Determination of susceptibility to diabetic foot ulcers

Abstract

To provide a device and method for measuring capacitance as an indicator of susceptibility to diabetic foot ulcer formation.SOLUTION: The apparatus includes a plurality of electrodes embedded in a substrate, wherein a pair of electrodes can form a capacitive sensor configured to measure a first capacitance of a first region of tissue proximate to the capacitive sensor, circuitry electrically coupled to the electrodes, a processor electrically coupled to the circuitry, and a non-transitory computer readable medium, wherein the non-transitory computer readable medium is electrically coupled to the processor and includes instructions stored thereon.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 62 / 454,482, filed February 3, 2017, and U.S. Provisional Application No. 62 / 521,917, filed June 19, 2017, each of which is incorporated herein by reference in its entirety.

[0002] The present disclosure provides devices and methods for assessing the foot of a patient at risk for developing a diabetic foot ulcer. [Background technology]

[0003] Diabetic foot ulcers are the cause of more hospitalizations than any other complication of diabetes. Nonenzymatic glycation induced by elevated blood glucose levels leads to stiffening of ligaments and increased cross-linking in collagen. These conditions can lead to damage to cell walls and blood vessels, resulting in an initial increase in extracellular fluid (ECF) volume. Peripheral neuropathy causes loss of protective sensation and loss of muscle coordination in the feet and legs. Neuropathy can cause increased mechanical stress in the foot during walking, which, combined with diabetes-induced tissue weakening, can withstand and progress to tissue death if the stress is not reduced. Neuropathy also reduces the patient's ability to sense pain, which is normally associated with stress and tissue damage, allowing the condition to progress.

[0004] Approximately 5% of people with diabetes develop a foot ulcer each year, and 1% will require amputation of a toe or part of the foot. Over the long term, 15% of people with diabetes will develop a foot ulcer, and 12-24% will require amputation. Diabetes is the leading cause of non-traumatic lower limb amputations in the United States. 20-30% of the total cost of diabetes care is related to the treatment and healing of foot ulcers after they have developed.

[0005] Current approaches to preventing diabetic foot ulcers include patient education, foot skin and toenail care, appropriate footwear selection, and preventive surgical measures. A means of detecting preulcer conditions could allow for the implementation of preventive techniques such as off-loading and improved hygiene. Summary of the Invention

[0006] In one aspect, the present disclosure provides and includes an apparatus for assessing susceptibility of tissue to the formation of a diabetic foot ulcer, the apparatus comprising: a plurality of electrodes embedded in a substrate, wherein a pair of the electrodes can form a capacitance sensor configured to measure a first capacitance of a first region of tissue proximate to the capacitance sensor; a circuit electrically coupled to the electrodes; a processor electrically coupled to the circuit; and a non-transitory computer-readable medium electrically coupled to the processor and comprising instructions stored on the non-transitory computer-readable medium, the instructions, when executed on the processor, performing the following steps: receiving information from the circuit regarding the first capacitance measured from the capacitance sensor; comparing the measured first capacitance to a first reference value; and providing a signal if the measured first capacitance differs from the first reference value by an amount greater than a first predetermined threshold.

[0007] In one aspect, the present disclosure provides and includes a method for assessing susceptibility of tissue to diabetic foot ulcer formation, the method including obtaining a first capacitance value at a first location on a patient's skin; obtaining a temperature measurement value at the first location on the patient's skin; and determining that the first location on the patient's skin is susceptible to diabetic foot ulcer formation when the first capacitance value differs from a first reference value by an amount greater than a first predetermined threshold and the temperature measurement value differs from a second reference value by an amount greater than a second predetermined threshold.

[0008] In one aspect, the present disclosure provides and includes a method for assessing susceptibility of tissue to the formation of a diabetic foot ulcer, the method including obtaining a first subepidermal moisture (SEM) value at a first location on a patient's skin; obtaining a temperature measurement at the first location on the patient's skin; and determining that the first location on the patient's skin is susceptible to the formation of a diabetic foot ulcer when the first SEM value differs from a first reference value by an amount greater than a first predetermined threshold and the temperature measurement differs from a second reference value by an amount greater than a second predetermined threshold.

[0009] In one aspect, the present disclosure provides and includes an integrated device for treating diabetic foot ulcers in a patient in need thereof, the device comprising: a plurality of sensors disposed on a flexible substrate, the plurality of sensors configured to measure subepidermal moisture (SEM) values ​​at respective locations on the patient's skin; two electrodes disposed on the flexible substrate; and an external controller electrically connected to the two electrodes, the external controller controlling the two electrodes to detect conductive contact with the patient's skin during an SEM measurement period, and the external controller controlling the two electrodes to apply therapeutic stimulation to the patient during a treatment phase.

[0010] In one aspect, the present disclosure provides and includes an integrated device for treating diabetic foot ulcers in a patient in need thereof, the device comprising: a sensor comprising two electrodes disposed on a flexible substrate such that a current passing between the electrodes passes through tissue adjacent to a location on the patient's skin; and an external controller electrically connected to the two electrodes. [Brief explanation of the drawings]

[0011] Aspects of the present disclosure are described herein, by way of example only, with reference to the accompanying drawings. With specific reference now made in detail to the drawings, it is emphasized that the items shown are examples and are intended for illustrative discussion of aspects of the present disclosure. In this regard, the description and the drawings, taken alone or together, will make apparent to those skilled in the art how aspects of the present disclosure may be practiced.

[0012] [Figure 1A] Describe the structure of the foot. [Figure 1B] FIG. 1B is an enlarged view of area A in FIG. 1A. [Figure 2A] The initial open ulcer at time 0 is depicted. [Figure 2B] 2B depicts the pressure profile created in the situation of FIG. 2A. [Figure 2C] The same area of ​​tissue as in Figure 2A at time point 1 is depicted. [Figure 2D] The same area of ​​tissue in Figures 2A and 2C at time point 2 is depicted. [Figure 3A] A toroidal bioimpedance sensor is disclosed. [Figure 3B] 3B discloses an idealized electric field map produced by the toroidal sensor of FIG. 3A upon activation. [Figure 3C] An SEM scanner comprising the sensor of FIG. 3A is disclosed. [Figure 4] 1 is a first exemplary electrode array. [Figure 5] 1 is an exemplary electrode array according to the present disclosure. [Figure 6A] 6 illustrates a first example of how an array of electrodes as disclosed in FIG. 5 can be configured to form a bioimpedance sensor, according to the present disclosure. [Figure 6B] 6 illustrates a first example of how an array of electrodes as disclosed in FIG. 5 can be configured to form a bioimpedance sensor, according to the present disclosure. [Figure 6C] 1 illustrates an example of a first sensor formed of an array of electrodes according to the present disclosure. [Figure 6D] 6D illustrates an example of how a second sensor may be formed to overlap the first sensor of FIG. 6C according to the present disclosure. [Figure 6E] 6B shows an example of how the sensor shown in FIG. 6A is formed from an array of electrodes that is larger than the portion of the patient's skin that is positioned in the array, according to the present disclosure. [Figure 6F]1 illustrates the positioning of the left and right feet for SEM measurements according to the present disclosure. [Figure 6G] 10 is a plot of SEM values ​​associated with known relative locations for identifying symmetric locations according to the present disclosure. [Figure 7A] 1 depicts a first example of a mat assembly incorporating multiple bioimpedance sensors according to the present disclosure. [Figure 7B] 10 depicts a second example of a mat assembly with an array of electrical sensors according to the present disclosure disposed under the left and right feet, respectively, of a patient while standing on the mat assembly. [Figure 7C] 10 depicts a third example of a mat assembly according to the present disclosure, including one or more sensors disposed within each of the contours. [Figure 8A] In accordance with the present disclosure, a foot cover incorporating a bioimpedance sensor is disclosed. [Figure 8B] 8B is a cross-sectional view of the foot cover of FIG. 8A showing the location of a bioimpedance sensor according to the present disclosure. [Figure 9] A sandal incorporating a bioimpedance sensor according to the present disclosure is disclosed. [Figure 10A] 6 depicts a first exemplary configuration of the addressable electrodes of FIG. 5 that alters the performance of the sensor, according to the present disclosure. [Figure 10B] 6 depicts a second exemplary configuration of the addressable electrodes of FIG. 5 that alters the performance of the sensor, according to the present disclosure. [Figure 10C] 6 depicts a third exemplary configuration of the addressable electrodes of FIG. 5 that alters the performance of the sensor, according to the present disclosure. [Figure 11A] 1 illustrates an exemplary configuration of a substrate shaped to be positioned at a known location on a patient's skin according to the present disclosure. [Figure 11B] 11B illustrates a front view of the exemplary configuration of FIG. 11A in accordance with the present disclosure. [Figure 12] 1 depicts a schematic diagram of an integrated system for measuring, evaluating, storing, and transmitting SEM values ​​in accordance with the present disclosure. [Figure 13]1 depicts a sensing band according to the present disclosure. [Figure 14A] 1 depicts an integrated sensor and stimulator assembly suitable for treating pressure sores according to the present disclosure. [Figure 14B] 1 depicts an integrated sensor and stimulator assembly suitable for treating pressure sores according to the present disclosure. [Figure 14C] 1 depicts an integrated sensor and stimulator assembly suitable for treating pressure sores according to the present disclosure. [Figure 14D] 1 depicts a dressing assembly suitable for treating pressure sores according to the present disclosure. [Figure 15A] 1 illustrates an exemplary method for performing SEM measurements beginning at the rear heel, according to the present disclosure. [Figure 15B] 1 illustrates an exemplary method for performing SEM measurements beginning at the lateral heel, according to the present disclosure. [Figure 15C] 1 illustrates an exemplary method for performing SEM measurements beginning at the medial heel, according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0013] This disclosure describes the measurement of various electrical characteristics and derivation of SEM values ​​indicative of increased amounts of ECF, and the application of this information to the assessment of diabetic foot ulcers and susceptibility to ulcer treatment.

[0014] Diabetic foot ulcers are known to occur in areas exposed to repetitive moderate loads, particularly in areas where bony prominences of the foot transfer weight onto adjacent tissues during standing. Damage may initially occur in tissues beneath the skin and therefore cannot be detected by visual inspection. Early damage will release fluid into the extracellular space, which can be detected through measurements of the electrical properties of subepidermal tissue, e.g., tissue capacitance. Monitoring ECF in potentially at-risk areas will detect tissue deterioration that, if left unchecked, could progress to an open ulcer.

[0015] This description is not intended to be a detailed listing of all the different ways in which the present disclosure may be implemented or all the features that may be added to the present disclosure. For example, features illustrated with respect to one embodiment may be incorporated into other embodiments, and features illustrated with respect to a particular embodiment may be deleted from that embodiment. Thus, the present disclosure contemplates that, in some embodiments of the present disclosure, any feature or combination of features described herein may be excluded or omitted. Moreover, numerous modifications and additions to the various embodiments proposed herein will be apparent to those skilled in the art in light of this disclosure without departing from the present disclosure. In other instances, well-known structures, interfaces, and processes have not been shown in detail so as not to unnecessarily obscure the present invention. It is intended that no part of this specification be construed as denying any portion of the entire scope of the present invention. Thus, the following description is intended to illustrate some specific embodiments of the present disclosure, but is not intended to exhaustively identify all permutations, combinations, and variations thereof.

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used in describing the disclosure herein is for the purpose of describing particular aspects or embodiments only and is not intended to be limiting of the disclosure.

[0017] All publications, patent applications, patents, and other references cited herein are incorporated by reference in their entirety for the teachings relevant to the sentence and / or paragraph in which the reference is presented. References to technology used herein are intended to refer to the technology as commonly understood in the art, including variations on or equivalent technical substitutions for these technologies that would be apparent to one of ordinary skill in the art.

[0018] U.S. Patent Application No. 14 / 827,375 discloses a device that uses radio frequency (RF) energy to measure subepidermal capacitance using a bipolar sensor similar to sensor 90 shown in Figure 3A, where the subepidermal capacitance corresponds to the moisture content of a target area of ​​a patient's skin. The '375 application also discloses arrays of these bipolar sensors of various sizes.

[0019] U.S. Patent Application No. 15 / 134,110 discloses an apparatus for measuring subepidermal moisture (SEM) similar to the device shown in FIG. 3C, in which the device emits and receives RF signals at a frequency of 32 kHz through a single coaxial sensor to produce a bioimpedance signal, which is then converted to an SEM value.

[0020] Both U.S. Patent Application Nos. 14 / 827,375 and 15 / 134,110 are incorporated herein by reference in their entirety.

[0021] Unless the content indicates otherwise, it is expressly intended that the various features of the present disclosure described herein can be used in any combination. Further, the present disclosure also contemplates that in some embodiments of the present disclosure, any feature or combination of features described herein may be excluded or omitted.

[0022] The methods disclosed herein include and comprise one or more steps or actions for achieving the described method. Method steps and / or actions may be interchanged with one another without departing from the scope of the present invention. In other words, unless a specific order of steps or actions is required for the correct operation of an embodiment, the order and / or use of specific steps and / or actions may be modified without departing from the scope of the present invention.

[0023] As used in the description of this disclosure and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the content clearly dictates otherwise.

[0024] As used herein, "and / or" refers to and includes any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted otherwise ("or").

[0025] The terms "about" and "approximately," as used herein when referring to a measurable value such as a length, frequency, or SEM value, are meant to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or even ±0.1% of the particular amount.

[0026] As used herein, phrases such as "between X and Y" and "between about X and Y" should be interpreted to include X and Y. As used herein, phrases such as "between about X and Y" mean "between about X and about Y," and phrases such as "about X to Y" mean "about X to about Y."

[0027] As used herein, the term "subepidermal moisture" or "SEM" refers to local edema caused by an increase in tissue fluid and vascular leakage and other changes that alter the infrastructure of damaged tissue in the presence of continuous pressure on the tissue, apoptosis, necrosis, and inflammatory processes.

[0028] As used herein, a "system" may be a collection of devices in wired or wireless communication with each other.

[0029] As used herein, "probing" refers to the use of radio frequency energy to penetrate the patient's skin.

[0030] As used herein, a "patient" can be a human or animal subject.

[0031] As used herein, "healthy" may describe tissue that does not show symptoms of damage to cell walls or blood vessels, where the presence of increased amounts of ECF is indicative of such damage.

[0032] As used herein, "extracellular fluid" or "ECF" refers to the bodily fluid contained outside of cells, including plasma, interstitial fluid, and intercellular fluid.

[0033] As used herein, "susceptible to the formation of a diabetic foot ulcer" can describe tissue that shows symptoms of damage to cell walls or blood vessels, such as edema or increased amounts of ECF, but no open ulcer is present.

[0034] As used herein, "time_0" refers to an initial time point, for example, when an open ulcer is first detected.

[0035] As used herein, "time_1" refers to a time point that is later than time_0.

[0036] As used herein, "time_2" refers to a time point later than time_1.

[0037] 1A is a side view of a portion of the anatomy of a foot 20. The areas of the foot most likely to develop diabetic foot ulcers are the heel, located under the calcaneus 21, and the ball of the foot, located under the metatarsal 22.

[0038] FIG. 1B is an enlarged view of area "A" in FIG. 1A. The ends of metatarsals 22 and adjacent phalanges 23 are shown adjacent to skin 24 on the bottom of foot 20. A portion of the patient's body weight creates a compressive force 30 applied by metatarsals 22 to tissue in region 40. Force 30 is opposed by a resistive force 36 applied by the floor to skin 24 below region 40 to support the patient. Muscle activity by the patient, walking, or simply balancing on the patient's foot while standing, creates a shear force 32 between metatarsals 22 and tissue 40, as well as a resistive shear force 38 between the floor and skin 24. Thus, tissue in region 40 is simultaneously subjected to both compressive and shear forces.

[0039] It has been observed that while standing still, a healthy patient shifts their weight from foot to foot, as well as shifting their center of mass relative to their foot. This limits the duration for which force is applied to any particular area of ​​tissue. However, peripheral neuropathy reduces the sensation within the tissue created by the patient's weight, thus reducing the patient's involuntary shifting of weight, and patients with peripheral neuropathy are observed to lack normal movement while standing. This results in prolonged periods of continuous compressive force being applied to localized areas of tissue, such as area 40. It is believed that prolonged exposure to such moderate levels of force contributes to the formation of ulcers in these areas.

[0040] Figures 2A, 2B, 2C, and 2D depict the state and progression of an open ulcer. Figure 2A depicts an initial open ulcer 50A at time 0. Ulcer 50A is surrounded by a ring of increased pressure 52A.

[0041] FIG. 2B shows the pressure profile created in the situation of FIG. 2A. Force applied by the floor or by shoes worn by the patient is applied as a localized uniform pressure 56 to the skin 24 of the foot 20. The applied pressure 56 is internally opposed by force 53. When tissue peels, pressure cannot be applied to the ulcer 50. Thus, the internal force in the toroidal region 52A increases to a peak 54, capturing the force that would have been applied to the ulcer 50. This peak force 54 is high enough to cause further tissue damage at the annulus 52A. A callus will typically form across region 52A as the body attempts to protect itself from the increased pressure. However, the tissue below the callus is still damaged and will exhibit an increase in ECF.

[0042] 2C depicts the same region of tissue at time point 1 following time point 0. The increased pressure level in region 52A results in tissue death in region 52A and tissue sloughing off in region 52B, resulting in ulcer 50B being larger than the previous ulcer 50A. The applied pressure 56 remains unchanged, but now the tissue in region 52B around the larger ulcer 50B must exert even greater force. This accelerates the expansion of ulcer 50B as the tissue in region 52B dies more rapidly under the greater applied load.

[0043] Figure 2D depicts the same region of tissue as Figures 2A and 2C at time point 2, following time point 1. Ulcer 50 has grown to a size 50C and region 52C of increased pressure greater than previous regions 52A, 52B.

[0044] In the situation shown in Figure 2A where an ulcer has formed, preventative treatment would be introduced to prevent the ulcer 50 from growing and allow the body to heal the open ulcer 50. Treatment may involve placing pressure-relieving pads around the ulcer to spread the pressure 56 over a larger area of ​​healthy tissue, eliminating peaks 54 that could cause further damage. However, determining whether the treatment is working can only be done by observing over time that the ulcer is not progressing.

[0045] FIG. 3A discloses a toroidal bioimpedance sensor 90. In this exemplary configuration, a central electrode 110 is surrounded by a ring electrode 120. Without being limited to a particular theory, the gap between the two electrodes affects the depth of penetration of the electric field into the substrate below the sensor 90. In one embodiment, a ground plate (not visible in FIG. 3A ) is parallel to and spaced from the electrode face, and in some embodiments, extends beyond the outer diameter of the ring electrode 120. Without being limited to a particular theory, the ground plate may confine the electric field between electrodes 110 and 120 to a single side of the face of electrodes 110 and 120, opposite the face of electrodes 110 and 120 from the ground plate.

[0046] Figure 3B discloses an idealized electric field map created by the toroidal sensor of Figure 3A when activated by a drive circuit (not shown in Figure 3B). When a voltage is applied across electrodes 110 and 120, an electric field 140 is produced between electrodes 110 and 120 that extends outward from the plane of electrodes 110 and 120 to the depth of electric field 150. The diameter of center electrode 110, the inner and outer diameters of ring electrode 120, and the gap between electrodes 110 and 120 can be varied to change the characteristics of electric field 140, for example, the depth of electric field 150.

[0047] In use, the driver circuitry can measure electrical properties or parameters, including one or more electrical characteristics selected from the group consisting of resistance, capacitance, inductance, impedance, magnetoresistance, and other electrical characteristics as sensed by the electric field 140. Depending on the type of driver circuitry used in the device, the device's sensors can be bipolar radio frequency sensors, bioimpedance sensors, capacitance sensors, or SEM sensors. In certain embodiments, the measured electrical parameters are related to the water content of the patient's epidermis at a depth determined by the placement of the electrodes 110 and 120, the frequency and strength of the electric field 140, and other operating characteristics of the device's driver circuitry. In one embodiment, the measured water content is equivalent to an SEM content having a value on a predetermined scale. In some embodiments, the predetermined scale can range from 0 to 20, such as 0 to 1, 0 to 2, 0 to 3, 0 to 4, 0 to 5, 0 to 6, 0 to 7, 0 to 8, 0 to 9, 0 to 10, 0 to 11, 0 to 12, 0 to 13, 0 to 14, 0 to 15, 0 to 16, 0 to 17, 0 to 18, 0 to 19, etc. In one embodiment, the predetermined scale can be scaled by one or more factors based on the values ​​provided herein. In some embodiments, multiple measurements are taken while varying one or more of these operating characteristics during a reading, thereby providing information related to water content at various depths of the skin.

[0048] One or more regions may be defined on the body. In some embodiments, measurements made within a region are considered comparable to one another. A region may be defined as an area on the skin of the body where measurements may be taken at any point within the area. In some embodiments, a region corresponds to an anatomical region (e.g., heel, ankle, hip). In some embodiments, a region may be defined as a set of two or more specific points on an anatomical feature where measurements are taken only at the specific points. In some embodiments, a region may include multiple non-contiguous areas on the body. In some embodiments, a set of specific locations may include points within multiple non-contiguous areas.

[0049] In some embodiments, the region is defined by a surface area. In some embodiments, the region is defined by a surface area, e.g., between 5 and 200 cm. 2 , 5~100cm 2 , 5~50cm 2 , or 10 to 50 cm 2 , 10~25cm 2 , or 5 to 25 cm 2 It could be.

[0050] In some embodiments, measurements can be made in a specific pattern or portion thereof. In some embodiments, a pattern of readings is made in a pattern that includes a central target area of ​​interest. In some embodiments, measurements are made in one or more circular patterns of increasing or decreasing size, a T-shaped pattern, a set of specific locations, or randomly across a tissue or region. In some embodiments, a pattern can be placed on the body by defining a first measurement location of the pattern relative to an anatomical feature, with the remaining measurement locations of the pattern defined as offsets from the first measurement location.

[0051] In some embodiments, multiple measurements are taken across a tissue or region, and the difference between the lowest and highest measurement of the multiple measurements is recorded as the delta value of the multiple measurements, hi some embodiments, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more measurements are taken across a tissue or region.

[0052] In some embodiments, a threshold value may be established for at least one region. In some embodiments, a threshold value of 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or other value may be established for at least one region. In some embodiments, a delta value is identified as significant when the delta values ​​of multiple measurements within a region meet or exceed the threshold value associated with that region. In some embodiments, each of the multiple regions has a different threshold value. In some embodiments, two or more regions may have a common threshold value.

[0053] In some embodiments, the threshold has both a delta value component and a time-dependent component, where a delta value is identified as significant when the delta value exceeds a predetermined number for a predetermined portion of the time interval. In some embodiments, the predetermined portion of the time interval is defined as the minimum number of X days during which multiple measurements taken on those days produce a delta value equal to or greater than the predetermined number within a total of Y consecutive days of measurements. In some embodiments, the predetermined portion of the time interval can be defined as 1, 2, 3, 4, or 5 consecutive days during which multiple measurements taken on those days produce a delta value equal to or greater than the predetermined number. In some embodiments, the predetermined portion of the time interval can be defined as a portion of different specific time periods (weeks, months, hours, etc.).

[0054] In some aspects, the threshold has a trend aspect, where changes in delta values ​​of consecutive measurements are compared to one another. In some aspects, the trend threshold is defined as a predetermined change in delta value over a predetermined amount of time, where a determination that the threshold is met or exceeded is significant. In some aspects, a significant determination may result in an alert being issued. In some aspects, a trend line may be calculated from a portion of the individual measurements of the consecutive measurements. In some aspects, a trend line may be calculated from a portion of the delta values ​​of the consecutive measurements.

[0055] In some embodiments, the number of measurements made within a single region may be less than the number of measurement locations defined in a pattern. In some embodiments, a delta value is calculated after a predetermined initial number of readings are made in a region that is less than the number of measurement locations defined in a pattern, and after each additional reading in the same region, and once the delta value meets or exceeds a threshold value associated with that region, no additional readings are taken.

[0056] In some embodiments, the number of measurements taken within a single area may exceed the number of measurement locations defined in a pattern, hi some embodiments, a delta value will be calculated after each additional reading.

[0057] In certain embodiments, a quality metric may be generated for each of the plurality of measurements. In certain embodiments, the quality metric is selected to assess the repeatability of the measurements. In certain embodiments, the quality metric is selected to assess the skill of the clinician who performed the measurements. In certain embodiments, the quality metric may include one or more statistical parameters, such as the mean, average, or standard deviation. In certain embodiments, the quality metric may include one or more comparisons of individual measurements to predetermined ranges. In certain embodiments, the quality metric may include a comparison of individual measurements to a pattern of values, such as a comparison of measurements at predetermined locations to a range associated with each predetermined location. In certain embodiments, the quality metric may include a determination of which measurements were made across healthy tissue and one or more assessments of consistency within this subset of "healthy" measurements, e.g., a range, standard deviation, or other parameter.

[0058] In one embodiment, the measurements, e.g., threshold values, are determined by an SEM scanner model 200 (Bruin Biometrics, LLC, Los Angeles, Calif.). In another embodiment, the measurements are determined by another SEM scanner.

[0059] In some embodiments, measurements are based on capacitance measurements by referencing a reference device. In some embodiments, capacitance measurements may depend on the location of any electrodes and other aspects of the device. Such variations may be compared to a reference SEM device, such as an SEM Scanner Model 200 (Bruin Biometrics, LLC, Los Angeles, CA). Those skilled in the art will understand that the measurements described herein can be adjusted to accommodate differential capacitance ranges by referencing a reference device.

[0060] 3C provides top and bottom views of an SEM scanner 170 including electronics that drive a sensor 174 similar to sensor 90 of FIG. 3A and measure the capacitance between electrodes 110 and 120. This capacitance can be converted into an SEM value that is displayed on a display 176.

[0061] Aspects of the sensor 90 and SEM scanner 170 are disclosed in WO2016 / 172263, a national phase filed version of U.S. patent application Ser. No. 15 / 134,110, all of which are incorporated herein by reference in their entireties.

[0062] FIG. 4 depicts an exemplary electrode array 290 according to the present disclosure. Array 290 is comprised of individual electrodes 300, which, in this example, are arranged in a regular pattern across substrate 292. In certain embodiments, each electrode 300 is remotely coupled (through conductive elements not shown in FIG. 4) to a circuit (not shown in FIG. 4) configured to measure an electrical parameter. In one embodiment, a "virtual sensor" is created by selectively connecting a predetermined subset of electrodes 300 to a common element of the circuit. In this example, a particular electrode 310 is connected as a center electrode similar to electrode 110 in FIG. 3A, and six electrodes 320A-320F are connected together as a "virtual ring" electrode similar to electrode 120 in FIG. 3A. In certain embodiments, two individual electrodes are individually connected to the circuit to form a virtual sensor; for example, electrodes 310 and 320A are each connected as two electrodes of a sensor. In one embodiment, one or more electrodes 300 are connected together to form one or the other of the electrodes of a two-electrode sensor.

[0063] Any pair of electrodes, whether comprised of a single electrode or a set of electrodes coupled together to form a virtual electrode, is coupled to electronics (not shown in FIG. 4 ) configured to measure an electrical property or parameter, including one or more of resistance, capacitance, inductance, impedance, magnetoresistance, or other electrical characteristics, including one or more of sensors 90, 174, 290, 430, 440, or other two-electrode sensors. The electronics of the present disclosure may be further configured to compare the measured first capacitance to a reference value and provide a signal if the measured capacitance differs from the reference value by more than a threshold amount. In certain aspects, one or both of the reference value and the threshold value are predetermined.

[0064] FIG. 5 depicts another exemplary array 400 of electrodes 410 according to the present disclosure. In this non-limiting example, each of the electrodes 410 is approximately hexagonal, separated from each of the surrounding electrodes 410 by a gap 420. In one embodiment, the electrodes 410 are circular, square, pentagonal, or one of other regular or irregular shapes. In some embodiments, the gap 420 is uniform among all of the electrodes 410. In one embodiment, the gap 420 varies among the various electrodes. In one embodiment, the gap 420 has a width narrower than the cross-section of each of the electrodes 410. The electrodes 410 may be interconnected to form a virtual sensor as described below with respect to FIGS. 6A-6B and 10A-10C.

[0065] FIG. 6A depicts an array 400 of electrodes 410 configured to form an exemplary sensor 430, e.g., connected to a measurement circuit, according to the present disclosure. A single hexagonal electrode 410 labeled "1" forms the center electrode, and a ring of electrodes 410 marked "2" are interconnected to form the ring electrode. In certain embodiments, the electrodes 410 between the center electrode and the ring electrode are electrically "floating." In one embodiment, the electrodes 410 between the center electrode and the ring electrode are grounded or connected to a floating ground. In certain embodiments, the electrodes 410 outside the ring electrode are electrically "floating." In one embodiment, the electrodes 410 outside the virtual ring electrode are grounded or connected to a floating ground.

[0066] 6B depicts an alternative embodiment in which an array 400 of electrodes 410 is configured to form a virtual sensor 440 according to the present disclosure. In one embodiment, multiple electrodes 410, designated "1," are interconnected to form a center electrode, and double-width ring electrodes, designated "2," are interconnected to form a ring electrode. In one embodiment, various numbers and positions of electrodes 410 are interconnected to form virtual electrodes of various sizes and shapes.

[0067] 6A and 6B depict an exemplary configuration of an electrode array 400 capable of forming sensors 430 at multiple overlapping locations according to the present disclosure. In FIG. 6A, a virtual sensor 430A is formed by a center electrode 432 formed by a single electrode 410, designated "1," and a ring electrode 434 formed by multiple electrodes 410, designated "2." This same array 400 is shown in FIG. 6B, where a new virtual sensor 430B is formed by a center electrode 436, designated "3," and a ring electrode 438, designated "4." The location of virtual sensor 430A is indicated by a black outline. It can be seen that virtual sensor 430B overlaps with the location of virtual sensor 430A, allowing measurements to be made with a resolution finer than the diameter of sensor 430.

[0068] FIG. 6E illustrates how a sensor 430 may be formed from an array of electrodes 400 larger than the portion of the patient's skin positioned relative to the array, in accordance with the present disclosure. In this example, the outline of a contact area 450 on the sole 22R of a patient's right foot, as viewed from directly underneath the foot, is shown superimposed on the array 400. In this example, a sensor 430C is formed where a portion of the sensor 430C extends beyond the edge of the contact area 450. In such a location, the capacitance or other electrical parameter measured by sensor 430C is less than the capacitance measured by sensor 430D, which is positioned entirely within the contact area 450. It will be appreciated that a sensor 430 may be formed at any point within the array 400 and may overlap the contact area to any level within a range of 0-100%, depending on the location of the sensor 430.

[0069] In some embodiments, two sensors may overlap by 0-50%, such as 0-10%, 5-15%, 10-20%, 15-25%, 20-30%, 25-35%, 30-40%, 35-45%, 40-50%, 0-25%, 15-35%, or 25-50%. In one embodiment, two sensors may overlap by 25-75%, such as 25-35%, 30-40%, 35-45%, 40-50%, 45-55%, 50-60%, 55-65%, 60-70%, 65-75%, 25-50%, 40-55%, or 50-75%. In one embodiment, the two sensors may overlap by 50-100%, such as 50-60%, 55-65%, 60-70%, 65-75%, 70-80%, 75%-85%, 80-90%, 85-95%, 90-100%, 50-75%, 65-85%, or 75-100%.

[0070] In one aspect, the array of sensors 400 may further comprise multiple contact sensors (not shown in FIG. 6E) on the same planar surface as and surrounding each of the electrodes to ensure full contact of the one or more virtual sensors with the skin surface. The multiple contact sensors may be multiple pressure sensors, multiple light sensors, multiple temperature sensors, multiple pH sensors, multiple sweat sensors, multiple ultrasound sensors, multiple bone growth stimulator sensors, or multiple combinations of these sensors. In some embodiments, the multiple contact sensors may comprise four, five, six, seven, eight, nine, ten, or more contact sensors surrounding each electrode.

[0071] 6F and 6G depict an example of how a comparison of SEM values ​​associated with sensors at known related locations may identify symmetrical locations according to the present disclosure. In this example, sensors 430 are formed at non-overlapping locations, marked "A" through "H" in FIG. 6F, across contact area 450R of right foot 20R. The SEM values ​​measured at each location are plotted on the graph in FIG. 6G. In this example, the SEM values ​​at locations "A" and "H" are low or zero, reflecting the non-overlapping sensors 430 that include contact area 450 at these locations. The SEM values ​​associated with locations "B" and "G" are higher because the sensors 430 overlap a portion of contact area 450 at these locations. The SEM values ​​for locations C-D-E-F are higher, and in this example, are approximately the same, indicating that the sensors 430 are completely within contact area 450 at these locations. In one embodiment, an SEM measurement device such as device 180 may determine that certain locations, e.g., locations "C" and "F," are symmetrical about centerline 452R of right foot 20R. A similar set of measurements is made at locations A'-H' on left foot 20L. In one embodiment, locations on each foot 20L and 20R, e.g., locations E and E', may be determined to be approximately symmetrical.

[0072] FIG. 7A depicts an exemplary mat assembly 500 incorporating multiple bioimpedance sensors 520 according to the present disclosure. While the sensors 520 are shown as toroidal sensors similar to the sensors 90 depicted in FIG. 3A, the sensors 520 can be any configuration of an electrometric sensor, including the configurations shown in FIGS. 4, 5, and 6A-6B. The sensors 520 are distributed across a substrate 510. In some embodiments, a portion of the substrate 510 is flexible. In some embodiments, a portion of the substrate 510 is rigid. In some embodiments, the electrodes of the sensors 520 are electrically bare, thereby allowing conductive electrical contact with a patient's feet when the patient is standing on the mat assembly 500. In one embodiment, the electrodes of the sensors 520 are electrically insulated, for example, by an insulating cover layer (not shown in FIG. 7A), thereby allowing only capacitive electrical contact with a patient's feet when the patient is standing on the mat assembly 500.

[0073] In some embodiments, the mat assembly 500 includes one or more temperature sensors (not shown in FIG. 7A) that detect the temperature at one or more locations on the foot. In one embodiment, the temperature sensors are co-located with the SEM sensor 520 to provide temperature and SEM measurements at a common location.

[0074] In one embodiment of the mat assembly 500, a signal is provided when the measured capacitance differs from the reference capacitance value by more than a first threshold and the measured temperature differs from the temperature reference value by more than a second threshold. In certain embodiments, one or both of the thresholds are predetermined. In one embodiment, the first threshold is set to the corresponding reference capacitance value plus at least 5%, such as at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500%. In one embodiment, the second threshold is set to at least 5%, such as the corresponding reference temperature value plus at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500%. In one embodiment, one or both of the capacitance and temperature reference values ​​are determined from a previous measurement, e.g., a rolling average of the last five sequential measurements, with an average of multiple measurements made over an earlier period, e.g., one month prior.

[0075] In one aspect, one or both of the capacitance and temperature reference values ​​are determined from measurements made while in a known healthy state, for example, while in a doctor's office, when a clinician examines the tissue and determines that the tissue is healthy, i.e., not susceptible to the formation of a diabetic foot ulcer.

[0076] 7B depicts another exemplary mat assembly 502 comprising arrays 530L and 530R of electrical sensors 520, where arrays 530L and 530R are disposed to under the left and right feet, respectively, of a patient while standing on mat assembly 502. In one embodiment, outlines 540L and 540R of the left and right feet are drawn across arrays 530L and 530R to guide the patient in standing in the correct location.

[0077] 7C depicts an embodiment of a mat assembly 504 having one or more sensors 520 disposed within each of contours 540L and 540R. In one embodiment, sensor 520A is placed in a location corresponding to the portion of the foot most likely to develop an ulcer, e.g., the ball of the foot. In one embodiment, sensor 520B may be placed under the heel or elsewhere on the foot.

[0078] In one embodiment, substrate 510 is partially transparent, and mat 504 includes a second substrate 512 on which one or more optical sensors 550 are mounted. In some embodiments, optical sensors 550 are cameras capable of imaging the soles of the feet of a patient standing on mat 504. In one embodiment, optical sensors 550 are sensitive to visible light. In some embodiments, optical sensors 550 are sensitive to infrared light.

[0079] Periodic use of mat assemblies 500, 502, 504, etc. by a patient can serve to detect changes in the patient's foot health. For example, a baseline may be established by measuring electrical characteristics, such as capacitance, of each foot at the time of examination by a clinician who verifies the patient has no ulcers or indicators of damage that would lead to the formation of an ulcer. The patient then places mats 500, 502, 504 in an easily accessible location in the patient's home, for example, in front of a bathroom sink. Periodically, such as while brushing their teeth each day, the patient triggers measurements of their foot with sensor 520. If the patient is standing in the same location, for example, guided by contours 540L and 540R, each sensor 520 and 550 measures the same location for each repeated measurement. In some embodiments, temperature measurements are made in mat assemblies 500, 502, 504 by infrared sensor 550 or one or more temperature sensors (not shown in FIG. 7C ). In one embodiment, images are captured in mat assembly 504 by optical sensor 550. This information is stored in local memory or transmitted to a remote storage location, such as a doctor's office. Each daily measurement is compared to a reference value derived from previous measurements, e.g., measurements made in the clinician's office, or an average of measurements from the past week. If the most recent measurement deviates from the reference value, the patient is notified of the deviation. The patient can then consult a clinician for further evaluation and possible action. In certain embodiments, a change in the measured SEM value greater than a threshold value triggers a notification. In one embodiment, a change in the measured SEM value greater than a first threshold and a change in the measured temperature greater than a second threshold both trigger a notification. In certain embodiments, either a change in the measured SEM value greater than a first threshold or a change in the measured temperature greater than a second threshold triggers a notification.In one embodiment, the first threshold is set at at least 5%, such as the corresponding reference SEM value plus at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500%. In one embodiment, the second threshold is set at at least 5%, such as at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500% of the corresponding baseline temperature value. In certain embodiments, information such as an image of the plantar surface of the patient's foot is routinely sent to a clinician for review.

[0080] In some embodiments, measurements from the left and right feet are compared to one another. For example, referring to Figures 6F and 6G, locations E and E' are compared to one another. In one embodiment, the difference between the left and right measurements is compared to a baseline value, and the patient is notified if the difference exceeds a threshold.

[0081] FIG. 8A discloses a foot covering 600 incorporating a bioimpedance sensor 520 as shown in cross-section in FIG. 8B according to the present disclosure. In one embodiment, the foot covering 600 comprises a sock or other flexible, form-fitting garment 610 into which the foot can be inserted. In one embodiment, the flexible, form-fitting garment 610 may be a flexible shoe similar to a "water shoe" made from a flexible, elastic material such as rubber. In one embodiment, the flexible, form-fitting garment 610 may be a traditional shoe, e.g., a leather shoe or sneaker. The sensor 520 is placed in one or more locations corresponding to areas of interest for ulcer development. In one embodiment, the sensor 520 is placed under or around the heel of the flexible, form-fitting garment 610. In one embodiment, the sensor 520 is placed on the sole of the flexible, form-fitting garment 610. In one embodiment, the sensor 520 is placed in the area around the toes (not visible in FIG. 8B) of the flexible, form-fitting garment 610.

[0082] 9 discloses a sandal 650 incorporating bioimpedance sensors 520 in accordance with the present disclosure. One or more sensors 520 are disposed on the sandal in locations corresponding to areas of potential ulcer development.

[0083] 10A, 10B, and 10C depict configurations of the addressable electrodes of FIG. 5 that alter sensor performance according to the present disclosure. FIG. 10A depicts an exemplary first configuration 700 in which electrodes 710 are connected to form a center electrode 720 and a ring electrode 730 similar to those of FIGS. 6A and 6B. The sensor configuration 700 has a gap 740 between the electrodes 710 in a single row, which produces a first electric field depth 150, with reference to FIG. 3B.

[0084] 10B depicts a second exemplary configuration 702 of the same array of sensors 710 in which one electrode is connected to form a center electrode 722 and multiple electrodes 710 are connected to form a ring electrode 732 that is larger in diameter than the ring electrode 730 and has a gap 742 that is larger than the gap 740. The sensor configuration 702 will have a second electric field depth 150 that is greater than the depth of the sensor configuration 700.

[0085] 10C depicts a third exemplary configuration 704 of the same array of sensors 710 in which one electrode is connected to form a center electrode 724 and multiple electrodes 710 are connected to form a ring electrode 734 that is larger in diameter than ring electrodes 730 and 732 and has a gap 744 that is larger than gaps 740 and 742. Sensor configuration 704 will have a third electric field depth 150 that is larger than either sensor configurations 700 or 702.

[0086] In one embodiment, mat assembly 500 comprises an array of electrodes 710 distributed across a portion of substrate 510. At a location in the array corresponding to an area of ​​interest on the patient's foot, mat assembly 500 is configured to form sensor configuration 700 and make a first measurement, and then reconfigure electrodes 710 to form sensor configuration 702 and make a second measurement. The first and second measurements provide information about differences in ECF at different depths below the skin of the foot, thereby providing improved knowledge of tissue status within the foot. In one embodiment, mat assembly 500 is then configured to form sensor configuration 704 and make a third measurement. Comparison of the three measurements provides greater resolution of internal tissue status.

[0087] 11A and 11B depict an exemplary embodiment of a sensor assembly 500 configured to be placed at a known location on a patient's skin in accordance with the present disclosure. In this example, the sensor assembly 500 has a shaped substrate 510 configured to conform to the rear and plantar surface of the heel of the foot 20. In one embodiment, the shaped substrate 510 is suitable for use with both the left foot 20L and the right foot 20R. The sensor assembly 500 includes one or more sensors 520 disposed on the interior surface of the shaped substrate 510. In this example, the sensors 520 are configured as toroidal sensors as shown in FIG. 1A. In one embodiment, the interior surface of the shaped substrate 510 is aligned with the array 400 of electrodes 410, with reference to FIG. 5, so that virtual sensors can be formed anywhere. In one embodiment, sensors of other shapes and configurations are provided on the interior surface of the shaped substrate 510. In some embodiments, the shaped substrate 510 is a flexible panel (not shown in FIG. 11A) that can conform to the patient's skin, for example, wrapped around the back of the ankle. In one embodiment, the sensor assembly 500 includes a cable 530 for connecting the sensor 520 to one or more of a power source, a circuit configured to measure one or more of capacitance or other electrical properties, a processor, a communication subsystem, or other type of electronic assembly (not shown in FIG. 11A).

[0088] FIG. 11B depicts an exemplary configuration of a sensor assembly 500 with multiple sensors 520 disposed on a shaped substrate 510, such as when the sensor assembly 500 is positioned against a patient's skin around the back, sides, and bottom of the center of the right heel. This allows for multiple SEM measurements to be taken at repeatable locations on the heel with the sensor assembly 500 in a single position. In one embodiment (not shown in FIGS. 11A and 11B ), the sensor assembly 500 is configured to be placed on a portion of the patient's posterior, thereby providing the ability to make measurements at symmetrical locations on the posterior. In certain embodiments, the shaped substrate 510 is configured to match the anatomical features of the patient's target area. In one embodiment, the shaped substrate 510 includes markings or other indicia that can match the patient's body features to enable measurements to be taken at the same location at time intervals over a period of time typically ranging from several hours to several weeks. In one embodiment, the sensor assembly 500 is integrated into a garment or the lining of a shoe or other garment. In some embodiments, the sensor assembly 500 is integrated into a sheet, blanket, liner, or other type of bedding. In one embodiment, the sensor assembly 500 includes wireless communication capabilities, such as passive radio frequency identification (RFID) or inductive coupling, allowing operation of the sensor 520 without a physical connection to the sensor assembly 500.

[0089] In certain embodiments, the sensor 520 is coupled to electronics (not shown in FIG. 11B) configured to compare a current set of measurements with each other and with previous measurements made at the same location. In certain embodiments, the electronics of the present disclosure may provide a signal when one or more of certain conditions are met. Such conditions may include, but are not limited to, a change in the difference between measurements made at two locations when compared to the difference between measurements made at the same two locations at an earlier time, and a change in the value measured at a particular location from a previous measurement at the same location that exceeds a threshold amount.

[0090] FIG. 12 depicts a schematic diagram of an integrated system 800 for measuring, evaluating, storing, and transmitting SEM values ​​according to the present disclosure. In this example, system 800 includes an SEM measurement device 810, e.g., SEM scanner 170, including the capability to wirelessly communicate with a WiFi access point 820. Device 810 communicates with one or more of an SEM application running on a server 850, a laptop computer 840, a “smartphone” 830, or an application running on another digital device. In one embodiment, laptop computer 840 and smartphone 830 are carried by a user of device 810, e.g., a nurse, and the application provides feedback and information to the user. In one embodiment, information about the patient received from device 180 is stored in database 850. In one embodiment, information about the patient received from device 810 is stored in database 860. In one embodiment, information received from device 810 is transferred over network 855 to another server 880 that stores a portion of the information in the patient's electronic medical record (EMR) 870. In one embodiment, information from device 810 or retrieved from database 860 or EMR 870 is transferred to an external server 890 and then to a computer 895, for example, a computer in the office of the physician providing care to the patient.

[0091] In one embodiment, the device 810 is one of the mat assembly 500, foot cover 600, or other measurement device, and one or both of the smartphone 830 and laptop 840 are used by the patient to receive information and notifications related to measurements made by the mat assembly 500.

[0092] FIG. 13 depicts a sensing band 550 according to the present disclosure. In one embodiment, an SEM sensor as described herein, e.g., sensor 90 or sensor 400, is embedded within a band 554, which can be wrapped around the calf 60 as shown in FIG. 13. In certain embodiments, band 554 comprises a sensor configured to measure one or more of tissue oxygenation, which can include measurements of one or both of oxyhemoglobin and deoxyhemoglobin, temperature at one or more points on the skin, pulse rate, blood volume, and blood pressure. In one embodiment, the combination of measurements made by band 554 provides information regarding blood flow to the leg, where a decrease in blood flow is a possible indicator of susceptibility to DFU formation. In certain embodiments, this information includes measurements of blood volume and refill time on a portion of calf 60 proximate band 554.

[0093] FIG. 14A depicts an integrated sensor and stimulator assembly 201 suitable for treating pressure sores according to the present disclosure. In some embodiments, the integrated sensor and stimulator assembly 201 is provided to a patient in need thereof. The assembly 201 has a substrate 210 having a plurality of sensors 90 disposed on a first surface. The sensors 90 are configured to measure subepidermal moisture (SEM) as an indicator of tissue health at the location of each sensor 90. In some embodiments, there are two electrodes 212A and 212B that are in conductive contact with the skin of a patient (not shown in FIG. 14A ) when the assembly 201 is placed on the skin. These electrodes 212A, 212B are connected to an external controller (not shown in FIG. 14A ) configured to apply therapeutic electrical stimulation to the tissue between the electrodes 212A, 212B, with stimulation applied for a period of time having a duration and time interval between the periods. In some embodiments, low-level voltage and / or current may improve healing of pressure sores. The sensors 90 are individually connected to an external controller (not shown in FIG. 14A ) configured to measure the capacitance of each sensor 90. In some embodiments, the capacitance is measured at time intervals during the stimulation period. In one embodiment, the time intervals can generally range from several hours to several weeks. In some embodiments, the assembly 201 includes an absorbent pad and a non-adhesive layer (not shown in FIG. 14A ) superimposed on the sensor 90 and electrodes 212A, 212B. In some embodiments, the assembly 201 includes an adhesive layer (not shown in FIG. 14A ) superimposed on a portion of the substrate 210 to enable adhesive attachment of the assembly 201 to the patient's skin. In some embodiments, the substrate 201 can be permeable to gases but impermeable to liquids.

[0094] The combination of a standard dressing (absorbent pad, non-adhesive layer, and covering substrate) with a therapeutic device such as electrodes 212A, 212B and an external controller associated with one or more sensors 90 provides a means to protect the wound, improve the healing process, and monitor healing without interfering with the assembly 201.

[0095] FIG. 14B depicts the sole of a patient's foot 20 having a pressure sore 205 .

[0096] 14C depicts assembly 201 adhered to the bottom of foot 20 over pressure ulcer 205. In one embodiment, assembly 201 is placed over ulcer 205 and left in place for several days. In one embodiment, assembly 201 comprises a toroidal pad that relieves pressure on pressure ulcer 205. An external controller for electrodes 212A, 212B periodically attaches to electrodes 212A, 212B to apply therapeutic stimulation. During the intervals between these stimulations, an external controller for sensors 90 is attached to one or more of sensors 90 to make SEM measurements.

[0097] In certain embodiments, assembly 201 includes a battery and wireless communication capabilities that allow an external controller to apply stimulation through electrodes 212A, 212B without a wired connection to the assembly. Similarly, the assembly can be configured to allow an external controller to communicate with sensor 90 to make and receive SEM measurements without a wired connection. In certain embodiments, assembly 201 includes a microcontroller configured to apply therapeutic stimulation, make SEM measurements, and wirelessly transmit information such as SEM values.

[0098] It will be apparent to those skilled in the art that the concept of combining a therapeutic device and an SEM sensor can be applied to other types of wounds and to other locations on the body other than the sole of the foot, such as the ankle or bony prominences.

[0099] FIG. 14D depicts a bandage assembly 202 adapted for placement over a suprasacral pressure ulcer on a patient in need thereof. Assembly 202 includes a substrate 220 that is porous to gas but impermeable to liquids. Assembly 202 includes a pad 222 (seen from the outside in FIG. 14D ) that provides both protective padding and absorption. In this example, a single sensor 90 is positioned on the underside of pad 222 so that when the assembly is applied over an early-stage pressure ulcer containing intact skin, the sensor is directly over the pressure ulcer. Electrodes 214A, 214B are positioned on the same underside, adjacent to sensor 90, for contact with the patient's skin. In this configuration, assembly 202 can be placed over an early-stage ulcer to protect and improve the healing process and monitor healing progress upon removal of assembly 202 or disturbance of the wound.

[0100] Having generally described the invention, it will be more readily understood through reference to the following examples, which are provided by way of illustration and are not intended to limit the disclosure unless otherwise specified. [Example]

[0101] Example 1: Performing SEM measurements at multiple locations on the foot To ensure complete contact of the electrodes with the skin of human patients, SEM measurements were performed on the feet using one of the following three methods:

[0102] 15A illustrates the method used to perform SEM measurements beginning at the rear heel using a device according to the present disclosure. First, the forefoot was dorsiflexed so that the toes were pointing toward the shin. Second, the bioimpedance sensor 1520 was positioned at the base of the heel 1530. The electrodes were adjusted to ensure full contact with the heel, and multiple SEM measurements were taken in a straight line toward the toes, including the ball of the foot 1540. The ball of the foot is one of the primary locations for diabetic foot ulcers.

[0103] Figure 15B illustrates the method used to take SEM measurements beginning at the lateral heel using a device according to the present disclosure. First, the toes were rotated inward toward the inside of the body, pointing away from the body. Second, electrodes were placed on the lateral side of the heel 1550. The bioimpedance sensor 1520 was adjusted to make full contact with the heel, and multiple SEM measurements were taken in a straight line toward the bottom of the foot. The ball of the foot 1540 is also shown in Figure 15B.

[0104] 15C illustrates the method used to perform SEM measurements beginning at the medial heel using a device according to the present disclosure. First, the toes were turned away from the body and rotated outward toward the side of the body. Second, an electrode was placed on the medial side of the heel 1560. The bioimpedance sensor 1520 was adjusted to make full contact with the heel, and multiple measurements were taken in a curve around the rear of the heel.

[0105] From the foregoing, it will be appreciated that the present invention can be embodied in a variety of ways, including but not limited to the following.

[0106] Embodiment 1. An apparatus for assessing susceptibility of tissue to the formation of a diabetic foot ulcer, the apparatus comprising: a plurality of electrodes embedded in a substrate, wherein a pair of the electrodes can form a capacitance sensor, the capacitance sensor configured to measure a first capacitance of a first region of the tissue proximate to the capacitance sensor; a drive circuit electrically coupled to the electrodes; a processor electrically coupled to the drive circuit; and a non-transitory computer-readable medium electrically coupled to the processor and comprising instructions stored on the non-transitory computer-readable medium, the instructions, when executed on the processor, perform the following steps: receive information regarding the measured first capacitance from the drive circuit; compare the measured first capacitance to a first reference value; and provide a signal if the measured first capacitance differs from the first reference value by an amount greater than a first predetermined threshold.

[0107] Embodiment 2. The apparatus of embodiment 1, wherein the first reference value is predetermined.

[0108] Embodiment 3. The device of embodiment 1, wherein the first reference value is determined by a first capacitance measurement when the first region of tissue is healthy.

[0109] Embodiment 4. The device of embodiment 1, wherein the first reference value is determined from a measurement of the first capacitance in the first region of the tissue at one or more time points prior to the most recent measurement of the first capacitance.

[0110] Embodiment 5. The device of embodiment 1, wherein the first reference value is determined by measurements from bilaterally symmetrical locations.

[0111] Embodiment 6. The device of embodiment 1, wherein the first reference value is a measurement of a second capacitance of a second region of tissue that is distant from the first region of tissue.

[0112] Embodiment 7. The device of embodiment 6, wherein the second region of tissue is known to be healthy.

[0113] Embodiment 8. The apparatus of embodiment 6, wherein the second capacitance is measured substantially simultaneously with the first capacitance.

[0114] Embodiment 9. The device of embodiment 1, wherein the device further comprises one or more temperature sensors configured to measure the temperature of a first region of tissue and coupled to the processor, and the instructions further include steps of receiving information regarding the measured temperature from the one or more temperature sensors, comparing the measured temperature to a second reference value, and providing a signal if the measured first capacitance differs from the first reference value by an amount that is greater than a predetermined first threshold and the measured temperature differs from the second reference value by an amount that is greater than a predetermined second threshold.

[0115] Embodiment 10. The device of embodiment 1, wherein the device further comprises one or more optical sensors configured to image the soles of the patient's feet while the patient is standing on the substrate.

[0116] Embodiment 11. A method for assessing susceptibility of tissue to the formation of a diabetic foot ulcer, the method comprising: obtaining a first capacitance value at a first location on a patient's skin; obtaining a temperature measurement value at the first location on the patient's skin; and determining that the first location on the patient's skin is susceptible to the formation of a diabetic foot ulcer when the first capacitance value differs from a first reference value by an amount greater than a first predetermined threshold and the temperature measurement value differs from a second reference value by an amount greater than a second predetermined threshold.

[0117] Embodiment 12. The method of embodiment 11, wherein the first reference value is predetermined.

[0118] Embodiment 13. The method of embodiment 11, wherein the first reference value is determined by a first capacitance measurement when the first location on the patient's skin is healthy.

[0119] Embodiment 14. The method of embodiment 11, wherein the first reference value is determined from a measurement of a first capacitance at a first location on the patient's skin at one or more time points prior to the most recent measurement of the first capacitance.

[0120] Embodiment 15. The method of embodiment 11, wherein the first reference value is a measurement of a second capacitance at a second location on the patient's skin that is distant from the first location on the patient's skin.

[0121] Embodiment 16. The method of embodiment 15, wherein the second area of ​​the patient's skin is known to be healthy.

[0122] Embodiment 17. The method of embodiment 15, wherein the second capacitance is measured substantially simultaneously with the first capacitance.

[0123] Embodiment 18. A method for assessing susceptibility of tissue to the formation of a diabetic foot ulcer, the method comprising: obtaining a first subepidermal moisture (SEM) value at a first location on a patient's skin; obtaining a temperature measurement at the first location on the patient's skin; and determining that the first location on the patient's skin is susceptible to the formation of a diabetic foot ulcer when the first SEM value differs from a first reference value by an amount greater than a first predetermined threshold and the temperature measurement differs from a second reference value by an amount greater than a second predetermined threshold.

[0124] Embodiment 19. The method of embodiment 18, wherein the first reference value is predetermined.

[0125] Embodiment 20. The method of embodiment 18, wherein the first reference value is determined by measuring a first SEM value when the first location on the patient's skin is healthy.

[0126] Embodiment 21. The method of embodiment 18, wherein the first reference value is determined from measurements of a first SEM value at a first location on the patient's skin at one or more time points prior to the most recent measurement of the first SEM value.

[0127] Embodiment 22. The method of embodiment 18, wherein the first reference value is a measurement of a second SEM value at a second location on the patient's skin that is distant from the first location on the patient's skin.

[0128] Embodiment 23. The method of embodiment 22, wherein the second location of the patient's skin is known to be healthy.

[0129] Embodiment 24. The method of embodiment 22, wherein the second SEM value is measured at approximately the same time as the first SEM value.

[0130] Embodiment 25. An integrated device for treating diabetic foot ulcers in a patient in need thereof, the device comprising: a plurality of sensors arranged on a flexible substrate, the plurality of sensors configured to measure subepidermal moisture (SEM) values ​​at respective locations on the patient's skin; two electrodes arranged on the flexible substrate; and an external controller electrically connected to the two electrodes, wherein the external controller controls the two electrodes to detect conductive contact with the patient's skin during an SEM measurement period, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during a treatment phase.

[0131] Embodiment 26. The device of embodiment 25, further comprising an absorbent pad.

[0132] Embodiment 27. The device of embodiment 25, further comprising a layer of adhesive.

[0133] Embodiment 28. A device according to embodiment 25, wherein the flexible substrate is permeable to gases but impermeable to liquids.

[0134] Embodiment 29. An integrated device for treating diabetic foot ulcers in a patient in need thereof, the device comprising: a sensor having two electrodes, the two electrodes being disposed on a flexible substrate such that a current passing between the electrodes passes through tissue adjacent to a location on the patient's skin; and an external controller electrically connected to the two electrodes.

[0135] Embodiment 30. An integrated device as described in embodiment 29, wherein the external controller controls the two electrodes to detect conductive contact with the patient's skin during the SEM measurement period, and the external controller controls the two electrodes to apply therapeutic stimulation to the patient during the treatment phase.

[0136] While the present invention has been described with reference to particular embodiments, those skilled in the art will recognize that various modifications may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from its scope. Therefore, it is intended that the present invention not be limited to the particular embodiments disclosed, but will include all embodiments coming within the scope and spirit of the appended claims.

Claims

1. 1. An integrated device for treating diabetic foot ulcers in a patient in need thereof, said integrated device comprising: a sensor comprising a first electrode and a second electrode disposed on a shaped substrate, the plurality of sensors configured to measure subepidermal moisture (SEM) values ​​at respective locations on the patient's skin during an SEM measurement period, the shaped substrate configured to conform to a portion of the patient's foot, the measured SEM values ​​corresponding to extracellular fluid (ECF) levels at respective locations on the patient's skin during the SEM measurement period, and the sensors electrically insulated by an insulating cover layer to allow only capacitive electrical contact with the patient's foot; a third electrode and a fourth electrode disposed on the molded substrate; an external controller electrically connected to the third and fourth electrodes, the external controller configured to control the third and fourth electrodes to detect conductive contact with the patient's skin during the SEM measurement period, the external controller configured to control the third and fourth electrodes to apply a therapeutic stimulus to the patient during a treatment phase, the therapeutic stimulus being applied in a plurality of periods, the plurality of periods having a duration and a time interval between the plurality of periods, the therapeutic stimulus being a low-level voltage or a low-level current that improves healing of the diabetic foot ulcer; An integrated device comprising:

2. 10. The integrated device of claim 1, wherein the external controller and the sensor are configured to measure tissue capacitance at each location on the patient's skin during time intervals between multiple stimulation periods.

3. 3. The integrated device of claim 1 or 2, wherein the shaped substrate is integrated into a lining of a garment.

4. 3. The integrated device of claim 1 or 2, wherein the molded substrate is integrated into a shoe liner.

5. 3. The integrated device of claim 1 or 2, wherein the shaped substrate is integrated into a sensing band.

6. 6. The integrated device of claim 5, further comprising a plurality of sensors configured to measure one or more of tissue oxyhemoglobin and / or deoxyhemoglobin, skin temperature, pulse rate, blood volume, and blood pressure.

7. The integrated device of claim 1 further comprising the capability to wirelessly communicate with a WiFi access point.

8. The integrated apparatus of claim 1 , further configured to communicate with one or more SEM applications running on one or more digital devices, such as a server, a computer, a laptop computer, or a smartphone.

9. An integrated system comprising the integrated apparatus of claim 8 and one or more digital devices, wherein one or more SEM applications are operable on the one or more digital devices.

10. The integrated apparatus of claim 8 or the integrated system of claim 9, wherein the one or more digital devices are selected from the group consisting of a server, a computer, a laptop computer, and a smartphone.

11. 11. The integrated device of claim 7, 8, or 10, configured to transfer information to and receive information from an electronic medical record (EMR).

12. 10. The integrated device of claim 1 further comprising an absorbent pad.

13. 13. The integrated device of claim 1 or 12, further comprising a layer of adhesive.

14. 14. The integrated device of claim 1, 12, or 13, wherein the shaped substrate is permeable to gases but impermeable to liquids.

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