Strain-isolated soft bioelectronics for wearable sensor devices

Abstract

Exemplary systems and methods are disclosed for a wearable soft bioelectronic system configured with a strain isolator that can isolate its sensor electrodes or other sensors in close proximity to or in contact with the skin from the global movements of the body, e.g., the transient stretching and relative movement of the skin due to walking. The exemplary system employs rigid-soft materials and isolation structures that facilitate the use of wearable sensors that can be placed on the surface of the skin and can minimize motion artifacts in signals acquired during physical movements by the wearer. The exemplary system can employ stretchable sensors in combination with strain isolators.

Description

[Technical field]

[0001] Government Statement of Interest This invention was made with Government support under Grant No. 2024742 awarded by the National Science Foundation. The Government has certain rights in this invention.

[0002] Related Applications This PCT application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 194,109, filed May 27, 2021, entitled “Strain-Isolated Soft Bioelectronics for Wireless, Continuous, Motion Artifact-Controlled Health Monitoring in Real-Life Activities,” which is incorporated by reference in its entirety. [Background technology]

[0003] Portable, long-term, continuous monitoring of biophysical signals acquired via wearable devices is commonly desired in everyday IoT wearable devices, e.g., smart watches, as well as in clinical settings, e.g., wearable electrocardiograms. Collecting high-quality data remains challenging due to motion artifacts.

[0004] Movement artifacts (MA) generally include temporary changes in the measured voltage caused by the movement of the sensor and / or the body on which the sensor is located. For example, walking can create a downward force on the skin and sensor device with each step, which can cause a temporary stretching of the skin and a relative movement of the skin with the electrode. These two disturbances together can change the half-cell potential of the skin and the contact impedance with the electrode, respectively. These temporary changes in the measured voltage can have the same amplitude and frequency as other body signals, such as cardiac contractions, and are often difficult to distinguish from many physiological signals. Software algorithms and signal filtering are commonly used to improve signal quality, but they can be computationally expensive, especially for long-term monitoring, and they can still only provide an estimate of the actual biological signal.

[0005] There would be advantages to improved acquisition of biophysical signals, with or without reduced motion artifacts. Summary of the Invention

[0006] Exemplary systems and methods are disclosed for a wearable soft bioelectronic system (also referred to herein as "SIS") configured with a strain isolator that can isolate its sensor electrodes or other sensors in close proximity to or in contact with the skin from the transient stretching and relative movement of the skin due to the overall movement of the body (e.g., walking). The exemplary system employs rigid-soft materials and isolation structures that facilitate the use of wearable sensors that can be placed on the surface of the skin and can minimize motion artifacts in signals acquired during physical movement by the wearer. Exemplary soft bioelectronic systems can also employ stretchable sensors in combination with strain isolators.

[0007] In some embodiments, the wearable soft bioelectronic system and strain-isolated sensor electrodes can be used in combination with inertial sensors, for example, for health monitoring during daily activities, e.g., portable ECG devices, health monitoring devices. Studies have been conducted through analytical and computational analysis and dynamic experiments that confirm the utility of this exemplary system in removing or reducing motion artifacts in wearable sensor devices.

[0008] In one aspect, a system (e.g., a sensor system or device system) is disclosed. The system includes a flexible substrate comprising two or more low modulus layers, including an upper low modulus layer and a lower low modulus layer, the flexible substrate having a first side on the upper low modulus layer and a second side on the lower low modulus layer, the second side configured as a breathable soft membrane configured for direct contact and adhesion with an area of ​​human skin, and one or more pads (e.g., an electrode, a stretchable electrode, a pair of pads for mounting a sensor IC, or a pair of stretchable pads) fixably attached to the second side of the flexible substrate, the one or more pads including a first pad attached to the second side over a first area, and one or more The pads may include one or more pads, each having a side exposed for direct contact with a portion of the skin area, and one or more strain isolation structures fixably attached to the upper low modulus layer, including a first strain isolation structure, the first strain isolation structure being attached to the upper low modulus layer in an area corresponding to a first area of ​​the first pad and shaped to have an outer dimension that forms a perimeter around the first pad (e.g., the strain isolation structure prevents or reduces temporary changes in pad impedance caused by skin strain and pad movement or sliding).

[0009] In some embodiments, the first strain isolation structure has an inner dimension that extends beyond the first area of ​​the first pad.

[0010] In some embodiments, the first pad has a first shape and the first strain isolation structure has a second shape, and the first shape of the first pad is the same as the second shape of the first strain isolation structure.

[0011] In some embodiments, the first pad has a first shape and the first strain isolation structure has a second shape, and the first shape of the first pad is different from the second shape of the first strain isolation structure.

[0012] In some embodiments, the first pad has a shape selected from the group consisting of a square region, a rectangular region, a circular region, or an oval region.

[0013] In some embodiments, the first pad has a planar geometric shape.

[0014] In some embodiments, the upper low modulus layer comprises a thin low modulus silicone elastomeric material having an average thickness of less than 1000 μm.

[0015] In some embodiments, the lower low modulus layer comprises a low modulus silicone gel material having a modulus value of less than 20 kPa.

[0016] In some embodiments, the upper low modulus layer comprises a first material having a first elastic modulus value and the lower low modulus layer comprises a second material having a second elastic modulus value, and the first elastic modulus value of the upper low modulus layer is at least twice the second elastic modulus value of the lower low modulus layer.

[0017] In some embodiments, the one or more pads form an array.

[0018] In some embodiments, one or more of the pads are configured as an open mesh stretchable electrode.

[0019] In some embodiments, the open mesh stretchable electrode includes multiple stretchable pads (e.g., circular, oval, square, rectangular, or other geometric shapes) each connected together by a serpentine or serpentine mesh connection.

[0020] In some embodiments, the system is configured as a smartwatch configured for at least one of optical, impedance, capacitance, or potential measurements through a stretchable pad.

[0021] In some embodiments, the system includes a second stretchable pad attached to a second side over a second area, and a second strain isolation structure attached to the upper low modulus layer in a third area corresponding to the second area of ​​the second stretchable pad and shaped to have an outer dimension forming a perimeter around the second stretchable pad.

[0022] In some embodiments, one or more pads (e.g., stretchable pads) including the first pad form a pair of stretchable contacts that are fixably attached to a second side of the flexible substrate across a second area, and the system further includes an active integrated sensor component coupled to the pair of stretchable contacts.

[0023] In some embodiments, the active integrated sensor component includes a light emitting diode or a photodiode.

[0024] In some embodiments, the system is configured as an electrocardiogram probe.

[0025] In some embodiments, the electrocardiogram probe includes a pair of flexible pads, a multi-axis accelerator (eg, a three-axis accelerator), and a multi-axis gyroscope (eg, a three-axis gyroscope).

[0026] In some embodiments, the electrocardiogram probe further comprises an optical sensor, a photodiode, a capacitance, and / or a temperature sensor.

[0027] In some embodiments, the system includes an active integrated chip assembly mounted on a flexible substrate, the active integrated chip assembly including at least one active integrated circuit including a transimpedance amplifier circuit and a digital-to-analog converter.

[0028] In some embodiments, the system includes an encapsulation layer that encapsulates the active integrated chip assembly.

[0029] In some embodiments, the active integrated chip circuitry further includes a local processing unit or controller (e.g., silicon or IC) configured to provide the measured signal data to a device processing unit or controller (e.g., for a smart watch).

[0030] In some embodiments, the device processing unit or controller is configured to employ at least one of an electrocardiogram signal, a heart rate signal, a respiratory rate signal, or a combination thereof obtained through electrodes or sensors associated with one or more pads (e.g., stretchable pads).

[0031] Those skilled in the art will understand that the drawings, described below, are for illustration purposes only. [Brief description of the drawings]

[0032] [Figure 1] 1 illustrates an exemplary wearable soft bioelectronic system device configured with strain-isolated sensors, according to an exemplary embodiment. [Figure 2A] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2B]2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2C] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2D] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2E] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2F] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2G] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2H] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2I] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 2J] 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment. [Figure 3A] 3A-3E each provide an example of a strain isolator configuration according to an example embodiment. [Figure 3B] 3A-3E each provide an example of a strain isolator configuration according to an example embodiment. [Figure 3C] 3A-3E each provide an example of a strain isolator configuration according to an example embodiment. [Figure 3D] 3A-3E each provide an example of a strain isolator configuration according to an example embodiment. [Figure 3E] 3A-3E each provide an example of a strain isolator configuration according to an example embodiment. [Figure 4] 1 illustrates a method for fabricating a breathable substrate for use in a strain isolated sensor device according to an illustrative embodiment. [Figure 5A] 2 illustrates an exemplary fabrication method for the isolated sensor device of FIG. 1 according to an exemplary embodiment. [Figure 5B] 1 illustrates an exemplary fabrication method for a stretchable sensor electrode or pad that may be used in a strain isolated sensor device, according to an exemplary embodiment. [Figure 6a] 6a-6b provide an overview of studies conducted to develop and evaluate health monitoring devices constructed from strain isolation materials and structures, according to example embodiments. [Figure 6b] 6a-6b provide an overview of studies conducted to develop and evaluate health monitoring devices constructed from strain isolation materials and structures, according to example embodiments. [Figure 7a] 7a-7b show the analytical framework for the strain isolation physics and computational modeling carried out in the study of FIGS. 6a-b. [Figure 7b] 7a-7b show the analytical framework for the strain isolation physics and computational modeling carried out in the study of FIGS. 6a-b. [Figure 8] 6a and 6b show results from an evaluation of the signal processing and classification performance of the strain-isolated sensor system in the study. [Figure 9] The results of a comparative study between a strain-isolated sensor system and a commercially available sensor system are shown in the study in Figures 6a and 6b. [Figure 10] For example, we show the long-term performance of the strain-isolated sensor system for measuring physiological signals during real-life activities evaluated in the study in Figures 6a and 6b. [Figure 11a] 11a-11c show a detailed implementation of the classification algorithm of FIG. [Figure 11b] 11a-11c show a detailed implementation of the classification algorithm of FIG. [Figure 11c] 11a-11c show a detailed implementation of the classification algorithm of FIG. [Figure 12] 1 shows an experimental setup for measuring adhesive strength on a sensor device placed on a person's forearm. [Figure 13] We present a skin electrode impedance experiment that identified distortion as a cause of motion artifacts in wearable devices. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] Several references, which may include various patents, patent applications, and publications, are cited in the reference list and discussed in the disclosure provided herein. Citation and / or discussion of such references is provided merely to clarify the description of the present disclosure and is not an admission that any such reference is "prior art" to any aspect of the present disclosure described herein. For purposes of notation, "[n]" corresponds to the nth reference in the list. All references cited and discussed herein are incorporated herein by reference in their entirety and to the same extent as if each reference was incorporated by reference separately.

[0034] Several references, which may include various patents, patent applications, and publications, are cited in the reference list and discussed in the disclosure provided herein. Citation and / or discussion of such references is provided merely to clarify the description of the disclosed technology, and is not an admission that any such reference is "prior art" to any aspect of the disclosed technology described herein. For purposes of notation, "[n]" corresponds to the nth reference in the list. For example, [1] refers to the first reference in the list. All references cited and discussed herein are incorporated herein by reference in their entirety and to the same extent as if each reference was incorporated by reference separately.

[0035] Exemplary System 1 illustrates an exemplary wearable soft bioelectronic system device 100 configured with a strain isolated sensor 102 (shown as 102a) according to an exemplary embodiment. The strain isolated sensor 102 includes or is formed from a flexible substrate 104 having one or more low modulus layers 106 (shown including at least a first low modulus layer 106a and a second low modulus layer 106b), which is fixably connected to one or more sensor pads 108 (shown as 108a, 108b) and corresponding strain isolators 110 (shown as 110a, 110b) (also referred to as strain isolation structures). In the example shown in FIG. 1, the flexible substrate 104 can be made of silicone elastomer as the first low modulus layer and silicone gel as the second low modulus layer, the second low modulus layer having a lower modulus than the first low modulus layer. The flexible substrate 104 includes a contact portion (e.g., second low modulus layer 106b) that includes a breathable soft membrane material configured to adhere to a person's skin. One or more sensor pads 108 (shown as 108a, 108b) are preferably formed on or attached to the flexible substrate 104 to function either (i) as electrodes of a sensor or (ii) as connection pads for an integrated sensor that may contact or be in close proximity to the skin. Non-limiting examples of integrated sensors that may be included to be mounted on the pads 108 include optical sensors, photodiodes, capacitance, temperature sensors, combinations thereof, or other sensors described herein.

[0036] The location of the strain isolators 110 can correspond to the location of each sensor pad 108. The strain isolators 110 can have an outer dimension 112 that is shaped to form a perimeter around the sensor pads (e.g., 108a). By forming a perimeter 114 around the sensor pads (e.g., 108a), the strain isolators 110 can prevent or reduce temporary changes in pad impedance caused by skin strain and pad movement or slippage. An illustration of the concept is shown in schematic diagram 116. In schematic diagram 116, the sensor electrodes are shown formed on the elastomer without the strain isolators 114. When tension 118 (e.g., uniaxial strain) from temporary stretching of the skin or relative movement of the skin with the electrodes is applied to the elastomer 106', the resulting deformation is also observed on the sensor 120. In contrast, when tension 118 is applied to the strain isolated sensor 108 (shown as 108'), there is no corresponding tension or stretch observed at the strain isolated sensor 108'.

[0037] Plot 122 shows an example biophysical signal 124' obtained from a commercially available electrocardiogram (ECG) electrode. Plot 126 shows a biophysical signal 124 obtained from an ECG electrode configured with a strain isolator sensor as described herein. It can be observed in plot 126 that the same signal has a higher signal-to-noise ratio (SNR) (32.58 dB compared to 9.62 dB) and that artifacts 128 produced by body motion in plot 122 are not present in plot 126 providing a higher quality signal and higher SNR.

[0038] The low modulus layer 106 of the flexible substrate 104 can form a unitary structure that can bend or flex in a predetermined orientation. In some embodiments, the flexible substrate 104 can have a single low modulus layer with a graded or varying modulus between its upper region and its lower region. In other embodiments, the flexible substrate 104 can be formed of multiple layers, each with different modulus characteristics.

[0039] 1, the strain isolated sensor 102 (shown as 102a') may be formed of a thin low modulus silicone elastomer material (e.g., having an average thickness of less than 1000 μm) as the first low modulus layer 106a, and the second low modulus layer 106b is formed of a low modulus silicone gel material having a modulus value of less than 20 kPa. In fact, the modulus value of the first low modulus layer 106a is at least twice the modulus value of the second low modulus layer 106b.

[0040] In some embodiments, one or more sensor pads 108 can form an array, which can be disposed separately within the perimeter of the strain isolator 114, or an array having multiple sensor pads can be disposed within the strain isolator 114.

[0041] In some embodiments, the sensor pad 108 is configured as an open mesh stretchable electrode or stretchable pad that provides additional tension or strain relief to the pad structure due to applied tension 118 from the skin-sensor interaction.

[0042] Exemplary Isolated Sensor System The isolated sensor 102 may be configured as an isolated sensor device that includes IC components. In the example of Fig. 1, the isolated sensor 102a is configured with a flexible printed circuit layer 130 (also shown as "PCB" 130') that may carry front-end acquisition circuitry or components 132 (shown as "components" 132'), such as an amplifier (e.g., a transimpedance amplifier), a filter, and / or an analog-to-digital converter (ADC). In that example, the isolated sensor 102a includes an analog-to-digital converter 134, a filter 136, and an amplifier 138.

[0043] An isolated sensor device (e.g., 102a') can be coupled to an external sensor system including a controller 140, a network interface 142 (e.g., a wireless network interface), and additional sensors 144 (e.g., an inertial measurement unit (IMU) 144 including one or more inertial sensors). The controller 140, the network interface 142, and / or the additional sensors 144 can be mounted on a flexible printed circuit layer 130 along with front-end acquisition circuitry or components 132. Non-limiting examples of additional sensors that may be included in the sensor system include temperature sensors, magnetic-based sensors, and acoustic sensors.

[0044] In some embodiments, an isolated sensor device (e.g., 102a') can be fabricated as an integrated sensor system that includes the components described above. In the example shown in Figure 1, the isolated sensor device as a sensor system can include a controller 140, a network interface 142, and / or additional sensors 144 as part of the components 132'.

[0045] Exemplary Strain Isolation Structures 2A-2J each illustrate an example configuration of a strain isolation structure in the isolated sensor device or system of FIG. 1, according to an example embodiment.

[0046] 2A illustrates an exemplary strain isolated sensor 102 (shown as 200a) that includes a first low modulus layer 106a and a second low modulus layer 106b having a sensor pad 108 (shown as 202). A strain isolation structure 110 (shown as 204) is disposed on a top surface of the first low modulus layer 106a.

[0047] Figure 2B illustrates another exemplary strain isolated sensor 102 (shown as 200b) including the first and second low modulus layers 106a and 106b of Figure 2A and a strain isolated structure. The second low modulus layer 106b includes an electrode array 108 (shown as 206).

[0048] 2C illustrates another exemplary strain isolated sensor 102 (shown as 200c) including the first and second low modulus layers 106a and 106b of FIG. 2A and a strain isolated structure. The second low modulus layer 106b includes an electrode array 108 (shown as 208) having a sensor (e.g., an active integrated sensor component) coupled thereto. Non-limiting examples of active integrated sensor components include light emitting and photodiodes, capacitance, and / or temperature sensors.

[0049] 2D illustrates another exemplary strain isolated sensor 102 (shown as 200d) including the first and second low modulus layers 106a and 106b of FIG. 2A and a strain isolated structure. The flexible substrate further includes a third low modulus layer 212. The second low modulus layer 106b includes an electrode array 108 (shown as 202). In practice, the flexible substrate may further include additional layers.

[0050] 2E and 2F show another exemplary strain isolated sensor 102 (shown as 200e and 200f, respectively) including the first and second low modulus layers 106a and 106b of FIG. 2A and a strain isolated structure. Here, the strain isolation structure 110 (shown as 214) is disposed in a flexible substrate. In FIG. 2E, the strain isolation structure 110 (shown as 214) is disposed in a portion of the first low modulus layer 106a and a portion of the second low modulus layer 106b. In FIG. 2F, the strain isolation structure 110 (shown as 216) is disposed in a portion of the second low modulus layer 106b (e.g., a recess in the second low modulus layer).

[0051] 2D illustrates another exemplary strain isolated sensor 102 (shown as 200d) including the first and second low modulus layers 106a and 106b of FIG. 2A and a strain isolated structure. The flexible substrate further includes a third low modulus layer 212. The second low modulus layer 106b includes an electrode array 108 (shown as 202). In practice, the flexible substrate may further include additional layers.

[0052] 2G and 2H, another set of exemplary strain isolated sensors 102 (shown as 200g and 200h, respectively) are shown, each including the components illustrated in device 102a of FIG. 1, but additionally including an integrated circuit ("IC") 218. In FIG. 2G, the IC is mounted to a (flexible or conventional) printed circuit board 220, which is then mounted to sensor device 200g. In the example shown in FIG. 2G, PCB 220 is mounted to sensor device 200g via low modulus elastomer layer 130. In FIG. 2H, the IC is mounted directly to low modulus elastomer layer 130, e.g., via adhesive. The IC can be connected via printable traces, e.g., conductive paint. As described in connection with FIG. 1, IC (silicon or packaged) 218 ​​can include controller 140, network interface 142, and / or additional sensors 144 as part of components 132'.

[0053] 2I illustrates another example strain isolated sensor 102 (designated as 200i) that includes the components illustrated in the device 102a of FIG. 2H, but additionally has an integrated circuit ("IC") 218 ​​connected to another PCB circuit 222. The PCB circuit 222 includes an additional IC component 224 (e.g., silicon or IC) that may be configured to provide measurement signal data from the strain isolated sensor device 102a to a device processing unit or controller (e.g., for a smart watch or other wearable device). The IC 224 may be a device processing unit or controller configured to employ at least one of the electrocardiogram signal, heart rate signal, respiration rate signal, or combinations thereof in local or remote storage for analysis or for display via a display integrated into the PCB 222, for example.

[0054] The processing unit may be a standard programmable processor that performs arithmetic and logic operations necessary for the operation of the computing device. Multiple processors may be employed. As used herein, processing unit and processor refer to physical hardware devices that execute coded instructions to perform functions on inputs and create outputs, including, but not limited to, microprocessors (MCUs), microcontrollers, graphic processing units (GPUs), and application specific circuits (ASICs). Thus, although instructions may be discussed as being executed by a processor, the instructions may be executed simultaneously, sequentially, or otherwise by one or more processors. A computing device may also include a bus or other communication mechanism for communicating information between various components of the computing device.

[0055] It should be understood that the logical operations described above can be implemented (1) as a sequence of computer-implemented operations or program modules executing on a computing system, and / or (2) as interconnected machine logic circuits or circuit modules within a computing system. The implementation is a matter of choice dependent on the performance and other requirements of the computing system. Thus, the logical operations described herein are variously referred to as state operations, operations, or modules. These operations, operations, and / or modules can be implemented in software, firmware, special purpose digital logic, hardware, and any combination thereof. It should also be understood that more or fewer operations may be performed than those shown in the figures and described herein. These operations may also be performed in a different order than that described herein.

[0056] One or more programs may implement or utilize the processes described in connection with the presently disclosed subject matter, for example through the use of an application programming interface (API), reusable controls, or the like. Such programs may be implemented in a high level procedural or object-oriented programming language to communicate with a computer system. However, the programs may also be implemented in assembly or machine language, if desired. In any case, the language may be a compiled or interpreted language, and combined with hardware implementations.

[0057] Additionally, some or all of the components illustrated and described with reference to Figures 1-2I may be encapsulated in an encapsulation layer (not shown).

[0058] Exemplary Smart Watch with Strain-Isolated Sensors With reference to Figure 2J, embodiments of the present disclosure (e.g., those described with reference to Figures 1A-2I) can be packaged such that some or all of the components are inside or supported by a housing. In the exemplary embodiment 200j illustrated in Figure 2J, the components illustrated and described with reference to Figure 2I are positioned within a housing 226. The housing 226 can include or be adapted to connect to a strap (e.g., a wristband).

[0059] The housing 226 may also include one or more display devices 228 (e.g., digital screens) mounted on a PCB 230. The display PCB 230 may be connected to a PCB 222 via a connector 232 and a spacer 234. The PCB 222 may be connected to the strain isolated sensor device through an IC component 218 through a flexible cable 236. In the example shown in FIG. 2J, the strain isolated sensor device and system is configured as a wearable, flexible, hybrid electronic system (WFHE).

[0060] The smartwatch can be configured to perform measurements including optical, impedance, capacitance, or potential measurements through the stretchable pad. In the example shown in FIG. 2J, a schematic diagram 240 illustrates the operation of a wearable device (e.g., 200j) configured with a strain-isolated sensor (e.g., 102). According to the schematic diagram 240, either a PPG sensor (e.g., LED and photodiode) or electrodes (shown as 242) made with the strain-isolated sensor can acquire a biophysical signal along with an accelerometer signal (from accelerometer 244) that is provided to a local controller 246 (shown as “microcontroller” 246). The local controller 246 performs processing operations 252 to pre-process the acquired data to determine and display heart rate, ECG, and / or respiration rate measurements 254, as well as activity monitors 256. Heart rate measurements 254 can be determined using the acquired biophysical signals that are not affected by motion artifacts. Various activity monitors can be used, including those described herein.

[0061] Indeed, strain-isolated sensors can use the natural adhesive forces of a breathable soft membrane to provide skin-friendly, comfortable, continuous recording of ECG, HR, and RR on the skin, as well as real-time classification of various activities via, for example, machine learning algorithms.

[0062] In an alternative embodiment, the strain-isolated sensor devices and systems can be configured as wrist-worn, skin-conformal, soft material-enabled bioelectronic systems. An exemplary description is provided in Shinjae Kwon et al., "Skin-conformal, soft material-enabled bioelectronic system with minimized motion artifacts for reliable health and performance monitoring of athletes," Biosensors and Bioelectronics 151 (2020), which is incorporated by reference in its entirety.

[0063] Distortion Isolator Configuration Examples 3A-3E provide examples of strain isolator configurations. Figure 3A shows an exemplary strain isolator 110 (shown as 310) for a given sensor pad 108 (shown as 308) and its associated design. The dimensions and thickness of the strain isolator structure can be defined using the geometry of the electrodes and associated materials.

[0064] 3B-3E, embodiments of the strain isolated structure can include different configurations with sensor pads. Indeed, the strain isolated structure can be formed with different orientations, different shapes, and using different proportions. In FIG. 3D, multiple sensor pads, electrodes, sensors, or arrays thereof can be surrounded by the strain isolated structure.

[0065] In some embodiments, the first strain isolation structure has an inner dimension that extends beyond the first area of ​​the first pad.

[0066] In some embodiments, the first pad has a first shape and the first strain isolation structure has a second shape, and the first shape of the first stretchable pad is the same as the second shape of the first strain isolation structure.

[0067] In some embodiments, the first pad has a first shape and the first strain isolation structure has a second shape, and the first shape of the first pad is different from the second shape of the first strain isolation structure.

[0068] In some embodiments, the first pad has a shape selected from the group consisting of a square region, a rectangular region, a circular region, or an oval region.

[0069] Exemplary configurations for strain-isolated structures The strain-isolated structure can be designed based on the device thickness, material, and Young's modulus, and an example of this design is presented below.

[0070] Material Characterization. For a sheet modeled as a cantilever beam fixed at one end, the deflection from a tip force is calculated according to Equation 1:

number

[0071] where δ is the deflection of the free end, P is the force (320), L is the length of the beam, E is Young's modulus, I is the moment of inertia of the rectangular beam (323), and I=bh 3 From this formula, the elastic modulus can be calculated according to Equation 2:

number

[0072] where (P / δ) is the measured value from a bending test and is determined by a linear least squares fit of the data. An example of a bending test is described in connection with Figures 7a, 7b, plots 760 and 770. An exemplary elastic modulus E is 1.22 GPa.

[0073] Optimization of Strain Layers. Using the calculated elastic modulus E and the master mechanics equations, the minimum and maximum thicknesses can be calculated to minimize in-plane strains while allowing expected out-of-plane bending to maintain conformal contact with the skin. First, the elongation value of the middle section 322 can be calculated for a sheet modeled as a prismatic beam according to Equation 3:

number

[0074] where A is the cross-sectional area of ​​the rectangular beam and L is the inside dimension of the strain isolated structure. The two end sections can be modeled as supported beams with point loads and maximum deflection at the center given by Equation 4.

number

[0075] Together, the midsection stretch and edge bending add up to a total strain inside the perimeter of the strain-isolated structure. Combining equations 2-4 and solving for h gives us equation 5:

number

[0076] In the formula, h min is the elongation δ allow Example values ​​of P=1N, L=21 mm, E=1.22 GPa, w=5.5 mm, and δallow=0.64 mm, based on a 2% strain in the inner dimension L, are min =14.2μm.

[0077] The bending of the sheet and the adhesion forces (324) can then be modeled as a supported beam with a distributed load given by Equation 6:

number

[0078] In the formula, δ max is the deflection of the center of the beam, q is the distributed adhesive force per length, L is the length of the beam, E is Young's modulus, and I is the moment of inertia of the rectangular beam. To maintain conformal contact with the skin, the adhesive force needs to be greater than the stiffness of the beam for a given deflection. The deflection (following 324) can be determined through the relevant geometry and radii of curvature by Equation 7:

number

[0079] Substituting I, δmax and solving for h gives Equation 8.

number

[0080] In the formula, h max is the maximum sheet thickness capable of maintaining conformal contact with the skin when bent around a radius of curvature r. Exemplary values ​​of q=18.32 N / m, L=32 mm, E=1.22 GPa, b=11 mm, and r=15 mm based on adhesion testing with Silbione are h max =0.31mm.

[0081] Modeling skin strain. The circular electrode and the skin are in an unstrained steady-state configuration (326), and the skin is stretched at a stretch ratio λ 1 , λ 2The skin is under a biaxial strain (328) with . The area of ​​skin in contact with the electrodes remains the same. As the skin experiences strain, the electrodes move with the skin but remain relatively unstrained. This loading scenario causes the portion of the skin initially in contact with the electrodes to slip out of contact with the electrodes. If the skin strain is kept constant, a new steady state can be reached at the current skin / electrode interface. One source of MA is caused by the impedance change that occurs as the skin moves relative to the electrodes. The sensitivity of the skin / electrode interface was quantified by the change in area of ​​contact at the skin / electrode interface. The stretch ratio can be defined as:

number

[0082] where L is the original length and δ i is elongation, ε i is the distortion. Rearranging equation 9, we can write the new length according to equation 10:

number

[0083] From the diagram of biaxial strain 328, it can be shown that the draw ratio also defines the new half length according to Equation 11.

number

[0084] The change in area can be calculated using the area of ​​the ellipse minus the area of ​​the circular electrode according to Equation 12.

number

[0085] Substituting a and b, we obtain Equation 13.

number

[0086] The mesh electrode (330) has a radius r 1 can be modeled as a numbered array of N small electrodes with radius r 2 and the relationship is given by Equation 14.

number

[0087] Thus, the total change in area, for a given total electrode area, regardless of the discrete radii, is shown below to be directly proportional to the strain by Equation 15.

number

[0088] Exemplary Breathable Substrates 4 illustrates a method 400 for fabricating a breathable substrate for use in a strain isolated sensor device, according to an example embodiment. Method 400 can be used to fabricate an epoxy mold with a needle array. In step 402, holes are laser cut in an acrylic sheet. In step 404, the pattern is replicated in flexible DragonSkin needles. In step 406, the flexible DragonSkin holes are formed by a replication process. In step 408, a final casting mold of the epoxy needle array is created.

[0089] 4 also illustrates the complete epoxy needle array 414 and breathable layer 416 after curing and removal. Embodiments may include a smooth surface for mounting electrodes. An illustration of a CAD model 418 of the epoxy mold is also shown in FIG. 4, along with needle and spacing dimensions. An illustration of a section 422 of the epoxy mold (e.g., the epoxy mold of CAD model 418 shown in FIG. 4) includes non-limiting examples of needle 424 dimensions and spacing.

[0090] The method of fabricating a breathable substrate described in FIG. 4 can be used to form a substrate that minimizes skin irritation during and after use. Illustration 440 of FIG. 4 shows skin 442 from which an exemplary device 444 has been removed, with arrow 446 illustrating the path of device 444 being peeled away from skin 442. Skin 442 shows minimal irritation, indicating that the device is breathable. Indeed, this exemplary device can include enhanced breathability compared to devices fabricated using other methods, and can be suitable for continuous data to be recorded during various daily activities. Overall, the exemplary embodiment of the SIS shows unique performance in distortion reduction and continuous recording of practically applicable health data compared to existing wearable ECG monitoring systems.

[0091] Exemplary Methods for Fabricating an Isolated Sensor Device FIG. 5A illustrates an exemplary fabrication method 500 for the isolated sensor device of FIG. 1 according to an exemplary embodiment. In the example shown in FIG. 5A, the method 500 includes preparing an elastomer (e.g., 8 g of Ecoflex 00-30 (Smooth-On)) (502), pouring the elastomer into a container (e.g., a polystyrene petri dish to create a 500 μm thick elastomer film), and curing it (e.g., curing Ecoflex at room temperature for 5 hours). Then, the method 500 includes preparing an elastomer gel (e.g., 8 g of silbione gel A-4717 (FactorII)) (504), pouring it onto the Ecoflex, curing it (e.g., for 24 hours at room temperature), and cutting it to an appropriate size. Then, the method 500 can include fabricating a PCB layer (506). The elastomer can be inverted onto a clean surface with the Ecoflex facing up and the circuitry can be attached using a thin film of silbione gel A-4717.

[0092] The method 500 can then include attaching (508) a strain isolation layer (e.g., using a thin encapsulation layer of Ecoflex without attaching any material directly onto the electrodes). The method 500 can then include positioning (510) the electrodes, for example, by inverting the elastomer onto a surface (e.g., by having a notch in the circuitry so that it is horizontal with the silbione layer facing up). The surface can be washed with IPA. The method 500 can then include attaching the circuitry IC (e.g., using a thin film of silbione gel A-4717).

[0093] The method 500 can then include transferring the flexible electrodes to the silbione (eg, by using water-soluble tape and removing the water-soluble table with deionized water).

[0094] The method 500 may then include connecting the flexible electrodes to the circuit IC using a flexible conductive film (ACF) (e.g., fast drying silver paint (TedPella)). The method 500 then includes attaching the battery (514). The method 500 then includes encapsulating (516) the exposed portions of the ACF connections (e.g., with Ecoflex).

[0095] Exemplary Methods for Fabricating Stretchable Sensor Electrodes or Pads FIG. 5B illustrates an example fabrication method 520 for a stretchable sensor electrode or pad that may be used in a strain isolated sensor device, according to an example embodiment.

[0096] In the example of FIG. 5B, the method 520 includes forming (or providing) a Si wafer (522). The method 520 then includes spin coating the wafer with PDMS (524). The method 520 can then include spin coating polyimide onto the PDMS (526). The method 520 can then include depositing a gold layer and a chrome layer (528). The method 520 can then include performing PR patterning (530). The method 520 can then include performing a gold / chrome etch (532). The method 520 can then include removing the PR and the polyimide that was spin coated (566) on the exposed circuitry. The method 520 can then include performing PR patterning 568 (538) and then etching the portions exposed to the circuitry (540). The method 520 can then include removing the photoresist (542).

[0097] Experimental Results and Examples 6a and 6b illustrate studies that were performed to develop and evaluate health monitoring devices (eg, 100) constructed from strain isolation materials and structures.

[0098] This study developed a new class of strain-isolated physics, rigid-soft material integration, and integrated system packaging to enable an integrated, wireless, long-term usable health monitor. Through analytical, computational, and experimental evaluation, the study observed that the developed wireless wearable ECG electronic system (e.g., 100) can physically limit excessive movement artifacts (MA) during continuous real-life daily activities without losing data. The studied strain-isolated soft bioelectronics (SIS) use a breathable soft membrane to provide natural adhesion that can provide skin-friendly, comfortable, and continuous recording of ECG, heart rate (HR), and respiration rate (RR) on the skin, as well as real-time classification of various activities via machine learning algorithms.

[0099] The study experimentally evaluated the strain-isolated soft bioelectronics against two physiological signal monitoring commercially available wireless devices. The study observed the exceptional performance of the SIS in maintaining conformal skin contact, enhanced comfort, and high quality data ignoring MA effects. The SIS was tested simultaneously with the two commercially available wireless devices and demonstrated MA reduction during various physical activities of daily living. Finally, the devices were worn by multiple participants for over 8 hours, all while performing various daily activities ranging from desk work to exercise.

[0100] A summary of the design overview of the SIS employed in the study, structural layout, strain isolation mechanics, and device functionality is provided in Figure 6a, Figure 6b. The integrated soft imperceptible system (shown as 100a in Figure 6A) can have a very small form factor that can be securely and discretely adhered to the chest area for continuous health and movement monitoring throughout various daily activities.

[0101] Initial Skin Electrode Impedance Analysis. A systematic experimental study was conducted to measure skin electrode impedance first to identify the causes of impedance changes in the wearable device. FIG. 13 shows the test setup for wire 1330 disturbance, direct pressure on the electrode 1332, and pressure on the skin 1334 surrounding the electrode. Plot 1340 shows the percentage of impedance change for each category of disturbance, relative to the initial value. Plot 1350 shows a plot of measured impedance versus time for a gel electrode, and plot 1360 shows a plot of measured impedance change versus time for a dry electrode 1360. Impedance testing was performed at 100 kHz.

[0102] It was observed that among the three candidates (sensor connection wire, skin-mounted electrode, and adjacent skin), the measured impedance experienced the most significant disturbance from the applied strain to the electrode. Strain-isolated sensors were developed, in part, to address this finding.

[0103] Strain isolation device. The study developed a pair of strain isolators to reduce the applied strain, with a strain isolator positioned on each electrode. The study also developed a pair of nanomembrane mesh electrodes for direct contact with the skin to measure non-invasive physiological signals such as ECG, HR, and RR. The study designed the open mesh stretchable electrodes to withstand at least 100% excessive tensile strain without failure. The study also developed a health monitoring device with a bottom layer having an extremely low modulus silicone gel (e.g., E=5 kPa) to provide excellent adhesive properties to adhere the device to the skin, in which the top layer has a low modulus silicone elastomer (e.g., E=68.9 kPa) to provide a sturdy platform to mount the circuitry, making the device more comfortable to handle and preventing unwanted sticking to clothing. In Figure 6a, Figure 6b, the studied device is shown as 610.

[0104] The studied device 610 included a miniaturized PCB with a rechargeable lithium-ion battery (3.7V, 110mAh) where the PCB was encapsulated in silicone elastomer. The studied device was configured to charge during recording sessions using a magnetic connection protruding from the PCB base through the elastomer. The circuitry was mounted in the center of a thin layer of silicone gel to allow a larger range of bending without skin peeling. The studied device included strain isolators placed above each electrode to surround the electrodes and protect them from excessive or sudden strain while exposing the elastomer directly on the electrodes to freely maintain conformal contact at the skin-electrode interface. The studied device 610 was configured to be placed on the chest area and was evaluated under various daily activities such as standing, walking, running, and sudden arm movements.

[0105] Mechanical Properties The studied device 610 was constructed with all necessary components and a rechargeable battery to have mechanical flexibility and stretchability. Panel 650 shows the studied device 610 being able to twist, bend, and stretch beyond the expected deformation of the intended application site on the upper torso.

[0106] The data processing system and workflow diagram 660 shows the data processing workflow for the strain isolated sensor 610 and its corresponding data acquisition system, which included a portable smart device 662 for signal monitoring / storage. Measurement data from the electrodes (e.g., sensor pad 108 shown as "nano membrane electrodes" 664) and on-board accelerometer (shown as "6-axis accelerometer" 666) are transmitted via Bluetooth circuitry (668) to the user's smartphone or tablet 662 for real-time display or recording of physiological signals. Circuitry 690 shows the layout of the studied device (31 mm x 21 mm), including antenna, accelerometer, Bluetooth microcontroller, voltage regulator, charging / power management circuitry, amplifier, ADC circuitry, and electrode inputs.

[0107] The handheld smart device 662 was configured with a specially designed application to display real-time ECG data, 3-axis angular orientation data, and 3-axis acceleration. During the study, ECG annotations and long-term health data were calculated at the end of each session.

[0108] Performance Validation. Figures 7a, 7b show the analytical framework for strain isolation physics and computational modeling. Model 702 shows a portion of skin and a single circular electrode subjected to biaxial strain. The shaded area (exaggerated for emphasis) represents human skin previously in contact with the electrode before stretching. Model 702 shows that the area change (δA) is directly proportional to the local strain at the electrode. The strain defines a stretch ratio (λ1, λ2) calculated from the final dimensions (a, b) and the electrode radius (r). This is applicable to electrodes of any size. Mesh electrodes that can stretch with the skin are also subjected to disturbances proportional to the strain at each mesh pad. The objective of the modeling is to prevent temporary changes in contact impedance caused by skin strain and electrode movement or slippage.

[0109] Finite Element Analysis. This analysis quantified the stretch ratio and the proportional relationship between strain and area change. A finite element analysis (FEA) was performed and the results are shown in the results output 712 with a tensile strain (15%) applied in the vertical direction to mimic stretched human skin.

[0110] The commercial software ABAQUS was used to validate the analytical calculations and optimize the mechanical performance. The three main components considered were the elastomer substrate, the PCB circuitry, and the strain isolation layer. All components were meshed using hexahedral elements, namely, elastomer (C3D8RH), PCB circuitry (C3D8), and strain isolation layer (C3D8R), with a total of 787 elements and a total of 1876 nodes. The elastomer substrate was meshed using a coefficient D 1 =10.152, C 10 =4.8E -02 The material was modeled as a hyperelastic Neo-Hooke material with the elastic modulus (E) and Poisson's ratio (ν) of EPCB = 24 GPa, νPCB = 0.12, ESIL = 1.22 GPa, and νSIL = 0.43.

[0111] The FEA results showed that without an integrated SIL, the bottom electrode experienced a strain of 36%, while the top electrode, protected by the strain isolator, had a calculated strain of 3%. The results also showed that the change in contact area of ​​each electrode was proportional to the strain, meaning that the total area of ​​skin sliding through each tiny electrode pad on the bottom electrode can be more than 12 times the change that occurs in the top electrode. It is clear from the FEA results that the strain isolator has a smaller change in strain and contact area.

[0112] Physical Experimentation. This study hypothesized that the strain isolator should be stiff enough to withstand in-plane strain, yet flexible enough to bend out of plane for conformal lamination to non-flat human skin. Physical experiments were performed using sheets of polypropylene to fabricate strain isolators. The strain isolator had a Young's modulus (E) of E=1.22 GPA using a bending test. Plot 760 shows the force versus displacement measurements, and plot 770 shows the force versus displacement measurements for the converted force and Young's modulus.

[0113] Adhesion Test. Plot 720 shows the results of the adhesion test from thickness versus bend radius for two samples for each trial. The area 722 in the plot is bounded at the top by analytical calculations for the adhesion energy of the elastomer. The results showed that a maximum allowable strain isolator thickness (for this material) of about 0.3 mm is capable of maintaining adhesion while bending around an assumed radius of 15 mm. The results also showed that the minimum thickness that allows for reducing strain in the electrodes is about 14 μm. An explanation for determining the strain isolator parameters is discussed in connection with FIG. 3A.

[0114] FIG. 12 shows an experimental setup 1202 for measuring the adhesion strength of a sensor device (with and without strain isolators) placed on a person's forearm. Plot 1204 shows the adhesion versus displacement measurements for the two tested cases. The sensor device with the strain isolator was observed to have an adhesion strength of 0.2614 N / cm on average (e.g., 34 mm to 70 mm when the initial stiffness from the circuit components is overcome) compared to an adhesion strength of 0.1832 N / cm for the sensor device without the strain isolator.

[0115] Simulation of Principal Strains and Mises Stresses Figures 7a, 7b show additional FEA results 730 for the evaluation of principal strains and Mises stresses for maximum and minimum SIL thicknesses. Results 732 for a strain isolator device (0.3 mm thick) show a 3% strain in the electrodes and a stress of 4.9 MPa within the SIL. Results 734 for a strain isolator device (14 μm thick) show a 21% strain in the electrodes and an increase in internal stress of 58 MPa, which is higher than the yield strength of the material and results in partial plastic deformation. The study followed this evaluation to build a device 610 with a 0.3 mm thick strain isolator.

[0116] Evaluation of Daily Activities. To evaluate the performance of the fabricated strain-isolated sensor, this study conducted a series of short, reproducible comparative trials on an indoor course. Each trial (each 3 minutes long) consisted of 30 second intervals for a series of activities: idle (0 mph), walking (2 mph), brisk walking (4 mph), jogging (6 mph), walking (2 mph), and idle (0 mph). The same device was used for a total of eight trials, four of which were performed before the strain isolators were mounted on the bare elastomer substrate, and four trials were performed with the strain isolators integrated into the sensor device. Plot 740 shows representative data. It can be observed that the strain-isolated sensor achieved a clear reduction in motion artifacts compared to the bare elastomer case without the strain isolator structure.

[0117] Plot 750 shows the calculated signal-to-noise ratio (SNR) from all trials. It can be observed that the average SNR reduction from idle to jogging was 30.3-22.0 dB for the distortion-isolated devices, whereas it was 31.6-16.9 dB for the non-distortion-isolated devices.

[0118] Signal Processing and Classification Performance. FIG. 8 shows results from an evaluation of the signal processing and classification performance of a strain-isolated sensor system in a study. The study employed a sensor system including a pair of electrodes, a three-axis accelerometer, and a three-axis gyroscope. Flowchart 802 shows the signal processing operations for deriving ECG annotations, HR data, RR data, and activity classification. Examples of acquired signals are shown: HR peak finding (according to graph 822), RR peak detection (824), running averages of HR and RR (826), and accelerometer data (828) with activity labels (idle, walk, brisk walk, and jog) for a 3-minute test routine.

[0119] According to flow chart 802, the raw ECG signal was first filtered using a 0.5-30 Hz band pass filter to remove high frequency noise such as low frequency baseline drift movement and chest muscle activity caused by arm movement. A peak finding algorithm was used to identify local maximum data points known as R-peaks in the ECG waveform, shown as dots in HR peak finding graph 822. The HR data was averaged using a 10 second window. At the same time, the HR peaks were determined using cubic spline interpolation. The resulting waveform, shown as a red dashed line in 824, can be attributed to the cyclic expansion and contraction of the chest during breathing, which caused the electrodes to move farther away from each other and farther away from the heart with each inhalation. This change in R-peak amplitude can be processed using a separate peak finding algorithm to identify the RR peaks (black triangles in RR peak detection 824), which were averaged using a 30 second window. The running averages of HR and RR (826) were displayed for the entire 3 minute test routine in units of heart beats per minute and breaths per minute, respectively.

[0120] Separately, the accelerometer data 828 was processed to classify activity levels. The three-axis linear acceleration is expressed as: atotal=sqrt(a x 2 +a y 2 +a z 2 ) was used to calculate the total linear acceleration, shown as the black line, which provided a consistent measure of body movement independent of the device's orientation. A machine learning algorithm based on a residual convolutional neural network (CNN) classified the user's activities, shown as idle (832), walking (834), brisk walking (836), and jogging (838) in the accelerometer data. The total time in each category was used to track daily activity.

[0121] Classification Algorithm. Diagram 840 shows a high-level CNN configuration used for classification of 6-axis accelerometer / gyroscope data. As shown in graph 850, 12 recorded datasets were used to train the model, giving an overall accuracy of 99.3% for recognizing real-time user activity. The detailed model with the required layer components, residual connections, and training test process is shown in Fig. 11a, Fig. 11b, Fig. 11c.

[0122] 11a, 11b, and 11c show a detailed example of the classification algorithm of FIG. 8. An ActivityResNet model 1102 is shown, which includes a set of convolutional and deconvolutional layers. A schematic diagram 1130 shows a detailed implementation of the ActivityResNet model 1102. Each individual convolutional layer is shown in the model 1110. A graph of the test loss and training loss 1120 is also shown. This study observed that an embodiment including an integrated SIS can successfully measure multiple health-related data by using a computing device (e.g., a user's smartphone). Primary data available in real time, such as average HR or activity score, can help patients or athletes evaluate their daily health status. More than that, access to raw data allows health care providers to learn much more about the patient's physiological status through deeper analysis performed after the recording session is over. The CNN activity classifier was trained using data from one participant, giving a reference point that can be used to classify data from any participant, ensuring a baseline score for each activity. This model can be retrained to adapt to individual movement patterns or desired fitness goals.Clearly, the advantage of a chest-mounted, strain-isolated sensor is that it can be more accurate in ECG, HR, RR, and activity detection than existing wrist-worn, commercially available health monitors.

[0123] Comparative Study. This study validated the performance of the strain-isolated sensor in comparison with commercially available devices. The study utilized two commercially available wireless cardiac monitors via simultaneous ECG recordings in the chest area. Figure 9 shows the results from the comparative study.

[0124] In schematic 902, the strain isolated device 610 is shown together with a commercially available all-in-one device 906 (MAX-ECG Monitor, Maxim Integrated) placed on the chest. Both devices were observed to have a similar footprint, but the commercially available all-in-one device 906 included a stiffer adhesive gel electrode patch backed with fabric that could be observed to constrict and peel away from the skin. Strain experienced over the entire length of the patch would likely become concentrated at the edges where the circuitry is connected, resulting in peeling (908) directly on the electrodes. This observation highlights the advantage of the SIS in that the stiffness is specifically tailored at the electrodes while still allowing the remainder of the device to have a conformal contact to the skin that can withstand body movement.

[0125] Plot 910 shows the SNR results from four simultaneous tests with the average idle values ​​normalized for comparison. The average SNR reduction for "idle" and "jogging" was 25.7 dB and 21.6 dB, respectively, for the commercial device, and 25.7 dB and 12.1 dB for the distortion isolated device. This is a 16% signal quality reduction for the SIS compared to 53% for the commercial device when compared to their respective baseline idle signals.

[0126] Plot 920 shows a comparison of raw ECG plots (2 seconds) for idle, walking, and jogging from one trial. The results show that as the user's activity level increases, the motion artifacts increase in the commercial device, but not in the case of the strain-isolated sensor.

[0127] Plot 930 shows a complete exercise session with two devices: normalized ECG waveform (top), extracted HR and RR (middle), and acceleration data with corresponding activity (bottom).

[0128] Plot 940 shows a comparison of measured ECG data from a strain isolated device and a commercial device when the subject had constant arm movement. The plot shows significant motion artifacts with the commercial device.

[0129] A second commercially available wireless device with gel electrodes (BioRadio, Great Lakes NeuroTechnologies) was also evaluated. As described by previous articles [23, 30, 36], the BioRadio with its hanging wires and gel electrodes showed a significant reduction in SNR and more variability, as well as MA vulnerability.

[0130] Long-Term Performance Evaluation. Figure 10 shows the results of a study to evaluate the long-term performance of a strain-isolated sensor system to measure physiological signals during real-life activities including, for example, rest (1004), desk work (1006), housework (1008), and exercise (1010).

[0131] Plot 1022 shows a representative set of recorded ECG data for eight consecutive hours of real-time continuous recording of physiological data. Plot 1024 shows HR and RR data recorded over the same period. Plot 1024 shows the classification output of a machine learning trained over the same period. No motion artifact issues or events were observed.

[0132] Plot 1040 shows a comparison of the percentage of time spent in the four types of activity. To facilitate long-term continuous physiological monitoring on the skin, the strain isolation device was configured for continuous skin-electrode contact and low impedance. The device was also configured to maximize air permeability to minimize excess sweating during recording sessions by employing a breathable, long-term, wearable, perforated substrate. Image 1050 shows the substrate of the strain isolation device studied. The soft elastomeric substrate 1052 contains an array of stretchable ventilation holes. Image 1056 shows a cross-section of the holes.

[0133] Consideration Cardiovascular disease affects 48% of the adult population in the United States and remains the leading cause of death worldwide [1]. Portable, long-term, continuous monitoring of ECG is urgently needed to detect the onset of various arrhythmias that may occur at any time during daily activities. Many ambulatory ECG devices have been developed to provide a smaller form factor than the gold-standard Holter monitor. Collecting high-quality data outside of clinical settings remains challenging due to motion artifacts. ECG motion artifacts (MA) are defined here as temporary changes in the measured voltage caused by the movement of the sensor and / or the body on which the sensor is located. For example, walking creates a downward force on the skin and the ECG device with each step, which causes a temporary stretching of the skin and a relative movement of the skin with the electrodes. These two disturbances together change the half-cell potential of the skin, as well as the contact impedance with the electrodes, respectively [2]. These temporary changes in the measured voltage can have the same amplitude and frequency as the heart rate [3], making them difficult to distinguish from many physiological signals. Software algorithms and signal filtering are commonly used to improve signal quality, but they can be computationally expensive, especially for long-term monitoring, and they still only provide an estimate of the actual biological signal [4-7]. Filtering can also be done on any signal as a secondary improvement method, but it cannot improve the raw data. Another solution is to use a pressurized, rigid strap to limit device movement on the skin [8, 9]. However, this method causes severe discomfort and restrictions on the user's activities. When the user relaxes the strap pressure, the sensor loses proper contact with the skin, resulting in signal degradation. Some devices use conductive gels to reduce impedance or strong adhesives to reduce movement, but this often causes skin rashes after extended use or even damages the skin when removed [10-14]. Recent studies have shown the feasibility of applying dry, adhesive-free electrodes that make a gentle layering on the skin [15-17].However, they are still subject to excess MA caused by the stiffness of multiple wires, sensors and electronics, as well as electrode movement on the skin. Dry electrodes are particularly sensitive to skin strain and vibration induced by physical movement during walking, reaching, and other daily activities [4, 18-20]. One improvement in dry electrode design has been the development of thin-film open mesh electrodes that can stretch with the skin. Previous studies have shown some reduction in MA using mesh electrodes compared to rigid electrodes due to conformal contact [21-25]. Other studies have shown a correlation between signal quality and electrode contact area [25-27]. This led the authors to show that skin strain at the electrode is the primary cause of MA for dry electrodes, focusing on the mechanisms that lead to changes in conformal contact and electrode contact area. Recently reported devices have used soft materials [28-32] or serpentine patterns [33-35], but previous studies have not shown the ability of wearable devices to significantly reduce MA caused by skin-electrode strain from external sources.

[0134] The embodiments of the present disclosure include a fully integrated wireless long-term use system (SIS) that can physically limit MA during multiple hours of real-life activities. The embodiments of the present disclosure can include a breathable soft membrane with natural adhesion to provide skin-friendly, comfortable, and continuous recording of multiple biopotentials on the skin. The work described herein includes materials, mechanical design, and soft packaging strategies along with details of the strain mechanics at the skin-electrode interface. In addition, the work described strain isolation design parameters necessary for the device to maintain conformal contact to the skin while simultaneously protecting the electrodes from excessive skin strain and vibration during patient movement. A set of computational and experimental studies validate the mechanical reliability of the flexible and stretchable device. An embodiment of a signal processing workflow is also disclosed and described, showing monitoring of ECG, heart rate (HR), respiration rate (RR), and activity classification. In the work described herein, the SIS was simultaneously tested with two commercially available wireless devices to show MA reduction during various physical activities in daily life. In one aspect of the study described herein, the device was worn by multiple participants for over 8 hours. During the 8-hour period, the participants performed a variety of daily activities ranging from desk work to exercise. In the study described herein, the exemplary embodiment of the soft wearable SIS was shown to be superior in performance for high-quality, continuous, wireless detection of multiple physiological data without loss of MA-based data.

[0135] This is a continuation of our previous efforts to record high-quality physiological data using skin-friendly devices [15, 23, 30, 36]. Some device designs presented by other groups aim to reduce strain at the electrodes using hard adhesive patches or backings [8, 9], but they result in increased device stiffness and rigidity, losing conformal electrode contact to the skin as well as consistent signal quality. In contrast, the exemplary strain-isolated sensor maintains the quality of the skin-electrode contact through a soft elastomeric membrane while limiting excessive strain transfer to the electrodes through strain isolator integration. Thus, the strain-isolated sensor can provide continuous, high-quality health monitoring during real-life activities in home or clinical environments.

[0136] Although exemplary embodiments of the present disclosure have been described in detail herein in certain instances, it should be understood that other embodiments are contemplated. Thus, the present disclosure is not intended to be limited in scope to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The present disclosure is capable of other embodiments and of being practiced or carried out in various ways.

[0137] It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Ranges may be expressed herein as from "about" or "approximately 5" one particular value, and / or to "about" or "approximately" another particular value. When such a range is expressed, other exemplary embodiments include the one particular value and / or the other particular value.

[0138] "Comprising" or "containing" or "including" means that at least the named compound, element, particle, or method step is present in a composition or article or method, but does not exclude the presence of other compounds, materials, particles, or method steps, even if other such compounds, materials, particles, or method steps have the same function as the named one.

[0139] In describing the exemplary embodiments, technical terms will be used for clarity. Each term is intended to assume the broadest meaning of that term as understood by those skilled in the art and to include all technical equivalents that operate in a similar manner to achieve a similar purpose. It should also be understood that the reference to one or more steps of a method does not preclude the presence of additional or intervening method steps between those steps explicitly identified. The steps of the method may be performed in a different order than described herein without departing from the scope of the present disclosure. Similarly, it should also be understood that the reference to one or more components in a device or system does not preclude the presence of additional or intervening components between those components explicitly identified.

[0140] As discussed herein, a "subject" may be any applicable human, animal, or other organism, living or dead, or other biological or molecular structure or chemical environment, and may relate to a particular component of the subject, such as a particular tissue or bodily fluid of the subject (e.g., human tissue within a particular area of ​​the body of a living subject), which may be in a particular location of the subject, referred to herein as an "area of ​​interest" or "region of interest."

[0141] It is to be understood that, as discussed herein, the subject may be a human or any animal. It is to be understood that the animal may be of any of a variety of applicable types, including, but not limited to, mammals, veterinary animals, livestock animals, or pet-type animals. By way of example, the animal may be a laboratory animal (e.g., rats, dogs, pigs, monkeys), etc., specifically selected to have certain characteristics similar to humans. It is to be understood that the subject may be, for example, any applicable human patient.

[0142] The term "about" as used herein means approximately, in the region of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the stated numerical values. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 10%. In one embodiment, the term "about" means ±10% of the numerical value of the number with which the term is used. Thus, about 50% means within a range of 45% to 55%. Numerical ranges recited herein by endpoints include all numbers and fractions subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.90, 4, 4.24, and 5).

[0143] Similarly, numerical ranges recited herein by endpoints include the subranges subsumed within that range (e.g., 1 to 5 includes 1 to 1.5, 1.5 to 2, 2 to 2.75, 2.75 to 3, 3 to 3.90, 3.90 to 4, 4 to 4.24, 4.24 to 5, 2 to 5, 3 to 5, 1 to 4, and 2 to 4). It is also to be understood that all numbers and fractions thereof are presumed to be modified by the term "about."

[0144] The following patents, applications, and publications listed below and throughout the specification are hereby incorporated by reference in their entireties. [1]Benjamin,E.J.et al.Heart Disease and Stroke Statistics-2019 Update:A Report From the American Heart Association.Circulation 139,e56-e528 (2019). [2]Zhang,Z.et al.Adaptive motion artefact reduction in respiration and ECG signals for wearable healthcare monitoring systems.Medical and Biological Engineering and Computing 52,1019-1030 (2014). [3]Kirst,M.,Glauner,B.&Ottenbacher,J.Using DWT for ECG motion artifact reduction with noise-correlating signals.Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society,EMBS,4804-4807 (2011). [4]Liu,Y.&Pecht,M.G.Reduction of Skin Stretch Induced Motion Artifacts in Electrocardiogram Monitoring Using Adaptive Filtering.Proceedings of the 28th IEEE EMBS Annual International Conference (2006). [5]Kalra,A.&Lowe,A.Development and validation of Motion Artefact Rejection System (MARS) for electrocardiography using novel skin-stretch estimation approach.Sensors and Actuators,A:Physical 301,111726-111726 (2020). [6]Zhang,H.&Zhao,J.Motion artefact suppression method for wearable ECGs.Feature Engineering and Computational Intelligence in ECG Monitoring,73-88 (2020). [7]Lee,S.C.&Kim,S.M.Motion artifact reduction algorithm in wearable healthcare system.Journal of Medical Devices,Transactions of the ASME 10 (2016). [8]Porr,B.&Howell,L.R-peak detector stress test with a new noisy ECG database reveals significant performance differences amongst popular detectors.bioRxiv,1-27,doi:10.1101 / 722397 (2019). [9]MAX-ECG-MONITOR User Guide.15 (2018).

[10] Barrett,P.M.et al.Comparison of 24-hour Holter monitoring with 14-day novel adhesive patch electrocardiographic monitoring.American Journal of Medicine 127,95.e11-95.e17 (2014).

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Claims

1. A system comprising: A flexible substrate having two or more low elastic modulus layers including an upper low elastic modulus layer and a lower low elastic modulus layer, the flexible substrate having a first side on the upper low elastic modulus layer and a second side on the lower low elastic modulus layer, the second side being configured as a breathable soft film configured to directly contact and adhere to a human skin area; a flexible substrate; One or more pads fixedly attachable to the second side of the flexible substrate, the one or more pads including a first pad attached to the second side over a first area, the one or more pads each having a side exposed to directly contact a portion of the skin area; one or more pads; One or more strain isolation structures fixedly attachable to the upper low elastic modulus layer, including a first strain isolation structure, the first strain isolation structure being attached to the upper low elastic modulus layer in an area corresponding to the first area of the first pad and shaped to have an outer dimension forming an outer periphery around the first pad; a system comprising.

2. The system according to claim 1, wherein the first strain isolation structure has an inner dimension extending beyond the first region of the first pad.

3. The system according to claim 1, wherein the first pad has a first shape, the first strain isolation structure has a second shape, and the first shape of the first pad is the same as the second shape of the first strain isolation structure.

4. The system according to claim 1, wherein the first pad has a first shape, the first strain isolation structure has a second shape, and the first shape of the first pad is different from the second shape of the first strain isolation structure.

5. The system according to claim 1, wherein the first pad has a shape selected from the group consisting of a square region, a rectangular region, a circular region, or an oval region.

6. The system according to claim 1, wherein the first pad has a planar geometric shape.

7. The system according to claim 1, wherein the upper low elastic modulus layer comprises a thin low elastic modulus silicone elastomer material having an average thickness of less than 1000 μm.

8. The system according to claim 1, wherein the lower low elastic modulus layer comprises a low elastic modulus silicone gel material having an elastic modulus value of less than 20 kPa.

9. The system according to claim 1, wherein the upper low elastic modulus layer comprises a first material having a first elastic modulus value, the lower low elastic modulus layer comprises a second material having a second elastic modulus value, and the first elastic modulus value of the upper low elastic modulus layer is at least twice the second elastic modulus value of the lower low elastic modulus layer.

10. The system according to claim 1, wherein the one or more pads form an array.

11. The system according to claim 1, wherein the one or more pads are configured as open mesh stretchable electrodes.

12. The system according to claim 11, wherein the open mesh stretchable electrodes comprise a plurality of stretchable pads connected together by a meshed connection that is curved or serpentine.

13. The system according to claim 1, wherein the system is configured as a smartwatch configured for at least one of optical measurement, impedance measurement, capacitance measurement, or potential measurement through the stretchable pads.

14. A second stretchable pad attached to the second side over a second area, and A second strain isolation structure attached to the upper low elastic modulus layer in a third area corresponding to the second area of the second stretchable pad and shaped to have an outer dimension that forms an outer periphery around the second stretchable pad. The system according to claim 1, further comprising.

15. One or more pads including the first pad are fixedly attached to the second side of the flexible substrate over a second area to form a pair of stretchable contacts, The system is The system according to claim 14, further comprising an active integrated sensor component coupled to the pair of stretchable contacts.

16. The system according to claim 15, wherein the active integrated sensor component includes a light emitting diode or a photodiode.

17. The system according to claim 1, wherein the system is configured as an electrocardiogram probe.

18. The system according to claim 17, wherein the electrocardiogram probe includes a pair of the flexible pads, a multi-axis accelerometer, and a multi-axis gyroscope.

19. The electrocardiogram probe of claim 17, further comprising an optical sensor, a photodiode, a capacitance, and / or a temperature sensor.

20. The system of claim 1, further comprising an active integrated chip assembly mounted on the flexible substrate, the active integrated chip assembly comprising at least one or more active integrated circuits including a transimpedance amplifier circuit and a digital-to-analog converter.

21. The system of claim 20, further comprising a encapsulation layer encapsulating the active integrated chip assembly.

22. The system of claim 20, wherein the active integrated chip circuit further comprises a local processing unit or controller configured to provide measured signal data to a device processing unit or controller.

23. The system of claim 21, wherein the device processing unit or controller is configured to employ at least one of an electrocardiogram signal, a heart rate signal, a respiration rate signal, or a combination thereof obtained through an electrode or sensor associated with the one or more pads.

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