EP4746766A1

EP4746766A1 - Multiplexed wireless sensors for physiological monitoring

Info

Publication number: EP4746766A1
Application number: EP24846291.3A
Authority: EP
Inventors: John A. Rogers; Ha Uk CHUNG; Seyong Oh; Jaeyoung Yoo; Shuai Xu
Original assignee: Northwestern University
Current assignee: Northwestern University
Priority date: 2023-07-21
Filing date: 2024-07-19
Publication date: 2026-05-27
Also published as: WO2025024314A1

Abstract

An apparatus for non-invasively measuring physiological parameters of a mammal subject, comprising: a microcontroller unit adapted in wireless communication; at least one temperature sensing unit; and a pair of thermally conductive electrodes placed underneath the temperature sensing unit. The temperature sensing unit is thermally insulated to limit the temperature change by environmental effect from radiant heating, convection, and humidity to be within 0.5 °C. The pair of thermally conductive electrodes enables the thermal time constant less than 60 seconds. The microcontroller unit wirelessly transmits any sensor generated data and features to a base station.

Description

MULTIPLEXED WIRELESS SENSORS FOR PHYSIOLOGICAL MONITORING

CROSS-REFERENCE TO RELATED PATENT APPLICATION

This application claims priority to and the benefit of U.S. Provisional Application No. 63/528,096, filed July 21, 2023, which is incorporated herein in its entirety by reference.

FIELD OF THE INVENTION

The invention relates generally to the field of electrotherapy, and more particularly to multiplexed wireless sensors for physiological monitoring.

BACKGROUND OF THE INVENTION

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.

Temperature is the most commonly collected vital sign in clinical medicine. Clinical thermometers remain one of the most widely deployed medical devices globally. Measurements of body and skin temperature are essential for clinical decision-making related to infection, inflammation, sleep, fertility and others. Most assessments of temperature involve episodic measurements at specific anatomical locations (e.g., axilla, rectum, temporal artery, or oral cavity), conducted manually by clinicians or caregivers. This cumbersome process of monitoring involves additional challenges when applied to vulnerable patient populations. For example, wired probes represent the standard of care in pediatric medicine, to avoid hypothermia or overheating in the context of radiant warming in incubator units. Such measurements are essential for neonates of significant prematurity, where thermal homeostasis typically requires active control and/or medical intervention.

A growing body of scientific evidence supports the use of continuous physiological monitoring with wireless, skin-interfaced sensors to identify clinical deterioration at early stages, to prevent unplanned intensive care unit admissions, to enhance patient comfort, and to reduce hospital stays. For temperature, several such wireless options are now commercially available (e.g., TempTraq from BlueSpark, Core® from greenTEG AG, and Tucky from E-TakesCare. While these systems offer continuous measurements without cables, they suffer from key limitations. First, many exist only as single-use disposables, with associated cost barriers that prevent their use in low-income settings. Second, all existing options are too rigid and/or too large for neonates. Third, sensitivity to the environment including ambient temperature and/or humidity hinders accurate temperature measurements. Fourth, none offers the ability for multisite, time-synchronized operation. Fifth, capabilities do not extend beyond assessments of skin temperature.

Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.

SUMMARY OF THE INVENTION

In one aspect, the invention relates to an apparatus for non-invasively measuring physiological parameters of a mammal subject, comprising a microcontroller unit (MCU) adapted in wireless communication; at least one temperature sensing unit; and a pair of thermally conductive electrodes placed underneath the temperature sensing unit. The temperature sensing unit is thermally insulated to limit the temperature change by environmental effect from radiant heating, convection, and humidity to be within 0.5 °C. The thermally conductive electrodes enable the thermal time constant less than 60 seconds. The MCU wirelessly transmits any sensor generated data and features to a base station.

In one embodiment, the pair of thermally conductive electrodes connected to circuitry measuring the connectivity between the skin of the mammal subject and electrodes.

In one embodiment, the MCU calculates the wearing time by measuring how long the connectivity between the skin and electrodes are maintained.

In one embodiment, the apparatus further includes an inertial measurement unit (IMU) measuring motion and acoustic signatures.

In one embodiment, the MCU calculates heart rate and respiratory rate from the motion and acoustic signatures when mounted on chest of the mammal subject.

In one embodiment, the MCU calculates the vocal features including crying events, swallowing when mounted close to the suprasternal notch of the mammal subject.

In one embodiment, the MCU calculates the body posture of the mammal subject.

In another aspect, the invention relates to a wirelessly controlled thermoregulating system, comprising a plurality of wireless apparatuses for measuring temperatures of a mammal subject; and a base station capable of controlling radiant heating, or convective heating, or humidity. The wireless apparatuses are capable of autonomously configuring settings of the base station to maintain the temperature of the mammal subject in a configured value. The base station is configured to generate alarm and alerts triggered by the wireless apparatuses. The base station operably displays the temperature readings of at least one of the wireless apparatuses for the temperature measurement.

In one embodiment, the plurality of wireless apparatuses is time-synchronized to each other.

In one embodiment, the plurality of wireless apparatuses is conformably attached to multiple regions of the skin of the mammal subject for measuring the temperatures therein for spatiotemporal temperature mapping.

In one embodiment, the system further comprises a customized app with a graphical user interface operating on the base station, configured to support real-time control of operations of the wireless apparatuses, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

In one embodiment, the base station includes a mobile device, a smartphone, a tablet, a computer, a cloud server, or any electronic device with data reading/processing/displaying capability.

In a further aspect, the invention relates to An apparatus for non-invasively measuring physiological parameters of a mammal subject, comprising a sensor unit comprising a sensor member for measuring at least one physiological parameter of the mammal subject, and a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data therefrom and processing the received data, and for wireless data communications; and an elastomeric encapsulation layer at least partially surrounding the sensor unit to form a skinfacing surface and an ambient-facing surface.

In one embodiment, the sensor member comprises a temperature sensor for measuring temperature of the mammal subject.

In one embodiment, the temperature sensor comprises two negative temperature coefficient (NTC) thermistors fold in a manner that orients one toward the skin-facing surface and the other toward the ambient-facing surface.

In one embodiment, the temperature sensor comprises one or more resistance temperature detectors and/or one or more semiconductor-based temperature sensors.

In one embodiment, the sensor member further comprises an inertial measurement unit (IMU) mounted in mechanical communication with the skin measuring vital signs including a heart rate, a respiratory rate, a physical activity, and/or a body position.

In one embodiment, the sensor member further comprises one or more of an SpCh sensor for measuring a blood oxygen saturation; an electrocardiogram (ECG) sensor for measuring ECG signal; and a photoplethysmography (PPG) sensor for measuring a PPG signal.

In one embodiment, the sensor unit further comprises a power management integrated circuit (PMIC); an LED indicator; and magnets, wherein all mounted on a flexible printed circuit board (fPCB) using surface-mounted technology (SMT).

In one embodiment, output of the PMIC supports skin-facing and ambient-facing temperature measurements and mechano-acoustic data collection.

In one embodiment, the LED indicator is configured to serve as a visual alarm that is activatable based on the measured physiological parameters and/or user-defined threshold settings.

In one embodiment, the elastomeric encapsulation layer is a waterproof and biocompatible silicone enclosure.

In one embodiment, the elastomeric encapsulation layer has a base encapsulation layer that forms the skin-facing surface to reduce the thermal mass at the interface between the bottom NTC and the skin.

In one embodiment, the apparatus further comprises a top thermal insulating layer and a bottom thermal insulating layer disposed between the sensor unit and the elastomeric encapsulation layer to at least partially cover the sensor unit for minimizing the influence of the ambient on measurements of the temperature of the skin.

In one embodiment, the bottom thermal insulating layer has an air cavity in which the bottom NTC thermistor is placed, so as to mechanically isolate the bottom NTC thermistor from the other parts of the apparatus. In one embodiment, the remaining space inside the elastomeric encapsulation layer of the apparatus is filled with a silicone elastomer.

In one embodiment, the apparatus is a battery-free apparatus configured to operate in a battery -free mode, or a battery-powered apparatus configured to operate in a battery-powered mode.

In one embodiment, the battery-free apparatus further comprises a wireless power harvesting unit in communication with the sensor unit for wireless power harvesting.

In one embodiment, the wireless power harvesting unit comprises a power receiving (Rx) coil connecting through flexible copper traces to a rectifier, a voltage regulator, supercapacitors, a PMIC, and magnets for mechanically coupled interconnects.

In one embodiment, the wireless power harvesting unit is detachably connected to the sensor unit.

In one embodiment, the battery-free mode relies on near-field communication (NFC) for wireless power transfer from an external transmitting coil to the power receiving coil (Rx).

In one embodiment, the battery-powered apparatus further comprises a battery unit having a battery.

In one embodiment, the battery unit is detachably connected to the sensor unit.

In one embodiment, the battery is a rechargeable battery.

In one embodiment, the SoC comprises a Bluetooth interface and/or a near-field communication (NFC) interface for the wireless data communications between the SOC and an externa device.

In one embodiment, the apparatus further comprises a customized app with a graphical user interface operating on the external device, configured to support real-time control of operations of the sensor unit, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

In one embodiment, the external device is a base station including a mobile device, a smartphone, a tablet, a computer, a cloud server, or any electronic device with data reading/processing/displaying capability.

In one embodiment, the apparatus is characterized by miniaturized dimensions and a soft, skin-compatible encapsulation structure.

In one embodiment, the apparatus is configured to enable continuous monitoring in the most challenging care environments, and conformable placement in specific anatomical locations including a floor of the axilla where the axillary artery is most superficial to the skin for enhanced accuracy, and targeted application to areas of localized skin inflammation or infection.

In one embodiment, the apparatus is configured to enable accurate sensing even in highly variable ambient temperature conditions including those associated with direct radiant warming and high humidity.

In one embodiment, the apparatus is configured to enable simultaneously recording relevant physiological parameters including a heart rate, a respiratory rate, a body position, vocalizations, and movement via mechano-acoustic measurements of body motions and sounds captured using a high-bandwidth accelerometer.

In one embodiment, the apparatus is stretchable and bendable.

In one aspect, the invention relates to a sensor network system for non-invasively measuring physiological parameters of a mammal subject, comprising a plurality of wireless apparatuses time-synchronized to each other, wherein each wireless apparatus is placed on a respective region of the skin of the mammal subject and comprises a sensor unit comprising a sensor member for measuring at least one physiological parameter of the mammal subject, and a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data therefrom and processing the received data, and for wireless data communications; and a base station adapted in wireless communication with the plurality of wireless apparatuses and configured to support real-time control of operations of the wireless apparatuses, to receive, from the wireless apparatuses, to process, and to display the physiological parameters.

In one embodiment, each wireless apparatus further comprises an elastomeric encapsulation layer at least partially surrounding the sensor unit to form a skin-facing surface and an ambient-facing surface.

In one embodiment, each wireless apparatus further comprises a top thermal insulating layer and a bottom thermal insulating layer disposed between the sensor unit and the elastomeric encapsulation layer to at least partially cover the sensor unit for minimizing the influence of the ambient on measurements of the temperature of the skin.

In one embodiment, the bottom thermal insulating layer has an air cavity in which the bottom NTC thermistor is placed, so as to mechanically isolate the bottom NTC thermistor from the other parts of the apparatus.

In one embodiment, each apparatus is a battery-free apparatus configured to operate in a battery -free mode, or a battery-powered apparatus configured to operate in a battery-powered mode.

In one embodiment, the SoC comprises a Bluetooth interface and/or a near-field communication (NFC) interface for the wireless data communications between the SOC and the base station.

In one embodiment, the base station is capable of controlling radiant heating, or convective heating, or humidity.

In one embodiment, the wireless apparatuses are capable of autonomously configuring settings of the base station to maintain the temperature of the mammal subject in a configured value.

In one embodiment, the base station is configured to generate alarm and alerts triggered by at least one of the wireless apparatuses.

In one embodiment, the base station is configured to display the temperature readings of the wireless apparatus(s) for temperature measurement.

In one embodiment, the sensor network system enables continuous, full-body measurements of temperature distributions for spatiotemporal temperature mapping.

In one embodiment, the sensor network system enables measurements of temperature differentials between the central skin and the peripheral skin, which are particularly valuable in tracking for early signs of sepsis in neonates.

In one embodiment, the sensor network system further comprises a customized app with a graphical user interface operating on the base station, configured to support real-time control of operations of the wireless apparatuses, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

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 disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.

FIG. 1 shows device architecture, use cases and options in power sources of a wirelessly controlled thermoregulating system according to embodiments of the invention. Panel A: Schematic illustrations of modes for continuous vital signal monitoring using a ‘button’ device with different modes of power supply. Panel B: Photographs of devices on a realistic neonate model. The upper and bottom panels show the battery-free and battery-powered versions, respectively. Panel C: Photographs of three sub-systems; the sensor, wireless power harvesting unit, and battery unit. Panels D-E: Exploded view schematic illustrations of these three units. Panels F-G: Experimental data and functional block diagram of a closed-loop warmer system for temperature regulation in an incubator. The system includes a button device, a customized user interface, and a wireless module for heating the local environment of the incubator. Multiple devices wirelessly connect to a single user interface (UI), as a time-synchronized multi-sensor system.

FIG. 2 shows performance benchmarking of a wirelessly controlled thermoregulating system for temperature sensing according to embodiments of the invention. Panel A: Schematic illustration of the device. The skin and ambient temperature can be monitored by the skin- and ambient-facing NTCs, respectively. Panel B: 3D FEA results for the distribution of temperature across a device without any thermal insulation (control). Panel C: 3D FEA results for the distribution of temperature across a device with thermally insulating air cavity structure. Panels D-E: Comparison of the accuracy of temperatures measured with a button device and a clinical- grade, hard-wired sensor (DeRoyal), for temperatures from 30 to 45 °C, with a residence time of 30 mins at each setting. Panel F: Continuous temperature monitoring with the button and DeRoyal devices for temperature cycling from 25 to 45 °C and then 45 to 25 °C, for four iterations. Panel G: Tests of sensitivity to humidity for these two devices. The bottom panel shows the results after temperature saturation. Panel H: Tests of endurance, involving measurements at 35 C after storage for 24-hour in an oven at 60 °C, followed by a repeat of this measurement after 24 hours storage at -20 °C. Panels I-J: Measurements of response time, involving rise and decay times (63.2 % transition from an initial to a final temperature) following rapid changes in temperature.

FIG. 3 shows monitoring of local skin temperature using a wirelessly controlled thermoregulating system according to embodiments of the invention. Panel A: Skin temperature at the chest collected using a button device and a commercial wireless device (Core) during exercising and sleeping. Panel B: Corresponding Bland-Altman plots. Panel C: Circadian rhythms appear in temperatures measured across a period of three days. Panel D: Results for mapping of skin temperature at eight different mounting locations (#1-8) using a wirelessly time- synchronized collection of devices and weight factors of corresponding body parts (%) before (left) and after (right) a 20-min exercise. Panel E: Continuous measurements of skin temperature at these locations and mean skin temperature (TMST) calculated via a weighted sum of the local temperature. Panel F: Similarity factor (R-squared, R²) between TMST and temperatures of each location (upper panel). The temperature variations for the eight locations and T ST during a workout test (lower panel).

FIG. 4 shows monitoring of core body temperature using a wirelessly controlled thermoregulating system according to embodiments of the invention. Panel A: Photograph of a battery-powered device mounted under the arm of a realistic neonate model. Panel B: Skin temperature collected from a device and a digital thermometer at the axillary region of a healthy adult. The inset graph shows the temperature 45 mins after mounting both sensors. Panel C: Core-body temperature estimated using a device mounted at the axillary region and using an ingestible sensor (E-pill) during exercising and sleeping. Here, the core-body temperature estimate corresponds to the addition of 1.2 °C to the axillary skin temperature (T_COre = TButton + 1.2 °C), d) Corresponding Bland-Altman plot for these core-body temperatures. Panel E: Bland- Altman plot for core-body temperatures measured for 24 h from a healthy adult subject, repeated three times in sequence. Panel F: Bland- Altman plot for similar measurements from three healthy adults. Panel G: Circadian rhythms revealed by core-body temperatures measured at the axillary region for 24 h. Panel H: Variations in core-body temperature for 24 h from four health adult subjects.

FIG. 5 shows additional capabilities: heart rate, respiratory rate, and body orientation from neonates according to embodiments of the invention. Panel A: Photograph of a button device and hard-wired ECG and temperature sensors mounted on a realistic neonate doll. Panel B: Body orientation and activity data extracted from the 3-axis accelerometer. Panel C: Filtered acceleration data for various body positions. The x, y, and z-axis data were normalized and subtracted from each other. Panels D-F: Representative HR results from analysis of device data compared to those obtained with an ECG sensor. Panels G-I: Corresponding RR results. FIG. 6 shows representative data collected from patients in the NICU according to embodiments of the invention. Panels A-B: Photographs of infants mounted with a device on a suprasternal notch (SN) for tracking of cardiopulmonary activity. Panel C: Photograph of an infant mounted with two devices on alternative locations for collecting global movements of the body. Panel D: Representative data obtained from a neonate (gestational age, GA: 39 weeks) in the NICU before, during, and after a blood draw. Panels E-F: Corresponding HR and RR changes for three healthy infant subjects, g) Average HR and RR data for 11 infant subjects. Panel H: Skin temperature data in response to crying for a newborn baby (GA:42 weeks).

FIG. 7 shows a schematic structure of a battery-powered apparatus according to one embodiment of the invention.

FIG. 8 shows circuit configurations of the button sensor with two powering modules.

FIG. 9 shows current consumption of the button device.

FIG. 10 shows temperature calibration.

FIG. 11 shows FEA simulation for the button device.

FIG. 12 shows Bluetooth® signal strength.

FIG. 13 shows temperature accuracy and Humidity effect test setup.

FIG. 14 shows FDA guidance for temperature accuracy.

FIG. 15 shows skin-sided and ambient-sided temperatures.

FIG. 16 shows time response measurement setup.

FIG. 17 shows size comparisons between the button sensor and commercial wireless sensor (Core).

FIG. 18 shows a time-synchronization test.

FIG. 19 shows skin temperature data recorded from subjects during sleep and exposure to a sauna.

FIG. 20 shows core body temperature estimation using dual temperature monitoring.

FIG. 21 shows extracted body orientation and rotation data for body position.

FIG. 22 shows one embodiment (ADAM 9.1) description. Calibration testing of two embodiments of skin temperature sensors utilizing technology described above compared against another gold standard, GE Giraffe Infant Probe.

FIG. 23 shows performance of the two embodiments in a GE Giraffe incubator in open air setting on a simulated human body compared against the GE Infant Probe.

FIG. 24 shows an effect of mylar reflective film on both one embodiment of the skin temperature sensor (ADAM 9.1) and GE infant probe.

FIG. 25 shows an effect of humidity to both embodiments compared to GE infant probe.

FIG. 26 shows an effect of mylar reflective film with radiant heating using FEA modeling.

FIG. 27 shows performance of one embodiment (ADAM 9.1) without any insulation in convective setting in incubator using FEA modeling.

FIG. 28 shows performance of one embodiment (ADAM 9.1) when insulation is added suing FEA modeling.

FIG. 29 shows a breakout view of one embodiment including thermal contact beneath the temperature sensing element to enhance the thermal conductivity and insulation layer for reducing ambient effect.

FIG. 30 shows one embodiment of the sensor including multiple temperature sensing elements to detect degradation of temperature reading.

FIG. 31 shows one embodiment of the sensor including bi-polar metal contact connected with DC lead-off circuit to detect sensor’s contact to patient and to measure wearing time.

FIG. 32 shows a schematic sensor network system according to one embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.

The terms used in this specification generally have their ordinary meanings in the art, within the context of the invention, and in the specific context where each term is used. Certain terms that are used to describe the invention are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the invention. For convenience, certain terms may be highlighted, for example using italics and/or quotation marks. The use of highlighting has no influence on the scope and meaning of a term; the scope and meaning of a term is the same, in the same context, whether or not it is highlighted. It will be appreciated that same thing can be said in more than one way. Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein, nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.

One of ordinary skill in the art will appreciate that starting materials, biological materials, reagents, synthetic methods, purification methods, analytical methods, assay methods, and biological methods other than those specifically exemplified can be employed in the practice of the invention without resort to undue experimentation. All art-known functional equivalents, of any such materials and methods are intended to be included in this invention. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

Whenever a range is given in the specification, for example, a temperature range, a time range, or a composition or concentration range, all intermediate ranges and subranges, as well as all individual values included in the ranges given are intended to be included in the invention. It will be understood that any subranges or individual values in a range or subrange that are included in the description herein can be excluded from the claims herein.

It will be understood that, as used in the description herein and throughout the claims that follow, the meaning of “a”, “an”, and “the” includes plural reference unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and equivalents thereof known to those skilled in the art. As well, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, and “having” can be used interchangeably. It will be understood that when an element is referred to as being “on”, “attached” to, “connected” to, “coupled” with, “contacting”, etc., another element, it can be directly on, attached to, connected to, coupled with or contacting the other element or intervening elements may also be present. In contrast, when an element is referred to as being, for example, “directly on”, “directly attached” to, “directly connected” to, “directly coupled” with or “directly contacting” another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the invention.

Furthermore, relative terms, such as “lower” or “bottom” and “upper” or “top,” may be used herein to describe one element’s relationship to another element as illustrated in the figures. It will be understood that relative terms are intended to encompass different orientations of the device in addition to the orientation depicted in the figures. For example, if the device in one of the figures is turned over, elements described as being on the “lower” side of other elements would then be oriented on “upper” sides of the other elements. The exemplary term “lower”, can therefore, encompasses both an orientation of “lower” and “upper,” depending of the particular orientation of the figure. Similarly, if the device in one of the figures is turned over, elements described as “below” or “beneath” other elements would then be oriented “above” the other elements. The exemplary terms “below” or “beneath” can, therefore, encompass both an orientation of above and below.

It will be further understood that the terms “comprises” and/or “comprising”, or “includes” and/or “including”, or “has” and/or “having”, or “carry” and/or “carrying”, or “contain” and/or “containing”, or “involve” and/or “involving”, “characterized by”, and the like are to be open-ended, i.e., to mean including but not limited to. When used in this disclosure, they specify the presence of stated features, regions, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof.

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the invention, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

As used in the disclosure, “around”, “about”, “approximately” or “substantially” shall generally mean within 20 percent, preferably within 10 percent, and more preferably within 5 percent of a given value or range. Numerical quantities given herein are approximate, meaning that the term “around”, “about”, “approximately” or “substantially” can be inferred if not expressly stated.

As used in the disclosure, the phrase “at least one of A, B, and C” should be construed to mean a logical (A or B or C), using a non-exclusive logical OR. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.

The term “flexibility” or “bendability”, as used in the disclosure, refers to the ability of a material, structure, device or device component to be deformed into a curved or bent shape without undergoing a transformation that introduces significant strain, such as strain characterizing the failure point of a material, structure, device or device component. In an exemplary embodiment, a flexible material, structure, device or device component may be deformed into a curved shape without introducing strain larger than or equal to 5%, for some applications larger than or equal to 1%, and for yet other applications larger than or equal to 0.5% in strain-sensitive regions. A used herein, some, but not necessarily all, flexible structures are also stretchable. A variety of properties provide flexible structures (e.g., device components) of the invention, including materials properties such as a low modulus, bending stiffness and flexural rigidity; physical dimensions such as small average thickness (e.g., less than 100 microns, optionally less than 10 microns and optionally less than 1 micron) and device geometries such as thin film and open or mesh geometries.

The term “bending stiffness” refers to a mechanical property of a material, device or layer describing the resistance of the material, device or layer to an applied bending moment. Generally, bending stiffness is defined as the product of the modulus and area moment of inertia of the material, device or layer. A material having an inhomogeneous bending stiffness may optionally be described in terms of a “bulk” or “average” bending stiffness for the entire layer of material.

The term “elastomer”, as used in the disclosure, refers to a polymeric material which can be stretched or deformed and return to its original shape without substantial permanent deformation. Elastomers commonly undergo substantially elastic deformations. Useful elastomers include those comprising polymers, copolymers, composite materials or mixtures of polymers and copolymers. Elastomeric layer refers to a layer comprising at least one elastomer. Elastomeric layers may also include dopants and other non-elastomeric materials. Useful elastomers useful include, but are not limited to, thermoplastic elastomers, styrenic materials, olefenic materials, polyolefin, polyurethane thermoplastic elastomers, polyamides, synthetic rubbers, PDMS, polybutadiene, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, polychloroprene and silicones. Exemplary elastomers include, but are not limited to, silicon containing polymers such as polysiloxanes including poly(dimethyl siloxane) (i.e., PDMS and h- PDMS), poly(methyl siloxane), partially alkylated poly(methyl siloxane), poly(alkyl methyl siloxane) and poly(phenyl methyl siloxane), silicon modified elastomers, thermoplastic elastomers, styrenic materials, olefenic materials, polyolefin, polyurethane thermoplastic elastomers, polyamides, synthetic rubbers, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, polychloroprene and silicones. In one embodiment, a flexible polymer is a flexible elastomer.

The term “encapsulate” or “encapsulation”, as used in the disclosure, refers to the orientation of one structure such that it is at least partially, and in some cases completely, surrounded by one or more other structures. “Partially encapsulated” refers to the orientation of one structure such that it is partially surrounded by one or more other structures. “Completely encapsulated” refers to the orientation of one structure such that it is completely surrounded by one or more other structures. The invention includes devices having partially or completely encapsulated electronic devices, device components and/or inorganic semiconductor components.

Embodiments of the invention are illustrated in detail hereinafter with reference to accompanying drawings. The description below is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. The broad teachings of the invention can be implemented in a variety of forms. Therefore, while this invention includes particular examples, the true scope of the invention should not be so limited since other modifications will become apparent upon a study of the drawings, the specification, and the following claims. For purposes of clarity, the same reference numbers will be used in the drawings to identify similar elements. It should be understood that one or more steps within a method may be executed in different order (or concurrently) without altering the principles of the invention.

Temperature monitoring is essential in healthcare settings - particularly in neonatal / pediatric monitoring. Current sensor systems are wired creating a barrier to skin to skin contact and create a greater skin injury risk.

In view of the foregoing, one of the objectives of this invention is to provide a wireless sensor technology with a focus on capturing skin temperature integrated within a care management system. While the sensor technology can be applied to patients of all ages - the primary focus is on neonatal monitoring where thermoregulation is key. The technology further offers the ability to estimate core body temperature. In addition, the sensor provides the ability to continuously measure heart rate, respiratory rate, and body position. The sensor communicates wirelessly and can be multiplexed to a display unit, which may represent a mobile device, incubator, warmer, ventilator, or medical monitor.

One aspect of the key invention is a miniaturized flexible sensor that meets the unique anatomical and physiological needs of neonates. One embodiment of the temperature sensing element is a negative temperature coefficient thermistor (NTC) as it provides larger resistance changes based on small changes in temperature. However, alternative temperature sensing elements maybe used. This includes resistance temperature detectors and semiconductor-based temperature sensors. The configuration of the thermal sensing element is closest to the heat source (in this case the skin) with minimally thermal insulating material between the thermal sensing element and the source. The configuration of the sensor also includes insulation of the thermal sensing element from the ambient with placement of the electronics and batteries separating the thermal sensing element from the ambient. Additional thermal insulating material maybe added. A second thermal sensing element is placed farther away from the heat source (e.g., skin) to measure ambient temperature. The sensor also includes a 3 -axis accelerometer mounted in mechanical communication with the skin to assess other vital signs such as heart rate, respiratory rate, physical activity, and body position.

Without intent to limit the scope of the invention, exemplary embodiments of the invention are given below.

In one embodiment, the MCU calculates the body posture of the mammal subject.

In another aspect, the invention relates to a wirelessly controlled thermoregulating system, As shown in FIG. 32, the system 100 comprises a plurality of wireless apparatuses 110, 130, . . . 150 for measuring temperatures of a mammal subject; and a base station 190 capable of controlling radiant heating, or convective heating, or humidity. The wireless apparatuses are capable of autonomously configuring settings of the base station to maintain the temperature of the mammal subject in a configured value. The base station is configured to generate alarm and alerts triggered by the wireless apparatuses. The base station operably displays the temperature readings of at least one of the wireless apparatuses for the temperature measurement.

In one embodiment, the remaining space inside the elastomeric encapsulation layer of the apparatus is filled with a silicone elastomer.

In one embodiment, the battery unit is detachably connected to the sensor unit.

In one embodiment, the battery is a rechargeable battery. In one embodiment, the SoC comprises a Bluetooth interface and/or a near-field communication (NFC) interface for the wireless data communications between the SOC and an externa device.

In one embodiment, the apparatus is stretchable and bendable.

In one aspect, the invention relates to a sensor network system for non-invasively measuring physiological parameters of a mammal subject. FIG. 32 shows one exemplary embodiment of the sensor network system 100, comprising a plurality of wireless apparatuses 110, 130, . . . 150 time-synchronized to each other, wherein each wireless apparatus is placed on a respective region of the skin of the mammal subject and comprises a sensor unit comprising a sensor member for measuring at least one physiological parameter of the mammal subject, and a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data therefrom and processing the received data, and for wireless data communications; and a base station 190 adapted in wireless communication with the plurality of wireless apparatuses and configured to support real-time control of operations of the wireless apparatuses, to receive, from the wireless apparatuses, to process, and to display the physiological parameters.

In one embodiment, the sensor unit further comprises a PMIC; an LED indicator; and magnets, wherein all mounted on a fPCB using surface-mounted technology (SMT).

In one embodiment, each wireless apparatus further comprises a top thermal insulating layer and a bottom thermal insulating layer disposed between the sensor unit and the elastomeric encapsulation layer to at least partially cover the sensor unit for minimizing the influence of the ambient on measurements of the temperature of the skin. In one embodiment, the bottom thermal insulating layer has an air cavity in which the bottom NTC thermistor is placed, so as to mechanically isolate the bottom NTC thermistor from the other parts of the apparatus.

In one embodiment, the sensor network system enables measurements of temperature differentials between the central skin and the peripheral skin, which are particularly valuable in tracking for early signs of sepsis in neonates. In one embodiment, the sensor network system further comprises a customized app with a graphical user interface operating on the base station, configured to support real-time control of operations of the wireless apparatuses, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

The invention has, among other things, applications in, but are not limited to, neonatal monitoring, fever tracking, sepsis prediction, hypothermia monitoring, heat stress monitoring, and worker safe.

The key advantages to this technology include, but are not limited to, miniaturized wireless design enabling mounting and use in neonatal populations; time synchronization to allow for continuous temperature monitoring in different anatomical mounting locations; sensor stack up enabling thermal shielding and isolation; and alarm management and integration with existing monitoring solutions.

Without intent to limit the scope of the invention, exemplary instruments, apparatus, methods and their related results according to the embodiments of the 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.

EXAMPLE: 1

SIMPLE, MINIATURIZED BIOSENSORS FOR WIRELESS MAPPING OF THERMOREGULATORY RESPONSES

Temperature is the most commonly collected vital sign in all of clinical medicine; it plays a critical role in care decisions related to topics ranging from infection to inflammation, sleep, and fertility. Most assessments of body temperature occur at isolated anatomical locations (e.g., axilla, rectum, temporal artery, or oral cavity). Even this relatively primitive mode for monitoring can be challenging with vulnerable patient populations due to physical encumbrances and artifacts associated with the sizes, weights, shapes, and mechanical properties of the sensors and, for continuous monitoring, their hard-wired interfaces to data collection units.

In this exemplary example, we introduce a simple, miniaturized, lightweight sensor as a wireless alternative, designed to address demanding applications such as those related to the care of neonates in high ambient humidity environments with radiant heating found in incubators in intensive care units. Such devices can be deployed onto specific anatomical locations of premature infants for homeostatic assessments. Time-synchronized, multi-device operation across multiple body locations supports additional modes of determining tissue health status in the context of sepsis detection and various environmental exposures. In addition to thermal sensing, these same devices support measurements of a range of other essential vital signs derived from thermo-mechanical coupling to the skin, for applications ranging from women’s health to sleep medicine.

Specifically, the advanced, wireless temperature sensor is characterized by miniaturized dimensions and a soft, skin-compatible encapsulation structure. Optimized designs enable continuous monitoring in the most challenging care environments (e.g., the neonatal intensive care unit), conformable placement in specific anatomical locations such as the floor of the axilla where the axillary artery is most superficial to the skin for enhanced accuracy, and targeted application to areas of localized skin inflammation or infection. Additional engineering strategies and material selections enable accurate sensing even in highly variable ambient temperature conditions including those associated with direct radiant warming and high humidity. The devices can deploy at multiple sites across the body, wirelessly networked for time-synchronized operation to a single mobile device. The result enables continuous, full-body measurements of temperature distributions. Resulting differentials between central and peripheral skin temperature, obtained without the burden of additional cables or excessive medical adhesives on fragile skin, are particularly valuable in tracking for early signs of sepsis in neonates. As an additional set of features, this system simultaneously records other relevant physiological parameters (e.g., heart rate, respiratory rate, body position, vocalizations, and movement) via mechano-acoustic measurements of body motions and sounds captured using a high-bandwidth accelerometer. The following sections present (i) device configurations and applicable systems, (ii) rigorous evaluations of performance metrics in temperature sensing, (iii) time-synchronized operation of multiple sensor systems for spatiotemporal temperature mapping, (iv) estimations of core body temperature via axillary measurements, (v) demonstrations of tracking of additional vital signs and related information on patient status, and (iv) examples of the use on newborn babies in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

METHODS

Encapsulating the electronics in a soft enclosure

A milling machine (MDX 540, Roland) produced customized aluminum molds with concave shapes to define top encapsulating layers in a medical grade, skin-compatible silicone elastomer (Silbione RTV-4420, Elkem) with white and blue pigments (Silicone Pigment, Smooth-On, 9:1) using a hot press machine (Auto Series Press, Carver) at 115 °C and 3000 kPa for 2 min. The bottom layers had thicknesses of 120 pm, separately prepared by spin-coating a silicone elastomer on an acrylic plate at 500 rpm for 1 min and curing at 70 °C in an oven for 20 min. Six layers of an insulating film (RTAZS, 0.2 mm, 0.038 W/mK, Blueshift) with a squareshaped hole was mounted onto the bottom encapsulating layer in a manner that covered the skinfacing NTC thermistor to form an air cavity (3x3x 1.2 mm³). Filling the top encapsulating layer in the mold with a silicone elastomer (Ecoflex 0030, Smooth-On) and then placing the electronics on the bottom encapsulating layer completed the process by clamping the entire assembly and curing at 60 °C in an oven for 40 min. After cooling to room temperature, the encapsulated device was removed from the mold and the excess outline was cut away using a CO2 laser (VLS3.60DT, Universal Laser Systems).

Circuit-level operation of the device

FIG. 8 shows the circuit-level aspects of device operation. In the main sensor unit, two LDOs (TPS7A02, Texas Instruments) convert the transferred power to a constant voltage of 1.8 V. One of the two LDOs remains active to enable Bluetooth communication; the other activates only when collecting data, to minimize standby power consumption, as shown in FIG. 9. The BLE SoC (ISP 1807, Insight SIP) controls these LDOs and provides power to the sensors through Analog-to-Digital Converting (ADC) pins with 16-bit resolution and digital General-Purpose Input/Output (GPIO) pins. Voltage divider circuits that include the NTC thermistors (lOkQ, 3380K, Murata Electronics) and reference resistors (lOkQ, 0.1%, Vishay Dale) support robust capabilities in temperature sensing, as shown in FIG. 10. The IMU (BMI160, Bosch) can effectively capture not only changes in body orientation but also high frequency signals originating from cardiac cycles, respirations, and vocalizations such as crying. The resonance frequency of the Rx coil was set to the NFC standard (13.56 MHz) by adjusting capacitors connected in parallel. The rectifier (BAS4002, Infineon Tech.) converts the transferred AC voltage into a DC voltage, with a voltage regulator (LP2985, Texas Instruments) that maintains the output at 3.2 V. A pair of supercapacitors act as a charge reservoir to ensure stable operation during periods of low power transfer. A comparator (MIC842, Microchip Tech.) activates the LDO when the supercapacitors have sufficient charge to operate the main sensor unit.

3D finite element analysis (FEA) modeling

The commercial software COMSOL Multiphysics enabled finite element analysis (FEA) modeling of heat transfer mechanisms through the device from the skin to the ambient. The three- dimensional (3D) FEA model simulated the device resting on the top surface of a 10-mm thick slab of PDMS as a skin phantom. The COMSOL interface used a 3D CAD file of the device layout with different material parts. The COMSOL simulation applied Fourier’s law to model heat conduction in the device mathematically. The differential form of the heat equation is q = - kVT, where q is the local heat flux density, Aris the material’s thermal conductivity, and V 7' is the temperature gradient. With the assumptions of constant pressure, negligible device deformation and no fluid movement in the device, the energy conservation was modeled in terms of temperature by the following differential equation: Cp(dT'dt) = • (k^T) + Q, where p is the material’s density, Cp is the specific heat capacity, and 0 is the volumetric heat source. The left term reaches zero when the model reaches steady state, and Q = 0 indicates that the device does not generate heat. Thermal convection of air at a temperature of T_air defined heat transfer at the outer surfaces of the device with a heat transfer coefficient hconvection. The bottom surface of the phantom had a fixed temperature of 37 C to simulate the core-body temperature. Heat transfer from the phantom to the device and the ambient air caused a temperature gradient sensed by two probes (NTC1 and NTC2) at different locations. The FEA model evaluated different configurations of the devices and analyzed the effects of T_air and hconvection by parametric sweeps. The temperature gradients between NTC1 and NTC2 simulated from different configurations helped to optimize the device design for enhanced temperature gradient and accurate skin temperature measurements. The results of temperature gradients and thermal profiles are summarized in FIG. 11. Various models with mesh densities ranging from 60 elements per cubic millimeter to 83 elements per cubic millimeter were analyzed to check the mesh independence and computational convergence, to a temperature difference less than 0.1 °C. The following parameters were used in the computations: thermal conductivity of 0.3 W/mK for the tissue; 0.21 W/mK for the electronics; 0.21 W/mK for the NTC thermistors; 0.038 W/mK for the insulating films; 0.2 W/mK for Ecoflex 00-30; 0.15 W/mK for Silbione 4420.

Measuring temperatures and body motions

A double-sided medical-grade silicone adhesive (2477P, 3M) secured the device on the skin. The temperature data were collected using a voltage divider circuit made of the series connection of the NTC thermistor (lOkQ, 3380K, Murata Electronics) and a reference resistor (lOkQ, 0.1%, Vishay Dale). Motion data were captured using an IMU (BMI 160, Bosch) with 16-bit resolution, 0.061-mg sensitivity, 1666-Hz sampling rate (adjustable up to IM Hz), and ± 2g acceleration range (adjustable up to ±16g).

Procedure for monitoring the eczema patient

Wiping the skin with a 70% isopropyl alcohol pad (Alcohol Prep Pads, TopCare) removed oils and residue prior to measurements. Data collection occurred for 15 mins from eight devices after waiting for 15 mins following mounting to ensure temperature stabilization. A process of removing the devices, applying the topical steroid cream and waiting for 1 h preceded additional measurements following these same procedures.

Protocols for human subject studies (from Hyoyoung’s dual sensor paper)

The studies were approved by the Northwestern University Institutional Review Board, Chicago, IL, USA (STU00202449 and STU00212522) and were registered on ClinicalTrials.gov (NCT02865070 and NCT04393558). All study-related procedures were carried out in accordance with the standards listed in the Declaration of Helsinki, 1964. For all subjects in the NICU and PICU, a double-sided medical silicone adhesive (3M, 2477P) secured the device to the skin at the axillary and suprasternal notch for a few hours. Clinical staff assisted in placing the device. After each measurement session, the device was sterilized using 70% isopropyl alcohol, repeated twice.

RESULTS

Device architecture, use cases and options in power sources

Panel A of FIG. 1 presents illustrations of use cases that range from care in neonatal intensive-care units (NICUs) in hospitals to cribs in home settings. The system includes a miniaturized wireless biosensor, referred to in the following as a button due to its small size and circular shape to maximize ease of use and anatomical placement, with options in both battery- free and battery-powered modes of operation. The former relies on magnetic inductive coupling (Near-Field Communication, NFC, standards) for wireless power transfer from an external transmitting coil to a receiving coil built into the structure of the device. This design minimizes the size and weight of the system, with an operating range (tens of centimeters) that can support coverage throughout a standard incubator or crib. Replacing the antenna with a small battery eliminates the need for proximity to a transmission coil (FIG. 12). Both configurations use Bluetooth protocols for two-way wireless data communication, over distances of tens of meters. Panels B-C of FIG. 1 display photographs of such devices on a realistic doll and on the hand of an adult. The small sizes, versatile designs, and optimized thermal sensing capabilities of these devices represent important distinguishing characteristics over previously reported technologies of this general type.

Panels D-E of FIG. 1 show exploded-view illustrations of the main sensor and the wireless power harvesting sub-system, respectively. The former includes a Power Management Integrated Circuit (PMIC), a Bluetooth Low Energy (BLE) System-on-Chip (SoC), temperature/motion sensor units, an LED indicator, and magnets, all mounted on a flexible printed circuit board (fPCB) using Surface-Mounted Technology (SMT). An emphasis here is on accurate measurements of temperature, with adequate time response. To this end, a commercial insulating foam and reflective film cover the body of the device to minimize the influence of the ambient on measurements of the temperature of the skin. Two Negative Temperature Coefficient (NTC) thermistors fold in a manner that orients one toward the skin and the other toward the ambient. A molded medical-grade silicone elastomer serves as a soft encapsulating structure. In the wireless power harvesting unit, the power receiving (Rx) coil connects through flexible copper traces to a rectifier, a voltage regulator, supercapacitors, a PMIC, and magnets for mechanically coupled interconnects.

The output of the PMIC supports skin-facing and ambient-facing temperature measurements and mechano-acoustic data collection using two NTC thermistors and a 3-axis Inertial Measurement Unit (IMU), respectively. These data pass to an embedded flash memory on the BLE SoC and then wirelessly transmit to a user interface on a BLE-enabled device such as a smartphone. An LED indicator serves as a visual alarm that can be activated based on the measured data and various, user-defined threshold settings. These data can also be transferred to external life support systems for automated control. An example involves active regulation of the temperature of a neonatal incubator according to the body temperature. Panels F-G of FIG. 1 show a closed-loop system that includes a button device, a customized user interface, and a wireless module for heating the local environment of the incubator. Regulation of the temperature follows from comparisons of the temperature of the baby to a desired body temperature (T_set = 36 °C, here). Multiple devices can be located at different regions of the body, for time-synchronized operation. The data can also be uploaded to a secure Cloud platform for remote monitoring and analysis.

Performance benchmarking for temperature sensing

Panel A of FIG. 2 and FIG. 7 shows a simplified schematic diagram of the battery- powered embodiment. Six layers of a thermal insulating film (RTAZS, 0.2 mm, 0.038 W/mK, Blueshift) cover the electronics and battery to reduce the influence of environmental effects on measurements of temperature. The bottom insulating layer includes a square-shaped hole to form an air cavity (3 *3 * 1.2 mm³) that isolates the bottom NTC thermistor from the other parts of the device. This design improves the reliability of measurements of skin temperature. A base encapsulation layer with a thickness of 120-pm reduces the thermal mass at the interface between the bottom NTC and the skin. This layout enhances the time response, for capturing dynamic changes in temperature. A silicone elastomer (Ecoflex 00-30, 0.15 W/mK, Smooth-On) fills the other areas of the device. A molded elastomer with a different chemical formulation forms an encapsulating structure for the entire system (Silbione RTV-4420, 0.15 W/mK).

Panels B-C of FIG. 2 present finite element analysis (FEA) results for the temperature distribution inside the device, including locations of the skin- and ambient-facing NTC thermistors, with a thermally insulating air cavity structure (cavity) and without this cavity (control). For an ambient temperature of 18 °C, the skin-facing and ambient-facing regions of the former design are 0.1 °C higher and 0.65 °C lower, respectively, than the corresponding temperatures of the latter. This result highlights the importance of the cavity in thermal isolation.

Detailed comparisons of capabilities for measurements of temperature involve clinical standard, hard-wired sensors (DeRoyal) designed for use in the NICU. Quantitative assessments focus on the accuracy, cyclic stability, humidity response, endurance and response time. Panels D-E of FIG. 2 display the results of tests that involve suspending these two types of devices in the air in an environmental chamber (LH-1.5, Associated Environmental Systems), as shown in FIG. 13, with set temperatures from 30 to 45 °C maintained for 30 min each, at a relative humidity (RH) of 5%, based on guidance from the Food and Drug Administration (FDA). The results show excellent agreement (panel D of FIG. 2). Panel E of FIG. 2 displays the average temperature values and differences for 10 s (0.5 samples per sec, 20 data points) after the 30 min hold times. The differences in region 3 (37 °C < Temperature < 39 °C) are ±0.1 °C, consistent with FDA requirements (FIG. 14). The standard deviations at 25 °C and 45 °C during cycle tests for the button device are 0.03 °C and 0.07 °C, respectively (panel E of FIG. 2). Tests of sensitivity to humidity involve a set temperature of 36.5 °C for RH between 25.2 and 80.3 % (panel G of FIG. 2). Temperature fluctuations occur immediately after changing the RH for both sensors (the upper panel), but without any significant systematic dependence on RH (the lower panel), consistent with requirements for clinical use in an incubator. Panel H of FIG. 2 shows the results of tests of the effects of storage of the devices at high (60 °C) and low (-20 °C) temperatures, as an additional practical requirement. For a set temperature of 35 °C, the percent error after storage at 60 °C and -20 °C for 24 h is 0.3 % and 0.2 %, respectively. FIG. 15 also displays that the temperatures obtained from the skin- and ambient-facing NTC thermistors show good agreement according to the restricted temperature environment in the chamber, which indicates that both NTCs follow the external temperature. Panels I-J of FIG. 2 display the times to respond to abrupt changes in temperature for devices mounted first on a skin phantom placed on a hot plate at a temperature of 30 °C and then on another at 45 °C (FIG. 16). The response time refers to the time for the temperature to change from the initial value to 63.2 % of the total change. For the button device with the cavity structure, rising and decaying times are 7.6 s and 5 s, respectively. The results of additional benchmarking studies with commercial sensors and those reported in the published literature appear in Tables 1-2, respectively.

Table 1. Summary of key characteristics of the reported devices and wireless commercial alternatives.

Table 2. Summary of key characteristics of the reported devices and alternative technologies in the published literature.

Monitoring of local skin temperature

Panel A of FIG. 3 shows data from a study that involves measuring the skin temperature from a healthy adult subject during a 5-hour period of work and a 10-hour period of sleep using a button device and a commercial wireless skin temperature sensor (Core, green TEG AG) attached side-by-side on the lower chest. Bland-Altman (BA) plots show that the mean differences of the temperatures measured by these two devices are only 0.02 °C, and the upper and lower limits of the 95 % confidence intervals (+1.96 SD and -1.96 SD) are 0.46 °C and -0.42 °C, respectively (panel B of FIG. 3). Similar levels of the agreement appear in data collected continuously over a period of three days (panel C of FIG. 3) from the chest area, except for times during device removal for showering. The button device offers advantages due to its small size, where the volume and weight are 11.8 and 3.9 % of the average values of other wireless sensors, respectively. For example, mounting can occur on a wide range of anatomical locations of neonates including the chest, arms, legs, and even the axilla (FIG. 17).

Wirelessly time-synchronized collections of these devices enable mapping of skin temperature across regions of interest, with good spatial resolution due to their miniaturized sizes (FIG. 18). Panel D of FIG. 3 shows an example using eight devices mounted on the hands of an atopic dermatitis patient before and after applying a medium potency topical steroid cream (Triamcinolone Acetonide Cream USP, 0.1%, Perrigo). The target areas are the back of the hand (normal skin, blue color) and the base of the finger (inflamated skin by eczema, red color). Panels E-F of FIG. 3 present the average skin temperature of the normal and inflamed regions of the skin before and after the steroid application, respectively. The temperature of the normal and inflamed skin decreases from 31.3 to 29.3 °C and from 30.5 to 26.6 °C, respectively (panel G of FIG. 3). Several potential clinical applications of this capability can be considered. First, the measurements may serve as a marker of inflammation (e g., atopic dermatitis) or infection (e.g., superficial skin infections) not readily apparent by visual inspection. Because the main mechanism of topical steroids is vasoconstriction of peripheral skin vasculature, associated changes in temperature offer a surrogate to assessments of potency typically performed with laboratory calibrated chromameter to assess skin blanching.

As another application example, panel H of FIG. 3 shows changes before (left) and after (right) a 20-min exercise across eight representative body locations (forehead, back, upperarm, chest, forearm, hand, thigh, and calf from the top to bottom). The percentage value (P) corresponds to the ratio of the area of a local body part to the area of the entire body surface. Panel I of FIG. 3 presents the results for each body region and the mean skin temperature (TMST), defined as a weighted sum of the local skin temperature (T ocai); TMST = XP^/Ti <>cai over eight local body parts. The data indicate that T ST decreases during exercise and recovers slowly afterward, consistent with expectations. Panel J of FIG. 3 shows the similarity factor (R-squared, R²) between TMST and each local temperature (upper panel), along with variations in local skin temperatures and T ST during exercise (lower panel). Here, the R² values for each location follow from a linear fitting model compared to TMST. The R² of the chest and calf areas are the highest (0.69) and lowest (0.09), respectively. The average temperatures are highest at the forehead and lowest at the calf area. The maximum and minimum temperature changes occur at the hand and upper arm, respectively. The abilities for track both central and peripheral temperature measurements have implications for occupational health and for wellness. For instance, hypothermia and hyperthermia are both life-threatening conditions that have significant biological variations. Thus, exposure risk depends on physical fitness, ambient conditions and clothing. In cold temperatures, frostbite, a major risk for military personnel, also applies to workers in outdoor occupations (e.g., construction workers) and to homeless individuals, with a cumulative lifetime incidence of 11 %. Peripheral skin temperature is a key indicator of tissue injury. Miniaturized sensors such as these, when multiplexed and mounted on the extremities, may serve as an early warning system for high-risk individuals.

FIG. 19 displays similar skin temperature data recorded from subjects during sleep and exposure to a sauna. As expected, the TMST during sleep is lower than that during exercise. The temperature on the back (#2) is relatively high, due likely to contact with the bed. Compared to the sauna case, the temperatures in distal body parts including hands and calves are higher during sleep. In the sauna, the overall skin temperature increases shortly after exposure to an infrared heater and recovers slowly afterward. The highest temperature change occurs on the hand, likely because these distal parts of the body have enhanced sensitivity to the ambient temperature. Tracking changes in temperature during sleep-wake cycles may reveal disruptions in circadian rhythms, or signs of sleep related disorders.

Monitoring of core body temperature

Core body temperature represents an essential parameter in defining health status, of particular importance for infants. Traditional measurements rely on sensors interfaced to oral, rectal or axillary locations. Panel A of FIG. 4 shows examples of a button device mounted under the arm of a realistic neonate model, enabled by the small size. Panel B of FIG. 4 compares data collected from an adult at this location, with simultaneous measurements captured using a digital thermometer (TC0521, PerfectPrime) at the same location. The miniaturized design allows the button device to be placed deep at the curvilinear pockets of the axilla, for improved core body temperature estimations compared to those based on existing systems. During the initial 15 mins after attaching the sensors, both sets of data show sharp increases to steady state values of approximately 36.6 °C. Panel C of FIG. 4 displays the temperature data from this region of a healthy adult subject along with results from an ingestible electronic pill (E-pill, e-Celsius, green TEG), during working hours and sleeping. Elere, a simple estimate of core body temperature that corresponds to the temperature of the skin plus 1.2 °C agrees well with data captured by the E-pill. Bland-Altman analysis indicates that the mean differences in temperature are only -0.05 °C, and the +1.96 SD/-1.96 SD are 0.19 °C/-0.29 °C, respectively (panel D of FIG. 4). The BA plot in panel E of FIG. 4 shows that the mean differences of the core body temperature data collected from a healthy male adult three times in a row are only 0.02 °C, and the +1.96 SD/-1.96 SD are 0.3 °C/-0.25 °C, respectively. In addition, the mean differences collected from three healthy adult subjects are only -0.03 °C, and the +1.96 SD/-1.96 SD are 0.25 °C/-0.32 °C, respectively (panel F of FIG. 4). FIG. 20 shows another core body temperature estimation technique using the dual temperature monitoring capability, following schemes reported in the previous work. The core body temperature estimated via the 1-D heat transfer equation shows good agreement with oral temperature. 3D FEA results support the use of this 1- D approximation.

Core body temperature is also an excellent indicator of circadian rhythms. Panel G of FIG. 4 presents variations over a 24-hour period captured with these two devices. The results largely coincide even across this relatively narrow range of temperatures, approximately 1 °C. Panel H of FIG. 4 presents similar data from six healthy adult subjects. The average temperatures of the female subjects studied here are 0.35 °C higher than those of males; the variations in temperature over a day are similar, approximately 1 °C. Overall, the results indicate that the system meets all key accuracy and performance criteria of ISO 80601-2-56:2017, a consensus standard for clinical-grade thermometers.

Additional capabilities: heart rate, respiratory rate, and body orientation from neonates

As mentioned previously, the small size and weight of the devices make them well-suited for use with infants. Panel A of FIG. 5 shows a photograph of a realistic neonate doll mounted with a device, a set of wired electrocardiogram (ECG) electrodes, and a wired temperature sensor (DeRoyal), to illustrate the burden of clinical standard monitoring equipment. The data from the button yield body orientations and motions, with vocalizations, respiratory sounds and cardiac amplitudes, along with heart rate, heart rate variability and respiratory rate. Panel B of FIG. 5 shows three-axis acceleration data with respect to body orientations and activities. Here, the unit g represents the acceleration caused by gravity, and phi (<p) and theta (0) denote the angle of the body from the supine position (supine) and the rotation angle of the central axis of the body, respectively. For the supine position, only the x-axis accelerates to approximately 1 g, and the other axes remain at 0. The kangaroo care (KC) scenario, where the mother holds the baby close to her chest while seated, leads to a y-axis acceleration of 1 g. The right body facing (RBF) position causes an acceleration of -1 g along the z-axis. The correlated rotation data show that the supine and prone positions have the same ( value of 0, but their 0 values are different by -180°. In the case of the KC position, the (p value increases to approximately 90°, and the RBF position shows the 0 value of -90°. The activity level data also include high-frequency features associated with crying and patting. These data agree with previously reported results. Panel C of FIG. 5 and FIG. 21 display extracted body orientation and rotation data for various situations. The distinguishable features in the acceleration and angle data enable clear classifications, important not only in tracking KC but also in setting alarms for dangerous positions that could lead to choking or impaired respiration.

Panel D of FIG. 5 shows seismocardiography (SCG) and ECG data collected by the device and a clinical standard system (Dash 4000, GE), respectively. Post-processing the mechano-acoustic data using a bandpass filter from 0.5 to 50 Hz facilitates extraction of the heart rate (HR) by dividing 60 by the time interval (A/) between the Si peaks in the SCG signal (HR = 60/ AZ). Panel E of FIG. 5 illustrates agreement between HR values from SCG and ECG. The BA plot indicates mean differences of 0.53 bpm, and the +1.96 SD/-1.96 SD are 2.55 bpm/-1.48 bpm, respectively (panel F of FIG. 5). Respiration data follow from chest motions in the z-axis direction (normal to the surface of the skin). Post-processing in this case involves a lowpass filter with a cutoff of 0.5 Hz. Panels G-I of FIG. 5 show the respiration rates collected from these data and the ECG waveforms. The BA plot shows the mean difference of the RR data is only 0.30 bpm, and the +1.96 SD/-1.96 SD are 1.57 bpm/-0.97 bpm, respectively.

Representative data collected from patients in the NICU

Panels A-B of FIG. 6 show photographs of infants mounted with a device on a suprasternal notch (SN) for tracking of cardiopulmonary activity. Panel C of FIG. 6 highlights alternative mounting locations, for collecting global movements of the body using two devices. Panel D of FIG. 6 presents representative data from a neonate (gestational age, GA: 39 weeks) in the NICU before, during, and after a blood draw. The crying events recorded by the device during the procedure coincide with increases in HR and RR from 128 to 138 bpm and from 69 to 74 bpm, respectively. Panels E-F of FIG. 6 show similar changes in HR and RR for three healthy infant subjects. The graph in panel G of FIG. 6 corresponds to the average HR and RR data for 11 infant subjects, indicating increases of 8 and 3 bpm, respectively.

Panel H of FIG. 6 displays an example that highlights the utility of temperature measurements. Newborns have underdeveloped function for thermoregulation. As a result, the body temperature of an infant can be strongly influenced by various factors, such as ambient temperature, health status, and even mental status. The first graph shows normalized raw and envelop data of vocal activity (mostly crying) of a newborn baby (GA: 42 weeks) obtained through a cell phone (iPhone 14 Pro, Apple). The second graph shows the overall change in skin temperature measured from the chest area. The values decrease gradually from 36.3 to 36.2 °C, but with subtle variations that appear as increases in temperature. Applying a high-pass-filter (HPF) to these data highlights these changes. These features track with patterns of vocal activity, likely due to activation of the sympathetic nervous system during crying as a physical activity that also leads to coincidental vasodilation and increases in skin temperature. Furthermore, the amplitude of the crying correlates with the magnitude of the temperature change, as highlighted in the last graph. The combination of advanced thermal sensing capabilities with additional physiological monitoring might have important utility in the area of neonatal health.

DISCUSSION AND CONCLUSION

This exemplary study introduces a miniature wireless sensor with specific capabilities in advanced thermal monitoring, designed to operate continuously and reliably across a range of conditions and applications, including those related to the care of neonates in high ambient humidity environments with radiant heating such as those in incubators in the NICU. The key advances are in small, lightweight designs that can be deployed onto premature infants for homeostatic assessments, at specific locations for tracking inflammation or infection, and across optimized anatomical positions for accurate measurements of core body temperature. The device design strategies and material selections result in a sensor with excellent performance in temperature sensing in terms of accuracy (temperature difference <0.1 C at region 3), insensitivity to humidity (without degradation at RH > 80%), and thermal response dynamics (rising and decaying time = 7.6 and 5 s, respectively). In the data obtained from healthy subjects, the measurement errors are in the range of 0.05 °C, exceeding regulatory requirements. Additional capabilities are in continuous monitoring of vital signals, especially for newborn babies and other vulnerable patient populations, in ways that are highly insensitive to ambient conditions. Time-synchronized operation across multiple body locations enables continuous, full-body measurements of spatiotemporal variations in temperature, including differentials between central and peripheral skin temperature for tracking of early signs of sepsis in neonates. Beyond thermal sensing, the ability of the sensor to measure other essential vital signs (e.g., respiratory rate and heart rate), physical activity levels, body orientation, and respiratory sounds provides further clinical value for a range of other applications from neonatal and infant care to sleep medicine and even pulmonary medicine.

EXAMPLE: 2

OTHER EMBODIMENTS OF TEMPERATURE SENSORS

Apart from embodiments described through FIGS. 1-21, there is yet another embodiment measuring accurate temperature sensor through MEMS based thermometer elements (FIG. 22). The performance of this embodiment and previously described embodiment (FIG. 1) are compared against another gold standard temperature probe (Giraffe Infant Probe, GE) and the accuracy out of calibration shows within guidelines between 0.1 - 0.2 °C from 15 °C to 45 °C range.

FIG. 23 describes the testing setting inside of an incubator (Giraffe Incubator, GE) including a simulated body model as a form of waterbag connected to a calibrated water bath supplying water at a fixed temperature. When mounted on the simulated body model, both embodiments of the skin temperature sensors show similar performance compared to GE Infant Probe in an open-chamber environment with no radiant heating.

FIG. 24 describes the effect of an insulation, using mylar reflective film in this case, to both ADAM 9.1 and GE infant probe when radiant heater is on. Both sensors show similar performance to the radiant heating in cases where reflective film are attached to top of the temperature sensing element or not attached to. This shows that the importance of insulating materials to be added around temperature sensing element to prevent radiant heating effect, which is commonly used incubator setting.

Both embodiments show negligible effect by humidity settings when placed inside incubator. FIG. 25 shows that both embodiments do not change the temperature significantly when humidity setting changed from 30% to 70%, while the GE infant probe also remains generally steady. FIG. 26 describes the FEA modeling work to characterize the effect the mylar fdm attached in different ways when radiant heating is available. ADAM 9.1 shows different temperature reading when the film is attached vertically on top of the temperature element versus when the film is attached to the element area in tilted angle introducing the air gap. This shows the importance of the controlling attachment method of the insulation film to ensure the best performance of the skin temperature sensor against the ambient effect.

FIG. 27 describes the FEA modeling work to characterize the effect of not having insulation materials during convective setting inside incubator. In both cases, where air temperature is set higher than core temperature or vice versa, there is a significant difference in temperature reading between the ADAM (ADvanced Acousto-Mechanic) sensor and GE Infant probes. This shows the importance of the insulation film during the convective setting, which is one of the common use cases of incubator.

FIG. 28 shows the performance of the ADAM sensor using FEA modeling, now an insulation material layer is embedded inside the encapsulation. In both convective cases, ADAM sensor now predicts the core temperature closer than GE probes. This is not only making the sensor reading highly reliable in environmental effects, but also the sensor is not losing the reusability. If mylar reflective film is used instead of the insulation material embedded inside the encapsulation, the film would introduce the dirt and increase workflow burden to hospital staff for disinfection procedure. By fully embedding the insulation layer, this embodiment provides simple way of disinfection, which is simply cleaning the silicone surface with general hospital cleaning procedure such as IPA wipes.

FIG. 29 shows another embodiment now adding the thermal contact below the temperature sensing element. By introducing the thermal conductive metal element to the temperature sensing unit, the thermal contact area increases. This in return increases the available heat capacity and there reducing the response time. This embodiment would further optimize the performance metric as a clinical-grade skin temperature probe.

FIG. 30 shows another embodiment providing multiple redundancy mechanism detecting degradation of temperature reading. To avoid a situation where the primary skin temperature reading element is malfunctioning and starts degrading the performance potentially leading inaccurate skin temperature reading, one embodiment may have additional temperature sensors in the same board to routinely check the accuracy of the primary sensing unit. The sensor would activate alert for degradation by closed-loop operation through the in-sensor state machine processed inside of the MCU.

FIG. 31 shows another embodiment where the metal contact providing high thermal conductivity is in a form of two divided bipolar contacts. Each contact is then connected to a DC lead off sensing circuit to identify the presence of contact to skin. This embodiment can then provide closed-loop alarm/alert for lead-off events during the use. In addition, the MCU can calculate the wearing time and the wearing time can be displayed on the incubator or other mobile display.

In some embodiments, the sensor contains high-frequency accelerometer. Mounted on a patient’s chest, the sensor outputs chest wall movement-driven heart rate reading, respiratory rate reading. The sensor also measures body position, crying, swallowing, patting. The sensor may be used in resuscitation during labor and delivery to assist clinicians and nurses for the continuous heart rate.

The foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.

The embodiments were chosen and described in order to explain the principles of the invention and their practical application so as to enable others skilled in the art to utilize the invention and various embodiments and with various modifications as are suited to the particular use contemplated. Alternative embodiments will become apparent to those skilled in the art to which the invention pertains without departing from its spirit and scope. Accordingly, the scope of the invention is defined by the appended claims rather than the foregoing description and the exemplary embodiments described therein.

Some references, which may include patents, patent applications and various publications, are cited and discussed in the description of this invention. The citation and/or discussion of such references is provided merely to clarify the description of the 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.

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Claims

CLAIMS What is claimed is:

1. An apparatus for non-invasively measuring physiological parameters of a mammal subject, comprising: a microcontroller unit (MCU) adapted in wireless communication; at least one temperature sensing unit; and a pair of thermally conductive electrodes placed underneath the temperature sensing unit; wherein the temperature sensing unit is thermally insulated to limit the temperature change by environmental effect from radiant heating, convection, and humidity to be within 0.5 °C; wherein the pair of thermally conductive electrodes enables the thermal time constant less than 60 seconds; and wherein the MCU wirelessly transmits any sensor generated data and features to a base station.

2. The apparatus of claim 1, wherein the pair of thermally conductive electrodes is connected to circuitry measuring the connectivity between the skin of the mammal subject and the electrodes.

3. The apparatus of claim 2, wherein the MCU calculates a wearing time by measuring how long the connectivity between the skin and the electrodes are maintained.

4. The apparatus of claim 1, further comprising: an inertial measurement unit (IMU) measuring motion and acoustic signatures.

5. The apparatus of claim 4, wherein the MCU calculates heart rate and respiratory rate from motion and acoustic signatures when mounted on chest of the mammal subject.

6. The apparatus of claim 4, wherein the MCU calculates vocal features including crying events, swallowing when mounted close to the suprasternal notch of the mammal subject.

7. The apparatus of claim 4, wherein the MCU calculates a body posture of the mammal subject.

8. A wirelessly controlled thermoregulating system, comprising: a plurality of wireless apparatuses for measuring temperatures of a mammal subject; and a base station capable of controlling radiant heating, or convective heating, or humidity; wherein the wireless apparatuses are capable of autonomously configuring settings of the base station to maintain the temperature of the mammal subject in a configured value; wherein the base station is configured to generate alarm and alerts triggered by the wireless apparatuses; and wherein the base station operably displays the temperature readings of at least one of the wireless apparatuses for the temperature measurement.

9. The system of claim 8, wherein the plurality of wireless apparatuses is time-synchronized to each other.

10. The system of claim 9, wherein the plurality of wireless apparatuses is conformably attached to multiple regions of the skin of the mammal subject for measuring the temperatures therein for spatiotemporal temperature mapping.

11. The system of any one of claims 8-10, further comprising: a customized app with a graphical user interface operating on the base station, configured to support real-time control of operations of the wireless apparatuses, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

12. The system of claim 11, wherein the base station includes a mobile device, a smartphone, a tablet, a computer, a cloud server, or any electronic device with data reading/processing/ di spl aying capability .

13. An apparatus for non-invasively measuring physiological parameters of a mammal subject, comprising: a sensor unit comprising a sensor member for measuring at least one physiological parameter of the mammal subject, and a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data therefrom and processing the received data, and for wireless data communications; and an elastomeric encapsulation layer at least partially surrounding the sensor unit to form a skin-facing surface and an ambient-facing surface.

14. The apparatus of claim 13, wherein the sensor member comprises a temperature sensor for measuring temperature of the mammal subject.

15. The apparatus of claim 14, wherein the temperature sensor comprises two negative temperature coefficient (NTC) thermistors fold in a manner that orients one toward the skin-facing surface and the other toward the ambient-facing surface.

16. The apparatus of claim 14, wherein the temperature sensor comprises one or more resistance temperature detectors and/or one or more semiconductor-based temperature sensors.

17. The apparatus of claim 14, wherein the sensor member further comprises an inertial measurement unit (IMU) mounted in mechanical communication with the skin measuring vital signs including a heart rate, a respiratory rate, a physical activity, and/or a body position.

18. The apparatus of claim 17, wherein the sensor member further comprises one or more of an SpO₂ sensor for measuring a blood oxygen saturation; an electrocardiogram (ECG) sensor for measuring ECG signal; and a photoplethysmography (PPG) sensor for measuring a PPG signal.

19. The apparatus of claim 18, wherein the sensor unit further comprises a power management integrated circuit (PMIC); an LED indicator; and/or magnets, wherein all of them are mounted on a flexible printed circuit board (fPCB) using surface-mounted technology (SMT).

20. The apparatus of claim 19, wherein an output of the PMIC supports skin-facing and ambient-facing temperature measurements and mechano-acoustic data collection.

21. The apparatus of claim 19, wherein the LED indicator is configured to serve as a visual alarm that is activatable based on the measured physiological parameters and/or user- defined threshold settings.

22. The apparatus of any one of claims 11-19, wherein the elastomeric encapsulation layer is a waterproof and biocompatible silicone enclosure.

23. The apparatus of claim 22, wherein the elastomeric encapsulation layer has a base encapsulation layer that forms the skin-facing surface to reduce the thermal mass at the interface between the bottom NTC and the skin.

24. The apparatus of claim 22, further comprising: a top thermal insulating layer and a bottom thermal insulating layer disposed between the sensor unit and the elastomeric encapsulation layer to at least partially cover the sensor unit for minimizing the influence of the ambient on measurements of the temperature of the skin.

25. The apparatus of claim 24, wherein the bottom thermal insulating layer has an air cavity in which the bottom NTC thermistor is placed, so as to mechanically isolate the bottom NTC thermistor from the other parts of the apparatus.

26. The apparatus of claim 13, wherein the remaining space inside the elastomeric encapsulation layer of the apparatus is filled with a silicone elastomer.

27. The apparatus of claim 13, wherein the apparatus is a battery-free apparatus configured to operate in a battery-free mode, or a battery-powered apparatus configured to operate in a battery-powered mode.

28. The apparatus of claim 27, wherein the battery-free apparatus further comprises a wireless power harvesting unit in communication with the sensor unit for wireless power harvesting.

29. The apparatus of claim 28, wherein the wireless power harvesting unit comprises a power receiving (Rx) coil connecting through flexible copper traces to a rectifier, a voltage regulator, supercapacitors, a PMIC, and/or magnets for mechanically coupled interconnects.

30. The apparatus of claim 28, wherein the wireless power harvesting unit is detachably connected to the sensor unit.

31. The apparatus of claim 27, wherein the battery-free mode relies on near-field communication (NFC) for wireless power transfer from an external transmitting coil to the power receiving coil (Rx).

32. The apparatus of claim 27, wherein the battery-powered apparatus further comprises a battery unit having a battery.

33. The apparatus of claim 32, wherein the battery unit is detachably connected to the sensor unit.

34. The apparatus of claim 32, wherein the battery is a rechargeable battery.

35. The apparatus of claim 13, wherein the SoC comprises a Bluetooth interface and/or a near-field communication (NFC) interface for the wireless data communications between the SOC and an externa device.

36. The apparatus of claim 35, further comprising a customized app with a graphical user interface operating on the external device, configured to support real-time control of operations of the sensor unit, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

37. The apparatus of claim 36, wherein the external device is a base station including a mobile device, a smartphone, a tablet, a computer, a cloud server, or any electronic device with data reading/processing/displaying capability.

38. The apparatus of any one of claims 13-37, wherein the apparatus is characterized by miniaturized dimensions and a soft, skin-compatible encapsulation structure.

39. The apparatus of any one of claims 13-37, wherein the apparatus is configured to enable continuous monitoring in the most challenging care environments, and conformable placement in specific anatomical locations including a floor of the axilla where the axillary artery is most superficial to the skin for enhanced accuracy, and targeted application to areas of localized skin inflammation or infection.

40. The apparatus of any one of claims 13-37, wherein the apparatus is configured to enable accurate sensing even in highly variable ambient temperature conditions including those associated with direct radiant warming and high humidity.

41. The apparatus of any one of claims 13-37, wherein the apparatus is configured to enable simultaneously recording relevant physiological parameters including a heart rate, a respiratory rate, a body position, vocalizations, and movement via mechano-acoustic measurements of body motions and sounds captured using a high-bandwidth accelerometer.

42. The apparatus of any one of claims 13-37, wherein the apparatus is stretchable and bendable.

43. A sensor network system for non-invasively measuring physiological parameters of a mammal subject, comprising: a plurality of wireless apparatuses time-synchronized to each other, wherein each wireless apparatus is placed on a respective region of the skin of the mammal subject and comprises a sensor unit comprising a sensor member for measuring at least one physiological parameter of the mammal subject, and a system on a chip (SoC) having a microprocessor coupled to the sensor member for receiving data therefrom and processing the received data, and for wireless data communications; and a base station adapted in wireless communication with the plurality of wireless apparatuses and configured to support real-time control of operations of the wireless apparatuses, to receive, from the wireless apparatuses, to process, and to display the physiological parameters.

44. The sensor network system of claim 43, wherein the sensor member comprises a temperature sensor for measuring temperature of the mammal subject.

45. The sensor network system of claim 44, wherein the temperature sensor comprises two negative temperature coefficient (NTC) thermistors fold in a manner that orients one toward the skin-facing surface and the other toward the ambient-facing surface.

46. The sensor network system of claim 44, wherein the temperature sensor comprises one or more resistance temperature detectors and/or one or more semiconductor-based temperature sensors.

47. The sensor network system of claim 44, wherein the sensor member further comprises an inertial measurement unit (IMU) mounted in mechanical communication with the skin measuring vital signs including a heart rate, a respiratory rate, a physical activity, and/or a body position.

48. The sensor network system of claim 47, wherein the sensor member further comprises one or more of an SpCh sensor for measuring a blood oxygen saturation; an electrocardiogram (ECG) sensor for measuring ECG signal; and a photoplethysmography (PPG) sensor for measuring a PPG signal.

49. The sensor network system of claim 48, wherein the sensor unit further comprises a power management integrated circuit (PMIC); an LED indicator; and/or magnets, wherein all of them are mounted on a flexible printed circuit board (fPCB) using surfacemounted technology (SMT).

50. The sensor network system of claim 49, wherein an output of the PMIC supports skinfacing and ambient-facing temperature measurements and mechano-acoustic data collection.

51. The sensor network system of claim 49, wherein the LED indicator is configured to serve as a visual alarm that is activatable based on the measured physiological parameters and/or user-defined threshold settings.

52. The sensor network system of any one of claims 43-51, wherein each wireless apparatus further comprises an elastomeric encapsulation layer at least partially surrounding the sensor unit to form a skin-facing surface and an ambient-facing surface.

53. The sensor network system of claim 52, wherein the elastomeric encapsulation layer is a waterproof and biocompatible silicone enclosure.

54. The sensor network system of claim 52, wherein each wireless apparatus further comprises: a top thermal insulating layer and a bottom thermal insulating layer disposed between the sensor unit and the elastomeric encapsulation layer to at least partially cover the sensor unit for minimizing the influence of the ambient on measurements of the temperature of the skin.

55. The sensor network system of claim 54, wherein the bottom thermal insulating layer has an air cavity in which the bottom NTC thermistor is placed, so as to mechanically isolate the bottom NTC thermistor from the other parts of the apparatus.

56. The sensor network system of claim 43, wherein each apparatus is a battery-free apparatus configured to operate in a battery-free mode, or a battery-powered apparatus configured to operate in a battery-powered mode.

57. The sensor network system of claim 56, wherein the battery-free apparatus further comprises a wireless power harvesting unit in communication with the sensor unit for wireless power harvesting.

58. The sensor network system of claim 57, wherein the wireless power harvesting unit comprises: a power receiving (Rx) coil connecting through flexible copper traces to a rectifier, a voltage regulator, supercapacitors, a PMIC, and magnets for mechanically coupled interconnects.

59. The sensor network system of claim 58, wherein the battery-free mode relies on nearfield communication (NFC) for wireless power transfer from an external transmitting coil to the power receiving coil (Rx).

60. The sensor network system of claim 56, wherein the battery-powered apparatus further comprises a battery unit having a battery.

61. The sensor network system of any one of claims 43-60, wherein the SoC comprises a Bluetooth interface and/or a near-field communication (NFC) interface for the wireless data communications between the SOC and the base station.

62. The sensor network system of any one of claims 43-60, wherein the wireless apparatuses are capable of autonomously configuring settings of the base station to maintain the temperature of the mammal subject in a configured value.

63. The sensor network system of any one of claims 43-60, wherein the base station is configured to generate alarm and alerts triggered by at least one of the wireless apparatuses.

64. The sensor network system of any one of claims 43-60, wherein the base station is configured to display the temperature readings of the wireless apparatus(s) for temperature measurement.

65. The sensor network system of any one of claims 43-60, wherein the sensor network system enables continuous, full-body measurements of temperature distributions for spatiotemporal temperature mapping.

66. The sensor network system of any one of claims 43-60, wherein the sensor network system enables measurements of temperature differentials between the central skin and the peripheral skin, which are particularly valuable in tracking for early signs of sepsis in neonates.

67. The sensor network system of any one of claims 43-60, wherein the base station is capable of controlling radiant heating, or convective heating, or humidity.

68. The sensor network system of claim 67, further comprising: a customized app with a graphical user interface operating on the base station, configured to support real-time control of operations of the wireless apparatuses, and/or serve as an interface to display the measured physiological parameters and/or monitor conditions of the mammal subject and the ambient.

69. The sensor network system of claim 68, wherein the base station includes a mobile device, a smartphone, a tablet, a computer, a cloud server, or any electronic device with data reading/processing/displaying capability.