labor
Worker health represents another area of opportunity given the need to continuously monitor key cardiopulmonary parameters in hostile environments. Demanding occupations that involve work in construction, mining, firefighting, and related areas could benefit from noninvasive, high-fidelity monitoring systems to detect fatigue, heat exhaustion, and performance in ways that are seamless and compatible with high motion artifacts and extreme ambient conditions in temperature, sounds, and other.
An area of urgent interest is in digital monitoring of the key symptoms of patients with COVID-19 to track the progress of recovery and the response to therapies in the hospital and the home. In addition to RR, HR, body movements, and body temperature, measurements also capture the intensity and frequency of coughing, talking, and laughing events. Collectively, these factors are important for symptomatic evaluation of the disease and for indirect assessments of aerosol production. Studies reported here involve a COVID-19-positive patient (49 years old; female; height, 170 cm; weight, 107 kg; type 2 diabetes mellitus, obesity, hypertension, and cerebrovascular accident in 2018) provided with the dual-sensing platform and instructions for use in recording over the course of 8 days, as shown in
Top and bottom molded layers of a low-modulus elastomer (Silbione 4420; each 300 μm thick) form a soft encapsulating structure for the electronics. The fabrication process involved placing the electronics onto the bottom layer and then casting a uniform overcoat of a liquid prepolymer to a silicone elastomer (Ecoflex 0030). Mounting the top molded layer with a spacer on each of the short sides of the mold and clamping the assembly together enclosed the system for thermal curing at 70° C. in an oven for 20 min. Cooling to room temperature, removing the device, and eliminating excess elastomer from the perimeter using a die cutter completed the process.
A three-axis milling machine (Roland MDX 540) created an aluminum mold with a concave shape. Casting a liquid precursor to a polyurethane foam material (mixing ratio of A to B is 2:3; FlexFoam-iT! III, Smooth-On, USA) on the mold after coating its surface with a releasing agent (Ease Release 200, Smooth-On, USA) and then pressing a flat aluminum plate on top side produced insulation foams upon curing on a hot plate at 100° C. for 30 min. A reflective film (thermal blanket; Swiss Safe Products) attached to the flat bottom surface of the foam layer using a 5-μm-thick double-sided tape (No. 5600, Nitto Denko Co., Japan) further improved the insulating properties. The final step of the process involved a CO2 laser (Universal Laser System Inc.) to cut the perimeter of the material into the final geometry.
The commercial software ABAQUS (ABAQUS Analysis User's Manual 2010, version 6.10) defined the strain c in the metal layers of the system. The simulations allowed selection of design parameters to ensure that the strain in the copper (Cu) remains below the fracture limit (6=1%), to avoid mechanical failure during assembly of the device and during different types of deformations (stretching, bending, and twisting). The thin Cu and PI films were modeled by composite shell elements (S4R). The number of elements in the model was ˜2×105, and the minimal element size was ⅛ of the width of the narrowest interconnects (100 μm). The mesh convergence of the simulation was guaranteed for all cases. The elastic modulus (E) and Poisson's ratio (v) of are ECu=119 GPa and vCu=0.34 for copper and EPI=2.5 GPa and VPI=0.34 for PI.
Transient heat transfer analysis determined the effects of thermal conduction and natural convection on the responses of the temperature sensors. The tissue and internal sensor components were modeled by hexahedron elements (DC3D8). The encapsulation layer was modeled using tetrahedron elements (DC3D4). The number of elements in the model was ˜6×105, and mesh convergence of the simulation was ensured for all cases. The boundary conditions included a constant temperature (Tcore) at the bottom surface of the tissue layer and convection conditions with the ambient air (Tamb) at the free surfaces. The following parameters were used in the computations: room temperature Tamb=18° to 24° C.; convection coefficient h=(5 to 30) W m−2 K−1; thermal conductivity, heat capacity, and mass density of 0.3 W m−1 K−1, 1460 J kg−1 K−1, and 960 kg m−3 for the tissue; 0.21 W m−1 K−1, 1090 J kg′ K−1, and 1420 kg m−3 for the thermoplastic chips; 0.343 W m−1 K−1, 1150 J kg−1 K−1, and 1850 kg m−3 for FR4; 0.03 W m−1 K−1, 1200 J kg′ K−1, and 85 kg m−3 for the urethane foam; 0.21 W m−1 K−1, 2100 J kg′ K−1, and 909 kg m−3 for PI; 0.2 W m−1 K−1, 1460 J kg′ K−1, and 1070 kg m−3 for Ecoflex 00-30; and 0.15 W m−1 K−1, 1460 J kg′ K−1, and 970 kg m′ for Silbione 4420.
The experiments involved recordings from four synchronized high-speed area scan cameras (2048×1088 resolution; HT-2000M, Emergent) with 35-mm imaging lenses (F1.4 manual focus; Kowa) at the frame rate of 200 fps. The process focused on tracking of 300 fiducial points marked in a grid pattern across the neck covering the SN, the SM, and adjacent areas. The investigation volume was 10 cm by 8 cm by 10 cm illuminated by six arrays for 600 lumen light-emitting diode light bars. Preprocessing, calibration, 3D reconstruction, tracking, and postprocessing used customized 3D-PTV code. Image sequences were preprocessed by subtracting the background noise and enhancing the contrast. 3D calibration exploited the structure-from-motion technique from multiple views. After removing effects of lens distortion, intrinsic parameters of a single camera were estimated using the checkboard calibration method. Extrinsic parameters of all four cameras, including 3D translation and rotation matrices, were obtained by using a sparse set of points matched across the views. Once all camera parameters were estimated, a dense set of fiducial points across multiviews were detected in a subpixel level and reconstructed in 3D coordinate. 3D reconstructed fiducial points were tracked using the Hungarian algorithm and linked by performing a five-frame gap closing to produce long trajectories. Displacement, velocity, and Lagrangian acceleration were filtered and computed using fourth-order B splines. 3D displacement and vector contour fields were obtained by interpolating scattered fiducial points at each frame based on the Delaunay triangulation. Image sequences during cardiac activities were magnified using the Eulerian video magnification method.
A double-sided medical silicone adhesive (3M, 2477P) secured the sensors to the neck area (aligned IMU1 on the SN and IMU2 on the SM). The authors affirm that all subjects in the study provided written informed consent for study images to be published with faces blurred. All data in this study were captured using IMUS with sensitivity of 0.061 mg (gravitational acceleration), 1666-Hz sampling rates (adjustable up to 6664 Hz), and ±2 g acceleration measurement range (adjustable up to ±16 g).
The studies were approved by the Northwestern University Institutional Review Board, Chicago, IL, USA (STU00202449 and STU00212522) and were registered on ClinicalTrials.gov (NCT02865070 and NCT04393558). All study-related procedures were carried in accordance with the standards listed in the Declaration of Helsinki, 1964. For COVID-19-positive patients, double-sided medical silicone adhesive (3M, 2477P) secured the sensor to the neck area (aligned IMU1 on the SN and IMU2 on the SM) for more than 12 hours. For multiple days of use, medical-grade transparent film (Tegaderm, 3M) was applied between the skin and the double-sided adhesive to eliminate irritation from the adhesive. Clinical staff assisted the patient in placing the sensor. After each data measurement session, the device was sterilized with 70% isopropyl alcohol and left to dry at room temperature, and the sterilization process was repeated twice.
It is assumed that the skin/tissue thickness and thermal properties are approximately the same for both sensors since the horizontal distance between them is relatively small. In this way, the core body temperature is determined from temperature variations through the thickness direction of the device. A 1-D heat transfer model based on the device material layers (thickness ti and thermal conductivity ki, listed in
where z denotes the coordinate along the thickness direction in
The boundary conditions based on heat conduction through the device layers for the IMU1 sensor can be expressed as
Based on these boundary conditions the temperature of the IMU1 sensor can be expressed as
Similarly, the boundary conditions based on the conduction through the device layers IMU2 sensor can be expressed as
Where, the ratios (B/A) and (D/C) are given below and depend h.
If the device is attached to a different body location with different thermal properties (e.g., neck, head, arm, etc.) then the skin/tissue thermal properties (i.e., thickness and thermal conductivity) would have to be adjusted accordingly (depending on the anatomy of the skin/tissue layers) for each location. Experiments show that the temperature of the battery changes by a negligible amount (<0.06° C.) during device operation (
Although most of the capabilities in differential accelerometry arise from intrinsic differences in motions at the SN and SM, additional contributions can arise from details associated with the device layout. A schematic illustration of an analytical model that captures these structural differences is in
u=A
0 sin(w0t) (20)
to cause both sensors to accelerate along the z-axis. IMU1, located at the SN, is tied to the rigid platform (i.e. same displacement as equation (20)), considered as the chest wall. IMU2, at the SM, connects to this rigid platform by a spring of stiffness k with magnitude k=ΣiEiSi/Li, where Ei, Si, and Li are the Young modulus, effective area, and height, respectively, of different material/electronic layers between the platform and IMU2 (e.g. battery, device and silicone gel) and a damper with damping ratio ζ. Both IMU1 and IMU2 have a mass m. The damper in IMU2 provides a damping force proportional to the relative velocity F=−cv, where the damping ratio
depends on the damping factor c and the critical damping factor cc. In the dual sensor, silicone gel acts as a damper with a damping ratio ζ=1%˜12%. Since IMU1 is tied to the rigid platform, its acceleration is also the same as
a
IMU1
=
0
2
A
0 sin(w0t) (21)
The acceleration of IMU1 is described by the ordinary differential equation (ODE) kinematic equation
m
Equation (22) has a solution of the form
The first term in equation (23) is the general solution and the second term is the solution. Using the initial conditions x(t=0)=0, {dot over (x)}(t=0)=0, the constants A and θ can be determined. For body motions, w0=1˜3(2π) s−1=6˜20 s−1. For the “spring materials” (battery, gel, device) in the sensor, the total height is — 8 mm and the mass of accelerator is −0.07 g, sow should be larger than ˜1000 s−1. The solution of A and θ is not relevant in this case since the first term will decay very fast in a few seconds, thereby simplifying equation (23) to
x=bA
0 sin(w0t−ε) (24)
Therefore, the acceleration of IMU2 can be determined as
a
IMU2
=
0
2
A
0 sin(w0t−ε) (25)
The differential (IMU1-IMU2) is then
so ε→0 and there is no phase difference between IMU1 and IMU2. Meanwhile, b→1, so b0→0 and the amplitude difference between IMU1 and IMU2 is very small.
This exemplary example presents, among other things, a low-profile, lightweight, flexible, and wireless sensor that intimately couples to the skin as a dual measurement interface to the SN and SM with modalities for differential sensing of temperature and MA signatures of body processes. The results allow for measurements of a broad range of physiological parameters and activity behaviors that overcome a fundamental challenge in nearly every existing monitoring system: motion artifacts. Comparisons with previous studies on the mechano-acoustic sensing method are presented in Table 1. Specific examples reported here include tracking of cardiac activity, respiratory activity, respiratory sounds, body temperature, and overall activity across a range of controlled settings and natural activities in sports, manual labor, and clinical medicine. These technologies and underlying ideas have many other implications. Examples include rehabilitation for patients with aphasia and/or dysphagia, where measurements of vocal activity and swallowing are possible during daily life, outside hospitals or rehabilitation clinics, of particular relevance to stroke survivors and patients with chronic obstructive pulmonary disease. Capabilities in tracking these processes without privacy concerns associated with microphone recordings and in a manner that is independent of ambient sounds represent key features of the approach. The availability of multiaxial information, including three-axis acceleration measurements, three-axis gyroscope data, and three-axis magnetometer information, suggests additional opportunities for these same platforms. Examples include quantitative measurements of neck movements (
The foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.
The embodiments were chosen and described in order to explain the principles of the invention and their practical application so as to enable others skilled in the art to utilize the invention and various embodiments and with various modifications as are suited to the particular use contemplated. Alternative embodiments will become apparent to those skilled in the art to which the present invention pertains without departing from its spirit and scope. Accordingly, the scope of the present invention is defined by the appended claims rather than the foregoing description and the exemplary embodiments described therein.
Some references, which may include patents, patent applications and various publications, are cited and discussed in the description of this invention. The citation and/or discussion of such references is provided merely to clarify the description of the present invention and is not an admission that any such reference is “prior art” to the invention described herein. All references cited and discussed in this specification are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference.
This application claims priority to and the benefit of U.S. Provisional Patent Application Ser. No. 63/108,514, filed Nov. 2, 2020. This application is also a continuation-in-part application of U.S. patent application Ser. No. 16/970,023, filed Aug. 14, 2020, which is a national stage entry of PCT Patent Application Serial No. PCT/US2019/018318, filed Feb. 15, 2019, which itself claims priority to and the benefit of U.S. Provisional Patent Application Serial Nos. 62/710,324, filed Feb. 16, 2018, 62/631,692, filed Feb. 17, 2018, and 62/753,203, filed Oct. 31, 2018. Each of the above-identified applications is incorporated herein by reference in its entirety.
This invention was made with government support under 75A50119C00043 awarded by the Office of the Assistant Secretary for Preparedness and Response, and AG062023 and AG060812 awarded by the National Institutes of Health. The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/057686 | 11/2/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63108514 | Nov 2020 | US | |
| 62753203 | Oct 2018 | US | |
| 62631692 | Feb 2018 | US | |
| 62710324 | Feb 2018 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16970023 | Aug 2020 | US |
| Child | 18034893 | US |
