JP2023530683A - Moisture content sensor and its application for monitoring and diagnosing skin diseases under any environment - Google Patents

Abstract

The present invention relates to a moisture content sensor comprising a sensing module operably disposed over a target area of interest of the skin of a living body to detect data associated with thermal properties of the skin; and a wireless platform coupled to the sensing module for wireless data transmission between and an external device. The sensing module comprises a thermal actuator for operatively heating its target area of interest and a sensing circuit for simultaneously detecting transient temperature changes thereof to determine the thermal properties of the skin.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit from U.S. Provisional Patent Application No. 63/037,092, filed June 10, 2020, which is hereby incorporated by reference in its entirety. It is.

This application, which is incorporated herein by reference in its entirety, is itself US Filed March 29, 2019, claiming priority to and benefit from Provisional Patent Application No. 62/791,390 and U.S. Provisional Patent Application No. 62/696,685 filed July 11, 2018 It is also a continuation-in-part of US patent application Ser.

The present invention relates generally to biosensors, and more particularly to wireless moisture sensors for rapid multi-sensor measurement of moisture levels in healthy and/or diseased skin. is.

The background discussion 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 any mention of the prior art in the Background of the Invention section. Likewise, it should not be assumed that the problems mentioned in the Background of the Invention section or associated with the subject matter of the Background of the Invention section have already been recognized in the prior art.

The skin, the largest organ of the human body, is a complex multi-layered functional structure supporting an essential set of protective, sensory, thermoregulatory, and immunological functions. A primary function of the skin is to serve as a protective interface to the surrounding environment. The three major layers of the skin, the stratum corneum (SC), epidermis, and dermis, serve as dynamic physical barriers against exogenous stimuli and as active interfaces to maintain homeostasis. Impairment of protective function can lead to a variety of adverse health effects, as infections, insensitive water loss, tissue necrosis, and death can occur when the skin barrier is compromised. Defects in barrier function are also the underlying cause of atopic dermatitis (AD), commonly known as eczema. AD is the most common inflammatory skin disease, affecting 20% of children and 3% of adults worldwide. Dry skin, or xerostomia (XC), is another common skin disorder associated with barrier disorders, affecting 85% of the elderly. Skin barrier dysfunction in neonates can also predict the development of AD within the next few years. These and other types of degradation increase the body's absorption of foreign chemicals and toxic metals and can lead to serious health consequences.

Quantitative assessment of skin barrier function can provide essential information to guide clinical decision making. Current methods involve determining transepidermal water loss (TEWL) via measurement of water vapor pressure at the skin surface, or assessing the high frequency electrical properties of the skin itself as a surrogate marker of its water content. Existing TEWL meters and skin capacitance methods can be affected by small changes in ambient temperature, subtle variations in skin interface angle and pressure, and small user-related differences in testing protocols. Only available on expensive devices. Such limitations limit the use of these methods to highly controlled clinical and research studies. Alternatively, recent studies have shown that the transient plane source (TPS) method can be adapted for the non-invasive measurement of the heat transport properties of the skin, a simple model of the thermal properties of the skin and its moisture level. It has been demonstrated to quantitatively link Accurate quantitative measurements of skin hydration status provide important insights into skin health and additional relevance to essential processes of skin structure and function, as well as other features of thermoregulation and basic physiology. be able to. Existing tools for determining skin moisture content utilize surrogate electrical assessments performed with bulky, stiff, and expensive equipment that are difficult to use in a reproducible manner.

Accordingly, a heretofore unmet need exists in the art to address the aforementioned deficiencies and inadequacies.

In one aspect, the present invention relates to a moisture content sensor operably disposed on a target area of interest of the skin of a living body to detect data associated with thermal properties of the skin. A sensing module and a wireless platform coupled to the sensing module for wireless data transmission between the sensing module and an external device.

In one embodiment, the sensing module includes a thermal actuator operably disposed on the target area of interest of the skin to heat the target area of interest and a transient temperature change thereof to determine the thermal properties of the skin. and a sensing circuit for simultaneously detecting (ΔT).

In one embodiment, the thermal actuator and sensing circuitry are interconnected by serpentine traces to form a flexible structure that facilitates soft intimate contact to the skin with robust mechanical and thermal coupling.

In one embodiment, the thermal actuator includes at least one resistor.

In one embodiment, the thermal actuator comprises two or more of surface mount thin film resistors, thick film resistors, through hole resistors, and ultra thin film metal resistors coupled in series with each other.

In one embodiment, the sensing circuit comprises one or more of a negative temperature coefficient thermistor, a positive temperature coefficient thermistor, a resistance temperature detector (RTD), and a thermocouple.

In one embodiment, the sensing circuit comprises a first pair of negative temperature coefficient thermistors (NTC) arranged in a first Wheatstone bridge circuit.

In one embodiment, the first pair of NTCs is disposed on a different layer than the thermal actuators and the first pair of NTCs directly overlies the thermal actuators. In another embodiment, the first pair of NTCs are disposed on the same layer as the thermal actuator, each first NTC having a first distance from the thermal actuator.

In one embodiment, the sensing circuit further comprises a second pair of NTCs arranged in a second Wheatstone bridge circuit that serves to compensate for changes in ambient temperature.

In one embodiment, the second pair of NTCs are disposed on the same layer as the first pair of NTCs, each second NTC being spatially separated from the first pair of NTCs and thermally It has a second distance from the actuator.

In one embodiment, the first and second distances are determined by design requirements for depth sensitivity into the skin and range from tens of microns to several millimeters.

In one embodiment, the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols.

In one embodiment, the wireless platform comprises a Bluetooth low energy system on a chip (BLE SoC).

In one embodiment, the BLE SoC is a general purpose input/output (GPIO) electrically coupled to the thermal actuator to provide a periodic current to activate the thermal actuator and a bridge voltage to amplify the difference. a differential amplifier (AMP) electrically coupled to the sensing circuit, an analog-to-digital converter (ADC) electrically coupled to the AMP for digitizing the output voltage of the AMP; skin moisture; A BLE configured to wirelessly transmit the output signal of the ADC to an external device for processing to determine refueling status, receive data from the external device and enable a GPIO pin to provide periodic current to the thermal actuator. and a radio.

In one embodiment, a digital on/off switch controlled through a custom application on the external device is adapted to enable BLE connections and activation of GPIO pins to supply periodic current to the thermal actuators. .

In one embodiment, the BLE SoC further comprises a microcontroller (μC) configured to activate a GPIO pin to supply periodic current to the thermal actuator.

In one embodiment, the moisture content sensor further comprises a power module for powering the sensing circuitry and the wireless platform.

In one embodiment, the power module comprises a battery.

In one embodiment, the battery is a rechargeable battery that is operably rechargeable with wireless charging.

In one embodiment, the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery.

In one embodiment, the power module further comprises fault protection elements including short circuit protection components or circuits to avoid malfunction of the battery.

In one embodiment, the moisture content sensor further comprises a flexible substrate in the form of a flexible printed circuit board (fPCB) having circuit traces interconnecting the skin-side thermal actuator, the air-side NTC, and the BLE SoC.

In one embodiment, the flexible substrate is formed from flexible materials including polyimide (PI) and/or polyethylene terephthalate (PET).

In one embodiment, the flexible substrate is a flexible copper clad polyimide (Cu/PI/Cu) sheet.

In one embodiment, the moisture content sensor further comprises an encapsulating enclosure surrounding the thermal actuator, wireless platform, battery, and fPCB.

In one embodiment, the encapsulation enclosure provides a top layer for thermally, chemically, and mechanically isolating the moisture sensor from the environment, and a direct interface between the thermal actuator on the skin side of the fPCB and the skin. a bottom layer for providing.

In one embodiment, the top layer is a shell-like top encapsulation layer that contains small voids to thermally, mechanically, and chemically insulate the critical sensing components.

In one embodiment, the top layer is formed from flexible materials including silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon®, and various other flexible polymers. be.

In one embodiment, the bottom layer comprises a flexible adhesive for attaching the moisture sensor to the skin.

In one embodiment, the bottom layer further comprises a micro-woven fiberglass/stiffener embedded in the flexible adhesive layer to increase the mechanical robustness of the moisture sensor.

In one embodiment, the stiffener is flexible and has varying mesh densities and thicknesses to impart tear resistance to the bottom layer.

In one embodiment, the flexible adhesive layer is formed from silicone or silicone gel, or a double-sided skin safe adhesive, the ratio of silicone and silicone gel simultaneously optimizing the mechanical integrity and tackiness of the adhesive. adjusted to

In one embodiment, the external device is a smart phone, tablet, computer, or any electronic device with data reading/processing capabilities.

In one embodiment, the thermal properties of the skin include the thermal conductivity and thermal diffusivity of the skin which are related to the moisture content of the skin, which is a function of skin depth.

In one embodiment, the moisture content is determined from the measured temperature change ΔT versus time t.

In one embodiment, moisture content and skin surface temperature are used to determine the normal or diseased state of the skin.

In one embodiment, moisture content and skin surface temperature serve as quantitative metrics for the efficacy of treating skin conditions or other health and wellness products, including skin moisturizers, lotions, and/or creams.

In one embodiment, the moisture sensor can be used to monitor skin conditions in clinical settings and/or home settings.

In one embodiment, the hydration sensor is used to administer treatment, monitor efficacy, modify treatment protocols as needed, and/or initiate flares based on quantitative personalized measurements for specific lesion sites. Can be used to potentially predict.

In one embodiment, the water content sensor can be used to monitor the water content of internal organs for various diseases where conventional monitoring techniques cannot provide a continuous assessment of organ health.

In one embodiment, the water content sensor can be used to monitor organs during organ transportation for organ transplantation applications.

In one embodiment, the moisture content sensor can be used to measure thermal conductivity, thermal diffusivity, heat capacity, and other thermal properties of any material as a function of depth.

In one embodiment, the moisture content sensor detects moisture on any material surface, including hydrogels, plants (irrigation and agricultural applications), food storage (dry food, grains, fruits, meats), and/or concrete (industrial applications). It can be used in applications to measure content as a function of depth.

In one embodiment, the moisture content sensor can be used to monitor the composition of food/beverages, pharmaceuticals/industrial chemicals.

In one embodiment, the moisture sensor is reusable and removable without skin irritation or damage to the moisture sensor.

In one embodiment, the moisture sensor is compatible with an alcohol-based cleaning wipe that allows reuse between different users without damage to the moisture sensor or loss of efficacy of the moisture sensor adhesive. be.

In one embodiment, the moisture content sensor is sterilizable using alcohol, autoclave steam sterilization, and vapor phase sterilization.

In another aspect, the invention relates to a method of fabricating a moisture content sensor. In one embodiment, the method includes forming a flexible printed circuit board (fPCB) interconnecting the moisture sensor electronics and forming an encapsulating enclosure surrounding the sensing module, the wireless platform, and the fPCB. , the encapsulating enclosure comprises a top layer and a bottom layer.

In one embodiment, the fPCB is formed from a flexible material including polyimide (PI), polyethylene terephthalate (PET), or any one of these in combination with a rigid PCB material including FR-4.

In one embodiment, the bottom layer comprises a first flexible layer, a second flexible layer, and fiberglass/fiberglass embedded between the first and second flexible layers. Contains layers of reinforcing fabric.

In one embodiment, each of the first flexible layer and the second flexible layer is formed from silicone or silicone gel, or a double-sided skin safe adhesive, the ratio of silicone and silicone gel being the mechanical strength of the adhesive. adjusted to simultaneously optimize physical integrity and stickiness.

In one embodiment, the stiffener is flexible and has varying mesh densities and thicknesses to impart tear resistance to the bottom layer.

In one embodiment, the bottom layer adheres to the f-PCB through the use of silicone adhesives, epoxies, adhesives, or commercial adhesives.

In one embodiment, the top shell layer is formed from silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon®, and various other flexible polymers.

In one embodiment, the electronics are coupled to the sensing module for detecting data associated with thermal properties of the skin and wireless data transmission between the sensing module and an external device. a wireless platform;

In one embodiment, the sensing module includes a thermal actuator for heating a target area of interest on the skin and a sensing circuit for simultaneously detecting transient temperature changes (ΔT) thereof to determine the thermal properties of the skin. Prepare.

In one embodiment, the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols.

In one embodiment, the wireless platform comprises a Bluetooth low energy system on a chip (BLE SoC).

In yet another aspect, the present invention relates to methods of monitoring and/or diagnosing skin conditions. In one embodiment, the method is to attach a moisture content sensor on the target area of interest of the skin, the moisture content sensor for bi-directional data communication with the thermal actuator, the sensing circuit, and an external device. a wireless platform; attaching a moisture content sensor; heating a target area of interest of the skin with a thermal actuator; simultaneously detecting data associated with thermal properties of the skin with a sensing circuit; , wirelessly transmitting by a wireless platform to an external device to determine its transient temperature change (Δt); obtaining from the temperature change (ΔT) the moisture content of the target area of interest of the skin; determining the condition of the skin at the target area of interest based on the obtained moisture content.

In one embodiment, the water content comprises an epidermal water content Φ _E and a dermal water content Φ _D .

In one embodiment, obtaining the moisture content comprises separately determining Φ _E and Φ _D from the temperature change ΔT.

In one embodiment, the wireless platform transmits data through wireless communication protocols including Near Field Communication (NFC), Wifi/Internet, Bluetooth/Bluetooth low energy (BLE), or GSM/cellular communication.

In one embodiment, said heating of the target area of interest of the skin is provided by applying a periodic electrical current to a thermal actuator.

In one embodiment, enabling of the periodic current is controlled by a digital on/off switch through a custom application on the external device.

In one embodiment, said determining the condition of the skin in the target area of interest comprises comparing the obtained moisture content to a standard moisture content in the target area of interest to determine a normal or diseased condition of the skin. including doing

In one embodiment, said determining the condition of the skin in the target area of interest comprises diagnosing a skin disease in the target area of interest based on the obtained moisture content.

In one embodiment, said determining the condition of the skin in the target area of interest comprises assessing the efficacy of a treatment for a skin condition.

In one embodiment, said obtaining the moisture content of the target area of interest of the skin and said determining the condition of the skin are performed in an external device.

In one embodiment, the method further comprises displaying the skin condition of the target area of interest on the external device.

In one embodiment, the method further comprises forwarding the skin condition at the target area of interest to a professional and/or service provider.

In one embodiment, the method comprises administering treatment, monitoring efficacy, modifying the treatment protocol if necessary, and/or flaring out based on quantitative personalized measurements of specific lesion sites. further comprising one or more of the steps of potentially predicting .

In one embodiment, the method is performed under one or more optimized measurement conditions, which conditions are (1) the natural process of water vapor release from the skin due to the presence of the moisture sensor; (2) very light or zero pressure is used during the measurement to minimize perturbation to the skin; and (3) the adhesive is present only over the area of the moisture sensor device adjacent to the sensor itself and is patterned to avoid peeling of the skin at the measurement site during peeling and improve reproducibility. (4) the temperature of the moisture sensor should be similar to that of the skin; and (5) the skin itself should be able to acclimatize to the environment prior to the measurement.

These and other aspects of the present invention will become apparent from the following description of the preferred embodiments taken in conjunction with the following drawings, the variations and modifications described therein being novel features of the present invention. can be influenced without departing from the spirit and scope of the concept.

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 will be used throughout the drawings to refer to the same or like elements of an embodiment.

Bluetooth Low Energy (BLE) communication capability on the tip of the index finger showing a soft skin-interfaced platform for automatic wireless sensing of skin heat transport properties according to embodiments of the present invention. A photograph showing a thin flexible thermal actuator/sensor (TAS) module integrated with electronics to provide an inset featuring an image of the device bent between the thumb and forefinger. It is a diagram. Schematic and block diagram of a design showing a soft skin interface platform for automatic wireless sensing of heat transport properties of skin according to embodiments of the present invention, where the TAS module is a thermal actuator (Joule heater, _RH × 2) and a Wheatstone bridge circuit with two thermistors (NTC ₊ , NTC ₋ ) with a known resistor (R) in each bridge, and is versatile with a digital on/off switch on the user interface Enables an input/output (GPIO) pin to supply a predetermined periodic current (6.8 mA for 10 seconds and 0 mA for 50 seconds with a period of 1 minute) to the resistive heater to provide a differential within the BLE system-on-chip (SoC). A dynamic amplifier (AMP) amplifies the difference in bridge voltages (V ₊ , V ₋ ) and a subsequent analog-to-digital converter (ADC) samples the AMP output voltage for transmission to a smartphone over BLE wireless communication, in FIG. be. Constituent layers and components: silicone encapsulation layer, battery, and thermal actuator (skin side), NTC, showing a soft skin interface platform for automatic wireless sensing of skin heat transport properties according to embodiments of the present invention. (air side), and a flexible copper-clad polyimide (Cu/PI/Cu) sheet containing circuit traces interconnecting the BLE SoC, with the inset showing the top silicone as insulation around the TAS module. FIG. 10 highlights the air pocket structure defined by the encapsulation layer; FIG. 10 shows a photograph of an encapsulation device adhered to the ball of the foot showing a soft skin interface platform for automatic wireless sensing of skin heat transport properties according to embodiments of the present invention. FIG. 4 is a schematic layered view of a TAS module showing a soft skin interface platform for automatic wireless sensing of skin heat transport properties according to embodiments of the present invention. FIG. 10 is a schematic top view of a TAS module showing a soft skin interface platform for automatic wireless sensing of skin heat transport properties according to embodiments of the present invention. Two pairs of thermistors, namely NTC ₁ (NTC ₁₊ , NTC ₁₋ , on top of the thermal actuator, showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. Fig. 2 is a schematic diagram of a thermal actuator (R _H ×2) with NTC ₂ (NTC ₂₊ , NTC ₂₋ , resting at the same distance d from the actuator); Schematic diagrams of FEA models of double-sided (left) and single-sided (right) sensor designs, showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. A short time (t 1.0 s, top) and long time (t=10 s, bottom) for the temperature distribution of skin with 50% water by volume. A short time ( _t = _{1.0 sec} , t=1.0 s, FIG. 2D) shows the relationship between ΔT ₁₂ and the moisture level of the epidermis (Φ _E ) and dermis (Φ _D ). Long time (t=10 s, t=10 s, FIG. 2E, where ΔT ₁₂ =ΔT ₁ −ΔT ₂ showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. ) and the moisture levels of the _epidermis (Φ _E ) and dermis (Φ _D ). Thick layers of PDMS S184 (red) and S170 (blue), and different thicknesses on top of S170, showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. FIG. 2F shows wireless measurements of ΔT ₁₂ at long times (FIG. 2F, t=1 to 10 s) for samples containing thin layers of S184 of thickness (70 μm, black, 100 μm, green, 200 μm, yellow). Thick layers of PDMS S184 (red) and S170 (blue), and different thicknesses on top of S170, showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. 2G shows wireless measurements of ΔT ₁₂ at short times (FIG. 2G, t=0.5 to 1 sec) for samples containing thin layers of S184 of thickness (70 μm, black, 100 μm, green, 200 μm, yellow). . Finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. It is a diagram. ΔT measured on the skin (forearm) throughout the measurement period (t = 0 to 10 s) showing finite element analysis (FEA) of heat transport throughout the system as a basis for device optimization and data analysis. ₁₂ (SD<4.5%) FEA curve fit and resulting Φ _D and Φ _E. FIG. FIG. 3A shows experimental studies under various practical conditions at various ambient temperatures (T _A ) in an oven and refrigerator (red and blue background, respectively), and T ₁ (blue) at room temperature (RT). and T ₂ (red) wireless measurements. FIG. 3B shows measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) as a function of _TA , showing experimental studies under various practical conditions. . FIG. 3C shows experimental studies under various practical conditions: T ₁ (blue), T ₂ (red), and substrate temperature (T _S , Dashed green line) wireless measurements as a function of time with different levels of airflow, where the surface temperature of the top encapsulation corresponds directly above the heating/sensing element of the device (T _D , purple). , Ambient temperature (T _A , black) determined using a commercially available thermometer. FIG. 3D shows measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) in (FIG. 3D) as a function of _TA , showing experimental studies under various practical conditions. FIG. 12 shows a pneumatic flow valve controlling the flow of air over the device. FIG. 3E shows the measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) as a function of time (FIG. 3E), showing experimental studies under various practical conditions. FIG. 12 shows a pneumatic flow valve controlling the flow of air over the device. FIG. 3F shows wireless measurements of T ₁ (blue), T ₂ (red), and difference (T ₁ −T ₂ , black) as a function of time, showing experimental studies under various practical conditions. It is a figure which shows. FIG. 3G shows wireless measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) as a function of time in water, showing experimental studies under various practical conditions. is. FIG. 3H shows an experimental study under various practical conditions with a BLE device (Φ _BLE ) and measuring tissue water content (Φ _CML,1 ) and skin surface moisture level (Φ _CML,2 ). Figure 3F shows the skin hydration levels (Φ) measured by three users in the same set of body placements using a commercially available device for 5 different body placements, the forehead (Fig. 3F). ), right arm (A _R ), left arm (A _L ), right leg (L _R ), and left leg (L _L ). FIG. 4A shows an experimental study on porcine skin samples with near-surface layers of skin and different known levels of moisture content, a simple method for uniformly removing fixed areas of SC from skin. FIG. 10 shows an optical image of a detachment disc (D-Squame, CuDerm) on the forearm as an analgesic procedure. FIG. 4B shows experimental studies on porcine skin samples with near-surface layers of skin and different known levels of moisture content as a function of the number of cycles of adhesive disc peeling, commercially available devices (MoistureMeter SC, Fig. 2 shows measurements of Φ _BLE (black) and ΦC _ML,1 (blue) and SC moisture level (Φ _CML,3 , red) measured using Delfin Technologies). FIG. 4C shows experimental studies on samples of porcine skin with near-surface layers of skin and different known levels of moisture content, short (t=1 s, black) and long (t=10 s). , red) Measured ΔT ₁₂ in heating time as a function of the number of cycles of debonding, where the vertical bars indicate the spread associated with three repeated measurements. FIG. 4D shows an experimental study on the near-surface layer of skin and porcine skin samples with different known levels of moisture, a commercially available device for measuring SC moisture levels (MoistureMeterSC, Delfin FIG. 3 shows an optical image of the device mounted on a sample of porcine skin, next to the Technologies. FIG. 4E shows experimental studies on porcine skin samples with different known levels of water content, layers near the surface of the skin, and controlled by placing the samples in a food dehydrator (33° C.). Figure 2 shows the measured Φ of pig skin samples with different known moisture levels. FIG. 4F shows experimental studies on the near-surface layer of skin and pig skin samples with different known levels of moisture content, short (t = 1 s) and long (t = 10 s) heating times and a linear fit (solid line) of ΔT ₁₂ (squares), showing that the change in ΔT ₁₂ is positively correlated with water loss, ΔT ₁₂ (10 sec) = 6.9 + 0.3 x water loss (R ² = 0.97) and ΔT ₁₂ (1 sec) = 5.6 + 0.1 x water loss (R ² = 0.85). , Fig. FIG. 5A shows a photograph of a device worn on the forehead of a healthy female volunteer showing physical measurements of skin moisture levels. FIG. 5B shows a photograph of a device worn on the forearm of a healthy female volunteer showing physical measurements of skin moisture levels. FIG. 5C shows a photograph of a device worn on the leg of a healthy female volunteer showing physical measurements of skin moisture levels. FIG. 5D shows physical measurements of skin hydration levels for 3 females (subjects 1, 2, 9, age range: 25 to 27) and 7 males (subjects 3 to 8, 10, age range). :17 to 37) wireless measurements of AT from NTC ₁ and NTC ₂ obtained from healthy volunteers and the differences (ΔT ₁ , ΔT ₂ , ΔT ₁₂ , respectively) on the body. FIG. 14 shows the positions, forehead (F), right arm ( _AR ), left arm ( _AL ), right leg ( _LR ), and left leg ( _LL ). FIG. 5E shows the results of physical measurements of skin moisture levels, skin moisture level (Φ) from values of ΔT ₁₂ , i.e., Φ _BLE , and skin moisture level (Φ) from a commercial medical device, i.e. Φ _CML,1 , data showing a strong correlation between Φ _BLE and Φ _CML, 1: Φ _CML,1 =Φ _BLE ×0.80−0.20. FIG. 6A shows wireless measurements of skin hydration of a human subject with atopic dermatitis on the back of the hand (atopic eczema) and forearm (control) of a young adult patient with severe AD (subject 1, FIG. 6A). The study involved three replicate measurements at each placement using a wireless and commercial device before and 15 minutes after application of the moisturizer, insets show the placement of the moisturizer. FIG. 6A shows an optical image of the back of the hand and forearm immediately after application of C. (FIG. 6A), and of the device on inflamed (left, FIG. 6A) skin. FIG. 6B shows wireless measurements of skin moisture in a human subject with atopic dermatitis in the chest of an elderly patient with inflammatory AD (Subject 2, FIG. 6B) (from left to right inflammation, near lesion site, and clinically unaffected skin), the study included three replicates at each placement using wireless and commercial devices before and 15 minutes after moisturizer application. Accompanied by the measurements, the inset shows an optical image of the device on the skin near the lesion site (right, FIG. 6B). FIG. 6C shows wireless measurements of skin hydration in human subjects with atopic dermatitis, showing wireless measurements of ΔT ₁₂ before and after (B&A) application of moisturizer from Subject 1 (FIG. 6C). FIG. 4 is a diagram showing; FIG. 6D shows wireless measurements of skin hydration of a human subject with atopic dermatitis, showing wireless measurements of ΔT ₁₂ before and after (B&A) application of moisturizer from subject 2 (FIG. 6D). FIG. 4 is a diagram showing; FIG. 6E shows wireless measurements of skin moisture in a human subject with atopic dermatitis using a commercially available product to measure tissue moisture (Φ _CML,1 ) and skin surface moisture (Φ _CML,2 ). Figure 6 shows skin hydration levels (Φ) measured using the device, and ΔT ₁₂ (Φ _BLE ) values from subject 1 (Fig. 6E), where the Φ _CML,1 results are after calibration. Fig. 10 shows a strong correlation with Φ _BLE (Φ _{BLE, Cal} = Φ _BLE × 0.78-0.08); FIG _. 6F shows wireless measurements of skin moisture in a human subject with atopic dermatitis _. Figure 6 shows skin hydration levels (Φ) measured using the device, and ΔT ₁₂ (Φ _BLE ) values from Subject 2 (Fig. 6F), where Φ _CML,1 results are after calibration. Fig. 10 shows a strong correlation with Φ _BLE (Φ _{BLE, Cal} = Φ _BLE × 0.78-0.08); FIG. 6G shows a photograph of a device worn on the forehead of an infant (FIG. 6G) showing wireless measurements of skin hydration in a human subject with atopic dermatitis. FIG. 6H shows a photograph of the device worn on an infant's leg (FIG. 6H, visibly dry skin) showing wireless measurements of skin hydration in a human subject with atopic dermatitis. be. FIG. 6I shows wireless measurements of skin hydration in human subjects with atopic dermatitis Φ _BLE (blue) in left leg (L _L ), right leg (R _L ) and forehead (F _H ). ), Φ _CML,1 (black), TEWL (red), and SCH (green), vertical lines indicate error bars. FIG. 7A shows the changes in Φ _CML,1 and Φ _BLE from three different skin placements without moisturizer (control, FIG. 7A) showing a study of the effect of moisturizers on healthy adults. Fig. 10. Measurements are normalized to their respective initial values determined at time=0. FIG. 7B shows a study of the effect of moisturizers on healthy adults, 1 minute after application of the moisturizer on the forearm of subject 1 (FIG. 7B) (short, from three different skin placements in FIG. 7B). Figure 7C shows changes in Φ _CML,1 and Φ _BLE , where the measured values are normalized to their respective initial values determined at time = 0. Figure 7C shows the results of moisturizing agents for healthy adults. Fig. 7C shows changes in Φ _CML,1 and Φ _BLE from three different skin placements 15 minutes after applying moisturizer on the forearm of subject 1 (Fig. 7C) (long, Fig. 7C). Figure 7D shows the measured values normalized to their respective initial values determined at time = 0. Figure 7D shows a study of the effect of moisturizer on healthy adults, without moisturizer ( FIG. 7D shows changes in Φ _CML,1 and Φ _BLE from three different skin placements after applying moisturizer on the forearm of control, FIG. 7D), and subject 2 (FIG. 7D). are normalized to their respective initial values determined at time = 0. Figure 7E shows a study of the effect of moisturizer on healthy adults, with moisturizer applied on the forearm of Subject 2 (Figure 7E). FIG. 7E shows the changes in Φ _CML,1 and Φ _BLE from three different skin placements 1 minute after application of . Figure 7F shows a study of the effect of moisturizing agents on healthy adults, 15 minutes after applying the moisturizing agent on the forearm of subject 2 (Fig. 7F) (long , FIG. 7F ) changes in Φ _CML,1 and Φ _BLE from three different skin placements, where the measured values are normalized to their respective initial values determined at time=0. Figure 7G shows a study of the effect of a moisturizer on healthy adults, without moisturizer (control, Figure 7G), and after applying moisturizer on the forearm of subject 3 (Figure 7G). Figure 7H shows changes in Φ _CML,1 and Φ _BLE from skin placement, where measurements are normalized to their respective initial values determined at time = 0. Figure 7H is a healthy adult. Φ _{CML,1 and Φ CML,1} from three different skin placements 1 minute after applying moisturizer on the forearm of subject 3 (Fig. 7H) (short, Fig. 7H), showing a study of the effect of moisturizers on Figure 7I shows changes in _BLE , with measurements normalized to their respective initial values determined at time = 0. Figure 7I shows a study of the effect of moisturizers on healthy adults. Fig. 7I shows changes in Φ _CML,1 and Φ _BLE from three different skin placements 15 minutes after application of moisturizer on the forearm of subject 3 (Fig. 7I) (long, Fig. 7I); Fig. 10. Measurements are normalized to their respective initial values determined at time=0. FIG. 3 shows a photograph of the encapsulated device next to a 12 mAh lithium polymer battery. Wireless readings of temperature change measured from NTC ₁ (ΔT ₁ ) and NTC ₂ (ΔT ₂ ) as a function of time for 10 seconds of heating every minute, where ΔT ₁₂ = ΔT ₁ −ΔT _2. FIG. FIG. 10A is a schematic of the FEA model for a two-sided (FIG. 10A) sensor design. FIG. 10B is a schematic of the FEA model for a single-sided (FIG. 10B) sensor design. FIG. 10C Sensitivity of the temperature difference (ΔT ₁₂ ) between NTC ₁ (ΔT ₁ ) and NTC ₂ (ΔT ₂ ) to skin moisture levels for the double-sided (FIG. 10C) design 10 seconds after heater activation. It is a figure which shows. FIG. 10D Sensitivity of the temperature difference (ΔT ₁₂ ) between NTC ₁ (ΔT ₁ ) and NTC ₂ (ΔT ₂ ) to skin moisture level for the single-sided (FIG. 10D) design 10 seconds after heater activation. It is a figure which shows. FIG. 11A shows a comparison between FEA and measurements for a thick layer of S184 (FIG. 11A). FIG. 11B shows a comparison between FEA and measurements for S170 (FIG. 11B). FIG. 11C shows a comparison between FEA and measurements for a thin layer of S184 (70 μm, FIG. 11C) on top of S170. FIG. 11D shows a comparison between FEA and measurements for a thin layer of S184 (100 μm, FIG. 11D) on top of S170. FIG. 11E shows a comparison between FEA and measurements for a thin layer of S184 (200 μm, FIG. 11E) on top of S170. FIG. 12A shows calculated predicted values of ΔT as a function of skin hydration level (Φ) with different values of d (FIG. 12A, Q=20.4 mW, t=10.0 sec). FIG. 12B shows the calculated predicted value of ΔT as a function of Q (FIG. 12B, d=1.2 mm, t=10.0 seconds). FIG. 13A shows the calculated prediction of ΔT ₁₂ with different size actuators (RH width and length) for 30% (FIG. 13A) hydrated skin. FIG. 13B shows the calculated prediction of ΔT ₁₂ with different size actuators (RH width and length) for 95% (FIG. 13B) hydrated skin. FIG. 14A is a simplified analytical model of a disc-shaped thermal actuator (radius, R) and an NTC showing the effect of design parameters on temperature change. FIG. 14B is an analytical scaling law for ΔT ₁₂ showing the effect of design parameters on temperature change. Ambient temperature diagram showing measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) as a function of time (minutes) at the moment the device entered and exited the oven. FIG. 10 shows that the values of ΔT ₁ and ΔT ₂ are varying (yellow background). FIG. 16A is based on skin capacitance measurements for monitoring tissue moisture content (MoistureMeterD, top), SC moisture level (MoistureMeterSC, middle top), and skin surface moisture level (Gpskin, middle bottom). FIG. 2 shows photographs of a conventional device and a BLE device (bottom); Figure 16B shows a photograph of a device on the forearm, according to an embodiment of the present invention, showing that the commercially available device requires the user's discretion to hold the probe and apply constant pressure to the skin for each measurement. FIG. Fig. 3 shows the mounting positions on the body, forehead (F), right arm (A _R ), left arm (A _L ), right leg (L _R ), and left leg (L _L ). _{BLE (} Φ _{BLE ) and} Fig. 3 shows SD against Φ tested by three users using commercially available (Φ _CML,1 , Φ _CML,2 ) devices; Fig. 3 shows positive correlations between Φ _BLE and Φ _CML,1 (black) and Φ _BLE and Φ _CML,2 (red) and their linear fits (lines); FIG. 20A shows a Bland-Altman plot between Φ _BLE,Cal1 and Φ _CML,1 (FIG. 20A), with horizontal lines representing the mean of ΦBLE, Cal−Φ _CML (red), and the mean ± 1.96 SD values (blue), SD represents standard deviation, mean ± SD values of the differences (Φ _CML,1 −Φ _BLE,Cal1 and Φ _CML,2 −Φ _BLE,Cal2 ), respectively , 0.00±0.02, 0.00±0.04. FIG. 20B shows a Bland-Altman plot between Φ _BLE,Cal2 and Φ _CML,2 (FIG. 20B), with horizontal lines representing the mean of ΦBLE, Cal−Φ _CML (red), and the mean ± 1.96 SD values (blue), SD represents standard deviation, mean ± SD values of the differences (Φ _CML,1 −Φ _BLE,Cal1 and Φ _CML,2 −Φ _BLE,Cal2 ), respectively , 0.00±0.02, 0.00±0.04. FIG. 13 shows a photograph of an encapsulation device placed on a child's hand. ΔT ₁ , ΔT 2 , ΔT ₂ , at five different body positions for subjects 1 to 10: forehead (F), right arm (A _R ), left arm (A _L ), right leg (L _R ), left leg (L _L ) and SD versus _ΔT12 . Positive correlation between skin hydration levels from wireless devices (Φ _BLE ) and commercial devices (Φ _CML,1 ) and their linear fit (red line), where the linear fit is Φ _{CML, 1} = Φ _BLE × 0.80-0.20 with a coefficient of determination of R ² = 0.66. Bland-Altman plots (difference plots) of Φ _BLE,Cal1 and Φ _CML,1 , with horizontal lines representing the mean of Φ _BLE,Cal1 −Φ _CML,1 (red, ~0.00), and the mean ± 1.96·SD (blue, ˜0.00±1.96·0.05), where SD is the standard deviation. FIG. 25A shows photographs of the device on a subject's leg before (left) and after (right) shaving the skin, with the inset showing the sensing points. FIG. 25B shows wireless measurements of ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) before and after shaving the sensing area. FIG. 3 shows an optical image of the device worn on the forehead of a healthy male subject. FIG. 10 shows wireless measurements of Φ _BLE before, during, and after workout, where vertical bars represent error bars across three measurements. 1 shows an optical image of the device worn on Subject 1's atopic hand next to a BLE-enabled smartphone; FIG.

The invention will now be described in more detail below 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 numbers refer to like elements throughout.

The terms used herein generally have their ordinary meaning in the art within the context of the present invention and within the specific context in which each term is used. Certain terms used to describe the invention are described below or elsewhere in the specification to provide those skilled in the art with further guidance in describing the invention. For convenience, some terms may be highlighted using, for example, italics and/or quotation marks. Use of highlighting does not affect the scope and meaning of the terms, which are the same in the same context with or without highlighting. It will be appreciated that the same thing can be said in multiple ways. Accordingly, alternative language and synonyms may be used for one or more of the terms discussed herein, and no particular meaning is given to whether a term is elaborated herein. Not that there is. Synonyms are provided for some terms. A listing 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 term described herein, is illustrative only and does not imply any indication of the scope and meaning of the invention or exemplified term. is in no way limiting. Likewise, the invention is not limited to the various embodiments given herein.

Starting materials, biological materials, reagents, synthetic methods, purification methods, analytical techniques, assay methods, and biological methods other than those specifically exemplified will be readily apparent to those skilled in the art without resort to undue experimentation. It will be appreciated that it may be used in the practice of the invention. All art-known functional equivalents, of such materials and methods are intended to be included in this invention. The terms and expressions, which have been used, are used as terms of description rather than of limitation, and no use of such terms and expressions is intended to exclude equivalents of the features illustrated and described, or portions thereof. It is understood that there is not, and that various modifications are possible within the scope of the claimed invention. Thus, although the present invention has been specifically disclosed in terms of preferred embodiments and optional features, those skilled in the art may resort to modifications and variations of the concepts disclosed herein as a last resort, It should also be understood that such modifications and variations are considered within the scope of the invention as defined by the appended claims.

When ranges are given herein, e.g., temperature ranges, time ranges, or composition or concentration ranges, all intermediate and subranges, as well as all individual values within a given range, are included in the present invention. intended to be included in It will be understood that subranges or individual values within ranges or subranges included in the description herein may be excluded from the claims of the present invention.

As used throughout this description and the claims that follow, the meaning of "a," or where not stated ("a," "an," and "the") is: It will be understood to include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to a "cell" includes a plurality of such cells and equivalents thereof known to those skilled in the art. Similarly, the phrases "one" ("a" or "an" in the original English text (sometimes not used in the Japanese text), "one or more", and "at least one" are The terms may be used interchangeably in the specification, and it should also be noted that the terms "comprising," "including," and "having" can be used interchangeably.

An element "overlies" another element, is "attached to" another element, is "connected to" another element, is "joined with" another element, or is another element. When it is referred to as "in contact with" an element of a It will be understood that there may be additional or intervening elements. In contrast, an element is, for example, "directly on" another element, "directly attached to" another element, or "directly connected" to another element, or When it is said to be "directly coupled to" or "directly in contact with" another element, there are no intervening elements present. Also, those skilled in the art will recognize that a reference to a structure or feature that is disposed “adjacent” another feature has portions that are above or below the adjacent feature. You will also understand what you get.

The terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, although 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 present invention.

Moreover, relative terms such as “lower” or “bottom” and “upper” or “top” are used herein to describe the relationship of one element to another as shown. can be used in writing. It will be appreciated that relative terms are intended to encompass different orientations of the device in addition to the orientation depicted in the figures. For example, when one device in the figures is flipped over, elements described as being "under" the other element would be oriented "above" the other element. Thus, the exemplary term "bottom" can include both "bottom" and "top" orientations, depending on the particular orientation of the figure. Similarly, when the device in one of those figures is flipped over, elements described as being "below" or "beneath" the other element are oriented "above" the other element. Will. Thus, the exemplary terms "below" or "beneath" can encompass both an orientation of above and below.

"comprise" and/or "provide" or "include" and/or "include" or "have" and/or "have" or "carry" and/or "carry" or "accommodate" "have" and/or "accommodate", or "accompany" and/or "accompany", "characterized by", "characterized by" and similar phrases are understood to be non-limiting should be, ie, will be further understood to mean including but not limited to. As used in this disclosure, they designate the presence of a stated feature, region, integer, step, act, element, and/or component and one or more other features, regions, integers, It does not exclude the presence or addition of steps, acts, elements, components and/or groups thereof.

Unless defined otherwise, 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. Terms, such as those defined in commonly used dictionaries, are to be construed as having meanings consistent with those in the context of the relevant art and the present invention, and are not expressly defined herein. It will further be understood that the terms are not to be construed in an idealized or overly formal sense unless so defined.

As used in this disclosure, “approximately,” “about,” “approximately,” or “substantially” are generally within 20 percent, preferably within 10 percent, and more of a given value or range. It preferably means within 5%. Numerical values set forth herein are approximations, and where not expressly stated, the terms "approximately," "about," "approximately," or "substantially" are inferred. means that it can be

As used in this disclosure, the phrase "at least one of A, B, and C" is interpreted to mean logical (A or B or C) using non-exclusive logical OR. It should be. As used herein, the term "and/or" includes any and all combinations of the associated listed items.

"Interfacing" refers to positioning a device with tissue such that the device can affect the tissue and the tissue can affect the device. For example, a thermal actuator of the device can result in a thermal load being provided to the tissue in the form of "heat input". The heat input is preferably heating operation, but the device is also adapted for cooling operation. Thus, "thermally interfacing" refers to the ability of the device to exert a thermal challenge on the underlying tissue and detect responses such as changes in temperature over time, including the period after the thermal input ceases. Point. In this manner, one or more tissue parameters such as tissue water content, inflammation, blood flow, UV damage, etc. may be determined.

The phrases "flexible" and "bendable" are used synonymously herein to indicate that a material, structure, device, or device component has a breaking point of the material, structure, device, or device component. Refers to the ability to be deformed into curved or bent shapes without undergoing transformations that introduce significant distortions, such as characterizing distortions. In an exemplary embodiment, the flexible material, structure, device, or device component is 5% or more in the strain sensitive area, 1% or more for some applications, and It may be deformed into a curved shape without introducing more than 0.5% strain. As used herein, some, but not necessarily all, flexible structures are also extensible. Various properties include material properties such as low longitudinal modulus, flexural stiffness, and flexural stiffness, small average thickness (e.g., less than 100 microns, optionally less than 10 microns, and optionally less than 1 micron), and thin films and implement flexible structures (eg, device components) of the present invention, including device geometries such as mesh geometries.

Any of the devices provided herein can be described in terms of elasticity or elasticity. "Elasticity" includes conditions under which it is subjected to repeated cycles of deformation stress and stress relaxation, such as deformation that can undergo stress relaxation and return to its original undeformed state without undergoing substantial creep. , refers to a measure of non-plastic deformation. Creep may be defined as a permanent deformation or change in original material properties of less than 5%, less than 2%, or less than 1%.

“Stretchable” refers to the ability of a material, structure, device, or device component to be strained without fracture. In an exemplary embodiment, the extensible material, structure, device, or device component can be strained greater than 0.5% without fracture, and for some applications greater than 1% without fracture. Strain, and for other applications can be subjected to strains of 3% or more without fracturing. As used herein, many extensible structures are also flexible. Some extensible structures (eg, device components) are designed so that they can be deformed under compression, elongation, and/or torsion without fracture. Extensible structures include thin film structures comprising extensible materials, such as elastomers, bent structures capable of undergoing stretching, compressive, and/or twisting motions, and structures having island/bridge geometries. Stretchable device components include structures having stretchable interconnects, such as stretchable electrical interconnects.

"Two-way communication" is defined as a device in which power, commands, or queries can be sent to the device to act on the device, and the device itself can send information or diagnostics to an external controller wirelessly connected to the device. refers to the ability to wirelessly communicate with An "external controller" thus refers to an off-board component that can control a device and receive information from a device. Examples include handheld devices, computers, smartphones, and the like.

The devices and methods provided herein are suitable for long-term use in that the devices can be "worn" and maintained functional for extended periods of time. Accordingly, "continuously" refers to a period of time during which any of the devices provided herein are deployed on or in biological tissue and are ready for use. While the device is continuously deployed, measurements are described as intermittent or periodic measurements, such as continuous measurement times on the order of minutes, such as 1 minute, 5 minutes, 10 minutes, or 20 minutes or longer. obtain. However, periodic measurements can be repeated over the period the device is worn, eg, in the morning, during the day, and in the evening, on the order of 12 hours or more, 1 day or more, or 7 days or more.

A "thermal parameter" or "heat transport property" may refer to the rate of change of a temperature-related tissue property, such as a heat-related tissue property over time and/or distance (velocity). In some embodiments, the heat related tissue property can be temperature, conductivity, or humidity. Heat-related tissue properties may be used to determine the heat transport properties of tissue, where "heat transport properties" relate to heat flow or heat distribution at or near the tissue surface. In some embodiments, heat transport properties include temperature distribution over the tissue surface, thermal conductivity, thermal diffusivity, and heat capacity. Heat transport properties, as assessed in the methods and systems of the present invention, can be correlated with physical or physiological properties of tissue. In some embodiments, heat transport properties can be correlated with tissue temperature. In some embodiments, heat transport properties can be correlated with properties of the vasculature such as blood flow and/or direction.

"Substrate" refers to the portion of the device that provides mechanical support for components disposed on or within the substrate. The substrate can have at least one skin-related function or purpose. For example, the substrate may have mechanical functionality that provides physical and mechanical properties for establishing conformable contact at an interface with tissue, such as the skin or nail surface. The substrate may have a sufficiently small heat load or mass to avoid interfering with tissue parameter measurements and/or characterization. The substrate of any of the devices and methods of the invention may be biocompatible and/or bioinert. The substrate may be used in a subject such that the mechanical, thermal, chemical and/or electrical properties of the substrate and tissue are within 20%, or within 15%, or within 10%, or within 5% of each other. It can facilitate mechanical, thermal, chemical and/or electrical matching to underlying tissue such as skin or nails.

A flexible substrate that mechanically matches tissue, such as skin, provides a conformable interface that is useful, for example, in establishing conformable contact with a tissue surface. The devices and methods described herein may incorporate mechanically functional substrates comprising soft materials exhibiting flexibility and/or stretchability, such as, for example, polymeric and/or elastomeric materials. The mechanically matched substrate can have a Young's modulus of 100 MPa or less, and optionally for some embodiments, 10 MPa or less, optionally for some embodiments, 1 MPa or less. . In one embodiment, the mechanically matched substrate is 0.5 mm or less, and optionally for some embodiments, 1 cm or less, optionally for some embodiments, 3 mm or less. , with thickness. In one embodiment, the mechanically matched substrate has a bending stiffness of 1 nNm or less, optionally 0.5 nNm or less.

In some embodiments, the mechanically matched substrate is one or more mechanically matched substrates within a specified factor of the same parameter for the epidermal layer of the skin or nail, such as a factor of 10 or a factor of 2. characterized by physical and/or physical properties. For example, the substrate may be within a factor of 20, or optionally a factor of 10 for some applications, of tissue, such as the epidermal layer of the skin or nail surface, at the interface with the device of the present invention. It may have a Young's modulus or thickness within the range, or optionally within a factor of two for some applications. The mechanically matched substrate may have a mass or longitudinal modulus equal to or less than that of skin.

In some embodiments, the substrate thermally matched to the skin is small enough that tissue such as skin is not thermally loaded as a result of deployment of the device or is suitable for measuring and/or characterizing physiological parameters. It has a sufficiently small thermal mass to have no effect. In some embodiments, for example, the substrate thermally matched to the skin has a temperature rise of 2° C. or less as a result of deployment on the skin, and optionally 1° C. or less for some applications, and optionally Optionally has a sufficiently low thermal mass of 0.5° C. or less for some applications, and optionally 0.1° C. or less for some applications. In some embodiments, for example, the substrate thermally matched to the skin has a sufficiently low thermal mass that does not significantly disrupt water loss from the skin, such as avoiding changes in water loss by a factor of 1.2 or more. have Thus, the device does not substantially induce perspiration or significantly disrupt transcutaneous water loss from the skin while remaining effective in determining skin hydration adequacy.

The substrate may have a Young's modulus of 100 MPa or less, or 50 MPa or less, or 10 MPa or less, or 100 kPa or less, or 80 kPa or less, or 50 kPa or less. Further, in some embodiments, the device has a thickness of 5 mm or less, or 2 mm or less, or 100 μm or less, or 50 μm or less, and a net bending stiffness of 1 nNm or less, or 0.5 nNm or less, or 0.2 nNm or less. It is good to have. For example, assuming the device has a net bending stiffness selected from the range of 0.1 to 1 nNm, or 0.2 to 0.8 nNm, or 0.3 to 0.7 nNm, or 0.4 to 0.6 nNm. good.

In one embodiment, "epidermal tissue" refers to the outermost layer or epidermis of the skin. The epidermis consists of the following non-limiting layers (beginning with the outermost layer): stratum corneum, stratum lucidum (palms and soles, i.e. palmar area), stratum granulosum, stratum spinosum, stratum germinativum (also called stratum basale). called). In one embodiment, the epidermal tissue is human epidermal tissue.

"Encapsulate" is such that it is at least partially, and in some cases completely, surrounded by one or more other structures, such as a substrate, adhesive layer, or encapsulating layer Refers to the orientation of one structure. "Partially enclosed" means that one structure is partially surrounded by one or more other structures, e.g., 30%, or optionally 50%, of the outer surface of the structure, or Optionally refers to the orientation of a structure such that 90% is surrounded by one or more structures. "Fully enclosed" refers to an orientation of one structure such that it is completely surrounded by one or more other structures. Encapsulation may be described in functional terms such as being a fluid or electrical barrier, particularly in locations where fluid or electric fields would adversely affect the device.

"Conformable" means that a device, material, or substrate conforms to a desired contour, e.g. Refers to a device, material, or substrate that has sufficiently low bending stiffness that it can be contoured to allow conformable contact with curved surfaces, including surfaces that may change over time, such as by movement.

"Conformal contact" refers to contact established between a device and a receiving surface. In one aspect, conformal contact involves macroscopic adaptation of one or more surfaces (eg, contact surfaces) of the device to the overall shape of the surface. In another aspect, conformal contact is one or more surfaces (e.g., contact surfaces) of a device that microscopically conforms to the surface, resulting in substantially void-free intimate contact. Accompany. In one embodiment, conformable contact involves adapting the contact surface of the device to the receiving surface such that intimate contact is achieved, e.g., less than 20% of the surface area of the contact surface of the device is physically on the receiving surface. or optionally less than 10% of the contact surface of the device does not physically contact the receiving surface, or optionally less than 5% of the contact surface of the device physically contacts the receiving surface. no contact. Devices of some embodiments are capable of establishing conforming contact with internal and external tissue. Devices of some embodiments are characterized by various surface morphologies including planar, curved, contoured, macro-featured, and micro-featured surfaces, and any combination thereof. Conformable contact can be established with the tissue surface. Devices of some embodiments are capable of establishing conforming contact with tissue surfaces corresponding to tissue subjected to motion, including internal organs or skin.

"Young's modulus" is a mechanical property of a material, device, or layer that refers to the ratio of stress to strain for a given substance. Young's modulus is given by the formula

well as given by
E is the Young's modulus, _L0 is the natural length, ΔL is the change in length under applied stress, F is the applied force, A is the area over which the force is applied be. Young's modulus is given by the formula

can also be expressed in terms of Lame constants via where λ and μ are Lame constants. High Young's modulus (or "high modulus of elasticity") and low Young's modulus (or "low modulus of elasticity") are relative descriptors of the magnitude of Young's modulus in a given material, layer, or device. In some embodiments, the high Young's modulus is greater than the low Young's modulus, preferably about 10 times greater for some applications, more preferably about 100 times greater for other applications, even more preferably Still about 1000 times larger for other applications. In one embodiment, the low modulus layer has a Young's modulus of less than 100 MPa, optionally less than 10 MPa, and optionally a Young's modulus selected from the range of 0.1 MPa to 50 MPa. In one embodiment, the high modulus layer has a Young's modulus greater than 100 MPa, optionally greater than 10 GPa, and optionally selected from the range of 1 GPa to 100 GPa. In one embodiment, a device of the invention has one or more components with a low Young's modulus. In one embodiment, the device of the invention has an overall low Young's modulus.

"Low longitudinal modulus" refers to materials having a Young's modulus of 10 MPa or less, 5 MPa or less, or 1 MPa or less.

Use of the term "effective" with any physical parameter reflects an average or bulk parameter. This reflects, for example, that devices are not formed from a single material, but can have elastomers, adhesives, thin films, metals, semiconductors, integrated circuits, and other materials spanning several orders of magnitude. there is The effective device modulus corresponds to the overall physical properties of the device, along with the particular geometry and configuration of the components to ensure that the bulk behavior of the device is tailored to the application of interest. can be reflected. For the skin, the entire device can be constructed to be highly flexible and extensible, with some portions necessarily less flexible and extensible due to material requirements. For nails, the overall device does not need to be very extensible, but should still conform to the curved contours of the nail.

"Bending stiffness" is a mechanical property of a material, device or layer that describes the resistance of the material, device or layer to an applied bending moment. Generally, bending stiffness is defined as the product of the longitudinal elastic modulus and the moment of inertia of a material, device, or layer. Materials with non-uniform bending stiffness can optionally be described in terms of "bulk" or "average" bending stiffness for an entire layer of material.

"Tissue parameters" refer to properties of tissue including physical properties, physiological properties, electronic properties, optical properties, and/or chemical composition. Tissue parameters may refer to surface properties, subsurface properties, or properties of tissue-derived materials such as biological fluids. Tissue parameters include temperature, hydration status, chemical composition of tissue, chemical composition of tissue-derived fluid, pH of tissue-derived fluid, presence or absence of biomarkers, intensity of electromagnetic radiation delivered to tissue, tissue delivered It may refer to parameters corresponding to in vivo tissue, such as the wavelength of electromagnetic radiation, the amount of environmental contaminants to which the tissue is exposed, and the like. Some embodiments of the device either apply hydrating substances (e.g., moisturizers) in low-water conditions, or UV-blocking (e.g., sunscreen) in UV-damaging conditions or alert the user to take appropriate action. can generate a response corresponding to one or more tissue parameters for alerting an individual wearing a device such as a haptic feedback actuator that provides a vibrational, optical, or electrical signal to . Tissue parameters can provide useful information about tissue health. For example, a tissue parameter that is a "suntan parameter" is used to assess the effectiveness of a compound as a sunscreen, to alert a user, or to automatically apply a treatment, including the application of sunscreen. obtain. A tanning parameter may be an optical property such as color or even a hydration property related to the thermal conductivity of the underlying tissue.

Any of the devices and methods provided herein can be personalized to the user. In this context, "personalized" means tailored to an individual user, recognizing that there may be relatively significant inter-individual variability regarding one or more baseline tissue parameters and tissue behavior to stimuli. It describes a device or method that has been reworked. For example, some people may have a higher intrinsic thermal conductivity, or a higher resting water level. The device or method may accurately determine a baseline tissue parameter, with therapeutic monitoring and corresponding therapy tailored to the individual's baseline tissue parameter.

A "tactile feedback element" refers to a device component that produces a stimulus physically detectable by a user, such as a tactile feedback element selected from the group consisting of vibrators, light sources, or electrodes.

"Environmental parameters" refer to characteristics of the environment of a device, such as a device in conforming contact with tissue. Environmental parameters may include physical properties, electronic properties, optical properties, and/or chemical composition, e.g., intensity of electromagnetic radiation directed to the device, wavelength of electromagnetic radiation directed to the device, environment to which the device is exposed. It may refer to the chemical composition of the element, the chemical composition of the environmental element to which the device is exposed, the amount of environmental contaminant to which the device is exposed, and/or the chemical composition of the environmental contaminant to which the device is exposed. A device of some embodiments can generate a response corresponding to one or more environmental parameters. For example, in low humidity conditions, applying a hydrating material, in high UV conditions, applying a UV blocking material.

"Power harvesting" refers to the process by which energy can be derived from an external source, thereby avoiding the need for relatively large, bulky and expensive primary or secondary battery systems. Of course, the devices provided herein may be compatible with batteries and/or supercapacitors, depending on the application of interest. For example, relatively heavy or bulky systems can be incorporated into clothing, shoes, hats, gloves, scarves, face masks, and the like in a manner that is non-obtrusive or minimally obtrusive to the user. .

Embodiments of the invention are illustrated in detail below with reference to the accompanying drawings. The following description is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses. The broad teachings of the present invention may be implemented in various forms. Thus, although the invention includes specific examples, the true scope of the invention should be so limited as other modifications will become apparent after inspection of the drawings, specification, and the following claims. not. For clarity, the same reference numbers are used in the drawings to identify similar elements. It will be appreciated that one or more steps in the method may be performed in a different order (or concurrently) without altering the principles of the invention.

Accurate quantitative measurements of skin hydration status provide important insights into skin health and additional relevance to essential processes of skin structure and function, as well as other features of thermoregulation and basic physiology. be able to. Existing tools for determining skin moisture content utilize surrogate electrical assessments performed with bulky, stiff, and expensive equipment that are difficult to use in a reproducible manner. A recent alternative is to use soft wireless devices that adhere gently and noninvasively to the surface of the skin, but have a limited operating range (~1 cm) and high sensitivity to subtle environmental variations. It makes use of measurements.

Accordingly, the present invention overcomes these shortcomings by using, among other things, a graphical user interface to a standard smartphone to develop a long-range (~10m) Bluetooth Low Energy (BLE) system-on-chip (SoC). We disclose a series of ideas and techniques that enable fast, robust, long-range automated measurements of heat transport properties via compact multi-sensor modules controlled by . The soft contact on the skin surface reduces the burden on the user to almost zero, has a high reproducibility level, and is immune to ambient temperature changes. yields a record that can be quantitatively connected to both moisture levels. A systematic study of polymers of layered composition similar to human skin, porcine skin with known moisture levels, and human subjects, with benchmarking against clinical devices, demonstrated the measurement approach and associated sensor hardware. Checking validity. These results support the ability in characterizing skin barrier function, assessing the severity of skin disease, and evaluating efficacy of cosmetic and pharmaceutical products for clinic or home use.

The following exemplary embodiments further illustrate the invention and should not be construed as limiting the scope of the invention in any way.

As shown in FIGS. 1A-1E, a moisture content sensor was operatively disposed over a target area of interest of the skin of a living subject to detect data associated with thermal properties of the skin. A sensing module, or thermal actuator/sensor (TAS) module, and a wireless platform coupled to the sensing module for wireless data transmission between the sensing module and an external device.

The TAS module combines a thermal actuator operably disposed on the target area of interest of the skin to heat the target area of interest and its transient temperature change (ΔT) to determine the thermal properties of the skin simultaneously. and a sensing circuit for detecting. Thermal actuators and sensing circuits are interconnected by serpentine traces (Fig. 1E), flexible structures that facilitate soft intimate contact to the skin with robust mechanical and thermal coupling (Fig. 1A, inset). to form

In some embodiments, the thermal actuator includes at least one resistor.

In some embodiments, the thermal actuator comprises two or more of surface mount thin film resistors, thick film resistors, through hole resistors, and ultra thin film metal resistors coupled in series with each other. . As shown in FIG. 1B, the thermal actuator comprises two resistors _RH connected in series.

In some embodiments, the sensing circuit comprises a temperature sensor including one or more of a negative temperature coefficient thermistor, a positive temperature coefficient thermistor, a resistance temperature detector (RTD), and a thermocouple.

In some embodiments, the sensing circuit comprises a first pair of negative temperature coefficient thermistors NTC1 (NTC ₊ , NTC ₊ ) arranged in a first Wheatstone bridge circuit, as shown in FIG. 1B. Prepare. Data readout from only one sensing unit (the first pair of negative temperature coefficient thermistors, NCT1) can cause data fluctuations due to changes in the temperature of the test material over time, which can be compensated for by using a second sensing unit. In some embodiments, the sensing circuit also includes a second pair of NTCs (NTC2, FIGS. 1E and 2A) arranged in a second Wheatstone bridge circuit that serves to compensate for changes in ambient temperature. can have

In one embodiment shown in FIG. 2B (left), the first pair of NTCs (NTC1) is disposed on a different layer than the thermal actuators (heating devices). In this case the two NTCs 1 are placed directly above the heating device. In another embodiment shown in FIG. 2B (right), two NTCs 1 are arranged on the same layer as the heating device. In this case each NTC 1 has a first distance from the heating device. In some embodiments, a second pair of NTCs (NTC2) is disposed on the same layer as the first pair of NTCs, each NTC2 being spatially separated from NTC1 (FIG. 1E), It has a second distance from the heating device (Fig. 2A, inset). In some embodiments, the first and second distances are determined by design requirements for depth sensitivity into the skin and range from tens of microns to several millimeters.

The compact two-sided sensor design (Fig. 2B, left) approximately triples the sensitivity to skin hydration level (Figs. 10C-10D) compared to the corresponding single-sided layout (Fig. 2B, right).

In some embodiments, the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols.

In one embodiment shown in FIG. 1B, the wireless platform comprises a Bluetooth low energy system on a chip (BLE SoC). In some embodiments, the BLE SoC amplifies the difference between a general purpose input/output (GPIO) electrically coupled to the thermal actuator to provide a periodic current to activate the thermal actuator and a bridge voltage. a differential amplifier (AMP) electrically coupled to the sensing circuit to perform the sensing; and an analog-to-digital converter (ADC) electrically coupled to the AMP to sample/digitize the output voltage of the AMP. configured to wirelessly transmit the output signal of the ADC to an external device for processing to determine skin hydration status, receive data from the external device and enable a GPIO pin to provide periodic current to the thermal actuator; and a BLE radio.

Among other things, the BLE-based device according to the present invention is characterized by, but not limited to, small size, automatic/remote wireless updates, no external device (e.g. phone) need to be held on the sensor, and different external It offers many advantages, including superior performance across devices.

In some embodiments, a digital on/off switch controlled through a custom software application, including a user interface (UI) on the external device, enables BLE connection and GPIO pin activation to provide periodic current flow. adapted to supply a thermal actuator;

In one exemplary embodiment, the periodic current has 6.8 mA for 10 seconds and 0 mA for 50 seconds in a 1 minute cycle. This current can generate a thermal power Q=20.4 mW at the top surface of the l-actuator, thereby supplying heat to the underlying skin via thermal diffusion. Heat transfer from the actuator to the NTC depends on the thermal properties of the skin and thus serves as the basis for measuring skin hydration. The Wheatstone bridge circuit transforms the resistance of the NTC into corresponding voltages (V ₊ , V ₋ ) that vary with temperature changes, with opposite polarities (ΔV ₊ =−ΔV ₋ ).

In some embodiments, a custom software application within the external device converts voltages to corresponding temperature values based on calibration factors. Theoretical models can then be used to convert these data into heat transport properties of the skin, which in turn can be used to determine health-related parameters such as hydration status using appropriate models.

In some embodiments, the BLE SoC may also include a microcontroller (μC) configured to enable the GPIO pin and supply periodic current to the thermal actuator. The μC may also be configured to process detected data locally and then transmit the processed data to an external device.

In some embodiments, the moisture content sensor further comprises a flexible substrate in the form of a flexible printed circuit board (fPCB) having circuit traces interconnecting the skin-side thermal actuator, the air-side NTC, and the BLE SoC. Prepare. In some embodiments, the flexible substrate is formed from flexible materials including polyimide (PI) and/or polyethylene terephthalate (PET). In one example, the flexible substrate is a flexible copper clad polyimide (Cu/PI/Cu) sheet.

In some embodiments, the moisture content sensor further comprises a power module for powering the sensing circuitry and the wireless platform. In some embodiments, the power module comprises a battery (Fig. 1C). In some embodiments, the battery is a rechargeable battery that is operably rechargeable with wireless charging.

In some embodiments, the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery.

In some embodiments, the power module further comprises fault protection elements including short circuit protection components or circuits to avoid battery malfunction. For example, as shown in FIG. 1C, the battery is encapsulated within an encapsulation layer.

In some embodiments, the moisture content sensor further comprises an encapsulating enclosure surrounding the thermal actuator, wireless platform, battery, and fPCB, as shown in FIGS. 1C and 1D.

In some embodiments, the encapsulation enclosure is a top layer for thermally, chemically, and mechanically isolating the moisture sensor from the environment, and a skin side of the fPCB directly between the thermal actuator and the skin. and a bottom layer for providing an interface.

In some embodiments, the top layer is a shell-like top encapsulation layer that contains small voids to thermally, mechanically, and chemically insulate the critical sensing components.

In some embodiments, the top layer is made from flexible materials including silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon®, and various other flexible polymers. It is formed.

In some embodiments, the bottom layer comprises a flexible adhesive for attaching the moisture sensor to the skin.

In some embodiments, the bottom layer further comprises a microwoven fiberglass/stiffener embedded in the flexible adhesive layer to increase the mechanical robustness of the moisture sensor. In some embodiments, the stiffeners are flexible and have varying mesh densities and thicknesses to impart tear resistance to the bottom layer.

In some embodiments, the flexible adhesive layer is formed from silicone or silicone gel, or a double-sided skin-safe adhesive, wherein the ratio of silicone and silicone gel simultaneously optimizes the adhesive's mechanical integrity and adhesion. adjusted to fit. In one exemplary embodiment shown in FIG. 2B, the adhesive layer has a thickness of about 180 μm.

In some embodiments, the mesh fiber/silicone bottom layer encapsulation allows for ultra-thin bottom layers from 25 microns to 700 microns.

In some embodiments, the external device is a smartphone, tablet, computer, or having data reading/processing capabilities, e.g., comprising a central processing unit (CPU), or a microcontroller unit (MCU), or an external controller; Any electronic device.

In some embodiments, the thermal properties of the skin include the thermal conductivity and thermal diffusivity of the skin which are related to the moisture content of the skin, the moisture content being a function of skin depth.

In some embodiments, moisture content is determined from the measured temperature change ΔT versus time t.

In some embodiments, moisture content and skin surface temperature are used to determine the normal or diseased state of skin.

In some embodiments, moisture content and skin surface temperature serve as quantitative metrics for the efficacy of treating skin conditions or other health and wellness products, including skin moisturizers, lotions, and/or creams.

In some embodiments, the moisture sensor can be used to monitor skin conditions in clinical settings and/or home settings.

In some embodiments, the hydration sensor is used to administer treatment, monitor efficacy, modify treatment protocols if necessary, and/or provide quantitative personalized measurements of specific lesion sites. It can be used to potentially predict flares.

In some embodiments, the water content sensor can be used to monitor internal organ water content for various diseases where conventional monitoring techniques cannot provide a continuous assessment of organ health.

In some embodiments, the water content sensor can be used to monitor organs during organ transportation for organ transplantation applications.

In some embodiments, moisture content sensors can be used to measure thermal conductivity, thermal diffusivity, heat capacity, and other thermal properties of any material as a function of depth.

In some embodiments, the moisture content sensor can be applied to any material surface, including hydrogels, plants (irrigation and agricultural applications), food storage (dry foods, grains, fruits, meats), and/or concrete (industrial applications). It can be used in applications to measure the moisture content of water as a function of depth.

In some embodiments, moisture sensors can be used to monitor the composition of food/beverages, pharmaceuticals/industrial chemicals.

In some embodiments, the moisture sensor is reusable and removable without skin irritation or damage to the moisture sensor.

In some embodiments, the moisture sensor is compatible with alcohol-based cleaning wipes that allow reuse between different users without damage to the moisture sensor or loss of efficacy of the moisture sensor adhesive. have a nature.

In some embodiments, the moisture content sensor is sterilizable using alcohol, autoclave steam sterilization, and vapor phase sterilization.

In another aspect, the invention relates to a method of fabricating a moisture content sensor. In some embodiments, the method comprises forming a flexible printed circuit board (fPCB) interconnecting the electronics of the moisture sensor; forming an encapsulating enclosure surrounding the sensing module, the wireless platform, and the fPCB; including. The encapsulating enclosure comprises a top layer and a bottom layer.

In some embodiments, the fPCB is formed from a flexible material including polyimide (PI), polyethylene terephthalate (PET), or any one of these in combination with a rigid PCB material including FR-4. be.

In some embodiments, the bottom layer comprises a first flexible layer, a second flexible layer, and glass embedded between the first flexible layer and the second flexible layer. It contains a fabric layer structure of fibers/reinforcement.

In some embodiments, each of the first flexible layer and the second flexible layer is formed from silicone or silicone gel, or a double-sided skin-safe adhesive, wherein the ratio of silicone and silicone gel is are tuned to simultaneously optimize the mechanical integrity and cohesion of the

In some embodiments, the stiffeners are flexible and have varying mesh densities and thicknesses to impart tear resistance to the bottom layer.

In some embodiments, the bottom layer adheres to the f-PCB through the use of silicone adhesives, epoxies, adhesives, or commercial adhesives.

In some embodiments, the top shell layer is formed from silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon®, and various other flexible polymers.

In some embodiments, the electronics are coupled to the sensing module for detecting data associated with thermal properties of the skin and wireless data transmission between the sensing module and an external device. and a wireless platform.

In some embodiments, the sensing module includes a thermal actuator for heating a target area of interest on the skin and a sensing circuit for simultaneously detecting transient temperature changes (ΔT) thereof to determine the thermal properties of the skin. and

In some embodiments, the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols.

In some embodiments, the wireless platform comprises a BLE SoC.

In yet another aspect, the present invention relates to methods of monitoring and/or diagnosing skin conditions. In some embodiments, the method includes attaching a moisture content sensor onto the target area of interest of the skin, the moisture content sensor in bi-directional data communication with the thermal actuator, the sensing circuit, and an external device. a wireless platform for attaching a moisture content sensor; heating a target area of interest of the skin with a thermal actuator; Wirelessly transmitting data by a wireless platform to an external device to determine its transient temperature change (Δt) and deriving from the temperature change (ΔT) the moisture content of a target area of interest of the skin. and determining the condition of the skin at the target area of interest based on the obtained moisture content.

In some embodiments, the water content comprises an epidermal water content Φ _E and a dermal water content Φ _D .

In some embodiments, obtaining the moisture content comprises separately determining Φ _E and Φ _D from the temperature change ΔT.

In some embodiments, the wireless platform transmits data through wireless communication protocols including Near Field Communication (NFC), Wifi/Internet, Bluetooth/Bluetooth low energy (BLE), or GSM/cellular communication.

In some embodiments, said heating of the target area of interest of the skin is formed by supplying a periodic electrical current to a thermal actuator.

In some embodiments, enabling of the periodic current is controlled by a digital on/off switch through a custom application on the external device.

In some embodiments, said determining the condition of the skin in the target area of interest comprises comparing the obtained moisture content to a standard moisture content in the target area of interest to determine whether the skin is in a normal or diseased condition. including determining

In some embodiments, said determining the condition of the skin in the target area of interest comprises diagnosing a skin disease in the target area of interest based on the obtained moisture content.

In some embodiments, said determining the condition of the skin in the target area of interest comprises assessing the efficacy of a treatment for a skin condition.

In some embodiments, said obtaining the moisture content of the target area of interest of the skin and said determining the condition of the skin are performed in an external device.

In some embodiments, the method further comprises displaying on the external device the skin condition of the target area of interest.

In some embodiments, the method further comprises forwarding or alerting a specialist, caregiver, and/or service provider of the skin condition in the target area of interest. For example, important tissue parameters can be obtained even for users outside of a controlled medical setting. These parameters can be communicated remotely for real-time assessment or later by the user or a third party such as a medical caregiver, friend or family member. Devices and methods are more proactive, from warnings provided to the user to automated responses such as applying hydration compounds, sunscreen compounds, or any other response depending on the application of interest. intervention.

In some embodiments, the method includes administering treatment, monitoring efficacy, modifying the treatment protocol if necessary, and/or making quantitative personalized measurements of specific lesion sites. further including one or more of the steps of potentially predicting flares based on.

In some embodiments, measurement conduction is optimized to obtain accurate and reproducible results. Thus, the method may be performed under one or more of the optimized measurement conditions, which conditions are: (1) occlusion of the natural process of water vapor release from the skin due to the presence of the moisture content sensor; (2) very light or zero compression is used during the measurement to minimize perturbation to the skin; and (3) the adhesive is present only over the area of the moisture sensor device adjacent to the sensor itself and is patterned to avoid peeling of the skin at the measurement site during peeling and improve reproducibility. (4) the temperature of the moisture sensor should be similar to that of the skin; and (5) the skin itself should be able to acclimatize to the environment prior to the measurement.

Wireless electronics for monitoring skin hydration in a quantitative manner have broad relevance to understanding dermatological health and skin architecture both in the clinical setting and in the home setting. According to the present invention, a compact long-range automated system that gently adheres to the skin to obtain quantitative recordings of skin moisture content for both the epidermis and dermis, with a high level of reproducibility and insensitivity to surroundings. , characterizes the skin barrier, assesses the severity of skin diseases, and supports functions in evaluating the efficacy of cosmetics and drugs. Tabletop and pilot studies in dermatologic patients highlight key features of these devices and their potential for broad utility in clinical research and home settings to guide the management of skin disorders. ing. These and other aspects of the invention are further described in the following sections. Without intending to limit the scope of the invention, further exemplary implementations of the invention according to embodiments of the invention are presented below. Note that although titles or subtitles may be used in the examples for the convenience of the reader, this in no way limits the scope of the invention. Further, although certain theories are proposed and disclosed herein, whether they are true or false, the present invention may be practiced in accordance with the present invention without regard to any particular theory or mode of operation. Insofar as it should in no way limit the scope of the invention.

Wireless Soft Electronics for Rapid Multi-Sensor Measurement of Moisture Levels in Healthy and Diseased Skin In this illustrative example, routine and reliable moisture level measurements are performed in healthy and diseased skin. A wireless system for doing so is disclosed. The computational methods applied to the resulting data define hydration levels using a bilayer model of the skin, with a level of clinical grade accuracy. With respect to other technologies, significant advances in wireless systems include, but are not limited to: 1) long-range wireless capability and high sampling rates through the mobile phone's Bluetooth interface; 3) multiple redundant measurement modalities with minimal sensitivity to environmental, physiological, and user-related parasitic factors, and 4) determination of both epidermal and dermal hydration levels. and includes full-waveform data analysis techniques with additional sensitivity to SC. Numerical modeling results and bench-top characterization tests under various practical conditions clarify the implications of important physical effects and guide the selection of optimized designs and modes of operation. Validation studies involve porcine skin with known moisture levels and human subjects with benchmarks for clinical devices. Again, and in other practical scenarios, the sensor's soft-mechanical properties and compliant structure apply force to avoid angle- or pressure-related sources of variation that degrade the accuracy and repeatability of conventional devices. It allows a tight bond to the skin without holding it in place. These same features in form factor and performance allow routine measurements to be made on virtually any placement on the body and on subjects of any age.

This collective set of attributes forms the basis of a device that allows rapid and accurate assessment of skin hydration and skin barrier function with almost zero user effort. A simple interface leveraging smart phone technology suggests the potential for frequent use in the home setting as early management of skin disease prior to flare-ups for conditions such as AD or XC. Pilot-scale clinical trials have demonstrated these and other abilities to track improvements in skin hydration associated with application of topical moisturizers to patients with various inflammatory skin conditions. Overall, this system has the potential to improve the quality of care for patients by providing an objective and accurate measure of skin barrier function.

Materials and Methods Electronics Fabrication: Prototype devices were fabricated by laser ablation (Protolaser U4, LPKF) on flexible copper-clad polyimide substrates (AP8535R, Pyralux ), resulting in a flexible printed circuit board ( fPCB) was obtained. The results of the prototype fPCB research were used as the basis for the design provided to an ISO-9001 compliant vendor (PCBWay Inc.) for the final design. With solder wire (MM01019, Multicore) and solder paste (SMDLTLFP10T5, Chip Quik), the BLE SoC was bonded to the fPCB by heating at 400°C and various other surface mount components by heating at 190°C.

Software development environment: BLE mesh kit board (nRF52 DK, Nordic Semiconductor) facilitated software development of BLE SoC. A PC connected to the nRF52 DK with a USB cable for power enabled programming of the onboard BLE SoC. A source code editor (Visual Studio Code, Microsoft) supported authoring, modifying, compiling, deploying, and debugging software for BLE SoCs. A power profiler kit board (NRF6707, Nordic Semiconductor) interfaced with the nRF52 DK provided real-time measurement of the current consumption of the embedded application. Android's official integrated development environment (IDE) (Android Studio, Google) provided tools for developing and building custom Android applications (user interfaces) on smartphones.

Encapsulation enclosure design: silicone (Ecoflex 00-30, Smooth-On)/silicone gel (Ecoflex gel, Smooth-On), fiberglass cloth (optional, not explicitly shown in FIG. 1C), and different formulations of silicone (Silbione RTV 4420 A 3-layer structure (80 μm/20 μm/80-μm thickness) of (80 μm/20 μm/80-μm thickness) of Elkem Silicones) served as the bottom encapsulation layer of the device. The bottom adhesive silicone/silicone gel layer provides a direct interface between the heating device on the bottom side of the fPCB and the skin, which is a three-step process, 1) applying a silicone/silicone gel layer onto a glass slide at 2500 rpm for 30 seconds. 2) Gently place a glass fiber cloth over the silicone/silicone gel layer, 3) Spin the next silicone layer at 1500 rpm for 30 seconds. Using a process that coats, places the device on the uncured silicone layer with the heater side facing down, and cures on a hotplate at 85°C for 10 minutes to achieve adhesion between the fPCB and the silicone layer. was formed. The silicone inside a custom aluminum mold (Silbione RTV 4420, Elkem Silicones) was cured on a hotplate at 85° C. for 20 minutes to form the top shell of the device (˜4 mm height). The entire system was sealed by curing the top shell and bottom layers together on a hot plate at 85° C. for 20 minutes using a small amount of silicone (Silbione RTV 4420, Elkem Silicones) as an adhesive. A die cutter was used to cut the structure to complete the fabrication process. Adequate cleaning (contamination/debris removal) using alcohol wipes (Sterile Alcohol Prep Pads, Dynarex) restores adhesion due to van der Waals forces. Additional adhesives (3M 1524, 3M Tegaderm, etc.) may be used to improve adhesion to the skin if desired.

Adhesive Peeling Measurements: Repeated application and removal of adhesive discs (D-Squame, CuDerm, 14 mm diameter, ˜100 μm thickness) on the same area of skin gradually peeled off the SC. Each disc was replaced after 5 cycles. Measurements after 0, 10, 20, and 35 cycles involved two commercial devices (MoistureMeterSC and Moistur-eMeterD, Delfin Technologies) and a BLE device.

Pig Skin Water Loss Measurements: Pig skin pieces (˜25 mm thick, 200×100 mm) were thawed in DPBS solution (Gibco Dulbecco's Phosphate Buffered Saline, 14190-136, Life Technologies) for 12 hours at room temperature. A commercial dehydrator (Sedona Combo Rawfood Dehydrator SD-P9150, Tribest) controlled the water content of the pig skin for 10 minutes at 33° C. for each measurement. The measured weight of the pig skin determined with a balance (Ohaus Ax622 Adventurer Precision Balance, Ohaus) allowed the calculation of water loss.

Human Subject Evaluation: The objective was to validate the difference in thermal conductivity between dry/hydrated skin and tissue affected and unaffected by skin diseases such as atopic dermatitis. It was to confirm that it is appropriate as a detection means. The sensor presents low to minimal risk to the patient as no electrical components touch the skin. More than 10 healthy control adults/children and 3 patients with mild, moderate or severe atopic dermatitis were presented to a dermatologist and had the sensors applied to the skin in different placements on the body. Measured by A baseline reference for determining skin TEWL was also obtained using a commercially available device based on the capacitance measurement of the dielectric medium of the skin.

Body placements selected for the study included forehead, left/right forearm, and left/right lower extremity. Prior to BLE measurements, conventional devices with different probing depths provided baseline reference values for skin hydration on three occasions at each body placement. A 5-minute continuous measurement using the BLE device was then performed, requiring no waiting time for the sensor to reach thermal equilibrium with the skin. During the BLE measurements, subjects were allowed to move freely with no restrictions on their activities. The tests were performed indoors under an air-conditioned environment.

Moisturizer study on two patients with AD. The experimental protocol consisted of four steps: 1) performing triplicate measurements on diseased and non-diseased skin; 2) applying a moisturizer (Extremely Dry Skin Rescue Lotion, Vaseline) and waiting 15 minutes; and 4) repeating the measurement three times at each location.

Moisturizer study on 3 healthy adults. A thin, standardized layer (˜1 to 2 g/cm ² ) of a commercial fragrance-free moisturizer was applied to each placement. Repeated measurements were performed 1 and 15 minutes after moisturizer application.

Recruited patients (Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL) and healthy/normal subjects (Northwestern University, Evanston, IL) were voluntary and provided full informed consent. bottom. This study was approved by the Institutional Review Board (IRB) of Northwestern University (IRB Study STU00209010). Sterilization of BLE and commercial devices was performed with disposable alcohol wipes (Sterile Alcohol Prep Pads, Dynarex).

Results and Discussion System Configuration: The device (Fig. 1A, shown here without batteries) is a compact wireless platform designed for non-invasive measurement of skin temperature and heat transport properties. The width, length, height, and weight of this example, excluding the battery, are 14.6 mm, 25.6 mm, 1.2 mm, and 193.0 mg, respectively. The system comprises a thermal actuator and multi-sensor (TAS) module interconnected by serpentine traces to form a flexible structure that facilitates soft intimate contact with the skin with robust mechanical and thermal coupling (Differential drawing). FIG. 1B is a schematic diagram highlighting a Bluetooth Low Energy (BLE) system-on-chip (SoC) for wireless data communication to a control and user interface (UI) (typically on a mobile device such as a smartphone) and It is a block diagram. The TAS module is equipped with a thermal actuator (Joule heating with 221Ω x 2 resistors, RH x 2) and a Wheatstone bridge circuit with a pair of negative temperature coefficient thermistors (NTC ₊ , NTC _{- )} on each bridge for primary measurement purposes. ) and a known resistor (R). Another pair of NTC and bridge circuits serve to compensate for changes in ambient temperature. A digital on/off switch, controlled through the UI, enables BLE connectivity and general purpose input/output (GPIO) pins to drive periodic current to the thermal actuator (6.8 mA for 10 seconds, 0 mA for 50 seconds in a 1 minute cycle). ). This current generates thermal power (Q=20.4 mW) at the top surface of the structure, thereby supplying heat to the skin below via thermal diffusion. Heat transfer from the actuator to the NTC depends on the thermal properties of the skin and thus serves as the basis for measuring skin hydration. The Wheatstone bridge circuit transforms the resistance of the NTC into corresponding voltages (V ₊ , V ₋ ) that vary with temperature changes, with opposite polarities (ΔV ₊ =−ΔV ₋ ). This configuration supports enhanced sensitivity compared to schemes used in conventional implementations of TPS methods. A differential amplifier (AMP) in a BLE SoC further amplifies the voltage difference and rejects common-mode noise to increase the signal-to-noise ratio (SNR). A subsequent analog-to-digital converter (ADC) samples the voltage and transmits it to the UI via the BLE wireless communication protocol. A software application converts the voltages to corresponding temperature values based on the calibration coefficients. Theoretical models can then be used to convert these data into heat transport properties of the skin, which in turn can be used to determine health-related parameters such as hydration status using appropriate models.

In the schematic exploded view illustrated in FIG. 1C, the constituent layers and components of the system: a shell structure made of biocompatible silicone material for packaging and thermal insulation, a lithium polymer battery (12 mAh), and a thermal actuator. (skin side), NTC (air side), and flexible copper-clad polyimide substrates (AP8535R, Pyr- Alux). The shell (inset) forms an air pocket around the TAS module to optimize heat flow to the skin-facing side of the device and insulate this area from the surroundings. The small dimensions of the TAS module (0.9 mm width and 2.6 mm length, respectively) facilitate proper alignment and compliance with the skin, which is necessary for accurate measurements. A photograph of the encapsulation device attached to the ball of the foot is shown in FIG. 1D. The system performs temperature measurements at a sampling rate of 200 Hz, transmits averages to the UI every 0.1 seconds (10 Hz), and measures moisture over 1 minute per day (actuator off for 50 seconds, on for 10 seconds). A 12 mAh battery (FIG. 8) supports an expected lifetime of approximately 10 days, assuming to measure refueling.

In this exemplary embodiment, the system is not shown to have wireless charging capability, although such functionality could easily be included. For example, in some embodiments, the system may include a rechargeable battery that may be wirelessly charged through a wireless battery charging module.

Application to heat transport physics and measurement of skin moisture: A standard module for TPS measurements measures the time-dependent difference (ΔT) in temperature when the thermal actuator is off and on (T _off and T _on , respectively). It captures. The simplest analytical approach uses the value ΔT=T _on −T _off at a single point in time, often in a quasi-steady state region where the rate of temperature change over time is relatively small. This parameter then determines the effective heat transport properties using appropriate models and calibration procedures. Full time-dependent measurements and analysis starting immediately after the actuator is turned on and continuing into the quasi-steady-state region can yield substantial information on heat transport, as will be explained later. In all cases, changes in skin temperature or fluctuating environmental conditions (airflow, ambient temperature fluctuations) that may occur between or during T _off and T _on measurements within a given measurement cycle are value, thereby reducing the accuracy and accuracy of the system. A key feature of the TAS module in some embodiments is that it contains two pairs of NTCs (NTC ₁ and NTC ₂ ), as shown in FIG. 2A. The primary measurement is the difference in the values of ΔT measured from NTC ₁ and NTC ₂ (ΔT ₁ and ΔT ₂ respectively, FIG. 9), i.e. ΔT ₁₂ =ΔT ₁ −ΔT ₂ =(T _on,1 −T _off,1 )−(T _on,2 −T _off,2 ). Here, NTC ₂ captures the temperature at a location remote from the thermal actuator, eliminating the effects of uncontrolled temperature fluctuations, as demonstrated under various conditions in a later section.

An exploded view of the TAS module (Fig. 2A) shows the constituent layers and components: adhesive (180 μm thick), thermal actuator (two resistors in series, R _H ×2), NTC ₁ (NTC ₁₊ , NTC ₁₋ ), NTC ₂ (NTC ₂₊ , NTC ₂₋ ), emphasizing air-shelled silicone capsules. The inset is a top view of the assembled module. NTC ₁ and NTC ₂ are located directly above and 1.15 mm from the center of the thermal actuator, respectively. The width (w) and length (l) of _RH and NTC are 0.3 mm and 0.6 mm, respectively. The compact two-sided sensor design (Fig. 2B, left) approximately triples the sensitivity to skin hydration level (Figs. 10A-10D) compared to the corresponding single-sided layout (Fig. 2B, right). FIG. 2C shows skin with a volume composition of 50% of water (k _skin =0.35 W) at short (t=1.0 s, top) and long (t=10 s, bottom) times after the start of heating. ^finite _element ^analysis ( ^FEA below ^macro Figure 3 shows the temperature distribution obtained from the scale modelling). At a typical epidermis thickness (h=100 μm), for short times (eg t=1.0 s) heat transport occurs substantially only through the epidermis. For long times (eg t=10 seconds) heat passes through the epidermis and is significantly transferred into the dermis. Modeling the skin as a bilayer of epidermis (E) and dermis (D), one can extract the approximate averaged moisture level of each layer separately from the ΔT ₁₂ measurements. At the macroscale, thermophysical properties (thermal conductivity k, diffusivity α) of the epidermis (E) and dermis (D), namely k _E , α _E , k _D , and α _D to ΔT ₁₂ (time t=0 to 10 seconds) were derived and quantitative correlations were established by FEA modeling. A microscale model of hydrated skin (described below in Micromechanical Models for Thermal Properties of Hydrated Skin) defines the relationship between k and α, and the heat transport problem is determined It can be solved with only two parameters, namely the epidermis and dermis hydration levels Φ _E and Φ _D , respectively. At short times (eg, t=1.0 s), ΔT ₁₂ is more sensitive to Φ _E than Φ _D , as shown in FIG. 2D. Conversely, at long times (eg, t=10 seconds), ΔT ₁₂ is more sensitive to _ΦD than _ΦE , as shown in FIG. 2E. Analysis in these two time domains, or over the entire measurement period, can yield both Φ _D and Φ _E.

Test structures constructed with formulations of poly(dimethylsiloxane) (PDMS) with heat transport properties similar to dehydrated (S184) and hydrated (S170) skin illustrate significant effects. Figures 2F-2G show the long plots, respectively, for samples containing a thick layer of S184 (red) and S170 (blue), and a thin layer of S184 (70 µm, black, 100 µm, green, 200 µm, yellow) on top of S170. Wireless measurements of ΔT ₁₂ are shown for short time (FIG. 2F, t=1 to 10 sec) and short time (FIG. 2G, t=0.5 to 1 sec). For long times (eg t=10 s) heat passes through the top layer (˜100 μm thick) and substantially penetrates the bottom substrate. This process yields similar values of ΔT ₁₂ for the S184/S170 and S170 structures. On the other hand, for short times (eg, t=0.5 to ˜1 s, FIG. 2G) the heat generated from the device remains confined to the top layer (˜100 μm thick) and the ΔT from the S184/S170 structure ₁₂ is similar to that of S184. Figures 11A-11E highlight FEA results and experimental data for the samples described above. The FEA results are in good agreement with experimental values (Exp.) with SD less than 3.5%, as shown in FIG. 2H. These effects support a mode of operation in which analysis of data over different time intervals allows separate measurements of epidermal and dermal hydration. FIG. 2I presents the results for ΔT ₁₂ obtained from the forearm over the entire measurement period (t=0 to 10 seconds). The extracted values of Φ _D and Φ _E are consistent with expected water content at different skin depths. Similar considerations applied to even shorter time intervals allow separate measurements of SC and epidermis. Unless otherwise stated, the studies described below use a single measurement at 10 seconds (ie, ΔT ₁₂ at 10 seconds) with a single-layer skin model for simplicity. The reported value of water content is referred to as Φ (Φ=0 for dehydrated skin, Φ=1 for water) and corresponds to the weighted average of _ΦD and _ΦE . The measurement properties also depend on the layout and size of the thermal actuator and sensor components, as detailed in the simplified analytical model below.

Macro-scale modeling by finite element method (FEA): At the macro-scale, FEA calculates ΔT ₁₂ and epidermal and dermal thermal conductivity and thermal diffusivity (k _E , α _E , k _D , and α _D ). A schematic of the FEA model is given in FIG. 10A. A fine mesh (~1 million elements) with a mesh size much smaller than the device's finest feature size (18 μm, copper thickness) and a refined mesh that limits the maximum temperature change to less than 0.5° C. at each increment The time increment ensures convergence and accuracy of the simulation. Literature values for the material parameters are k _copper =377 W/(m−K), α _copper =109 mm ² /s, kPI=0.55 W/(m−K), αPI=0.32 mm2/s, _{k Ecoflex} =0. .21 W/(mK), α _Ecoflex =0.11 mm ² /s. The thermal conductivity of polyimide (PI) is higher than that of materials with known thermal properties (S170, k _S170 =0.40 W·m ⁻¹ ·K ⁻¹ , α _S170 =0.14 mm ² ·s ⁻¹ ). It is determined as kPI=0.55 W·m ⁻¹ ·K ⁻¹ from the measurement results. For validation, different materials (S184) with known thermal properties (k _S184 =0.20 W·m ⁻¹ ·K ⁻¹ , α _S184 =0.11 mm ² ·s ⁻¹ ) and thick Bilayer materials of thin S184 (70-200 μm thick) on S170 have been tested and the FEA results are in good agreement with experiments without additional fitting (FIGS. 11A-11E).

Micromechanical Model of Thermal Properties of Hydrating Skin: The micromechanical model establishes the relationship between the thermal properties of hydrating skin and moisture level 0 (volumetric water content). The hydrated skin consisted of dry skin (thermal conductivity k _dry =0.2 W·m ⁻¹ ·K ⁻¹ , thermal diffusivity α _dry =0.15 mm ² ·s ⁻¹ ) and water (kW=0.6 W·K −1 ). m ⁻¹ ·K ⁻¹ , αW=0.14 mm ² ·s ⁻¹ ), which modulates the thermal conductivity k _skin and thermal diffusivity α _skin , respectively, of the hydrated skin by the formula

give as

In the bilayer model of epidermal and dermal layers for skin, the above micromechanical model is applied to each layer, substituting "skin" with "E" and "D" for epidermis and dermis, respectively.

Simplified analytical model: A simplified model for the relationship between the NTC ₁ -NTC ₂ spacing and their temperature difference is useful. The data in FIGS. 12A-12B show ΔT (Q=20.4 mW, t=10 sec) as a function of cb with different distances (d) between NTC ₁ and NTC ₂ and Corresponding FEA results for ΔT (t=10 s, d=1.2 mm, Φ=0.3). As d and Q increase and Φ decreases, the value of ΔT ₁₂ increases. The effect of actuator size (RH width and length) on ΔT ₁₂ is shown in FIGS. 13A-13B. As shown in FIG. 14A, a disk-shaped heating device (radius R and heating power Q) and two very small sensors are semi-infinite with the properties of skin (thermal conductivity k _skin and thermal diffusivity α _skin ). resting on a homogeneous substrate. The thickness of the heating device and sensor is negligible. The position of NTC ₁ is directly above the heating device (r=0 in the polar coordinate system) and NTC ₂ is at distance d from NTC ₁ . The temperature changes of NTC ₁ and NTC ₂ are, respectively,

where J ₀ (x) and J ₁ (x) are Bessel functions of the first kind of 0th and 1st order, respectively, and erfc(x) is the complementary error function. Therefore, the temperature difference between the two sensors is in the dimensionless form

can be expressed as

The function f is plotted in FIG. 14B. Measurement sensitivity increases with tα _skin /R ² or d/R.

Experimental study: The use of ΔT ₁₂ , as measured by the two pairs of NTCs described above (NTC ₁ and NTC ₂ ), minimizes sensitivity to changes in skin temperature or fluctuations in environmental conditions (airflow, ambient temperature, etc.). to Demonstration of the effect of S184 in an oven or refrigerator or on a hot plate as a basis for varying ambient temperature (T _A , FIGS. 3A-3B) and substrate temperature (T _S , FIGS. 3C-3D), respectively. of samples. A pneumatic valve controls the flow of air over the device at velocities from 0 to 13.6 m/s (FIGS. 3C and 3E). FIG. 3A shows wireless measurements of T ₁ (blue) and T ₂ (red) over time under conditions of varying ambient temperature T _A (black), measured with a commercial thermometer (GM1361, BENETECH). shown as a function. _TA values increased from 23.3 to 36.6 °C for 15 minutes in the oven (red background), then in room temperature environment (RT, white background) and then in the refrigerator (blue background) for an additional 9 minutes. decreases from 36.6 to 8.0°C. Wireless measurements of ΔT ₁ (black), ΔT ₂ (red), and ΔT ₁₂ (blue) as a function of T _A are shown in FIG. 3B. The SD for ΔT ₁₂ spanning a _TA of 8.0 to 36.6° C. was 0.03° C., roughly ten-fold that associated with ΔT ₁ and ΔT ₂ (0.27 and 0.29° C., respectively). small. The values of ΔT ₁ and ΔT ₂ fluctuate with the rapid increase and decrease of _TA at the moment the device enters and exits the oven, respectively (Fig. 15). FIG. 3C has temperature TS (green) varying over a physiologically relevant range (24.2 to 41.0° C., FIG. 3D) and air velocity from 0 to −13.6 m/s (FIG. 3E). Wireless measurements of T ₁ (blue) and T ₂ (red) on a sample with , are shown as a function of time. TS (green dashed line) is the base temperature measured from NTC ₁ while the thermal actuator is off for 50 seconds every 1 minute cycle. For the 90 min measurements, _TS increased from 25.5 to 41.0 °C in the session labeled "heating" and from 41.0 to 24.2 in the session labeled "cooling". °C. The surface temperature of the shell structure above the actuator of the device (T _D , purple) changes accordingly (from 23.9° C. to 35.5° C., then back to 21.8° C.) and T _A (black) is constant as -22.2±0.3°C. Varying airflow velocity from the top (blue background) causes abrupt changes in temperature towards the middle and end of the heating and cooling processes, respectively. ΔT ₁ (blue), ΔT ₂ (red), and ΔT ₁₂ (black) as a function of T _S (Fig. 3D) and as a function of time for airflow velocities from 0 to ~13.6 m/s The measurements (FIG. 3E) are shown in FIGS. 3D-3E, respectively. When T _S and airflow rate were varied, ΔT ₁₂ exhibited an SD of 0.03°C, approximately 6 more than those associated with ΔT ₁ and ΔT ₂ (0.17 and 0.17°C, respectively). twice as small, SNR as shown in Table 1, SNR(dB)=20* _log10 ([Delta _]T12,mean /[Delta] _T12,SD )>50dB. These results show that the signal is typically >300 times the noise. FIGS. 3F and _3G show T ₁ (blue), T ₂ (red) and the difference (T ₁ − T ₂ , black), and ΔT ₁ (black), ΔT ₂ (red), and ΔT ₁₂ (blue) results are shown. The biocompatible silicone packaging is robust against water penetration such that the SDs of ΔT ₁ , ΔT ₂ , and ΔT ₁₂ are 0.07, 0.04, and 0.03° C., respectively, over a 30-minute measurement. provide protection. Hermetic sealing of the device eliminates the effects of ambient environmental humidity on the circuit components.

These devices can be laminated gently to the skin without applying pressure to determine Φ via the measurement of ΔT ₁₂ as previously described. The BLE interface supports wireless long-range communication with smartphones using user protocols that require little training or specialized skills (Fig. 3H). The basic tests were a device according to an embodiment of the present invention (Φ _BLE ) and tissue water content (Φ _CML,1 , MoistureMeterD, Delfin Technologies) and skin surface moisture (Φ _CML,2 , Gpskin, gpower) and three different healthy subjects using a commercially available (CML) device to measure Φ in a given body configuration (FIGS. 16A-16B) by three different users. ). The measurement depth of the former is 500 to 2,500 μm, and the measurement depth of the latter is 10 to 20 μm. Commercially available devices require the user's attention to hold the probe and manually apply some steady pressure to the skin for several seconds between each measurement. FIG. 3H shows Φ for five different body positions (FIG. 17): forehead (F), right arm (A _R ), left arm (A _L ), right leg (L _R ), and left leg (L _L ). shows the results. User variability associated with Φ _BLE , Φ _CML,1 , and Φ _CML,2 at the same body placement yields average SD values of 0.00, 0.02, and 0.03, respectively. The SDs of Φ _CML,1 and Φ _CML,2 are greatest on the forehead of subjects 2 and 1, respectively (0.04 and 0.09, respectively), and those associated with Φ _BLE are It is constant (~0.00) across five body configurations, each with different curvature and stiffness (Fig. 18). The data show that the Φ _BLE result yields the maximum repeatable value of Φ. Φ _BLE results correlate with results from both Φ _CML,1 and Φ _CML,2 (FIG. 19). The linear fit is Φ _CML,1 =Φ _BLE ×0.76−0.08 (R ² =0.76), and Φ _CML,2 =Φ _BLE ×0.85+0.04 (R ² =0.51). is shown. Bland-Altman plots (difference plots) shown in FIGS _. 20A-20B show calibrated Φ (Φ _{BLE , Cal1} = Φ _BLE × 0.76-0.08, Φ _BLE,Cal2 = Φ _BLE × 0.85 + 0.04). These results suggest that Φ _BLE with calibration yields a higher correlation with Φ _CML,1 compared to Φ _CML,2, possibly due to comparable sensing depths for Φ BLE and Φ _{CML,1 .} is shown.

The measurement is sensitive to the presence and properties of layers near the surface of the skin, including the SC. As a demonstration, FIG. 4B shows measurements of Φ _BLE and Φ _CML,1 (MoistureMeterD, Delfin Technologies) and adhesive discs (D-Squame, CuDerm, FIG. 4A) as a simple, painless means to remove SCs. Figure 4 shows the SC moisture level (Φ _CML,3 ) determined using a commercial device (MoistureMeterSC, Delfin Technologies, measurement depth 40 μm) as a function of the number of cycles of application and removal of . To increase the number of cycles, Φ _BLE increases in a systematic manner as evidence of the sensitivity of the measurement to SC. The data show a strong correlation between the values of Φ _BLE and SC water levels (Φ _CML,3 ) and the number of ablation cycles, whereas the tissue water content (Φ _CML,1 ) Almost unchanged. The values of ΔT ₁₂ at short time (t=1 s) and long time (t=10 s) as a function of peel cycle, as in FIG. % and 2.8%. These results indicate that short-time measurements are more sensitive to the properties of the near-surface layers of the skin, consistent with previous discussions of heat transport physics.

A study of pig skin samples (Fig. 4D) with different known moisture levels is shown in Fig. 4E. The change in Φ normalized to the value of Φ immediately after placing the sample in the food dehydrator (33 °C) shows a strong correlation with independent measurements of sample moisture loss (see Methods section for details). ). Measurements of ΔT ₁₂ at short time (t=1 sec) and long time (t=10 sec) as a function of water loss are shown in FIG. 4F. The change in ΔT ₁₂ was, as expected, positively correlated with water loss: ΔT ₁₂ (10 sec) = 6.9 + 0.3 x water loss (R ² = 0.97) and ΔT ₁₂ (1 sec) = 5 .6+0.1×moisture loss (R ² =0.85).

Human Subject Evaluation: These miniaturized flexible ratforms include spanning over highly curved or highly sensitive areas of the anatomy, adults and children (e.g. hands of pediatric subjects, Figure 21) can be used on almost any part of the human body as well. Figures 5A-5C show photographs of the device worn on the forehead (Figure 5A), forearm (Figure 5B), and calf (Figure 5C) of a human subject. The inset of FIG. 5A features a tilted side view. A study of skin hydration levels in 10 healthy volunteers was performed on the forehead (F), right arm (A _R ), left arm (A _L ), right leg (L _R ), and left leg (L _L ). It involves evaluation in 5 different body positions (Fig. 17). FIG. 5D shows three female (subjects 1, 2, and 9, age range, 25 to 27) and seven male (subjects 3 to 8, 10, age range, 17 to 37) healthy volunteers (Table 2 (see Table _{2 )} ) for _a 3 minute measurement period. These results indicate that the forehead had the highest hydration level (lowest values of ΔT ₁ , ΔT ₂ and ΔT ₁₂ ) across all subjects. The SD values for ΔT ₁ , ΔT ₂ , and ΔT ₁₂ at each configuration for all subjects are less than ˜0.06, 0.08, and 0.01° C., respectively (FIG. 22). This data indicates that ΔT ₁₂ yields the most consistent values of Φ, consistent with the findings described in the previous section. A comparison of Φ from the ΔT ₁₂ values and Φ determined using a conventional handheld medical device (MoistureMeterD, Delfin Technologies, FIG. 16A) is shown in FIG. 5E. As before, Φ(Φ _BLE ) determined using the device introduced here correlates strongly with that from the commercial device (Φ _CML,1 , FIG. 23). The measured value of Φ using the calibration factor (Φ _BLE,Cal1 =Φ _BLE ×0.80-0.20) is e=|Φ _BLE,Cal1 −Φ _CML,1 |/Φ _CML,1 =0. corresponds to Φ _CML,1 with an average error (e) of 09 (FIG. 24).

Additional experiments demonstrate the effect of hairy skin on measurements of ΔT ₁ , ΔT ₂ , and ΔT ₁₂ (FIGS. 25A-25B). Mean±SD values of ΔT ₁ , ΔT ₂ , and ΔT ₁₂ in 5-minute measurements before and after shaving the skin were 8.76±0.03, 1.78±0.03, and 6.98, respectively. ±0.01° C. (before), and 8.78±0.03, 1.80±0.03, and 6.98±0.01° C. (after). The effect of perspiration on skin moisture levels before workout (no perspiration), during workout (perspiration), and after workout (sweat wipe) is shown in FIG. 26B. Sweat increased the skin hydration level (Φ _BLE ) from 0.92 to 0.96 (no wipe)/0.94 (wipe), which is consistent with previous studies.

Assessment of hydration status of diseased and healthy skin: Water leaves from deep in the epidermal layer and gradually diffuses upwards to moisten the cells of the SC, eventually comparable to the amount routinely lost through urination. Leaves the skin via evaporation in small amounts. This TEWL increases when the normal function of the skin is impaired due to loss of barrier function from desiccation, infection and mechanical stress. The next study examined changes in the hydration status of diseased and clinically unaffected skin. Validation studies included two patients with AD (Subjects 1 and 2, Tables 3-5), infants with visibly dry skin (Figures 6A-6I), and 3 young adults with healthy skin (FIGS. 7A-7I). Figures 6A-6B show the back of the hand (atopic eczema) and forearm (control) of Subject 1 (Figure 6A) and the chest of Subject 2 (from left to right inflamed skin, perilesional skin, and non-lesional skin; 6B) shows the mounting arrangement. The insets in FIGS. 6A-6B show photographs of the forearm of Subject 1 after application of a moisturizer, and the platform attached to the inflamed skin (left) and near-lesion skin (right) of Subject 2's chest. characterize each.

The optical image of Figure 27 shows a platform on Subject 1's atopic dermatitis next to a smart phone for collecting/displaying/storing measurements. Results for ΔT ₁₂ from Subjects 1 and 2 are shown in FIGS. 6C-6D, respectively. Compared to healthy skin (control), lesional skin (eczema in FIG. _6C , inflammation in FIG. 6D) had higher and A decrease in ΔT ₁₂ is shown (see methods section for details). 6E-6F show the values of Φ from ΔT ₁₂ (Φ _BLE , red) and MoistureMeterD (Φ _CML,1 , sky blue) and Gpskin (Φ _CML,2 , light green) for subjects 1 and 2, respectively. showing. Compared to perilesional and non-lesional skin, atopic eczema and inflammation show lower values of Φ _BLE (before) and increased Φ _BLE after moisturizer application. Tissue water content (Φ _CML,1 value) correlates with the calibration value of Φ _BLE (Φ _{BLE, Cal} = Φ _BLE × 0.76-0.08, pink), and the mean error (e) is e =|Φ _BLE,Cal −Φ _CML,1 |/Φ _CML,1 =0.09. Values of Φ _CML,1 yielded the highest SD for lesions, nodules, and congealed areas (0.03 for atopic eczema and inflamed skin, 0.01 for others), with an average SD of 0.01. 01 and greater than the value associated with Φ _BLE,Cal (0.00). Moisturizing the skin significantly increases the skin surface moisture level (Φ _CML,2 value) to nearly 1 (0.91 in atopic eczema and 1.00 in inflamed skin). Figures 6G-6H are applied to the forehead (Figure 6G) and legs (skin determined to be visibly dry by a dermatologist, Figure 6H) of an infant (male, 2 years old). 1 shows an optical image of a device with Φ _BLE ( _blue ), Φ _CML,1 (black), TEWL (red), and SC water content (SCH, green) in left leg (L _L ), right leg (R L ), and forehead (FH) is shown in FIG. 6I. TEWL and SCH measured using the Gpskin device, and Φ _BLE values are higher in the forehead, where higher water levels are expected compared to the legs.

A validation study on three healthy adults (subject 1 with visible dry skin, subjects 2 and 3 with invisible dry skin as determined by a dermatologist) was performed after applying a moisturizer (~ The emphasis is on observing the variation of b during 4 hours). The experimental protocol consists of five steps: 1) soaping the forearm, 2) performing measurements at 3 different placements of the forearm (“control”, “short” and “long”), 3) short and short. Apply moisturizer (Extremely Dry Skin Rescue Lotion, Vaseline) to the long area, wait 1 minute for short, 15 minutes for long, step 4) wipe off excess moisturizer from the surface of the skin, and 5) each placement. It involves repeating the measurement at . The normalized variation of Φ _BLE and Φ _CML,1 for each initial value in the control region is shown in FIGS. 7A-7I. These results indicate that there is a strong correlation between Φ _BLE and Φ _CML,1 . Compared to the initial value of Φ _BLE in the control region (FIG. 7A) of Subject 1, the values of Φ _BLE in the short region (FIG. 7B) and long region (FIG. 7C) were 5% and 1%, respectively, at 0 min. Low and 20% and 23% higher immediately after moisturizer application. At 80 minutes, Φ _BLE in the long region approaches 20% higher than Φ _BLE in the control region. Compared to the initial value of Φ _BLE in the control region (FIG. 7D) of Subject 2, the values of Φ _BLE in the short region (FIG. 7E) and long region (FIG. 7F) were 20% and 23% after application of the moisturizer. High, approaching 10% and 11% higher values after ~4 hours. Compared to the initial value of Φ _BLE in the control region (FIG. 7G) of subject 3, the values of Φ _BLE in the short region (FIG. 7H) and long region (FIG. 7I) were 5% and 4% after application of the moisturizer. High, approaching 0% and 1% high values after ~3 hours. The increase in Φ _BLE after moisturizer application decreases with time.

Optimized measurement conditions: Optimization of measurement conditions is very important to obtain accurate/precise and reproducible results. For example, the best results are: (1) the measurement is performed quickly, minimizing the effects of occluding the natural process of releasing water vapor from the skin due to the presence of the device; very light or zero pressure is used to minimize perturbation to the skin; (3) the adhesive is patterned to reside only over the area of the device adjacent to the sensor itself; (4) the temperature of the device is similar to that of the skin; (5) the skin itself is exposed to the surrounding environment prior to measurement; Adaptation is allowed, sometimes gained.

CONCLUSIONS The miniature soft wireless platform disclosed in the present disclosure demonstrates healthy skin across a wide range of skin conditions, body geometries, and subject backgrounds with superior accuracy and precision compared to existing clinical or research grade devices. and the water content of diseased skin non-invasively and rapidly.

An optimized bifacial TAS module in combination with multiple redundant measurement modalities provides a highly reproducible, robust and user-friendly measurement under a variety of conditions relevant to both clinical and home settings. Supports independent measurements. A BLE SoC interface with a phone enables rapid data acquisition suitable for operation with minimal training or specialized skills. Full-waveform fitting of the data captured using these systems to a bilayer model of heat transport yields both epidermal and dermal hydration levels. Evaluation of skin phantoms and partially hydrated porcine skin validates these measurement and analytical approaches. Pilot-scale clinical studies (n=19) in healthy and diseased subjects demonstrate a variety of clinically relevant capabilities. These results define the basis for a versatile skin interface device that can support personalized, topical skin hydration strategies, thereby diagnosing skin disease states, such as AD and XC. Potential use as a grading tool for neonates at high risk of developing cervical cancer, and as a basis for objective evaluation of the efficacy of topical agents and personal care products (e.g., topical moisturizers). Additional potential applications include monitoring thermoregulatory processes and managing heat-related disorders.

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

The embodiments have been chosen and described in order to explain the principles of the technology and its practical application, thereby enabling those skilled in the art to fully understand the invention and its various modifications along with such various modifications as are suitable for the particular application contemplated. It enables the use of various embodiments. Alternate embodiments will become apparent to those skilled in the art to which this invention pertains without departing from its spirit and scope. Accordingly, the scope of the present invention is defined by the appended claims rather than by the foregoing description and exemplary embodiments described therein.

Several references, which may include patents, patent applications, and various non-patent literature publications, are cited and discussed in the description of this invention. Citation and/or discussion of such references is provided merely to clarify the description of the invention, and such references are " It is not an admission that it is "prior art". All references cited and discussed herein are hereby incorporated by reference in their entirety and to the same extent as if each reference were individually incorporated by reference. .

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Claims (72)

a moisture content sensor,
a sensing module operably disposed on a target area of interest of a living body's skin for detecting data associated with thermal properties of said skin;
a wireless platform coupled to the sensing module for wireless data transmission between the sensing module and an external device. The sensing module is
a thermal actuator operably disposed on the target area of interest of the skin to heat the target area of interest;
and a sensing circuit for simultaneously detecting transient temperature changes (ΔT) thereof to determine said thermal properties of said skin. 3. The thermal actuator and sensing circuit of claim 2, wherein the thermal actuator and the sensing circuit are interconnected by serpentine traces to form a flexible structure that facilitates soft intimate contact to the skin with robust mechanical and thermal coupling. moisture content sensor. 3. The moisture content sensor of Claim 2, wherein the thermal actuator comprises at least one resistor. 5. The thermal actuator of claim 4, wherein the thermal actuator comprises two or more of surface mount thin film resistors, thick film resistors, through hole resistors, and ultra thin film metal resistors coupled in series with each other. moisture content sensor. 3. The moisture content sensor of claim 2, wherein the sensing circuit comprises one or more of a negative temperature coefficient thermistor, a positive temperature coefficient thermistor, a resistance temperature detector (RTD), and a thermocouple. 3. The moisture sensor of claim 2, wherein the sensing circuit comprises a first pair of negative temperature coefficient thermistors (NTC) arranged in a first Wheatstone bridge circuit. The first pair of NTCs is disposed on a different layer than the thermal actuator, the first pair of NTCs directly overlies the thermal actuator, or the first pair of NTCs 8. The moisture content sensor of claim 7, wherein pairs are disposed on the same layer as the thermal actuator and each first NTC has a first distance from the thermal actuator. 9. The moisture content sensor of claim 8, wherein the sensing circuit further comprises a second pair of NTCs arranged in a second Wheatstone bridge circuit operable to compensate for changes in ambient temperature. The second pair of NTCs are disposed on the same layer as the first pair of NTCs, each second NTC being spatially separated from the first pair of NTCs, and the thermal actuator 10. The moisture sensor of claim 9, having a second distance from . 11. The moisture sensor of claim 10, wherein the first and second distances are determined by design requirements for depth sensitivity into the skin and range from tens of microns to several millimeters. 2. The moisture sensor of claim 1, wherein the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols. 13. The moisture sensor of claim 12, wherein the wireless platform comprises a Bluetooth low energy system on chip (BLE SoC). The BLE SoC is
a general purpose input/output (GPIO) electrically coupled to the thermal actuator for supplying a periodic current to activate the thermal actuator;
a differential amplifier (AMP) electrically coupled to the sensing circuit for amplifying the bridge voltage difference;
an analog-to-digital converter (ADC) electrically coupled to the AMP for digitizing the output voltage of the AMP;
wirelessly transmitting the output signal of the ADC to the external device for processing to determine the hydration status of the skin; 14. The moisture content sensor of claim 13, comprising a BLE radio configured to supply an actuator. 15. A digital on/off switch controlled through a custom application on said external device is adapted to enable enabling of BLE connections and GPIO pins to supply said periodic current to said thermal actuator. Moisture content sensor as described in . 15. The moisture sensor of claim 14, wherein the BLE SoC further comprises a microcontroller ([mu]C) configured to enable the GPIO pin and supply the periodic current to the thermal actuator. 15. The moisture sensor of claim 14, further comprising a power module for powering said sensing circuitry and said wireless platform. 18. The moisture sensor of Claim 17, wherein the power module comprises a battery. 19. The moisture content sensor of claim 18, wherein the battery is a rechargeable battery operably wirelessly charged. 20. The moisture content sensor of claim 19, wherein the power module further comprises a wireless charging module for wirelessly charging the rechargeable battery. 19. The moisture sensor of claim 18, wherein the power module further comprises a fault protection element including a short circuit protection component or circuit to avoid battery malfunction. 22. Any of claims 1-21, further comprising a flexible substrate in the form of a flexible printed circuit board (fPCB) having circuit traces interconnecting the thermal actuator on the skin side, the NTC on the air side, and the BLE SoC. or the moisture content sensor according to claim 1. 23. The moisture content sensor of claim 22, wherein the flexible substrate is formed from a flexible material including polyimide (PI) or polyethylene terephthalate (PET). 23. The moisture sensor of Claim 22, further comprising an encapsulating enclosure surrounding said thermal actuator, said wireless platform, said battery, and said fPCB. The encapsulating enclosure includes:
a top layer for thermally, chemically and mechanically isolating the moisture sensor from the environment;
25. The moisture sensor of claim 24, comprising a bottom layer for providing a direct interface between the thermal actuator on the skin side of the fPCB and the skin. 26. The moisture sensor of claim 25, wherein the top layer is a shell-like top encapsulant layer containing small voids for thermally, mechanically and chemically insulating critical sensing components. 4. The top layer is formed from flexible materials including silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon®, and various other flexible polymers. 27. The water content sensor according to 26. 26. The moisture sensor of Claim 25, wherein the bottom layer comprises a flexible adhesive for adhering the moisture sensor to the skin. 29. The moisture sensor of claim 28, wherein the bottom layer further comprises a micro-woven fiberglass/stiffener embedded in the flexible adhesive layer to enhance the mechanical robustness of the moisture sensor. . 30. The moisture sensor of claim 29, wherein said stiffener is flexible and has varying mesh densities and thicknesses to impart tear resistance to said bottom layer. The flexible adhesive layer is formed from silicone or silicone gel, or a double-sided skin-safe adhesive, with the ratio of silicone and silicone gel adjusted to simultaneously optimize the mechanical integrity and adhesion of the adhesive. 29. The moisture content sensor of claim 28, wherein Moisture content sensor according to any one of the preceding claims, wherein the external device is a smart phone, tablet, computer or any electronic device with data reading/processing capabilities. 3. The moisture content of claim 2, wherein said thermal properties of said skin comprise thermal conductivity and thermal diffusivity of said skin which are related to moisture content of said skin, said moisture content being a function of skin depth. sensor. 34. The moisture sensor of claim 33, wherein the moisture content is determined from the measured change in temperature [Delta]T versus time t. 34. The moisture sensor of claim 33, wherein the moisture content and skin surface temperature are used to determine the normal or diseased state of the skin. 34. The method of claim 33, wherein said moisture content and skin surface temperature serve as quantitative metrics of effectiveness of treatment of skin diseases or other health and wellness products including skin moisturizers, lotions, and/or creams. moisture sensor. 37. A moisture sensor according to any one of the preceding claims, usable for monitoring the skin condition in a clinical setting and/or in a home environment. It can be used to administer treatment, monitor efficacy, adjust treatment protocols as needed, and/or potentially predict flare based on quantitative personalized measurements of specific lesion sites. Moisture content sensor according to any one of claims 1 to 36, wherein A water content according to any one of claims 1 to 36, which can be used to monitor the water content of internal organs for various diseases where conventional monitoring techniques cannot provide a continuous assessment of organ health. sensor. 37. A water content sensor according to any one of the preceding claims, usable for monitoring organs during organ transport for organ transplantation applications. A moisture sensor according to any one of the preceding claims, usable for measuring thermal conductivity, thermal diffusivity, heat capacity and other thermal properties of any material as a function of depth. . Measure moisture content on any material surface as a function of depth, including hydrogels, plants (irrigation and agricultural applications), food preservation (dried foods, grains, fruits, meat), and/or concrete (industrial applications) The water content sensor according to any one of claims 1 to 36, which can be used for applications for. Moisture content sensor according to any one of the preceding claims, usable for monitoring the composition of food/beverages, pharmaceuticals/industrial chemicals. Moisture content sensor according to any one of the preceding claims, wherein the moisture content sensor is reusable and removable without irritation to the skin or damage to the moisture content sensor. of claims 1-36, compatible with alcohol-based cleaning wipes allowing reuse between different users without damage to the moisture sensor or loss of efficacy of the moisture sensor adhesive. Moisture content sensor according to any one of the paragraphs. A moisture content sensor according to any one of the preceding claims, sterilizable using alcohol, autoclave steam sterilization, and vapor phase sterilization. A method of making a moisture content sensor, comprising:
forming a flexible printed circuit board (fPCB) interconnecting the electronics of the moisture sensor;
forming an encapsulation enclosure surrounding a sensing module, a wireless platform, and the fPCB, the encapsulation enclosure comprising a top layer and a bottom layer. 48. The fPCB as recited in claim 47, wherein the fPCB is formed from a flexible material including polyimide (PI), polyethylene terephthalate (PET), or any one of these combined with a rigid PCB material including FR-4. described method. The bottom layer comprises a first flexible layer, a second flexible layer, and fiberglass/stiffeners embedded between the first flexible layer and the second flexible layer. 48. The method of claim 47, comprising a fabric layer structure of Each of said first flexible layer and said second flexible layer is formed from silicone or silicone gel, or a double-sided skin safe adhesive, the ratio of said silicone and silicone gel being the mechanical strength of said adhesive. 50. The method of claim 49, adjusted to simultaneously optimize integrity and cohesion. 50. The method of claim 49, wherein the stiffener is flexible and has varying mesh densities and thicknesses to impart tear resistance to the bottom layer. 50. The method of claim 49, wherein the bottom layer adheres to the f-PCB through the use of silicone adhesive materials, epoxies, adhesives, or commercial adhesives. 48. The claim 47, wherein the top shell layer is formed from silicone or silicone gel, low/high density polyethylene (LDPE/HDPE), polystyrene, Teflon(R), and various other flexible polymers. Method. The electronic device
a sensing module for detecting data associated with thermal properties of the skin;
54. The method of any one of claims 47-53, comprising a wireless platform coupled to the sensing module for wireless data transmission between the sensing module and an external device. The sensing module is
a thermal actuator for heating the target area of interest of the skin;
55. The method of claim 54, comprising sensing circuitry for simultaneously detecting transient temperature changes ([Delta]T) thereof to determine thermal properties of said skin. 55. The method of claim 54, wherein the wireless platform includes at least one of Wi-Fi, BLE, and NFC communication protocols. 57. The method of Claim 56, wherein the wireless platform comprises a Bluetooth low energy system on chip (BLE SoC). A method of monitoring and/or diagnosing a skin condition, comprising:
Affixing a moisture content sensor on the target area of interest of the skin, the moisture content sensor comprising a thermal actuator, a sensing circuit, and a wireless platform for bi-directional data communication with an external device. , step and
heating the target area of interest of the skin by the thermal actuator; concurrently detecting data associated with thermal properties of the skin by the sensing circuit; transmitting the detected data to the external device by the wireless platform; wirelessly transmitting to a device to determine its transient temperature change (Δt);
obtaining the moisture content of the target area of interest of the skin from the temperature change (ΔT);
determining the condition of the skin at the target area of interest based on the obtained moisture content. 59. The method of claim 58, wherein the water content comprises an epidermal water content [Phi] _E and a dermal water content [Phi] _D . 60. The method of claim 59, wherein obtaining the moisture content comprises separately determining Φ _E and Φ _D from the temperature change ΔT. 59. The method of claim 58, wherein the wireless platform transmits data through wireless communication protocols including Near Field Communication (NFC), Wifi/Internet, Bluetooth/Bluetooth low energy (BLE), or GSM/cellular communication. 59. The method of claim 58, wherein the heating of the target area of interest of the skin is produced by supplying a periodic electrical current to the thermal actuator. 63. The method of claim 62, wherein enabling of said periodic current is controlled by a digital on/off switch through a custom application on said external device. The step of determining the condition of the skin in the target area of interest includes comparing the obtained moisture content to a standard moisture content in the target area of interest to determine a normal or diseased condition of the skin. 59. The method of claim 58, comprising determining. 65. The method of claim 64, wherein the step of determining the condition of the skin in the target area of interest comprises diagnosing a skin disease in the target area of interest based on the obtained moisture content thereof. the method of. 66. The method of claim 65, wherein determining the condition of the skin in the target area of interest comprises assessing efficacy of treatment for the skin condition. 66. The method of claim 65, wherein the steps of obtaining the moisture content of the target area of interest of the skin and determining the condition of the skin are performed in the external device. 59. The method of claim 58, further comprising displaying on the external device the condition of the skin at the target area of interest. 59. The method of claim 58, further comprising forwarding the condition of the skin at the target area of interest to a professional and/or service provider. A method according to any one of claims 58 to 69, wherein said external device is a smart phone, tablet, computer or any electronic device with data reading/processing capabilities. of administering treatment, monitoring efficacy, adjusting treatment protocols as necessary, and/or potentially predicting flare based on quantitative personalized measurements for specific lesion sites. 71. The method of any one of claims 58-70, further comprising one or more of: performed under one or more optimized measurement conditions, the optimized measurement conditions comprising:
the measurements are performed quickly to minimize the effects of blocking the natural process of water vapor release from the skin due to the presence of the moisture sensor;
very light or zero compression is used during the measurement to minimize perturbation to the skin;
An adhesive is present only over the area of the moisture sensor device adjacent to the sensor itself and is patterned to avoid peeling of the skin at the measurement site and improve reproducibility during peeling. matter,
59. The method of claim 58, wherein the temperature of the moisture sensor is equivalent to the temperature of the skin; and the skin itself is allowed to acclimate to the environment prior to the measurement.

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