Patent Application
20210393155
The invention relates generally to healthcare, and more particularly, to apparatus and method for measuring physiological parameters of a mammal subject 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.
Every year, 300,000 neonates are admitted to the neonatal care unit (NICU) in the U.S. The Global Fetal and Neonatal Care Equipment market is expected to grow from $7.32 billion in 2016 to reach $11.86 billion by 2022. Vital sign monitoring systems, however, have largely remained locked in time since the 1970s. Large base units with extensive wires are still attached to numerous electrodes.
Continuous monitoring of vital signs in the NICU is essential to the survival of critically-ill neonates. Conventional medical platforms in the NICU fail, however, to offer a safe, patient-centric mode of operation, largely due to the use of hard-wired, rigid interfaces to the neonate's fragile, under-developed skin. Some groups have developed neonatal vests with embedded sensors and wireless communication capabilities. Others have instrumented neonatal beds. Those systems are impractical because they are bulky and cover a significant surface area of the neonate—which further complicates medical care instead of simplifying it. Up to 90% of NICU babies have scars by age 7, with the number one cause from devices, including sensor leads. Furthermore, the web of wires prevents effective therapeutic skin-to-skin contact and hinders the ability to turn or position the baby. The existing sensor systems also suffer limited capabilities beyond basic vital monitoring parameters and are fundamentally incapable of being realistically adapted for home or remote monitoring.
In addition, none of those systems have been rigorously tested, including in operating NICUs. Other technology is still in the research phase, requiring multiple wires and lacks the intimate skin connection that enables high fidelity sensing, particularly in the context of a neonate that is moving.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.
One aspect of the invention is to provide a highly differentiated product with advanced monitoring capabilities, and greater safety features applicable to various market segments, including: low-resource settings where wireless vital sign monitoring systems have not penetrated into neonatal care; and high-resource settings where the invented systems represent the cutting edge, next generation systems for neonatal monitoring. According to the invention, the systems are reliable and safe sensor systems that are fully wireless and compatible with conformal contact with neonatal skin surfaces, and that are compatible with common procedures in the NICU, including under imaging and/or operating conditions, where conventional systems require time and effort with respect to ensuring multiple wires and leads are appropriately connected and in patient contact to ensure appropriate monitoring.
In one aspect, the invention relates to an apparatus for measuring physiological parameters of a mammal subject. The physiological parameters include, but are not limited to, one or more of heart activities including a stroke volume and ejection fraction, oxygenation level, temperature, skin temperature differentials, body movement, body position, breathing parameters, blood pressure, crying time, crying frequency, swallow count, swallow frequency, chest wall displacement, heart sounds, core body position, asynchronous limb motion, speaking, and biomechanical perturbation. The mammal subject can be a living human subject or a living non-human subject. In certain embodiments, physiological parameters of neonates or infants are monitored and measured. It should be appreciated to one skilled in the art that physiological parameters of children or adults can also be monitored and measured in practice the invention.
In one embodiment, the apparatus includes a first sensor system and a second sensor system that are time-synchronized to each other. Each of the first sensor system and the second sensor system has a plurality of electronic components and plurality of flexible and stretchable interconnects that are electrically connecting to different electronic components, and an elastomeric encapsulation layer at least partially surrounding the plurality of electronic components and the plurality of flexible and stretchable interconnects to form a tissue-facing surface and an environment-facing surface. In one embodiment, each of the first sensor system and the second sensor system is attached to a respective position on the mammal subject so that the first sensor system and the second sensor system are spatially separated by a distance. In certain embodiments, the distance between the first sensor system and the second sensor system is adjustable between a minimal distance and a maximal distance.
In one embodiment, the plurality of flexible and stretchable interconnects comprise at least one of serpentine interconnects and zigzag interconnects.
In one embodiment, the plurality of electronic components comprises a sensor member for measuring at least one physiological parameter of the mammal subject, a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data from the sensor member and processing the received data, and a transceiver coupled to the SoC for wireless data transmission and wireless power harvesting.
In one embodiment, the SoC comprises at least one of a near-field communication (NFC) interface and a Bluetooth interface. In one embodiment, said transceiver comprises a magnetic loop antenna tuned to compliance with the NFC protocol and configured to allow simultaneous wireless data transmission and wireless power harvesting through a single link.
In another embodiment, the plurality of electronic components of each of the first sensor system and the second sensor systems further comprises a battery for provide power to said sensor system, and the elastomeric encapsulation layer is configured to electrically isolate the battery from the mammal subject during use. In one embodiment, the battery is a rechargeable battery operably recharged with wireless recharging. In one embodiment, the plurality of electronic components of each of the first sensor system and the second sensor system further comprises a failure prevention element that is a short-circuit protection component or a battery circuit to avoid battery malfunction.
In yet another embodiment, the plurality of electronic components of each of the first sensor system and the second sensor system further comprises a power management unit electrically coupled between the SoC and the transceiver.
In one embodiment, each of the first sensor system and the second sensor system further comprises a microfluidic chamber positioned between the tissue-facing surface and the plurality of electronic components configured to mechanically isolate the plurality of electronic components from a skin surface during use. In one embodiment, the microfluidic chamber is at least partially filled with at least one of an ionic liquid and a gel.
In one embodiment, the encapsulation layer comprises channels or conduits configured to facilitate sweat evaporation during use. In another embodiment, the encapsulation layer is optically transparent so as to be compatible with visual inspection of underlying tissue. In certain embodiments, the encapsulation layer is configured to electrically isolate each of the first sensor system and the second sensor system from an electroshock applied to the mammal subject. In one embodiment, the encapsulation layer comprises a flame retardant material.
In one embodiment, each of the first sensor system and the second sensor system is radio translucent and thermally stable so as to be compatible with medical imaging.
In one embodiment, each of the first sensor system and the second sensor system is formed to be stretchable and bendable.
In one embodiment, each of the first sensor system and the second sensor system is formed in a multi-layer structure to mechanically isolate mechanically stiff components in a mechanical island configuration to accommodate bending, twisting or stretching without fracture or substantial degradation of an operating parameter.
In one embodiment, each of the first sensor system and the second sensor system is configured to conformally attach to a skin surface in a conformal contact without an adhesive, wherein a contact force is generated by Van der Waals interaction between the tissue facing surface of each of the first sensor system and the second sensor system and a skin surface during use.
In one embodiment, the adhesive-free conformal contact comprises a wrapped geometry, the sensor member of at least one of the first sensor system and the second sensor system further comprises a fastener connected to an external surface of the encapsulation layer to fasten the sensor member in the wrapped geometry to a mammal subject.
In one embodiment, each of the first sensor system and the second sensor system further comprises an adhesive layer operably attached to the tissue-facing surface of the encapsulation layer, wherein the adhesive layer has a pattern of perforations through open regions.
In one embodiment, the first sensor system is a conformable torso sensor system configured to attach and conform to a torso region of the mammal subject, and the second sensor system is a conformable extremity sensor system configured to attach and conform to a limb or appendage region of the mammal subject.
In one embodiment, the torso sensor system comprises a first electrode and a second electrode as the sensor member; a Bluetooth low energy (BLE) SoC as the SoC; an ECG analog front-end (AFE)/inertial measurement unit (IMU); and a power management integrated circuit (PMIC) and a memory.
In one embodiment, the sensor member of the torso sensor system comprises at least two electrodes spatially separated from each other by an electrode distance, D, for electrocardiogram (ECG) generation. In one embodiment, the at least two electrodes comprise at least one of mesh electrodes and solid electrodes. In one embodiment, the electrode distance D is adjustable between a minimal electrode distance, Dmin, and a maximal electrode distance, Dmax, wherein the minimal electrode distance Dmin is a distance of said two electrodes when the torso sensor system is in a non-stretched state, and the maximal electrode distance Dmax is a distance of said two electrodes when the torso sensor system is in a maximally stretched state along the distance.
In another embodiment, the sensor member of the torso sensor system further comprises one or more of an accelerometer for measuring at least one of a position and a movement; an inertial measurement unit (IMU) for measuring at least one of seismocardiography (SCG) and a respiratory rate; and a temperature sensor for measuring temperature.
In one embodiment, the extremity sensor system comprises a Bluetooth low energy (BLE) SoC as the SoC; a PPG analog front-end (AFE); a photodiode/light emitted diode (LED) and an optical detector as the sensor member; and a power management integrated circuit (PMIC) and a memory.
In one embodiment, the extremity sensor system is configured such that a main circuit component including at least the SoC and the transceiver is aligned and operably wrapped around a limb or appendage in a wrap direction; and the sensor member is spatially separated from and electronically connected to the main circuit component, and operably extends in a direction different from the wrap direction to attach to a sensor region that is spatially distinct from the wrapped portion during use.
In one embodiment, the sensor member of the extremity sensor system is conformable to a skin surface and configured as a soft wrap for circumferential attaching to the limb or appendage region.
In one embodiment, the sensor member of the extremity sensor system comprises a photoplethysmogram (PPG) sensor comprising an optical source and an optical detector located within a sensor footprint. In one embodiment, the optical light source comprises light emitting diodes (LEDs).
In another embodiment, the sensor member of the extremity sensor system further comprises one or more of an accelerometer for measuring at least one of a position and a movement; an inertial measurement unit (IMU) for a motion artifact reduction algorithm; and a temperature sensor for measuring temperature.
In one embodiment, at least one of the first sensor system and the second sensor system further comprises a dynamic baseline control module configured to automatically compensate for mammal subject-to-mammal subject variability and generate an effective driving current to ensure sufficient signal-to-noise and avoid saturation. In one embodiment, the driving current is supplied to an LED to generate an optimized light intensity provided to an underlying mammal subject region.
In one embodiment, each of the first sensor system and the second sensor system is encapsulated with a thin film of silicone elastomer so that said sensor system is waterproof.
In one embodiment, each of the first sensor system and the second sensor system has a thickness less than or equal 3 mm.
In one embodiment, each of the first sensor system and the second sensor system has a Young's modulus less than or equal to 1 GPa.
In one embodiment, the apparatus further comprises a reader system that comprises an antenna in communication with said transceiver of each of the first sensor system and the second sensor system for simultaneous wireless data transmission and wireless power delivery. In one embodiment, the reader system further comprises an NFC reader module for receiving wirelessly transmitted data from each of the first sensor system and the second sensor system, and a Bluetooth low energy (BLE) module for transmitting the received data to an external computing device for at least one of real-time display of the monitored physiological parameters, recording of the monitored physiological parameters, and alarm.
In another embodiment, the apparatus further comprises an alarm device for providing at least one of an optical alert and an audio alert when a physiological parameter is out of a pre-defined range. In one embodiment, the alarm device is at least one of an on-board device and an off-board device.
In another aspect, the invention relates to an apparatus for measuring physiological parameters of a mammal subject. In one embodiment, the apparatus includes one or more sensor systems, each of the one or more sensor systems comprises a plurality of electronic components and plurality of flexible and stretchable interconnects that are electrically connecting to different electronic components, wherein the plurality of electronic components comprises a sensor member for measuring at least one physiological parameter of the mammal subject, an SoC having a microprocessor coupled to the sensor member for receiving data from the sensor member and processing the received data, and a transceiver coupled to the SoC for wireless data transmission and wireless power harvesting; and an elastomeric encapsulation layer at least partially surrounding the plurality of electronic components and the plurality of flexible and stretchable interconnects to form a tissue-facing surface and an environment-facing surface, wherein each of the one or more sensor systems is configured to attach and conform to a pre-determined region of the mammal subject, and to be ready time-synchronized with one another.
In one embodiment, the apparatus further includes a reader system that comprises an antenna in communication with said transceiver of each of the first sensor system and the second sensor system for simultaneous wireless data transmission and wireless power delivery. In one embodiment, the reader system further comprises an NFC reader module for receiving wirelessly transmitted data from each of the first sensor system and the second sensor system, and a Bluetooth low energy (BLE) module for transmitting the received data to an external computing device for at least one of real-time display of the monitored physiological parameters, recording of the monitored physiological parameters, and alarm.
In one embodiment, the one or more sensor systems comprises a first sensor system and a second sensor system that are time-synchronized to each other, wherein the first sensor system is a conformable torso sensor system configured to attach and conform to a torso region of the mammal subject, and the second sensor system is a conformable extremity sensor system configured to attach and conform to a limb or appendage region of the mammal subject.
In one embodiment, the sensor member of the torso sensor system comprises at least two electrodes spatially apart from each other for electrocardiogram (ECG) generation.
In one embodiment, the sensor member of the extremity sensor system comprises a photoplethysmogram (PPG) sensor comprising an optical source and an optical detector located within a sensor footprint.
In one embodiment, the sensor member of each of the torso sensor system and the extremity sensor system further comprises one or more of an accelerometer for measuring at least one of a position and a movement; an inertial measurement unit (IMU) for measuring at least one of a movement, a force, an angular rate, and an orientation; and a temperature sensor for measuring temperature.
In one embodiment, the extremity sensor system is configured such that a main circuit component including at least the SoC and the transceiver is aligned and operably wrapped around a limb or appendage in a wrap direction; and the sensor member is spatially separated from and electronically connected to the main circuit component, and operably extends in a direction different from the wrap direction to attach to a sensor region that is spatially distinct from the wrapped portion during use.
In one embodiment, the one or more sensor systems comprises three or more sensor systems time-synchronized to each other, wherein at least one of the three or more sensor systems is a conformable torso sensor system configured to attach and conform to a torso region of the mammal subject. In one embodiment, at least one of the three or more sensor systems is a conformable extremity sensor system configured to attach and conform to a limb or appendage region of the mammal subject.
In yet another aspect, the invention relates to a method for making a sensor system including a plurality of electronic components and a plurality of interconnects electrically connecting to the plurality of electronic components. In one embodiment, the method includes forming an elastomeric layer of an elastomeric material on a substrate; forming a first electrically conductive film on the elastomeric layer; lithographically patterning the interconnects in the first electrically conductive film; assembling the plurality of electronic components onto the patterned interconnects; and encapsulating an entire area of the assembled electronic components onto the patterned interconnects with the elastomeric material, followed by detaching from the substrate, to fabricate the sensor system.
In one embodiment, the elastomeric material comprises PDMS.
In one embodiment, the electrically conductive film is formed of an electrically conductive material including a metal material comprises Au, Ag, or Cu.
In one embodiment, said forming the electrically conductive film comprises laminating a double layered film of the electrically conductive material on the elastomeric layer; and removing a top layer of the double layered film.
In one embodiment, said assembling the plurality of electronic components onto the patterned interconnects comprises connecting a second electrically conductive film for a bridge and a light source to the patterned interconnects.
In one embodiment, the method further includes forming a microfluidic chamber below the plurality of electronic components.
In one embodiment, said forming the microfluidic chamber comprises attaching a layer of the elastomeric material having the microfluidic chamber defined therein to the bottom surface of the elastomeric layer.
In another embodiment, the method further includes injecting a blended solution of at least one of ionic liquid and silica gel into the microfluidic chamber.
In yet another embodiment, the method further includes forming a silicone layer on the bottom of the sensor system.
In a further aspect, the invention relates to a method of non-invasively measuring physiological parameters of a mammal subject. In one embodiment, the method includes conformally contacting a first sensor system at a torso region of the mammal subject and a second sensor system at a limb or appendage region of the mammal subject, respectively, wherein the first sensor system and the second sensor system are spatially separated by a distance, and configured to measuring a torso physiological parameter and an extremity physiological parameter, respectively; and continuously wirelessly transmitting the time synchronized measured torso physiological parameter and extremity physiological parameter to an external reader, thereby non-invasively measuring the physiological parameters of the mammal subject.
In one embodiment, the distance between the first sensor system and the second sensor system is adjustable between a minimum distance and a maximum distance.
In one embodiment, the physiological parameter is obtained from electrical sensing by electrodes; and oxygen sensing by a plethysmograph.
In one embodiment, the method further includes applying a hydrogel between the first sensor system and the second sensor system and underlying tissue of the mammal subject.
In another embodiment, the method further includes measuring at least one additional physiological parameter related to temperature; movement; spatial position; sound; and blood pressure.
In yet another embodiment, the method further includes determining a mammal subject and region-specific optimized driving voltage provided to an optical light source; and powering an LED optical light source with the optimized driving voltage, thereby ensuring the LED optical light source intensity provides sufficient signal to an optical detector without saturating the optical detector.
In one aspect, the invention relates to a non-transitory tangible computer-readable medium storing instructions which, when executed by one or more processors, cause the above-disclosed method.
These and other aspects of the 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 invention.
The following drawings form part of the present specification and are included to further demonstrate certain aspects of the invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. The drawings described below are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the present invention are shown. The present 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 disclosure 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 and/or capital letters has no influence on the scope and meaning of a term; the scope and meaning of a term are the same, in the same context, whether or not it is highlighted and/or in capital letters. It will be appreciated that the 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.
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 can be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
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. Also, 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” to another feature may have portions that overlap or underlie the adjacent feature.
It will be further understood that the terms “comprises” and/or “comprising,” or “includes” and/or “including” or “has” and/or “having” when used in this specification 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.
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 shown 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 the “upper” sides of the other elements. The exemplary term “lower” can, therefore, encompass both an orientation of lower and upper, depending on 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.
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 the present 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 present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
As used in this 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 this 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.
As used in this disclosure, the term “spatially separated” refers to two different locations on skin, wherein the two sensor systems disposed on those locations are not in physical contact. For example, one sensor system may be on the torso, and another sensor system on the foot.
As used in this disclosure, the term “mammal subject” refers to a living human subject or a living non-human subject. For the purpose of illustration of the invention, the apparatus and method are applied to monitor and/or measure physiological parameters of neonates or infants. It should be appreciated to one skilled in the art that the apparatus can also be applied to monitor and/or measure physiological parameters of children or adults in practice the invention.
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.
To address the aforementioned deficiencies and inadequacies, the invention in one aspect discloses a pair of ultrathin, battery-free, skin-conformable electronic sensor systems capable of coordinated, wireless collection of vital signs information at clinical-grade levels of precision and accuracy, without any of the limitations of standard, FDA-cleared systems. The foundational advances in engineering science involve strategies for (1) high bandwidth, high fidelity and wireless modes of battery-free operation based on a single, magnetically coupled inductive link, (2) real-time data processing, analytics and adaptive gain modulation performed using computational resources on the sensor platforms themselves, (3) time-synchronized, continuous streaming of data from a complementary pair of devices mounted on different regions of the body and (4) transparent and radiolucent device designs compatible with visual inspection of underlying tissue and by medical imaging techniques based on magnetic resonance, X-rays and others. Successful demonstrations on neonates with gestational ages ranging from 28 weeks to full term, validated in operating NICUs against clinical ‘gold’ standards indicates the devices have a strong positive clinical impact.
The skin-conformable electronic sensor systems according certain embodiments of the invention have advanced capabilities in data transfer, in-sensor analytics and bi-nodal function enable wireless, high fidelity measurement of full vital signs information, including from fragile neonates. The sensors are optionally battery-free, but can be used with batteries and particularly batteries that can be wirelessly charged. The sensor systems also have broad software interoperability, and so are compatible with a range of hardware readers, including handhelds, computers and conventional monitor systems and displays.
The sensors systems are lightweight and in a convenient patch-like form, that are detachably attachable/mountable to skin, for example, with a weight less than 2 g, and dimensions on the order of 6 cm×3.5 cm×0.2 cm, or less, including less than 3 cm×3 cm×0.2 cm.
Physiological parameters that can be measured include, but are not limited to, one or more of heart activities including a stroke volume and ejection fraction, oxygenation level, temperature, skin temperature differentials, body movement, body position, breathing parameters, ballistocardiography, respiratory effort, blood pressure, crying time, crying frequency, swallow count, swallow frequency, chest wall displacement, heart sounds, core body position, asynchronous limb motion, speaking, and biomechanical perturbation.
One aspect of the invention discloses an apparatus for measuring physiological parameters of a mammal subject.
In one exemplary embodiment shown in
The plurality of flexible and stretchable interconnects 130 are serpentine interconnects as shown in
The plurality of electronic components 120 includes a sensor member for measuring the physiological parameters such as ECG data. The sensor member includes, but is not limited to, two electrodes 121 and 122 spatially separated from each other by an electrode distance, D, for ECG generation. The electrodes 121 and 122 can be either mesh electrodes (
As shown in
Referring to
Still referring to
In addition, referring back to
In one embodiment, the encapsulation layer further comprises channels or conduits configured to facilitate sweat evaporation during use. In another embodiment, the encapsulation layer is optically transparent so as to be compatible with visual inspection of underlying tissue. In certain embodiments, the encapsulation layer is configured to electrically isolate the first sensor system from an electroshock applied to the mammal subject. In one embodiment, the encapsulation layer comprises a flame retardant material.
In one exemplary embodiment shown in
The plurality of flexible and stretchable interconnects 170 are serpentine interconnects as shown in
The plurality of electronic components 160 includes a sensor member for measuring the physiological parameters such as PPG data. As shown in
Referring to
Still referring to
In addition, referring back to
In one embodiment, the encapsulation layer further comprises channels or conduits configured to facilitate sweat evaporation during use. In another embodiment, the encapsulation layer is optically transparent so as to be compatible with visual inspection of underlying tissue. In certain embodiments, the encapsulation layer is configured to electrically isolate the second sensor system from an electroshock applied to the mammal subject. In one embodiment, the encapsulation layer comprises a flame retardant material.
In operation, the torso sensor system 110 (ECG EES 110) and the extremity sensor system 150 (PPG EES 150) are in wireless communication with a reader system 190, alternatively, a microcontroller unit (MCU), having an antenna 195. Specifically, the RF loop antennas 125 and 165 in both the torso sensor system 110 (ECG EES 110) and the extremity sensor system 150 (PPG EES 150) are in wireless communication with the antenna 195 and serve dual purposes in power transfer and in data communication, as shown in
In certain embodiments, the apparatus 100 may have an alarm device (not shown) for providing at least one of an optical alert and an audio alert when a physiological parameter is out of a pre-defined range. In one embodiment, the alarm device is at least one of an on-board device and an off-board device.
In another embodiment as shown in
In certain embodiments, the battery 205 is a rechargeable battery operably recharged with wireless recharging. In one embodiment, the plurality of electronic components of each of the first sensor system 210 and the second sensor system 250 further comprises a failure prevention element that is a short-circuit protection component or a battery circuit (not shown) to avoid battery malfunction.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 is radio translucent and thermally stable so that each of the first sensor system and the second sensor system is compatible with medical imaging including X-ray, CT and/or MRI imaging. According to the invention, with the specific advantage of having a lower radiological shadowing effect, the small thin sensors allow for less perturbation of CT/X-ray imaging. In addition, the sensors generate minimal heat during MRIs allowing for them to remain on body during this imaging modality.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 is formed to be stretchable and bendable.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 is formed in a multi-layer structure to mechanically isolate mechanically stiff components in a mechanical island configuration to accommodate bending, twisting or stretching without fracture or substantial degradation of an operating parameter.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 is configured to conformally attach to a skin surface in a conformal contact without an adhesive, wherein a contact force is generated by Van der Waals interaction between the tissue facing surface of each of the first sensor system and the second sensor system and a skin surface during use.
In certain embodiments, the adhesive-free conformal contact comprises a wrapped geometry, the sensor member of at least one of the first sensor system and the second sensor system further comprises a fastener connected to an external surface of the encapsulation layer to fasten the sensor member in the wrapped geometry to a mammal subject.
In one embodiment, each of the first sensor system and the second sensor system further comprises an adhesive layer operably attached to the tissue-facing surface of the encapsulation layer, wherein the adhesive layer has a pattern of perforations through open regions.
In certain embodiments, at least one of the first sensor system 110/210 and the second sensor system 150/250 comprises a dynamic baseline control module configured to automatically compensate for mammal subject-to-mammal subject variability and generate an effective driving current to ensure sufficient signal-to-noise and avoid saturation. In one embodiment, the driving current is supplied to an LED to generate an optimized light intensity provided to an underlying mammal subject region.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 is encapsulated with a thin film of silicone elastomer so that said sensor system is waterproof.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 has a thickness less than or equal 3 mm.
In certain embodiments, each of the first sensor system 110/210 and the second sensor system 150/250 has a Young's modulus less than or equal to 1 GPa.
As disclosed above, two sensor systems are utilized to measure the physiological parameters of a mammal subject. In certain aspects, the invention is not limited the two sensor systems. Instead, one sensor system that is discussed above can also be used to measure the physiological parameters. Furthermore, three or more of these sensor systems, each of which is time-synchronized to each other, and spatial separately attached on a respective position of a mammal subject, can also be used to measure the physiological parameters of the mammal subject. In one embodiment, at least one of the three or more sensor systems is a conformable torso sensor system configured to attach and conform to a torso region of the mammal subject, and at least one of the three or more sensor systems is a conformable torso sensor system configured to attach and conform to a torso region of the mammal subject.
Referring now to
In one embodiment, the elastomeric material comprises PDMS or other elastomers.
In one embodiment, the electrically conductive film is formed of an electrically conductive material including a metal material comprises Au, Ag, or Cu.
In one embodiment, said forming the electrically conductive film comprises laminating a double layered film 1020 and 1022 of the electrically conductive material on the elastomeric layer 1010 (
In one embodiment, said assembling the plurality of electronic components 1041 onto the patterned interconnects 1021 comprises connecting a second electrically conductive film 1025 for a bridge and a light source to the patterned interconnects 1021 (
In one embodiment, the method further includes forming a microfluidic chamber 1035 below the plurality of electronic components 1041 (
In one embodiment, said forming the microfluidic chamber 1035 comprises attaching a layer 1030 of the elastomeric material having the microfluidic chamber 1035 defined therein to the bottom surface of the elastomeric layer 1010.
In another embodiment, the method further includes injecting a blended solution of at least one of ionic liquid and silica gel into the microfluidic chamber 1035.
In yet another embodiment, the method further includes forming a silicone layer 1002 on the bottom of the sensor system (
In addition, the invention also relates to a method of non-invasively measuring physiological parameters of a mammal subject. In one embodiment, the method includes conformally contacting a first sensor system at a torso region of the mammal subject and a second sensor system at a limb or appendage region of the mammal subject, respectively, wherein the first sensor system and the second sensor system are spatially separated by a distance, and configured to measuring a torso physiological parameter and an extremity physiological parameter, respectively; and continuously wirelessly transmitting the time synchronized measured torso physiological parameter and extremity physiological parameter to an external reader, thereby non-invasively measuring the physiological parameters of the mammal subject.
In one embodiment, the distance between the first sensor system and the second sensor system is adjustable between a minimum distance and a maximum distance.
In one embodiment, the physiological parameter is obtained from electrical sensing by electrodes; and oxygen sensing by a plethysmograph.
In one embodiment, the method further includes applying a hydrogel between the first sensor system and the second sensor system and underlying tissue of the mammal subject.
In another embodiment, the method further includes measuring at least one additional physiological parameter related to temperature; movement; spatial position; sound; and blood pressure.
In yet another embodiment, the method further includes determining a mammal subject and region-specific optimized driving voltage provided to an optical light source; and powering an LED optical light source with the optimized driving voltage, thereby ensuring the LED optical light source intensity provides sufficient signal to an optical detector without saturating the optical detector.
In one aspect, the invention relates to a non-transitory tangible computer-readable medium storing instructions which, when executed by one or more processors, cause the above-disclosed method.
It should be noted that all or a part of the methods according to the embodiments of the invention is implemented by hardware or a program instructing relevant hardware.
Yet another aspect of the invention provides a non-transitory computer readable storage medium/memory which stores computer executable instructions or program codes. The computer executable instructions or program codes enable a computer or a similar computing apparatus to complete various operations in the above disclosed method of non-invasively measuring physiological parameters of a mammal subject. The storage medium/memory may include, but is not limited to, high-speed random access medium/memory such as DRAM, SRAM, DDR RAM or other random access solid state memory devices, and non-volatile memory such as one or more magnetic disk storage devices, optical disk storage devices, flash memory devices, or other non-volatile solid state storage devices.
Certain aspects of the invention also relate to an epidermal-mountable device for monitoring physiological parameters of a patient comprising at least two electronically-coupled sensor systems. Each sensor system comprises a plurality of electronic components, including an antenna for wireless transmissions from a sensor to an external reader; an interconnect that electrically interconnects different electronic components; an elastomeric encapsulation layer that surrounds the plurality of electronic components and interconnect to form a bottom tissue-facing surface and a top environment-facing surface; wherein each of the at least two electronically-coupled sensor systems are configured to conform to spatially separate positions on a patient.
In certain embodiments, the interconnect is a flexible and stretchable interconnect that electrically interconnects different strain-sensitive electronic components.
In certain embodiments, the flexible and stretchable interconnects comprise serpentine interconnects.
In certain embodiments, the first sensor system is a conformable torso sensor system configured to epidermally-mount and conform to a torso region; and the second sensor system is a conformable extremity sensor system configured to epidermally mount and conform to a limb or an appendage region.
In certain embodiments, the extremity sensor system comprises a main circuit component configured to wrap around an appendage in a wrapping direction to mount to the appendage during use; and a sensor that is mechanically decoupled and spatially separated from, and electronically connected to, the main circuit component, and that extends in a different direction than the wrapping direction to mount to a sensor region that is spatially distinct from the wrapped portion during use.
In certain embodiments, the sensor is a PPG sensor comprising an optical source and an optical detector located within a sensor footprint that is less than or equal to 5 mm2.
In certain embodiments, the PPG sensor mounts to an appendage region such as a foot or a nail with an adhesive and the main circuit component is configured to mount to an appendage such as an ankle without an adhesive.
In certain embodiments, the device further comprises a temperature sensor mechanically decoupled and spatially separated from, and electronically connected to, the main circuit component.
In certain embodiments, at least one of the sensor systems further comprise a microfluidic chamber positioned between the tissue-facing surface and the plurality of electronic components configured to mechanically isolate the plurality of electronic components from a skin surface during use.
In certain embodiments, the conformable torso sensor system electronic components comprise electrodes for electrocardiogram generation.
In certain embodiments, the conformable torso sensor system electronic components further comprise one or more of a three-axis accelerometer for position monitoring; and a temperature sensor for measuring temperature.
In certain embodiments, the conformable extremity sensor system electronic components comprise an optical detector for measuring oxygen level in tissue underlying the conformable limb sensor system by pulse oximetry. In certain embodiments, the extremity sensor is configured to conformally mount to any of a limb region of all four limbs, forehead, chest, back, abdomen for tissue oxygen determination. In certain embodiments, the conformable extremity sensor system electronic components further comprise an optical light source, such as a light emitting diode, and an optical detector.
In certain embodiments, the conformable extremity sensor system electronic components further comprise a three-axis accelerometer for position or movement monitoring; and a temperature sensor for measuring temperature.
In certain embodiments, the sensor systems are configured to measure a physiological parameter selected from one or more of the group consisting of heart activity, including stroke volume, ejection fraction; oxygenation level; temperature; patient movement; patient position; breathing parameter; blood pressure; and a biomechanical perturbation.
In certain embodiments, each of the sensor systems has a footprint area less than or equal to 10 cm2.
In certain embodiments, each of the sensor systems have a thickness less than or equal 3 mm.
In certain embodiments, the device wirelessly communicates with an externally-positioned reader and is wirelessly powered.
In certain embodiments, the device is configured to conformally mount to a skin surface without an adhesive, wherein a contact force is generated by Van der Waals interaction between the bottom surface and a skin surface during use.
In certain embodiments, the device has a peel force from the skin selected from a range that is greater than 0 Newton and less than 1 Newton.
In certain embodiments, the device further comprises an adhesive layer connected to the bottom tissue-facing surface of the encapsulation layer, wherein the adhesive layer has a pattern of perforations.
In certain embodiments, the bottom encapsulation layer comprises channels or conduits configured to facilitate sweat evaporation during use.
In certain embodiments, the device is configured to measure a plurality of physiological parameters from a neonate.
In certain embodiments, each of the limb and extremity sensor system have a Young's modulus less than or equal to 1 GPa.
In certain embodiments, the device is capable of undergoing a strain of up to 20% and bending radius as small as 5 mm without fracture.
In certain embodiments, the measurement of the physiological parameter is continuous for an extended time period that is greater than 4 hours.
In certain embodiments, the device further comprises a hydrogel positioned between the bottom-tissue facing surface and a tissue surface during use.
In certain embodiments, the conformal contact is adhesive-free.
In certain embodiments, the adhesive-free conformal contact comprises a wrapped geometry, the sensor member of at least one of the first sensor system and the second sensor system further comprises a fastener connected to an external surface of the encapsulation layer to fasten the sensor member in the wrapped geometry to a patient.
In certain embodiments, the extremity sensor system comprises an optical unit for photoplethysmography on a nail of an individual that is mechanically isolated from a main circuit component comprising a microprocessor and a wireless transmitter.
In certain embodiments, the sensors are conformable to a skin surface and configured as a soft wrap for circumferential mounting to a limb region.
In certain embodiments, the limb region corresponds to a hand or a foot of a neonate.
In certain embodiments, each of the sensors have a footprint less than or equal to 9 cm2.
In certain embodiments, the device further comprises a battery to power the sensors, and the elastomeric encapsulation layer is electrically insulative to electrically isolate the battery from a patient during use.
In certain embodiments, the encapsulation layer electrically isolates the sensor from an electroshock applied to a patient, including under an applied cardiac defibrillation stimulus.
In certain embodiments, the device further comprises a failure prevention element that is a short-circuit protection component or a battery circuit to avoid battery malfunction.
In certain embodiments, the elastomeric encapsulation layer comprises a flame retardant material.
In certain embodiments, the device further comprises a multi-layer structure to mechanically isolate mechanically stiff components in a mechanical island configuration to accommodate bending, twisting and/or stretching without fracture or substantial degradation of an operating parameter.
In certain embodiments, the pair of sensor systems wirelessly communicate time-synchronized data to an external reader, including for pulse arrival time and pulse transit time to determine blood pressure.
In certain embodiments, the device has a continuous stream rate that is greater than or equal to 600 bytes/second.
In certain embodiments, the device further comprises further comprises an external reader wirelessly connected to the pair of sensor systems to display and/or record wirelessly transmitted data from each of the sensors of the sensor systems.
In certain embodiments, the device further comprises further comprises a microprocessor operably connected to the sensors for on-board real-time data processing, analytics and adaptive gain modulation.
In certain embodiments, the antenna is a magnetic loop antenna for wireless power generation.
In certain embodiments, the device further comprises a loop antenna.
In certain embodiments, the device further comprises further comprises a rechargeable battery for wireless recharging.
In certain embodiments, the at least two sensor systems together have a peak current consumption of less than 3 mA.
In certain embodiments, the encapsulation layer is optically transparent and sensor systems have open regions for visual inspection of underlying tissue without monitor removal from skin.
In certain embodiments, the device is radio translucent and thermally stable for medical imaging without device removal during medical imaging.
In certain embodiments, spacing between the pair of sensor systems is adjustable.
In certain embodiments, the device further comprises further comprises an alarm for a physiological parameter that is out of a user-defined normal range.
In certain embodiments, the alarm is an optical alert and/or an audio alert on-board or off-board the device.
In certain embodiments, the microfluidic chamber has a volume that is less than or equal to 1 mL.
In certain embodiments, the microfluidic chamber is at least partially filled with a liquid or a gel.
In certain embodiments, the microfluidic chamber is at least partially filled with a blended solution of an ionic fluid and a silica gel.
In certain embodiments, the device further comprises a dynamic baseline control module to automatically compensate for patient-to-patient variability and generate an effective driving current to ensure sufficient signal-to-noise and avoid saturation.
In certain embodiments, the driving current is supplied to an LED to generate an optimized light intensity provided to an underlying patient region.
Certain aspects of the invention further includes method of non-invasively monitoring a physiological parameter of a patient, comprising the steps of providing the above-disclosed device; conformally contacting the sensor systems at spatially separated regions of the patient; continuously wirelessly transmitting a time synchronized measured torso physiological parameter and extremity physiological parameter to an external reader; thereby non-invasively monitoring a physiological parameter of a patient.
In certain embodiments, the conformal contact is without an adhesive and the conformal contact has a duration of at least 8 hours.
In certain embodiments, the method further comprises applying a hydrogel between the device and underlying tissue.
In certain embodiments, the physiological parameter is obtained from electrical sensing by microelectrodes; and oxygen sensing by a plethysmograph.
In certain embodiments, the method further comprises measuring at least one additional physiological parameter that is related to temperature; movement; spatial position; sound; or blood pressure.
In certain embodiments, the method further comprises determining a patient and region-specific optimized driving voltage provided to an optical light source; powering an LED optical light source with the optimized driving voltage; thereby ensuring the LED optical light source intensity provides sufficient signal to an optical detector without saturating the optical detector.
Certain aspects of the invention also disclose a device for measuring a physiological parameter comprising a main circuit component having a microprocessor and a wireless transmitter; a sensor that is mechanically decoupled and spatially separated from, and electronically connected to, the main circuit component; an encapsulation layer that encapsulates the main circuit component and the sensor; wherein during use the device is configured to mount to a patient surface and is completely wireless.
In certain embodiments, the device further comprises a flexible and stretchable interconnect that electronically connects the sensor to the main circuit.
In certain embodiments, the device further comprises a laterally extending wrap region configured to wrappably mount the main circuit component to a patient during use without an adhesive layer between the encapsulation layer and skin; and a sensor extending sensor region configured to mount the sensor in a direction independent of a wrap direction.
In certain embodiments, the sensor is configured to mount to a foot region or a toenail and the main circuit component around an ankle region.
In certain embodiments, the sensor is a PPG sensor.
According to the invention, among other things, relevant differences of the invented sensor systems from conventional sensor systems include: an ultra-low profile form factor with fully wireless functionality. This enables in-hospital and post-discharge monitoring without any wires. Furthermore, the form factor and encapsulation avoid use of harsh adhesives, so that, if necessary, ultra-low adhesives may be used, which is important for ultra-fragile skin and the entire device is compatible with common medical imaging techniques (CT, XR and MRI). Multiple measurements of a vital sign with different sensor platforms increases accuracy and reliability while decreasing risk of false-positives. The platform is versatile, characterized in that many different physiological parameters can be measured, including, but not limited to, the ones listed above. The digital nature of the sensor systems makes them particularly compatible with various software methodologies, including advanced analytics for predictive algorithms.
Provided herein are also methods of monitoring one or more physiological parameters using any of the devices or systems described herein. Also provided are devices for carrying out any of the methods described herein.
These and other aspects of the present invention are further described below. Without intent to limit the scope of the invention, examples 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.
Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) fail to offer a safe, patient-centric mode of operation, largely due to the necessity of multiple wires connected to rigid electrodes with strongly adherent interfaces to the skin to ensure good contact. Here, we introduce a pair of ultrathin, skin-like electronic sensors whose coordinated operation bypasses limitations of existing technologies. The enabling advances in engineering science include designs that support (1) wireless, battery-free operation, (2) real-time, in-sensor data analytics, (3) time-synchronized, continuous data streaming, (4) soft mechanics and light adhesive interfaces to the skin and (5) compatibility with advanced medical imaging techniques used in the NICU. Studies on neonates admitted to operating NICUs demonstrate performance capabilities that exceed those of the most advanced clinical-standard monitoring systems.
Continuous recording and real-time graphical display of vital signs is essential for critical care. Each year in the U.S., approximately 300,000 neonates, including a large fraction with exceptionally fragile health status due to severe prematurity and very low birth weight (<1500 g), are admitted to neonatal intensive care units (NICUs). Existing monitoring systems for the NICU require multiple electrode/sensor interfaces to the skin, with hard-wired connections to separately located base units that may be stand alone or wall-mounted for heart rate (HR), respiratory rate (RR), temperature, blood oxygenation (SpO2) and blood pressure (BP). Although such technologies are essential to clinical care, the associated web of wires greatly complicates even the most basic bedside tasks such as turning a neonate from prone to supine. This hardware also interferes with emergency clinical interventions and radiological studies, and impedes therapeutic skin-to-skin contact, colloquially known as kangaroo mother care, between parents and their infant. Most significantly, the adhesives that couple these wired electrodes to the fragile skin of the neonates are a frequent cause of iatrogenic injuries and subsequent scarring.
A fully wireless alternative that eliminates mechanical stresses and potentially reduces injury-risk, and that deploys effectively on the full range of gestational ages encountered in the NICU would represent a significant advance over the existing standard of care. While textile-based sensors are of interest, these technologies retain wired connections across the body and their inability to support an intimate connection to the skin precludes reliable operation at clinical-grade levels of accuracy, particularly with motion. Recent advances in materials science and biomedical engineering serve as the basis for devices that have an ideal, skin-like form factor. Although such systems can support various types of biophysical measurements of physiological health, significant additional advances are needed to meet the challenging requirements of the NICU, where comprehensive, continuous sensing with wireless functionality, clinical-grade measurement fidelity, and mechanical form factors that eliminate risk of harm to exceptionally fragile neonatal skin are essential.
In certain aspects, the invention discloses a wireless, battery-free vital signs monitoring system that exploits a bi-nodal pair of ultrathin, low-modulus measurement modules, each referred to as an epidermal electronic system (EES), capable of softly and non-invasively interfacing onto neonatal skin. Among other things, five essential advances include: (1) techniques for simultaneous wireless power transfer, low noise sensing and high speed data communications via a single link based on magnetic inductive coupling at a radio frequency band that has negligible absorption in biological tissues, (2) efficient algorithms for real-time data analytics, signal processing and dynamic baseline modulation implemented in the highly constrained computing resources available on the sensor platforms themselves, (3) strategies for time-synchronized, continuous streaming of wireless data from two, separately located devices, (4) mechanics designs and strategies in interface adhesion that minimize the risk of iatrogenic skin injury to fragile neonatal skin, and (5) optimized layouts that enable visual inspection of underlying tissue of the skin interface, and radiolucent electrical configurations that allow magnetic resonance imaging (MRI) and X-ray imaging (XR). Successful pilot phase demonstrations on neonates with gestational ages ranging from 28 weeks to full-term in two, tertiary-level NICUs establish quantitative equivalency to clinical standards.
In addition to advanced capabilities in monitoring, the skin-like profile and fully wireless nature of these platforms offer direct therapeutic value by reducing the barriers for skin-to-skin contact between parent and child. The result enables spontaneous interactions with neonates not further encumbered by ventilator support or central vascular lines. Studies indicate that such skin-to-skin contact reduces neonatal mortality, risk of severe infection, and hypothermia while increasing the rate of weight gain and head circumference growth.
In addition to the electronics, each EES incorporates a magnetic loop antenna (
The images shown in
Images shown in
The block diagram shown in
Since the standard NFC protocol at 13.56 MHz supports only low speed, low fidelity applications in contactless payments, wireless identification and others, significant modification in both the transponder and host reader systems at ISO15693 were required to enable data transfer rates sufficient for NICU monitoring (hundreds of Hz). The results enable continuous streaming of data at rates of up to 800 bytes/s with dual channels, which is orders of magnitude larger than those previously achieved in NFC sensors. A key to realizing such high rates is in minimizing the overhead associated with transfer by packaging data into 6 blocks (24 Bytes) in a circular buffer. Here, reading occurs with an NFC host interfaced to a microcontroller in a Bluetooth Low Energy (BLE) system configured with this type of customized circular buffer decoding routine shown in
The essential mechanics of these systems decrease risks for skin injury relative to existing clinical standards. The global incidence of skin breakdown in hospitalized neonates ranges between 31-45%, with medical devices and associated adhesives being a major iatrogenic cause. Additionally, pressure-related skin injuries occur in 26% of hospitalized infants <3 months of age with 80% directly related to medical devices, where PPG modules are the most common culprit. By age 7, more than 90% of children previously cared for in the NICU exhibit residual scars secondary to monitoring probes, adhesives and invasive medical interventions. Premature neonates are particularly high-risk given that their epidermis and dermis is 40-60% thinner than adult skin with incomplete cornification, greater trans-epidermal water loss and evaporative heat loss, decreased mechanical strength, and greater propensity to scar. The inherently thin, soft physical properties of the sensors reported here allow for significantly reduced skin contact stresses and adhesion via van der Waals forces alone, and without at least strong conventional adhesives. The result lowers the risk of iatrogenic skin injury in premature neonates by reducing the need for additional adhesives. The devices shown in
Experimental and theoretical studies reveal the fundamental aspects of soft adhesion in these systems. Simulations that use the cohesive zone model (
The presence of the microfluidic channel, as shown in
Further reductions can be achieved by the addition of perforations through the open regions of the EES platform, as shown in
Compatibility with Medical Imaging Techniques Used in the NICU
These open design layouts, taken together with certain favorable electromagnetic characteristics of the antennas and interconnects, also greatly improve compatibility with medical imaging and clinical inspections relative to existing clinical monitoring hardware. Magnetic resonance imaging (MRI) is one type of imaging modality that is essential in the NICU, due to its ability to deliver precise assessment of white matter, gray matter, and posterior fossa abnormalities with functional capabilities that exceed those of ultrasound. The EES platforms described here exploit designs that minimize disturbances in the time dependent magnetic fields associated with MRI scanning, thereby reducing distortions and shadowing artifacts in the final images and eliminating any parasitic heating from magnetically induced eddy currents. Calculations of the gradients of the magnetic field density near electrodes with different structures (mesh, solid and commercial electrodes, see
Additional simulations guide selection of designs that ensure that the resonant frequencies of the EES have no overlap with the working frequencies of typical MRI scanners (64 MHz, 128 MHz, 298 MHz and 400 MHz for 1.5, 3, 7 and 9.4 T MRI scanners, respectively,
Experiment and simulation results also yield information on parasitic heating during an MRI scan. Full three-dimensional multi-physics modeling shows that, at the end of single scan for 0.5 ms, the copper layer of an ECG EES undergoes heating by only 1° C. (
Experimental measurements support these findings.
Beyond benefits in MRI, the EES eliminates radiopaque wires, thereby improving evaluation by XR imaging, a modality required for 90% of low-birth weight neonates (26). Experimental results show that an ECG EES placed over the same tissue in a rodent model imaged using a CT/XR system (nanoScan PET/CT, Mediso) exhibits improved radiolucency in comparison to standard ECG electrodes and wires (
Exploiting this collection of attractive electronic, mechanical and radiolucent properties for practical use in a NICU environment requires in-sensor processing and data analytics to reduce bandwidth requirements on wireless transmission and to ensure operational robustness. For example, computational facilities on the NFC SoC of the ECG EES can support a streamlined version of the Pan-Tompkins algorithm for accurate, on-board analysis of the QRS complex of ECG signals in real-time to yield HR and HRV on a beat-to-beat basis.
The PPG EES relies on similar NFC protocols, but with in-sensor analytic methods that not only reduce requirements on transmission bandwidth but also provide, when used in conjunction with adaptive circuits, crucial functionality for stable operation. Specifically, the processing in this case can enable (i) dynamic baseline control to ensure that the input to the ADC on the NFC SoC lies within the linear response range and (ii) real-time calculation of SpO2 from the PPG traces (
where Vtr is the voltage output of the amplifier, Vpre is the voltage of the input signal, Rs is the input resistance, Rf is the feedback resistance. The voltage divider at V+ with resistor Rd1 and Rd2 governs following equation with Vref of 1.8V
Sixteen different baseline states can be accessed via activation of binary values from four general purpose input output pins (a0, a1, a2, a3) on the SoC (
Calculating SpO2 involves determining the ratio (Roa) between the alternating and direct components of the PPG signals according to
for data from the red and IR LEDs (
Beyond re-capitulation of well-established vital signs, the time synchronized outputs from the ECG EES and the PPG EES allow for determination of advanced physiological parameters that are of high clinical value but not regularly collected in routine practice in NICUs. A key example is the measurement of pulse arrival time (PAT), defined by the time lapse between the maximum fiducial point in the ECG signal (R peak) and the corresponding minimal fiducial point in the PPG signal at valley as in
Preliminary testing of the EES system in both healthy neonates (n=3) and premature infants in two tertiary level NICUs demonstrates feasibility and measurement validity.
Concomitant deployment with standard of care monitors (Intellivue MX800, Philips; Table 1) shows excellent agreement in HR, RR, and SpO2 (
Beyond efficacy and safety, the eventual diffusion of medical technologies depends on economic considerations. Table 2 outlines cost structures associated with all aspects of device construction, ranging from components, to fabrication processing fees and encapsulation materials. The results suggest costs (ECG EES and PPG EES) of less than $20 USDs per unit at scaled production. Full compatibility with autoclave sterilization (2540E, Heidolph) enables safe re-use (
The battery-free, wireless power transfer strategies described here offer advantages in form factor for extremely low birth weight neonates less than 27 weeks of gestational age, although the device requirements for proximity to a primary antenna is less than ideal. Strategies that implement small batteries for operation when wireless power is unavailable, or those that exploit multiple primary antennas can be pursued. The devices may further integrate additional sensors to measure parameters such as transcutaneous CO2 and O2, ballistocardiography, motion and crying time.
The NICU represents one of the most challenging environments to develop new medical technologies given the extreme fragility of the population, and the high acuity of care. The results reported here follow from a collection of advances in engineering science, to establish the basis for a wireless, skin-like technology that not only reproduces comprehensive vital signs monitoring capabilities currently provided by invasive, wired systems but that also adds multi-point sensing of temperature and continuous tracking of blood pressure. These sensors explicitly address the unique needs of the NICU due to their high mechanical compliance and non-invasive skin adhesive interface, their water resistance, and their compatibility with essential medical imaging and inspection. Further clinical validation and testing may lead to broad adoption in both high-resource and low-resource settings.
Fabrication: the fabrication involves a combination of semiconductor processing steps, lamination procedures, transfer printing processes and chip placement and solder bonding. Addition of a thin layer of PDMS layer bonded around the perimeter of the device and the electrodes allowed filling with an ionic liquid using a syringe to form the microfluidic channel. A coating of a soft silicone material on the bottom layer provides a light adhesive surface.
Sensor assessment: the primary antenna (size of 32 cm×34 cm;
The primary antenna was pre-embedded within existing NICU incubators. Sensors were placed on the skin without skin preparation for the neonate thereafter. Data was transmitted, collected, and stored for further data analysis on a table PC (e.g., Surface Pro 4, Microsoft®).
A double layered copper (Cu) foil (18/5 μm thick, Oak Mitsui MicroThin Series) provided the material for the NFC coil and interconnectors (
For the microfluidic channel, photolithography defined SU-8 mold (photoresist SU-8 2100, MicroChem; spin-casting at 3000 rpm for 30 sec, soft baking on a hot plate at 65° C. for 3 min and 95° C. for 20 min, UV irradiance for 380 mJ/cm2, post exposure baking on a hot plate at 65° C. for 3 min and 95° C. for 10 min, development for about 20 min with SU-8 developer, IPA rinsed, and hard baking at 120° C. for 30 min). Spin-casting polytetrafluoroethylene (PTFE, Sigma-Aldrich; thickness of about 100 nm) at 3000 rpm for 30 sec and baking at 110° C. for 5 min formed a thin antiadhesive layer on the SU-8 mold. An additional spin casting on top of the mold and curing at room temperature for 24 hours yielded a bottom PDMS (Sylgard 184, Dow-Corning; 10:1 weight ratio) substrate. Delamination from the SU-8 mold allowed sample placement on a glass substrate with the feature side facing up. Next, a thin film of a fluoropolymer (1 μm, OSCoR 2312 photoresist solution, Orthogonal INC) spincast on a PDMS substrate and then thermally annealed (50° C. for 1 min) yields a low energy coating.
After exposure to oxygen plasma generated at low power (8.5 W) RF at 500 mTorr (Plasma Cleaner PDC-32G, Harrick Plasma) for 20 sec, the upper part (electronic layer encapsulated by PDMS) and the lower part (thin PDMS layer with microfluidic channel) was aligned and bonded. Finally, the bottom side was covered with a Silbione layer and a syringe with a micro-needle injected a blended solution (82:18, volume ratio) of ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate [EMIM][EtSO4], Sigma-Aldrich) and silica gel (high-purity grade, pore size 6 nm, 200-425 mesh particle size, Sigma-Aldrich) into the microfluidic channel.
The commercial software ABAQUS (ABAQUS Analysis User's Manual 2010, V6.10) was used to study mechanics of the devices and to optimize the design layouts. The objectives are to ensure that (1) the interfacial normal and shear stresses on the skin are below the low somatosensory perception of the device on the human skin; and (2) the strain in the copper layers is below the elastic limit such that no plastic yielding occurs. The PDMS (elastic modulus 500 kPa and Poisson's ratio 0.5), Silbione (elastic modulus 3 kPa and Poisson's ratio 0.5) and ionic liquid were modeled by hexahedron elements (C3D8R) while the stiff copper (elastic modulus 119 GPa and Poisson's ratio 0.34) film was modeled by composite shell elements (S4R). The positions of the chips and the widths of serpentine interconnects were optimized to satisfy the competing requirements from mechanics and electromagnetical designs. For example, narrow interconnects improve the elasticity stretchability, but lead to the undesired increase in the electrical resistance. An iterative optimization process was adopted to carefully balance these competing requirements and other mechanical and electromagnetical considerations. The positions of the chips were optimized to avoid entanglement of interconnects and contact between components. The minimum work of adhesive Gmin required to prevent device delamination from the stretched skin was also shown in
A finite element method was used in the electromagnetic simulations to determine the inductance, Q factor and the scattering parameters S11 of the ECG EES and PPS EES in undeformed and deformed states. The simulations were performed using the commercial software Ansys HFSS (Ansys HFSS 13 User's guide, Ansys Inc. 2011), where the lumped port was used to obtain the scattering parameters S11 and port impendence Z. An adaptive mesh (tetrahedron elements) together with a spherical surface (1000 mm in radius) as the radiation boundary, was adopted to ensure computational accuracy. The inductance (L) and Q factor (Q) (shown in
The commercial software ABAQUS (ABAQUS Analysis User's Manual 2010, V6.10) was also used to study peel force of conventional adhesive (elastic modulus 5 MPa and Poisson's ratio 0.5), and EES adhesive with/without the ionic liquid layer (
Simulations of Electromagnetics Associated with MRI Imaging
The finite element method was used to determine the magnetic fields. The simulations were performed using a commercial software (Ansys HFSS 15 User's guide, Ansys Inc. 2012), where adaptive mesh (tetrahedron elements) together with a spherical surface (2000 mm in radius) as the radiation boundary, was adopted to ensure computational accuracy. The in-plane gradient of the magnetic field density underneath the electrodes (
The commercial software ABAQUS (ABAQUS Analysis User's Manual 2010, V6.10) was used to study the temperature change of the skin for one-time MRI scan. The oscillating magnetic field density in MRI is B=20 μT, and the working time for one-time scan of MRI is 0.5 ms. The received power of the ECG EES from the electromagnetic simulation is imported into ABAQUS for thermal analysis. The convective heat transfer coefficient of air is 6 W/(m2·K). Except for Cu, the hexahedron elements (DC3D8) were used, whereas thin Cu layer was modeled by the shell elements (DS4). The minimal mesh size was 1/10 of the thickness (10 μm) of the ionic layer, and the mesh convergence of the simulation was ensured. The thermal conductivity, heat capacity and mass density used in the simulations are 0.35 W·m−1·K−1, 2135 J·kg−1·K−1 and 1490 kg·m−3 for the skin; 0.15 W·m−1·K−1, 1510 J·kg“1·K−1 and 1000 kg·m−3 for PDMS; 0.15 W·m−1·K−1, 2200 J·kg”1·K−1 and 1100 kg·m−3 for ionic liquid; 0.15 W·m−1·K−1, 1460 J·kg−1·K−1 and 970 kg·m−3 for Silbione; and 386 W·m−1·K−1, 383 J·kg1·K−1 and 8954 kg·m−3 for Cu, respectively.
The apparatuses and methods provided herein have applications including, but not limited to: critical care monitoring in neonatal intensive care units; critical care monitoring in pediatric intensive care units; critical care monitoring in neonatal/pediatric cardiac care units; critical care monitoring in neonatal/pediatric neocritical care units; post-discharge home monitoring for high-risk neonates; critical care monitoring in adults; home monitoring for medical recovery; and monitoring for rehabilitation care.
The advantages of the apparatuses and methods include foundational concepts of skin-like, multi-modal sensors enabled by advances in in-sensor analytics and time-synchronized, multi-nodal wireless operation. This offers the ability to significantly improve the efficacy and safety of vital signs monitoring for newborns in neonatal intensive care units.
Ultra-low noise operation enables capture of low-power physiological signals such as fetal heart rate or miniscule movements of the chest wall reflective of breathing in a premature neonate.
Apparatuses may include two separate but software linked (e.g., “electronically-coupled”) sensor systems: a chest-deployed unit with ECG, skin temperature, and seismocardiograhy, and a limb-based unit with photoplethysmography for pulse oximetry.
Further embodiments include the deployment of multiple sensors at various locations dependent on the clinical use case. For instance, during skin-to-skin or “kangaroo care” where a baby is placed on the mom's chest, the ECG sensors can be placed on the back or flank of the neonate.
Advanced software function and interoperability enabling cloud storage, remote login, and secure communication. Further capabilities include the integration of third-party sensors, wearables, and other hardware systems.
Design features that enable immediate deployability in NICUs include: Radiolucency that is compatible to CT and XR imaging; MRI compatibility; and optically transparent design allows for clinical evaluation of the skin directly beneath sensor negating the need for removal that can be damaging to fragile skin.
Safety features that drastically decrease the risk of iatrogenic injury and support therapeutic skin-to-skin contact include: The soft, mechanical nature of the sensor itself enables intimate skin coupling without the need of powerful adhesives. The removal of traditional electrodes and sensors with adhesives lead to skin stripping and iatrogenic injuries including permanent scarring. The devices and systems provided herein exhibit peel forces orders of magnitude lower than existing systems. Soft, thin, wearable nature allows for skin-to-skin contact that is unobstructed between mother and baby.
Advanced physiological monitoring capabilities that exceed current standard of care capabilities includes: continuous measurement of skin temperature at multiple locations of the neonate; thus, this allows for the development of novel metrics of peripheral perfusion; lows for calculation of pulse arrival time and pulse transit time—these measures are surrogate markers of blood pressure but can be measured continuously and non-invasively. A high-frequency 3-axis accelerometer within the sensor system can be placed directly on the chest enabling continuous, wearable seismocardiography (SCG) of neonates. This enables continuous recording of heart sounds, and assessment of chest wall movements with breathing for more accurate respiratory rate. The apparatuses may enable correlation of SCG with stroke volume and ejection fraction measured by echocardiography. The accelerometer also allows analysis of a baby's position including when a baby is upright. This can be used to quantify important parameters such as how long a baby is being held for kangaroo care, being fed, resting, crying and the like. The output of the sensor can be used to determine whether a baby has sustained an injury that is consistent with non-accidental trauma (e.g., child abuse).
The multi-nodal (and multi-modal) aspect of the devices provided herein facilitate at least dual measurement systems to capture accurate respiratory rate. The measurement of respiratory rate derived through the ECG via impedance pneumonography is often times inaccurate and overestimates the true respiratory rate. Herein, we describe the ability to measure chest wall movement to derive respiratory rate along with traditional impedance pneumonography.
Each sensor system may have a form factor in a patch-like geometry that occupies a small surface area (less than 2.0 cm×4.0 cm) that facilitates placement on a premature neonate.
Embodiments include: where the form factor includes a single chest unit sensor with all electronics and vital sign monitoring functionality; where the electrode spacing or sensor elements are adjustable; the ability to create alarms based on pre-programmed or physician specified inputs. These alarms include both visual and audio notifications. These notifications can be displayed on an external display unit or onboard the sensor itself (either via an onboard LED or sound).
A sensor system having an optical unit for the photoplethysmograph may be located on the infant's nail (toenail or fingernail).
The sensors may be wrapped circumferentially around a limb or body structure and fastened with a mechanical mechanism (e.g., hook in loop, clasps, buttons, magnets).
Embodiments include where the pulse oximeter unit is placed on various locations of the body to derive a measure location specific pulse oximetry. Locations include, but are not limited to, all 4 limbs, chest, back, abdomen, forehead.
Embodiments include where the same power management and antennae schema is applied to Bluetooth rather than NFC.
Embodiments include the sensors having an onboard battery—but wireless charging is implemented in instances where a wireless power source is detected which simultaneously powers the sensor and charges the battery.
Here we report foundational concepts for a wireless, battery-free vital signs monitoring system that exploits an at least bi-nodal pair of ultrathin, low-modulus measurement modules, each referred to here as an epidermal electronic systems (EES), capable of gently and non-invasively interfacing onto the skin of neonates, even at gestational ages that approach the limit of viability. The materials choices and device architectures leverage the most advanced concepts in soft electronic systems, with modes of operation that follow from four essential advances reported here: (1) techniques for simultaneous wireless power transfer, low noise sensing and data communications via a single link based on magnetic inductive coupling at a radio frequency band that has negligible absorption in biological tissues, (2) efficient algorithms for real-time data analytics, signal processing and dynamic baseline modulation implemented in the highly constrained computing resources available on the sensor platforms themselves, (3) strategies for time-synchronized, continuous streaming of wireless data from two, separately located devices and (4) fully transparent and radiolucent designs that enable visual inspection of underlying tissue of the skin interface, and magnetic resonance (MRI) and X-ray imaging (XR) of the neonate. The resulting systems are qualitatively smaller in size, lighter in weight and less adhesive to the skin than clinical standard hardware, with potential for costs that are orders of magnitude lower. Other embodiments of the sensor include the coupling of Bluetooth communication and small embedded batteries.
The images shown in
Because the standard NFC protocol at 13.56 MHz supports only low speed, low fidelity applications in contactless payments, wireless identification and others, significant optimization is necessary in both the transponder and host reader systems at ISO15693 to enable required data transfer rates for NICU monitoring (hundreds of Hz). These optimizations enable continuous streaming of data at rates of up to 800 bytes/s with dual channels, which is orders of magnitude larger than previously reported NFC sensing devices and represents a first example of bi-nodal, time-synchronized operation. A key is in minimizing the overhead associated with transfer by packaging data into 6 Blocks (24 Bytes) in a circular buffer. Here, reading occurs with an NFC host (LRM1002, Feig Electronics) interfaced to a microcontroller (MCU, ARM® Cortex™-M4F) in a Bluetooth Low Energy (BLE) system (SoC, nRF52832, Nordic Semiconductor) configured this type of customized circular buffer decoding routine. The receiver antenna (size of 32 cm×34 cm) connects to the host system for simultaneous transfer of RF power to the ECG EES and the PPG EES. The low current consumption of these platforms (about 450 μA and 2 mA as peak current, respectively) can be satisfied by RF power (5 W; compliant to EN 50364; standard for human exposure) at vertical distances of up to 25 cm, through biological tissues, bedding, blankets, padded mattresses, wires, sensors and other materials found in NICU isolettes, and across lateral areas of 32 cm×34 cm, for full coverage wireless operation in a typical incubator. The BLE radio allows transmission of data to a personal computer, tablet computer or smartphone with a range of up to 20 m. Further software embodiments would enable direct communication and telemetry with legacy systems in the NICU including electronic medical records.
In-sensor processing and data analytics further reduce bandwidth requirements on wireless transmission and greatly improve the robustness in operation. For example, computational facilities on the NFC SoC of the ECG EES can support a streamlined version of the Pan-Tompkins algorithm for accurate, on-board analysis of the QRS complex of ECG signals in real-time to yield HR, HRV, and RR on a beat to beat basis.
Measurements of skin temperature rely on sensors internal to the NFC SoC in each EES, where transmission at a sampling frequency of 1 Hz is sufficient for monitoring purposes. The exceptionally low thermal mass of the EES and the small thickness of the substrate layer (PDMS; 50 μm in thickness) that separates the SoC from the skin ensure fast thermal response times and excellent thermal coupling, respectively. Comparisons against readings from an FDA-approved thermometer serve as means to calibrate the sensor (
The PPG EES relies on similar NFC protocols, but with in-sensor analytic methods that not only reduce requirements on transmission bandwidth but also provide, when used in conjunction with adaptive circuits, crucial functionality for stable operation. Specifically, the processing in this case enables (i) dynamic baseline control to ensure that the input to the ADC on the NFC SoC lies within the linear response range and (ii) real-time calculation of SpO2 from the PPG traces (
V
tr
=−Z
f
i
PD+(1+Zf/Rs)V+=−Rf/((jwR
fCf+1))iPD+(1+Rf/Rs)V+ (4)
where Vtr is output of the amplifier, Zf is impedance of feedback loop, Rs is series resistance, Cf is feedback capacitor, Rf is feedback resistor, iPD is current output of photodiode and,
V
+
=
V
dd
R
d2/(Rd2+a2(4Rg+Rd1)+a1(2Rg+Rd1)+a0(Rg+Rd1)). (5)
Four different baseline levels can be accessed via activation of three GPIO outputs (a0, a1, a2).
Calculating SpO2 involves determining the ratio (Roa) between the alternating component and the direct component of PPG signals according to the following equation
R
oa((AC
RED)/
DC
RED)/(
AC
IR/
DC
IR) (6)
for data from the red and IR LEDs (
The time synchronized outputs from the ECG EES and the PPG EES allow determination of the pulse arrival time (PAT), as defined by the time lapse between the maximum fiducial point in the ECG signal (R peak) and the corresponding minimal fiducial point in the PPG signal at valley as in (
A full demonstration of the wireless bi-nodal system on a neonate (38 wks 3/7, 2.75 kg) validates the performance a clinical environment. Here, the NFC antenna for power transfer and data communication lies beneath the mattress inside an incubator (
A hardware modification for further enhancement in functionality including 6-axial inertial movement unit (IMU; 3-axial accelerometer and 3-axial gyroscope; BMI160, Bosch Sensortec), a Bluetooth SoC with 32-bit ARM Cortex-M4F microprocessor (nRF52832, Nordic Semiconductor), and on-board flash memory (S25FS512, Cypress).
While certain embodiment of the sensor systems are purely wirelessly powered, other embodiments of the sensor systems with onboard power when a neonate or infant is moved away from the inductive antennae are disclosed. Furthermore, a hardware modification is also disclosed to include a secondary power supply plan using a small battery embedded in the sensors through power supply and management units with three mechanisms: (1) charging battery when wireless power transfer (WPT) is activated, sensed through WPT sensing circuit, (2) activating primary power source through WPT that continuously supplies power to the sensors via full wave rectifier and voltage regulator, (3) activating secondary power supply based battery when wireless power transfer is not sensed. Extremely low-power nature of our sensors is achieved by optimizing power management using both on-board memory and down-sampled real-time wireless transmission such that the raw data is stored into flash memory while power demanding real-time transmission event is effectively duty cycled to minimized power consumption without loss of signal quality. The outcome is facilitating 24-hour battery power operation using small non-magnetic embedded battery (12 mAh, 9 mm×9 mm×3 mm (W×L×H)) without affecting the overall dimension or thickness of the sensor significantly.
Also, further software innovations to the sensor systems according embodiments of the invention distinguish this invention from prior works. Currently, the wireless sensors each communicate via Bluetooth Low Energy (BLE) with mobile devices (e.g., Microsoft® SurfacePro and Samsung® smartphones). Software enables continued transmission of captured data to a cloud-based server. The cloud will decouple a neonate's data from the mobile devices by centralizing the data with an HIPAA-compliant data storage (Amazon Simple Storage) and database (Amazon Relational Database). It will also provide opportunities to integrate with existing systems including Electronic health record (EHR) and Hospital information system (HIS) with GE Healthcare MUSE eDoc Connect. By utilizing the cloud's computation nodes with General-purpose computing on graphics processing units (GPGPU) and Field-programmable gate array (FPGA), the platform can perform accelerated real-time analytics and machine learning, and provide a base to do distributed computation on cloud clusters with big-data engines such as Apache Spark. By developing interfaces to the server via Representational State Transfer (REST) Application programming interface (API) and web interface, authorized doctors and researchers will have a secure remote access to the data and tools to execute post-hoc analysis. Relevant parameters for in-clinical care use include 24-hour battery power operation, cloud integration, and a web-interface.
The foregoing description of the exemplary embodiments of the present 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 activate 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.
This PCT application claims priority to and the benefit of U.S. Provisional Patent Application Serial Nos. 62/753,303, 62/753,453 and 62/753,625, each of which was filed Oct. 31, 2018, and is incorporated herein by reference in its entirety, respectively. This PCT application is related to a co-pending PCT patent application, entitled “SENSOR NETWORK FOR MEASURING PHYSIOLOGICAL PARAMETERS OF MAMMAL SUBJECT AND APPLICATIONS OF SAME”, by John A. Rogers et al., with Attorney Docket No. 0116936.214W02, and a co-pending US patent application entitled “APPARATUS AND METHOD FOR NON-INVASIVELY MEASURING BLOOD PRESSURE OF MAMMAL SUBJECT”, by John A. Rogers et al., with Attorney Docket No. 0116936.215US2, each of which is filed on the same day that this PCT application is filed, and with the same assignee as that of this application, and is incorporated herein by reference in its entirety, respectively. 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.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2019/059131 | 10/31/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62753303 | Oct 2018 | US | |
| 62753453 | Oct 2018 | US | |
| 62753625 | Oct 2018 | US |
